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Sample records for blood-retinal barrier cells

  1. The development of blood-retinal barrier during the interaction of astrocytes with vascular wall cells

    Institute of Scientific and Technical Information of China (English)

    Huanling Yao; Tianshi Wang; Jiexin Deng; Ding Liu; Xiaofei Li; Jinbo Deng

    2014-01-01

    Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the development of the retinal vascular system and the formation of the blood-ret-inal barrier in mice were investigated using immunolfuorescence staining, gelatin-ink perfusion, and transmission electron microscopy. The results showed that the retinal vascular system of mice develops from the optic disc after birth, and radiates out gradually to cover the entire retina, taking the papilla optica as the center. First, the superifcial vasculature is formed on the inner retinal layer;then, the vasculature extends into the inner and outer edges of the retinal inner nuclear layer, forming the deep vasculature that is parallel to the superifcial vasculature. The blood-retinal barrier is mainly composed of endothelium, basal lamina and the end-feet of astrocytes, which become mature during mouse development. Initially, the naive endothelial cells were immature with few organelles and many microvilli. The basal lamina was uniform in thickness, and the glial end-feet surrounded the outer basal lamina incompletely. In the end, the blood-retinal barrier matures with smooth endothelia connected through tight junctions, rela-tively thin and even basal lamina, and relatively thin glial cell end-feet. These ifndings indicate that the development of the vasculature in the retina follows the rules of“center to periphery”and“superifcial layer to deep layers”. Its development and maturation are spatially and tempo-rally consistent with the functional performance of retinal neurons and photosensitivity. The blood-retinal barrier gradually becomes mature via the process of interactions between astro-cytes and blood vessel cells.

  2. TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes.

    Science.gov (United States)

    Jiang, Feng; Chen, Qingzhong; Huang, Liming; Wang, Ying; Zhang, Zhuhong; Meng, Xiangda; Liu, Yuanyuan; Mao, Chunjie; Zheng, Fang; Zhang, Jingkai; Yan, Hua

    2016-01-01

    Tumor necrosis factor superfamily 15 (TNFSF15) is an endogenous neovascularization inhibitor and an important negative regulator of vascular homeostasis. This study aimed to explore the potential role of TNFSF15 in diabetic retinopathy. Vitreous TNFSF15 and VEGF levels in proliferative diabetic retinopathy (PDR) patients were detected by ELISA. Retinal expression of TNFSF15 and the content of tight junction proteins (TJPs) in rats were detected by immunohistochemistry and Western blot, respectively. The blood retinal barrier (BRB) permeability was evaluated using Evans Blue (EB) dye. The TNFSF15/VEGF ratio was decreased in the vitreous fluid of patients with PDR relative to the controls, even though the expression levels of TNFSF15 were higher. TNFSF15 was dramatically decreased one month later after diabetes induction (p treatment significantly protected the BRB in the diabetic animals. Diabetes decreased TJPs levels in the retina, and these changes were inhibited by TNFSF15 treatment. Moreover, TNFSF15 decreased activation of VEGF both in mRNA and protein levels caused by diabetes. These results indicate that TNFSF15 is an important inhibitor in the progression of DR and suggest that the regulation of TNFSF15 shows promise for the development of diabetic retinopathy treatment strategies. PMID:27120595

  3. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction

    Science.gov (United States)

    Coburn, Phillip S.; Wiskur, Brandt J.; Miller, Frederick C.; LaGrow, Austin L.; Astley, Roger A.; Elliott, Michael H.; Callegan, Michelle C.

    2016-01-01

    The blood-retinal barrier (BRB) functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE) cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE), a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3) was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu) of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB permeability is

  4. Bloodstream-To-Eye Infections Are Facilitated by Outer Blood-Retinal Barrier Dysfunction.

    Directory of Open Access Journals (Sweden)

    Phillip S Coburn

    Full Text Available The blood-retinal barrier (BRB functions to maintain the immune privilege of the eye, which is necessary for normal vision. The outer BRB is formed by tightly-associated retinal pigment epithelial (RPE cells which limit transport within the retinal environment, maintaining retinal function and viability. Retinal microvascular complications and RPE dysfunction resulting from diabetes and diabetic retinopathy cause permeability changes in the BRB that compromise barrier function. Diabetes is the major predisposing condition underlying endogenous bacterial endophthalmitis (EBE, a blinding intraocular infection resulting from bacterial invasion of the eye from the bloodstream. However, significant numbers of EBE cases occur in non-diabetics. In this work, we hypothesized that dysfunction of the outer BRB may be associated with EBE development. To disrupt the RPE component of the outer BRB in vivo, sodium iodate (NaIO3 was administered to C57BL/6J mice. NaIO3-treated and untreated mice were intravenously injected with 108 colony forming units (cfu of Staphylococcus aureus or Klebsiella pneumoniae. At 4 and 6 days postinfection, EBE was observed in NaIO3-treated mice after infection with K. pneumoniae and S. aureus, although the incidence was higher following S. aureus infection. Invasion of the eye was observed in control mice following S. aureus infection, but not in control mice following K. pneumoniae infection. Immunohistochemistry and FITC-dextran conjugate transmigration assays of human RPE barriers after infection with an exoprotein-deficient agr/sar mutant of S. aureus suggested that S. aureus exoproteins may be required for the loss of the tight junction protein, ZO-1, and for permeability of this in vitro barrier. Our results support the clinical findings that for both pathogens, complications which result in BRB permeability increase the likelihood of bacterial transmigration from the bloodstream into the eye. For S. aureus, however, BRB

  5. Blood-retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management.

    Science.gov (United States)

    Kaur, C; Foulds, W S; Ling, E A

    2008-11-01

    The blood-retinal barrier (BRB) plays an important role in the homeostatic regulation of the microenvironment in the retina. It consists of inner and outer components, the inner BRB (iBRB) being formed by the tight junctions between neighbouring retinal capillary endothelial cells and the outer barrier (oBRB) by tight junctions between retinal pigment epithelial cells. Astrocytes, Müller cells and pericytes contribute to the proper functioning of the iBRB. In many clinically important conditions including diabetic retinopathy, ischaemic central retinal vein occlusion, and some respiratory diseases, retinal hypoxia results in a breakdown of the iBRB. Disruption of the iBRB associated with increased vascular permeability, results in vasogenic oedema and tissue damage, with consequent adverse effects upon vision. Factors such as enhanced production of vascular endothelial growth factor (VEGF), NO, oxidative stress and inflammation underlie the increased permeability of the iBRB and inhibition of these factors is beneficial. Experimental studies in our laboratory have shown melatonin to be a protective agent for the iBRB in hypoxic conditions. Although oBRB breakdown can occur in conditions such as accelerated hypertension and the toxaemia of pregnancy, both of which are associated with choroidal ischaemia and in age-related macular degeneration (ARMD), and is a feature of exudative (serous) retinal detachment, our studies have shown that the oBRB remains intact in hypoxic/ischaemic conditions. Clinically, anti-VEGF therapy has been shown to improve vision in diabetic maculopathy and in neovascular ARMD. The visual benefit in both conditions appears to arise from the restoration of BRB integrity with a reduction of retinal oedema. PMID:18940262

  6. A novel transgenic zebrafish model for blood-brain and blood-retinal barrier development

    Directory of Open Access Journals (Sweden)

    Sugimoto Masahiko

    2010-07-01

    Full Text Available Abstract Background Development and maintenance of the blood-brain and blood-retinal barrier is critical for the homeostasis of brain and retinal tissue. Despite decades of research our knowledge of the formation and maintenance of the blood-brain (BBB and blood-retinal (BRB barrier is very limited. We have established an in vivo model to study the development and maintenance of these barriers by generating a transgenic zebrafish line that expresses a vitamin D-binding protein fused with enhanced green fluorescent protein (DBP-EGFP in blood plasma, as an endogenous tracer. Results The temporal establishment of the BBB and BRB was examined using this transgenic line and the results were compared with that obtained by injection of fluorescent dyes into the sinus venosus of embryos at various stages of development. We also examined the expression of claudin-5, a component of tight junctions during the first 4 days of development. We observed that the BBB of zebrafish starts to develop by 3 dpf, with expression of claudin-5 in the central arteries preceding it at 2 dpf. The hyaloid vasculature in the zebrafish retina develops a barrier function at 3 dpf, which endows the zebrafish with unique advantages for studying the BRB. Conclusion Zebrafish embryos develop BBB and BRB function simultaneously by 3 dpf, which is regulated by tight junction proteins. The Tg(l-fabp:DBP-EGFP zebrafish will have great advantages in studying development and maintenance of the blood-neural barrier, which is a new application for the widely used vertebrate model.

  7. Radionuclide detection of blood-retinal barrier disruption in diabetes mellitus

    International Nuclear Information System (INIS)

    Diabetic retinopathy is one of the leading causes of blindness in the United States today. Because early treatment of proliferative retinopathy offers the best chance for visual salvation, there is an essential need for methods of identifying eyes at high risk. Recent research has shown that subclinical leakage from retinal blood vessels is one of the earliest signs of retinopathy. The feasibility of using radionuclide techniques to quantitate blood-retinal barrier disruption is demonstrated by a study in which 23 diabetics and 7 nondiabetics were imaged with an Anger camera in the anterior Waters projection at 2 hours after the administration of Tc-99m DTPA. In the digitized images, regions of interest were placed over each orbit and over one of the cerebral hemispheres. Orbital counts were then compared to cerebral counts on a per pixel basis. Eye to brain ratios were found to be lowest for nondiabetics and highest for patients with proliferative retinopathy. Additionally, the dynamic analysis of the same radiopharmaceutical may allow investigators to further study the pathophysiology of the diabetic eye

  8. Lycium barbarum polysaccharides reduce neuronal damage, blood-retinal barrier disruption and oxidative stress in retinal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Suk-Yee Li

    Full Text Available Neuronal cell death, glial cell activation, retinal swelling and oxidative injury are complications in retinal ischemia/reperfusion (I/R injuries. Lycium barbarum polysaccharides (LBP, extracts from the wolfberries, are good for "eye health" according to Chinese medicine. The aim of our present study is to explore the use of LBP in retinal I/R injury. Retinal I/R injury was induced by surgical occlusion of the internal carotid artery. Prior to induction of ischemia, mice were treated orally with either vehicle (PBS or LBP (1 mg/kg once a day for 1 week. Paraffin-embedded retinal sections were prepared. Viable cells were counted; apoptosis was assessed using TUNEL assay. Expression levels of glial fibrillary acidic protein (GFAP, aquaporin-4 (AQP4, poly(ADP-ribose (PAR and nitrotyrosine (NT were investigated by immunohistochemistry. The integrity of blood-retinal barrier (BRB was examined by IgG extravasations. Apoptosis and decreased viable cell count were found in the ganglion cell layer (GCL and the inner nuclear layer (INL of the vehicle-treated I/R retina. Additionally, increased retinal thickness, GFAP activation, AQP4 up-regulation, IgG extravasations and PAR expression levels were observed in the vehicle-treated I/R retina. Many of these changes were diminished or abolished in the LBP-treated I/R retina. Pre-treatment with LBP for 1 week effectively protected the retina from neuronal death, apoptosis, glial cell activation, aquaporin water channel up-regulation, disruption of BRB and oxidative stress. The present study suggests that LBP may have a neuroprotective role to play in ocular diseases for which I/R is a feature.

  9. The blood-retinal barrier permeability to fluorescein in normal subjects and in juvenile diabetics without retinopathy

    DEFF Research Database (Denmark)

    Krogsaa, B; Lund-Andersen, H; Mehlsen, J;

    1986-01-01

    The blood-retinal barrier permeability to fluorescein was determined in 20 eyes from 17 normal volunteers (mean age 31 years) and in 20 eyes from 19 juvenile diabetics without apparent retinopathy (mean age 35 years - mean duration of diabetes 6 years). The permeability was in normal subjects (1.......1 +/- 0.4) X 10(-7) cm/sec (mean +/- 2 X SD) and in juvenile diabetics (1.1 +/- 0.7) X 10(-7) cm/sec (mean +/- 2 X SD). Thus a break-down of the blood-retinal barrier cannot be demonstrated as a very early and general phenomenon in the early course of the diabetic disease. The fluorescein diffusion...... coefficient in the vitreous body was determined and juvenile diabetics without apparent retinopathy showed a diffusion coefficient of (0.80 +/- 0.25) X 10(-5) cm2/sec (mean +/- 2 X SD), which was the same as in normals where the diffusion coefficient was (0.69 +/- 0.46) X 10(-5) cm2/sec (mean +/- 2 X SD)....

  10. Blood-retinal barrier glycerol permeability in diabetic macular edema and healthy eyes: estimations from macular volume changes after peroral glycerol

    DEFF Research Database (Denmark)

    Thornit, Dorte Nellemann; Vinten, Carl Martin; Sander, Birgit;

    2010-01-01

    PURPOSE: To compare the changes in macular volume (MV) between healthy subjects and patients with diabetic macular edema (DME) after an osmotic load and to determine the glycerol permeability (P(gly)) of the blood-retinal barrier (BRB). METHODS: In this unmasked study, 13 patients with DME and 5...

  11. Inhibition of Advanced Glycation and Absence of Galectin-3 Prevent Blood-Retinal Barrier Dysfunction during Short-Term Diabetes

    Directory of Open Access Journals (Sweden)

    Paul Canning

    2007-01-01

    Full Text Available Breakdown of the inner blood-retinal barrier (iBRB occurs early in diabetes and is central to the development of sight-threatening diabetic macular edema (DME as retinopathy progresses. In the current study, we examined how advanced glycation end products (AGEs forming early in diabetes could modulate vasopermeability factor expression in the diabetic retina and alter inter-endothelial cell tight junction (TJ integrity leading to iBRB dysfunction. We also investigated the potential for an AGE inhibitor to prevent this acute pathology and examined a role of the AGE-binding protein galectin-3 (Gal-3 in AGE-mediated cell retinal pathophysiology. Diabetes was induced in C57/BL6 wild-type (WT mice and in Gal-3−/− transgenic mice. Blood glucose was monitored and AGE levels were quantified by ELISA and immunohistochemistry. The diabetic groups were subdivided, and one group was treated with the AGE-inhibitor pyridoxamine (PM while separate groups of WT and Gal-3−/− mice were maintained as nondiabetic controls. iBRB integrity was assessed by Evans blue assay alongside visualisation of TJ protein complexes via occludin-1 immunolocalization in retinal flat mounts. Retinal expression levels of the vasopermeability factor VEGF were quantified using real-time RT-PCR and ELISA. WT diabetic mice showed significant AGE -immunoreactivity in the retinal microvasculature and also showed significant iBRB breakdown (P<.005. These diabetics had higher VEGF mRNA and protein expression in comparison to controls (P<.01. PM-treated diabetics had normal iBRB function and significantly reduced diabetes-mediated VEGF expression. Diabetic retinal vessels showed disrupted TJ integrity when compared to controls, while PM-treated diabetics demonstrated near-normal configuration. Gal-3−/− mice showed significantly less diabetes-mediated iBRB dysfunction, junctional disruption, and VEGF expression changes than their WT counterparts. The data suggests an AGE

  12. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress

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    David eArredondo Zamarripa

    2014-10-01

    Full Text Available Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK production contributes to the increased transport through the blood-retina barrier (BRB in diabetes. Here, we studied if vasoinhibins regulate BRB permeability by targeting the vascular endothelium and retinal pigment epithelium (RPE components of this barrier. Intravitreal injection of BK in male rats increased BRB permeability. Vasoinhibins prevented this effect, as did the B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal and brain capillary endothelial monolayer resistance that was blocked by vasoinhibins. Both vasoinhibins and the nitric oxide (NO synthase inhibitor L-NAME, but not the antioxidant N-acetyl cysteine (NAC, blocked the transient decrease in bovine umbilical vein endothelial cell (BUVEC monolayer resistance induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME. BK transiently decreased human RPE (ARPE-19 cell monolayer resistance, and this effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton redistribution. Intravitreal injection of vasoinhibins reduced the levels of reactive oxygen species (ROS in retinas of streptozotocin-induced diabetic rats, particularly in the RPE and capillary-containing layers. Thus, vasoinhibins reduce BRB permeability by targeting both its main inner and outer components through NO- and ROS-dependent pathways, offering potential treatment strategies against diabetic retinopathies.

  13. Intravenously administered gold nanoparticles pass through the blood-retinal barrier depending on the particle size, and induce no retinal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Hun; Kim, Jin Hyoung; Yu, Young Suk [Department of Ophthalmology, Seoul National University College of Medicine and Seoul Artificial Eye Center, Clinical Research Institute, Seoul National University Hospital, Seoul 151744 (Korea, Republic of); Kim, Kyu-Won [NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151742 (Korea, Republic of); Kim, Myung Hun, E-mail: hunin315@paran.com, E-mail: ysyu@snu.ac.kr [Department of Chemistry, Yonsei University, 134 Shinchon-dong, Seodaemun-ku, Seoul 120749 (Korea, Republic of)

    2009-12-16

    The retina maintains homeostasis through the blood-retinal barrier (BRB). Although it is ideal to deliver the drug to the retina via systemic administration, it is still challenging due to the BRB strictly regulating permeation from blood to the retina. Herein, we demonstrated that intravenously administered gold nanoparticles could pass through the BRB and are distributed in all retinal layers without cytotoxicity. After intravenous injection of gold nanoparticles into C57BL/6 mice, 100 nm nanoparticles were not detected in the retina whereas 20 nm nanoparticles passed through the BRB and were distributed in all retinal layers. 20 nm nanoparticles in the retina were observed in neurons (75 {+-} 5%), endothelial cells (17 {+-} 6%) and peri-endothelial glial cells (8 {+-} 3%), where nanoparticles were bound on the membrane. In the retina, cells containing nanoparticles did not show any structural abnormality and increase of cell death compared to cells without nanoparticles. Gold nanoparticles never affected the viability of retinal endothelial cells, astrocytes and retinoblastoma cells. Furthermore, gold nanoparticles never led to any change in expression of representative biological molecules including zonula occludens-1 and glut-1 in retinal endothelial cells, neurofilaments in differentiated retinoblastoma cells and glial fibrillary acidic protein in astrocytes. Therefore, our data suggests that small gold nanoparticles (20 nm) could be an alternative for drug delivery across the BRB, which could be safely applied in vivo.

  14. Consumption of Polyphenol-Rich Zingiber Zerumbet Rhizome Extracts Protects against the Breakdown of the Blood-Retinal Barrier and Retinal Inflammation Induced by Diabetes

    Directory of Open Access Journals (Sweden)

    Thing-Fong Tzeng

    2015-09-01

    Full Text Available The present study investigates the amelioration of diabetic retinopathy (DR by Zingiber zerumbet rhizome ethanol extracts (ZZRext in streptozotocin-induced diabetic rats (STZ-diabetic rats. ZZRext contains high phenolic and flavonoid contents. STZ-diabetic rats were treated orally with ZZRext (200, 300 mg/kg per day for three months. Blood-retinal barrier (BRB breakdown and increased vascular permeability were found in diabetic rats, with downregulation of occludin, and claudin-5. ZZRext treatment effectively preserved the expression of occludin, and claudin-5, leading to less BRB breakdown and less vascular permeability. Retinal histopathological observation showed that the disarrangement and reduction in thickness of retinal layers were reversed in ZZRext-treated diabetic rats. Retinal gene expression of tumor necrosis factor-α, interleukin (IL-1β, IL-6, vascular endothelial growth factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in ZZRext-treated diabetic rats. Moreover, ZZRext treatment not only inhibited the nuclear factor κB (NF-κB activation, but also downregulated the protein expression of p38 mitogen-activated protein kinase (MAPK in diabetic retina. In conclusion, the results suggest that the retinal protective effects of ZZRext occur through improved retinal structural change and inhibiting retinal inflammation. The antiretinopathy property of ZZRext might be related to the downregulation of p38 MAPK and NF-κB signal transduction induced by diabetes.

  15. Blood cells and endothelial barrier function

    OpenAIRE

    Rodrigues, Stephen F.; Granger, D Neil

    2015-01-01

    The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An impairment of endothelial barrier function has been implicated in the genesis and/or progression of a variety of pathological conditions, including pulmonary edema, ischemic stroke, neurodegenerative disorders, angioedema, sepsis and cancer. The altered barrier function in these conditions is often linked to the release of solub...

  16. Blood cells and endothelial barrier function.

    Science.gov (United States)

    Rodrigues, Stephen F; Granger, D Neil

    2015-01-01

    The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An impairment of endothelial barrier function has been implicated in the genesis and/or progression of a variety of pathological conditions, including pulmonary edema, ischemic stroke, neurodegenerative disorders, angioedema, sepsis and cancer. The altered barrier function in these conditions is often linked to the release of soluble mediators from resident cells (e.g., mast cells, macrophages) and/or recruited blood cells. The interaction of the mediators with receptors expressed on the surface of endothelial cells diminishes barrier function either by altering the expression of adhesive proteins in the inter-endothelial junctions, by altering the organization of the cytoskeleton, or both. Reactive oxygen species (ROS), proteolytic enzymes (e.g., matrix metalloproteinase, elastase), oncostatin M, and VEGF are part of a long list of mediators that have been implicated in endothelial barrier failure. In this review, we address the role of blood borne cells, including, neutrophils, lymphocytes, monocytes, and platelets, in the regulation of endothelial barrier function in health and disease. Attention is also devoted to new targets for therapeutic intervention in disease states with morbidity and mortality related to endothelial barrier dysfunction. PMID:25838983

  17. Glial and endothelial blood-retinal barrier responses to amyloid-β in the neural retina of the rat

    OpenAIRE

    Anderson, Peter

    2008-01-01

    Peter JB Anderson1,a, HR Watts1,a, CJ Hille3, KL Philpott3, P Clark4, M Croucher, S Gentleman2, Ling-Sun Jen11Department of Cellular and Molecular Neuroscience; 2Department of Clinical Neuroscience, Division of Neuroscience and Mental Health, Imperial College London, Charing Cross Hospital Campus, London, UK; 3Neurosciences, Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, Harlow, Essex, UK; 4Leukocyte Biology Section, National Heart and Lung Institute, Imperial Colle...

  18. Molten carbonate fuel cell integral matrix tape and bubble barrier

    International Nuclear Information System (INIS)

    A molten carbonate fuel cell matrix material is described made up of a matrix tape portion and a bubble barrier portion. The matrix tape portion comprises particles inert to molten carbonate electrolyte, ceramic particles and a polymeric binder, the matrix tape being flexible, pliable and having rubber-like compliance at room temperature. The bubble barrier is a solid material having fine porosity preferably being bonded to the matrix tape. In operation in a fuel cell, the polymer binder burns off leaving the matrix and bubble barrier providing superior sealing, stability and performance properties to the fuel cell stack

  19. Dual role of vinculin in barrier-disruptive and barrier-enhancing endothelial cell responses.

    Science.gov (United States)

    Birukova, Anna A; Shah, Alok S; Tian, Yufeng; Moldobaeva, Nurgul; Birukov, Konstantin G

    2016-06-01

    Endothelial cell (EC) barrier disruption induced by edemagenic agonists such as thrombin is a result of increased actomyosin contraction and enforcement of focal adhesions (FA) anchoring contracting stress fibers, which leads to cell retraction and force-induced disruption of cell junctions. In turn, EC barrier enhancement by oxidized phospholipids (OxPAPC) and other agonists is a result of increased tethering forces due to enforcement of the peripheral actin rim and enhancement of cell-cell adherens junction (AJ) complexes promoting EC barrier integrity. This study tested participation of the mechanosensitive adaptor, vinculin, which couples FA and AJ to actin cytoskeleton, in control of the EC permeability response to barrier disruptive (thrombin) and barrier enhancing (OxPAPC) stimulation. OxPAPC and thrombin induced different patterns of FA remodeling. Knockdown of vinculin attenuated both, OxPAPC-induced decrease and thrombin-induced increase in EC permeability. Thrombin stimulated the vinculin association with FA protein talin and suppressed the interaction with AJ protein, VE-cadherin. In contrast, OxPAPC stimulated the vinculin association with VE-cadherin. Thrombin and OxPAPC induced different levels of myosin light chain (MLC) phosphorylation and caused different patterns of intracellular phospho-MLC distribution. Thrombin-induced talin-vinculin and OxPAPC-induced VE-cadherin-vinculin association were abolished by myosin inhibitor blebbistatin. Expression of the vinculin mutant unable to interact with actin attenuated EC permeability changes and MLC phosphorylation caused by both, thrombin and OxPAPC. These data suggest that the specific vinculin interaction with FA or AJ in different contexts of agonist stimulation is defined by development of regional actyomyosin-based tension and participates in both, the barrier-disruptive and barrier-enhancing endothelial responses. PMID:26923917

  20. Barriers to the development of fuel-cell electric vehicles

    International Nuclear Information System (INIS)

    The study is structured as follows: Fuel cells (with focus on proton exchange membrane fuel cells (PEMFC)); Fuel cell electric vehicles; Barriers to commercial use of fuel cell vehicles in the following areas: price; hydrogen production; hydrogen infrastructure; hydrogen storage; other barriers (safety; lifetime; use in extreme conditions; control system errors). The major barriers include too high price and problems with a stable and sustainable hydrogen source. Also, the following must be ensured for a wider use of FCEVs: reduction in the weight and volume of the drive unit; improved lifetime of the PEMFC system; usability within wide weather conditions; existence of an adequate infrastructure (a dense hydrogen service station network and their hydrogen supply); and implementation of related legislation including safety standards. (P.A.)

  1. Electrolyte creepage barrier for liquid electrolyte fuel cells

    Science.gov (United States)

    Li, Jian; Farooque, Mohammad; Yuh, Chao-Yi

    2008-01-22

    A dielectric assembly for electrically insulating a manifold or other component from a liquid electrolyte fuel cell stack wherein the dielectric assembly includes a substantially impermeable dielectric member over which electrolyte is able to flow and a barrier adjacent the dielectric member and having a porosity of less than 50% and greater than 10% so that the barrier is able to measurably absorb and chemically react with the liquid electrolyte flowing on the dielectric member to form solid products which are stable in the liquid electrolyte. In this way, the barrier inhibits flow or creepage of electrolyte from the dielectric member to the manifold or component to be electrically insulated from the fuel cell stack by the dielectric assembly.

  2. InGaP Heterojunction Barrier Solar Cells

    Science.gov (United States)

    Welser, Roger E. (Inventor)

    2014-01-01

    A new solar cell structure called a heterojunction barrier solar cell is described. As with previously reported quantum-well and quantum-dot solar cell structures, a layer of narrow band-gap material, such as GaAs or indium-rich InGaP, is inserted into the depletion region of a wide band-gap PN junction. Rather than being thin, however, the layer of narrow band-gap material is about 400-430 nm wide and forms a single, ultrawide well in the depletion region. Thin (e.g., 20-50 nm), wide band-gap InGaP barrier layers in the depletion region reduce the diode dark current. Engineering the electric field and barrier profile of the absorber layer, barrier layer, and p-type layer of the PN junction maximizes photogenerated carrier escape. This new twist on nanostructured solar cell design allows the separate optimization of current and voltage to maximize conversion efficiency.

  3. Mucosal barrier injury and stem cell transplant recipients

    NARCIS (Netherlands)

    Blijlevens, Nicolina Maria Anna

    2005-01-01

    The intensive chemotherapy with or without radiation therapy used to prepare for a haematopoietic stem cell transplant (HSCT) is unfortunately complicated by damage to the mucosa of the digestive tract. The resultant, mucosal barrier injury (MBI) causes painful ulcerations, which are readily apparen

  4. Recent key technical barriers in solid oxide fuel cell technology

    Directory of Open Access Journals (Sweden)

    Milewski Jarosław

    2014-03-01

    Full Text Available High-temperature solid oxide fuel cells (SOFCs are considered as suitable components of future large-scale clean and efficient power generation systems. However, at its current stage of development some technical barriers exists which limit SOFC’s potential for rapid large-scale deployment. The present article aims at providing solutions to key technical barriers in SOFC technology. The focus is on the solutions addressing thermal resistance, fuel reforming, energy conversion efficiency, materials, design, and fuel utilisation issues.

  5. Molecular barriers to processes of genetic reprogramming and cell transformation.

    Science.gov (United States)

    Chestkov, I V; Khomyakova, E A; Vasilieva, E A; Lagarkova, M A; Kiselev, S L

    2014-12-01

    Genetic reprogramming by ectopic expression of transcription factor genes induces the pluripotent state in somatic cells. This technology provides an opportunity to establish pluripotent stem cells for each person, as well as to get better understanding of epigenetic mechanisms controlling cell state. Interestingly, some of the molecular processes that accompany somatic cell reprogramming in vitro are also characteristic for tumor manifestation. Thus, similar "molecular barriers" that control the stability of epigenetic state exist for both processes of pluripotency induction and malignant transformation. The reprogramming of tumor cells is interesting in two aspects: first, it will determine the contribution of epigenetic changes in carcinogenesis; second, it gives an approach to evaluate tumor stem cells that are supposed to form the entire cell mass of the tumor. This review discusses the key stages of genetic reprogramming, the similarity and difference between the reprogramming process and malignant transformation. PMID:25716723

  6. Barrier Functionality of Porcine and Bovine Brain Capillary Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ailar Nakhlband

    2011-09-01

    Full Text Available Introduction: To date, isolated cell based blood-brain barrier (BBB models have been widely used for brain drug delivery and targeting, due to their relatively proper bioelectrical and permeability properties. However, primary cultures of brain capillary endothelial cells (BCECs isolated from different species vary in terms of bioelectrical and permeability properties. Methods: To pursue this, in the current investigation, primary porcine and bovine BCECs (PBCECs and BBCECs, respectively were isolated and used as an in vitro BBB model. The bioelectrical and permeability properties were assessed in BCECs co-cultured with C6 cells with/without hydrocortisone (550 nM. The bioelectrical properties were further validated by means of the permeability coefficients of transcellular and paracellular markers. Results: The primary PBCECs displayed significantly higher trans-endothelial electrical resistance (~900 W.cm2 than BBCECs (~700 W.cm2 - both co-cultured with C6 cells in presence of hydrocortisone. Permeability coefficients of propranolol/diazepam and mannitol/sucrose in PBCECs were ~21 and ~2 (×10-6 cm.sec-1, where these values for BBCECs were ~25 and ~5 (×10-6 cm.sec-1. Conclusion: Upon our bioelectrical and permeability findings, both models display discriminative barrier functionality but porcine BCECs seem to provide a better platform than bovine BCECs for drug screening and brain targeting.

  7. Japanese encephalitis virus disrupts cell-cell junctions and affects the epithelial permeability barrier functions.

    Directory of Open Access Journals (Sweden)

    Tanvi Agrawal

    Full Text Available Japanese encephalitis virus (JEV is a neurotropic flavivirus, which causes viral encephalitis leading to death in about 20-30% of severely-infected people. Although JEV is known to be a neurotropic virus its replication in non-neuronal cells in peripheral tissues is likely to play a key role in viral dissemination and pathogenesis. We have investigated the effect of JEV infection on cellular junctions in a number of non-neuronal cells. We show that JEV affects the permeability barrier functions in polarized epithelial cells at later stages of infection. The levels of some of the tight and adherens junction proteins were reduced in epithelial and endothelial cells and also in hepatocytes. Despite the induction of antiviral response, barrier disruption was not mediated by secreted factors from the infected cells. Localization of tight junction protein claudin-1 was severely perturbed in JEV-infected cells and claudin-1 partially colocalized with JEV in intracellular compartments and targeted for lysosomal degradation. Expression of JEV-capsid alone significantly affected the permeability barrier functions in these cells. Our results suggest that JEV infection modulates cellular junctions in non-neuronal cells and compromises the permeability barrier of epithelial and endothelial cells which may play a role in viral dissemination in peripheral tissues.

  8. Barrier-protective effects of activated protein C in human alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ferranda Puig

    Full Text Available Acute lung injury (ALI is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC on mechanical tension and barrier integrity in human alveolar epithelial cells (A549 exposed to thrombin. Cells were pretreated for 3 h with APC (50 µg/ml or vehicle (control. Subsequently, thrombin (50 nM or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

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

    OpenAIRE

    Hee Soon Shin; Sun Young Jung; Su Yeon Back; Jeong-Ryong Do; Dong-Hwa Shon

    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 ...

  10. Fingolimod (FTY720-P Does Not Stabilize the Blood–Brain Barrier under Inflammatory Conditions in an in Vitro Model

    Directory of Open Access Journals (Sweden)

    Michael K. Schuhmann

    2015-12-01

    Full Text Available Breakdown of the blood-brain barrier (BBB is an early hallmark of multiple sclerosis (MS, a progressive inflammatory disease of the central nervous system. Cell adhesion in the BBB is modulated by sphingosine-1-phosphate (S1P, a signaling protein, via S1P receptors (S1P1. Fingolimod phosphate (FTY720-P a functional S1P1 antagonist has been shown to improve the relapse rate in relapsing-remitting MS by preventing the egress of lymphocytes from lymph nodes. However, its role in modulating BBB permeability—in particular, on the tight junction proteins occludin, claudin 5 and ZO-1—has not been well elucidated to date. In the present study, FTY720-P did not change the transendothelial electrical resistance in a rat brain microvascular endothelial cell (RBMEC culture exposed to inflammatory conditions and thus did not decrease endothelial barrier permeability. In contrast, occludin was reduced in RBMEC culture after adding FTY720-P. Additionally, FTY720-P did not alter the amount of endothelial matrix metalloproteinase (MMP-9 and MMP-2 in RBMEC cultures. Taken together, our observations support the assumption that S1P1 plays a dual role in vascular permeability, depending on its ligand. Thus, S1P1 provides a mechanistic basis for FTY720-P-associated disruption of endothelial barriers—such as the blood-retinal barrier—which might result in macular edema.

  11. Glucocorticoids induce transactivation of tight junction genes occludin and claudin-5 in retinal endothelial cells via a novel cis-element.

    Science.gov (United States)

    Felinski, Edward A; Cox, Amy E; Phillips, Brett E; Antonetti, David A

    2008-06-01

    Tight junctions between vascular endothelial cells help to create the blood-brain and blood-retinal barriers. Breakdown of the retinal tight junction complex is problematic in several disease states including diabetic retinopathy. Glucocorticoids can restore and/or preserve the endothelial barrier to paracellular permeability, although the mechanism remains unclear. We show that glucocorticoid treatment of primary retinal endothelial cells increases content of the tight junction proteins occludin and claudin-5, co-incident with an increase in barrier properties of endothelial monolayers. The glucocorticoid receptor antagonist RU486 reverses both the glucocorticoid-stimulated increase in occludin content and the increase in barrier properties. Transcriptional activity from the human occludin and claudin-5 promoters increases in retinal endothelial cells upon glucocorticoid treatment, and is dependent on the glucocorticoid receptor (GR) as demonstrated by siRNA. Deletion analysis of the occludin promoter reveals a 205bp sequence responsible for the glucocorticoid response. However, this region does not possess a canonical glucocorticoid response element and does not bind to the GR in a chromatin immunoprecipitation (ChIP) assay. Mutational analysis of this region revealed a novel 40bp occludin enhancer element (OEE), containing two highly conserved regions of 10 and 13 base pairs, that is both necessary and sufficient for glucocorticoid-induced gene expression in retinal endothelial cells. These data suggest a novel mechanism for glucocorticoid induction of vascular endothelial barrier properties through increased occludin and claudin-5 gene expression. PMID:18501346

  12. RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border.

    Science.gov (United States)

    Marcos-Ramiro, Beatriz; García-Weber, Diego; Barroso, Susana; Feito, Jorge; Ortega, María C; Cernuda-Morollón, Eva; Reglero-Real, Natalia; Fernández-Martín, Laura; Durán, Maria C; Alonso, Miguel A; Correas, Isabel; Cox, Susan; Ridley, Anne J; Millán, Jaime

    2016-05-01

    Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new proteins essential to the human endothelial inflammatory response, we have found that the endosomal GTPase RhoB is up-regulated in response to inflammatory cytokines and expressed in the endothelium of some chronically inflamed tissues. We show that although RhoB and the related RhoA and RhoC play additive and redundant roles in various aspects of endothelial barrier function, RhoB specifically inhibits barrier restoration after acute cell contraction by preventing plasma membrane extension. During barrier restoration, RhoB trafficking is induced between vesicles containing RhoB nanoclusters and plasma membrane protrusions. The Rho GTPase Rac1 controls membrane spreading and stabilizes endothelial barriers. We show that RhoB colocalizes with Rac1 in endosomes and inhibits Rac1 activity and trafficking to the cell border during barrier recovery. Inhibition of endosomal trafficking impairs barrier reformation, whereas induction of Rac1 translocation to the plasma membrane accelerates it. Therefore, RhoB-specific regulation of Rac1 trafficking controls endothelial barrier integrity during inflammation. PMID:27138256

  13. Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development.

    Science.gov (United States)

    Wong, Bernice H; Chan, Jia Pei; Cazenave-Gassiot, Amaury; Poh, Rebecca W; Foo, Juat Chin; Galam, Dwight L A; Ghosh, Sujoy; Nguyen, Long N; Barathi, Veluchamy A; Yeo, Sia W; Luu, Chi D; Wenk, Markus R; Silver, David L

    2016-05-13

    Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth. Here we demonstrate that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of Mfsd2a expression in the eye. Eyes from whole body Mfsd2a-deficient (KO) mice, but not endothelium-specific Mfsd2a-deficient mice, were DHA-deficient and had significantly reduced LPC/DHA transport in vivo Fluorescein angiography indicated normal blood-retinal barrier function. Histological and electron microscopic analysis indicated that Mfsd2a KO mice exhibited a specific reduction in outer rod segment length, disorganized outer rod segment discs, and mislocalization of and reduction in rhodopsin early in postnatal development without loss of photoreceptors. Minor photoreceptor cell loss occurred in adult Mfsd2a KO mice, but electroretinography indicated visual function was normal. The developing eyes of Mfsd2a KO mice had activated microglia and up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of LPC transport. These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs. PMID:27008858

  14. Biomaterials as carrier, barrier and reactor for cell-based regenerative medicine

    OpenAIRE

    Qi, Chunxiao; Yan, Xiaojun; Huang, Chenyu; Melerzanov, Alexander; Du, Yanan

    2015-01-01

    Cell therapy has achieved tremendous success in regenerative medicine in the past several decades. However, challenges such as cell loss, death and immune-rejection after transplantation still persist. Biomaterials have been designed as carriers to deliver cells to desirable region for local tissue regeneration; as barriers to protect transplanted cells from host immune attack; or as reactors to stimulate host cell recruitment, homing and differentiation. With the assistance of biomaterials, ...

  15. Micronucleus formation induced by dielectric barrier discharge plasma exposure in brain cancer cells

    Science.gov (United States)

    Kaushik, Nagendra K.; Uhm, Hansup; Ha Choi, Eun

    2012-02-01

    Induction of micronucleus formation (cytogenetic damage) in brain cancer cells upon exposure of dielectric barrier discharge plasma has been investigated. We have investigated the influence of exposure and incubation times on T98G brain cancer cells by using growth kinetic, clonogenic, and micronucleus formation assay. We found that micronucleus formation rate directly depends on the plasma exposure time. It is also shown that colony formation capacity of cells has been inhibited by the treatment of plasma at all doses. Cell death and micronucleus formation are shown to be significantly elevated by 120 and 240 s exposure of dielectric barrier discharge plasma.

  16. Development of microfluidic cell culture devices towards an in vitro human intestinal barrier model

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin

    displaying folds that closely resembled the intestinal villi and formation of a tight barrier. Furthermore, the microelectrodes embedded in the microchip also allow real-time monitoring of the barrier integrity by means of measuring the trans-epithelial electrical resistance. Demonstrations of transport...... enable real-time detection of cell responses, adjustment of cellular stimulation etc. leading to establishment of conditional experiments. In this project, microfluidic systems engineering was leveraged to develop an eight chamber multi-layer microchip for intestinal barrier studies. Sandwiched between...... without compromising the epithelial cell viability and barrier function. Such a platform paves the way towards an alternative in vitro intestinal model for high throughput screening of drugs, chemicals, pathogens, intestinal diseases as well as toxicological studies....

  17. Interleukin-4 and interleukin-13 cause barrier dysfunction in human airway epithelial cells

    OpenAIRE

    Saatian, Bahman; Rezaee, Fariba; Desando, Samantha; Emo, Jason; Chapman, Tim; Knowlden, Sara; Steve N. Georas

    2013-01-01

    Emerging evidence indicates that airway epithelial barrier function is compromised in asthma, a disease characterized by Th2-skewed immune response against inhaled allergens, but the mechanisms involved are not well understood. The purpose of this study was to investigate the effects of Th2-type cytokines on airway epithelial barrier function. 16HBE14o- human bronchial epithelial cells monolayers were grown on collagen coated Transwell inserts. The basolateral or apical surfaces of airway epi...

  18. Barriers to Mental Health Service Use among Hematopoietic Stem Cell Transplant Survivors

    OpenAIRE

    Mosher, Catherine E.; DuHamel, Katherine N.; Rini, Christine M.; Li, Yuelin; Isola, Luis; Labay, Larissa; Rowley, Scott; Papadopoulos, Esperanza; Moskowitz, Craig; Scigliano, Eileen; Grosskreutz, Celia; Redd, William H.

    2009-01-01

    Summary This study examined barriers to mental health service use and their demographic, medical, and psychosocial correlates among hematopoietic stem cell transplant (HSCT) survivors. A sample of 253 HSCT survivors who were 1- to 3-years post-transplant completed measures of demographic, physical, psychological, and social characteristics as well as a newly modified measure of barriers to mental health service use. Only 50% of distressed HSCT survivors had received mental health services. An...

  19. Breaching the kinetic barrier to in vitro somatic stem cell propagation

    OpenAIRE

    Merok, Joshua R.; Sherley, James L.

    2001-01-01

    Abstract Here we have reviewed the conventional definitions and fundamental characteristics of the two basic types of stem cells, embryonic stem cells (ESCs) and somatic stem cells (SSCs). By taking into account the often-overlooked asymmetric cell kinetics of SSCs, we consider the evidence that should SSCs retain these growth kinetics in vitro, a natural kinetic barrier to SSC propagation exists. Recent discoveries showing that the tumor suppressor gene p53 can act as a regulator of asymmetr...

  20. Effect of Toxoplasma gondii infection on the junctional complex of retinal pigment epithelial cells.

    Science.gov (United States)

    Nogueira, Alanderson R; Leve, Fernanda; Morgado-Diaz, José; Tedesco, Roberto Carlos; Pereira, Mirian Claudia S

    2016-04-01

    Ocular toxoplasmosis is the most frequent cause of uveitis, leading to partial or total loss of vision, with the retina the main affected structure. The cells of the retinal pigment epithelium (RPE) play an important role in the physiology of the retina and formation of the blood-retinal barrier. Several pathogens induce barrier dysfunction by altering tight junction (TJ) integrity. Here, we analysed the effect of infection by Toxoplasma gondii on TJ integrity in ARPE-19 cells. Loss of TJ integrity was demonstrated in T. gondii-infected ARPE-19 cells, causing increase in paracellular permeability and disturbance of the barrier function of the RPE. Confocal microscopy also revealed alteration in the TJ protein occludin induced by T. gondii infection. Disruption of junctional complex was also evidenced by scanning and transmission electron microscopy. Cell-cell contact loss was noticed in the early stages of infection by T. gondii with the visualization of small to moderate intercellular spaces. Large gaps were mostly observed with the progression of the infection. Thus, our data suggest that the alterations induced by T. gondii in the structural organization of the RPE may contribute to retinal injury evidenced by ocular toxoplasmosis. PMID:26928468

  1. Iron serves as diffusion barrier in thermally regenerative galvanic cell

    Science.gov (United States)

    Crouthamel, C. E.

    1967-01-01

    Pure iron or iron-coated diaphragm provides a hydrogen diffusion electrode for a thermally regenerative galvanic cell. It allows the gas to diffuse through its interatomic spaces and resists the corrosive action of the cell environment.

  2. Microfluidic-based single cell trapping using a combination of stagnation point flow and physical barrier

    Science.gov (United States)

    Yu, Miao; Chen, Zongzheng; Xiang, Cheng; Liu, Bo; Xie, Handi; Qin, Kairong

    2016-03-01

    Single cell trapping in vitro by microfluidic device is an emerging approach for the study of the relationship between single cells and their dynamic biochemical microenvironments. In this paper, a hydrodynamic-based microfluidic device for single cell trapping is designed using a combination of stagnation point flow and physical barrier. The microfluidic device overcomes the weakness of the traditional ones, which have been only based upon either stagnation point flows or physical barriers, and can conveniently load dynamic biochemical signals to the trapped cell. In addition, it can connect with a programmable syringe pump and a microscope to constitute an integrated experimental system. It is experimentally verified that the microfluidic system can trap single cells in vitro even under flow disturbance and conveniently load biochemical signals to the trapped cell. The designed micro-device would provide a simple yet effective experimental platform for further study of the interactions between single cells and their microenvironments.

  3. Microfluidic-based single cell trapping using a combination of stagnation point flow and physical barrier

    Science.gov (United States)

    Yu, Miao; Chen, Zongzheng; Xiang, Cheng; Liu, Bo; Xie, Handi; Qin, Kairong

    2016-06-01

    Single cell trapping in vitro by microfluidic device is an emerging approach for the study of the relationship between single cells and their dynamic biochemical microenvironments. In this paper, a hydrodynamic-based microfluidic device for single cell trapping is designed using a combination of stagnation point flow and physical barrier. The microfluidic device overcomes the weakness of the traditional ones, which have been only based upon either stagnation point flows or physical barriers, and can conveniently load dynamic biochemical signals to the trapped cell. In addition, it can connect with a programmable syringe pump and a microscope to constitute an integrated experimental system. It is experimentally verified that the microfluidic system can trap single cells in vitro even under flow disturbance and conveniently load biochemical signals to the trapped cell. The designed micro-device would provide a simple yet effective experimental platform for further study of the interactions between single cells and their microenvironments.

  4. BARRIERS TO COMMERCIALIZATION OF PASSIVE DIRECT METHANOL FUEL CELLS: A REVEIW

    OpenAIRE

    N. K. Shrivastava; S. B. THOMBRE

    2011-01-01

    Fuel cells are electro-chemical reactors which realize the direct conversion of the chemical energy of reactants to electrical energy, with high efficiency and high environmental compatibility. This article is concerned with one of the most advance fuel cells- direct methanol fuel cells (DMFCs). We present a comprehensive review on the commercialization barriers of passive DMFCs. The paper also summarizes past research efforts and possible future directions towards these problems.

  5. 3D In Vitro Model of a Functional Epidermal Permeability Barrier from Human Embryonic Stem Cells and Induced Pluripotent Stem Cells

    OpenAIRE

    Anastasia Petrova; Anna Celli; Laureen Jacquet; Dimitra Dafou; Debra Crumrine; Melanie Hupe; Matthew Arno; Carl Hobbs; Aleksandra Cvoro; Panagiotis Karagiannis; Liani Devito; Richard Sun; Lillian C. Adame; Robert Vaughan; John A. McGrath

    2014-01-01

    Summary Cornification and epidermal barrier defects are associated with a number of clinically diverse skin disorders. However, a suitable in vitro model for studying normal barrier function and barrier defects is still lacking. Here, we demonstrate the generation of human epidermal equivalents (HEEs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). HEEs are structurally similar to native epidermis, with a functional permeability barrier. We exposed a pure p...

  6. Enteric glia cells attenuate cytomix-induced intestinal epithelial barrier breakdown.

    Directory of Open Access Journals (Sweden)

    Gerald A Cheadle

    Full Text Available BACKGROUND: Intestinal barrier failure may lead to systemic inflammation and distant organ injury in patients following severe injury. Enteric glia cells (EGCs have been shown to play an important role in maintaining gut barrier integrity through secretion of S-Nitrosoglutathione (GSNO. We have recently shown than Vagal Nerve Stimulation (VNS increases EGC activation, which was associated with improved gut barrier integrity. Thus, we sought to further study the mechanism by which EGCs prevent intestinal barrier breakdown utilizing an in vitro model. We postulated that EGCs, through the secretion of GSNO, would improve intestinal barrier function through improved expression and localization of intestinal tight junction proteins. METHODS: Epithelial cells were co-cultured with EGCs or incubated with GSNO and exposed to Cytomix (TNF-α, INF-γ, IL-1β for 24 hours. Barrier function was assessed by permeability to 4kDa FITC-Dextran. Changes in tight junction proteins ZO-1, occludin, and phospho-MLC (P-MLC were assessed by immunohistochemistry and immunoblot. KEY RESULTS: Co-culture of Cytomix-stimulated epithelial monolayers with EGCs prevented increases in permeability and improved expression and localization of occludin, ZO-1, and P-MLC. Further, treatment of epithelial monolayers with GSNO also prevented Cytomix-induced increases in permeability and exhibited a similar improvement in expression and localization of occludin, ZO-1, and P-MLC. CONCLUSIONS & INFERENCES: The addition of EGCs, or their secreted mediator GSNO, prevents epithelial barrier failure after injury and improved expression of tight junction proteins. Thus, therapies that increase EGC activation, such as VNS, may be a novel strategy to limit barrier failure in patients following severe injury.

  7. Electroporation of Brain Endothelial Cells on Chip toward Permeabilizing the Blood-Brain Barrier.

    Science.gov (United States)

    Bonakdar, Mohammad; Wasson, Elisa M; Lee, Yong W; Davalos, Rafael V

    2016-01-19

    The blood-brain barrier, mainly composed of brain microvascular endothelial cells, poses an obstacle to drug delivery to the brain. Controlled permeabilization of the constituent brain endothelial cells can result in overcoming this barrier and increasing transcellular transport across it. Electroporation is a biophysical phenomenon that has shown potential in permeabilizing and overcoming this barrier. In this study we developed a microengineered in vitro model to characterize the permeabilization of adhered brain endothelial cells to large molecules in response to applied pulsed electric fields. We found the distribution of affected cells by reversible and irreversible electroporation, and quantified the uptaken amount of naturally impermeable molecules into the cells as a result of applied pulse magnitude and number of pulses. We achieved 81 ± 1.7% (N = 6) electroporated cells with 17 ± 8% (N = 5) cell death using an electric-field magnitude of ∼580 V/cm and 10 pulses. Our results provide the proper range for applied electric-field intensity and number of pulses for safe permeabilization without significantly compromising cell viability. Our results demonstrate that it is possible to permeabilize the endothelial cells of the BBB in a controlled manner, therefore lending to the feasibility of using pulsed electric fields to increase drug transport across the BBB through the transcellular pathway. PMID:26789772

  8. Recombination barrier layers in solid-state quantum dot-sensitized solar cells

    KAUST Repository

    Roelofs, Katherine E.

    2012-06-01

    By replacing the dye in the dye-sensitized solar cell design with semiconductor quantum dots as the light-absorbing material, solid-state quantum dot-sensitized solar cells (ss-QDSSCs) were fabricated. Cadmium sulfide quantum dots (QDs) were grown in situ by successive ion layer adsorption and reaction (SILAR). Aluminum oxide recombination barrier layers were deposited by atomic layer deposition (ALD) at the TiO2/hole-conductor interface. For low numbers of ALD cycles, the Al2O3 barrier layer increased open circuit voltage, causing an increase in device efficiency. For thicker Al2O3 barrier layers, photocurrent decreased substantially, leading to a decrease in device efficiency. © 2012 IEEE.

  9. Barrier height determination on Schottky contacts formed at the back contact-semiconductor interface of degraded solar cells

    Science.gov (United States)

    Misiakos, K.; Lathrop, J. W.

    A method is described of determining an equivalent circuit for solar cells which have degraded as a result of the formation of a rectifying Schottky barrier at the back contact. An excellent fit of experimental data has been achieved using SCEPTRE with an equivalent circuit derived from the shape of the measured current voltage characteristics. One key parameter of the Schottky barrier diode, the reverse saturation current, can be used to determine the barrier potential. The barrier potential increases as the cell is stressed with 0.5 volts being a typical experimentally determined value for a degraded cell.

  10. Cell-penetrating peptides for drug delivery across membrane barriers

    DEFF Research Database (Denmark)

    Foged, Camilla; Nielsen, Hanne Moerck

    2008-01-01

    -penetrating peptides as transmembrane drug delivery agents, according to the recent literature, and discusses critical issues and future challenges in relation to fully understanding the fundamental principles of the cell-penetrating peptide-mediated membrane translocation of cargoes and the exploitation of their...

  11. Improvement of Electrical Properties of Silicon Quantum Dot Superlattice Solar Cells with Diffusion Barrier Layers

    Science.gov (United States)

    Yamada, Shigeru; Kurokawa, Yasuyoshi; Miyajima, Shinsuke; Konagai, Makoto

    2013-04-01

    We investigate the effects of a niobium-doped titanium dioxide (TiO2:Nb) diffusion barrier layer on the performance of silicon quantum dot superlattice (Si-QDSL) solar cells. The insertion of a 2-nm-thick TiO2:Nb layer significantly reduces phosphorus diffusion from a highly doped n-type layer into a Si-QDSL layer during thermal annealing at 900 °C. The phosphorous concentration in the Si-QDSL layer of the solar cell with the TiO2:Nb diffusion barrier layer was found to be less than 1018 cm-3, which is approximately two orders of magnitude lower than that of the solar cell without the diffusion barrier layer. The reduction in phosphorous concentration leads to the improvement of photo-generated carrier collection in the Si-QDSL layer. The short circuit current density of the solar cell with the diffusion barrier layer was dramatically improved to 1.6 mA/cm2 without the degradation of open circuit voltage and fill factor.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Hee Soon Shin

    2015-01-01

    Full Text Available 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.

  14. Swiss Hydrogen & Fuel Cell Activities : Opportunities, barriers and public support

    OpenAIRE

    Vuille, François; Hart, David; Lehner, Franz; Bertuccioli, Luca; Ripken, Ralph

    2014-01-01

    Switzerland has a small but internationally recognised set of competences and actors in fuel cells and hydrogen, from fundamental research to technology and product development. Swiss organisations are prominent in a number of research partnerships, and some have either major international co-operation or are partly or fully owned by overseas companies. However, the sector in Switzerland remains somewhat fragmented, with many actors pursuing their own niches and relatively little cross-fertil...

  15. Particle-in-cell modeling of gas-confined barrier discharge

    Science.gov (United States)

    Levko, Dmitry; Raja, Laxminarayan L.

    2016-04-01

    Gas-confined barrier discharge is studied using the one-dimensional Particle-in-Cell Monte Carlo Collisions model for the conditions reported by Guerra-Garcia and Martinez-Sanchez [Appl. Phys. Lett. 106, 041601 (2015)]. Depending on the applied voltage, two modes of discharge are observed. In the first mode, the discharge develops in the entire interelectrode gap. In the second mode, the discharge is ignited and develops only in the gas layer having smaller breakdown voltage. The one-dimensional model shows that for the conditions considered, there is no streamer stage of breakdown as is typical for a traditional dielectric barrier discharge.

  16. Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures.

    Directory of Open Access Journals (Sweden)

    Cara L Sherwood

    Full Text Available 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.

  17. Live cell imaging techniques to study T cell trafficking across the blood-brain barrier in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Coisne Caroline

    2013-01-01

    Full Text Available Abstract Background The central nervous system (CNS is an immunologically privileged site to which access for circulating immune cells is tightly controlled by the endothelial blood–brain barrier (BBB located in CNS microvessels. Under physiological conditions immune cell migration across the BBB is low. However, in neuroinflammatory diseases such as multiple sclerosis, many immune cells can cross the BBB and cause neurological symptoms. Extravasation of circulating immune cells is a multi-step process that is regulated by the sequential interaction of different adhesion and signaling molecules on the immune cells and on the endothelium. The specialized barrier characteristics of the BBB, therefore, imply the existence of unique mechanisms for immune cell migration across the BBB. Methods and design An in vitro mouse BBB model maintaining physiological barrier characteristics in a flow chamber and combined with high magnification live cell imaging, has been established. This model enables the molecular mechanisms involved in the multi-step extravasation of T cells across the in vitro BBB, to be defined with high-throughput analyses. Subsequently these mechanisms have been verified in vivo using a limited number of experimental animals and a spinal cord window surgical technique. The window enables live observation of the dynamic interaction between T cells and spinal cord microvessels under physiological and pathological conditions using real time epifluorescence intravital imaging. These in vitro and in vivo live cell imaging methods have shown that the BBB endothelium possesses unique and specialized mechanisms involved in the multi-step T cell migration across this endothelial barrier under physiological flow. The initial T cell interaction with the endothelium is either mediated by T cell capture or by T cell rolling. Arrest follows, and then T cells polarize and especially CD4+ T cells crawl over long distances against the direction of

  18. Interleukin-4 and interleukin-13 cause barrier dysfunction in human airway epithelial cells.

    Science.gov (United States)

    Saatian, Bahman; Rezaee, Fariba; Desando, Samantha; Emo, Jason; Chapman, Tim; Knowlden, Sara; Georas, Steve N

    2013-04-01

    Emerging evidence indicates that airway epithelial barrier function is compromised in asthma, a disease characterized by Th2-skewed immune response against inhaled allergens, but the mechanisms involved are not well understood. The purpose of this study was to investigate the effects of Th2-type cytokines on airway epithelial barrier function. 16HBE14o- human bronchial epithelial cells monolayers were grown on collagen coated Transwell inserts. The basolateral or apical surfaces of airway epithelia were exposed to human interleukin-4 (IL-4), IL-13, IL-25, IL-33, thymic stromal lymphopoietin (TSLP) alone or in combination at various concentrations and time points. We analyzed epithelial apical junctional complex (AJC) function by measuring transepithelial electrical resistance (TEER) and permeability to FITC-conjugated dextran over time. We analyzed AJC structure using immunofluorescence with antibodies directed against key junctional components including occludin, ZO-1, β-catenin and E-cadherin. Transepithelial resistance was significantly decreased after both basolateral and apical exposure to IL-4. Permeability to 3 kDa dextran was also increased in IL-4-exposed cells. Similar results were obtained with IL-13, but none of the innate type 2 cytokines examined (TSLP, IL-25 or IL-33) significantly affected barrier function. IL-4 and IL-13-induced barrier dysfunction was accompanied by reduced expression of membrane AJC components but not by induction of claudin- 2. Enhanced permeability caused by IL-4 was not affected by wortmannin, an inhibitor of PI3 kinase signaling, but was attenuated by a broad spectrum inhibitor of janus associated kinases. Our study indicates that IL-4 and IL-13 have disruptive effect on airway epithelial barrier function. Th2-cytokine induced epithelial barrier dysfunction may contribute to airway inflammation in allergic asthma. PMID:24665390

  19. Characterization of the human immune cell network at the gingival barrier.

    Science.gov (United States)

    Dutzan, N; Konkel, J E; Greenwell-Wild, T; Moutsopoulos, N M

    2016-09-01

    The oral mucosa is a barrier site constantly exposed to rich and diverse commensal microbial communities, yet little is known of the immune cell network maintaining immune homeostasis at this interface. We have performed a detailed characterization of the immune cell subsets of the oral cavity in a large cohort of healthy subjects. We focused our characterization on the gingival interface, a particularly vulnerable mucosal site, with thin epithelial lining and constant exposure to the tooth adherent biofilm. In health, we find a predominance of T cells, minimal B cells, a large presence of granulocytes/neutrophils, a sophisticated network of professional antigen-presenting cells (APCs), and a small population of innate lymphoid cells (ILCs) policing the gingival barrier. We further characterize cellular subtypes in health and interrogate shifts in immune cell populations in the common oral inflammatory disease periodontitis. In disease, we document an increase in neutrophils and an upregulation of interleukin-17 (IL-17) responses. We identify the main source of IL-17 in health and Periodontitis within the CD4(+) T-cell compartment. Collectively, our studies provide a first view of the landscape of physiologic oral immunity and serve as a baseline for the characterization of local immunopathology. PMID:26732676

  20. Induced Pluripotent Stem Cells and Outer Retinal Disease

    Directory of Open Access Journals (Sweden)

    Jin Yang

    2016-01-01

    Full Text Available The retina, which is composed of multiple layers of differing cell types, has been considered the first choice for gene therapy, disease modeling, and stem cell-derived retinal cell transplant therapy. Because of its special characteristics, the retina, located in the posterior part of the eye, can be well observed directly after gene therapy or transplantation. The blood-retinal barrier is part of a specialized ocular microenvironment that is immune privileged. This protects transplanted cells and tissue. Having two eyes makes perfect natural control possible after a single eye receives gene or stem cell therapy. For this reason, research about exploring retinal diseases’ underlying molecular mechanisms and potential therapeutic approach using stem cell technique has been developing rapidly. This review is to present an up-to-date summary of the iPSC’s sources, variations, differentiation methods, and the wide-ranging application of iPSCs-RPCS or iPSCs-RPE on retinal disease modeling, diagnostics, and therapeutics.

  1. Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development.

    Directory of Open Access Journals (Sweden)

    Ariane Willems

    Full Text Available The observation that mice with a selective ablation of the androgen receptor (AR in Sertoli cells (SC (SCARKO mice display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin. Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2. It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

  2. Microfluidic-based single cell trapping using a combination of stagnation point flow and physical barrier

    Institute of Scientific and Technical Information of China (English)

    Miao Yu; Zongzheng Chen; Cheng Xiang; Bo Liu; Handi Xie; Kairong Qin

    2016-01-01

    Single cell trapping in vitro by microfluidic device is an emerging approach for the study of the rela-tionship between single cells and their dynamic biochemical microenvironments. In this paper, a hydrodynamic-based microfluidic device for single cell trapping is designed using a combination of stagnation point flow and physical barrier. The microfluidic device overcomes the weakness of the tra-ditional ones, which have been only based upon either stag-nation point flows or physical barriers, and can conveniently load dynamic biochemical signals to the trapped cell. In addi-tion, it can connect with a programmable syringe pump and a microscope to constitute an integrated experimental system. It is experimentally verified that the microfluidic system can trap single cells in vitro even under flow disturbance and con-veniently load biochemical signals to the trapped cell. The designed micro-device would provide a simple yet effective experimental platform for further study of the interactions between single cells and their microenvironments.

  3. Sodium caprate transiently opens claudin-5-containing barriers at tight junctions of epithelial and endothelial cells

    DEFF Research Database (Denmark)

    Del Vecchio, Giovanna; Tscheik, Christian; Tenz, Kareen;

    2012-01-01

    Claudin-5 is a tight junction (TJ) protein which limits the diffusion of small hydrophilic molecules. Thus, it represents a potential pharmacological target to improve drug delivery to the tissues protected by claudin-5-dependent barriers. Sodium caprate is known as an absorption enhancer which...... microscopy on live and fixed cells and isolated mouse brain capillaries, Western blotting and permeability assays were employed. Caprate reversibly reduced claudin-5 trans-interactions in TJ-free human embryonic kidney-293 cells expressing claudin-5-YFP. It decreased the membranous claudin-5 and the F...

  4. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  5. Breaking down the barriers to commercialization of fuel cells in transportation through Government - industry R&D programs

    Energy Technology Data Exchange (ETDEWEB)

    Chalk, S.G. [Dept. of Energy, Washington, DC (United States); Venkateswaran, S.R. [Energetics, Inc., Columbia, MD (United States)

    1996-12-31

    PEM fuel cell technology is rapidly emerging as a viable propulsion alternative to the internal combustion engine. Fuel cells offer the advantages of low emissions, high efficiency, fuel flexibility, quiet and continuous operation, and modularity. Over the last decade, dramatic advances have been achieved in the performance and cost of PEM fuel cell technologies for automotive applications. However, significant technical barriers remain to making fuel cell propulsion systems viable alternatives to the internal combustion engine. This paper focuses on the progress achieved and remaining technical barriers while highlighting Government-industry R&D efforts that are accelerating fuel cell technology toward commercialization.

  6. Interface Engineering of Organic Schottky Barrier Solar Cells and Its Application in Enhancing Performances of Planar Heterojunction Solar Cells

    Science.gov (United States)

    Jin, Fangming; Su, Zisheng; Chu, Bei; Cheng, Pengfei; Wang, Junbo; Zhao, Haifeng; Gao, Yuan; Yan, Xingwu; Li, Wenlian

    2016-05-01

    In this work, we describe the performance of organic Schottky barrier solar cells with the structure of ITO/molybdenum oxide (MoOx)/boron subphthalocyanine chloride (SubPc)/bathophenanthroline (BPhen)/Al. The SubPc-based Schottky barrier solar cells exhibited a short-circuit current density (Jsc) of 2.59 mA/cm2, an open-circuit voltage (Voc) of 1.06 V, and a power conversion efficiency (PCE) of 0.82% under simulated AM1.5 G solar illumination at 100 mW/cm2. Device performance was substantially enhanced by simply inserting thin organic hole transport material into the interface of MoOx and SubPc. The optimized devices realized a 180% increase in PCE of 2.30% and a peak Voc as high as 1.45 V was observed. We found that the improvement is due to the exciton and electron blocking effect of the interlayer and its thickness plays a vital role in balancing charge separation and suppressing quenching effect. Moreover, applying such interface engineering into MoOx/SubPc/C60 based planar heterojunction cells substantially enhanced the PCE of the device by 44%, from 3.48% to 5.03%. Finally, we also investigated the requirements of the interface material for Schottky barrier modification.

  7. Interface Engineering of Organic Schottky Barrier Solar Cells and Its Application in Enhancing Performances of Planar Heterojunction Solar Cells

    Science.gov (United States)

    Jin, Fangming; Su, Zisheng; Chu, Bei; Cheng, Pengfei; Wang, Junbo; Zhao, Haifeng; Gao, Yuan; Yan, Xingwu; Li, Wenlian

    2016-01-01

    In this work, we describe the performance of organic Schottky barrier solar cells with the structure of ITO/molybdenum oxide (MoOx)/boron subphthalocyanine chloride (SubPc)/bathophenanthroline (BPhen)/Al. The SubPc-based Schottky barrier solar cells exhibited a short-circuit current density (Jsc) of 2.59 mA/cm2, an open-circuit voltage (Voc) of 1.06 V, and a power conversion efficiency (PCE) of 0.82% under simulated AM1.5 G solar illumination at 100 mW/cm2. Device performance was substantially enhanced by simply inserting thin organic hole transport material into the interface of MoOx and SubPc. The optimized devices realized a 180% increase in PCE of 2.30% and a peak Voc as high as 1.45 V was observed. We found that the improvement is due to the exciton and electron blocking effect of the interlayer and its thickness plays a vital role in balancing charge separation and suppressing quenching effect. Moreover, applying such interface engineering into MoOx/SubPc/C60 based planar heterojunction cells substantially enhanced the PCE of the device by 44%, from 3.48% to 5.03%. Finally, we also investigated the requirements of the interface material for Schottky barrier modification. PMID:27185635

  8. Cell-to-Cell Transmission Can Overcome Multiple Donor and Target Cell Barriers Imposed on Cell-Free HIV

    OpenAIRE

    Zhong, Peng; Agosto, Luis M.; Ilinskaya, Anna; Dorjbal, Batsukh; Truong, Rosaline; Derse, David; Uchil, Pradeep D; Heidecker, Gisela; Mothes, Walther

    2013-01-01

    Virus transmission can occur either by a cell-free mode through the extracellular space or by cell-to-cell transmission involving direct cell-to-cell contact. The factors that determine whether a virus spreads by either pathway are poorly understood. Here, we assessed the relative contribution of cell-free and cell-to-cell transmission to the spreading of the human immunodeficiency virus (HIV). We demonstrate that HIV can spread by a cell-free pathway if all the steps of the viral replication...

  9. The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells.

    Science.gov (United States)

    Ifergan, Igal; Kébir, Hania; Bernard, Monique; Wosik, Karolina; Dodelet-Devillers, Aurore; Cayrol, Romain; Arbour, Nathalie; Prat, Alexandre

    2008-03-01

    Trafficking of antigen-presenting cells into the CNS is essential for lymphocyte reactivation within the CNS compartment. Although perivascular dendritic cells found in inflammatory lesions are reported to polarize naive CD4+ T lymphocytes into interleukin-17-secreting-cells, the origin of those antigen-presenting cells remains controversial. We demonstrate that a subset of CD14+ monocytes migrate across the inflamed human blood-brain barrier (BBB) and differentiate into CD83+CD209+ dendritic cells under the influence of BBB-secreted transforming growth factor-beta and granulocyte-macrophage colony-stimulating factor. We also demonstrate that these dendritic cells secrete interleukin-12p70, transforming growth factor-beta and interleukin-6 and promote the proliferation and expansion of distinct populations of interferon-gamma-secreting Th1 and interleukin-17-secreting Th17 CD4+ T lymphocytes. We further confirmed the abundance of such dendritic cells in situ, closely associated with microvascular BBB-endothelial cells within acute multiple sclerosis lesions, as well as a significant number of CD4+ interleukin-17+ T lymphocytes in the perivascular infiltrate. Our data support the notion that functional perivascular myeloid CNS dendritic cells arise as a consequence of migration of CD14+ monocytes across the human BBB, through the concerted actions of BBB-secreted transforming growth factor-beta and granulocyte-macrophage colony-stimulating factor. PMID:18156156

  10. An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos.

    Science.gov (United States)

    Monier, Bruno; Pélissier-Monier, Anne; Brand, Andrea H; Sanson, Bénédicte

    2010-01-01

    Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries. PMID:19966783

  11. Role of Microfluidics in Blood-Brain Barrier Permeability Cell Culture Modeling: Relevance to CNS Disorders.

    Science.gov (United States)

    Rusanov, Alexander L; Luzgina, Natalia G; Barreto, George E; Aliev, Gjumrakch

    2016-01-01

    In vitro modeling of the human blood-brain barrier (BBB) is critical for pre-clinical evaluation and predicting the permeability of newly developed potentially neurotoxic and neurotrophic drugs. Here we summarize the specific structural and functional features of endothelial cells as a key component of the BBB and compare analysis of different cell culture models in reflecting these features. Particular attention is paid to cellular models of the BBB in microfluidic devices capable of circulating nutrient media to simulate the blood flow of the brain. In these conditions, it is possible to reproduce a number of factors affecting endothelial cells under physiological conditions, including shear stress. In comparison with static cell models, concentration gradients, which determine the velocity of transport of substances, reproduce more accurately conditions of nutrient medium flow, since they eliminate the accumulation of substances near the basal membrane of cells, not typical for the situation in vivo. Co-cultivation of different types of cells forming the BBB, in separate cell chambers connected by microchannels, allows to evaluate the mutual influences of cells under normal conditions and when exposed to the test substance. New experimental possibilities that can be achieved through modeling of BBB in microfluidic devices determine the feasibility of their use in the practice for pre-clinical studies of novel drugs against neurodegenerative diseases. PMID:26831260

  12. Eicosapentaenoic acid enhances heat stress-impaired intestinal epithelial barrier function in Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Guizhen Xiao

    Full Text Available OBJECTIVE: Dysfunction of the intestinal epithelial tight junction (TJ barrier is known to have an important etiologic role in the pathophysiology of heat stroke. N-3 polyunsaturated fatty acids (PUFAs, including eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, play a role in maintaining and protecting the TJ structure and function. This study is aimed at investigating whether n-3 PUFAs could alleviate heat stress-induced dysfunction of intestinal tight junction. METHODS: Human intestinal epithelial Caco-2 cells were pre-incubated with EPA, DHA or arachidonic acid (AA and then exposed to heat stress. Transepithelial electrical resistance (TEER and Horseradish Peroxidase (HRP permeability were measured to analyze barrier integrity. Levels of TJ proteins, including occludin, ZO-1 and claudin-2, were analyzed by Western blot and localized by immunofluorescence microscopy. Messenger RNA levels were determined by quantitative real time polymerase chain reaction (Q-PCR. TJ morphology was observed by transmission electron microscopy. RESULTS: EPA effectively attenuated the decrease in TEER and impairment of intestinal permeability in HRP flux induced by heat exposure. EPA significantly elevated the expression of occludin and ZO-1, while DHA was less effective and AA was not at all effective. The distortion and redistribution of TJ proteins, and disruption of morphology were also effectively prevented by pretreatment with EPA. CONCLUSION: This study indicates for the first time that EPA is more potent than DHA in protecting against heat-induced permeability dysfunction and epithelial barrier damage of tight junction.

  13. Trafficking of Endogenous Immunoglobulins by Endothelial Cells at the Blood-Brain Barrier

    OpenAIRE

    Villaseñor, Roberto; Ozmen, Laurence; Messaddeq, Nadia; Grüninger, Fiona; Loetscher, Hansruedi; Keller, Annika; Betsholtz, Christer; Freskgård, Per-Ola; Collin, Ludovic

    2016-01-01

    The Blood-Brain Barrier (BBB) restricts access of large molecules to the brain. The low endocytic activity of brain endothelial cells (BECs) is believed to limit delivery of immunoglobulins (IgG) to the brain parenchyma. Here, we report that endogenous mouse IgG are localized within intracellular vesicles at steady state in BECs in vivo. Using high-resolution quantitative microscopy, we found a fraction of endocytosed IgG in lysosomes. We observed that loss of pericytes (key components of the...

  14. Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation

    Directory of Open Access Journals (Sweden)

    Wang Ting

    2012-08-01

    Full Text Available Abstract Background Exposure to particulate matter (PM is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation. Objectives We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC barrier integrity and enhanced cardiopulmonary dysfunction. Methods Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm. Biochemical assessment of ROS generation and Ca2+ mobilization were also measured. Results PM exposure induced tight junction protein Zona occludens-1 (ZO-1 relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin. N-acetyl-cysteine (NAC, 5 mM reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2, in a ROS-dependent manner with subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro. Conclusions These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes.

  15. Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis

    International Nuclear Information System (INIS)

    Deoxynivalenol (DON), one of the most common mycotoxin contaminants of raw and processed cereal food, adversely affects the gastrointestinal tract. Since DON acts as a protein synthesis inhibitor, the constantly renewing intestinal epithelium could be particularly sensitive to DON. We analyzed the toxicological effects of DON on intestinal epithelial protein synthesis and barrier integrity. Differentiated Caco-2 cells, as a widely used model of the human intestinal barrier, were exposed to realistic intestinal concentrations of DON (50, 500 and 5000 ng/ml) during 24 h. DON caused a concentration-dependent decrease in total protein content associated with a reduction in the incorporation of [3H]-leucine, demonstrating its inhibitory effect on protein synthesis. DON simultaneously increased the paracellular permeability of the monolayer as reflected through a decreased transepithelial electrical resistance associated with an increased paracellular flux of the tracer [3H]-mannitol. A concentration-dependent reduction in the expression level of the tight junction constituent claudin-4 was demonstrated by Western blot, which was not due to diminished transcription, increased degradation, or NF-κB, ERK or JNK activation, and was also observed for a tight junction independent protein, i.e. intestinal alkaline phosphatase. These results demonstrate a dual toxicological effect of DON on differentiated Caco-2 cells consisting in an inhibition of protein synthesis as well as an increase in monolayer permeability, and moreover suggest a possible link between them through diminished synthesis of the tight junction constituent claudin-4.

  16. Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier

    Directory of Open Access Journals (Sweden)

    Ping-Chang Yang

    2009-06-01

    Full Text Available Background: Food allergy and chronic intestinal inflammation are common in western countries. The complex of antigen/IgE is taken up into the body from the gut lumen with the aid of epithelial cell-derived CD23 (low affinity IgE receptor II that plays an important role in the pathogenesis of intestinal allergy. This study aimed to elucidate the role of mast cell on modulation of antigen/IgE complex transport across intestinal epithelial barrier. Methods: Human intestinal epithelial cell line HT29 cell monolayer was used as a study platform. Transepithelial electric resistance (TER and permeability to ovalbumin (OVA were used as the markers of intestinal epithelial barrier function that were recorded in response to the stimulation of mast cell-derived chemical mediators. Results: Conditioned media from naïve mast cell line HMC-1 cells or monocyte cell line THP-1 cells significantly upregulated the expression of CD23 and increased the antigen transport across the epithelium. Treatment with stem cell factor (SCF, nerve growth factor (NGF, retinoic acid (RA or dimethyl sulphoxide (DMSO enhanced CD23 expression in HT29 cells. Conditioned media from SCF, NGF or RA-treated HMC-1 cells, and SCF, NGF, DMSO or RA-treated THP-1 cells enhanced immune complex transport via enhancing the expression of the CD23 in HT29 cells and the release of inflammatory mediator TNF-α. Nuclear factor kappa B inhibitor, tryptase and TNF-α inhibited the increase in CD23 in HT29 cells and prevents the enhancement of epithelial barrier permeability. Conclusions: Mast cells play an important role in modulating the intestinal CD23 expression and the transport of antigen/IgE/CD23 complex across epithelial barrier.

  17. Multimodal investigations of trans-endothelial cell trafficking under condition of disrupted blood-brain barrier integrity

    OpenAIRE

    Masaryk Thomas; Desai Nirav K; Franic Linda; Nguyen Minh T; Teng Qingshan; Marchi Nicola; Rasmussen Peter; Trasciatti Silvia; Janigro Damir

    2010-01-01

    Abstract Background Stem cells or immune cells targeting the central nervous system (CNS) bear significant promises for patients affected by CNS disorders. Brain or spinal cord delivery of therapeutic cells is limited by the blood-brain barrier (BBB) which remains one of the recognized rate-limiting steps. Osmotic BBB disruption (BBBD) has been shown to improve small molecule chemotherapy for brain tumors, but successful delivery of cells in conjunction with BBBD has never been reported. We h...

  18. Control of the blood-brain barrier function in cancer cell metastasis.

    Science.gov (United States)

    Blecharz, Kinga G; Colla, Ruben; Rohde, Veit; Vajkoczy, Peter

    2015-10-01

    Cerebral metastases are the most common brain neoplasms seen clinically in the adults and comprise more than half of all brain tumours. Actual treatment options for brain metastases that include surgical resection, radiotherapy and chemotherapy are rarely curative, although palliative treatment improves survival and life quality of patients carrying brain-metastatic tumours. Chemotherapy in particular has also shown limited or no activity in brain metastasis of most tumour types. Many chemotherapeutic agents used systemically do not cross the blood-brain barrier (BBB), whereas others may transiently weaken the BBB and allow extravasation of tumour cells from the circulation into the brain parenchyma. Increasing evidence points out that the interaction between the BBB and tumour cells plays a key role for implantation and growth of brain metastases in the central nervous system. The BBB, as the tightest endothelial barrier, prevents both early detection and treatment by creating a privileged microenvironment. Therefore, as observed in several in vivo studies, precise targetting the BBB by a specific transient opening of the structure making it permeable for therapeutic compounds, might potentially help to overcome this difficult clinical problem. Moreover, a better understanding of the molecular features of the BBB, its interrelation with metastatic tumour cells and the elucidation of cellular mechanisms responsible for establishing cerebral metastasis must be clearly outlined in order to promote treatment modalities that particularly involve chemotherapy. This in turn would substantially expand the survival and quality of life of patients with brain metastasis, and potentially increase the remission rate. Therefore, the focus of this review is to summarise the current knowledge on the role and function of the BBB in cancer metastasis. PMID:26032862

  19. Role of interfacial oxide in high-efficiency graphene-silicon Schottky barrier solar cells.

    Science.gov (United States)

    Song, Yi; Li, Xinming; Mackin, Charles; Zhang, Xu; Fang, Wenjing; Palacios, Tomás; Zhu, Hongwei; Kong, Jing

    2015-03-11

    The advent of chemical vapor deposition (CVD) grown graphene has allowed researchers to investigate large area graphene/n-silicon Schottky barrier solar cells. Using chemically doped graphene, efficiencies of nearly 10% can be achieved for devices without antireflective coatings. However, many devices reported in past literature often exhibit a distinctive s-shaped kink in the measured I/V curves under illumination resulting in poor fill factor. This behavior is especially prevalent for devices with pristine (not chemically doped) graphene but can be seen in some cases for doped graphene as well. In this work, we show that the native oxide on the silicon presents a transport barrier for photogenerated holes and causes recombination current, which is responsible for causing the kink. We experimentally verify our hypothesis and propose a simple semiconductor physics model that qualitatively captures the effect. Furthermore, we offer an additional optimization to graphene/n-silicon devices: by choosing the optimal oxide thickness, we can increase the efficiency of our devices to 12.4% after chemical doping and to a new record of 15.6% after applying an antireflective coating. PMID:25685934

  20. A new stochastic model of carcinogenesis induced by ionizing radiation and the concept of breaking barrier cell mechanisms

    International Nuclear Information System (INIS)

    In this report we present a new multiple-pathway dynamic stochastic model of leukemia development, which combines and further extends ideas used in: i) models of hematopoietic system; ii) multistage mechanistic models of carcinogenesis and leukemia, and iii) population models of aging, cancer morbidity, and mortality. The model represents three levels of the organism's vital organization: i) a cellular level, where dynamics of the processes of cell kinetics, repair, and apoptosis, are defined, ii) a level of human organism, where covariates describing health states are measured, and iii) a population, where such characteristics as incidence and mortality rates associated with cancer are predicted. The new approach considers breaking the barrier mechanisms of a cell as key feature of carcinogenesis. The barrier mechanisms (e.g., antioxidant defense, repair, apoptosis) represent the complex of cell responses to primary cell damages caused by exogenious and endogenious factors. Detrimental phenotypic changes in the cells result from insufficiency of respective barrier mechanisms. The advantage of suggested modeling approach is in the possibility of natural combining of different measurements including age-specific hazard rate and measures, characterizing fractions of cells with breaking barriers. Another advantage is in the opportunity to study effects of protracted low-dose Ionizing Radiation (IR) where such barrier mechanisms play an important role. Simulation studies show that the model parameters can be identified from joint analyses of epidemiological data and the results of individual biomolecular measurements of barrier states. Application of the results to the analyses of SEER data on leukemia risks demonstrates the strong predictive power of the model. Further generalizations of the model, possible applications to available data on subjects chronically exposed to IR, and incorporating IR-induced genomic instability are discussed. (author)

  1. In vitro model of the blood-brain barrier established by co-culture of primary cerebral microvascular endothelial and astrocyte cells

    OpenAIRE

    Yan Wang; Ning Wang; Biao Cai; Guang-yun Wang; Jing Li; Xing-xing Piao

    2015-01-01

    Drugs for the treatment and prevention of nervous system diseases must permeate the blood-brain barrier to take effect. In vitro models of the blood-brain barrier are therefore important in the investigation of drug permeation mechanisms. However, to date, no unified method has been described for establishing a blood-brain barrier model. Here, we modified an in vitro model of the blood-brain barrier by seeding brain microvascular endothelial cells and astrocytes from newborn rats on a polyest...

  2. Intercellular transfer of P-glycoprotein in human blood-brain barrier endothelial cells is increased by histone deacetylase inhibitors

    OpenAIRE

    Andreas Noack; Sandra Noack; Manuela Buettner; Naim, Hassan Y.; Wolfgang Löscher

    2016-01-01

    The blood–brain barrier (BBB) controls the entry of compounds into the brain, thereby regulating brain homeostasis. Efflux transporters such as P-glycoprotein (Pgp) significantly contribute to BBB function. Multiple signaling pathways modulate the expression and activity of Pgp in response to xenobiotics and disease. A non-genetic way of intercellular transfer of Pgp occurs in cancer cells, but whether this also occurs in non-cancer cells such as endothelial cells that form the BBB is not kno...

  3. Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization

    Energy Technology Data Exchange (ETDEWEB)

    Novak, Petr; Jensen, Taylor J.; Garbe, James C.; Stampfer, Martha R.; Futscher, Bernard W.

    2009-04-20

    The timing and progression of DNA methylation changes during carcinogenesis are not completely understood. To develop a timeline of aberrant DNA methylation events during malignant transformation, we analyzed genome-wide DNA methylation patterns in an isogenic human mammary epithelial cell (HMEC) culture model of transformation. To acquire immortality and malignancy, the cultured finite lifespan HMEC must overcome two distinct proliferation barriers. The first barrier, stasis, is mediated by the retinoblastoma protein and can be overcome by loss of p16(INK4A) expression. HMEC that escape stasis and continue to proliferate become genomically unstable before encountering a second more stringent proliferation barrier, telomere dysfunction due to telomere attrition. Rare cells that acquire telomerase expression may escape this barrier, become immortal, and develop further malignant properties. Our analysis of HMEC transitioning from finite lifespan to malignantly transformed showed that aberrant DNA methylation changes occur in a stepwise fashion early in the transformation process. The first aberrant DNA methylation step coincides with overcoming stasis, and results in few to hundreds of changes, depending on how stasis was overcome. A second step coincides with immortalization and results in hundreds of additional DNA methylation changes regardless of the immortalization pathway. A majority of these DNA methylation changes are also found in malignant breast cancer cells. These results show that large-scale epigenetic remodeling occurs in the earliest steps of mammary carcinogenesis, temporally links DNA methylation changes and overcoming cellular proliferation barriers, and provides a bank of potential epigenetic biomarkers that mayprove useful in breast cancer risk assessment.

  4. Oligodendrocyte precursor cells support blood-brain barrier integrity via TGF-β signaling.

    Directory of Open Access Journals (Sweden)

    Ji Hae Seo

    Full Text Available Trophic coupling between cerebral endothelium and their neighboring cells is required for the development and maintenance of blood-brain barrier (BBB function. Here we report that oligodendrocyte precursor cells (OPCs secrete soluble factor TGF-β1 to support BBB integrity. Firstly, we prepared conditioned media from OPC cultures and added them to cerebral endothelial cultures. Our pharmacological experiments showed that OPC-conditioned media increased expressions of tight-junction proteins and decreased in vitro BBB permeability by activating TGB-β-receptor-MEK/ERK signaling pathway. Secondly, our immuno-electron microscopic observation revealed that in neonatal mouse brains, OPCs attach to cerebral endothelial cells via basal lamina. And finally, we developed a novel transgenic mouse line that TGF-β1 is knocked down specifically in OPCs. Neonates of these OPC-specific TGF-β1 deficient mice (OPC-specific TGF-β1 partial KO mice: PdgfraCre/Tgfb1flox/wt mice or OPC-specific TGF-β1 total KO mice: PdgfraCre/Tgfb1flox/flox mice exhibited cerebral hemorrhage and loss of BBB function. Taken together, our current study demonstrates that OPCs increase BBB tightness by upregulating tight junction proteins via TGF-β signaling. Although astrocytes and pericytes are well-known regulators of BBB maturation and maintenance, these findings indicate that OPCs also play a pivotal role in promoting BBB integrity.

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

    Science.gov (United States)

    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. PMID:25847917

  6. Thin tantalum-silicon-oxygen/tantalum-silicon-nitrogen films as high-efficiency humidity diffusion barriers for solar cell encapsulation

    International Nuclear Information System (INIS)

    Flexible thin-film solar cells require flexible encapsulation to protect the copper-indium-2 selenide (CIS) absorber layer from humidity and aggressive environmental influences. Tantalum-silicon-based diffusion barriers are currently a favorite material to prevent future semiconductor devices from copper diffusion. In this work tantalum-silicon-nitrogen (Ta-Si-N) and tantalum-silicon-oxygen (Ta-Si-O) films were investigated and optimized for thin-film solar cell encapsulation of next-generation flexible solar modules. CIS solar modules were coated with tantalum-based barrier layers. The performance of the thin-film barrier encapsulation was determined by measuring the remaining module efficiency after a 1000 h accelerated aging test. A significantly enhanced stability against humidity diffusion in comparison to non-encapsulated modules was reached with a reactively sputtered thin-film system consisting of 250 nm Ta-Si-O and 15 nm Ta-Si-N

  7. Barrier effect of AlN film in flexible Cu(In,Ga)Se2 solar cells on stainless steel foil and solar cell

    International Nuclear Information System (INIS)

    Highlights: • The adhension between AlN film and Mo are verygood. • AlN film can be effectively used as the barrier of flexible CIGS solar cell on SS substrate. • AlN film is suitable as the insulation barrier of flexible CIGS solar cell on SS substrate. - Abstract: The AlN film deposited by DC magnetron sputtering on stainless steel (SS) foils was used as the barrier in flexible Cu(In,Ga)Se2 (CIGS) solar cells on stainless steel foil and characterized comprehensively by X-ray diffraction (XRD), scanning electron microscopy (SEM), I–V, and QE measurements study. The study of AlN as insulation barrier in the flexible CIGS solar cell showed that the adhesion strength between the SS foil and the deposited AlN film was very strong even after annealing at high temperature at 530 °C. More importantly, a high resistance of over 10 MΩ was remained with the film with thickness of around 200 nm after annealing. This indicates that the AlN film is suitable as an effective insulation barrier in flexible CIGS solar cells based on SS foil. In addition, the XRD and SEM results showed that the AlN film did not influence the crystal structure of the Mo film which was deposited upon the AlN layer and used as the electrical contact in CIGS solar cells. It was found that the AlN film contributed to an improved crystallinity of the Mo contact layer compared to the bare SS foil. The combined results of secondary ion mass spectrometry, I–V and EQE measurements of the corresponding flexible CIGS solar cells confirmed that 1 μm-thick AlN film could be used as an efficient barrier layer in CIGS solar cells on SS foil

  8. Loss of EP2 receptor subtype in colonic cells compromise epithelial barrier integrity by altering claudin-4.

    Science.gov (United States)

    Lejeune, Manigandan; Moreau, France; Chadee, Kris

    2014-01-01

    Prostaglandin E2 (PGE2) is a bioactive lipid mediator that exerts its biological function through interaction with four different subtypes of E-Prostanoid receptor namely EP1, EP2, EP3 and EP4. It has been known that EP2 receptor is differentially over-expressed in the epithelia of inflamed human colonic mucosa. However, the significance of the differential expression in altering epithelial barrier function is not known. In this study, we used Caco-2 cells expressing EP2 receptor, either high (EP2S) or low (EP2A), as a model epithelia and determined the barrier function of these cell monolayers by measuring the trans epithelial resistance (TER). Basal TER of EP2A (but not EP2S) monolayer was significantly lower suggesting a loss of colonic epithelial barrier integrity. In comparison, the TER of wild type Caco-2 was decreased in response to an EP2 receptor specific antagonist (AH-6809) indicating an important role for EP2 receptor in the maintenance of epithelial barrier function. The decrease TER in EP2A monolayer corresponded with a significant loss of the tight junction (TJ) protein claudin-4 without affecting other major TJ proteins. Similarly, EP2 receptor antagonism/siRNA based silencing significantly decreased claudin-4 expression in EP2S cells. Surprisingly, alteration in claudin-4 was not transcriptionally regulated in EP2A cells but rather undergoes increased proteosomal degradation. Moreover, among the TER compromising cytokines examined (IL-8, IL-1β, TNF-α, IFN-γ) only IFN-γ was significantly up regulated in EP2A cells. However, IFN-γ did not significantly decreased claudin-4 expression in Caco-2 cells indicating no role for IFN-γ in degrading claudin-4. We conclude that differential down-regulation of EP2 receptor play a major role in compromising colonic epithelial barrier function by selectively increasing proteosomal degradation of claudin-4. PMID:25396731

  9. Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke.

    Science.gov (United States)

    Lopes Pinheiro, Melissa A; Kooij, Gijs; Mizee, Mark R; Kamermans, Alwin; Enzmann, Gaby; Lyck, Ruth; Schwaninger, Markus; Engelhardt, Britta; de Vries, Helga E

    2016-03-01

    Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood-brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental

  10. Origins and consequences of hyperosmolar stress in retinal pigmented epithelial cells

    Directory of Open Access Journals (Sweden)

    ChristineDelporte

    2014-05-01

    Full Text Available The retinal pigmented epithelium (RPE is, composed of retinal pigmented epithelial cells joined by tight junctions and, represents the outer blood-retinal barrier (BRB. The inner BRB is made of the endothelial cells joined by tight junctions and glial extensions surrounding all the retinal blood vessels. One of the functions of the RPE is to maintain an osmotic transepithelial gradient created by ionic pumps and channels, and avoiding paracellular flux. Under such physiological conditions, transcellular water movement follows theis osmotic gradient and is flowingflows normally from the retina to the choroid through the RPE. Several diseases, such as diabetic retinopathy, are characterized by the BRB breakdown leading to leakage of solutes, proteins and fluid from the retina and the choroid. The prevailing hypothesis explaining macular edema formation during diabetic retinopathy relies onincriminates the inner BRB breakdown resulting in increased osmotic pressure leading in turn to massive water accumulation that can affect vision. Under these conditions, it has been hypothesized that RPE is likely to be exposed to hyperosmolar stress at its apical side. This review summarizes the origins and consequences of osmotic stress in the RPE. Ongoing and further research advances will clarify the mechanisms, at the molecular level, involved in the response of the RPE to osmotic stress and delineate potential novel therapeutic targets and tools.

  11. Contribution of nanoclays to the barrier properties of a model proton exchange membrane for fuel cell application

    OpenAIRE

    Thomassin, Jean-Michel; Pagnoulle, Christophe; Caldarella, Giuseppe; Germain, Albert; Jérôme, Robert

    2006-01-01

    Direct methanol fuel cells (DMFCs) that use a proton exchange membrane (PEM) as electrolyte, is a promising alternative source of energy for the future. However, methanol crossover from the anodic side to the cathodic one is a major problem in DMFC. Proper dispersion of layered silicates within the fuel cell membrane has been proposed as a strategy for improving the barrier properties of the membrane. The validity of this approach has been tested in case of a model membrane consisting of phos...

  12. Study on AlxNiy Alloys as Diffusion Barriers in Flexible Thin Film Solar Cells%Study on AlxNiy Alloys as Diffusion Barriers in Flexible Thin Film Solar Cells

    Institute of Scientific and Technical Information of China (English)

    岳红云; 吴爱民; 秦福文; 李廷举

    2011-01-01

    Co-sputtered AlxNiy thin films were used as diffusion barriers between aluminum and hydrogenated microcrystalline silicon (μc-Si:H) for flexible thin film solar cells. The stoichiometric ratio of AlxNiy showed a significant effect on the structures of the films. The obtained Al3Ni2 film was amorphous, while polycrystalline films were obtained when the ratio of aluminum to nickel was 1:1 and 2:3. An auger electron spectroscope and four-point probe system were applied to test the resistance to the interdiffusion between aluminum and silicon, as well as the conductivities of the AlxNiy barriers. The data of auger depth profile showed that the content of silicon was the minimum in the aluminum layer after sputtering for 4 min using AlNi thin film as the barrier layer. Compared to other AlxNiy alloys, the AlNi thin film possessed the lowest sheet resistance.

  13. Efficient, air-stable colloidal quantum dot solar cells encapsulated using atomic layer deposition of a nanolaminate barrier

    KAUST Repository

    Ip, Alexander H.

    2013-12-23

    Atomic layer deposition was used to encapsulate colloidal quantum dot solar cells. A nanolaminate layer consisting of alternating alumina and zirconia films provided a robust gas permeation barrier which prevented device performance degradation over a period of multiple weeks. Unencapsulated cells stored in ambient and nitrogen environments demonstrated significant performance losses over the same period. The encapsulated cell also exhibited stable performance under constant simulated solar illumination without filtration of harsh ultraviolet photons. This monolithically integrated thin film encapsulation method is promising for roll-to-roll processed high efficiency nanocrystal solar cells. © 2013 AIP Publishing LLC.

  14. Preferential killing of human lung cancer cell lines with mitochondrial dysfunction by nonthermal dielectric barrier discharge plasma

    OpenAIRE

    Panngom, K; Baik, K Y; Nam, M K; Han, J. H.; Rhim, H; Choi, E. H.

    2013-01-01

    The distinctive cellular and mitochondrial dysfunctions of two human lung cancer cell lines (H460 and HCC1588) from two human lung normal cell lines (MRC5 and L132) have been studied by dielectric barrier discharge (DBD) plasma treatment. This cytotoxicity is exposure time-dependent, which is strongly mediated by the large amount of H2O2 and NOx in culture media generated by DBD nonthermal plasma. It is found that the cell number of lung cancer cells has been reduced more than that of the lun...

  15. Na effect on flexible Cu(In,Ga)Se2 photovoltaic cell depending on diffusion barriers (SiOx, i-ZnO) on stainless steel

    International Nuclear Information System (INIS)

    Cu(In,Ga)Se2 (CIGS) based-photovoltaic (PV) cells with different diffusion barriers of SiOx and i-ZnO were fabricated on stainless steel (STS) substrate and their electrical characteristics were investigated by measuring J–V curves under illuminated and dark conditions. The physical properties of the CIGS film depending on type of diffusion barrier were also analyzed using X-ray diffraction and secondary ion mass spectroscopy. The efficiency of the CIGS-PV cell with i-ZnO barrier was approximately 2% higher than that with the SiOx barrier. Through the analysis of dark J–V curves, we discovered that distinctive defects were formed in the band gap of CIGS based on which diffusion barrier contacted the STS. The diffraction pattern showed a slightly different tendency of the peak intensity ratio of (220/204)/(112) in the PV cell with the i-ZnO barrier, which was slightly higher than that in the PV cell with SiOx barrier. In elemental depth profile, a deficient Ga profile was observed near the surface of the CIGS film with the SiOx barrier, and an abundant Na profile within the CIGS film with the i-ZnO barrier was detected. This is attributed to a difference in thermal conduction through the diffusion barriers during CIGS film growth, originating from the larger thermal conductivity of ZnO compared with SiOx. - Highlights: • We fabricated CIGS-PV cells with diffusion barriers of SiOx and i-ZnO on STS. • The efficiency of CIGS-PV cell with i-ZnO was ∼2% higher than that with SiOx. • Distinctive defects were formed into CIGS absorber depending on diffusion barrier

  16. Na effect on flexible Cu(In,Ga)Se{sub 2} photovoltaic cell depending on diffusion barriers (SiOx, i-ZnO) on stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Woo-Jung; Cho, Dae-Hyung; Wi, Jae-Hyung; Han, Won Seok [Electronics and Telecommunications Research Institute, Daejeon 305-700 (Korea, Republic of); Kim, Jeha [Insitute of Photovoltaics, Cheongju University, Cheongju 360-764 (Korea, Republic of); Chung, Yong-Duck, E-mail: ydchung@etri.re.kr [Electronics and Telecommunications Research Institute, Daejeon 305-700 (Korea, Republic of); Department of Advanced Device Engineering, Korea University of Science and Technology, Daejeon 305-350 (Korea, Republic of)

    2014-10-15

    Cu(In,Ga)Se{sub 2} (CIGS) based-photovoltaic (PV) cells with different diffusion barriers of SiOx and i-ZnO were fabricated on stainless steel (STS) substrate and their electrical characteristics were investigated by measuring J–V curves under illuminated and dark conditions. The physical properties of the CIGS film depending on type of diffusion barrier were also analyzed using X-ray diffraction and secondary ion mass spectroscopy. The efficiency of the CIGS-PV cell with i-ZnO barrier was approximately 2% higher than that with the SiOx barrier. Through the analysis of dark J–V curves, we discovered that distinctive defects were formed in the band gap of CIGS based on which diffusion barrier contacted the STS. The diffraction pattern showed a slightly different tendency of the peak intensity ratio of (220/204)/(112) in the PV cell with the i-ZnO barrier, which was slightly higher than that in the PV cell with SiOx barrier. In elemental depth profile, a deficient Ga profile was observed near the surface of the CIGS film with the SiOx barrier, and an abundant Na profile within the CIGS film with the i-ZnO barrier was detected. This is attributed to a difference in thermal conduction through the diffusion barriers during CIGS film growth, originating from the larger thermal conductivity of ZnO compared with SiOx. - Highlights: • We fabricated CIGS-PV cells with diffusion barriers of SiOx and i-ZnO on STS. • The efficiency of CIGS-PV cell with i-ZnO was ∼2% higher than that with SiOx. • Distinctive defects were formed into CIGS absorber depending on diffusion barrier.

  17. ITO/p+nc-Si:H contact barrier effects on n-i-p′-p silicon solar cell performances

    International Nuclear Information System (INIS)

    Highlights: ► Effect of the front contact barrier height for electrons (φb0) or holes (φh) on n-i-p′-p based solar cell performances. ► Current–voltage characteristics (J–V), under dark and illumination conditions, for the studied structure are calculated. ► The reverse bias currents do not depend on the front contact barrier heights. ► In forward direction, the contact barrier influences strongly the J–V characteristic in the dark and under illumination. ► Output cell parameters are improved, when φb0 increases. -- Abstract: The computer program AMPS-1D (analysis of microelectronic and photonic structures) has been used to explore the effect of front contact barrier heights for electrons (φb0) or holes (φh) on the performances of n-i-p′-p amorphous/nanocrystalline silicon based solar cell, with a p type hydrogenated nanocrystalline silicon double layer and with no back reflector. φb0 is the result of band bending at the indium tin oxide (ITO)/p+doped hydrogenated nanocrystalline silicon (p nc-Si:H) interface. This paper presents results for a n-i-p′-p device, when the p nc-Si:H layer is used as a window and the p′-nc-Si:H layer as a buffer. Band diagram at thermodynamic equilibrium and current–voltage characteristics (J–V), under dark and illumination conditions, for the considered solar cell structure, are calculated. The modeling showed that the reverse bias currents do not depend on the front contact barrier heights. However, in the forward direction, this contact barrier influences strongly the J–V characteristic in the dark and under illumination. As a result, when φb0 increases, output cell parameters, like open circuit voltage (VOC), fill factor (FF) and efficiency (Eff) increase. The best values obtained are 0.893 V, 0.757 and 8.04%, respectively. These values correspond to a front contact barrier height (φb0) equal to 1.65 eV. Such a value of φb0 can be realized experimentally by using an indium tin oxide (ITO) front

  18. Adaptation of innate lymphoid cells to nutrient deprivation promotes type 2 barrier immunity

    Science.gov (United States)

    Survival of the host relies on the establishment of site-specific barrier defense tailored to constrain pressures imposed by commensal and parasitic exposures. The host is confronted with the additional challenge of maintaining barrier immunity in fluctuating states of dietary availability, yet how ...

  19. Trafficking of Endogenous Immunoglobulins by Endothelial Cells at the Blood-Brain Barrier.

    Science.gov (United States)

    Villaseñor, Roberto; Ozmen, Laurence; Messaddeq, Nadia; Grüninger, Fiona; Loetscher, Hansruedi; Keller, Annika; Betsholtz, Christer; Freskgård, Per-Ola; Collin, Ludovic

    2016-01-01

    The Blood-Brain Barrier (BBB) restricts access of large molecules to the brain. The low endocytic activity of brain endothelial cells (BECs) is believed to limit delivery of immunoglobulins (IgG) to the brain parenchyma. Here, we report that endogenous mouse IgG are localized within intracellular vesicles at steady state in BECs in vivo. Using high-resolution quantitative microscopy, we found a fraction of endocytosed IgG in lysosomes. We observed that loss of pericytes (key components of the BBB) in pdgf-b(ret/ret) mice affects the intracellular distribution of endogenous mouse IgG in BECs. In these mice, endogenous IgG was not detected within lysosomes but instead accumulate at the basement membrane and brain parenchyma. Such IgG accumulation could be due to reduced lysosomal clearance and increased sorting to the abluminal membrane of BECs. Our results suggest that, in addition to low uptake from circulation, IgG lysosomal degradation may be a downstream mechanism by which BECs further restrict IgG access to the brain. PMID:27149947

  20. Ceramic barrier layers for flexible thin film solar cells on metallic substrates: a laboratory scale study for process optimization and barrier layer properties.

    Science.gov (United States)

    Delgado-Sanchez, Jose-Maria; Guilera, Nuria; Francesch, Laia; Alba, Maria D; Lopez, Laura; Sanchez, Emilio

    2014-11-12

    Flexible thin film solar cells are an alternative to both utility-scale and building integrated photovoltaic installations. The fabrication of these devices over electrically conducting low-cost foils requires the deposition of dielectric barrier layers to flatten the substrate surface, provide electrical isolation between the substrate and the device, and avoid the diffusion of metal impurities during the relatively high temperatures required to deposit the rest of the solar cell device layers. The typical roughness of low-cost stainless-steel foils is in the hundred-nanometer range, which is comparable or larger than the thin film layers comprising the device and this may result in electrical shunts that decrease solar cell performance. This manuscript assesses the properties of different single-layer and bilayer structures containing ceramics inks formulations based on Al2O3, AlN, or Si3N4 nanoparticles and deposited over stainless-steel foils using a rotogravure printing process. The best control of the substrate roughness was achieved for bilayers of Al2O3 or AlN with mixed particle size, which reduced the roughness and prevented the diffusion of metals impurities but AlN bilayers exhibited as well the best electrical insulation properties. PMID:25296706

  1. In vitro model of the blood-brain barrier established by co-culture of primary cerebral microvascular endothelial and astrocyte cells

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2015-01-01

    Full Text Available Drugs for the treatment and prevention of nervous system diseases must permeate the blood-brain barrier to take effect. In vitro models of the blood-brain barrier are therefore important in the investigation of drug permeation mechanisms. However, to date, no unified method has been described for establishing a blood-brain barrier model. Here, we modified an in vitro model of the blood-brain barrier by seeding brain microvascular endothelial cells and astrocytes from newborn rats on a polyester Transwell cell culture membrane with 0.4-µm pores, and conducted transepithelial electrical resistance measurements, leakage tests and assays for specific blood-brain barrier enzymes. We show that the permeability of our model is as low as that of the blood-brain barrier in vivo. Our model will be a valuable tool in the study of the mechanisms of action of neuroprotective drugs.

  2. Neisseria meningitidis subverts the polarized organization and intracellular trafficking of host cells to cross the epithelial barrier.

    Science.gov (United States)

    Barrile, Riccardo; Kasendra, Magdalena; Rossi-Paccani, Silvia; Merola, Marcello; Pizza, Mariagrazia; Baldari, Cosima; Soriani, Marco; Aricò, Beatrice

    2015-09-01

    Translocation of the nasopharyngeal barrier by Neisseria meningitidis occurs via an intracellular microtubule-dependent pathway and represents a crucial step in its pathogenesis. Despite this fact, the interaction of invasive meningococci with host subcellular compartments and the resulting impact on their organization and function have not been investigated. The influence of serogroup B strain MC58 on host cell polarity and intracellular trafficking system was assessed by confocal microscopy visualization of different plasma membrane-associated components (such as E-cadherin, ZO-1 and transferrin receptor) and evaluation of the transferrin uptake and recycling in infected Calu-3 monolayers. Additionally, the association of N. meningitidis with different endosomal compartments was evaluated through the concomitant staining of bacteria and markers specific for Rab11, Rab22a, Rab25 and Rab3 followed by confocal microscopy imaging. Subversion of the host cell architecture and intracellular trafficking system, denoted by mis-targeting of cell plasma membrane components and perturbations of transferrin transport, was shown to occur in response to N. meningitidis infection. Notably, the appearance of all of these events seems to positively correlate with the efficiency of N. meningitidis to cross the epithelial barrier. Our data reveal for the first time that N. meningitidis is able to modulate the host cell architecture and function, which might serve as a strategy of this pathogen for overcoming the nasopharyngeal barrier without affecting the monolayer integrity. PMID:25801707

  3. Baicalein induces CD4+Foxp3+ T cells and enhances intestinal barrier function in a mouse model of food allergy

    Science.gov (United States)

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Kwon, Da-Ae; Shon, Dong-Hwa

    2016-01-01

    The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy. PMID:27561877

  4. Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis

    OpenAIRE

    Shigehisa Yanagi; Hironobu Tsubouchi; Ayako Miura; Nobuhiro Matsumoto; Masamitsu Nakazato

    2015-01-01

    Individual alveolar epithelial cells (AECs) collaboratively form a tight barrier between atmosphere and fluid-filled tissue to enable normal gas exchange. The tight junctions of AECs provide intercellular sealing and are integral to the maintenance of the AEC barrier integrity. Disruption and failure of reconstitution of AEC barrier result in catastrophic consequences, leading to alveolar flooding and subsequent devastating fibrotic scarring. Recent evidences reveal that many of the fibrotic ...

  5. Efficiency enhancement of solid-state PbS quantum dot-sensitized solar cells with Al2O3 barrier layer

    KAUST Repository

    Brennan, Thomas P.

    2013-01-01

    Atomic layer deposition (ALD) was used to grow both PbS quantum dots and Al2O3 barrier layers in a solid-state quantum dot-sensitized solar cell (QDSSC). Barrier layers grown prior to quantum dots resulted in a near-doubling of device efficiency (0.30% to 0.57%) whereas barrier layers grown after quantum dots did not improve efficiency, indicating the importance of quantum dots in recombination processes. © 2013 The Royal Society of Chemistry.

  6. Intercellular transfer of P-glycoprotein in human blood-brain barrier endothelial cells is increased by histone deacetylase inhibitors.

    Science.gov (United States)

    Noack, Andreas; Noack, Sandra; Buettner, Manuela; Naim, Hassan Y; Löscher, Wolfgang

    2016-01-01

    The blood-brain barrier (BBB) controls the entry of compounds into the brain, thereby regulating brain homeostasis. Efflux transporters such as P-glycoprotein (Pgp) significantly contribute to BBB function. Multiple signaling pathways modulate the expression and activity of Pgp in response to xenobiotics and disease. A non-genetic way of intercellular transfer of Pgp occurs in cancer cells, but whether this also occurs in non-cancer cells such as endothelial cells that form the BBB is not known. A human brain endothelial cell line (hCMEC/D3) was used to study whether cell-to-cell Pgp transfer occurs during co-culturing with Pgp-EGFP expressing hCMEC/D3 cells. The Pgp-EGFP fusion protein was transferred from donor to recipient cells by cell-to-cell contact and Pgp-EGFP enriched vesicles, which were exocytosed by donor cells and endocytosed by adherent recipient cells. Flow cytometry experiments with the Pgp substrate eFLUXX-ID Gold demonstrated that the transferred Pgp is functional in the recipient cells. Exposure of the donor cells with inhibitors of histone deacetylases (HDACs) resulted in an enhanced intercellular Pgp transfer. Non-genetic transfer of a resistance phenotype and its regulation by HDACs is a novel mechanism of altering BBB functionality. This mechanism may have important implications for understanding drug-induced alterations in Pgp expression and activity. PMID:27375084

  7. Oxygen- and water-induced degradation of an inverted polymer solar cell: the barrier effect

    DEFF Research Database (Denmark)

    Vesterager Madsen, Morten; Norrman, Kion; Krebs, Frederik C

    2011-01-01

    The work focuses on the degradation of performance induced by both water and oxygen in an inverted geometry organic photovoltaic device with emphasis on the accumulated barrier effect of the layers comprising the layer stack. By studying the exchange of oxygen in the zinc oxide (ZnO) layer......, the barrier effect is reported in both a dry oxygen atmosphere and an oxygen-free humid atmosphere. The devices under study are comprised of a bulk heterojunction formed by poly(3-hexylthiophene) and [6,6]-phenyl-C61-butyric acid methyl ester sandwiched between a layer of zinc oxide (electron transporting...... layer) and a layer of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (hole transport layer) and the two electrodes indium tin oxide and silver. Time-of-flight secondary ion mass spectrometry is employed to characterize the accumulated barrier effect. A pronounced barrier effect is observed...

  8. Thin film metallic glass as a diffusion barrier for copper indium gallium selenide solar cell on stainless steel substrate: A feasibility study

    Science.gov (United States)

    Diyatmika, Wahyu; Xue, Lingjun; Lin, Tai-Nan; Chang, Chia-wen; Chu, Jinn P.

    2016-08-01

    The feasibility of using Zr53.5Cu29.1Al6.5Ni10.9 thin-film metallic glass (TFMG) as a diffusion barrier for copper indium gallium selenide (CIGS) solar cells on stainless steel (SS) is investigated. The detrimental Fe diffusion from SS into CIGS is found to be effectively hindered by the introduction of a 70-nm-thick TFMG barrier; the cell performance is thus improved. Compared with the 2.73% of CIGS on bare SS, a higher efficiency of 5.25% is obtained for the cell with the Zr52Cu32Al9Ni7 TFMG barrier.

  9. On the contribution of mucosal mast cells to the regulation of mouse intestinal barrier function

    OpenAIRE

    Rychter, J.

    2010-01-01

    The primary functions of the small intestine are the digestion and transport of luminal content and the absorption of nutrients. During these processes the intestinal mucosa is exposed to various ingested and resident pathogens. The ability of the intestinal wall to prevent transmucosal passage of toxins or of harmful micro-organisms and their products is defined as the intestinal barrier function. Defective intestinal barrier function plays a role in a number of disorders such as inflammator...

  10. HYDROGEN-RICH MEDIUM AMELIORATES LIPOPOLYSACCHARIDE-INDUCED BARRIER DYSFUNCTION VIA RHOA-MDIA1 SIGNALING IN CACO-2 CELLS

    Science.gov (United States)

    Yang, Tao; Wang, Lu; Sun, Ruiqiang; Chen, Hongguang; Zhang, Hongtao; Yu, Yang; Wang, Yanyan; Wang, Guolin; Yu, Yonghao; Xie, Keliang

    2016-01-01

    ABSTRACT Gastrointestinal barrier dysfunction is associated with the severity and prognosis of sepsis. Hydrogen gas (H2) can ameliorate multiple organ damage in septic animals. Ras homolog gene family member A (RhoA) and mammalian diaphanous-related formin 1 (mDia1) are important to regulate tight junction (TJ) and adherens junction (AJ), both of which determine the integrity of the intestinal barrier. This study was aimed to investigate whether H2 could modulate lipopolysaccharide (LPS)-stimulated dysfunction of the intestinal barrier and whether RhoA-mDia1 signaling is involved. Caco-2 cells were exposed to different concentrations of LPS (1 μg/mL–1 mg/mL). The permeability of the intestinal barrier was evaluated by transepithelial resistance (TER) and fluorescein-isothiocyanate-dextran flux. Expression and distribution of occludin and E-cadherin were analyzed by Western blot and immunofluorescence. RhoA activity was measured by G-Lisa assay, and mDia1 expression was assessed by Western blot. LPS (100 μg/mL) decreased TER and increased fluorescein-isothiocyanate-dextran flux, which were alleviated by H2-rich medium. Also, H2 down-regulated LPS-induced oxidative stress. Moreover, H2 improved the down-regulated expression and redistribution of occludin and E-cadherin caused by LPS. Additionally, H2 alleviated LPS-caused RhoA activation, and the beneficial effects of H2 on barrier were counteracted by RhoA agonist CN03. Rho inhibitor C3 exoenzyme mitigated LPS-induced barrier breakdown. Furthermore, H2-rich medium increased mDia1 expression, and mDia1 knockdown abolished protections of H2 on barrier permeability. mDia1 knockdown eliminated H2-induced benefits for occludin and E-cadherin. These findings suggest that H2 improves LPS-induced hyperpermeability of the intestinal barrier and disruptions of TJ and AJ by moderating RhoA-mDia1 signaling. PMID:26529665

  11. Effects of phenol on barrier function of a human intestinal epithelial cell line correlate with altered tight junction protein localization

    International Nuclear Information System (INIS)

    Phenol contamination of soil and water has raised concerns among people living near phenol-producing factories and hazardous waste sites containing the chemical. Phenol, particularly in high concentrations, is an irritating and corrosive substance, making mucosal membranes targets of toxicity in humans. However, few data on the effects of phenol after oral exposure exist. We used an in vitro model employing human intestinal epithelial cells (SK-CO15) cultured on permeable supports to examine effects of phenol on epithelial barrier function. We hypothesized that phenol disrupts epithelial barrier by altering tight junction (TJ) protein expression. The dose-response effect of phenol on epithelial barrier function was determined using transepithelial electrical resistance (TER) and FITC-dextran permeability measurements. We studied phenol-induced changes in cell morphology and expression of several tight junction proteins by immunofluorescence and Western blot analysis. Effects on cell viability were assessed by MTT, Trypan blue, propidium iodide and TUNEL staining. Exposure to phenol resulted in decreased TER and increased paracellular flux of FITC-dextran in a dose-dependent manner. Delocalization of claudin-1 and ZO-1 from TJs to cytosol correlated with the observed increase in permeability after phenol treatment. Additionally, the decrease in TER correlated with changes in the distribution of a membrane raft marker, suggesting phenol-mediated effects on membrane fluidity. Such observations were independent of effects of phenol on cell viability as enhanced permeability occurred at doses of phenol that did not cause cell death. Overall, these findings suggest that phenol may affect transiently the lipid bilayer of the cell membrane, thus destabilizing TJ-containing microdomains.

  12. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg-/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg-/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  13. PRIMARY CULTURE OF CHOROIDAL EPITHELIAL CELLS: CHARACTERIZATION OF AN IN VITRO MODEL OF BLOOD-CSF BARRIER

    Science.gov (United States)

    ZHENG, WEI; ZHAO, QIUQU; GRAZIANO, JOSEPH H.

    2016-01-01

    Summary A primary rat choroidal epithelial cell culture system was developed to investigate mechanisms of heavy metal toxicity on the blood-cerebrospinal fluid (CSF) barrier. Epithelial cells were dissociated from choroidal tissue by pronase digestion and cultured in standard DMEM culture media supplemented with 10% fetal bovine serum and 10 ng epithelial growth factor per ml. The procedure yielded 2–5 × 104 cells from pooled plexuses of three to four rats, and a viability of 77–85%. The cultures displayed a dominant polygonal type of epithelial cells, with a population doubling time of 2–3 d. The cultures were of distinct choroidal epithelial origins. For example, immunocytochemical studies using monospecific rabbit anti-rat TTR polyclonal antibody revealed a strong positive stain of transthyretin (TTR), a thyroxine transport protein exclusively produced by the choroidal epithelia. Also, reverse-transcriptase polymerase chain reaction (PCR) confirmed the presence of specific TTR mRNA in the cultures. The cultures were further adapted to grow on a freely permeable membrane sandwiched between two culture chambers. The formation of an impermeable confluent monolayer occurred within 5 d after seeding and was verified by the presence of a steady electrical resistance across the membrane (80 ± 10 ohm per cm2). The epithelial barriers appeared to actively transport [125I]-thyroxine from the basal to apical chamber. These results suggest that this primary cell culture system possesses typical choroidal epithelial characteristics and appears to be a suitable model for in vitro mechanistic investigations of blood–CSF barrier. PMID:9542634

  14. Internal benchmarking of a human blood-brain barrier cell model for screening of nanoparticle uptake and transcytosis.

    Science.gov (United States)

    Ragnaill, Michelle Nic; Brown, Meredith; Ye, Dong; Bramini, Mattia; Callanan, Sean; Lynch, Iseult; Dawson, Kenneth A

    2011-04-01

    Transport of drugs across the blood-brain barrier, which protects the brain from harmful agents, is considered the holy grail of targeted delivery, due to the extreme effectiveness of this barrier at preventing passage of non-essential molecules through to the brain. This has caused severe limitations for therapeutics for many brain-associated diseases, such as HIV and neurodegenerative diseases. Nanomaterials, as a result of their small size (in the order of many protein-lipid clusters routinely transported by cells) and their large surface area (which acts as a scaffold for proteins thereby rendering nanoparticles as biological entities) offer great promise for neuro-therapeutics. However, in parallel with developing neuro-therapeutic applications based on nanotechnology, it is essential to ensure their safety and long-term consequences upon reaching the brain. One approach to determining safe application of nanomaterials in biology is to obtain a deep mechanistic understanding of the interactions between nanomaterials and living systems (bionanointeractions). To this end, we report here on the establishment and internal round robin validation of a human cell model of the blood-brain barrier for use as a tool for screening nanoparticles interactions, and assessing the critical nanoscale parameters that determine transcytosis. PMID:21236340

  15. Mechanisms and regulation of iron trafficking across the capillary endothelial cells of the blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Daniel J. Kosman

    2015-07-01

    Full Text Available The transcellular trafficking of iron from the blood into the brain interstitium depends on iron uptake proteins in the apical membrane of brain microvascular capillary endothelial cells and efflux proteins at the basolateral, abluminal membrane. In this review, we discuss the three mechanisms by which these cells take-up iron from the blood and the sole mechanism by which they efflux this iron into the abluminal space. We then focus on the regulation of this efflux pathway by exocrine factors that are released from neighboring astrocytes. Also discussed are the cytokines secreted by capillary cells that regulate the expression of these glial cell signals. Among the interstitial factors that regulate iron efflux into the brain is the amyloid precursor protein. The role of this amyliodogenic species in brain iron metabolism is discussed. Last, we speculate on the potential relationship between iron transport at the blood-brain barrier and neurological disorders associated with iron mismanagement.

  16. Multimodal investigations of trans-endothelial cell trafficking under condition of disrupted blood-brain barrier integrity

    Directory of Open Access Journals (Sweden)

    Masaryk Thomas

    2010-03-01

    Full Text Available Abstract Background Stem cells or immune cells targeting the central nervous system (CNS bear significant promises for patients affected by CNS disorders. Brain or spinal cord delivery of therapeutic cells is limited by the blood-brain barrier (BBB which remains one of the recognized rate-limiting steps. Osmotic BBB disruption (BBBD has been shown to improve small molecule chemotherapy for brain tumors, but successful delivery of cells in conjunction with BBBD has never been reported. We have used a clinically relevant model (pig of BBBD to attempt brain delivery of TALL-104, a human leukemic T cell line. TALL-104 cells are potent tumor killers and have demonstrated potential for systemic tumor therapy. The pig model used is analogous to the clinical BBBD procedure. Cells were injected in the carotid artery after labeling with the MRI T1 contrast agent GdHPDO3A. Contrast CT scans were used to quantify BBBD and MRI was used to detect Gd++-loaded cells in the brain. Transcranial Doppler was used to monitor cerebral blood flow. EEG recordings were used to detect seizures. Immunocytochemical detection (Cresyl Violet, anti-human CD8 for TALL-104, Evans Blue for BBB damage, GFAP and NEUN was performed. Results At the concentration used TALL-104 cells were tolerated. Incomplete BBBD did not allow cell entry into the brain. MRI scans at 24 and 48 hours post-injection allowed visualization of topographically segregated cells in the hemisphere that underwent successful BBBD. Perivascular location of TALL-104 was confirmed in the BBBD hemisphere by Cresyl violet and CD8 immunocytochemistry. No significant alteration in CBF or EEG activity was recorded during cell injections. Conclusions Our data show that targeted CNS cell therapy requires blood-brain barrier disruption. MRI-detectable cytotoxic anti-neoplastic cells can be forced to transverse the BBB and accumulate in the perivascular space. The virtual absence of toxicity, the high anti-tumor activity

  17. Cholera toxin disrupts barrier function by inhibiting exocyst-mediated trafficking of host proteins to intestinal cell junctions

    Science.gov (United States)

    Guichard, Annabel; Moreno, Beatriz Cruz; Aguilar, Berenice; van Sorge, Nina M.; Kuang, Jennifer; Kurkciyan, Adrianne A.; Wang, Zhipeng; Hang, Saiyu; Pineton de Chambrun, Guillaume P.; McCole, Declan F.; Watnick, Paula; Nizet, Victor; Bier, Ethan

    2013-01-01

    Summary Cholera toxin (CT), a virulence factor elaborated by Vibrio cholerae, is sufficient to induce the severe diarrhea characteristic of cholera. The enzymatic moiety of CT (CtxA) increases cAMP synthesis in intestinal epithelial cells, leading to chloride ion (Cl−) efflux through the CFTR Cl− channel. To preserve electroneutrality and osmotic balance, sodium ions and water also flow into the intestinal lumen via a paracellular route. We find that CtxA-driven cAMP increase also inhibits Rab11/exocyst-mediated trafficking of host proteins including E-cadherin and Notch signaling components to cell-cell junctions in Drosophila, human intestinal epithelial cells, and ligated mouse ileal loops, thereby disrupting barrier function. Additionally, CtxA induces junctional damage, weight loss, and dye leakage in the Drosophila gut, contributing to lethality from live V. cholerae infection, all of which can be rescued by Rab11 over-expression. These barrier-disrupting effects of CtxA may act in parallel with Cl− secretion to drive the pathophysiology of cholera. PMID:24034615

  18. Comparison of immortalized bEnd5 and primary mouse brain microvascular endothelial cells as in vitro blood–brain barrier models for the study of T cell extravasation

    OpenAIRE

    Steiner, Oliver; Coisne, Caroline; Engelhardt, Britta; Lyck, Ruth

    2010-01-01

    Important insights into the molecular mechanism of T cell extravasation across the blood–brain barrier (BBB) have already been obtained using immortalized mouse brain endothelioma cell lines (bEnd). However, compared with bEnd, primary brain endothelial cells have been shown to establish better barrier characteristics, including complex tight junctions and low permeability. In this study, we asked whether bEnd5 and primary mouse brain microvascular endothelial cells (pMBMECs) were equally sui...

  19. Apoplasmic barriers and oxygen transport properties of hypodermal cell walls in roots from four amazonian tree species.

    Science.gov (United States)

    De Simone, Oliviero; Haase, Karen; Müller, Ewald; Junk, Wolfgang J; Hartmann, Klaus; Schreiber, Lukas; Schmidt, Wolfgang

    2003-05-01

    The formation of suberized and lignified barriers in the exodermis is suggested to be part of a suite of adaptations to flooded or waterlogged conditions, adjusting transport of solutes and gases in and out of roots. In this study, the composition of apoplasmic barriers in hypodermal cell walls and oxygen profiles in roots and the surrounding medium of four Amazon tree species that are subjected to long-term flooding at their habitat was analyzed. In hypodermal cell walls of the deciduous tree Crateva benthami, suberization is very weak and dominated by monoacids, 2-hydroxy acids, and omega-hydroxycarboxylic acids. This species does not show any morphological adaptations to flooding and overcomes the aquatic period in a dormant state. Hypodermal cells of Tabernaemontana juruana, a tree which is able to maintain its leaf system during the aquatic phase, are characterized by extensively suberized walls, incrusted mainly by the unsaturated C(18) omega-hydroxycarboxylic acid and the alpha,omega-dicarboxylic acid analogon, known as typical suberin markers. Two other evergreen species, Laetia corymbulosa and Salix martiana, contained 3- to 4-fold less aliphatic suberin in the exodermis, but more than 85% of the aromatic moiety of suberin are composed of para-hydroxybenzoic acid, suggesting a function of suberin in pathogen defense. No major differences in the lignin content among the species were observed. Determination of oxygen distribution in the roots and rhizosphere of the four species revealed that radial loss of oxygen can be effectively restricted by the formation of suberized barriers but not by lignification of exodermal cell walls. PMID:12746526

  20. Hypoxia-ischemia and retinal ganglion cell damage

    Directory of Open Access Journals (Sweden)

    Charanjit Kaur

    2008-08-01

    Full Text Available Charanjit Kaur1, Wallace S Foulds2, Eng-Ang Ling11Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Singapore Eye Research Institute, SingaporeAbstract: Retinal hypoxia is the potentially blinding mechanism underlying a number of sight-threatening disorders including central retinal artery occlusion, ischemic central retinal vein thrombosis, complications of diabetic eye disease and some types of glaucoma. Hypoxia is implicated in loss of retinal ganglion cells (RGCs occurring in such conditions. RGC death occurs by apoptosis or necrosis. Hypoxia-ischemia induces the expression of hypoxia inducible factor-1α and its target genes such as vascular endothelial growth factor (VEGF and nitric oxide synthase (NOS. Increased production of VEGF results in disruption of the blood retinal barrier leading to retinal edema. Enhanced expression of NOS results in increased production of nitric oxide which may be toxic to the cells resulting in their death. Excess glutamate release in hypoxic-ischemic conditions causes excitotoxic damage to the RGCs through activation of ionotropic and metabotropic glutamate receptors. Activation of glutamate receptors is thought to initiate damage in the retina by a cascade of biochemical effects such as neuronal NOS activation and increase in intracellular Ca2+ which has been described as a major contributing factor to RGC loss. Excess production of proinflammatory cytokines also mediates cell damage. Besides the above, free-radicals generated in hypoxic-ischemic conditions result in RGC loss because of an imbalance between antioxidant- and oxidant-generating systems. Although many advances have been made in understanding the mediators and mechanisms of injury, strategies to improve the damage are lacking. Measures to prevent neuronal injury have to be developed.Keywords: retinal hypoxia, retinal ganglion cells, glutamate receptors, neuronal injury, retina

  1. Actin related protein complex subunit 1b controls sperm release, barrier integrity and cell division during adult rat spermatogenesis.

    Science.gov (United States)

    Kumar, Anita; Dumasia, Kushaan; Deshpande, Sharvari; Gaonkar, Reshma; Balasinor, N H

    2016-08-01

    Actin remodeling is a vital process for signaling, movement and survival in all cells. In the testes, extensive actin reorganization occurs at spermatid-Sertoli cell junctions during sperm release (spermiation) and at inter Sertoli cell junctions during restructuring of the blood testis barrier (BTB). During spermiation, tubulobulbar complexes (TBCs), rich in branched actin networks, ensure recycling of spermatid-Sertoli cell junctional molecules. Similar recycling occurs during BTB restructuring around the same time as spermiation occurs. Actin related protein 2/3 complex is an essential actin nucleation and branching protein. One of its subunits, Arpc1b, was earlier found to be down-regulated in an estrogen-induced rat model of spermiation failure. Also, Arpc1b was found to be estrogen responsive through estrogen receptor beta in seminiferous tubule culture. Here, knockdown of Arpc1b by siRNA in adult rat testis led to defects in spermiation caused by failure in TBC formation. Knockdown also compromised BTB integrity and caused polarity defects of mature spermatids. Apart from these effects pertaining to Sertoli cells, Arpc1b reduction perturbed ability of germ cells to enter G2/M phase thus hindering cell division. In summary, Arpc1b, an estrogen responsive gene, is a regulator of spermiation, mature spermatid polarity, BTB integrity and cell division during adult spermatogenesis. PMID:27113856

  2. Physics of a magnetic barrier in low-temperature bounded plasmas: insight from particle-in-cell simulations

    International Nuclear Information System (INIS)

    The use of magnetic fields is quite common in low-pressure, low-temperature, gas-discharge devices for industrial applications. However, transport in such devices is still not very well clarified, mainly due to the presence of walls playing a crucial role and to the variety of configurations studied. The latter often obstruct the underlying basic physical phenomena and make the different studies valid only for very specific configurations. This work presents a numerical study of particle transport in low-pressure (0.3 Pa) plasmas across a localized transverse magnetic field (magnetic barrier) by means of the 2D3V particle-in-cell with Monte Carlo collisions method. The problem is treated as generally as possible while trying to reveal the basic physics, using very simplified chemistry and considering a simple rectangular configuration. The conditions chosen for the magnetic field are common to many applications—magnetized electrons and almost unmagnetized ions. Two basic configurations with different magnetic field directions are analyzed in detail: magnetic field perpendicular to the simulation plane and along the simulation plane. An extensive parametric study is carried out in order to obtain the main trends and scaling laws for particle transport with respect to different parameters: plasma density, magnetic barrier size and magnetic field magnitude. The total current of electrons crossing the barrier is found to scale linearly with the plasma density, which extends the validity of the obtained results to a wide range of plasma density values. (paper)

  3. Eicosapentaenoic Acid Enhances Heat Stress-Impaired Intestinal Epithelial Barrier Function in Caco-2 Cells

    OpenAIRE

    Guizhen Xiao; Liqun Tang; Fangfang Yuan; Wei Zhu; Shaoheng Zhang; Zhifeng Liu; Yan Geng; Xiaowen Qiu; Yali Zhang; Lei Su

    2013-01-01

    OBJECTIVE: Dysfunction of the intestinal epithelial tight junction (TJ) barrier is known to have an important etiologic role in the pathophysiology of heat stroke. N-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a role in maintaining and protecting the TJ structure and function. This study is aimed at investigating whether n-3 PUFAs could alleviate heat stress-induced dysfunction of intestinal tight junction. METHODS: Human i...

  4. Role of mast cells and probiotics in the regulation of intestinal barrier function

    OpenAIRE

    Carlsson, Anders

    2013-01-01

    The intestinal mucosa is the largest contact area and one of the most important barriers to the outside environment. It is highly specialized in aiding us digest and absorb nutrients. It is daily exposed to several potentially dangerous substances and microorganisms, which if they were allowed to pass into the body, could give rise to diseases. Throughout the small intestine certain sites specialized in antigen sampling are found. These sites are named Peyer’s patches and are lymphoid follicl...

  5. A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell

    OpenAIRE

    Lori Clay; Fabrice Caudron; Annina Denoth-Lippuner; Barbara Boettcher; St\\xfdphanie Buvelot Frei; Erik Lee Snapp; Yves Barral

    2014-01-01

    eLife digest Cell division isn't always about splitting a cell into two identical parts. The diversity of many of our own cells relies on asymmetric cell divisions. The yeast used to make bread rely on a process called ‘budding’ that involves a small daughter cell emerging from the surface of the mother cell. Mother cells can only produce around 20–50 daughter cells before dying from old age. However, their daughters are always born rejuvenated, and not aged like their mothers. Budding involv...

  6. Immunological Barriers to Stem Cell Therapy in the Central Nervous System

    OpenAIRE

    Tullis, Gregory E.; Kathleen Spears; Kirk, Mark D.

    2014-01-01

    The central nervous system is vulnerable to many neurodegenerative disorders such as Alzheimer's disease that result in the extensive loss of neuronal cells. Stem cells have the ability to differentiate into many types of cells, which make them ideal for treating such disorders. Although stem cell therapy has shown some promising results in animal models for many brain disorders it has yet to translate into the clinic. A major hurdle to the translation of stem cell therapy into the clinic is ...

  7. Dye-Sensitized Carbon Nano-Yarn Based Photovoltaic Cells with Enhanced Electron-Hole Separation and Barrier Characteristics

    Science.gov (United States)

    Moore, H. Justin; Leal, Miguel; Grissom, Glenn; Trad, Tarek; Islam, Nazmul; Touhami, Ahmed; Uddin, M. Jasim

    Over the last 30 years dye-sensitized solar cells have received considerable interest as an alternative energy source due to their low-cost, environmental sustainability, flexibility, and an abundant number of other practical applications. Flexible carbon nanotube-yarn based photo voltaic cells have shown considerable advantages over metal wire based solar cells or non-flexible substrates like indium-doped tin oxide glass. Carbon nanotubes are superior for photo voltaic cells due to their lower electrical resistance, excellent electrocatalytic activity, and high mechanical integrity. Here, we introduce the use of poly(3-hexylthiophene-2,5-diyl), [6.6] diphenyl C62 bis(butyric acid methyl ester), cadmium sulfide-cadmium selenide quantum dots, and ruthenium-based dye N719 to locally increase electron generation, decrease electron-hole pair recombination, as well as enhancing barrier characteristics. Our prototype 3-dimensional carbon nano-yarn based photovoltaic cells show an enhancement in photon to energy conversion efficiency (>6.5%). This along with prolonged environmental stability makes for a very promising solar cell. NIH, NSF, Welch Foundation.

  8. Target or barrier? The cell wall of early- and later- diverging plants vs cadmium toxicity: differences in the response mechanisms

    Directory of Open Access Journals (Sweden)

    Luigi eParrotta

    2015-03-01

    Full Text Available Increasing industrialization and urbanization result in emission of pollutants in the environment including toxic heavy metals, as cadmium and lead. Among the different heavy metals contaminating the environment, cadmium raises great concern, as it is ecotoxic and as such can heavily impact ecosystems. The cell wall is the first structure of plant cells to come in contact with heavy metals. Its composition, characterized by proteins, polysaccharides and in some instances lignin and other phenolic compounds, confers the ability to bind non-covalently and/or covalently heavy metals via functional groups. A strong body of evidence in the literature has shown the role of the cell wall in heavy metal response: it sequesters heavy metals, but at the same time its synthesis and composition can be severely affected. The present review analyzes the dual property of plant cell walls, i.e. barrier and target of heavy metals, by taking Cd toxicity as example. Following a summary of the known physiological and biochemical responses of plants to Cd, the review compares the wall-related mechanisms in early- and later-diverging land plants, by considering the diversity in cell wall composition. By doing so, common as well as unique response mechanisms to metal/cadmium toxicity are identified among plant phyla and discussed. After discussing the role of hyperaccumulators’ cell walls as a particular case, the review concludes by considering important aspects for plant engineering.

  9. Adverse effects of antipsychotics on micro-vascular endothelial cells of the human blood-brain barrier.

    Science.gov (United States)

    Elmorsy, Ekramy; Elzalabany, Laila M; Elsheikha, Hany M; Smith, Paul A

    2014-10-01

    Although the mechanisms of action of antipsychotics (APs) on neuronal function are well understood, very little is known about their effects on cells of the blood-brain barrier (BBB); one function of which is to limit the access of these amphiphilic compounds to the central nervous system. To address this question we have investigated the cytological and functional effects of four APs: chlorpromazine (CLP), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ), at concentrations typical of high therapeutic dosage on a human brain microvascular endothelial cell (HBMEC) model of the BBB. At ~10 µM all four APs impaired the ability of HBMECs to reduce MTT which was followed by decreased Trypan blue exclusion and increased Lactate dehydrogenase release. These effects were associated with oxidative stress which was partly reversed by incubation in 10mM glutathione. At their EC50 concentrations for MTT reduction, all four APs disrupted cellular ultrastructure and morphology. HAL, CPZ and CLZ increased Caspase -3, -8 and -9 activity, chromatin condensation and fragmentation, data indicative of apoptosis. These events were associated with decreased transcytosis of Evans blue and increased transendothelial potential difference and electrical resistance of this BBB model. These findings suggest that at high therapeutic concentrations, CPZ and CLZ are likely to incur cytoxic effects and apoptosis of BBB endothelia with an impairment of barrier functionality. Such events may underlie the aetiology of neuroleptic associated cerebral oedema and neuroleptic malignant syndrome. PMID:25139421

  10. Analytical Estimate of Open-Circuit Voltage of a Schottky-Barrier Solar Cell Under High Level Injection

    Directory of Open Access Journals (Sweden)

    Pramila Mahala

    2011-01-01

    Full Text Available The open-circuit voltage developed across a Schottky-Barrier (SB solar cell was theoretically modeled to estimate it under high level injection conditions. An Open-circuit voltage (Voc of 0.709 V was obtained for specific metal/n-Si SB solar cell. A substantial increase of 42.6 % in Voc was noticed while comparing our result with that previously calculated in low level injection conditions. Four different metals suitable for making Schottky contact with n-Si were investigated and calculated the variation of Voc with different values of doping concentrations in the semiconductor. The effect of surface recombination velocities (SRV of charge carriers on Voc was also estimated at such high level injections.

  11. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites

    Energy Technology Data Exchange (ETDEWEB)

    Cordon-Cardo, C.; O' Brien, J.P.; Casals, D.; Biedler, J.L.; Melamed, M.R.; Bertino, J.R. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA)); Rittman-Grauer, L. (Hybritech, Inc., San Diego, CA (USA))

    1989-01-01

    Endothelial cells of human capillary blood vessels at the blood-brain and other blood-tissue barrier sites express P-glycoprotein as detected by mouse monoclonal antibodies against the human multidrug-resistance gene product. This pattern of endothelial cell expression may indicate a physiological role for P-glycoprotein in regulating the entry of certain molecules into the central nervous system and other anatomic compartments, such as the testes. These tissues, which limit the access of systemic drugs, are known pharmacologic sanctuaries for metastatic cancer. P-glycoprotein expression in capillary endothelium of brain and testes and not other tissues (i.e., kidney and placenta) may in part explain this phenomenon and could have important implications in cancer chemotherapy.

  12. Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models.

    Directory of Open Access Journals (Sweden)

    Eduard Urich

    Full Text Available Brain microvascular endothelial cells (BEC constitute the blood-brain barrier (BBB which forms a dynamic interface between the blood and the central nervous system (CNS. This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local

  13. Human Brain Microvascular Endothelial Cells Derived from the BC1 iPS Cell Line Exhibit a Blood-Brain Barrier Phenotype.

    Science.gov (United States)

    Katt, Moriah E; Xu, Zinnia S; Gerecht, Sharon; Searson, Peter C

    2016-01-01

    The endothelial cells that form capillaries in the brain are highly specialized, with tight junctions that minimize paracellular transport and an array of broad-spectrum efflux pumps that make drug delivery to the brain extremely challenging. One of the major limitations in blood-brain barrier research and the development of drugs to treat central nervous system diseases is the lack of appropriate cell lines. Recent reports indicate that the derivation of human brain microvascular endothelial cells (hBMECs) from human induced pluripotent stem cells (iPSCs) may provide a solution to this problem. Here we demonstrate the derivation of hBMECs extended to two new human iPSC lines: BC1 and GFP-labeled BC1. These hBMECs highly express adherens and tight junction proteins VE-cadherin, ZO-1, occludin, and claudin-5. The addition of retinoic acid upregulates VE-cadherin expression, and results in a significant increase in transendothelial electrical resistance to physiological values. The permeabilities of tacrine, rhodamine 123, and Lucifer yellow are similar to values obtained for MDCK cells. The efflux ratio for rhodamine 123 across hBMECs is in the range 2-4 indicating polarization of efflux transporters. Using the rod assay to assess cell organization in small vessels and capillaries, we show that hBMECs resist elongation with decreasing diameter but show progressive axial alignment. The derivation of hBMECs with a blood-brain barrier phenotype from the BC1 cell line highlights that the protocol is robust. The expression of GFP in hBMECs derived from the BC1-GFP cell line provides an important new resource for BBB research. PMID:27070801

  14. Cell Phones in the Classroom: Teachers' Perspectives of Inclusion, Benefits, and Barriers

    Science.gov (United States)

    Thomas, Kevin M.; O'Bannon, Blanche W.; Bolton, Natalie

    2013-01-01

    Historically viewed as a disruption by teachers, cell phones have been banned from 69% of classrooms (Common Sense Media, 2009). The increased ubiquity and instructional features of cell phones have prompted some teachers to re-evaluate the ban and consider the benefits associated with allowing cell phones in the classroom. This study surveyed 79…

  15. Implication of actin microfilaments in maintenance of intercellular bridges and the Sertoli cell barrier in the rat seminiferous epithelium

    International Nuclear Information System (INIS)

    Within the seminiferous epithelium, germ cells are connected to one another by intercellular bridges. Additionally, young germ cells are separated from more advanced germ cells by the Sertoli cell barrier, the occluding junctions of which are associated with actin microfilaments. To examine how microfilaments influence these structures in the rat the actin-disrupting agent cytochalasin D (CD) was injected intratesticularly (i.t.). In preliminary studies the optical injection volume was found to be 50 μl and, by using the dye trypan blue, the injected solution was shown to enter the lymphatic system and rapidly spread throughout the testis. A 50% clearance of 3H-insulin from the testis was achieved at 3 hr and 95% by 24 hr. Vehicles with varying solubility properties did not cause testicular damage. Intercellular bridges were found to be dynamic structures. As spermatogenesis progressed, the bridge diameter gradually increased. The formation and degradation of bridge partitioning complexes within pre-existing bridges of dividing cells were described

  16. Influences of follicle-stimulating hormone, proteases, and antiproteases on permeability of the barrier generated by Sertoli cells in a two-chambered assembly

    International Nuclear Information System (INIS)

    Factors have been identified that influence the integrity of the barrier generated by Sertoli cells (SC) in culture in a two-chambered assembly. The permeability of the barrier was assessed by determining rates of equilibration of [3H]methoxyinulin or [86Rb]Cl across the Sertoli cell monolayer. The complete system consisted of a confluent monolayer of SC maintained on an extracellular matrix (Matrigel)-coated filter together with peritubular cells on the opposite side of the filter. In confirmation of previous results, levels of plasminogen activator (PA) activity secreted were increased by treatment of SC with FSH or with cAMP derivatives [(Bu)2cAMP (dbcAMP)]. PA levels in the culture medium were inversely related to times required for 50% equilibration of [3H]methoxyinulin across the SC monolayer. Thus, elevated PA levels, elicited by stimulation with FSH or dbcAMP, were associated with a decreased integrity of the barrier generated by SC preparations maintained in serum-free medium in the complete system. The increase in permeability of the barrier in SC elicited by FSH dbcAMP could be prevented, however, by the addition of various antiproteases. FSH actions on barrier function were complex. Effects of FSH that favored barrier integrity were most readily detected when proteolytic activity was inhibited. The addition of intact serum increased the integrity of the barrier, but acid-treated serum depleted of antiproteases had no such effect. We advance the hypothesis that proteases are implicated in modulation of the formation and maintenance of the seminiferous tubule barrier by SC

  17. Analysis of Al diffusion processes in TiN barrier layers for the application in silicon solar cell metallization

    Science.gov (United States)

    Kumm, J.; Samadi, H.; Chacko, R. V.; Hartmann, P.; Wolf, A.

    2016-07-01

    An evaporated Al layer is known as an excellent rear metallization for highly efficient solar cells, but suffers from incompatibility with a common solder process. To enable solar cell-interconnection and module integration, in this work the Al layer is complemented with a solder stack of TiN/Ti/Ag or TiN/NiV/Ag, in which the TiN layer acts as an Al diffusion barrier. X-ray photoelectron spectroscopy measurements prove that diffusion of Al through the stack and the formation of an Al2O3 layer on the stack's surface are responsible for a loss of solderability after a strong post-metallization anneal, which is often mandatory to improve contact resistance and passivation quality. An optimization of the reactive TiN sputter process results in a densification of the TiN layer, which improves its barrier quality against Al diffusion. However, measurements with X-ray diffraction and scanning electron microscopy show that small grains with vertical grain boundaries persist, which still offer fast diffusion paths. Therefore, the concept of stuffing is introduced. By incorporating oxygen into the grain boundaries of the sputtered TiN layer, Al diffusion is strongly reduced as confirmed by secondary ion mass spectroscopy profiles. A quantitative analysis reveals a one order of magnitude lower Al diffusion coefficient for stuffed TiN layers. This metallization system maintains its solderability even after strong post-metallization annealing at 425 °C for 15 min. This paper thus presents an industrially feasible, conventionally solderable, and long-term stable metallization scheme for highly efficient silicon solar cells.

  18. Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells

    DEFF Research Database (Denmark)

    Hiemstra, I. H.; Klaver, E. J.; Vrijland, K.; Kringel, Helene; Andreasen, Annette; Bouma, G.; Kraal, G.; Die, I. van; Haan, J. M. M. den

    2014-01-01

    . This resulted in an increased passage of soluble compounds to the basolateral side that affected DC function. In addition, T. suis E/S suppressed LPS-induced pro-inflammatory cytokine production by CMT93/69 cells, whereas the production of the TH2 response-inducing cytokine thymic stromal lymphopoietin....... The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the...... barrier function of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner...

  19. Transmigration of breast cancer and melanoma cells through the blood-brain barrier: similarities and differences

    OpenAIRE

    Molnár Judit

    2016-01-01

    Brain metastases are common and devastating complications of both breast cancer and melanoma. Although mammary carcinoma brain metastases are more frequent than those originating from melanoma, this latter has the highest tropism to the brain. Using static and dynamic in vitro approaches, here we show that melanoma cells have increased adhesion to the brain endothelium in comparison to breast cancer cells. Moreover, melanoma cells can transmigrate more rapidly and in a higher number through b...

  20. Disruption of colonic barrier function and induction of mediator release by strains of Campylobacter jejuni that invade epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Johannes Beltinger; Jo del Buono; Maeve M Skelly; John Thornley; Robin C Spiller; William A Stack; Christopher J Hawkey

    2008-01-01

    AIM:To study the mechanisms by which Campylobacter jejuni (C.jejuni) causes inflammation and diarrhea.In particular,direct interactions with intestinal epithelial cells and effects on barrier function are poorly understood.METHODS:To model the initial pathogenic effects of C.jejuni on intestinal epithelium,polarized human colonic HCA-7 monolayerswere grown on permeabilized filters and infected apically with clinical isolates of C.jejuni.Integrity of the monolayer was monitored by changes in monolayer resistance,release of lactate dehydrogenase,mannitol fluxes and electron microscopy.Invasion of HCA-7 cells was assessed by a modified gentamicin protection assay,translocation by counting colony forming units in the basal chamber,stimulation of mediator release by immunoassays and secretory responses in monolayers stimulated by bradykinin in an Ussing chamber.RESULTS:All strains translocated across monolayers but only a minority invaded HCA-7 cells.Strains that invaded HCA-7 cells destroyed rnonolayer resistance over 6 h,accompanied by increased release of lactate dehydrogenase,a four-fold increase in permeability to [3H] mannitol,and ultrastructural disruption of tight junctions,with rounding and lifting of cells off the filter membrane.Synthesis of interleukin (IL)-8 and prostaglandin E2 was increased with strains that invaded the rnonolayer but not with those that did not.CONCLUSION:These data demonstrate two distinct effects of C.jejuni on colonic epithelial cells and provide an informative model for further investigation of initial host cell responses to C.jejuni.

  1. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources

    Science.gov (United States)

    Lippmann, Ethan S.; Al-Ahmad, Abraham; Azarin, Samira M.; Palecek, Sean P.; Shusta, Eric V.

    2014-02-01

    Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

  2. Autonomous immunity in mucosal epithelial cells: fortifying the barrier against infection.

    Science.gov (United States)

    Ross, Karen F; Herzberg, Mark C

    2016-06-01

    Mucosal epithelial cells express an autonomous innate immune response that controls the overgrowth of invaded bacteria, mitigates the harmful effects of the bacteria carried within, and does not rely on other external arms of the immune response. Epithelial cell autonomous innate immunity "respects" the social biology of invading bacteria to achieve symbiosis, and is the primary protective mechanism against pathogens. PMID:27005450

  3. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier

    OpenAIRE

    Tominaga, Naoomi; Kosaka, Nobuyoshi; Ono, Makiko; Katsuda, Takeshi; Yoshioka, Yusuke; Tamura, Kenji; Lötvall, Jan; Nakagama, Hitoshi; Ochiya, Takahiro

    2015-01-01

    Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood–brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell–cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the de...

  4. Mesenchymal Stem Cells Regulate Blood Brain Barrier Integrity in Traumatic Brain Injury Through Production of the Soluble Factor TIMP3

    Science.gov (United States)

    Menge, Tyler; Zhao, Yuhai; Zhao, Jing; Wataha, Kathryn; Geber, Michael; Zhang, Jianhu; Letourneau, Phillip; Redell, John; Shen, Li; Wang, Jing; Peng, Zhalong; Xue, Hasen; Kozar, Rosemary; Cox, Charles S.; Khakoo, Aarif Y.; Holcomb, John B.; Dash, Pramod K.; Pati, Shibani

    2013-01-01

    Mesenchymal stem cells (MCSs) have been shown to have therapeutic potential in multiple disease states associated with vascular instability including traumatic brain injury (TBI). In the present study, Tissue Inhibitor of Matrix Metalloproteinase-3 (TIMP3) is identified as the soluble factor produced by MSCs that can recapitulate the beneficial effects of MSCs on endothelial function and blood brain barrier (BBB) compromise in TBI. Attenuation of TIMP3 expression in MSCs completely abrogates the effect of MSCs on BBB permeability and stability, while intravenous administration of rTIMP3 alone can inhibit BBB permeability in TBI. Our results demonstrate that MSCs increase circulating levels of soluble TIMP3, which inhibits VEGF-A induced breakdown of endothelial AJs in vitro and in vivo. These findings elucidate a clear molecular mechanism for the effects of MSCs on the BBB in TBI, and directly demonstrate a role for TIMP3 in regulation of BBB integrity. PMID:23175708

  5. Properties of Plasma Enhanced Chemical Vapor Deposition Barrier Coatings and Encapsulated Polymer Solar Cells

    International Nuclear Information System (INIS)

    In this paper, we report silicon oxide coatings deposited by plasma enhanced chemical vapor deposition technology (PECVD) on 125 μm polyethyleneterephthalate (PET) surfaces for the purpose of the shelf lifetime extension of sealed polymer solar cells. After optimization of the processing parameters, we achieved a water vapor transmission rate (WVTR) of ca. 10−3 g/m2/day with the oxygen transmission rate (OTR) less than 0.05 cc/m2/day, and succeeded in extending the shelf lifetime to about 400 h in encapsulated solar cells. And then the chemical structure of coatings related to the properties of encapsulated cell was investigated in detail. (plasma technology)

  6. Vorinostat Modulates the Imbalance of T Cell Subsets, Suppresses Macrophage Activity, and Ameliorates Experimental Autoimmune Uveoretinitis.

    Science.gov (United States)

    Fang, Sijie; Meng, Xiangda; Zhang, Zhuhong; Wang, Yang; Liu, Yuanyuan; You, Caiyun; Yan, Hua

    2016-03-01

    The purpose of the study was to investigate the anti-inflammatory efficiency of vorinostat, a histone deacetylase inhibitor, in experimental autoimmune uveitis (EAU). EAU was induced in female C57BL/6J mice immunized with interphotoreceptor retinoid-binding protein peptide. Vorinostat or the control treatment, phosphate-buffered saline, was administrated orally from 3 days before immunization until euthanasia at day 21 after immunization. The clinical and histopathological scores of mice were graded, and the integrity of the blood-retinal barrier was examined by Evans blue staining. T helper cell subsets were measured by flow cytometry, and the macrophage functions were evaluated with immunohistochemistry staining and immunofluorescence assays. The mRNA levels of tight junction proteins were measured by qRT-PCR. The expression levels of intraocular cytokines and transcription factors were examined by western blotting. Vorinostat relieved both clinical and histopathological manifestations of EAU in our mouse model, and the BRB integrity was maintained in vorinostat-treated mice, which had less vasculature leakage and higher mRNA and protein expressions of tight junction proteins than controls. Moreover, vorinostat repressed Th1 and Th17 cells and increased Th0 and Treg cells. Additionally, the INF-γ and IL-17A expression levels were significantly decreased, while the IL-10 level was increased by vorinostat treatment. Furthermore, due to the reduced TNF-α level, the macrophage activity was considerably inhibited in EAU mice. Finally, transcription factors, including STAT1, STAT3, and p65, were greatly suppressed by vorinostat treatment. Our data suggest that vorinostat might be a potential anti-inflammatory agent in the management of uveitis and other autoimmune inflammatory diseases. PMID:26798022

  7. A Choroid Plexus Epithelial Cell-based Model of the Human Blood-Cerebrospinal Fluid Barrier to Study Bacterial Infection from the Basolateral Side.

    Science.gov (United States)

    Dinner, Stefanie; Borkowski, Julia; Stump-Guthier, Carolin; Ishikawa, Hiroshi; Tenenbaum, Tobias; Schroten, Horst; Schwerk, Christian

    2016-01-01

    The epithelial cells of the choroid plexus (CP), located in the ventricular system of the brain, form the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB functions in separating the cerebrospinal fluid (CSF) from the blood and restricting the molecular exchange to a minimum extent. An in vitro model of the BCSFB is based on cells derived from a human choroid plexus papilloma (HIBCPP). HIBCPP cells display typical barrier functions including formation of tight junctions (TJs), development of a transepithelial electrical resistance (TEER), as well as minor permeabilities for macromolecules. There are several pathogens that can enter the central nervous system (CNS) via the BCSFB and subsequently cause severe disease like meningitis. One of these pathogens is Neisseria meningitidis (N. meningitidis), a human-specific bacterium. Employing the HIBCPP cells in an inverted cell culture filter insert system enables to study interactions of pathogens with cells of the BCSFB from the basolateral cell side, which is relevant in vivo. In this article, we describe seeding and culturing of HIBCPP cells on cell culture inserts. Further, infection of the cells with N. meningitidis along with analysis of invaded and adhered bacteria via double immunofluorescence is demonstrated. As the cells of the CP are also involved in other diseases, including neurodegenerative disorders like Alzheimer`s disease and Multiple Sclerosis, as well as during the brain metastasis of tumor cells, the model system can also be applied in other fields of research. It provides the potential to decipher molecular mechanisms and to identify novel therapeutic targets. PMID:27213495

  8. Hematopoietic stem cell transplantation in children with hematological malignancies across HLA barriers--reasonable alternative?

    Science.gov (United States)

    Sedlácek, P; Starý, J; Vodváková, S; Poloucková, A; Gasová, Z; Marinov, I; Formánková, R

    2001-01-01

    The aim of this study was to evaluate the efficiency and risks of T-cell depletion in prevention of graft versus host disease (GVHD) using HLA haploidentical family donors as an alternative source of hematopoietic stem cells (HSC) in children with hematological malignancies without suitable matched donor. Ten children, median age 12 years (range, 3-17), were transplanted from haploidentical family donors for acute lymphoblastic leukemia (n = 4), acute myelogenous leukemia (n=2), chronic myelogenous leukemia (n = 2), non-Hodgkin lymphoma (n = 1) and myelodysplastic syndrome (n = 1). Parents were donors for nine, sibling for one patient. T-cell depletion of HSC was performed using CellPro followed by antiCD2/CD3 depletion in 7, and CliniMacs magnetic sorting in 3 grafts. Primary engraftment was achieved in nine patients. Patient with graft failure was successfully re-grafted. Primary acute GVHD was diagnosed in one patient who got higher amount of T-cells in the graft. Secondary GVHD was induced by add-backs of lymphocytes in four patients. Three patients developed chronic GVHD. Four patients died due to transplant related mortality (40%), one from veno-occlusive disease, two due to CMV pneumonia and one of aspergillosis with extensive chronic GVHD. Four patients relapsed with leukemia within 35-98 days post transplant, three without previous signs of GVHD, and all died. Two patients are alive and well 26 and 42 months after transplant. Haploidentical family donors appear to be a reasonable alternative option for patients with urgent indications for allogeneic transplant and/or without a matched donor. PMID:11712683

  9. Species Barrier Prevents an Abnormal Isoform of Prion Protein from Accumulating in Follicular Dendritic Cells of Mice with Creutzfeldt-Jakob Disease

    OpenAIRE

    Muramoto, Tamaki; Kitamoto, Tetsuyuki; Hoque, Mohammad Zahirul; Tateishi, Jun; Goto, Ikuo

    1993-01-01

    The accumulation of abnormal prion protein in follicular dendritic cells did not occur in mice inoculated with materials from human Creutzfeldt-Jakob disease, whereas it always occurred in mice inoculated with mouse-adapted agents, suggesting an intense expression of the species barrier in the lymphoreticular system.

  10. Breakdown of blood-brain barrier function in the murine lymphocytic choriomeningitis virus infection mediated by virus-specific CD8+ T cells

    DEFF Research Database (Denmark)

    Andersen, I H; Marker, O; Thomsen, Allan Randrup

    1991-01-01

    Intracerebral inoculation of lymphocytic choriomeningitis virus (LCMV) generally results in a fatal T cell-mediated meningitis. In a previous study we have demonstrated a compromised blood-brain barrier (BBB) under such conditions. Using semi-quantitative radiography and the low molecular tracer ...

  11. Candida albicans infection leads to barrier breakdown and a MAPK/NF-κB mediated stress response in the intestinal epithelial cell line C2BBe1.

    Science.gov (United States)

    Böhringer, Michael; Pohlers, Susann; Schulze, Sylvie; Albrecht-Eckardt, Daniela; Piegsa, Judith; Weber, Michael; Martin, Ronny; Hünniger, Kerstin; Linde, Jörg; Guthke, Reinhard; Kurzai, Oliver

    2016-07-01

    Intestinal epithelial cells (IEC) form a tight barrier to the gut lumen. Paracellular permeability of the intestinal barrier is regulated by tight junction proteins and can be modulated by microorganisms and other stimuli. The polymorphic fungus Candida albicans, a frequent commensal of the human mucosa, has the capacity of traversing this barrier and establishing systemic disease within the host. Infection of polarized C2BBe1 IEC with wild-type C. albicans led to a transient increase of transepithelial electric resistance (TEER) before subsequent barrier disruption, accompanied by a strong decline of junctional protein levels and substantial, but considerably delayed cytotoxicity. Time-resolved microarray-based transcriptome analysis of C. albicans challenged IEC revealed a prominent role of NF-κB and MAPK signalling pathways in the response to infection. Hence, we inferred a gene regulatory network based on differentially expressed NF-κB and MAPK pathway components and their predicted transcriptional targets. The network model predicted activation of GDF15 by NF-κB was experimentally validated. Furthermore, inhibition of NF-κB activation in C. albicans infected C2BBe1 cells led to enhanced cytotoxicity in the epithelial cells. Taken together our study identifies NF-κB activation as an important protective signalling pathway in the response of epithelial cells to C. albicans. PMID:26752615

  12. Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis

    Directory of Open Access Journals (Sweden)

    Shigehisa Yanagi

    2015-01-01

    Full Text Available Individual alveolar epithelial cells (AECs collaboratively form a tight barrier between atmosphere and fluid-filled tissue to enable normal gas exchange. The tight junctions of AECs provide intercellular sealing and are integral to the maintenance of the AEC barrier integrity. Disruption and failure of reconstitution of AEC barrier result in catastrophic consequences, leading to alveolar flooding and subsequent devastating fibrotic scarring. Recent evidences reveal that many of the fibrotic lung diseases involve AECs both as a frequent target of injury and as a driver of ongoing pathological processes. Aberrantly activated AECs express most of the growth factors and chemokines responsible for the proliferation, migration, and activation of fibroblasts. Current evidences suggest that AECs may acquire overdrive activation in the initial step of fibrosis by several mechanisms, including abnormal recapitulation of the developmental pathway, defects of the molecules essential for epithelial integrity, and acceleration of aging-related properties. Among these initial triggering events, epithelial Pten, a multiple phosphatase that negatively regulates the PI3K/Akt pathway and is crucial for lung development, is essential for the prevention of alveolar flooding and lung fibrosis through the regulation of AEC barrier integrity after injury. Reestablishment of AEC barrier integrity also involves the deployment of specialized stem/progenitor cells.

  13. Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells.

    Science.gov (United States)

    Jumnongprakhon, Pichaya; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

    2016-09-01

    Melatonin is a neurohormone and has high potent of antioxidant that is widely reported to be active against methamphetamine (METH)-induced toxicity to neuron, glial cells, and brain endothelial cells. However, the role of melatonin on the inflammatory responses which are mostly caused by blood-brain barrier (BBB) impairment by METH administration has not been investigated. This study used the primary rat brain microvascular endothelial cells (BMVECs) to determine the protective mechanism of melatonin on METH-induced inflammatory responses in the BBB via nuclear factor-ĸB (NF-κB) and nuclear factor erythroid 2-related factor-2 (Nrf2) signaling. Herein, we demonstrated that melatonin reduced the level of the inflammatory mediators, including intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, matrix metallopeptidase (MMP)-9, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) caused by METH. These responses were related to the decrease of the expression and translocation of the NF-κB p65 subunit and the activity of NADPH oxidase (NOX)-2. In addition, melatonin promoted the antioxidant processes, modulated the expression and translocation of Nrf2, and also increased the level of heme oxygenase (HO)-1, NAD (P) H: quinone oxidoreductase (NQO)-1, γ-glutamylcysteine synthase (γ-GCLC), and the activity of superoxide dismutase (SOD) through NOX2 mechanism. In addition, we found that the protective role of melatonin in METH-induced inflammatory responses in the BBB was mediated through melatonin receptors (MT1/2). We concluded that the interaction of melatonin with its receptor prevented METH-induced inflammatory responses by suppressing the NF-κB signaling and promoting the Nrf2 signaling before BBB impairment. PMID:27268413

  14. Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood-brain barrier

    DEFF Research Database (Denmark)

    Thomsen, Maj Schneider; Birkelund, Svend; Burkhart, Annette;

    2016-01-01

    The brain vascular basement membrane is important for both blood-brain barrier (BBB) development, stability, and barrier integrity and the contribution hereto from brain capillary endothelial cells (BCECs), pericytes, and astrocytes of the BBB is probably significant. The aim of the present study......-culture, in co-culture with pericytes or mixed glial cells, or as a triple-culture with both pericytes and mixed glial cells. The integrity of the BBB models was validated by measures of transendothelial electrical resistance (TEER) and passive permeability to mannitol. The expression of basement membrane...... proteins was analysed using RT-qPCR, mass spectrometry, and immunocytochemistry. Co-culturing mBCECs with pericytes, mixed glial cells, or both significantly increased the TEER compared to the mono-culture, and a low passive permeability was correlated with high TEER. The mBCECs expressed all major...

  15. Clinical Trial Decision Making in Pediatric Sickle Cell Disease: A Qualitative Study of Perceived Benefits and Barriers to Participation.

    Science.gov (United States)

    Patterson, Chavis A; Chavez, Veronica; Mondestin, Valerie; Deatrick, Janet; Li, Yimei; Barakat, Lamia P

    2015-08-01

    Clinical trial research forms the foundation for advancing treatments; yet, children with sickle cell disease (SCD) are currently underrepresented. This qualitative study examines decision-making processes of youth with SCD and their caregivers regarding enrollment in clinical trial research. A subsample of participants from a study of clinical trial decision making among youth with health disparity conditions, 23 caregivers and 29 children/teens/young adults with SCD (age, 10 to 29 y), indicated whether or not they would participate in hypothetical medical and psychosocial clinical trials and prioritized barriers and benefits to participation via card sort and semistructured interviews. Audio recordings were transcribed and coded for themes. Participants reported that concerns of potential harm most affected their decision. Secondary factors were potential benefit, manageable study demands, and trust in the medical staff. Caregivers weighed potential harm more heavily than their children. Young children were more likely to endorse potential benefit. Overall, participants stated they would be willing to participate in research if the potential benefit outweighs potential harm and unmanageable study demands. To optimize recruitment, results suggest addressing potential harm first while highlighting potential benefits, creating manageable study demands, and endorsing the future benefits of research to the sickle cell community. PMID:25072368

  16. Helicobacter pylori antigens, acetylsalicylic acid, LDL and 7-ketocholesterol - their potential role in destabilizing the gastric epithelial cell barrier. An in vitro model of Kato III cells.

    Science.gov (United States)

    Gajewski, Adrian; Mnich, Eliza; Szymański, Karol; Hinc, Krzysztof; Obuchowski, Michał; Moran, Anthony P; Chmiela, Magdalena

    2016-01-01

    Colonization of gastric tissue in humans by H. pylori Gram-negative bacteria initiates gastric and duodenal ulcers and even gastric cancers. Infections promote inflammation and damage to gastric epithelium which might be followed by the impairment of its barrier function. The role of H. pylori components in these processes has not been specified. H. pylori cytotoxicity may potentially increase in the milieu of anti-inflammatory drugs including acetylsalicylic acid (ASA). The lipid transport-associated molecule such as low density lipoprotein (LDL), which is a classic risk factor of coronary heart disease (CHD) and 7-ketocholesterol (7-kCh) a product of cholesterol oxidation, which may occur during the oxidative stress in LDL could also be considered as pro-inflammatory. The aim of this study was to evaluate the cytotoxicity of H. pylori antigens, ASA, LDL and 7-kCh towards Kato III gastric epithelial cells, on the basis of the cell ability to reduce tetrazolium salt (MTT) and morphology of cell nuclei assessed by 4',6-diamidino-2-phenylindole (DAPI) staining. Kato III cells were stimulated for 24 h, at 37°C and 5% CO2, with H. pylori antigens: cytotoxin associated gene A (CagA) protein, the urease A subunit (UreA), lipopolysaccharide (LPS) and ASA, LDL or 7-kCh. H. pylori LPS, ASA, LDL and 7-kCh, but not H. pylori glycine acid extract (GE), demonstrated cytotoxicity against Kato III cells, which was related to a diminished percentage of MTT reducing cells and to an increased cell population with the signs of DNA damage. The results suggest that damage to gastric epithelial cells can be induced independently by H. pylori antigens, ASA and endogenous lipid transport-associated molecules. During H. pylori infection in vivo, especially in CHD patients, synergistic or antagonistic interactions between these factors might possibly influence the disease course. Further study is necessary to explain these potential effects. PMID:26619253

  17. Barriers in transition from pediatrics to adult medicine in sickle cell anemia

    OpenAIRE

    Lebensburger JD; Bemrich-Stolz CJ; Howard TH

    2012-01-01

    Jeffrey D Lebensburger, Christina J Bemrich-Stolz, Thomas H HowardDepartment of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.Abstract: Transition of care from pediatric to adult providers is an essential step in the care of young adults with sickle cell anemia. Transition programs should be developed by individual institutions to systematically enhance the transition process for their patients. Prior to transfer, patients must be educated about their disease and person...

  18. Donor parity no longer a barrier for female-to-male hematopoietic stem cell transplantation

    OpenAIRE

    van Halteren, Astrid GS; Miranda P Dierselhuis; Netelenbos, Tanja; Fechter, Mirjam

    2014-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely applied treatment for disorders mainly involving the hematopoietic system. The success of this treatment depends on many different patient- and donor-specific factors. Based on higher CD34+ yields and superior clinical outcomes associated with the use of male donors, males are generally seen as the preferred HSCT donor. In addition, female donors are notorious for bearing memory type lymphocytes induced by previous pregnanc...

  19. Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

    Directory of Open Access Journals (Sweden)

    W. Cui

    2010-04-01

    Full Text Available The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-α on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-α (10 or 100 ng/mL for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-α treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-α decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-α did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-α increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

  20. Development of Screen-Printed Texture-Barrier Paste for Single-Side Texturization of Interdigitated Back-Contact Silicon Solar Cell Applications

    OpenAIRE

    Chi-Cheng Chen; Chin-Lung Cheng; Thou-Jen Whang; Yu-Shun Chiu

    2013-01-01

    Continuous cost reduction of silicon-based solar cells is needed to lower the process time and increase efficiency. To achieve lower costs, screen-printed texture-barrier (SPTB) paste was first developed for single-side texturization (ST) of the interdigitated back-contact (IBC) for silicon-based solar cell applications. The SPTB paste was screen-printed on silicon substrates. The SPTB paste was synthesized from intermixed silicate glass (75 wt %), a resin binder (ethyl cellulose ethoce: 20 w...

  1. Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras

    OpenAIRE

    Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R; Sauer, Martin G.

    2009-01-01

    Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cel...

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

    DEFF Research Database (Denmark)

    Smith, Ida Mosbech; Baker, A; Arneborg, Nils; Jespersen, Lene

    2015-01-01

    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...

  3. Magnetron sputtered gadolinia-doped ceria diffusion barriers for metal-supported solid oxide fuel cells

    DEFF Research Database (Denmark)

    Sønderby, Steffen; Klemensø, Trine; Christensen, Bjarke H.; Almtoft, Klaus P.; Lu, Jun; Nielsen, Lars Peter; Eklund, Per

    2014-01-01

    substrate bias voltage. A GDC layer thickness of 0.6 μm is found to effectively block Sr diffusion when bias voltage and deposition temperature is tuned to promote dense coatings. The adatom mobility has a large influence on the film density. Low temperature and bias voltage result in underdense column...... boundaries which function as channels for Sr to diffuse to the GDC-ScYSZ interface. By tuning deposition temperature, bias voltage and film thickness area specific resistances down to 0.34 Ω cm2 are achieved at cell tests performed at an operating temperature of 650 °C. © 2014 Elsevier B.V. All rights...

  4. An experimentally supported model for the origin of charge transport barrier in Zn(O,S)/CIGSSe solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Chua, Rou Hua [Energy Research Institute @ NTU - ERI@N, Interdisciplinary Graduate School, Nanyang Technological University, Singapore 639798 (Singapore); School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Robert Bosch (SEA) Pte Ltd, 11 Bishan St. 21, Singapore 573943 (Singapore); Li, Xianglin [Energy Research Institute @ NTU - ERI@N, Interdisciplinary Graduate School, Nanyang Technological University, Singapore 639798 (Singapore); Walter, Thomas [Hochschule Ulm, Albert-Einstein-Allee 55, 89081 Ulm (Germany); Teh, Lay Kuan [Robert Bosch (SEA) Pte Ltd, 11 Bishan St. 21, Singapore 573943 (Singapore); Hahn, Thomas; Hergert, Frank [Bosch Solar CISTech GmbH, Münstersche Str. 24, 14772 Brandenburg an der Havel (Germany); Mhaisalkar, Subodh; Wong, Lydia Helena, E-mail: lydiawong@ntu.edu.sg [Energy Research Institute @ NTU - ERI@N, Interdisciplinary Graduate School, Nanyang Technological University, Singapore 639798 (Singapore); School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2016-01-25

    Zinc oxysulfide buffer layers with [O]:[S] of 1:0, 6:1, 4:1, 2:1, and 1:1 ratios were deposited by atomic layer deposition on Cu(In,Ga)(S,Se){sub 2} absorbers and made into finished solar cells. We demonstrate using Time-Resolved Photoluminescence that the minority carrier lifetime of Zn(O,S) buffered solar cells is dependent on the sulfur content of the buffer layer. τ{sub 1} for devices with [O]:[S] of 1:0–4:1 are <10 ns, indicating efficient charge separation in devices with low sulfur content. An additional τ{sub 2} is observed for relaxed devices with [O]:[S] of 2:1 and both relaxed and light soaked devices with [O]:[S] of 1:1. Corroborated with one-dimensional electronic band structure simulation results, we attribute this additional decay lifetime to radiative recombination in the absorber due to excessive acceptor-type defects in sulfur-rich Zn(O,S) buffer layer that causes a buildup in interface-barrier for charge transport. A light soaking step shortens the carrier lifetime for the moderately sulfur-rich 2:1 device when excess acceptors are passivated in the buffer, reducing the crossover in the dark and illuminated I-V curves. However, when a high concentration of excess acceptors exist in the buffer and cannot be passivated by light soaking, as with the sulfur-rich 1:1 device, then cell efficiency of the device will remain low.

  5. An experimentally supported model for the origin of charge transport barrier in Zn(O,S)/CIGSSe solar cells

    International Nuclear Information System (INIS)

    Zinc oxysulfide buffer layers with [O]:[S] of 1:0, 6:1, 4:1, 2:1, and 1:1 ratios were deposited by atomic layer deposition on Cu(In,Ga)(S,Se)2 absorbers and made into finished solar cells. We demonstrate using Time-Resolved Photoluminescence that the minority carrier lifetime of Zn(O,S) buffered solar cells is dependent on the sulfur content of the buffer layer. τ1 for devices with [O]:[S] of 1:0–4:1 are <10 ns, indicating efficient charge separation in devices with low sulfur content. An additional τ2 is observed for relaxed devices with [O]:[S] of 2:1 and both relaxed and light soaked devices with [O]:[S] of 1:1. Corroborated with one-dimensional electronic band structure simulation results, we attribute this additional decay lifetime to radiative recombination in the absorber due to excessive acceptor-type defects in sulfur-rich Zn(O,S) buffer layer that causes a buildup in interface-barrier for charge transport. A light soaking step shortens the carrier lifetime for the moderately sulfur-rich 2:1 device when excess acceptors are passivated in the buffer, reducing the crossover in the dark and illuminated I-V curves. However, when a high concentration of excess acceptors exist in the buffer and cannot be passivated by light soaking, as with the sulfur-rich 1:1 device, then cell efficiency of the device will remain low

  6. Breaking the barriers of all-polymer solar cells: Solving electron transporter and morphology problems

    Science.gov (United States)

    Gavvalapalli, Nagarjuna

    All-polymer solar cells (APSC) are a class of organic solar cells in which hole and electron transporting phases are made of conjugated polymers. Unlike polymer/fullerene solar cell, photoactive material of APSC can be designed to have hole and electron transporting polymers with complementary absorption range and proper frontier energy level offset. However, the highest reported PCE of APSC is 5 times less than that of polymer/fullerene solar cell. The low PCE of APSC is mainly due to: i) low charge separation efficiency; and ii) lack of optimal morphology to facilitate charge transfer and transport; and iii) lack of control over the exciton and charge transport in each phase. My research work is focused towards addressing these issues. The charge separation efficiency of APSC can be enhanced by designing novel electron transporting polymers with: i) broad absorption range; ii) high electron mobility; and iii) high dielectric constant. In addition to with the above parameters chemical and electronic structure of the repeating unit of conjugated polymer also plays a role in charge separation efficiency. So far only three classes of electron transporting polymers, CN substituted PPV, 2,1,3-benzothiadiazole derived polymers and rylene diimide derived polymers, are used in APSC. Thus to enhance the charge separation efficiency new classes of electron transporting polymers with the above characteristics need to be synthesized. I have developed a new straightforward synthetic strategy to rapidly generate new classes of electron transporting polymers with different chemical and electronic structure, broad absorption range, and high electron mobility from readily available electron deficient monomers. In APSCs due to low entropy of mixing, polymers tend to micro-phase segregate rather than forming the more useful nano-phase segregation. Optimizing the polymer blend morphology to obtain nano-phase segregation is specific to the system under study, time consuming, and not

  7. Localization of Cellular Retinol-Binding Protein and Retinol-Binding Protein in Cells Comprising the Blood-Brain Barrier of Rat and Human

    Science.gov (United States)

    MacDonald, Paul N.; Bok, Dean; Ong, David E.

    1990-06-01

    Brain is not generally recognized as an organ that requiries vitamin A, perhaps because no obvious histologic lesions have been observed in severely vitamin A-deficient animals. However, brain tissue does contain cellular vitamin A-binding proteins and a nuclear receptor protein for retinoic acid. In the present study, immunohistochemical techniques were used to determine the cell-specific location of cellular retinol-binding protein in human and rat brain tissue. Cellular retinol-binding protein was localized specifically within the endothelial cells of the brain microvasculature and within the cuboidal epithelial cells of the choroid plexus, two primary sites of the mammalian blood-brain barrier. In addition, autoradiographic procedures demonstrated binding sites for serum retinol-binding protein in the choroidal epithelium. These observations suggest that a significant movement of retinol across the blood-brain barrier may occur.

  8. Effect of Al 2 O 3 Recombination Barrier Layers Deposited by Atomic Layer Deposition in Solid-State CdS Quantum Dot-Sensitized Solar Cells

    KAUST Repository

    Roelofs, Katherine E.

    2013-03-21

    Despite the promise of quantum dots (QDs) as a light-absorbing material to replace the dye in dye-sensitized solar cells, quantum dot-sensitized solar cell (QDSSC) efficiencies remain low, due in part to high rates of recombination. In this article, we demonstrate that ultrathin recombination barrier layers of Al2O3 deposited by atomic layer deposition can improve the performance of cadmium sulfide (CdS) quantum dot-sensitized solar cells with spiro-OMeTAD as the solid-state hole transport material. We explored depositing the Al2O3 barrier layers either before or after the QDs, resulting in TiO2/Al2O3/QD and TiO 2/QD/Al2O3 configurations. The effects of barrier layer configuration and thickness were tracked through current-voltage measurements of device performance and transient photovoltage measurements of electron lifetimes. The Al2O3 layers were found to suppress dark current and increase electron lifetimes with increasing Al 2O3 thickness in both configurations. For thin barrier layers, gains in open-circuit voltage and concomitant increases in efficiency were observed, although at greater thicknesses, losses in photocurrent caused net decreases in efficiency. A close comparison of the electron lifetimes in TiO2 in the TiO2/Al2O3/QD and TiO2/QD/Al2O3 configurations suggests that electron transfer from TiO2 to spiro-OMeTAD is a major source of recombination in ss-QDSSCs, though recombination of TiO2 electrons with oxidized QDs can also limit electron lifetimes, particularly if the regeneration of oxidized QDs is hindered by a too-thick coating of the barrier layer. © 2013 American Chemical Society.

  9. A hematopoietic contribution to microhemorrhage formation during antiviral CD8 T cell-initiated blood-brain barrier disruption

    Directory of Open Access Journals (Sweden)

    Johnson Holly L

    2012-03-01

    Full Text Available Abstract Background The extent to which susceptibility to brain hemorrhage is derived from blood-derived factors or stromal tissue remains largely unknown. We have developed an inducible model of CD8 T cell-initiated blood-brain barrier (BBB disruption using a variation of the Theiler's murine encephalomyelitis virus (TMEV model of multiple sclerosis. This peptide-induced fatal syndrome (PIFS model results in severe central nervous system (CNS vascular permeability and death in the C57BL/6 mouse strain, but not in the 129 SvIm mouse strain, despite the two strains' having indistinguishable CD8 T-cell responses. Therefore, we hypothesize that hematopoietic factors contribute to susceptibility to brain hemorrhage, CNS vascular permeability and death following induction of PIFS. Methods PIFS was induced by intravenous injection of VP2121-130 peptide at 7 days post-TMEV infection. We then investigated brain inflammation, astrocyte activation, vascular permeability, functional deficit and microhemorrhage formation using T2*-weighted magnetic resonance imaging (MRI in C57BL/6 and 129 SvIm mice. To investigate the contribution of hematopoietic cells in this model, hemorrhage-resistant 129 SvIm mice were reconstituted with C57BL/6 or autologous 129 SvIm bone marrow. Gadolinium-enhanced, T1-weighted MRI was used to visualize the extent of CNS vascular permeability after bone marrow transfer. Results C57BL/6 and 129 SvIm mice had similar inflammation in the CNS during acute infection. After administration of VP2121-130 peptide, however, C57BL/6 mice had increased astrocyte activation, CNS vascular permeability, microhemorrhage formation and functional deficits compared to 129 SvIm mice. The 129 SvIm mice reconstituted with C57BL/6 but not autologous bone marrow had increased microhemorrhage formation as measured by T2*-weighted MRI, exhibited a profound increase in CNS vascular permeability as measured by three-dimensional volumetric analysis of

  10. Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, P.N.; Ong, D.E. (Vanderbilt Univ., Nashville, TN (USA)); Bok, D. (Univ. of California, Los Angeles (USA))

    1990-06-01

    Brain is not generally recognized as an organ that requires vitamin A, perhaps because no obvious histologic lesions have been observed in severely vitamin A-deficient animals. However, brain tissue does contain cellular vitamin A-binding proteins and a nuclear receptor protein for retinoic acid. In the present study, immunohistochemical techniques were used to determine the cell-specific location of cellular retinol-binding protein in human and rat brain tissue. Cellular retinol-binding protein was localized specifically within the cuboidal epithelial cells of the choroid plexus, two primary sites of the mammalian blood-brain barrier. In addition, autoradiographic procedures demonstrated binding sites for serum retinol-binding protein in the choroidal epithelium. These observations suggest that a significant movement of retinol across the blood-brain barrier may occur.

  11. The Staphylococcus aureus Alpha-Toxin Perturbs the Barrier Function in Caco-2 Epithelial Cell Monolayers by Altering Junctional Integrity

    OpenAIRE

    Kwak, Young-Keun; Vikström, Elena; Magnusson, Karl-Eric; Vécsey-Semjén, Beatrix; Colque-Navarro, Patricia; Möllby, Roland

    2012-01-01

    Increased microvascular permeability is a hallmark of sepsis and septic shock. Intestinal mucosal dysfunction may allow translocation of bacteria and their products, thereby promoting sepsis and inflammation. Although Staphylococcus aureus alpha-toxin significantly contributes to sepsis and perturbs the endothelial barrier function, little is known about possible effects of S. aureus alpha-toxin on human epithelial barrier functions. We hypothesize that S. aureus alpha-toxin in the blood can ...

  12. Human epithelial cells in vitro – Are they an advantageous tool to help understand the nanomaterial-biological barrier interaction?

    OpenAIRE

    Rothen-Rutishauser, Barbara; Clift, Martin J. D.; Jud, Corinne; Fink, Alke; Wick, Peter

    2013-01-01

    The human body can be exposed to nanomaterials through a variety of different routes. As nanomaterials get in contact with the skin, the gastrointestinal tract, and the respiratory tract, these biological compartments are acting as barriers to the passage of nano-sized materials into the organism. These structural and functional barriers are provided by the epithelia serving as an interface between biological compartments. In order to initiate the reduction, refinement and replacement of time...

  13. Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay.

    Science.gov (United States)

    Romero, Alejandro; Ares, Irma; Ramos, Eva; Castellano, Víctor; Martínez, Marta; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Martínez, María-Aránzazu

    2016-04-15

    Aflatoxin B1 (AFB1), fumonisin B1 (FB1), ochratoxin A (OTA) and T-2 toxin (T2) are mycotoxins that commonly contaminate the food chain and cause various toxicological effects. Their global occurrence is regarded as an important risk factor for human and animal health. In this study, the results demonstrate that, in human Caco-2 cells, AFB1, FB1, OTA and T2 origin cytotoxic effects, determining cell viability through MTT assay and LDH leakage, and decrease trans-epithelial electrical resistance (TEER). The decrease in barrier properties is concomitant with a reduction in the expression levels of the tight junction constituents claudin-3, claudin-4 and occludin. The protective effect of mineral clays (diosmectite, montmorillonite and illite) on alterations in cell viability and epithelial barrier function induced by the mycotoxins was also evaluated. Illite was the best clay to prevent the mycotoxin effects. Illite plus mycotoxin co-treatment completely abolished AFB1 and FB1-induced cytotoxicity. Also, the decreases in the gene expression of claudins and the reduction of TEER induced by mycotoxins were reversed by the illite plus mycotoxin co-treatment. In conclusion, these results demonstrated that mycotoxins AFB1, FB1, T2 and OTA disrupt the intestinal barrier permeability by a mechanism involving reduction of claudin isoform expressions, and illite counteracts this disruption. PMID:27153755

  14. TcpC protein from E. coli Nissle improves epithelial barrier function involving PKCζ and ERK1/2 signaling in HT-29/B6 cells.

    Science.gov (United States)

    Hering, N A; Richter, J F; Fromm, A; Wieser, A; Hartmann, S; Günzel, D; Bücker, R; Fromm, M; Schulzke, J D; Troeger, H

    2014-03-01

    The probiotic Escherichia coli Nissle 1917 (EcN) is widely used to maintain remission in ulcerative colitis. This is thought to be mediated by various immunomodulatory and barrier-stabilizing effects in the intestine. In this study, the mechanisms of barrier modulation by EcN were studied in the human epithelial HT-29/B6 cell culture model.EcN supernatant increased transepithelial resistance (TER) and reduced permeability to mannitol because of sealing of the paracellular passage pathway as revealed by two-path impedance spectroscopy. This increase in TER was attributed to the TcpC protein of EcN. TcpC induced protein kinase C-ζ (PKCζ) and extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation, which in turn resulted in upregulation of the barrier-forming tight junction protein claudin-14. By specific silencing of protein expression by small interfering RNA (siRNA), the sealing function of claudin-14 was confirmed. In conclusion, the TcpC protein of EcN affects innate immunity by improving intestinal barrier function through upregulation of claudin-14 via PKCζ and ERK1/2 signaling. PMID:23900194

  15. Healthcare Burden, Risk Factors, and Outcomes of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections after Stem Cell Transplantation.

    Science.gov (United States)

    Dandoy, Christopher E; Haslam, David; Lane, Adam; Jodele, Sonata; Demmel, Kathy; El-Bietar, Javier; Flesch, Laura; Myers, Kasiani C; Pate, Abigail; Rotz, Seth; Daniels, Paulina; Wallace, Gregory; Nelson, Adam; Waters, Heather; Connelly, Beverly; Davies, Stella M

    2016-09-01

    Mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBIs) lead to significant morbidity, mortality, and healthcare resource utilization in hematopoietic stem cell transplant (HSCT) patients. Determination of the healthcare burden of MBI-LCBIs and identification of patients at risk of MBI-LCBIs will allow researchers to identify strategies to reduce MBI-LCBI rates. The objective of our study was to describe the incidence, risk factors, timing, and outcomes of MBI-LCBIs in hematopoietic stem cell transplant patients. We performed a retrospective analysis of 374 patients who underwent HSCT at a large free-standing academic children's hospital to determine the incidence, risk factors, and outcomes of patients that developed a bloodstream infection (BSI) including MBI-LCBI, central line-associated BSI (CLABSI), or secondary BSI in the first year after HSCT. Outcome measures included nonrelapse mortality (NRM), central venous catheter removal within 7 days of positive culture, shock, admission to the pediatric intensive care unit (PICU) within 48 hours of positive culture, and death within 10 days of positive culture. One hundred seventy BSIs were diagnosed in 100 patients (27%): 80 (47%) MBI-LCBIs, 68 (40%) CLABSIs, and 22 (13%) secondary infections. MBI-LCBIs were diagnosed at a significantly higher rate in allogeneic HSCT patients (18% versus 7%, P = .007). Reduced-intensity conditioning (OR, 1.96; P = .015) and transplant-associated thrombotic microangiopathy (OR, 2.94; P = .0004) were associated with MBI-LCBI. Nearly 50% of all patients with a BSI developed septic shock, 10% died within 10 days of positive culture, and nearly 25% were transferred to the PICU. One-year NRM was significantly increased in patients with 1 (34%) and more than 1 (56%) BSIs in the first year post-HSCT compared with those who did not develop BSIs (14%) (P ≤ .0001). There was increased 1-year NRM in patients with at least 1 MBI-LCBI (OR, 1.94; P

  16. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    International Nuclear Information System (INIS)

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug

  17. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Blazquez, Alba G., E-mail: albamgb@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Briz, Oscar, E-mail: obriz@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Gonzalez-Sanchez, Ester, E-mail: u60343@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); Perez, Maria J., E-mail: mjperez@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); University Hospital of Salamanca, IECSCYL-IBSAL, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Ghanem, Carolina I., E-mail: cghanem@ffyb.uba.ar [Instituto de Investigaciones Farmacologicas, Facultad de Farmacia y Bioquimica, CONICET, Universidad de Buenos Aires, Buenos Aires (Argentina); Marin, Jose J.G., E-mail: jjgmarin@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain)

    2014-05-15

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug.

  18. Effects of infrasound on Ca2 +-activated-K + channel of the bovine retinal microvascular endothelial cells%次声对视网膜微血管内皮细胞钙激活钾通道的影响

    Institute of Scientific and Technical Information of China (English)

    邱萍; 李泱; 高伟; 郭群; 张作明; 姜勇; 王士雯

    2005-01-01

    背景:次声暴露导致大鼠血-视网膜屏障通透性增加.但由于视网膜微血管内皮细胞来源困难,关于其屏障损伤的离子机制报道较少.目的:探讨次声对视网膜微血管内皮细胞钙激活钾通道的影响.设计:完全随机实验对照的开放性研究.地点和材料:实验在第四军医大学航空临床教研室膜片钳实验室进行,实验对象为培养牛视网膜微血管内皮细胞.干预:取传代的牛视网膜微血管内皮细胞8 Hz,130 dB次声暴露0.5 h.主要观察指标:视网膜微血管内皮细胞钙激活钾通道的活动情况.结果:8 Hz,130dB次声暴露0.5 h后,视网膜微血管内皮细胞KCA通道活性增加,暴露后置于孵箱内0.5 h再行膜片钳离子电流的检测,则离子通道的活性也有所下降.结论:次声通过增加视网膜微血管内皮细胞钙激活钾通道的活性,导致膜去极化,引起钙离子进入细胞,内皮细胞收缩,造成一定程度的血-视网膜屏障通透性的损害.%BACKGROUND: The permeability of blood-retinal barrier in rats can be increased due to the exposure under infrasound. There is rare research on ionic mechanism of such damage to barrier because of lacking the sources of retinal microvascular endothelial cells.OBJECTIVE: To investigate the impact of infrasound on calcium-activated potassium channel(BKca) of bovine retinal microvascular endothelial cells (BRECs).DESIGN: A completely randomized controlled opening study.SETTING and MATERIALS: The research was conducted in the Laboratory for patch-clamp, Department of Clinical Aerospace Medicine, Fourth Military Medical University of Chinese PLA. Experimental subjects were BRECs cultured.INTERVENTIONS: The cultured BRECs were exposed to the infrasound of 8 Hz, 130 dB for 30 minutes.MAIN OUTCOME MEASURES: The activity of BKCa in BRECs was observed.RESULTS: The activity of BKCa channel in BRECs increased after the exposure of infrasound of 8 Hz, 130 dB for 30 minutes. BRECs were

  19. Information barriers

    International Nuclear Information System (INIS)

    An information barrier (IB) consists of procedures and technology that prevent the release of sensitive information during a joint inspection of a sensitive nuclear item, and provides confidence that the measurement system into which it has been integrated functions exactly as designed and constructed. Work in the U.S. on radiation detection system information barriers dates back at least to 1990, even though the term is more recent. In January 1999, an Information Barrier Working Group (IBWG) was formed in the United States to help coordinate technical efforts related to information barrier research and development (R and D). This paper presents an overview of the efforts of this group, by its present and former Chairs, as well as recommendations for further information barrier R and D. Progress on the demonstration of monitoring systems containing IBs is also provided. From the U.S. IBWG perspective, the top-level functional requirements for the information barrier portion of an integrated radiation signature-information barrier inspection system are twofold: The host must be assured that its classified information is protected from disclosure to the inspecting party; and The inspecting party must be confident that the integrated inspection system measures, processes, and presents the radiation-signature-based measurement conclusion in an accurate and reproducible manner. It is the position in the United States that in the absence of any agreement to share classified nuclear weapons design information while implementing an inspection regime, the need to protect host country classified warhead design information is paramount and overrules the need to provide confidence to the inspecting party regarding the accuracy and reproducibility of the measurements. The U.S. IBWG has reached a consensus on several critical design elements that define a general standard for radiation signature information barrier design. Technical specialists from cooperating parties must be

  20. Development of Screen-Printed Texture-Barrier Paste for Single-Side Texturization of Interdigitated Back-Contact Silicon Solar Cell Applications

    Directory of Open Access Journals (Sweden)

    Chi-Cheng Chen

    2013-10-01

    Full Text Available Continuous cost reduction of silicon-based solar cells is needed to lower the process time and increase efficiency. To achieve lower costs, screen-printed texture-barrier (SPTB paste was first developed for single-side texturization (ST of the interdigitated back-contact (IBC for silicon-based solar cell applications. The SPTB paste was screen-printed on silicon substrates. The SPTB paste was synthesized from intermixed silicate glass (75 wt %, a resin binder (ethyl cellulose ethoce: 20 wt %, and a dispersing agent (fatty acid: 5 wt %. The silicate glass is a necessity for contact formation during firing. A resin binder and a dispersing agent determine the rheology of the SPTB paste. In this work, by modulating various parameters, including post SPTB firing, alkali texturing, and removal of the SPTB, the ST of IBC silicon solar cells was achieved. Since the advantages of the SPTB paste include low toxicity and prompt formation of the texture-barrier, SPTB is potentially suited for simple fabrication at low-cost for solar cell applications. The cost of the SPTB is around $100/kg which is lower than the SiH4/NH3 gas ambient used in plasma-enhanced chemical vapor deposition (PECVD. Thus, the expensive Si3N4 film deposited by PECVD using SiH4 and NH3 gas ambient for silicon solar cells can be replaced by this SPTB.

  1. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells.

    Directory of Open Access Journals (Sweden)

    Mehrnaz Nouri

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE, the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers. These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms and at 14 days (i.e., at the stage of paralysis after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.

  2. Observation of "wired" cell communication over 10-μm and 20-μm poly(dimethylsiloxane) barriers in tetracycline inducible expression systems

    Science.gov (United States)

    Kuo, Ching-Te; Chi, Cheng-Yu; Wu, Pei-Yi; Chuang, Fang-Tzu; Lin, Yueh-Chien; Liu, Hao-Kai; Huang, Guan-Syuan; Tsai, Tzu-Ching; Wo, Andrew M.; Lee, Hsinyu; Lee, Si-Chen

    2016-01-01

    Communication between cells and extracellular environments is of interest because of its critical roles in cell development and differentiation. Particularly, this signal transduction is commonly believed to rely on the contact and binding of the participating molecules/proteins, suggesting that the binding distance needed is less than a few nanometers. However, it is difficult to precisely match the rapidly binding interaction which depends on the probability of molecular collision in living systems, raising a hypothesis that another mechanism exists, could promote this signal communication, and remains unknown. Here we report that a long-range signal delivery over 10-μm and 20-μm polydimethylsiloxane (PDMS) barriers can be observed in microfluidically tetracycline (Tet) inducible expression systems. Results show that a significant increment of the long-range induced green fluorescent protein in human embryonic kidney 293T (HEK 293T) cells by the stimulation of Tet is demonstrated, and that such a signal induction is not dominated by Tet diffusion and displays a specific bindingless property. In addition, our experimental results, combined with theoretical modeling, suggest that this communication exhibits a bump-shaped characteristic depending on barrier thickness, materially structural property, surface roughness, and agonist concentration. It strongly relies on the PDMS barrier to delivery signal; therefore, we call such a mechanism as "wired" cell communication instead of wireless. These results could ignite interests in the novel and "wired" cell communication, which we call it X-signal, and in the use of such systems for the study of cellular biology and development of new drug.

  3. Investigation of barrier cell and auxilliary heating in a tandem mirror. Annual progress report, October 1, 1979-September 30, 1980

    International Nuclear Information System (INIS)

    A number of areas relating to RF heating and thermal barrier formation in a tandem mirror have been investigated. The possibility of creating axisymmetric confinement through the use of sloshing-ions has been investigated. We have also suggested the complimentary concept of sloshing-electrons. Self-consistent thermal barrier formation has been studied and ion drift orbits in non-axisymmetric barriers are being investigated. The study of dynamic stabilization of the DCLC by RF fields has been extended to ω near 2 ω/sub ci/; significant stabilization is found. Fast and slow wave heating have been extensively studied using single particle theory. A new theory of relativistic ECH is under development

  4. Endothelial cells derived from the blood-brain barrier and islets of Langerhans differ in their response to the effects of bilirubin on oxidative stress under hyperglycemic conditions

    Directory of Open Access Journals (Sweden)

    JaimeKapitulnik

    2012-07-01

    Full Text Available Unconjugated bilirubin (UCB is a neurotoxic degradation product of heme. Its toxic effects include induction of apoptosis, and ultimately neuronal cell death. However, at low concentrations, UCB is a potent antioxidant that may protect cells and tissues against oxidative stress by neutralizing toxic metabolites such as reactive oxygen species (ROS. High glucose levels (hyperglycemia generate reactive metabolites. Endothelial cell dysfunction, an early vascular complication in diabetes, has been associated with hyperglycemia-induced oxidative stress. Both glucose and UCB are substrates for transport proteins in microvascular endothelial cells of the blood-brain barrier (BBB. In the current study we show that UCB (1-40 M induces apoptosis and reduces survival of bEnd3 cells, a mouse brain endothelial cell line which serves as an in vitro model of the BBB. These deleterious effects of UCB were enhanced in the presence of high glucose (25 mM levels. Interestingly, the bEnd3 cells exhibited an increased sensitivity to the apoptotic effects of UCB when compared to the MS1 microcapillary endothelial cell line. MS1 cells originate from murine pancreatic islets of Langherans, and are devoid of the barrier characteristics of BBB-derived endothelial cells. ROS production was increased in both bEnd3 and MS1 cells exposed to high glucose, as compared with cells exposed to normal (5.5 mM glucose levels. While UCB (0.1-40 M did not alter ROS production in cells exposed to normal glucose, relatively low ('physiological' UCB concentrations (0.1-5 M attenuated ROS generation in both cell lines exposed to high glucose levels. Most strikingly, higher UCB concentrations (20-40 M increased ROS generation in bEnd3 cells exposed to high glucose, but not in similarly treated MS1 cells. These results may be of critical importance for understanding the vulnerability of the BBB endothelium upon exposure to increasing UCB levels under hyperglycemic conditions.

  5. Bone marrow transplantation across major histocompatibility barriers in mice: II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    International Nuclear Information System (INIS)

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatability barriers.Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 100-rad TLI. In TLI plus CY-conditioned recipients, it was also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed

  6. Enhanced tumor cell killing following BNCT with hyperosmotic mannitol-induced blood-brain barrier disruption and intracarotid injection of boronophenylalanine

    International Nuclear Information System (INIS)

    The delivery of boronophenylalanine (BPA) by means of intracarotid injection combined with opening the blood-brain barrier (BBB) have been shown significantly enhanced the tumor boron concentration and the survival time of glioma-bearing rats. However, no direct evidence demonstrates whether this treatment protocol can enhance the cell killing of tumor cells or infiltrating tumor cells and the magnitude of enhanced cell killing. The purpose of the present study was to determine if the tumor cell killing of boron neutron capture therapy could be enhanced by hyperosmotic mannitol-induced BBB disruption using BPA-Fr as the capture agent. F98 glioma-bearing rats were injected intravenously or intracarotidly with BPA at doses of 500 mg/kg body weight (b.w.) and with or without mannitol-induced hyperosmotic BBB disruption. The rats were irradiated with an epithermal neutron beam at the reactor of National Tsing-Hua University (THOR). After neutron beam irradiation, the rats were euthanized and the ipsilateral brains containing intracerebral F98 glioma were removed to perform in vivo/in vitro soft agar clonogenic assay. The results demonstrate BNCT with optimizing the delivery of BPA by means of intracarotid injection combined with opening the BBB by infusing a hyperosmotic solution of mannitol significantly enhanced the cell killing of tumor cells and infiltrating tumor cells, the tumor boron concentration and the boron ratio of tumor to normal brain tissues. (author)

  7. Information barriers

    International Nuclear Information System (INIS)

    Full text: An information barrier (IB) consists of procedures and technology that prevent the release of sensitive information during a joint inspection of a sensitive nuclear item, and provides confidence that the measurement system into which it has been integrated functions exactly as designed and constructed. Work in the U.S. on radiation detection system information barriers dates back at least to 1990, even though the terminology is more recent. In January 1999 the Joint DoD-DOE Information Barrier Working Group was formed in the United States to help coordinate technical efforts related to information barrier R and D. This paper presents an overview of the efforts of this group, by its Chairs, as well as recommendations for further information barrier R and D. Progress on the demonstration of monitoring systems containing IBs is also provided. From the U.S. perspective, the basic, top-level functional requirements for the information barrier portion of an integrated radiation signature-information barrier inspection system are twofold: The host must be assured that his classified information is protected from disclosure to the inspecting party; and The inspecting party must be confident that the integrated inspection system measures, processes, and presents the radiation-signature-based measurement conclusion in an accurate and reproducible manner. It is the position of the United States that in the absence of any agreement to share classified nuclear weapons design information in the conduct of an inspection regime, the requirement to protect host country classified warhead design information is paramount and admits no tradeoff versus the confidence provided to the inspecting party in the accuracy and reproducibility of the measurements. The U.S. has reached an internal consensus on several critical design elements that define a general standard for radiation signature information barrier design. These criteria have stood the test of time under intense

  8. Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding.

    Science.gov (United States)

    Chen, Rui-Cong; Xu, Lan-Man; Du, Shan-Jie; Huang, Si-Si; Wu, He; Dong, Jia-Jia; Huang, Jian-Rong; Wang, Xiao-Dong; Feng, Wen-Ke; Chen, Yong-Ping

    2016-01-22

    Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced Treg cell population while increased TH17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of Treg and TH17 cells in the role of LGG-s application. PMID:26617183

  9. Electron Barrier Formation at the Organic-Back Contact Interface is the First Step in Thermal Degradation of Polymer Solar Cells

    KAUST Repository

    Sachs-Quintana, I. T.

    2014-03-24

    Long-term stability of polymer solar cells is determined by many factors, one of which is thermal stability. Although many thermal stability studies occur far beyond the operating temperature of a solar cell which is almost always less than 65 °C, thermal degradation is studied at temperatures that the solar cell would encounter in real-world operating conditions. At these temperatures, movement of the polymer and fullerenes, along with adhesion of the polymer to the back contact, creates a barrier for electron extraction. The polymer barrier can be removed and the performance can be restored by peeling off the electrode and depositing a new one. X-ray photoelectron spectroscopy measurements reveal a larger amount of polymer adhered to electrodes peeled from aged devices than electrodes peeled from fresh devices. The degradation caused by hole-transporting polymer adhering to the electrode can be suppressed by using an inverted device where instead of electrons, holes are extracted at the back metal electrode. The problem can be ultimately eliminated by choosing a polymer with a high glass transition temperature. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Effect of Mast Cell on the Animal Intestinal Mucosal Immune Barrier%肥大细胞在动物肠道黏膜免疫屏障中的作用

    Institute of Scientific and Technical Information of China (English)

    姜楠; 胡易; 陈耀星; 王子旭; 曹静; 董玉兰; 白鹤

    2011-01-01

    肠道黏膜屏障包括机械屏障和免疫屏障等,后者主要由肠黏膜吸收上皮细胞和肠道相关淋巴组织构成.肠道黏膜免疫细胞包括淋巴细胞、杯状细胞、肥大细胞等.其中肥大细胞是天然免疫的效应细胞之一,其不仅在天然免疫中发挥重要作用,且能通过所分泌的细胞因子参与获得性免疫.笔者综述了肥大细胞的生物学特性及其在肠道免疫屏障中的作用.%Intestinal mucosal barrier include mechanical barrier and immune barrier etc. The immune barrier mainly is composed of intestinal epithelial absorbed cells and gut-associated lymphoid tissue. Intestinal mucosal immune cells can be included by lymphocytes > goblet cells > mast cell and so on. And mast cell is one of the innate immune effector cells. It can not only play a key role in the innate immunity but also play an important role in the acquired immune by secreting of cytokine. Here we make a brief summary about biological characteristics of mast cell, and its function in intestinal immunological barrier.

  11. Anandamide rescues retinal barrier properties in Müller glia through nitric oxide regulation.

    Science.gov (United States)

    Krishnan, G; Chatterjee, N

    2015-01-22

    The blood retinal barrier (BRB) can mitigate deleterious immune response. Dysfunction at the BRB can affect disease progression. Under inflammatory conditions Müller glia produce increased pro-inflammatory factors, like nitric oxide (NO). In this study we describe molecular events at the Müller glia during inflammation which could affect inner BRB properties. Griess assay and 4,5-diaminofluorescein diacetate (DAF-2DA) time-lapse fluorescence were used to measure NO production. Western blot was used to analyze the expression of inducible nitric oxide synthase (iNOS) and mitogen-activated protein kinases (MAPK) components. Lucifer Yellow was used to measure permeability. Griess assay and DAF-2DA time-lapse fluorescence images revealed that lipopolysaccharide (LPS) induced inflammation and increased NO production. In parallel, changes were observed in tight junction proteins, zona occludens 1 (ZO-1), connexin 43 (Cx43), and permeability. This was mediated through activation of iNOS and mitogen-activated protein kinase phosphatase-1 (MKP-1), implicated in immune response. Endocannabinoids can exert a protective and anti-inflammatory effect. Exogenous arachidonoyl ethanolamide (AEA) inhibited NO generation and also abolished LPS-induced increase in permeability. Our work suggests that subtle changes in Müller glia function, which act as part of the BRB, could contribute to retinal health. AEA which can reduce inflammatory cytotoxicity has potential as treatment in several ocular manifestations where the integrity of the BRB is crucial. PMID:25453774

  12. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin

    OpenAIRE

    Nikitas G; Deschamps C; Disson O; Niault T; Cossart P; Lecuit M

    2011-01-01

    Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminat...

  13. Oxidative stress pathways involved in cytotoxicity and genotoxicity of titanium dioxide (TiO2) nanoparticles on cells constitutive of alveolo-capillary barrier in vitro.

    Science.gov (United States)

    Hanot-Roy, Maïté; Tubeuf, Emilie; Guilbert, Ariane; Bado-Nilles, Anne; Vigneron, Pascale; Trouiller, Bénédicte; Braun, Anne; Lacroix, Ghislaine

    2016-06-01

    The health risks of nanoparticles remain a serious concern given their prevalence from industrial and domestic use. The primary route of titanium dioxide nanoparticle exposure is inhalation. The extent to which nanoparticles contribute to cellular toxicity is known to associate induction of oxidative stress. To investigate this problem further, the effect of titanium dioxide nanoparticles was examined on cell lines representative of alveolo-capillary barrier. The present study showed that all nanoparticle-exposed cell lines displayed ROS generation. Macrophage-like THP-1 and HPMEC-ST1.6R microvascular cells were sensitive to endogenous redox changes and underwent apoptosis, but not alveolar epithelial A549 cells. Genotoxic potential of titanium dioxide nanoparticles was investigated using the activation of γH2AX, activation of DNA repair proteins and cell cycle arrest. In the sensitive cell lines, DNA damage was persistent and activation of DNA repair pathways was observed. Moreover, western blot analysis showed that specific pathways associated with cellular stress response were activated concomitantly with DNA repair or apoptosis. Nanoparticles-induced oxidative stress is finally signal transducer for further physiological effects including genotoxicity and cytotoxicity. Within activated pathways, HSP27 and SAPK/JNK proteins appeared as potential biomarkers of intracellular stress and of sensitivity to endogenous redox changes, respectively, enabling to predict cell behavior. PMID:26928046

  14. Organization of Endothelial Cells, Pericytes, and Astrocytes into a 3D Microfluidic in Vitro Model of the Blood-Brain Barrier.

    Science.gov (United States)

    Wang, Jack D; Khafagy, El-Sayed; Khanafer, Khalil; Takayama, Shuichi; ElSayed, Mohamed E H

    2016-03-01

    The endothelial cells lining the capillaries supplying the brain with oxygen and nutrients form a formidable barrier known as the blood-brain barrier (BBB), which exhibits selective permeability to small drug molecules and virtually impermeable to macromolecular therapeutics. Current in vitro BBB models fail to replicate this restrictive behavior due to poor integration of the endothelial cells with supporting cells (pericytes and astrocytes) following the correct anatomical organization observed in vivo. We report the coculture of mouse brain microvascular endothelial cells (b.End3), pericytes, with/without C8-D1A astrocytes in layered microfluidic channels forming three-dimensional (3D) bi- and triculture models of the BBB. The live/dead assay indicated high viability of all cultured cells up to 21 days. Trans-endothelial electrical resistance (TEER) values confirmed the formation of intact monolayers after 3 days in culture and showed statistically higher values for the triculture model compared to the single and biculture models. Screening the permeability of [(14)C]-mannitol and [(14)C]-urea showed the ability of bi- and triculture models to discriminate between different markers based on their size. Further, permeability of [(14)C]-mannitol across the triculture model after 18 days in culture matched its reported permeability across the BBB in vivo. Mathematical calculations also showed that the radius of the tight junctions pores (R) in the triculture model is similar to the reported diameter of the BBB in vivo. Finally, both the bi- and triculture models exhibited functional expression of the P-glycoprotein efflux pump, which increased with the increase in the number of days in culture. These results collectively indicate that the triculture model is a robust in vitro model of the BBB. PMID:26751280

  15. The relation between doses or post-plasma time points and apoptosis of leukemia cells induced by dielectric barrier discharge plasma

    Science.gov (United States)

    Wang, Chao; Zhang, Haixia; Xue, Zhixiao; Yin, Huijuan; Niu, Qing; Chen, Hongli

    2015-12-01

    The dielectric barrier discharge (DBD) plasma was applied to induce apoptosis of LT-12 leukemia cells. Plasma effects on cell death was evaluated by MTT assay and FCM apoptosis assay with Annexin V/PI double staining, suggesting that plasma killing cells rate and inducing cell apoptosis rate both positively were related to the plasma doses or the post-plasma time points. The cell death rates increased from 15.2% to 33.1% and the apoptosis rate raise from 23.8% to 28% when the dose raise from 60s to 120 s at 8 h post-plasma, while they increased from 15.4% to 34.9% and from 48% to 55.3% respectively at the same doses at 12 h post-plasma. Furthermore, the production of reactive oxygen species (ROS), gene and protein expression for Caspases and Bcl-2 family members were measured for exploring the related apoptotic mechanisms phenomenon. We found ROS immediately increased to 1.24 times of the original amount, then increasing to 5.39-fold at 20 h after treatment. The gene and protein expression for Caspases and Bcl-2 family members are very active at 8-12 h post-plasma. Our results demonstrate that DBD plasma can effectively induce tumor cell death through primarily related apoptotic mechanisms.

  16. Interfacial barrier height modification of indium tin oxide/a-Si:H(p) via control of density of interstitial oxygen for silicon heterojunction solar cell application

    International Nuclear Information System (INIS)

    An indium tin oxide (ITO) film with low carrier concentration (n), high mobility (μ) and high work function (ΦITO) is a beneficial material for the front electrode in heterojunction silicon (HJ) solar cells due to its low free-carrier absorption in the near-infrared wavelength and low Schottky barrier height at the ITO/emitter-layer front contact. This low free-carrier absorption as well as the low Schottky barrier height increase the open-circuit voltage (Voc) and the short-circuit current density (Jsc), which in turn increases the overall cell efficiency (η). Hence, ITO films with lower n, higher μ and higher ΦITO were prepared by controlling the density of the interstitial oxygen [Oi] in the films and used as anti-reflection electrodes in HJ solar cells. With increasing [Oi] in the ITO, the preferential orientation of the (222) crystalline plane became more dominant. The ΦITO and μ increased from 4.87 eV and 38.9 cm2 V−1 s−1 to 5.04 eV and 48.79 cm2 V−1 s−1, respectively, whereas n decreased from 4.7 × 1020 cm−3 to 2.8 × 1020 cm−3. We attribute these changes to the chemisorbed oxygen into the ITO films, while the decrease of n is due to the ability of interstitial oxygen to capture electron, and the increase of μ is due to the reduction in free-carrier scattering. These ITO films were used to fabricate HJ solar cells. As [Oi] in the ITO film increased, the device performance improved and the best cell performance was obtained with Voc of 714 mV, Jsc 34.79 mA/cm2 and η of 17.82%. By computer simulation, we found that the higher ΦITO and μ but lower n were responsible for the enhanced cell performance. The cell performance, however, deteriorated due to poor film properties when [Oi] exceeded concentration limit from 3.2 × 1020 cm−3. - Highlights: • The carrier concentration (n) decreases with increasing interstitial oxygen ([Oi]). • The Hall mobility (μ) and the work function (ΦITO) increases with increasing ([Oi]. • High μ and

  17. Bright/Arid3A Acts as a Barrier to Somatic Cell Reprogramming through Direct Regulation of Oct4, Sox2, and Nanog

    Directory of Open Access Journals (Sweden)

    Melissa Popowski

    2014-01-01

    Full Text Available We show here that singular loss of the Bright/Arid3A transcription factor leads to reprograming of mouse embryonic fibroblasts (MEFs and enhancement of standard four-factor (4F reprogramming. Bright-deficient MEFs bypass senescence and, under standard embryonic stem cell (ESC culture conditions, spontaneously form clones that in vitro express pluripotency markers, differentiate to all germ lineages, and in vivo form teratomas and chimeric mice. We demonstrate that BRIGHT binds directly to the promoter/enhancer regions of Oct4, Sox2, and Nanog to contribute to their repression in both MEFs and ESCs. Thus, elimination of the BRIGHT barrier may provide an approach for somatic cell reprogramming.

  18. Features of T cells causing H-2-restricted lethal graft-vs.-host disease across minor histocompatibility barriers

    International Nuclear Information System (INIS)

    Evidence is presented that T cells that produce lethal graft-vs.-host disease (GVHD) to minor histocompatibility antigens (minor HA) comprise discrete subgroups of H-2K- and H-2D-restricted T cells; double negative selection of T cells in irradiated H-2 recombinant mice was used to separate these two subgroups. No evidence could be found that I-restricted T cells contributed to GVHD, either as effector cells or helper cells. The (unprimed) precursor cells for GVHD expressed the Thy-1+, Lyt-1+/-2, Ia- phenotype. Studies in which H-2-semiallogeneic bone marrow chimeras were used as hosts for negative selection suggested that presentation of minor HA to T cells during the induction phase is controlled by marrow-derived cells; indirect evidence was obtained that these latter cells can ''process'' minor HA presented on H-2 different cells and thereby render the antigens immunogenic. Studies in which minor HA-different, H-2-compatible chimeras were re-irradiated and then injected with donor-vs.-host T cells suggested that the effector phase of lethal GVHD involves contact of antigen on non-marrow-derived cells

  19. NG2, a common denominator for neuroinflammation, blood-brain barrier alteration, and oligodendrocyte precursor response in EAE, plays a role in dendritic cell activation.

    Science.gov (United States)

    Ferrara, Giovanni; Errede, Mariella; Girolamo, Francesco; Morando, Sara; Ivaldi, Federico; Panini, Nicolò; Bendotti, Caterina; Perris, Roberto; Furlan, Roberto; Virgintino, Daniela; Kerlero de Rosbo, Nicole; Uccelli, Antonio

    2016-07-01

    In adult CNS, nerve/glial-antigen 2 (NG2) is expressed by oligodendrocyte progenitor cells (OPCs) and is an early marker of pericyte activation in pathological conditions. NG2 could, therefore, play a role in experimental autoimmune encephalomyelitis (EAE), a disease associated with increased blood-brain barrier (BBB) permeability, inflammatory infiltrates, and CNS damage. We induced EAE in NG2 knock-out (NG2KO) mice and used laser confocal microscopy immunofluorescence and morphometry to dissect the effect of NG2 KO on CNS pathology. NG2KO mice developed milder EAE than their wild-type (WT) counterparts, with less intense neuropathology associated with a significant improvement in BBB stability. In contrast to WT mice, OPC numbers did not change in NG2KO mice during EAE. Through FACS and confocal microscopy, we found that NG2 was also expressed by immune cells, including T cells, macrophages, and dendritic cells (DCs). Assessment of recall T cell responses to the encephalitogen by proliferation assays and ELISA showed that, while WT and NG2KO T cells proliferated equally to the encephalitogenic peptide MOG35-55, NG2KO T cells were skewed towards a Th2-type response. Because DCs could be responsible for this effect, we assessed their expression of IL-12 by PCR and intracellular FACS. IL-12-expressing CD11c+ cells were significantly decreased in MOG35-55-primed NG2KO lymph node cells. Importantly, in WT mice, the proportion of IL-12-expressing cells was significantly lower in CD11c+ NG2- cells than in CD11c+ NG2+ cells. To assess the relevance of NG2 at immune system and CNS levels, we induced EAE in bone-marrow chimeric mice, generated with WT recipients of NG2KO bone-marrow cells and vice versa. Regardless of their original phenotype, mice receiving NG2KO bone marrow developed milder EAE than those receiving WT bone marrow. Our data suggest that NG2 plays a role in EAE not only at CNS/BBB level, but also at immune response level, impacting on DC activation and

  20. Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood–brain barrier in rats

    Directory of Open Access Journals (Sweden)

    Valiante S

    2015-03-01

    Full Text Available Salvatore Valiante,1,* Annarita Falanga,2,3,* Luisa Cigliano,1 Giuseppina Iachetta,1 Rosa Anna Busiello,1 Valeria La Marca,1 Massimiliano Galdiero,4 Assunta Lombardi,1 Stefania Galdiero1,2 1Department of Biology, 2Department of Pharmacy, 3DFM Scarl, University of Naples Federico II, 4Department of Experimental Medicine, II University of Naples, Naples, Italy *These authors contributed equally to this paper and are considered joint first authors Abstract: Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood–brain barrier (BBB. In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human diseases. Keywords: drug delivery, neurons, astrocytes, blood–brain barrier, peptide

  1. A novel method to achieve selective emitter for silicon solar cell using low cost pattern-able a-Si thin films as the semi-transparent phosphorus diffusion barrier

    International Nuclear Information System (INIS)

    Highlights: ► a-Si thin films as semitransparent phosphorus diffusion barriers for solar cell. ► a-Si thin films on silicon wafers were patterned by the alkaline solution. ► Selective emitter was formed with patterned a-Si as diffusion barrier for solar cell. -- Abstract: Selective emitter for silicon solar cell was realized by employing a-Si thin films as the semi-transparent diffusion barrier. The a-Si thin films with various thicknesses (∼10–40 nm) were deposited by the electron-beam evaporation technique. Emitters with sheet resistances from 37 to 145 Ω/□ were obtained via POCl3 diffusion process. The thickness of the a-Si diffusion barrier was optimized to be 15 nm for selective emitter in our work. Homemade mask which can dissolve in ethanol was screen-printed on a-Si film to make pattern. The a-Si film was then patterned in KOH solution to form finger-like design. Selective emitter was obtainable with one-step diffusion with patterned a-Si film on. Combinations of sheet resistances for the high-/low-level doped regions of 39.8/112.1, 36.2/88.8, 35.4/73.9 were obtained. These combinations are suitable for screen-printed solar cells. This preparation method of selective emitter based on a-Si diffusion barrier is a promising approach for low cost industrial manufacturing.

  2. Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro.

    Directory of Open Access Journals (Sweden)

    Roberta Paolinelli

    Full Text Available Reproducing the characteristics and the functional responses of the blood-brain barrier (BBB in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation.

  3. Polarization Energies at Organic-Organic Interfaces: Impact on the Charge Separation Barrier at Donor-Acceptor Interfaces in Organic Solar Cells.

    Science.gov (United States)

    Ryno, Sean M; Fu, Yao-Tsung; Risko, Chad; Brédas, Jean-Luc

    2016-06-22

    We probe the energetic landscape at a model pentacene/fullerene (C60) interface to investigate the interactions between positive and negative charges, which are critical to the processes of charge separation and recombination in organic solar cells. Using a polarizable force field, we find that polarization energy, i.e., the stabilization a charge feels due to its environment, is larger at the interface than in the bulk for both a positive and a negative charge. The combination of the charge being more stabilized at the interface and the Coulomb attraction between the charges results in a barrier to charge separation at the pentacene/C60 interface that can be in excess of 0.7 eV for static configurations of the donor and acceptor locations. However, the impact of molecular motions, i.e., the dynamics, at the interface at room temperature results in a distribution of polarization energies and in charge separation barriers that can be significantly reduced. The dynamic nature of the interface is thus critical, with the polarization energy distributions indicating that sites along the interface shift in time between favorable and unfavorable configurations for charge separation. PMID:27244215

  4. Polarization Energies at Organic–Organic Interfaces: Impact on the Charge Separation Barrier at Donor–Acceptor Interfaces in Organic Solar Cells

    KAUST Repository

    Ryno, Sean

    2016-05-31

    We probe the energetic landscape at a model pentacene/fullerene-C60 interface to investigate the interactions between positive and negative charges, which are critical to the processes of charge separation and recombination in organic solar cells. Using a polarizable force field, we find that polarization energy, i.e. the stabilization a charge feels due to its environment, is larger at the interface than in the bulk for both a positive and a negative charge. The combination of the charge being more stabilized at the interface and the Coulomb attraction between the charges, results in a barrier to charge separation at the pentacene-C60 interface that can be in excess of 0.7 eV for static configurations of the donor and acceptor locations. However, the impact of molecular motions, i.e., the dynamics, at the interface at room temperature results in a distribution of polarization energies and in charge separation barriers that can be significantly reduced. The dynamic nature of the interface is thus critical, with the polarization energy distributions indicating that sites along the interface shift in time between favorable and unfavorable configurations for charge separation.

  5. Phosphoinositide 3-kinase γ affects LPS-induced disturbance of blood-brain barrier via lipid kinase-independent control of cAMP in microglial cells.

    Science.gov (United States)

    Frister, Adrian; Schmidt, Caroline; Schneble, Nadine; Brodhun, Michael; Gonnert, Falk A; Bauer, Michael; Hirsch, Emilio; Müller, Jörg P; Wetzker, Reinhard; Bauer, Reinhard

    2014-12-01

    The breakdown of the blood-brain barrier (BBB) is a key event in the development of sepsis-induced brain damage. BBB opening allows blood-born immune cells to enter the CNS to provoke a neuroinflammatory response. Abnormal expression and activation of matrix metalloproteinases (MMP) was shown to contribute to BBB opening. Using different mouse genotypes in a model of LPS-induced systemic inflammation, our present report reveals phosphoinositide 3-kinase γ (PI3Kγ) as a mediator of BBB deterioration and concomitant generation of MMP by microglia. Unexpectedly, microglia expressing lipid kinase-deficient mutant PI3Kγ exhibited similar MMP regulation as wild-type cells. Our data suggest kinase-independent control of cAMP phosphodiesterase activity by PI3Kγ as a crucial mediator of microglial cell activation, MMP expression and subsequent BBB deterioration. The results identify the suppressive effect of PI3Kγ on cAMP as a critical mediator of immune cell functions. PMID:25033932

  6. Highly efficient betanin dye based ZnO and ZnO/Au Schottky barrier solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Thankappan, Aparna, E-mail: aparna.subhash@gmail.com [International School of Photonics (ISP), Cochin University of Science and Technology, Kochi (India); Inter University Centre for Nanomaterials and Devices (IUCND), Cochin University of Science and Technology, Kochi (India); Divya, S.; Augustine, Anju K.; Girijavallaban, C.P.; Radhakrishnan, P.; Thomas, Sheenu; Nampoori, V.P.N. [International School of Photonics (ISP), Cochin University of Science and Technology, Kochi (India)

    2015-05-29

    Performance of dye sensitized solar cells based on betanin natural dye from red beets with various nanostructured photoanodes on transparent conducting glass has been investigated. In four different electrolyte systems cell efficiency of 2.99% and overall photon to current conversion efficiency of 20% were achieved using ZnO nanosheet electrode with iodide based electrolyte in acetonitrile solution. To enhance solar harvesting in organic solar cells, uniform sized metal nanoparticles (gold (Au) of ~ 8 nm) synthesized via microwave irradiation method were incorporated into the device consisting of ZnO. Enhanced power conversion efficiency of 1.71% was achieved with ZnO/Au nanocomposite compared to the 0.868% efficiency of the bare ZnO nanosheet cell with ferrocene based electrolyte. - Highlights: • The influence of electrolytes has been studied. • Cell efficiency of 2.99% was achieved by ZnO. • Enhancement of efficiency with incorporation of Au nano.

  7. Highly efficient betanin dye based ZnO and ZnO/Au Schottky barrier solar cell

    International Nuclear Information System (INIS)

    Performance of dye sensitized solar cells based on betanin natural dye from red beets with various nanostructured photoanodes on transparent conducting glass has been investigated. In four different electrolyte systems cell efficiency of 2.99% and overall photon to current conversion efficiency of 20% were achieved using ZnO nanosheet electrode with iodide based electrolyte in acetonitrile solution. To enhance solar harvesting in organic solar cells, uniform sized metal nanoparticles (gold (Au) of ~ 8 nm) synthesized via microwave irradiation method were incorporated into the device consisting of ZnO. Enhanced power conversion efficiency of 1.71% was achieved with ZnO/Au nanocomposite compared to the 0.868% efficiency of the bare ZnO nanosheet cell with ferrocene based electrolyte. - Highlights: • The influence of electrolytes has been studied. • Cell efficiency of 2.99% was achieved by ZnO. • Enhancement of efficiency with incorporation of Au nano

  8. Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood–brain barrier and glioma cells

    DEFF Research Database (Denmark)

    Bruun, Jonas; Larsen, Trine Bjørnbo; Jølck, Rasmus Irming;

    2015-01-01

    Clinical applications of siRNA for treating disorders in the central nervous system require development of systemic stable, safe, and effective delivery vehicles that are able to cross the impermeable blood–brain barrier (BBB). Engineering nanocarriers with low cellular interaction during systemic...... release of four glutamic acid residues, providing a charge switch that triggers a shift of the LNP charge from weakly negative to positive, thus favoring cellular endocytosis and release of siRNA for high silencing efficiency. This work describes the development of this two-stage nanocarrier-system and...... evaluates the performance in brain endothelial and glioblastoma cells with respect to uptake and gene silencing efficiency. The ability of activation by MMP-triggered dePEGylation and charge shift is demonstrated to substantially increase the uptake and the silencing efficiency of the LNPs....

  9. Opiates Upregulate Adhesion Molecule Expression in Brain MicroVascular Endothelial Cells (BMVEC: Implications for Altered Blood Brain Barrier (BBB Permeability

    Directory of Open Access Journals (Sweden)

    Madhavan P.N. Nair

    2006-01-01

    Full Text Available The blood-brain barrier (BBB is an intricate cellular system composed of vascular endothelial cells and perivascular astrocytes that restrict the passage of immunocompetent cells into the central nervous system (CNS. Expression of the adhesion molecules, intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 on brain microvascular endothelial cells (BMVEC and their interaction with human immunodeficiency virus (HIV-1 viral proteins may help enhance viral adhesion and virus-cell fusion resulting in increased infectivity. Additionally, transmigration through the BBB is facilitated by both endothelial and monocyte/macrophage-derived nitric oxide (NO. Dysregulated production of NO by BMVEC due to opiates and HIV-1 viral protein interactions play a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB. Opioids act as co-factors in the neuropathogenesis of HIV-1 by facilitating BBB dysfunction however, no studies have been done to investigate the role of opiates alone or in combination with HIV-1 viral proteins on adhesion molecule expression in BMVEC. We hypothesize that opiates such as heroin and morphine in conjunction with the HIV-1 viral protein gp120 increase the expression of adhesion molecules ICAM-1 and VCAM-1 and these effects are mediated via the modulation of NO. Results show that opiates alone and in synergy with gp120 increase both the genotypic and phenotypic expression of ICAM-1 and VCAM-1 by BMVEC, additionally, these opiate induced effects may be the result of increased NO production. These studies will provide a better understanding of how opiate abuse in conjunction with HIV-1 infection facilitates the breakdown of the BBB and exacerbates the neuropathogenesis of HIV-1. Elucidation of the mechanisms of BBB modulation will provide new therapeutic approaches to maintain BBB integrity

  10. Molecular Pathways: Breaking the Epithelial Cancer Barrier for Chimeric Antigen Receptor and T-cell Receptor Gene Therapy.

    Science.gov (United States)

    Hinrichs, Christian S

    2016-04-01

    Adoptive transfer of T cells genetically engineered to express a tumor-targeting chimeric antigen receptor (CAR) or T-cell receptor (TCR) can mediate cancer regression in some patients. CARs are synthetic single-chain proteins that use antibody domains to target cell surface antigens. TCRs are natural heterodimeric proteins that can target intracellular antigens through recognition of peptides bound to human leukocyte antigens. CARs have shown promise in B-cell malignancies and TCRs in melanoma, but neither approach has achieved clear success in an epithelial cancer. Treatment of epithelial cancers may be particularly challenging because of a paucity of target antigens expressed by carcinomas and not by important healthy tissues. In addition, epithelial cancers may be protected by inhibitory ligands and soluble factors in the tumor microenvironment. One strategy to overcome these negative regulators is to modulate expression of T-cell genes to enhance intrinsic T-cell function. Programmable nucleases, which can suppress inhibitory genes, and inducible gene expression systems, which can enhance stimulatory genes, are entering clinical testing. Other work is delineating whether control of genes for immune checkpoint receptors (e.g.,PDCD1, CTLA4) and cytokine and TCR signaling regulators (e.g.,CBLB, CISH, IL12, IL15) can increase the antitumor activity of therapeutic T cells.Clin Cancer Res; 22(7); 1559-64. ©2016 AACR. PMID:27037253

  11. The novel porcine Lactobacillus sobrius strain protects intestinal cells from enterotoxigenic Escherichia coli K88 infection and prevents membrane barrier damage.

    Science.gov (United States)

    Roselli, Marianna; Finamore, Alberto; Britti, Maria Serena; Konstantinov, Sergey R; Smidt, Hauke; de Vos, Willem M; Mengheri, Elena

    2007-12-01

    Lactobacilli have a potential to overcome intestinal disorders; however, the exact mode of action is still largely unknown. In this study, we have used the intestinal porcine intestinal IPEC-1 epithelial cells as a model to investigate a possible protective activity of a new Lactobacillus species, the L. sobrius DSM 16698(T), against intestinal injury induced by enterotoxigenic Escherichia coli (ETEC) K88 infection and the underlying mechanisms. Treatment of infected cells with L. sobrius strongly reduced the pathogen adhesion. L. sobrius was also able to prevent the ETEC-induced membrane damage by inhibiting delocalization of zonula occludens (ZO)-1, reduction of occludin amount, rearrangement of F-actin, and dephosphorylation of occludin caused by ETEC. RT-PCR and ELISA experiments showed that L. sobrius counteracted the ETEC-induced increase of IL-8 and upregulated the IL-10 expression. The involvement of IL-8 in the deleterious effects of ETEC was proven by neutralization of IL-8 with a specific antibody. A crucial role of IL-10 was indicated by blockage of IL-10 production with neutralizing anti-IL-10 antibody that fully abrogated the L. sobrius protection. L. sobrius was also able to inhibit the internalization of ETEC, which was likely favored by the leaking barrier. The protective effects were not found with L. amylovorus DSM 20531(T) treatment, a strain derived from cattle waste but phylogenetically closely related to L. sobrius. Together, the data indicate that L. sobrius exerts protection against the harmful effects of ETEC by different mechanisms, including pathogen adhesion inhibition and maintenance of membrane barrier integrity through IL-10 regulation. PMID:18029488

  12. Plasma texturing of multicrystalline silicon for solar cell using remote-type pin-to-plate dielectric barrier discharge

    International Nuclear Information System (INIS)

    Multicrystalline silicon (mc-Si) was etched using a pin-to-plate-type remote dielectric barrier discharge, and the effect of adding NF3 to N2 (40 slm) and O2 to N2 (40 slm)/NF3 (1 slm) on the characteristics of mc-Si etching and texturing was investigated. The addition of NF3 at flow rates up to that of N2 increased the mc-Si etch rate continuously by increasing the number of F radicals in the gas mixture. Furthermore, the addition of O2 at flow rates of up to 400 sccm to N2 (40 slm)/NF3 (1 slm) further increased the mc-Si etch rate by more than two times (749.6 nm/scan, 0.25 m min-1), as compared with that without oxygen by the further dissociation of NF3 caused by oxygen. In particular, the addition of O2 to N2/NF3 increased the surface roughness, due to the micromasking (local surface oxidation) effect and, by adding 600 sccm O2, a reflectance of 20-30% in the visible wavelength could be obtained due to the formation of optimal wave-type surface morphology.

  13. Regulatory and junctional proteins of the blood-testis barrier in human Sertoli cells are modified by monobutyl phthalate (MBP) and bisphenol A (BPA) exposure.

    Science.gov (United States)

    de Freitas, André Teves Aquino Gonçalves; Ribeiro, Mariana Antunes; Pinho, Cristiane Figueiredo; Peixoto, André Rebelo; Domeniconi, Raquel Fantin; Scarano, Wellerson R

    2016-08-01

    The blood-testis barrier (BTB) is responsible for providing a protected environment and coordinating the spermatogenesis. Endocrine disruptors (EDs) might lead to infertility, interfering in the BTB structure and modulation. This study aimed to correlate the actions of two EDs, monobutyl phthalate (MBP) and bisphenol A (BPA) in different periods of exposure, in a low toxicity dose to the human Sertoli cells (HSeC) and its effects on the proteins of the BTB and regulatory proteins involved in its modulation. HSeC cells were exposed to MBP (10μM) and BPA (20μM) for 6 and 48h. Western Blot assay indicated that MBP was able to reduce the expression of occludin, ZO-1, N-cadherin and Androgen Receptor (AR), while BPA leads to a reduction of occludin, ZO-1, β-catenin and AR. TGF-β2 and F-actin were not modified. Phalloidin and Hematoxylin and Eosin assay revealed phenotically disruption in Sertoli cells adhesion, without changes in F-actin expression or localization. Our data suggested both EDs present potential for disrupting the structure and maintenance of the human BTB by AR dependent pathway. PMID:26922907

  14. Intracerebroventricular transplantation of ex vivo expanded endothelial colony-forming cells restores blood-brain barrier integrity and promotes angiogenesis of mice with traumatic brain injury.

    Science.gov (United States)

    Huang, Xin-Tao; Zhang, Yong-Qiang; Li, Sheng-Jie; Li, Sheng-Hui; Tang, Qing; Wang, Zhi-Tao; Dong, Jing-Fei; Zhang, Jian-Ning

    2013-12-15

    Endothelial progenitor cells (EPCs) play a key role in tissue repair and regeneration. Previous studies have shown a positive correlation between the number of circulating EPCs and clinical outcomes of patients with traumatic brain injury (TBI). A recent study has further shown that intravenous infusion of human umbilical cord blood-derived endothelial colony-forming cells (ECFCs) improves outcomes of mice subjected to experimental TBI. This follow-up study was designed to determine whether intracerebroventricular (i.c.v.) infusion of ECFCs, which may reduce systemic effects of these cells, could repair the blood-brain barrier (BBB) and promote angiogenesis of mice with TBI. Adult nude mice were exposed to fluid percussion injury and transplanted i.c.v. with ECFCs on day 1 post-TBI. These ECFCs were detected at the TBI zone 3 days after transplantation by SP-DiIC18(3) and fluorescence in situ hybridization. Mice with ECFCs transplant had reduced Evans blue extravasation and brain water content, increased expression of ZO-1 and claudin-5, and showed a higher expression of angiopoietin 1. Consistent with the previous report, mice with ECFCs transplant had also increased microvascular density. Modified neurological severity score and Morris water maze test indicated significant improvements in motor ability, spatial acquisition and reference memory in mice receiving ECFCs, compared to those receiving saline. These data demonstrate the beneficial effects of ECFC transplant on BBB integrity and angiogenesis in mice with TBI. PMID:23957220

  15. Sprache als Barriere (Language as a Barrier)

    Science.gov (United States)

    Mattheier, Klaus

    1974-01-01

    The concept of language barrier has its derivations in the fields of dialectology, sociology and psychology. In contemporary usage however, the concept has two meanings i.e. regional-cultural barrier and socio-cultural barrier. (Text is in German.) (DS)

  16. Treatment of poly(ethylene terephthalate) foils by atmospheric pressure air dielectric barrier discharge and its influence on cell growth

    Czech Academy of Sciences Publication Activity Database

    Kuzminova, A.; Vandrovcová, Marta; Shelemin, A.; Kylián, O.; Choukourov, A.; Hanuš, J.; Bačáková, Lucie; Slavínská, D.; Biederman, H.

    2015-01-01

    Roč. 357, part A (2015), s. 689-695. ISSN 0169-4332 R&D Projects: GA ČR(CZ) GBP108/12/G108 Institutional support: RVO:67985823 Keywords : plasma treatment * DBD plasma * cells growth Subject RIV: JJ - Other Materials Impact factor: 2.711, year: 2014

  17. Toll-like receptor 2 activation by β2→1-fructans protects barrier function of t84 human intestinal epithelial cells in a chain length-dependent manner

    NARCIS (Netherlands)

    Vogt, L.M.; Meyer, D.; Pullens, G.; Faas, M.M.; Venema, K.; Ramasamy, U.; Schols, H.A.; Vos, P. de

    2014-01-01

    Dietary fiber intake is associated with lower incidence and mortality from disease, but the underlying mechanisms of these protective effects are unclear.We hypothesized that β2→1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2),

  18. TiO 2 Conduction Band Modulation with In 2 O 3 Recombination Barrier Layers in Solid-State Dye-Sensitized Solar Cells

    KAUST Repository

    Brennan, Thomas P.

    2013-11-21

    Atomic layer deposition (ALD) was used to grow subnanometer indium oxide recombination barriers in a solid-state dye-sensitized solar cell (DSSC) based on the spiro-OMeTAD hole-transport material (HTM) and the WN1 donor-π-acceptor organic dye. While optimal device performance was achieved after 3-10 ALD cycles, 15 ALD cycles (∼2 Å of In2O 3) was observed to be optimal for increasing open-circuit voltage (VOC) with an average improvement of over 100 mV, including one device with an extremely high VOC of 1.00 V. An unexpected phenomenon was observed after 15 ALD cycles: the increasing VOC trend reversed, and after 30 ALD cycles VOC dropped by over 100 mV relative to control devices without any In2O3. To explore possible causes of the nonmonotonic behavior resulting from In2O3 barrier layers, we conducted several device measurements, including transient photovoltage experiments and capacitance measurements, as well as density functional theory (DFT) studies. Our results suggest that the VOC gains observed in the first 20 ALD cycles are due to both a surface dipole that pulls up the TiO2 conduction band and recombination suppression. After 30 ALD cycles, however, both effects are reversed: the surface dipole of the In2O3 layer reverses direction, lowering the TiO 2 conduction band, and mid-bandgap states introduced by In 2O3 accelerate recombination, leading to a reduced V OC. © 2013 American Chemical Society.

  19. Gastrointestinal mucosal barrier function and diseases.

    Science.gov (United States)

    Oshima, Tadayuki; Miwa, Hiroto

    2016-08-01

    The gastrointestinal mucosal barrier plays an essential role in the separation of the inside of the body from the outside environment. Tight junctions (TJs) are the most important component for construction of a constitutive barrier of epithelial cells, and they regulate the permeability of the barrier by tightly sealing the cell-cell junctions. TJ proteins are represented by claudins, occludin, junctional adhesion molecules, and scaffold protein zonula occludens. Among these TJ proteins, claudins are the major components of TJs and are responsible for the barrier and the polarity of the epithelial cells. Gastrointestinal diseases including reflux esophagitis, inflammatory bowel disease, functional gastrointestinal disorders, and cancers may be regulated by these molecules, and disruption of their functions leads to chronic inflammatory conditions and chronic or progressive disease. Therefore, regulation of the barrier function of epithelial cells by regulating the expression and localization of TJ proteins is a potential new target for the treatment of these diseases. Treatment strategies for these diseases might thus be largely altered if symptom generation and/or immune dysfunction could be regulated through improvement of mucosal barrier function. Since TJ proteins may also modify tumor infiltration and metastasis, other important goals include finding a good TJ biomarker of cancer progression and patient prognosis, and developing TJ protein-targeted therapies that can modify patient prognosis. This review summarizes current understanding of gastrointestinal barrier function, TJ protein expression, and the mechanisms underlying epithelial barrier dysregulation in gastrointestinal diseases. PMID:27048502

  20. The interaction between plasma filaments in dielectric barrier discharges and liquid covered wounds: electric fields delivered to model platelets and cells

    International Nuclear Information System (INIS)

    The treatment of wounds by atmospheric pressure plasmas in the context of plasma medicine typically proceeds through a liquid layer covering exposed cells. The wounds and their liquid covering often have irregular shapes with electrical properties (i.e. conductivity and permittivities) that may differ not only from wound-to-wound but also for a single wound as healing proceeds. The differing shapes and electrical properties extend into the liquid within the wound that typically contains cellular materials such as blood platelets. The plasma, wound, liquid and intra-liquid cellular components represent an interacting system of mutual dependence. In this paper, we discuss the results from a computational investigation of the treatment of small, liquid-covered wounds by filamentary dielectric barrier discharges. The sizes of the wounds are of the order of the plasma filaments and the liquid within the wound, an approximation of blood serum, contains idealized blood platelets. We find that the electrical properties of a wound can have significant effects on the spreading of the plasma on its surface by virtue of the deformation of the vacuum electric fields due to the shape, the effective capacitance of the wound and the discontinuities in electrical permittivity. This in turn effects the penetration of the electric field to cells under the liquid. The orientation and permittivity of the platelets relative to the liquid determines the electric fields that may stimulate the platelets. (paper)

  1. Transport of Twelve Coumarins from Angelicae Pubescentis Radix across a MDCK-pHaMDR Cell Monolayer-An in Vitro Model for Blood-Brain Barrier Permeability.

    Science.gov (United States)

    Yang, Yan-Fang; Xu, Wei; Song, Wei; Ye, Min; Yang, Xiu-Wei

    2015-01-01

    Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine, is reported to have central nervous system activities. The purpose of this study was to characterize the blood-brain barrier permeability of twelve coumarins from APR including umbelliferone (1), osthol (2), scopoletin (3), peucedanol (4), ulopterol (5), angepubebisin (6), psoralen (7), xanthotoxin (8), bergapten (9), isoimperatorin (10), columbianadin (11), and columbianetin acetate (12) with an in vitro model using a MDCK-pHaMDR cell monolayer. The cell monolayer was validated to be suitable for the permeation experiments. The samples' transports were analyzed by high performance liquid chromatography and their apparent permeability coefficients (Papp) were calculated. According to the Papp value, most coumarins could be characterized as well-absorbed compounds except for 4, 10 and 11 which were moderately absorbed ones, in concentration-dependent and time-dependent manners. The results of P-glycoprotein (P-gp) inhibitor (verapamil) experiments showed that the transport of coumarin 4 was affected by the transport protein P-gp. Sigmoid functions between permeability log(Papp AP-BL*MW0.5) and log D (at pH 7.4) were established to analyze the structure-activity relationship of coumarins. The results provide useful information for discovering the substance basis for the central nervous system activities of APR, and predicting the permeability of other coumarins through BBB. PMID:26121397

  2. Transport of Twelve Coumarins from Angelicae Pubescentis Radix across a MDCK-pHaMDR Cell Monolayer—An in Vitro Model for Blood-Brain Barrier Permeability

    Directory of Open Access Journals (Sweden)

    Yan-Fang Yang

    2015-06-01

    Full Text Available Angelicae Pubescentis Radix (APR, a widely used traditional Chinese medicine, is reported to have central nervous system activities. The purpose of this study was to characterize the blood-brain barrier permeability of twelve coumarins from APR including umbelliferone (1, osthol (2, scopoletin (3, peucedanol (4, ulopterol (5, angepubebisin (6, psoralen (7, xanthotoxin (8, bergapten (9, isoimperatorin (10, columbianadin (11, and columbianetin acetate (12 with an in vitro model using a MDCK-pHaMDR cell monolayer. The cell monolayer was validated to be suitable for the permeation experiments. The samples’ transports were analyzed by high performance liquid chromatography and their apparent permeability coefficients (Papp were calculated. According to the Papp value, most coumarins could be characterized as well-absorbed compounds except for 4, 10 and 11 which were moderately absorbed ones, in concentration-dependent and time-dependent manners. The results of P-glycoprotein (P-gp inhibitor (verapamil experiments showed that the transport of coumarin 4 was affected by the transport protein P-gp. Sigmoid functions between permeability log(Papp AP-BL*MW0.5 and log D (at pH 7.4 were established to analyze the structure-activity relationship of coumarins. The results provide useful information for discovering the substance basis for the central nervous system activities of APR, and predicting the permeability of other coumarins through BBB.

  3. Interleukin 7 from maternal milk crosses the intestinal barrier and modulates T-cell development in offspring.

    Directory of Open Access Journals (Sweden)

    Richard Aspinall

    Full Text Available BACKGROUND: Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. METHODS AND FINDINGS: We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL-7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. CONCLUSIONS/SIGNIFICANCE: Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue.

  4. CdTe solar cells with open-circuit voltage breaking the 1 V barrier

    Science.gov (United States)

    Burst, J. M.; Duenow, J. N.; Albin, D. S.; Colegrove, E.; Reese, M. O.; Aguiar, J. A.; Jiang, C.-S.; Patel, M. K.; Al-Jassim, M. M.; Kuciauskas, D.; Swain, S.; Ablekim, T.; Lynn, K. G.; Metzger, W. K.

    2016-03-01

    CdTe solar cells have the potential to undercut the costs of electricity generated by other technologies, if the open-circuit voltage can be increased beyond 1 V without significant decreases in current. However, in the past decades, the open-circuit voltage has stagnated at around 800-900 mV. This is lower than in GaAs solar cells, even though GaAs has a smaller bandgap; this is because it is more difficult to achieve simultaneously high hole density and lifetime in II-VI materials than in III-V materials. Here, by doping the CdTe with a Group V element, we report lifetimes in single-crystal CdTe that are nearly radiatively limited and comparable to those in GaAs over a hole density range relevant for solar applications. Furthermore, the deposition on CdTe of nanocrystalline CdS layers that form non-ideal heterointerfaces with 10% lattice mismatch impart no damage to the CdTe surface and show excellent junction transport properties. These results enable the fabrication of CdTe solar cells with open-circuit voltage greater than 1 V.

  5. Correlation of Ultrastructural Changes of Endothelial Cells and Astrocytes Occurring during Blood Brain Barrier Damage after Traumatic Brain Injury with Biochemical Markers of Blood Brain Barrier Leakage and Inflammatory Response

    Czech Academy of Sciences Publication Activity Database

    Vajtr, D.; Benada, Oldřich; Kukačka, J.; Průša, R.; Houšťava, L.; Toupalík, P.; Kizek, R.

    2009-01-01

    Roč. 58, č. 2 (2009), s. 263-268. ISSN 0862-8408 Institutional research plan: CEZ:AV0Z50200510 Keywords : Blood brain barrier * Expansive contusion * Metalloproteinases Subject RIV: EE - Microbiology, Virology Impact factor: 1.430, year: 2009

  6. POCl3 diffusion with in-situ SiO2 barrier for selective emitter multicrystalline solar grade silicon solar cells

    OpenAIRE

    Urrejola, Elias; Kristian, Peter; Soiland, Anne-Karin; Enebakk, Erik

    2009-01-01

    We present an innovative process for the formation of a selective emitter by using an advanced phosphorous glass as a barrier layer against subsequent diffusion. The advanced barrier glass was achieved by the formation of a standard phosphorous glass treated with additional thermal oxidation immediately after deposition in the same process tube. The resistant layer is used as a barrier for the second diffusion after selective opening of the finger contact areas by screen printing of a SiO2 et...

  7. Cytokines and the Skin Barrier

    Directory of Open Access Journals (Sweden)

    Jens Malte Baron

    2013-03-01

    Full Text Available The skin is the largest organ of the human body and builds a barrier to protect us from the harmful environment and also from unregulated loss of water. Keratinocytes form the skin barrier by undergoing a highly complex differentiation process that involves changing their morphology and structural integrity, a process referred to as cornification. Alterations in the epidermal cornification process affect the formation of the skin barrier. Typically, this results in a disturbed barrier, which allows the entry of substances into the skin that are immunologically reactive. This contributes to and promotes inflammatory processes in the skin but also affects other organs. In many common skin diseases, including atopic dermatitis and psoriasis, a defect in the formation of the skin barrier is observed. In these diseases the cytokine composition within the skin is different compared to normal human skin. This is the result of resident skin cells that produce cytokines, but also because additional immune cells are recruited. Many of the cytokines found in defective skin are able to influence various processes of differentiation and cornification. Here we summarize the current knowledge on cytokines and their functions in healthy skin and their contributions to inflammatory skin diseases.

  8. Inflammation Modulates RLIP76/RALBP1 Electrophile-Glutathione Conjugate Transporter and Housekeeping Genes in Human Blood-Brain Barrier Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Barbara Bennani-Baiti

    Full Text Available Endothelial cells are often present at inflammation sites. This is the case of endothelial cells of the blood-brain barrier (BBB of patients afflicted with neurodegenerative disorders such as Alzheimer's, Parkinson's, or multiple sclerosis, as well as in cases of bacterial meningitis, trauma, or tumor-associated ischemia. Inflammation is a known modulator of gene expression through the activation of transcription factors, mostly NF-κB. RLIP76 (a.k.a. RALBP1, an ATP-dependent transporter of electrophile-glutathione conjugates, modulates BBB permeability through the regulation of tight junction function, cell adhesion, and exocytosis. Genes and pathways regulated by RLIP76 are transcriptional targets of tumor necrosis factor alpha (TNF-α pro-inflammatory molecule, suggesting that RLIP76 may also be an inflammation target. To assess the effects of TNF-α on RLIP76, we faced the problem of choosing reference genes impervious to TNF-α. Since such genes were not known in human BBB endothelial cells, we subjected these to TNF-α, and measured by quantitative RT-PCR the expression of housekeeping genes commonly used as reference genes. We find most to be modulated, and analysis of several inflammation datasets as well as a metaanalysis of more than 5000 human tissue samples encompassing more than 300 cell types and diseases show that no single housekeeping gene may be used as a reference gene. Using three different algorithms, however, we uncovered a reference geneset impervious to TNF-α, and show for the first time that RLIP76 expression is induced by TNF-α and follows the induction kinetics of inflammation markers, suggesting that inflammation can influence RLIP76 expression at the BBB. We also show that MRP1 (a.k.a. ABCC1, another electrophile-glutathione transporter, is not modulated in the same cells and conditions, indicating that RLIP76 regulation by TNF-α is not a general property of glutathione transporters. The reference geneset

  9. Role of the Endothelium during Tumor Cell Metastasis: Is the Endothelium a Barrier or a Promoter for Cell Invasion and Metastasis?

    Directory of Open Access Journals (Sweden)

    Claudia Tanja Mierke

    2008-01-01

    Full Text Available The malignancy of cancer disease depends on the ability of the primary tumor to metastasize to distant organs. The process of the metastasis formation has largely been analyzed, but still main pathways regarding the extravasation step at the end of the metastasis formation process are controversially discussed. An agreement has been reached about the importance of the endothelium to promote metastasis formation either by enhancing the growth of the primary tumor or by homing (targeting the tumor cells to blood or lymph vessels. The mechanical properties of the invading tumor cells become the focus of several studies, but the endothelial cell mechanical properties are still elusive. This paper describes the different roles of the endothelium in the process of metastasis formation and focuses on a novel role of the endothelium in promoting tumor cell invasion. It discusses how novel biophysical tools and in vivo animal models help to determine the role of the endothelium in the process of tumor cell invasion. Evidence is provided that cell mechanical properties, for example, contractile force generation of tumor cells, are involved in the process of tumor cell invasion.

  10. Oral and Fecal Campylobacter concisus Strains induce Barrier dysfunction by Apoptosis in HT-29/B6 Intestinal Epithelial Cells

    DEFF Research Database (Denmark)

    Nielsen, Hans Linde; Nielsen, Henrik Ib; Ejlertsen, Tove;

    Campylobacter concisus infections of the gastrointestinal tract can be accompanied by diarrhea and inflammation, whereas colonization of the human oral cavity might have a commensal nature. We focus on the pathophysiology of C. concisus and the effects of different clinical oral and fecal C....... concisus strains on human HT-29/B6 colon cells. Six oral and eight fecal strains of C. concisus were isolated. Mucus-producing HT-29/B6 epithelial monolayers were infected with the C. concisus strains. Transepithelial electrical resistance (R(t)) and tracer fluxes of different molecule size were measured...... in Ussing chambers. Tight junction (TJ) protein expression was determined by Western blotting, and subcellular TJ distribution was analyzed by confocal laser-scanning microscopy. Apoptosis induction was examined by TUNEL-staining and Western blot of caspase-3 activation. All strains invaded confluent...

  11. Energy Systems Based on Polyacetylene: Rechargeable Batteries and Schottky Barrier Solar Cells. Final Report, March 1, 1981-February 29, 1984

    Science.gov (United States)

    MacDiarmid, A. G.

    1984-02-01

    The chief thrust of the research has been directed towards the evaluation of polyacetylene (CH){sub x}, the prototype conducting polymer as an electrode- active material in novel, rechargeable batteries employing nonaqueous electrolytes. The p-doped material, [(CH{sup +y})A{sub y}{sup -}]{sub x}, (where A{sup -} is an anion) in conjunction with a Li anode, shows excellent discharge characteristics, e.g., very little change in discharge voltage with change in discharge current and a high power density. Its energy density is also good but it shows poor shelf life. When (CH){sub x} is used as a cathode (Li anode), which results in the formation of the n-doped polymer, [Li{sub y} {sup +}(CH/sup -y/)]{sub x}, during discharge, good discharge plateaus and power densities are obtained together with excellent shelf life and good recyclability. The energy density is, however only moderate. Cells employing an [M{sub y}{sup +}(CH/sup -y/)]{sub x} (where M = Li, Na) anode and a TiS{sub 2} cathode show very good discharge and recycling characteristics but their energy density is poor.

  12. Energy systems based on polyacetylene: rechargeable batteries and Schottky barrier solar cells. Final report, March 1, 1981-February 29, 1984

    Energy Technology Data Exchange (ETDEWEB)

    MacDiarmid, A.G.

    1984-02-01

    The chief thrust of the research has been directed towards the evaluation of polyacetylene (CH)/sub x/, the prototype conducting polymer as an electrode-active material in novel, rechargeable batteries employing nonaqueous electrolytes. The p-doped material, ((CH/sup +y/)A/sub y//sup -/)/sub x/, (where A/sup -/ is an anion) in conjunction with a Li anode, shows excellent discharge characteristics, e.g., very little change in discharge voltage with change in discharge current and a high power density. Its energy density is also good but it shows poor shelf life. When (CH)/sub x/ is used as a cathode (Li anode), which results in the formation of the n-doped polymer, (Li/sub y//sup +/(CH/sup -y/))/sub x/, during discharge, good discharge plateaus and power densities are obtained together with excellent shelf life and good recyclability. The energy density is, however only moderate. Cells employing an (M/sub y//sup +/(CH/sup -y/))/sub x/ (where M = Li, Na) anode and a TiS/sub 2/ cathode show very good discharge and recycling characteristics but their energy density is poor.

  13. Degradation of SS316L bipolar plates in simulated fuel cell environment: Corrosion rate, barrier film formation kinetics and contact resistance

    Science.gov (United States)

    Papadias, Dionissios D.; Ahluwalia, Rajesh K.; Thomson, Jeffery K.; Meyer, Harry M.; Brady, Michael P.; Wang, Heli; Turner, John A.; Mukundan, Rangachary; Borup, Rod

    2015-01-01

    A potentiostatic polarization method is used to evaluate the corrosion behavior of SS316L in simulated anode and cathode environments of polymer electrolyte fuel cells. A passive barrier oxide film is observed to form and reach steady state within ∼10 h of polarization, after which time the total ion release rates are low and nearly constant at ∼0.4 μg cm-2 h-1 for all potentials investigated. The equilibrium film thickness, however, is a function of the applied potential. The main ionic species dissolved in the liquid are predominately Fe followed by Ni, that account for >90% of the steady-state corrosion current. The dissolution rate of Cr is low but increases systematically at potentials higher than 0.8 V. The experimental ion release rates can be correlated with a point defect model using a single set of parameters over a broad range of potentials (0.2-1 V) on the cathode side. The interfacial contact resistance measured after 48 h of polarization is observed to increase with increase in applied potential and can be empirically correlated with applied load and oxide film thickness. The oxide film is substantially thicker at 1.5 V possibly because of alteration in film composition to Fe-rich as indicated by XPS data.

  14. Mast Cell Tryptase Reduces Junctional Adhesion Molecule-A (JAM-A) Expression in Intestinal Epithelial Cells: Implications for the Mechanisms of Barrier Dysfunction in Irritable Bowel Syndrome.

    LENUS (Irish Health Repository)

    Wilcz-Villega, Ewa M

    2013-07-01

    The objective of this study was to investigate how mast cell tryptase may influence intestinal permeability and tight junction (TJ) proteins in vitro and explore translation to irritable bowel syndrome (IBS).

  15. The blood-brain barrier.

    Science.gov (United States)

    Obermeier, Birgit; Verma, Ajay; Ransohoff, Richard M

    2016-01-01

    In autoimmune neurologic disorders, the blood-brain barrier (BBB) plays a central role in immunopathogenesis, since this vascular interface is an entry path for cells and effector molecules of the peripheral immune system to reach the target organ, the central nervous system (CNS). The BBB's unique anatomic structure and the tightly regulated interplay of its cellular and acellular components allow for maintenance of brain homeostasis, regulation of influx and efflux, and protection from harm; these ensure an optimal environment for the neuronal network to function properly. In both health and disease, the BBB acts as mediator between the periphery and the CNS. For example, immune cell trafficking through the cerebral vasculature is essential to clear microbes or cell debris from neural tissues, while poorly regulated cellular transmigration can underlie or worsen CNS pathology. In this chapter, we focus on the specialized multicellular structure and function of the BBB/neurovascular unit and discuss how BBB breakdown can precede or be a consequence of neuroinflammation. We introduce the blood-cerebrospinal fluid barrier and include a brief aside about evolutionary aspects of barrier formation and refinements. Lastly, since restoration of barrier function is considered key to ameliorate neurologic disease, we speculate about new therapeutic avenues to repair a damaged BBB. PMID:27112670

  16. Long distance relationships : the secret for fuel cell success? fuel cell developers and integrators form trans-oceanic partnerships to crash through cultural barriers

    International Nuclear Information System (INIS)

    The varieties of viable fuel cell applications and widely varying regional market conditions have created global partnerships among entities with complementary attributes. Although it may appear that domestic liaisons among culturally similar players spawned from industry clusters should provide the clearest route to success in this industry, it is the intercontinental groupings which are demonstrating the most potential. This paper discussed the global fuel cell challenge and the vertical integration of multi-national partnerships. The paper also discussed the current global stationary market in perspective. Fuel cells require unique maintenance, support, and refueling including operator instruction and a new supply infrastructure. The paper addressed the fact that fuel cells represent a disruptive technology. A telecom backup status report was also presented. Other topics that were discussed included developing markets as well as specific examples of global organizations such as Canadian Ballard and Danish Dantherm Power and their fuel cell application solutions. It was concluded that after an inconsistent history, fuel cells have finally achieved viability in the real world. However, there is significant cultural resistance to their implementation in the United States. 4 figs

  17. Penetration through the Skin Barrier.

    Science.gov (United States)

    Nielsen, Jesper Bo; Benfeldt, Eva; Holmgaard, Rikke

    2016-01-01

    The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates. During recent decades, the latter has received increased attention as a route for intentionally delivering drugs to patients. This has stimulated research in methods for sampling, measuring and predicting percutaneous penetration. Previous chapters have described how different endogenous, genetic and exogenous factors may affect barrier characteristics. The present chapter introduces the theory for barrier penetration (Fick's law), and describes and discusses different methods for measuring the kinetics of percutaneous penetration of chemicals, including in vitro methods (static and flow-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous penetration. Finally, a short discussion of the advantages and challenges of each method is provided, which will hopefully allow the reader to improve decision making and treatment planning, as well as the evaluation of experimental studies of percutaneous penetration of chemicals. PMID:26844902

  18. Barrier Certificates Revisited

    OpenAIRE

    Dai, Liyun; Gan, Ting; Xia, Bican; Zhan, Naijun

    2013-01-01

    A barrier certificate can separate the state space of a con- sidered hybrid system (HS) into safe and unsafe parts ac- cording to the safety property to be verified. Therefore this notion has been widely used in the verification of HSs. A stronger condition on barrier certificates means that less expressive barrier certificates can be synthesized. On the other hand, synthesizing more expressive barrier certificates often means high complexity. In [9], Kong et al consid- ered how to relax the ...

  19. Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-α, releasing matrix metalloproteinase-9 and migrating in vitro

    Directory of Open Access Journals (Sweden)

    Miyaji Haruki

    2011-08-01

    Full Text Available Abstract Background Increased matrix metalloproteinase (MMP-9 in the plasma and brain is associated with blood-brain barrier (BBB disruption through proteolytic activity in neuroinflammatory diseases. MMP-9 is present in the brain microvasculature and its vicinity, where brain microvascular endothelial cells (BMECs, pericytes and astrocytes constitute the BBB. Little is known about the cellular source and role of MMP-9 at the BBB. Here, we examined the ability of pericytes to release MMP-9 and migrate in response to inflammatory mediators in comparison with BMECs and astrocytes, using primary cultures isolated from rat brains. Methods The culture supernatants were collected from primary cultures of rat brain endothelial cells, pericytes, or astrocytes. MMP-9 activities and levels in the supernatants were measured by gelatin zymography and western blot, respectively. The involvement of signaling molecules including mitogen-activated protein kinases (MAPKs and phosphoinositide-3-kinase (PI3K/Akt in the mediation of tumor necrosis factor (TNF-α-induced MMP-9 release was examined using specific inhibitors. The functional activity of MMP-9 was evaluated by a cell migration assay. Results Zymographic and western blot analyses demonstrated that TNF-α stimulated pericytes to release MMP-9, and this release was much higher than from BMECs or astrocytes. Other inflammatory mediators [interleukin (IL-1β, interferon-γ, IL-6 and lipopolysaccharide] failed to induce MMP-9 release from pericytes. TNF-α-induced MMP-9 release from pericytes was found to be mediated by MAPKs and PI3K. Scratch wound healing assay showed that in contrast to BMECs and astrocytes the extent of pericyte migration was significantly increased by TNF-α. This pericyte migration was inhibited by anti-MMP-9 antibody. Conclusion These findings suggest that pericytes are most sensitive to TNF-α in terms of MMP-9 release, and are the major source of MMP-9 at the BBB. This pericyte

  20. Prevention of Escherichia coli K1 Penetration of the Blood-Brain Barrier by Counteracting the Host Cell Receptor and Signaling Molecule Involved in E. coli Invasion of Human Brain Microvascular Endothelial Cells▿

    OpenAIRE

    Zhu, Longkun; Pearce, Donna; Kim, Kwang Sik

    2010-01-01

    Escherichia coli meningitis is an important cause of mortality and morbidity, and a key contributing factor is our incomplete understanding of the pathogenesis of E. coli meningitis. We have shown that E. coli penetration into the brain requires E. coli invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. E. coli invasion of HBMEC involves its interaction with HBMEC receptors, such as E. coli cytotoxic necrotizing factor 1 (CNF1) interacti...

  1. Cultured bovine brain capillary endothelial cells (BBCEC) - a blood-brain barrier model for studying the binding and internalization of insulin and insulin-like growth factor 1

    Energy Technology Data Exchange (ETDEWEB)

    Keller, B.T.; Borchardt, R.T.

    1987-05-01

    Cultured bovine brain capillary endothelial cells (BBCEC) have previously been reported by their laboratory as a working model for studying nutrient and drug transport and metabolism at the blood-brain barrier. In the present study, they have utilized this culture system to investigate the binding and internalization of (/sup 125/I)-labelled insulin (INS) and insulin-like growth factor 1(IGF-1) by BBCEC. After 2 hrs at 23/sup 0/C, the specific binding of INS and IGF-1 was 1.6% and 13.6%, respectively. At 37/sup 0/C, the maximum specific binding was 0.9% for INS and 5.8% for IGF-1. Using an acid-wash technique to assess peptide internalization, it was observed that, at 37/sup 0/C, approximately 60% of the bound INS rapidly became resistant to acid treatment, a value which was constant over 2 hr. With IGF-1, a similar proportion of the bound material, 62%, became resistant by 30 min, but subsequently decreased to 45% by 2 hr. Scatchard analysis of competitive binding studies indicated the presence of two binding sites for each protein, having K/sub d/'s of 0.82 nM and 19.2 nM for INS and 0.39 nM and 3.66 nM for IGF-1. Little change in the amount of INS binding was observed over a four-day interval as the cultures became a confluent monolayer. The present report of binding and internalization of these proteins suggests that the BBCEC may utilize a receptor-mediated process to internalize and/or transport (transcytosis) INS and IGF-1 from the circulation.

  2. The Blood-Brain Barrier Permeability of Lignans and Malabaricones from the Seeds of Myristica fragrans in the MDCK-pHaMDR Cell Monolayer Model

    Directory of Open Access Journals (Sweden)

    Ni Wu

    2016-01-01

    Full Text Available The blood-brain barrier (BBB permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (Papp were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane-type and arylnaphthalene-type lignans showed poor to moderate permeabilities with Papp values at 10−8–10−6 cm/s; those of 8-O-4′-neolignan and tetrahydrofuran-lignan were at 10−6–10−5 cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their Papp values were at 10−8–10−7 cm/s. To 5-methoxy-dehydrodiisoeugenol (2, erythro-2-(4-allyl-2,6-dimethoxyphenoxy-1-(3,4-dimethoxyphenyl-propan-1-ol acetate (6, verrucosin (8, and nectandrin B (9, an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1, myrislignan (7 and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg.

  3. A large-scale electrophoresis- and chromatography-based determination of gene expression profiles in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties

    Directory of Open Access Journals (Sweden)

    Duban-Deweer Sophie

    2010-11-01

    Full Text Available Abstract Background Brain capillary endothelial cells (BCECs form the physiological basis of the blood-brain barrier (BBB. The barrier function is (at least in part due to well-known proteins such as transporters, tight junctions and metabolic barrier proteins (e.g. monoamine oxidase, gamma glutamyltranspeptidase and P-glycoprotein. Our previous 2-dimensional gel proteome analysis had identified a large number of proteins and revealed the major role of dynamic cytoskeletal remodelling in the differentiation of bovine BCECs. The aim of the present study was to elaborate a reference proteome of Triton X-100-soluble species from bovine BCECs cultured in the well-established in vitro BBB model developed in our laboratory. Results A total of 215 protein spots (corresponding to 130 distinct proteins were identified by 2-dimensional gel electrophoresis, whereas over 350 proteins were identified by a shotgun approach. We classified around 430 distinct proteins expressed by bovine BCECs. Our large-scale gene expression analysis enabled the correction of mistakes referenced into protein databases (e.g. bovine vinculin and constitutes valuable evidence for predictions based on genome annotation. Conclusions Elaboration of a reference proteome constitutes the first step in creating a gene expression database dedicated to capillary endothelial cells displaying BBB characteristics. It improves of our knowledge of the BBB and the key proteins in cell structures, cytoskeleton organization, metabolism, detoxification and drug resistance. Moreover, our results emphasize the need for both appropriate experimental design and correct interpretation of proteome datasets.

  4. Safety-barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian networks...... are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information...... from risk analysis with operational safety management....

  5. Safety-barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2007-01-01

    Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian networks...... are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information...... from risk analysis with operational safety management....

  6. Safety- barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2008-01-01

    Safety-barrier diagrams and the related so-called 'bow-tie' diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation of safety-barrier diagrams to other methods such as fault...... trees and Bayesian networks is discussed. A simple method for quantification of safety-barrier diagrams is proposed. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk analysis with operational safety management....

  7. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Directory of Open Access Journals (Sweden)

    Kelsey Roe

    Full Text Available Characterizing the mechanisms by which West Nile virus (WNV causes blood-brain barrier (BBB disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE. Infection with WNV (NY99 strain significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1 did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101 strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  8. Blood-brain barrier permeability imaging using perfusion computed tomography

    Directory of Open Access Journals (Sweden)

    Avsenik Jernej

    2015-06-01

    Full Text Available Background. The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases.

  9. Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood–brain barrier and glioma cells

    Directory of Open Access Journals (Sweden)

    Bruun J

    2015-09-01

    Full Text Available Jonas Bruun,1 Trine B Larsen,1 Rasmus I Jølck,1 Rasmus Eliasen,1 René Holm,2 Torben Gjetting,1 Thomas L Andresen11Department of Micro- and Nanotechnology, Center for Nanomedicine and Theranostics, Technical University of Denmark, DTU Nanotech, Lyngby, Denmark; 2H Lundbeck A/S, Biologics and Pharmaceutical Science, Valby, DenmarkAbstract: Clinical applications of siRNA for treating disorders in the central nervous system require development of systemic stable, safe, and effective delivery vehicles that are able to cross the impermeable blood–brain barrier (BBB. Engineering nanocarriers with low cellular interaction during systemic circulation, but with high uptake in targeted cells, is a great challenge and is further complicated by the BBB. As a first step in obtaining such a delivery system, this study aims at designing a lipid nanoparticle (LNP able to efficiently encapsulate siRNA by a combination of titratable cationic lipids. The targeted delivery is obtained through the design of a two-stage system where the first step is conjugation of angiopep to the surface of the LNP for targeting the low-density lipoprotein receptor-related protein-1 expressed on the BBB. Second, the positively charged LNPs are masked with a negatively charged PEGylated (poly(ethylene glycol cleavable lipopeptide, which contains a recognition sequence for matrix metalloproteinases (MMPs, a class of enzymes often expressed in the tumor microenvironment and inflammatory BBB conditions. Proteolytic cleavage induces PEG release, including the release of four glutamic acid residues, providing a charge switch that triggers a shift of the LNP charge from weakly negative to positive, thus favoring cellular endocytosis and release of siRNA for high silencing efficiency. This work describes the development of this two-stage nanocarrier-system and evaluates the performance in brain endothelial and glioblastoma cells with respect to uptake and gene silencing efficiency. The

  10. Hexavalent chromium at low concentration alters Sertoli cell barrier and connexin 43 gap junction but not claudin-11 and N-cadherin in the rat seminiferous tubule culture model

    Energy Technology Data Exchange (ETDEWEB)

    Carette, Diane [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Perrard, Marie-Hélène, E-mail: marie-helene.durand@ens-lyon.fr [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Prisant, Nadia [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Gilleron, Jérome; Pointis, Georges [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); Segretain, Dominique [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Durand, Philippe [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Kallistem SAS Ecole Normale Supérieure de Lyon, Lyon (France)

    2013-04-01

    Exposure to toxic metals, specifically those belonging to the nonessential group leads to human health defects and among them reprotoxic effects. The mechanisms by which these metals produce their negative effects on spermatogenesis have not been fully elucidated. By using the Durand's validated seminiferous tubule culture model, which mimics the in vivo situation, we recently reported that concentrations of hexavalent chromium, reported in the literature to be closed to that found in the blood circulation of men, increase the number of germ cell cytogenetic abnormalities. Since this metal is also known to affect cellular junctions, we investigated, in the present study, its potential influence on the Sertoli cell barrier and on junctional proteins present at this level such as connexin 43, claudin-11 and N-cadherin. Cultured seminiferous tubules in bicameral chambers expressed the three junctional proteins and ZO-1 for at least 12 days. Exposure to low concentrations of chromium (10 μg/l) increased the trans-epithelial resistance without major changes of claudin-11 and N-cadherin expressions but strongly delocalized the gap junction protein connexin 43 from the membrane to the cytoplasm of Sertoli cells. The possibility that the hexavalent chromium-induced alteration of connexin 43 indirectly mediates the effect of the toxic metal on the blood–testis barrier dynamic is postulated. - Highlights: ► Influence of Cr(VI) on the Sertoli cell barrier and on junctional proteins ► Use of cultured seminiferous tubules in bicameral chambers ► Low concentrations of Cr(VI) (10 μg/l) altered the trans-epithelial resistance. ► Cr(VI) did not alter claudin-11 and N-cadherin. ► Cr(VI) delocalized connexin 43 from the membrane to the cytoplasm of Sertoli cells.

  11. The importance of dye chemistry and TiCl4 surface treatment in the behavior of Al2O3 recombination barrier layers deposited by atomic layer deposition in solid-state dye-sensitized solar cells

    KAUST Repository

    Brennan, Thomas P.

    2012-01-01

    Atomic layer deposition (ALD) was used to fabricate Al 2O 3 recombination barriers in solid-state dye-sensitized solar cells (ss-DSSCs) employing an organic hole transport material (HTM) for the first time. Al 2O 3 recombination barriers of varying thickness were incorporated into efficient ss-DSSCs utilizing the Z907 dye adsorbed onto a 2 μm-thick nanoporous TiO 2 active layer and the HTM spiro-OMeTAD. The impact of Al 2O 3 barriers was also studied in devices employing different dyes, with increased active layer thicknesses, and with substrates that did not undergo the TiCl 4 surface treatment. In all instances, electron lifetimes (as determined by transient photovoltage measurements) increased and dark current was suppressed after Al 2O 3 deposition. However, only when the TiCl 4 treatment was eliminated did device efficiency increase; in all other instances efficiency decreased due to a drop in short-circuit current. These results are attributed in the former case to the similar effects of Al 2O 3 ALD and the TiCl 4 surface treatment whereas the insulating properties of Al 2O 3 hinder charge injection and lead to current loss in TiCl 4-treated devices. The impact of Al 2O 3 barrier layers was unaffected by doubling the active layer thickness or using an alternative ruthenium dye, but a metal-free donor-π-acceptor dye exhibited a much smaller decrease in current due to its higher excited state energy. We develop a model employing prior research on Al 2O 3 growth and dye kinetics that successfully predicts the reduction in device current as a function of ALD cycles and is extendable to different dye-barrier systems. © This journal is the Owner Societies 2012.

  12. Retinal Vascular Endothelial Growth Factor Induces Intercellular Adhesion Molecule-1 and Endothelial Nitric Oxide Synthase Expression and Initiates Early Diabetic Retinal Leukocyte Adhesion in Vivo

    OpenAIRE

    Joussen, Antonia M; Poulaki, Vassiliki; Qin, Wenying; Kirchhof, Bernd; Mitsiades, Nicholas; Wiegand, Stanley J; Rudge, John; George D. Yancopoulos; Adamis, Anthony P.

    2002-01-01

    Leukocyte adhesion to the diabetic retinal vasculature results in early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Previous work has shown that intercellular adhesion molecule-1 (ICAM-1) and CD18 are required for these processes. However the relevant in vivo stimuli for ICAM-1 and CD18 expression in diabetes remain unknown. The current study investigated the causal role of endogenous vascular endothelial growth factor (VEGF) and nitric oxid...

  13. Photoreceptor Degeneration Changes Magnetic Resonance Imaging Features in a Mouse Model of Retinitis Pigmentosa

    OpenAIRE

    Wang, Qing; Song, Sheng-Kwei; Zhang, Huiying; Berkowitz, Bruce A.; Chen, Shiming; Wickline, Samuel A.; Chen, Junjie

    2011-01-01

    Retinal degeneration-1 (rd1) mice are animal models of retinitis pigmentosa, a blinding disease caused by photoreceptor cell degeneration. This study aims to determine magnetic resonance imaging (MRI) changes in retinas of 1- and 3-month-old rd1 mice. Apparent diffusion coefficient in retina was measured using diffusion MRI. The blood-retinal barrier leakage was evaluated using gadolinium-diethylenetriaminepentaacetic acid-enhanced T1-weighted MRI before and after systemic gadolinium-diethyle...

  14. Multilayer moisture barrier

    Energy Technology Data Exchange (ETDEWEB)

    Pankow, Joel W; Jorgensen, Gary J; Terwilliger, Kent M; Glick, Stephen H; Isomaki, Nora; Harkonen, Kari; Turkulainen, Tommy

    2015-04-21

    A moisture barrier, device or product having a moisture barrier or a method of fabricating a moisture barrier having at least a polymer layer, and interfacial layer, and a barrier layer. The polymer layer may be fabricated from any suitable polymer including, but not limited to, fluoropolymers such as polyethylene terephthalate (PET) or polyethylene naphthalate (PEN), or ethylene-tetrafluoroethylene (ETFE). The interfacial layer may be formed by atomic layer deposition (ALD). In embodiments featuring an ALD interfacial layer, the deposited interfacial substance may be, but is not limited to, Al.sub.2O.sub.3, AlSiO.sub.x, TiO.sub.2, and an Al.sub.2O.sub.3/TiO.sub.2 laminate. The barrier layer associated with the interfacial layer may be deposited by plasma enhanced chemical vapor deposition (PECVD). The barrier layer may be a SiO.sub.xN.sub.y film.

  15. "Targeted disruption of the epithelial-barrier by Helicobacter pylori"

    Directory of Open Access Journals (Sweden)

    Wroblewski Lydia E

    2011-11-01

    Full Text Available Abstract Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gastric epithelial barrier.

  16. Toward guided tissue and bone regeneration: morphology, attachment, proliferation, and migration of cells cultured on collagen barrier membranes. A systematic review.

    NARCIS (Netherlands)

    Behring, J.; Junker, R.; Walboomers, X.F.; Chessnut, B.; Jansen, J.A.

    2008-01-01

    Collagen barrier membranes are frequently used in both guided tissue regeneration (GTR) and guided bone regeneration (GBR). Collagen used for these devices is available from different species and is often processed to alter the properties of the final product. This is necessary because unprocessed c

  17. The blood-tendon barrier: identification and characterisation of a novel tissue barrier in tendon blood vessels.

    Science.gov (United States)

    Lehner, C; Gehwolf, R; Ek, J C; Korntner, S; Bauer, H; Bauer, H C; Traweger, A; Tempfer, H

    2016-01-01

    Tissue barriers function as "gate keepers" between different compartments (usually blood and tissue) and are formed by specialised membrane-associated proteins, localising to the apicolateral plasma membrane domain of epithelial and endothelial cells. By sealing the paracellular space, the free diffusion of solutes and molecules across epithelia and endothelia is impeded. Thereby, tissue barriers contribute to the establishment and maintenance of a distinct internal and external environment, which is crucial during organ development and allows maintenance of an organ-specific homeostatic milieu. So far, various epithelial and endothelial tissue barriers have been described, including the blood-brain barrier, the blood-retina barrier, the blood-testis barrier, the blood-placenta barrier, and the cerebrospinal fluid (CSF)-brain barrier, which are vital for physiological function and any disturbance of these barriers can result in severe organ damage or even death. Here, we describe the identification of a novel barrier, located in the vascular bed of tendons, which we term the blood-tendon barrier (BTB). By using immunohistochemistry, transmission electron microscopy, and tracer studies we demonstrate the presence of a functional endothelial barrier within tendons restricting the passage of large blood-borne molecules into the surrounding tendon tissue. We further provide in vitro evidence that the BTB potentially contributes to the creation of a distinct internal tissue environment impacting upon the proliferation and differentiation of tendon-resident cells, effects which might be fundamental for the onset of tendon pathologies. PMID:27227787

  18. Penetration through the Skin Barrier

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Benfeldt, Eva; Holmgaard, Rikke

    2016-01-01

    . During recent decades, the latter has received increased attention as a route for intentionally delivering drugs to patients. This has stimulated research in methods for sampling, measuring and predicting percutaneous penetration. Previous chapters have described how different endogenous, genetic and...... exogenous factors may affect barrier characteristics. The present chapter introduces the theory for barrier penetration (Fick's law), and describes and discusses different methods for measuring the kinetics of percutaneous penetration of chemicals, including in vitro methods (static and flow......-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous...

  19. Liquid metal hydrogen barriers

    International Nuclear Information System (INIS)

    Hydrogen barriers are disclosed which comprise liquid metals in which the solubility of hydrogen is low and which have good thermal conductivities at operating temperatures of interest. Such barriers are useful in nuclear fuel elements containing a metal hydride moderator which has a substantial hydrogen dissociation pressure at reactor operating temperatures. 2 claims, 3 figures

  20. Catalytic thermal barrier coatings

    Science.gov (United States)

    Kulkarni, Anand A.; Campbell, Christian X.; Subramanian, Ramesh

    2009-06-02

    A catalyst element (30) for high temperature applications such as a gas turbine engine. The catalyst element includes a metal substrate such as a tube (32) having a layer of ceramic thermal barrier coating material (34) disposed on the substrate for thermally insulating the metal substrate from a high temperature fuel/air mixture. The ceramic thermal barrier coating material is formed of a crystal structure populated with base elements but with selected sites of the crystal structure being populated by substitute ions selected to allow the ceramic thermal barrier coating material to catalytically react the fuel-air mixture at a higher rate than would the base compound without the ionic substitutions. Precious metal crystallites may be disposed within the crystal structure to allow the ceramic thermal barrier coating material to catalytically react the fuel-air mixture at a lower light-off temperature than would the ceramic thermal barrier coating material without the precious metal crystallites.

  1. Transport of Twelve Coumarins from Angelicae Pubescentis Radix across a MDCK-pHaMDR Cell Monolayer—An in Vitro Model for Blood-Brain Barrier Permeability

    OpenAIRE

    Yan-Fang Yang; Wei Xu; Wei Song; Min Ye; Xiu-Wei Yang

    2015-01-01

    Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine, is reported to have central nervous system activities. The purpose of this study was to characterize the blood-brain barrier permeability of twelve coumarins from APR including umbelliferone (1), osthol (2), scopoletin (3), peucedanol (4), ulopterol (5), angepubebisin (6), psoralen (7), xanthotoxin (8), bergapten (9), isoimperatorin (10), columbianadin (11), and columbianetin acetate (12) with an in vitro model usi...

  2. Uropathogenic E. coli Promote a Paracellular Urothelial Barrier Defect Characterized by Altered Tight Junction Integrity, Epithelial Cell Sloughing and Cytokine Release

    OpenAIRE

    Wood, M W; Breitschwerdt, E B; Nordone, S.K.; Linder, K. E.; Gookin, J.L.

    2011-01-01

    The urinary bladder is a common site of bacterial infection with a majority of cases attributed to uropathogenic Escherichia coli. Sequels of urinary tract infections (UTIs) include the loss of urothelial barrier function and subsequent clinical morbidity secondary to the permeation of urine potassium, urea and ammonia into the subepithelium. To date there has been limited research describing the mechanism by which this urothelial permeability defect develops. The present study models acute u...

  3. Investigation of auxiliary heating in tandem mirrors and tokamaks and barrier cell pumping. Annual progress report, October 1, 1980 to December 31, 1981

    International Nuclear Information System (INIS)

    The research has focussed on physics questions concerned with ECRH heating in tandem mirror plugs, pumping of tandem mirror thermal barriers by drift orbits, ICRH heating in tokamaks, and bundle divertors. We have concluded that drift-orbit pumping of thermal barriers is not feasible because the azimuthal E Vector X B Vector drift limits the excursion of trapped ions from a flux surface. We have developed a three-dimensional weakly relativistic (T/sub e/ less than or equal to 50 keV) ray tracing and absorption code for electron cyclotron heating in tandem mirror plugs and barriers. Cases run for TMX, MFTF-B and reactors at T/sub e/ > 10 keV show that strong absorption per pass is present and a careful choice of wave frequency and launch angle is required to ensure wave penetration and absorption in the plasma core. In the area of ion cyclotron frequency range heating in tokamaks, a three-dimensional hot plasma ray tracing theory and code has been developed to handle rays launched from any poloidal angle in the tokamak cross section. Wave heating in the central strong absorption zones is currently being investigated using a full wave solution for the various heating regimes

  4. Complementary barrier infrared detector (CBIRD)

    Science.gov (United States)

    Ting, David Z. (Inventor); Bandara, Sumith V. (Inventor); Hill, Cory J. (Inventor); Gunapala, Sarath D. (Inventor)

    2013-01-01

    An infrared detector having a hole barrier region adjacent to one side of an absorber region, an electron barrier region adjacent to the other side of the absorber region, and a semiconductor adjacent to the electron barrier.

  5. Mucus as a Barrier to Drug Delivery

    DEFF Research Database (Denmark)

    Bøgh, Marie; Nielsen, Hanne Mørck

    2015-01-01

    Viscoelastic mucus lines all mucosal surfaces of the body and forms a potential barrier to mucosal drug delivery. Mucus is mainly composed of water and mucins; high-molecular weight glycoproteins forming an entangled network. Consequently, mucus forms a steric barrier and due to its negative charge...... complex gel barrier to drug delivery. Current knowledge of mucus characteristics and barrier properties, as achieved by state-of-the-art methodologies, is the topic of this MiniReview emphasizing the gastrointestinal mucus and an overall focus on oral drug delivery. Cell culture-based in vitro models are...... well-established as essential tools in drug research and development, but traditionally, mucus-containing models have only rarely been applied. However, a number of mucus-containing in vitro models have recently been described in the literature and their properties and applications will be reviewed and...

  6. Converse Barrier Certificate Theorem

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2013-01-01

    This paper presents a converse barrier certificate theorem for a generic dynamical system.We show that a barrier certificate exists for any safe dynamical system defined on a compact manifold. Other authors have developed a related result, by assuming that the dynamical system has no singular...... points in the considered subset of the state space. In this paper, we redefine the standard notion of safety to comply with generic dynamical systems with multiple singularities. Afterwards, we prove the converse barrier certificate theorem and illustrate the differences between ours and previous work by...

  7. Recycler barrier RF buckets

    Energy Technology Data Exchange (ETDEWEB)

    Bhat, C.M.; /Fermilab

    2011-03-01

    The Recycler Ring at Fermilab uses a barrier rf systems for all of its rf manipulations. In this paper, I will give an overview of historical perspective on barrier rf system, the longitudinal beam dynamics issues, aspects of rf linearization to produce long flat bunches and methods used for emittance measurements of the beam in the RR barrier rf buckets. Current rf manipulation schemes used for antiproton beam stacking and longitudinal momentum mining of the RR beam for the Tevatron collider operation are explained along with their importance in spectacular success of the Tevatron luminosity performance.

  8. Recycler barrier RF buckets

    CERN Document Server

    Bhat, C M

    2012-01-01

    The Recycler Ring at Fermilab uses a barrier rf system for all of its rf manipulations. In this paper, I will give an overview of historical perspective on barrier rf systems, the longitudinal beam dynamics issues, aspects of rf linearization to produce long flat bunches and methods used for emittance measurements of the beam in the RR barrier rf buckets. Current rf manipulation schemes used for antiproton beam stacking and longitudinal momentum mining of the RR beam for the Tevatron collider operation are explained along with their importance in spectacular success of the Tevatron luminosity performance.

  9. Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Deng Xiaolu

    2011-04-01

    Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α, a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC barrier dysfunction. Methods Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL. RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER. p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability. Results We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER. Conclusions Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF

  10. Protective barrier development: Overview

    International Nuclear Information System (INIS)

    Protective barrier and warning marker systems are being developed to isolate wastes disposed of near the earth's surface at the Hanford Site. The barrier is designed to function in an arid to semiarid climate, to limit infiltration and percolation of water through the waste zone to near-zero, to be maintenance free, and to last up to 10,000 yr. Natural materials (e.g., fine soil, sand, gravel, riprap, clay, asphalt) have been selected to optimize barrier performance and longevity and to create an integrated structure with redundant features. These materials isolate wastes by limiting water drainage; reducing the likelihood of plant, animal, and human intrusion; controlling emission of noxious gases; and minimizing erosion. Westinghouse Hanford Company and Pacific Northwest Laboratory efforts to assess the performance of various barrier and marker designs will be discussed

  11. Information barriers and authentication

    International Nuclear Information System (INIS)

    Acceptance of nuclear materials into a monitoring regime is complicated if the materials are in classified shapes or have classified composition. An attribute measurement system with an information barrier can be emplo,yed to generate an unclassified display from classified measurements. This information barrier must meet two criteria: (1) classified information cannot be released to the monitoring party, and (2) the monitoring party must be convinced that the unclassified output accurately represents the classified input. Criterion 1 is critical to the host country to protect the classified information. Criterion 2 is critical to the monitoring party and is often termed the 'authentication problem.' Thus, the necessity for authentication of a measurement system with an information barrier stems directly from the description of a useful information barrier. Authentication issues must be continually addressed during the entire development lifecycle of the measurement system as opposed to being applied only after the system is built.

  12. Hemicellulose as barrier material

    OpenAIRE

    Jonas, Hartman

    2006-01-01

    Polysaccharides constitute an important source of raw materials for the packaging industry today. Polysaccharides have good natural barrier properties which are necessary for packaging films. Cellulose is the forerunner among renewable polymers for such applications. Hemicelluloses represent a new interesting breed of barrier materials. We have chosen to work with the hemicellulose O-acetyl-galactoglucomannan (AcGGM). The high water solubility of this particular hemicellulose extracted from p...

  13. Barriers to SCM implementing

    OpenAIRE

    M.E. Rosli; B. Md Dero; A.R. Ismail; M.N. Ab Rahman

    2008-01-01

    Purpose: This paper explores the barriers faced by Malaysian manufacturing companies in successfullyimplementing the Supply Chain Management (SCM). The study has highlighted some pertinent factorsperforming the barriers that are most frequently reported by the studied companies. Sixteen companies, fromservice and manufacturing companies were studied over a period of two years to assess their SCM practicesthrough survey and interview processes.Design/methodology/approach: This part discusses t...

  14. Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood–brain barrier model for drug permeability studies

    OpenAIRE

    Eigenmann, Daniela E; Xue, Gongda; Kwang S Kim; Moses, Ashlee V.; Hamburger, Matthias; Oufir, Mouhssin

    2013-01-01

    Background Reliable human in vitro blood–brain barrier (BBB) models suitable for high-throughput screening are urgently needed in early drug discovery and development for assessing the ability of promising bioactive compounds to overcome the BBB. To establish an improved human in vitro BBB model, we compared four currently available and well characterized immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, with respect to barrier tightness and paracellu...

  15. Electrochemical reduction of CO2 and H2O into fuels: Cell types and kinetic barriers

    OpenAIRE

    Mogensen, Mogens Bjerg

    2013-01-01

    Some water electrolysers like alkaline electrolyser cells (AEC) and polymer electrolyte membrane electrolyser cell (PEMEC) have been commercially available for many decades, but for production of hydrogen for fuel using renewable electricity they are not yet affordable because of a too low ratio of production rate/cost. Production rate is determined mainly by electrode kinetics. Therefore, parallel to improving the electrodes of these electrolyser cells, other cell types, which have faster el...

  16. Stretchable graphene barriers for organic optoelectronic devices

    Science.gov (United States)

    Kong, Casey

    This thesis describes the use of a transparent, stretchable gas barrier film used to encapsulate organic devices in order to protect them from chemical degradation. One of the major issues with current organic semiconductor materials is that they are susceptible to degradation when exposed to oxygen and water vapor in the ambient atmosphere. In order to take advantage of these materials, stretchable barrier films must also be developed. Solar cell devices were fabricated using an organic bulk heterojunction blend of poly(3-heptylthiophene) and phenyl-C61-butyric acid methyl ester (P3HpT:PCBM). Stretchable barrier films were fabricated with graphene and polyurethane (PU) using a simple dip coating process. Devices encapsulated with an unstrained graphene/PU barrier film retained 60.6 +/- 3.7% efficiency after 10 days, exhibiting barrier properties similar to that of a control device encapsulated with glass (61.1 +/- 3.2%). Measurements over the course of 1 day showed that graphene/PU films strained up to 20% were still able to maintain 91.5 +/- 2.8% efficiency. Electrical resistance measurements showed that graphene cracks around 6% strain. This work highlights the potential impact graphene/PU barrier films may have on stretchable electronics.

  17. DNA nanovehicles and the biological barriers

    DEFF Research Database (Denmark)

    Okholm, Anders Hauge; Kjems, Jørgen

    2016-01-01

    modules. The applications of DNA nanostructures are still in its infancy, but one of the high expectations are to deliver solutions for targeted therapy. Nucleic acids, however, do not easily enter cells unassisted and biological barriers and harsh nucleolytic conditions in the human body must also be...

  18. Tandem mirror reactor with thermal barriers

    International Nuclear Information System (INIS)

    This report gives detailed information in the form of the following chapters: (1) overview, (2) plasma physics, (3) magnets, (4) end-plug neutral beams, (5) barrier pump neutral beams, (6) ecr heating, (7) plasma direct converter, and (8) central cell

  19. DNA nanovehicles and the biological barriers

    DEFF Research Database (Denmark)

    Okholm, Anders Hauge; Kjems, Jørgen

    2016-01-01

    modules. The applications of DNA nanostructures are still in its infancy, but one of the high expectations are to deliver solutions for targeted therapy. Nucleic acids, however, do not easily enter cells unassisted and biological barriers and harsh nucleolytic conditions in the human body must also...

  20. Enhanced Densification of SDC Barrier Layers

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, John S.; Templeton, Jared W.; Lu, Zigui; Stevenson, Jeffry W.

    2011-09-12

    This technical report explores the Enhanced Densification of SCD Barrier Layers A samaria-doped ceria (SDC) barrier layer separates the lanthanum strontium cobalt ferrite (LSCF) cathode from the yttria-stabilized zirconia (YSZ) electrolyte in a solid oxide fuel cell (SOFC) to prevent the formation of electrically resistive interfacial SrZrO{sub 3} layers that arise from the reaction of Sr from the LSCF with Zr from the YSZ. However, the sintering temperature of this SDC layer must be limited to {approx}1200 C to avoid extensive interdiffusion between SDC and YSZ to form a resistive CeO{sub 2}-ZrO{sub 2} solid solution. Therefore, the conventional SDC layer is often porous and therefore not as impervious to Sr-diffusion as would be desired. In the pursuit of improved SOFC performance, efforts have been directed toward increasing the density of the SDC barrier layer without increasing the sintering temperature. The density of the SDC barrier layer can be greatly increased through small amounts of Cu-doping of the SDC powder together with increased solids loading and use of an appropriate binder system in the screen print ink. However, the resulting performance of cells with these barrier layers did not exhibit the expected increase in accordance with that achieved with the prototypical PLD SDC layer. It was determined by XRD that increased sinterability of the SDC also results in increased interdiffusivity between the SDC and YSZ, resulting in formation of a highly resistive solid solution.

  1. Method of installing subsurface barrier

    Science.gov (United States)

    Nickelson, Reva A.; Richardson, John G.; Kostelnik, Kevin M.; Sloan, Paul A.

    2007-10-09

    Systems, components, and methods relating to subterranean containment barriers. Laterally adjacent tubular casings having male interlock structures and multiple female interlock structures defining recesses for receiving a male interlock structure are used to create subterranean barriers for containing and treating buried waste and its effluents. The multiple female interlock structures enable the barriers to be varied around subsurface objects and to form barrier sidewalls. The barrier may be used for treating and monitoring a zone of interest.

  2. Improved conversion efficiency of Ag2S quantum dot-sensitized solar cells based on TiO2 nanotubes with a ZnO recombination barrier layer

    Directory of Open Access Journals (Sweden)

    Chen Chong

    2011-01-01

    Full Text Available Abstract We improve the conversion efficiency of Ag2S quantum dot (QD-sensitized TiO2 nanotube-array electrodes by chemically depositing ZnO recombination barrier layer on plain TiO2 nanotube-array electrodes. The optical properties, structural properties, compositional analysis, and photoelectrochemistry properties of prepared electrodes have been investigated. It is found that for the prepared electrodes, with increasing the cycles of Ag2S deposition, the photocurrent density and the conversion efficiency increase. In addition, as compared to the Ag2S QD-sensitized TiO2 nanotube-array electrode without the ZnO layers, the conversion efficiency of the electrode with the ZnO layers increases significantly due to the formation of efficient recombination layer between the TiO2 nanotube array and electrolyte.

  3. Skin barrier in rosacea.

    Science.gov (United States)

    Addor, Flavia Alvim Sant'Anna

    2016-01-01

    Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea. PMID:26982780

  4. Fuzzy barrier distributions

    International Nuclear Information System (INIS)

    Heavy-ion collisions often produce a fusion barrier distribution with structures displaying a fingerprint of couplings to highly collective excitations [1]. Basically the same distribution can be obtained from large-angle quasi-elastic scattering, though here the role of the many weak direct-reaction channels is unclear. For 20Ne + 90Zr we have observed the barrier structures expected for the highly deformed neon projectile, but for 20Ne + 92Zr we find completely smooth distribution (see Fig.1). We find that transfer channels in these systems are of similar strength but single particle excitations are significantly stronger in the latter case. They apparently reduce the 'resolving power' of the quasi-elastic channel, what leads to smeared out, or 'fuzzy' barrier distribution. This is the first case when such a phenomenon has been observed.(author)

  5. Y0.08Sr0.88TiO3-CeO2 composite as a diffusion barrier layer for stainless-steel supported solid oxide fuel cell

    Science.gov (United States)

    Kim, Kun Joong; Kim, Sun Jae; Choi, Gyeong Man

    2016-03-01

    A new diffusion barrier layer (DBL) is proposed for solid oxide fuel cells (SOFCs) supported on stainless-steel where DBL prevents inter-diffusion of atoms between anode and stainless steel (STS) support during fabrication and operation of STS-supported SOFCs. Half cells consisting of dense yttria-stabilized zirconia (YSZ) electrolyte, porous Ni-YSZ anode layer, and ferritic STS support, with or without Y0.08Sr0.88TiO3-CeO2 (YST-CeO2) composite DBL, are prepared by tape casting and co-firing at 1250 and 1350 °C, respectively, in reducing (H2) atmosphere. The porous YST-CeO2 layer (t ∼ 60 μm) blocks inter-diffusion of Fe and Ni, and captures the evaporated Cr during cell fabrication (1350 °C). The cell with DBL and La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) cathode achieved a maximum power density of ∼220 mW cm-2 which is stable at 700 °C. In order to further improve the power performance, Ni coarsening in anode during co-firing must be prevented or alternative anode which is resistive to coarsening is suggested. This study demonstrates that the new YST-CeO2 layer is a promising as a DBL for stainless-steel-supported SOFCs fabricated with co-firing process.

  6. Four-level nonvolatile small-molecule memory-cell embedded with Fe nanocrystals surrounded with an FeO and Fe{sub 2}O{sub 3} tunneling barrier

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Sung-Ho; Nam, Woo-Sik; Park, Kwang-Hee; Park, Jea-Gun [Hanyang University, Seoul (Korea, Republic of)

    2010-12-15

    We developed a nonvolatile cross-bar 4F{sup 2} small molecule (Alq{sub 3}: aluminum tris (8-hydroxyquinoline)) memory cell embedded with Fe nanocrystals surrounded by an FeO and Fe{sub 2}O{sub 3} tunneling barrier. The memory cell demonstrates a memory margin (I{sub on}/I{sub off} ratio) of {approx}7.44 x 10{sup 2} and a retention-time of {approx}10{sup 5} sec for four current levels (I{sub off}: 2.73 x 10{sup -8}, I{sub int2}: 5.87 x 10{sup -7}, I{sub int1}: 3.64 x 10{sup -6}, and I{sub on}: 2.03 x 10{sup -5} A), which can probably be extended to ten years. Memory cells of this type follow a current conduction mechanism with space-charge-limited-current and F-N tunneling for nonvolatile memory cell operation.

  7. Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation

    Directory of Open Access Journals (Sweden)

    Floor Twiss

    2012-09-01

    Proper regulation of the formation and stabilization of epithelial cell–cell adhesion is crucial in embryonic morphogenesis and tissue repair processes. Defects in this process lead to organ malformation and defective epithelial barrier function. A combination of chemical and mechanical cues is used by cells to drive this process. We have investigated the role of the actomyosin cytoskeleton and its connection to cell–cell junction complexes in the formation of an epithelial barrier in MDCK cells. We find that the E-cadherin complex is sufficient to mediate a functional link between cell–cell contacts and the actomyosin cytoskeleton. This link involves the actin binding capacity of α-catenin and the recruitment of the mechanosensitive protein Vinculin to tensile, punctate cell–cell junctions that connect to radial F-actin bundles, which we name Focal Adherens Junctions (FAJ. When cell–cell adhesions mature, these FAJs disappear and linear junctions are formed that do not contain Vinculin. The rapid phase of barrier establishment (as measured by Trans Epithelial Electrical Resistance (TER correlates with the presence of FAJs. Moreover, the rate of barrier establishment is delayed when actomyosin contraction is blocked or when Vinculin recruitment to the Cadherin complex is prevented. Enhanced presence of Vinculin increases the rate of barrier formation. We conclude that E-cadherin-based FAJs connect forming cell–cell adhesions to the contractile actomyosin cytoskeleton. These specialized junctions are sites of Cadherin mechanosensing, which, through the recruitment of Vinculin, is a driving force in epithelial barrier formation.

  8. The transplantation barrier of nude mice

    OpenAIRE

    Moll, Heidrun; Bösing-Schneider, Rita

    2010-01-01

    Syngeneic memory cells can be stimulated to yield a secondary immune response after their transfer into irradiated euthymie recipients as well as into young thymusless nude mice. It is shown that nude mice older than twelve weeks of age are not permissive towards memory cell activation as it is found in non-irradiated euthymie animals. This barrier to isogeneie or congeneic cells seems to be caused by a pool of cyclophosphamide-sensitive cells. Since young nude mice could be rendered as unper...

  9. Asthma: the importance of dysregulated barrier immunity.

    Science.gov (United States)

    Lambrecht, Bart N; Hammad, Hamida

    2013-12-01

    Chronic asthma is an inflammatory disease of the airway wall that leads to bronchial smooth muscle hyperreactivity and airway obstruction, caused by inflammation, goblet cell metaplasia, and airway wall remodeling. In response to allergen presentation by airway DCs, T-helper lymphocytes of the adaptive immune system control many aspects of the disease through secretion of IL-4, IL-5, IL-13, IL-17, and IL-22, and these are counterbalanced by cytokines produced by Treg cells. Many cells of the innate immune system such as mast cells, basophils, neutrophils, eosinophils, and innate lymphoid cells also play an important role in disease pathogenesis. Barrier epithelial cells are being ever more implicated in disease pathogenesis than previously thought, as these cells have in recent years been shown to sense exposure to allergens via pattern recognition receptors and to activate conventional and inflammatory-type DCs and other innate immune cells through the secretion of thymic stromal lymphopoietin, granulocyte-macrophage colony stimulating factor, IL-1, IL-33, and IL-25. Understanding this cytokine crosstalk between barrier epithelial cells, DCs, and immune cells provides important insights into the mechanisms of allergic sensitization and asthma progression as discussed in this review. PMID:24165907

  10. Barriers in Quantum Gravity

    OpenAIRE

    Ambjorn, Jan

    1994-01-01

    I discuss recent progress in our understanding of two barriers in quantum gravity: $c > 1$ in the case of 2d quantum gravity and $D > 2$ in the case of Euclidean Einstein-Hilbert gravity formulated in space-time dimensions $D >2$.

  11. Breaking Down Barriers.

    Science.gov (United States)

    Watkins, Beverly T.

    1994-01-01

    Faculty at 11 higher education institutions in California, New Mexico, Texas, and northern Mexico have been experimenting with computer conferencing on the BESTNET (Bilingual English-Spanish Telecommunications Network). The growing system is credited with creating an international student-faculty community that crosses cultural barriers for…

  12. Electrochemical reduction of CO2 and H2O into fuels: Cell types and kinetic barriers

    DEFF Research Database (Denmark)

    Mogensen, Mogens Bjerg

    2013-01-01

    Some water electrolysers like alkaline electrolyser cells (AEC) and polymer electrolyte membrane electrolyser cell (PEMEC) have been commercially available for many decades, but for production of hydrogen for fuel using renewable electricity they are not yet affordable because of a too low ratio of.......e. ceramics that can take up H2O and become proton conducting. Electrodes may be similar to those used for SOEC. It may be operated between 500 – 700 °C. Molten carbonate electrolyser cell (MCEC) has molten Li2CO3 electrolyte, Ti-Al-metal alloy as cathode (CO evolution) and graphite as anode (O2 evolution...

  13. A study of solar cells with a Schottky barrier based on the polycrystalline film Zn(x)Cd(1-x)S

    Energy Technology Data Exchange (ETDEWEB)

    Akhmedov, R.; Rasulov, D.T.; Ergashev, E.

    1984-01-01

    Au-Zn(x)Cd(1-x)S solar cells have been fabricated by thermal evaporation in vacuum on the chemically polished surface of a Zn(x)Cd(1-x)S film. Films with various zinc contents have been deposited on preoxidized molybdenum foil substrates by a gas transport reaction in a quasi-closed volume in a hydrogen flux. The photoelectrical properties of the solar cells are investigated, and it is shown that the spectral region of photosensitivity and the efficiency of Au-Zn(x)Cd(1-x)S cells are largely determined by the zinc content of the solid solution and by the grain size.

  14. Barrier Data Base user's guide

    International Nuclear Information System (INIS)

    A special purpose data base for physical security barriers has been developed. In addition to barriers, the entities accommodated by the Barrier Data Base (BDB) include threats and references. A threat is established as a configuration of people and equipment which has been employed to penetrate (or attempt to penetrate) a barrier. References are used to cite publications pertinent to the barriers and threats in the data base. Utilization and maintenance of the Barrier Data Base is achieved with LIST, QUERY, ENTER, DELETE, and CHANGE commands which are used to manipulate the data base entities

  15. Barriers to SCM implementing

    Directory of Open Access Journals (Sweden)

    M.E. Rosli

    2008-12-01

    Full Text Available Purpose: This paper explores the barriers faced by Malaysian manufacturing companies in successfullyimplementing the Supply Chain Management (SCM. The study has highlighted some pertinent factorsperforming the barriers that are most frequently reported by the studied companies. Sixteen companies, fromservice and manufacturing companies were studied over a period of two years to assess their SCM practicesthrough survey and interview processes.Design/methodology/approach: This part discusses the research design and methodological issues upon whichthe research is based. The explanation includes two types of research methods, short survey and follow-upinterviews that were identified as being suitable to achieve the aims of this study, which is to identify the currentproblem of SCM practices within the Malaysian SMEs. Research design is a framework or plan for researchused as a guide in collecting and analysing data.Findings: The results showed that the barriers are depending on the types or group of companies business; suchas either it is an SME or a big company. The barriers inhibiting the practice of SCM can be summarized inthe following factors: partnership with suppliers, limited expertise, management commitment, understanding ofSCM, supported technologies and customer satisfaction. The findings are also compared with the results of asimilar study on SCM in other country.Practical implications: Some suggestions are also offered, which is believed to be a good strategy to the companiesto manage the SCM that will lead to sustainable competitive advantage and hence improve their market share.Originality/value: There are interesting barriers between the companies in Malaysia and other country in therespect of SCM implementation. These findings can be used by both Malaysian and other companies to worktogether or review the SCM strategies that will lead to sustainable competitive advantage and hence improvetheir business performance.

  16. Epidermal Growth Factor and Intestinal Barrier Function

    Science.gov (United States)

    Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  17. Intestinal Cell Tight Junctions Limit Invasion of Candida albicans through Active Penetration and Endocytosis in the Early Stages of the Interaction of the Fungus with the Intestinal Barrier.

    Directory of Open Access Journals (Sweden)

    Marianne Goyer

    Full Text Available C. albicans is a commensal yeast of the mucous membranes in healthy humans that can also cause disseminated candidiasis, mainly originating from the digestive tract, in vulnerable patients. It is necessary to understand the cellular and molecular mechanisms of the interaction of C. albicans with enterocytes to better understand the basis of commensalism and pathogenicity of the yeast and to improve the management of disseminated candidiasis. In this study, we investigated the kinetics of tight junction (TJ formation in parallel with the invasion of C. albicans into the Caco-2 intestinal cell line. Using invasiveness assays on Caco-2 cells displaying pharmacologically altered TJ (i.e. differentiated epithelial cells treated with EGTA or patulin, we were able to demonstrate that TJ protect enterocytes against invasion of C. albicans. Moreover, treatment with a pharmacological inhibitor of endocytosis decreased invasion of the fungus into Caco-2 cells displaying altered TJ, suggesting that facilitating access of the yeast to the basolateral side of intestinal cells promotes endocytosis of C. albicans in its hyphal form. These data were supported by SEM observations of differentiated Caco-2 cells displaying altered TJ, which highlighted membrane protrusions engulfing C. albicans hyphae. We furthermore demonstrated that Als3, a hypha-specific C. albicans invasin, facilitates internalization of the fungus by active penetration and induced endocytosis by differentiated Caco-2 cells displaying altered TJ. However, our observations failed to demonstrate binding of Als3 to E-cadherin as the trigger mechanism of endocytosis of C. albicans into differentiated Caco-2 cells displaying altered TJ.

  18. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... adults using immunohistochemistry and confocal microscopy. Antibodies against claudin-11, BLBP, collagen 1, SSEA-4, MAP2, YKL-40, and its receptor IL-13Rα2 and EAAT1 were used to describe morphological characteristics and functional aspects of the outer brain barriers. Claudin-11 was a reliable marker of...... the arachnoid blood-CSF barrier. Collagen 1 delineated the subarachnoid space and stained pial surface layer. BLBP defined radial glial end feet layer and SSEA-4 and YKL-40 were present in both leptomeningeal cells and end feet layer, which transformed into glial limitans. IL-13Rα2 and EAAT1 were...

  19. Malaria-associated L-arginine deficiency induces mast cell-associated disruption to intestinal barrier defenses against nontyphoidal Salmonella bacteremia.

    Science.gov (United States)

    Chau, Jennifer Y; Tiffany, Caitlin M; Nimishakavi, Shilpa; Lawrence, Jessica A; Pakpour, Nazzy; Mooney, Jason P; Lokken, Kristen L; Caughey, George H; Tsolis, Renee M; Luckhart, Shirley

    2013-10-01

    Coinfection with malaria and nontyphoidal Salmonella serotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, develop L-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal of L-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasive Escherichia coli Nissle and Salmonella enterica serotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice with L-arginine or L-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation with L-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasing L-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans. PMID:23690397

  20. Geophysical characterization of subsurface barriers

    International Nuclear Information System (INIS)

    An option for controlling contaminant migration from plumes and buried waste sites is to construct a subsurface barrier of a low-permeability material. The successful application of subsurface barriers requires processes to verify the emplacement and effectiveness of barrier and to monitor the performance of a barrier after emplacement. Non destructive and remote sensing techniques, such as geophysical methods, are possible technologies to address these needs. The changes in mechanical, hydrologic and chemical properties associated with the emplacement of an engineered barrier will affect geophysical properties such a seismic velocity, electrical conductivity, and dielectric constant. Also, the barrier, once emplaced and interacting with the in situ geologic system, may affect the paths along which electrical current flows in the subsurface. These changes in properties and processes facilitate the detection and monitoring of the barrier. The approaches to characterizing and monitoring engineered barriers can be divided between (1) methods that directly image the barrier using the contrasts in physical properties between the barrier and the host soil or rock and (2) methods that reflect flow processes around or through the barrier. For example, seismic methods that delineate the changes in density and stiffness associated with the barrier represents a direct imaging method. Electrical self potential methods and flow probes based on heat flow methods represent techniques that can delineate the flow path or flow processes around and through a barrier

  1. Blood-Brain Barrier Genomics, Proteomics, and New Transporter Discovery

    OpenAIRE

    Shusta, Eric V.

    2005-01-01

    Summary: The blood-brain barrier (BBB) is an impermeable cellular interface that physically separates the blood from the interstices of the brain. The endothelial cells lining the brain blood vessels form the principle barrier, and their unique phenotype is a consequence of dynamic interactions with several perivascular cell types present in the brain parenchyma. In addition, BBB dysfunction has been observed in the large majority of neurological diseases, but the causes of aberrant vascular ...

  2. Astrocytes drive upregulation of the multidrug resistance transporter ABCB1 (P-Glycoprotein) in endothelial cells of the blood-brain barrier in mutant superoxide dismutase 1-linked amyotrophic lateral sclerosis.

    Science.gov (United States)

    Qosa, Hisham; Lichter, Jessica; Sarlo, Mark; Markandaiah, Shashirekha S; McAvoy, Kevin; Richard, Jean-Philippe; Jablonski, Michael R; Maragakis, Nicholas J; Pasinelli, Piera; Trotti, Davide

    2016-08-01

    The efficacy of drugs targeting the CNS is influenced by their limited brain access, which can lead to complete pharmacoresistance. Recently a tissue-specific and selective upregulation of the multidrug efflux transporter ABCB1 or P-glycoprotein (P-gp) in the spinal cord of both patients and the mutant SOD1-G93A mouse model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that prevalently kills motor neurons has been reported. Here, we extended the analysis of P-gp expression in the SOD1-G93A ALS mouse model and found that P-gp upregulation was restricted to endothelial cells of the capillaries, while P-gp expression was not detected in other cells of the spinal cord parenchyma such as astrocytes, oligodendrocytes, and neurons. Using both in vitro human and mouse models of the blood-brain barrier (BBB), we found that mutant SOD1 astrocytes were driving P-gp upregulation in endothelial cells. In addition, a significant increase in reactive oxygen species production, Nrf2 and NFκB activation in endothelial cells exposed to mutant SOD1 astrocytes in both human and murine BBB models were observed. Most interestingly, astrocytes expressing FUS-H517Q, a different familial ALS-linked mutated gene, also drove NFκB-dependent upregulation of P-gp. However, the pathway was not dependent on oxidative stress but rather involved TNF-α release. Overall, these findings indicated that nuclear translocation of NFκB was a converging mechanism used by endothelial cells of the BBB to upregulate P-gp expression in mutant SOD1-linked ALS and possibly other forms of familial ALS. GLIA 2016 GLIA 2016;64:1298-1313. PMID:27158936

  3. Minutes of Fish Barrier Workshop

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Minutes of Fish Barrier Workshop held 27 May 2009 at DOC Waikato Area Office. Lists attendees and highlights topics to be covered in Fish Barrier Workshop.

  4. Design of engineered sorbent barriers

    International Nuclear Information System (INIS)

    A sorbent barrier uses sorbent material such as activated carbon or natural zeolites to prevent the migration of radionuclides from a low-level waste site to the aquifer. The sorbent barrier retards the movement of radioactive contaminants, thereby providing time for the radionuclides to decay. Sorbent barriers can be a simple, effective, and inexpensive method for reducing the migration of radionuclides to the environment. Designing a sorbent barrier consists of using soil and sorbent material properties and site conditions as input to a model which will determine the necessary sorbent barrier thickness to meet contaminant limits. The paper covers the following areas: techniques for measuring sorption properties of barrier materials and underlying soils, use of a radionuclide transport model to determine the required barrier thickness and performance under a variety of site conditions, and cost estimates for applying the barrier

  5. Overcoming immunological barriers in regenerative medicine.

    Science.gov (United States)

    Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

    2014-08-01

    Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists. PMID:25093888

  6. Multilayer thermal barrier coating systems

    Science.gov (United States)

    Vance, Steven J.; Goedjen, John G.; Sabol, Stephen M.; Sloan, Kelly M.

    2000-01-01

    The present invention generally describes multilayer thermal barrier coating systems and methods of making the multilayer thermal barrier coating systems. The thermal barrier coating systems comprise a first ceramic layer, a second ceramic layer, a thermally grown oxide layer, a metallic bond coating layer and a substrate. The thermal barrier coating systems have improved high temperature thermal and chemical stability for use in gas turbine applications.

  7. Energy barrier at the N719-dye/CsSnI3 interface for photogenerated holes in dye-sensitized solar cells

    Science.gov (United States)

    Zhang, Jin; Yu, Chunhui; Wang, Lili; Li, Yizhi; Ren, Yuhang; Shum, Kai

    2014-01-01

    This report is to address the question if black γ-polymorph of cesium tin tri-iodide (B-γ-CsSnI3) can be used as a solid-state hole-transport material in the conventional DSSCs with the N719 dye to replace the liquid electrolyte as reported by I. Chung et al. on Nature 485, 486, (2012). Here we demonstrate rigorously that B-γ-CsSnI3 is not energetically possible to collect photogenerated holes because of the large energy barrier at the interface of N719/B-γ-CsSnI3. Therefore, it cannot serve as a hole-transporter for the conventional DSSCs although it is a good hole-conducting material. A solution-based method was employed to synthesize the B-γ-CsSnI3 polycrystalline thin-films used for this work. These thin-films were then characterized by X-ray diffraction, Hall measurements, optical reflection, and photoluminescence (PL). Particularly, spatially resolved PL intensity images were taken after B-γ-CsSnI3 was incorporated in the DSSC structure to insure the material integrity. The means of ultraviolet photoemission spectroscopy (UPS) was used to reveal why B-γ-CsSnI3 could not act as the substitute of liquid electrolyte in the conventional DSSCs. For the completeness, other two related compounds, one is the yellow polymorph of CsSnI3 and other is Cs2SnI6 with tetravalent tin instead of double-valent tin in CsSnI3 were also investigated by UPS. PMID:25378076

  8. Thermal barrier coating materials

    OpenAIRE

    Clarke, David R.; Simon R. Phillpot

    2005-01-01

    Improved thermal barrier coatings (TBCs) will enable future gas turbines to operate at higher gas temperatures. Considerable effort is being invested, therefore, in identifying new materials with even better performance than the current industry standard, yttria-stabilized zirconia (YSZ). We review recent progress and suggest that an integrated strategy of experiment, intuitive arguments based on crystallography, and simulation may lead most rapidly to the development of new TBC materials.

  9. PHARMACOVIGILANCE: BARRIERS AND CHALLENGES

    OpenAIRE

    Varma, S. K.; RAPELLIWAR A; S. Sutradhar; THAWARE P; Misra, A. K.

    2013-01-01

    Pharmacovigilance is a new discipline which deals with adverse drug or any drug related problems. Pharmacovigilance programme was not bed of roses but its path is laid with challenges and barriers. It is facing obstacles from deficiency from professional health personal to web-based sale of drugs, counterfeit drug to self-medication, etc. It is an integral part of the health sector and identification and reporting of adverse drug effects will have a positive impact on the public health. Impro...

  10. Sonic Crystal Noise Barriers

    OpenAIRE

    Chong, Yung

    2012-01-01

    An alternative road traffic noise barrier using an array of periodically arranged vertical cylinders known as a Sonic Crystal (SC) is investigated. As a result of multiple (Bragg) scattering, SCs exhibit a selective sound attenuation in frequency bands called band gaps or stop bands related to the spacing and size of the cylinders. Theoretical studies using Plane Wave Expansion (PWE), Multiple Scattering Theory (MST) and Finite Element Method (FEM) have enabled study of the performance of SC ...

  11. Dependence of efficiency of thin-film CdS/CdTe solar cell on parameters of absorber layer and barrier structure

    International Nuclear Information System (INIS)

    Dependences of the open-circuit voltage, short-circuit current, fill factor, and efficiency of a CdS/CdTe solar cell on the resistivity and thickness of the p-CdTe absorber layer, the noncompensated acceptor concentration Na-Nd, and carrier lifetime τ in CdTe, are investigated, and optimization of these parameters in order to improve the solar cell efficiency is performed. It has been shown that the observed low efficiency of CdS/CdTe solar cells is caused by the too short electron lifetime in the range of 10-10-10-9 s and too thin (3-5 μm) CdTe layer currently used for fabrication of CdTe/CdS solar cells. To achieve an efficiency of 28-30%, the resistivity and thickness of the CdTe absorber layer, the noncompensated acceptor concentration, and carrier lifetime should be ∼ 0.1 Ω.cm, ≥ 20-30 μm, ≥ 1016 cm-3, and ≥ 10-6 s, respectively

  12. Pathogenic E. coli exploits SslE mucinase activity to translocate through the mucosal barrier and get access to host cells.

    Directory of Open Access Journals (Sweden)

    Maria Valeri

    Full Text Available SslE is a zinc-metalloprotease involved in the degradation of mucin substrates and recently proposed as a potential vaccine candidate against pathogenic E. coli. In this paper, by exploiting a human in vitro model of mucus-secreting cells, we demonstrated that bacteria expressing SslE have a metabolic benefit which results in an increased growth rate postulating the importance of this antigen in enhancing E. coli fitness. We also observed that SslE expression facilitates E. coli penetration of the mucus favouring bacteria adhesion to host cells. Moreover, we found that SslE-mediated opening of the mucosae contributed to the activation of pro-inflammatory events. Indeed, intestinal cells infected with SslE-secreting bacteria showed an increased production of IL-8 contributing to neutrophil recruitment. The results presented in this paper conclusively designate SslE as an important colonization factor favouring E. coli access to both metabolic substrates and target cells.

  13. Barrier infrared detector

    Science.gov (United States)

    Ting, David Z. (Inventor); Khoshakhlagh, Arezou (Inventor); Soibel, Alexander (Inventor); Hill, Cory J. (Inventor); Gunapala, Sarath D. (Inventor)

    2012-01-01

    A superlattice-based infrared absorber and the matching electron-blocking and hole-blocking unipolar barriers, absorbers and barriers with graded band gaps, high-performance infrared detectors, and methods of manufacturing such devices are provided herein. The infrared absorber material is made from a superlattice (periodic structure) where each period consists of two or more layers of InAs, InSb, InSbAs, or InGaAs. The layer widths and alloy compositions are chosen to yield the desired energy band gap, absorption strength, and strain balance for the particular application. Furthermore, the periodicity of the superlattice can be "chirped" (varied) to create a material with a graded or varying energy band gap. The superlattice based barrier infrared detectors described and demonstrated herein have spectral ranges covering the entire 3-5 micron atmospheric transmission window, excellent dark current characteristics operating at least 150K, high yield, and have the potential for high-operability, high-uniformity focal plane arrays.

  14. A quasi-Delphi study on technological barriers to the uptake of hydrogen as a fuel for transport applications - Production, storage and fuel cell drivetrain considerations

    Energy Technology Data Exchange (ETDEWEB)

    Hart, David; Vuille, Francois [E4tech Sarl, Avenue Juste-Olivier 2, 1006 Lausanne (Switzerland); Anghel, Alexandra T.; Huijsmans, Joep [Shell Hydrogen B.V., Carel van Bylandtlaan 23, 2596 HR The Hague (Netherlands)

    2009-08-01

    The introduction of hydrogen in transport, particularly using fuel cell vehicles, faces a number of technical and non-technical hurdles. However, their relative importance is unclear, as are the levels of concern accorded them within the expert community conducting research and development within this area. To understand what issues are considered by experts working in the field to have significant potential to slow down or prevent the introduction of hydrogen technology in transport, a study was undertaken, primarily during 2007. Three key technology areas within hydrogen transport were selected - hydrogen storage, fuel cell drivetrains, and small-scale hydrogen production - and interviews with selected experts conducted. Forty-nine experts from 34 organisations within the fuel cell, automotive, industrial gas and other related industries participated, in addition to some key academic and government figures. The survey was conducted in China, Japan, North America and Europe, and analysed using conventional mathematical techniques to provide weighted and averaged rankings of issues viewed as important by the experts. It became clear both from the interviews and the subsequent analysis that while a primary concern in China was fundamental technical performance, in the other regions cost and policy were rated more highly. Although a few individual experts identified possible technical showstoppers, the overall message was that pre-commercial hydrogen fuel cell vehicles could realistically be on the road in tens of thousands within 5 years, and that full commercialisation could take place within 10-15 years, without the need for radical technical breakthroughs. Perhaps surprisingly, the performance of hydrogen storage technologies was not viewed as a showstopper, though cost was seen as a significant challenge. Overall, however, coherent policy development was more frequently identified as a major issue to address. (author)

  15. 12(S)-HETE increases intracellular Ca(2+) in lymph-endothelial cells disrupting their barrier function in vitro; stabilization by clinical drugs impairing calcium supply.

    Science.gov (United States)

    Nguyen, Chi Huu; Brenner, Stefan; Huttary, Nicole; Li, Yuanfang; Atanasov, Atanas Georgiev; Dirsch, Verena M; Holzner, Silvio; Stadler, Serena; Riha, Juliane; Krieger, Sigurd; Milovanovic, Danijela; Fristiohardy, Adryan; Simonitsch-Klupp, Ingrid; Dolznig, Helmut; Saiko, Philipp; Szekeres, Thomas; Giessrigl, Benedikt; Jäger, Walter; Krupitza, Georg

    2016-09-28

    Secretion of 12(S)-HETE by breast cancer emboli provokes "circular chemorepellent induced defects" (CCIDs) in the adjacent lymphatic vasculature facilitating their intravasation and lymph node metastasis which determines prognosis. Therefore, elucidating the mechanism of lymph endothelial cell (LEC) wall disintegration may provide cues for anti-metastatic intervention. The role of intracellular free Ca(2+) for CCID formation was investigated in LECs using MCF-7 or MDA-MB231 breast cancer cell spheroids in a three-dimensional cell co-culture model. 12(S)-HETE elevated the Ca(2+) level in LEC by activating PLC/IP3. Downstream, the Ca(2+)-calmodulin kinase MYLK contributed to the phosphorylation of Ser19-MLC2, LEC contraction and CCID formation. Approved clinical drugs, lidoflazine, ketotifen, epiandrosterone and cyclosporine, which reportedly disturb cellular calcium supply, inhibited 12(S)-HETE-induced Ca(2+) increase, Ser19-MLC2 phosphorylation and CCID formation. This treatment strategy may reduce spreading of breast cancer through lymphatics. PMID:27390016

  16. Multilayer barrier films comprising nitrogen spacers between free-standing barrier layers

    Science.gov (United States)

    Granstrom, Jimmy Erik

    water vapor transmission rates of 0.00021 g/m2, day or below can be achieved with low-cost materials in this architecture. This WVTR correlates to a predicted lifetime of more than 10 years for inverted organic bulk heterojunction solar cell modules fabricated and tested by Konarka Technologies (Lowell, MA, USA). The use of thin instability suppressed barriers, deposited by solution, can be used to further optimize the cost/performance ratio of encapsulation architectures comprising nitrogen spacers.

  17. Breakdown of the Blood-Brain Barrier during Tick-Borne Encephalitis in Mice Is Not Dependent on CD8(+) T-Cells

    Czech Academy of Sciences Publication Activity Database

    Růžek, Daniel; Salát, Jiří; Singh, S. K.; Kopecký, Jan

    2011-01-01

    Roč. 6, č. 5 (2011), e20472. E-ISSN 1932-6203 R&D Projects: GA ČR GPP302/10/P438; GA ČR GAP502/11/2116; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : CENTRAL-NERVOUS-SYSTEM * WEST-NILE-VIRUS * MICROVASCULAR ENDOTHELIAL-CELLS * TIGHT JUNCTION PROTEINS * MULTIPLE-SCLEROSIS * INFLAMMATORY RESPONSE * PERMEABILITY CHANGES Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.092, year: 2011

  18. Stratum corneum barrier lipids in cholesteatoma

    DEFF Research Database (Denmark)

    Svane-Knudsen, V; Halkier-Sørensen, L; Rasmussen, G; Ottosen, P

    2000-01-01

    emerged. When the corneocyte reaches the transitional stage to the stratum corneum, the Odland bodies accumulate near the cell membrane and discharge their contents of lipid and enzymes. The lipids are reorganized into multiple long sheets of lamellar structures that embrace the keratinized corneocytes...... structures in the intercellular space. In theory, the failure to desquamate seen in cholesteatomas could be caused by partial or total failure of Odland body delivery to the intercellular region, or to local breakdown of the permeability barrier....

  19. Tearing Down Disciplinary Barriers

    Science.gov (United States)

    Roederer, Juan G.

    1988-05-01

    Profesor Hannes Alfvén's life-long battle against scientific narrow-mindedness and parochial approaches to the solution of scientific problems is well known and deeply appreciated by this author. In this article the new interdisciplinary trends in science are critically examined and the psychological impacts of crumbling disciplinary barriers on the participating scientists are analyzed. Several examples of interdisciplinary research programs are discussed and some thoughts on the structural reform of scientific organizations, agencies, and universities needed to face these trends are given.

  20. Barriers to entry : abolishing the barriers to understanding

    OpenAIRE

    Keppler, Jan Horst

    2009-01-01

    BARRIERS TO ENTRY: ABOLISHING THE BARRIERS TO UNDERSTANDING by Jan-Horst Keppler Professor of economics Université Paris – Dauphine, LEDa, and Université Paris I Panthéon-Sorbonne, PHARE Port.: (+33 6) 77 81 37 46; Email: . Abstract The concept of a barrier to entry has been discussed least since Bain (1956) with important contributions by Spence (1977), Dixit (1980) or Milgrom and Roberts (1982). The more recent discussion is synth...

  1. Optimum Barrier Height for SiC Schottky Barrier Diode

    OpenAIRE

    Mohamed Abd El-Latif; Alaa El-Din Sayed Hafez

    2013-01-01

    The study of barrier height control and optimization for Schottky barrier diode (SBD) from its physical parameters have been introduced using particle swarm optimization (PSO) algorithm. SBD is the rectifying barrier for electrical conduction across the metal semiconductor (MS) junction and, therefore, is of vital importance to the successful operation of any semiconductor device. 4H-SiC is used as a semiconductor material for its good electrical characteristics with high-power semiconductor ...

  2. Inhibition of p38 mitogen-activated protein kinase may decrease intestinal epithelial cell apoptosis and improve intestinal epithelial barrier function after ischemia- reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shu-Yun Zheng; Xiao-Bing Fu; Jian-Guo Xu; Jing-Yu Zhao; Tong-Zhu Sun; Wei Chen

    2005-01-01

    AIM: To investigate the role of p38 mitogen-activated protein kinase in rat small intestine after ischemia-reperfusion (I/R)insult and the relationship between activation of p38 MAPK and apoptotic cell death of intestine.METHODS: Ninety Wistar rats were divided randomly into three groups, namely sham-operated group (C), I/R vehicle group (R) and SB203580 pre-treated group(S).In groups R and S, the superior mesenteric artery(SMA)was separated and occluded for 45 min, then released for reperfusion for0.25, 0.5, 1, 2, 6, 12 and 24 h. In group C, SMA was separated without occlusion. Plasma D-lactate levels were examined and histological changes were observed under a light microscope. The activity of p38 MAPK was determined by Western immunoblotting and apoptotic cells were detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUDP-biotin nick end labeling (TUNEL).RESULTS: Intestinal ischemia followed by reperfusion activated p38 MAPK, and the maximal level of activation (7.3-fold vs sham-operated group) was reached 30 min after I/R. Treatment with SB 203580, a p38 MAPK inhibitor,reduced intestinal apoptosis (26.72±3.39% vs62.50±3.08%in I/R vehicle, P<0.01) and decreased plasma D-lactate level (0.78±0.15 mmol/L in I/R vehicle vs0.42±0.17 mmol/L in SB-treated group) and improved post-ischemic intestinal histological damage.CONCLUSION: p38 MAPK plays a crucial role in the signal transduction pathway mediating post-ischemic intestinal apoptosis, and inhibition of p38 MAPK may attenuate ischemia-reperfusion injury.

  3. [Blood-nerve barrier: structure and function].

    Science.gov (United States)

    Kanda, Takashi

    2011-06-01

    The blood-nerve barrier (BNB) is a dynamic interface between the endoneurial microenvironment and surrounding extracellular space or blood contents, and is localized the innermost layer of multilayered ensheathing perineurium and endoneurial microvessels. Since the BNB is a key structure controlling the internal milieu of the peripheral nerve parenchyma, adequate understanding of the BNB is crucial for developing treatment strategies for human peripheral nervous system disorders, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and diabetic and various metabolic/toxic neuropathies. However, fewer studies have been conducted on the BNB, if we compare against the number of studies on the blood-brain barrier. This is because of the lack of adequate human cell lines originating from the BNB. In our laboratory, human immortal cell lines from the BNB, namely, the endothelial cell line and pericyte cell line, have recently been established and vigorous investigations of their biological and physiological properties are now underway. Pericytes constituting the BNB were found to possess robust ability of controlling BNB integrity via secretion of various cytokines and growth factors including bFGF, VEGF, GDNF, BDNF, and angiopoietin-1. Unknown soluble factors secreted by pericytes also contribute to the upregulation of claudin-5 in endothelial cells in the BNB and thus, strengthen the barrier function of the BNB. In diabetic neuropathy, pericytes were shown to regulate the vascular basement membrane, while AGEs were shown to induce basement membrane hypertrophy and disrupt the BNB by increasing the autocrine secretion of VEGF and TGF-beta from pericytes. In this review article, we discuss the macroscopic and microscopic anatomy of the human BNB as well as the molecular mechanisms of mononuclear cell infiltration across the BNB. PMID:21613659

  4. Gut barrier in health and disease: focus on childhood.

    Science.gov (United States)

    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

  5. The intestinal barrier function and its involvement in digestive disease

    Directory of Open Access Journals (Sweden)

    Eloísa Salvo-Romero

    2015-11-01

    Full Text Available The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra- and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism.

  6. The intestinal barrier function and its involvement in digestive disease.

    Science.gov (United States)

    Salvo Romero, Eloísa; Alonso Cotoner, Carmen; Pardo Camacho, Cristina; Casado Bedmar, Maite; Vicario, María

    2015-11-01

    The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra- and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism. PMID:26541659

  7. Novel attributes in modeling and optimizing of the new graphene based In{sub x}Ga{sub 1−x}N Schottky barrier solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Arefinia, Zahra [Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz 51666-14766 (Iran, Islamic Republic of); Asgari, Asghar, E-mail: asgari@tabrizu.ac.ir [Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz 51666-14766 (Iran, Islamic Republic of); School of Electrical, Electronic, and Computer Engineering, University of Western Australia, Crawley, WA 6009 (Australia)

    2014-05-21

    Based on the ability of In{sub x}Ga{sub 1−x}N materials to optimally span the solar spectrum and their superior radiation resistance, solar cells based on p-type In{sub x}Ga{sub 1−x}N with low indium contents and interfacing with graphene film (G/In{sub x}Ga{sub 1−x}N), is proposed to exploit the benefit of transparency and work function tunability of graphene. Then, their solar power conversion efficiency modeled and optimized using a new analytical approach taking into account all recombination processes and accurate carrier mobility. Furthermore, their performance was compared with graphene on silicon counterparts and G/p-In{sub x}Ga{sub 1−x}N showed relatively smaller short-circuits current (∼7 mA/cm{sup 2}) and significantly higher open-circuit voltage (∼4 V) and efficiency (∼30%). The thickness, doping concentration, and indium contents of p-In{sub x}Ga{sub 1−x}N and graphene work function were found to substantially affect the performance of G/p-In{sub x}Ga{sub 1−x}N.

  8. Cathode-Electrolyte Interfaces with CGO Barrier Layers in SOFC

    DEFF Research Database (Denmark)

    Knibbe, Ruth; Hjelm, Johan; Menon, Mohan;

    2010-01-01

    10) barrier layer, the other had a barrier layer deposited by pulsed laser deposition (PLD) CGO10. Scanning electron microscopy, transmission electron microscopy (TEM), and electron backscattered diffraction (EBSD) investigations conclude that the major source of the cell performance difference is...... attributed to CGO–YSZ interdiffusion in the sprayed-cosintered barrier layer. From TEM and EBSD work, a dense CGO10 PLD layer is found to be deposited epitaxially on the 8YSZ electrolyte substrate—permitting a small amount of SrZrO3 formation and minimizing CGO–YSZ interdiffusion....

  9. Surface barrier for tritium permeation

    International Nuclear Information System (INIS)

    To apply the surface barrier to reduce hydrogen permeation, the influence of the surface barrier on both the permeation and retention has been investigated considering physical and chemical stability of the barrier in fusion environment. Since energetic hydrogen from the plasma not only impinges directly into subsurface but also removes the front surface barrier, only the back surface barrier works reliably. Oxides, carbide and nitride are candidates as the barrier but their mechanical as well as chemical stability is an important concern, because very large thermal gradient and thermal cycling in fusion environment could enhance the crack initiation and exfoliation of the barrier. Therefore an appropriate barrier which is stable under a particular operating condition must be developed. The most reliable way to reduce the permeation is to use a metallic layer, but it must be rather thick. It should be noted that the back surface barrier to suppress the permeation inevitably increases the retention. Therefore an optimization between the permeation decrease and retention increase is necessary. An alternative way to reduce the plasma or ion driven permeation is to decrease the recombination coefficient at the back surface. However, large uncertainty in the observed recombination coefficients does not allow us to rely on the recombination limited process and further work is needed. 20 refs., 6 figs

  10. TMX-U Tandem-Mirror thermal-barrier experiments

    International Nuclear Information System (INIS)

    Thermal-barrier experiments have been carried out in the Tandem Mirror Experiment-Upgrade (TMX-U). Measurements of nonambipolar and ambipolar radial transport show that these transport processes, as well as end losses, can be controlled at modest densities and durations. Central-cell heating methods using ion-cyclotron heating (ICH) and neutral-beam injection have been demonstrated. Potential measurements with recently developed methods indicate that deep thermal barriers can be established

  11. Endocannabinoids modulate human blood–brain barrier permeability in vitro

    OpenAIRE

    Hind, William H.; Tufarelli, Cristina; Neophytou, Maria; Anderson, Susan I; England, Timothy J.; O'Sullivan, Saoirse E

    2015-01-01

    Background and Purpose Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. Experimental Approach Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was mo...

  12. Transport of monocarboxylic acids at the blood-brain barrier: Studies with monolayers of primary cultured bovine brain capillary endothelial cells

    International Nuclear Information System (INIS)

    The kinetics and mechanism of the transport of monocarboxylic acids (MCAs) were studied by using primary cultured bovine brain capillary endothelial cells. Concentration-dependent uptake of acetic acid was observed, and the kinetic parameters were estimated as follows: the Michaelis constant, Kt, was 3.41 ± 1.87 mM, the maximum uptake rate, Jmax, was 144.7 ± 55.7 nmol/mg of protein/min and the nonsaturable first-order rate constant, Kd, was 6.66 ± 1.98 microliters/mg of protein/min. At medium pH below 7.0, the uptake rate of [3H]acetic acid increased markedly with decreasing medium pH, whereas pH-independent uptake was observed in the presence of 10 mM acetic acid. An energy requirement for [3H]acetic acid uptake was also demonstrated, because metabolic inhibitors (2,4-dinitrophenol and rotenone) reduced significantly the uptake rate (P less than .05). Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone, a protonophore, inhibited significantly the uptake of [3H]acetic acid at medium pH of 5.0 and 6.0, whereas 4,4'-diisothiocyanostilben-2,2'-disulfonic acid did not. Several MCAs inhibited significantly the uptake rate of [3H]acetic acid, whereas di- and tricarboxylic acids did not. The uptake of [3H]acetic acid was competitively inhibited by salicylic acid, with an inhibition constant, Ki, of 3.60 mM, suggesting a common transport system between acetic acid and salicylic acid. Moreover, at the medium pH of 7.4, salicylic acid and valproic acid inhibited significantly the uptake of [3H]acetic acid, demonstrating that the transport of MCA drugs could also be ascribed to the MCA transport system at the physiologic pH

  13. Transport of monocarboxylic acids at the blood-brain barrier: Studies with monolayers of primary cultured bovine brain capillary endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Terasaki, T.; Takakuwa, S.; Moritani, S.; Tsuji, A. (Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University (Japan))

    1991-09-01

    The kinetics and mechanism of the transport of monocarboxylic acids (MCAs) were studied by using primary cultured bovine brain capillary endothelial cells. Concentration-dependent uptake of acetic acid was observed, and the kinetic parameters were estimated as follows: the Michaelis constant, Kt, was 3.41 {plus minus} 1.87 mM, the maximum uptake rate, Jmax, was 144.7 {plus minus} 55.7 nmol/mg of protein/min and the nonsaturable first-order rate constant, Kd, was 6.66 {plus minus} 1.98 microliters/mg of protein/min. At medium pH below 7.0, the uptake rate of (3H)acetic acid increased markedly with decreasing medium pH, whereas pH-independent uptake was observed in the presence of 10 mM acetic acid. An energy requirement for (3H)acetic acid uptake was also demonstrated, because metabolic inhibitors (2,4-dinitrophenol and rotenone) reduced significantly the uptake rate (P less than .05). Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone, a protonophore, inhibited significantly the uptake of (3H)acetic acid at medium pH of 5.0 and 6.0, whereas 4,4{prime}-diisothiocyanostilben-2,2{prime}-disulfonic acid did not. Several MCAs inhibited significantly the uptake rate of (3H)acetic acid, whereas di- and tricarboxylic acids did not. The uptake of (3H)acetic acid was competitively inhibited by salicylic acid, with an inhibition constant, Ki, of 3.60 mM, suggesting a common transport system between acetic acid and salicylic acid. Moreover, at the medium pH of 7.4, salicylic acid and valproic acid inhibited significantly the uptake of (3H)acetic acid, demonstrating that the transport of MCA drugs could also be ascribed to the MCA transport system at the physiologic pH.

  14. Modification of photoelectrode with thiol-functionalized Calix[4]arenes as interface energy barrier for high efficiency in dye-sensitized solar cells

    Science.gov (United States)

    Akın, Seçkin; Gülen, Mahir; Sayın, Serkan; Azak, Hacer; Yıldız, Hüseyin Bekir; Sönmezoğlu, Savaş

    2016-03-01

    We successfully synthesize a series of bis-thiol-substituted calix[4]arene derivatives bearing diverse groups on the upper-rim/lower-rim (C@SH-1, C@SH-2, C@SH-3, C@SH-4, C@SH-5). For the first time, we apply these derivatives as interface modifiers for improving the photovoltaic response of a Ru-bipy dye (N-719)-sensitized TiO2 photoanode in dye-sensitized solar cells (DSSCs). We use FT-IR, H- and C-NMR, UV-vis spectrophotometry, and elemental analysis techniques to characterize the structures of the calix[4]arene derivatives. We achieve an overall photon-to-electron conversion efficiency (PCE) of 12.97% with the DSSCs based on 25,27-bis(5-thiol-1-oxypentane)-26,28-dihydroxycalix[4]arene (C@SH-3)-modified TiO2 photoanode (Jsc = 9.49 mA cm-2, Voc = 672 mV, FF = 61.1%) compared with a system of bare TiO2 (PCE: 6.82%) under AM 1.5G illumination of 300 W/m2. In addition, we also study the influence of the chain length (C@SH-2; with 3 carbons and C@SH-3; with 5 carbons) and subsidiary ligand groups such as alkyl (C@SH-1), nitro (C@SH-4), and amine (C@SH-5) on the surface morphology, spectral response, and photovoltaic performance. Our results reveal that the C@SH-3 calixarene is the best derivative for modifiying the TiO2 photoanode. Thiol-functionalized Calix[4]arene molecules play a role in assisting charge separation and preventing back recombination, which accounts for the observed enhancement in photovoltaic performance.

  15. Structural failures of the blood–gas barrier and the epithelial–epithelial cell connections in the different vascular regions of the lung of the domestic fowl, Gallus gallus variant domesticus, at rest and during exercise

    Directory of Open Access Journals (Sweden)

    John N. Maina

    2013-01-01

    Structural failure of blood–gas barrier (BGB and epithelial–epithelial cell connections (EECCs in different vascular regions of the exchange tissue of the lung was studied in rested and exercised chickens. The number of red blood cells (nRBCs was counted and protein concentration (PC measured after lavaging the respiratory system, and blood was sampled to determine the blood lactate levels (BLLs. The numbers of complete BGB breaks (nBGBBs and those of the EECCs (nEECCBs were counted in the different vascular territories of the lung. The nRBCs and the PCs increased with increasing exercise intensities but the rate of increase decreased at higher workloads. From rest to the fastest experimental treadmill speed of 2.95 m.sec−1, BLLs increased 4-fold. In all cases, the nEECCBs exceeded those of the BGB, showing that structurally the BGB is relatively weaker than the EECC. The increase in the number of breaks with increasing exercise can be attributed to increase in the pulmonary capillary blood pressure (PCBP from faster heart rates and higher cardiac outputs, while the leveling out of the measurements made at higher workloads may have arisen from hemodynamic changes that initially ensued from exudation of blood plasma and then flow of blood into the air capillaries on failure of the BGB. The relative differences in the nBGBBs and the nEECCBs in the different vascular regions of the lung were ascribed to diameters of the branches and their points of origin and angles of bifurcation from the pulmonary artery. Presence of RBCs in the air capillaries of the lungs of rested chickens showed that failure of the BGB commonly occurs even in healthy and unstressed birds. Rapid repair and/or defense responses, which were observed, may explain how birds cope with mechanical injuries of the BGB.

  16. Racial Trade Barriers?

    DEFF Research Database (Denmark)

    Bjerre, Jacob Halvas

    Aryanization is associated with Nazi Germany's policies to exclude Jews in the Germany from the economy in the pre-war years, but I will show it was a global policy from 1937. The utopian goal of international Aryanization was the total removal of Jews who traded with Germany anywhere in the world....... This paper analyzes the racial policies pursued in the foreign trade and argues that we need to recognize Aryanization as a world-wide policy in order to fully understand its character and possible consequences. I focus on the pre-war period and analyze the case of Denmark from three different perspectives......: perpetrators, victims and bystanders. The analysis will show that race, economy and foreign trade were combined in an attempt to raise racial trade barriers. This forced the question of German racial policies on the Danish government, Danish-Jewish businesses, and German companies involved in foreign trade...

  17. PHARMACOVIGILANCE: BARRIERS AND CHALLENGES

    Directory of Open Access Journals (Sweden)

    VARMA S. K

    2013-01-01

    Full Text Available Pharmacovigilance is a new discipline which deals with adverse drug or any drug related problems. Pharmacovigilance programme was not bed of roses but its path is laid with challenges and barriers. It is facing obstacles from deficiency from professional health personal to web-based sale of drugs, counterfeit drug to self-medication, etc. It is an integral part of the health sector and identification and reporting of adverse drug effects will have a positive impact on the public health. Improvement in knowledge in pharmacovigilance and communication from the top level to the grass-root level in the health sector will help in proper implementation of the programme. Patient should be educated to report any adverse effects after taking drug and stop relaying on acquiring information related to drugs in web. Proper detection, reporting and analysis would help to implement the programme for the betterment of society.

  18. Exposure, Uptake, and Barriers

    Science.gov (United States)

    Baeza-Squiban, Armelle; Lanone, Sophie

    The nanotechnologies market is booming, e.g., in the food industry (powder additives, etc.) and in medical applications (drug delivery, prosthetics, diagnostic imaging, etc.), but also in other industrial sectors, such as sports, construction, cosmetics, and so on. In this context, with an exponential increase in the number of current and future applications, it is particularly important to evaluate the problem of unintentional (i.e., non-medical) exposure to manufactured nanoparticles (so excluding nanoparticles found naturally in the environment). In this chapter, we begin by discussing the various parameters that must be taken into account in any serious assessment of exposure to man-made nanoparticles. We then list the potential routes by which nanoparticles might enter into the organism, and outline the mechanisms whereby they could get past the different biological barriers. Finally, we describe the biodistribution of nanoparticles in the organism and the way they are eliminated.

  19. Countermeasures and barriers

    International Nuclear Information System (INIS)

    In 1973 Haddon proposed ten strategies for reducing and avoiding damages based on a model of potential harmful energy transfer (Haddon, 1973). The strategies apply to a large variety of unwanted phenomena. Haddon's pioneering work on countermeasures has had a major influence on later thinking about safety. Considering its impact it is remarkable that the literature offers almost no discussions related to the theoretical foundations of Haddon's countermeasure strategies. The present report addresses a number of theoretical issues related to Haddon's countermeasure strategies, which are: 1) A reformulation and formalization of Haddon's countermeasure strategies. 2) An identification and description of some of the problems associated with the term 'barrier'. 3) Suggestions for a more precise terminology based on the causal structure of countermeasures. 4) Extending the scope of countermeasures to include sign-based countermeasures. (au)

  20. Countermeasures and barriers

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, Johannes [Oersted - DTU, Automation, Kgs. Lyngby (Denmark)

    2005-10-01

    In 1973 Haddon proposed ten strategies for reducing and avoiding damages based on a model of potential harmful energy transfer (Haddon, 1973). The strategies apply to a large variety of unwanted phenomena. Haddon's pioneering work on countermeasures has had a major influence on later thinking about safety. Considering its impact it is remarkable that the literature offers almost no discussions related to the theoretical foundations of Haddon's countermeasure strategies. The present report addresses a number of theoretical issues related to Haddon's countermeasure strategies, which are: 1) A reformulation and formalization of Haddon's countermeasure strategies. 2) An identification and description of some of the problems associated with the term 'barrier'. 3) Suggestions for a more precise terminology based on the causal structure of countermeasures. 4) Extending the scope of countermeasures to include sign-based countermeasures. (au)

  1. The damage of pulmonary microvascular endothelial cell barrier and acute respiratory distress syndrome%肺微血管内皮细胞屏障功能损伤与急性呼吸窘迫综合征

    Institute of Scientific and Technical Information of China (English)

    韩凤

    2015-01-01

    急性呼吸窘迫综合征( ARDS)是急性呼吸衰竭发生的主要原因,其特征是弥漫性的肺泡损伤,伴透明膜形成,肺泡腔高蛋白性水肿、毛细血管损伤和肺泡上皮破裂,它最突出的临床表现为顽固的低氧血症. 尽管在最佳的通气支持和液体平衡的治疗改善后,它仍有很高的死亡率及短、长期的并发症. 因此,对这种综合征的早期识别和治疗性干预措施的早期应用至关重要. 本综述描述了肺微血管内皮细胞( PMVECs )屏障功能损伤与ARDS发生、发展的相互关系.具体来说是描述了ARDS定义、PMVECs的屏障功能,以及在ARDS的发生、发展时PMVECs的通透性改变,异常凋亡、分泌和功能失调,以期深入探讨ARDS可能的病理生理学机制.%The acute respiratory distress syndrome ( ARDS) is a major cause of acute respiratory failure characterized by a diffused alveolar damage , formation of hyaline membranes , protein -rich edema fluid in the alveolar spaces , capillary injury and disruption of the alveolar epithelium , and the most prominent clinical manifestation of ARDS is refractory hypoxemia . Despite improvements in intensive care with optimal ventilation support and fluid balance , its development also leads to high mortality, as well as short -and long -term complications.Therefore, early recognition of this syndrome and application of demonstrated therapeutic interventions are essential to change the natural course of this devastating entity .In this review article , we describe the mutual relation between the damage of pulmonary microvascular endothelial cell ( PMVECs ) barrier and the occurrence and development of ARDS .Specifically , we describe the Berlin definition of ARDS and barrier function of PMVECs, as well as the permeability changes , the abnormal apoptosis and secretion and the dysfunction of PMVECs in the development of ARDS in order to further discuss its possible pathophysiological mechanism.

  2. Role of the intestinal barrier in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Mike G Laukoetter; Porfirio Nava; Asma Nusrat

    2008-01-01

    A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the interstitium. The single layer of intestinal epithelial cells (IECs) serves as a dynamic interface between the host and its environment. Cell polarity and structural properties of the epithelium is complex and is important in the development of epithelial barrier function. Epithelial cells associate with each other via a series of intercellular junctions. The apical most intercellular junctional complex referred to as the Apical Junction Complex (AJC) is important in not only cell-cell recognition, but also in the regulation of paracellular movement of fluid and solutes. Defects in the intestinal epithelial barrier function have been observed in a number of intestinal disorders such as inflammatory bowel disease (IBD). It is now becoming evident that an aberrant epithelial barrier function plays a central role in the pathophysiology of IBD. Thus, a better understanding of the intestinal epithelial barrier structure and function in healthy and disease states such as IBD will foster new ideas for the development of therapies for such chronic disorders.

  3. Skin Barrier Function and Allergens

    DEFF Research Database (Denmark)

    Engebretsen, Kristiane Aasen; Thyssen, Jacob Pontoppidan

    2016-01-01

    The skin is an important barrier protecting us from mechanical insults, microorganisms, chemicals and allergens, but, importantly, also reducing water loss. A common hallmark for many dermatoses is a compromised skin barrier function, and one could suspect an elevated risk of contact sensitization...

  4. Hanford Protective Barriers Program asphalt barrier studies -- FY 1988

    International Nuclear Information System (INIS)

    The Hanford Protective Barrier (HPB) Program is evaluating alternative barriers to provide a means of meeting stringent water infiltration requirements. One type of alternative barrier being considered is an asphalt-based layer, 1.3 to 15 cm thick, which has been shown to be very effective as a barrier for radon gas and, hence, should be equally effective as a barrier for the larger molecules of water. Fiscal Year 1988 studies focused on the selection and formulation of the most promising asphalt materials for further testing in small-tube lysimeters. Results of laboratory-scale formulation and hydraulic conductivity tests led to the selection of a rubberized asphalt material and an admixture of 24 wt% asphalt emulsion and concrete sand as the two barriers for lysimeter testing. Eight lysimeters, four each containing the two asphalt treatments, were installed in the Small Tube Lysimeter Facility on the Hanford Site. The lysimeter tests allow the performance of these barrier formulations to be evaluated under more natural environmental conditions

  5. Dehydroepiandrosterone Sulfate Stimulates Expression of Blood-Testis-Barrier Proteins Claudin-3 and -5 and Tight Junction Formation via a Gnα11-Coupled Receptor in Sertoli Cells

    Science.gov (United States)

    Papadopoulos, Dimitrios; Dietze, Raimund; Shihan, Mazen; Kirch, Ulrike; Scheiner-Bobis, Georgios

    2016-01-01

    Dehydroepiandrosterone sulfate (DHEAS) is a circulating sulfated steroid considered to be a pro-androgen in mammalian physiology. Here we show that at a physiological concentration (1 μM), DHEAS induces the phosphorylation of the kinase Erk1/2 and of the transcription factors CREB and ATF-1 in the murine Sertoli cell line TM4. This signaling cascade stimulates the expression of the tight junction (TJ) proteins claudin-3 and claudin-5. As a consequence of the increased expression, tight junction connections between neighboring Sertoli cells are augmented, as demonstrated by measurements of transepithelial resistance. Phosphorylation of Erk1/2, CREB, or ATF-1 is not affected by the presence of the steroid sulfatase inhibitor STX64. Erk1/2 phosphorylation was not observed when dehydroepiandrosterone (DHEA) was used instead of DHEAS. Abrogation of androgen receptor (AR) expression by siRNA did not affect DHEAS-stimulated Erk1/2 phosphorylation, nor did it change DHEAS-induced stimulation of claudin-3 and claudin-5 expression. All of the above indicate that desulfation and conversion of DHEAS into a different steroid hormone is not required to trigger the DHEAS-induced signaling cascade. All activating effects of DHEAS, however, are abolished when the expression of the G-protein Gnα11 is suppressed by siRNA, including claudin-3 and -5 expression and TJ formation between neighboring Sertoli cells as indicated by reduced transepithelial resistance. Taken together, these results are consistent with the effects of DHEAS being mediated through a membrane-bound G-protein-coupled receptor interacting with Gnα11 in a signaling pathway that resembles the non-classical signaling pathways of steroid hormones. Considering the fact that DHEAS is produced in reproductive organs, these findings also suggest that DHEAS, by acting as an autonomous steroid hormone and influencing the formation and dynamics of the TJ at the blood-testis barrier, might play a crucial role for the

  6. Development of engineered barrier

    International Nuclear Information System (INIS)

    Engineered barrier development was carried out into the three research fields : waste form, disposal container, and buffer. The waste form field dealt with long-term leaching tests with borosilicate waste glasses surrounded by compacted bentonite. The leach rate decreased with increasing time, and was higher for the waste specimen rich in U and Na. In the container field, preliminary concepts of disposal containers were recommended by conducting structural analysis, thermal analysis, and shielding analysis, and major properties of stainless steel, copper, and titanium as a container material were surveyed. The sensitization degrees of SUS 316 and 316L were lower than those of SUS 304 and 304L, respectively. The crevice corrosion of sensitized stainless steel was sensitive to the content of salt. Researches into the buffer included establishment of its performance criteria followed by investigating major properties of buffer using potential material in Korea. Experiments were made for measuring hydraulic conductivities, swelling properties, mechanical properties, thermal conductivities, pore-water chemistry properties, and adsorption properties was also investigated. (author)

  7. Development of engineered barrier

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Kwan Sik; Cho, Won Jin; Lee, Jae Owan; Kim, Seung Soo; Kang, Mu Ja

    1999-03-01

    Engineered barrier development was carried out into the three research fields : waste form, disposal container, and buffer. The waste form field dealt with long-term leaching tests with borosilicate waste glasses surrounded by compacted bentonite. The leach rate decreased with increasing time, and was higher for the waste specimen rich in U and Na. In the container field, preliminary concepts of disposal containers were recommended by conducting structural analysis, thermal analysis, and shielding analysis, and major properties of stainless steel, copper, and titanium as a container material were surveyed. The sensitization degrees of SUS 316 and316L were lower than those of SUS 304 and 304L, respectively. The crevice corrosion of sensitized stainless steel was sensitive to the content of salt. Researches into the buffer included establishment of its performance criteria followed by investigating major properties of buffer using potential material in Korea. Experiments were made for measuring hydraulic conductivities, swelling properties, mechanical properties, thermal conductivities, pore-water chemistry properties, and adsorption properties was also investigated. (author)

  8. Controlling ferrofluid permeability across the blood–brain barrier model

    International Nuclear Information System (INIS)

    In the present study, an in vitro blood–brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood–brain barrier model was completed by examining the permeability of FITC-Dextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood–brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood–brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood–brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood–brain barrier (e.g. CPB). (paper)

  9. Controlling ferrofluid permeability across the blood–brain barrier model.

    Science.gov (United States)

    Shi, Di; Sun, Linlin; Mi, Gujie; Sheikh, Lubna; Bhattacharya, Soumya; Nayar, Suprabha; Webster, Thomas J

    2014-02-21

    In the present study, an in vitro blood–brain barrier model was developed using murine brain endothelioma cells (b.End3 cells). Confirmation of the blood–brain barrier model was completed by examining the permeability of FITCDextran at increasing exposure times up to 96 h in serum-free medium and comparing such values with values from the literature. After such confirmation, the permeability of five novel ferrofluid (FF) nanoparticle samples, GGB (ferrofluids synthesized using glycine, glutamic acid and BSA), GGC (glycine, glutamic acid and collagen), GGP (glycine, glutamic acid and PVA), BPC (BSA, PEG and collagen) and CPB (collagen, PVA and BSA), was determined using this blood–brain barrier model. All of the five FF samples were characterized by zeta potential to determine their charge as well as TEM and dynamic light scattering for determining their hydrodynamic diameter. Results showed that FF coated with collagen passed more easily through the blood–brain barrier than FF coated with glycine and glutamic acid based on an increase of 4.5% in permeability. Through such experiments, diverse magnetic nanomaterials (such as FF) were identified for: (1) MRI use since they were less permeable to penetrate the blood–brain barrier to avoid neural tissue toxicity (e.g. GGB) or (2) brain drug delivery since they were more permeable to the blood–brain barrier (e.g. CPB). PMID:24457539

  10. Tritium/hydrogen barrier development

    International Nuclear Information System (INIS)

    A review of the hydrogen permeation barriers which can be applied to the structural metals used in fusion power plants is presented. Both implanted and chemically available hydrogen isotopes must be controlled in fusion plants. The need for permeation barriers appears strongest in Pb-17Li blanket designs, although barriers are also necessary for other blanket and coolant systems. Barriers which provide greater than a 1000- fold reduction in the permeation of structural metals are desired. In laboratory experiments, aluminide and titanium ceramic coatings provide permeation reduction factors (PRFs) of 1000 to over 100000 with a wide range of scatter. The rate-controlling mechanism for hydrogen permeation through these barriers may be related to the number and type of defects in the barriers. Although these barriers appear robust and resistant to liquid metal corrosion, irradiation tests which simulate blanket environments result in very low PRFs in comparison with laboratory experiments, i.e. less than 150. It is anticipated from fundamental research activities that the radiation- and electric-field-induced enhancement of hydrogen diffusion in oxides may contribute to the lower PRFs during in-reactor experiments. (orig.)

  11. Tritium/hydrogen barrier development

    International Nuclear Information System (INIS)

    A review of hydrogen permeation barriers that can be applied to structural metals used in fusion power plants is presented. Both implanted and chemically available hydrogen isotopes must be controlled in fusion plants. The need for permeation barriers appears strongest in Li17-Pb blanket designs, although barriers also appear necessary for other blanket and coolant systems. Barriers that provide greater than a 1000 fold reduction in the permeation of structural metals are desired. In laboratory experiments, aluminide and titanium ceramic coatings provide permeation reduction factors, PRFS, from 1000 to over 100,000 with a wide range of scatter. The rate-controlling mechanism for hydrogen permeation through these barriers may be related to the number and type of defects in the barriers. Although these barriers appear robust and resistant to liquid metal corrosion, irradiation tests which simulate blanket environments result in very low PRFs in comparison to laboratory experiments, i.e., <150. It is anticipated from fundamental research activities that the REID enhancement of hydrogen diffusion in oxides may contribute to the lower permeation reduction factors during in-reactor experiments

  12. Vehicle barrier with access delay

    Science.gov (United States)

    Swahlan, David J; Wilke, Jason

    2013-09-03

    An access delay vehicle barrier for stopping unauthorized entry into secure areas by a vehicle ramming attack includes access delay features for preventing and/or delaying an adversary from defeating or compromising the barrier. A horizontally deployed barrier member can include an exterior steel casing, an interior steel reinforcing member and access delay members disposed within the casing and between the casing and the interior reinforcing member. Access delay members can include wooden structural lumber, concrete and/or polymeric members that in combination with the exterior casing and interior reinforcing member act cooperatively to impair an adversarial attach by thermal, mechanical and/or explosive tools.

  13. A LOOK AT CULTURAL BARRIERS

    Directory of Open Access Journals (Sweden)

    Carmen A. VRÂNCEANU

    2015-06-01

    Full Text Available Nowadays the global market allows each individual to work in foreign countries. This fact is a great opportunity for business development, but also puts into light the problem of cultural barriers. Ineffective cross-cultural communication and collaboration can harm employees, customers, and other stakeholders. A company with employees from different cultures must acknowledge and understand these barriers in order to overcome them and to obtain the desired performance. The present study aims to expose the cultural barriers encountered by foreigners in a multinational company from Romania.

  14. Ethanol Disrupts Vascular Endothelial Barrier: Implication in Cancer Metastasis

    OpenAIRE

    Xu, Mei; Chen, Gang; Fu, Wei; Liao, Mingjun; FRANK, JACQUELINE A.; Bower, Kimberly A.; Fang, Shengyun; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2012-01-01

    Both epidemiological and experimental studies indicate that ethanol exposure enhances tumor progression. Ethanol exposure promotes cancer cell invasion and is implicated in tumor metastasis. Metastasis consists of multiple processes involving intravasation and extravasation of cancer cells across the blood vessel walls. The integrity of the vascular endothelial barrier that lines the inner surface of blood vessels plays a critical role in cancer cell intravasation/extravasation. We examined t...

  15. Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood–Brain Barrier in Vitro Model

    Directory of Open Access Journals (Sweden)

    Peng-Yi Hu

    2016-03-01

    Full Text Available The objectives of the present investigation were to: (1 elucidate the transport mechanism of paeoniflorin (PF across MDCK-MDR1 monolayers; and (2 evaluate the effect of ligustilide (LIG, senkyunolide I (SENI and senkyunolide A (SENA on the transport of PF through blood–brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B and from basolateral to apical sides (B→A. Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp ranging from 0.587 × 10−6 to 0.705 × 10−6 cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na2 suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA.

  16. Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model.

    Science.gov (United States)

    Hu, Peng-Yi; Liu, Dan; Zheng, Qin; Wu, Qing; Tang, Yu; Yang, Ming

    2016-01-01

    The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood-brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (A→B) and from basolateral to apical sides (B→A). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 × 10(-6) to 0.705 × 10(-6) cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The B→A/A→B permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in A→B direction by EDTA-Na₂ suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in A→B direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in A→B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA. PMID:26950101

  17. Probiotics the Good Neighbor: Guarding the Gut Mucosal Barrier

    Directory of Open Access Journals (Sweden)

    R. K. Rao

    2009-01-01

    Full Text Available Problem statement: The disruption of gut barrier function plays a crucial role in the pathogenesis of not only gastrointestinal diseases, but also the diseases of liver and other organs. Mucosal protective factors that preserve the gut barrier integrity are beneficial in the prevention and treatment of such diseases. Probiotics is a group of helpful bacteria that protect the gastrointestinal mucosa from a variety of insults. Therefore, understanding the mechanism of probiotic-mediated protection of gut barrier function is an important area of investigation. Approach: Several studies had addressed the role of probiotics in the protection of gut barrier integrity. In a recent study, we investigated the role of Lactobacillus rhamnosus GG and two soluble proteins, p40 and p75, in the protection of gut barrier function in Caco-2 cell monolayer, a model of the intestinal epithelium. Results: Studies demonstrated that live or dead Lactobacillus rhamnosus GG prevents oxidative stress-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. The isolated soluble proteins of this probiotic, p40 and p75, also prevent hydrogen peroxide-induced tight junction disruption. This protective effect of probiotic proteins was mediated by the activation of ERK1/2 and protein kinase C isoforms, PKCβI and PKCε. Conclusion: Lactobacillus rhamnosus GG prevent oxidative stress-induced disruption of intestinal epithelial tight junctions and barrier function, suggesting that preservation of epithelial barrier function is one of the mechanisms involved in the mucosal protective role of probiotics in the gut.

  18. Small-scale experimental tests of tandem mirror machines with thermal barriers

    International Nuclear Information System (INIS)

    A summary is given of current physical understanding of tandem mirrors with thermal barriers. Physicists who understand tandem mirrors can use this document as a preliminary guide to the physical issues and experimental problems involved. This report will focus upon the issues that can be tested experimentally, and on the areas needing experimental and theoretical inventions. The next section discusses the plasma potentials and plasma confinement which correspond to a tandem mirror with thermal barriers, assuming the barriers exist in steady-state. The creation of a barrier is discussed, i.e., the natural tendency of the barrier cell to fill with plasma must be countered by pumping ions out of the barrier. The design of a barrier-pumping experiment for TMX is described

  19. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper;

    2014-01-01

    ) with in total 111 children (53 boys) from fourth grade, with a mean age of 10.4 years. The focus groups included an open group discussion, go-along group interviews, and a gender segregated post-it note activity. A content analysis of the post-it notes was used to rank the children's perceived barriers......BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...

  20. Barriers that do not fall

    OpenAIRE

    Velasco Arroyo, Juan Carlos

    2014-01-01

    * Full title: "Barriers that do not fall. Access to citizenship and the right to vote in a comparative perspective: Germany / Spain". * Presentation in Conference "Border Transgressions" - Bonn Universität (Germany) - 8-9th May 2014

  1. Engineered barriers: current status 1989

    International Nuclear Information System (INIS)

    This report summarises the current state of research relevant to assessing the performance of engineered barriers made of steel and concrete in radioactive waste repositories. The objective of these barriers is to contain substantially the radionuclides within them by providing both physical and chemical impediment to their release. The physical barriers are of most value for highly soluble isotopes with relatively short half-lives (eg 137Cs), since they can provide a measure of containment until a large fraction of the activity has decayed. In addition they can facilitate retrievability for some period after disposal. The chemical barriers operate by beneficial conditioning of the near field groundwater and providing sites for sorption of radionuclides. Both of these reduce the aqueous concentration of radionuclides in the near field. (author)

  2. Coastal Structures and Barriers 2012

    Data.gov (United States)

    California Department of Resources — This dataset is a compilation of the UCSC Sand Retention Structures, MC Barriers, and USACE Coastal Structures. UCSC Sand Retention Structures originate from a...

  3. Translating barriers into potential improvements

    DEFF Research Database (Denmark)

    Altintzoglou, Themistoklis; Hansen, Karina Birch; Valsdottir, Thora;

    2010-01-01

    Purpose: The aim of this study is to explore potential barriers to seafood consumption by The aim of this study is to explore potential barriers to seafood consumption by young adults and the parents of young children. Knowledge of these barriers will be used to assist the development of new....... Practical implications: Inputs for NPD related to convenience, attractiveness, quality, Inputs for NPD related to convenience, attractiveness, quality, trustworthiness, knowledge and requirements about seafood preparation are discussed. Originality/value: The present study combines qualitative methods to...... lead to practical input The present study combines qualitative methods to lead to practical input for NPD focusing on overcoming the barriers that keep consumers from choosing existing healthy seafood products. The importance of the consumers' confidence in their ability to successfully prepare a...

  4. Barriers to Effective Strategic Planning

    OpenAIRE

    Bilal Latif

    2012-01-01

    Despite the best intentions and a lot of hard work, strategic planning most predictably fails. It’s not that strategic planning is a bad idea but there are some barriers which involve in its failure. This paper explores how and where strategic planning goes awry and what executives can do about it. The study finds some of the most common barriers in effective strategic planning like, strict time limits, identical procedures, lack of accountability, power and influence which organizations freq...

  5. Barriers in diabetes self management

    OpenAIRE

    Rising, Carl Johan; Lauwersen, Asbjørn Flyger; Stoustrup, Sune Wiingaard

    2013-01-01

    This project seeks to expand on the question: What barriers may occur in diabetes patients' self-care, and how can doctors and patients communicate across professionalism? This project deals with the barrier that may arise between the transfer of highly professional knowledge and patient. The project seeks to create an understanding on how diabetes patients, which is the target audience, understands and experience their illness, and thereby mapping key elements for further focus, to better th...

  6. Superheavy nuclei and fission barriers

    Science.gov (United States)

    Lu, Bing-Nan; Zhao, Jie; Zhao, En-Guang; Zhou, Shan-Gui

    In this chapter, we will present relativistic mean field (RMF) description of heavy and superheavy nuclei (SHN). We will discuss the shell structure and magic numbers in the mass region of SHN, binding energies and α decay Q values, shapes of ground states and potential energy surfaces and fission barriers. We particularly focus on the multidimensionally-constrained covariant density functional theories (CDFT) and the applications of CDFT to the study of exotic nuclear shapes and fission barriers.

  7. Economic alternatives for containment barriers

    Energy Technology Data Exchange (ETDEWEB)

    Nicholson, P.J.; Jasperse, B.H.; Fisher, M.J. [Geo-Con, Inc., Monroeville, PA (United States)

    1997-12-31

    Fixation, barriers, and containment of existing landfills and other disposal areas are often performed by insitu auger type soil mixing and jet grouting. Cement or other chemical reagents are mixed with soil to form both vertical and horizontal barriers. Immobilization of contaminants can be economically achieved by mixing soil and the contaminants with reagents that solidify or stabilize the contaminated area. Developed in Japan, and relatively new to the United States, the first large scale application was for a vertical barrier at the Jackson Lake Dam project in 1986. This technology has grown in both the civil and environmental field since. The paper describes current United States practice for Deep Soil Mixing (over 12 meters in depth), and Shallow Soil Mixing for vertical barriers and stabilization/solidification, and Jet Grouting for horizontal and vertical barriers. Creating very low permeability barriers at depth with minimal surface return often makes these techniques economical when compared to slurry trenches. The paper will discuss equipment, materials, soil and strength parameters, and quality control.

  8. Global interrupt and barrier networks

    Science.gov (United States)

    Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E; Heidelberger, Philip; Kopcsay, Gerard V.; Steinmacher-Burow, Burkhard D.; Takken, Todd E.

    2008-10-28

    A system and method for generating global asynchronous signals in a computing structure. Particularly, a global interrupt and barrier network is implemented that implements logic for generating global interrupt and barrier signals for controlling global asynchronous operations performed by processing elements at selected processing nodes of a computing structure in accordance with a processing algorithm; and includes the physical interconnecting of the processing nodes for communicating the global interrupt and barrier signals to the elements via low-latency paths. The global asynchronous signals respectively initiate interrupt and barrier operations at the processing nodes at times selected for optimizing performance of the processing algorithms. In one embodiment, the global interrupt and barrier network is implemented in a scalable, massively parallel supercomputing device structure comprising a plurality of processing nodes interconnected by multiple independent networks, with each node including one or more processing elements for performing computation or communication activity as required when performing parallel algorithm operations. One multiple independent network includes a global tree network for enabling high-speed global tree communications among global tree network nodes or sub-trees thereof. The global interrupt and barrier network may operate in parallel with the global tree network for providing global asynchronous sideband signals.

  9. Immune responses at brain barriers and implications for brain development and neurological function in later life

    Directory of Open Access Journals (Sweden)

    Helen B. Stolp

    2013-08-01

    Full Text Available For a long time the brain has been considered an immune-privileged site due to a muted inflammatory response and the presence of protective brain barriers. It is now recognised that neuroinflammation may play an important role in almost all neurological disorders and that the brain barriers may be contributing through either normal immune signalling, or disruption of their basic physiological mechanisms. The distinction between normal function and dysfunction at the barriers is difficult to dissect, partly due to a lack of understanding of normal barrier function and partly because of physiological changes that occur as part of normal development and ageing. Brain barriers consist of a number of interacting structural and physiological elements including tight junctions between adjacent barrier cells and an array of influx and efflux transporters. Despite these protective mechanisms, the capacity for immune-surveillance of the brain is maintained, and there is evidence of inflammatory signalling at the brain barriers that may be an important part of the body’s response to damage or infection. This signalling system appears to change both with normal ageing, and during disease. Changes may affect diapedesis of immune cells and active molecular transfer, or cause rearrangement of the tight junctions and an increase in passive permeability across barrier interfaces. Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging. The implications of inflammation–induced barrier dysfunction for brain development and subsequent neurological function are also discussed.

  10. Role of the Blood-Brain Barrier in the Formation of Brain Metastases

    OpenAIRE

    Krizbai, István A.; János Haskó; Csilla Fazakas; Judit Molnár; Imola Wilhelm

    2013-01-01

    The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB). The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting ...

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

    Science.gov (United States)

    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

  12. The Blood-Brain Barrier: An Engineering Perspective

    Directory of Open Access Journals (Sweden)

    Andrew eWong

    2013-08-01

    Full Text Available 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 it 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 advances in treatment of 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.

  13. Diabetes and diet: Managing dietary barriers.

    NARCIS (Netherlands)

    Friele, R.D.

    1989-01-01

    This thesis reports on the barriers diabetic patients experience with their diet, and the ways they cope with these barriers. A dietary barrier is a hinderance to a person's well-being, induced by being advised a diet. First inventories were made of possible dietary barriers and ways of coping with

  14. Characterization of geochemical barriers in a former uranium mining district

    International Nuclear Information System (INIS)

    Full text: Geochemical barriers are epigenetic zones in which selected elements are retained and their further transport is prevented. Microorganisms can enhance metal retention by direct reduction of metals or radionuclides or by formation of reducing agents like Fe(II) or sulphide. The aim of this study was to investigate if microbial activities contribute to heavy metal and radionuclide retention in a heavy metal contaminated soil. The study site was located in the former uranium mining district Ronneburg (Thuringia, Germany). In a soil profile two distinct geochemical barriers for heavy metals and uranium were identified. One manganese-rich barrier showed accumulation of Cu, Ni, Cd, Co, Zn and La and an iron-rich barrier showed accumulation of Cr and U. Throughout the soil profile total cell numbers counted after staining with DAPI approximated 106 cells/ g soil (ww). Aerobic CO2-formation rates were low with about 2 nmol g soil (ww)-1 h-1. No anaerobic microbial activities were observed in anoxic soil microcosms. After addition of 0.1 % yeast extract, nitrate- and iron-reduction were initiated. Microorganisms were probably limited by carbon availability due to the low organic carbon content of the soil. Numbers of culturable cells detected in oxic pH 5 groundwater media approximated 105 cells/ g soil (ww). Higher numbers of cells were detected in media enriched with Ni than with Cu. DGGE was used to detect differences in microbial populations between the soil horizons. The low cell abundances and microbial activities indicated that the accumulation of heavy metals and radionuclides in both geochemical barriers was not caused or significantly enhanced by microbial activities. (author)

  15. Engineered Barriers and Geological Disposal

    International Nuclear Information System (INIS)

    A geological disposal system comprises a system of multiple barriers, both natural and man-made, to provide long-term isolation and containment of radioactive waste. Various geological formations are stable and potentially suitable for geological disposal. Engineered barriers are designed to work in an integrated fashion together with the host geological formation. Much research has been carried out to develop engineered barrier systems suitable for use in different host rocks and with different waste types. These studies continue both nationally and within the framework of multilateral international projects, in facilities such as underground research laboratories. Geological disposal is the preferred method for long term management of radioactive waste. In each repository the long-term isolation and containment of the waste is achieved by the host geological formation and the system of engineered barriers. Any engineered barrier system (EBS) is made of several components, each taking different safety roles that are relied upon at different times in the lifetime of the repository. Research, demonstration and development of EBS materials, as well as of their manufacturing and emplacement technologies are important endeavours in national waste management programmes and the subject of international cooperation. These studies and demonstrations have considerably enhanced confidence in the production of the EBS components and in their performance under repository conditions

  16. Transport barriers in helical systems

    International Nuclear Information System (INIS)

    There are some publications with indications that the formation of transport barriers in toroidal devices could take place in the vicinity of low order rational surfaces (RS). It is necessary to note that the environs of RS have very important peculiarities. In particular, a stochastic layer of magnetic field lines forms instead of separaterix which must separate the island surfaces from the adjacent to them non-island surfaces in stellarator magnetic configurations. The attempt to realize the formation of transport barriers near RS and to study their influence on the RF discharge plasma confinement was undertaken in presented experiments on the U-3M torsatron. The presupposition was made that the radial electric field profile would have sharp change on the width of stochastic layer near RS in the case of collisionless longitudinal motion of electrons in this layer. Experimental data obtained on the U-3M torsatron during the formation of interior and edge transport barriers are in a good agreement with this presupposition. The results of experiments on the U-3M torsatron are discussed in comparison with data of other helical systems. It is shown that the number of dependences (the threshold power and density, the time of barrier formation, the localization of radial electric field shear layer) are in a good agreement for all these systems. In conclusion, the common features of formation of transport barriers in non- axisymmetric and non-axisymmetric systems are discussed. (author)

  17. The gut barrier: new acquisitions and therapeutic approaches.

    Science.gov (United States)

    Scaldaferri, Franco; Pizzoferrato, Marco; Gerardi, Viviana; Lopetuso, Loris; Gasbarrini, Antonio

    2012-10-01

    The intestinal barrier serves 2 critical functions for the survival of the individual: first, it allows nutrient absorption and second, it defends the body from dangerous macromolecule penetration. It is a complex multilayer system, consisting of an external "anatomic" barrier and an inner "functional" immunological barrier. The interaction of these 2 barriers enables equilibrated permeability to be maintained. Many factors can alter this balance: gut microflora modifications, mucus layer alterations, and epithelial damage can increase intestinal permeability, allowing the translocation of luminal content to the inner layer of intestinal wall. Several techniques are now available that enable us to study gut permeability: "in vitro" models (Caco-2 and HT29-MTX cells) and "in vivo" not invasive tests (sugar tests and radioisotope scanning tests) are used to estimate permeability and to suggest molecular pathophysiological mechanisms of intestinal permeability in health and diseases. Many medicinal products used in the treatment of gastrointestinal diseases have also found to play an active role in modulate intestinal permeability: corticosteroids, 5-aminosalicylic acid, anti-tumor necrosis factor, probiotics, and mucosal protectors, like gelatin tannate. This review will particularly address the role of the gut barrier in maintaining intestinal permeability (microbiota, mucus, and epithelial cells), the techniques used for estimating intestinal permeability and the therapeutic approaches able to modify it. PMID:22955350

  18. A coculture model mimicking the intestinal mucosa reveals a regulatory role for myofibroblasts in immune-mediated barrier disruption.

    Science.gov (United States)

    Willemsen, L E M; Schreurs, C C H M; Kroes, H; Spillenaar Bilgen, E J; Van Deventer, S J H; Van Tol, E A F

    2002-10-01

    The pathogenesis of Crohn's disease involves a mucosal inflammatory response affecting the barrier function of the gut. Myofibroblasts directly underlining the intestinal epithelium may have a regulatory role in immune-mediated barrier disruption. A coculture system of T84 epithelial and CCD-18Co myofibroblasts was established in order to mimic the in situ spatial interactions between these cell types and to evaluate their role in barrier: integrity. Lamina propria mononuclear cells (LPMC) were introduced in co- and monocultures. Effects of immune cells on barrier integrity was determined by measuring resistance and permeability for macromolecules. Introduction of LPMC in both culture systems caused a time-dependent decrease in barrier integrity. This was found to be less pronounced in cocultures indicating a regulatory role for mesenchymal cells. The effects were also found to depend on the route of LPMC stimulation. Additional analyses suggested that the regulatory role of myofibroblasts in barrier integrity involves production of growth factors. PMID:12395905

  19. Programmer's description of the Barrier Data Base

    International Nuclear Information System (INIS)

    The Barrier Data Base is a body of information concerning different kinds of barriers that are used in safeguarding nuclear materials and installations. The two programs written for creating, updating, and manipulating the Barrier Data Base are discussed. The BARRIER program is used to add, delete, modify, display, or search for specific data in the data base. A utility program named NUMBER is used to compress and renumber the barrier and threat tables

  20. Structure information from fusion barriers

    Indian Academy of Sciences (India)

    S V S Sastry; S Santra

    2000-06-01

    It is shown that the analysis of fusion barrier distributions is not always an unambiguous test or a ‘fingerprint’ of the structure information of the colliding nuclei. Examples are presented with same fusion barrier distributions for nuclei having different structures. The fusion excitation functions for 16O+208Pb, using the coupled reaction channel (CRC) method and correct structure information, have been analysed. The barrier distributions derived from these excitation functions including many of the significant channels are featureless, although these channels have considerable effects on the fusion excitation function. However, a simultaneous analysis of the fusion, elastic and quasi-elastic channels would fix the structure and the reaction unambiguously

  1. PROMOTION, SWITCHING BARRIERS, AND LOYALTY

    Directory of Open Access Journals (Sweden)

    Gu-Shin Tung

    2011-06-01

    Full Text Available This paper investigates the causal relationships among promotion effects, switching barriers, and loyalty in the department stores. The relationship between switching barriers and loyalty reveals partially the same results as the switching barriers theory of Jones et al. (2000. The reasons arise from “too often” and “too similar” sales promotion programs of competitive department stores in Taiwan, leading the promotion effects to not contribute to the attractiveness of competitors. The promotion effects have a positive and significant influence on loyalty, which is consistent with the prior literature. Promotion effects are also the most important weight to loyalty in our tested model but it reveals a seeming loyalty, because the loyalty depends on the reward of promotion. The negative relationship between promotion effects and attractiveness of alternative supports the promotion effects, which can lower the attractiveness of competitors, but these similar promotion plans are not attributed to interpersonal relationships.

  2. Barriers to Effective Strategic Planning

    Directory of Open Access Journals (Sweden)

    Bilal Latif

    2012-12-01

    Full Text Available Despite the best intentions and a lot of hard work, strategic planning most predictably fails. It’s not that strategic planning is a bad idea but there are some barriers which involve in its failure. This paper explores how and where strategic planning goes awry and what executives can do about it. The study finds some of the most common barriers in effective strategic planning like, strict time limits, identical procedures, lack of accountability, power and influence which organizations frequently face in strategy formulation and implementation. It is concluded that, in order to achieve the goal of effective strategic planning, effective change management and leadership are indispensable. On the one hand, it is mandatory for the leadership to involve employees in decision making process, along with the explicit description of their roles within the organization, and on the other hand, full mechanism of employees’ accountability and regular checks are required to remove these barriers.

  3. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage

    NARCIS (Netherlands)

    P. Aparicio-Domingo (Patricia); M. Romera-Hernandez (Monica); J.J. Karrich (Julien J.); F.H.J. Cornelissen (Ferry); N. Papazian (Natalie); D.J. Lindenbergh-Kortleve (Dicky); J.A. Butler (James A.); L. Boon (Louis); M. Coles (Mark); J.N. Samsom (Janneke); T. Cupedo (Tom)

    2015-01-01

    textabstractDisruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence

  4. Drug transporters, the blood–testis barrier, and spermatogenesis

    OpenAIRE

    Su, Linlin; Mruk, Dolores D.; Cheng, C. Yan

    2010-01-01

    The blood–testis barrier (BTB), which is created by adjacent Sertoli cells near the basement membrane, serves as a ‘gatekeeper’ to prohibit harmful substances from reaching developing germ cells, most notably postmeiotic spermatids. The BTB also divides the seminiferous epithelium into the basal and adluminal (apical) compartment so that postmeiotic spermatid development, namely spermiogenesis, can take place in a specialized microenvironment in the apical compartment behind the BTB. The BTB ...

  5. The Solution to Green Barrier

    Institute of Scientific and Technical Information of China (English)

    Cui Yan

    2009-01-01

    @@ The recovery process of world economy is rough and full of twists and turns.Especially the trade protectionism,having reemerged under the mask of"green barrier",is making a great impact on the slowly recovering world economy and trade.Then,what are the characteristics of trade barriers in the post-crisis era?Where is the outlet of Chinese manufacturing industry?With these questions,ourreporter interviewed Professor Zhou Shijian,Standing Director to China Association of International Trade and Senior Researcher to SINO-US Relationship Research Centre of Tsinghua University.

  6. Systems study on engineered barriers: barrier performance analysis

    International Nuclear Information System (INIS)

    A performance assessment model for multiple barrier packages containing unreprocessed spent fuel has been modified and applied to several package designs. The objective of the study was to develop information to be used in programmatic decision making concerning engineered barrier package design and development. The assessment model, BARIER, was developed in previous tasks of the System Study on Engineered Barriers (SSEB). The new version discussed in this report contains a refined and expanded corrosion rate data base which includes pitting, crack growth, and graphitization as well as bulk corrosion. Corrosion rates for oxic and anoxic conditions at each of the two temperature ranges are supplied. Other improvements include a rigorous treatment of radionuclide release after package failure which includes resistance of damaged barriers and backfill, refined temperature calculations that account for convection and radiation, a subroutine to calculate nuclear gamma radiation field at each barrier surface, refined stress calculations with reduced conservatism and various coding improvements to improve running time and core usage. This report also contains discussion of alternative scenarios to the assumed flooded repository as well as the impact of water exclusion backfills. The model was used to assess post repository closure performance for several designs which were all variation of basic designs from the Spent Unreprocessed Fuel (SURF) program. Many designs were found to delay the onset of leaching by at least a few hundreds of years in all geologic media. Long delay times for radionuclide release were found for packages with a few inches of sorption backfill. Release of uranium, plutonium, and americium was assessed

  7. Systems study on engineered barriers: barrier performance analysis

    Energy Technology Data Exchange (ETDEWEB)

    Stula, R.T.; Albert, T.E.; Kirstein, B.E.; Lester, D.H.

    1980-09-01

    A performance assessment model for multiple barrier packages containing unreprocessed spent fuel has been modified and applied to several package designs. The objective of the study was to develop information to be used in programmatic decision making concerning engineered barrier package design and development. The assessment model, BARIER, was developed in previous tasks of the System Study on Engineered Barriers (SSEB). The new version discussed in this report contains a refined and expanded corrosion rate data base which includes pitting, crack growth, and graphitization as well as bulk corrosion. Corrosion rates for oxic and anoxic conditions at each of the two temperature ranges are supplied. Other improvements include a rigorous treatment of radionuclide release after package failure which includes resistance of damaged barriers and backfill, refined temperature calculations that account for convection and radiation, a subroutine to calculate nuclear gamma radiation field at each barrier surface, refined stress calculations with reduced conservatism and various coding improvements to improve running time and core usage. This report also contains discussion of alternative scenarios to the assumed flooded repository as well as the impact of water exclusion backfills. The model was used to assess post repository closure performance for several designs which were all variation of basic designs from the Spent Unreprocessed Fuel (SURF) program. Many designs were found to delay the onset of leaching by at least a few hundreds of years in all geologic media. Long delay times for radionuclide release were found for packages with a few inches of sorption backfill. Release of uranium, plutonium, and americium was assessed.

  8. Epigenetic control of intestinal barrier function and inflammation in zebrafish.

    Science.gov (United States)

    Marjoram, Lindsay; Alvers, Ashley; Deerhake, M Elizabeth; Bagwell, Jennifer; Mankiewicz, Jamie; Cocchiaro, Jordan L; Beerman, Rebecca W; Willer, Jason; Sumigray, Kaelyn D; Katsanis, Nicholas; Tobin, David M; Rawls, John F; Goll, Mary G; Bagnat, Michel

    2015-03-01

    The intestinal epithelium forms a barrier protecting the organism from microbes and other proinflammatory stimuli. The integrity of this barrier and the proper response to infection requires precise regulation of powerful immune homing signals such as tumor necrosis factor (TNF). Dysregulation of TNF leads to inflammatory bowel diseases (IBD), but the mechanism controlling the expression of this potent cytokine and the events that trigger the onset of chronic inflammation are unknown. Here, we show that loss of function of the epigenetic regulator ubiquitin-like protein containing PHD and RING finger domains 1 (uhrf1) in zebrafish leads to a reduction in tnfa promoter methylation and the induction of tnfa expression in intestinal epithelial cells (IECs). The increase in IEC tnfa levels is microbe-dependent and results in IEC shedding and apoptosis, immune cell recruitment, and barrier dysfunction, consistent with chronic inflammation. Importantly, tnfa knockdown in uhrf1 mutants restores IEC morphology, reduces cell shedding, and improves barrier function. We propose that loss of epigenetic repression and TNF induction in the intestinal epithelium can lead to IBD onset. PMID:25730872

  9. Architectural Barriers Removal: Resource Guide.

    Science.gov (United States)

    Office of Human Development (DHEW), Washington, DC. Office for Handicapped Individuals.

    The guide presents information on resources for eliminating architectural barriers for handicapped persons. Entries are grouped according to information resources, funding sources, and publications available from the federal government. Seven organizations are described in terms of agency goals, publications, and materials. Federal programs…

  10. Injectable barriers for waste isolation

    International Nuclear Information System (INIS)

    In this paper the authors report laboratory work and numerical simulation done in support of development and demonstration of injectable barriers formed from either of two fluids: colloidal silica or polysiloxane. Two principal problems addressed here are control of gel time and control of plume emplacement in the vadose zone. Gel time must be controlled so that the viscosity of the barrier fluid remains low long enough to inject the barrier, but increases soon enough to gel the barrier in place. During injection, the viscosity must be low enough to avoid high injection pressures which could uplift or fracture the formation. To test the grout gel time in the soil, the injection pressure was monitored as grouts were injected into sandpacks. When grout is injected into the vadose zone, it slumps under the influence of gravity, and redistributes due to capillary forces as it gels. The authors have developed a new module for the reservoir simulator TOUGH2 to model grout injection into the vadose zone, taking into account the increase of liquid viscosity as a function of gel concentration and time. They have also developed a model to calculate soil properties after complete solidification of the grout. The numerical model has been used to design and analyze laboratory experiments and field pilot tests. The authors present the results of computer simulations of grout injection, redistribution, and solidification

  11. Injectable barriers for waste isolation

    Energy Technology Data Exchange (ETDEWEB)

    Persoff, P.; Finsterle, S.; Moridis, G.J.; Apps, J.; Pruess, K. [Lawrence Berkeley National Lab., CA (United States). Earth Sciences Div.; Muller, S.J. [Univ. of California, Berkeley, CA (United States). Dept. of Chemical Engineering

    1995-03-01

    In this paper the authors report laboratory work and numerical simulation done in support of development and demonstration of injectable barriers formed from either of two fluids: colloidal silica or polysiloxane. Two principal problems addressed here are control of gel time and control of plume emplacement in the vadose zone. Gel time must be controlled so that the viscosity of the barrier fluid remains low long enough to inject the barrier, but increases soon enough to gel the barrier in place. During injection, the viscosity must be low enough to avoid high injection pressures which could uplift or fracture the formation. To test the grout gel time in the soil, the injection pressure was monitored as grouts were injected into sandpacks. When grout is injected into the vadose zone, it slumps under the influence of gravity, and redistributes due to capillary forces as it gels. The authors have developed a new module for the reservoir simulator TOUGH2 to model grout injection into the vadose zone, taking into account the increase of liquid viscosity as a function of gel concentration and time. They have also developed a model to calculate soil properties after complete solidification of the grout. The numerical model has been used to design and analyze laboratory experiments and field pilot tests. The authors present the results of computer simulations of grout injection, redistribution, and solidification.

  12. Overcoming Barriers: Women in Superintendency

    Science.gov (United States)

    Miller, Claire M.

    2009-01-01

    Women currently represent the largest number of teachers in the United States but remain underrepresented in the superintendent position. This suggests that the superintendency has been influenced by patriarchy. If women are to break through the barriers that prevent them from attaining a superintendency, we will need to understand the social…

  13. Communities Address Barriers to Connectivity.

    Science.gov (United States)

    Byers, Anne

    1996-01-01

    Rural areas lag behind urban areas in access to information technologies. Public institutions play a critical role in extending the benefits of information technologies to those who would not otherwise have access. The most successful rural telecommunications plans address barriers to use, such as unawareness of the benefits, technophobia, the…

  14. TREM-1 Promotes Pancreatitis-Associated Intestinal Barrier Dysfunction

    Directory of Open Access Journals (Sweden)

    Shengchun Dang

    2012-01-01

    Full Text Available Severe acute pancreatitis (SAP can cause intestinal barrier dysfunction (IBD, which significantly increases the disease severity and risk of mortality. We hypothesized that the innate immunity- and inflammatory-related protein-triggering receptor expressed on myeloid cells-1 (TREM-1 contributes to this complication of SAP. Thus, we investigated the effect of TREM-1 pathway modulation on a rat model of pancreatitis-associated IBD. In this study we sought to clarify the role of TREM-1 in the pathophysiology of intestinal barrier dysfunction in SAP. Specifically, we evaluated levels of serum TREM-1 and membrane-bound TREM-1 in the intestine and pancreas from an animal model of experimentally induced SAP. TREM-1 pathway blockade by LP17 treatment may suppress pancreatitis-associated IBD and ameliorate the damage to the intestinal mucosa barrier.

  15. Interaction of Botulinum Toxin with the Epithelial Barrier

    Directory of Open Access Journals (Sweden)

    Yukako Fujinaga

    2010-01-01

    Full Text Available Botulinum neurotoxin (BoNT is a protein toxin (~150 kDa, which possesses a metalloprotease activity. Food-borne botulism is manifested when BoNT is absorbed from the digestive tract to the blood stream and enters the peripheral nerves, where the toxin cleaves core proteins of the neuroexocytosis apparatus and elicits the inhibition of neurotransmitter release. The initial obstacle to orally ingested BoNT entering the body is the epithelial barrier of the digestive tract. Recent cell biology and molecular biology studies are beginning to elucidate the mechanism by which this large protein toxin crosses the epithelial barrier. In this review, we provide an overview of the structural features of botulinum toxins (BoNT and BoNT complex and the interaction of these toxins with the epithelial barrier.

  16. Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity

    Directory of Open Access Journals (Sweden)

    Jiehao Zhou

    2010-01-01

    Full Text Available We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE. The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP- 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P<.05. Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P<.05 and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier.

  17. Isolation of a Mouse Motoneuron-Enriched Fraction from Mouse Spinal Cord on a Density Barrier

    OpenAIRE

    John Graham

    2002-01-01

    After a combined enzymic and mechanical disruption of the spinal cord tissue, the low-density motoneurons band at the interface of a 1.06-g/ml barrier through which other contaminating cells sediment.

  18. Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function

    DEFF Research Database (Denmark)

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis;

    2013-01-01

    antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic...

  19. Involvement of local lamellipodia in endothelial barrier function.

    Science.gov (United States)

    Breslin, Jerome W; Zhang, Xun E; Worthylake, Rebecca A; Souza-Smith, Flavia M

    2015-01-01

    Recently we observed that endothelial cells cultured in tightly confluent monolayers display frequent local lamellipodia, and that thrombin, an agent that increases endothelial permeability, reduces lamellipodia protrusions. This led us to test the hypothesis that local lamellipodia contribute to endothelial barrier function. Movements of subcellular structures containing GFP-actin or VE-cadherin-GFP expressed in endothelial cells were recorded using time-lapse microscopy. Transendothelial electrical resistance (TER) served as an index of endothelial barrier function. Changes in both lamellipodia dynamics and TER were assessed during baseline and after cells were treated with either the barrier-disrupting agent thrombin, or the barrier-stabilizing agent sphingosine-1-phosphate (S1P). The myosin II inhibitor blebbistatin was used to selectively block lamellipodia formation, and was used to test their role in the barrier function of endothelial cell monolayers and isolated, perfused rat mesenteric venules. Myosin light chain (MLC) phosphorylation was assessed by immunofluorescence microscopy. Rac1 and RhoA activation were evaluated using G-LISA assays. The role of Rac1 was tested with the specific inhibitor NSC23766 or by expressing wild-type or dominant negative GFP-Rac1. The results show that thrombin rapidly decreased both TER and the lamellipodia protrusion frequency. S1P rapidly increased TER in association with increased protrusion frequency. Blebbistatin nearly abolished local lamellipodia protrusions while cortical actin fibers and stress fibers remained intact. Blebbistatin also significantly decreased TER of cultured endothelial cells and increased permeability of isolated rat mesenteric venules. Both thrombin and S1P increased MLC phosphorylation and activation of RhoA. However, thrombin and S1P had differential impacts on Rac1, correlating with the changes in TER and lamellipodia protrusion frequency. Overexpression of Rac1 elevated, while NSC23766 and

  20. Involvement of local lamellipodia in endothelial barrier function.

    Directory of Open Access Journals (Sweden)

    Jerome W Breslin

    Full Text Available Recently we observed that endothelial cells cultured in tightly confluent monolayers display frequent local lamellipodia, and that thrombin, an agent that increases endothelial permeability, reduces lamellipodia protrusions. This led us to test the hypothesis that local lamellipodia contribute to endothelial barrier function. Movements of subcellular structures containing GFP-actin or VE-cadherin-GFP expressed in endothelial cells were recorded using time-lapse microscopy. Transendothelial electrical resistance (TER served as an index of endothelial barrier function. Changes in both lamellipodia dynamics and TER were assessed during baseline and after cells were treated with either the barrier-disrupting agent thrombin, or the barrier-stabilizing agent sphingosine-1-phosphate (S1P. The myosin II inhibitor blebbistatin was used to selectively block lamellipodia formation, and was used to test their role in the barrier function of endothelial cell monolayers and isolated, perfused rat mesenteric venules. Myosin light chain (MLC phosphorylation was assessed by immunofluorescence microscopy. Rac1 and RhoA activation were evaluated using G-LISA assays. The role of Rac1 was tested with the specific inhibitor NSC23766 or by expressing wild-type or dominant negative GFP-Rac1. The results show that thrombin rapidly decreased both TER and the lamellipodia protrusion frequency. S1P rapidly increased TER in association with increased protrusion frequency. Blebbistatin nearly abolished local lamellipodia protrusions while cortical actin fibers and stress fibers remained intact. Blebbistatin also significantly decreased TER of cultured endothelial cells and increased permeability of isolated rat mesenteric venules. Both thrombin and S1P increased MLC phosphorylation and activation of RhoA. However, thrombin and S1P had differential impacts on Rac1, correlating with the changes in TER and lamellipodia protrusion frequency. Overexpression of Rac1 elevated

  1. Involvement of Local Lamellipodia in Endothelial Barrier Function

    Science.gov (United States)

    Breslin, Jerome W.; Zhang, Xun E.; Worthylake, Rebecca A.; Souza-Smith, Flavia M.

    2015-01-01

    Recently we observed that endothelial cells cultured in tightly confluent monolayers display frequent local lamellipodia, and that thrombin, an agent that increases endothelial permeability, reduces lamellipodia protrusions. This led us to test the hypothesis that local lamellipodia contribute to endothelial barrier function. Movements of subcellular structures containing GFP-actin or VE-cadherin-GFP expressed in endothelial cells were recorded using time-lapse microscopy. Transendothelial electrical resistance (TER) served as an index of endothelial barrier function. Changes in both lamellipodia dynamics and TER were assessed during baseline and after cells were treated with either the barrier-disrupting agent thrombin, or the barrier-stabilizing agent sphingosine-1-phosphate (S1P). The myosin II inhibitor blebbistatin was used to selectively block lamellipodia formation, and was used to test their role in the barrier function of endothelial cell monolayers and isolated, perfused rat mesenteric venules. Myosin light chain (MLC) phosphorylation was assessed by immunofluorescence microscopy. Rac1 and RhoA activation were evaluated using G-LISA assays. The role of Rac1 was tested with the specific inhibitor NSC23766 or by expressing wild-type or dominant negative GFP-Rac1. The results show that thrombin rapidly decreased both TER and the lamellipodia protrusion frequency. S1P rapidly increased TER in association with increased protrusion frequency. Blebbistatin nearly abolished local lamellipodia protrusions while cortical actin fibers and stress fibers remained intact. Blebbistatin also significantly decreased TER of cultured endothelial cells and increased permeability of isolated rat mesenteric venules. Both thrombin and S1P increased MLC phosphorylation and activation of RhoA. However, thrombin and S1P had differential impacts on Rac1, correlating with the changes in TER and lamellipodia protrusion frequency. Overexpression of Rac1 elevated, while NSC23766 and

  2. Barriers to Physical Activity Among Gay Men.

    Science.gov (United States)

    Cary, Miranda A; Brittain, Danielle R; Dinger, Mary K; Ford, Melissa L; Cain, Meagan; Sharp, Teresa A

    2016-09-01

    Gay men may not be physically active at recommended levels to achieve health benefits. Thus, a need exists to identify general (i.e., common across populations) and population-specific barriers that hinder or stop gay men from participating in physical activity (PA). Salient barriers may be identified through the extent each barrier limits PA (i.e., barrier limitation) and the level of one's confidence to overcome barriers and engage in PA (i.e., self-regulatory efficacy). The purposes of this study were to (1) provide a description of general and population-specific barriers to PA among sufficiently and insufficiently active gay men, (2) identify barrier limitation and self-regulatory efficacy for the reported barriers, and (3) examine the associations between meeting the current PA recommendation, barrier limitation, and self-regulatory efficacy. Participants were 108 self-identified gay males aged 21 to 64 years who completed a web-based survey. A total of 35 general barriers and no population-specific barriers were identified by the sufficiently and insufficiently active groups. The sufficiently active group reported higher self-regulatory efficacy and lower barrier limitation for nearly all reported barriers. A binary logistic regression used to examine the associations between PA, barrier limitation, and self-regulatory efficacy was statistically significant, χ(2)(2, N = 108) = 19.26, p < .0001, R(2) = .16. Only barrier limitation significantly contributed to the model. Future research should continue to examine barriers to PA among gay men to determine whether an intervention needs to be designed specifically for gay men or whether a one-size-fits-all intervention would be effective in helping all men overcome common barriers to engaging in PA. PMID:25643585

  3. Barriers to improvements in energy efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the ``barriers`` literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  4. Barriers to improvements in energy efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the barriers'' literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  5. Gliomas and the vascular fragility of the blood brain barrier

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo eDubois

    2014-12-01

    Full Text Available Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB. By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM, characterized by a highly heterogeneous cell population (including tumor stem cells, extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the blood brain barrier and the concerns that arise when this barrier is affected.

  6. Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation

    OpenAIRE

    Chu, Ling-Yun; Wang, Yi-Fu; Cheng, Huei-Hsuan; Kuo, Cheng-Chin; Wu, Kenneth K.

    2016-01-01

    The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP) as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier fun...

  7. "Targeted disruption of the epithelial-barrier by Helicobacter pylori"

    OpenAIRE

    Wroblewski Lydia E; Peek Richard M

    2011-01-01

    Abstract Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gas...

  8. Exocyst Sec10 protects epithelial barrier integrity and enhances recovery following oxidative stress, by activation of the MAPK pathway

    OpenAIRE

    Park, Kwon Moo; Fogelgren, Ben; Zuo, Xiaofeng; Kim, Jinu; Chung, Daniel C.; LIPSCHUTZ, Joshua H.

    2010-01-01

    Cell-cell contacts are essential for epithelial cell function, and disruption is associated with pathological conditions including ischemic kidney injury. We hypothesize that the exocyst, a highly-conserved eight-protein complex that targets secretory vesicles carrying membrane proteins, is involved in maintaining renal epithelial barrier integrity. Accordingly, increasing exocyst expression in renal tubule cells may protect barrier function from oxidative stress resulting from ischemia and r...

  9. Performance evaluation of intermediate cover soil barrier for removal of heavy metals in landfill leachate.

    Science.gov (United States)

    Suzuki, Kazuyuki; Anegawa, Aya; Endo, Kazuto; Yamada, Masato; Ono, Yusaku; Ono, Yoshiro

    2008-11-01

    This pilot-scale study evaluated the use of intermediate cover soil barriers for removing heavy metals in leachate generated from test cells for co-disposed fly ash from municipal solid waste incinerators, ash melting plants, and shredder residue. Cover soil barriers were mixtures of Andisol (volcanic ash soil), waste iron powder, (grinder dust waste from iron foundries), and slag fragments. The cover soil barriers were installed in the test cells' bottom layer. Sorption/desorption is an important process in cover soil bottom barrier for removal of heavy metals in landfill leachate. Salt concentrations such as those of Na, K, and Ca in leachate were extremely high (often greater than 30 gL(-1)) because of high salt content in fly ash from ash melting plants. Concentrations of all heavy metals (nickel, manganese, copper, zinc, lead, and cadmium) in test cell leachates with a cover soil barrier were lower than those of the test cell without a cover soil barrier and were mostly below the discharge limit, probably because of dilution caused by the amount of leachate and heavy metal removal by the cover soil barrier. The cover soil barriers' heavy metal removal efficiency was calculated. About 50% of copper, nickel, and manganese were removed. About 20% of the zinc and boron were removed, but lead and cadmium were removed only slightly. Based on results of calculation of the Langelier saturation index and analyses of core samples, the reactivity of the cover soil barrier apparently decreases because of calcium carbonate precipitation on the cover soil barriers' surfaces. PMID:18842283

  10. Informatization barriers of logistics process management in production company

    Directory of Open Access Journals (Sweden)

    Joanna WALASEK

    2015-09-01

    Full Text Available This article is an attempt to characterize informatization barriers of logistics processes management in a production company which provides automotive parts. Threats of successful implementation of Enterprise Resource Planning Systems include: community barriers; organizational barriers; communication barriers; formal barriers; legal barriers; not prepared implementation team barrier; substantive barrier. Proper identification of barriers and solving them are the right way to implement Enterprise Resource Planning Systems in a company.

  11. Ultrasonic wave transducer for high temperature barrier

    International Nuclear Information System (INIS)

    This transducer is made by a metallic body pivoting on a support fixed to the barrier and an internal vitroceramic waveguide in contact on the barrier and on the other end on a piezoelectric ceramic element

  12. Prototype Hanford Surface Barrier: Design basis document

    International Nuclear Information System (INIS)

    The Hanford Site Surface Barrier Development Program (BDP) was organized in 1985 to develop the technology needed to provide a long-term surface barrier capability for the Hanford Site and other arid sites. This document provides the basis of the prototype barrier. Engineers and scientists have momentarily frozen evolving barrier designs and incorporated the latest findings from BDP tasks. The design and construction of the prototype barrier has required that all of the various components of the barrier be brought together into an integrated system. This integration is particularly important because some of the components of the protective barreir have been developed independently of other barreir components. This document serves as the baseline by which future modifications or other barrier designs can be compared. Also, this document contains the minutes of meeting convened during the definitive design process in which critical decisions affecting the prototype barrier's design were made and the construction drawings

  13. Overcoming Barriers to Shared Decision Making

    Science.gov (United States)

    ... team to break it down. Barriers to shared decision making and solutions to overcome them include: Barrier: Fear, anger, stress or other emotions Solution: Strong emotions can interfere with your ability ...

  14. Blood-brain barrier properties in vitro depend on composition and assembly of endogenous extracellular matrices.

    Science.gov (United States)

    Zobel, Kathrin; Hansen, Uwe; Galla, Hans-Joachim

    2016-08-01

    Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), are enveloped by the extracellular matrix (ECM) produced by endothelial cells, pericytes and astrocytes. The contribution of matrix components secreted by the various cell types at the neurovascular unit, however, remains unclear with respect to their effect on endothelial barrier function. In this study, a new in vitro model was established by growing endothelial cells on an ECM produced by pericytes, astrocytes or a serial combination of both. The last-mentioned was found to be more in vivo-like. We investigated the role of the composition and morphology of ECM supra-structures in maintaining BBB function. The composition was analysed by protein analysis (enzyme-linked immunosorbent assay) and the ultrastructure of generated matrices was analysed by transmission electron microscopy including immunogold labelling. We could show by electric cell-substrate impedance sensing measurements that pericytes and combined matrices significantly improved the barrier tightness of porcine brain capillary endothelial cells (PBCEC). The increase of the resistance was verified by enhanced expression of tight junction proteins. Thus, for the first time, we have shown that barrier integrity is strictly controlled by the ECM, which is a product of all cells involved in the secretion of ECM components and their modification by corresponding cells. Moreover, we have demonstrated that complex matrices by the various cells of the BBB induce barrier marker enzymes in PBCEC, such as alkaline phosphatase. PMID:27053246

  15. Development of an in vitro blood-brain barrier model-cytotoxicity of mercury and aluminum.

    Science.gov (United States)

    Toimela, Tarja; Mäenpää, Hanna; Mannerström, Marika; Tähti, Hanna

    2004-02-15

    In this study, in vitro blood-brain barrier (BBB) models composed of two different cell types were compared. The aim of our study was to find an alternative human cell line that could be used in BBB models. Inorganic and organic mercury and aluminum were studied as model chemicals in the testing of the system. BBB models were composed of endothelial RBE4 cell line or retinal pigment epithelial (RPE) cell line ARPE-19 and neuronal SH-SY5Y cells as target cells. Glial U-373 MG cells were included in part of the tests to induce the formation of a tighter barrier. Millicell CM filter inserts were coated with rat-tail collagen, and RBE4 or ARPE-19 cells were placed on the filters at the density of 3.5-4 x 10(5) cells/filter. During culture, the state of confluency was microscopically observed and confirmed by the measurement of electrical resistance caused by the developing cell layer. The target cells, SH-SY5Y neuroblastoma cells, were plated on the bottom of cell culture wells at the density of 100000 cells/cm(2). In part of the studies, glial U-373 MG cells were placed on the under side of the membrane filter. When confluent filters with ARPE-19 or RBE4 cells were placed on top of the SH-SY5Y cells, different concentrations of mercuric chloride, methyl mercury chloride, and aluminum chloride were added into the filter cups along with a fluorescent tracer. Exposure time was 24 h, after which the cytotoxicity in the SH-SY5Y cell layer, as well as in the ARPE-19 or RBE4 cell layer, was evaluated by the luminescent measurement of total ATP. The leakage of the fluorescent tracer was also monitored. The results showed that both barrier cell types were induced by glial cells. Inorganic and organic mercury caused a leakage of the dye and cytotoxicity in SH-SY5Y cells. Especially, methyl mercury chloride could exert an effect on target cells before any profound cytotoxicity in barrier cells could be seen. Aluminum did not cause any leakage in the barrier cell layer, and even

  16. Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype.

    Science.gov (United States)

    Phoenix, Timothy N; Patmore, Deanna M; Boop, Scott; Boulos, Nidal; Jacus, Megan O; Patel, Yogesh T; Roussel, Martine F; Finkelstein, David; Goumnerova, Liliana; Perreault, Sebastien; Wadhwa, Elizabeth; Cho, Yoon-Jae; Stewart, Clinton F; Gilbertson, Richard J

    2016-04-11

    The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels of intra-tumoral chemotherapy and a robust therapeutic response. In contrast, SHH-medulloblastoma, a less curable disease subtype, contains an intact blood brain barrier, rendering this tumor impermeable and resistant to chemotherapy. The medulloblastoma-endothelial cell paracrine axis can be manipulated in vivo, altering chemotherapy permeability and clinical response. Thus, medulloblastoma genotype dictates tumor vessel phenotype, explaining in part the disparate prognoses among medulloblastoma subtypes and suggesting an approach to enhance the chemoresponsiveness of other brain tumors. PMID:27050100

  17. Market barriers to welfare product innovations

    OpenAIRE

    Binnekamp, M.H.A.; Ingenbleek, P. T. M.

    2006-01-01

    New products that are based on higher animal welfare standards encounter several barriers on the road to market acceptance. The authors focus on the Dutch poultry sector and distinguish between retailer and consumer barriers. Retailer barriers include the powerful position of retailers, the price competition, and the price-orientation of decision-makers. At the consumer level, potential barriers are: involving the consumer in animal welfare, making him understand the welfare benefits, convinc...

  18. NON-TARIFF TRADE BARRIERS IN AGRICULTURE

    OpenAIRE

    Mattson, Jeremy W.; Koo, Won W.; Taylor, Richard D.

    2004-01-01

    As trade agreements lower tariff rates throughout the world, other barriers to trade emerge. These non-tariff barriers can be just as troublesome for exporting companies. Non-tariff barriers include technical measures, customs rules and procedures, transport regulations or costs, lack of knowledge of regional markets, and import policies. The objective of this study is to identify non-tariff barriers faced by U.S., and more specifically North Dakota, exporting businesses, especially those inv...

  19. Expression of Astrocytic Type 2 Angiotensin Receptor in Central Nervous System Inflammation Correlates With Blood-Brain Barrier Breakdown

    DEFF Research Database (Denmark)

    Füchtbauer, Laila; Toft-Hansen, Henrik; Khorooshi, Reza;

    2010-01-01

    The blood-brain barrier (BBB), a complex of endothelial and glial barriers, controls passage of cells and solutes between the blood and central nervous system (CNS). Blood-brain barrier breakdown refers to entry of cells and/or solutes. We were interested whether the renin-angiotensin system is...... involved during BBB breakdown. We studied the type 2 angiotensin receptor AT(2) because of its suggested neuroprotective role. Two models of brain inflammation were used to distinguish solute versus cellular barrier functions. Both leukocytes and horseradish peroxidase (HRP) accumulated in the perivascular...

  20. Security barriers with automated reconnaissance

    Science.gov (United States)

    McLaughlin, James O; Baird, Adam D; Tullis, Barclay J; Nolte, Roger Allen

    2015-04-07

    An intrusion delaying barrier includes primary and secondary physical structures and can be instrumented with multiple sensors incorporated into an electronic monitoring and alarm system. Such an instrumented intrusion delaying barrier may be used as a perimeter intrusion defense and assessment system (PIDAS). Problems with not providing effective delay to breaches by intentional intruders and/or terrorists who would otherwise evade detection are solved by attaching the secondary structures to the primary structure, and attaching at least some of the sensors to the secondary structures. By having multiple sensors of various types physically interconnected serves to enable sensors on different parts of the overall structure to respond to common disturbances and thereby provide effective corroboration that a disturbance is not merely a nuisance or false alarm. Use of a machine learning network such as a neural network exploits such corroboration.

  1. Perceptions regarding strategic and structural entry barriers

    NARCIS (Netherlands)

    Lutz, Clemens H. M.; Kemp, Ron G. M.; Dijkstra, S. Gerhard

    2010-01-01

    This article uses factor analysis to identify the underlying dimensions of strategic and structural entry barriers. We find that, in the perception of firms, both types of barriers are important and that the effectiveness of strategic barriers depends on attributes of the market structure. Based on

  2. Barriers to Mammography among Inadequately Screened Women

    Science.gov (United States)

    Stoll, Carolyn R. T.; Roberts, Summer; Cheng, Meng-Ru; Crayton, Eloise V.; Jackson, Sherrill; Politi, Mary C.

    2015-01-01

    Mammography use has increased over the past 20 years, yet more than 30% of women remain inadequately screened. Structural barriers can deter individuals from screening, however, cognitive, emotional, and communication barriers may also prevent mammography use. This study sought to identify the impact of number and type of barriers on mammography…

  3. Article Including Environmental Barrier Coating System

    Science.gov (United States)

    Lee, Kang N. (Inventor)

    2015-01-01

    An enhanced environmental barrier coating for a silicon containing substrate. The enhanced barrier coating may include a bond coat doped with at least one of an alkali metal oxide and an alkali earth metal oxide. The enhanced barrier coating may include a composite mullite bond coat including BSAS and another distinct second phase oxide applied over said surface.

  4. Sea sand for reactive barriers

    International Nuclear Information System (INIS)

    Some phosphates have the property to suck in radioactive metals in solution, what it is taken in advance to make reactive barriers which are placed in the nuclear waste repositories. In an effort for contributing to the study of this type of materials, it has been obtained the zirconium silicate (ZrSiO4) and the alpha zirconium hydrogen phosphate (Zr(HPO4) 2H2O) starting from sea sand in an easy and economic way. (Author)

  5. Removing Barriers to Interdisciplinary Research

    CERN Document Server

    Jacobs, Naomi

    2010-01-01

    A significant amount of high-impact contemporary scientific research occurs where biology, computer science, engineering and chemistry converge. Although programmes have been put in place to support such work, the complex dynamics of interdisciplinarity are still poorly understood. In this paper we interrogate the nature of interdisciplinary research and how we might measure its "success", identify potential barriers to its implementation, and suggest possible mechanisms for removing these impediments.

  6. Overcome barriers to career success

    Energy Technology Data Exchange (ETDEWEB)

    Raudsepp, E.

    1983-04-01

    A test is given to determine if an engineer suffers from one of the three barriers to technical success: fear of success, fear of failure, or perfectionism. As in most such tests, the middle way is best. Successful engineers know that perfection cannot be attained, that they don't have time to worry about failure or success, and that by aiming and perservering in doing things well, success can be achieved.

  7. Barrier RF stacking at Fermilab

    International Nuclear Information System (INIS)

    A key issue to upgrade the luminosity of the Tevatron Run2 program and to meet the neutrino requirement of the NuMI experiment at Fermilab is to increase the proton intensity on the target. This paper introduces a new scheme to double the number of protons FR-om the Main Injector (MI) to the pbar production target (Run2) and to the pion production target (NuMI). It is based on the fact that the MI momentum acceptance is about a factor of four larger than the momentum spread of the Booster beam. Two RF barriers--one fixed, another moving--are employed to confine the proton beam. The Booster beams are injected off-momentum into the MI and are continuously reflected and compressed by the two barriers. Calculations and simulations show that this scheme could work provided that the Booster beam momentum spread can be kept under control. Compared with slip stacking, a main advantage of this new method is small beam loading effect thanks to the low peak beam current. The RF barriers can be generated by an inductive device, which uses nanocrystal magnet alloy (Finemet) cores and fast high voltage MOSFET switches. This device has been designed and fabricated by a Fermilab-KEK-Caltech team. The first bench test was successful. Beam experiments are being planned

  8. Filamentary and diffuse barrier discharges

    International Nuclear Information System (INIS)

    Barrier discharges, sometimes also referred to as dielectric-barrier discharges or silent discharges, are characterized by the presence of at least one insulating layer in contact with the discharge between two planar or cylindrical electrodes connected to an ac power supply. The main advantage of this type of electrical discharge is, that non-equilibrium plasma conditions in atmospheric-pressure gases can be established in an economic and reliable way. This has led to a number of important applications including industrial ozone generation, surface modification of polymers, plasma chemical vapor deposition, excitation of CO2 lasers, excimer lamps and, most recently, large-area flat plasma display panels. Depending on the application, the width of the discharge gap can range from less than 0.1 mm to about 100 mm and the applied frequency from below line frequency to several gigahertz. Typical materials used for the insulating layer (dielectric barrier) are glass, quartz, ceramics but also thin enamel or polymer layers

  9. Cryogenic Barrier Demonstration Project. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, L.A.; Yarmak, E.; Long, E.L.

    2000-03-01

    A long-term frozen soil barrier was implemented at the HRE (Homogeneous Reactor Experiment) Pond facility at the Oak Ridge National Laboratory in 1997. This was performed to verify the technical feasibility and costs of deploying a frozen barrier at a radiologically contaminated site. Work began in September 1996 and progressed through to December 1999. The frozen barrier has been operational since November 1997. Verification of the barrier integrity was performed independently by the EPA's SITE Program. This project showed frozen barriers offer a proven technology to retain below grade hazardous substances at relatively low costs with minimal effect on the environment.

  10. The influence of different types of barrier creams on skin barrier function / Sonette du Plessis

    OpenAIRE

    Du Plessis, Sonette

    2012-01-01

    Aims and objectives: The research aims and objectives of this study were: Firstly to determine the positive effects and possible disadvantages of three types of barrier creams on skin barrier function by determining skin barrier function by measuring stratum corneum hydration transepidermal water loss (TEWL) and skin surface pH. Secondly to compare different racial skin types (African skin to Caucasian skin) by determining the effects of barrier cream on skin barrier function. Finally to comp...

  11. Activation of toll like receptor-3 induces corneal epithelial barrier dysfunction.

    Science.gov (United States)

    Wei, Jie; Jiang, Hua; Gao, Hongrui; Wang, Guangjie

    2015-06-01

    The epithelial barrier is critical in the maintenance of the homeostasis of the cornea. A number of eye disorders are associated with the corneal epithelial barrier dysfunction. Viral infection is one common eye disease type. This study aims to elucidate the mechanism by which the activation of toll like receptor 3 (TLR3) in the disruption of the corneal epithelial barrier. In this study, HCE cells (a human corneal epithelial cell line) were cultured into epithelial layers using as an in vitro model of the corneal epithelial barrier. PolyI:C was used as a ligand of TLR3. The transepithelial electric resistance (TER) and permeability of the HCE epithelial layer were assessed using as the parameters to evaluate the corneal epithelial barrier integrity. The results showed that exposure to PolyI:C markedly decreased the TER and increased the permeability of the HCE epithelial layers; the levels of cell junction protein, E-cadherin, were repressed by PolyI:C via increasing histone deacetylase-1 (HDAC1), the latter binding to the promoter of E-cadherin and repressed the transcription of E-cadherin. The addition of butyrate (an inhibitor of HDAC1) to the culture blocked the corneal epithelial barrier dysfunction caused by PolyI:C. In conclusion, activation of TLR3 can disrupt the corneal epithelial barrier, which can be blocked by the inhibitor of HDAC1. PMID:25912142

  12. Avoiding barriers in control of mowing robot

    Institute of Scientific and Technical Information of China (English)

    QIU Bai-jing; QIAN Guo-hong; XIANG Zhong-ping; LI Zuo-peng

    2006-01-01

    Due to complicated barriers,it is difficult to track the path of the mowing robot and to avoid barriers.In order to solve the problem,a method based on distance-measuring sensors and fuzzy control inputs was proposed.Its track was composed of beelines and was easy to tail.The fuzzy control inputs were based on the front barrier distance and the difference between the left and right barrier distance measured by ultrasonic sensors;the output was the direction angle.The infrared sensors around the robot improved its safety in avoiding barriers.The result of the method was feasible,agile,and stable.The distance between the robot and the barriers could be changed by altering the inputs and outputs of fuzzy control and the length of the beelines.The disposed sensors can fulfill the need of the robot in avoiding barriers.

  13. Dielectric barrier discharges in analytical chemistry.

    Science.gov (United States)

    Meyer, C; Müller, S; Gurevich, E L; Franzke, J

    2011-06-21

    The present review reflects the importance of dielectric barrier discharges in analytical chemistry. Special about this discharge is-and in contrast to usual discharges with direct current-that the plasma is separated from one or two electrodes by a dielectric barrier. This gives rise to two main features of the dielectric barrier discharges; it can serve as dissociation and excitation device and as ionization mechanism, respectively. The article portrays the various application fields for dielectric barrier discharges in analytical chemistry, for example the use for elemental detection with optical spectrometry or as ionization source for mass spectrometry. Besides the introduction of different kinds of dielectric barrier discharges used for analytical chemistry from the literature, a clear and concise classification of dielectric barrier discharges into capacitively coupled discharges is provided followed by an overview about the characteristics of a dielectric barrier discharge concerning discharge properties and the ignition mechanism. PMID:21562672

  14. Non-thermal dielectric-barrier discharge plasma damages human keratinocytes by inducing oxidative stress

    OpenAIRE

    Kim, Ki Cheon; Piao, Mei Jing; Hewage, Susara Ruwan Kumara Madduma; Han, Xia; Kang, Kyoung Ah; JO, JIN OH; Mok, Young Sun; Shin, Jennifer H.; Park, Yeunsoo; Yoo, Suk Jae; Hyun, Jin Won

    2015-01-01

    The aim of this study was to identify the mechanisms through which dielectric-barrier discharge plasma damages human keratinocytes (HaCaT cells) through the induction of oxidative stress. For this purpose, the cells were exposed to surface dielectric-barrier discharge plasma in 70% oxygen and 30% argon. We noted that cell viability was decreased following exposure of the cells to plasma in a time-dependent manner, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay....

  15. Changes in intestinal mucosal immune barrier in rats with endotoxemia

    Institute of Scientific and Technical Information of China (English)

    Chong Liu; Ang Li; Yi-Bing Weng; Mei-Li Duan; Bao-En Wang; Shu-Wen Zhang

    2009-01-01

    AIM: To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS: Male Wistar rats were randomly distributed into two groups: control group and lipopolysaccharide (LPS) group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold (M)-cells, dendritic cells (DCs), CD4~+ T cells, CD8~+ T cells, regulatory T (Tr) cells and IgA~+ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin (IL)-4, interferon (IFN)-γ and forkhead box P3 (Foxp3) in mucosal homogenates were measured by ELISA. The secretory IgA (sIgA) content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay. RESULTS: This research demonstrated that LPS LPSinduced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~+ T cells, and IgA~+ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4~+ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-γ increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased. CONCLUSION: Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.

  16. Double barrier system for an in situ conversion process

    Science.gov (United States)

    McKinzie, Billy John [Houston, TX; Vinegar, Harold J [Bellaire, TX; Cowan, Kenneth Michael [Sugar land, TX; Deeg, Wolfgang Friedrich Johann [Houston, TX; Wong, Sau-Wai [Rijswijk, NL

    2009-05-05

    A barrier system for a subsurface treatment area is described. The barrier system includes a first barrier formed around at least a portion of the subsurface treatment area. The first barrier is configured to inhibit fluid from exiting or entering the subsurface treatment area. A second barrier is formed around at least a portion of the first barrier. A separation space exists between the first barrier and the second barrier.

  17. Die epitheliale Barriere als Zielstruktur pathogener und probiotischer Bakterien

    OpenAIRE

    Hering, Nina A.

    2011-01-01

    Yersinia enterocolitica is a common cause of acute gastroenteritis. In order to clarify the mechanisms leading to diarrhea and barrier dysfunction the pathomechanisms of this infection were studied in detail. Exposure of human colonic HT-29/B6 cells to Y. enterocolitica resulted in a decrease in transepithelial resistance (Rt, TER) with a parallel increase in mannitol (182 Da) and fluorescein (332 Da) permeability. Active ion transport measured as short circuit current was unchanged. The Y. e...

  18. Dielectric-barrier discharges in two-dimensional lattice potentials

    OpenAIRE

    Sinclair, Josiah; Walhout, Matthew

    2011-01-01

    We use a pin-grid electrode to introduce a corrugated electrical potential into a planar dielectric-barrier discharge (DBD) system, so that the amplitude of the applied electric field has the profile of a two-dimensional square lattice. The lattice potential provides a template for the spatial distribution of plasma filaments in the system and has pronounced effects on the patterns that can form. The positions at which filaments become localized within the lattice unit cell vary with the widt...

  19. An analytical solution for transverse thermal conductivities of unidirectional fibre composites with thermal barrier

    Energy Technology Data Exchange (ETDEWEB)

    Zou Mingqing; Zhang Duanming; Yu Boming [Department of Physics and the State Key Laboratory of Laser, Huazhong University of Science and Technology, Wuhan (China)]. E-mail: yu3838@public.wh.hb.cn

    2002-08-07

    In this paper, an analytical expression for transverse thermal conductivities of unidirectional fibre composites with thermal barrier is derived based on the electrical analogy technique and on the cylindrical filament-square packing array unit cell model (C-S model). The present analytical expressions both with and without thermal barrier between fibre and matrix are presented. The present theoretical predictions without thermal barrier are found to be in excellent agreement with the existing analytical model and nomogram from the finite difference method (FDM), and in good agreement with existing experimental data. Furthermore, the present analytical predictions with thermal barrier can best fit the experimental data and can provide a higher accuracy than the finite element method (FEM). The validity of the present analytical solution is thus verified for transverse thermal conductivities of unidirectional fibre composites with thermal barrier. (author)

  20. An analytical solution for transverse thermal conductivities of unidirectional fibre composites with thermal barrier

    International Nuclear Information System (INIS)

    In this paper, an analytical expression for transverse thermal conductivities of unidirectional fibre composites with thermal barrier is derived based on the electrical analogy technique and on the cylindrical filament-square packing array unit cell model (C-S model). The present analytical expressions both with and without thermal barrier between fibre and matrix are presented. The present theoretical predictions without thermal barrier are found to be in excellent agreement with the existing analytical model and nomogram from the finite difference method (FDM), and in good agreement with existing experimental data. Furthermore, the present analytical predictions with thermal barrier can best fit the experimental data and can provide a higher accuracy than the finite element method (FEM). The validity of the present analytical solution is thus verified for transverse thermal conductivities of unidirectional fibre composites with thermal barrier. (author)

  1. Tunneling without barriers with gravity

    OpenAIRE

    Kanno, Sugumi; Sasaki, Misao; Soda, Jiro

    2012-01-01

    We consider the vacuum decay of the flat Minkowski space to an anti-de Sitter space. We find a one-parameter family of potentials that allow exact, analytical instanton solutions describing tunneling without barriers in the presence of gravity. In the absence of gravity such instantons were found and discussed by Lee and Weinberg more than a quarter of a century ago. The bounce action is also analytically computed. We discuss possible implications of these new instantons to cosmology in the c...

  2. Overcoming cultural barriers to change.

    Science.gov (United States)

    Hill, S; McNulty, D

    1998-01-01

    This article is a case study which focuses on organisational and cultural change associated with the incorporation of a college which provided pre- and post-registration nursing and midwifery education into a much larger institution within the university sector. Among the issues addressed is whether transformational change, such as that represented by incorporation or merger, can be used by managers to successfully refashion the culture of the organisation, making more effective than traditional or discipline-based management structures. It examines the barriers to change and the various considerations that arose in determining the fit of managerial styles and assesses the outcomes of the process of change. PMID:10346302

  3. Alteration of blood-brain barrier integrity by retroviral infection.

    Directory of Open Access Journals (Sweden)

    Philippe V Afonso

    2008-11-01

    Full Text Available The blood-brain barrier (BBB, which forms the interface between the blood and the cerebral parenchyma, has been shown to be disrupted during retroviral-associated neuromyelopathies. Human T Lymphotropic Virus (HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP is a slowly progressive neurodegenerative disease associated with BBB breakdown. The BBB is composed of three cell types: endothelial cells, pericytes and astrocytes. Although astrocytes have been shown to be infected by HTLV-1, until now, little was known about the susceptibility of BBB endothelial cells to HTLV-1 infection and the impact of such an infection on BBB function. We first demonstrated that human cerebral endothelial cells express the receptors for HTLV-1 (GLUT-1, Neuropilin-1 and heparan sulfate proteoglycans, both in vitro, in a human cerebral endothelial cell line, and ex vivo, on spinal cord autopsy sections from HAM/TSP and non-infected control cases. In situ hybridization revealed HTLV-1 transcripts associated with the vasculature in HAM/TSP. We were able to confirm that the endothelial cells could be productively infected in vitro by HTLV-1 and that blocking of either HSPGs, Neuropilin 1 or Glut1 inhibits this process. The expression of the tight-junction proteins within the HTLV-1 infected endothelial cells was altered. These cells were no longer able to form a functional barrier, since BBB permeability and lymphocyte passage through the monolayer of endothelial cells were increased. This work constitutes the first report of susceptibility of human cerebral endothelial cells to HTLV-1 infection, with implications for HTLV-1 passage through the BBB and subsequent deregulation of the central nervous system homeostasis. We propose that the susceptibility of cerebral endothelial cells to retroviral infection and subsequent BBB dysfunction is an important aspect of HAM/TSP pathogenesis and should be considered in the design of future therapeutics strategies.

  4. Centromeric barrier disruption leads to mitotic defects in Schizosaccharomyces pombe.

    Science.gov (United States)

    Gaither, Terilyn L; Merrett, Stephanie L; Pun, Matthew J; Scott, Kristin C

    2014-04-01

    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-A(Cnp1) 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

  5. Saving the Barrier by Prevention.

    Science.gov (United States)

    Weisshaar, Elke

    2016-01-01

    One third of all occupation-related diseases are diseases of the skin, and in most of these cases the skin barrier is involved. Professions such as metalworkers, hairdressers, and health care and construction workers are mainly affected. Among them, contact dermatitis is the leading skin disease. It usually presents as hand eczema caused by or leading to impaired barrier function. All this significantly impacts the function of the hands, reduces the ability to work and especially impairs the patient's quality of life. Diagnostics and therapy are of great importance; in addition, prevention programs are meanwhile an important mainstay of the overall therapeutic concept. They comprise measures of secondary (outpatient) and tertiary (inpatient) prevention. Secondary prevention measures include occupation-tailored teaching and prevention programs, and the dermatologist's examination and report. In severe cases or if therapy is not successful in the long term, or if the diagnosis is not clear, measures of tertiary prevention may come into action. They are offered as an inpatient treatment and prevention program. The aims are prevention of the job loss, but especially to reach a long-term healing up and getting back to normal occupational and leisure life in the sense of attaining full quality of life. During the last years, research in Germany has shown that the different measures of prevention in occupational dermatology are very effective. This integrated concept of an in-/outpatient disease management reveals remarkable pertinent efficacy for patients with severe occupational dermatoses in at-risk professions. PMID:26844907

  6. Triggering mechanisms for transport barriers

    International Nuclear Information System (INIS)

    The radial shear ωExB of the ExB flow is evaluated with the Monte Carlo orbit following code ASCOT at the onset of the L-H transition and internal transport barriers (ITB) in JET, TFTR, ASDEX Upgrade, TEXTOR, and FT-2 tokamaks. Systematically, a large shear (sufficient for turbulence suppression) is found for local parameters close to the experimental threshold conditions at the barrier location. For L-H transition in JET and ASDEX Upgrade, the large shear is obtained by increasing the edge ion temperature. For TEXTOR, the radial electric field and the electrode current bifurcate at a threshold electrode voltage. In a JET database study, toroidal rotation is found to be dominant in triggering the JET ITB, and an empirical s-ωExB fit is found for the transition threshold. For TFTR and FT-2, in which toroidal rotation does not play a role, ASCOT predicts a significant ωExB shear for the ITB conditions. The ripple-induced transport is not found to be important here. (author)

  7. Barriers to medical error reporting

    Directory of Open Access Journals (Sweden)

    Jalal Poorolajal

    2015-01-01

    Full Text Available Background: This study was conducted to explore the prevalence of medical error underreporting and associated barriers. Methods: This cross-sectional study was performed from September to December 2012. Five hospitals, affiliated with Hamadan University of Medical Sciences, in Hamedan,Iran were investigated. A self-administered questionnaire was used for data collection. Participants consisted of physicians, nurses, midwives, residents, interns, and staffs of radiology and laboratory departments. Results: Overall, 50.26% of subjects had committed but not reported medical errors. The main reasons mentioned for underreporting were lack of effective medical error reporting system (60.0%, lack of proper reporting form (51.8%, lack of peer supporting a person who has committed an error (56.0%, and lack of personal attention to the importance of medical errors (62.9%. The rate of committing medical errors was higher in men (71.4%, age of 50-40 years (67.6%, less-experienced personnel (58.7%, educational level of MSc (87.5%, and staff of radiology department (88.9%. Conclusions: This study outlined the main barriers to reporting medical errors and associated factors that may be helpful for healthcare organizations in improving medical error reporting as an essential component for patient safety enhancement.

  8. Westinghouse thermal barrier coatings development

    Energy Technology Data Exchange (ETDEWEB)

    Goedjen, J.G.; Wagner, G. [Westinghouse Electric Corp., Orlando, FL (United States)

    1995-10-01

    Westinghouse, in conjunction with the Department of Energy and Oak Ridge National Laboratory, has embarked upon a program for the development of advanced thermal barrier coatings for industrial gas turbines. Development of thermal barrier coatings (TBC`s) for industrial gas turbines has relied heavily on the transfer of technology from the aerospace industry. Significant differences in the time/temperature/stress duty cycles exist between these two coating applications. Coating systems which perform well in aerospace applications may not been optimized to meet power generation performance requirements. This program will focus on development of TBC`s to meet the specific needs of power generation applications. The program is directed at developing a state-of-the-art coating system with a minimum coating life of 25,000 hours at service temperatures required to meet increasing operating efficiency goals. Westinghouse has assembled a team of university and industry leaders to accomplish this goal. Westinghouse will coordinate the efforts of all program participants. Chromalloy Turbine Technologies, Inc. and Sermatech International, Inc. will be responsible for bond coat and TBC deposition technology. Praxair Specialty Powders, Inc. will be responsible for the fabrication of all bond coat and ceramic powders for the program. Southwest Research Institute will head the life prediction modelling effort; they will also be involved in coordinating nondestructive evaluation (NDE) efforts. Process modelling will be provided by the University of Arizona.

  9. Richards Barrier LA Reference Design Feature Evaluation

    International Nuclear Information System (INIS)

    The Richards Barrier is one of the design features of the repository to be considered for the License Application (LA), Richards was a soil scientist who first described the diversion of moisture between two materials with different hydrologic properties. In this report, a Richards Barrier is a special type of backfill with a fine-grained material (such as sand) overlaying a coarse-grained material (such as gravel). Water that enters an emplacement drift will first encounter the fine-grained material and be transported around the coarse-grained material covering the waste package, thus protecting the waste package from contact with most of the groundwater. The objective of this report is to discuss the benefits and liabilities to the repository by the inclusion of a Richards Barrier type backfill in emplacement drifts. The Richards Barrier can act as a barrier to water flow, can reduce the waste package material dissolution rate, limit mobilization of the radionuclides, and can provide structural protection for the waste package. The scope of this report is to: (1) Analyze the behavior of barrier materials following the intrusion of groundwater for influxes of 1 to 300 mm per year. The report will demonstrate diversion of groundwater intrusions into the barrier over an extended time period when seismic activity and consolidation may cause the potential for liquefaction and settlement of the Richards Barrier. (2) Review the thermal effects of the Richards Barrier on material behavior. (3) Analyze the effect of rockfall on the performance of the Richards Barrier and the depth of the barrier required to protect waste packages under the barrier. (4) Review radiological and heating conditions on placement of multiple layers of the barrier. Subsurface Nuclear Safety personnel will perform calculations to determine the radiation reduction-time relationship and shielding capacity of the barrier. (5) Evaluate the effects of ventilation on cooling of emplacement drifts and

  10. Origin of translocation barriers for polyelectrolyte chains.

    Science.gov (United States)

    Kumar, Rajeev; Muthukumar, M

    2009-11-21

    For single-file translocations of a charged macromolecule through a narrow pore, the crucial step of arrival of an end at the pore suffers from free energy barriers, arising from changes in intrachain electrostatic interaction, distribution of ionic clouds and solvent molecules, and conformational entropy of the chain. All contributing factors to the barrier in the initial stage of translocation are evaluated by using the self-consistent field theory for the polyelectrolyte and the coupled Poisson-Boltzmann description for ions without radial symmetry. The barrier is found to be essentially entropic due to conformational changes. For moderate and high salt concentrations, the barriers for the polyelectrolyte chain are quantitatively equivalent to that of uncharged self-avoiding walks. Electrostatic effects are shown to increase the free energy barriers, but only slightly. The degree of ionization, electrostatic interaction strength, decreasing salt concentration, and the solvent quality all result in increases in the barrier. PMID:19929072

  11. Barrier experiment: Shock initiation under complex loading

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-12

    The barrier experiments are a variant of the gap test; a detonation wave in a donor HE impacts a barrier and drives a shock wave into an acceptor HE. The question we ask is: What is the trade-off between the barrier material and threshold barrier thickness to prevent the acceptor from detonating. This can be viewed from the perspective of shock initiation of the acceptor subject to a complex pressure drive condition. Here we consider key factors which affect whether or not the acceptor undergoes a shock-to-detonation transition. These include the following: shock impedance matches for the donor detonation wave into the barrier and then the barrier shock into the acceptor, the pressure gradient behind the donor detonation wave, and the curvature of detonation front in the donor. Numerical simulations are used to illustrate how these factors affect the reaction in the acceptor.

  12. Strain-dependent disruption of blood-cerebrospinal fluid barrier by Streptoccocus suis in vitro.

    Science.gov (United States)

    Tenenbaum, Tobias; Adam, Rüdiger; Eggelnpöhler, Ingo; Matalon, David; Seibt, Annette; K Novotny, Gerd E; Galla, Hans-Joachim; Schroten, Horst

    2005-04-01

    Streptococcus suis capsular type 2 is an important agent of diseases including meningitis among pigs worldwide, and is also a zoonotic agent. The barrier function of the choroid plexus epithelium that constitutes the structural basis for the blood-cerebrospinal fluid (CSF) barrier has not been elucidated yet in bacterial meningitis. We investigated the influence of various S. suis isolates on the barrier function of cultured porcine choroid plexus epithelial cells with respect to the transepithelial resistance and paracellular [(3)H]-mannitol flux. Preferentially apical application of S. suis isolates significantly decreased transepithelial resistance and significantly increased paracellular [(3)H]-mannitol flux in a time-, dose- and strain-dependent manner. Viable S. suis isolates caused cytotoxicity determined by lactate dehydrogenase assay and electron microscopy, whereas S. suis sonicates and UV-inactivated S. suis did not cause cytotoxicity. The observed effects on porcine choroid plexus epithelial cells barrier function could not exclusively be ascribed to known virulence factors of S. suis such as suilysin. In conclusion, S. suis isolates induce loss of blood-cerebrospinal fluid barrier function in an in vitro model. Thus, S. suis may facilitate trafficking of bacteria and leucocytes across the blood-cerebrospinal fluid barrier. The underlying mechanisms for the barrier breakdown have yet to be determined. PMID:15780575

  13. MicroRNA-126 contributes to Niaspan treatment induced vascular restoration after diabetic retinopathy.

    Science.gov (United States)

    Wang, Yang; Yan, Hua

    2016-01-01

    Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early diabetic retinopathy is characterized by a loss of pericytes and vascular endothelial cells, a breakdown of the blood-retinal barrier, vascular dysfunction and vascular-neuroinflammation. However, optimal treatment options and related mechanisms are still unclear. MicroRNA-126 (miR-126) plays a potential role in the pathogenesis in DR, which may regulate VEGF, Ang-1 and VCAM-1 expressions. This study investigated the therapeutic effects and mechanisms of Niaspan treatment of DR in diabetes (DM) rats. DM rats exhibits significantly decreased miR-126 and tight junction Claudin-5/Occludin/ZO-1 genes expression, and increased Blood retinal-barrier (BRB) breakdown, retinal apoptosis and VEGF/VEGFR, as well as VCAM-1/CD45 expressions in the retina compared to normal control group. Niaspan treatment significantly improved clinical and histopathological outcomes; decreased the expressions of VEGF/VEGFR, VCAM-1/CD45, apoptosis and BRB breakdown, significantly increased tight junction proteins and Ang-1/Tie-2 expressions, as well as increased retinal miR-126 expression compared to non-treatment diabetic rats. These data are the first to show that Niaspan treatment ameliorates DR through its repair vascular and inhibits inflammatory effects, and also suggest that the miR-126 pathway may contribute to Niaspan treatment induced benefit effects. PMID:27225425

  14. Transcriptome analysis of the ependymal barrier during murine neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Mishra Pramod

    2012-06-01

    Full Text Available Abstract Background Central nervous system (CNS barriers play a pivotal role in the protection and homeostasis of the CNS by enabling the exchange of metabolites while restricting the entry of xenobiotics, blood cells and blood-borne macromolecules. While the blood–brain barrier and blood-cerebrospinal fluid barrier (CSF control the interface between the blood and CNS, the ependyma acts as a barrier between the CSF and parenchyma, and regulates hydrocephalic pressure and metabolic toxicity. Neurocysticercosis (NCC is an infection of the CNS caused by the metacestode (larva of Taenia solium and a major cause of acquired epilepsy worldwide. The common clinical manifestations of NCC are seizures, hydrocephalus and symptoms due to increased intracranial pressure. The majority of the associated pathogenesis is attributed to the immune response against the parasite. The properties of the CNS barriers, including the ependyma, are affected during infection, resulting in disrupted homeostasis and infiltration of leukocytes, which correlates with the pathology and disease symptoms of NCC patients. Results In order to characterize the role of the ependymal barrier in the immunopathogenesis of NCC, we isolated ependymal cells using laser capture microdissection from mice infected or mock-infected with the closely related parasite Mesocestoides corti, and analyzed the genes that were differentially expressed using microarray analysis. The expression of 382 genes was altered. Immune response-related genes were verified by real-time RT-PCR. Ingenuity Pathway Analysis (IPA software was used to analyze the biological significance of the differentially expressed genes, and revealed that genes known to participate in innate immune responses, antigen presentation and leukocyte infiltration were affected along with the genes involved in carbohydrate, lipid and small molecule biochemistry. Further, MHC class II molecules and chemokines, including CCL12, were found

  15. Sunk Costs and Antitrust Barriers to Entry

    OpenAIRE

    SCHMALENSEE, Richard

    2004-01-01

    US antitrust policy takes as its objective consumer welfare, not total economic welfare. With that objective, Joe Bain's definition of entry barriers is more useful than George Stigler's or definitions based on economic welfare. It follows that economies of scale that involve sunk costs may create antitrust barriers to entry. A simple model shows that sunk costs without scale economies may discourage entry without creating an antitrust entry barrier.

  16. Transport Properties for Triangular Barriers in Graphene

    OpenAIRE

    Mouhafid, Abderrahim El; Jellal, Ahmed

    2013-01-01

    We theoretically study the electronic transport properties of Dirac fermions through one and double triangular barriers in graphene. Using the transfer matrix method, we determine the transmission, conductance and Fano factor. They are obtained to be various parameters dependent such as well width, barrier height and barrier width. Therefore, different discussions are given and comparison with the previous significant works is done. In particular, it is shown that at Dirac point the Dirac fer...

  17. Barriers to nursing care in emergency wards

    OpenAIRE

    Mahmoudi, Hosein; Mohmmadi, Eesa; Abbas EBADI

    2013-01-01

    Background: Caring is the essence of nursing. Since care is influenced by cultural, economic, and social factors, various diverse barriers exist in the realization of care. The aim of the study was to clarify barriers to caring in emergency patients based on experiences of nurses and patients and their relatives. Materials and Methods: A qualitative design of content analysis was used to identify the barriers to caring in emergency patients. In-depth interviews were conducted with 18 Iranian ...

  18. Identification of Key Barriers in Workforce Development

    Energy Technology Data Exchange (ETDEWEB)

    None

    2008-03-31

    This report documents the identification of key barriers in the development of an adequate national security workforce as part of the National Security Preparedness Project, being performed under a Department of Energy/National Nuclear Security Administration grant. Many barriers exist that prevent the development of an adequate number of propertly trained national security personnel. Some barriers can be eliminated in a short-term manner, whereas others will involve a long-term strategy that takes into account public policy.

  19. Assessing Non-tariff Barriers in Syria

    OpenAIRE

    Chemingui, Mohamed Abdelbasset; Dessus, Sebastien

    2008-01-01

    International trade in Syria is highly regulated through a combination of tariffs and non-tariff barriers. At 8% of the value of imports on average, effective tariffs are relatively low. However, non-tariff barriers to trade actually make Syria's trade restrictiveness very high. Comparing world and domestic prices of imports indeed suggests that non-tariff barriers increase the domestic price of imported goods by 17% on average, notably the result of significant quantitative restrictions. Usi...

  20. Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model

    DEFF Research Database (Denmark)

    Andersson, O.; Badisco, L.; Hansen, A. H.;

    2014-01-01

    In earlier studies insects were proposed as suitable models for vertebrate blood–brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain...... vertebrates, the locust brain–barrier function is morphologically confined to one specific cell layer and by using a whole-brain ex vivo drug exposure technique our locust model may retain the major cues that maintain and modulate the physiological function of the brain barrier. We show that the locust model...

  1. Permeation barrier properties of thin oxide films on flexible polymer substrates

    International Nuclear Information System (INIS)

    Solar cells and organic electronic devices require an encapsulation to ensure sufficient lifetime. Key parameters of the encapsulation are permeation barrier, UV stability, temperature stability, optical transmission spectra and mechanical stability. The requirements depend very much on the specific application. Many work groups suggest multilayer stacks to meet the permeation requirements. In this paper the permeation barrier properties of the different constituents of such a multilayer stack are characterized. Different layer materials are compared regarding their water vapour and oxygen permeability as well as the influence of process parameters is examined. Finally temperature dependent permeation measurements are used to characterize the permeation mechanisms in the different constituents of the multilayer barrier

  2. Barriers for realisation of energy savings in buildings; Barrierer for realisering af energibesparelser i bygninger

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, O.M.

    2004-07-01

    Many years' efforts within the energy labelling area have shown large saving potentials in heating and use of electricity in buildings. At the same time it has been proved that these saving potentials, even when economically advantageous, only are cashed to a limited extent. The reason to this is ascribed to barriers that meet the individual building owner who wants to start saving energy. Most barriers are known and a lot of these have been sought overcome for some time. The questions are how many barriers still exist, have new barriers arisen and the character of these barriers. On this background the objective of this survey has been to concretize and study the barriers, which are blocking reasonable energy savings. Focus has especially been on barriers for realisation of heating savings, but through a general evaluation of energy savings of barriers other forms of energy saving methods have been taken into consideration. Special interest has been directed towards houses, typically one family houses, which are affected by the Energy Labelling Scheme. The concept barriers include all kinds of barriers, also barriers that not are acknowledged as barriers by the individual house owner, or that on closer inspection turn out to be something else than actual barriers. This note suggests an alternative inertia model, in order to create an idea of the inertness characteristic of the many house owners who understand the message but fail to act on it. (BA)

  3. Edge transport barriers in magnetic fusion plasmas

    International Nuclear Information System (INIS)

    The present level of understanding of the physics of the formation and sustainment of edge transport barriers in magnetically confined fusion plasmas is presented. The formation of edge transport barriers is studied through evolution of mechanisms which can suppress plasma turbulence and so reduce turbulent driven transport, such as E x B flow shear stabilization of turbulence. Comparisons of theoretical studies with experimental results are described including investigations of zonal flows, which are considered important for saturation and self-regulation of turbulence and turbulence-driven transport. Processes that affect the dynamics and spatial structure of the edge barrier are described with emphasis on the width of the transport barrier. (authors)

  4. Water and contaminant movement: migration barriers

    International Nuclear Information System (INIS)

    Migration barriers are used in shallow land burial facilities to slow or stop the movement of water and contaminants and are discussed here as a single component embedded in a complex environmental system. Analytical solutions to solute transport equations are used to approximate the behavior of migration barriers and to derive design criteria for control of subsurface water and contaminant migration. Various types of migration barriers are compared and design recommendations are made for shallow land burial trench caps and liners. Needed improvements and suggested field experiments for future designs of migration barriers are then discussed relative to the management of low-level radioactive wastes

  5. Engineered Barrier Testing at the INEEL Engineered Barriers Test Facility: FY-1997 and FY-1998

    International Nuclear Information System (INIS)

    Engineered barriers of two designs are being tested at the Engineered Barriers Test Facility (EBTF) at the Idaho National Engineering and Environmental Laboratory. This report describes the test facility, barrier designs, and instruments used to monitor the test plots. Wetting tests conducted on the test plots in FY-97 are described and data collected from monitoring the test plots before, during and after the wetting tests are used to evaluate the performance of the covers during FY-97 and FY-98. Replicates of two engineered barrier designs were constructed in the EBTF cells. The first design comprises a thick, vegetated soil cover. The second design incorporates a capillary/biobarrier within the vegtated soil cover. The capillary barrier uses the textural break between an upper, fine textured soil and a lower, coarser-textured gravel layer to inhibit drainage under unsaturated conditions while increasing soil moisture storage in the root zone. Evaporation and transpiration by plants (although the test plots have not yet been vegetated) are used to recycle water stored in the soil back to the atmosphere. A geotextile fabric is used to maintain separation of the soil and gravel layers. A thick layer of cobbles beneath the gravel layer serves as a biobarrier to prevent intrusion of plant roots and burrowing animals into underlying waste (there is no waste in the test plots). Each test plot was instrumented with time domain reflectometry probes and neutron probe access tubes to measure moisture contents, tensiometers, heat dissipation sensors, and thermocouple psychrometers to measure matric potentials, thermocouples to measure soil temperature, and ion-exchange resin beads to monitor tracer movement. Each drainage sump is equipped with a tipping bucket instrument and pressure transducer to measure drainage. Precipitation is measured using a heated rain gauge located at the EBTF. Instrument calibration equation coefficients are presented, and data reduction

  6. STIM1 Controls Endothelial Barrier Function Independently of Orai1 and Ca2+ Entry

    OpenAIRE

    Shinde, Arti V.; Motiani, Rajender K.; Zhang, Xuexin; Abdullaev, Iskandar F.; Adam, Alejandro P.; González-Cobos, José C.; Zhang, Wei; Matrougui, Khalid; Vincent, Peter A.; Trebak, Mohamed

    2013-01-01

    Endothelial barrier function is critical for tissue fluid homeostasis and its disruption contributes to various pathologies, including inflammation and sepsis. Thrombin is an endogenous agonist that impairs endothelial barrier function. Here, we showed that the thrombin-induced decrease in transendothelial electric resistance of cultured human endothelial cells required the endoplasmic reticulum-localized, calcium-sensing protein STIM1, but was independent of Ca2+ entry across the plasma memb...

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

    OpenAIRE

    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

    2011-01-01

    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 epithel...

  8. Spatial Configuration and Composition of Charge Modulates Transport into a Mucin Hydrogel Barrier

    OpenAIRE

    Li, Leon D.; Crouzier, Thomas; Sarkar, Aniruddh; Dunphy, Laura; Han, Jongyoon; Ribbeck, Katharina

    2013-01-01

    The mucus barrier is selectively permeable to a wide variety of molecules, proteins, and cells, and establishes gradients of these particulates to influence the uptake of nutrients, the defense against pathogens, and the delivery of drugs. Despite its importance for health and disease, the criteria that govern transport through the mucus barrier are largely unknown. Studies with uniformly functionalized nanoparticles have provided critical information about the relevance of particle size and ...

  9. Adrenomedullin stabilizes the lymphatic endothelial barrier in vitro and in vivo

    OpenAIRE

    Dunworth, William P.; Fritz-Six, Kimberly L.; Caron, Kathleen M.

    2008-01-01

    The lymphatic vascular system functions to maintain fluid homeostasis by removing fluid from the interstitial space and returning it to venous circulation. This process is dependent upon the maintenance and modulation of a semi-permeable barrier between lymphatic endothelial cells of the lymphatic capillaries. However, our understanding of the lymphatic endothelial barrier and the molecular mechanisms that govern its function remains limited. Adrenomedullin (AM) is a 52 amino acid secreted pe...

  10. Understanding the rules of the road: proteomic approaches to interrogate the blood brain barrier

    OpenAIRE

    Torbett, Bruce E.; Baird, Andrew; Eliceiri, Brian P

    2015-01-01

    The blood brain barrier (BBB) is often regarded as a passive barrier that protects brain parenchyma from toxic substances, circulating leukocytes, while allowing the passage of selected molecules. Recently, a combination of molecular profiling techniques have characterized the constituents of the BBB based on in vitro models using isolated endothelial cells and ex vivo models analyzing isolated blood vessels. Characterization of gene expression profiles that are specific to the endothelium of...

  11. WDX Studies on Ceramic Diffusion Barrier Layers of Metal Supported SOECs

    OpenAIRE

    Wiedenmann, Daniel; Vogt, Ulrich; Soltmann, Christian; Patz, Olaf; Schiller, Günter; Grobety, B.

    2009-01-01

    Solid oxide electrolyser cells (SOECs) have great potential for efficient and economical production of hydrogen fuel. Element diffusion between the Ni-cermet electrode and the metal substrate of metal supported cells (MSC) is a known problem in fuel cell and electrolysis technology. In order to hinder this unintentional mass transport, different ceramic diffusion barrier layers (DBLs) are included in recent cell design concepts. This paper is based on wavelength dispersive X-ray fluorescence ...

  12. Gliomas and the vascular fragility of the blood brain barrier

    Science.gov (United States)

    Dubois, Luiz Gustavo; Campanati, Loraine; Righy, Cassia; D’Andrea-Meira, Isabella; Spohr, Tania Cristina Leite de Sampaio e; Porto-Carreiro, Isabel; Pereira, Claudia Maria; Balça-Silva, Joana; Kahn, Suzana Assad; DosSantos, Marcos F.; Oliveira, Marcela de Almeida Rabello; Ximenes-da-Silva, Adriana; Lopes, Maria Celeste; Faveret, Eduardo; Gasparetto, Emerson Leandro; Moura-Neto, Vivaldo

    2014-01-01

    Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB). By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM), characterized by a highly heterogeneous cell population (including tumor stem cells), extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the BBB and the concerns that arise when this barrier is affected. PMID:25565956

  13. Religious culture as a barrier?

    DEFF Research Database (Denmark)

    Agergaard, Sine

    2016-01-01

    Political interventions, media coverage and research often refer to the underrepresentation of ethnic minorities, particularly girls and women, participating in physical activity and organised sports. In both public and academic debates, reference is made to the religious culture as a particular...... barrier to participation in sports among Muslim girls and women. This article aims to provide a counter-narrative by focusing on young Muslim girls who simultaneously practice their religion and sports. The main research question was: How do young Danish Muslim girls align participation in sports with...... their religious and cultural frames of reference? The study uses a case study approach with interviews of ten 13–17-year-old Danish Muslim girls, as well as explorative observations in two football clubs and interviews with five coaches and club leaders. In further developing an analytical model for...

  14. Pratt & Whitney thermal barrier coatings

    Energy Technology Data Exchange (ETDEWEB)

    Bornstein, N. [United Technologies Research Center, East Hartford, CT (United States); Marcin, J. [Pratt & Whitney Aircraft Co., East Hartford, CT (United States)

    1995-10-01

    The objective of the Advanced Turbine Systems (ATS) Program is to develop ultra-high efficient, environmentally superior, and cost competitive gas turbine systems. The operating profiles of these industrial gas turbines are long, less cyclic with fewer transients-compared with those for aircraft gas turbine engines. Therefore, creep rather than thermal fatigue, becomes primary life-limiting for hot section components. Thermal barrier coatings (TBCs) will be used to achieve the objectives of the program. TBCs allow surface temperatures to increase without compromising the structural properties of the alloy. TBCs typically consist of a ceramic insulating layer, deposited onto the substrate with an intervening metallic layer, which imparts oxidation protection to the substrate and provides a surface to which the ceramic layer can adhere.

  15. 3 CFR 13505 - Executive Order 13505 of March 9, 2009. Removing Barriers to Responsible Scientific Research...

    Science.gov (United States)

    2010-01-01

    ... purpose of this order is to remove these limitations on scientific inquiry, to expand NIH support for the... Barriers to Responsible Scientific Research Involving Human Stem Cells 13505 Order 13505 Presidential... Scientific Research Involving Human Stem Cells By the authority vested in me as President by the...

  16. Emergent Behavior of Coupled Barrier Island - Resort Systems

    Science.gov (United States)

    McNamara, D. E.; Werner, B. T.

    2004-12-01

    Barrier islands are attractive sites for resorts. Natural barrier islands experience beach erosion and island overwash during storms, beach accretion and dune building during inter-storm periods, and migration up the continental shelf as sea level rises. Beach replenishment, artificial dune building, seawalls, jetties and groins have been somewhat effective in protecting resorts against erosion and overwash during storms, but it is unknown how the coupled system will respond to long-term sea level rise. We investigate coupled barrier island - resort systems using an agent-based model with three components: natural barrier islands divided into a series of alongshore cells; resorts controlled by markets for tourism and hotel purchases; and coupling via storm damage to resorts and resort protection by government agents. Modeled barrier islands change by beach erosion, island overwash and inlet cutting during storms, and beach accretion, tidal delta growth and dune and vegetation growth between storms. In the resort hotel market, developer agents build hotels and hotel owning agents purchase them using predictions of future revenue and property appreciation, with the goal of maximizing discounted utility. In the tourism market, hotel owning agents set room rental prices to maximize profit and tourist agents choose vacation destinations maximizing a utility based on beach width, price and word-of-mouth. Government agents build seawalls, groins and jetties, and widen the beach and build up dunes by adding sand to protect resorts from storms, enhance beach quality, and maximize resort revenue. Results indicate that barrier islands and resorts evolve in a coupled manner to resort size saturation, with resorts protected against small-to-intermediate-scale storms under fairly stable sea level. Under extended, rapidly rising sea level, protection measures enhance the effect of large storms, leading to emergent behavior in the form of limit cycles or barrier submergence

  17. Barrier fuel demonstrated at Quad Cities 2

    International Nuclear Information System (INIS)

    The article describes the nuclear design of the 144 zirconium barrier bundles inserted in the Quad Cities 2 core in December 1981, their locations and power history during their first cycle of irradiation, and the resulting linear heat generation rates (LHGRs) and fuel rod burnups when 16 of these zirconium barrier bundles were power ramped in March 1983. (author)

  18. Complementary Barrier Infrared Detector (CBIRD) Contact Methods

    Science.gov (United States)

    Ting, David Z.; Hill, Cory J.; Gunapala, Sarath D.

    2013-01-01

    The performance of the CBIRD detector is enhanced by using new device contacting methods that have been developed. The detector structure features a narrow gap adsorber sandwiched between a pair of complementary, unipolar barriers that are, in turn, surrounded by contact layers. In this innovation, the contact adjacent to the hole barrier is doped n-type, while the contact adjacent to the electron barrier is doped p-type. The contact layers can have wider bandgaps than the adsorber layer, so long as good electrical contacts are made to them. If good electrical contacts are made to either (or both) of the barriers, then one could contact the barrier(s) directly, obviating the need for additional contact layers. Both the left and right contacts can be doped either n-type or ptype. Having an n-type contact layer next to the electron barrier creates a second p-n junction (the first being the one between the hole barrier and the adsorber) over which applied bias could drop. This reduces the voltage drop over the adsorber, thereby reducing dark current generation in the adsorber region.

  19. Barriers to adherence in cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf

    2012-01-01

    Danish patients with cystic fibrosis aged 14 to 25 years and their parents. Conclusions: The present study showed that the majority of adolescents with CF and their parents experienced barriers to treatment adherence. Patients and parents agreed that the three most common barriers encountered lack of...

  20. Rotational barriers in perylene fluorescent dyes

    OpenAIRE

    Langhals, Heinz; Demmig, Stefan; Huber, Helmut

    1988-01-01

    Rotational barriers in N-substituted perylene dyes have been determined. Phenyl substituents with tert-butyl groups in the o-position give rigid systems, whereas secondary alkyl groups cause low rotational barriers. In spite of that, fluorescent quantum yields are high in both cases. Conformations in solution are discussed.

  1. A STUDY OF BARRIERS IN BRIDGING COMMUNICATION

    OpenAIRE

    Niteen V. Dandekar

    2014-01-01

    The main objective of this paper is to make a thought provoking discussion on the role barriers in bridging communication. It focuses on the concept of communication, process and the role of language related barriers in bridging communication. It studies the significance of communication in modern human life.

  2. K-Basin isolation barrier seal

    International Nuclear Information System (INIS)

    This report documents various aspects of the design, analysis, procurement, and fabrication of the hydraulic seal on the isolation barriers to be installed in the 100-K Area spent nuclear fuel basin. The isolation barrier is used to keep water in the basin in the event of an earthquake

  3. Barrier properties of natural clay minerals

    OpenAIRE

    Дудар, Т.В.; С.П. Бугера; В.М. Кадошніков; Б.П. Злобенко

    2009-01-01

     Clay minerals is a perfect material for geochemical barrier due to their high water resistivity, plasticity, high sorbing capacity, well developed surface and cheapness in extraction and processing. This work studies the peculiarities of uranium sorbtion on clay minerals on the example of bentonite and palygorskite clay from Cherkassy deposit, and clay usage as a barrier material.

  4. Barrier properties of natural clay minerals

    Directory of Open Access Journals (Sweden)

    Т.В. Дудар

    2009-01-01

    Full Text Available  Clay minerals is a perfect material for geochemical barrier due to their high water resistivity, plasticity, high sorbing capacity, well developed surface and cheapness in extraction and processing. This work studies the peculiarities of uranium sorbtion on clay minerals on the example of bentonite and palygorskite clay from Cherkassy deposit, and clay usage as a barrier material.

  5. Alternative approach to study fusion barrier distribution

    International Nuclear Information System (INIS)

    Fusion reactions induced by heavy-ions (HIs) at around barrier energies, play an important role in nuclear physics since they enable to study the nuclei away from the valley of stability. On the other hand, heavy-ion collisions, at below and near barrier energies, provide an ideal opportunity to study quantum tunneling phenomena in systems with many degrees of freedom. In a simple model, a potential barrier for the relative motion between the interacting nuclei is created by the strong interplay of the repulsive Coulomb and the attractive nuclear force. It has, now, been well recognized that heavy-ion collisions at energies around the Coulomb barrier are strongly affected by the internal structure of interacting nuclei. The couplings of the relative motion to the intrinsic degrees of freedom (such as collective inelastic excitations of the colliding nuclei and/or transfer processes) replaced a single potential barrier to a number of distributed barriers, leading to the enhancement in heavy ion fusion cross sections at energies near and below the Coulomb barrier than those expected from single one-dimensional barrier

  6. Addressing Regulatory Software Barriers to Business Growth

    OpenAIRE

    Kularatne, Chandana; Lopez-Calix, Jose

    2012-01-01

    This policy paper explores the relative importance of the software regulatory barriers to growth in Pakistan. Such software barriers have been identified as part of the major constraint in the Framework for Economic Growth of the Government of Pakistan. Indeed, adequate software is needed to provide an environment in which the hardware of growth (physical infrastructure) could be expanded ...

  7. Intracellular Ascorbate Prevents Endothelial Barrier Permeabilization by Thrombin.

    Science.gov (United States)

    Parker, William H; Qu, Zhi-chao; May, James M

    2015-08-28

    Intracellular ascorbate (vitamin C) has previously been shown to tighten the endothelial barrier and maintain barrier integrity during acute inflammation in vitro. However, the downstream effectors of ascorbate in the regulation of endothelial permeability remain unclear. In this study, we evaluated ascorbate as a mediator of thrombin-induced barrier permeabilization in human umbilical vein endothelial cells and their immortalized hybridoma line, EA.hy926. We found that the vitamin fully prevented increased permeability to the polysaccharide inulin by thrombin in a dose-dependent manner, and it took effect both before and after subjection to thrombin. Thrombin exposure consumed intracellular ascorbate but not the endogenous antioxidant GSH. Likewise, the antioxidants dithiothreitol and tempol did not reverse permeabilization. We identified a novel role for ascorbate in preserving cAMP during thrombin stimulation, resulting in two downstream effects. First, ascorbate maintained the cortical actin cytoskeleton in a Rap1- and Rac1-dependent manner, thus preserving stable adherens junctions between adjacent cells. Second, ascorbate prevented actin polymerization and formation of stress fibers by reducing the activation of RhoA and phosphorylation of myosin light chain. Although ascorbate and thrombin both required calcium for their respective effects, ascorbate did not prevent thrombin permeabilization by obstructing calcium influx. However, preservation of cAMP by ascorbate was found to depend on both the production of nitric oxide by endothelial nitric-oxide synthase, which ascorbate is known to activate, and the subsequent generation cGMP by guanylate cyclase. Together, these data implicate ascorbate in the prevention of inflammatory endothelial barrier permeabilization and explain the underlying signaling mechanism. PMID:26152729

  8. Fungal penetration of defensive barriers of plants

    International Nuclear Information System (INIS)

    Plants, like all other living organisms, are packaged in an outer envelope which acts as the barrier between the plant and its environment. The outer envelop of the aerial parts of plants (the cuticle) consists of a polyester, called cutin, which is embedded in a soluble mixture of relatively nonpolar lipids, collectively called waxes. The insoluble structural polymer, cutin, constitutes the major barrier to invasion by pathogenic microbes. The underground parts and aerially formed periderms and barks are protected by a different type of insoluble polymeric material called suberin. This polymer is also associated with waxes which make this layer resistant to diffusion. It has been known for a long period of time that these protective barriers are breached by pathogenic fungi. In this chapter, the nature of these barriers and how pathogenic fungi penetrate such barriers during infection are discussed. Topics include the composition, location and ultrastructure of cutin and suberin; and the isolation and properties of cutinase

  9. Green Barrier Promotes SustainableDevelopment of Our Foreign Trade

    OpenAIRE

    Yongning Wang

    2009-01-01

    Green barrier is a kind of new non-tariff barrier in the current international trade. This paper based on the meaning of green barrier, analyzed green barrier can promote Sustainable Development of our foreign trade, and proposed counter strategies to green barrier.

  10. 49 CFR 587.18 - Dimensions of fixed rigid barrier.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Dimensions of fixed rigid barrier. 587.18 Section... TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) DEFORMABLE BARRIERS Offset Deformable Barrier § 587.18 Dimensions of fixed rigid barrier. (a) The fixed rigid barrier has a mass of...

  11. Potential in vitro model for testing the effect of exposure to nanoparticles on the lung alveolar epithelial barrier

    Directory of Open Access Journals (Sweden)

    Raymond Derk

    2015-03-01

    Full Text Available Pulmonary barrier function plays a pivotal role in protection from inhaled particles. However, some nano-scaled particles, such as carbon nanotubes (CNT, have demonstrated the ability to penetrate this barrier in animal models, resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying mechanism and specific bio-effect of inhaled nanoparticles in respiratory toxicity, models of lung epithelial barriers are required that allow accurate representation of in vivo systems; however, there is currently a lack of consistent methods to do so. Thus, this work demonstrates a well-characterized in vitro model of pulmonary barrier function using Calu-3 cells, and provides the experimental conditions required for achieving tight junction complexes in cell culture, with trans-epithelial electrical resistance measurement used as a biosensor for proper barrier formation and integrity. The effects of cell number and serum constituents have been examined and we found that changes in each of these parameters can greatly affect barrier formation. Our data demonstrate that use of 5.0 × 104 Calu-3 cells/well in the Transwell cell culture system, with 10% serum concentrations in culture media is optimal for assessing epithelial barrier function. In addition, we have utilized CNT exposure to analyze the dose-, time-, and nanoparticle property-dependent alterations of epithelial barrier permeability as a means to validate this model. Such high throughput in vitro cell models of the epithelium could be used to predict the interaction of other nanoparticles with lung epithelial barriers to mimic respiratory behavior in vivo, thus providing essential tools and bio-sensing techniques that can be uniformly employed.

  12. Mucosal barrier, bacteria and inflammatory bowel disease: possibilities for therapy.

    Science.gov (United States)

    Merga, Yvette; Campbell, Barry J; Rhodes, Jonathan M

    2014-01-01

    The mucosal barrier has three major components, the mucus layer, the epithelial glycocalyx and the surface epithelium itself, whose integrity largely depends on tight junction function. In health, there is relatively little direct interaction between the luminal microbiota and the epithelium - the continuous mucus layer in the colon keeps the surface epithelium out of contact with bacteria and the ileo-caecal valve ensures that the distal small intestine is relatively microbe free. Most interaction takes place at the Peyer's patches in the distal ileum and their smaller colonic equivalents, the lymphoid follicles. Peyer's patches are overlain by a 'dome' epithelium, 5% of whose cells are specialised M (microfold) epithelial cells, which act as the major portal of entry for bacteria. There are no goblet cells in the dome epithelium and M cells have a very sparse glycocalyx allowing easy microbial interaction. It is intriguing that the typical age range for the onset of Crohn's disease (CD) is similar to the age at which the number of Peyer's patches is greatest. Peyer's patches are commonly the sites of the initial lesions in CD and the 'anti-pancreatic' antibody associated with CD has been shown to have as its epitope the glycoprotein 2 that is the receptor for type-1 bacterial fimbrial protein (fimH) on M cells. There are many reasons to believe that the mucosal barrier is critically important in the pathogenesis of inflammatory bowel disease (IBD). These include (i) associations between both CD and ulcerative colitis (UC) with genes that are relevant to the mucosal barrier; (ii) increased intestinal permeability in unaffected relatives of CD patients; (iii) increased immune reactivity against bacterial antigens, and (iv) animal models in which altered mucosal barrier, e.g. denudation of the mucus layer associated with oral dextran sulphate in rodents, induces colitis. Whilst some IBD patients may have genetic factors leading to weakening of the mucosal barrier

  13. Sensing of EGTA Mediated Barrier Tissue Disruption with an Organic Transistor

    Directory of Open Access Journals (Sweden)

    Scherrine Tria

    2013-01-01

    Full Text Available Barrier tissue protects the body against external factors by restricting the passage of molecules. The gastrointestinal epithelium is an example of barrier tissue with the primary purpose of allowing the passage of ions and nutrients, while restricting the passage of pathogens and toxins. It is well known that the loss of barrier function can be instigated by a decrease in extracellular calcium levels, leading to changes in protein conformation and an increase in paracellular transport. In this study, ethylene glycol-bis(beta-aminoethyl ether-N,N,N',N'-tetra acetic acid (EGTA, a calcium chelator, was used to disrupt the gastrointestinal epithelial barrier. The effect of EGTA on barrier tissue was monitored by a novel label-free method based on an organic electrochemical transistor (OECT integrated with living cells and validated against conventional methods for measuring barrier tissue integrity. We demonstrate that the OECT can detect breaches in barrier tissue upon exposure to EGTA with the same sensitivity as existing methods but with increased temporal resolution. Due to the potential of low cost processing techniques and the flexibility in design associated with organic electronics, the OECT has great potential for high-throughput, disposable sensing and diagnostics.

  14. Institutional distributed energy interconnection barriers

    International Nuclear Information System (INIS)

    This PowerPoint presentation provided an introduction to Encorp Inc., a leading provider of network technology and infrastructure management solutions for the distributed energy market. Encorp develops and markets software and hardware technology solutions for communications, control and networking of distributed energy. It is developing and implementing real-time, distributed energy-focused solutions for a wide variety of applications through new products and services which are technology neutral, and easily networked. Encorp controls more than 500 MW of distributed power with a total of 127 customers. This paper reviewed 3 barriers (regulatory, contractual/tariffs, and business practices) based on US experience. The challenge remaining is to determine if microgrids can be used effectively, and to determine the limitations of bi-directional power flows. The key issues regarding how end-users can share the costs and maximize on the benefits of distributed energy resources include: standby service charges, departing load charges, regulatory uncertainty, rate class degradation, lack of incentives for utility cost reduction, and lack of ability to create experimental tariffs. tabs., figs

  15. Numerical simulations of capillary barrier field tests

    Energy Technology Data Exchange (ETDEWEB)

    Morris, C.E. [Univ. of Wollongong (Australia); Stormont, J.C. [Univ. of New Mexico, Albuquerque, NM (United States)

    1997-12-31

    Numerical simulations of two capillary barrier systems tested in the field were conducted to determine if an unsaturated flow model could accurately represent the observed results. The field data was collected from two 7-m long, 1.2-m thick capillary barriers built on a 10% grade that were being tested to investigate their ability to laterally divert water downslope. One system had a homogeneous fine layer, while the fine soil of the second barrier was layered to increase its ability to laterally divert infiltrating moisture. The barriers were subjected first to constant infiltration while minimizing evaporative losses and then were exposed to ambient conditions. The continuous infiltration period of the field tests for the two barrier systems was modelled to determine the ability of an existing code to accurately represent capillary barrier behavior embodied in these two designs. Differences between the field test and the model data were found, but in general the simulations appeared to adequately reproduce the response of the test systems. Accounting for moisture retention hysteresis in the layered system will potentially lead to more accurate modelling results and is likely to be important when developing reasonable predictions of capillary barrier behavior.

  16. HgCdTe barrier infrared detectors

    Science.gov (United States)

    Kopytko, M.; Rogalski, A.

    2016-05-01

    In the last decade, new strategies to achieve high-operating temperature (HOT) detectors have been proposed, including barrier structures such as nBn devices, unipolar barrier photodiodes, and multistage (cascade) infrared detectors. The ability to tune the positions of the conduction and valence band edges independently in a broken-gap type-II superlattices is especially helpful in the design of unipolar barriers. This idea has been also implemented in HgCdTe ternary material system. However, the implementation of this detector structure in HgCdTe material system is not straightforward due to the existence of a valence band discontinuity (barrier) at the absorber-barrier interface. In this paper we present status of HgCdTe barrier detectors with emphasis on technological progress in fabrication of MOCVD-grown HgCdTe barrier detectors achieved recently at the Institute of Applied Physics, Military University of Technology. Their performance is comparable with state-of-the-art of HgCdTe photodiodes. From the perspective of device fabrication their important technological advantage results from less stringent surface passivation requirements and tolerance to threading dislocations.

  17. Advances in research on labyrinth membranous barriers

    Institute of Scientific and Technical Information of China (English)

    Wenfang Sun; Wuqing Wang

    2015-01-01

    Integrity of the membranous labyrinth barrier system is of critical importance, which promotes inner ear homeostasis and maintains its features. The membranous labyrinth barrier system is divided into several subsets of barriers which, although independent from each other, are interrelated. The same substance may demonstrate different permeability characteristics through different barriers and under different conditions, while different substances can have different permeability features even in the same barrier under the same condition. All parts of the mem-branous labyrinth barrier structure, including their morphology, enzymes and channel proteins, and theirs permeability characteristics under various physiological and pathological conditions are reviewed in this paper. Infections, noise exposure, ototoxicity may all increase perme-ability of the barriers and lead to disturbances in inner ear homeostasis. Copyright © 2015 The Authors. Production & hosting by Elsevier (Singapore) Pte Ltd On behalf of PLA General Hospital Department of Otolaryngology Head and Neck Surgery. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  18. Implementation of power barrier option valuation

    Science.gov (United States)

    Cahyani, Agatha C. P.; Sumarti, Novriana

    2015-09-01

    Options are financial instruments that can be utilized to reduce risk in stock investment. Barrier options are one of the major types of options actively used in financial markets where its life period depends on the path of the underlying stock prices. The features of the barrier option can be used to modify other types of options. In this research, the barrier option will be implemented into power option, so it is called power barrier option. This option is an extension of the vanilla barrier options where the Call payoff being considered is defined as P C =max (STβ-Kβ,0 ) , and the Put payoff being considered is defined as P P =max (Kβ-STβ,0 ) . Here β > 0 and β ≠ 1, K is the strike price of the option, and ST is the price of the underlying stock at time maturity T. In this paper, we generate the prices of stock using binomial method which is adjusted to the power option. In the conclusion, the price of American power barrier option is more expensive than the price of European power barrier option.

  19. Numerical simulations of capillary barrier field tests

    International Nuclear Information System (INIS)

    Numerical simulations of two capillary barrier systems tested in the field were conducted to determine if an unsaturated flow model could accurately represent the observed results. The field data was collected from two 7-m long, 1.2-m thick capillary barriers built on a 10% grade that were being tested to investigate their ability to laterally divert water downslope. One system had a homogeneous fine layer, while the fine soil of the second barrier was layered to increase its ability to laterally divert infiltrating moisture. The barriers were subjected first to constant infiltration while minimizing evaporative losses and then were exposed to ambient conditions. The continuous infiltration period of the field tests for the two barrier systems was modelled to determine the ability of an existing code to accurately represent capillary barrier behavior embodied in these two designs. Differences between the field test and the model data were found, but in general the simulations appeared to adequately reproduce the response of the test systems. Accounting for moisture retention hysteresis in the layered system will potentially lead to more accurate modelling results and is likely to be important when developing reasonable predictions of capillary barrier behavior

  20. Permanent isolation surface barrier development plan

    International Nuclear Information System (INIS)

    The exhumation and treatment of wastes may not always be the preferred alternative in the remediation of a waste site. In-place disposal alternatives, under certain circumstances, may be the most desirable alternatives to use in the protection of human health and the environment. The implementation of an in-place disposal alternative will likely require some type of protective covering that will provide long-term isolation of the wastes from the accessible environment. Even if the wastes are exhumed and treated, a long-term barrier may still be needed to adequately dispose of the treated wastes or any remaining waste residuals. Currently, no open-quotes provenclose quotes long-term barrier is available. The Hanford Site Permanent Isolation Surface Barrier Development Program (BDP) was organized to develop the technology needed to provide a long-term surface barrier capability for the Hanford Site. The permanent isolation barrier technology also could be used at other sites. Permanent isolation barriers use engineered layers of natural materials to create an integrated structure with redundant protective features. Drawings of conceptual permanent isolation surface barriers are shown. The natural construction materials (e.g., fine soil, sand, gravel, riprap, asphalt) have been selected to optimize barrier performance and longevity. The objective of current designs is to use natural materials to develop a maintenance-free permanent isolation surface barrier that isolates wastes for a minimum of 1,000 years by limiting water drainage to near-zero amounts; reducing the likelihood of plant, animal, and human intrusion; controlling the exhalation of noxious gases; and minimizing erosion-related problems