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Sample records for junction tj permeability

  1. Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components

    NARCIS (Netherlands)

    Ulluwishewa, D.; Anderson, R.C.; McNabb, W.C.; Moughan, P.J.; Wells, J.; Roy, N.C.

    2011-01-01

    The human intestinal epithelium is formed by a single layer of epithelial cells that separates the intestinal lumen from the underlying lamina propria. The space between these cells is sealed by tight junctions (TJ), which regulate the permeability of the intestinal barrier. TJ are complex protein s

  2. Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components

    NARCIS (Netherlands)

    Ulluwishewa, D.; Anderson, R.C.; McNabb, W.C.; Moughan, P.J.; Wells, J.; Roy, N.C.

    2011-01-01

    The human intestinal epithelium is formed by a single layer of epithelial cells that separates the intestinal lumen from the underlying lamina propria. The space between these cells is sealed by tight junctions (TJ), which regulate the permeability of the intestinal barrier. TJ are complex protein

  3. The reversible increase in tight junction permeability induced by capsaicin is mediated via cofilin-actin cytoskeletal dynamics and decreased level of occludin.

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    Tomoko Shiobara

    Full Text Available Previous results demonstrated that capsaicin induces the reversible tight junctions (TJ opening via cofilin activation. The present study investigated the mechanisms underlying the reversible TJ opening and compared the effect to the irreversible opening induced by actin inhibitors. Capsaicin treatment induced the F-actin alteration unique to capsaicin compared to actin-interacting agents such as latrunculin A, which opens TJ irreversibly. Along with TJ opening, capsaicin decreased the level of F-actin at bicellular junctions but increased it at tricellular junctions accompanied with its concentration on the apical side of the lateral membrane. No change in TJ protein localization was observed upon exposure to capsaicin, but the amount of occludin was decreased significantly. In addition, cosedimentation analyses suggested a decrease in the interactions forming TJ, thereby weakening TJ tightness. Introduction of cofilin, LIMK and occludin into the cell monolayers confirmed their contribution to the transepithelial electrical resistance decrease. Finally, exposure of monolayers to capsaicin augmented the paracellular passage of both charged and uncharged compounds, as well as of insulin, indicating that capsaicin can be employed to modulate epithelial permeability. Our results demonstrate that capsaicin induces TJ opening through a unique mechanism, and suggest that it is a new type of paracellular permeability enhancer.

  4. Actin-interacting protein 1 controls assembly and permeability of intestinal epithelial apical junctions.

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    Lechuga, Susana; Baranwal, Somesh; Ivanov, Andrei I

    2015-05-01

    Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis.

  5. Poly-L-arginine-Induced internalization of tight junction proteins increases the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules.

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    Yamaki, Tsutomu; Ohtake, Kazuo; Ichikawa, Keiko; Uchida, Masaki; Uchida, Hiroyuki; Oshima, Shinji; Ohshima, Shinji; Juni, Kazuhiko; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

    2013-01-01

    We investigated whether poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 monolayer to hydrophilic macromolecules and clarified the disposition of tight junction (TJ) proteins. The transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran (FD-4) permeation were determined after treatment with PLA. TJ proteins were visualized using immunofluorescence microscopy after PLA exposure and depletion, and their expression levels were determined. The barrier function of TJs was also evaluated by measuring the alterations in the TEER and in the localization of TJ proteins. PLA induced an increase in hydrophilic macromolecule, FD-4, permeation through Caco-2 cell monolayers and a decrease in the TEER in a concentration-dependent manner, without any significant impact on the cell viability. This increased paracellular permeability induced by PLA was found to be internalized of claudin-4, ZO-1, tricellulin and mainly occludin from cell-cell junction to the subcellular space. ZO-1 appeared to play an important role in the reconstitution of TJ strand structures following PLA depletion. These results indicate that the PLA led to the internalization of TJ proteins to the subcellular space, subsequently increasing the permeability of the Caco-2 cell monolayer to FD-4 via a paracellular route.

  6. Dietary fat and bile juice, but not obesity, are responsible for the increase in small intestinal permeability induced through the suppression of tight junction protein expression in LETO and OLETF rats

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    Suzuki Takuya

    2010-03-01

    Full Text Available Abstract Background An increase in the intestinal permeability is considered to be associated with the inflammatory tone and development in the obesity and diabetes, however, the pathogenesis of the increase in the intestinal permeability is poorly understood. The present study was performed to determine the influence of obesity itself as well as dietary fat on the increase in intestinal permeability. Methods An obese rat strain, Otsuka Long Evans Tokushima Fatty (OLETF, and the lean counter strain, Long Evans Tokushima Otsuka (LETO, were fed standard or high fat diets for 16 weeks. Glucose tolerance, intestinal permeability, intestinal tight junction (TJ proteins expression, plasma bile acids concentration were evaluated. In addition, the effects of rat bile juice and dietary fat, possible mediators of the increase in the intestinal permeability in the obesity, on TJ permeability were explored in human intestinal Caco-2 cells. Results The OLETF rats showed higher glucose intolerance than did the LETO rats, which became more marked with the prolonged feeding of the high fat diet. Intestinal permeability in the OLETF rats evaluated by the urinary excretion of intestinal permeability markers (Cr-EDTA and phenolsulfonphthalein was comparable to that in the LETO rats. Feeding the high fat diet increased intestinal permeability in both the OLETF and LETO rats, and the increases correlated with decreases in TJ proteins (claudin-1, claudin-3, occludin and junctional adhesion molecule-1 expression in the small, but not in the large intestine (cecum or colon. The plasma bile acids concentration was higher in rats fed the high fat diet. Exposure to bile juice and the fat emulsion increased TJ permeability with concomitant reductions in TJ protein expression (claudin-1, claudin-3, and junctional adhesion molecule-1 in the Caco-2 cell monolayers. Conclusion Excessive dietary fat and/or increased levels of luminal bile juice, but not genetic obesity, are

  7. Selective permeability of gap junction channels.

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    Goldberg, Gary S; Valiunas, Virginijus; Brink, Peter R

    2004-03-23

    Gap junctions mediate the transfer of small cytoplasmic molecules between adjacent cells. A family of gap junction proteins exist that form channels with unique properties, and differ in their ability to mediate the transfer of specific molecules. Mutations in a number of individual gap junction proteins, called connexins, cause specific human diseases. Therefore, it is important to understand how gap junctions selectively move molecules between cells. Rules that dictate the ability of a molecule to travel through gap junction channels are complex. In addition to molecular weight and size, the ability of a solute to transverse these channels depends on its net charge, shape, and interactions with specific connexins that constitute gap junctions in particular cells. This review presents some data and interpretations pertaining to mechanisms that govern the differential transfer of signals through gap junction channels.

  8. The Effect of Capsaicin Derivatives on Tight-Junction Integrity and Permeability of Madin-Darby Canine Kidney Cells.

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    Kaiser, Mathias; Chalapala, Sudharani; Gorzelanny, Christian; Perali, Ramu Sridhar; Goycoolea, Francisco Martin

    2016-02-01

    Capsaicin is known to interfere with tight junctions (TJs) of epithelial cells and therefore to enhance paracellular permeability of poorly absorbable drugs. However, due to its low water solubility, pungency, and cytotoxicity, its pharmacologic use is limited. In this study, we investigated the effect of capsaicin derivatives of synthetic (e.g., 10-hydroxy-N-(4-hydroxy-3-methoxybenzyl)decanamide, etc.) and natural (olvanil and dihydrocapsaicin) origin on Madin-Darby Canine Kidney-C7 cells. Impedance spectroscopy was used to determine the transepithelial electrical resistance and the capacitance. Permeability assays with fluorescein isothiocyanate-dextran were carried out to evaluate the impact on cell permeability. The results show that lipophilicity could play an important role for the interference with TJ and that the mechanism is independent from the ion channel TRPV-1 and hence on the flux of calcium into the cells. In summary, we synthesized 4 derivatives of capsaicin of lower lipophilicity and compared their properties with other well-known vanilloids. We show that these compounds are able to enhance the permeability of a hydrophilic macromolecule, by opening the TJ for a shorter time than capsaicin. This behavior is dependent on the lipophilicity of the molecule. Understanding of these phenomena may lead to better control of administration of therapeutic molecules.

  9. Gap junction protein connexin43 exacerbates lung vascular permeability.

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    James J O'Donnell

    Full Text Available Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins. Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43. Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.

  10. Expressions of tight junction proteins Occludin and Claudin-1 are under the circadian control in the mouse large intestine: implications in intestinal permeability and susceptibility to colitis.

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    Oh-oka Kyoko

    Full Text Available BACKGROUND & AIMS: The circadian clock drives daily rhythms in behavior and physiology. A recent study suggests that intestinal permeability is also under control of the circadian clock. However, the precise mechanisms remain largely unknown. Because intestinal permeability depends on tight junction (TJ that regulates the epithelial paracellular pathway, this study investigated whether the circadian clock regulates the expression levels of TJ proteins in the intestine. METHODS: The expression levels of TJ proteins in the large intestinal epithelium and colonic permeability were analyzed every 4, 6, or 12 hours between wild-type mice and mice with a mutation of a key clock gene Period2 (Per2; mPer2(m/m. In addition, the susceptibility to dextran sodium sulfate (DSS-induced colitis was compared between wild-type mice and mPer2(m/m mice. RESULTS: The mRNA and protein expression levels of Occludin and Claudin-1 exhibited daily variations in the colonic epithelium in wild-type mice, whereas they were constitutively high in mPer2(m/m mice. Colonic permeability in wild-type mice exhibited daily variations, which was inversely associated with the expression levels of Occludin and Claudin-1 proteins, whereas it was constitutively low in mPer2(m/m mice. mPer2(m/m mice were more resistant to the colonic injury induced by DSS than wild-type mice. CONCLUSIONS: Occludin and Claudin-1 expressions in the large intestine are under the circadian control, which is associated with temporal regulation of colonic permeability and also susceptibility to colitis.

  11. Prostaglandin E2 Produced by Entamoeba histolytica Signals via EP4 Receptor and Alters Claudin-4 to Increase Ion Permeability of Tight Junctions

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    Lejeune, Manigandan; Moreau, France; Chadee, Kris

    2011-01-01

    Entamoeba histolytica is a protozoan parasite that causes amebic dysentery characterized by severe watery diarrhea. Unfortunately, the parasitic factors involved in the pathogenesis of diarrhea are poorly defined. Prostaglandin E2 (PGE2) is a host lipid mediator associated with diarrheal diseases. Intriguingly, E. histolytica produces and secretes this inflammatory molecule. We investigated the mechanism whereby ameba-derived PGE2 induces the onset of diarrhea by altering ion permeability of paracellular tight junctions (TJs) in colonic epithelia. PGE2 decreased barrier integrity of TJs in a dose- and time-dependent manner, as measured by transepithelial resistance. PGE2 signals were selectively transduced via the EP4 receptor. Furthermore, PGE2 signaling decreased TJ integrity, as revealed by EP receptor-specific agonist and antagonist studies. Loss of mucosal barrier integrity corresponded with increased ion permeability across TJs. Subcellular fractionation and confocal microscopy studies highlighted a significant spatial alteration of an important TJ protein, claudin-4, that corresponded with increased sodium ion permeability through TJs toward the lumen. Moreover, PGE2-induced luminal chloride secretion was a prerequisite for alterations at TJs. Thus, the gradient of NaCl created across epithelia could serve as a trigger for osmotic water flow that leads to diarrhea. Our results highlight a pathological role for E. histolytica-derived PGE2 in the onset of diarrhea. PMID:21683675

  12. Lipopolysaccharide Causes an Increase in Intestinal Tight Junction Permeability in Vitro and in Vivo by Inducing Enterocyte Membrane Expression and Localization of TLR-4 and CD14

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    Guo, Shuhong; Al-Sadi, Rana; Said, Hamid M.; Ma, Thomas Y.

    2014-01-01

    Bacterial-derived lipopolysaccharides (LPS) play an essential role in the inflammatory process of inflammatory bowel disease. A defective intestinal tight junction (TJ) barrier is an important pathogenic factor of inflammatory bowel disease and other inflammatory conditions of the gut. Despite its importance in mediating intestinal inflammation, the physiological effects of LPS on the intestinal epithelial barrier remain unclear. The major aims of this study were to determine the effects of physiologically relevant concentrations of LPS (0 to 1 ng/mL) on intestinal barrier function using an in vitro (filter-grown Caco-2 monolayers) and an in vivo (mouse intestinal perfusion) intestinal epithelial model system. LPS, at physiologically relevant concentrations (0 to 1 ng/mL), in the basolateral compartment produced a time-dependent increase in Caco-2 TJ permeability without inducing cell death. Intraperitoneal injection of LPS (0.1 mg/kg), leading to clinically relevant plasma concentrations, also caused a time-dependent increase in intestinal permeability in vivo. The LPS-induced increase in intestinal TJ permeability was mediated by an increase in enterocyte membrane TLR-4 expression and a TLR-4–dependent increase in membrane colocalization of membrane-associated protein CD14. In conclusion, these studies show for the first time that LPS causes an increase in intestinal permeability via an intracellular mechanism involving TLR-4–dependent up-regulation of CD14 membrane expression. PMID:23201091

  13. 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).

  14. Endothelial Cell Permeability and Adherens Junction Disruption Induced by Junín Virus Infection

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    Lander, Heather M.; Grant, Ashley M.; Albrecht, Thomas; Hill, Terence; Peters, Clarence J.

    2014-01-01

    Junín virus (JUNV) is endemic to the fertile Pampas of Argentina, maintained in nature by the rodent host Calomys musculinus, and the causative agent of Argentine hemorrhagic fever (AHF), which is characterized by vascular dysfunction and fluid distribution abnormalities. Clinical as well as experimental studies implicate involvement of the endothelium in the pathogenesis of AHF, although little is known of its role. JUNV has been shown to result in productive infection of endothelial cells (ECs) in vitro with no visible cytopathic effects. In this study, we show that direct JUNV infection of primary human ECs results in increased vascular permeability as measured by electric cell substrate impedance sensing and transwell permeability assays. We also show that EC adherens junctions are disrupted during virus infection, which may provide insight into the role of the endothelium in the pathogenesis of AHF and possibly, other viral hemorrhagic fevers. PMID:24710609

  15. Experimental investigation of the influence of junctions on concrete gas permeability; Etude experimentale de l'influence des jonctions sur la permeabilite au gaz des betons

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    Poyet, St. [CEA Saclay, Dept. de Physico-Chimie (DEN/DANS/DPC/SCCME/LECBA), 91 - Gif sur Yvette (France); Pineau, F. [Agence Nationale pour la Gestion des Dechets Radioactifs, 92 - Chatenay-Malabry (France)

    2007-07-01

    Permeability is a key parameter in the case of nuclear waste disposal containers (evacuation of hydrogen generated by radiolysis and long-term containment of radionuclides) and nuclear power plants (confinement of radioactive gas in accidental conditions). The presence of construction junctions (formed between previously laid concrete and fresh concrete) might cause an increase of the permeability and question the durability of such concrete structures. In order to quantify the influence of the junctions on the permeability, specimens including a vertical junction were cast. Two different methods for the junction preparation were used: abrasion and chemical deactivation. The permeability was characterized for each specimen using nitrogen. The results show that the permeability to gas of the specimens increases depending on the type of preparation of the junction. The permeability of the junction zone is estimated using elementary homogenization. (authors)

  16. Autophagy enhances intestinal epithelial tight junction barrier function by targeting claudin-2 protein degradation.

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    Nighot, Prashant K; Hu, Chien-An Andy; Ma, Thomas Y

    2015-03-13

    Autophagy is an intracellular degradation pathway and is considered to be an essential cell survival mechanism. Defects in autophagy are implicated in many pathological processes, including inflammatory bowel disease. Among the innate defense mechanisms of intestinal mucosa, a defective tight junction (TJ) barrier has been postulated as a key pathogenic factor in the causation and progression of inflammatory bowel disease by allowing increased antigenic permeation. The cross-talk between autophagy and the TJ barrier has not yet been described. In this study, we present the novel finding that autophagy enhances TJ barrier function in Caco-2 intestinal epithelial cells. Nutrient starvation-induced autophagy significantly increased transepithelial electrical resistance and reduced the ratio of sodium/chloride paracellular permeability. Nutrient starvation reduced the paracellular permeability of small-sized urea but not larger molecules. The role of autophagy in the modulation of paracellular permeability was confirmed by pharmacological induction as well as pharmacological and genetic inhibition of autophagy. Consistent with the autophagy-induced reduction in paracellular permeability, a marked decrease in the level of the cation-selective, pore-forming TJ protein claudin-2 was observed after cell starvation. Starvation reduced the membrane presence of claudin-2 and increased its cytoplasmic, lysosomal localization. Therefore, our data show that autophagy selectively reduces epithelial TJ permeability of ions and small molecules by lysosomal degradation of the TJ protein claudin-2.

  17. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease.

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    Lerner, Aaron; Matthias, Torsten

    2015-06-01

    The incidence of autoimmune diseases is increasing along with the expansion of industrial food processing and food additive consumption. The intestinal epithelial barrier, with its intercellular tight junction, controls the equilibrium between tolerance and immunity to non-self-antigens. As a result, particular attention is being placed on the role of tight junction dysfunction in the pathogenesis of AD. Tight junction leakage is enhanced by many luminal components, commonly used industrial food additives being some of them. Glucose, salt, emulsifiers, organic solvents, gluten, microbial transglutaminase, and nanoparticles are extensively and increasingly used by the food industry, claim the manufacturers, to improve the qualities of food. However, all of the aforementioned additives increase intestinal permeability by breaching the integrity of tight junction paracellular transfer. In fact, tight junction dysfunction is common in multiple autoimmune diseases and the central part played by the tight junction in autoimmune diseases pathogenesis is extensively described. It is hypothesized that commonly used industrial food additives abrogate human epithelial barrier function, thus, increasing intestinal permeability through the opened tight junction, resulting in entry of foreign immunogenic antigens and activation of the autoimmune cascade. Future research on food additives exposure-intestinal permeability-autoimmunity interplay will enhance our knowledge of the common mechanisms associated with autoimmune progression.

  18. Tight Junctions in Salivary Epithelium

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    Olga J. Baker

    2010-01-01

    Full Text Available Epithelial cell tight junctions (TJs consist of a narrow belt-like structure in the apical region of the lateral plasma membrane that circumferentially binds each cell to its neighbor. TJs are found in tissues that are involved in polarized secretions, absorption functions, and maintaining barriers between blood and interstitial fluids. The morphology, permeability, and ion selectivity of TJ vary among different types of tissues and species. TJs are very dynamic structures that assemble, grow, reorganize, and disassemble during physiological or pathological events. Several studies have indicated the active role of TJ in intestinal, renal, and airway epithelial function; however, the functional significance of TJ in salivary gland epithelium is poorly understood. Interactions between different combinations of the TJ family (each with their own unique regulatory proteins define tissue specificity and functions during physiopathological processes; however, these interaction patterns have not been studied in salivary glands. The purpose of this review is to analyze some of the current data regarding the regulatory components of the TJ that could potentially affect cellular functions of the salivary epithelium.

  19. Alterations of intercellular junctions in peritoneal mesothelial cells from patients undergoing dialysis: effect of retinoic Acid.

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    Retana, Carmen; Sanchez, Elsa; Perez-Lopez, Alejandro; Cruz, Armando; Lagunas, Jesus; Cruz, Carmen; Vital, Socorro; Reyes, Jose L

    2015-01-01

    Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression. Copyright © 2015 International Society for Peritoneal Dialysis.

  20. EMP-induced alterations of tight junction protein expression and disruption of the blood-brain barrier.

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    Ding, Gui-Rong; Qiu, Lian-Bo; Wang, Xiao-Wu; Li, Kang-Chu; Zhou, Yong-Chun; Zhou, Yan; Zhang, Jie; Zhou, Jia-Xing; Li, Yu-Rong; Guo, Guo-Zhen

    2010-07-15

    The blood-brain barrier (BBB) is critical to maintain cerebral homeostasis. In this study, we examined the effects of exposure to electromagnetic pulse (EMP) on the functional integrity of BBB and, on the localization and expression of tight junction (TJ) proteins (occludin and ZO-1) in rats. Animals were sham or whole-body exposed to EMP at 200 kV/m for 400 pulses. The permeability of BBB in rat cerebral cortex was examined by using Evans Blue (EB) and lanthanum nitrate as vascular tracers. The localization and expression of TJ proteins were assessed by western blot and immunofluorescence analysis, respectively. The data indicated that EMP exposure caused: (i) increased permeability of BBB, and (ii) altered localization as well as decreased levels of TJ protein ZO-1. These results suggested that the alteration of ZO-1 may play an important role in the disruption of tight junctions, which may lead to dysfunction of BBB after EMP exposure.

  1. A membrane fusion protein αSNAP is a novel regulator of epithelial apical junctions.

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    Nayden G Naydenov

    Full Text Available Tight junctions (TJs and adherens junctions (AJs are key determinants of the structure and permeability of epithelial barriers. Although exocytic delivery to the cell surface is crucial for junctional assembly, little is known about the mechanisms controlling TJ and AJ exocytosis. This study was aimed at investigating whether a key mediator of exocytosis, soluble N-ethylmaleimide sensitive factor (NSF attachment protein alpha (αSNAP, regulates epithelial junctions. αSNAP was enriched at apical junctions in SK-CO15 and T84 colonic epithelial cells and in normal human intestinal mucosa. siRNA-mediated knockdown of αSNAP inhibited AJ/TJ assembly and establishment of the paracellular barrier in SK-CO15 cells, which was accompanied by a significant down-regulation of p120-catenin and E-cadherin expression. A selective depletion of p120 catenin effectively disrupted AJ and TJ structure and compromised the epithelial barrier. However, overexpression of p120 catenin did not rescue the defects of junctional structure and permeability caused by αSNAP knockdown thereby suggesting the involvement of additional mechanisms. Such mechanisms did not depend on NSF functions or induction of cell death, but were associated with disruption of the Golgi complex and down-regulation of a Golgi-associated guanidine nucleotide exchange factor, GBF1. These findings suggest novel roles for αSNAP in promoting the formation of epithelial AJs and TJs by controlling Golgi-dependent expression and trafficking of junctional proteins.

  2. Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis

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    Claire Bardet

    2017-05-01

    Full Text Available Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL. Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC, were recently shown to be also involved in Amelogenesis Imperfecta (AI. In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO mice displayed abnormal enamel formation. Claudin-3, an ubiquitous claudin expressed in epithelia including kidney, acts as a barrier-forming tight junction protein. We determined that, similarly to claudin-16 and claudin-19, claudin-3 was expressed in the tooth germ, more precisely in the TJ located at the apical end of secretory ameloblasts. The observation of Claudin-3 KO teeth revealed enamel defects associated to impaired TJ structure at the secretory ends of ameloblasts and accumulation of matrix proteins in the forming enamel. Thus, claudin-3 protein loss-of-function disturbs amelogenesis similarly to claudin-16 loss-of-function, highlighting the importance of claudin proteins for the TJ structure. These findings unravel that loss-of-function of either pore or barrier-forming TJ proteins leads to enamel defects. Hence, the major structural function of claudin proteins appears essential for amelogenesis.

  3. Effect of FCCP on tight junction permeability and cellular distribution of ZO-1 protein in epithelial (MDCK) cells.

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    Li, C X; Poznansky, M J

    1990-12-14

    The effect of the uncoupler of oxidative phosphorylation, FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone), on the tight junction of Madin-Darby canine kidney cells was examined. FCCP induced an abrupt decrease in the transepithelial electrical resistance of the confluent monolayers over a period of 20 s. When FCCP was withdrawn from the incubation medium, the monolayer resistance recovered to close to the original level in less than 2 h. Staining of the tight junction-associated protein ZO-1 showed that the changes in transepithelial electrical resistance were accompanied by a diffusing of the protein away from cell peripheries and a reconcentration to the tight junction areas following resistance recovery. Intracellular pH was decreased by FCCP on a similar time-scale with no obvious changes in ATP levels over this time-course. These data suggest that the uncoupler FCCP has a profound effect on tight junction permeability and cellular distribution of the tight junction protein ZO-1 in the epithelial cells and that it probably acts by breaking down proton gradients and altering intracellular pH.

  4. Tight junction regulates epidermal calcium ion gradient and differentiation

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    Kurasawa, Masumi; Maeda, Tetsuo; Oba, Ai; Yamamoto, Takuya [Pola Chemical Industries Inc., 560 Kashio-cho, Totsuka-ku, Yokohama 244-0812 (Japan); Sasaki, Hiroyuki, E-mail: sasakih@jikei.ac.jp [Division of Fine Morphology, Core Research Facilities, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461 (Japan); The Center for Advanced Medical Engineering and Infomatics, Osaka University, Osaka 565-0871 (Japan)

    2011-03-25

    Research highlights: {yields} We disrupted epidermal tight junction barrier in reconstructed epidermis. {yields} It altered Ca{sup 2+} distribution and consequentially differentiation state as well. {yields} Tight junction should affect epidermal homeostasis by maintaining Ca{sup 2+} gradient. -- Abstract: It is well known that calcium ions (Ca{sup 2+}) induce keratinocyte differentiation. Ca{sup 2+} distributes to form a vertical gradient that peaks at the stratum granulosum. It is thought that the stratum corneum (SC) forms the Ca{sup 2+} gradient since it is considered the only permeability barrier in the skin. However, the epidermal tight junction (TJ) in the granulosum has recently been suggested to restrict molecular movement to assist the SC as a secondary barrier. The objective of this study was to clarify the contribution of the TJ to Ca{sup 2+} gradient and epidermal differentiation in reconstructed human epidermis. When the epidermal TJ barrier was disrupted by sodium caprate treatment, Ca{sup 2+} flux increased and the gradient changed in ion-capture cytochemistry images. Alterations of ultrastructures and proliferation/differentiation markers revealed that both hyperproliferation and precocious differentiation occurred regionally in the epidermis. These results suggest that the TJ plays a crucial role in maintaining epidermal homeostasis by controlling the Ca{sup 2+} gradient.

  5. [Antiarrhythmic effect of TJ0711].

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    Zhang, Xiao-Jing; Qiu, Jun; Li, Gao

    2014-03-01

    To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be

  6. Large intestine permeability is increased in patients with compensated liver cirrhosis.

    Science.gov (United States)

    Pijls, Kirsten E; Koek, Ger H; Elamin, Elhaseen E; de Vries, Hanne; Masclee, Ad A M; Jonkers, Daisy M A E

    2014-01-01

    Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Increased intestinal permeability has been found in patients with liver cirrhosis, but data on small and large intestine permeability and tight junctions (TJs) in patients with compensated cirrhosis are scarce. We aimed to investigate both small and large intestine permeability in patients with stable compensated cirrhosis compared with healthy controls and evaluated the expression of TJ proteins in mucosal biopsies at duodenal and sigmoid level. Intestinal permeability was assessed in 26 patients with compensated cirrhosis and 27 matched controls using a multisugar test. Duodenal and sigmoid biopsies were available from a subgroup for analyses of gene transcription and expression of key TJ proteins by qRT-PCR and ELISA, respectively. Median 0-5-h urinary sucrose excretion and lactulose/rhamnose ratio were comparable between patients with compensated cirrhosis and controls, whereas 5-24-h urinary sucralose/erythritol ratio was increased in these patients. Downregulation of gene transcription was found for claudin-3 in duodenal biopsies and claudin-4 in sigmoid biopsies, and at the protein level occludin expression was significantly increased in both duodenal and sigmoid biopsies. This study shows that gastroduodenal and small intestine permeability are not altered, whereas large intestine permeability is increased in patients with stable compensated cirrhosis. Only limited alterations were found regarding the expression of TJ proteins in both the small and large intestine.

  7. ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development.

    Directory of Open Access Journals (Sweden)

    Jeongwoo Kwon

    Full Text Available ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10 is a cell surface protein with a unique structure possessing both potential adhesion and protease domains. However, the role of ADAM10 in preimplantation stage embryos is not clear. In this study, we examined the expression patterns and functional roles of ADAM10 in porcine parthenotes during preimplantation development. The transcription level of ADAM10 dramatically increased from the morula stage onward. Immunostaining revealed that ADAM10 was present in both the nucleus and cytoplasm in early cleavage stage embryos, and localized to the apical region of the outer cells in morula and blastocyst embryos. Knockdown (KD of ADAM10 using double strand RNA did not alter preimplantation embryo development until morula stage, but resulted in significantly reduced development to blastocyst stage. Moreover, the KD blastocyst showed a decrease in gene expression of adherens and tight junction (AJ/TJ, and an increase in trophectoderm TJ permeability by disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor, GI254023X, at the morula stage also inhibited blastocyst development and led to disruption of TJ assembly. An in situ proximity ligation assay demonstrated direct interaction of ADAM10 with coxsackie virus and adenovirus receptor (CXADR, supporting the involvement of ADAM10 in TJ assembly. In conclusion, our findings strongly suggest that ADADM10 is important for blastocyst formation rather than compaction, particularly for TJ assembly and stabilization in preimplantation porcine parthenogenetic development.

  8. Tight junction disruption induced by type 3 secretion system effectors injected by Enteropathogenic and Enterohemorrhagic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Paul Ugalde-Silva

    2016-08-01

    Full Text Available The intestinal epithelium consists of a single cell layer, which is a critical selectively permeable barrier to both absorb nutrients and avoid the entry of potentially harmful entities, including microorganisms. Epithelial cells are held together by the apical junctional complexes, consisting of adherens junctions and tight junctions (TJs, and by underlying desmosomes. TJs lay in the apical domain of epithelial cells and are mainly composed by transmembrane proteins such as occludin, claudins, JAMs, and tricellulin, that are associated with the cytoplasmic plaque formed by proteins from the MAGUK family, such as ZO-1/2/3, connecting TJ to the actin cytoskeleton, and cingulin and paracingulin connecting TJ to the microtubule network. Extracellular bacteria such as EPEC and EHEC living in the intestinal lumen inject effectors proteins directly from the bacterial cytoplasm to the host cell cytoplasm, where they play a relevant role in the manipulation of the eukaryotic cell functions by modifying or blocking cell signaling pathways. TJ integrity depends on various cell functions such as actin cytoskeleton, microtubule network for vesicular trafficking, membrane integrity, inflammation, and cell survival. EPEC and EHEC effectors target most of these functions. Effectors encoded inside or outside of locus of enterocyte effacement (LEE disrupt the TJ strands. EPEC and EHEC exploit the TJ dynamics to open this structure, for causing diarrhea. EPEC and EHEC secrete effectors that mimic host proteins to manipulate the signaling pathways, including those related to TJ dynamics. In this review, we focus on the known mechanisms exploited by EPEC and EHEC effectors for causing TJ disruption.

  9. Chlorogenic acid decreases intestinal permeability and increases expression of intestinal tight junction proteins in weaned rats challenged with LPS.

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    Zheng Ruan

    Full Text Available Chlorogenic acid, a natural phenolic acid present in fruits and plants, provides beneficial effects for human health. The objectives of this study were to investigate whether chlorogenic acid (CHA could improve the intestinal barrier integrity for weaned rats with lipopolysaccharide (LPS challenge. Thirty-two weaned male Sprague Dawley rats (21 ± 1 d of age; 62.26 ± 2.73 g were selected and randomly allotted to four treatments, including weaned rat control, LPS-challenged and chlorogenic acid (CHA supplemented group (orally 20 mg/kg and 50 mg/kg body. Dietary supplementation with CHA decreased (P<0.05 the concentrations of urea and albumin in the serum, compared to the LPS-challenged group. The levels of IFN-γ and TNF-α were lower (P<0.05 in the jejunal and colon of weaned rats receiving CHA supplementation, in comparison with the control group. CHA supplementation increased (P<0.05 villus height and the ratio of villus height to crypt depth in the jejunal and ileal mucosae under condictions of LPS challenge. CHA supplementation decreased (P<0.05 intestinal permeability, which was indicated by the ratio of lactulose to mannitol and serum DAO activity, when compared to weaned rats with LPS challenge. Immunohistochemical analysis of tight junction proteins revealed that ZO-1 and occludin protein abundances in the jejunum and colon were increased (P<0.05 by CHA supplementation. Additionally, results of immunoblot analysis revealed that the amount of occludin in the colon was also increased (P<0.05 in CHA-supplemented rats. In conclusion, CHA decreases intestinal permeability and increases intestinal expression of tight junction proteins in weaned rats challenged with LPS.

  10. Autophagy and tight junction proteins in the intestine and intestinal diseases

    Directory of Open Access Journals (Sweden)

    Chien-An A. Hu

    2015-09-01

    Full Text Available The intestinal epithelium (IE forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus and antigens. The apical intercellular tight junctions (TJ are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD, necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6

  11. JAM-A regulates permeability and inflammation in the intestine in vivo.

    Science.gov (United States)

    Laukoetter, Mike G; Nava, Porfirio; Lee, Winston Y; Severson, Eric A; Capaldo, Christopher T; Babbin, Brian A; Williams, Ifor R; Koval, Michael; Peatman, Eric; Campbell, Jacquelyn A; Dermody, Terence S; Nusrat, Asma; Parkos, Charles A

    2007-12-24

    Recent evidence has linked intestinal permeability to mucosal inflammation, but molecular studies are lacking. Candidate regulatory molecules localized within the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of barrier function and leukocyte migration. Thus, we analyzed the intestinal mucosa of JAM-A-deficient (JAM-A(-/-)) mice for evidence of enhanced permeability and inflammation. Colonic mucosa from JAM-A(-/-) mice had normal epithelial architecture but increased polymorphonuclear leukocyte infiltration and large lymphoid aggregates not seen in wild-type controls. Barrier function experiments revealed increased mucosal permeability, as indicated by enhanced dextran flux, and decreased transepithelial electrical resistance in JAM-A(-/-) mice. The in vivo observations were epithelial specific, because monolayers of JAM-A(-/-) epithelial cells also demonstrated increased permeability. Analyses of other TJ components revealed increased expression of claudin-10 and -15 in the colonic mucosa of JAM-A(-/-) mice and in JAM-A small interfering RNA-treated epithelial cells. Given the observed increase in colonic inflammation and permeability, we assessed the susceptibility of JAM-A(-/-) mice to the induction of colitis with dextran sulfate sodium (DSS). Although DSS-treated JAM-A(-/-) animals had increased clinical disease compared with controls, colonic mucosa showed less injury and increased epithelial proliferation. These findings demonstrate a complex role of JAM-A in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation.

  12. Peanut Allergens Alter Intestinal Barrier Permeability and Tight Junction Localisation in Caco-2 Cell Cultures1

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    Dwan B. Price

    2014-05-01

    Full Text Available Background/Aims: Allergen absorption by epithelia may play an important role in downstream immune responses. Transport mechanisms that can bypass Peyer's patches include transcellular and paracellular transport. The capacity of an allergen to cross via these means can modulate downstream processing of the allergen by the immune system. The aim of this study was to investigate allergen-epithelial interactions of peanut allergens with the human intestinal epithelium. Methods: We achieved this using the human Caco-2 cell culture model, exposed to crude peanut extract. Western and immunofluorescence analysis were used to identify the cellular and molecular changes of peanut extract on the intestinal epithelium. Results: Following exposure of Caco-2 cells to peanut extract, binding of the peanut allergens Ara h 1 and Ara h 2 to the apical cellular membrane and transcytosis across the monolayers were observed. Additionally, the co-localisation of the transmembrane tight junction proteins occludin, JAM-A and claudin-1, with the intracellular adhesion protein ZO-1 was modified. Conclusion: Disruption of Caco-2 barrier integrity through tight junction disruption may enable movement of peanut proteins across the intestinal epithelium. This accounts for peanut's increased allergenicity, compared to other food allergens, and provides an explanation for the potency of peanut allergens in immune response elicitation.

  13. Protein tyrosine phosphatase σ targets apical junction complex proteins in the intestine and regulates epithelial permeability.

    Science.gov (United States)

    Murchie, Ryan; Guo, Cong-Hui; Persaud, Avinash; Muise, Aleixo; Rotin, Daniela

    2014-01-14

    Protein tyrosine phosphatase (PTP)σ (PTPRS) was shown previously to be associated with susceptibility to inflammatory bowel disease (IBD). PTPσ(-/-) mice exhibit an IBD-like phenotype in the intestine and show increased susceptibility to acute models of murine colitis. However, the function of PTPσ in the intestine is uncharacterized. Here, we show an intestinal epithelial barrier defect in the PTPσ(-/-) mouse, demonstrated by a decrease in transepithelial resistance and a leaky intestinal epithelium that was determined by in vivo tracer analysis. Increased tyrosine phosphorylation was observed at the plasma membrane of epithelial cells lining the crypts of the small bowel and colon of the PTPσ(-/-) mouse, suggesting the presence of PTPσ substrates in these regions. Using mass spectrometry, we identified several putative PTPσ intestinal substrates that were hyper-tyrosine-phosphorylated in the PTPσ(-/-) mice relative to wild type. Among these were proteins that form or regulate the apical junction complex, including ezrin. We show that ezrin binds to and is dephosphorylated by PTPσ in vitro, suggesting it is a direct PTPσ substrate, and identified ezrin-Y353/Y145 as important sites targeted by PTPσ. Moreover, subcellular localization of the ezrin phosphomimetic Y353E or Y145 mutants were disrupted in colonic Caco-2 cells, similar to ezrin mislocalization in the colon of PTPσ(-/-) mice following induction of colitis. Our results suggest that PTPσ is a positive regulator of intestinal epithelial barrier, which mediates its effects by modulating epithelial cell adhesion through targeting of apical junction complex-associated proteins (including ezrin), a process impaired in IBD.

  14. Hyperthermia Differently Affects Connexin43 Expression and Gap Junction Permeability in Skeletal Myoblasts and HeLa Cells

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    Ieva Antanavičiūtė

    2014-01-01

    Full Text Available Stress kinases can be activated by hyperthermia and modify the expression level and properties of membranous and intercellular channels. We examined the role of c-Jun NH2-terminal kinase (JNK in hyperthermia-induced changes of connexin43 (Cx43 expression and permeability of Cx43 gap junctions (GJs in the rabbit skeletal myoblasts (SkMs and Cx43-EGFP transfected HeLa cells. Hyperthermia (42°C for 6 h enhanced the activity of JNK and its target, the transcription factor c-Jun, in both SkMs and HeLa cells. In SkMs, hyperthermia caused a 3.2-fold increase in the total Cx43 protein level and enhanced the efficacy of GJ intercellular communication (GJIC. In striking contrast, hyperthermia reduced the total amount of Cx43 protein, the number of Cx43 channels in GJ plaques, the density of hemichannels in the cell membranes, and the efficiency of GJIC in HeLa cells. Both in SkMs and HeLa cells, these changes could be prevented by XG-102, a JNK inhibitor. In HeLa cells, the changes in Cx43 expression and GJIC under hyperthermic conditions were accompanied by JNK-dependent disorganization of actin cytoskeleton stress fibers while in SkMs, the actin cytoskeleton remained intact. These findings provide an attractive model to identify the regulatory players within signalosomes, which determine the cell-dependent outcomes of hyperthermia.

  15. Hyperthermia differently affects connexin43 expression and gap junction permeability in skeletal myoblasts and HeLa cells.

    Science.gov (United States)

    Antanavičiūtė, Ieva; Mildažienė, Vida; Stankevičius, Edgaras; Herdegen, Thomas; Skeberdis, Vytenis Arvydas

    2014-01-01

    Stress kinases can be activated by hyperthermia and modify the expression level and properties of membranous and intercellular channels. We examined the role of c-Jun NH2-terminal kinase (JNK) in hyperthermia-induced changes of connexin43 (Cx43) expression and permeability of Cx43 gap junctions (GJs) in the rabbit skeletal myoblasts (SkMs) and Cx43-EGFP transfected HeLa cells. Hyperthermia (42°C for 6 h) enhanced the activity of JNK and its target, the transcription factor c-Jun, in both SkMs and HeLa cells. In SkMs, hyperthermia caused a 3.2-fold increase in the total Cx43 protein level and enhanced the efficacy of GJ intercellular communication (GJIC). In striking contrast, hyperthermia reduced the total amount of Cx43 protein, the number of Cx43 channels in GJ plaques, the density of hemichannels in the cell membranes, and the efficiency of GJIC in HeLa cells. Both in SkMs and HeLa cells, these changes could be prevented by XG-102, a JNK inhibitor. In HeLa cells, the changes in Cx43 expression and GJIC under hyperthermic conditions were accompanied by JNK-dependent disorganization of actin cytoskeleton stress fibers while in SkMs, the actin cytoskeleton remained intact. These findings provide an attractive model to identify the regulatory players within signalosomes, which determine the cell-dependent outcomes of hyperthermia.

  16. Mild hypothermia alleviates brain oedema and blood-brain barrier disruption by attenuating tight junction and adherens junction breakdown in a swine model of cardiopulmonary resuscitation

    Science.gov (United States)

    Li, Jiebin; Li, Chunsheng; Yuan, Wei; Wu, Junyuan; Li, Jie; Li, Zhenhua; Zhao, Yongzhen

    2017-01-01

    Mild hypothermia improves survival and neurological recovery after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). However, the mechanism underlying this phenomenon is not fully elucidated. The aim of this study was to determine whether mild hypothermia alleviates early blood–brain barrier (BBB) disruption. We investigated the effects of mild hypothermia on neurologic outcome, survival rate, brain water content, BBB permeability and changes in tight junctions (TJs) and adherens junctions (AJs) after CA and CPR. Pigs were subjected to 8 min of untreated ventricular fibrillation followed by CPR. Mild hypothermia (33°C) was intravascularly induced and maintained at this temperature for 12 h, followed by active rewarming. Mild hypothermia significantly reduced cortical water content, decreased BBB permeability and attenuated TJ ultrastructural and basement membrane breakdown in brain cortical microvessels. Mild hypothermia also attenuated the CPR-induced decreases in TJ (occludin, claudin-5, ZO-1) and AJ (VE-cadherin) protein and mRNA expression. Furthermore, mild hypothermia decreased the CA- and CPR-induced increases in matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression and increased angiogenin-1 (Ang-1) expression. Our findings suggest that mild hypothermia attenuates the CA- and resuscitation-induced early brain oedema and BBB disruption, and this improvement might be at least partially associated with attenuation of the breakdown of TJ and AJ, suppression of MMP-9 and VEGF expression, and upregulation of Ang-1 expression. PMID:28355299

  17. Loss of occludin expression and impairment of blood-testis barrier permeability in rats with autoimmune orchitis: effect of interleukin 6 on Sertoli cell tight junctions.

    Science.gov (United States)

    Pérez, Cecilia Valeria; Sobarzo, Cristian Marcelo; Jacobo, Patricia Verónica; Pellizzari, Eliana Herminia; Cigorraga, Selva Beatriz; Denduchis, Berta; Lustig, Livia

    2012-11-01

    Inflammation of the male reproductive tract is accepted as being an important etiological factor of infertility. Experimental autoimmune orchitis (EAO) is characterized by interstitial lymphomononuclear cell infiltration and severe damage of seminiferous tubules with germ cells that undergo apoptosis and sloughing. Because the blood-testis barrier (BTB) is relevant for the protection of haploid germ cells against immune attack, the aim of this study was to analyze BTB permeability and the expression of tight junction proteins (occludin, claudin 11, and tight junction protein 1 [TJP1]) in rats during development of autoimmune orchitis. The role of IL6 as modulator of tight junction dynamics was also evaluated because intratesticular content of this cytokine is increased in EAO rats. Orchitis was induced in Sprague-Dawley adult rats by active immunization with testicular homogenate and adjuvants. Control rats (C) were injected with saline solution and adjuvants. Untreated (N) rats were also studied. Concomitant with early signs of germ cell sloughing, a reduced expression of occludin and delocalization of claudin 11 and TJP1 were detected in the testes of rats with EAO compared to C and N groups. The use of tracers showed increased BTB permeability in EAO rats. Intratesticular injection of IL6 induced focal testicular inflammation, which is associated with damaged seminiferous tubules. Rat Sertoli cells cultured in the presence of IL6 exhibited a redistribution of tight junction proteins and reduced transepithelial electrical resistance. These data indicate the possibility that IL6 might be involved in the downregulation of occludin expression and in the modulation of BTB permeability that occur in rats undergoing autoimmune orchitis.

  18. Designing of TJ VCSEL based on nitride materials

    Science.gov (United States)

    Sarzała, R. P.; Pijanowski, K.; Gebski, M.; Marciniak, M.; Nakwaski, W.

    2016-12-01

    Different structures of nitride Vertical-Cavity Surface-Emitting Lasers (VCSELs) have been developed in recent years. However there is still many problems with such constructions, especially with electrical and optical confinement, current injection and construction and fabrication of mirrors. In this paper we present novel approach to nitride VCSEL designing. We investigated structure with tunnel junction (TJ) and top and bottom dielectric distributed Bragg reflectors (DBRs). Using our three-dimensional self-consistent model we investigated thermal and electrical properties of such laser. We also proposed replacing bottom DBR by monolithic high contrast grating mirror (MHCG) and presented optical properties of VCSEL with such mirrors.

  19. Tjæreborg Wind Turbine (Esbjerg)

    DEFF Research Database (Denmark)

    Øye, Stig

    1991-01-01

    This paper presents the first measured timeseries for the Tjæreborg (Tjaereborg) Wind Turbine during operation with stepwise pitch angle changes.......This paper presents the first measured timeseries for the Tjæreborg (Tjaereborg) Wind Turbine during operation with stepwise pitch angle changes....

  20. Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

    Science.gov (United States)

    Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

    2016-07-01

    Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.

  1. Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins.

    Science.gov (United States)

    Chen, Xin; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Matsumoto, Takayuki; Miwa, Hiroto

    2011-08-01

    Experimental models for esophageal epithelium in vitro either suffer from poor differentiation or complicated culture systems. An air-liquid interface system with normal human bronchial epithelial cells can serve as a model of esophageal-like squamous epithelial cell layers. Here, we explore the influence of bile acids on barrier function and tight junction (TJ) proteins. The cells were treated with taurocholic acid (TCA), glycocholic acid (GCA), or deoxycholic acid (DCA) at different pH values, or with pepsin. Barrier function was measured by transepithelial electrical resistance (TEER) and the diffusion of paracellular tracers (permeability). The expression of TJ proteins, including claudin-1 and claudin-4, was examined by Western blotting of 1% Nonidet P-40-soluble and -insoluble fractions. TCA and GCA dose-dependently decreased TEER and increased paracellular permeability at pH 3 after 1 h. TCA (4 mM) or GCA (4 mM) did not change TEER and permeability at pH 7.4 or pH 4. The combination of TCA and GCA at pH 3 significantly decreased TEER and increased permeability at lower concentrations (2 mM). Pepsin (4 mg/ml, pH 3) did not have any effect on barrier function. DCA significantly decreased the TEER and increased permeability at pH 6, a weakly acidic condition. TCA (4 mM) and GCA (4 mM) significantly decreased the insoluble fractions of claudin-1 and claudin-4 at pH 3. In conclusion, acidic bile salts disrupted the squamous epithelial barrier function partly by modulating the amounts of claudin-1 and claudin-4. These results provide new insights for understanding the role of TJ proteins in esophagitis.

  2. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis.

    Science.gov (United States)

    Nighot, Prashant; Al-Sadi, Rana; Rawat, Manmeet; Guo, Shuhong; Watterson, D Martin; Ma, Thomas

    2015-12-15

    Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9(-/-) mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9(-/-) mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9(-/-) mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK(-/-) mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9(-/-) mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK.

  3. Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

    Science.gov (United States)

    Nighot, Prashant; Al-Sadi, Rana; Guo, Shuhong; Watterson, D. Martin; Ma, Thomas

    2015-01-01

    Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/− mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/− mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/− mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/− mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/− mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK. PMID:26514773

  4. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    Science.gov (United States)

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.

  5. Tjæreborg Wind Turbine

    DEFF Research Database (Denmark)

    Øye, Stig

    1991-01-01

    This paper presents results from the fourth measurement camapign at the Tjæreborg (Tjaereborg) WInd Turbine during operation with stepwise pitch angle changes. The measurements cover one hour of operation at wind speeds between 7 and 10 m/s aceraging approximately 8.7 m/s.......This paper presents results from the fourth measurement camapign at the Tjæreborg (Tjaereborg) WInd Turbine during operation with stepwise pitch angle changes. The measurements cover one hour of operation at wind speeds between 7 and 10 m/s aceraging approximately 8.7 m/s....

  6. The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Gian Carlo Alghisi

    Full Text Available Cilengitide is a high-affinity cyclic pentapeptdic alphaV integrin antagonist previously reported to suppress angiogenesis by inducing anoikis of endothelial cells adhering through alphaVbeta3/alphaVbeta5 integrins. Angiogenic endothelial cells express multiple integrins, in particular those of the beta1 family, and little is known on the effect of cilengitide on endothelial cells expressing alphaVbeta3 but adhering through beta1 integrins. Through morphological, biochemical, pharmacological and functional approaches we investigated the effect of cilengitide on alphaVbeta3-expressing human umbilical vein endothelial cells (HUVEC cultured on the beta1 ligands fibronectin and collagen I. We show that cilengitide activated cell surface alphaVbeta3, stimulated phosphorylation of FAK (Y(397 and Y(576/577, Src (S(418 and VE-cadherin (Y(658 and Y(731, redistributed alphaVbeta3 at the cell periphery, caused disappearance of VE-cadherin from cellular junctions, increased the permeability of HUVEC monolayers and detached HUVEC adhering on low-density beta1 integrin ligands. Pharmacological inhibition of Src kinase activity fully prevented cilengitide-induced phosphorylation of Src, FAK and VE-cadherin, and redistribution of alphaVbeta3 and VE-cadherin and partially prevented increased permeability, but did not prevent HUVEC detachment from low-density matrices. Taken together, these observations reveal a previously unreported effect of cilengitide on endothelial cells namely its ability to elicit signaling events disrupting VE-cadherin localization at cellular contacts and to increase endothelial monolayer permeability. These effects are potentially relevant to the clinical use of cilengitide as anticancer agent.

  7. Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids.

    Directory of Open Access Journals (Sweden)

    Cyrill Géraud

    Full Text Available Liver sinusoidal endothelium is strategically positioned to control access of fluids, macromolecules and cells to the liver parenchyma and to serve clearance functions upstream of the hepatocytes. While clearance of macromolecular debris from the peripheral blood is performed by liver sinusoidal endothelial cells (LSECs using a delicate endocytic receptor system featuring stabilin-1 and -2, the mannose receptor and CD32b, vascular permeability and cell trafficking are controlled by transcellular pores, i.e. the fenestrae, and by intercellular junctional complexes. In contrast to blood vascular and lymphatic endothelial cells in other organs, the junctional complexes of LSECs have not yet been consistently characterized in molecular terms. In a comprehensive analysis, we here show that LSECs express the typical proteins found in endothelial adherens junctions (AJ, i.e. VE-cadherin as well as α-, β-, p120-catenin and plakoglobin. Tight junction (TJ transmembrane proteins typical of endothelial cells, i.e. claudin-5 and occludin, were not expressed by rat LSECs while heterogenous immunreactivity for claudin-5 was detected in human LSECs. In contrast, junctional molecules preferentially associating with TJ such as JAM-A, B and C and zonula occludens proteins ZO-1 and ZO-2 were readily detected in LSECs. Remarkably, among the JAMs JAM-C was considerably over-expressed in LSECs as compared to lung microvascular endothelial cells. In conclusion, we show here that LSECs form a special kind of mixed-type intercellular junctions characterized by co-occurrence of endothelial AJ proteins, and of ZO-1 and -2, and JAMs. The distinct molecular architecture of the intercellular junctional complexes of LSECs corroborates previous ultrastructural findings and provides the molecular basis for further analyses of the endothelial barrier function of liver sinusoids under pathologic conditions ranging from hepatic inflammation to formation of liver metastasis.

  8. Modulation of intercellular junctions by cyclic-ADT peptides as a method to reversibly increase blood-brain barrier permeability.

    Science.gov (United States)

    Laksitorini, Marlyn D; Kiptoo, Paul K; On, Ngoc H; Thliveris, James A; Miller, Donald W; Siahaan, Teruna J

    2015-03-01

    It is challenging to deliver molecules to the brain for diagnosis and treatment of brain diseases. This is primarily because of the presence of the blood-brain barrier (BBB), which restricts the entry of many molecules into the brain. In this study, cyclic-ADT peptides (ADTC1, ADTC5, and ADTC6) have been shown to modify the BBB to enhance the delivery of marker molecules [e.g., (14) C-mannitol, gadolinium-diethylenetriaminepentacetate (Gd-DTPA)] to the brain via the paracellular pathways of the BBB. The hypothesis is that these peptides modulate cadherin interactions in the adherens junctions of the vascular endothelial cells forming the BBB to increase paracellular drug permeation. In vitro studies indicated that ADTC5 had the best profile to inhibit adherens junction resealing in Madin-Darby canine kidney cell monolayers in a concentration-dependent manner (IC50 = 0.3 mM) with a maximal response at 0.4 mM. Under the current experimental conditions, ADTC5 improved the delivery of (14) C-mannitol to the brain about twofold compared with the negative control in the in situ rat brain perfusion model. Furthermore, ADTC5 peptide increased in vivo delivery of Gd-DTPA to the brain of Balb/c mice when administered intravenously. In conclusion, ADTC5 has the potential to improve delivery of diagnostic and therapeutic agents to the brain.

  9. β-Conglycinin Reduces the Tight Junction Occludin and ZO-1 Expression in IPEC-J2

    Directory of Open Access Journals (Sweden)

    Yuan Zhao

    2014-01-01

    Full Text Available Soybean allergy presents a health threat to humans and animals. The mechanism by which food/feed allergen β-conglycinin injures the intestinal barrier has not been well understood. In this study, the changes of epithelial permeability, integrity, metabolic activity, the tight junction (TJ distribution and expression induced by β-conglycinin were evaluated using IPEC-J2 model. The results showed a significant decrease of trans-epithelial electrical resistance (TEER (p < 0.001 and metabolic activity (p < 0.001 and a remarkable increase of alkaline phosphatase (AP activity (p < 0.001 in a dose-dependent manner. The expression levels of tight junction occludin and ZO-1 were decreased (p < 0.05. The reduced fluorescence of targets and change of cellular morphology were recorded. The tight junction occludin and ZO-1 mRNA expression linearly declined with increasing β-conglycinin (p < 0.001.

  10. Escherichia coli STb enterotoxin dislodges claudin-1 from epithelial tight junctions.

    Directory of Open Access Journals (Sweden)

    Hassan Nassour

    Full Text Available Enterotoxigenic Escherichia coli produce various heat-labile and heat-stable enterotoxins. STb is a low molecular weight heat-resistant toxin responsible for diarrhea in farm animals, mainly young pigs. A previous study demonstrated that cells having internalized STb toxin induce epithelial barrier dysfunction through changes in tight junction (TJ proteins. These modifications contribute probably to the diarrhea observed. To gain insight into the mechanism of increased intestinal permeability following STb exposure we treated human colon cells (T84 with purified STb toxin after which cells were harvested and proteins extracted. Using a 1% Nonidet P-40-containing solution we investigated the distribution of claudin-1, a major structural and functional TJ protein responsible for the epithelium impermeability, between membrane (NP40-insoluble and the cytoplasmic (NP-40 soluble location. Using immunoblot and confocal microscopy, we observed that treatment of T84 cell monolayers with STb induced redistribution of claudin-1. After 24 h, cells grown in Ca++-free medium treated with STb showed about 40% more claudin-1 in the cytoplasm compare to the control. Switching from Ca++-free to Ca++-enriched medium (1.8 mM increased the dislodgement rate of claudin-1 as comparable quantitative delocalization was observed after only 6 h. Medium supplemented with the same concentration of Mg++ or Zn++ did not affect the dislodgement rate compared to the Ca++-free medium. Using anti-phosphoserine and anti-phosphothreonine antibodies, we observed that the loss of membrane claudin-1 was accompanied by dephosphorylation of this TJ protein. Overall, our findings showed an important redistribution of claudin-1 in cells treated with STb toxin. The loss of phosphorylated TJ membrane claudin-1 is likely to be involved in the increased permeability observed. The mechanisms by which these changes are brought about remain to be elucidated.

  11. Escherichia coli STb enterotoxin dislodges claudin-1 from epithelial tight junctions.

    Science.gov (United States)

    Nassour, Hassan; Dubreuil, J Daniel

    2014-01-01

    Enterotoxigenic Escherichia coli produce various heat-labile and heat-stable enterotoxins. STb is a low molecular weight heat-resistant toxin responsible for diarrhea in farm animals, mainly young pigs. A previous study demonstrated that cells having internalized STb toxin induce epithelial barrier dysfunction through changes in tight junction (TJ) proteins. These modifications contribute probably to the diarrhea observed. To gain insight into the mechanism of increased intestinal permeability following STb exposure we treated human colon cells (T84) with purified STb toxin after which cells were harvested and proteins extracted. Using a 1% Nonidet P-40-containing solution we investigated the distribution of claudin-1, a major structural and functional TJ protein responsible for the epithelium impermeability, between membrane (NP40-insoluble) and the cytoplasmic (NP-40 soluble) location. Using immunoblot and confocal microscopy, we observed that treatment of T84 cell monolayers with STb induced redistribution of claudin-1. After 24 h, cells grown in Ca++-free medium treated with STb showed about 40% more claudin-1 in the cytoplasm compare to the control. Switching from Ca++-free to Ca++-enriched medium (1.8 mM) increased the dislodgement rate of claudin-1 as comparable quantitative delocalization was observed after only 6 h. Medium supplemented with the same concentration of Mg++ or Zn++ did not affect the dislodgement rate compared to the Ca++-free medium. Using anti-phosphoserine and anti-phosphothreonine antibodies, we observed that the loss of membrane claudin-1 was accompanied by dephosphorylation of this TJ protein. Overall, our findings showed an important redistribution of claudin-1 in cells treated with STb toxin. The loss of phosphorylated TJ membrane claudin-1 is likely to be involved in the increased permeability observed. The mechanisms by which these changes are brought about remain to be elucidated.

  12. Transport with Astra in TJ-II; Transporte con Astra en TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Bruna, D.; Castejon, F.; Fontdecaba, J. M.

    2004-07-01

    This report describes the adaptation of the numerical transport shell ASTRA for performing plasma calculations in the TJ-II stellarator device. Firstly, an approximation to the TJ-II geometry is made and a simple transport model is shared with two other codes in order to compare these codes (PROCTR, PRETOR-Stellarator) with ASTRA as calculation tool for TJ-II plasmas are provided: interpretative and predictive transport. The first consists in estimating the transport coefficients from real experimental data, thes being taken from three TJ-II discharges. The predictive facet is illustrated using a model that is able to includes self-consistently thedynamics of transport barriers. The report includes this model, written in the ASTRA programming language, to illustrate the use of ASTRA. (Author) 26 refs.

  13. Characterization and significance of adhesion and junction-related proteins in mouse ovarian follicles.

    Science.gov (United States)

    Mora, Jocelyn M; Fenwick, Mark A; Castle, Laura; Baithun, Marianne; Ryder, Timothy A; Mobberley, Margaret; Carzaniga, Raffaella; Franks, Stephen; Hardy, Kate

    2012-05-01

    In the ovary, initiation of follicle growth is marked by cuboidalization of flattened granulosa cells (GCs). The regulation and cell biology of this shape change remains poorly understood. We propose that characterization of intercellular junctions and associated proteins is key to identifying as yet unknown regulators of this important transition. As GCs are conventionally described as epithelial cells, this study used mouse ovaries and isolated follicles to investigate epithelial junctional complexes (tight junctions [TJ], adherens junctions [AJ], and desmosomes) and associated molecules, as well as classic epithelial markers, by quantitative PCR and immunofluorescence. These junctions were further characterized using ultrastructural, calcium depletion and biotin tracer studies. Junctions observed by transmission electron microscopy between GCs and between GCs and oocyte were identified as AJs by expression of N-cadherin and nectin 2 and by the lack of TJ and desmosome-associated proteins. Follicles were also permeable to biotin, confirming a lack of functional TJs. Surprisingly, GCs lacked all epithelial markers analyzed, including E-cadherin, cytokeratin 8, and zonula occludens (ZO)-1alpha+. Furthermore, vimentin was expressed by GCs, suggesting a more mesenchymal phenotype. Under calcium-free conditions, small follicles maintained oocyte-GC contact, confirming the importance of calcium-independent nectin at this stage. However, in primary and multilayered follicles, lack of calcium resulted in loss of contact between GCs and oocyte, showing that nectin alone cannot maintain attachment between these two cell types. Lack of classic markers suggests that GCs are not epithelial. Identification of AJs during GC cuboidalization highlights the importance of AJs in regulating initiation of follicle growth.

  14. The role of tight junctions in mammary gland function.

    Science.gov (United States)

    Stelwagen, Kerst; Singh, Kuljeet

    2014-03-01

    Tight junctions (TJ) are cellular structures that facilitate cell-cell communication and are important in maintaining the three-dimensional structure of epithelia. It is only during the last two decades that the molecular make-up of TJ is becoming unravelled, with two major transmembrane-spanning structural protein families, called occludin and claudins, being the true constituents of the TJ. These TJ proteins are linked via specific scaffolding proteins to the cell's cytoskeleton. In the mammary gland TJ between adjacent secretory epithelial cells are formed during lactogenesis and are instrumental in establishing and maintaining milk synthesis and secretion, whereas TJ integrity is compromised during mammary involution and also as result of mastitis and periods of mammary inflamation (including mastitis). They prevent the paracellular transport of ions and small molecules between the blood and milk compartments. Formation of intact TJ at the start of lactation is important for the establishment of the lactation. Conversely, loss of TJ integrity has been linked to reduced milk secretion and mammary function and increased paracellular transport of blood components into the milk and vice versa. In addition to acting as a paracellular barrier, the TJ is increasingly linked to playing an active role in intracellular signalling. This review focusses on the role of TJ in mammary function of the normal, non-malignant mammary gland, predominantly in ruminants, the major dairy producing species.

  15. Relationship of gelatinases-tight junction proteins and blood-brain barrier permeability in the early stage of cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Haolin Xin; Wenzhao Liang; Jing Mang; Lina Lin; Na Guo; Feng Zhang; Zhongxin Xu

    2012-01-01

    Gelatinases matrix metalloproteinase-2 and matrix metalloproteinase-9 have been shown to mediate claudin-5 and occludin degradation, and play an important regulatory role in blood-brain barrier permeability. This study established a rat model of 1.5-hour middle cerebral artery occlusion with reperfusion. Protein expression levels of claudin-5 and occludin gradually decreased in the early stage of reperfusion, which corresponded to the increase of the gelatinolytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9. In addition, rats that received treatment with matrix metalloproteinase inhibitor N-[(2R)-2-(hydroxamidocarbonylmethyl)-4-methylpenthanoyl]-L- tryptophan methylamide (GM6001) showed a significant reduction in Evans blue leakage and an inhibition of claudin-5 and occludin protein degradation in striatal tissue. These data indicate that matrix metalloproteinase-2 and matrix metalloproteinase-9-mediated claudin-5 and occludin degradation is an important reason for blood-brain barrier leakage in the early stage of reperfusion. The leakage of the blood-brain barrier was present due to gelatinases-mediated degradation of claudin-5 and occludin proteins. We hypothesized that the timely closure of the structural component of the blood-brain barrier (tight junction proteins) is of importance.

  16. Endocytosis and Recycling of Tight Junction Proteins in Inflammation

    Directory of Open Access Journals (Sweden)

    Markus Utech

    2010-01-01

    Full Text Available A critical function of the epithelial lining is to form a barrier that separates luminal contents from the underlying interstitium. This barrier function is primarily regulated by the apical junctional complex (AJC consisting of tight junctions (TJs and adherens junctions (AJs and is compromised under inflammatory conditions. In intestinal epithelial cells, proinflammatory cytokines, for example, interferon-gamma (IFN-γ, induce internalization of TJ proteins by endocytosis. Endocytosed TJ proteins are passed into early and recycling endosomes, suggesting the involvement of recycling of internalized TJ proteins. This review summarizes mechanisms by which TJ proteins under inflammatory conditions are internalized in intestinal epithelial cells and point out comparable mechanism in nonintestinal epithelial cells.

  17. Increased gut permeability and bacterial translocation after chronic chlorpyrifos exposure in rats.

    Directory of Open Access Journals (Sweden)

    Claire Joly Condette

    Full Text Available The epithelium's barrier function is crucial for maintaining homeostasis and preventing the passage of food antigens and luminal bacteria. This function is essentially subserved by tight junctions (TJs, multiprotein complexes located in the most apical part of the lateral membrane. Some gastrointestinal disease states are associated with elevated intestinal permeability to macromolecules. In a study on rats, we determined the influence of chronic, daily ingestion of chlorpyrifos (CPF, a pesticide that crosses the placental barrier during pre- and postnatal periods on intestinal permeability and TJ characteristics in the pups. Fluorescein isothiocyanate (FITC-dextran was used as a marker of paracellular transport and mucosal barrier dysfunction. Pups were gavaged with FITC-dextran solution and blood samples were collected every 30 min for 400 min and analyzed spectrofluorimetrically. At sacrifice, different intestinal segments were resected and prepared for analysis of the transcripts (qPCR and localization (using immunofluorescence of ZO-1, occludin and claudins (scaffolding proteins that have a role in the constitution of TJs. In rats that had been exposed to CPF in utero and after birth, we observed a progressive increase in FITC-dextran passage across the epithelial barrier from 210 to 325 min at day 21 after birth (weaning but not at day 60 (adulthood. At both ages, there were significant changes in intestinal TJ gene expression, with downregulation of ZO-1 and occludin and upregulation of claudins 1 and 4. In some intestinal segments, there were changes in the cellular localization of ZO-1 and claudin 4 immunostaining. Lastly, bacterial translocation to the spleen was also observed. The presence of CPF residues in food may disturb epithelial homeostasis in rats. Changes in TJ protein expression and localization may be involved in gut barrier dysfunction in this model. Uncontrolled passage of macromolecules and bacteria across the intestinal

  18. The protein kinase A pathway contributes to Hg2+-induced alterations in phosphorylation and subcellular distribution of occludin associated with increased tight junction permeability of salivary epithelial cell monolayers.

    Science.gov (United States)

    Kawedia, Jitesh D; Jiang, Mengmeng; Kulkarni, Amit; Waechter, Holly E; Matlin, Karl S; Pauletti, Giovanni M; Menon, Anil G

    2008-09-01

    Hg(2+) is commonly used as an inhibitor of many aquaporins during measurements of transcellular water transport. To investigate whether it could also act on the paracellular water transport pathway, we asked whether addition of Hg(2+) affected transport of radiolabeled probes through tight junctions of a salivary epithelial cell monolayer. Inclusion of 1 mM Hg(2+) decreased transepithelial electrical resistance by 8-fold and augmented mannitol and raffinose flux by 13-fold, which translated into an estimated 44% increase in pore radius at the tight junction. These Hg(2+)-induced effects could be partially blocked by the protein kinase A (PKA) inhibitor N-[2-((p-bromocinnamyl) amino) ethyl]-5-isoquinolinesulfonamide, 2HCl (H89), suggesting that both-PKA dependent and PKA-independent mechanisms contribute to tight junction regulation. Western blot analyses showed a 2-fold decrease in tight junction-associated occludin after Hg(2+) treatment and the presence of a novel hyperphosphorylated form of occludin in the cytoplasmic fraction. These findings were corroborated by confocal imaging. The results from this study reveal a novel contribution of the PKA pathway in Hg(2+)-induced regulation of tight junction permeability in the salivary epithelial barrier. Therapeutically, this could be explored for pharmacological intervention in the treatment of dry mouth, Sjögren's syndrome, and possibly other disorders of fluid transport.

  19. Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29.

    Science.gov (United States)

    Jeong, Chang Hee; Seok, Jin Sil; Petriello, Michael C; Han, Sung Gu

    2017-03-15

    Arsenic is a naturally occurring metalloid that often is found in foods and drinking water. Human exposure to arsenic is associated with the development of gastrointestinal problems such as fluid loss, diarrhea and gastritis. Arsenic is also known to induce toxic responses including oxidative stress in cells of the gastrointestinal track. Tight junctions (TJs) regulate paracellular permeability and play a barrier role by inhibiting the movement of water, solutes and microorganisms in the paracellular space. Since oxidative stress and TJ damage are known to be associated, we examined whether arsenic produces TJ damage such as downregulation of claudins in the human colorectal cell line, HT-29. To confirm the importance of oxidative stress in arsenic-induced TJ damage, effects of the antioxidant compound (e.g., N-acetylcysteine (NAC)) were also determined in cells. HT-29 cells were treated with arsenic trioxide (40μM, 12h) to observe the modified expression of TJ proteins. Arsenic decreased expression of TJ proteins (i.e., claudin-1 and claudin-5) and transepithelial electrical resistance (TEER) whereas pretreatment of NAC (5-10mM, 1h) attenuated the observed claudins downregulation and TEER. Arsenic treatment produced cellular oxidative stress via superoxide generation and lowering glutathione (GSH) levels, while NAC restored cellular GSH levels and decreased oxidative stress. Arsenic increased phosphorylation of p38 and nuclear translocation of nuclear factor-kappa B (NF-κB) p65, while NAC attenuated these intracellular events. Results demonstrated that arsenic can damage intestinal epithelial cells by proinflammatory process (oxidative stress, p38 and NF-κB) which resulted in the downregulation of claudins and NAC can protect intestinal TJs from arsenic toxicity.

  20. Tight junction changes in epithelial cells by Campylobacter jejuni and non-jejuni Campylobacter species

    DEFF Research Database (Denmark)

    Bücker, Roland; Nielsen, Hans Linde; Krüg, S

    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 HT-29...

  1. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhao [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States); Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC

  2. Hepatic tight junctions:From viral entry to cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Nikki; P; Lee; John; M; Luk

    2010-01-01

    The tight junction (TJ) is a critical cellular component for maintenance of tissue integrity, cellular interactions and cell-cell communications, and physiologically functions as the "great wall" against external agents and the surrounding hostile environment. During the host-pathogen evolution, viruses somehow found the key to unlock the gate for their entry into cells and to exploit and exhaust the host cells. In the liver, an array of TJ molecules is localized along the bile canaliculi forming the blood-...

  3. Degeneration of noradrenergic fibres from the locus coeruleus causes tight-junction disorganisation in the rat brain.

    Science.gov (United States)

    Kalinin, Sergey; Feinstein, Douglas L; Xu, Hao-Liang; Huesa, Gema; Pelligrino, Dale A; Galea, Elena

    2006-12-01

    Although functional studies demonstrate that noradrenaline controls the permeability of the blood-brain barrier, it has never been determined whether this neurotransmitter regulates the tight junction (TJ) assembly that confers the barrier property to brain microvessels. We thus tested in rats the effect of pharmacological depletion of noradrenaline with the noradrenergic toxin DSP4 (5 mg/kg) on the expression of the TJ proteins zonula occludens-1 (ZO1) and occludin. The effectiveness of the lesion was confirmed by tyrosine hydroxylase immunoreactivity, which showed noradrenergic fibre reduction accompanied by debris and swollen fibres in DSP4-treated brains. Noradrenergic fibre degeneration caused: (i) gliosis; (ii) disappearance of TJ proteins in vascular cell-to-cell contacts (49.9 and 38.3% reductions for occludin and ZO1, respectively); (iii) a 49.2% decrease in total ZO1 protein, measured by Western blot analysis, parallel to a 39.5% decrease in ZO1 mRNA, measured by real-time PCR; and (iv) a relative increase in the beta occludin isoform (62.9%), with no change in total occludin protein or mRNA. The expression of endothelial brain antigen, a marker of a functionally competent brain endothelium, was also reduced. We conclude that damage to the ascending fibres from the locus coeruleus caused TJ disruption and gliosis, a sign of inflammation. These results imply that the locus coeruleus degeneration reported in Alzheimer's and Parkinson's diseases may contribute to these disorders by causing blood-brain barrier dysfunction. Whether the vascular damage is the result of impaired noradrenergic transmission or secondary to the inflammatory reaction remains to be determined.

  4. Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Serge C Thal

    Full Text Available Disruption of the blood-brain barrier (BBB results in cerebral edema formation, which is a major cause for high mortality after traumatic brain injury (TBI. As anesthetic care is mandatory in patients suffering from severe TBI it may be important to elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ such as zonula occludens-1 (ZO-1 and claudin-5 (cl5 play a central role for BBB stability. First, the influence of the volatile anesthetics sevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER in murine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression of ZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled cortical impact (CCI. In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours after exposure. In BBB co-cultures mimicking the neurovascular unit (NVU volatile anesthetics had no impact on TEER. In healthy mice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water content increased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expression was significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analyses revealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The study demonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed to modulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence the barrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Future research is required to investigate

  5. Present status of the TJ-II remote participation system

    Energy Technology Data Exchange (ETDEWEB)

    Vega, J. [Asociacion EURATOM/CIEMAT para Fusion., Avda. Complutense 22, 28040 Madrid (Spain)]. E-mail: jesus.vega@ciemat.es; Sanchez, E. [Asociacion EURATOM/CIEMAT para Fusion., Avda. Complutense 22, 28040 Madrid (Spain); Lopez, A. [Asociacion EURATOM/CIEMAT para Fusion., Avda. Complutense 22, 28040 Madrid (Spain); Portas, A. [Asociacion EURATOM/CIEMAT para Fusion., Avda. Complutense 22, 28040 Madrid (Spain); Ochando, M. [Asociacion EURATOM/CIEMAT para Fusion., Avda. Complutense 22, 28040 Madrid (Spain); Ascasibar, E. [Asociacion EURATOM/CIEMAT para Fusion., Avda. Complutense 22, 28040 Madrid (Spain); Mollinedo, A. [CIEMAT. Computing Center, Avda. Complutense 22, 28040 Madrid (Spain); Munoz, J. [CIEMAT. Computing Center, Avda. Complutense 22, 28040 Madrid (Spain); Sanchez, A. [CIEMAT. Computing Center, Avda. Complutense 22, 28040 Madrid (Spain); Ruiz, M. [Universidad Politecnica de Madrid. Dpto. Sistemas Electronicos y de Control, Campus Sur. Ctra. Valencia, km 7, 28031 Madrid (Spain); Barrera, E. [Universidad Politecnica de Madrid. Dpto. Sistemas Electronicos y de Control, Campus Sur. Ctra. Valencia, km 7, 28031 Madrid (Spain); Lopez, S. [Universidad Politecnica de Madrid. Dpto. Sistemas Electronicos y de Control, Campus Sur. Ctra. Valencia, km 7, 28031 Madrid (Spain); Castro, R. [Red.es-RedIRIS, Edificio Bronce, Plaza Manuel Gomez Moreno, s/n, 28020 Madrid (Spain); Lopez, D. [Red.es-RedIRIS, Edificio Bronce, Plaza Manuel Gomez Moreno, s/n, 28020 Madrid (Spain)

    2005-11-15

    The TJ-II remote participation system (RPS) was designed to extend to Internet the working capabilities provided in the TJ-II local environment, i.e., tracking the TJ-II operation, monitoring/programming data acquisition and control systems, and accessing databases. The TJ-II RPS was based on web and Java technologies because of their open character, security properties and technological maturity. A web server acts as a communication front-end between remote participants and local TJ-II elements. From the server side, web services are provided by means of resources supplied by JSP pages. The client part makes use of web browsers and ad hoc Java applications. The operation requires the use of a distributed authentication and authorization system. This development employs the PAPI System. At present, approximately 1000 digitisation channels can be managed from the TJ-II RPS. Furthermore, processing software based on a 4GL language (LabView) can be downloaded to multiprocessor data acquisition systems. Also, 15 diagnostic control systems, databases and the operation logbook are available from the RPS. The system even allows for the physicist in charge of operation to be in a remote location. Four Spanish universities make use of the TJ-II remote participation system capabilities for joint collaborations: these are the Universidad Politecnica de Madrid (UPM), Universidad Nacional de Educacion a Distancia (UNED), Universidad Complutense de Madrid (UCM) and Universidad Politecnica de Cataluna (UPC)

  6. Overview of TJ-II flexible heliac results

    Energy Technology Data Exchange (ETDEWEB)

    Ascasibar, E. E-mail: enrique.ascasibar@ciemat.es; Alejaldre, C.; Alonso, J.; Almoguera, L.; Baciero, A.; Balbin, R.; Blaumoser, M.; Botija, J.; Branas, B.; Cal, E. de la; Cappa, A.; Castellano, J.; Carrasco, R.; Castejon, F.; Cepero, J.R.; Cremy, C.; Doncel, J.; Eguilior, S.; Estrada, T.; Fernandez, A.; Fuentes, C.; Garcia, A.; Garcia-Cortes, I.; Guasp, J.; Herranz, J.; Hidalgo, C.; Jimenez, J.A.; Kirpitchev, I.; Krivenski, V.; Labrador, I.; Lapayese, F.; Likin, K.; Liniers, M.; Lopez-Fraguas, A.; Lopez-Sanchez, A.; Luna, E. de la; Martin, R.; Martinez-Laso, L.; Medrano, M.; Mendez, P.; McCarthy, K.J.; Medina, F.; Milligen, B. van; Ochando, M.; Pacios, L.; Pastor, I.; Pedrosa, M.A.; Pena, A. de la; Portas, A.; Qin, J.; Rodriguez-Rodrigo, L.; Romero, J.; Salas, A.; Sanchez, E.; Sanchez, J.; Tabares, F.; Tafalla, D.; Tribaldos, V.; Vega, J.; Zurro, B

    2001-10-01

    The TJ-II is a four period, low magnetic shear stellarator, with high degree of configuration flexibility (rotational transform from 0.9 to 2.5) which has been operating in Madrid since 1998 (R=1.5 m, a<0.22 m, B{sub 0}=1 T, P{sub ECRH}{<=}600 kW, P{sub NBI}{<=}3 MW under installation). This paper reviews the main technical aspects of the TJ-II heliac as well as the principal physics results obtained in the most recent TJ-II experimental campaign carried out in 2000.

  7. Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent MAPK/ERK1/2-pathway.

    Science.gov (United States)

    Petecchia, Loredana; Sabatini, Federica; Usai, Cesare; Caci, Emanuela; Varesio, Luigi; Rossi, Giovanni A

    2012-08-01

    Epithelial barrier permeability is altered in inflammatory respiratory disorders by a variety of noxious agents through modifications of the epithelial cell structure that possibly involve tight junction (TJ) organization. To evaluate in vitro whether pro-inflammatory cytokines involved in the pathogenesis of respiratory disorders could alter TJ organization and epithelial barrier integrity, and to characterize the signal transduction pathway involved Calu-3 airway epithelial cells were exposed to TNF-a, IL-4 and IFN-g to assess changes in: (a) TJ assembly, that is, occludin and zonula occludens (ZO)-1 expression and localization, evaluated by confocal microscopy; (b) apoptotic activity, quantified using terminal transferase deoxyuridine triphosphate nick-end labeling staining; (c) epithelial barrier integrity, detected as transmembrane electrical resistance and expressed as G(T) values; (d) epidermal growth factor receptor (EGFR)-dependent mitogenactivated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinases (ERK)1/2 phosphorylation, assessed by western blotting. Exposure to cytokines for 48 h induced a noticeable downregulation of the TJ transmembrane proteins. The degree ZO-1 and occludin colocalization was 62±2% in control cultures and significantly decreased in the presence of TNF-a (47±3%), IL-4 (43±1%) and INF-g (35±3%). Although no apoptosis induction was detected following exposure to cytokines, changes in the epithelial barrier integrity were observed, with a significant enhancement in paracellular conductance. G(T) values were, respectively, 1.030±0.0, 1.300±0.04, 1.260±0.020 and 2.220±0.015 (mS/cm²)1000 in control cultures and in those exposed to TNF-a, IFN-g and IL-4. The involvement of EGFR-dependent MAPK/ERK1/2 signaling pathway in cytokine-induced damage was demonstrated by a significant increase in threonine/tyrosine phosphorylation of ERK1/2, already detectable after 5 min incubation. All these cytokine-induced changes were

  8. Bifidobacterium animalis subsp lactis CNCM-I2494 restores gut barrier permeability in chronically low-grade inflamed mice

    Directory of Open Access Journals (Sweden)

    Rebeca eMartín

    2016-05-01

    Full Text Available Growing evidence supports the efficacy of many probiotic strains in the management of gastrointestinal disorders associated with deregulated intestinal barrier function and/or structure. In particular, bifidobacteria have been studied for their efficacy to both prevent and treat a broad spectrum of animal and/or human gut disorders. The aim of the current work was thus to evaluate effects on intestinal barrier function of Bifidobacterium animalis subsp lactis CNCM-I2494, a strain used in fermented dairy products. A chronic DNBS-induced low-grade inflammation model causing gut dysfunction in mice was used in order to study markers of inflammation, intestinal permeability and immune function in the presence of the bacterial strain. In this chronic low-grade inflammation mice model several parameters pointed out the absence of an over active inflammation process. However, gut permeability, lymphocyte populations and colonic cytokines were found to be altered. B. animalis subsp lactis CNCM-I2494 was able to protect barrier functions by restoring intestinal permeability, colonic goblet cell populations and cytokine levels. Furthermore, tight junction (TJ proteins levels were also measured by qRT-PCR showing the ability of this strain to specifically normalize the level of several TJ proteins, in particular for claudin-4. Finally, B. lactis strain counterbalanced CD4+ lymphocyte alterations in both spleen and mesenteric lymphoid nodes (MLN. It restores the Th1/Th2 ratio altered by the DNBS challenge (which locally augments CD4+ Th1 cells by increasing the Th2 response as measured by the increase in the production of major representative Th2 cytokines (IL-4, IL-5 and IL-10. Altogether, these data suggest that B. animalis subsp lactis CNCM-I2494 may efficiently prevent disorders associated with increased barrier permeability.

  9. The EhCPADH112 complex of Entamoeba histolytica interacts with tight junction proteins occludin and claudin-1 to produce epithelial damage.

    Directory of Open Access Journals (Sweden)

    Abigail Betanzos

    Full Text Available Entamoeba histolytica, the protozoan responsible for human amoebiasis, causes between 30,000 and 100,000 deaths per year worldwide. Amoebiasis is characterized by intestinal epithelial damage provoking severe diarrhea. However, the molecular mechanisms by which this protozoan causes epithelial damage are poorly understood. Here, we studied the initial molecular interactions between the E. histolytica EhCPADH112 virulence complex and epithelial MDCK and Caco-2 cells. By confocal microscopy, we discovered that after contact with trophozoites or trophozoite extracts (TE, EhCPADH112 and proteins forming this complex (EhCP112 and EhADH112 co-localize with occludin and claudin-1 at tight junctions (TJ. Immunoprecipitation assays revealed interaction between EhCPADH112 and occludin, claudin-1, ZO-1 and ZO-2. Overlay assays confirmed an interaction of EhCP112 and EhADH112 with occludin and claudin-1, whereas only EhADH112 interacted also with ZO-2. We observed degradation of all mentioned TJ proteins after incubation with TE. Importantly, inhibiting proteolytic activity or blocking the complex with a specific antibody not only prevented TJ protein degradation but also epithelial barrier disruption. Furthermore, we discovered that TE treatment induces autophagy and apoptosis in MDCK cells that could contribute to the observed barrier disruption. Our results suggest a model in which epithelial damage caused by E. histolytica is initiated by the interaction of EhCP112 and EhADH112 with TJ proteins followed by their degradation. Disruption of TJs then induces increased paracellular permeability, thus facilitating the entry of more proteases and other parasite molecules leading eventually to tissue destruction.

  10. Remote Control of TJ-II Diagnostics; Control Remoto de Diagnosticos del Dispositivo TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Sanchez, A.; Vega, J.; Montoro, A.; Encabo, J.

    2001-07-01

    The present paper is about the design and development of ten remote control diagnostic systems used in the study of plasma fusion in the TJ-II device installed at CIEMAT. This development goes from the definition of sensors and devices necessary in carrying out these remote controls, to its assembly, wiring, development of electronic circuits inserted between sensors and PLC, development of programs for these PLC, connections and administration of the real time automation network, and later development of the necessary programs via the appropriate software tools for web access through a navigator to a specific web page, allowing visual and real time access over the auxiliary systems that make up all the diagnostics. (Author)

  11. Incommensurate Antiferromagnetism in the Extended t-J Model

    Institute of Scientific and Technical Information of China (English)

    LIANG Ying; MA Tian-Xing; FENG Shi-Ping; CHEN Wei-Yeu

    2002-01-01

    The effect of the extra second neighbor hopping t' on the incommensurate spin correlation in the t-J modelin the underdoped regime is studied within the fermion-spin theory. It is shown that although the extra second neighborhopping t' is systematically accompanied with the increasing of the weight of the incommensurate peaks in the dynamicalspin structure factor, for the physical reasonable small value of t' the qualitative behavior of the incommensurate spincorrelation in the t-t'-J model is the same as in the case of t-J model.

  12. miR-200b inhibits TNF-α-induced IL-8 secretion and tight junction disruption of intestinal epithelial cells in vitro.

    Science.gov (United States)

    Shen, Yujie; Zhou, Min; Yan, Junkai; Gong, Zizhen; Xiao, Yongtao; Zhang, Cong; Du, Peng; Chen, Yingwei

    2017-02-01

    Inflammatory bowel diseases (IBDs) are chronic, inflammatory disorders of the gastrointestinal tract with unclear etiologies. Intestinal epithelial cells (IECs), containing crypt and villus enterocytes, occupy a critical position in the pathogenesis of IBDs and are a major producer of immunoregulatory cytokines and a key component of the intact epithelial barrier. Previously, we have reported that miR-200b is involved in the progression of IBDs and might maintain the integrity of the intestinal epithelial barrier via reducing the loss of enterocytes. In this study, we further investigated the impact of miR-200b on intestinal epithelial inflammation and tight junctions in two distinct differentiated states of Caco-2 cells after TNF-α treatment. We demonstrated that TNF-α-enhanced IL-8 expression was decreased by microRNA (miR)-200b in undifferentiated IECs. Simultaneously, miR-200b could alleviate TNF-α-induced tight junction (TJ) disruption in well-differentiated IECs by reducing the reduction in the transepithelial electrical resistance (TEER), inhibiting the increase in paracellular permeability, and preventing the morphological redistribution of the TJ proteins claudin 1 and ZO-1. The expression levels of the JNK/c-Jun/AP-1 and myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) pathways were attenuated in undifferentiated and differentiated enterocytes, respectively. Furthermore, a dual-luciferase reporter gene detection system provided direct evidence that c-Jun and MLCK were the specific targets of miR-200b. Collectively, our results highlighted that miR-200b played a positive role in IECs via suppressing intestinal epithelial IL-8 secretion and attenuating TJ damage in vitro, which suggested that miR-200b might be a promising strategy for IBD therapy.

  13. Altered expression of epithelial junctional proteins in atopic asthma: Possible role in inflammation

    NARCIS (Netherlands)

    W.I. de Boer (Pim); H.S. Sharma (Hari); S.M. Baelemans (Sophia); H.C. Hoogsteden (Henk); B.N.M. Lambrecht (Bart); G.J. Braunstahl (Gert-Jan)

    2008-01-01

    textabstractEpithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the

  14. ROCK activity regulates functional tight junction assembly during blastocyst formation in porcine parthenogenetic embryos

    Directory of Open Access Journals (Sweden)

    Jeongwoo Kwon

    2016-04-01

    Full Text Available The Rho-associated coiled-coil-containing protein serine/threonine kinases 1 and 2 (ROCK1 and ROCK2 are Rho subfamily GTPase downstream effectors that regulate cell migration, intercellular adhesion, cell polarity, and cell proliferation by stimulating actin cytoskeleton reorganization. Inhibition of ROCK proteins affects specification of the trophectoderm (TE and inner cell mass (ICM lineages, compaction, and blastocyst cavitation. However, the molecules involved in blastocyst formation are not known. Here, we examined developmental competence and levels of adherens/tight junction (AJ/TJ constituent proteins, such as CXADR, OCLN, TJP1, and CDH1, as well as expression of their respective mRNAs, after treating porcine parthenogenetic four-cell embryos with Y-27632, a specific inhibitor of ROCK, at concentrations of 0, 10, 20, 100 µM for 24 h. Following this treatment, the blastocyst development rates were 39.1, 20.7, 10.0, and 0% respectively. In embryos treated with 20 µM treatment, expression levels of CXADR, OCLN, TJP1, and CDH1 mRNA and protein molecules were significantly reduced (P < 0.05. FITC-dextran uptake assay revealed that the treatment caused an increase in TE TJ permeability. Interestingly, the majority of the four-cell and morula embryos treated with 20 µM Y-27643 for 24 h showed defective compaction and cavitation. Taken together, our results indicate that ROCK activity may differentially affect assembly of AJ/TJs as well as regulate expression of genes encoding junctional proteins.

  15. Strongly Enhanced Superconductivity in Coupled t-J Segments.

    Science.gov (United States)

    Reja, Sahinur; van den Brink, Jeroen; Nishimoto, Satoshi

    2016-02-12

    The t-J Hamiltonian is one of the cornerstones in the theoretical study of strongly correlated copper-oxide based materials. Using the density-matrix renormalization group method we obtain the phase diagram of the one-dimensional t-J chain in the presence of a periodic hopping modulation, as a prototype of coupled-segment models. While in the uniform 1D t-J model the near half-filling superconducting state dominates only at unphysically large values of the exchange coupling constant J/t>3; we show that a small hopping and exchange modulation very strongly reduces the critical coupling to be as low as J/t∼1/3--well within the physical regime. The phase diagram as a function of the electron filling also exhibits metallic, insulating line phases and regions of phase separation. We suggest that a superconducting state is easily stabilized if t-J segments creating local spin-singlet pairing are coupled to each other--another example is the ladder system.

  16. Lamellar granule secretion starts before the establishment of tight junction barrier for paracellular tracers in mammalian epidermis.

    Directory of Open Access Journals (Sweden)

    Akemi Ishida-Yamamoto

    Full Text Available Defects in epidermal barrier function and/or vesicular transport underlie severe skin diseases including ichthyosis and atopic dermatitis. Tight junctions (TJs form a single layered network in simple epithelia. TJs are important for both barrier functions and vesicular transport. Epidermis is stratified epithelia and lamellar granules (LGs are secreted from the stratum granulosum (SG in a sequential manner. Previously, continuous TJs and paracellular permeability barriers were found in the second layer (SG2 of SG in mice, but their fate and correlation with LG secretion have been poorly understood. We studied epidermal TJ-related structures in humans and in mice and found occludin/ZO-1 immunoreactive multilayered networks spanning the first layer of SG (SG1 and SG2. Paracellular penetration tracer passed through some TJs in SG2, but not in SG1. LG secretion into the paracellular tracer positive spaces started below the level of TJs of SG1. Our study suggests that LG-secretion starts before the establishment of TJ barrier in the mammalian epidermis.

  17. 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...... opens the paracellular space acting on TJ proteins and actin cytoskeleton. Its action on claudin-5 is not understood so far. Epithelial and endothelial systems were used to evaluate the effect of caprate on claudin-5 in TJ-free cells and on claudin-5 fully integrated in TJ. To this aim, confocal...... of endothelial and epithelial cells. In conclusion, the study further elucidates the cellular effects of caprate at the tight junctions....

  18. L. plantarum prevents Enteroinvasive Escherichia coli-induced tight junction proteins changes in intestinal epithelial cells

    Directory of Open Access Journals (Sweden)

    Hang Xiaomin

    2009-03-01

    Full Text Available Abstract Background It is increasingly recognized that Lactobacillus plantarum (L. plantarum has the ability to protect against Enteropathogenic Escherichia coli (EPEC-induced damage of the epithelial monolayer barrier function by preventing changes in host cell morphology, attaching/effacing (A/E lesion formation, monolayer resistance, and macromolecular permeability. However, the cellular mechanism involved in this protective effect still remained to be clarified. Methods This study was to investigate the effect of L. plantarum on the changes of Caco-2 cells responding to Enteroinvasive Escherichia coli (EIEC, the permeability of cell monolayer and the transmissivity of dextran, and the distribution and expression of the tight junction (TJ proteins, such as Claudin-1, Occludin, JAM-1 and ZO-1 were examined when infected with EIEC or adhesived of L. plantarum after infection by confocal laser scanning microscopy (CLSM, immunohistochemistry and Western blotting, the cytoskeleton protein F-actin were observed with FITC-phalloidin. Results This study demonstrated that the transepithelial electrical resistance (TER step down and dextran integrated intensity (DII step up with time after infected with EIEC, but after treating with L. plantarum, the changes of TER and DII were improved as compared with EIEC group. L. plantarum prevented the damage of expression and rearrangement of Claudin-1, Occludin, JAM-1 and ZO-1 proteins induced by EIEC, and could ameliorate the injury of cytoskeleton protein F-actin infected with EIEC. Conclusion L. plantarum exerted a protective effect against the damage to integrity of Caco-2 monolayer cells and the structure and distribution of TJ proteins by EIEC infection.

  19. Peripheral Codes in ASTRA for the TJ-II; Programas Perifericos de ASTRA para el TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Bruna, D.; Reynolds, J. M.; Cappa, A.; Martinell, J.; Garcia, J.; Gutierrez-Tapia, C.

    2010-05-01

    The study of data from the TJ-II device is often done with transport calculations based on the ASTRA transport system. However, complicated independent codes are used to obtain fundamental ingredients in these calculations, such as the particle and/or energy sources. These codes are accessible from ASTRA through the procedures explained in this report. (Author) 37 refs.

  20. Endophilin-1 regulates blood-brain barrier permeability by controlling ZO-1 and occludin expression via the EGFR-ERK1/2 pathway.

    Science.gov (United States)

    Liu, Wenjing; Wang, Ping; Shang, Chao; Chen, Lin; Cai, Heng; Ma, Jun; Yao, Yilong; Shang, Xiuli; Xue, Yixue

    2014-07-21

    The blood-brain barrier (BBB) plays a pivotal role in maintenance and regulation of the neural microenvironment. Brain endothelial cells (BECs), held together by tight junctions (TJs), have a primary role in restricting the permeability of the BBB. Endophilin-1 is a multifunctional protein that influences epithelial growth factor receptor (EGFR) endocytosis and degradation and plays an important role in regulating the glomerular filtration barrier in the kidney. Endophilin-1 likely plays a similar role in controlling BBB permeability. In this study, we therefore analyzed the expression and function of endophilin-1 in the human BEC line hCMEC/D3. Our results show that endophilin-1 over-expression reduced the expression of the TJ-associated proteins ZO-1 and occludin and increased the paracellular permeability of hCMEC/D3 cells, whereas silencing of endogenous endophilin-1 yielded the opposite results. Over-expression of ZO-1 and occludin prevented the increase in permeability induced by endophilin-1 over-expression, whereas down-regulation of ZO-1 and occludin prevented the reduction in permeability induced by endophilin-1 silencing. Co-localization and co-immunoprecipitation experiments suggested that endophilin-1 interacts with the EGFR. The levels of EGFR and its downstream effector phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) are significantly decreased when endophilin-1 is over-expressed. Conversely, endophilin-1 down-regulation led to markedly increased levels of these proteins. In addition, the reduced permeability induced by endophilin-1 down-regulation was blocked by AG1478 and PD98059, inhibitors of EGFR and ERK1/2, respectively. Up-regulation of ZO-1 and occludin was blocked by the EGFR and ERK1/2 inhibitors. These results suggest that endophilin-1 regulates BBB permeability by controlling ZO-1 and occludin expression via the EGFR-ERK1/2 pathway in BECs.

  1. Parallel impurity dynamics in the TJ-II stellarator

    CERN Document Server

    Alonso, J A; Estrada, T; Fontdecaba, J M; García-Regaña, J M; Geiger, J; Landreman, M; McCarthy, K J; Medina, F; Van Milligen, B Ph; Ochando, M A; Parra, F I; Velasco, J L

    2016-01-01

    We review in a tutorial fashion some of the causes of impurity density variations along field lines and radial impurity transport in the moment approach framework. An explicit and compact form of the parallel inertia force valid for arbitrary toroidal geometry and magnetic coordinates is derived and shown to be non-negligible for typical TJ-II plasma conditions. In the second part of the article, we apply the fluid model including main ion-impurity friction and inertia to observations of asymmetric emissivity patterns in neutral beam heated plasmas of the TJ-II stellarator. The model is able to explain qualitatively several features of the radiation asymmetry, both in stationary and transient conditions, based on the calculated in-surface variations of the impurity density.

  2. Doppler reflectometer system in the stellarator TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Happel, T.; Estrada, T.; Blanco, E.; Tribaldos, V.; Cappa, A.; Bustos, A. [Laboratorio Nacional de Fusion, Asociacion Euratom-CIEMAT, 28040 Madrid (Spain)

    2009-07-15

    A Doppler reflectometer system has recently been installed in the stellarator TJ-II. The system is optimized for the Q-band (33-50 GHz) and the high-curvature plasmas produced in TJ-II. The launch angle of the microwave beam can be controlled by a steerable mirror to obtain angles between {+-}20 deg. enabling the measurement of perpendicular wave numbers in the range of 3-15 cm{sup -1}. The available angular range allows for comparisons between positive and negative values and additionally for calibration of the system. Localization and k{sub perpendicular}-estimation is done via the three-dimensional ray/beam-tracing code TRUBA. First measured spectra and radial profiles of the perpendicular velocity of plasma density fluctuations are presented.

  3. Parallel impurity dynamics in the TJ-II stellarator

    Science.gov (United States)

    Alonso, J. A.; Velasco, J. L.; Calvo, I.; Estrada, T.; Fontdecaba, J. M.; García-Regaña, J. M.; Geiger, J.; Landreman, M.; McCarthy, K. J.; Medina, F.; Van Milligen, B. Ph; Ochando, M. A.; Parra, F. I.; the TJ-II Team; the W7-X Team

    2016-07-01

    We review in a tutorial fashion some of the causes of impurity density variations along field lines and radial impurity transport in the moment approach framework. An explicit and compact form of the parallel inertia force valid for arbitrary toroidal geometry and magnetic coordinates is derived and shown to be non-negligible for typical TJ-II plasma conditions. In the second part of the article, we apply the fluid model including main ion-impurity friction and inertia to observations of asymmetric emissivity patterns in neutral beam heated plasmas of the TJ-II stellarator. The model is able to explain qualitatively several features of the radiation asymmetry, both in stationary and transient conditions, based on the calculated in-surface variations of the impurity density.

  4. Beam waveguide for ECRH at TJ-II experiment

    Energy Technology Data Exchange (ETDEWEB)

    Ayza, M.S.; Del Rio Bocio, C. [Universidad Publica de Navarra, Pamplona (Spain); Garcia, R.M.; Cepero Diaz, J.R.; Likin, K.M. [Asociacion Euratom-Ciemat para Fusion, Madrid (Spain)] [and others

    1995-12-31

    In this paper the authors present the main parameters of the transmission line system for Electron Cyclotron Resonance Heating (ECRH) for TJ-II experiment in Madrid. This system is based upon two quasioptical transmission lines to carry 400 kW and 0.5 sec of pulse length each line operating at the frequency of 53.2 GHz. The principal parameters of the designed mirrors and that of the guided beams are given in next paragraphs.

  5. Electron cyclotron emission measurements at the stellarator TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Sichardt, Gabriel; Ramisch, Mirko [Institut fuer Grenzflaechenverfahrenstechnik und Plasmatechnologie, Universitaet Stuttgart (Germany); Koehn, Alf [Max-Planck-Institut fuer Plasmaphysik, Garching (Germany)

    2016-07-01

    Electron temperature (T{sub e}) measurements in the magnetised plasmas of the stellarator TJ-K are currently performed by means of Langmuir probes. The use of these probes is restricted to relatively low temperatures and the measurement of temperature profiles requires the acquisition of the local current-voltage characteristics which limits strongly the sampling rate. As an alternative, T{sub e} can be measured using the electron cyclotron emission (ECE) that is generated by the gyration of electrons in magnetised plasmas. Magnetic field gradients in the plasma lead to a spatial distribution of emission frequencies and thus the measured intensity at a given frequency can be related to its point of origin. The T{sub e} dependence of the intensity then leads to a temperature profile along the line of sight for Maxwellian velocity distributions. A diagnostic system for T{sub e} measurements using ECE is currently being set up at TJ-K. When non-thermal electrons are present the emission spectrum changes dramatically. Therefore, the ECE can also be used to investigate the contribution of fast electrons to previously observed toroidal net currents in TJ-K. Simulations are used to examine the role of electron drift orbits in generating these currents.

  6. Emerging relationship between CFTR, actin and tight junction organization in cystic fibrosis airway epithelium.

    Science.gov (United States)

    Castellani, Stefano; Favia, Maria; Guerra, Lorenzo; Carbone, Annalucia; Abbattiscianni, Anna Claudia; Di Gioia, Sante; Casavola, Valeria; Conese, Massimo

    2017-05-01

    Cystic fibrosis (CF), one of the most common genetic disorders affecting primarily Caucasians, is due to mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, encoding for a chloride channel also acting as regulator of other transmembrane proteins. In healthy subjects, CFTR is maintained in its correct apical plasma membrane location via the formation of a multiprotein complex in which scaffold proteins (such as NHERF1) and signaling molecules (such as cAMP and protein kinases) guarantee its correct functioning. In CF, a disorganized and dysfunctional airway epithelium brings an altered flux of ions and water into the lumen of bronchioles, consequent bacterial infections and an enormous influx of inflammatory cells (mainly polymorphonuclear neutrophils) into the airway lumen. Recent evidence in healthy airway cells supports the notion that CFTR protein/function is strictly correlated with the actin cytoskeleton and tight junctions status. In CF cells, the most frequent CFTR gene mutation, F508del, has been shown to be associated with a disorganized actin cytoskeleton and altered tight junction permeability. Thus, the correct localization of CFTR on the apical plasma membrane domain through the formation of the scaffolding and signaling complex is likely fundamental to determine a physiological airway epithelium. The correction of CFTR mutations by either gene or drug therapies, as well as by stem cell-based interventions, can determine the resumption of a physiological organization of actin stress fibers and TJ structure and barrier function, further indicating the close interrelationship among these processes.

  7. Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Nianting Tong

    Full Text Available BACKGROUND AND PURPOSE: Retinal swelling, leading to irreversible visual impairment, is an important early complication in retinal ischemia/reperfusion (I/R injury. Diosmin, a naturally occurring flavonoid glycoside, has been shown to have antioxidative and anti-inflammatory effects against I/R injury. The present study was performed to evaluate the retinal microvascular protective effect of diosmin in a model of I/R injury. METHODS: Unilateral retinal I/R was induced by increasing intraocular pressure to 110 mm Hg for 60 min followed by reperfusion. Diosmin (100 mg/kg or vehicle solution was administered intragastrically 30 min before the onset of ischemia and then daily after I/R injury until the animals were sacrificed. Rats were evaluated for retinal functional injury by electroretinogram (ERG just before sacrifice. Retinas were harvested for HE staining, immunohistochemistry assay, ELISA, and western blotting analysis. Evans blue (EB extravasation was determined to assess blood-retinal barrier (BRB disruption and the structure of tight junctions (TJ was examined by transmission electron microscopy. RESULTS: Diosmin significantly ameliorated the reduction of b-wave, a-wave, and b/a ratio in ERG, alleviated retinal edema, protected the TJ structure, and reduced EB extravasation. All of these effects of diosmin were associated with increased zonular occluden-1 (ZO-1 and occludin protein expression and decreased VEGF/PEDF ratio. CONCLUSIONS: Maintenance of TJ integrity and reduced permeability of capillaries as well as improvements in retinal edema were observed with diosmin treatment, which may contribute to preservation of retinal function. This protective effect of diosmin may be at least partly attributed to its ability to regulate the VEGF/PEDF ratio.

  8. Myosin light chain kinase inhibitor ML7 improves vascular endothelial dysfunction via tight junction regulation in a rabbit model of atherosclerosis.

    Science.gov (United States)

    Cheng, Xiaowen; Wang, Xiaobian; Wan, Yufeng; Zhou, Qing; Zhu, Huaqing; Wang, Yuan

    2015-09-01

    Vascular endothelial dysfunction (VED) is an important factor in the initiation and development of atherosclerosis (AS). Previous studies have demonstrated that endothelial permeability is increased in diet‑induced AS. However, the precise underlying mechanisms remain poorly understood. The present study aimed to analyze whether the myosin light chain kinase (MLCK) inhibitor ML7 is able to improve VED and AS by regulating the expression of the tight junction (TJ) proteins zona occludens (ZO)‑1 and occludin via mechanisms involving MLCK and MLC phosphorylation in high‑fat diet‑fed rabbits. New Zealand white rabbits were randomly divided into three groups: Control group, AS group and ML7 group. The rabbits were fed a standard diet (control group), a high‑fat diet (AS group) or a high‑fat diet supplemented with 1 mg/kg/day ML7 (ML7 group). After 12 weeks, endothelium‑dependent relaxation and endothelium‑independent relaxation were measured using high-frequency ultrasound. Administration of a high‑fat diet significantly increased the levels of serum lipids and inflammatory markers in the rabbits in the AS group, as compared with those in the rabbits in the control group. Furthermore, a high‑fat diet contributed to the formation of a typical atherosclerotic plaque, as well as an increase in endothelial permeability and VED. These symptoms of AS were significantly improved following treatment with ML7, as demonstrated in the ML7 group. Hematoxylin & eosin and immunohistochemical staining indicated that ML7 was able to decrease the expression of MLCK and MLC phosphorylation in the arterial wall of rabbits fed a high‑fat diet. A similar change was observed for the TJ proteins ZO‑1 and occludin. In addition, western blot analysis demonstrated that ML7 increased the expression levels of occludin in the precipitate, but reduced its expression in the supernatant of lysed aortas. These results indicated that occludin, which is a dynamic protein at the TJ

  9. Moderate hypoxia followed by reoxygenation results in blood-brain barrier breakdown via oxidative stress-dependent tight-junction protein disruption.

    Directory of Open Access Journals (Sweden)

    Christoph M Zehendner

    Full Text Available Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR on the evolution of reactive oxygen species (ROS and blood-brain barrier (BBB integrity in brain endothelial cells (BEC. BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC or towards occlusion of the arteria cerebri media (MCAO with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER and transwell permeability assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCF, MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1 and claudin 5 (Cl5, decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role

  10. Entamoeba histolytica EhCP112 Dislocates and Degrades Claudin-1 and Claudin-2 at Tight Junctions of the Intestinal Epithelium

    Directory of Open Access Journals (Sweden)

    Patricia Cuellar

    2017-08-01

    Full Text Available During intestinal invasion, Entamoeba histolytica opens tight junctions (TJs reflected by transepithelial electrical resistance (TEER dropping. To explore the molecular mechanisms underlying this, we studied in vitro and in vivo the damage produced by the recombinant E. histolytica cysteine protease (rEhCP112 on TJ functions and proteins. rEhCP112 reduced TEER in Caco-2 cells in a dose- and time-dependent manner; and EhCP112-overexpressing trophozoites provoked major epithelial injury compared to control trophozoites. rEhCP112 penetrated through the intercellular space, and consequently the ion flux increased and the TJs fence function was disturbed. However, macromolecular flux was not altered. Functional in vitro assays revealed specific association of rEhCP112 with claudin-1 and claudin-2, that are both involved in regulating ion flux and fence function. Of note, rEhCP112 did not interact with occludin that is responsible for regulating macromolecular flux. Moreover, rEhCP112 degraded and delocalized claudin-1, thus affecting interepithelial adhesion. Concomitantly, expression of the leaky claudin-2 at TJ, first increased and then it was degraded. In vivo, rEhCP112 increased intestinal epithelial permeability in the mouse colon, likely due to apical erosion and claudin-1 and claudin-2 degradation. In conclusion, we provide evidence that EhCP112 causes epithelial dysfunction by specifically altering claudins at TJ. Thus, EhCP112 could be a potential target for therapeutic approaches against amoebiasis.

  11. Moderate hypoxia followed by reoxygenation results in blood-brain barrier breakdown via oxidative stress-dependent tight-junction protein disruption.

    Science.gov (United States)

    Zehendner, Christoph M; Librizzi, Laura; Hedrich, Jana; Bauer, Nina M; Angamo, Eskedar A; de Curtis, Marco; Luhmann, Heiko J

    2013-01-01

    Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR) on the evolution of reactive oxygen species (ROS) and blood-brain barrier (BBB) integrity in brain endothelial cells (BEC). BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC) or towards occlusion of the arteria cerebri media (MCAO) with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER) and transwell permeability assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCF), MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ) integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI) was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1) and claudin 5 (Cl5), decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role in this

  12. Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions

    OpenAIRE

    1994-01-01

    Occludin is an integral membrane protein localizing at tight junctions (TJ) with four transmembrane domains and a long COOH-terminal cytoplasmic domain (domain E) consisting of 255 amino acids. Immunofluorescence and laser scan microscopy revealed that chick full- length occludin introduced into human and bovine epithelial cells was correctly delivered to and incorporated into preexisting TJ. Further transfection studies with various deletion mutants showed that the domain E, especially its C...

  13. Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver

    Science.gov (United States)

    Gamal, Wesam; Treskes, Philipp; Samuel, Kay; Sullivan, Gareth J.; Siller, Richard; Srsen, Vlastimil; Morgan, Katie; Bryans, Anna; Kozlowska, Ada; Koulovasilopoulos, Andreas; Underwood, Ian; Smith, Stewart; del-Pozo, Jorge; Moss, Sharon; Thompson, Alexandra Inés; Henderson, Neil C.; Hayes, Peter C.; Plevris, John N.; Bagnaninchi, Pierre-Olivier; Nelson, Leonard J.

    2017-01-01

    Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization. PMID:28134251

  14. Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver.

    Science.gov (United States)

    Gamal, Wesam; Treskes, Philipp; Samuel, Kay; Sullivan, Gareth J; Siller, Richard; Srsen, Vlastimil; Morgan, Katie; Bryans, Anna; Kozlowska, Ada; Koulovasilopoulos, Andreas; Underwood, Ian; Smith, Stewart; Del-Pozo, Jorge; Moss, Sharon; Thompson, Alexandra Inés; Henderson, Neil C; Hayes, Peter C; Plevris, John N; Bagnaninchi, Pierre-Olivier; Nelson, Leonard J

    2017-01-30

    Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization.

  15. Eya1 protein phosphatase regulates tight junction formation in lung distal epithelium.

    Science.gov (United States)

    El-Hashash, Ahmed H K; Turcatel, Gianluca; Varma, Saaket; Berika, Mohamed; Al Alam, Denise; Warburton, David

    2012-09-01

    Little is known about the regulatory mechanisms underlying lung epithelial tight junction (TJ) assembly, which is inextricably linked to the preservation of epithelial polarity, and is highly coordinated by proteins that regulate epithelial cell polarity, such as aPKCζ. We recently reported that Eya1 phosphatase functions through aPKCζ-Notch1 signaling to control cell polarity in the lung epithelium. Here, we have extended these observations to TJ formation to demonstrate that Eya1 is crucial for the maintenance of TJ protein assembly in the lung epithelium, probably by controlling aPKCζ phosphorylation levels, aPKCζ-mediated TJ protein phosphorylation and Notch1-Cdc42 activity. Thus, TJs are disassembled after interfering with Eya1 function in vivo or during calcium-induced TJ assembly in vitro. These effects are reversed by reintroduction of wild-type Eya1 or partially inhibiting aPKCζ in Eya1siRNA cells. Moreover, genetic activation of Notch1 rescues Eya1(-/-) lung epithelial TJ defects. These findings uncover novel functions for the Eya1-aPKCζ-Notch1-Cdc42 pathway as a crucial regulatory mechanism of TJ assembly and polarity of the lung epithelium, providing a conceptual framework for future mechanistic and translational studies in this area.

  16. Tracer-Encapsulated Solid Pellet (TESPEL) Injection System for the TJ-II Stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, N. [National Institute for Fusion Science, Toki, Japan; McCarthy, K. J. [EURATOM-CIEMAT, Madrid, Spain; Hayashi, H. [National Institute for Fusion Science, Toki, Japan; Combs, Stephen Kirk [ORNL; Foust, Charles R [ORNL; Garcia, R. [Laboratory Nacional de Fusion, Madrid, Spain; Panadero, N. [CIEMAT, Laboratory Nacional de Fusion, Spain; Pawelec, E. [Opole University, Poland; Sanchez, J. Hernandez [Laboratory Nacional de Fusion, Madrid, Spain; Navarro, M. [CIEMAT, Laboratory Nacional de Fusion, Spain; Soleto, A. [CIEMAT, Laboratory Nacional de Fusion, Spain

    2016-01-01

    A tracer-encapsulated solid pellet (TESPEL) injection system for the TJ-II stellarator was recently developed. In order to reduce the time and cost for the development, we combined a TESPEL injector provided by National Institute for Fusion Science with an existing TJ-II cryogenic pellet injection system. Consequently, the TESPEL injection into the TJ-II plasma was successfully achieved, which was confirmed by several pellet diagnostics including a normal-incidence spectrometer for monitoring a tracer impurity behavior.

  17. Effective t-J model of pairing: singlet versus triplet

    Directory of Open Access Journals (Sweden)

    J.Spałek

    2008-09-01

    Full Text Available The t-J model is regarded as a canonical model of spin-singlet pairing induced by the kinetic exchange interaction also responsible for an antiferromagnetic ordering in the strongly correlated narrow-band systems. In the orbitally degenerate systems both ferromagnetic and antiferromagnetic kinetic exchange interactions occur. I briefly review the analogy between the singlet and triplet types of pairing, as well as draw some general conclusions about the pairing induced by these exchange interactions. The general discussion is also illustrated with a concrete case of a two-dimensional lattice with the spin triplet pairing.

  18. Theoretical provisions for the discharge at TJ-1 (Preliminary study); Previsiones teoricas para la descarga del TJ-1 (Estudio preliminar)

    Energy Technology Data Exchange (ETDEWEB)

    Guasp, J.

    1981-07-01

    Using the transport code PLASMATOR a numerical study about the TJ-1 discharge (a Tokamak close to be installed at JEN) has been made, observing the behaviour under huge variations on the transport coefficients as well as on density and current. Noteworthy a scaling law of the kind {tau}{sub E}{approx}n{sub {theta}} has been contested at not too high density, The model insensibility upon the initial values has been confirmed and the effects of variations on the recycling coefficient and the rate rise of current studied too. Finally comparisons with alternative models have been accomplished. (Author) 29 refs.

  19. Curvature dependance of blob dynamics in TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Garland, Stephen; Ramisch, Mirko [Institut fuer Grenzflaechenverfahrenstechnik und Plasmatechnologie, Universitaet Stuttgart (Germany); Fuchert, Golo [Institut Jean Lamour, Universite de Lorraine (France)

    2014-07-01

    Turbulent transport in the scrape-off layer (SOL) is an important area of investigation in magnetic confinement fusion research. Relatively dense and hot, field-aligned, filament-like structures (blobs) have been observed to propagate radially through the SOL in many fusion devices, and contribute significantly to SOL transport. The torsatron TJ-K operates with a low-temperature plasma, allowing Langmuir probe measurements in the entire plasma volume. Despite the low temperature, investigations are relevant to fusion research due to dimensionless plasma parameters similar to those in the edge region of fusion plasmas. Analytical blob models link blob velocity in the SOL to blob polarisation, which can be driven by magnetic field line curvature. In TJ-K, average blob dynamics can be studied in detail using a 2D movable probe and a conditional averaging technique. In addition, a fast camera can be used to supplement probe data, and provide information on individual blob trajectories. With these tools, the connection between magnetic field line curvature and the poloidal component of blob velocity has been studied. Taking into account background E x B flows, initial investigations suggest a correlation between the poloidal component of blob velocity and averaged geodesic magnetic field line curvature.

  20. Solar cell junction temperature measurement of PV module

    KAUST Repository

    Huang, B.J.

    2011-02-01

    The present study develops a simple non-destructive method to measure the solar cell junction temperature of PV module. The PV module was put in the environmental chamber with precise temperature control to keep the solar PV module as well as the cell junction in thermal equilibrium with the chamber. The open-circuit voltage of PV module Voc is then measured using a short pulse of solar irradiation provided by a solar simulator. Repeating the measurements at different environment temperature (40-80°C) and solar irradiation S (200-1000W/m2), the correlation between the open-circuit voltage Voc, the junction temperature Tj, and solar irradiation S is derived.The fundamental correlation of the PV module is utilized for on-site monitoring of solar cell junction temperature using the measured Voc and S at a short time instant with open circuit. The junction temperature Tj is then determined using the measured S and Voc through the fundamental correlation. The outdoor test results show that the junction temperature measured using the present method, Tjo, is more accurate. The maximum error using the average surface temperature Tave as the junction temperature is 4.8 °C underestimation; while the maximum error using the present method is 1.3 °C underestimation. © 2010 Elsevier Ltd.

  1. Notional Permeability

    NARCIS (Netherlands)

    Kik, R.; Van den Bos, J.P.; Maertens, J.; Verhagen, H.J.; Van der Meer, J.W.

    2012-01-01

    Different layer design of a rock slope and under layers has a large effect on the strengths on the rock slope itself. In the stability formula developed of VAN DER MEER [1988] this effect is represented by the term Notional Permeability with symbol P. A more open, or permeable, structure underneath

  2. Modulation of Tight Junction Structure and Function by Kinases and Phosphatases Targeting Occludin

    Directory of Open Access Journals (Sweden)

    Max Johannes Dörfel

    2012-01-01

    Full Text Available Tight junctions (TJs typically represent the most apical contacts in epithelial and endothelial cell layers where they play an essential role in the separation of extracellular or luminal spaces from underlying tissues in the body. Depending on the protein composition, TJs define the barrier characteristics and in addition maintain cell polarity. Two major families of integral membrane proteins form the typical TJ strand network, the tight junction-associated MARVEL protein (TAMP family members occludin, tricellulin, and MarvelD3 as well as a specific set of claudins. Occludin was the first identified member of these tetraspanins and is now widely accepted as a regulator of TJ assembly and function. Therefore, occludin itself has to be tightly regulated. Phosphorylation of occludin appears to be of central importance in this context. Here we want to summarize current knowledge on the kinases and phosphatases directly modifying occludin, and their role in the regulation of TJ structure, function, and dynamics.

  3. Experimental study of TJ-1 plasma using scattering and radiation emission techniques; Analisis experimental del plasma TJ-1 con tecnicas de scattering y emision de radiacion

    Energy Technology Data Exchange (ETDEWEB)

    Pardo, C.; Zurro, B.

    1987-07-01

    The Thomson scattering system of TJ-1 is described in detail. The radial profiles of Te and ne obtained in TJ-1 discharges are presented. This data make possible to deduce characteristic parameters of the plasma confinement in this machine, as energy confinement times, Zeff B. Using also radiation measurements (global and in the visible range) we obtained the particle confinement time and Zeff without non experimental assumptions. (Author) 52 refs.

  4. Automated System for Control of the Vacuum Diagnostic System for the TJ-II; Control Automatico de los Sistemas de Vacio de Diagnosticos del Dispositivos TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Sanchez, A.; Montoro Peinado, A.; Encabo Fernandez, J.; Gama de la Serrano, J.; Sanchez Sarabia, E. [Ciemat, Madrid (Spain)

    2000-07-01

    This report describes the monitorization and remote control systems belonging to the high vacuum systems of the TJ-II diagnostics. These systems are part of each diagnostic and their control has been integrated into the automata that carries out this task. All the controllers are connected through a Profibus network, so as to interchange data between themselves as well as between the general system of TJ-II. (Author)

  5. Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability through ROS/RhoA/PI3K/PKB signaling pathway.

    Science.gov (United States)

    Gu, Yan-ting; Xue, Yi-xue; Wang, Yan-feng; Wang, Jin-hui; Chen, Xia; ShangGuan, Qian-ru; Lian, Yan; Zhong, Lei; Meng, Ying-nan

    2013-12-01

    Adenosine 5'-triphosphate-sensitive potassium channel (KATP channel) activator, minoxidil sulfate (MS), can selectively increase the permeability of the blood-tumor barrier (BTB); however, the mechanism by which this occurs is still under investigation. Using a rat brain glioma (C6) model, we first examined the expression levels of occludin and claudin-5 at different time points after intracarotid infusion of MS (30 μg/kg/min) by western blotting. Compared to MS treatment for 0 min group, the protein expression levels of occludin and claudin-5 in brain tumor tissue of rats showed no changes within 1 h and began to decrease significantly after 2 h of MS infusion. Based on these findings, we then used an in vitro BTB model and selective inhibitors of diverse signaling pathways to investigate whether reactive oxygen species (ROS)/RhoA/PI3K/PKB pathway play a key role in the process of the increase of BTB permeability induced by MS. The inhibitor of ROS or RhoA or PI3K or PKB significantly attenuated the expression of tight junction (TJ) protein and the increase of the BTB permeability after 2 h of MS treatment. In addition, the significant increases in RhoA activity and PKB phosphorylation after MS administration were observed, which were partly inhibited by N-2-mercaptopropionyl glycine (MPG) or C3 exoenzyme or LY294002 pretreatment. The present study indicates that the activation of signaling cascades involving ROS/RhoA/PI3K/PKB in BTB was required for the increase of BTB permeability induced by MS. Taken together, all of these results suggested that MS might increase BTB permeability in a time-dependent manner by down-regulating TJ protein expression and this effect could be related to ROS/RhoA/PI3K/PKB signal pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Expression of Tight Junction Proteins and Cadherin 17 in the Small Intestine of Young Goats Offered a Reduced N and/or Ca Diet

    Science.gov (United States)

    Wilkens, Mirja R.; Breves, Gerhard; Langeheine, Marion; Brehm, Ralph; Muscher-Banse, Alexandra S.

    2016-01-01

    Diets fed to ruminants should contain nitrogen (N) as low as possible to reduce feed costs and environmental pollution. Though possessing effective N-recycling mechanisms to maintain the N supply for rumen microbial protein synthesis and hence protein supply for the host, an N reduction caused substantial changes in calcium (Ca) and phosphate homeostasis in young goats including decreased intestinal transepithelial Ca absorption as reported for monogastric species. In contrast to the transcellular component of transepithelial Ca transport, the paracellular route has not been investigated in young goats. Therefore, the aim of the present study was to characterise the effects of dietary N and/or Ca reduction on paracellular transport mechanisms in young goats. Electrophysiological properties of intestinal epithelia were investigated by Ussing chamber experiments. The expression of tight junction (TJ) and adherens junction (AJ) proteins in intestinal epithelia were examined on mRNA level by qPCR and on protein level by western blot analysis. Dietary N reduction led to a segment specific increase in tissue conductances in the proximal jejunum which might be linked to concomitantly decreased expression of cadherin 17 mRNA. Expression of occludin (OCLN) and zonula occludens protein 1 was increased in mid jejunal epithelia of N reduced fed goats on mRNA and partly on protein level. Reduced dietary Ca supply resulted in a segment specific increase in claudin 2 and claudin 12 expression and decreased the expression of OCLN which might have been mediated at least in part by calcitriol. These data show that dietary N as well as Ca reduction affected expression of TJ and AJ proteins in a segment specific manner in young goats and may thus be involved in modulation of paracellular Ca permeability. PMID:27120348

  7. Expression of Tight Junction Proteins and Cadherin 17 in the Small Intestine of Young Goats Offered a Reduced N and/or Ca Diet.

    Directory of Open Access Journals (Sweden)

    Kristin Elfers

    Full Text Available Diets fed to ruminants should contain nitrogen (N as low as possible to reduce feed costs and environmental pollution. Though possessing effective N-recycling mechanisms to maintain the N supply for rumen microbial protein synthesis and hence protein supply for the host, an N reduction caused substantial changes in calcium (Ca and phosphate homeostasis in young goats including decreased intestinal transepithelial Ca absorption as reported for monogastric species. In contrast to the transcellular component of transepithelial Ca transport, the paracellular route has not been investigated in young goats. Therefore, the aim of the present study was to characterise the effects of dietary N and/or Ca reduction on paracellular transport mechanisms in young goats. Electrophysiological properties of intestinal epithelia were investigated by Ussing chamber experiments. The expression of tight junction (TJ and adherens junction (AJ proteins in intestinal epithelia were examined on mRNA level by qPCR and on protein level by western blot analysis. Dietary N reduction led to a segment specific increase in tissue conductances in the proximal jejunum which might be linked to concomitantly decreased expression of cadherin 17 mRNA. Expression of occludin (OCLN and zonula occludens protein 1 was increased in mid jejunal epithelia of N reduced fed goats on mRNA and partly on protein level. Reduced dietary Ca supply resulted in a segment specific increase in claudin 2 and claudin 12 expression and decreased the expression of OCLN which might have been mediated at least in part by calcitriol. These data show that dietary N as well as Ca reduction affected expression of TJ and AJ proteins in a segment specific manner in young goats and may thus be involved in modulation of paracellular Ca permeability.

  8. Feasibility Study on a Neutral Beam Diagnostic Injector for TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, K. J.; Balbin, R.; Lopez-Fraguas, A.

    2003-07-01

    A diagnostic neutral beam system is proposed for the TJ-II stellarator. The main goal of installing such a system in TJ-II is to increase the signal to noise ratio and provide spatial resolution in diagnostic systems based on Charge Exchange Recombination Spectroscopy and Neutral Particle Analysis, while also opening up new opportunities for physics studies in this magnetically confined plasma device. After outlining the unique characteristics of the TJ-II and reviewing available diagnostic injector systems, the compact system selected for TJ-II is presented together with estimates of the resulting increased signal levels Finally other important aspects are discussed, in particular its location and orientation, as well as possible solutions to avoid perturbing the TJ-II magnetic configurations in the heliac device. (Author) 31 refs.

  9. Electron Bernstein waves emission in the TJ--II Stellarator

    CERN Document Server

    García-Regaña, J M; Castejón, F; Caughman, J B O; Tereshchenko, M; Ros, A; Rasmussen, D A; Wilgen, J B

    2010-01-01

    Taking advantage of the electron Bernstein waves heating (EBWH) system of the TJ--II stellarator, an electron Bernstein emission (EBE) diagnostic was installed. Its purpose is to investigate the B--X--O radiation properties in the zone where optimum theoretical EBW coupling is predicted. An internal movable mirror shared by both systems allows us to collect the EBE radiation along the same line of sight that is used for EBW heating. The theoretical EBE has been calculated for different orientations of the internal mirror using the TRUBA code as ray tracer. A comparison with experimental data obtained in NBI discharges is carried out. The results provide a valuable information regarding the experimental O--X mode conversion window expected in the EBW heating experiments. Furthermore, the characterization of the radiation polarization shows evidence of the underlying B--X--O conversion process.

  10. Electron Bernstein waves emission in the TJ-II stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Regana, J M; Cappa, A; Castejon, F; Ros, A [Laboratorio Nacional de Fusion, CIEMAT, 28040, Madrid (Spain); Caughman, J B O; Rasmussen, D A; Wilgen, J B [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Tereshchenko, M, E-mail: josemanuel.garcia@ciemat.es [Prokhorov General Physics Institute, Russian Academy of Sciences, Moscow (Russian Federation)

    2011-06-15

    Taking advantage of the electron Bernstein waves heating system of the TJ-II stellarator, an electron Bernstein emission (EBE) diagnostic was installed. Its purpose is to investigate the B-X-O radiation properties in the zone where optimum theoretical electron Bernstein wave (EBW) coupling is predicted. An internal movable mirror shared by both systems allows us to collect the EBE radiation along the same line of sight that is used for EBW heating. The theoretical EBE has been calculated for different orientations of the internal mirror using the TRUBA code as the ray tracer. A comparison with experimental data obtained in NBI discharges is carried out. The results provide valuable information regarding the experimental O-X-mode conversion window expected in the EBW heating experiments. Furthermore, the characterization of the radiation polarization shows evidence of the underlying B-X-O conversion process.

  11. Perturbative Heat Transport Experiments on TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Eguilor, S.; Castejon, F.; Luna, E. de la; Cappa, A.; Likin, K.; Fernandez, A.; Tj-II, T.

    2002-07-01

    Heat wave experiments are performed on TJ-II stellarator plasmas to estimate both heat diffusivity and power deposition profiles. High frequency ECRH modulation experiments are used to obtain the power deposition profiles, which is observed to be wider and duller than estimated by tracing techniques. The causes of this difference are discussed in the paper. Fourier analysis techniques are used to estimate the heat diffusivity in low frequency ECRH modulation experiments. This include the power deposition profile as a new ingredient. ECHR switch on/off experiments are exploited to obtain power deposition and heat diffusivities profile. Those quantities are compared with the obtained by modulation experiments and transport analysis, showing a good agreement. (Author) 18 refs.

  12. Exact solution of a t-J chain with impurity

    Energy Technology Data Exchange (ETDEWEB)

    Beduerftig, G. [Hannover Univ. (Germany). Inst. fuer Theoretische Physik; Essler, F.H.L. [Oxford Univ. (United Kingdom). Dept. of Theoretical Physics; Frahm, H. [Hannover Univ. (Germany). Inst. fuer Theoretische Physik

    1997-04-07

    We study the effects of an integrable impurity in a periodic t-J chain. The impurity couples to both spin and charge degrees of freedom and has the interesting feature that the interaction with the bulk can be varied continuously without losing integrability. We first consider ground state properties close to half-filling in the presence of a small bulk magnetic field. We calculate the impurity contributions to the (zero-temperature) susceptibilities and the low-temperature specific heat and determine the high-temperature characteristics of the impurity. We then investigate transport properties by computing the spin and charge stiffnesses at zero temperature. Finally the impurity phase shifts are calculated and the existence of an impurity bound state in the holon sector is established. (orig.).

  13. Anomalous superconductivity in the tJ model; moment approach

    DEFF Research Database (Denmark)

    Sørensen, Mads Peter; Rodriguez-Nunez, J.J.

    1997-01-01

    By extending the moment approach of Nolting (Z, Phys, 225 (1972) 25) in the superconducting phase, we have constructed the one-particle spectral functions (diagonal and off-diagonal) for the tJ model in any dimensions. We propose that both the diagonal and the off-diagonal spectral functions...... Hartree shift which in the end result enlarges the bandwidth of the free carriers allowing us to take relative high values of J/t and allowing superconductivity to live in the T-c-rho phase diagram, in agreement with numerical calculations in a cluster, We have calculated the static spin susceptibility......, chi(T), and the specific heat, C-v(T), within the moment approach. We find that all the relevant physical quantities show the signature of superconductivity at T-c in the form of kinks (anomalous behavior) or jumps, for low density, in agreement with recent published literature, showing a generic...

  14. Hybrid Tunnel Junction-Graphene Transparent Conductive Electrodes for Nitride Lateral Light Emitting Diodes.

    Science.gov (United States)

    Wang, Liancheng; Cheng, Yan; Liu, Zhiqiang; Yi, Xiaoyan; Zhu, Hongwei; Wang, Guohong

    2016-01-20

    Graphene transparent conductive electrode (TCE) applications in nitride light emitting diodes (LEDs) are still limited by the large contact resistance and interface barrier between graphene and p-GaN. We propose a hybrid tunnel junction (TJ)-graphene TCE approach for nitride lateral LEDs theoretically and experimentally. Through simulation using commercial advanced physical models of semiconductor devices (APSYS), we found that low tunnel resistance can be achieved in the n(+)-GaN/u-InGaN/p(+)-GaN TJ, which has a lower tunneling barrier and an enhanced electric field due to the polarization effect. Graphene TCEs and hybrid graphene-TJ TCEs are then modeled. The designed hybrid TJ-graphene TCEs show sufficient current diffusion length (Ls), low introduced series resistance, and high transmittance. The assembled TJ LED with the triple-layer graphene (TLG) TCEs show comparable optoelectrical performance (3.99 V@20 mA, LOP = 10.8 mW) with the reference LED with ITO TCEs (3.36 V@20 mA, LOP = 12.6 mW). The experimental results further prove that the TJ-graphene structure can be successfully incorporated as TCEs for lateral nitride LEDs.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Notional Permeability

    OpenAIRE

    Kik, R.; Van den Bos, J.P.; Maertens, J.; Verhagen, H.J.; van der Meer, J W

    2012-01-01

    Different layer design of a rock slope and under layers has a large effect on the strengths on the rock slope itself. In the stability formula developed of VAN DER MEER [1988] this effect is represented by the term Notional Permeability with symbol P. A more open, or permeable, structure underneath the armour layer has the ability to dissipate more wave energy and therefore requires less weight of the armour layer. The influence of this parameter is thus very important in economic sense. Up u...

  17. Application for TJ-II Signals Visualization: User's Guide; Aplicacion para la Visualizacion de Senales de TJ-II: Guia del Usuario

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, E.; Portas, A. B.; Vega, J. [Ciemat, Madrid (Spain)

    2000-07-01

    In this documents are described the functionalities of the application developed by the Data Acquisition Group for TJ-II signal visualization. There are two versions of the application, the On-line version, used for signal visualization during TJ-II operation, and the Off-line version, used for signal visualization without TJ-II operation. Both versions of the application consist in a graphical user interface developed for X/Motif, in which most of the actions can be done using the mouse buttons. The functionalities of both versions of the application are described in this user's guide, beginning at the application start-up and explaining in detail all the options that it provides and the actions that can be done with each graphic control. (Author) 8 refs.

  18. Experimental Electron Heat Diffusion in TJ-II ECRH Plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, V.I.; Lopez-Bruna, D.; Herranz, J.; Castejon, F.

    2006-07-01

    Interpretative transport has been used to revisit the global scalings of TJ-II ECRH plasmas from a local perspective. Density, rotational transform and ERCH power scans were analysed based upon Thomson Scattering data (electron density and temperature) in steady state discharges. A simple formula to obtain the thermal conductivity, assuming pure diffusion and negligible convective heat fluxes was used in a set of 161 discharges. All the analysis was performed with the ASTRA transport shell. The density scan indicates that inside n=0,4 there is no significant change of e with density in the range studied (0.4 (1019m-3) 1.0), while in 0,5 <0,8 approximately, e decreases with density. In the rotational transform scan it is found that the values of e when a low order rational of the rotational transform is present locally seem to be smaller for the corresponding range, although it is apparent a general beneficial effect of the corresponding change in magnetic structure. Finally, in the ECRH power scan, e is found to have an overall increment in 0,2

  19. Transient Particle Transport Analysis on TJ-II Stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Eguilior, S.; Castejon, F.; Guasp, J.; Estrada, T.; Medina, F.; Tabares, F.L.; Branas, B.

    2006-12-18

    Particle diffusivity and convective velocity have been determined in ECRH plasmas confined in the stellarator TJ-II by analysing the evolving density profile. This is obtained from an amplitude modulation reflectometry system in addition to an X-ray tomographic reconstruction. The source term, which is needed as an input for transport equations, is obtained using EIRENE code. In order to discriminate between the diffusive and convective contributions, the dynamics of the density evolution has been analysed in several perturbative experiments. This evolution has been considered in discharges with injection of a single pulse of H2 as well as in those that present a spontaneous transition to an enhanced confinement mode and whose confinement properties are modified by inducing an ohmic current. The pinch velocity and diffusivity are parameterized by different expressions in order to fit the experimental time evolution of density profile. The profile evolution is very different from one case to another due to the different values of convective velocities and diffusivities, besides the different source terms. (Author) 19 refs.

  20. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  1. Claudin-1 induced sealing of blood–brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis

    OpenAIRE

    Pfeiffer, Friederike; Schäfer, Julia; Lyck, Ruth; Makrides, Victoria; Brunner, Sarah; Schaeren-Wiemers, Nicole; Deutsch, Urban; ENGELHARDT, Britta

    2011-01-01

    In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), loss of the blood–brain barrier (BBB) tight junction (TJ) protein claudin-3 correlates with immune cell infiltration into the CNS and BBB leakiness. Here we show that sealing BBB TJs by ectopic tetracycline-regulated expression of the TJ protein claudin-1 in Tie-2 tTA//TRE-claudin-1 double transgenic C57BL/6 mice had no influence on immune cell trafficking across the BBB during EAE and furthermore...

  2. An Important Member of Tight Junctions: Claudins

    Directory of Open Access Journals (Sweden)

    Ozlem Demirpence

    2016-01-01

    Full Text Available The tight junction (TJs, the most apically located of the intercellular junctional complexes, inhibits solute and water flow through the paracellular space, termed the %u201Cbarrier%u201D function. TJs participate in signal transduction mechanisms that regulate epithelial cell proliferation, gene expression, differentiation and morphogenesis. The claudin family of transmembrane proteins localized to the TJ. Loss of expression of Claudin causes of suppression TJs function. Recent studies have shown that altered levels of the different claudins may be related to invasion and progression of carcinoma cells in several primary neoplasms. A better knowledge of the mechanisms underlying carcinogenesis will likely result in the development of novel approaches for the diagnosis and therapy.

  3. Gap Junctions

    Science.gov (United States)

    Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L.; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

    2013-01-01

    Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981-2035, 2012. PMID:23723031

  4. Gap junctions.

    Science.gov (United States)

    Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

    2012-07-01

    Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1853-1872, 2012.

  5. Particle Transport in ECRH Plasmas of the TJ-II; Transporte de Particulas en Plasmas ECRH del TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, V. I.; Lopez-Bruna, D.; Estrada, T.; Guasp, J.; Reynolds, J. M.; Velasco, J. L.; Herranz, J.

    2007-07-01

    We present a systematic study of particle transport in ECRH plasmas of TJ-II with different densities. The goal is to fi nd particle confinement time and electron diffusivity dependence with line-averaged density. The experimental information consists of electron temperature profiles, T{sub e} (Thomson Scattering TS) and electron density, n{sub e}, (TS and reflectometry) and measured puffing data in stationary discharges. The profile of the electron source, Se, was obtained by the 3D Monte-Carlo code EIRENE. The analysis of particle balance has been done by linking the results of the code EIRENE with the results of a model that reproduces ECRH plasmas in stationary conditions. In the range of densities studied (0.58 {<=}n{sub e}> (10{sup 1}9m{sup -}3) {<=}0.80) there are two regions of confinement separated by a threshold density, {approx}0.65 10{sup 1}9m{sup -}3. Below this threshold density the particle confinement time is low, and vice versa. This is reflected in the effective diffusivity, D{sub e}, which in the range of validity of this study, 0.5 <{rho}<0.9 being {rho} normalized plasma radius, decreased significantly above the threshold density. The profiles of D{sub e} are flat for {>=}0,63(10{sup 1}9m{sup -}3). (Author) 35 refs.

  6. Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct involvement of claudins in tight junction barrier.

    Science.gov (United States)

    Sonoda, N; Furuse, M; Sasaki, H; Yonemura, S; Katahira, J; Horiguchi, Y; Tsukita, S

    1999-10-04

    Claudins, comprising a multigene family, constitute tight junction (TJ) strands. Clostridium perfringens enterotoxin (CPE), a single approximately 35-kD polypeptide, was reported to specifically bind to claudin-3/RVP1 and claudin-4/CPE-R at its COOH-terminal half. We examined the effects of the COOH-terminal half fragment of CPE (C-CPE) on TJs in L transfectants expressing claudin-1 to -4 (C1L to C4L, respectively), and in MDCK I cells expressing claudin-1 and -4. C-CPE bound to claudin-3 and -4 with high affinity, but not to claudin-1 or -2. In the presence of C-CPE, reconstituted TJ strands in C3L cells gradually disintegrated and disappeared from their cell surface. In MDCK I cells incubated with C-CPE, claudin-4 was selectively removed from TJs with its concomitant degradation. At 4 h after incubation with C-CPE, TJ strands were disintegrated, and the number of TJ strands and the complexity of their network were markedly decreased. In good agreement with the time course of these morphological changes, the TJ barrier (TER and paracellular flux) of MDCK I cells was downregulated by C-CPE in a dose-dependent manner. These findings provided evidence for the direct involvement of claudins in the barrier functions of TJs.

  7. Indigenous lactobacilli strains of food and human sources reverse enteropathogenic E. coli O26:H11-induced damage in intestinal epithelial cell lines: effect on redistribution of tight junction proteins.

    Science.gov (United States)

    Jariwala, Ruchi; Mandal, Hemanti; Bagchi, Tamishraha

    2017-09-01

    The aim of the study was to investigate the neutralizing effect of lactobacilli isolated from indigenous food and human sources on enteropathogenic Escherichia coli (EPEC) O26 : H11-induced epithelial barrier dysfunction in vitro. This was assessed by transepithelial electrical resistance (TEER) and permeability assays using intestinal cell lines, HT-29 and Caco-2. Furthermore, the expression and distribution of tight junction (TJ) proteins were analysed by qRT-PCR and immunofluorescence assay, respectively. The nine strains used in the study were from different species viz. Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus salivarius and Lactobacillus plantarum. All strains were able to reverse the decrease in TEER and corresponding increase in permeability across E. coli-infected monolayers. Maximum reversal was observed after 18 h [up to 93.8±2.0 % by L. rhamnosus GG followed by L. fermentum IIs11.2 (92.6±2.2 %) and L. plantarum GRI-2 (91.9±0.9 %)] of lactobacilli exposure following EPEC O26 : H11 infection. All strains were able to redistribute the TJ proteins to the cell periphery either partially or completely. Moreover, L. helveticus FA-7 was also able to significantly increase the mRNA expression of ZO-1 and claudin-1 (2.5-fold and 3.0-fold, respectively; PGRI-2 were good in all the aspects studied, and the other strains were good in some aspects. L. helveticus FA-7, L. fermentum FA-1 and L. plantarum GRI-2 can therefore be used for potential therapeutic purpose against intestinal epithelial dysfunction.

  8. Microcomputer Based System to control the Load of a Capacitor Array in the TJ-1 Tokamak; Sistema de Control de Carga de Condensadores del TJ-1

    Energy Technology Data Exchange (ETDEWEB)

    Alberdi, J.; Asenso, L.; Sanz, J. A.

    1990-07-01

    The power to create the magnetic fields in the TJ-1 Tokamak is provides by an array of 16 capacitor sets. The total capacity of this array is 8. 1F. This work describes a computer system based on the Motorola M-6800 micro- processor which controls the load of the capacitor set and stablished the conditions for the reactor trigger. (Author)

  9. Microcomputer based system to control the load of a capacitor array in the TJ-1 Tokamak; Sistema de control de carga de condensadores del TJ-1

    Energy Technology Data Exchange (ETDEWEB)

    Alberdi, J.; Asenjo, L.; Sanz, J.A.

    1990-12-31

    The power to create the magnetic field in the TJ-1 TOKAMAK is provide by an array of 16 capacitor sets. The total capacity of this array is 8.1F. This work describes a computer system based on the Motorola M-6800 microprocessor which controls the load of the capacitor set-and stablishes the conditions for the reactor trigger. (author)

  10. Microcomputer based system to control the load of a capacitor array in the TJ-1 Tokamak. Sistema de control de carga de condensadores del TJ-1

    Energy Technology Data Exchange (ETDEWEB)

    Alberdi, J.; Asenjo, L.; Sanz, J.A.

    1990-01-01

    The power to create the magnetic field in the TJ-1 TOKAMAK is provide by an array of 16 capacitor sets. The total capacity of this array is 8.1F. This work describes a computer system based on the Motorola M-6800 microprocessor which controls the load of the capacitor set-and stablishes the conditions for the reactor trigger. (author)

  11. The meaning of tri-junction point in laparoscopic gastric cancer surgery

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:It is admitted that, within gastric cancer surgery, the right layers as well as appropriate spaces demobilized between the target carcinoma mass and peripheral parts are worthy properly researching. This article is trying to delineate the entrances to the right layers in alimentary tract cancer surgery, especially in laparoscopic gastric cancer, with a brand new conception called ‘Tri-junction Point’, abbreviated as TJ point.Methods: Based on experienced laparoscopic surgeons indications and microscopy histological slices observation on dissected peripheral adipose tissues in laparoscopic gastric cancer surgery.Results:The TJ points have been found located in different parts of abdominal mesenteries.Conclusion:The four TJ points in gastric peripheral adipose can be useful to guide a bloodless laparoscopic surgery with a promising start.

  12. Demonstration of a III-nitride vertical-cavity surface-emitting laser with a III-nitride tunnel junction intracavity contact

    Science.gov (United States)

    Leonard, J. T.; Young, E. C.; Yonkee, B. P.; Cohen, D. A.; Margalith, T.; DenBaars, S. P.; Speck, J. S.; Nakamura, S.

    2015-08-01

    We report on a III-nitride vertical-cavity surface-emitting laser (VCSEL) with a III-nitride tunnel junction (TJ) intracavity contact. The violet nonpolar VCSEL employing the TJ is compared to an equivalent VCSEL with a tin-doped indium oxide (ITO) intracavity contact. The TJ VCSEL shows a threshold current density (Jth) of ˜3.5 kA/cm2, compared to the ITO VCSEL Jth of 8 kA/cm2. The differential efficiency of the TJ VCSEL is also observed to be significantly higher than that of the ITO VCSEL, reaching a peak power of ˜550 μW, compared to ˜80 μW for the ITO VCSEL. Both VCSELs display filamentary lasing in the current aperture, which we believe to be predominantly a result of local variations in contact resistance, which may induce local variations in refractive index and free carrier absorption. Beyond the analyses of the lasing characteristics, we discuss the molecular-beam epitaxy (MBE) regrowth of the TJ, as well as its unexpected performance based on band-diagram simulations. Furthermore, we investigate the intrinsic advantages of using a TJ intracavity contact in a VCSEL using a 1D mode profile analysis to approximate the threshold modal gain and general loss contributions in the TJ and ITO VCSEL.

  13. Demonstration of a III-nitride vertical-cavity surface-emitting laser with a III-nitride tunnel junction intracavity contact

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, J. T., E-mail: jtleona01@gmail.com; Young, E. C.; Yonkee, B. P.; Cohen, D. A.; Margalith, T.; Speck, J. S. [Materials Department, University of California, Santa Barbara, California 93106 (United States); DenBaars, S. P.; Nakamura, S. [Materials Department, University of California, Santa Barbara, California 93106 (United States); Department of Electrical and Computer Engineering, University of California, Santa Barbara, California 93106 (United States)

    2015-08-31

    We report on a III-nitride vertical-cavity surface-emitting laser (VCSEL) with a III-nitride tunnel junction (TJ) intracavity contact. The violet nonpolar VCSEL employing the TJ is compared to an equivalent VCSEL with a tin-doped indium oxide (ITO) intracavity contact. The TJ VCSEL shows a threshold current density (J{sub th}) of ∼3.5 kA/cm{sup 2}, compared to the ITO VCSEL J{sub th} of 8 kA/cm{sup 2}. The differential efficiency of the TJ VCSEL is also observed to be significantly higher than that of the ITO VCSEL, reaching a peak power of ∼550 μW, compared to ∼80 μW for the ITO VCSEL. Both VCSELs display filamentary lasing in the current aperture, which we believe to be predominantly a result of local variations in contact resistance, which may induce local variations in refractive index and free carrier absorption. Beyond the analyses of the lasing characteristics, we discuss the molecular-beam epitaxy (MBE) regrowth of the TJ, as well as its unexpected performance based on band-diagram simulations. Furthermore, we investigate the intrinsic advantages of using a TJ intracavity contact in a VCSEL using a 1D mode profile analysis to approximate the threshold modal gain and general loss contributions in the TJ and ITO VCSEL.

  14. The effect of phytic acid on tight junctions in the human intestinal Caco-2 cell line and its mechanism.

    Science.gov (United States)

    Fu, Qingxue; Wang, Huizhen; Xia, Mengxin; Deng, Bing; Shen, Hongyi; Ji, Guang; Li, Guowen; Xie, Yan

    2015-12-01

    This study investigated the effect of phytic acid (IP6), a potential absorption enhancer of flavonoid components, on tight junction (TJ) integrity in Caco-2 cell monolayers and its possible mechanisms. Transepithelial electrical resistance (TEER) across the monolayers decreased rapidly, and the flux of fluorescein sodium (a paracellular marker) increased after treating with IP6 in a concentration-dependent manner. Confocal microscopy results showed that IP6 produced a concentration-dependent attenuation in the distribution of occludin, ZO-1, and claudin-1. Immunoblot analysis revealed that IP6 could down-regulate the expression level of these TJ proteins, which resulted in the opening of TJ. Additionally, the divalent cations Ca(2+) and Mg(2+) influenced the IP6-induced distribution of occludin, ZO-1, and claudin-1 in different directions, which enhanced barrier function. In conclusion, IP6 can decrease the integrity of Caco-2 cell monolayers by modulating the TJ proteins' localization and down-regulating the expression levels of TJ proteins including claudin-1, occludin, and ZO-1; the reduction effects of divalent cations such as Ca(2+) and Mg(2+) on the regulation of TJ induced by IP6 should be addressed. The present work will offer some useful guidance for the application of IP6 in drug delivery area. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions.

    Science.gov (United States)

    Furuse, M; Itoh, M; Hirase, T; Nagafuchi, A; Yonemura, S; Tsukita, S; Tsukita, S

    1994-12-01

    Occludin is an integral membrane protein localizing at tight junctions (TJ) with four transmembrane domains and a long COOH-terminal cytoplasmic domain (domain E) consisting of 255 amino acids. Immunofluorescence and laser scan microscopy revealed that chick full-length occludin introduced into human and bovine epithelial cells was correctly delivered to and incorporated into preexisting TJ. Further transfection studies with various deletion mutants showed that the domain E, especially its COOH-terminal approximately 150 amino acids (domain E358/504), was necessary for the localization of occludin at TJ. Secondly, domain E was expressed in Escherichia coli as a fusion protein with glutathione-S-transferase, and this fusion protein was shown to be specifically bound to a complex of ZO-1 (220 kD) and ZO-2 (160 kD) among various membrane peripheral proteins. In vitro binding analyses using glutathione-S-transferase fusion proteins of various deletion mutants of domain E narrowed down the sequence necessary for the ZO-1/ZO-2 association into the domain E358/504. Furthermore, this region directly associated with the recombinant ZO-1 produced in E. coli. We concluded that occludin itself can localize at TJ and directly associate with ZO-1. The coincidence of the sequence necessary for the ZO-1 association with that for the TJ localization suggests that the association with underlying cytoskeletons through ZO-1 is required for occludin to be localized at TJ.

  16. Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

    Directory of Open Access Journals (Sweden)

    Cuzzocrea Salvatore

    2007-10-01

    Full Text Available Abstract In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1 TNF-α production in pleural exudates and in the lung tissues, (2 the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity, (3 the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry and (4 apoptosis (TUNEL staining, Bax, Bcl-2 expression. Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction.

  17. Calcium-mediated oxidative stress: a common mechanism in tight junction disruption by different types of cellular stress.

    Science.gov (United States)

    Gangwar, Ruchika; Meena, Avtar S; Shukla, Pradeep K; Nagaraja, Archana S; Dorniak, Piotr L; Pallikuth, Sandeep; Waters, Christopher M; Sood, Anil; Rao, RadhaKrishna

    2017-02-20

    The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction (TJ) disruption was investigated in Caco-2 cell monolayers in vitro and restraint stress-induced barrier dysfunction in mouse colon in vivo Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca(2+) by 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Knockdown of CaV1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated TJ disruption and barrier dysfunction. N-Acetyl l-cysteine (NAC) and l-N(G)-Nitroarginine methyl ester (l-NAME) blocked stress-induced TJ disruption and barrier dysfunction. NAC and l-NAME also blocked stress-induced activation of c-Jun N-terminal kinase (JNK) and c-Src. ROS was colocalized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, TJ disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and TJ disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca(2+), activation of JNK and c-Src, and disruption of TJ in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, TJ disruption and protein thiol oxidation in colonic mucosa. The present study demonstrates that oxidative stress is a common signal in the mechanism of TJ disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo.

  18. Tight junction modulation of the blood brain barrier: CNS delivery of small molecules.

    Science.gov (United States)

    Greene, Chris; Campbell, Matthew

    2016-01-01

    The blood brain barrier (BBB) represents a major obstacle for targeted drug delivery to the brain for the treatment of central nervous system (CNS) disorders. Significant advances in barrier research over the past decade has led to the discovery of an increasing number of structural and regulatory proteins in tight junctions (TJ) and adherens junctions (AJ). These discoveries are providing the framework for the development of novel TJ modulators which can act specifically and temporarily to alter BBB function and regulate paracellular uptake of molecules. TJ modulators that have shown therapeutic potential in preclinical models include claudin-5 and occludin siRNAs, peptides derived from zonula occludens toxin as well as synthetic peptides targeting the extracellular loops of TJs. Adding to the array of modulating agents are novel mechanisms of BBB regulation such as focused ultrasound (FUS). This review will give a succinct overview of BBB biology and TJ modulation in general. Novel insights into BBB regulation in health and disease will also be summarized.

  19. Iterative noise removal from temperature and density profiles in the TJ-II Thomson scattering

    Energy Technology Data Exchange (ETDEWEB)

    Farias, G., E-mail: gonzalo.farias@ucv.cl [Pontificia Universidad Católica de Valparaíso, Av. Brasil 2147, Valparaíso (Chile); Dormido-Canto, S., E-mail: sebas@dia.uned.es [Departamento de Informática y Automática, UNED, 28040 Madrid (Spain); Vega, J., E-mail: jesus.vega@ciemat.es [Asociación EURATOM/CIEMAT para Fusión, Avd. Complutense 22, 28040 Madrid (Spain); Santos, M., E-mail: msantos@ucm.es [Departamento de Arquitectura de Computadores y Automática, Universidad Complutense de Madrid, 28040 Madrid (Spain); Pastor, I., E-mail: ignacio.pastor@ciemat.es [Asociación EURATOM/CIEMAT para Fusión, Avd. Complutense 22, 28040 Madrid (Spain); Fingerhuth, S., E-mail: sebastian.fingerhuth@ucv.cl [Pontificia Universidad Católica de Valparaíso, Av. Brasil 2147, Valparaíso (Chile); Ascencio, J., E-mail: j_ascencio21@hotmail.com [Pontificia Universidad Católica de Valparaíso, Av. Brasil 2147, Valparaíso (Chile)

    2014-05-15

    TJ-II Thomson Scattering diagnostic provides temperature and density profiles of plasma. The CCD camera acquires images that are corrupted with some kind of noise called stray-light. This noise degrades both image contrast and measurement accuracy, which could produce unreliable profiles of the diagnostic. So far, several approaches have been applied in order to decrease the noise in the TJ-II Thomson scattering images. Since the presence of the noise is not global but located in some particular regions of the image, advanced processing techniques are needed. However such methods require of manual fine-tuning of parameters to reach a good performance. In this contribution, an iterative image processing approach is applied in order to reduce the stray light effects in the images of the TJ-II Thomson scattering diagnostic. The proposed solution describes how the noise can be iteratively reduced in the images when a key parameter is automatically adjusted during the iterative process.

  20. Calculation of the bootstrap current profile for the TJ-II stellarator

    CERN Document Server

    Velasco, J L; Lopez-Fraguas, A; Beidler, C D; Maassberg, H; Kernbichler, W; Castejon, F; Jimenez, J A

    2011-01-01

    Calculations of the bootstrap current for the TJ-II stellarator are presented. DKES and NEO-MC codes are employed; the latter has allowed, for the first time, the precise computation of the bootstrap transport coefficient in the long mean free path regime of this device. The low error bars allow a precise convolution of the monoenergetic coefficients, which is confirmed by error analysis. The radial profile of the bootstrap current is presented for the fist time for the 100_44_64 configuration of TJ-II for three different collisionality regimes. The bootstrap coefficient is then compared to that of other configurations of TJ-II regularly operated. The results show qualitative agreement with toroidal current measurements; precise comparison with real discharges is ongoing.

  1. [Remodeling of cardiac gap junctions and arrhythmias].

    Science.gov (United States)

    Yu, Zhi-Bin; Sheng, Juan-Juan

    2011-12-25

    In the heart, gap junctions mediate electrical and chemical coupling between adjacent cardiomyocytes, forming the cell-to-cell pathways for orderly spread of the wave of electrical excitation responsible for a functional syncytium. Three principal connexins are expressed in cardiomyocytes, connexin 43 (CX43), CX40, and CX45. CX43 predominates in ventricular muscle cells. Most of the gap junctions, assembled from CX43, are located at the intercalated discs, often with larger junctional plaques at the disc periphery. The gap junctions are rarely distributed to the sides of the cardiomyocyte. The ischemia-reperfusion, cardiac hypertrophy, heart failure, hypercholesterolemia, and diabetes mellitus induce gap junction remodeling. The gap junction remodeling induced by above-mentioned diseases shows similar characteristics, including down-regulation of CX43, reduction in gap junction plaque size, increased heterogeneity and lateralization of gap junction distribution, and dephosphorylation of CX43. The elevated angiotensin II concentration in local myocardium may play an important role in the gap junction remodeling. The down-regulation of CX43 and lateralization of gap junction distribution alter anisotropic spread of the impulse of ventricular myocardium. The dephosphorylation of CX43 not only reduces electrical conductance, but also decreases permeability of chemicals between cardiomyocytes. The lateralization of gap junctions may increase the number of hemichannels formed by CX43. The opening of hemichannels induces ATP efflux and Na(+) influx, which forms a delayed after-depolarization. The gap junction remodeling in pathological condition produces arrhythmia substrate in the ventricles. In this review, the current knowledge on the relationship between the remodeling of cardiac gap junctions and arrhythmias were summarized.

  2. Calculation of the magnetic vector potential in the TJ-II; Calculo del Potencial Magnetico Vector en el TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Fraguas, A.; Lopez Bruna, D.; Romero, J. A.

    2005-07-01

    The properties of the vector magnetic potential and its usefulness to calculate magnetic fluxes in both stationary and time-dependent conditions are p revised in this report. We have adapted to the TJ-II Flexible Heliac efficient numerical expressions to calculate the vector potential, calculating in addition the magnetic flux with this formalism in circumstances whose complexity makes very convenient the use of the vector potential. The result on induced voltages offer theoretical support to the measurements of induced voltage due to the OH coils in the plasma, like the measurements provided by the loop voltage diagnostic installed in the TJ-II, as well as to the cylindrical approximation of the plasma often used to interpret experimental data. (Author) 11 refs.

  3. Controlling Confinement with Induced Toroidal Current in the Flexible Heliac TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Romero, J. A.; Lopez-Bruna, D.; Lopez-Fraguas, A.; Ascasibar, E.; TJ-II Team

    2002-07-01

    A method to control plasma particle an energy confinement in the TJ-II Heliac devices is reported A small toroidal current is induced in the plasma with the aid of a 0.2 Wb air core transformer. Plasma particle and energy confinement improve (degrade) with negative (positive) plasma current. For typical TJ-II discharges plasma density and temperature broaden considerably when plasma current is sufficiently negative, accounting for a 40% increase in stored energy. The experimental results agree qualitatively with the paradigm of instability growth rate modifications with magnetic shear. (Author) 18 refs.

  4. Search for Quasi-isodynamic Effects in TJ-II; Busqueda de efectos quasi-isodinamicos en el TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Guasp, J.; Liniers, M. [Ciemat. Madrid (Spain)

    2000-07-01

    The possibility of quasi-isodynamics effects (QID) in the TJ-II helical axis Stellarator has been explored maintaining the present setting for the toroidal field coils (TFC). In order to do this it has been necessary to implement a new method of calculation, using real space coordinates to follow the particle trajectories, instated the Boozer coordinates as was usual formerly. The result for the exploration of the flexibility diagram of TJ-II, including magnetic axis a shift effects, has been negative. It seems that there are not useful QID regions in TJ-II with the present setting of TFC carrying equal currents in all coils. Nevertheless, in spite of this negative result, the calculation in real space and, mainly, the grater number of configurations analysed, have produced a series of new important results, some of them unexpected. The influence of rational surfaces is very important. Optima and minima of confinement alternate at both sides of the rational values (mainly for the 1/2 by period) in a way very similar to the radial electric field resonance cases. This effect originates in the peculiar orbit topology in the presence of diffusion. Some lines of study are proposed to deal with this problem. Finally, the negative result of the QID search suggests the convenience to start a similar search without the restriction of equal currents on all the TEC. (Author) 18 refs.

  5. Geometry of the TJ-II in Astra 6.0; Geometria del TJ-II en Astra 6.0

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Bruna, D.; Romero, J.A.; Castejon, F.

    2006-07-01

    One of the most exploited features of the TJ-II Heliac, a facility in the Laboratorio Nacional de Fusion (CIEMAT, Madrid), is its ability to explore plasmas in different magnetic configurations. For this reason, there are available libraries that provide the metrics and associated magnitudes for many among all possible configurations. On the other hand, the transport codes that can normally be used to perform transport calculations cannot dea properly with these geometries, which is especially delicate when there are induced plasma currents. In the present work we adopt ASTRA, a transport analysis shell, to study the approximations performed when calculations that impose axi-symmetry (as ASTRA does) are performed on magnetic configurations that are not really axi-symmetric. After describing how we obtain those TJ-II metric averages that must be set in ASTRA, we perform two comparisons: (i) we obtain the vacuum rotational transform as deduced from the metric coefficients but imposing axisymmetry, and compare the results with the rotational transform yielded by the existing libraries; and (ii) we build a ID transport code with TJ-II metrics so its results can be compared with those of ASTRA. In both cases, the differences found indicate that evaluating the evolution of the rotational transform under ohmic induction and transport evolution is acceptable assuming that the geometry itself does not evolve. (Author) 11 refs.

  6. TJ-41 Induces Apoptosis and Potentiates the Apoptotic Effects of 5-FU in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Suresh Volate

    2009-01-01

    Full Text Available Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer cells lines. TJ-41 inhibited the proliferation of human breast cancer cell lines dose dependently. Flow cytometric analysis showed that this decrease in DNA synthesis is to be associated with induction of apoptosis. In both cell lines, apoptosis was abolished by caspase-9 inhibitor Z-LEHD-fmk but was weakly inhibited by caspase-8 inhibitor Z-IETD-fmk, indicating that caspase-9 activation was involved in TJ-41 induced apoptosis. Additionally, TJ-41 stimulated phosphorylation of c-Jun NH2-terminal kinase (JNK and pretreatment of breast cancer cells with JNK inhibitor SP600125 completely abolished TJ-41 induced apoptosis. Our data also demonstrate that combined treatment of TJ-41 and 5-FU significantly potentiates the apoptotic effects of 5-FU in both breast cancer cell lines. Taken together, these data suggest that TJ-41 might provide a novel chemotherapeutic treatment for breast cancer.

  7. The spectrometer of the High-Resolution Multi position Thomson Scattering Diagnostic for TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Herranz, J.; Barth, C.J.; Castejon, F.; Lopez-Sanchez, A.; Mirones, E.; Pastor, I.; Perez, D.; Rodriguez, C.

    2001-07-01

    Since 1998, a high-resolution multiposition thompson scattering system is in operation at the stellarator TJ-II, combining high accuracy and excellent spatial resolution. A description of the diagnostic spectrometer is presented. The main characteristics of the spectrometer that allow YJ-II Thomson scattering diagnostic to have high spatial and spectral resolution are described in this paper. (Author)

  8. A New Four-Barrel Pellet Injection System for the TJ-II Stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephen Kirk [ORNL; Foust, Charles R [ORNL; McGill, James M [ORNL; Baylor, Larry R [ORNL; Caughman, John B [ORNL; Fehling, Dan T [ORNL; Harris, Jeffrey H [ORNL; Meitner, Steven J [ORNL; Rasmussen, David A [ORNL; McCarthy, K. J. [EURATOM-CIEMAT, Madrid, Spain; Chamorro, M. [Laboratory Nacional de Fusion, Madrid, Spain; Garcia, R. [Laboratory Nacional de Fusion, Madrid, Spain; Hildago, C. [Laboratory Nacional de Fusion, Madrid, Spain; Medrano, M. [Laboratory Nacional de Fusion, Madrid, Spain; Unamuno, R. [Laboratory Nacional de Fusion, Madrid, Spain

    2011-01-01

    A new pellet injection system for the TJ-II stellarator has been developed/constructed as part of a collaboration between the Oak Ridge National Laboratory (ORNL) and the Centro de Investigaciones Energ ticas, Medioambientales y Tecnol gicas (CIEMAT). ORNL is providing most of the injector hardware and instrumentation, the pellet diagnostics, and the pellet transport tubes; CIEMAT is responsible for the injector stand/interface to the stellarator, cryogenic refrigerator, vacuum pumps/ballast volumes, gas manifolds, remote operations, plasma diagnostics, and data acquisition. The pellet injector design is an upgraded version of that used for the ORNL injector installed on the Madison Symmetric Torus (MST). It is a four-barrel system equipped with a cryogenic refrigerator for in situ hydrogen pellet formation and a combined mechanical punch/propellant valve system for pellet acceleration (speeds ~100 to 1000 m/s). On TJ-II, it will be used as an active diagnostic and for fueling. To accommodate the plasma experiments planned for TJ-II, pellet sizes significantly smaller than those typically used for the MST application are required. The system will initially be equipped with four different pellet sizes, with the gun barrel bores ranging between ~0.5 to 1.0 mm. The new system is almost complete and is described briefly here, highlighting the new features added since the original MST injector was constructed. Also, the future installation on TJ-II is reviewed.

  9. Doping dependence of the spectral function in the t-J model

    NARCIS (Netherlands)

    Eder, R; Ohta, Y.

    1996-01-01

    We study the doping dependence of the electronic spectral function in small clusters of the t-J model. We find rigid-band behaviour near the chemical potential and weight transfer from deep below E(F) to above the chemical potential; the latter originates from strong dressing of hobs by spin fluctua

  10. [6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway

    Directory of Open Access Journals (Sweden)

    Sung Ok Kim

    2013-01-01

    Full Text Available To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP activities; transepithelial electrical resistance (TER and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO- 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.

  11. Lipopolysaccharide disrupts the milk-blood barrier by modulating claudins in mammary alveolar tight junctions.

    Directory of Open Access Journals (Sweden)

    Ken Kobayashi

    Full Text Available Mastitis, inflammation of the mammary gland, is the most costly common disease in the dairy industry, and is caused by mammary pathogenic bacteria, including Escherichia coli. The bacteria invade the mammary alveolar lumen and disrupt the blood-milk barrier. In normal mammary gland, alveolar epithelial tight junctions (TJs contribute the blood-milk barrier of alveolar epithelium by blocking the leakage of milk components from the luminal side into the blood serum. In this study, we focused on claudin subtypes that participate in the alveolar epithelial TJs, because the composition of claudins is an important factor that affects TJ permeability. In normal mouse lactating mammary glands, alveolar TJs consist of claudin-3 without claudin-1, -4, and -7. In lipopolysaccharide (LPS-induced mastitis, alveolar TJs showed 2-staged compositional changes in claudins. First, a qualitative change in claudin-3, presumably caused by phosphorylation and participation of claudin-7 in alveolar TJs, was recognized in parallel with the leakage of fluorescein isothiocyanate-conjugated albumin (FITC-albumin via the alveolar epithelium. Second, claudin-4 participated in alveolar TJs with claudin-3 and claudin-7 12 h after LPS injection. The partial localization of claudin-1 was also observed by immunostaining. Coinciding with the second change of alveolar TJs, the severe disruption of the blood-milk barrier was recognized by ectopic localization of β-casein and much leakage of FITC-albumin. Furthermore, the localization of toll-like receptor 4 (TLR4 on the luminal side and NFκB activation by LPS was observed in the alveolar epithelial cells. We suggest that the weakening and disruption of the blood-milk barrier are caused by compositional changes of claudins in alveolar epithelial TJs through LPS/TLR4 signaling.

  12. Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK.

    Directory of Open Access Journals (Sweden)

    Xiao Xiao Tang

    Full Text Available The tight junctions (TJs, characteristically located at the apicolateral borders of adjacent epithelial cells, are required for the proper formation of epithelial cell polarity as well as for sustaining the mucosal barrier to the external environment. The observation that lymphocytes are recruited by epithelial cells to the sites of infection [1] suggests that they may play a role in the modulation of epithelial barrier function and thus contribute to host defense. To test the ability of lymphocytes to modulate tight junction assembly in epithelial cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin-Darby canine kidney (MDCK cells, a well-established model cell line for studying epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an infection state. In a typical calcium switch experiment, the TJ assembly in co-culture was found to be accelerated compared to that in MDCK cells alone. This accelaration was found to be mediated by AMP-activated protein kinase (AMPK. AMPK activation was independent of changes in cellular ATP levels but it was found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated the accelerating effect of lymphocytes on TJ formation. Similar results were also observed in a co-culture with lymphocytes and Calu-3 human airway epithelial cells, suggesting that the activation of AMPK may be a general mechanism underlying lymphocyte-accelerated TJ assembly in different epithelia. These results suggest that signals from lymphocytes, such as cytokines, facilitate TJ assembly in epithelial cells via the activation of AMPK.

  13. Comparison of nonpolar III-nitride vertical-cavity surface-emitting lasers with tunnel junction and ITO intracavity contacts

    Science.gov (United States)

    Leonard, J. T.; Young, E. C.; Yonkee, B. P.; Cohen, D. A.; Shen, C.; Margalith, T.; Ng, T. K.; DenBaars, S. P.; Ooi, B. S.; Speck, J. S.; Nakamura, S.

    2016-02-01

    We report on the lasing of III-nitride nonpolar, violet, vertical-cavity surface-emitting lasers (VCSELs) with IIInitride tunnel-junction (TJ) intracavity contacts and ion implanted apertures (IIAs). The TJ VCSELs are compared to similar VCSELs with tin-doped indium oxide (ITO) intracavity contacts. Prior to analyzing device results, we consider the relative advantages of III-nitride TJs for blue and green emitting VCSELs. The TJs are shown to be most advantageous for violet and UV VCSELs, operating near or above the absorption edge for ITO, as they significantly reduce the total internal loss in the cavity. However, for longer wavelength III-nitride VCSELs, TJs primarily offer the advantage of improved cavity design flexibility, allowing one to make the p-side thicker using a thick n-type III-nitride TJ intracavity contact. This offers improved lateral current spreading and lower loss, compare to using ITO and p-GaN, respectively. These aspects are particularly important for achieving high-power CW VCSELs, making TJs the ideal intracavity contact for any III-nitride VCSEL. A brief overview of III-nitride TJ growth methods is also given, highlighting the molecular-beam epitaxy (MBE) technique used here. Following this overview, we compare 12 μm aperture diameter, violet emitting, TJ and ITO VCSEL experimental results, which demonstrate the significant improvement in differential efficiency and peak power resulting from the reduced loss in the TJ design. Specifically, the TJ VCSEL shows a peak power of ~550 μW with a threshold current density of ~3.5 kA/cm2, while the ITO VCSELs show peak powers of ~80 μW and threshold current densities of ~7 kA/cm2.

  14. Comparison of nonpolar III-nitride vertical-cavity surface-emitting lasers with tunnel junction and ITO intracavity contacts

    KAUST Repository

    Leonard, J. T.

    2016-03-01

    We report on the lasing of III-nitride nonpolar, violet, vertical-cavity surface-emitting lasers (VCSELs) with III-nitride tunnel-junction (TJ) intracavity contacts and ion implanted apertures (IIAs). The TJ VCSELs are compared to similar VCSELs with tin-doped indium oxide (ITO) intracavity contacts. Prior to analyzing device results, we consider the relative advantages of III-nitride TJs for blue and green emitting VCSELs. The TJs are shown to be most advantageous for violet and UV VCSELs, operating near or above the absorption edge for ITO, as they significantly reduce the total internal loss in the cavity. However, for longer wavelength III-nitride VCSELs, TJs primarily offer the advantage of improved cavity design flexibility, allowing one to make the p-side thicker using a thick n-type III-nitride TJ intracavity contact. This offers improved lateral current spreading and lower loss, compare to using ITO and p-GaN, respectively. These aspects are particularly important for achieving high-power CW VCSELs, making TJs the ideal intracavity contact for any III-nitride VCSEL. A brief overview of III-nitride TJ growth methods is also given, highlighting the molecular-beam epitaxy (MBE) technique used here. Following this overview, we compare 12 mu m aperture diameter, violet emitting, TJ and ITO VCSEL experimental results, which demonstrate the significant improvement in differential efficiency and peak power resulting from the reduced loss in the TJ design. Specifically, the TJ VCSEL shows a peak power of similar to 550 mu W with a threshold current density of similar to 3.5 kA/cm(2), while the ITO VCSELs show peak powers of similar to 80 mu W and threshold current densities of similar to 7 kA/cm

  15. Alteration of Tight and Adherens Junctions on 50-Hz Magnetic Field Exposure in Madin Darby Canine Kidney (MDCK Cells

    Directory of Open Access Journals (Sweden)

    Zoltán Somosy

    2004-01-01

    Full Text Available Adherens (AJ and tight junctions (TJ, as integrated parts of the junctional complex, are multifunctional specialized regions of the cell membrane in epithelial cells. They are responsible for cell-to-cell interactions and also have great importance in cellular signaling processes including Wnt protein-mediated signals. As electromagnetic field (EMF exposure is known to cause alterations in the function as well as supramolecular organization of different cell contacts, our goal was to investigate the effect of 50-Hz magnetic field (MF exposures on the subcellular distribution of some representative structural proteins (occludin, β-catenin, and cadherin found in AJ and TJ. Additionally, cellular β-catenin content was also quantified by Western blot analysis. 50-Hz MF exposures seemed to increase the staining intensity (amount of occludin, cadherins, and β-catenin in the junctional area of MDCK cells, while Western blot data indicated the quantity of b-catenin was found significantly decreased at both time points after EM exposures. Our results demonstrate that MF are able to modify the distribution of TJ and AJ structural proteins, tending to stabilize these cell contacts. The quantitative changes of β-catenin suggest a causative relationship between MF effects on the cell junctional complex and the Wnt signaling pathway.

  16. Transmission of the Neutral Beam Heating Beams at TJ-II; Transmision del Haz de Neutros de Calentamiento en TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Fuentes Lopez, C.

    2007-09-27

    Neutral beam injection heating has been development for the TJ-II stellarator. The beam has a port-through power between 700-1500 kW and injection energy 40 keV. The sensibility of the injection system to the changes of several parameters is analysed. Beam transmission is limited by losses processes since beam is born into the ions source until is coming into the fusion machine. For the beam transmission optimization several beam diagnostics have been developed. A carbon fiber composite (CFC) target calorimeter has been installed at TJ-II to study in situ the power density distribution of the neutral beams. The thermographic print of the beam can be recorded and analysed in a reliable way due to the highly anisotropic thermal conductivity of the target material. With the combined thermographic and calorimetric measurements it has been possible to determine the power density distribution of the beam. It has been found that a large beam halo is present, which can be explained by the extreme misalignment of the grids. This kind of halo has a deleterious effect on beam transport and must be minimized in order to improve the plasma heating capability of the beams. (Author) 155 refs.

  17. Impurity Dynamics under Neutral Beam Injection at TJ-II (simulation); Dinamica de Impurezas durante la Inyeccion de Haces Neutros en el TJ-II (simulacion)

    Energy Technology Data Exchange (ETDEWEB)

    Guasp, J.; Fuentes, C.; Liniers, M.

    2001-07-01

    In this study the simulations of plasma transport under NBI for TJ-II, previously performed, are extended. Since than a considerable number of important modifications have been introduced in the model: change of magnetic configuration, use of experimental initial profiles, expansion of the Data base from NBI calculations and, mainly, a detailed handling of impurities with inclusion of sputtering effects. Moreover there is now a particular emphasis on the analysis of the conditions for discharge collapse and on the possible effects of single beam injection. This analysis of impurity behaviour with sputtering shows that in the expected usual cases there is no radioactive collapse and that if the recycling coefficients remain lower the unity it is always possible to find a strategy for external gas puffing leading to a stationary state, with densities below the limit and efficient NBI absorption (>50%). The radioactive collapse can appear either at high densities (central value higher than 1.4x10''20 m''3), excessive influx of impurities (i. e. with sputtering rates higher than twice the expected values) o for insufficient injected beam power (less than 45 kW). The present study analyses only the 100{sub 4}4{sub 6}4 configuration of TJ-II, but future works will start a systematic scan of configuration using this same model. (Author) 12 Refs.

  18. Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing.

    Science.gov (United States)

    Volksdorf, Thomas; Heilmann, Janina; Eming, Sabine A; Schawjinski, Kathrin; Zorn-Kruppa, Michaela; Ueck, Christopher; Vidal-Y-Sy, Sabine; Windhorst, Sabine; Jücker, Manfred; Moll, Ingrid; Brandner, Johanna M

    2017-06-01

    Tight junction (TJ) proteins are known to be involved in proliferation and differentiation. These processes are essential for normal skin wound healing. Here, we investigated the TJ proteins claudin-1 and occludin in ex vivo skin wound healing models and tissue samples of acute and chronic human wounds and observed major differences in localization/expression of these proteins, with chronic wounds often showing a loss of the proteins at the wound margins and/or in the regenerating epidermis. Knockdown experiments in primary human keratinocytes showed that decreased claudin-1 expression resulted in significantly impaired scratch wound healing, with delayed migration and reduced proliferation. Activation of AKT pathway was significantly attenuated after claudin-1 knockdown, and protein levels of extracellular signal-related kinase 1/2 were reduced. For occludin, down-regulation had no impact on wound healing in normal scratch assays, but after subjecting the cells to mechanical stress, which is normally present in wounds, wound healing was impaired. For both proteins we show that most of these actions are independent from the formation of barrier-forming TJ structures, thus demonstrating nonbarrier-related functions of TJ proteins in the skin. However, for claudin-1 effects on scratch wound healing were more pronounced when TJs could form. Together, our findings provide evidence for a role of claudin-1 and occludin in epidermal regeneration with potential clinical importance. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. Tight junctions: a barrier to the initiation and progression of breast cancer?

    LENUS (Irish Health Repository)

    Brennan, Kieran

    2010-01-01

    Breast cancer is a complex and heterogeneous disease that arises from epithelial cells lining the breast ducts and lobules. Correct adhesion between adjacent epithelial cells is important in determining the normal structure and function of epithelial tissues, and there is accumulating evidence that dysregulated cell-cell adhesion is associated with many cancers. This review will focus on one cell-cell adhesion complex, the tight junction (TJ), and summarize recent evidence that TJs may participate in breast cancer development or progression. We will first outline the protein composition of TJs and discuss the functions of the TJ complex. Secondly we will examine how alterations in these functions might facilitate breast cancer initiation or progression; by focussing on the regulatory influence of TJs on cell polarity, cell fate and cell migration. Finally we will outline how pharmacological targeting of TJ proteins may be useful in limiting breast cancer progression. Overall we hope to illustrate that the relationship between TJ alterations and breast cancer is a complex one; but that this area offers promise in uncovering fundamental mechanisms linked to breast cancer progression.

  20. Broad-band time-resolved near infrared spectroscopy in the TJ-II stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, M.C.; Pastor, I.; Cal, E. de la; McCarthy, K.J. [Laboratorio Nacional de Fusion, CIEMAT, Madrid (Spain); Diaz, D. [Universidad Autonoma de Madrid, Dept Quimica Fisica Aplicada, Madrid (Spain)

    2014-11-15

    First experimental results on broad-band, time-resolved Near Infrared (NIR;here loosely defined as covering from 750 to 1650 nm) passive spectroscopy using a high sensitivity InGaAs detector are reported for the TJ-II Stellarator. Experimental set-up is described together with its main characteristics, the most remarkable ones being its enhanced NIR response, broadband spectrum acquisition in a single shot, and time-resolved measurements with up to 1.8 kHz spectral rate. Prospects for future work and more extended physics studies in this newly open spectral region in TJ-II are discussed. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  1. Charge-Exchange Neutral Particle Analyzer Diagnostic of TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Fontdecaba, J. M.; Balbin, R.; Petrov, S.; TJ-II team

    2003-07-01

    A description of the Charge Exchange Neutral Particle Analyzers in operation in the heliac flexible TJ-II is reported. A description of the detectors, as well as the operation characteristics, hardware and software used in the control and analysis of the data obtained with the diagnostic is detailed. Two NPAs are in operation in TJ-II. One of them is a 5-channel analyzer and another one is an Acord-12. The 5-channel analyzer provides measurements of charge exchange neutral fluxes at five energy channels, whereas the Acord-12 can measure simultaneously two different hydrogen isotopes (H and D) at six energy channels. Their lines of sight can be varied poloidally in order to observe the different sections of the plasma. (Author) 10 refs.

  2. Studies of the fast ion energy spectra in TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Bustos, A. [Laboratorio Nacional de Fusion, EURATOM-CIEMAT, 28040 Madrid (Spain); Max-Planck-Institut fur Plasmaphysik, EURATOM Association, 85748 Garching (Germany); Fontdecaba, J. M.; Arevalo, J. [Laboratorio Nacional de Fusion, EURATOM-CIEMAT, 28040 Madrid (Spain); Castejon, F.; Velasco, J. L. [Laboratorio Nacional de Fusion, EURATOM-CIEMAT, 28040 Madrid (Spain); Instituto de Biocomputacion y Fisica de los Sistemas Complejos (BIFI), Universidad de Zaragoza, 50018 Zaragoza (Spain); Tereshchenko, M. [Instituto de Biocomputacion y Fisica de los Sistemas Complejos (BIFI), Universidad de Zaragoza, 50018 Zaragoza (Spain)

    2013-02-15

    The dynamics of the neutral beam injection fast ions in the TJ-II stellarator is studied in this paper from both the theoretical and experimental points of view. The code Integrator of Stochastic Differential Equations for Plasmas (ISDEP) is used to estimate the fast ion distribution function in 3D:1D in real space and 2D in velocity space, considering the 3D structure of TJ-II, the electrostatic potential, non turbulent collisional transport, and charge exchange losses. The results of ISDEP are compared with the experimental data from the compact neutral particle analyzer, which measures the outgoing neutral flux spectra in the energy range E Element-Of (1-45) keV.

  3. Superconducting correlations and thermodynamic properties in 2D square and triangular t-J model

    Science.gov (United States)

    Ogata, Masao

    2006-03-01

    Equal-time superconducting correlation functions of the two-dimensional t-J model on the square lattice are studied using high-temperature expansion method.[1] The sum of the pairing correlation, its spatial dependence and correlation length are obtained down to T ˜0.2t. By comparison of single-particle contributions in the correlation functions, we find effective attractive interactions between quasi-particles in dx^2-y^2-wave channel. It is shown that d-wave correlation grows rapidly at low temperatures for the doping 0.1 0 with hole doping, a rapid growth of effective d-wave paring interaction is found that indicates the resonating-valence-bond superconductivity. In contrast, when tJ. Phys. Soc. Japan 74, 1390 (2005). [2] T. Koretsune and M. Ogata, Phys. Rev. Lett. 89, 116401 (2002), and Phys. Rev. B72, 134513 (2005).

  4. Experimental and numerical investigations of the energy confinement times in the stellarator TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Ahmed; Koehn, Alf; Munoz, Alejandro; Holzhauer, Eberhard; Ramisch, Mirko [Institute of Interfacial Process Engineering and Plasma Technology IGVP, Uni Stuttgart, Stuttgart (Germany); Birkenmeier, Gregor [Max-Planck Institute fuer Plasmaphysik, Garching (Germany)

    2015-05-01

    A particle and power balance model has been employed to numerically simulate and qualitatively understand transport processes, which determine equilibrium density and temperature profiles in the stellarator TJ-K. To quantify losses by these processes, the e-folding time of density and energy after switching off the heating source is used as a measure of the corresponding confinement times. For comparison with numerical simulation, both quantities are investigated experimentally in TJ-K. The particle confinement can be directly deduced from an interferometer or from Langmuir probes measuring the ion-saturation current. A commercial satellite receiver is used to measure the emitted radiation around 12 GHz, which is assumed to be dominated by Bremsstrahlung. In addition, the signal from a fast diode, which is sensitive in the visible range of light, is used. Results of the comparative numerical and experimental studies are presented.

  5. Biodegradation of 2-methylquinoline by Enterobacter aerogenes TJ-D isolated from activated sludge.

    Science.gov (United States)

    Wang, Lin; Li, Yongmei; Duan, Jingyuan

    2013-07-01

    Bacterial strain Enterobacter aerogenes TJ-D capable of utilizing 2-methylquinoline as the sole carbon and energy source was isolated from acclimated activated sludge under denitrifying conditions. The ability to degrade 2-methylquinoline by E. aerogenes TJ-D was investigated under denitrifying conditions. Under optimal conditions of temperature (35 degrees C) and initial pH 7, 2-methylquinoline of 100 mg/L was degraded within 176 hr. The degradation of 2-methylquinoline by E. aerogenes TJ-D could be well described by the Haldane model (R2 > 0.91). During the degradation period of 2-methylquinoline (initial concentration 100 mg/L), nitrate was almost completely consumed (the removal efficiency was 98.5%), while nitrite remained at low concentration (< 0.62 mg/L) during the whole denitrification period. 1,2,3,4-Tetrahydro-2-methylquinoline, 4-ethyl-benzenamine, N-butyl-benzenamine, N-ethyl-benzenamine and 2,6-diethyl-benzenamine were metabolites produced during the degradation. The degradation pathway of 2-methylquinoline by E. aerogenes TJ-D was proposed. 2-Methylquinoline is initially hydroxylated at C-4 to form 2-methyl-4-hydroxy-quinoline, and then forms 2-methyl-4-quinolinol as a result of tautomerism. Hydrogenation of the heterocyclic ring at positions 2 and 3 produces 2,3-dihydro-2-methyl-4-quinolinol. The carbon-carbon bond at position 2 and 3 in the heterocyclic ring may cleave and form 2-ethyl-N-ethyl-benzenamine. Tautomerism may result in the formation of 2,6-diethyl-benzenamine and N-butyl-benzenamine. 4-Ethyl-benzenamine and N-ethyl-benzenamine were produced as a result of losing one ethyl group from the above molecules.

  6. Power supply for the Spanish stellarator TJ-II, design, construction, and tests

    Energy Technology Data Exchange (ETDEWEB)

    Perez, A.; Lucia, C.; Alberdi, B.; Del Rio, J.M. [JEMA SA, Lasarte-Oria (Spain); Almoguera, L.; Blaumoser, M.; Kirpitchev, I.; Mendez, P. [Asociacion EURATOM-CIEMAT para Fusion, Madrid (Spain)

    1995-12-31

    Most of the components of the electrical power supply system of the new TJ-II stellarator, which is under construction in Madrid (Spain), are now constructed and tested. The flywheel synchronous generator is still under construction and its tests are planned for the end of 1995. The power plant is described in detail as well as the tests which have been carried out and their results.

  7. TJ-II data retrieving by means of a client/server model

    Science.gov (United States)

    Vega, J.; Sánchez, E.; Crémy, C.; Portas, A.; Dulya, C. M.; Nilsson, J.

    1999-01-01

    The database of the TJ-II flexible heliac is centralized in a Unix server. This computer also commands the on-line processes related to data acquisition during TJ-II discharges: programming of measurement systems, connectivity with control systems, data visualization, and computations. The server has to provide access to the data so that signal analysis can be performed by local users or even from remote hosts. Data retrieving is accomplished by means of a client/server architecture in which two data servers are permanently running in the background of the Unix computer. One of them serves data requests from local clients and the other one sends data to remote clients. The communication protocol in both cases has been developed by using TCP/IP and Berkeley sockets. The client part consists of a set of routines (FORTRAN and C callable), which, in a transparent way, provide connectivity with the servers. This structure allows access to TJ-II data exactly in the same way from any computer, hiding not only specific aspects of the database, but hardware architecture of the server computer as well. In addition, the remote access makes it possible to distribute computations and to reduce the load on the Unix server from analysis and visualization tasks. At present, this software is running in four different environments: the Unix server itself, various types of Unix workstations, a CRAY J90 and a CRAY T3E. Finally, due to the fact that visualization is essential for TJ-II data analysis, a powerful and a very flexible visualization tool has been developed. It is a point and click application based on X Window/Motif. Data access is carried out through the client/server processes mentioned above and the software runs in the client computer.

  8. Blood flow and permeability in microvessels

    Science.gov (United States)

    Sugihara-Seki, Masako; Fu, Bingmei M.

    2005-07-01

    The mechanics of blood flow in microvessels and microvessel permeability are reviewed. In the first part, characteristics of blood flow in vivo and in vitro are described from a fluid-mechanical point of view, and mathematical models for blood flow in microvessels are presented. Possible causes of the increased flow resistance obtained in vivo compared to in vitro are examined, including the effects of irregularities of vessel lumen, the presence of endothelial surface glycocalyx and white blood cells. In the second part, the ultrastructural pathways and mechanisms whereby endothelial cells and the clefts between the cells modulate microvessel permeability to water and solutes are introduced. Previous and current models for microvessel permeability to water and solutes are reviewed. These models examine the role of structural components of interendothelial cleft, such as junction strands and surface glycocalyx, in the determination of water and solute transport across the microvessel walls. Transport models in the tissue space surrounding the microvessel are also described.

  9. Visual Data Analysis in the TJ-II Remote Participation System

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, E.; Portas, A.; Pereira, A.; Vega, J.

    2006-07-01

    A general-purpose data visualization tool has been developed to provide the TJ-II remote participation system with the same visualization capabilities already available in the TJ-II local environment. The visualization software has been developed in the Java language. It provides a user-friendly graphical interface that permits users on-demand plotting of time traces in a very flexible manner. In order to facilitate on-line tracking of experimental operation, the application also allows automatic refreshing of data. This software has been integrated into the TJ-II remote participation system distributed environment. Data are accessed remotely using web technologies and HTTP protocol and are transferred in a compressed format, which reduces bandwidth requirements. Both metadata and binary compressed data are transported in multipart messages. Message oriented middleware software is used to distribute information on-line, in particular notifications of data availability for automatic data refreshing or local events. Plot layouts can be stored in a centralized database for subsequent recovery from anywhere. Finally, this software is integrated into the general security framework provided by the PAPI system. (Author)

  10. Visual Data Analysis in the TJ-II Remote Participation System

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, E.; Porta, A.; Pereira, A.; Vega, J.

    2007-07-20

    A general-purpose data visualization tool has been developed to provide the TJ-II remote participation system with the same visualization capabilities already available in the TJ-II local environment. The visualization software has been developed in the Java language. It provides a user-friendly graphical interface that permits users on-demand plotting of time traces in a very flexible manner. In order to facilitate on-line tracking of experimental operation, the application also allows automatic refreshing of data. This software has been integrated into the TJ-II remote participation system distributed environment. Data are accessed remotely using web technologies and HTTP protocol and are transferred in a compressed format, which reduces bandwidth requirements. Both metadata and binary compressed data are transported in multi part messages. Message oriented middle ware software is used to distribute information on-line, in particular notifications of data availability for automatic data refreshing or local events. Plot layouts can be stored in a centralized database for subsequent recovery from anywhere. Finally, this software is integrated into the general security framework provided by the PAPI system. (Author) 16 refs.

  11. A traditional herbal medicine, rikkunshi-to (TJ-43), prevents intracellular signaling disorders in gastric smooth muscle of diabetic rats.

    Science.gov (United States)

    Sakai, Yasushi; Nobe, Koji; Maruyama, Yoshiaki; Momose, Kazutaka; Homma, Ikuo

    2004-01-01

    Prevention of diabetic gastrointestinal dysfunction is of utmost importance. The present study demonstrated that diacylglycerol kinase (DGK) activity in diabetic gastric smooth muscle in the resting state was approximately 3.5-fold greater than that in controls. However, oral administration of TJ-43 (1% of food intake) or subcutaneous insulin injection (12 units/kg/day) in streptozotocin-induced diabetic rats (DM) for 2 weeks prevented DGK abnormalities based on the control level. Increased DGK activity in the resting state of DM was inhibited significantly by R59022, neomycin or staurosporine; in contrast, these drugs did not affect DGK activity in controls, insulin-treated DM or TJ-43-treated DM. In controls, the endogenous phosphatidic acid (PA) level was inhibited significantly by R59022 or neomycin but not affected by staurosporine. On the other hand, these three drugs significantly inhibited endogenous PA levels in DM, and neomycin significantly inhibited endogenous PA levels in insulin-treated and TJ-43-treated DM. This suggests that TJ-43 could prevent alteration of DGK activity and PA formation without reduction of blood glucose levels. Moreover, these effects were greater than those of insulin treatment. Results suggested that TJ-43 treatment influenced the hyperreactivity of DGK and DAG formation via phospholipase C activity. In conclusion, TJ-43 can be recommended with respect to enhancement of the quality of life in patients displaying diabetic gastrointestinal complications.

  12. Modulation of tight junctions does not predict oral absorption of hydrophilic compounds: use of Caco-2 and Calu-3 cells.

    Science.gov (United States)

    Kamath, Amrita V; Morrison, Richard A; Mathias, Neil R; Dando, Sandra A; Marino, Anthony M; Chong, Saeho

    2007-08-01

    Permeability estimates using Caco-2 cells do not accurately predict the absorption of hydrophilic drugs that are primarily absorbed via the paracellular pathway. The objective of this study was to investigate whether modulation of tight junctions would help differentiation of paracellularly absorbed compounds. Tight junctions in Caco-2 cell monolayers were manipulated using calcium depletion approaches to decrease the transepithelial electrical resistance (TEER) of the monolayers, and permeability of hydrophilic compounds were measured under these conditions. Permeability of these compounds were also measured in Calu-3 cells, which have tighter junctions than Caco-2 cells. Calcium depletion loosened the tight junctions of Caco-2 cells to varying levels as measured by the decrease in TEER values of the monolayers. While the absolute permeability of all the model compounds increased as the tight junctions were loosened, the ratios of their permeability relative to mannitol permeability were similar. The permeability of these compounds in the tighter Calu-3 cells were also found to be similar to each other. Altering the tight junctions of Caco-2 cells to obtain leakier cell monolayers, or using a cell line with tighter junctions like Calu-3 cells, did not improve differentiation between well absorbed and poorly absorbed hydrophilic drugs. Mere manipulation of the tight junctions to increase or decrease transepithelial electrical resistance does not appear to be a viable approach to predict human absorption for hydrophilic compounds that are primarily absorbed via the paracellular pathway.

  13. The Wnt/planar cell polarity signaling pathway contributes to the integrity of tight junctions in brain endothelial cells

    OpenAIRE

    2013-01-01

    Wnt morphogens released by neural precursor cells were recently reported to control blood–brain barrier (BBB) formation during development. Indeed, in mouse brain endothelial cells, activation of the Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, was shown to stabilize endothelial tight junctions (TJs) through transcriptional regulation of the expression of TJ proteins. Because Wnt proteins activate several distinct β-catenin-dependent and independent signaling path...

  14. Volatile Anesthetics Influence Blood-Brain Barrier Integrity by Modulation of Tight Junction Protein Expression in Traumatic Brain Injury

    OpenAIRE

    Thal, Serge C.; Clara Luh; Eva-Verena Schaible; Ralph Timaru-Kast; Jana Hedrich; Luhmann, Heiko J.; Kristin Engelhard; Zehendner, Christoph M.

    2012-01-01

    Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortalityrnafter traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be importantrnto elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonularnoccludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anesthet...

  15. Spectroscopic system for impurity measurements in the TJ-1 Tokamak of JEN; Un sistema espectroscopico para medidas de impurezas en el Tokamak TJ-1 de la JEN

    Energy Technology Data Exchange (ETDEWEB)

    Navas, G.; Zurro, B.

    1982-07-01

    we describe a spectroscopic system with spatial resolution capability that has been configured for plasma diagnostic in the TJ-1 Tokamak of JEN. The experimental system, based on a one meter monochromator, has been absolutely calibrated using a tungsten-halogen lamp. The calibration procedures and the absolute spectral sensitivity are presented as well as its dependence with the polarization. A simplified spectroscopic model of the radiation emitted by the intrinsic plasma impurities (C, 0, . . . ) has been developed. A one dimensional model of the temporal evolution of various ionization stages in coronal equilibrium is used to predict the electron temperature and impurity concentration. This model has been applied to experimental data from several Tokamaks. (Author) 23 refs.

  16. Conditioning of TJ-II Stellarator during the ECRH Plasmas Period; Acondicionamiento del Stellarator TJ-II durante la Etapa de Plasmas ECRH

    Energy Technology Data Exchange (ETDEWEB)

    Tafalla, D.; Tabares, F.L.

    2001-07-01

    The TJ-II stellarator has been conditioned by glow discharge (GD) during the first campaigns of operation, working only with ECR heating and all metal walls. The application of a He GD during the overnight period before the operation has been required in order to obtain reproducible discharges. However, the density control of the ECRH discharges was not possible because of the He implanted on the wall during GS. An short Ar GD({<=}30 min) applied before the operation allows desorbes part of the implanted He. By applying this procedure (HeGD+ArGD), reproducible and density controlled plasmas have been achieved in H{sub 2} and He. (Author) 20 refs.

  17. Using tunnel junctions to grow monolithically integrated optically pumped semipolar III-nitride yellow quantum wells on top of electrically injected blue quantum wells.

    Science.gov (United States)

    Kowsz, Stacy J; Young, Erin C; Yonkee, Benjamin P; Pynn, Christopher D; Farrell, Robert M; Speck, James S; DenBaars, Steven P; Nakamura, Shuji

    2017-02-20

    We report a device that monolithically integrates optically pumped (20-21) III-nitride quantum wells (QWs) with 560 nm emission on top of electrically injected QWs with 450 nm emission. The higher temperature growth of the blue light-emitting diode (LED) was performed first, which prevented thermal damage to the higher indium content InGaN of the optically pumped QWs. A tunnel junction (TJ) was incorporated between the optically pumped and electrically injected QWs; this TJ enabled current spreading in the buried LED. Metalorganic chemical vapor deposition enabled the growth of InGaN QWs with high radiative efficiency, while molecular beam epitaxy was leveraged to achieve activated buried p-type GaN and the TJ. This initial device exhibited dichromatic optically polarized emission with a polarization ratio of 0.28. Future improvements in spectral distribution should enable phosphor-free polarized white light emission.

  18. Estimation of soil permeability

    Directory of Open Access Journals (Sweden)

    Amr F. Elhakim

    2016-09-01

    Full Text Available Soils are permeable materials because of the existence of interconnected voids that allow the flow of fluids when a difference in energy head exists. A good knowledge of soil permeability is needed for estimating the quantity of seepage under dams and dewatering to facilitate underground construction. Soil permeability, also termed hydraulic conductivity, is measured using several methods that include constant and falling head laboratory tests on intact or reconstituted specimens. Alternatively, permeability may be measured in the field using insitu borehole permeability testing (e.g. [2], and field pumping tests. A less attractive method is to empirically deduce the coefficient of permeability from the results of simple laboratory tests such as the grain size distribution. Otherwise, soil permeability has been assessed from the cone/piezocone penetration tests (e.g. [13,14]. In this paper, the coefficient of permeability was measured using field falling head at different depths. Furthermore, the field coefficient of permeability was measured using pumping tests at the same site. The measured permeability values are compared to the values empirically deduced from the cone penetration test for the same location. Likewise, the coefficients of permeability are empirically obtained using correlations based on the index soil properties of the tested sand for comparison with the measured values.

  19. Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS.

    LENUS (Irish Health Repository)

    Wilcz-Villega, E

    2013-11-29

    Increased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and claudin (CLD)-1 and associations with IBS symptoms.

  20. Hybrid tunnel junction contacts to III-nitride light-emitting diodes

    Science.gov (United States)

    Young, Erin C.; Yonkee, Benjamin P.; Wu, Feng; Oh, Sang Ho; DenBaars, Steven P.; Nakamura, Shuji; Speck, James S.

    2016-02-01

    In this work, we demonstrate highly doped GaN p-n tunnel junction (TJ) contacts on III-nitride heterostructures where the active region of the device and the top p-GaN layers were grown by metal organic chemical vapor deposition and highly doped n-GaN was grown by NH3 molecular beam epitaxy to form the TJ. The regrowth interface in these hybrid devices was found to have a high concentration of oxygen, which likely enhanced tunneling through the diode. For optimized regrowth, the best tunnel junction device had a total differential resistivity of 1.5 × 10-4 Ω cm2, including contact resistance. As a demonstration, a blue-light-emitting diode on a (20\\bar{2}\\bar{1}) GaN substrate with a hybrid tunnel junction and an n-GaN current spreading layer was fabricated and compared with a reference sample with a transparent conducting oxide (TCO) layer. The tunnel junction LED showed a lower forward operating voltage and a higher efficiency at a low current density than the TCO LED.

  1. Hybrid tunnel junction contacts to III–nitride light-emitting diodes

    KAUST Repository

    Young, Erin C.

    2016-01-26

    In this work, we demonstrate highly doped GaN p–n tunnel junction (TJ) contacts on III–nitride heterostructures where the active region of the device and the top p-GaN layers were grown by metal organic chemical vapor deposition and highly doped n-GaN was grown by NH3 molecular beam epitaxy to form the TJ. The regrowth interface in these hybrid devices was found to have a high concentration of oxygen, which likely enhanced tunneling through the diode. For optimized regrowth, the best tunnel junction device had a total differential resistivity of 1.5 × 10−4 Ω cm2, including contact resistance. As a demonstration, a blue-light-emitting diode on a ($20\\\\bar{2}\\\\bar{1}$) GaN substrate with a hybrid tunnel junction and an n-GaN current spreading layer was fabricated and compared with a reference sample with a transparent conducting oxide (TCO) layer. The tunnel junction LED showed a lower forward operating voltage and a higher efficiency at a low current density than the TCO LED.

  2. Expression of tight junction molecules in breast carcinomas analysed by array PCR and immunohistochemistry.

    Science.gov (United States)

    Tőkés, Anna-Mária; Szász, Attila Marcell; Juhász, Eva; Schaff, Zsuzsa; Harsányi, László; Molnár, István Arthur; Baranyai, Zsolt; Besznyák, István; Zaránd, Attila; Salamon, Ferenc; Kulka, Janina

    2012-07-01

    In the past few decades an enormous amount of data became known to clarify the molecular composition and architecture of tight junctions (TJs). Despite the efforts, the expression and function of several TJ genes and proteins in breast carcinoma are still not known and some of the data are contradictory. The expression of forty-four TJ associated genes was examined at mRNA level in eighteen invasive ductal breast carcinoma samples and corresponding normal breast tissues by using low density array PCR. Expressions of claudins (CLDNs) 5, 10, 16, 17, and 18, and ZO-1, ZO-2 were evaluated by immunohistochemistry as well. Using immunohistochemical phenotype as a surrogate for the genetic subtype, 11 luminal A, 3 luminal B, 3 triple negative and one HER2+ cases were included. Ten genes were significantly downregulated in tumors compared with normal breast tissues (CLDNs 5, 10, 16, 18, 19, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3), whereas one gene (CLDN17) was significantly up-regulated in tumors when compared with normal breast. At protein level CLDNs 5, 10, 16, 18, ZO-1 and ZO-2 were downregulated in tumors as compared with normal breast tissue. CLDN17 showed variable expression in tumor tissues in comparison to normal breast. In the single HER2+ tumor when compared with the other subtypes CLDNs 5, 16, 17, 18, CTNNAL1, JAM-B, ZO-1, ZO-2 and PARD3 genes were found to be upregulated. We found altered TJ genes and proteins whose expression has not yet been associated with breast carcinoma. Our findings show a tendency of TJ genes and proteins to be downregulated in breast cancer. Further studies are necessary to examine whether the downregulation of the above mentioned TJ associated genes and proteins may contribute to the malignant progression of invasive ductal breast carcinomas.

  3. Paracellular drug absorption enhancement through tight junction modulation

    OpenAIRE

    Lemmer, Hendrik Jacobus Righard; Josias H. Hamman

    2013-01-01

    Introduction: Inclusion of absorption-enhancing agents in dosage forms is one approach to improve the bioavailability of active pharmaceutical ingredients with low membrane permeability. Tight junctions are dynamic protein structures that form a regulated barrier for movement of molecules through the intercellular spaces across the intestinal epithelium. Some drug absorption enhancers are capable of loosening tight junctions and thereby facilitate paracellular absorption of drug molecules. ...

  4. Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall.

    Science.gov (United States)

    Blank, Fabian; Wehrli, Marc; Lehmann, Andrea; Baum, Oliver; Gehr, Peter; von Garnier, Christophe; Rothen-Rutishauser, Barbara M

    2011-01-01

    The human airway epithelium serves as structural and functional barrier against inhaled particulate antigen. Previously, we demonstrated in an in vitro epithelial barrier model that monocyte derived dendritic cells (MDDC) and monocyte derived macrophages (MDM) take up particulate antigen by building a trans-epithelial interacting network. Although the epithelial tight junction (TJ) belt was penetrated by processes of MDDC and MDM, the integrity of the epithelium was not affected. These results brought up two main questions: (1) Do MDM and MDDC exchange particles? (2) Are those cells expressing TJ proteins, which are believed to interact with the TJ belt of the epithelium to preserve the epithelial integrity? The expression of TJ and adherens junction (AJ) mRNA and proteins in MDM and MDDC monocultures was determined by RT-PCR, and immunofluorescence, respectively. Particle uptake and exchange was quantified by flow cytometry and laser scanning microscopy in co-cultures of MDM and MDDC exposed to polystyrene particles (1 μm in diameter). MDM and MDDC constantly expressed TJ and AJ mRNA and proteins. Flow cytometry analysis of MDM and MDDC co-cultures showed increased particle uptake in MDDC while MDM lost particles over time. Quantitative analysis revealed significantly higher particle uptake by MDDC in co-cultures of epithelial cells with MDM and MDDC present, compared to co-cultures containing only epithelial cells and MDDC. We conclude from these findings that MDM and MDDC express TJ and AJ proteins which could help to preserve the epithelial integrity during particle uptake and exchange across the lung epithelium.

  5. Active gate driving method for reliability improvement of IGBTs via junction temperature swing reduction

    DEFF Research Database (Denmark)

    Luo, Haoze; Iannuzzo, Francesco; Ma, Ke

    2016-01-01

    This paper introduces an advanced gate driver used as thermal swing control method for the reduction of AC load current-related ΔTj in Insulated-Gate Bipolar Transistors (IGBTs). A switchable gate resistor network is applied to the advanced gate driver, so that the switching power losses can...... be changed according to the amplitude of AC current. Accordingly, a closed-loop thermal control method including the functions of root-mean-square calculation and phase analysis is proposed. Hence ΔTj can be reduced by means of changing losses-related gate resistors on the basis of output fundamental...... frequency and amplitude of AC load current. As a result, longer device useful life duration can be achieved. Furthermore, the maximum junction temperature under high-temperature operation can be reduced by means of the proposed method. Simulations and experiments are provided to validate the effectiveness...

  6. 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.

  7. Single hole spectral function and spin-charge separation in the t-J model

    OpenAIRE

    Mishchenko, A.; Prokof'ev, N. V.; Svistunov, B. V.

    2001-01-01

    Worm algorithm quantum Monte Carlo simulations of the hole Green function with subsequent spectral analysis were performed for J/t 0.1, 0.2, 0.4 on lattices with up to LxL=32x32 sites at temperatures as low as T=J/40, and present, apparently, the hole spectral function in the thermodynamic limit. Spectral analysis reveals a delta-function-sharp quasiparticle peak at the lower edge of the spectrum which is incompatible with the power-law singularity and thus rules out the possibility of spin-c...

  8. t-J Model Then and Now: a Personal Perspective from the Pioneering Times

    Science.gov (United States)

    Spałek, J.

    2007-04-01

    In this overview we sketch briefly the path to the so-called t-J model derived for the first time 30 years ago and provide its original meaning within the theory of strongly correlated magnetic metals with a non-Fermi (non-Landau) liquid ground state. An emergence of the concept of real space pairing is discussed in a historical prospective. A generalization of this model to the many-orbital situation is briefly discussed. The emphasis is put on didactical exposition of ideas, as they were transformed into mathematical language. The concept of hybrid pairing is introduced in the same context at the end.

  9. Current ripple in the coils of the TJ-II Spanish stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Perez, A.; Acero, J.; Alberdi, B.; Del Rio, J.M. [JEMA SA, Lasarte-Oria (Spain); Almoguera, L.; Blaumoser, M.; Kirpitchev, I.; Mendez, P. [Asociacion EURATOM-CIEMAT para Fusion, Madrid (Spain)

    1995-12-31

    High precision coil current control, stability and ripple content are very important aspects for a stellarator design. The TJ-II coils will be supplied by network commutated current converters and therefore the coil currents will contain harmonics which have to be kept to a very low level. An analytical investigation as well as numerous simulations with EMTP, SABER{reg_sign} and other softwares, have been done in order to predict the harmonic currents and to verify the completion with the specified maximum levels. The calculations and the results are presented.

  10. Permeability prediction in chalks

    DEFF Research Database (Denmark)

    Alam, Mohammad Monzurul; Fabricius, Ida Lykke; Prasad, Manika

    2011-01-01

    The velocity of elastic waves is the primary datum available for acquiring information about subsurface characteristics such as lithology and porosity. Cheap and quick (spatial coverage, ease of measurement) information of permeability can be achieved, if sonic velocity is used for permeability....... The relationships between permeability and porosity from core data were first examined using Kozeny’s equation. The data were analyzed for any correlations to the specific surface of the grain, Sg, and to the hydraulic property defined as the flow zone indicator (FZI). These two methods use two different approaches...... to enhance permeability prediction fromKozeny’s equation. The FZI is based on a concept of a tortuous flow path in a granular bed. The Sg concept considers the pore space that is exposed to fluid flow and models permeability resulting from effective flow parallel to pressure drop. The porosity-permeability...

  11. Feasibility Studies of the Two Filters Method in TJ-II for Electron Temperature Measurements in High Density Plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Baiao, D.; Medina, F.; Ochando, M.; Varandas, C.

    2009-07-01

    The TJ-II plasma soft X-ray emission was studied in order to establish an adequate setup for an electron temperature diagnostic suitable for high density, with spatial and temporal resolutions, based on the two-filters method. The preliminary experimental results reported were obtained with two diagnostics (an X-ray PHA based on a Ge detector and a tomography system) already installed in TJ-II stellarator. These results lead to the conclusion that the two-filters method was a suitable option for an electron temperature diagnostic for high-density plasmas in TJ-II. We present the design and fi rst results obtained with a prototype for the measurement of electron temperature in TJ-II plasmas heated with energetic neutral beams. This system consists in two AXUV20A detectors which measure the soft X-ray plasma emissivity trough beryllium filters of different thickness. From the two-filters technique it is possible to estimate the electron temperature. The analyses carried out allowed concluding which filter thicknesses are most suited for TJ-II plasmas, and enhanced the need of a computer code to simulate signals and plasma compositions. (Author) 7 refs.

  12. The TJ-II Relational Database Access Library: A User's Guide; Libreria de Acceso a la Base de Datos Relacional de TJ-II: Guia del Usuario

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, E.; Portas, A. B.; Vega, J.

    2003-07-01

    A relational database has been developed to store data representing physical values from TJ-II discharges. This new database complements the existing TJ-EI raw data database. This database resides in a host computer running Windows 2000 Server operating system and it is managed by SQL Server. A function library has been developed that permits remote access to these data from user programs running in computers connected to TJ-II local area networks via remote procedure cali. In this document a general description of the database and its organization are provided. Also given are a detailed description of the functions included in the library and examples of how to use these functions in computer programs written in the FORTRAN and C languages. (Author) 8 refs.

  13. Molecular electronic junction transport

    DEFF Research Database (Denmark)

    Solomon, Gemma C.; Herrmann, Carmen; Ratner, Mark

    2012-01-01

    Whenasinglemolecule,oracollectionofmolecules,isplacedbetween two electrodes and voltage is applied, one has a molecular transport junction. We discuss such junctions, their properties, their description, and some of their applications. The discussion is qualitative rather than quantitative, and f...

  14. Performance of Surfactant Methyl Ester Sulphonate solution for Oil Well Stimulation in reservoir sandstone TJ Field

    Science.gov (United States)

    Eris, F. R.; Hambali, E.; Suryani, A.; Permadi, P.

    2017-05-01

    Asphaltene, paraffin, wax and sludge deposition, emulsion and water blocking are kinds ofprocess that results in a reduction of the fluid flow from the reservoir into formation which causes a decrease of oil wells productivity. Oil well Stimulation can be used as an alternative to solve oil well problems. Oil well stimulation technique requires applying of surfactant. Sodium Methyl Ester Sulphonate (SMES) of palm oil is an anionic surfactant derived from renewable natural resource that environmental friendly is one of potential surfactant types that can be used in oil well stimulation. This study was aimed at formulation SMES as well stimulation agent that can identify phase transitions to phase behavior in a brine-surfactant-oil system and altered the wettability of rock sandstone and limestone. Performance of SMES solution tested by thermal stability test, phase behavioral examination and rocks wettability test. The results showed that SMES solution (SMES 5% + xylene 5% in the diesel with addition of 1% NaCl at TJformation water and SMES 5% + xylene 5% in methyl ester with the addition of NaCl 1% in the TJ formation water) are surfactant that can maintain thermal stability, can mostly altered the wettability toward water-wet in sandstone reservoir, TJ Field.

  15. Radial electric field computations with DKES and neoclassical models in TJ-II stellarator

    Science.gov (United States)

    Martinell, Julio; Gutierrez-Tapia, Cesar; Lopez-Bruna, Daniel

    2015-11-01

    Radial electric fields arise due to the non-ambipolar transport in stellarator plasmas and play an important role in determining some improved confinement regimes. In order to calculate this electric field it is necessary to take all particle fluxes that are not ambipolar. The most important contribution to these fluxes comes from neoclassical transport. Here we use particle fluxes obtained from kinetic equation computations using the code DKES to evaluate the radial electric field profiles for certain discharges of the heliac TJ-II. Experimental profiles for the density and temperatures are used together with the diffusion coefficients obtained with DKES. A similar computation of the electric field is performed with three analytical neoclassical models that use an approximation for the magnetic geometry. The ambipolar electric field from the models is compared with the one given by DKES and we find that they are all qualitatively similar. They are also compared with experimental measurements of the electric field obtained with HIBP. It is shown that, although the electric field is reasonably well reproduced by the neoclassical computations, especially in high temperature regimes, the particle fluxes are not. Thus, neoclassical theory provides good Er estimates in TJ-II. Support from CONACyT 152905 and DGAPA IN109115 projects is acknowledged.

  16. Software architecture of data acquisition control process during TJ-II operation

    Science.gov (United States)

    Vega, J.; Crémy, C.; Sánchez, E.; Portas, A.; Dormido, S.

    1997-01-01

    Data from the diagnostics on the TJ-II device will be collected by several independent systems linked to local area networks (LANs). Some of these systems will consist of digitizers based on well-known standards: CAMAC, VME, VXI, etc. Other allowable systems would be personal computers or workstations with direct control over a specific diagnostic. In principal, any equipment capable of being linked in a LAN can be used as a controller for data collection. All systems will be programmed from a central computer. In this computer, an application program will allow the set up of data acquisition in any system. This will be achieved by communicating systems through a network standard protocol: TCP/IP. The central computer will also centralize the database of discharges. For this purpose, immediately after a discharge, data will be sent from the autonomous systems to the main computer. The latter will coordinate data reception, organize discharge information, and compress data. Data will be transferred rapidly so all diagnostic signals will be available to users for immediate analysis. The computer processes outlined here will provide an application program to provide users with an interface for all operations related to data acquisition, fast signal analysis, and remote control of diagnostics. A second functionality will be the management of TJ-II discharge database.

  17. Investigation of three-dimensional turbulent structures in the torsatron TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Mahdizadeh, N.

    2007-02-14

    In this work, for the first time, the three-dimensional nature of drift waves has been verified experimentally inside the confinement region of the toroidal plasma in TJ-K. The perpendicular dynamics of turbulence has been studied with the focus on the poloidal wavenumber spectra and the scaling of the turbulent structure with the drift scale. To this end, a 64 tip Langmuir probe array has been used, which is poloidally positioned on a flux surface. For the first time, the parallel dynamics of turbulence has been investigated in the core of a toroidally confined plasma. In contrast to previous experiments, multi-probe measurements were carried out to get simultaneous information on the shape and the propagation direction of the turbulent structures. The results for the parallel wave number and the parallel propagation velocity have been compared with results from the simulation code GEM3. It is demonstrated that the propagation in the direction parallel to the magnetic field is affected by Alfven dynamics. Together, these results strongly confirm previous investigations, which have demonstrated the importance of drift-wave turbulence in TJ-K and therefore also in fusion edge plasma. (orig.)

  18. Plasma density determination by microwave interferometry .- The 2 mm interferometer of the TJ-1 Tokamak; Determinacion de la densidad de un plasma por interferometria de microondas. El interferometro de 2 mm del Tokamak TJ-1

    Energy Technology Data Exchange (ETDEWEB)

    Martin, R.; Manero, F.

    1984-07-01

    In this paper a description is given of the microwave interferometer used for measuring the plasma electronic density in the TJ-1 Tokamak of Fusion Division of JEN. The principles of the electronic density measurement are discussed in detail, as well as those concerning the determination of density pro files from experimental data. A description of the interferometer used in the TJ-1 Tokamak is given, together with a detailed analysis of the circuits which constitute the measuring chain. The working principles of the klystron reflex and hybrid rings are also presented. (Author) 23 refs.

  19. Exit points, on plasma, of lost fast ions during NBI in TJ-II; Puntos de salida en el plasma de los iones rapidos durante NBI en el TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Guasp, J.

    1995-07-01

    The distribution of the exit points, on plasma border, for the lost fast ions during tangential balanced NBI in TJ-II helical axis Stellarator is theoretically analysed, as well for direct as for delayed losses. The link between, the position of those exit points and the corresponding at birth, orbits and drifts is analysed also. It is shown that such relation is rather independent of beam energy and plasma density and is mainly related to the magnetic configuration characteristics. This study is a needed intermediate step to the analysis of impacts of those ions on the vacuum vessel of TJ-II. (Author) 2 refs.

  20. Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway.

    Science.gov (United States)

    Sivagurunathan, Suganya; Palanisamy, Karthikka; Arunachalam, Jayamuruga Pandian; Chidambaram, Subbulakshmi

    2017-03-01

    PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected. Further analysis showed that the expression of tight junction (TJ) proteins, CLDN1, and TJP1 were altered in HIWI2 knockdown. Moreover, confocal imaging revealed disrupted TJP1 assembly at the TJ. Previous studies report the role of GSK3β in regulating TJ proteins. Accordingly, phospho-kinase proteome profiler array indicated increased phosphorylation of Akt and GSK3α/β in HIWI2 knockdown, suggesting that HIWI2 might affect TJ proteins through Akt-GSK3α/β signaling axis. Moreover, treating the HIWI2 knockdown cells with wortmannin increased the levels of TJP1 and CLDN1. Taken together, our study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt.

  1. NBI Calculations for the TJ-II Experimental Discharges; Ajustes de los Perfiles Radiales de Densidad y Temperatura para las Descargas con NBI del TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Guasp, J.; Fuentes, C.; Liniers, M.

    2005-07-01

    The density and electron temperature radial profiles, corresponding to the experimental TJ-II campaigns 2003-2004, with NBI, have been fitted to simple functionals in order to allow a fast approximative evaluation for any given density and injected power... The fits have been calculated, separately, for the four possibilities: ECRH and NBI Phases as well as On and Off Axis ECRH injection. The average difference between the experimental profiles for the individual discharges and the fit predictions are around 8% for the density and 10% for the temperature. The behaviour of the predicted profiles with average line density and injected power has been analysed. The central electron temperature decreases monotonically with increasing density and the ECRH phase On Axis central value is clearly higher than the Off axis one. The radial density profiles narrow with increasing density and the NBI On axis case is clearly wider than de Off one. The electron temperature profile widens slightly with increasing density and the width of the On Axix case is lesser than for the Off case in all phases. There exist Fortran subroutines, available at the three CIEMAT computers, allowing the fast approximative evaluation of all these profiles. (Author) 8 refs.

  2. The Normal-incidence Vacuum-ultraviolet Spectrometer for the TJ-II and First Experimental Results

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, K.J.; Zurro, B.; Baciero, A.

    2002-07-01

    A normal-incidence spectrometer, operating in the extreme-ultraviolet and ultraviolet wavelength regions, has been commissioned for the TJ-II stellarator. The instrument has been custom built by McPherson, Chelmsford, MA, and has several unique features and accessories that are described here. The instrument and CCD detector has been tested and calibrated, and its performance evaluated, using spectral lines from glow discharges and a RF excited flow lamp. Finally, the first spectra collected with the instrument of TJ-II plasmas are presented and a preliminary estimation of an oxygen ion temperature is made. (Author) 23 refs.

  3. Hot spices influence permeability of human intestinal epithelial monolayers.

    Science.gov (United States)

    Jensen-Jarolim, E; Gajdzik, L; Haberl, I; Kraft, D; Scheiner, O; Graf, J

    1998-03-01

    Indirect evidence suggests that hot spices may interact with epithelial cells of the gastrointestinal tract to modulate their transport properties. Using HCT-8 cells, a cell line from a human ileocoecal carcinoma, we studied the effects of spices on transepithelial electrical resistance (TER), permeability for fluorescein isothiocyanate (FITC)-labeled dextrans with graded molecular weight, and morphological alterations of tight junctions by immunofluorescence using an anti-ZO-1 antibody, a marker for tight junction integrity. Two different reactivity patterns were observed: paprika and cayenne pepper significantly decreased the TER and increased permeability for 10-, 20- and 40-kDa dextrans but not for -70 kDa dextrans. Simultaneously, tight junctions exhibited a discontinuous pattern. Applying extracts from black or green pepper, bay leaf or nutmeg increased the TER and macromolecular permeability remained low. Immunofluorescence ZO-1 staining was preserved. In accordance with the above findings, capsaicin transiently reduced resistance and piperine increased resistance, making them candidates for causing the effects seen with crude spice extracts. The observation that Solanaceae spices (paprika, cayenne pepper) increase permeability for ions and macromolecules might be of pathophysiological importance, particularly with respect to food allergy and intolerance.

  4. Magnetic Shear and Transport in ECRH Discharges of the TJ-II under Ohmic Induction

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Bruna, D.; Castejon, F.; Romero, J. A.; Estrada, T.; Medina, F.; Ochando, M.; Lopez-Fraguas, A.; Ascasibar, E.; Herranz, J.; Sanchez, E.; Luna, E. de la; Pastor, I.

    2006-07-01

    TJ-II is ha heliac type stellarator characterised by high, but almost constant, vacuum rotational transform throughout the confining volume. In ECRH plasmas, moderate induced ohmic currents (negligible heating and modification of the magnetic field nodules) are enough to disregard the bootstrap contribution, which allows us performing a fair calculation of the evolution of the rotational transform. We use the loop voltage diagnostic to estimate the plasma electrical conductivity. Then the evolution of the rotational transform and shear is related to changes in the profiles of electron and thermal diffusivities: negative shear correlates with decreasing diffusivities in the region of steepest density gradient; transport increases toward zero shear but the achieved positive values are too small to draw conclusions. The radial sweeping of lowest order rational magnetic surfaces does not determine the observed trends in transport. (Author)43 refs.

  5. Image processing methods for noise reduction in the TJ-II Thomson Scattering diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    Dormido-Canto, S., E-mail: sebas@dia.uned.es [Departamento de Informatica y Automatica, UNED, Madrid 28040 (Spain); Farias, G. [Pontificia Universidad Catolica de Valparaiso, Valparaiso (Chile); Vega, J.; Pastor, I. [Asociacion EURATOM/CIEMAT para Fusion, Madrid 28040 (Spain)

    2012-12-15

    Highlights: Black-Right-Pointing-Pointer We describe an approach in order to reduce or mitigate the stray-light on the images and show the exceptional results. Black-Right-Pointing-Pointer We analyze the parameters to take account in the proposed process. Black-Right-Pointing-Pointer We report a simplified exampled in order to explain the proposed process. - Abstract: The Thomsom Scattering diagnostic of the TJ-II stellarator provides temperature and density profiles. The CCD camera acquires images corrupted with noise that, in some cases, can produce unreliable profiles. The main source of noise is the so-called stray-light. In this paper we describe an approach that allows mitigation of the effects that stray-light has on the images: extraction regions with connected-components. In addition, the robustness and effectiveness of the noise reduction technique is validated in two ways: (1) supervised classification and (2) comparison of electron temperature profiles.

  6. Dynamics of zonal flow-like structures in the edge of the TJ-II stellarator

    CERN Document Server

    Alonso, J A; Arévalo, J; Hidalgo, C; Pedrosa, M A; Van Milligen, B Ph; Carralero, D

    2012-01-01

    The dynamics of fluctuating electric field structures in the edge of the TJ-II stellarator, that display zonal flow-like traits, is studied. These structures have been shown to be global and affect particle transport dynamically [J.A. Alonso et al., Nucl. Fus. 52 063010 (2012)]. In this article we discuss possible drive (Reynolds stress) and damping (Neoclassical viscosity, geodesic transfer) mechanisms for the associated ExB velocity. We show that: (a) while the observed turbulence-driven forces can provide the necessary perpendicular acceleration, a causal relation could not be firmly established, possibly because of the locality of the Reynolds stress measurements, (b) the calculated neoclassical viscosity and damping times are comparable to the observed zonal flow relaxation times, and (c) although an accompanying density modulation is observed to be associated to the zonal flow, it is not consistent with the excitation of pressure side-bands, like those present in geodesic acoustic oscillations, caused b...

  7. Multi-tier approach for data acquisition programming in the TJ-II remote participation system

    Science.gov (United States)

    Vega, J.; Sánchez, E.; Portas, A.; Ruiz, M.; Barrera, E.; López, S.

    2004-10-01

    Programming software to setup acquisition channels during device operation has been developed for the TJ-II remote participation system. The software follows a three-tier model. A first tier (client tier) groups client software containing only user interface code. A second tier (middle tier) includes code for authorization, authentication, and query processing. A third tier (data tier) consists of a relational database server for managing configurations. Multi-platform characteristics are provided by web browsers (client tier) and web servers (middle tier). This architecture avoids that data acquisition system controllers provide access control, database support, or graphic user interface resources. Therefore, computation capabilities of these systems can mainly be devoted to data handling. LabView (from National Instruments) has been used as programming language in the acquisition systems. This design allows a very transparent management of signals, independently on hardware modules and systems.

  8. Exact thermodynamics and phase diagram of integrable t-J model with chiral interaction

    Science.gov (United States)

    Tavares, T. S.; Ribeiro, G. A. P.

    2016-09-01

    We study the phase diagram and finite temperature properties of an integrable generalization of the one-dimensional super-symmetric t-J model containing interactions explicitly breaking parity-time reversal (PT) symmetries. To this purpose, we apply the quantum transfer matrix method which results in a finite set of non-linear integral equations. We obtain numerical solutions to these equations leading to results for thermodynamic quantities as a function of temperature, magnetic field, particle density and staggering parameter. Studying the maxima lines of entropy at low but non zero temperature reveals the phase diagram of the model. There are ten different phases which we may classify in terms of the qualitative behaviour of auxiliary functions, closely related to the dressed energy functions.

  9. Doped Heisenberg chains: Spin-S generalizations of the supersymmetric t-J model

    Energy Technology Data Exchange (ETDEWEB)

    Frahm, Holger E-mail: frahm@itp.uni-hannover.de

    1999-10-25

    A family of exactly solvable models describing a spin S Heisenberg chain doped with mobile spin-(S - ((1)/(2))) carriers is constructed from gl(2|1)-invariant solutions of the Yang-Baxter equation. The models are generalizations of the supersymmetric t-J model which is obtained for S ((1)/(2)). We solve the model by means of the algebraic Bethe Ansatz and present results for the zero temperature and thermodynamic properties. At low temperatures the models show spin charge separation, i.e. contain contributions of a free bosonic theory in the charge sector and an SU(2)-invariant theory describing the magnetic excitations. For small carrier concentration the latter can be decomposed further into an SU(2) level-2S Wess-Zumino-Novikov-Witten model and the minimal unitary model M{sub p} with p 2S + 1.

  10. Breakdown of the Nagaoka phase in the two-dimensional t-J model

    Science.gov (United States)

    Eisenberg, E.; Berkovits, R.; Huse, David A.; Altshuler, B. L.

    2002-04-01

    In the limit of weak exchange J at low hole concentration δ the ground state of the two-dimensional t-J model is believed to be ferromagnetic. We study the leading instability of this Nagaoka state, which emerges with increasing J. Both exact diagonalization of small clusters, and a semiclassical analytical calculation of larger systems show that above a certain critical value of the exchange, Jcr~tδ2, Nagaoka's state is unstable to phase separation. In a finite-size system a bubble of antiferromagnetic Mott insulator appears in the ground state above this threshold. The size of this bubble depends on δ and scales as a power of the system size N.

  11. A Farewell to modernism? Re-reading T.J. Clark

    Directory of Open Access Journals (Sweden)

    Raymond Spiteri

    2010-12-01

    Full Text Available 'Farewell to an Idea: Episodes from a History of Modernism' offers an opportunity to consider T.J. Clark’s contribution to the discipline of art history. Farewell transforms the polemical tone of the social history of art into to an elegy for modernism’s unrealized promise. Yet an attentive reading of its argument discloses a far more subtle intervention within recent attempts to revise the history of modernism. This paper will consider these issues through a discussion of Farewell, focusing of the performative dimension of Clark’s argument, which renders on a rhetorical level the aesthetic strategies of the modernist avant-garde. Clark’s program for the social history of art may remain unfulfilled, yet it is exemplary in this failure.

  12. An experimental system for spectral line ratio measurements in the TJ-II stellarator.

    Science.gov (United States)

    Zurro, B; Baciero, A; Fontdecaba, J M; Peláez, R; Jiménez-Rey, D

    2008-10-01

    The chord-integrated emissions of spectral lines have been monitored in the TJ-II stellarator by using a spectral system with time and space scanning capabilities and relative calibration over the entire UV-visible spectral range. This system has been used to study the line ratio of lines of different ionization stages of carbon (C(5+) 5290 A and C(4+) 2271 A) for plasma diagnostic purposes. The local emissivity of these ions has been reconstructed, for quasistationary profiles, by means of the inversion Fisher method described previously. The experimental line ratio is being empirically studied and in parallel a simple spectroscopic model has been developed to account for that ratio. We are investigating whether the role played by charge exchange processes with neutrals and the existence of non-Maxwellian electrons, intrinsic to Electron Cyclotron Resonance Heating (ECRH) heating, leave any distinguishable mark on this diagnostic method.

  13. Finite-Temperature Phase Diagram of the d=3 tJ Model with Quenched Disorder

    Science.gov (United States)

    Berker, A. Nihat; Hinczewski, Michael

    2008-03-01

    We study a quenched disordered d=3 tJ Hamiltonian with static vacancies as a model of nonmagnetic impurities in high-Tc materials.[1,2] Using a position-space renormalization-group approach, we calculate the evolution of the finite-temperature phase diagram with impurity concentration p, and find several features with close experimental parallels: away from half-filling we see the rapid destruction of a spin-singlet liquid phase (analogous to the superconducting phase in cuprates) which is eliminated for p >=0.05; in the same region for these dilute impurity concentrations we observe an enhancement of antiferromagnetism. The antiferromagnetic phase near half-filling is robust against impurity addition, and disappears only for p >=0.40. [1] M. Hinczewski and A.N. Berker, Eur. Phys. J. B 51, 461 (2006). [2] M. Hinczewski and A.N. Berker, arXiv:cond-mat/0607171v1 [cond-mat.str-el].

  14. Density Dependence of Particle Transport in ECH Plasmas of the TJ-II Stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, V. I.; Lopez-Bruna, D.; Guasp, J.; Herranz, J.; Estrada, T.; Medina, F.; Ochando, M.A.; Velasco, J.L.; Reynolds, J.M.; Ferreira, J.A.; Tafalla, D.; Castejon, F.; Salas, A.

    2009-05-21

    We present the experimental dependence of particle transport on average density in electron cyclotron heated (ECH) hydrogen plasmas of the TJ-II stellarator. The results are based on: (I) electron density and temperature data from Thomson Scattering and reflectometry diagnostics; (II) a transport model that reproduces the particle density profiles in steady state; and (III) Eirene, a code for neutrals transport that calculates the particle source in the plasma from the particle confinement time and the appropriate geometry of the machine/plasma. After estimating an effective particle diffusivity and the particle confinement time, a threshold density separating qualitatively and quantitatively different plasma transport regimes is found. The poor confinement times found below the threshold are coincident with the presence of ECH-induced fast electron losses and a positive radial electric field all over the plasma. (Author) 40 refs.

  15. Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.

    Science.gov (United States)

    Bardet, Claire; Courson, Frédéric; Wu, Yong; Khaddam, Mayssam; Salmon, Benjamin; Ribes, Sandy; Thumfart, Julia; Yamaguti, Paulo M; Rochefort, Gael Y; Figueres, Marie-Lucile; Breiderhoff, Tilman; Garcia-Castaño, Alejandro; Vallée, Benoit; Le Denmat, Dominique; Baroukh, Brigitte; Guilbert, Thomas; Schmitt, Alain; Massé, Jean-Marc; Bazin, Dominique; Lorenz, Georg; Morawietz, Maria; Hou, Jianghui; Carvalho-Lobato, Patricia; Manzanares, Maria Cristina; Fricain, Jean-Christophe; Talmud, Deborah; Demontis, Renato; Neves, Francisco; Zenaty, Delphine; Berdal, Ariane; Kiesow, Andreas; Petzold, Matthias; Menashi, Suzanne; Linglart, Agnes; Acevedo, Ana Carolina; Vargas-Poussou, Rosa; Müller, Dominik; Houillier, Pascal; Chaussain, Catherine

    2016-03-01

    Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients. © 2015 American Society for Bone and Mineral Research.

  16. Plasma fuelling with cryogenic pellets in the stellarator TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, K. J. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain); Panadero, N. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain); Velasco, J. L. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain); Combs, S. K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Caughman, J. B. O. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Fontdecaba, J. M. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain); Foust, C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); García, R. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain); Hernández Sánchez, J. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain); Navarro, M. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain); Pastor, I. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain); Soleto, A. [Research Centre for Energy, Environment and Technology (CIEMAT), Madrid (Spain)

    2017-04-04

    Cryogenic pellet injection is a widely used technique for delivering fuel to the core of magnetically confined plasmas. Indeed, such systems are currently functioning on many tokamak, reversed field pinch and stellarator devices. A pipe-gun-type pellet injector is now operated on the TJ-II, a low-magnetic shear stellarator of the heliac type. Cryogenic hydrogen pellets, containing between 3×1018 and 4×1019 atoms, are injected at velocities between 800 and 1200 m s-1 from its low-field side into plasmas created and/or maintained in this device by electron cyclotron resonance and/or neutral beam injection heating. In this paper, the first systematic study of pellet ablation, particle deposition and fuelling efficiency is presented for TJ-II. From this, light-emission profiles from ablating pellets are found to be in reasonable agreement with simulated pellet ablation profiles (created using a neutral gas shielding-based code) for both heating scenarios. In addition, radial offsets between recorded light-emission profiles and particle deposition profiles provide evidence for rapid outward drifting of ablated material that leads to pellet particle loss from the plasma. Finally, fuelling efficiencies are documented for a range of target plasma densities (~4×1018– ~2×1019 m-3). These range from ~20%– ~85% and are determined to be sensitive to pellet penetration depth. Additional observations, such as enhanced core ablation, are discussed and planned future work is outlined.

  17. Plasma fuelling with cryogenic pellets in the stellarator TJ-II

    Science.gov (United States)

    McCarthy, K. J.; Panadero, N.; Velasco, J. L.; Combs, S. K.; Caughman, J. B. O.; Fontdecaba, J. M.; Foust, C.; García, R.; Hernández Sánchez, J.; Navarro, M.; Pastor, I.; Soleto, A.; the TJ-II Team

    2017-05-01

    Cryogenic pellet injection is a widely used technique for delivering fuel to the core of magnetically confined plasmas. Indeed, such systems are currently functioning on many tokamak, reversed field pinch and stellarator devices. A pipe-gun-type pellet injector is now operated on the TJ-II, a low-magnetic shear stellarator of the heliac type. Cryogenic hydrogen pellets, containing between 3  ×  1018 and 4  ×  1019 atoms, are injected at velocities between 800 and 1200 m s-1 from its low-field side into plasmas created and/or maintained in this device by electron cyclotron resonance and/or neutral beam injection heating. In this paper, the first systematic study of pellet ablation, particle deposition and fuelling efficiency is presented for TJ-II. From this, light-emission profiles from ablating pellets are found to be in reasonable agreement with simulated pellet ablation profiles (created using a neutral gas shielding-based code) for both heating scenarios. In addition, radial offsets between recorded light-emission profiles and particle deposition profiles provide evidence for rapid outward drifting of ablated material that leads to pellet particle loss from the plasma. Finally, fuelling efficiencies are documented for a range of target plasma densities (~4  ×  1018-  ~2  ×  1019 m-3). These range from ~20%-  ~85% and are determined to be sensitive to pellet penetration depth. Additional observations, such as enhanced core ablation, are discussed and planned future work is outlined.

  18. One-dimensional t-J model with next-nearest-neighbor hopping : Breakdown of the Luttinger liquid

    NARCIS (Netherlands)

    Eder, R; Ohta, Y.

    1997-01-01

    We investigate the effect of a next-nearest-neighbor hopping integral t' in the one-dimensional t-J model, using Lanczos diagonalization of finite chains. Even moderate values of t' have a dramatic effect on the dynamical correlation functions and Fermi-surface topology. The high-energy holon bands

  19. Boundary state of $U_q(\\hat{gl}(N|N))$ analog of half-infinite $t-J$ model

    CERN Document Server

    Kojima, Takeo

    2015-01-01

    The $U_q(\\hat{gl}(N|N))$-analog of the half-infinite $t-J$ model with a boundary is considered by using the vertex operator approach. We find explicit bosonic formula of the boundary state in the integrable highest-weight module over the quantum superalgebra $U_q(\\hat{gl}(N|N))$.

  20. Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis.

    Science.gov (United States)

    Nakamoto, Hidetomo; Mimura, Taku; Honda, Nobuko

    2008-10-01

    Maintenance of the red blood cell volume is a fundamental aspect of ensuring oxygen supply to the tissue. Recombinant human erythropoietin (rHuEPO) was approved for marketing in Japan in 1990 for the treatment of anemia in patients on dialysis. Recombinant human erythropoietin caused a significant increase in hemoglobin (Hb) levels in patients on dialysis. However, not all have a good response to rHuEPO therapy; the causes of rHuEPO failure include iron deficiency, infection, uremia, and interaction of some drugs. Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia, or fatigue. To clarify the effect of TJ-48 on erythropoietin-resistant anemia, we studied the effect of TJ-48 in patients on hemodialysis with erythropoietin-resistant anemia. We divided 42 end-stage renal disease patients on hemodialysis with erythropoietin-resistant anemia (Hbrenal disease patients. This effect was, at least in part, due to the anti-inflammatory effect of TJ-48 in patients on hemodialysis.

  1. Permeability of edible coatings.

    Science.gov (United States)

    Mishra, B; Khatkar, B S; Garg, M K; Wilson, L A

    2010-01-01

    The permeabilities of water vapour, O2 and CO2 were determined for 18 coating formulations. Water vapour transmission rate ranged from 98.8 g/m(2).day (6% beeswax) to 758.0 g/m(2).day (1.5% carboxymethyl cellulose with glycerol). O2 permeability at 14 ± 1°C and 55 ± 5% RH ranged from 1.50 to 7.95 cm(3)cm cm(-2)s(-1)Pa(-1), with CO2 permeability 2 to 6 times as high. Permeability to noncondensable gases (O2 and CO2) was higher for hydrophobic (peanut oil followed by beeswax) coatings as compared to hydrophilic (whey protein concentrate and carboxymethyl cellulose).

  2. Permeability of edible coatings

    OpenAIRE

    B Mishra; Khatkar, B. S.; Garg, M. K.; Wilson, L.A.

    2010-01-01

    The permeabilities of water vapour, O2 and CO2 were determined for 18 coating formulations. Water vapour transmission rate ranged from 98.8 g/m2.day (6% beeswax) to 758.0 g/m2.day (1.5% carboxymethyl cellulose with glycerol). O2 permeability at 14 ± 1°C and 55 ± 5% RH ranged from 1.50 to 7.95 cm3cm cm−2s−1Pa−1, with CO2 permeability 2 to 6 times as high. Permeability to noncondensable gases (O2 and CO2) was higher for hydrophobic (peanut oil followed by beeswax) coatings as compared to hydrop...

  3. Soils - Mean Permeability

    Data.gov (United States)

    Kansas Data Access and Support Center — This digital spatial data set provides information on the magnitude and spatial pattern of depth-weighted, mean soil permeability throughout the State of Kansas. The...

  4. Permeable pavement study (Edison)

    Data.gov (United States)

    U.S. Environmental Protection Agency — While permeable pavement is increasingly being used to control stormwater runoff, field-based, side-by-side investigations on the effects different pavement types...

  5. Claudin-2 knockout by TALEN-mediated gene targeting in MDCK cells: claudin-2 independently determines the leaky property of tight junctions in MDCK cells.

    Directory of Open Access Journals (Sweden)

    Shinsaku Tokuda

    Full Text Available Tight junctions (TJs regulate the movements of substances through the paracellular pathway, and claudins are major determinants of TJ permeability. Claudin-2 forms high conductive cation pores in TJs. The suppression of claudin-2 expression by RNA interference in Madin-Darby canine kidney (MDCK II cells (a low-resistance strain of MDCK cells was shown to induce a three-fold increase in transepithelial electrical resistance (TER, which, however, was still lower than in high-resistance strains of MDCK cells. Because RNA interference-mediated knockdown is not complete and only reduces gene function, we considered the possibility that the remaining claudin-2 expression in the knockdown study caused the lower TER in claudin-2 knockdown cells. Therefore, we investigated the effects of claudin-2 knockout in MDCK II cells by establishing claudin-2 knockout clones using transcription activator-like effector nucleases (TALENs, a recently developed genome editing method for gene knockout. Surprisingly, claudin-2 knockout increased TER by more than 50-fold in MDCK II cells, and TER values in these cells (3000-4000 Ω·cm2 were comparable to those in the high-resistance strains of MDCK cells. Claudin-2 re-expression restored the TER of claudin-2 knockout cells dependent upon claudin-2 protein levels. In addition, we investigated the localization of claudin-1, -2, -3, -4, and -7 at TJs between control MDCK cells and their respective knockout cells using their TALENs. Claudin-2 and -7 were less efficiently localized at TJs between control and their knockout cells. Our results indicate that claudin-2 independently determines the 'leaky' property of TJs in MDCK II cells and suggest the importance of knockout analysis in cultured cells.

  6. Magnetic tunnel junctions (MTJs)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We review the giant tunnel magnetoresistance (TMR) in ferromagnetic-insulator-ferromagnetic junctions discovered in recent years, which is the magnetoresistance (MR) associated with the spin-dependent tunneling between two ferromagnetic metal films separated by an insulating thin tunnel barrier. The theoretical and experimental results including junction conductance, magnetoresistance and their temperature and bias dependences are described.

  7. Stacked Josephson Junctions

    DEFF Research Database (Denmark)

    Madsen, Søren Find; Pedersen, Niels Falsig; Christiansen, Peter Leth

    2010-01-01

    Long Josephson junctions have for some time been considered as a source of THz radiation. Solitons moving coherently in the junctions is a possible source for this radiation. Analytical computations of the bunched state and bunching-inducing methods are reviewed. Experiments showing THz radiation...

  8. Claudin-4 Overexpression in Epithelial Ovarian Cancer Is Associated with Hypomethylation and Is a Potential Target for Modulation of Tight Junction Barrier Function Using a C-Terminal Fragment of Clostridium perfringens Enterotoxin

    Directory of Open Access Journals (Sweden)

    Babak Litkouhi

    2007-04-01

    Full Text Available BACKGROUND: Claudin-4, a tight junction (TJ protein and receptor for the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE, is overexpressed in epithelial ovarian cancer (EOC. Previous research suggests DNA methylation is a mechanism for claudin-4 overexpression in cancer and that C-CPE acts as an absorption-enhancing agent in claudin-4expressing cells. We sought to correlate claudin-4 overexpression in EOC with clinical outcomes and TJ barrier function, investigate DNA methylation as a mechanism for overexpression, and evaluate the effect of C-CPE on the TJ. METHODS: Claudin-4 expression in EOC was quantified and correlated with clinical outcomes. Claudin-4 methylation status was determined, and claudin-4-negative cell lines were treated with a demethylating agent. Electric cell-substrate impedance sensing was used to calculate junctional (paracellular resistance (Rb in EOC cells after claudin-4 silencing and after C-CPE treatment. RESULTS: Claudin4 overexpression in EOC does not correlate with survival or other clinical endpoints and is associated with hypomethylation. Claudin-4 overexpression correlates with Rb and C-CPE treatment of EOC cells significantly decreased Rb in a dose- and claudin-4-dependent noncytotoxic manner. CONCLUSIONS: C-CPE treatment of EOC cells leads to altered TJ function. Further research is needed to determine the potential clinical applications of C-CPE in EOC drug delivery strategies.

  9. Biostable glucose permeable polymer

    DEFF Research Database (Denmark)

    2017-01-01

    A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing...... a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer...

  10. Estimation of the average junction temperature of two phosphors-converted white LED array based on (B + Y + R)/B ratio

    Science.gov (United States)

    Ke, Hong-Liang; Jing, Lei; Hao, Jian; Gao, Qun; Wang, Yao; Wang, Xiao-xun; Sun, Qiang; Xu, Zhi-Jun

    2016-07-01

    The method of non-contact measurement of the junction temperature (Tj) for phosphor-converted white LEDs based on W/B ratio, the ratio of the total radiant energy (W) to the radiant energy of blue emission (B), is verified firstly. It is shown that for two phosphors (Y3Al5O12:Ce and CaAlSiN3:Eu)-converted white LEDs, an significant uncertainty is introduced into the linearity between Tj and W/B ratio. Then a new approach is proposed which uses (B + Y + R)/B ratio, the ratio of the sum of radiant energies of blue emission (B), yellow emission (Y) and red emission (R) to the radiant energy of blue emission, to establish the correlation with Tj. Result shows that the proposed approach is of a satisfactory linearity between Tj and (B + Y + R)/B ratio, with R-square equal to 0.9906 and RMSE equal to 2.27 °C. It is also demonstrated that the proposed method is applicable to actual LED lighting system composed of large number of LEDs.

  11. Gap-junction-mediated cell-to-cell communication.

    Science.gov (United States)

    Hervé, Jean-Claude; Derangeon, Mickaël

    2013-04-01

    Cells of multicellular organisms need to communicate with each other and have evolved various mechanisms for this purpose, the most direct and quickest of which is through channels that directly connect the cytoplasms of adjacent cells. Such intercellular channels span the two plasma membranes and the intercellular space and result from the docking of two hemichannels. These channels are densely packed into plasma-membrane spatial microdomains termed "gap junctions" and allow cells to exchange ions and small molecules directly. A hemichannel is a hexameric torus of junctional proteins around an aqueous pore. Vertebrates express two families of gap-junction proteins: the well-characterized connexins and the more recently discovered pannexins, the latter being related to invertebrate innexins ("invertebrate connexins"). Some gap-junctional hemichannels also appear to mediate cell-extracellular communication. Communicating junctions play crucial roles in the maintenance of homeostasis, morphogenesis, cell differentiation and growth control in metazoans. Gap-junctional channels are not passive conduits, as previously long regarded, but use "gating" mechanisms to open and close the central pore in response to biological stimuli (e.g. a change in the transjunctional voltage). Their permeability is finely tuned by complex mechanisms that have just begun to be identified. Given their ubiquity and diversity, gap junctions play crucial roles in a plethora of functions and their dysfunctions are involved in a wide range of diseases. However, the exact mechanisms involved remain poorly understood.

  12. Detecting the Exchange Phase of Majorana Bound States in a Corbino Geometry Topological Josephson Junction.

    Science.gov (United States)

    Park, Sunghun; Recher, Patrik

    2015-12-11

    A phase from an adiabatic exchange of Majorana bound states (MBS) reveals their exotic anyonic nature. For detecting this exchange phase, we propose an experimental setup consisting of a Corbino geometry Josephson junction on the surface of a topological insulator, in which two MBS at zero energy can be created and rotated. We find that if a metallic tip is weakly coupled to a point on the junction, the time-averaged differential conductance of the tip-Majorana coupling shows peaks at the tip voltages eV=±(α-2πl)ℏ/T_{J}, where α=π/2 is the exchange phase of the two circulating MBS, T_{J} is the half rotation time of MBS, and l an integer. This result constitutes a clear experimental signature of Majorana fermion exchange.

  13. Dynamical Simulation of Recycling and Particle Fueling in TJ-II Plasmas; Simulacion Dinamica del Reciclado y de la Inyeccion de Particulas en los Plasmas del TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Bruna, D.; Ferreira, J. A.; Tabares, F. L.; Castejon, F.; Guasp, J.

    2007-07-20

    With the aim of improving the calculation tools for transport analysis in TJ-II plasmas, in this work we analyze the simplified model for a kinetic equation that ASTRA uses to calculate the neutral particle distribution in the plasma. Next, we act on the boundary conditions for this kinetic equation (particularly on the neutral density in the plasma boundary) so we can simulate the recycling conditions for the TJ-II in a simple way. With the resulting transport models we can easily analyze the sensibility of these plasmas to the cold gas puffing depending on the recycling conditions. These transport models evidence the problem of density control in the TJ-II. Likewise, we estimate the importance of recycling in the plasmas heated by energetic neutral beam injection. The experimentally observed increments in density when the energetic neutrals are injected would respond, according to the calculations here presented, to a large increment of the neutrals influx that cannot be explained by the beam itself. (Author) 22 refs.

  14. Origin of the Degradation of Triple Junction Solar Cells at low Temperature

    Directory of Open Access Journals (Sweden)

    Park Seonyong

    2017-01-01

    Full Text Available The degradation of solar cells under irradiation by high energy particles (electrons, protons is the consequence of the introduction of defects trapping minority carriers, which are then not collected by the junction. However, at low temperature, defects located in the space charge region can also induce a tunneling current that results in an apparent decreases of the maximum power. The degradation produced by this tunneling current can depend on temperature, since the concentration of defects created by an irradiation is usually temperature dependent, and can be larger than the degradation associated with carrier recombination. For instance, as we shall see below, an irradiation with 1 MeV electrons at 120 K with a fluence of 3.0 × 1015 /cm2 induces a decrease of less than 10 % in the short-circuit current (Isc and open-circuit voltage (Voc of triple junction (TJ cells, but a decrease of about 40 % in the maximum power (Pmax, which implies that more than half of the total degradation of Pmax should be assigned to another loss mechanism, tunneling in this case. In this work, we demonstrate that this additional degradation must indeed be ascribed to a tunneling process and we investigate the variation of the tunneling current versus fluence induced by electron irradiation in TJ cells, in order to tentatively ascribe the tunneling components to specific sub-cells.

  15. Effect of fast electrons on the stability of resistive interchange modes in the TJ-II stellarator

    Energy Technology Data Exchange (ETDEWEB)

    García, L. [Universidad Carlos III de Madrid, Avda. de la Universidad 30, 28911 Leganés, Madrid (Spain); Ochando, M. A.; Hidalgo, C.; Milligen, B. Ph. van [CIEMAT - Laboratorio Nacional de Fusión, Avda. Complutense 40, 28040 Madrid (Spain); Carreras, B. A. [BACV Solutions, 110 Mohawk Road, Oak Ridge, Tennessee 37830 (United States); Carralero, D. [Max-Planck-Institute for Plasma Physics, Boltzmannstr. 2, Garching (Germany)

    2016-06-15

    In this paper, we report on electromagnetic phenomena in low-β plasmas at the TJ-II stellarator, controlled by external heating. To understand the observations qualitatively, we introduce a simple modification of the standard resistive MHD equations, to include the potential impact of fast electrons on instabilities. The dominant instabilities of the modeling regime are resistive interchange modes, and calculations are performed in a configuration with similar characteristics as the TJ-II stellarator. The main effect of the trapping of fast electrons by magnetic islands induced by MHD instabilities is to increase the magnetic component of the fluctuations, changing the character of the instability to tearing-like and modifying the frequency of the modes. These effects seem to be consistent with some of the experimental observations.

  16. Kundupplevd tjänstekvalitet inom logistiken i ett företagsnätverk : En fallstudie ur Stockmannvaruhusens perspektiv

    OpenAIRE

    Fagerström, Hans-Christian

    2009-01-01

    Avsikten med detta arbete var att studera kundupplevd tjänstekvalitet och problem i ett logistiskt företagsnätverk. Nätverket, en företagstriad i Finland, bestående av en leverantör av färdigvaruprodukter inom hemelektronik, en speditör, som levererar produkterna till kunder och en kund som fungerar som återförsäljare av färdigvaruprodukterna. Undersökningen utfördes som en kvalitativ fallstudie där man genom teori om företags-nätverk, logistikens flödesperspektiv och tjänstekvalitet gic...

  17. Dependence of intermittent density fluctuations on collisionality in TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Reuther, Kyle; Garland, Stephen; Ramisch, Mirko [Institut fuer Grenzflaechenverfahrenstechnikund Plasmatechnologie, Universitaet Stuttgart (Germany); Manz, Peter [Physik-Department E28, Technische Universitaet Muenchen, Garching (Germany)

    2016-07-01

    Particle and heat transport losses due to edge turbulence are well known phenomena commonly seen in toroidal magnetic confinement devices. Furthermore in the scrape-off layer (SOL), turbulent density fluctuations are often observed to be intermittent and dominate particle transport to the vessel walls. In the adiabatic limit (small collisionality), of the two-field Hasegawa-Wakatani model, simulated turbulent density fluctuations are observed to couple to potential fluctuations and exhibit Gaussian behavior. However, in the hydrodynamic limit (large collisionality) the density and potential decouple. As a result, the density becomes passively advected, evolves towards the vorticity, and exhibits intermittent behavior. The relationship between collisionality and intermittency is investigated experimentally at the stellarator TJ-K. To vary the plasma collisionality, which is related to electron density and temperature, parameters such as gas type, neutral gas pressure, magnetic field, and heating power are varied. Radial profiles of plasma density, temperature, floating potential, and vorticity are recorded via a scanning 7-tip Langmuir probe array. First results are presented.

  18. Edge and Plasma -Wall Interaction Diagnostics in the TJ-II Stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Tabares, F. L.; Tafalla, D.; Branas, B.; Hidalgo, A.; Garcia-Cortes, I.; Lopez-Fraguas, A.; Ortiz, P.

    2003-07-01

    The operation of the TJ-II stellarator, carried out under ECR heating conditions until now, the plasma edge parameters and those processes has been identified. Therefore, an important , has implieda careful control of partied e sources and the associated plasma-wall interaction processes. A clear coupling between the plasma edge parameters and those processes has been identified. Therefore, an important effort has been devoted to the development of dedicated diagnostics in both fields. Remarkable success has been attained in the development of atomic-beam based edge diagnostics, namely, thermal Li and supersonic He beams. In particular, fast (up to 200 Hz) sampling of temperature and density profiles has been made possible thorough an upgraded version of the pulsed, supersonic He beam diagnostic. In this paper, whorl devoted to the upgrading of these techniques is described. Also, preliminary experiments oriented to the validation of the collisional radiative models use din the beam-based diagnostic interpretaron as well as simulations of Laser Induced Fluorescence (LIF) studies of level populations of electronically excited He atoms are shown. (Author) 17 refs.

  19. Effects of increased microwave heating power in the stellarator TJ-K

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, Alejandro; Koehn, Alf; Ali, Ahmed; Ramisch, Mirko [Institute of Interfacial Process Engineering and Plasma Technology, University of Stuttgart, Stuttgart (Germany)

    2015-05-01

    One of the microwave heating systems at the stellarator TJ-K has been recently upgraded: a third klystron has been installed, increasing the heating power from 4 kW to 6 kW operating at 14 GHz. A phased-array antenna is used which allows to vary the injection angle by sweeping the microwave frequency in order control the coupling mechanism of the microwave to the plasma. With the two klystrons already installed, ionization degrees of α ≅ 1 have been reached. We expect that an increased heating power, by means of the third klystron put into operation, leads to an increase in the electron temperature T{sub e} only, rather than in electron density n{sub e}, and thus a decrease in the collision frequency ν{sub ei} ∝ n{sub e}T{sub e}{sup -3/2} which has an impact on heating flow damping and neoclassical properties. Parameter scans have been performed in order to characterize the new heating scenario. A radial movable Langmuir probe has been used to obtain radial profiles of the electron density and temperature. An arrangement of bolometers and an optical diode have been used to obtain the power losses by radiation. A particle and power balance model is used to obtain estimated densities and temperatures in order to compare with the experimental results.

  20. Continuous Plasma density measurement in TJ-II infrared interferometer-Advanced signal processing based on FPGAs

    OpenAIRE

    2010-01-01

    This work presents the behavioral simulation in an FPGA of a novel processing system for measuring line average electronic density in the TJ-II stellarator diagnostic, Infra-Red Two-Color Interferometer. Line average electronic density is proportional to phase difference between probing and reference signals of the interferometer, as the Appleton–Hartree cold plasma model states. The novelty of the approach is the development of a real time measuring system where research work has been carrie...

  1. Adriamycin increases podocyte permeability: evidence and molecular mechanism

    Institute of Scientific and Technical Information of China (English)

    李晓忠; 袁海涛; 张学光

    2003-01-01

    Objective To investigate the increased podocyte permeability by evidence of adriamycin (AD) and its molecular mechanism.Methods In this study, we explored the direct effects of AD on cultured mouse podocytes and the potential protection effects of Dexamethasome (Dex).Results After 24-hour AD (5×10-7 mol/L) treatment, albumin passage through podocyte monolayers was increased by 2.27-fold (P<0.01). AD caused a 62% decrease in Zonula Occluden -1 (ZO-1) protein (P<0.05), suggesting that AD might increase podocyte permeability by disrupting tight junctions. Dex (1×10-6 mol/L), co-administered with AD, protected podocytes from AD-induced increased albumin passage. This may be linked with an increased P-cadherin protein level to 1.93 fold of control (P<0.01).Conclusions AD has a direct, detrimental effect on podocyte permeability, probably through disrupting tight junctions; Dex could protect against AD-induced high podocyte permeability by upregulating adherent protein P-cadherin.

  2. Equivalent Josephson junctions

    Science.gov (United States)

    Boyadjiev, T. L.; Semerdjieva, E. G.; Shukrinov, Yu. M.

    2008-01-01

    The magnetic field dependences of critical current are numerically constructed for a long Josephson junction with a shunt-or resistor-type microscopic inhomogeneities and compared to the critical curve of a junction with exponentially varying width. The numerical results show that it is adequate to replace the distributed inhomogeneity of a long Josephson junction by an inhomogeneity localized at one of its ends, which has certain technological advantages. It is also shown that the critical curves of junctions with exponentially varying width and inhomogeneities localized at the ends are unaffected by the mixed fluxon-antifluxon distributions of the magnetic flow. This fact may explain the improvement of the spectra of microwave radiation noted in the literature.

  3. Quantum Junction Solar Cells

    KAUST Repository

    Tang, Jiang

    2012-09-12

    Colloidal quantum dot solids combine convenient solution-processing with quantum size effect tuning, offering avenues to high-efficiency multijunction cells based on a single materials synthesis and processing platform. The highest-performing colloidal quantum dot rectifying devices reported to date have relied on a junction between a quantum-tuned absorber and a bulk material (e.g., TiO 2); however, quantum tuning of the absorber then requires complete redesign of the bulk acceptor, compromising the benefits of facile quantum tuning. Here we report rectifying junctions constructed entirely using inherently band-aligned quantum-tuned materials. Realizing these quantum junction diodes relied upon the creation of an n-type quantum dot solid having a clean bandgap. We combine stable, chemically compatible, high-performance n-type and p-type materials to create the first quantum junction solar cells. We present a family of photovoltaic devices having widely tuned bandgaps of 0.6-1.6 eV that excel where conventional quantum-to-bulk devices fail to perform. Devices having optimal single-junction bandgaps exhibit certified AM1.5 solar power conversion efficiencies of 5.4%. Control over doping in quantum solids, and the successful integration of these materials to form stable quantum junctions, offers a powerful new degree of freedom to colloidal quantum dot optoelectronics. © 2012 American Chemical Society.

  4. The visible intensified cameras for plasma imaging in the TJ-II stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Cal, E. de la; Carralero, D.; Pablos, J.L. de; Alonso, A.; Rios, L.; Garcia Sanchez, P.; Hidalgo, C. (Laboratorio Nacional de Fusion, Asociacion Euratom-Ciemat, Av. Complutense 22, E-28040 Madrid)

    2011-09-15

    Visible cameras are widely used in fusion experiments for diagnosis and for machine safety issues. They are generally used to monitor the plasma emission, but are also sensible to surface Blackbody radiation and Bremsstrahlung. Fast or high speed cameras capable of operating in the 10{sup 5} frames per second speed range are today commercially available and offer the opportunity to plasma fusion researchers of two-dimensional (2D) imaging of fast phenomena such as turbulence, ELMs, disruptions, dust, etc. The tracking of these fast phenomena requires short exposure times down to the {mu} s range and the light intensity can be often near the signal to noise ratio limit especially in low plasma emission regions such as the far SOL Additionally, when using interference filters to monitor, e.g. impurity line emission, the photon flux is strongly reduced and the emission cannot be imaged at high speed. Therefore, the use of image intensifiers that amplify the light intensity onto the camera sensor can be of great help. The present work describes the use of intensifiers in the visible fast cameras of TJ-II stellarator. We have achieved spectroscopic plasma imaging of filtered impurity atomic line emission at short exposure times down to the 10 {mu} s range depending on atomic line and concentration. Additionally, plasma movies at velocities of 2x10{sup 5} frames per second near the camera operation limit can be recorded with exposure times well below 1 {mu} s with sufficient signal to noise ratio. Although an increasing degradation of the image quality appears when raising the light amplification, an effective gain of up to two orders of magnitude of the light intensity is feasible for many applications (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  5. Structure of the gap junction channel and its implications for its biological functions.

    Science.gov (United States)

    Maeda, Shoji; Tsukihara, Tomitake

    2011-04-01

    Gap junctions consist of arrays of intercellular channels composed of integral membrane proteins called connexin in vertebrates. Gap junction channels regulate the passage of ions and biological molecules between adjacent cells and, therefore, are critically important in many biological activities, including development, differentiation, neural activity, and immune response. Mutations in connexin genes are associated with several human diseases, such as neurodegenerative disease, skin disease, deafness, and developmental abnormalities. The activity of gap junction channels is regulated by the membrane voltage, intracellular microenvironment, interaction with other proteins, and phosphorylation. Each connexin channel has its own property for conductance and molecular permeability. A number of studies have tried to reveal the molecular architecture of the channel pore that should confer the connexin-specific permeability/selectivity properties and molecular basis for the gating and regulation. In this review, we give an overview of structural studies and describe the structural and functional relationship of gap junction channels.

  6. The epithelial membrane protein 1 is a novel tight junction protein of the blood-brain barrier.

    Science.gov (United States)

    Bangsow, Thorsten; Baumann, Ewa; Bangsow, Carmen; Jaeger, Martina H; Pelzer, Bernhard; Gruhn, Petra; Wolf, Sabine; von Melchner, Harald; Stanimirovic, Danica B

    2008-06-01

    In the central nervous system, a constant microenvironment required for neuronal cell activity is maintained by the blood-brain barrier (BBB). The BBB is formed by the brain microvascular endothelial cells (BMEC), which are sealed by tight junctions (TJ). To identify genes that are differentially expressed in BMEC compared with peripheral endothelial cells, we constructed a subtractive cDNA library from porcine BMEC (pBMEC) and aortic endothelial cells (AOEC). Screening the library for differentially expressed genes yielded 26 BMEC-specific transcripts, such as solute carrier family 35 member F2 (SLC35F2), ADP-ribosylation factor-like 5B (ARL5B), TSC22 domain family member 1 (TSC22D1), integral membrane protein 2A (ITM2A), and epithelial membrane protein 1 (EMP1). In this study, we show that EMP1 transcript is enriched in pBMEC compared with brain tissue and that EMP1 protein colocalizes with the TJ protein occludin in mouse BMEC by coimmunoprecipitation and in rat brain vessels by immunohistochemistry. Epithelial membrane protein 1 expression was transiently induced in laser-capture microdissected rat brain vessels after a 20-min global cerebral ischemia, in parallel with the loss of occludin immunoreactivity. The study identifies EMP1 as a novel TJ-associated protein of the BBB and suggests its potential role in the regulation of the BBB function in cerebral ischemia.

  7. Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood–brain barrier primary triple coculture model

    Directory of Open Access Journals (Sweden)

    Xu L

    2015-09-01

    Full Text Available Liming Xu,1,2,* Mo Dan,1,* Anliang Shao,1 Xiang Cheng,1,3 Cuiping Zhang,4 Robert A Yokel,5 Taro Takemura,6 Nobutaka Hanagata,6 Masami Niwa,7,8 Daisuke Watanabe7,81National Institutes for Food and Drug Control, No 2, Temple of Heaven, Beijing, 2School of Information and Engineering, Wenzhou Medical University, Wenzhou, 3School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 4Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China; 5College of Pharmacy, University of Kentucky, Lexington, KY, USA; 6Nanotechnology Innovation Station for Nanoscale Science and Technology, National Institute for Materials Science, Tsukuba, Ibaraki, 7Department of Pharmacology, Nagasaki University, 8BBB Laboratory, PharmaCo-Cell Company, Ltd., Nagasaki, Japan*These authors contributed equally to this workBackground: Silver nanoparticles (Ag-NPs can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood–brain barrier (BBB and the underlying mechanism(s of action on the BBB and the brain are not well understood.Method: To investigate Ag-NP suspension (Ag-NPS-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM. Global gene expression of astrocytes was measured using a DNA microarray.Results: A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200 Ω·cm2. After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the

  8. Reversible Opening of Intercellular Junctions of Intestinal Epithelial and Brain Endothelial Cells With Tight Junction Modulator Peptides.

    Science.gov (United States)

    Bocsik, Alexandra; Walter, Fruzsina R; Gyebrovszki, Andrea; Fülöp, Lívia; Blasig, Ingolf; Dabrowski, Sebastian; Ötvös, Ferenc; Tóth, András; Rákhely, Gábor; Veszelka, Szilvia; Vastag, Monika; Szabó-Révész, Piroska; Deli, Mária A

    2016-02-01

    The intercellular junctions restrict the free passage of hydrophilic compounds through the paracellular clefts. Reversible opening of the tight junctions of biological barriers is investigated as one of the ways to increase drug delivery to the systemic circulation or the central nervous system. Six peptides, ADT-6, HAV-6, C-CPE, 7-mer (FDFWITP, PN-78), AT-1002, and PN-159, acting on different integral membrane and linker junctional proteins were tested on Caco-2 intestinal epithelial cell line and a coculture model of the blood-brain barrier. All peptides tested in nontoxic concentrations showed a reversible tight junctions modulating effect and were effective to open the paracellular pathway for the marker molecules fluorescein and albumin. The change in the structure of cell-cell junctions was verified by immunostaining for occludin, claudin-4,-5, ZO-1, β-catenin, and E-cadherin. Expression levels of occludin and claudins were measured in both models. We could demonstrate a selectivity of C-CPE, ADT-6, and HAV-6 peptides for epithelial cells and 7-mer and AT-1002 peptides for brain endothelial cells. PN-159 was the most effective modulator of junctional permeability in both models possibly acting via claudin-1 and -5. Our results indicate that these peptides can be effectively and selectively used as potential pharmaceutical excipients to improve drug delivery across biological barriers.

  9. GaInP/GaAs tandem solar cells with highly Te-and Mg-doped GaAs tunnel junctions grown by MBE

    Institute of Scientific and Technical Information of China (English)

    郑新和; 刘三姐; 夏宇; 甘兴源; 王海啸; 王乃明; 杨辉

    2015-01-01

    We report a GaInP/GaAs tandem solar cell with a novel GaAs tunnel junction (TJ) with using tellurium (Te) and magnesium (Mg) as n- and p-type dopants via dual-filament low temperature effusion cells grown by molecular beam epitaxy (MBE) at low temperature. The test Te/Mg-doped GaAs TJ shows a peak current density of 21 A/cm2. The tandem solar cell by the Te/Mg TJ shows a short-circuit current density of 12 mA/cm2, but a low open-circuit voltage range of 1.4 V∼1.71 V under AM1.5 illumination. The secondary ion mass spectroscopy (SIMS) analysis reveals that the Te doping is unexpectedly high and its doping profile extends to the Mg doping region, thus possibly resulting in a less abrupt junction with no tunneling carriers effectively. Furthermore, the tunneling interface shifts from the intended GaAs n++/p++junction to the AlGaInP/GaAs junction with a higher bandgap AlGaInP tunneling layers, thereby reducing the tunneling peak. The Te concentration of∼2.5 × 1020 in GaAs could cause a lattice strain of 10−3 in magnitude and thus a surface roughening, which also negatively influences the subsequent growth of the top subcell and the GaAs contacting layers. The doping features of Te and Mg are discussed to understand the photovoltaic response of the studied tandem cell.

  10. Bovine Colostrum Supplementation During Running Training Increases Intestinal Permeability

    Directory of Open Access Journals (Sweden)

    Grant D. Brinkworth

    2009-12-01

    Full Text Available Endurance exercise training can increase intestinal permeability which may contribute to the development of gastrointestinal symptoms in some athletes. Bovine colostrum (BC supplementation reduces intestinal permeability induced by non-steroidal anti-inflammatory drugs. This study aimed to determine whether BC could also reduce intestinal permeability induced by endurance exercise. Thirty healthy adult males (25.0 ± 4.7 yr; mean ± SD completed eight weeks of running three times per week for 45 minutes at their lactate threshold while consuming 60 g/day of BC, whey protein (WP or control (CON. Intestinal permeability was assessed at baseline and after eight weeks by measuring the ratio of urinary lactulose (L and rhamnose (R excretion. After eight weeks the L/R ratio increased significantly more in volunteers consuming BC (251 ± 140% compared with WP (21 ± 35%, P < 0.05 and CON (−7 ± 13%, P < 0.02. The increase in intestinal permeability with BC may have been due to BC inducing greater leakiness of tight junctions between enterocytes or by increasing macromolecular transport as it does in neonatal gut. Further research should investigate the potential for BC to increase intestinal macromolecular transport in adults.

  11. Application of TJ281-BEP new waterproof coiled materials in the tunnel project%TJ281-BEP新型防水卷材在隧道工程中的应用

    Institute of Scientific and Technical Information of China (English)

    武秀萍

    2001-01-01

    针对隧道施工过程中常见的隧道渗漏水问题,结合具体工程实例,提出了采用TJ281-BEP隧道专用型背贴背吊带式高分子土工复合排防水卷材是解决该问题的有效方法,并叙述了该方法在施工中的施工工艺、注意事项及工艺特点,得到了较好的应用效果.

  12. First Toroidal Rotation Measurements of Protons and Impurities in the TJ-II Stellarator; Primeras Medidas de Rotacion Toroidal de Protones e Impurezas en el Stellarator TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Rapisarda, D.; Zurro, B.; Baciero, A.

    2006-07-01

    First absolute toroidal rotation measurements in the TJ-II stellarator, by using passive emission spectroscopy, are presented. The wavelength calibration is performed by using a spectral system which combines the spectra coming from the plasma and from a lamp in real time. Measurements have been made both for protons and some impurity ions (C4+, He+), in discharges created by electron cyclotron resonance heating, and in discharges with neutral beam injection heating. In addition, a description of the systems as well as the calibration procedures an data analysis is addressed. (Author) 10 refs.

  13. Relative permeability through fractures

    Energy Technology Data Exchange (ETDEWEB)

    Diomampo, Gracel, P.

    2001-08-01

    The mechanism of two-phase flow through fractures is of importance in understanding many geologic processes. Currently, two-phase flow through fractures is still poorly understood. In this study, nitrogen-water experiments were done on both smooth and rough parallel plates to determine the governing flow mechanism for fractures and the appropriate methodology for data analysis. The experiments were done using a glass plate to allow visualization of flow. Digital video recording allowed instantaneous measurement of pressure, flow rate and saturation. Saturation was computed using image analysis techniques. The experiments showed that gas and liquid phases flow through fractures in nonuniform separate channels. The localized channels change with time as each phase path undergoes continues breaking and reforming due to invasion of the other phase. The stability of the phase paths is dependent on liquid and gas flow rate ratio. This mechanism holds true for over a range of saturation for both smooth and rough fractures. In imbibition for rough-walled fractures, another mechanism similar to wave-like flow in pipes was also observed. The data from the experiments were analyzed using Darcy's law and using the concept of friction factor and equivalent Reynold's number for two-phase flow. For both smooth- and rough-walled fractures a clear relationship between relative permeability and saturation was seen. The calculated relative permeability curves follow Corey-type behavior and can be modeled using Honarpour expressions. The sum of the relative permeabilities is not equal one, indicating phase interference. The equivalent homogeneous single-phase approach did not give satisfactory representation of flow through fractures. The graphs of experimentally derived friction factor with the modified Reynolds number do not reveal a distinctive linear relationship.

  14. 乳酸菌对感染肠上皮细胞通透性及紧密连接蛋白表达的影响%Effect of Lactobacillus plantarun onlly regulating intestinal epithelial permeability and tight junction response to pathogenic bacteria

    Institute of Scientific and Technical Information of China (English)

    张中伟; 秦环龙

    2007-01-01

    目的:研究乳酸菌对侵袭性大肠杆菌(EIEC) 感染肠上皮细胞(Caco-2)后,对其通透性和紧密连接(TJ)蛋白表达的影响. 方法:建立Caco-2 单层细胞感染模型.实验分为正常组、感染组、乳酸菌组和庆大霉素组.用电阻仪测定单层细胞的跨膜电阻值(TER),用高效液相法(HPLC)测定甘露醇透过率的变化,采用免疫组化法观察TJ相关蛋白,如Claudin-1蛋白,Occludin蛋白, JAM-1蛋白,ZO-1蛋白的分布和结构变化. 结果:EIEC感染Caco-2细胞后,单层细胞的TER值和甘露醇的透过率随时间延长而升高,而经乳酸菌处理后,TER值升高趋缓(P<0.05),甘露醇的透过率降低(P<0.05);EIEC感染后,相邻Caco-2细胞间TJ结构遭到破坏,TJ相关蛋白的表达亦减少,而乳酸菌处理后可使EIEC引起的TJ结构受损减轻、相关蛋白的表达增多. 结论:乳酸菌黏附于肠上皮细胞Caco-2后,可抑制EIEC破坏单层细胞的完整性,并改善TJ的结构变化和相关蛋白的表达分布.

  15. Permeability measuremens of brazilian Eucalyptus

    Directory of Open Access Journals (Sweden)

    Marcio Rogério da Silva

    2010-09-01

    Full Text Available The permeability of Brazilian Eucalyptus grandis and Eucalyptus citriodora wood was measured in a custom build gas analysis chamber in order to determine which species could be successfully treated with preservatives. Liquid permeability was tested using an emulsion of Neen oil and a control of distillated water. Air was used to test the gas phase permeability. For both Eucalyptus grandis and Eucalyptus citriodora, the longitudinal permeability of gas was shown to be about twice as great as the liquid phase permeability. No radial permeability was observed for either wood. The permeability of air and water through the sapwood of Eucalyptus grandis was greater than that through the sapwood of Eucalyptus citriodora. The permeability of neen oil preservative through the sapwood of Eucalyptus grandis was also greater than through the sapwood of E. Citradora, but the difference was not statistically significant. Scanning Electron Microscopy images showed that the distribution and obstruction in the vessels could be correlated with observed permeability properties. Irrespective of the causes of differences in permeability between the species, the fluid phase flux through the sapwood of both species was significant, indicating that both Eucalyptus grandis and Eucalyptus citriodora could be successfully treated with wood preservative.

  16. Dopamine enhances duodenal epithelial permeability via the dopamine D5 receptor in rodent.

    Science.gov (United States)

    Feng, X-Y; Zhang, D-N; Wang, Y-A; Fan, R-F; Hong, F; Zhang, Y; Li, Y; Zhu, J-X

    2017-05-01

    The intestinal barrier is made up of epithelial cells and intercellular junctional complexes to regulate epithelial ion transport and permeability. Dopamine (DA) is able to promote duodenal epithelial ion transport through D1-like receptors, which includes subtypes of D1 (D1 R) and D5 (D5 R), but whether D1-like receptors influence the duodenal permeability is unclear. FITC-dextran permeability, short-circuit current (ISC ), Western blot, immunohistochemistry and ELISA were used in human D5 R transgenic mice and hyperendogenous enteric DA (HEnD) rats in this study. Dopamine induced a downward deflection in ISC and an increase in FITC-dextran permeability of control rat duodenum, which were inhibited by the D1-like receptor antagonist, SCH-23390. However, DA decreased duodenal transepithelial resistance (TER), an effect also reversed by SCH-23390. A strong immunofluorescence signal for D5 R, but not D1 R, was observed in the duodenum of control rat. In human D5 R knock-in transgenic mice, duodenal mucosa displayed an increased basal ISC with high FITC-dextran permeability and decreased TER with a lowered expression of tight junction proteins, suggesting attenuated duodenal barrier function in these transgenic mice. D5 R knock-down transgenic mice manifested a decreased basal ISC with lowered FITC-dextran permeability. Moreover, an increased FITC-dextran permeability combined with decreased TER and tight junction protein expression in duodenal mucosa were also observed in HEnD rats. This study demonstrates, for the first time, that DA enhances duodenal permeability of control rat via D5 R, which provides new experimental and theoretical evidence for the influence of DA on duodenal epithelial barrier function. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  17. Exact solution of the one-dimensional super-symmetric t-J model with unparallel boundary fields

    CERN Document Server

    Zhang, Xin; Yang, Wen-Li; Shi, Kangjie; Wang, Yupeng

    2013-01-01

    The exact solution of the one-dimensional super-symmetric t-J model under generic integrable boundary conditions is obtained via the Bethe ansatz methods. With the coordinate Bethe ansatz, the corresponding R-matrix and K-matrices are derived for the second eigenvalue problem associated with spin degrees of freedom. It is found that the second eigenvalue problem can be transformed to that of the transfer matrix of the inhomogeneous XXX spin chain, which allows us to obtain the spectrum of the Hamiltonian and the associated Bethe ansatz equations by the off-diagonal Bethe ansatz method.

  18. Comparison of ATF and TJ-II stellarator equilibria as computed by the 3-D VMEC and PIES codes

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J.L.; Monticello, D.A.; Reiman, A.H. (Princeton Univ., NJ (United States). Plasma Physics Lab.); Salas, A.; Fraguas, A.L. (Association Euratom-Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas, Madrid (Spain)); Hirshman, S.P. (Oak Ridge National Lab., TN (United States))

    1992-01-01

    A comparison is made of results from the PIES code, which determines the equilibrium properties of three-dimensional toroidal configurations by direct integration along the magnetic field lines, with those from the VMEC code, which uses an energy minimization in a flux representation to determine the equilibrium configuration, for two devices: the ATF stellarator at Oak Ridge and the TJ-11 heliac which is being built in Madrid. The results obtained from the two codes are in good agreement, providing additional validation for the codes.

  19. Integrable open-boundary conditions for the supersymmetric t-J model the quantum group invariant case

    CERN Document Server

    González-Ruiz, A

    1994-01-01

    We consider integrable open-boundary conditions for the supersymmetric t-J model commuting with the number operator $n$ and $S^{z}$. We find four families, each one depending on two arbitrary parameters. The associated eigenvalue problem is solved by generalizing the Nested Algebraic Bethe Ansatz of the quantum group invariant case (which is obtained as a special limit). For the quantum group invariant case the Bethe ansatz states are shown to be highest weights of $spl_{q}(2,1)$. We also discuss the relation between Sklyanin's method of constructing open boundary conditions and the one for the quantum group invariant case based on Markov traces.

  20. A non-erasable magnetic memory based on the magnetic permeability

    Energy Technology Data Exchange (ETDEWEB)

    Petrie, J.R.; Wieland, K.A.; Burke, R.A.; Newburgh, G.A. [U.S. Army Research Laboratory, 2800 Powder Mill Rd, Adelphi, MD (United States); Burnette, J.E. [Spin Transfer Technologies, 33 Arch Street # 3200, Boston, MA (United States); Fischer, G.A. [U.S. Army Research Laboratory, 2800 Powder Mill Rd, Adelphi, MD (United States); Edelstein, A.S., E-mail: alan.s.edelstein.civ@us.army.mil [U.S. Army Research Laboratory, 2800 Powder Mill Rd, Adelphi, MD (United States)

    2014-06-01

    A non-erasable memory based on using differences in the magnetic permeability is demonstrated. The method can potentially store information indefinitely. Initially the high permeability bits were 10–50 μm wide lines of sputtered permalloy (Ni{sub 81}Fe{sub 19}) on a glass substrate. In a second writing technique a continuous film of amorphous, high permeability ferromagnetic Metglas (Fe{sub 78}Si{sub 13}B{sub 9}) was sputtered onto a similar glass substrate. Low permeability, crystalline 50 μm wide lines were then written in the film by laser heating. Both types of written media were read by applying an external probe field that is locally modified by the permeability of each bit. The modifications in the probe field were read by a nearby set of 10 micron wide magnetic tunnel junctions with a signal-to-noise ratio of up to 45 dB. This large response to changes in bit permeability is not altered after the media has been exposed to a 6400 Oe field. While being immediately applicable for data archiving and secure information storage, higher densities are possible with smaller read and write heads. - Highlights: • We demonstrate a non-erasable memory based on changes in the magnetic permeability. • Large change in permeability occur when Metglas changes from amorphous to crystalline. • Micron size regions of Metglas can be crystallized using a laser. • Permeability changes read by observing deviations of a probe field with an MTJ.

  1. The human myotendinous junction

    DEFF Research Database (Denmark)

    Knudsen, A B; Larsen, M; Mackey, Abigail

    2015-01-01

    The myotendinous junction (MTJ) is a specialized structure in the musculotendinous system, where force is transmitted from muscle to tendon. Animal models have shown that the MTJ takes form of tendon finger-like processes merging with muscle tissue. The human MTJ is largely unknown and has never ...

  2. Doped semiconductor nanocrystal junctions

    Energy Technology Data Exchange (ETDEWEB)

    Borowik, Ł.; Mélin, T., E-mail: thierry.melin@isen.iemn.univ-lille1.fr [Institut d’Electronique, de Microélectronique et de Nanotechnologie, CNRS-UMR8520, Avenue Poincaré, F-59652 Villeneuve d’Ascq (France); Nguyen-Tran, T.; Roca i Cabarrocas, P. [Laboratoire de Physique des Interfaces et des Couches Minces, CNRS-UMR7647, Ecole Polytechnique, F-91128 Palaiseau (France)

    2013-11-28

    Semiconductor junctions are the basis of electronic and photovoltaic devices. Here, we investigate junctions formed from highly doped (N{sub D}≈10{sup 20}−10{sup 21}cm{sup −3}) silicon nanocrystals (NCs) in the 2–50 nm size range, using Kelvin probe force microscopy experiments with single charge sensitivity. We show that the charge transfer from doped NCs towards a two-dimensional layer experimentally follows a simple phenomenological law, corresponding to formation of an interface dipole linearly increasing with the NC diameter. This feature leads to analytically predictable junction properties down to quantum size regimes: NC depletion width independent of the NC size and varying as N{sub D}{sup −1/3}, and depleted charge linearly increasing with the NC diameter and varying as N{sub D}{sup 1/3}. We thus establish a “nanocrystal counterpart” of conventional semiconductor planar junctions, here however valid in regimes of strong electrostatic and quantum confinements.

  3. Low Permeability Polyimide Insulation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Resodyn Technologies proposes a new technology that enables the application of polyimide based cryogenic insulation with low hydrogen permeability. This effort...

  4. Matrix metalloproteinase-9-deficient dendritic cells have impaired migration through tracheal epithelial tight junctions.

    Science.gov (United States)

    Ichiyasu, Hidenori; McCormack, Joanne M; McCarthy, Karin M; Dombkowski, David; Preffer, Frederic I; Schneeberger, Eveline E

    2004-06-01

    When sampling inhaled antigens, dendritic cells (DC) must penetrate the tight junction (TJ) barrier while maintaining the TJ seal. In matrix metalloproteinase (MMP)-9-deficient mice, in vivo experiments suggest that migration of DC into air spaces is impaired. To examine the underlying mechanisms, we established a well-defined in vitro model using mouse tracheal epithelial cells and mouse bone marrow DC (BMDC). Transmigration was elicited with either macrophage inflammatory protein (MIP)-1alpha or MIP-3beta in a time-dependent manner. Control MMP-9(+/+) BMDC cultured with granulocyte macrophage-colony-stimulating factor for 7 d showed a 30-fold greater transepithelial migration toward MIP-3beta than MIP-1alpha, indicating a more mature DC phenotype. MMP-9(-/-) BMDC as well as MMP-9(+/+) BMDC in the presence of the MMP inhibitor GM6001, although showing a similar preference for MIP-3beta, were markedly impaired in their ability to traverse the epithelium. Expression levels of CCR5 and CCR7, however, were similar in both MMP-9(-/-) and MMP-9(+/+) BMDC. Expression of the integral TJ proteins, occludin and claudin-1, were examined in BMDC before and after transepithelial migration. Interestingly, occludin but not claudin-1 was degraded following transepithelial migration in both MMP-9(-/-) and control BMDC. In addition, there was a > 2-fold increase in claudin-1 expression in MMP-9(-/-) as compared with control BMDC. These observations indicate that occludin and claudin-1 are differentially regulated and suggest that the lack of MMP-9 may affect claudin-1 turnover.

  5. Junction trees of general graphs

    Institute of Scientific and Technical Information of China (English)

    Xiaofei WANG; Jianhua GUO

    2008-01-01

    In this paper,we study the maximal prime subgraphs and their corresponding structure for any undirected graph.We introduce the notion of junction trees and investigate their structural characteristics,including junction properties,induced-subtree properties,running-intersection properties and maximum-weight spanning tree properties.Furthermore,the characters of leaves and edges on junction trees are discussed.

  6. Male reproductive toxicity of CrVI: In-utero exposure to CrVI at the critical window of testis differentiation represses the expression of Sertoli cell tight junction proteins and hormone receptors in adult F1 progeny rats.

    Science.gov (United States)

    Kumar, Kathiresh M; Aruldhas, Mariajoseph Michael; Banu, Sheerin L; Sadasivam, Balaji; Vengatesh, Ganapathy; Ganesh, Karthik M; Navaneethabalakrishnan, Shobana; Navin, Ajith Kumar; Michael, Felicia Mary; Venkatachalam, Sankar; Stanley, Jone A; Ramachandran, Ilangovan; Banu, Sakhila K; Akbarsha, Mohammad Abdulkader

    2017-02-10

    The effect of gestational exposure to CrVI (occupational/environmental pollutant and target to Sertoli cells(SC)) was tested in a rat model during the testicular differentiation from the bipotential gonad may interrupt spermatogenesis by disrupting SC tight junctions(TJ) and it's proteins and hormone receptors. Pregnant Wistar rats were exposed to 50/100/200ppm CrVI through drinking water during embryonic days 9-14. On Postnatal day 120, testes were subjected to ion exchange chromatographic analysis and revealed increased level of CrIII in SCs and germ cells, serum and testicular interstitial fluid(TIF). Microscopic analyses showed seminiferous tubules atrophy and disruption of SC TJ, which also recorded decreased testosterone in TIF. mRNA and Protein expression analyses attested decreased level of Fshr, Ar, occludin and claudin-11 in SCs. Immunofluorescent detection revealed weak signal of TJ proteins. Taken together, we concluded that gestational exposure to CrVI interferes with the expression of SC TJ proteins due to attenuated expression of hormone receptors.

  7. Continuous plasma density measurement in TJ-II infrared interferometer-Advanced signal processing based on FPGAs

    Energy Technology Data Exchange (ETDEWEB)

    Esteban, L., E-mail: luis.esteban-hernandez@ciemat.e [Laboratorio Nacional de Fusion, Asociacion EURATOM-CIEMAT, Avenida Complutense No. 22, E-28040 Madrid (Spain); Sanchez, M. [Laboratorio Nacional de Fusion, Asociacion EURATOM-CIEMAT, Avenida Complutense No. 22, E-28040 Madrid (Spain); Lopez, J.A.; Nieto-Taladriz, O. [Departamento de Ingeniera Electronica, ETSI Telecomunicacion, Universidad Politcnica de Madrid, Avenida Complutense No. 30, E-28040 Madrid (Spain); Sanchez, J. [Laboratorio Nacional de Fusion, Asociacion EURATOM-CIEMAT, Avenida Complutense No. 22, E-28040 Madrid (Spain)

    2010-07-15

    This work presents the behavioral simulation in an FPGA of a novel processing system for measuring line average electronic density in the TJ-II stellarator diagnostic, Infra-Red Two-Color Interferometer. Line average electronic density is proportional to phase difference between probing and reference signals of the interferometer, as the Appleton-Hartree cold plasma model states. The novelty of the approach is the development of a real time measuring system where research work has been carried out in two ways: a new interpolation algorithm and the implementation of a new specific processor on an FPGA. The main goal of this new system is to measure line plasma electronic density for several channels in real time, also it will be useful to eliminate intermediate mixing frequency stages (the output signals coming from the interferometer are going to be directly sampled) and finally to generate real time density signals for control purposes in TJ-II and in other diagnostics. This device is intended to be the new data acquisition-processing system for the future six channel infrared interferometer that requires at least 14 input signals. The knowledge acquired could be useful in the design of W7-X and ITER IR-interferometer data acquisition and processing systems.

  8. Testing of a pulsed He supersonic beam for plasma edge diagnostic in the TJ-IU torsatron

    Science.gov (United States)

    Tabarés, F. L.; Tafalla, D.; Herrero, V.; Tanarro, I.

    1997-02-01

    A new, compact atomic beam source based on the supersonic expansion of He has been developed for application as a plasma edge diagnostic. The beam is produced from a pulsed valve with a duration between 0.2 to 2 ms and a nominal repetition rate 10 and a divergence of ± 1° have been achieved at stagnation pressures below 2 bar. The diagnostic has been tested in ECRH plasmas on the TJ-IU torsatron, representing the first application of a supersonic beam to plasma characterization, to our knowledge. Operational conditions which minimized the total amount of He injected into the plasma were chosen. Non-perturbative injection conditions in the low density plasmas could be obtained at local He densities of ⋍ 1 × 10 11 cm -3 and a beam diameter < 1 cm. Due to the relatively low electron density of the ECRH plasmas, and to the good penetration characteristics of the supersonic He beam, the diagnostic could be used up to fairly low values of the normalized plasma minor radius, {r}/{a} (a = 12 cm) . Details of the optimization of the atomic beam diagnostics and typical results for steady state conditions in the TJ-IU plasmas are presented.

  9. Testing of a pulsed He supersonic beam for plasma edge diagnostic in the TJ-IU torsatron

    Energy Technology Data Exchange (ETDEWEB)

    Tabares, F.L. [Association EURATOM/CIEMAT, Madrid (Spain); Tafalla, D. [Association EURATOM/CIEMAT, Madrid (Spain); Herrero, V. [Instituto de Estructura de la Materia, CSIC, 28006 Madrid (Spain); Tanarro, I. [Instituto de Estructura de la Materia, CSIC, 28006 Madrid (Spain)

    1997-02-01

    A new, compact atomic beam source based on the supersonic expansion of He has been developed for application as a plasma edge diagnostic. The beam is produced from a pulsed valve with a duration between 0.2 to 2 ms and a nominal repetition rate <500 Hz. A terminal speed ratio >10 and a divergence of {+-}1 have been achieved at stagnation pressures below 2 bar. The diagnostic has been tested in ECRH plasmas on the TJ-IU torsatron, representing the first application of a supersonic beam to plasma characterization, to our knowledge. Operational conditions which minimized the total amount of He injected into the plasma were chosen. Non-perturbative injection conditions in the low density plasmas could be obtained at local He densities of {approx_equal}1 x 10{sup 11} cm{sup -3} and a beam diameter <1 cm. Due to the relatively low electron density of the ECRH plasmas, and to the good penetration characteristics of the supersonic He beam, the diagnostic could be used up to fairly low values of the normalized plasma minor radius, r/a (a=12 cm). Details of the optimization of the atomic beam diagnostics and typical results for steady state conditions in the TJ-IU plasmas are presented. (orig.).

  10. Effect of magnetic configuration on frequency of NBI-driven Alfvén modes in TJ-II

    Science.gov (United States)

    Melnikov, A. V.; Ochando, M.; Ascasibar, E.; Castejon, F.; Cappa, A.; Eliseev, L. G.; Hidalgo, C.; Krupnik, L. I.; Lopez-Fraguas, A.; Liniers, M.; Lysenko, S. E.; de Pablos, J. L.; Perfilov, S. V.; Sharapov, S. E.; Spong, D. A.; Jimenez, J. A.; Ufimtsev, M. V.; Breizman, B. N.; HIBP Group; the TJ-II Team

    2014-12-01

    Excitation of modes in the Alfvénic frequency range, 30 kHz values, 1.51advantage of the unique TJ-II capabilities, a dynamic magnetic configuration experiment with \\unicode{7548} (ρ , t) variation during discharges has shown strong effects on the mode frequency via both vacuum \\unicode{7548} changes and induced net plasma current. A drastic frequency increase from ˜50 to ˜250 kHz was observed for some modes when plasma current as low as ±2 kA was induced by small (10%) changes in the vertical field. A comprehensive set of diagnostics including a heavy ion beam probe, magnetic probes and a multi-chord bolometer made it possible to identify the spatial spread of the modes and deduce the internal amplitudes of their plasma density and magnetic field perturbations. A simple analytical model for fAE, based on the local Alfvén eigenmode (AE) dispersion relation, was proposed to characterize the observation. It was shown that all the observations, including vacuum iota and plasma current variations, may be fitted by the model, so the linear mode frequency dependence on \\unicode{7548} (plasma current) and one over square root density dependence present the major features of the NBI-induced AEs in TJ-II, and provide the framework for further experiment-to-theory comparison.

  11. The Dynamics Of Inner Solar System Bodies With 2.8 < Tj < 3.2 And The Implications For The Origin Of Main-Belt Comets

    Science.gov (United States)

    Haghighipour, Nader; Hsieh, Henry H.

    2014-05-01

    Main-belt comets (MBCs) have attracted a great deal of interest since their identification as a new class of bodies by Hsieh and Jewitt in 2006. Much of this interest is due to the implication that MBC activity is driven by the sublimation of volatile material (presumed to be water ice) presenting these bodies as probable candidates for the delivery of a significant fraction of the Earth’s water. An interesting characteristic of these objects is that while similar to comets, they have comae and dusty tails, they resemble asteroids, dynamically (i.e., their Tisserand numbers with respect to Jupiter, Tj, are larger than 3). The Tisserand parameter is a conserved quantity in the restricted three-body problem, and the Tisserand parameter with respect to Jupiter is frequently used to distinguish between asteroids (Tj>3), which are thought to be stable on Gyr timescales, and comets (Tjfact not as distinct as the common use of the Tisserand parameter would suggest. We studied the dynamical evolution of test particles with Tisserand numbers ranging from 2.8 to 3.2 to explore the behavior of solar system objects (such as MBCs) with Tj values close to the canonical asteroid-comet boundary of 3. We find, as expected, that Tj is not a hard boundary between asteroids and comets, and that we can expect to find objects that are dynamically stable (over the time period of integrations) with Tj3. Dynamical stability can be seen to be a function of not just Tj, but also other orbital elements such as the eccentricity and aphelion distance. We will report on the detailed findings of our analysis and discuss their implications for the origin of MBCs.

  12. Molecular and cellular mechanisms of tight junction dysfunction in the irritable bowel syndrome.

    Science.gov (United States)

    Cheng, Peng; Yao, Jianning; Wang, Chunfeng; Zhang, Lianfeng; Kong, Wuming

    2015-09-01

    The pathophysiological mechanisms of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, are complex and have not been fully elucidated. The present study aimed to investigate the molecular and cellular mechanisms of tight junction (TJ) dysfunction in IBS. Intestinal tissues of IBS and non‑IBS patients were examined to observe cellular changes by cell chemical tracer electron microscopy and transmission electron microscopy, and intestinal claudin‑1 protein was detected by immunohistochemistry, western blot analysis and fluorescence quantitative polymerase chain reaction. Compared with the control group, TJ broadening and the tracer extravasation phenomenon were observed in the diarrhea‑predominant IBS group, and a greater number of neuroendocrine cells and mast cells filled with high‑density particles in the endocrine package pulp as well as a certain extent of vacuolization were present. The expression of claudin‑1 in diarrhea‑predominant IBS patients was decreased, while it was increased in constipation‑predominant IBS patients. In conclusion, the results of the present study indicated that changes in cellular structure and claudin‑1 levels were associated with Tjs in IBS.

  13. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation

    Directory of Open Access Journals (Sweden)

    Luissint Anny-Claude

    2012-11-01

    Full Text Available Abstract The Blood–brain barrier (BBB, present at the level of the endothelium of cerebral blood vessels, selectively restricts the blood-to-brain paracellular diffusion of compounds; it is mandatory for cerebral homeostasis and proper neuronal function. The barrier properties of these specialized endothelial cells notably depend on tight junctions (TJs between adjacent cells: TJs are dynamic structures consisting of a number of transmembrane and membrane-associated cytoplasmic proteins, which are assembled in a multimolecular complex and acting as a platform for intracellular signaling. Although the structural composition of these complexes has been well described in the recent years, our knowledge about their functional regulation still remains fragmentary. Importantly, pericytes, embedded in the vascular basement membrane, and perivascular microglial cells, astrocytes and neurons contribute to the regulation of endothelial TJs and BBB function, altogether constituting the so-called neurovascular unit. The present review summarizes our current understanding of the structure and functional regulation of endothelial TJs at the BBB. Accumulating evidence points to a correlation between BBB dysfunction, alteration of TJ complexes and progression of a variety of CNS diseases, such as stroke, multiple sclerosis and brain tumors, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s diseases. Understanding how TJ integrity is controlled may thus help improve drug delivery across the BBB and the design of therapeutic strategies for neurological disorders.

  14. Estimation of the effective intercellular diffusion coefficient in cell monolayers coupled by gap junctions

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Hofgaard, Johannes P; von Holstein-Rathlou, Niels-Henrik;

    2012-01-01

    A recently developed dye-based assay to study gap junction permeability is analysed. The assay is based on electroporation of dye into a large number of connexin 43 expressing cells, grown to confluency on electrically conductive slides. The subsequent intercellular spread of dye to non-electroporated...

  15. Holliday junction resolvases.

    Science.gov (United States)

    Wyatt, Haley D M; West, Stephen C

    2014-09-02

    Four-way DNA intermediates, called Holliday junctions (HJs), can form during meiotic and mitotic recombination, and their removal is crucial for chromosome segregation. A group of ubiquitous and highly specialized structure-selective endonucleases catalyze the cleavage of HJs into two disconnected DNA duplexes in a reaction called HJ resolution. These enzymes, called HJ resolvases, have been identified in bacteria and their bacteriophages, archaea, and eukaryotes. In this review, we discuss fundamental aspects of the HJ structure and their interaction with junction-resolving enzymes. This is followed by a brief discussion of the eubacterial RuvABC enzymes, which provide the paradigm for HJ resolvases in other organisms. Finally, we review the biochemical and structural properties of some well-characterized resolvases from archaea, bacteriophage, and eukaryotes. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

  16. Wireless Josephson Junction Arrays

    Science.gov (United States)

    Adams, Laura

    2015-03-01

    We report low temperature, microwave transmission measurements on a wireless two- dimensional network of Josephson junction arrays composed of superconductor-insulator -superconductor tunnel junctions. Unlike their biased counterparts, by removing all electrical contacts to the arrays and superfluous microwave components and interconnects in the transmission line, we observe new collective behavior in the transmission spectra. In particular we will show emergent behavior that systematically responds to changes in microwave power at fixed temperature. Likewise we will show the dynamic and collective response of the arrays while tuning the temperature at fixed microwave power. We discuss these spectra in terms of the Berezinskii-Kosterlitz-Thouless phase transition and Shapiro steps. We gratefully acknowledge the support Prof. Steven Anlage at the University of Maryland and Prof. Allen Goldman at the University of Minnesota. Physics and School of Engineering and Applied Sciences.

  17. Behaviour of direct and delayed fast ion losses during NBI on TJ-II; Comportamiento de las perdidas instantaneas y retardadas en la inyeccion de neutros del TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Guasp, J.; Liniers, M.

    1995-07-01

    The dependence with density and beam energy of the different kind of fast ion losses, direct and delayed, during tangential balanced NBI injection in TJ-II helical axis stellarator has been analysed. Direct losses increase with energy and a strong difference between the two injection directions appears, are produced by passing particles that loss confinement in a few {mu}sec and the influence of birth profiles produces an increase with density. Delayed losses are very well separated in time from direct ones, are produced by particles experimenting pitch angle scattering and, most o them, correspond to trapped particles. Are much less important than the direct ones (about 1/3), decrease slowly with energy and, with C X, increase with density (an effect of initial profile). The absorption is rather independent of energy with low values at low density in reason of high shine through and C X losses, but recovers quickly with the density increase. (Author) 4 refs.

  18. Control of the Superconducting Magnets current Power Supplies of the TJ-II Gyrotrons; Control de las Fuentes de Corriente de las Bobinas Superconductoras de los Girotrones del TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Ros, A.; Fernandez, A.; Tolkachev, A.; Catalan, G.

    2006-07-01

    The TJ-II ECRH heating system consists of two gyrotrons, which can deliver a maximum power of 300 kW at a frequency of 53.2 GHz. Another 28 GHz gyrotron is going to be used in the Bernstein waves heating system. In order to get the required frequency, the gyrotrons need and homogeneous magnetic field of several tesla, which is generated by a superconducting coil field by a current source. This document describes the current source control as well as the high precision ammeters control. These ammeters measure the current in the superconducting coils. The user interface and the programming of the control system are described. The communication between devices is also explained. (author) 9 Refs.

  19. Remote Control System of the TJ-II Microwave Transmission Lines Mirrors; Sistema de Control Remoto de los Espejos de las Lineas de Transmision de Microondas del TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Sanchez, A.; Fernandez, A.; Cappa, A.; Gama, J. de la; Olivares, J.; Garcia, R.; Chamorro, M.

    2007-09-27

    The ECRH system of the TJ-II stellarator has two gyrotrons, which deliver a maximum power of 300 kW each at a frequency of 53.2 GHz. Another 28 GHz gyrotron will be used to heat the plasma by electron Bernstein waves (EBWH). The microwave power is transmitted from the gyrotrons to the vacuum chamber by two quasi-optical transmission lines for ECRH and a corrugated waveguide for EBWH. All transmission lines have an internal movable mirror inside the vacuum chamber to focus the beam and to be able to change the launching angle. The control of the beam polarization is very important and the lines have two corrugated mirrors, which actuate as polarizers. In this report the control system of the position of these three internal mirrors and the polarizers of the EBWH transmission line is described. (Author) 20 refs.

  20. Impacts of lost fast ions on the TJ-II Vacuum Vessel during NBI; Impactos de los iones rapidos en la Camara de Vacio del TJ-II durante NBI

    Energy Technology Data Exchange (ETDEWEB)

    Guasp, J.

    1995-07-01

    The possible deposition patterns, on the Vacuum Vessel, of lost fast ions during the balanced tangential NBI in TJ-II helical axis Stellarator are analysed theoretically, establishing the relation between those impact points, the plasma exit and birth positions and the magnetic configuration characteristics. It is shown that direct losses are the most important, mainly those produced by the beam injected with the same direction that the magnetic field, increasing with beam energy and plasma density but with impacts remaining fixed on well defined zones, a periodically distributed along the Hard Core cover plates, producing high loads at high densities. The remaining losses, except for the shine through ones that predominate at low density, are periodically distributed, with smooth maxima and produce very low loads. No overlapping between the different kind of losses or beams is observed. (Author) 6 refs.

  1. Impacts of the CX neutrals on the Vacuum Vessel of TJ-II during NBI; Impactos de los Neutros de CX en la Camara de Vacio del TJ-II durante NBF

    Energy Technology Data Exchange (ETDEWEB)

    Guasp, J.

    1995-07-01

    A numerical analysis of the impact patterns on the Vacuum Vessel produced by CX neutrals during the tangential balanced NBI in TJ-II Helical Axis Stellarator has been done. The results show periodical distributions with smooth maxima and mild loads, concentrated preferential on the HC plates. A certain preference of these neutral to emerge down wards from the plasma appears, as a consequence of a similar trend for the trapped particles. The differences between the impacts produced by the beam parallel to the magnetic field and the opposite one are small, once more as a consequence of the loss of memory of trapped particles to initial direction. The dependence of loads with plasma density and beam energy follows the trend of CX losses, decreasing strongly with increasing density and decreasing, more smoothly, with energy. (Author) 3 refs.

  2. Pharmacokinetics of TJ-8117 (Onpi-to), a drug for renal failure (I): Plasma concentration, distribution and excretion of [3H]-(-)epicatechin 3-O-gallate in rats and dogs.

    Science.gov (United States)

    Takizawa, Yukiho; Nishimura, Hiroaki; Morota, Takashi; Tomisawa, Hiroki; Takeda, Shuichi; Aburada, Masaki

    2004-01-01

    TJ-8117 (Onpi-to) is an herbal medicine extracted from a mixture of five crude medicinals (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), which has been developed as a drug for chronic renal failure. (-)Epicatechin 3-O-gallate (ECG), one of the active components of TJ-8117, was labeled with tritium and added to TJ-8117. Pharmacokinetics in plasma, tissue distribution and excretion of radioactivity were investigated following a single oral administration of TJ-8117 containing [3H]ECG ([3H]TJ-8117) in rats and dogs. 1. Following oral administration of [3H]TJ-8117, radioactivity exhibited linear pharmacokinetics in Cmax. Linearity of AUC(0-72 h) was lost at the highest dose of [3H]TJ-8117. Cmax and AUC(0-72 h) were higher in female rats than in male rats, a finding which suggested a sex difference in rats. Plasma levels of radioactivity displayed curves with one peak in dogs, which suggested a species difference between rats and dogs. 2. No accumulation was observed in any tissues in male rats. 3. Within 168 h after administration of [3H]TJ-8117 to male rats, 18.7%, 84.1% and 0.9% of the dose was excreted in urine, feces and expired air, respectively. Data from bile-duct cannulated rats indicated that at least 18.4% of the dose was absorbed.

  3. Permeability testing of biomaterial membranes

    Energy Technology Data Exchange (ETDEWEB)

    Dreesmann, L; Hajosch, R; Nuernberger, J Vaz; Schlosshauer, B [NMI Natural and Medical Sciences Institute at University Tuebingen, Markwiesenstr. 55, D-72770 Reutlingen (Germany); Ahlers, M [GELITA AG, Gammelsbacher Str. 2, D-69412 Eberbach (Germany)], E-mail: schlosshauer@nmi.de

    2008-09-01

    The permeability characteristics of biomaterials are critical parameters for a variety of implants. To analyse the permeability of membranes made from crosslinked ultrathin gelatin membranes and the transmigration of cells across the membranes, we combined three technical approaches: (1) a two-chamber-based permeability assay, (2) cell culturing with cytochemical analysis and (3) biochemical enzyme electrophoresis (zymography). Based on the diffusion of a coloured marker molecule in conjunction with photometric quantification, permeability data for a gelatin membrane were determined in the presence or absence of gelatin degrading fibroblasts. Cytochemical evaluation after cryosectioning of the membranes was used to ascertain whether fibroblasts had infiltrated the membrane inside. Zymography was used to investigate the potential release of proteases from fibroblasts, which are known to degrade collagen derivatives such as gelatin. Our data show that the diffusion equilibrium of a low molecular weight dye across the selected gelatin membrane is approached after about 6-8 h. Fibroblasts increase the permeability due to cavity formation in the membrane inside without penetrating the membrane for an extended time period (>21 days in vitro). Zymography indicates that cavity formation is most likely due to the secretion of matrix metalloproteinases. In summary, the combination of the depicted methods promises to facilitate a more rational development of biomaterials, because it provides a rapid means of determining permeability characteristics and bridges the gap between descriptive methodology and the mechanistic understanding of permeability alterations due to biological degradation.

  4. Microcirculation-on-a-Chip: A Microfluidic Platform for Assaying Blood- and Lymphatic-Vessel Permeability.

    Directory of Open Access Journals (Sweden)

    Miwa Sato

    Full Text Available We developed a microfluidic model of microcirculation containing both blood and lymphatic vessels for examining vascular permeability. The designed microfluidic device harbors upper and lower channels that are partly aligned and are separated by a porous membrane, and on this membrane, blood vascular endothelial cells (BECs and lymphatic endothelial cells (LECs were cocultured back-to-back. At cell-cell junctions of both BECs and LECs, claudin-5 and VE-cadherin were detected. The permeability coefficient measured here was lower than the value reported for isolated mammalian venules. Moreover, our results showed that the flow culture established in the device promoted the formation of endothelial cell-cell junctions, and that treatment with histamine, an inflammation-promoting substance, induced changes in the localization of tight and adherens junction-associated proteins and an increase in vascular permeability in the microdevice. These findings indicated that both BECs and LECs appeared to retain their functions in the microfluidic coculture platform. Using this microcirculation device, the vascular damage induced by habu snake venom was successfully assayed, and the assay time was reduced from 24 h to 30 min. This is the first report of a microcirculation model in which BECs and LECs were cocultured. Because the micromodel includes lymphatic vessels in addition to blood vessels, the model can be used to evaluate both vascular permeability and lymphatic return rate.

  5. Online Junction Temperature Cycle Recording of an IGBT Power Module in a Hybrid Car

    Directory of Open Access Journals (Sweden)

    Marco Denk

    2015-01-01

    Full Text Available The accuracy of the lifetime calculation approach of IGBT power modules used in hybrid-electric powertrains suffers greatly from the inaccurate knowledge of application typical load-profiles. To verify the theoretical load-profiles with data from the field this paper presents a concept to record all junction temperature cycles of an IGBT power module during its operation in a test vehicle. For this purpose the IGBT junction temperature is measured with a modified gate driver that determines the temperature sensitive IGBT internal gate resistor by superimposing the negative gate voltage with a high-frequency identification signal. An integrated control unit manages the TJ measurement during the regular switching operation, the exchange of data with the system controller, and the automatic calibration of the sensor system. To calculate and store temperature cycles on a microcontroller an online Rainflow counting algorithm was developed. The special feature of this algorithm is a very accurate extraction of lifetime relevant information with a significantly reduced calculation and storage effort. Until now the recording concept could be realized and tested within a laboratory voltage source inverter. Currently the IGBT driver with integrated junction temperature measurement and the online cycle recording algorithm is integrated in the voltage source inverter of first test vehicles. Such research will provide representative load-profiles to verify and optimize the theoretical load-profiles used in today’s lifetime calculation.

  6. The causal impact of magnetic fluctuations in slow and fast L-H transitions at TJ-II

    CERN Document Server

    van Milligen, B Ph; Carreras, B A; Ascasíbar, E; Hidalgo, C; Pastor, I; Fontdecaba, J M; Balbín, R

    2015-01-01

    This work focuses on the relationship between L-H transitions and MHD activity in the low shear TJ-II stellarator. It is shown that the presence of a low order rational in the plasma edge (gradient) region lowers the threshold density for H-mode access. MHD activity is systematically suppressed before or at the confinement transition. We apply a causality detection technique (the Transfer Entropy) to study the relation between magnetic oscillations and locally measured plasma rotation velocity (related to Zonal Flows). For this purpose, we study a large number of discharges in two magnetic configurations, corresponding to fast and slow transitions. With the slow transitions, the developing Zonal Flow prior to the transition leads to the gradual reduction of magnetic oscillations. The transition itself is marked by a strong spike of 'information transfer' from magnetic to velocity oscillations, suggesting the that the magnetic drive is important for setting up the final sheared flow responsible for the H-mode ...

  7. Reliability of the TJ-II power supply system: Collection and analysis of the operational experience data

    Energy Technology Data Exchange (ETDEWEB)

    Izquierdo, Jesus [Fusion Energy Engineering Laboratory, Seccio d' Enginyeria Nuclear, Universitat Politecnica de Catalunya, Avda. Diagonal 647, 08028 Barcelona (Spain)], E-mail: jesus.izquierdo@upc.edu; Dies, Javier; Garcia, Jeronimo; Tapia, Carlos [Fusion Energy Engineering Laboratory, Seccio d' Enginyeria Nuclear, Universitat Politecnica de Catalunya, Avda. Diagonal 647, 08028 Barcelona (Spain); Alonso, Javier; Ascasibar, Enrique; Medrano, Mercedes; Mendez, Purificacion; Rodriguez, Lina [Asociacion EURATOM-CIEMAT para la Fusion, Avda. Complutense 22, Madrid (Spain)

    2007-10-15

    During a TJ-II pulse, the provision of magnetic fields requires a total amount of power exceeding 80 MVA. Such amount of power is supplied by a 132 MVA flywheel generator (15 kV output voltage, 80-100 Hz output frequency) and the related motor, transformers, breakers, rectifiers, regulators, protections, busbars, connections, etc. Failure data of these main components have been collected identified and processed including information on failure modes and, where possible, causes of the failures. Main statistical values about failure rates for the period from May of 1998 to December of 2004 have been calculated and are ready to be compared with those of the International Fusion Component Failure Rate Database (FCFR-DB)

  8. Upgrade of the automatic analysis system in the TJ-II Thomson Scattering diagnostic: New image recognition classifier and fault condition detection

    NARCIS (Netherlands)

    Makili, L.; Vega, J.; Dormido-Canto, S.; Pastor, I.; Pereira, A.; Farias, G.; Portas, A.; Perez-Risco, D.; Rodriguez-Fernandez, M. C.; Busch, P.

    2010-01-01

    An automatic image classification system based on support vector machines (SVM) has been in operation for years in the TJ-II Thomson Scattering diagnostic. It recognizes five different types of images: CCD camera background, measurement of stray light without plasma or in a collapsed discharge, imag

  9. Methods to Measure Water Permeability.

    Science.gov (United States)

    Solenov, Evgeniy I; Baturina, Galina S; Katkova, Liubov E; Zarogiannis, Sotirios G

    2017-01-01

    Water permeability is a key feature of the cell plasma membranes and it has seminal importance for a number of cell functions such as cell volume regulation, cell proliferation, cell migration, and angiogenesis to name a few. The transport of water occurs mainly through plasma membrane water channels , the aquaporins, who have very important function in physiological and pathophysiological states. Due to the above the experimental assessment of the water permeability of cells and tissues is necessary. The development of new methodologies of measuring water permeability is a vibrant scientific field that constantly develops during the past three decades along with the advances in imaging mainly. In this chapter we describe and critically assess several methods that have been developed for the measurement of water permeability both in living cells as well as in tissues with a focus in the first category.

  10. Geothermal Permeability Enhancement - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Joe Beall; Mark Walters

    2009-06-30

    The overall objective is to apply known permeability enhancement techniques to reduce the number of wells needed and demonstrate the applicability of the techniques to other undeveloped or under-developed fields. The Enhanced Geothermal System (EGS) concept presented in this project enhances energy extraction from reduced permeability zones in the super-heated, vapor-dominated Aidlin Field of the The Geysers geothermal reservoir. Numerous geothermal reservoirs worldwide, over a wide temperature range, contain zones of low permeability which limit the development potential and the efficient recovery of heat from these reservoirs. Low permeability results from poorly connected fractures or the lack of fractures. The Enhanced Geothermal System concept presented here expands these technologies by applying and evaluating them in a systematic, integrated program.

  11. An induced junction photovoltaic cell

    Science.gov (United States)

    Call, R. L.

    1974-01-01

    Silicon solar cells operating with induced junctions rather than diffused junctions have been fabricated and tested. Induced junctions were created by forming an inversion layer near the surface of the silicon by supplying a sheet of positive charge above the surface. Measurements of the response of the inversion layer cell to light of different wavelengths indicated it to be more sensitive to the shorter wavelengths of the sun's spectrum than conventional cells. The greater sensitivity occurs because of the shallow junction and the strong electric field at the surface.

  12. Effects of Kampo medicine, Keishi-ka Shakuyaku-to (TJ-60) on alteration of diacylglycerol metabolism in gastrointestinal smooth muscle of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    NOBE Koji; MOMOSE Kazutaka; SAKAI Yasushi

    2002-01-01

    AIM: To examine the effects of Kampo medicine, Keishi-ka-Shakuyaku-to (TJ-60) on the signal transduction in diabetic gastrointestinal dysfunction. METHODS: Experimental diabetic models were prepared using streptozotocin (STZ)-treated Wistar rats. Randomly selected STZ rats were treated with insulin (12 U@kg-1@d-1) or TJ-60 (1% of food intake). Diacylglycerol (DG) and DG kinase activities were quantified in isolated aortic smooth muscle tissue.RESULTS: One of the key element of the PI-turnover, DG kinase activity in resting state in gastric smooth muscle was significantly increased compared to the control value, and carbachol (CCh)-induced response was not detectable,but it was detected in the control rats. On the other hand resting activity in ileum did not differ from the control, but the CCh-induced responses were suppressed. Treatment with TJ-60 indicated resistant effects for the alteration of DG kinase activities in diabetic intestinal tissues. In order to reveal the mechanism of the effects, total content of DG was measured, because the DG plays important role in the PI-turnover and the DG converted from not only PI but also incorporated glucose under high glucose condition. Patterns of the change in DG levels were similar to those in DG kinase. These results indicate that the effect of TJ-60 occurs at the cellular level of DG. CONCLUSION:Dysfunction of gastrointestinal smooth muscle in diabetes is mediated by an alternation of DG and DG kinase. TJ-60 influences the alteration and relief the dysfunction.

  13. Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice.

    Science.gov (United States)

    Diao, Lei; Mei, Qiao; Xu, Jian-Ming; Liu, Xiao-Chang; Hu, Jing; Jin, Juan; Yao, Qiang; Chen, Mo-Li

    2012-03-14

    To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

  14. Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice

    Institute of Scientific and Technical Information of China (English)

    Lei Diao; Qiao Mei; Jian-Ming Xu; Xiao-Chang Liu; Jing Hu; Juan Jin; Qiang Yao

    2012-01-01

    AIM:To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice.METHODS:Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally.A control group received the vehicle by gavage.Rebamipide (100 mg/kg,200 mg/kg,400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration.Intestinal permeability was evaluated by Evans blue and the FITC-dextran method.The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM).Mitochondrial function including mitochondrial swelling,mitochondrial membrane potential,mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels,succinate dehydrogenase (SDH) and ATPase activities were measured.Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity.RESULTS:Compared with the control group,intestinal permeability was significantly increased in the diclofenac group,which was accompanied by broken tight junctions,and significant increases in MDA content and MPO activity.Rebamipide significantly reduced intestinal permeability,improved inter-cellular tight junctions,and was associated with decreases in intestinal MDA content and MPO activity.At the mitochondrial level,rebamipide increased SDH and ATPase activities,NADH level and decreased mitochondrial swelling.CONCLUSION:Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide,which partially contributed to the protection of mitochondrial function.

  15. The Microvascular Gap Junction Channel: A Route to Deliver MicroRNAs for Neurological Disease Treatment.

    Science.gov (United States)

    Thuringer, Dominique; Solary, Eric; Garrido, Carmen

    2017-01-01

    Brain microvascular endothelial cells (BMECs) separate the peripheral blood from the brain. These cells, which are surrounded by basal lamina, pericytes and glial cells, are highly interconnected through tight and gap junctions. Their permeability properties restrict the transfer of potentially useful therapeutic agents. In such a hermetic system, the gap junctional exchange of small molecules between cerebral endothelial and non-endothelial cells is crucial for maintaining tissue homeostasis. MicroRNA were shown to cross gap junction channels, thereby modulating gene expression and function of the recipient cell. It was also shown that, when altered, BMEC could be regenerated by endothelial cells derived from pluripotent stem cells. Here, we discuss the transfer of microRNA through gap junctions between BMEC, the regeneration of BMEC from induced pluripotent stem cells that could be engineered to express specific microRNA, and how such an innovative approach could benefit to the treatment of glioblastoma and other neurological diseases.

  16. The Microvascular Gap Junction Channel: A Route to Deliver MicroRNAs for Neurological Disease Treatment

    Directory of Open Access Journals (Sweden)

    Dominique Thuringer

    2017-08-01

    Full Text Available Brain microvascular endothelial cells (BMECs separate the peripheral blood from the brain. These cells, which are surrounded by basal lamina, pericytes and glial cells, are highly interconnected through tight and gap junctions. Their permeability properties restrict the transfer of potentially useful therapeutic agents. In such a hermetic system, the gap junctional exchange of small molecules between cerebral endothelial and non-endothelial cells is crucial for maintaining tissue homeostasis. MicroRNA were shown to cross gap junction channels, thereby modulating gene expression and function of the recipient cell. It was also shown that, when altered, BMEC could be regenerated by endothelial cells derived from pluripotent stem cells. Here, we discuss the transfer of microRNA through gap junctions between BMEC, the regeneration of BMEC from induced pluripotent stem cells that could be engineered to express specific microRNA, and how such an innovative approach could benefit to the treatment of glioblastoma and other neurological diseases.

  17. aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation.

    Science.gov (United States)

    Iden, Sandra; Misselwitz, Steve; Peddibhotla, Swetha S D; Tuncay, Hüseyin; Rehder, Daniela; Gerke, Volker; Robenek, Horst; Suzuki, Atsushi; Ebnet, Klaus

    2012-03-05

    The PAR-3-atypical protein kinase C (aPKC)-PAR-6 complex has been implicated in the development of apicobasal polarity and the formation of tight junctions (TJs) in vertebrate epithelial cells. It is recruited by junctional adhesion molecule A (JAM-A) to primordial junctions where aPKC is activated by Rho family small guanosine triphosphatases. In this paper, we show that aPKC can interact directly with JAM-A in a PAR-3-independent manner. Upon recruitment to primordial junctions, aPKC phosphorylates JAM-A at S285 to promote the maturation of immature cell-cell contacts. In fully polarized cells, S285-phosphorylated JAM-A is localized exclusively at the TJs, and S285 phosphorylation of JAM-A is required for the development of a functional epithelial barrier. Protein phosphatase 2A dephosphorylates JAM-A at S285, suggesting that it antagonizes the activity of aPKC. Expression of nonphosphorylatable JAM-A/S285A interferes with single lumen specification during cyst development in three-dimensional culture. Our data suggest that aPKC phosphorylates JAM-A at S285 to regulate cell-cell contact maturation, TJ formation, and single lumen specification.

  18. Mixing in T-junctions

    NARCIS (Netherlands)

    Kok, Jacobus B.W.; van der Wal, S.

    1996-01-01

    The transport processes that are involved in the mixing of two gases in a T-junction mixer are investigated. The turbulent flow field is calculated for the T-junction with the k- turbulence model by FLOW3D. In the mathematical model the transport of species is described with a mixture fraction

  19. Short communication: Glucagon-like peptide-2 and coccidiosis alter tight junction gene expression in the gastrointestinal tract of dairy calves.

    Science.gov (United States)

    Walker, M P; Evock-Clover, C M; Elsasser, T H; Connor, E E

    2015-05-01

    Tight junction (TJ) proteins are integral factors involved in gut barrier function, and therapy with glucagon-like peptide-2 (GLP-2) enhances gut integrity. Our aim was to assess effects of GLP-2 treatment on mRNA expression of 8 TJ complex proteins in the intestine of dairy calves not infected or infected with Eimeria bovis at 11±3d of age. Mucosal epithelium from jejunum, ileum, and cecum was collected at slaughter from Holstein bull calves assigned to 4 groups: noninfected, buffer-treated (n=5); noninfected, GLP-2 treated (n=4); E. bovis-infected, buffer-treated (n=5); and E. bovis-infected, GLP-2-treated (n=4). Infected calves were orally dosed with 100,000 to 200,000 sporulated E. bovis oocysts on d 0; GLP-2-treated calves received 50 µg of GLP-2/kg of body weight subcutaneously twice daily for 10d beginning on d 18; and buffer-treated calves received an equal injection volume of 0.01 M Na bicarbonate buffer. All calves were killed on d 28. The mRNA expression of coxsackie and adenovirus receptor (CXADR), claudins 1, 2, and 4 (CLDN1, CLDN2, and CLDN4), F11 receptor (F11R), junction adhesion molecule 2 (JAM2), occludin (OCLN), and tight junction protein ZO-1 (TJP1) was determined by real-time quantitative PCR. In jejunum and ileum, an interaction of E. bovis infection and GLP-2 treatment on gene expression was noted. In jejunum of noninfected calves, GLP-2 increased CXADR, CLDN2, OCLN, and TJP1 mRNA expression but had no effect on mRNA expression in infected calves. Treatment with GLP-2 also increased tight junction protein ZO-1 protein expression in jejunum of noninfected calves as determined by immunohistochemistry. In ileum, E. bovis decreased expression of JAM2, OCLN, and TJP1 in buffer-treated calves, and GLP-2 increased TJP1 expression in infected calves. In cecum, E. bovis infection reduced expression of CXADR, CLDN4, F11R, and OCLN, and GLP-2 therapy increased expression of CLDN4, F11R, OCLN, and TJP1. Results are consistent with studies in

  20. An assay for permeability of the zebrafish embryonic neuroepithelium.

    Science.gov (United States)

    Chang, Jessica T; Sive, Hazel

    2012-10-24

    The brain ventricular system is conserved among vertebrates and is composed of a series of interconnected cavities called brain ventricles, which form during the earliest stages of brain development and are maintained throughout the animal's life. The brain ventricular system is found in vertebrates, and the ventricles develop after neural tube formation, when the central lumen fills with cerebrospinal fluid (CSF) (1,2). CSF is a protein rich fluid that is essential for normal brain development and function(3-6). In zebrafish, brain ventricle inflation begins at approximately 18 hr post fertilization (hpf), after the neural tube is closed. Multiple processes are associated with brain ventricle formation, including formation of a neuroepithelium, tight junction formation that regulates permeability and CSF production. We showed that the Na,K-ATPase is required for brain ventricle inflation, impacting all these processes (7,8), while claudin 5a is necessary for tight junction formation (9). Additionally, we showed that "relaxation" of the embryonic neuroepithelium, via inhibition of myosin, is associated with brain ventricle inflation. To investigate the regulation of permeability during zebrafish brain ventricle inflation, we developed a ventricular dye retention assay. This method uses brain ventricle injection in a living zebrafish embryo, a technique previously developed in our lab(10), to fluorescently label the cerebrospinal fluid. Embryos are then imaged over time as the fluorescent dye moves through the brain ventricles and neuroepithelium. The distance the dye front moves away from the basal (non-luminal) side of the neuroepithelium over time is quantified and is a measure of neuroepithelial permeability (Figure 1). We observe that dyes 70 kDa and smaller will move through the neuroepithelium and can be detected outside the embryonic zebrafish brain at 24 hpf (Figure 2). This dye retention assay can be used to analyze neuroepithelial permeability in a

  1. Bentonite Permeability at Elevated Temperature

    Directory of Open Access Journals (Sweden)

    Katherine A. Daniels

    2017-01-01

    Full Text Available Repository designs frequently favour geological disposal of radioactive waste with a backfill material occupying void space around the waste. The backfill material must tolerate the high temperatures produced by decaying radioactive waste to prevent its failure or degradation, leading to increased hydraulic conductivity and reduced sealing performance. The results of four experiments investigating the effect of temperature on the permeability of a bentonite backfill are presented. Bentonite is a clay commonly proposed as the backfill in repository designs because of its high swelling capacity and very low permeability. The experiments were conducted in two sets of purpose-built, temperature controlled apparatus, designed to simulate isotropic pressure and constant volume conditions within the testing range of 4–6 MPa average effective stress. The response of bentonite during thermal loading at temperatures up to 200 °C was investigated, extending the previously considered temperature range. The results provide details of bentonite’s intrinsic permeability, total stress, swelling pressure and porewater pressure during thermal cycles. We find that bentonite’s hydraulic properties are sensitive to thermal loading and the type of imposed boundary condition. However, the permeability change is not large and can mostly be accounted for by water viscosity changes. Thus, under 150 °C, temperature has a minimal impact on bentonite’s hydraulic permeability.

  2. Sensitivity analysis of permeability parameters for flows on Barcelona networks

    Science.gov (United States)

    Rarità, Luigi; D'Apice, Ciro; Piccoli, Benedetto; Helbing, Dirk

    We consider the problem of optimizing vehicular traffic flows on an urban network of Barcelona type, i.e. square network with streets of not equal length. In particular, we describe the effects of variation of permeability parameters, that indicate the amount of flow allowed to enter a junction from incoming roads. On each road, a model suggested by Helbing et al. (2007) [11] is considered: free and congested regimes are distinguished, characterized by an arrival flow and a departure flow, the latter depending on a permeability parameter. Moreover we provide a rigorous derivation of the model from fluid dynamic ones, using recent results of Bretti et al. (2006) [3]. For solving the dynamics at nodes of the network, a Riemann solver maximizing the through flux is used, see Coclite et al. (2005) [4] and Helbing et al. (2007) [11]. The network dynamics gives rise to complicate equations, where the evolution of fluxes at a single node may involve time-delayed terms from all other nodes. Thus we propose an alternative hybrid approach, introducing additional logic variables. Finally we compute the effects of variations on permeability parameters over the hybrid dynamics and test the obtained results via simulations.

  3. Yokukansan (TJ-54 for treatment of pervasive developmental disorder not otherwise specified and Asperger’s disorder: a 12-week prospective, open-label study

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    Miyaoka Tsuyoshi

    2012-11-01

    Full Text Available Abstract Background Numerous medications have been tested on patients with pervasive developmental disorder not otherwise specified (PDD-NOS and Asperger’s disorder. Although many of these medications have been demonstrated to be useful, no clear primary treatment for PDD-NOS and Asperger’s disorder has emerged. Despite the efficacy of some of the medicines, the acceptability and side effects have proven to be barriers to their use. Recent studies indicate that the traditional Japanese herbal medicine yokukansan (TJ-54 may be safe and useful in treating behavioral and psychological symptoms in dementia and some neuropsychiatric disorders. We aimed at evaluating both the efficacy and safety of TJ-54 in patients with well-defined PDD-NOS and Asperger’s disorder. Methods This was a 12-week prospective, open-label investigation of TJ-54 in 40 children, adolescents, and adults diagnosed with PDD-NOS or Asperger’s disorder. Primary outcome measures included the Clinical Global Impressions-Severity of Illness Scale (CGI-S and the Aberrant Behavior Checklist-Iritability subscale score (ABC-I. Results Forty subjects, ages 8–40 years (mean 22.7 ± 7.3 years received a mean final TJ-54 dosage of 6.4 ± 1.3 g/day (range 2.5-7.5 g/day. Full-scale intelligence quotient (IQ scores ranged from 70 to 110 (mean 88.9 ± 13.2. Thirty-six (90% of 40 subjects showed fewer interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-S of 1 or 2 (normal, not at all ill or borderline mentally ill and a 80% or greater improvement on the ABC-I. The mean CGI-S score at baseline was 6.8 ± 0.8 whereas scores at end point was 1.9 ± 0.1 ( Conclusions These preliminary data suggest that TJ-54 may be effective and well tolerated for treatment of severe irritability, lethargy/withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech in patients with PDD-NOS or Asperger’s disorder. However

  4. Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity.

    Science.gov (United States)

    Maherally, Zaynah; Fillmore, Helen L; Tan, Sim Ling; Tan, Suk Fei; Jassam, Samah A; Quack, Friederike I; Hatherell, Kathryn E; Pilkington, Geoffrey J

    2017-09-07

    The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL). Most in vitro models use nonhuman, monolayer cultures for therapeutic-delivery studies, relying on transendothelial electrical resistance (TEER) measurements without other tight-junction (TJ) formation parameters. We aimed to develop reliable, reproducible, in vitro 3-dimensional (3D) models incorporating relevant human, in vivo cell types and BL proteins. The 3D BBB models were constructed with human brain endothelial cells, human astrocytes, and human brain pericytes in mono-, co-, and tricultures. TEER was measured in 3D models using a volt/ohmmeter and cellZscope. Influence of BL proteins-laminin, fibronectin, collagen type IV, agrin, and perlecan-on adhesion and TEER was assessed using an electric cell-substrate impedance-sensing system. TJ protein expression was assessed by Western blotting (WB) and immunocytochemistry (ICC). Perlecan (10 µg/ml) evoked unreportedly high, in vitro TEER values (1200 Ω) and the strongest adhesion. Coculturing endothelial cells with astrocytes yielded the greatest resistance over time. ICC and WB results correlated with resistance levels, with evidence of prominent occludin expression in cocultures. BL proteins exerted differential effects on TEER, whereas astrocytes in contact yielded higher TEER values and TJ expression.-Maherally, Z., Fillmore, H. L., Tan, S. L., Tan, S. F., Jassam, S. A., Quack, F. I., Hatherell, K. E., Pilkington, G. J. Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity. © FASEB.

  5. Structural alteration of tight and adherens junctions in villous and crypt epithelium of the small and large intestine of conventional nursing piglets infected with porcine epidemic diarrhea virus.

    Science.gov (United States)

    Jung, Kwonil; Eyerly, Bryan; Annamalai, Thavamathi; Lu, Zhongyan; Saif, Linda J

    2015-06-12

    Integrity of the intestinal epithelium is critical for proper functioning of the barrier that regulates absorption of water and restricts uptake of luminal bacteria. It is maintained mainly by tight junctions (TJs) and adherens junctions (AJs). We conducted immunofluorescence (IF) staining for in situ identification of zonula occludin (ZO)-1 proteins for TJ and E-Cadherin proteins for AJ in the small and large intestinal villous and crypt epithelium of nursing pigs infected with porcine epidemic diarrhea virus (PEDV). Twenty 9-day-old piglets [PEDV-infected (n=9) and Mock (n=11)] from PEDV seronegative sows, were orally inoculated [8.9 log₁₀ genomic equivalents/pig] with PEDV PC21A strain or mock. At post-inoculation days (PIDs) 1-5, infected pigs showed severe watery diarrhea and/or vomiting and severe atrophic enteritis. By immunohistochemistry, PEDV antigens were evident in enterocytes lining the villous epithelium. At PIDs 1-5, PEDV-infected pigs exhibited mildly to extensively disorganized, irregular distribution and reduced expression of ZO-1 or E-Cadherin in villous, but not crypt epithelial cells of the jejunum and ileum, but not in the large intestine, when compared to the negative controls. The structural destruction and disorganization of TJ and AJ were extensive in PEDV-infected pigs at PIDs 1-3, but then appeared to reversibly recover at PID 5, as evident by increased numbers of ZO-1-positive epithelial cells and markedly improved appearance of E-Cadherin-positive villous epithelium. Our results suggest a possible involvement of structurally impaired TJ and AJ in the pathogenesis of PEDV, potentially leading to secondary bacterial infections.

  6. Claudin-binder C-CPE mutants enhance permeability of insulin across human nasal epithelial cells.

    Science.gov (United States)

    Kojima, Takashi; Kondoh, Masuo; Keira, Takashi; Takano, Ken-Ichi; Kakuki, Takuya; Kaneko, Yakuto; Miyata, Ryo; Nomura, Kazuaki; Obata, Kazufumi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo

    2016-10-01

    Intranasal insulin administration has therapeutic potential for Alzheimer's disease and in intranasal administration across the nasal mucosa, the paracellular pathway regulated by tight junctions is important. The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) binds the tight junction protein claudin and disrupts the tight junctional barrier without a cytotoxic effect. The C-CPE mutant called C-CPE 194 binds only to claudin-4, whereas the C-CPE 194 mutant called C-CPE m19 binds not only to claudin-4 but also to claudin-1. In the present study, to investigate the effects of C-CPE mutants on the tight junctional functions of human nasal epithelial cells (HNECs) and on the permeability of human recombinant insulin across the cells, HNECs were treated with C-CPE 194 and C-CPE m19. C-CPE 194 and C-CPE m19 disrupted the barrier and fence functions without changes in expression of claudin-1, -4, -7, and occludin or cytotoxicity, whereas they transiently increased the activity of ERK1/2 phosphorylation. The disruption of the barrier function caused by C-CPE 194 and C-CPE m19 was prevented by pretreatment with the MAPKK inhibitor U0126. Furthermore, C-CPE 194 and C-CPE m19 significantly enhanced the permeability of human recombinant insulin across HNECs and the permeability was also inhibited by U0126. These findings suggest that C-CPE mutants 194 and m19 can regulate the permeability of insulin across HNECs via the MAPK pathway and may play a crucial role in therapy for the diseases such as Alzheimer's disease via the direct intranasal insulin administration.

  7. Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice.

    Science.gov (United States)

    Chaudhry, Kamaljit K; Shukla, Pradeep K; Mir, Hina; Manda, Bhargavi; Gangwar, Ruchika; Yadav, Nikki; McMullen, Megan; Nagy, Laura E; Rao, RadhaKrishna

    2016-01-01

    Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of Gln in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed with Gln-free diet and absent in mice fed with Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury.

  8. Fibroblast growth factor signaling potentiates VE-cadherin stability at adherens junctions by regulating SHP2.

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    Kunihiko Hatanaka

    Full Text Available BACKGROUND: The fibroblast growth factor (FGF system plays a critical role in the maintenance of vascular integrity via enhancing the stability of VE-cadherin at adherens junctions. However, the precise molecular mechanism is not well understood. In the present study, we aimed to investigate the detailed mechanism of FGF regulation of VE-cadherin function that leads to endothelial junction stabilization. METHODS AND FINDINGS: In vitro studies demonstrated that the loss of FGF signaling disrupts the VE-cadherin-catenin complex at adherens junctions by increasing tyrosine phosphorylation levels of VE-cadherin. Among protein tyrosine phosphatases (PTPs known to be involved in the maintenance of the VE-cadherin complex, suppression of FGF signaling reduces SHP2 expression levels and SHP2/VE-cadherin interaction due to accelerated SHP2 protein degradation. Increased endothelial permeability caused by FGF signaling inhibition was rescued by SHP2 overexpression, indicating the critical role of SHP2 in the maintenance of endothelial junction integrity. CONCLUSIONS: These results identify FGF-dependent maintenance of SHP2 as an important new mechanism controlling the extent of VE-cadherin tyrosine phosphorylation, thereby regulating its presence in adherens junctions and endothelial permeability.

  9. Homoharringtonine increases intestinal epithelial permeability by modulating specific claudin isoforms in Caco-2 cell monolayers.

    Science.gov (United States)

    Watari, Akihiro; Hashegawa, Maki; Yagi, Kiyohito; Kondoh, Masuo

    2015-01-01

    Homoharringtonine (HHT), a natural alkaloid produced by various Cephalotaxus species, has antileukemic activity in acute and chronic myelogenous leukemia. However, HHT can also induce unanticipated effects in the gastrointestinal tract, such as diarrhea and nausea/vomiting, but the mechanism behind these adverse effects has not been clarified. In the present study, we show that HHT affects the epithelial permeability of intestinal Caco-2 cell monolayers. HHT reduced the transepithelial electrical resistance (TER) of Caco-2 cells in a dose- and time-dependent manner. The HHT effect was reversible and no cytotoxicity was observed at the concentrations used. HHT simultaneously increased the paracellular flux of the 4 kDa and 40 kDa FITC-dextrans associated with the TER reduction. Immunoblotting analysis revealed that HHT decreased the protein expression of TJ components such as claudin-3, -5, and -7. However, the transcription levels of these claudins were not repressed by HHT treatment. HHT also disturbed the cellular localization of claudin-1 and -4. These changes coincided with the reduced barrier function. Our findings suggest that HHT enhances the paracellular permeability of Caco-2 cell monolayers by modulating the protein expression and localization of claudin isoforms; these actions might be responsible for the gastrointestinal effects of HHT. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Metallic Junction Thermoelectric Device Simulations

    Science.gov (United States)

    Duzik, Adam J.; Choi, Sang H.

    2017-01-01

    Thermoelectric junctions made of semiconductors have existed in radioisotope thermoelectric generators (RTG) for deep space missions, but are currently being adapted for terrestrial energy harvesting. Unfortunately, these devices are inefficient, operating at only 7% efficiency. This low efficiency has driven efforts to make high-figure-of-merit thermoelectric devices, which require a high electrical conductivity but a low thermal conductivity, a combination that is difficult to achieve. Lowered thermal conductivity has increased efficiency, but at the cost of power output. An alternative setup is to use metallic junctions rather than semiconductors as thermoelectric devices. Metals have orders of magnitude more electrons and electronic conductivities higher than semiconductors, but thermal conductivity is higher as well. To evaluate the viability of metallic junction thermoelectrics, a two dimensional heat transfer MATLAB simulation was constructed to calculate efficiency and power output. High Seebeck coefficient alloys, Chromel (90%Ni-10%Cr) and Constantan (55%Cu-45%Ni), produced efficiencies of around 20-30%. Parameters such as the number of layers of junctions, lateral junction density, and junction sizes for both series- and parallel-connected junctions were explored.

  11. The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon.

    Science.gov (United States)

    Karaki, Shin-ichiro; Kaji, Izumi; Otomo, Yasuko; Tazoe, Hideaki; Kuwahara, Atsukazu

    2007-11-27

    The expression of a tight junction (TJ) component protein, claudin-4, in the enteric neurons was investigated in the rat distal colon by immunohistochemistry and RT-PCR. Claudin-4 immunoreactivity was detected in almost all neurofilament-positive enteric neurons both of the submucosal and the myenteric plexuses, and both of the cell bodies and the neurofibers. The immunoreactivity of enteric neurons for claudin-4 was divided into two types: strongly and weakly positive neurons. Especially in the myenteric plexus, the stained neurons were classified by Dogiel's morphological classification of enteric neurons. The strongly stained claudin-4 positive neurons show Dogiel type II morphology, while the weakly stained claudin-4 positive neurons show Dogiel type I morphology. These immunohistochemical data were supported by mRNA expression in the muscle plus submucosa preparation containing the submucosal and myenteric plexuses, as well as mucosa preparation. The physiological function of claudin-4 expressed on enteric neurons is unclear up to now. It is however suggested that claudin-4 expressed on enteric neurons might play roles for the neural activity, for example as insulation between neurofibers. In conclusion, the present study clearly shows that claudin-4 is expressed by enteric neurons. This is the first evidence that the neuron itself expresses the TJ component protein, claudin-4, in the nervous system.

  12. The tight junction protein ZO-2 associates with Jun, Fos and C/EBP transcription factors in epithelial cells.

    Science.gov (United States)

    Betanzos, Abigail; Huerta, Miriam; Lopez-Bayghen, Esther; Azuara, Elisa; Amerena, José; González-Mariscal, Lorenza

    2004-01-01

    ZO-2 is a membrane-associated guanylate kinase (MAGUK) protein present at the tight junction (TJ) of epithelial cells. While confluent monolayers have ZO-2 at their cellular borders, sparse cultures conspicuously show ZO-2 at the nuclei. To study the role of nuclear ZO-2, we tested by pull-down assays and gel shift analysis the interaction between ZO-2 GST fusion proteins and different transcription factors. We identified the existence of a specific interaction of ZO-2 with Fos, Jun and C/EBP (CCAAT/enhancer binding protein). To analyze if this association is present "in vivo", we performed immunoprecipitation and immunolocalization experiments, which revealed an interaction of ZO-2 with Jun, Fos and C/EBP not only at the nucleus but also at the TJ region. To test if the association of ZO-2 with AP-1 (activator protein-1) modulates gene transcription, we performed reporter gene assays employing chloramphenicol acetyltransferase (CAT) constructs with promoters under the control of AP-1 sites. We observed that the co-transfected ZO-2 down-regulates CAT expression in a dose-dependent manner. Since ZO-2 is a multidomain protein, we proceeded to determine which region of the molecule is responsible for the modulation of gene expression, and observed that both the amino and the carboxyl domains are capable of inhibiting gene transcription.

  13. An Impurity Emission Survey in the near UV and Visible Spectral Ranges of Electron Cyclotron Heated (ECH) Plasma in the TJ-II Stellarator

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, K. J.; Zurro, B.; Baciero, A.

    2001-07-01

    We report on a near-ultraviolet and visible spectroscopic survey (220-600 nm) of electron cyclotron resonance (ECR) heated plasmas created in the TJ-II stellarator, with central electron temperatures up to 2 keV and central electron densities up to 1.7 x 10 ''19 m''-3. Approximately 1200 lines from thirteen elements have been identified. The purpose of the work is to identify the principal impurities and spectral lines present in TJ-II plasmas, as well as their possible origin to search for transitions from highly ionised ions. This work will act as a base for identifying suitable transitions for following the evolution of impurities under different operating regimens and multiplet systems for line polarisation studies. It is intended to use the database creates as a spectral line reference for comparing spectra under different operating and plasma heating regimes. (Author)

  14. Ground-water flow and contaminant transport at a radioactive-materials processing site, Wood River Junction, Rhode Island

    Science.gov (United States)

    Ryan, Barbara J.; Kipp, Kenneth L.

    1997-01-01

    Liquid wastes from an enriched-uranium cold-scrap recovery plant at Wood River Junction, Rhode Island, were discharged to the environment through evaporation ponds and trenches from 1966 through 1980. Leakage from the ponds and trenches resulted in a plume of contaminated ground water extending northwestward to the Pawcatuck River through a highly permeable sand and gravel aquifer of glacial origin.

  15. Ileal tight junction gene expression in glucagon-like peptide 2-treated dairy bull calves with and without coccidiosis

    Science.gov (United States)

    Intestinal gut permeability is partially regulated by the intestinotrophic hormone glucagon-like peptide 2 (GLP-2). Specifically, disease models in mice and human cell lines have implicated GLP-2 in the regulation of the tight junction milieu within the intestinal tract. Therapeutic administration o...

  16. Tight junction gene expression in gastrointestinal tract of dairy calves with coccidiosis and treated with glucagon-like peptide-2

    Science.gov (United States)

    Selective permeability of the intestinal epithelium and efficient nutrient absorption are important functions for proper growth and development of calves. Damage to the intestinal mucosa can give rise to harmful long-term health effects and reduce productivity of the mature animal. Tight junction pr...

  17. Real-time data acquisition and parallel data processing solution for TJ-II Bolometer arrays diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    Barrera, E. [Departamento de Sistemas Electronicos y de Control, Universidad Politecnica de Madrid, Crta. Valencia Km. 7, 28031 Madrid (Spain)]. E-mail: eduardo.barrera@upm.es; Ruiz, M. [Grupo de Investigacion en Instrumentacion y Acustica Aplicada, Universidad Politecnica de Madrid, Crta. Valencia Km. 7, 28031 Madrid (Spain); Lopez, S. [Departamento de Sistemas Electronicos y de Control, Universidad Politecnica de Madrid, Crta. Valencia Km. 7, 28031 Madrid (Spain); Machon, D. [Departamento de Sistemas Electronicos y de Control, Universidad Politecnica de Madrid, Crta. Valencia Km. 7, 28031 Madrid (Spain); Vega, J. [Asociacion EURATOM/CIEMAT para Fusion, 28040 Madrid (Spain); Ochando, M. [Asociacion EURATOM/CIEMAT para Fusion, 28040 Madrid (Spain)

    2006-07-15

    Maps of local plasma emissivity of TJ-II plasmas are determined using three-array cameras of silicon photodiodes (AXUV type from IRD). They have assigned the top and side ports of the same sector of the vacuum vessel. Each array consists of 20 unfiltered detectors. The signals from each of these detectors are the inputs to an iterative algorithm of tomographic reconstruction. Currently, these signals are acquired by a PXI standard system at approximately 50 kS/s, with 12 bits of resolution and are stored for off-line processing. A 0.5 s discharge generates 3 Mbytes of raw data. The algorithm's load exceeds the CPU capacity of the PXI system's controller in a continuous mode, making unfeasible to process the samples in parallel with their acquisition in a PXI standard system. A new architecture model has been developed, making possible to add one or several processing cards to a standard PXI system. With this model, it is possible to define how to distribute, in real-time, the data from all acquired signals in the system among the processing cards and the PXI controller. This way, by distributing the data processing among the system controller and two processing cards, the data processing can be done in parallel with the acquisition. Hence, this system configuration would be able to measure even in long pulse devices.

  18. Verticase:a Fibrinolytic Enzyme Produced by Verticillium sp.Tj33,an Endophyte of Trachelospermum jasminoides

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Plant endophytes are among the most important resources of biologically active metabolites.Twenty-three endophyte strains residing in Trachelospermum jasminoides were cultivated In with the cultures assayed for the fibrinolytic substance production.As a result,the culture of Verticillium sp.Tj33 was shown to be the most active.A fibrinolytic enzyme designated as verticase was subsequently purified from the supernatant of Verticillium sp.culture broth by a combination of DEAE-52,Sephadex G-75 and hydrophobic column chromatographies.Verticase,with its molecular mass of 31 kDa and pl of 8.5,was demonstrated to be homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing electrophoresis.Verticase is an enzyme that hydrolyzes fibrin directly without activation of plaminogen.It was stable in a broad pH range from 4 through to 11 with the optimal reaction pH value and temperature shown to be around 9-10 and 50-60℃,respectively.The fibrinolytic activity of verticase was severely inhibited by phenylmethylsulfony fluoride,Indicating that verticase was a serine protease.

  19. Fault interaction and stresses along broad oceanic transform zone: Tjörnes Fracture Zone, north Iceland

    Science.gov (United States)

    Homberg, C.; Bergerat, F.; Angelier, J.; Garcia, S.

    2010-02-01

    Transform motion along oceanic transforms generally occurs along narrow faults zones. Another class of oceanic transforms exists where the plate boundary is quite large (˜100 km) and includes several subparallel faults. Using a 2-D numerical modeling, we simulate the slip distribution and the crustal stress field geometry within such broad oceanic transforms (BOTs). We examine the possible configurations and evolution of such BOTs, where the plate boundary includes one, two, or three faults. Our experiments show that at any time during the development of the plate boundary, the plate motion is not distributed along each of the plate boundary faults but mainly occurs along a single master fault. The finite width of a BOT results from slip transfer through time with locking of early faults, not from a permanent distribution of deformation over a wide area. Because of fault interaction, the stress field geometry within the BOTs is more complex than that along classical oceanic transforms and includes stress deflections close to but also away from the major faults. Application of this modeling to the 100 km wide Tjörnes Fracture Zone (TFZ) in North Iceland, a major BOT of the Mid-Atlantic Ridge that includes three main faults, suggests that the Dalvik Fault and the Husavik-Flatey Fault developed first, the Grismsey Fault being the latest active structure. Since initiation of the TFZ, the Husavik-Flatey Fault accommodated most of the plate motion and probably persists until now as the main plate structure.

  20. Light and scanning electron microscopic and immunohistochemical studies on permeability of hypertensive rat mesenteric arteries.

    Science.gov (United States)

    Suzuki, K; Kawaharada, U; Takatama, M; Ooneda, G

    1985-09-01

    Experimental hypertensive rats were intravenously injected with carbon and iron as tracers, and their mesenteric arteries exhibiting hypertensive arterial lesions were observed by light and scanning electron microscopy and immunohistochemistry. Early arterial lesions showing intense medial damages, deposition of fibrinoid substance consisting of fibrin in the intima and/or media, and granulation tissue in the adventitia were characterized by marked insudation of intravenously injected tracers. Scanning electron microscopy demonstrated numerous leukocytes and platelets adhering to endothelial surface, opened endothelial cell junctions, and desquamation of these cells. Immunohistochemistry revealed laminin and low stainability of fibronectin in the subendothelium. Advanced lesions showed deposition of a large amount of fibrinoid substance and no insudation of tracers in the intima, but scanning electron microscopy manifested opening of endothelial cell junctions, desquamation of endothelial cells, and adherence of leukocytes and platelets. Immunohistochemistry revealed fibronectin in the intima and laminin just beneath the endothelium. In the healed lesions disclosing fibrocellular intimal thickening, there was no insudation of tracers. Scanning electron microscopy showed opened endothelial cell junctions, endothelial cell defects, and adherence of leukocytes and platelets. There were fibronectin in the intima and laminin beneath the endothelium. It was suggested that the opening of endothelial cells junctions and desquamation of endothelial cells would be necessary for the arterial increased permeability in hypertensive rats, and that fibrin-fibronectin complex, fibronectin-acid mucopolysaccharide complex, and basement membrane would together inhibit the increased permeability in the mesenteric arteries of hypertensive rats in spite of endothelial cell injuries and their defects.

  1. Over-expression of Slit2 induces vessel formation and changes blood vessel permeability in mouse brain

    Institute of Scientific and Technical Information of China (English)

    Hai-xiong HAN; Jian-guo GENG

    2011-01-01

    Aim:To investigate the effect of the axon guidance cue Slit2 on the density of blood vessels and permeability of the blood-brain barrier in mouse brain.Methods:hSlit2 transgenic mouse line was constructed,and the phenotypes of the mice were compared with wild-type mice in respect to the lateral ventricle (LV),ventricle pressure,and the choroids plexus.An in vivo Miles permeability assay and an amyloid-β permeability assay were used to assess the permeability of brain blood vessels.Brain vessel casting and intracerebral hemorrhage models were built to investigate vessel density in the transgenic mice.An in vitro permeability assay was used to test whether Slit2 could change the permeability and tight junctions of blood vessel endothelial cells.Results:Hydrocephalus occurred in some transgenic mice,and a significantly larger lateral ventricle area and significantly higher ventricle pressure were observed in the transgenic mice.The transgenic mice displayed changed construction of the choroids plexus,which had more micro vessels,dilated vessels,gaps between epithelial cells and endothelial cells than wild-type mice.Slit2 significantly increased brain vessel density and the permeability of brain vessels to large molecules.These blood vessels were more sensitive to cues that induce brain hemorrhage.At the cellular level,Slit2 disturbed the integrity of tight junctions in blood vessel endothelial cells and improved the permeability of the endothelial cell layer.Thus,it promoted the entry of amyloid-β peptides from the serum into the central nervous system,where they bound to neurons.Conclusion:Slit2 increases vessel density and permeability in the brains of transgenic mice.Thus,Slit2 induces numerous changes in brain vessels and the barrier system.

  2. Capillary permeability in adipose tissue

    DEFF Research Database (Denmark)

    Paaske, W P; Nielsen, S L

    1976-01-01

    of about 7 ml/100 g-min. This corresponds to a capillary diffusion capacity of 2.0 ml/100 g-min which is half the value reported for vasodilated skeletal muscle having approximately twice as great capillary surface area. Thus, adipose tissue has about the same capillary permeability during slight metabolic...

  3. Liver injury induced by a Japanese herbal medicine, sairei-to (TJ-114, Bupleurum and Hoelen Combination, Chai-Ling-Tang) R1.

    Science.gov (United States)

    Aiba, Tsuneo; Takahashi, Toru; Suzuki, Kenji; Okoshi, Shogo; Nomoto, Minoru; Uno, Katsuji; Aoyagi, Yutaka

    2007-05-01

    The case is reported of a man who showed acute hepatitis with jaundice after he was given a Japanese herbal medicine, sairei-to (TJ-114, Bupleurum and Hoelen Combination, Chai-Ling-Tang). Unusually, the component thought to be responsible for the observed drug-induced liver injury was able to be identified. Lymphocyte migration inhibition testing indicated that the tuber of the perennial herbage Pinellia ternate was the causative agent.

  4. Imaging of cervicothoracic junction trauma

    Directory of Open Access Journals (Sweden)

    Wongwaisayawan S

    2013-01-01

    Full Text Available Sirote Wongwaisayawan,1 Ruedeekorn Suwannanon,2 Rathachai Kaewlai11Department of Radiology, Ramathibodi Hospital and Mahidol University, Bangkok, Thailand; 2Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, ThailandAbstract: Cervicothoracic junction trauma is an important cause of morbidity and mortality in trauma patients. Imaging has played an important role in identifying injuries and guiding appropriate, timely therapy. Computed tomography is currently a method of choice for diagnosing cervicothoracic junction trauma, in which the pattern of injuries often suggests possible mechanisms and potential injuries. In this article, the authors describe and illustrate common and uncommon injuries that can occur in the cervicothoracic junction.Keywords: cervicothoracic junction, cervical spine, trauma, imaging, radiology

  5. Oceanographic profile data collected from CTD casts aboard NOAA Ship THOMAS JEFFERSON as part of project OPR-D304-TJ-05 in the North Atlantic Ocean from 2005-06-02 to 2006-06-21 (NCEI Accession 0130802)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130802 includes physical and profile data collected aboard NOAA Ship THOMAS JEFFERSON during project OPR-D304-TJ-05 in the North Atlantic Ocean from...

  6. Oceanographic profile data collected from CTD casts aboard NOAA Ship THOMAS JEFFERSON as part of project OPR-B370-TJ-05 in the North Atlantic Ocean from 2005-04-04 to 2005-05-22 (NCEI Accession 0130797)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130797 includes physical and profile data collected aboard NOAA Ship THOMAS JEFFERSON during project OPR-B370-TJ-05 in the North Atlantic Ocean from...

  7. Oceanographic profile data collected from CTD casts aboard NOAA Ship THOMAS JEFFERSON as part of project OPR-B370-TJ-04 in the North Atlantic Ocean from 2004-09-14 to 2004-11-15 (NCEI Accession 0130292)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130292 includes physical and profile data collected aboard NOAA Ship THOMAS JEFFERSON during project OPR-B370-TJ-04 in the North Atlantic Ocean from...

  8. Oceanographic profile data collected from CTD casts aboard NOAA Ship THOMAS JEFFERSON as part of project OPR-J323-TJ-05 in the Gulf of Mexico from 2005-09-30 to 2005-11-03 (NCEI Accession 0130812)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130812 includes physical and profile data collected aboard NOAA Ship THOMAS JEFFERSON during project OPR-J323-TJ-05 in the Gulf of Mexico from...

  9. Oceanographic profile data collected from CTD casts aboard NOAA Ship THOMAS JEFFERSON as part of project OPR-A397-TJ-03 in the North Atlantic Ocean from 2003-08-19 to 2003-10-03 (NCEI Accession 0130794)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130794 includes physical and profile data collected aboard NOAA Ship THOMAS JEFFERSON during project OPR-A397-TJ-03 in the North Atlantic Ocean from...

  10. Oceanographic profile data collected from CTD casts aboard NOAA Ship THOMAS JEFFERSON as part of project OPR-B310-TJ-08 in the North Atlantic Ocean from 2000-06-12 to 2008-09-05 (NCEI Accession 0130773)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130773 includes physical and profile data collected aboard NOAA Ship THOMAS JEFFERSON during project OPR-B310-TJ-08 in the North Atlantic Ocean from...

  11. Oceanographic profile data collected from CTD casts aboard NOAA Ship THOMAS JEFFERSON as part of project S-B634-TJ-09 in the North Atlantic Ocean from 2009-09-13 to 2009-09-23 (NCEI Accession 0130670)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0130670 includes physical and profile data collected aboard NOAA Ship THOMAS JEFFERSON during project S-B634-TJ-09 in the North Atlantic Ocean from...

  12. Semi-quantitative analysis of cytokine mRNA expression induced by the herbal medicine Sho-saiko-to (TJ-9) using a Gel Doc system.

    Science.gov (United States)

    Huang, X X; Yamashiki, M; Nakatani, K; Nobori, T; Mase, A

    2001-01-01

    The RT-PCR method was employed to determine the cytokine mRNA expression of human peripheral lymphocytes induced by the Japanese herbal medicine Sho-saiko-to (TJ-9). The results showed that the mRNA expression of IL-12, IL-1beta, IL-10, TNF-alpha, G-CSF, and IFN-gamma increased after 6 hr in culture. This is the first reported finding that TJ-9 is an IFN-gamma inducer. Next, cytokine mRNA expression was semi-quantitatively measured using the Gel Doc system with a CCD camera and then statistically analyzed in order to determine which component of TJ-9 was the true cytokine inducer. The results showed that the scutellaria root is the main component inducing the cytokines, while the glycyrrhiza root is the secondary component. When the cytokine concentrations in the supernatants of cell cultures were measured by ELISA, the levels of IL-12, IL-1beta, IL-10, TNF-alpha, and G-CSF reflected mRNA expression levels in the cell fraction. However, the level of IFN-gamma was below the detectable limit. The effects of various reagents on many different kinds of cytokine mRNA expression could be analyzed objectively in a short time using the Gel Doc system. Many important findings could be demonstrated by this simple, easy, sensitive, and cheap method. After the clinical significance of cytokine analysis is confirmed, this method may become a useful clinical examination tool.

  13. Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery

    Science.gov (United States)

    Matsumoto, Yu; Nichols, Joseph W.; Toh, Kazuko; Nomoto, Takahiro; Cabral, Horacio; Miura, Yutaka; Christie, R. James; Yamada, Naoki; Ogura, Tadayoshi; Kano, Mitsunobu R.; Matsumura, Yasuhiro; Nishiyama, Nobuhiro; Yamasoba, Tatsuya; Bae, You Han; Kataoka, Kazunori

    2016-06-01

    Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named ‘eruptions’) into the tumour interstitial space. We propose that ‘dynamic vents’ form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug.

  14. Antibiotic treatment affects intestinal permeability and gut microbial composition in Wistar rats dependent on antibiotic class

    DEFF Research Database (Denmark)

    Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera;

    (AMX), cefataxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10-11 days. Bacterial composition, alpha diversity and cecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity...... in microbiota composition or function were observed following MTZ treatment. Permeability to 4 kDa FITC-dextran was decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes...... were found in any treatment group. Antibiotic induced changes in microbiota could be linked to intestinal permeability, although changes in permeability did not always result from major changes in microbiota and vice versa....

  15. Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery.

    Science.gov (United States)

    Matsumoto, Yu; Nichols, Joseph W; Toh, Kazuko; Nomoto, Takahiro; Cabral, Horacio; Miura, Yutaka; Christie, R James; Yamada, Naoki; Ogura, Tadayoshi; Kano, Mitsunobu R; Matsumura, Yasuhiro; Nishiyama, Nobuhiro; Yamasoba, Tatsuya; Bae, You Han; Kataoka, Kazunori

    2016-06-01

    Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named 'eruptions') into the tumour interstitial space. We propose that 'dynamic vents' form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug.

  16. Demonstrated Anomalous Pancreaticobiliary Ductal Junction

    OpenAIRE

    Koçkar, Cem; ?ENOL, Altu?; BA?TÜRK, Abdulkadir; AYDIN, Bünyamin; Cüre, Erkan

    2015-01-01

    Anomalies of the pancreaticobiliary junction are rare. Clinically anomalies of the pancreaticobiliary junction are uncommonly symptomatic but may present themselves with associated conditions ranging from benign acute abdominal pain to carcinomas. A 52 years old man was admitted to gastroenterology service with complaints of fever, nausea, vomiting and recurrent epigastric pain. He was diagnosed with biliary pancreatitis. Endoscopic retrograde cholangiopancreato-graphy was performed. Papilla ...

  17. Josephson junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Wild, Georg Hermann

    2012-03-04

    We report on the fabrication of superconductor/insulator/ferromagnetic metal/superconductor (Nb/AlO{sub x}/Pd{sub 0.82}Ni{sub 0.18}/Nb) Josephson junctions (SIFS JJs) with high critical current densities, large normal resistance times area products, and high quality factors. For these junctions, a transition from 0- to {pi}-coupling is observed for a thickness d{sub F}=6 nm of the ferromagnetic Pd{sub 0.82}Ni{sub 0.18} interlayer. The magnetic field dependence of the critical current of the junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd{sub 0.82}Ni{sub 0.18} has an out-of-plane anisotropy and large saturation magnetization indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes up to about 400 GHz provides valuable information on the junction quality factor and the relevant damping mechanisms. Whereas losses due to quasiparticle tunneling dominate at low frequencies, at high frequencies the damping is explained by the finite surface resistance of the junction electrodes. High quality factors of up to 30 around 200 GHz have been achieved. They allow to study the junction dynamics, in particular the switching probability from the zero-voltage into the voltage state with and without microwave irradiation. The experiments with microwave irradiation are well explained within semi-classical models and numerical simulations. In contrast, at mK temperature the switching dynamics without applied microwaves clearly shows secondary quantum effects. Here, we could observe for the first time macroscopic quantum tunneling in Josephson junctions with a ferromagnetic interlayer. This observation excludes fluctuations of the critical current as a consequence of an unstable magnetic domain structure of the ferromagnetic interlayer and affirms the suitability of SIFS Josephson junctions for quantum information processing.

  18. Electronic thermometry in tunable tunnel junction

    Energy Technology Data Exchange (ETDEWEB)

    Maksymovych, Petro

    2016-03-15

    A tunable tunnel junction thermometry circuit includes a variable width tunnel junction between a test object and a probe. The junction width is varied and a change in thermovoltage across the junction with respect to the change in distance across the junction is determined. Also, a change in biased current with respect to a change in distance across the junction is determined. A temperature gradient across the junction is determined based on a mathematical relationship between the temperature gradient, the change in thermovoltage with respect to distance and the change in biased current with respect to distance. Thermovoltage may be measured by nullifying a thermoelectric tunneling current with an applied voltage supply level. A piezoelectric actuator may modulate the probe, and thus the junction width, to vary thermovoltage and biased current across the junction. Lock-in amplifiers measure the derivatives of the thermovoltage and biased current modulated by varying junction width.

  19. Confocal Annular Josephson Tunnel Junctions

    Science.gov (United States)

    Monaco, Roberto

    2016-09-01

    The physics of Josephson tunnel junctions drastically depends on their geometrical configurations and here we show that also tiny geometrical details play a determinant role. More specifically, we develop the theory of short and long annular Josephson tunnel junctions delimited by two confocal ellipses. The behavior of a circular annular Josephson tunnel junction is then seen to be simply a special case of the above result. For junctions having a normalized perimeter less than one, the threshold curves in the presence of an in-plane magnetic field of arbitrary orientations are derived and computed even in the case with trapped Josephson vortices. For longer junctions, a numerical analysis is carried out after the derivation of the appropriate motion equation for the Josephson phase. We found that the system is modeled by a modified and perturbed sine-Gordon equation with a space-dependent effective Josephson penetration length inversely proportional to the local junction width. Both the fluxon statics and dynamics are deeply affected by the non-uniform annulus width. Static zero-field multiple-fluxon solutions exist even in the presence of a large bias current. The tangential velocity of a traveling fluxon is not determined by the balance between the driving and drag forces due to the dissipative losses. Furthermore, the fluxon motion is characterized by a strong radial inward acceleration which causes electromagnetic radiation concentrated at the ellipse equatorial points.

  20. Octagonal Defects at Carbon Nanotube Junctions

    Science.gov (United States)

    Jaskólski, W.; Pelc, M.; Chico, Leonor; Ayuela, A.

    2013-01-01

    We investigate knee-shaped junctions of semiconductor zigzag carbon nanotubes. Two dissimilar octagons appear at such junctions; one of them can reconstruct into a pair of pentagons. The junction with two octagons presents two degenerate localized states at Fermi energy (EF). The reconstructed junction has only one state near EF, indicating that these localized states are related to the octagonal defects. The inclusion of Coulomb interaction splits the localized states in the junction with two octagons, yielding an antiferromagnetic system. PMID:24089604

  1. Quantifying Evaporation in a Permeable Pavement System

    Science.gov (United States)

    Studies quantifying evaporation from permeable pavement systems are limited to a few laboratory studies and one field application. This research quantifies evaporation for a larger-scale field application by measuring the water balance from lined permeable pavement sections. Th...

  2. Papain Degrades Tight Junction Proteins of Human Keratinocytes In Vitro and Sensitizes C57BL/6 Mice via the Skin Independent of its Enzymatic Activity or TLR4 Activation.

    Science.gov (United States)

    Stremnitzer, Caroline; Manzano-Szalai, Krisztina; Willensdorfer, Anna; Starkl, Philipp; Pieper, Mario; König, Peter; Mildner, Michael; Tschachler, Erwin; Reichart, Ursula; Jensen-Jarolim, Erika

    2015-07-01

    Papain is commonly used in food, pharmaceutical, textile, and cosmetic industries and is known to induce occupational allergic asthma. We have previously shown that the papain-like cysteine protease Dermatophagoides pteronyssinus 1 from house dust mite exhibits percutaneous sensitization potential. We aimed here to investigate the potential of papain itself in epicutaneous sensitization. The effects of papain on tight junction (TJ) proteins were tested in vitro in human primary keratinocytes. Using C57BL/6 wild-type and Toll-like receptor 4 (TLR4)-deficient mice, we analyzed the sensitization potential of papain, its effects on the skin barrier, and immune cell recruitment. Our results show that papain affects the skin barrier by increasing transepidermal water loss, degrading TJ proteins and inducing vasodilation. When topically applied, papain exhibited a high epicutaneous inflammatory potential by recruiting neutrophils, mast cells, and CD3-positive cells and by induction of a TH2-biased antibody response. However, its high potency for specific sensitization via the skin was TLR4 independent and, in spite of its capacity to degrade epidermal TJ proteins, does not rely on its enzymatic function. From our data, we conclude that papain has all features to act as a strong allergen via the skin.

  3. Permeability of Non-Crimp Fabric Preforms

    NARCIS (Netherlands)

    Loendersloot, Richard; Lomov, Stepan V.

    2011-01-01

    Experimental permeability data of non-crimp fabrics (NCFs) is discussed in this chapter. The chapter starts with a general introduction on permeability, followed by a discussion on experimental permeability data. The infl uence of geometrical features of the textile architecture, in particular the s

  4. Different Methods of Predicting Permeability in Shale

    DEFF Research Database (Denmark)

    Mbia, Ernest Ncha; Fabricius, Ida Lykke; Krogsbøll, Anette

    Permeability is often very difficult to measure or predict in shale lithology. In this work we are determining shale permeability from consolidation tests data using Wissa et al., (1971) approach and comparing the results with predicted permeability from Kozeny’s model. Core and cuttings materials...

  5. Modelling of Dual-Junction Solar Cells including Tunnel Junction

    Directory of Open Access Journals (Sweden)

    Abdelaziz Amine

    2013-01-01

    Full Text Available Monolithically stacked multijunction solar cells based on III–V semiconductors materials are the state-of-art of approach for high efficiency photovoltaic energy conversion, in particular for space applications. The individual subcells of the multi-junction structure are interconnected via tunnel diodes which must be optically transparent and connect the component cells with a minimum electrical resistance. The quality of these diodes determines the output performance of the solar cell. The purpose of this work is to contribute to the investigation of the tunnel electrical resistance of such a multi-junction cell through the analysis of the current-voltage (J-V characteristics under illumination. Our approach is based on an equivalent circuit model of a diode for each subcell. We examine the effect of tunnel resistance on the performance of a multi-junction cell using minimization of the least squares technique.

  6. ROCK2 primes the endothelium for vascular hyperpermeability responses by raising baseline junctional tension.

    Science.gov (United States)

    Beckers, Cora M L; Knezevic, Nebojsa; Valent, Erik T; Tauseef, Mohammad; Krishnan, Ramaswamy; Rajendran, Kavitha; Hardin, C Corey; Aman, Jurjan; van Bezu, Jan; Sweetnam, Paul; van Hinsbergh, Victor W M; Mehta, Dolly; van Nieuw Amerongen, Geerten P

    2015-07-01

    Rho kinase mediates the effects of inflammatory permeability factors by increasing actomyosin-generated traction forces on endothelial adherens junctions, resulting in disassembly of intercellular junctions and increased vascular leakage. In vitro, this is accompanied by the Rho kinase-driven formation of prominent radial F-actin fibers, but the in vivo relevance of those F-actin fibers has been debated, suggesting other Rho kinase-mediated events to occur in vascular leak. Here, we delineated the contributions of the highly homologous isoforms of Rho kinase (ROCK1 and ROCK2) to vascular hyperpermeability responses. We show that ROCK2, rather than ROCK1 is the critical Rho kinase for regulation of thrombin receptor-mediated vascular permeability. Novel traction force mapping in endothelial monolayers, however, shows that ROCK2 is not required for the thrombin-induced force enhancements. Rather, ROCK2 is pivotal to baseline junctional tension as a novel mechanism by which Rho kinase primes the endothelium for hyperpermeability responses, independent from subsequent ROCK1-mediated contractile stress-fiber formation during the late phase of the permeability response.

  7. Cardiotoxic drugs Herceptin and doxorubicin inhibit cardiac microvascular endothelial cell barrier formation resulting in increased drug permeability

    Directory of Open Access Journals (Sweden)

    Emma L. Wilkinson

    2016-10-01

    Full Text Available Cardiotoxicity induced by anti-cancer therapeutics is a severe, and potentially fatal, adverse reaction of the heart in response to certain drugs. Current in vitro approaches to assess cardiotoxicity have focused on analysing cardiomyocytes. More recently it has become apparent that non-cardiomyocyte cells of the heart can potentially contribute to cardiotoxicity. Herceptin and doxorubicin are known to induce cardiotoxicity in the clinic. The effect of these drugs on the endothelial tight junction barrier was tested by analysing tight junction formation and zona occludens-1 (ZO-1 levels, revealing that Herceptin and doxorubicin are able to induce barrier perturbment and decrease barrier function in human cardiac microvascular endothelial cells (HCMECs leading to increased permeability. Herceptin treatment had no effect on the tight junction barrier function in human dermal and human brain microvascular endothelial cells. HCMECs showed detectable levels of HER2 compared with the other endothelial cells suggesting that Herceptin binding to HER2 in these cells may interfere with tight junction formation. Our data suggests that doxorubicin and Herceptin can affect tight junction formation in the cardiac microvasculature leading to increased drug permeability and adverse effects on the cardiac myocytes.

  8. Aβ(1-42) oligomer-induced leakage in an in vitro blood-brain barrier model is associated with up-regulation of RAGE and metalloproteinases, and down-regulation of tight junction scaffold proteins.

    Science.gov (United States)

    Wan, Wenbin; Cao, Lan; Liu, Lumei; Zhang, Chunyan; Kalionis, Bill; Tai, Xiantao; Li, Yaming; Xia, Shijin

    2015-07-01

    Accumulating evidence indicates that abnormal deposition of amyloid-β (Aβ) peptide in the brain is responsible for endothelial cell damage and consequently leads to blood-brain barrier (BBB) leakage. However, the mechanisms underlying BBB disruption are not well described. We employed an monolayer BBB model comprising bEnd.3 cell and found that BBB leakage was induced by treatment with Aβ(1-42), and the levels of tight junction (TJ) scaffold proteins (ZO-1, Claudin-5, and Occludin) were decreased. Through comparisons of the effects of the different components of Aβ(1-42), including monomer (Aβ(1-42)-Mono), oligomer (Aβ(1-42)-Oligo), and fibril (Aβ(1-42)-Fibril), our data confirmed that Aβ(1-42)-Oligo is likely to be the most important damage factor that results in TJ damage and BBB leakage in Alzheimer's disease. We found that the incubation of bEnd.3 cells with Aβ(1-42) significantly up-regulated the level of receptor for advanced glycation end-products (RAGE). Co-incubation of a polyclonal antibody to RAGE and Aβ(1-42)-Oligo in bEnd.3 cells blocked RAGE suppression of Aβ(1-42)-Oligo-induced alterations in TJ scaffold proteins and reversed Aβ(1-42)-Oligo-induced up-regulation of RAGE, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, we found that these effects induced by Aβ(1-42)-Oligo treatment were effectively suppressed by knockdown of RAGE using small interfering RNA (siRNA) transfection. We also found that GM 6001, a broad-spectrum MMP inhibitor, partially reversed the Aβ(1-42)-Oligo-induced inhibitor effects in bEnd.3 cells. Thus, these results suggested that RAGE played an important role in Aβ-induced BBB leakage and alterations of TJ scaffold proteins, through a mechanism that involved up-regulation of MMP-2 and MMP-9.

  9. Permeability equipment for porous friction surfaces

    Science.gov (United States)

    Standiford, D. L.; Graul, R. A.; Lenke, L. R.

    1985-04-01

    Hydroplaning is the loss of traction between tires and pavement due to the presence of a layer of water. This loss of traction can result in loss of vehicle control. A porous friction surface (PFS) applied over an existing pavement permits the water to drain laterally and vertically away from the tire path, effectively lowering hydroplaning potential. Equipment used to measure pavement drainage (permeability) is discussed with respect to usage on porous friction surface. Background information on hydroplaning, flow theory, and PFS field performance as they are affected by permeability are also presented. Two dynamic test devices and four static devices are considered for measuring PFS permeability. Permeability tests are recommended to measure PFS permeability for maintenance purposes and construction control. Dynamic devices cited could possibly estimate hydroplaning potential; further research must be done to determine this. Permeability devices cannot be used to accurately estimate friction of a pavement surface, however, decreased permeability of a pavement infers a decrease in friction.

  10. On the permeability of fractal tube bundles

    CERN Document Server

    Zinovik, I

    2011-01-01

    The permeability of a porous medium is strongly affected by its local geometry and connectivity, the size distribution of the solid inclusions and the pores available for flow. Since direct measurements of the permeability are time consuming and require experiments that are not always possible, the reliable theoretical assessment of the permeability based on the medium structural characteristics alone is of importance. When the porosity approaches unity, the permeability-porosity relationships represented by the Kozeny-Carman equations and Archie's law predict that permeability tends to infinity and thus they yield unrealistic results if specific area of the porous media does not tend to zero. The goal of this paper is an evaluation of the relationships between porosity and permeability for a set of fractal models with porosity approaching unity and a finite permeability. It is shown that the two-dimensional foams generated by finite iterations of the corresponding geometric fractals can be used to model poro...

  11. Gap junctions - guards of excitability.

    Science.gov (United States)

    Stroemlund, Line Waring; Jensen, Christa Funch; Qvortrup, Klaus; Delmar, Mario; Nielsen, Morten Schak

    2015-06-01

    Cardiomyocytes are connected by mechanical and electrical junctions located at the intercalated discs (IDs). Although these structures have long been known, it is becoming increasingly clear that their components interact. This review describes the involvement of the ID in electrical disturbances of the heart and focuses on the role of the gap junctional protein connexin 43 (Cx43). Current evidence shows that Cx43 plays a crucial role in organizing microtubules at the intercalated disc and thereby regulating the trafficking of the cardiac sodium channel NaV1.5 to the membrane.

  12. Slit2-Robo4 receptor responses inhibit ANDV directed permeability of human lung microvascular endothelial cells.

    Science.gov (United States)

    Gorbunova, Elena E; Gavrilovskaya, Irina N; Mackow, Erich R

    2013-08-01

    Hantaviruses nonlytically infect human endothelial cells (ECs) and cause edematous and hemorrhagic diseases. Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), and Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Hantaviruses enhance vascular endothelial growth factor directed EC permeability resulting in the disassembly of inter-endothelial cell adherens junctions (AJs). Recent studies demonstrate that Slit2 binding to Robo1/Robo4 receptors on ECs has opposing effects on AJ disassembly and vascular fluid barrier functions. Here we demonstrate that Slit2 inhibits ANDV and HTNV induced permeability and AJ disassembly of pulmonary microvascular ECs (PMECs) by interactions with Robo4. In contrast, Slit2 had no effect on the permeability of ANDV infected human umbilical vein ECs (HUVECs). Analysis of Robo1/Robo4 expression determined that PMECs express Robo4, but not Robo1, while HUVECs expressed both Robo4 and Robo1 receptors. SiRNA knockdown of Robo4 in PMECs prevented Slit2 inhibition of ANDV induced permeability demonstrating that Robo4 receptors determine PMEC responsiveness to Slit2. Collectively, this data demonstrates a selective role for Slit2/Robo4 responses within PMECs that inhibits ANDV induced permeability and AJ disassembly. These findings suggest Slit2s utility as a potential HPS therapeutic that stabilizes the pulmonary endothelium and antagonizes ANDV induced pulmonary edema.

  13. Structural determinants of glomerular permeability.

    Science.gov (United States)

    Deen, W M; Lazzara, M J; Myers, B D

    2001-10-01

    Recent progress in relating the functional properties of the glomerular capillary wall to its unique structure is reviewed. The fenestrated endothelium, glomerular basement membrane (GBM), and epithelial filtration slits form a series arrangement in which the flow diverges as it enters the GBM from the fenestrae and converges again at the filtration slits. A hydrodynamic model that combines morphometric findings with water flow data in isolated GBM has predicted overall hydraulic permeabilities that are consistent with measurements in vivo. The resistance of the GBM to water flow, which accounts for roughly half that of the capillary wall, is strongly dependent on the extent to which the GBM surfaces are blocked by cells. The spatial frequency of filtration slits is predicted to be a very important determinant of the overall hydraulic permeability, in keeping with observations in several glomerular diseases in humans. Whereas the hydraulic resistances of the cell layers and GBM are additive, the overall sieving coefficient for a macromolecule (its concentration in Bowman's space divided by that in plasma) is the product of the sieving coefficients for the individual layers. Models for macromolecule filtration reveal that the individual sieving coefficients are influenced by one another and by the filtrate velocity, requiring great care in extrapolating in vitro observations to the living animal. The size selectivity of the glomerular capillary has been shown to be determined largely by the cellular layers, rather than the GBM. Controversial findings concerning glomerular charge selectivity are reviewed, and it is concluded that there is good evidence for a role of charge in restricting the transmural movement of albumin. Also discussed is an effect of albumin that has received little attention, namely, its tendency to increase the sieving coefficients of test macromolecules via steric interactions. Among the unresolved issues are the specific contributions of the

  14. The Membrane Permeability Outcome study.

    Science.gov (United States)

    Locatelli, Francesco; Cavalli, Andrea; Manzoni, Celestina; Pontoriero, Giuseppe

    2011-01-01

    Many observational studies have consistently shown that high-flux hemodialysis has positive effects on the survival and morbidity of uremic patients when compared with low-flux hemodialysis. However, the HEMO study, a randomized trial designed to evaluate the effect of membrane permeability on patient survival, showed only an 8% non-statistically significant reduction of mortality, albeit a secondary analysis suggested an advantage for high-flux membranes in certain patient subgroups. The prospective, randomized Membrane Permeability Outcome (MPO) study investigated the impact of membrane permeability on survival in incident hemodialysis patients who had low albumin (≤4 g/dl) and normal albumin ( >4 g/dl) as separate randomization groups. Patients with serum albumin ≤4 g/dl had significantly better survival rates in the high-flux group compared with the low-flux group (p = 0.032). Moreover, a post-hoc secondary analysis showed that high-flux membranes may significantly improve survival in diabetic patients. No difference was found in patients with normal albumin levels. Considering the increasing number of dialysis patients with low serum albumin levels and with diabetes, the relevance of the MPO study led to the publication of a position statement by the European Renal Best Practice Advisory Board. This board strongly recommended that high-flux hemodialysis should be used for high-risk patients and, with a lower degree of evidence, even also for low-risk subjects due to the substantial reduction in β(2)-microglobulin levels observed in the high-flux group. Copyright © 2011 S. Karger AG, Basel.

  15. Towards cavitation-enhanced permeability in blood vessel on a chip

    Science.gov (United States)

    De Luca, R.; Silvani, G.; Scognamiglio, C.; Sinibaldi, G.; Peruzzi, G.; Chinappi, M.; Kiani, M. F.; Casciola, C. M.

    2017-08-01

    The development of targeted delivery systems releasing pharmaceutical agents directly at the desired site of action may improve their therapeutic efficiency while minimizing damage to healthy tissues, toxicity to the patient and drug waste. In this context, we have developed a bio-inspired microdevice mimicking the tumour microvasculature which represents a valuable tool for assessing the enhancement of blood vessel permeability due to cavitation. This novel system allows us to investigate the effects of ultrasound-driven microbubbles that temporarily open the endothelial intercellular junctions allowing drug to extravasate blood vessels into tumour tissues. The blood vessel on a chip consists of a tissue chamber and two independent vascular channels (width 200 µm, height 100 µm, length 2762 µm) cultured with endothelial cells placed side-by-side and separated by a series of 3 µm pores. Its geometry and dimensions mimic the three-dimensional morphology, size and flow characteristics of microvessels in vivo. The early stage of this project had a twofold objective: 1. To define the protocol for culturing of Human Umbilical Vein Endothelial Cells (HUVECs) within the vascular channel; 2. To develop a fluorescence based microscopy technique for measuring permeability. We have developed a reliable and reproducible protocol to culture endothelial cells within the artificial vessels in a realistic manner: HUVECs show the typical elongated shape in the direction of flow, exhibit tight junction formation and form a continuous layer with a central lumen that completely covers the channels wall. As expected, the permeability of cell-free device is higher than the one cultured with HUVECs in the vascular channels. The proposed blood vessel on a chip and the permeability measurement protocol have a significant potential to allow for the study of cavitation-enhanced permeability of the endothelium and improve efficiency in screening drug delivery systems.

  16. Permeability of normal versus carious dentin.

    Science.gov (United States)

    Pashley, E L; Talman, R; Horner, J A; Pashley, D H

    1991-10-01

    Although a number of reports have been published demonstrating that carious dentin is less permeable than normal dentin, these reports have been qualitative rather than quantitative. The purpose of this in vitro study was to apply a quantitative technique to the study of the permeability of carious human teeth before and after excavation, before and after removal of the smear layer and before and after preparation of a control cavity of similar size and depth in normal dentin subjected to the same measurements, for comparative purposes. Dentin permeability was measured as a hydraulic conductance. The permeability values measured at each step in the protocol were expressed as a percent of the maximum permeability of both cavities, permitting each tooth the serve as its own control. Carious lesions exhibited a slight degree of permeability (2.3 +/- 0.6% of controls) which remained unchanged after excavation of the lesions. Removal of the smear layer in the excavated carious lesions increased the permeability significantly to 6.9 +/- 3.2%. Preparation of a control cavity of the same area and depth increased the permeability slightly. Removal of its smear layer increased the permeability of the dentin 91%. These results confirm previous qualitative studies that carious dentin, even after excavation and removal of the smear layer has a very low permeability.

  17. Control over Rectification in Supramolecular Tunneling Junctions

    NARCIS (Netherlands)

    Wimbush, K.S.; Wimbush, Kim S.; Reus, William F.; van der Wiel, Wilfred Gerard; Reinhoudt, David; Whitesides, George M.; Nijhuis, C.A.; Velders, Aldrik

    2010-01-01

    In complete control: The magnitude of current rectification in well-defined supramolecular tunneling junctions can be controlled by changing the terminal functionality (red spheres) of dendrimers (gray spheres) immobilized on a supramolecular platform (see picture). Junctions containing biferrocene

  18. Superconducting states in frustrating t-J model. A model connecting high-T sub c cuprates, organic conductors and Na sub x CoO sub 2

    CERN Document Server

    Ogata, M

    2003-01-01

    A two-dimensional t-J model on a frustrating lattice is studied using mean-field variational theories with Gutzwiller approximation. We find that a superconducting state with broken time-reversal symmetry (d+id state) is realized in the parameter region close to the triangular lattice. The frustration enlarges the region of superconductivity when t 0 for electron doping. We also discuss SU(2) degeneracy at half-filling. The d + id state probably corresponds to the spin gap state at half-filling.

  19. Nano-Molecular Junctions on STM Tips

    Institute of Scientific and Technical Information of China (English)

    Chun Huang∗; Jianshu Yang

    2011-01-01

    We present a technique for building metal-organic-metal junctions, which contain ten or fewer conjugated molecules between each of such junction, and the investigations of the I-V response of these junctions. The junctions are made by self assembling thiolated molecules onto gold coated tips for use in scanning tunneling microscopy. We show that this easy technique probes the qualitative properties of the molecules. Current-voltage characteristics of a Tour wire and a new molecular rectifier are presented.

  20. Nano-Molecular Junctions on STM Tips

    Institute of Scientific and Technical Information of China (English)

    Chun Huang; Jianshu Yang

    2011-01-01

    We present a technique for building metal-organic-metal junctions, which contain ten or fewer conjugated molecules between each of such junction, and the investigations of the I-V response of these junctions.The junctions are made by self assembling thiolated molecules onto gold coated tips for use in scanning tunneling microscopy. We show that this easy technique probes the qualitative properties of the molecules. Currentvoltage characteristics of a Tour wire and a new molecular rectifier are presented.

  1. Current noise in tunnel junctions

    Energy Technology Data Exchange (ETDEWEB)

    Frey, Moritz; Grabert, Hermann [Physikalisches Institut, Universitaet Freiburg, Hermann-Herder-Strasse 3, 79104, Freiburg (Germany)

    2017-06-15

    We study current fluctuations in tunnel junctions driven by a voltage source. The voltage is applied to the tunneling element via an impedance providing an electromagnetic environment of the junction. We use circuit theory to relate the fluctuations of the current flowing in the leads of the junction with the voltage fluctuations generated by the environmental impedance and the fluctuations of the tunneling current. The spectrum of current fluctuations is found to consist of three parts: a term arising from the environmental Johnson-Nyquist noise, a term due to the shot noise of the tunneling current and a third term describing the cross-correlation between these two noise sources. Our phenomenological theory reproduces previous results based on the Hamiltonian model for the dynamical Coulomb blockade and provides a simple understanding of the current fluctuation spectrum in terms of circuit theory and properties of the average current. Specific results are given for a tunnel junction driven through a resonator. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.

    1993-01-01

    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc bias...

  3. Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability.

    Science.gov (United States)

    Chen, I-Chieh; Hsiao, I-Lun; Lin, Ho-Chen; Wu, Chien-Hou; Chuang, Chun-Yu; Huang, Yuh-Jeen

    2016-10-01

    An in vitro blood-brain barrier (BBB) model being composed of co-culture with endothelial (bEnd.3) and astrocyte-like (ALT) cells was established to evaluate the toxicity and permeability of Ag nanoparticles (AgNPs; 8nm) and TiO2 nanoparticles (TiO2NPs; 6nm and 35nm) in normal and inflammatory central nervous system. Lipopolysaccharide (LPS) was pre-treated to simulate the inflammatory responses. Both AgNPs and Ag ions can decrease transendothelial electrical resistance (TEER) value, and cause discontinuous tight junction proteins (claudin-5 and zonula occludens-1) of BBB. However, only the Ag ions induced inflammatory cytokines to release, and had less cell-to-cell permeability than AgNPs, which indicated that the toxicity of AgNPs was distinct from Ag ions. LPS itself disrupted BBB, while co-treatment with AgNPs and LPS dramatically enhanced the disruption and permeability coefficient. On the other hand, TiO2NPs exposure increased BBB penetration by size, and disrupted tight junction proteins without size dependence, and many of TiO2NPs accumulated in the endothelial cells were observed. This study provided the new insight of toxic potency of AgNPs and TiO2NPs in BBB.

  4. Cold exposure increases intestinal paracellular permeability to nutrients in the mouse.

    Science.gov (United States)

    Price, Edwin R; Ruff, Lisa J; Guerra, Alberto; Karasov, William H

    2013-11-01

    In situations of increased energy demand and food intake, animals can often acclimate within several days. The intestine generally responds to elevated digestive demand by increasing in size. However, there is likely a limit to how quickly the intestine can grow to meet the new demand. We investigated the immediate and longer-term changes to intestinal properties of the mouse when suddenly exposed to 4°C. We hypothesized that paracellular permeability to nutrients would increase as part of an immediate response to elevated absorptive demand. We measured absorption of l-arabinose, intestinal size and gene expression of several tight junction proteins (claudin-2, claudin-4, claudin-15 and ZO-1) at three time points: pre-exposure, and after 1 day and 2 weeks of cold exposure. Cold exposure increased food intake by 62% after 2 weeks but intake was not significantly increased after 1 day. Intestinal wet mass was elevated after 1 day and throughout the experiment. Absorption of arabinose rose by 20% after 1 day in the cold and was 33% higher after 2 weeks. Expression of claudin-2 increased after 1 day of cold exposure, but there were no changes in expression of any claudin genes when normalized to ZO-1 expression. Our results indicate that intestinal mass can respond rapidly to increased energy demand and that increased paracellular permeability is also part of that response. Increased paracellular permeability may be a consequence of enterocyte hyperplasia, resulting in more tight junctions across which molecules can absorb.

  5. Steam-water relative permeability

    Energy Technology Data Exchange (ETDEWEB)

    Ambusso, W.; Satik, C.; Home, R.N. [Stanford Univ., CA (United States)

    1997-12-31

    A set of relative permeability relations for simultaneous flow of steam and water in porous media have been measured in steady state experiments conducted under the conditions that eliminate most errors associated with saturation and pressure measurements. These relations show that the relative permeabilities for steam-water flow in porous media vary approximately linearly with saturation. This departure from the nitrogen/water behavior indicates that there are fundamental differences between steam/water and nitrogen/water flows. The saturations in these experiments were measured by using a high resolution X-ray computer tomography (CT) scanner. In addition the pressure gradients were obtained from the measurements of liquid phase pressure over the portions with flat saturation profiles. These two aspects constitute a major improvement in the experimental method compared to those used in the past. Comparison of the saturation profiles measured by the X-ray CT scanner during the experiments shows a good agreement with those predicted by numerical simulations. To obtain results that are applicable to general flow of steam and water in porous media similar experiments will be conducted at higher temperature and with porous rocks of different wetting characteristics and porosity distribution.

  6. Stability of large-area molecular junctions

    NARCIS (Netherlands)

    Akkerman, Hylke B.; Kronemeijer, Auke J.; Harkema, Jan; van Hal, Paul A.; Smits, Edsger C. P.; de Leeuw, Dago M.; Blom, Paul W. M.

    The stability of molecular junctions is crucial for any application of molecular electronics. Degradation of molecular junctions when exposed to ambient conditions is regularly observed. In this report the stability of large-area molecular junctions under ambient conditions for more than two years

  7. Soliton bunching in annular Josephson junctions

    DEFF Research Database (Denmark)

    Vernik, I.V; Lazarides, Nickos; Sørensen, Mads Peter

    1996-01-01

    By studying soliton (fluxon) motion in long annular Josephson junctions it is possible to avoid the influence of the boundaries and soliton-soliton collisions present in linear junctions. A new experimental design consisting of a niobium coil placed on top of an annular junction has been used...

  8. Long Range Magnetic Interaction between Josephson Junctions

    DEFF Research Database (Denmark)

    Grønbech-Jensen, Niels; Samuelsen, Mogens Rugholm

    1995-01-01

    A new model for magnetic coupling between long Josephson junctions is proposed. The coupling mechanism is a result of the magnetic fields outside the junctions and is consequently effective over long distances between junctions. We give specific expressions for the form and magnitude of the inter...

  9. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.;

    2002-01-01

    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current...

  10. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.

    2002-01-01

    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current...

  11. Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family

    Directory of Open Access Journals (Sweden)

    Balda Maria S

    2009-12-01

    Full Text Available Abstract Background Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. Results Here we identify a new transmembrane component of tight junctions: MarvelD3, a four-span transmembrane protein. Its predicted transmembrane helices form a Marvel (MAL and related proteins for vesicle traffic and membrane link domain, a structural motif originally discovered in proteins involved in membrane apposition and fusion events, such as the tight junction proteins occludin and tricellulin. In mammals, MarvelD3 is expressed as two alternatively spliced isoforms. Both isoforms exhibit a broad tissue distribution and are expressed by different types of epithelial as well as endothelial cells. MarvelD3 co-localises with occludin at tight junctions in intestinal and corneal epithelial cells. RNA interference experiments in Caco-2 cells indicate that normal MarvelD3 expression is not required for the formation of functional tight junctions but depletion results in monolayers with increased transepithelial electrical resistance. Conclusions Our data indicate that MarvelD3 is a third member of the tight junction-associated occludin family of transmembrane proteins. Similar to occludin, normal expression of MarvelD3 is not essential for the formation of functional tight junctions. However, MarvelD3 functions as a determinant of epithelial paracellular permeability properties.

  12. Vortex rings impinging on permeable boundaries

    Science.gov (United States)

    Mujal-Colilles, Anna; Dalziel, Stuart B.; Bateman, Allen

    2015-01-01

    Experiments with vortex rings impinging permeable and solid boundaries are presented in order to investigate the influence of permeability. Utilizing Particle Image Velocimetry, we compared the behaviour of a vortex ring impinging four different reticulated foams (with permeability k ˜ 26 - 85 × 10-8 m2) and a solid boundary. Results show how permeability affects the stretching phenomena of the vortex ring and the formation and evolution of the secondary vortex ring with opposite sign. Moreover, permeability also affects the macroscopic no-slip boundary condition found on the solid boundary, turning it into an apparent slip boundary condition for the most permeable boundary. The apparent slip-boundary condition and the flux exchange between the ambient fluid and the foam are jointly responsible for both the modified formation of the secondary vortex and changes on the vortex ring diameter increase.

  13. Clogging in permeable concrete: A review.

    Science.gov (United States)

    Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

    2017-05-15

    Permeable concrete (or "pervious concrete" in North America) is used to reduce local flooding in urban areas and is an important sustainable urban drainage system. However, permeable concrete exhibits reduction in permeability due to clogging by particulates, which severely limits service life. This paper reviews the clogging mechanism and current mitigating strategies in order to inform future research needs. The pore structure of permeable concrete and characteristics of flowing particulates influence clogging, which occurs when particles build-up and block connected porosity. Permeable concrete requires regular maintenance by vacuum sweeping and pressure washing, but the effectiveness and viability of these methods is questionable. The potential for clogging is related to the tortuosity of the connected porosity, with greater tortuosity resulting in increased potential for clogging. Research is required to develop permeable concrete that can be poured on-site, which produces a pore structure with significantly reduced tortuosity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Modelling of water permeability in cementitious materials

    DEFF Research Database (Denmark)

    Guang, Ye; Lura, Pietro; van Breugel, K.

    2006-01-01

    This paper presents a network model to predict the permeability of cement paste from a numerical simulation of its microstructure. Based on a linked list pore network structure, the effective hydraulic conductivity is estimated and the fluid flow is calculated according to the Hagen-Poiseuille law....... The pressure gradient at all nodes is calculated with the Gauss elimination method and the absolute permeability of the pore network is calculated directly from Darcy's law. Finally, the permeability model is validated by comparison with direct water permeability measurements. According to this model......, the predicted permeability of hydrating cement pastes is extremely sensitive to the particle size distribution of the cement and especially to the minimum size of the cement particles. Both in simulations and experiments, the permeability of cement pastes is mainly determined by the critical diameter...

  15. Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching

    Science.gov (United States)

    Kuzma-Kuzniarska, Maria; Yapp, Clarence; Pearson-Jones, Thomas W.; Jones, Andrew K.; Hulley, Philippa A.

    2014-01-01

    Abstract. Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows quantitative measurement of gap junction function in living cells. It is based on diffusion-dependent redistribution of a gap junction-permeable fluorescent dye. Using FRAP, we showed that human tenocytes form functional gap junctions in monolayer and three-dimensional (3-D) collagen I culture. Fluorescently labeled tenocytes following photobleaching rapidly reacquired the fluorescent dye from neighboring cells, while HeLa cells, which do not communicate by gap junctions, remained bleached. Furthermore, both 18 β-glycyrrhetinic acid and carbenoxolone, standard inhibitors of gap junction activity, impaired fluorescence recovery in tendon cells. In both monolayer and 3-D cultures, intercellular communication in isolated cells was significantly decreased when compared with cells forming many cell-to-cell contacts. In this study, we used FRAP as a tool to quantify and experimentally manipulate the function of gap junctions in human tenocytes in both two-dimensional (2-D) and 3-D cultures. PMID:24390370

  16. Permeability of Electrospun Superhydrophobic Nanofiber Mats

    Directory of Open Access Journals (Sweden)

    Sarfaraz U. Patel

    2012-01-01

    Full Text Available This paper discusses the fabrication and characterization of electrospun nanofiber mats made up of poly(4-methyl-1-pentene polymer. The polymer was electrospun in different weight concentrations. The mats were characterized by their basis weight, fiber diameter distribution, contact angles, contact angle hysteresis, and air permeability. All of the electrospun nonwoven fiber mats had water contact angles greater than 150 degrees making them superhydrophobic. The permeabilities of the mats were empirically fitted to the mat basis weight by a linear relation. The experimentally measured air permeabilities were significantly larger than the permeabilities predicted by the Kuwabara model for fibrous media.

  17. Vascular permeability in cerebral cavernous malformations.

    Science.gov (United States)

    Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao; Girard, Romuald; Shenkar, Robert; Guo, Xiaodong; Shah, Akash; Larsson, Henrik B W; Tan, Huan; Li, Luying; Wishnoff, Matthew S; Shi, Changbin; Christoforidis, Gregory A; Awad, Issam A

    2015-10-01

    Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive familial CCM disease had greater WMF permeability compared to those with milder disease phenotype, but similar lesion permeability. Subjects receiving statin medications for routine cardiovascular indications had a trend of lower WMF, but not lesion, permeability. This is the first demonstration of brain vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy.

  18. Gap junctions in cells of the immune system: structure, regulation and possible functional roles

    Directory of Open Access Journals (Sweden)

    J.C. Sáez

    2000-04-01

    Full Text Available Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.

  19. Octagonal Defects at Carbon Nanotube Junctions

    Directory of Open Access Journals (Sweden)

    W. Jaskólski

    2013-01-01

    Full Text Available We investigate knee-shaped junctions of semiconductor zigzag carbon nanotubes. Two dissimilar octagons appear at such junctions; one of them can reconstruct into a pair of pentagons. The junction with two octagons presents two degenerate localized states at Fermi energy (EF. The reconstructed junction has only one state near EF, indicating that these localized states are related to the octagonal defects. The inclusion of Coulomb interaction splits the localized states in the junction with two octagons, yielding an antiferromagnetic system.

  20. Fabrication of high quality ferromagnetic Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Weides, M. [Institute for Solid State Research, Research Centre Juelich, D-52425 Juelich (Germany) and CNI-Center of Nanoelectronic Systems for Information Technology, Research Centre Juelich, D-52425 Juelich (Germany)]. E-mail: m.weides@fz-juelich.de; Tillmann, K. [Institute for Solid State Research, Research Centre Juelich, D-52425 Juelich (Germany); Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons, Research Centre Juelich, D-52425 Juelich (Germany); Kohlstedt, H. [Institute for Solid State Research, Research Centre Juelich, D-52425 Juelich (Germany); CNI-Center of Nanoelectronic Systems for Information Technology, Research Centre Juelich, D-52425 Juelich (Germany); Department of Material Science and Engineering and Department of Physics, University of Berkeley, CA 94720 (United States)

    2006-05-15

    We present ferromagnetic Nb/Al{sub 2}O{sub 3}/Ni{sub 60}Cu{sub 40}/Nb Josephson junctions (SIFS) with an ultrathin Al{sub 2}O{sub 3} tunnel barrier. The junction fabrication was optimized regarding junction insulation and homogeneity of current transport. Using ion-beam-etching and anodic oxidation we defined and insulated the junction mesas. The additional 2 nm thin Cu-layer below the ferromagnetic NiCu (SINFS) lowered interface roughness and ensured very homogeneous current transport. A high yield of junctional devices with j {sub c} spreads less than 2% was obtained.

  1. A school peer mediation program as a context for exploring therapeutic jurisprudence (TJ): Can a peer mediation program inform the law?

    Science.gov (United States)

    McWilliam, Nicky

    2010-01-01

    This paper reports an exploratory study of a school peer mediation program implemented as an alternative way to manage bullying and other destructive conflict. The study explores the effects of the program on the well-being of members of the school community by examining perceptions of students, staff and a sample of parents and former students. Drawing on therapeutic jurisprudence (TJ) the study explores whether the component parts of the program, separately or together, promote intended or unintended therapeutic effects. The preliminary findings of the study emphasise the importance of peer mediation training and suggest that existing scholarship in the area of school conflict resolution and peer mediation, when viewed through a TJ lens, may provide valuable insights into how to optimally configure programs for development and adoption in schools and other community settings. The study highlights the lack of attention paid by the legal system to valuable scholarship in the area of school conflict resolution and peer mediation, which may have implications for the understanding and development of legal processes and the law in general.

  2. A LIBS method for simultaneous monitoring of the impurities and the hydrogenic composition present in the wall of the TJ-II stellarator

    Science.gov (United States)

    López-Miranda, B.; Zurro, B.; Baciero, A.; Martínez, M.

    2016-11-01

    The study of plasma-wall interactions and impurity transport in the plasma fusion devices is critical for the development of future fusion reactors. An experiment to perform laser induced breakdown spectroscopy, using minor modifications of our existing laser blow-off impurity injection system, has been set up thus making both experiments compatible. The radiation produced by the laser pulse focused at the TJ-II wall evaporates a surface layer of deposited impurities and the subsequent radiation produced by the laser-produced plasma is collected by two separate lens and fiber combinations into two spectrometers. The first spectrometer, with low spectral resolution, records a spectrum from 200 to 900 nm to give a survey of impurities present in the wall. The second one, with high resolution, is tuned to the wavelengths of the Hα and Dα lines in order to resolve them and quantify the hydrogen isotopic ratio present on the surface of the wall. The alignment, calibration, and spectral analysis method will be described in detail. First experimental results obtained with this setup will be shown and its relevance for the TJ-II experimental program discussed.

  3. A LIBS method for simultaneous monitoring of the impurities and the hydrogenic composition present in the wall of the TJ-II stellarator

    Energy Technology Data Exchange (ETDEWEB)

    López-Miranda, B., E-mail: belen.lopez@ciemat.es; Zurro, B.; Baciero, A. [Laboratorio Nacional de Fusión, CIEMAT, Av. Complutense, 40, 28040 Madrid (Spain); Martínez, M. [Universidad Carlos III de Madrid, Av de la Universidad, 30, 28911 Leganés, Madrid (Spain)

    2016-11-15

    The study of plasma-wall interactions and impurity transport in the plasma fusion devices is critical for the development of future fusion reactors. An experiment to perform laser induced breakdown spectroscopy, using minor modifications of our existing laser blow-off impurity injection system, has been set up thus making both experiments compatible. The radiation produced by the laser pulse focused at the TJ-II wall evaporates a surface layer of deposited impurities and the subsequent radiation produced by the laser-produced plasma is collected by two separate lens and fiber combinations into two spectrometers. The first spectrometer, with low spectral resolution, records a spectrum from 200 to 900 nm to give a survey of impurities present in the wall. The second one, with high resolution, is tuned to the wavelengths of the Hα and Dα lines in order to resolve them and quantify the hydrogen isotopic ratio present on the surface of the wall. The alignment, calibration, and spectral analysis method will be described in detail. First experimental results obtained with this setup will be shown and its relevance for the TJ-II experimental program discussed.

  4. Study of NBI-driven chirping mode properties and radial location by the heavy ion beam probe in the TJ-II stellarator

    Science.gov (United States)

    Melnikov, A. V.; Eliseev, L. G.; Castejón, F.; Hidalgo, C.; Khabanov, P. O.; Kozachek, A. S.; Krupnik, L. I.; Liniers, M.; Lysenko, S. E.; de Pablos, J. L.; Sharapov, S. E.; Ufimtsev, M. V.; Zenin, V. N.; HIBP Group; TJ-II Team

    2016-11-01

    Alfvén eigenmodes (AEs) were studied in low magnetic shear flexible heliac TJ-II (B 0  =  0.95 T, R 0  =  1.5 m,   =  0.22 m) neutral beam injection (NBI) heated plasmas (P NBI  ⩽  1.1 MW, E NBI  =  32 keV) using the heavy ion beam probe (HIBP). L-mode hydrogen plasmas heated with co-, counter- and balanced-NBI and electron cyclotron resonance heating (ECRH) were investigated in various magnetic configurations with rotational transform ι(a)/2π  =  1/q ~ 1.5-1.6. The HIBP diagnostic is capable of simultaneously measuring the oscillations of the plasma electric potential, density and poloidal magnetic field. In earlier studies chirping modes have been observed with 250 kHz  electric potential perturbations have a ballooning character, while the density and B pol perturbations are nearly symmetric for both ECRH  +  NBI and NBI-only plasmas. On TJ-II, the dominant effect on the nonlinear evolution of the AE from the chirping state to the steady-frequency state is the magnetic configuration, determined by the vacuum ι and plasma current I pl.

  5. A Monte Carlo study of the ``minus sign problem`` in the t-J model using an intel IPSC/860 hypercube

    Energy Technology Data Exchange (ETDEWEB)

    Kovarik, M.D.; Barnes, T. [Oak Ridge National Lab., TN (United States)]|[Tennessee Univ., Knoxville, TN (United States). Dept. of Physics

    1993-12-31

    We describe a Monte Carlo simulation of the 2-dimensional t-J model on an Intel iPSC/860 hypercube. The problem studied is the determination of the dispersion relation of a dynamical hole in the t-J model of the high temperature superconductors. Since this problem involves the motion of many fermions in more than one spatial dimensions, it is representative of the class of systems that suffer from the ``minus sign problem`` of dynamical fermions which has made Monte Carlo simulation very difficult. We demonstrate that for small values of the hole hopping parameter one can extract the entire hole dispersion relation using the GRW Monte Carlo algorithm, which is a simulation of the Euclidean time Schroedinger equation, and present results on 4 {times} 4 and 6 {times} 6 lattices. We demonstrate that a qualitative picture at higher hopping parameters may be found by extrapolating weak hopping results where the minus sign problem is less severe. Generalization to physical hopping parameter values will only require use of an improved trial wavefunction for importance sampling.

  6. Effect of acute, slightly increased intra-abdominal pressure on intestinal permeability and oxidative stress in a rat model.

    Directory of Open Access Journals (Sweden)

    Yuxin Leng

    Full Text Available INTRODUCTION: Intra-abdominal hypertension (IAH is known as a common, serious complication in critically ill patients. Bacterial translocation and permeability changes are considered the pathophysiological bases for IAH-induced enterogenic endotoxemia and subsequent multiorgan failure. Nevertheless, the effects of slightly elevated intra-abdominal pressures (IAPs on the intestinal mucosa and the associated mechanisms remain unclear. METHODS: To investigate the acute effects of different nitrogen pneumoperitoneum grades on colonic mucosa, male Sprague-Dawley rats were assigned to six groups with different IAPs (0 [control], 4, 8, 12, 16, and 20 mmHg, n = 6/group. During 90 min of exposure, we dynamically monitored the heart rate and noninvasive hemodynamic parameters. After gradual decompression, arterial blood gas analyses were conducted. Thereafter, structural injuries to the colonic mucosa were identified using light microscopy. Colon permeability was determined using the expression of tight junction proteins, combined with fluorescein isothiocyanate dextran (FD-4 absorption. The pro-oxidant-antioxidant balance was determined based on the levels of malondialdehyde (MDA and antioxidant enzymes. RESULTS: IAH significantly affected the histological scores of the colonic mucosa, tight junction protein expression, mucosal permeability, and pro-oxidant-antioxidant balance. Interestingly, elevations of IAP that were lower than the threshold for IAH also showed a similar, undesirable effect. In the 8 mmHg group, mild hyponatremia, hypocalcemia, and hypoxemia occurred, accompanied by reduced blood and abdominal perfusion pressures. Mild microscopic inflammatory infiltration and increased MDA levels were also detected. Moreover, an 8-mm Hg IAP markedly inhibited the expression of tight junction proteins, although no significant differences in FD-4 permeability were observed between the 0- and 8-mmHg groups. CONCLUSIONS: Acute exposure to slightly

  7. A claudin-9-based ion permeability barrier is essential for hearing.

    Directory of Open Access Journals (Sweden)

    Yoko Nakano

    2009-08-01

    Full Text Available Hereditary hearing loss is one of the most common birth defects, yet the majority of genes required for audition is thought to remain unidentified. Ethylnitrosourea (ENU-mutagenesis has been a valuable approach for generating new animal models of deafness and discovering previously unrecognized gene functions. Here we report on the characterization of a new ENU-induced mouse mutant (nmf329 that exhibits recessively inherited deafness. We found a widespread loss of sensory hair cells in the hearing organs of nmf329 mice after the second week of life. Positional cloning revealed that the nmf329 strain carries a missense mutation in the claudin-9 gene, which encodes a tight junction protein with unknown biological function. In an epithelial cell line, heterologous expression of wild-type claudin-9 reduced the paracellular permeability to Na+ and K+, and the nmf329 mutation eliminated this ion barrier function without affecting the plasma membrane localization of claudin-9. In the nmf329 mouse line, the perilymphatic K+ concentration was found to be elevated, suggesting that the cochlear tight junctions were dysfunctional. Furthermore, the hair-cell loss in the claudin-9-defective cochlea was rescued in vitro when the explanted hearing organs were cultured in a low-K+ milieu and in vivo when the endocochlear K+-driving force was diminished by deletion of the pou3f4 gene. Overall, our data indicate that claudin-9 is required for the preservation of sensory cells in the hearing organ because claudin-9-defective tight junctions fail to shield the basolateral side of hair cells from the K+-rich endolymph. In the tight-junction complexes of hair cells, claudin-9 is localized specifically to a subdomain that is underneath more apical tight-junction strands formed by other claudins. Thus, the analysis of claudin-9 mutant mice suggests that even the deeper (subapical tight-junction strands have biologically important ion barrier function.

  8. Inhibition of Rho and Rac geranylgeranylation by atorvastatin is critical for preservation of endothelial junction integrity.

    Directory of Open Access Journals (Sweden)

    Hongbing Xiao

    Full Text Available BACKGROUND: Small GTPases (guanosine triphosphate, GTP are involved in many critical cellular processes, including inflammation, proliferation, and migration. GTP loading and isoprenylation are two important post-translational modifications of small GTPases, and are critical for their normal function. In this study, we investigated the role of post-translational modifications of small GTPases in regulating endothelial cell inflammatory responses and junctional integrity. METHODS AND RESULTS: Confluent human umbilical vein endothelial cell (HUVECs treated with atorvastatin demonstrated significantly decreased lipopolysaccharide (LPS-mediated IL-6 and IL-8 generation. The inhibitory effect of atorvastatin (Atorva was attenuated by co-treatment with 100 µM mevalonate (MVA or 10 µM geranylgeranyl pyrophosphate (GGPP, but not by 10 µM farnesyl pyrophosphate (FPP. Atorvastatin treatment of HUVECs produced a time-dependent increase in GTP loading of all Rho GTPases, and induced the translocation of small Rho GTPases from the cellular membrane to the cytosol, which was reversed by 100 µM MVA and 10 µM GGPP, but not by 10 µM FPP. Atorvastatin significantly attenuated thrombin-induced HUVECs permeability, increased VE-cadherin targeting to cell junctions, and preserved junction integrity. These effects were partially reversed by GGPP but not by FPP, indicating that geranylgeranylation of small GTPases plays a major role in regulating endothelial junction integrity. Silencing of small GTPases showed that Rho and Rac, but not Cdc42, play central role in HUVECs junction integrity. CONCLUSIONS: In conclusion, our studies show that post-translational modification of small GTPases plays a vital role in regulating endothelial inflammatory response and endothelial junction integrity. Atorvastatin increased GTP loading and inhibited isoprenylation of small GTPases, accompanied by reduced inflammatory response and preserved cellular junction integrity.

  9. Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier.

    Science.gov (United States)

    Caron, Tyler J; Scott, Kathleen E; Fox, James G; Hagen, Susan J

    2015-10-28

    Long-term chronic infection with Helicobacter pylori (H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer, tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach, or dysfunction in the infected stomach, however, are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells, claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules, each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging, because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore, the role of H. pylori virulence factors, such as cytotoxin-associated gene A and vacoulating cytotoxin, in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo, likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study, as well, is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions, normally and in H. pylori infection, and make predictions about the consequences of claudin reorganization during H. pylori infection.

  10. Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain.

    Science.gov (United States)

    Morita, Shoko; Furube, Eriko; Mannari, Tetsuya; Okuda, Hiroaki; Tatsumi, Kouko; Wanaka, Akio; Miyata, Seiji

    2016-02-01

    Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB.

  11. Seebeck effect in molecular junctions

    Science.gov (United States)

    Zimbovskaya, Natalya A.

    2016-05-01

    Advances in the fabrication and characterization of nanoscale systems presently allow for a better understanding of their thermoelectric properties. As is known, the building blocks of thermoelectricity are the Peltier and Seebeck effects. In the present work we review results of theoretical studies of the Seebeck effect in single-molecule junctions and similar systems. The behavior of thermovoltage and thermopower in these systems is controlled by several factors including the geometry of molecular bridges, the characteristics of contacts between the bridge and the electrodes, the strength of the Coulomb interactions between electrons on the bridge, and of electron-phonon interactions. We describe the impact of these factors on the thermopower. Also, we discuss a nonlinear Seebeck effect in molecular junctions.

  12. Electron transport in molecular junctions

    DEFF Research Database (Denmark)

    Jin, Chengjun

    This thesis addresses the electron transport in molecular junctions, focusing on the energy level alignment and correlation effects. Various levels of theory have been applied to study the structural and electronic effects in different molecular junctions, starting from the single particle density...... charge position are in quantitative agreement with the experiments, while pure DFT is not. This is the consequence of the accurate energy level alignment, where the DFT+∑ method corrects the self-interaction error in the standard DFT functional and uses a static image charge model to include the image...... charge effect on the energy level renormalization. Additionally, the gating of the 4,4’-bipyridine (44BP) molecule contacted to either Ni or Au electrodes has been investigated. Here it is found that the gating mechanism is conceptually different between two cases. In the case of Ni contacts where...

  13. How coherent are Josephson junctions?

    CERN Document Server

    Paik, Hanhee; Bishop, Lev S; Kirchmair, G; Catelani, G; Sears, A P; Johnson, B R; Reagor, M J; Frunzio, L; Glazman, L; Schoelkopf, R J

    2011-01-01

    Attaining sufficient coherence is a requirement for realizing a large-scale quantum computer. We present a new implementation of a superconducting transmon qubit that is strongly coupled to a three-dimensional superconducting cavity. We observe a reproducible increase in the coherence times of qubit (both $T_1$ and $T_2$ > 10 microseconds) and cavity ($T_{cav}$ ~ 50 microseconds) by more than an order of magnitude compared to the current state-of-art superconducting qubits. This enables the study of the stability and quality of Josephson junctions at precisions exceeding one part per million. Surprisingly, we see no evidence for $1/f$ critical current noise. At elevated temperatures, we observe the dissipation due to a small density (< 1 - 10 ppm) of thermally-excited quasiparticles. The results suggest that the overall quality of Josephson junctions will allow error rates of a few $10^{-4}$, approaching the error correction threshold.

  14. Morphogenesis of rat myotendinous junction.

    Science.gov (United States)

    Curzi, Davide; Ambrogini, Patrizia; Falcieri, Elisabetta; Burattini, Sabrina

    2013-10-01

    Myotendinous junction (MTJ) is the highly specialized complex which connects the skeletal muscle to the tendon for transmitting the contractile force between the two tissues. The purpose of this study was to investigate the MTJ development and rat EDL was chosen as a model. 1, 15, 30 day animals were considered and the junctions were analyzed by light and electron microscopy. The MTJ interface architecture increased during the development, extending the interaction between muscle and tendon. 1-day-old rats showed disorganized myofibril bundles, spread cytosol and incomplete rough endoplasmic reticulum, features partially improved in 15-day-old rats, and completely developed in 30-day-old animals. These findings indicate that muscle-tendon interface displays, during rat lifetime, numerically increased and longer tendon interdigitations, correlated with an improved organization of both tissues and with a progressive acquirement of full functionality.

  15. Modulation of gap junction channels and hemichannels by growth factors.

    Science.gov (United States)

    Schalper, Kurt A; Riquelme, Manuel A; Brañes, María C; Martínez, Agustín D; Vega, José Luis; Berthoud, Viviana M; Bennett, Michael V L; Sáez, Juan C

    2012-03-01

    Gap junction hemichannels and cell-cell channels have roles in coordinating numerous cellular processes, due to their permeability to extra and intracellular signaling molecules. Another mechanism of cellular coordination is provided by a vast array of growth factors that interact with relatively selective cell membrane receptors. These receptors can affect cellular transduction pathways, including alteration of intracellular concentration of free Ca(2+) and free radicals and activation of protein kinases or phosphatases. Connexin and pannexin based channels constitute recently described targets of growth factor signal transduction pathways, but little is known regarding the effects of growth factor signaling on pannexin based channels. The effects of growth factors on these two channel types seem to depend on the cell type, cell stage and connexin and pannexin isoform expressed. The functional state of hemichannels and gap junction channels are affected in opposite directions by FGF-1 via protein kinase-dependent mechanisms. These changes are largely explained by channels insertion in or withdrawal from the cell membrane, but changes in open probability might also occur due to changes in phosphorylation and redox state of channel subunits. The functional consequence of variation in cell-cell communication via these membrane channels is implicated in disease as well as normal cellular responses.

  16. Thermoelectric efficiency of molecular junctions

    Science.gov (United States)

    Perroni, C. A.; Ninno, D.; Cataudella, V.

    2016-09-01

    Focus of the review is on experimental set-ups and theoretical proposals aimed to enhance thermoelectric performances of molecular junctions. In addition to charge conductance, the thermoelectric parameter commonly measured in these systems is the thermopower, which is typically rather low. We review recent experimental outcomes relative to several junction configurations used to optimize the thermopower. On the other hand, theoretical calculations provide estimations of all the thermoelectric parameters in the linear and non-linear regime, in particular of the thermoelectric figure of merit and efficiency, completing our knowledge of molecular thermoelectricity. For this reason, the review will mainly focus on theoretical studies analyzing the role of not only electronic, but also of the vibrational degrees of freedom. Theoretical results about thermoelectric phenomena in the coherent regime are reviewed focusing on interference effects which play a significant role in enhancing the figure of merit. Moreover, we review theoretical studies including the effects of molecular many-body interactions, such as electron-vibration couplings, which typically tend to reduce the efficiency. Since a fine tuning of many parameters and coupling strengths is required to optimize the thermoelectric conversion in molecular junctions, new theoretically proposed set-ups are discussed in the conclusions.

  17. Intercomparison on measurement of water vapour permeability

    DEFF Research Database (Denmark)

    Hansen, Kurt Kielsgaard

    Three different materials are tested - hard woodfibre board - damp proof course - underlay for roofing The water vapour permeability has been measured according to EN ISO 12572 (2001).......Three different materials are tested - hard woodfibre board - damp proof course - underlay for roofing The water vapour permeability has been measured according to EN ISO 12572 (2001)....

  18. Crustal permeability: Introduction to the special issue

    Science.gov (United States)

    Ingebritsen, Steven E.; Gleeson, Tom

    2015-01-01

    The topic of crustal permeability is of broad interest in light of the controlling effect of permeability on diverse geologic processes and also timely in light of the practical challenges associated with emerging technologies such as hydraulic fracturing for oil and gas production (‘fracking’), enhanced geothermal systems, and geologic carbon sequestration. This special issue of Geofluids is also motivated by the historical dichotomy between the hydrogeologic concept of permeability as a static material property that exerts control on fluid flow and the perspective of economic geologists, geophysicists, and crustal petrologists who have long recognized permeability as a dynamic parameter that changes in response to tectonism, fluid production, and geochemical reactions. Issues associated with fracking, enhanced geothermal systems, and geologic carbon sequestration have already begun to promote a constructive dialog between the static and dynamic views of permeability, and here we have made a conscious effort to include both viewpoints. This special issue also focuses on the quantification of permeability, encompassing both direct measurement of permeability in the uppermost crust and inferential permeability estimates, mainly for the deeper crust.

  19. Accurate determination of characteristic relative permeability curves

    Science.gov (United States)

    Krause, Michael H.; Benson, Sally M.

    2015-09-01

    A recently developed technique to accurately characterize sub-core scale heterogeneity is applied to investigate the factors responsible for flowrate-dependent effective relative permeability curves measured on core samples in the laboratory. The dependency of laboratory measured relative permeability on flowrate has long been both supported and challenged by a number of investigators. Studies have shown that this apparent flowrate dependency is a result of both sub-core scale heterogeneity and outlet boundary effects. However this has only been demonstrated numerically for highly simplified models of porous media. In this paper, flowrate dependency of effective relative permeability is demonstrated using two rock cores, a Berea Sandstone and a heterogeneous sandstone from the Otway Basin Pilot Project in Australia. Numerical simulations of steady-state coreflooding experiments are conducted at a number of injection rates using a single set of input characteristic relative permeability curves. Effective relative permeability is then calculated from the simulation data using standard interpretation methods for calculating relative permeability from steady-state tests. Results show that simplified approaches may be used to determine flowrate-independent characteristic relative permeability provided flow rate is sufficiently high, and the core heterogeneity is relatively low. It is also shown that characteristic relative permeability can be determined at any typical flowrate, and even for geologically complex models, when using accurate three-dimensional models.

  20. Problematika financování občanských sdružení ve sportu v konkrétních podmínkách TJ Sokol Radotín

    OpenAIRE

    Žežulková, Hana

    2008-01-01

    Title of tbesis: The problem of financing of sport CIVIC associations - a concrete example of TJ Sokol Radotín Targets: Methods: Results: The aim of the thesis is to identify the current trend of financing of civic associations operating in the field of sport according to the discovered indications. To analyse the current state of financing and taxation problems conceming TJ Sokol Radotín. To assess management of a typical civic association in sport. Consequently, to evaluate fulfilment of co...

  1. Permeability Tests on Eastern Scheldt Sand

    DEFF Research Database (Denmark)

    Jakobsen, Kim Parsberg

    The flow through porous media plays an important role in various engineering disciplines, as for example in ground water hydrology and soil mechanics. In the present study the permeability is determined for a fine, saturated sand. As the flow through a porous media strongly depends on the charact......The flow through porous media plays an important role in various engineering disciplines, as for example in ground water hydrology and soil mechanics. In the present study the permeability is determined for a fine, saturated sand. As the flow through a porous media strongly depends...... on the characteristics of the soil matrix, the permeability is determined for different void ratios. All tests are performed on reconstituted specimens of Eastern Scheldt Sand. The permeability is determined by use of a falling head apparatus. Finally the test results are briefly summarised and a relationship between...... void ratio and permeability is established....

  2. Macro fluid analysis of laminated fabric permeability

    Directory of Open Access Journals (Sweden)

    Qiu Li

    2016-01-01

    Full Text Available A porous jump model is put forward to predict the breathability of laminated fabrics by utilizing fluent software. To simplify the parameter setting process, the methods of determining the parameters of jump porous model by means of fabric layers are studied. Also, effects of single/multi-layer fabrics and thickness on breathability are analyzed, indicating that fabric breathability reduces with the increase of layers. Multi-layer fabric is simplified into a single layer, and the fabric permeability is calculated by proportion. Moreover, the change curve of fabric layer and face permeability, as well as the equation between the fabric layer and the face permeability are obtained. Then, face permeability and pressure-jump coefficient parameters setting of porous jump model could be integrated into single parameter (i. e. fabric layers, which simplifies the fluent operation process and realizes the prediction of laminated fabric permeability.

  3. Permeability measurement and control for epoxy composites

    Science.gov (United States)

    Chang, Tsun-Hsu; Tsai, Cheng-Hung; Wong, Wei-Syuan; Chen, Yen-Ren; Chao, Hsien-Wen

    2017-08-01

    The coupling of the electric and magnetic fields leads to a strong interplay in materials' permittivity and permeability. Here, we proposed a specially designed cavity, called the mu cavity. The mu cavity, consisting of a mushroom structure inside a cylindrical resonator, is exclusively sensitive to permeability, but not to permittivity. It decouples materials' electromagnetic properties and allows an accurate measurement of the permeability. With the help of an epsilon cavity, these two cavities jointly determine the complex permeability and permittivity of the materials at microwave frequencies. Homemade epoxy-based composite materials were prepared and tested. Measurement and manipulation of the permeability and permittivity of the epoxy composites will be shown. The results will be compared with the effective medium theories.

  4. Cell-cell junctions: a target of acoustic overstimulation in the sensory epithelium of the cochlea

    Directory of Open Access Journals (Sweden)

    Zheng Guiliang

    2012-06-01

    Full Text Available Abstract Background Exposure to intense noise causes the excessive movement of the organ of Corti, stretching the organ and compromising sensory cell functions. We recently revealed changes in the transcriptional expression of multiple adhesion-related genes during the acute phases of cochlear damage, suggesting that the disruption of cell-cell junctions is an early event in the process of cochlear pathogenesis. However, the functional state of cell junctions in the sensory epithelium is not clear. Here, we employed graded dextran-FITC, a macromolecule tracer that is impermeable to the organ of Corti under physiological conditions, to evaluate the barrier function of cell junctions in normal and noise-traumatized cochlear sensory epithelia. Results Exposure to an impulse noise of 155 dB (peak sound pressure level caused a site-specific disruption in the intercellular junctions within the sensory epithelium of the chinchilla cochlea. The most vulnerable sites were the junctions among the Hensen cells and between the Hensen and Deiters cells within the outer zone of the sensory epithelium. The junction clefts that formed in the reticular lamina were permeable to 40 and 500 but not 2,000 kDa dextran-FITC macromolecules. Moreover, this study showed that the interruption of junction integrity occurred in the reticular lamina and also in the basilar membrane, a site that had been considered to be resistant to acoustic injury. Finally, our study revealed a general spatial correlation between the site of sensory cell damage and the site of junction disruption. However, the two events lacked a strict one-to-one correlation, suggesting that the disruption of cell-cell junctions is a contributing, but not the sole, factor for initiating acute sensory cell death. Conclusions Impulse noise causes the functional disruption of intercellular junctions in the sensory epithelium of the chinchilla cochlea. This disruption occurs at an early phase of cochlear

  5. Compact rock material gas permeability properties

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huanling, E-mail: whl_hm@163.com [Key Laboratory of Coastal Disaster and Defence, Ministry of Education, Hohai University, Nanjing 210098 (China); LML, University of Lille, Cite Scientifique, 59655 Villeneuve d’Ascq (France); Xu, Weiya; Zuo, Jing [Institutes of Geotechnical Engineering, Hohai University, Nanjing 210098 (China)

    2014-09-15

    Natural compact rocks, such as sandstone, granite, and rock salt, are the main materials and geological environment for storing underground oil, gas, CO{sub 2,} shale gas, and radioactive waste because they have extremely low permeabilities and high mechanical strengths. Using the inert gas argon as the fluid medium, the stress-dependent permeability and porosity of monzonitic granite and granite gneiss from an underground oil storage depot were measured using a permeability and porosity measurement system. Based on the test results, models for describing the relationships among the permeability, porosity, and confining pressure of rock specimens were analyzed and are discussed. A power law is suggested to describe the relationship between the stress-dependent porosity and permeability; for the monzonitic granite and granite gneiss (for monzonitic granite (A-2), the initial porosity is approximately 4.05%, and the permeability is approximately 10{sup −19} m{sup 2}; for the granite gneiss (B-2), the initial porosity is approximately 7.09%, the permeability is approximately 10{sup −17} m{sup 2}; and the porosity-sensitivity exponents that link porosity and permeability are 0.98 and 3.11, respectively). Compared with moderate-porosity and high-porosity rocks, for which φ > 15%, low-porosity rock permeability has a relatively lower sensitivity to stress, but the porosity is more sensitive to stress, and different types of rocks show similar trends. From the test results, it can be inferred that the test rock specimens’ permeability evolution is related to the relative particle movements and microcrack closure.

  6. Gas and Water Permeability of Concrete

    Energy Technology Data Exchange (ETDEWEB)

    Villar, M. V.; Martin, P. L.; Romero, F. J.; Gutierrez-Rodirgo, V.; Barcala, J. M.

    2012-11-01

    The gas pressure of concrete samples was measured in an unsteady-state equipment working under low injection pressures and in a newly fine tuned steady-state setup working under different pressures. These measurements allowed the estimation of the intrinsic and relative gas permeability of the concrete and of the effect of boundary conditions on them. Permeability decreased with water content, but it was also greatly affected by the hydraulic history of concrete, i.e. if it had been previously dried or wetted. In particular, and for a given degree of saturation, the gas permeability of concrete previously saturated was lower than if the concrete had been just air dried or saturated after air drying. In any case, the gas permeability was about two orders of magnitude higher than the liquid water permeability (10-16 vs. 10-18 m2), probably due to the chemical reactions taking place during saturation (carbonation). The relative gas permeability of concrete increased sharply for water degrees of saturation smaller than 50%. The boundary conditions also affected the gas permeability, which seemed to be mostly conditioned by the back pressure and the confining pressure, increasing as the former increased and decreasing as the latter increased, i.e. decreasing as the effective pressure increased. Overall the increase of pressure head or injection pressure implied a decrease in gas permeability. External,microcracking during air-drying could not be ruled out as responsible for the decrease of permeability with confining pressure. The apparent permeability obtained applying the Klinkenberg method for a given effective pressure was only slightly smaller than the average of all the values measured for the same confining pressure range. For this reason it is considered that the Klinkenberg effect was not relevant in the range of pressures applied. (Author) 37 refs.

  7. Chaos induced by coupling between Josephson junctions

    Science.gov (United States)

    Shukrinov, Yu. M.; Azemtsa-Donfack, H.; Botha, A. E.

    2015-02-01

    It is found that, in a stack of intrinsic Josephson junctions in layered high temperature superconductors under external electromagnetic radiation, the chaotic features are triggered by interjunction coupling, i.e., the coupling between different junctions in the stack. While the radiation is well known to produce chaotic effects in the single junction, the effect of interjunction coupling is fundamentally different and it can lead to the onset of chaos via a different route to that of the single junction. A precise numerical study of the phase dynamics of intrinsic Josephson junctions, as described by the CCJJ+DC model, is performed. We demonstrate the charging of superconducting layers, in a bias current interval corresponding to a Shapiro step subharmonic, due to the creation of a longitudinal plasma wave along the stack of junctions. With increase in radiation amplitude chaotic behavior sets in. The chaotic features of the coupled Josephson junctions are analyzed by calculations of the Lyapunov exponents. We compare results for a stack of junctions to the case of a single junction and prove that the observed chaos is induced by the coupling between the junctions. The use of Shapiro step subharmonics may allow longitudinal plasma waves to be excited at low radiation power.

  8. Keratinocyte growth factor improves alterations of lung permeability and bronchial epithelium in allergic rats.

    Science.gov (United States)

    Tillie-Leblond, I; Gosset, P; Le Berre, R; Janin, A; Prangère, T; Tonnel, A B; Guery, B P H

    2007-07-01

    Chronic allergic asthma is associated with marked inflammatory reaction, microvascular leakage and epithelium injury. As previously shown in a rat model of chronic asthma, these alterations increase lung permeability and distal airway fluid clearance. Keratinocyte growth factor (KGF) has been shown to induce epithelial cell proliferation and to protect from acute lung injuries. Therefore, the current authors evaluated the potential role of KGF treatment on lung permeability and airway inflammation in rats with chronic asthma. KGF (1 mg x kg(-1)) was administered intravenously before the last ovalbumin (OVA) challenge in sensitised rats. Permeability was assessed by the leak of radiolabelled albumin from the alveolar and systemic compartments. Histopathological analysis was also performed. Treatment with KGF decreased the leak of both markers and decreased the level of extravascular lung water in sensitised rats challenged with OVA. KGF treatment also reduced the inflammatory cell number in bronchoalveolar lavage fluid but not in bronchial mucosa. KGF markedly limited the allergen-induced alterations in epithelium integrity and the expression of the intercellular junction proteins beta-catenin and zonula occludens protein-1. In conclusion, keratinocyte growth factor administration markedly limits lung permeability and airway inflammation, an effect associated with a decrease in epithelium alterations during chronic allergic asthma. These data open new prospects in the therapeutic strategy of asthma.

  9. Endothelial domes encapsulate adherent neutrophils and minimize increases in vascular permeability in paracellular and transcellular emigration.

    Directory of Open Access Journals (Sweden)

    Mia Phillipson

    Full Text Available Local edema, a cardinal sign of inflammation associates closely with neutrophil emigration. Neutrophil emigration has been described to occur primarily through endothelial junctions (paracellular and more rarely directly through endothelial cells (transcellular. Recently, we reported that unlike in wild-type (wt mice, Mac-1-/- (CD11b neutrophils predominantly emigrated transcellularly and was significantly delayed taking 20-30 min longer than the paracellular emigration (wt. In the present study we noted significant anatomical disruption of the endothelium and hypothesized that transcellular emigration would greatly increase vascular permeability. Surprisingly, despite profound disruption of the endothelial barrier as the neutrophils moved through the cells, the changes in vascular permeability during transcellular emigration (Mac-1-/- were not increased more than in wt mice. Instead increased vascular permeability completely tracked the number of emigrated cells and as such, permeability changes were delayed in Mac-1-/- mice. However, by 60 min neutrophils from both sets of mice were emigrating in large numbers. Electron-microscopy and spinning disk multichannel fluorescence confocal microscopy revealed endothelial docking structures that progressed to dome-like structures completely covering wt and Mac-1-/- neutrophils. These domes completely enveloped the emigrating neutrophils in both wt and Mac-1-/- mice making the mode of emigration underneath these structures extraneous to barrier function. In conclusion, predominantly paracellular versus predominantly transcellular emigration does not affect vascular barrier integrity as endothelial dome-like structures retain barrier function.

  10. Endothelial domes encapsulate adherent neutrophils and minimize increases in vascular permeability in paracellular and transcellular emigration.

    Science.gov (United States)

    Phillipson, Mia; Kaur, Jaswinder; Colarusso, Pina; Ballantyne, Christie M; Kubes, Paul

    2008-02-20

    Local edema, a cardinal sign of inflammation associates closely with neutrophil emigration. Neutrophil emigration has been described to occur primarily through endothelial junctions (paracellular) and more rarely directly through endothelial cells (transcellular). Recently, we reported that unlike in wild-type (wt) mice, Mac-1-/- (CD11b) neutrophils predominantly emigrated transcellularly and was significantly delayed taking 20-30 min longer than the paracellular emigration (wt). In the present study we noted significant anatomical disruption of the endothelium and hypothesized that transcellular emigration would greatly increase vascular permeability. Surprisingly, despite profound disruption of the endothelial barrier as the neutrophils moved through the cells, the changes in vascular permeability during transcellular emigration (Mac-1-/-) were not increased more than in wt mice. Instead increased vascular permeability completely tracked the number of emigrated cells and as such, permeability changes were delayed in Mac-1-/- mice. However, by 60 min neutrophils from both sets of mice were emigrating in large numbers. Electron-microscopy and spinning disk multichannel fluorescence confocal microscopy revealed endothelial docking structures that progressed to dome-like structures completely covering wt and Mac-1-/- neutrophils. These domes completely enveloped the emigrating neutrophils in both wt and Mac-1-/- mice making the mode of emigration underneath these structures extraneous to barrier function. In conclusion, predominantly paracellular versus predominantly transcellular emigration does not affect vascular barrier integrity as endothelial dome-like structures retain barrier function.

  11. Effect of Electromagnetic Pulse Exposure on Brain Micro Vascular Permeability in Rats

    Institute of Scientific and Technical Information of China (English)

    GUI-RONG DING; KANG-CHU LI; XIAO-WU WANG; YONG-CHUN ZHOU; LIAN-BO QIU; JUAN TAN; SHENG-LONG XU; GUO-ZHEN GUO

    2009-01-01

    Objective To observe the effect of electromagnetic pulse (EMP) exposure on cerebral micro vascular permeability in rats.Methods The whole-body of male Sprague-Dawley rats were exposed or sham exposed to 200 pulses or 400 pulses (1 Hz) of EMP at 200 kV/m.At 0.5,1,3,6,and 12 h after EMP exposure,the permeability of cerebral micro vascular was detected by transmission electron microscopy and immunohistochemistry using lanthanum nitrate and endogenous albumin as vascular tracers,respectively. Results The lanthanum nitrate tracer was limited to the micro vascular lumen with no lanthanum nitrate or albumin tracer extravasation in control rat brain.After EMP exposure,the lanthanum nitrate ions reached the tight junction,basal lamina and pericapillary tissue.Similarly,the albumin immunopositive staining was identified in pericapillary tissue.The changes in brain micro vascular permeability were transient,the leakage of micro vascular vessels appeared at 1 h,and reached its peak at 3 h,and nearly recovered at 12 h,after EMP exposure.In addition,the leakage of micro vascular was more obvious after exposure of EMP at 400 pulses than after exposure of EMP at 200 pulses. Conclusion Exposure to 200 and 400 pulses (1 Hz) of EMP at 200 kV/m can increase cerebral micro vascular permeability in rats,which is recoverable.

  12. Characterization of the tight junction protein ZO-2 localized at the nucleus of epithelial cells.

    Science.gov (United States)

    Jaramillo, Blanca Estela; Ponce, Arturo; Moreno, Jacqueline; Betanzos, Abigail; Huerta, Miriam; Lopez-Bayghen, Esther; Gonzalez-Mariscal, Lorenza

    2004-07-01

    ZO-2 is a MAGUK protein that in confluent epithelial sheets localizes at tight junctions (TJ) whereas in sparse cultures accumulates in clusters at the nucleus. Here, we have characterized several nuclear properties of ZO-2. We observe that ZO-2 is present in the nuclear matrix and co-immunoprecipitates with lamin B(1) and actin from the nuclei of sparse cultures. We show that ZO-2 presents several NLS at its amino region, that when deleted, diminish the nuclear import of the ZO-2 amino segment and impair the ability of the region to regulate the transcriptional activity of promoters controlled by AP-1. Several RS repeats are detected in the ZO-2 amino segment, however, their deletion does not preclude the display of a speckled nuclear pattern. ZO-2 displays two putative NES. However, only the second one appears to be functional, as when conjugated to ovalbumin (OV), it is able to translocate this protein from the nucleus to the cytoplasm in a leptomycin B-sensitive way.

  13. Plant actin controls membrane permeability.

    Science.gov (United States)

    Hohenberger, Petra; Eing, Christian; Straessner, Ralf; Durst, Steffen; Frey, Wolfgang; Nick, Peter

    2011-09-01

    The biological effects of electric pulses with low rise time, high field strength, and durations in the nanosecond range (nsPEFs) have attracted considerable biotechnological and medical interest. However, the cellular mechanisms causing membrane permeabilization by nanosecond pulsed electric fields are still far from being understood. We investigated the role of actin filaments for membrane permeability in plant cells using cell lines where different degrees of actin bundling had been introduced by genetic engineering. We demonstrate that stabilization of actin increases the stability of the plasma membrane against electric permeabilization recorded by penetration of Trypan Blue into the cytoplasm. By use of a cell line expressing the actin bundling WLIM domain under control of an inducible promotor we can activate membrane stabilization by the glucocorticoid analog dexamethasone. By total internal reflection fluorescence microscopy we can visualize a subset of the cytoskeleton that is directly adjacent to the plasma membrane. We conclude that this submembrane cytoskeleton stabilizes the plasma membrane against permeabilization through electric pulses. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Physics and Applications of NIS Junctions

    Energy Technology Data Exchange (ETDEWEB)

    Ullom, J N

    2001-08-24

    This paper reviews the physics and applications of Normal-Insulator-Superconductor (NIS) tunnel junctions. The current-voltage properties of NIS junctions are diode-like with a strong temperature dependence. Hence, these structures can be used as sensitive thermometers at temperatures well below the energy gap, {Delta}, of the superconducting electrode. For junction voltages comparable to {Delta}/q, current flow removes energy from the normal electrode. This property has been exploited to build refrigerators capable of cooling thin-film circuits from 0.3 K to 0.1 K. Calorimeters and bolometers for the detection of X-rays and millimeter-wave radiation, respectively, have successfully been built from NIS junctions. NIS junctions have also been used to probe the superconducting state. Finally, recent ideas for the use of NIS junctions as simple circuit elements are described.

  15. Algorithms for Junctions in Directed Acyclic Graphs

    CERN Document Server

    Ferreira, Carlos Eduardo

    2012-01-01

    Given a pair of distinct vertices u, v in a graph G, we say that s is a junction of u, v if there are in G internally vertex disjoint directed paths from s to u and from s to v. We show how to characterize junctions in directed acyclic graphs. We also consider the two problems in the following and derive efficient algorithms to solve them. Given a directed acyclic graph G and a vertex s in G, how can we find all pairs of vertices of G such that s is a junction of them? And given a directed acyclic graph G and k pairs of vertices of G, how can we preprocess G such that all junctions of k given pairs of vertices could be listed quickly? All junctions of k pairs problem arises in an application in Anthropology and we apply our algorithm to find such junctions on kinship networks of some brazilian indian ethnic groups.

  16. Gap Junction in the Teleost Fish Lineage: Duplicated Connexins May Contribute to Skin Pattern Formation and Body Shape Determination.

    Science.gov (United States)

    Watanabe, Masakatsu

    2017-01-01

    Gap junctions are intercellular channels that allow passage of ions and small molecules between adjacent cells. Gap junctions in vertebrates are composed of connexons, which are an assembly of six proteins, connexins. Docking of two connexons on the opposite cell surfaces forms a gap junction between the cytoplasm of two neighboring cells. Connexins compose a family of structurally related four-pass transmembrane proteins. In mammals, there are ~20 connexins, each of which contributes to unique permeability of gap junctions, and mutations of some connexin-encoding genes are associated with human diseases. Zebrafish has been predicted to contain 39 connexin-encoding genes; the high number can be attributed to gene duplication during fish evolution, which resulted in diversified functions of gap junctions in teleosts. The determination of body shapes and skin patterns in animal species is an intriguing question. Mathematical models suggest principle mechanisms explaining the diversification of animal morphology. Recent studies have revealed the involvement of gap junctions in fish morphological diversity, including skin pattern formation and body shape determination. This review focuses on connexins in teleosts, which are integrated in the mathematical models explaining morphological diversity of animal skin patterns and body shapes.

  17. Permeability and ultrastructure of human bladder epithelium

    DEFF Research Database (Denmark)

    Eldrup, J; Thorup, Jørgen Mogens; Nielsen, S L;

    1983-01-01

    Leakage of tight junctions as observed with electron microscopy and demonstration of solute transport across bladder epithelium was investigated in 13 patients with different bladder diseases: urinary retention and infection, bladder tumours and interstitial cystitis. The latter group showed cons...

  18. Molecular junctions: can pulling influence optical controllability?

    Science.gov (United States)

    Parker, Shane M; Smeu, Manuel; Franco, Ignacio; Ratner, Mark A; Seideman, Tamar

    2014-08-13

    We suggest the combination of single molecule pulling and optical control as a way to enhance control over the electron transport characteristics of a molecular junction. We demonstrate using a model junction consisting of biphenyl-dithiol coupled to gold contacts. The junction is pulled while optically manipulating the dihedral angle between the two rings. Quantum dynamics simulations show that molecular pulling enhances the degree of control over the dihedral angle and hence over the transport properties.

  19. A Negative Permeability Material at Red Light

    DEFF Research Database (Denmark)

    Yuan, Hsiao-Kuan; Chettiar, Uday K.; Cai, Wenshan;

    2007-01-01

    A negative permeability in a periodic array of pairs of thin silver strips is demonstrated experimentally for two distinct samples. The effect of the strip surface roughness on negative permeability is evaluated. The first sample, Sample A, is fabricated of thinner strips with a root mean square...... roughness of 7 nm, while Sample B is made of thicker strips with 3-nm roughness. The real part of permeability, μ ′ , is −1 at a wavelength of 770 nm in Sample A and −1.7 at 725 nm in Sample B. Relative to prototypes simulated with ideal strips, larger strip roughness acts to decrease μ ′ by a factor of 7...

  20. Gut Permeability in Autism Spectrum Disorders

    OpenAIRE

    2014-01-01

    ObjectiveTo test whether gut permeability is increased in autism spectrum disorders (ASD) by evaluating gut permeability in a population-derived cohort of children with ASD compared with age- and intelligence quotient-matched controls without ASD but with special educational needs (SEN).Patients and MethodsOne hundred thirty-three children aged 10–14 years, 103 with ASD and 30 with SEN, were given an oral test dose of mannitol and lactulose and urine collected for 6 hr. Gut permeability was a...

  1. Loss models for long Josephson junctions

    DEFF Research Database (Denmark)

    Olsen, O. H.; Samuelsen, Mogens Rugholm

    1984-01-01

    A general model for loss mechanisms in long Josephson junctions is presented. An expression for the zero-field step is found for a junction of overlap type by means of a perturbation method. Comparison between analytic solution and perturbation result shows good agreement.......A general model for loss mechanisms in long Josephson junctions is presented. An expression for the zero-field step is found for a junction of overlap type by means of a perturbation method. Comparison between analytic solution and perturbation result shows good agreement....

  2. Implementation of a multichannel soft x-ray diagnostic for electron temperature measurements in TJ-II high-density plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Baiao, D.; Varandas, C. [Associacao EURATOM/IST, Instituto de Plasmas e Fusao Nuclear, Instituto Superior Tecnico, Universidade Tecnica de Lisboa, 1049-001 Lisboa (Portugal); Medina, F.; Ochando, M.; Pastor, I. [Laboratorio Nacional de Fusion, Asociacion EURATOM-CIEMAT, 28040 Madrid (Spain); Molinero, A.; Chercoles, J. [Laboratorio General de Electronica y Automatica-CIEMAT, 28040 Madrid (Spain)

    2012-10-15

    Based on the multi-foil technique, a multichannel soft x-ray diagnostic for electron temperature measurements has been recently implemented in the TJ-II stellarator. The diagnostic system is composed by four photodiodes arrays with beryllium filters of different thickness. An in-vacuum amplifier board is coupled to each array, aiming at preventing induced noise currents. The Thomson scattering and the vacuum ultraviolet survey diagnostics are used for assessing plasma profiles and composition, being the analysis carried out with the radiation code IONEQ. The electron temperature is determined through the different signal-pair ratios with temporal and spatial resolution. The design and preliminary results from the diagnostic are presented.

  3. Effect of next-nearest-neighbour interaction on $d_{x^{2}−y^{2}}$ -wave superconducting phase in 2D t-J model

    Indian Academy of Sciences (India)

    N S Mondal; N K Ghosh

    2010-01-01

    n exact diagonalization calculation of the t-J model on 2D square cluster has been studied for the ground state properties of HTSC. Effect of next-nearest-neighbour hopping and magnetic (both antiferromagnetic and ferromagnetic) interaction on $d_{x^{2} −y^{2}}$-wave pairing has been shown. Relative strength of the next-nearest-neighbour interaction with respect to that of near-neighbour interaction for the strongest $d_{x^{2} −y^{2}}$-wave pairing has been estimated. A schematic phase diagram is shown. It is shown that a two-sublattice model with antiferromagnetic interaction between them and a small intra-ferromagnetic-type interaction in one sublattice favours $d_{x^{2} −y^{2}}$-wave superconductivity and moderate negative type NNN hopping adds flavours to this phase.

  4. Simulating the Euclidean time Schroedinger equations using an INTEL iPSC/860 hypercube: Application to the t-J model of high-T(sub c) superconductivity

    Science.gov (United States)

    Kovarik, M. D.; Barnes, T.

    We describe a Monte Carlo simulation of a dynamical fermion problem in two spatial dimensions on an Intel iPSC/860 hypercube. The problem studied is the determination of the dispersion relation of a dynamical hole in the t-J model of the high temperature superconductors. Since this problem involves the motion of many fermions in more than one spatial dimension, it is representative of the class of systems that suffer from the 'minus sign problem' of dynamical fermions which has made Monte Carlo simulation very difficult. We demonstrate that for small values of the hole hopping parameter one can extract the entire hole dispersion relation using the GRW Monte Carlo algorithm, which is a simulation of the Euclidean time Schroedinger equation, and present results on 4 x 4 and 6 x 6 lattices. Generalization to physical hopping parameter values will only require use of an improved trial wavefunction for importance sampling.

  5. Simulating the Euclidean time Schroedinger equations using an Intel iPSC/860 hypercube: Application to the t-J model of high-{Tc} superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Kovarik, M.D.; Barnes, T. [Oak Ridge National Lab., TN (United States)]|[Tennessee Univ., Knoxville, TN (United States). Dept. of Physics

    1993-10-01

    We describe a Monte Carlo simulation of a dynamical fermion problem in two spatial dimensions on an Intel iPSC/860 hypercube. The problem studied is the determination of the dispersion relation of a dynamical hole in the t-J model of the high temperature superconductors. Since this problem involves the motion of many fermions in more than one spatial dimensions, it is representative of the class of systems that suffer from the ``minus sign problem`` of dynamical fermions which has made Monte Carlo simulation very difficult. We demonstrate that for small values of the hole hopping parameter one can extract the entire hole dispersion relation using the GRW Monte Carlo algorithm, which is a simulation of the Euclidean time Schroedinger equation, and present results on 4 {times} 4 and 6 {times} 6 lattices. Generalization to physical hopping parameter values wig only require use of an improved trial wavefunction for importance sampling.

  6. Role of next-nearest-neighbour hopping in the internal structure of the ground state and finite temperature quantities of 2D t-J model

    Indian Academy of Sciences (India)

    N S Mondal; N K Ghosh

    2010-06-01

    An exact diagonalization calculation for a small cluster in the two-dimensional t-J model has been studied to calculate two-hole correlation. Calculations reveal dominant hole–hole correlation for holes sitting on next-nearest-neighbour (NNN) sites and critical coupling occurs at $J/t = 0.8$. With the increase in negative-type NNN hopping, correlation decreases at NNN sites whereas it increases at other sites. The thermodynamic properties such as entropy and specific heat are studied as functions of temperature with various NNN hopping strength. Results show that with the inclusion of negative NNN hopping, the system becomes more ordered. A qualitative transition temperature region has been estimated. It is shown that with the increase in NNN hopping strength, c increases. Specific heat results show non-Fermi liquid-type behaviour of the system. All our calculations establish the importance of negative-type NNN hopping.

  7. Assessing the permeability of engineered capillary networks in a 3D culture.

    Directory of Open Access Journals (Sweden)

    Stephanie J Grainger

    Full Text Available Many pathologies are characterized by poor blood vessel growth and reduced nutrient delivery to the surrounding tissue, introducing a need for tissue engineered blood vessels. Our lab has developed a 3D co-culture method to grow interconnected networks of pericyte-invested capillaries, which can anastamose with host vasculature following implantation to restore blood flow to ischemic tissues. However, if the engineered vessels contain endothelial cells (ECs that are misaligned or contain wide junctional gaps, they may function improperly and behave more like the pathologic vessels that nourish tumors. The purpose of this study was to test the resistance to permeability of these networks in vitro, grown with different stromal cell types, as a metric of vessel functionality. A fluorescent dextran tracer was used to visualize transport across the endothelium and the pixel intensity was quantified using a customized MATLAB algorithm. In fibroblast-EC co-cultures, the dextran tracer easily penetrated through the vessel wall and permeability was high through the first 5 days of culture, indicative of vessel immaturity. Beyond day 5, dextran accumulated at the periphery of the vessel, with very little transported across the endothelium. Quantitatively, permeability dropped from initial levels of 61% to 39% after 7 days, and to 7% after 2 weeks. When ECs were co-cultured with bone marrow-derived mesenchymal stem cells (MSCs or adipose-derived stem cells (AdSCs, much tighter control of permeability was achieved. Relative to the EC-fibroblast co-cultures, permeabilities were reduced 41% for the EC-MSC co-cultures and 50% for the EC-AdSC co-cultures after 3 days of culture. By day 14, these permeabilities decreased by 68% and 77% over the EC-fibroblast cultures. Co-cultures containing stem cells exhibit elevated VE-cadherin levels and more prominent EC-EC junctional complexes when compared to cultures containing fibroblasts. These data suggest the stromal

  8. Complete Sequence of pABTJ2, A Plasmid from Acinetobacter baumannii MDR-TJ, Carrying Many Phage-like Elements

    Institute of Scientific and Technical Information of China (English)

    He Huang; Yan Dong; Zhi-Liang Yang; Hao Luo; Xi Zhang; Feng Gao

    2014-01-01

    Acinetobacter baumannii is an important opportunistic pathogen in hospital, and the multidrug-resistant isolates of A. baumannii have been increasingly reported in recent years. A num-ber of different mechanisms of resistance have been reported, some of which are associated with plasmid-mediated acquisition of genes. Therefore, studies on plasmids in A. baumannii have been a hot issue lately. We have performed complete genome sequencing of A. baumannii MDR-TJ, which is a multidrug-resistant isolate. Finalizing the remaining large scaffold of the previous assem-bly, we found a new plasmid pABTJ2, which carries many phage-like elements. The plasmid pAB-TJ2 is a circular double-stranded DNA molecule, which is 110,967 bp in length. We annotated 125 CDSs from pABTJ2 using IMG ER and ZCURVE_V, accounting for 88.28%of the whole plasmid sequence. Many phage-like elements and a tRNA-coding gene were detected in pABTJ2, which is rarely reported among A. baumannii. The tRNA gene is specific for asparagine codon GTT, which may be a small chromosomal sequence picked up through incorrect excision during plasmid forma-tion. The phage-like elements may have been acquired during the integration process, as the GC content of the region carrying phage-like elements was higher than that of the adjacent regions. The finding of phage-like elements and tRNA-coding gene in pABTJ2 may provide a novel insight into the study of A. baumannii pan-plasmidome.

  9. The response of a fast scintillator screen (YAP:Ce) to low energy ions (0-40 keV) and its use to detect fast-ion-loss in stellarator TJ-II

    Energy Technology Data Exchange (ETDEWEB)

    Martínez, M., E-mail: marcos.martinez@externos.ciemat.es [Universidad Carlos III de Madrid, Leganés (Spain); Zurro, B.; Baciero, A.; Jiménez-Rey, D.; Malo, M. [Laboratorio Nacional de Fusión, CIEMAT, Madrid (Spain); Tribaldos, V. [Departamento de Física, Universidad Carlos III de Madrid, Leganés (Spain); Crespo, M. T.; Muñoz, D. [Laboratorio de Metrología de Radiaciones Ionizantes, CIEMAT, Madrid (Spain)

    2016-11-15

    A systematic study of scintillation materials was undertaken to improve the time resolution of the fast ion diagnostic currently installed at TJ-II stellarator. It was found that YAP:Ce (formula YAlO{sub 3}:Ce, Yttrium Aluminum Perovskite doped with Cerium) ionoluminescence offers better sensitivity and time response compared to the standard detector material, SrGa{sub 2}S{sub 4}:Eu (TG-Green), currently used in TJ-II. A comparison between both materials was carried out by irradiating them with H{sup +} ions of up to 40 keV using a dedicated laboratory setup. It is found that for the low energy ions of interest at TJ-II, YAP:Ce offers 20 times higher sensitivity than TG-Green and much faster decay time, 27 ns versus 540 ns. It is expected that the use of YAP:Ce in combination with a faster data acquisition and an ion counting software as part of the TJ-II ion luminescent probe will provide 20 times faster data on ion loss.

  10. The response of a fast scintillator screen (YAP:Ce) to low energy ions (0-40 keV) and its use to detect fast-ion-loss in stellarator TJ-II

    Science.gov (United States)

    Martínez, M.; Zurro, B.; Baciero, A.; Jiménez-Rey, D.; Tribaldos, V.; Malo, M.; Crespo, M. T.; Muñoz, D.

    2016-11-01

    A systematic study of scintillation materials was undertaken to improve the time resolution of the fast ion diagnostic currently installed at TJ-II stellarator. It was found that YAP:Ce (formula YAlO3:Ce, Yttrium Aluminum Perovskite doped with Cerium) ionoluminescence offers better sensitivity and time response compared to the standard detector material, SrGa2S4:Eu (TG-Green), currently used in TJ-II. A comparison between both materials was carried out by irradiating them with H+ ions of up to 40 keV using a dedicated laboratory setup. It is found that for the low energy ions of interest at TJ-II, YAP:Ce offers 20 times higher sensitivity than TG-Green and much faster decay time, 27 ns versus 540 ns. It is expected that the use of YAP:Ce in combination with a faster data acquisition and an ion counting software as part of the TJ-II ion luminescent probe will provide 20 times faster data on ion loss.

  11. Variability of permeability with diameter of conduit

    Indian Academy of Sciences (India)

    J A Adegoke; J A Olowofela

    2008-05-01

    An entry length is always observed before laminar flow is achieved in fluid flowing in a conduit. This depends on the Reynolds number of the flow and the degree of smoothness of the conduit. This work examined this region and the point where laminar flow commences in the context of flow through conduit packed with porous material like beads, of known porosity. Using some theoretical assumptions, it is demonstrated that permeability varies from zero at wall-fluid boundary to maximum at mid-stream, creating a permeability profile similar to the velocity profile. An equation was obtained to establish this. We also found that peak values of permeability increase with increasing porosity, and therefore entry length increases with increasing porosity with all other parameters kept constant. A plot of peak permeability versus porosity revealed that they are linearly related.

  12. Effect of temperature on sandstone permeability

    DEFF Research Database (Denmark)

    Rosenbrand, Esther; Kjøller, Claus

    assumptions would be required in order to estimate sandstone permeability based on the Kozeny equation. An effective specific surface area per pore volume for permeability was estimated by using image analysis and pore size distributions as from nuclear magnetic resonance (NMR) transverse relaxation data...... be determined based on the Klinkenberg (1941) procedure, which accounts for effects on permeability of gas slip on the fluid-solid interface by means of several permeability measurements with different pore pressures. A comparison between the equivalent pore sizes as estimated using the Kozeny equation...... at 80°C than at 20°C; at 80°C the main effect might be due to an alteration of pore fluid rheology, whereas at 20°C particles might be filtered in pore constrictions. DLVO theory (Derjaguin and Landau (1941); Verwey and Overbeek (1948)) was used to compare effects of temperature and salinity on surface...

  13. Measuring Permeability of Composite Cryotank Laminants

    Science.gov (United States)

    Oliver, Stanley T.; Selvidge, Shawn; Watwood, Michael C.

    2004-01-01

    This paper describes a test method developed to identify whether certain materials and material systems are suitable candidates for large pressurized reusable cryogenic tanks intended for use in current and future manned launch systems. It provides a quick way to screen numerous candidate materials for permeability under anticipated loading environments consistent with flight conditions, as well as addressing reusability issues. cryogenic tank, where the major design issue was hydrogen permeability. It was successfully used to evaluate samples subjected to biaxial loading while maintaining test temperatures near liquid hydrogen. After each sample was thermally preconditioned, a cyclic pressure load was applied to simulate the in-plane strain. First permeability was measured while a sample was under load. Then the sample was unloaded and allowed to return to ambient temperature. The test was repeated to simulate reusability, in order to evaluate its effects on material permeability.

  14. Lunar electrical conductivity and magnetic permeability

    Science.gov (United States)

    Dyal, P.; Parkin, C. W.; Daily, W. D.

    1975-01-01

    Improved analytical techniques are applied to a large Apollo magnetometer data set to yield values of electroconductivity, temperature, magnetic permeability, and iron abundance. Average bulk electroconductivity of the moon is calculated to be .0007 mho/m; a rapid increase with depth to about .003 mho/m within 250 km is indicated. The temperature profile, obtained from the electroconductivity profile for olivine, indicates high lunar temperatures at relatively shallow depths. Magnetic permeability of the moon relative to its environment is calculated to be 1.008 plus or minus .005; a permeability relative to free space of 1.012 plus 0.011, minus 0.008 is obtained. Lunar iron abundances corresponding to this permeability value are 2.5 plus 2.3, minus 1.7 wt% free iron and 5.0-13.5 wt% total iron for a moon composed of a combination of free iron, olivine, and orthopyroxene.

  15. Permeable landscapes for wildlife in the Northeast

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Landscape permeability, also referred to as "habitat connectivity," is the ability of a diverse land area to provide for passage of animals. This project will...

  16. Food Packaging Permeability Behaviour: A Report

    OpenAIRE

    Valentina Siracusa

    2012-01-01

    The use of polymer materials in food packaging field is one of the largest growing market area. Actually the optimization behaviour of packaging permeability is of crucial importance, in order to extend the food shelf-life and to reach the best engineering solution. Studying the permeability characterization of the different polymer material (homogeneous and heterogeneous polymer system) to the different packaging gases, in different environmental condition, is crucial to understand if the se...

  17. Pneumatic fracturing of low permeability media

    Energy Technology Data Exchange (ETDEWEB)

    Schuring, J.R. [New Jersey Institute of Technology, Newark, NJ (United States)

    1996-08-01

    Pneumatic fracturing of soils to enhance the removal and treatment of dense nonaqueous phase liquids is described. The process involves gas injection at a pressure exceeding the natural stresses and at a flow rate exceeding the permeability of the formation. The paper outlines geologic considerations, advantages and disadvantages, general technology considerations, low permeability media considerations, commercial availability, efficiency, and costs. Five case histories of remediation using pneumatic fracturing are briefly summarized. 11 refs., 2 figs., 1 tab.

  18. The Carboxyl Tail of Connexin32 Regulates Gap Junction Assembly in Human Prostate and Pancreatic Cancer Cells*

    Science.gov (United States)

    Katoch, Parul; Mitra, Shalini; Ray, Anuttoma; Kelsey, Linda; Roberts, Brett J.; Wahl, James K.; Johnson, Keith R.; Mehta, Parmender P.

    2015-01-01

    Connexins, the constituent proteins of gap junctions, are transmembrane proteins. A connexin (Cx) traverses the membrane four times and has one intracellular and two extracellular loops with the amino and carboxyl termini facing the cytoplasm. The transmembrane and the extracellular loop domains are highly conserved among different Cxs, whereas the carboxyl termini, often called the cytoplasmic tails, are highly divergent. We have explored the role of the cytoplasmic tail of Cx32, a Cx expressed in polarized and differentiated cells, in regulating gap junction assembly. Our results demonstrate that compared with the full-length Cx32, the cytoplasmic tail-deleted Cx32 is assembled into small gap junctions in human pancreatic and prostatic cancer cells. Our results further document that the expression of the full-length Cx32 in cells, which express the tail-deleted Cx32, increases the size of gap junctions, whereas the expression of the tail-deleted Cx32 in cells, which express the full-length Cx32, has the opposite effect. Moreover, we show that the tail is required for the clustering of cell-cell channels and that in cells expressing the tail-deleted Cx32, the expression of cell surface-targeted cytoplasmic tail alone is sufficient to enhance the size of gap junctions. Our live-cell imaging data further demonstrate that gap junctions formed of the tail-deleted Cx32 are highly mobile compared with those formed of full-length Cx32. Our results suggest that the cytoplasmic tail of Cx32 is not required to initiate the assembly of gap junctions but for their subsequent growth and stability. Our findings suggest that the cytoplasmic tail of Cx32 may be involved in regulating the permeability of gap junctions by regulating their size. PMID:25548281

  19. Relations Between Permeability and Structure of Wood

    Institute of Scientific and Technical Information of China (English)

    Bao Fucheng; Zhao Youke; Lü Jianxiong

    2003-01-01

    The permeability and the structure of heartwood and sapwood of the solvent-exchange dried and the air-dried green-wood of Chinese-fir (Cunninghamia lanceolata (Lamb.) Hook.) and masson pine (Pinus massoniana Lamb.) were measured inorder to study the relations between the permeability and the structure. The results showed that the permeability of sapwood of boththe air-dried and the solvent-exchange dried wood was higher than that of heartwood, and the permeability of the solvent-exchangeddried heartwood and sapwood was higher than that of the air-dried. A higher permeability of wood was attributed to, on the one hand,a bigger number of flow path per unit area of the wood perpendicular to the flow direction resulted from a bigger number ofunaspirated pits per unit area and a bigger number of effective pit openings per membrane, and on the other hand, a smaller numberof tracheid in series connection per unit length parallel to flow direction resulted from a longer tracheid length and an effectivetracheid length for permeability.

  20. Permeability of lateritic soil by various methods

    Directory of Open Access Journals (Sweden)

    Tatiana Tavares Rodriguez

    2015-10-01

    Full Text Available Soil Permeability is an important property of soil used to dimension several types of engineering works, and it can be quantified by the permeability rates. Despite of the great use, the type of the re doubts about the best way to determine de permeability rates. The main questions are: (1 the type of the method and (2 the reproducibility of samples in tropical soils. So, the objective of this work is to evaluate the permeability of a lateritic soil by comparing values of permeability coefficient determined for laboratory and in situ testing. For this, it was chosen the lateritic soil of Campo Experimental de Engenharia Geotécncia (CEEG of the Universidade Estadual de Londrina (UEL and four equipments: constant and variable head permeameters, Guelph permeameter and infiltrometer. The results show that all the methods present mean value of permeability coefficient on the order of 10-3 cm/s whit variation coefficient in range of 37% to 92% , except the constant permeameter. The heterogeneous structure of lateritic soil (in macro and micro pores is the probably determinant of the variability observed.

  1. Interleukin-6, desmosome and tight junction protein expression levels in reflux esophagitis-affected mucosa

    Institute of Scientific and Technical Information of China (English)

    Fei-Yue Li; Yan Li

    2009-01-01

    AIM: To investigate the correlation between the expression levels of interleukin (IL)-6 and proteins in tight junctions (TJs) in the esophageal mucosa of rats modeling different types of reflux esophagitis (RE), and the ability of aluminum phosphate to protect against RE-induced mucosal damage via these proteins. METHODS: Male SPF Wistar rats aged 56 d were divided randomly into acid RE, alkaline RE, mixed RE, and control groups. Various surgical procedures were performed to establish rat models of acid RE. At 14 d after the procedure, some of the rats started aluminum phosphate treatment. Transmission electron microscopy (TEM) was used to observe the morphological features of TJs and desmosomes in the esophageal epithelium. Immunohistochemical methods and Western blotting were used to measure expression of claudin 1, occludin, ZO-1, JAM-1, DSG-1 and IL-6; reverse transcription polymerase chain reaction (RTPCR) was used to measure expression of mRNA of claudin 1, occludin, ZO-1, JAM-1, DSG-1 and IL-6. RESULTS: At day 14 after the procedures, an RE model was established in all subsequently sacrificed rats of groups A, B and C. By both gross and microscopic observation, the mucosa was damaged and thickened as the disease progressed. With TEM observation, a widened intercellular space was noticed, with significantly fewer desmosomes. Immunohistochemistry showed significantly higher levels of all proteins in all RE models compared to control rats at 3 d after operation (65.5% ± 25.6% vs 20.5% ± 2.1%, P 0.05, treated vs untreated, respectively). These levels increased in the rat with alkaline RE, and this increase was accompanied by continued hyperplasia in comparison with controls (85.5% ± 25.6% vs 20.5% ± 2.1%, P < 0.05, respectively). Furthermore, the expression of TJ proteins was not correlated significantly with that of IL-6 in this group. CONCLUSION: These findings indicate that TJ proteins are highly expressed as an early molecular event involved in RE

  2. Nanoparticle Density: A Critical Biophysical Regulator of Endothelial Permeability.

    Science.gov (United States)

    Tay, Chor Yong; Setyawati, Magdiel Inggrid; Leong, David Tai

    2017-03-17

    The integrity of the vasculature system is intrinsically sensitive to a short list of biophysical cues spanning from nano to micro scales. We have earlier found that certain nanomaterials could induce endothelial leakiness (nanoparticle induced endothelial leakiness, nanoEL). In this study, we report that the density of the nanomaterial, a basic intrinsic material property not implicated in many nanoparticle-mediated biological effects, predominantly dictates the nanoEL effect. We demonstrated that the impinging force exerted by a library of increasing effective densities but consistently sized silica nanoparticles (SiNPs) could directly increase endothelial permeability. The crossover effective particle density that induced nanoEL was determined to be between 1.57 g/cm(3) to 1.72 g/cm(3). It was also found that a cumulative gravitational-mediated force of around 1.8 nN/μm along the boundaries of the vascular endothelial cadherin (VE-cad) adherens junctions appeared to be a critical threshold force required to perturb endothelial cell-cell adhesion. The net result is the "snapping" of the mechanically pretensed VE-cad (Nanosnap), leading to the formation of micron-sized gaps that would dramatically increase endothelial leakiness.

  3. Pathophysiology of increased intestinal permeability in obstructive jaundice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier.Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients' outcome.

  4. Comparative field permeability measurement of permeable pavements using ASTM C1701 and NCAT permeameter methods.

    Science.gov (United States)

    Li, Hui; Kayhanian, Masoud; Harvey, John T

    2013-03-30

    Fully permeable pavement is gradually gaining support as an alternative best management practice (BMP) for stormwater runoff management. As the use of these pavements increases, a definitive test method is needed to measure hydraulic performance and to evaluate clogging, both for performance studies and for assessment of permeability for construction quality assurance and maintenance needs assessment. Two of the most commonly used permeability measurement tests for porous asphalt and pervious concrete are the National Center for Asphalt Technology (NCAT) permeameter and ASTM C1701, respectively. This study was undertaken to compare measured values for both methods in the field on a variety of permeable pavements used in current practice. The field measurements were performed using six experimental section designs with different permeable pavement surface types including pervious concrete, porous asphalt and permeable interlocking concrete pavers. Multiple measurements were performed at five locations on each pavement test section. The results showed that: (i) silicone gel is a superior sealing material to prevent water leakage compared with conventional plumbing putty; (ii) both methods (NCAT and ASTM) can effectively be used to measure the permeability of all pavement types and the surface material type will not impact the measurement precision; (iii) the permeability values measured with the ASTM method were 50-90% (75% on average) lower than those measured with the NCAT method; (iv) the larger permeameter cylinder diameter used in the ASTM method improved the reliability and reduced the variability of the measured permeability.

  5. Frictional stability-permeability relationships for fractures in shales: Friction-Permeability Relationships

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Yi [Department of Energy and Mineral Engineering, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Elsworth, Derek [Department of Energy and Mineral Engineering, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Department of Geosciences, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Wang, Chaoyi [Department of Energy and Mineral Engineering, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Ishibashi, Takuya [Department of Energy and Mineral Engineering, EMS Energy Institute, and G3 Center, Pennsylvania State University, University Park Pennsylvania USA; Fukushima Renewable Energy Institute, National Institute of Advanced Industrial Science and Technology, Koriyama Japan; Fitts, Jeffrey P. [Department of Civil and Environmental Engineering, Princeton University, Princeton New Jersey USA

    2017-01-01

    There is wide concern that fluid injection in the subsurface, such as for the stimulation of shale reservoirs or for geological CO2 sequestration (GCS), has the potential to induce seismicity that may change reservoir permeability due to fault slip. However, the impact of induced seismicity on fracture permeability evolution remains unclear due to the spectrum of modes of fault reactivation (e.g., stable versus unstable). As seismicity is controlled by the frictional response of fractures, we explore friction-stability-permeability relationships through the concurrent measurement of frictional and hydraulic properties of artificial fractures in Green River shale (GRS) and Opalinus shale (OPS). We observe that carbonate-rich GRS shows higher frictional strength but weak neutral frictional stability. The GRS fracture permeability declines during shearing while an increased sliding velocity reduces the rate of permeability decline. By comparison, the phyllosilicate-rich OPS has lower friction and strong stability while the fracture permeability is reduced due to the swelling behavior that dominates over the shearing induced permeability reduction. Hence, we conclude that the friction-stability-permeability relationship of a fracture is largely controlled by mineral composition and that shale mineral compositions with strong frictional stability may be particularly subject to permanent permeability reduction during fluid infiltration.

  6. Adenosine receptor signaling modulates permeability of the blood-brain barrier.

    Science.gov (United States)

    Carman, Aaron J; Mills, Jeffrey H; Krenz, Antje; Kim, Do-Geun; Bynoe, Margaret S

    2011-09-14

    The blood-brain barrier (BBB) is comprised of specialized endothelial cells that form the capillary microvasculature of the CNS and is essential for brain function. It also poses the greatest impediment in the treatment of many CNS diseases because it commonly blocks entry of therapeutic compounds. Here we report that adenosine receptor (AR) signaling modulates BBB permeability in vivo. A(1) and A(2A) AR activation facilitated the entry of intravenously administered macromolecules, including large dextrans and antibodies to β-amyloid, into murine brains. Additionally, treatment with an FDA-approved selective A(2A) agonist, Lexiscan, also increased BBB permeability in murine models. These changes in BBB permeability are dose-dependent and temporally discrete. Transgenic mice lacking A(1) or A(2A) ARs showed diminished dextran entry into the brain after AR agonism. Following treatment with a broad-spectrum AR agonist, intravenously administered anti-β-amyloid antibody was observed to enter the CNS and bind β-amyloid plaques in a transgenic mouse model of Alzheimer's disease (AD). Selective AR activation resulted in cellular changes in vitro including decreased transendothelial electrical resistance, increased actinomyosin stress fiber formation, and alterations in tight junction molecules. These results suggest that AR signaling can be used to modulate BBB permeability in vivo to facilitate the entry of potentially therapeutic compounds into the CNS. AR signaling at brain endothelial cells represents a novel endogenous mechanism of modulating BBB permeability. We anticipate these results will aid in drug design, drug delivery and treatment options for neurological diseases such as AD, Parkinson's disease, multiple sclerosis and cancers of the CNS.

  7. Gap junctions and connexin-interacting proteins

    NARCIS (Netherlands)

    Giepmans, Ben N G

    2004-01-01

    Gap junctions form channels between adjacent cells. The core proteins of these channels are the connexins. Regulation of gap junction communication (GJC) can be modulated by connexin-associating proteins, such as regulatory protein phosphatases and protein kinases, of which c-Src is the best-studied

  8. Gap junctions and connexin-interacting proteins

    NARCIS (Netherlands)

    Giepmans, Ben N G

    2004-01-01

    Gap junctions form channels between adjacent cells. The core proteins of these channels are the connexins. Regulation of gap junction communication (GJC) can be modulated by connexin-associating proteins, such as regulatory protein phosphatases and protein kinases, of which c-Src is the

  9. Gap junctions and connexin-interacting proteins

    NARCIS (Netherlands)

    Giepmans, Ben N G

    2004-01-01

    Gap junctions form channels between adjacent cells. The core proteins of these channels are the connexins. Regulation of gap junction communication (GJC) can be modulated by connexin-associating proteins, such as regulatory protein phosphatases and protein kinases, of which c-Src is the best-studied

  10. Shot noise in YBCO bicrystal Josephson junctions

    DEFF Research Database (Denmark)

    Constantinian, K.Y.; Ovsyannikov, G.A.; Borisenko, I.V.;

    2003-01-01

    We measured spectral noise density in YBCO symmetric bicrystal Josephson junctions on sapphire substrates at bias voltages up to 100 mV and T 4.2 K. Normal state resistance of the Josephson junctions, R-N = 20-90 Omega and ICRN up to 2.2 mV have been observed in the experimental samples. Noise...

  11. Shear zone junctions: Of zippers and freeways

    Science.gov (United States)

    Passchier, Cees W.; Platt, John P.

    2017-02-01

    Ductile shear zones are commonly treated as straight high-strain domains with uniform shear sense and characteristic curved foliation trails, bounded by non-deforming wall rock. Many shear zones, however, are branched, and if movement on such branches is contemporaneous, the resulting shape can be complicated and lead to unusual shear sense arrangement and foliation geometries in the wall rock. For Y-shaped shear zone triple junctions with three joining branches and transport direction at a high angle to the branchline, only eight basic types of junction are thought to be stable and to produce significant displacement. The simplest type, called freeway junctions, have similar shear sense in all three branches. The other types show joining or separating behaviour of shear zone branches similar to the action of a zipper. Such junctions may have shear zone branches that join to form a single branch (closing zipper junction), or a single shear zone that splits to form two branches, (opening zipper junction). All categories of shear zone junctions show characteristic foliation patterns and deflection of markers in the wall rock. Closing zipper junctions are unusual, since they form a non-active zone with opposite deflection of foliations in the wall rock known as an extraction fault or wake. Shear zipper junctions can form domains of overprinting shear sense along their flanks. A small and large field example are given from NE Spain and Eastern Anatolia. The geometry of more complex, 3D shear zone junctions with slip parallel and oblique to the branchline is briefly discussed.

  12. Junction conditions of cosmological perturbations

    CERN Document Server

    Tomita, K

    2004-01-01

    The behavior of perturbations is studied in cosmological models which consist of two different homogeneous regions connected in a spherical shell boundary. The junction conditions for the metric perturbations and the displacements of the shell boundary are analyzed and the surface densities of the perturbed energy and momentum in the shell are derived, using Mukohyama's gauge-invariant formalism and the Israel discontinuity condition. In both homogeneous regions the perturbations of scalar, vector and tensor types are expanded using the 3-dimensional harmonic functions, but the model coupling among them is caused in the shell by the inhomogeneity. By treating the perturbations with odd and even parities separately, it is found, however, that we can have consistent displacements and surface densities for given metric parturbations

  13. Relative permeability in dual porosity porous media

    Energy Technology Data Exchange (ETDEWEB)

    Deghmoum, A. [SONATRACH CRD, Boumerdes (Algeria); Tiab, D. [Oklahoma Univ., Norman, OK (United States); Mazouzi, A. [SONATRACH PED (Algeria)

    2000-06-01

    One of the important factors in the field of reservoir simulation of dual-porosity systems is reliable relative permeability data. Laboratory limitations hinder measurements. The real behaviour of naturally fractures reservoirs is not reflected in the reservoir core samples, which as a rule originate from zones without induced or natural fractures. Therefore, it is commonly assumed that the relative permeability of a naturally fractured system is a straight line, which can cause errors. The authors undertook to conduct special core analyses on Berea outcrop core samples, to simulate fracture opening through the cutting of the samples to get different fracture apertures, to study the effects of dual porosity on the shape of capillary pressure curves, and to evaluate absolute and relative permeability, as they are affected by fracture opening. The correlation obtained between absolute permeability and fracture aperture was good, and capillary pressure curves permitted the observation of the effect of dual porosity. High residual oil saturation was present in the matrix, since the fractures became the easiest route for water flow, and this situation prevented the use of unsteady-state tests to measure relative permeability on the samples. Instead, the centrifuge technique was successfully used. A naturally fractured reservoir (NFR), the Tin Fouye Tabankort (TFT) reservoir in Algeria was selected to extend the findings. The site was principally selected due to the availability of naturally fractured cores and published data. Core observations, well test analysis and borehole imager tools were all TFT natural fracture indicators presented in the paper. Representative data of relative permeability was obtained by conducting a displacement test on a full diameter core to solve the laboratory limitations. The correlation between permeability and fracture opening was used to estimate the aperture of natural fractures in TFT reservoir. 17 refs., 2 tabs., 24 figs.

  14. Butyrate Enhances the Intestinal Barrier by Facilitating Tight Junction Assembly via Activation of AMP-Activated Protein Kinase in Caco-2 Cell Monolayers12

    Science.gov (United States)

    Peng, Luying; Li, Zhong-Rong; Green, Robert S.; Holzman, Ian R.; Lin, Jing

    2009-01-01

    Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier. PMID:19625695

  15. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers.

    Science.gov (United States)

    Peng, Luying; Li, Zhong-Rong; Green, Robert S; Holzman, Ian R; Lin, Jing

    2009-09-01

    Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier.

  16. In vivo human buccal permeability of nicotine

    DEFF Research Database (Denmark)

    Adrian, Charlotte L; Olin, Helle B D; Dalhoff, Kim

    2006-01-01

    The aim was to examine the in vivo buccal pH-dependent permeability of nicotine in humans and furthermore compare the in vivo permeability of nicotine to previous in vitro permeability data. The buccal permeability of nicotine was examined in a three-way cross-over study in eight healthy non......-smokers using a buccal perfusion cell. The disappearance of nicotine from perfusion solutions with pH 6.0, 7.4, and 8.1 was studied for 3h. The apparent permeability of nicotine (P(app)) was determined at each pH value. Parotid saliva was collected in an attempt to assess systemic levels of nicotine....... The disappearance rate of nicotine increased significantly as the pH increased, which resulted in P(app) values of 0.57+/-0.55 x 10(-4), 2.10+/-0.23 x 10(-4), and 3.96+/-0.54 x 10(-4)cms(-1) (mean+/-S.D.) at pH 6.0, 7.4, and 8.1, respectively. A linear relationship (R(2)=0.993) was obtained between the P...

  17. Permeability Tests on Silkeborg Sand No. 0000

    DEFF Research Database (Denmark)

    Lund, Willy; Jakobsen, Kim Parsberg

    The flow through porous media plays an important role in various engineering disciplines, as for example in ground water hydrology and soil mechanics. In the present study the permeability is determined for a fine, saturated sand. As the flow through a porous media strongly depends on the charact......The flow through porous media plays an important role in various engineering disciplines, as for example in ground water hydrology and soil mechanics. In the present study the permeability is determined for a fine, saturated sand. As the flow through a porous media strongly depends...... on the characteristics of the soil matrix, the permeability is determined for different void ratios. All tests are performed on reconstituted specimens of Silkeborg Sand No. 0000. The permeability is determined by use of a falling head apparatus. The apparatus, test procedures and the analysis method are described...... in the succeeding sections. Finally the test results are briefly summarised and a relationship between void ratio l and permeability is established....

  18. Vascular permeability in cerebral cavernous malformations

    DEFF Research Database (Denmark)

    Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao;

    2015-01-01

    Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observ......Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case......-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability...... correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive...

  19. Honeycomb Core Permeability Under Mechanical Loads

    Science.gov (United States)

    Glass, David E.; Raman, V. V.; Venkat, Venki S.; Sankaran, Sankara N.

    1997-01-01

    A method for characterizing the air permeability of sandwich core materials as a function of applied shear stress was developed. The core material for the test specimens was either Hexcel HRP-3/16-8.0 and or DuPont Korex-1/8-4.5 and was nominally one-half inch thick and six inches square. The facesheets where made of Hercules' AS4/8552 graphite/epoxy (Gr/Ep) composites and were nominally 0.059-in. thick. Cytec's Metalbond 1515-3M epoxy film adhesive was used for co-curing the facesheets to the core. The permeability of the specimens during both static (tension) and dynamic (reversed and non-reversed) shear loads were measured. The permeability was measured as the rate of air flow through the core from a circular 1-in2 area of the core exposed to an air pressure of 10.0 psig. In both the static and dynamic testing, the Korex core experienced sudden increases in core permeability corresponding to a core catastrophic failure, while the URP core experienced a gradual increase in the permeability prior to core failure. The Korex core failed at lower loads than the HRP core both in the transverse and ribbon directions.

  20. Glioblastoma cell-secreted interleukin-8 induces brain endothelial cell permeability via CXCR2.

    Directory of Open Access Journals (Sweden)

    Julie Dwyer

    Full Text Available Glioblastoma constitutes the most aggressive and deadly of brain tumors. As yet, both conventional and molecular-based therapies have met with limited success in treatment of this cancer. Among other explanations, the heterogeneity of glioblastoma and the associated microenvironment contribute to its development, as well as resistance and recurrence in response to treatments. Increased vascularity suggests that tumor angiogenesis plays an important role in glioblastoma progression. However, the molecular crosstalk between endothelial and glioblastoma cells requires further investigation. To examine the effects of glioblastoma-derived signals on endothelial homeostasis, glioblastoma cell secretions were collected and used to treat brain endothelial cells. Here, we present evidence that the glioblastoma secretome provides pro-angiogenic signals sufficient to disrupt VE-cadherin-mediated cell-cell junctions and promote endothelial permeability in brain microvascular endothelial cells. An unbiased angiogenesis-specific antibody array screen identified the chemokine, interleukin-8, which was further demonstrated to function as a key factor involved in glioblastoma-induced permeability, mediated through its receptor CXCR2 on brain endothelia. This underappreciated interface between glioblastoma cells and associated endothelium may inspire the development of novel therapeutic strategies to induce tumor regression by preventing vascular permeability and inhibiting angiogenesis.

  1. Coordinate transformation in the model of long Josephson junctions: geometrically equivalent Josephson junctions

    Science.gov (United States)

    Semerdzhieva, E. G.; Boyadzhiev, T. L.; Shukrinov, Yu. M.

    2005-10-01

    The transition from the model of a long Josephson junction of variable width to the model of a junction with a coordinate-dependent Josephson current amplitude is effected through a coordinate transformation. This establishes the correspondence between the classes of Josephson junctions of variable width and quasi-one-dimensional junctions with a variable thickness of the barrier layer. It is shown that for a junction of exponentially varying width the barrier layer of the equivalent quasi-one-dimensional junction has a distributed resistive inhomogeneity that acts as an attractor for magnetic flux vortices. The curve of the critical current versus magnetic field for a Josephson junction with a resistive microinhomogeneity is constructed with the aid of a numerical simulation, and a comparison is made with the critical curve of a junction of exponentially varying width. The possibility of replacing a distributed inhomogeneity in a Josephson junction by a local inhomogeneity at the end of the junction is thereby demonstrated; this can have certain advantages from a technological point of view.

  2. Atomically Abrupt Topological p-n Junction.

    Science.gov (United States)

    Kim, Sung Hwan; Jin, Kyung-Hwan; Kho, Byung Woo; Park, Byeong-Gyu; Liu, Feng; Kim, Jun Sung; Yeom, Han Woong

    2017-08-24

    Topological insulators (TI's) are a new class of quantum matter with extraordinary surface electronic states, which bear great potential for spintronics and error-tolerant quantum computing. In order to put a TI into any practical use, these materials need to be fabricated into devices whose basic units are often p-n junctions. Interesting electronic properties of a 'topological' p-n junction were proposed theoretically such as the junction electronic state and the spin rectification. However, the fabrication of a lateral topological p-n junction has been challenging because of materials, process, and fundamental reasons. Here, we demonstrate an innovative approach to realize a p-n junction of topological surface states (TSS's) of a three-dimensional (3D) topological insulator (TI) with an atomically abrupt interface. When a ultrathin Sb film is grown on a 3D TI of Bi2Se3 with a typical n-type TSS, the surface develops a strongly p-type TSS through the substantial hybridization between the 2D Sb film and the Bi2Se3 surface. Thus, the Bi2Se3 surface covered partially with Sb films bifurcates into areas of n- and p-type TSS's as separated by atomic step edges with a lateral electronic junction of as short as 2 nm. This approach opens a different avenue toward various electronic and spintronic devices based on well-defined topological p-n junctions with the scalability down to atomic dimensions.

  3. Gap junction communication in myelinating glia.

    Science.gov (United States)

    Nualart-Marti, Anna; Solsona, Carles; Fields, R Douglas

    2013-01-01

    Gap junction communication is crucial for myelination and axonal survival in both the peripheral nervous system (PNS) and central nervous system (CNS). This review examines the different types of gap junctions in myelinating glia of the PNS and CNS (Schwann cells and oligodendrocytes respectively), including their functions and involvement in neurological disorders. Gap junctions mediate intercellular communication among Schwann cells in the PNS, and among oligodendrocytes and between oligodendrocytes and astrocytes in the CNS. Reflexive gap junctions mediating transfer between different regions of the same cell promote communication between cellular compartments of myelinating glia that are separated by layers of compact myelin. Gap junctions in myelinating glia regulate physiological processes such as cell growth, proliferation, calcium signaling, and participate in extracellular signaling via release of neurotransmitters from hemijunctions. In the CNS, gap junctions form a glial network between oligodendrocytes and astrocytes. This transcellular communication is hypothesized to maintain homeostasis by facilitating restoration of membrane potential after axonal activity via electrical coupling and the re-distribution of potassium ions released from axons. The generation of transgenic mice for different subsets of connexins has revealed the contribution of different connexins in gap junction formation and illuminated new subcellular mechanisms underlying demyelination and cognitive defects. Alterations in metabolic coupling have been reported in animal models of X-linked Charcot-Marie-Tooth disease (CMTX) and Pelizaeus-Merzbarcher-like disease (PMLD), which are caused by mutations in the genes encoding for connexin 32 and connexin 47 respectively. Future research identifying the expression and regulation of gap junctions in myelinating glia is likely to provide a better understanding of myelinating glia in nervous system function, plasticity, and disease. This

  4. Fluxon dynamics in three stacked Josephson junctions

    DEFF Research Database (Denmark)

    Gorria, Carlos; Christiansen, Peter Leth; Gaididei, Yuri Borisovich

    2002-01-01

    /sub -/, the coupling between junctions leads to a repulsion of the fluxons with the same polarity. Above this critical velocity a fluxon will induce radiation in the neighboring junctions, leading to a bunching of the fluxons in the stacked junctions. Using the Sakai-Bodin-Pedersen model, three coupled perturbed sine......-Gordon equations are numerically studied for different values of coupling, damping, and bias parameters. In a narrow range of velocities bunching occurs. Outside this interval the fluxons split and new fluxons may be created. I-V characteristics are presented...

  5. Temperature dependence of thermopower in molecular junctions

    Science.gov (United States)

    Kim, Youngsang; Lenert, Andrej; Meyhofer, Edgar; Reddy, Pramod

    2016-07-01

    The thermoelectric properties of molecular junctions are of considerable interest due to their promise for efficient energy conversion. While the dependence of thermoelectric properties of junctions on molecular structure has been recently studied, their temperature dependence remains unexplored. Using a custom built variable temperature scanning tunneling microscope, we measured the thermopower and electrical conductance of individual benzenedithiol junctions over a range of temperatures (100 K-300 K). We find that while the electrical conductance is independent of temperature, the thermopower increases linearly with temperature, confirming the predictions of the Landauer theory.

  6. Phase qubits fabricated with trilayer junctions

    Energy Technology Data Exchange (ETDEWEB)

    Weides, M; Bialczak, R C; Lenander, M; Lucero, E; Mariantoni, Matteo; Neeley, M; O' Connell, A D; Sank, D; Wang, H; Wenner, J; Yamamoto, T; Yin, Y; Cleland, A N; Martinis, J, E-mail: martin.weides@nist.gov, E-mail: martinis@physics.ucsb.edu [Department of Physics, University of California, Santa Barbara, CA 93106 (United States)

    2011-05-15

    We have developed a novel Josephson junction geometry with minimal volume of lossy isolation dielectric, suitable for higher quality trilayer junctions implemented in qubits. The junctions are based on in situ deposited trilayers with thermal tunnel oxide, have micron-sized areas and a low subgap current. In qubit spectroscopy only a few avoided level crossings are observed, and the measured relaxation time of T{sub 1{approx}}400 ns is in good agreement with the usual phase qubit decay time, indicating low loss due to the additional isolation dielectric.

  7. Tunable permeability of magnetic wires at microwaves

    Science.gov (United States)

    Panina, L. V.; Makhnovskiy, D. P.; Morchenko, A. T.; Kostishin, V. G.

    2015-06-01

    This paper presents the analysis into microwave magnetic properties of magnetic microwires and their composites in the context of applications in wireless sensors and tunable microwave materials. It is demonstrated that the intrinsic permeability of wires has a wide frequency dispersion with relatively large values in the GHz band. In the case of a specific magnetic anisotropy this results in a tunable microwave impedance which could be used for distributed wireless sensing networks in functional composites. The other range of applications is related with developing the artificial magnetic dielectrics with large and tunable permeability. The composites with magnetic wires with a circumferential anisotropy have the effective permeability which differs substantially from unity for a relatively low concentration (less than 10%). This can make it possible to design the wire media with a negative and tunable index of refraction utilising natural magnetic properties of wires.

  8. Gyroid Nanoporous Membranes with Tunable Permeability

    DEFF Research Database (Denmark)

    Li, Li; Schulte, Lars; Clausen, Lydia D.

    2011-01-01

    Understanding the relevant permeability properties of ultrafiltration membranes is facilitated by using materials and procedures that allow a high degree of control on morphology and chemical composition. Here we present the first study on diffusion permeability through gyroid nanoporous cross......-sided skin membranes, much faster than expected by a naive resistance-in-series model; the flux through the two-sided skin membranes even increases with the membrane thickness. We propose a model that captures the physics behind the observed phenomena, as confirmed by flow visualization experiments...... the effective diffusion coefficients of a series of antibiotics, proteins, and other biomolecules; solute permeation is discussed in terms of hindered diffusion. The combination of uniform bulk morphology, isotropically percolating porosity, controlled surface chemistry, and tunable permeability is distinctive...

  9. Ammonia and urea permeability of mammalian aquaporins

    DEFF Research Database (Denmark)

    Litman, Thomas; Søgaard, Rikke; Zeuthen, Thomas

    2009-01-01

    The human aquaporins,AQP3,AQP7, AQP8,AQP9, and possibly AQP10, are permeable to ammonia, and AQP7, AQP9, and possibly AQP3, are permeable to urea. In humans, these aquaporins supplement the ammonia transport of the Rhesus (Rh) proteins and the urea transporters (UTs). The mechanism by which...... ammonium is transported by aquaporins is not fully resolved. A comparison of transport equations, models, and experimental data shows that ammonia is transported in its neutral form, NH(3). In the presence of NH(3), the aquaporin stimulates H(+) transport. Consequently, this transport of H(+) is only...... significant at alkaline pH. It is debated whether the H(+) ion passes via the aquaporin or by some external route; the investigation of this problem requires the aquaporin-expressing cell to be voltage-clamped. The ammonia-permeable aquaporins differ from other aquaporins by having a less restrictive aromatic...

  10. Permeability of Hollow Microspherical Membranes to Helium

    Science.gov (United States)

    Zinoviev, V. N.; Kazanin, I. V.; Pak, A. Yu.; Vereshchagin, A. S.; Lebiga, V. A.; Fomin, V. M.

    2016-01-01

    This work is devoted to the study of the sorption characteristics of various hollow microspherical membranes to reveal particles most suitable for application in the membrane-sorption technologies of helium extraction from a natural gas. The permeability of the investigated sorbents to helium and their impermeability to air and methane are shown experimentally. The sorption-desorption dependences of the studied sorbents have been obtained, from which the parameters of their specific permeability to helium are calculated. It has been established that the physicochemical modification of the original particles exerts a great influence on the coefficient of the permeability of a sorbent to helium. Specially treated cenospheres have displayed high efficiency as membranes for selective extraction of helium.

  11. Food Packaging Permeability Behaviour: A Report

    Directory of Open Access Journals (Sweden)

    Valentina Siracusa

    2012-01-01

    Full Text Available The use of polymer materials in food packaging field is one of the largest growing market area. Actually the optimization behaviour of packaging permeability is of crucial importance, in order to extend the food shelf-life and to reach the best engineering solution. Studying the permeability characterization of the different polymer material (homogeneous and heterogeneous polymer system to the different packaging gases, in different environmental condition, is crucial to understand if the selected material is adapted to the chosen food contact field. Temperature and humidity parameters are of crucial importance for food quality preservation, especially in real life situations, like food market, and house long-life use. The aim of this report was to collect information about the state of the art on the permeability characteristics of the polymer packages used on food field.

  12. Magnetohydrodynamic Flow Past a Permeable Bed

    Directory of Open Access Journals (Sweden)

    R. Venugopal

    1983-01-01

    Full Text Available The paper evaluates mass flow velocity heat transfer rates and velocity/temperature distributions in the viscous, incompressible and slightly conducting fluid past a permeable bed in three different configurations namely (1 Couette flow (2 Poiseuille flow and (3 free surface flow, under the influence of a uniform transverse magnetic field. To discuss the solution, the flow region is divided into two zones : Zone 1 (from the impermeable upper rigid plate to the permeable bed in which the flow is laminar and governed by Navier-Stokes equations, and Zone 2 (the permeable bed below the nominal surface in which the flow is governed by Darcy law. The paper also investigates the effects of magnetic field, porosity and Biot number on the physical quantities mentioned above.

  13. Quantifying porosity, compressibility and permeability in Shale

    DEFF Research Database (Denmark)

    Mbia, Ernest Ncha; Fabricius, Ida Lykke; Frykman, Peter

    (XRD) of shale samples show about 50% silt and high content of kaolinite in the clay fraction when compared with offshore samples from the Central Graben. Porosity measurements from helium porosimetry-mercury immersion (HPMI), mercury injection capillary pressure (MICP) and nuclear magnetic resonance...... (NMR) show that, the MICP porosity is 9-10% points lower than HPMI and NMR porosity. Compressibility result shows that deep shale is stiffer in situ than normally assumed in geotechnical modelling and that static compressibility corresponds with dynamic one only at the begining of unloading stress...... strain data. We found that Kozeny's modelled permeability fall in the same order of magnitude with measured permeability for shale rich in kaolinite but overestimates permeability by two to three orders of magnitudes for shale with high content of smectite. The empirical Yang and Aplin model gives good...

  14. Magnetic levitation from negative permeability materials

    Energy Technology Data Exchange (ETDEWEB)

    Coffey, Mark W., E-mail: mcoffey@mines.edu [Department of Physics, Colorado School of Mines, Golden, CO 80401 (United States)

    2012-09-03

    As left-handed materials and metamaterials are becoming more prevalent, we examine the effect of negative permeability upon levitation force. We first consider two half spaces of differing permeability and a point magnetic source, so that the method of images may be employed. We determine that the resulting force may be larger than for conventional magnetic materials. We then illustrate the inclusion of a finite sample thickness. -- Highlights: ► The effect of negative permeability upon levitation force is considered. ► Such an effect could be realized with metamaterials. ► The resulting force may be larger than with conventional materials. ► The analysis is extended to allow for a finite sample thickness. ► Representative numerical values are given.

  15. Melatonin Preserves Blood-Brain Barrier Integrity and Permeability via Matrix Metalloproteinase-9 Inhibition.

    Directory of Open Access Journals (Sweden)

    Himakarnika Alluri

    Full Text Available Microvascular hyperpermeability that occurs at the level of the blood-brain barrier (BBB often leads to vasogenic brain edema and elevated intracranial pressure following traumatic brain injury (TBI. At a cellular level, tight junction proteins (TJPs between neighboring endothelial cells maintain the integrity of the BBB via TJ associated proteins particularly, zonula occludens-1 (ZO-1 that binds to the transmembrane TJPs and actin cytoskeleton intracellularly. The pro-inflammatory cytokine, interleukin-1β (IL-1β as well as the proteolytic enzymes, matrix metalloproteinase-9 (MMP-9 are key mediators of trauma-associated brain edema. Recent studies indicate that melatonin a pineal hormone directly binds to MMP-9 and also might act as its endogenous inhibitor. We hypothesized that melatonin treatment will provide protection against TBI-induced BBB hyperpermeability via MMP-9 inhibition. Rat brain microvascular endothelial cells grown as monolayers were used as an in vitro model of the BBB and a mouse model of TBI using a controlled cortical impactor was used for all in vivo studies. IL-1β (10 ng/mL; 2 hours-induced endothelial monolayer hyperpermeability was significantly attenuated by melatonin (10 μg/mL; 1 hour, GM6001 (broad spectrum MMP inhibitor; 10 μM; 1 hour, MMP-9 inhibitor-1 (MMP-9 specific inhibitor; 5 nM; 1 hour or MMP-9 siRNA transfection (48 hours in vitro. Melatonin and MMP-9 inhibitor-1 pretreatment attenuated IL-1β-induced MMP-9 activity, loss of ZO-1 junctional integrity and f-actin stress fiber formation. IL-1β treatment neither affected ZO-1 protein or mRNA expression or cell viability. Acute melatonin treatment attenuated BBB hyperpermeability in a mouse controlled cortical impact model of TBI in vivo. In conclusion, one of the protective effects of melatonin against BBB hyperpermeability occurs due to enhanced BBB integrity via MMP-9 inhibition. In addition, acute melatonin treatment provides protection against BBB

  16. Theoretical calculation of performance enhancement in lattice-matched SiGeSn/GeSn p-channel tunneling field-effect transistor with type-II staggered tunneling junction

    Science.gov (United States)

    Wang, Hongjuan; Han, Genquan; Wang, Yibo; Peng, Yue; Liu, Yan; Zhang, Chunfu; Zhang, Jincheng; Hu, Shengdong; Hao, Yue

    2016-04-01

    In this work, a lattice-matched SiGeSn/GeSn heterostructure p-channel tunneling field-effect transistor (hetero-PTFET) with a type-II staggered tunneling junction (TJ) is investigated theoretically. Lattice matching and type-II band alignment at the Γ-point is obtained at the SiGeSn/GeSn interface by tuning Sn and Si compositions. A steeper subthreshold swing (SS) and a higher on state current (I ON) are demonstrated in SiGeSn/GeSn hetero-PTFET than in GeSn homo-PTFET. Si0.31Ge0.49Sn0.20/Ge0.88Sn0.12 hetero-PTFET achieves a 2.3-fold higher I ON than Ge0.88Sn0.12 homo-PTFET at V DD of 0.3 V. Hetero-PTFET achieves a more abrupt hole profile and a higher carrier density near TJ than the homo-PTFET, which contributes to the significantly enhanced band-to-band tunneling (BTBT) rate and tunneling current in hetero-PTFET.

  17. Small-bowel permeability in collagenous colitis

    DEFF Research Database (Denmark)

    Wildt, Signe; Madsen, Jan L; Rumessen, Jüri J

    2006-01-01

    Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies......, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability....

  18. Liquid Permeability of Ceramic Foam Filters

    OpenAIRE

    Zhang, Kexu

    2012-01-01

    This project is in support of the PhD project: ‘Removal of Inclusions from Liquid Aluminium using Electromagnetically Modified Filtration’. The purpose of this project was to measure the tortuosity, and permeability of ~50mm thick: 30, 40, 50 and 80 pores per inch (ppi) commercial alumina ceramic foam filters (CFFs). Measurements have been taken of: cell (pore), window and strut sizes, porosity, tortuosity and liquid permeability. Water velocity from ~0.015-0.77 m/s have been used ...

  19. Development of an Improved Permeability Modification Simulator

    Energy Technology Data Exchange (ETDEWEB)

    Gao, H.W.; Elphnick, J.

    1999-03-09

    This report describes the development of an improved permeability modification simulator performed jointly by BDM Petroleum Technologies and Schlumberger Dowell under a cooperative research and development agreement (CRADA) with the US Department of Energy. The improved simulator was developed by modifying NIPER's PC-GEL permeability modification simulator to include a radial model, a thermal energy equation, a wellbore simulator, and a fully implicit time-stepping option. The temperature-dependent gelation kinetics of a delayed gel system (DGS) is also included in the simulator.

  20. The Permeability of Rubble Mound Breakwaters

    DEFF Research Database (Denmark)

    Williams, A.F.; Burcharth, H. F.; Adel, H. den

    1992-01-01

    The results of an extensive series of permeability experiments originally analysed by Shih (1990) are reinterpreted in the light of new experiments. It is proposed that the Forchheimer equation might not fully describe flow at the high Reynolds numbers found in the interior of rubble material....... A new series of tests designed to test for deviations from the Forchheimer equation and investigate the effects of material shape are described. While no evidence can be found to indicate a deviation from the Forchheimer equation a dependency of permeability and the surface roughness the material...

  1. Increasing gap junctional coupling: a tool for dissecting the role of gap junctions.

    Science.gov (United States)

    Axelsen, Lene Nygaard; Haugan, Ketil; Stahlhut, Martin; Kjølbye, Anne-Louise; Hennan, James K; Holstein-Rathlou, Niels-Henrik; Petersen, Jørgen Søberg; Nielsen, Morten Schak

    2007-03-01

    Much of our current knowledge about the physiological and pathophysiological role of gap junctions is based on experiments where coupling has been reduced by either chemical agents or genetic modification. This has brought evidence that gap junctions are important in many physiological processes. In a number of cases, gap junctions have been implicated in the initiation and progress of disease, and experimental uncoupling has been used to investigate the exact role of coupling. The inverse approach, i.e., to increase coupling, has become possible in recent years and represents a new way of testing the role of gap junctions. The aim of this review is to summarize the current knowledge obtained with agents that selectively increase gap junctional intercellular coupling. Two approaches will be reviewed: increasing coupling by the use of antiarrhythmic peptide and its synthetic analogs and by interfering with the gating of gap junctional channels.

  2. Instigation of endothelial Nlrp3 inflammasome by adipokine visfatin promotes inter-endothelial junction disruption: role of HMGB1.

    Science.gov (United States)

    Chen, Yang; Pitzer, Ashley L; Li, Xiang; Li, Pin-Lan; Wang, Lei; Zhang, Yang

    2015-12-01

    Recent studies have indicated that the inflammasome plays a critical role in the pathogenesis of vascular diseases. However, the pathological relevance of this inflammasome activation, particularly in vascular cells, remains largely unknown. Here, we investigated the role of endothelial (Nucleotide-binding Oligomerization Domain) NOD-like receptor family pyrin domain containing three (Nlrp3) inflammasomes in modulating inter-endothelial junction proteins, which are associated with endothelial barrier dysfunction, an early onset of obesity-associated endothelial injury. Our findings demonstrate that the activation of Nlrp3 inflammasome by visfatin markedly decreased the expression of inter-endothelial junction proteins including tight junction proteins ZO-1, ZO-2 and occludin, and adherens junction protein VE-cadherin in cultured mouse vascular endothelial (VE) cell monolayers. Such visfatin-induced down-regulation of junction proteins in endothelial cells was attributed to high mobility group box protein 1 (HMGB1) release derived from endothelial inflammasome-dependent caspase-1 activity. Similarly, in the coronary arteries of wild-type mice, high-fat diet (HFD) treatment caused a down-regulation of inter-endothelial junction proteins ZO-1, ZO-2, occludin and VE-cadherin, which was accompanied with enhanced inflammasome activation and HMGB1 expression in the endothelium as well as transmigration of CD43(+) T cells into the coronary arterial wall. In contrast, all these HFD-induced alterations in coronary arteries were prevented in mice with Nlrp3 gene deletion. Taken together, these data strongly suggest that the activation of endothelial Nlrp3 inflammasomes as a result of the increased actions of injurious adipokines such as visfatin produces HMGB1, which act in paracrine or autocrine fashion to disrupt inter-endothelial junctions and increase paracellular permeability of the endothelium contributing to the early onset of endothelial injury during metabolic

  3. Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease.

    Science.gov (United States)

    Takeuchi, Hideyuki; Mizoguchi, Hiroyuki; Doi, Yukiko; Jin, Shijie; Noda, Mariko; Liang, Jianfeng; Li, Hua; Zhou, Yan; Mori, Rarami; Yasuoka, Satoko; Li, Endong; Parajuli, Bijay; Kawanokuchi, Jun; Sonobe, Yoshifumi; Sato, Jun; Yamanaka, Koji; Sobue, Gen; Mizuno, Tetsuya; Suzumura, Akio

    2011-01-01

    Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and essential glutamate signals, and inhibitors of microglial activation suppressed both neurotoxic/neuroprotective roles of microglia and hardly affected disease progression. We previously demonstrated that activated microglia release a large amount of glutamate specifically through gap junction hemichannel. Hence, blockade of gap junction hemichannel may be potentially beneficial in treatment of neurodegenerative diseases. In this study, we generated a novel blood-brain barrier permeable gap junction hemichannel blocker based on glycyrrhetinic acid. We found that pharmacologic blockade of gap junction hemichannel inhibited excessive glutamate release from activated microglia in vitro and in vivo without producing notable toxicity. Blocking gap junction hemichannel significantly suppressed neuronal loss of the spinal cord and extended survival in transgenic mice carrying human superoxide dismutase 1 with G93A or G37R mutation as an amyotrophic lateral sclerosis mouse model. Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid β deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model. Our results suggest that gap junction hemichannel blockers may represent a new therapeutic strategy to target neurotoxic microglia specifically and prevent microglia-mediated neuronal death in various neurodegenerative diseases.

  4. Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Hideyuki Takeuchi

    Full Text Available BACKGROUND: Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and essential glutamate signals, and inhibitors of microglial activation suppressed both neurotoxic/neuroprotective roles of microglia and hardly affected disease progression. We previously demonstrated that activated microglia release a large amount of glutamate specifically through gap junction hemichannel. Hence, blockade of gap junction hemichannel may be potentially beneficial in treatment of neurodegenerative diseases. METHODS AND FINDINGS: In this study, we generated a novel blood-brain barrier permeable gap junction hemichannel blocker based on glycyrrhetinic acid. We found that pharmacologic blockade of gap junction hemichannel inhibited excessive glutamate release from activated microglia in vitro and in vivo without producing notable toxicity. Blocking gap junction hemichannel significantly suppressed neuronal loss of the spinal cord and extended survival in transgenic mice carrying human superoxide dismutase 1 with G93A or G37R mutation as an amyotrophic lateral sclerosis mouse model. Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid β deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model. CONCLUSIONS: Our results suggest that gap junction hemichannel blockers may represent a new therapeutic strategy to target neurotoxic microglia specifically and prevent microglia-mediated neuronal

  5. Hypoxia/Aglycemia-induced endothelial barrier dysfunction and tight junction protein downregulation can be ameliorated by citicoline.

    Directory of Open Access Journals (Sweden)

    Xiaotang Ma

    Full Text Available This study explores the effect of citicoline on the permeability and expression of tight junction proteins (TJPs in endothelial cells under hypoxia/aglycemia conditions. Hypoxia or oxygen and glucose deprivation (OGD was utilized to induce endothelial barrier breakdown model on human umbilical vein endothelial cells (HUVECs and mouse brain microvascular endothelial cells (bEnd.3s. The effect of citicoline on endothelial barrier breakdown models was determined at either low or high concentrations. FITC-Dextran flux was used to examine the endothelial permeability. The expression of TJPs was measured by immunofluorescence, Real-time PCR and Western Blot methods. Results showed that hypoxia or OGD increased the permeability of HUVECs accompanied with down-regulation of occludens-1 (ZO-1 and occludin at both mRNA and protein levels. Similarly in bEnd.3s, hypoxia increased the permeability and decreased the expression of ZO-1 and claudin-5. Citicoline treatment dose-dependently decreased the permeability in these two models, which paralleled with elevated expression of TJPs. The data demonstrate that citicoline restores the barrier function of endothelial cells compromised by hypoxia/aglycemia probably via up-regulating the expression of TJPs.

  6. Hypoxia/Aglycemia-induced endothelial barrier dysfunction and tight junction protein downregulation can be ameliorated by citicoline.

    Science.gov (United States)

    Ma, Xiaotang; Zhang, Huiting; Pan, Qunwen; Zhao, Yuhui; Chen, Ji; Zhao, Bin; Chen, Yanfang

    2013-01-01

    This study explores the effect of citicoline on the permeability and expression of tight junction proteins (TJPs) in endothelial cells under hypoxia/aglycemia conditions. Hypoxia or oxygen and glucose deprivation (OGD) was utilized to induce endothelial barrier breakdown model on human umbilical vein endothelial cells (HUVECs) and mouse brain microvascular endothelial cells (bEnd.3s). The effect of citicoline on endothelial barrier breakdown models was determined at either low or high concentrations. FITC-Dextran flux was used to examine the endothelial permeability. The expression of TJPs was measured by immunofluorescence, Real-time PCR and Western Blot methods. Results showed that hypoxia or OGD increased the permeability of HUVECs accompanied with down-regulation of occludens-1 (ZO-1) and occludin at both mRNA and protein levels. Similarly in bEnd.3s, hypoxia increased the permeability and decreased the expression of ZO-1 and claudin-5. Citicoline treatment dose-dependently decreased the permeability in these two models, which paralleled with elevated expression of TJPs. The data demonstrate that citicoline restores the barrier function of endothelial cells compromised by hypoxia/aglycemia probably via up-regulating the expression of TJPs.

  7. Presynaptic spike broadening reduces junctional potential amplitude.

    Science.gov (United States)

    Spencer, A N; Przysiezniak, J; Acosta-Urquidi, J; Basarsky, T A

    1989-08-24

    Presynaptic modulation of action potential duration may regulate synaptic transmission in both vertebrates and invertebrates. Such synaptic plasticity is brought about by modifications to membrane currents at presynaptic release sites, which, in turn, lead to changes in the concentration of cytosolic calcium available for mediating transmitter release. The 'primitive' neuromuscular junction of the jellyfish Polyorchis penicillatus is a useful model of presynaptic modulation. In this study, we show that the durations of action potentials in the motor neurons of this jellyfish are negatively correlated with the amplitude of excitatory junctional potentials. We present data from in vitro voltage-clamp experiments showing that short duration voltage spikes, which elicit large excitatory junctional potentials in vivo, produce larger and briefer calcium currents than do long duration action potentials, which elicit small excitatory junctional potentials.

  8. Laparoscopically assisted pyeloplasty for ureteropelvic junction ...

    African Journals Online (AJOL)

    junction obstruction: a transperitoneal versus a retroperitoneal approach ... laparoscopic-assisted dismembered pyeloplasty (TLADP) ... to an open technique for two patients of the TLADP group; ... Annals of Pediatric Surgery 2012, 8:29–31.

  9. In vitro porcine blood-brain barrier model for permeability studies: pCEL-X software pKa(FLUX) method for aqueous boundary layer correction and detailed data analysis.

    Science.gov (United States)

    Yusof, Siti R; Avdeef, Alex; Abbott, N Joan

    2014-12-18

    In vitro blood-brain barrier (BBB) models from primary brain endothelial cells can closely resemble the in vivo BBB, offering valuable models to assay BBB functions and to screen potential central nervous system drugs. We have recently developed an in vitro BBB model using primary porcine brain endothelial cells. The model shows expression of tight junction proteins and high transendothelial electrical resistance, evidence for a restrictive paracellular pathway. Validation studies using small drug-like compounds demonstrated functional uptake and efflux transporters, showing the suitability of the model to assay drug permeability. However, one limitation of in vitro model permeability measurement is the presence of the aqueous boundary layer (ABL) resulting from inefficient stirring during the permeability assay. The ABL can be a rate-limiting step in permeation, particularly for lipophilic compounds, causing underestimation of the permeability. If the ABL effect is ignored, the permeability measured in vitro will not reflect the permeability in vivo. To address the issue, we explored the combination of in vitro permeability measurement using our porcine model with the pKa(FLUX) method in pCEL-X software to correct for the ABL effect and allow a detailed analysis of in vitro (transendothelial) permeability data, Papp. Published Papp using porcine models generated by our group and other groups are also analyzed. From the Papp, intrinsic transcellular permeability (P0) is derived by simultaneous refinement using a weighted nonlinear regression, taking into account permeability through the ABL, paracellular permeability and filter restrictions on permeation. The in vitro P0 derived for 22 compounds (35 measurements) showed good correlation with P0 derived from in situ brain perfusion data (r(2)=0.61). The analysis also gave evidence for carrier-mediated uptake of naloxone, propranolol and vinblastine. The combination of the in vitro porcine model and the software

  10. Androgen-Dependent Sertoli Cell Tight Junction Remodeling Is Mediated by Multiple Tight Junction Components

    National Research Council Canada - National Science Library

    Chakraborty, Papia; William Buaas, F; Sharma, Manju; Smith, Benjamin E; Greenlee, Anne R; Eacker, Stephen M; Braun, Robert E

    2014-01-01

    Sertoli cell tight junctions (SCTJs) of the seminiferous epithelium create a specialized microenvironment in the testis to aid differentiation of spermatocytes and spermatids from spermatogonial stem cells...

  11. Antiferromagnetic, metal-insulator, and superconducting phase transitions in underdoped cuprates: Slave-fermion t-J model in the hopping expansion

    Science.gov (United States)

    Shimizu, Akihiro; Aoki, Koji; Sakakibara, Kazuhiko; Ichinose, Ikuo; Matsui, Tetsuo

    2011-02-01

    We study a system of doped antiferromagnet in three dimensions at finite temperatures using the t-J model, a canonical model of strongly correlated electrons. We employ the slave-fermion representation of electrons, in which an electron is described as a composite of a charged spinless holon and a chargeless spinon. We introduce two kinds of U(1) gauge fields on links as auxiliary fields, one describing resonating valence bonds of antiferromagnetic nearest-neighbor spin pairs and the other for nearest-neighbor hopping amplitudes of holons and spinons in the ferromagnetic channel. To perform a numerical study of the system, we integrate out the fermionic holon field by using the hopping expansion in powers of the hopping amplitude, which is legitimate for the region in and near the insulating phase. The resultant effective model is described in terms of bosonic spinons, two U(1) gauge fields, and a collective field for hole pairs. We study this model by means of Monte Carlo simulations, calculating the specific heat, spin correlation functions, and instanton densities. We obtain a phase diagram in the hole concentration-temperature plane, which is in good agreement with that observed recently for clean and homogeneous underdoped samples.

  12. Oral glutamine supplementation improves intestinal permeability dysfunction in a murine acute graft-vs.-host disease model.

    Science.gov (United States)

    Noth, Rainer; Häsler, Robert; Stüber, Eckhard; Ellrichmann, Mark; Schäfer, Heiner; Geismann, Claudia; Hampe, Jochen; Bewig, Burkhard; Wedel, Thilo; Böttner, Martina; Schreiber, Stefan; Rosenstiel, Philip; Arlt, Alexander

    2013-04-01

    Although a profound barrier dysfunction has been reported, little is known about the pathophysiological mechanism evoking gastrointestinal graft-vs.-host disease (GI-GvHD) and apparent therapeutic options. The aim of this study was to evaluate the influence of oral glutamine on the course of GI-GvHD in an acute semiallogenic graft-vs.-host disease (GvHD) in irradiated B6D2F1 mice. An acute semiallogenic GvHD was induced by intraperitoneal injection of lymphocytes from C57BL/6 mice to irradiated B6D2F1 mice. Half of the GvHD animals received oral glutamine supplementation for 6 days started at the time of lymphocyte transfer. Six days after induction of the semiallogenic GvHD, jejunum specimens were prepared. The expression of the proinflammatory cytokine TNF-α and the tight junction protein occludin was investigated by PCR. Histological changes along with the apoptotic response were evaluated and intestinal permeability was assessed. Animals with GvHD showed a strong increase in paracellular permeability as a sign of the disturbed barrier function. TNF-α expression was significantly increased and the expression of the tight junction protein occludin decreased. GvHD led to mucosal atrophy, crypt hyperplasia, crypt apoptosis, and a disintegration of the tight junctions. Glutamine-treated mice showed reduced expression of TNF-α, increased occludin expression, fewer histological changes in the jejunum, smaller number of apoptotic cells in the crypt, and reduced gastrointestinal permeability. In conclusion, oral glutamine seems to have beneficial effects on the severity of inflammatory changes in the course of GvHD and might be a therapeutic option.

  13. Junction Plasmon-Induced Molecular Reorientation

    Energy Technology Data Exchange (ETDEWEB)

    El-Khoury, Patrick Z.; Hu, Dehong; Hess, Wayne P.

    2013-10-17

    Time and frequency dependent intensity variations in sequences of Raman spectra recorded at plasmonic junctions can be assigned to molecular reorientation. This is revealed through Raman trajectories recorded at a nanojunction formed between a silver AFM tip and a corrugated silver surface coated with biphenyl-4,4’-dithiol. Molecular motion is not observed when the tip is retracted and only surface enhancement is operative. In effect, junction plasmon induced molecular reorientation is tracked.

  14. [Clinical anatomy of the esophagogastric junction].

    Science.gov (United States)

    Tănase, M; Aldea, A S

    2012-01-01

    The esophagogastric junction is a controversial anatomical area, due to its sphincteric mechanism which does not show an obvious anatomical basis. The aim of this study is to investigate the anatomical components that endoscopically indicate the mucosal esophagogastric junction in hiatal hernia patients. The esophagogastric junction was investigated in 27 hiatal hernia patients undergoing surgery. Hiatal hernia is an extension of the stomach situated between the esophagogastric junction and the diaphragmatic indentation. The following types of hiatal hernia were found: sliding hiatal hernia (type I) in 4 patients (14.81%), rolling hiatal hernia (type II) in 2 (7.4%), mixed hiatal hernia (type III) in 12 (44.44%), type IV hiatal hernia in 4 (14.81%) and recurrent hiatal hernia in 5 (18.51%). Of the 27 hiatal hernia patients, 8 (29.6%) were operated using classical procedures: laparotomy--6 (75%) and laparoscopic surgery--2 (25%). The angle of His cannot be used for marking the mucosal esophagogastric junction due to the severe damage of the lower esophageal sphincter in hiatal hernia patients. The squamocolumnar junction is displaced in hiatal hernia patients and was not an option for the study group. The distal end of the esophageal longitudinal palisading vessels needs medication (proton pump inhibitors that reduce the gastric acid production), in order to enhance the visibility of these vessels. The proximal end of gastric longitudinal mucosal folds proved to be the most reliable site to identify endoscopically the mucosal esophagogastric junction. The anatomical structure of the esophagogastric junction differs in hiatal hernia patients and these peculiarities are very important in surgery.

  15. The Dissolution of Double Holliday Junctions

    DEFF Research Database (Denmark)

    Bizard, Anna H; Hickson, Ian D

    2014-01-01

    as "double Holliday junction dissolution." This reaction requires the cooperative action of a so-called "dissolvasome" comprising a Holliday junction branch migration enzyme (Sgs1/BLM RecQ helicase) and a type IA topoisomerase (Top3/TopoIIIα) in complex with its OB (oligonucleotide/oligosaccharide binding......) fold containing accessory factor (Rmi1). This review details our current knowledge of the dissolution process and the players involved in catalyzing this mechanistically complex means of completing homologous recombination reactions....

  16. Characterization of the Plasma Edge for Technique of Atomic Helium Beam in the CIEMAT Fusion Device; Caracterizacion del Borde del Plasma del Dispositivo de Fusion TJ-II del CIEMAT mediante el Diagnostico del Haz Supersonico de Helio

    Energy Technology Data Exchange (ETDEWEB)

    Hidalgo, A.

    2003-07-01

    In this report, the measurement of Electron Temperature and Density in the Boundary Plasma of TJ-II with a Supersonic Helium Beam Diagnostic and work devoted to the upgrading of this technique are described. Also, simulations of Laser Induced Fluorescence (LIF) studies of level populations of electronically excited He atoms are shown. This last technique is now being installed in the CIEMAT fusion device. (Author ) 36 refs.

  17. Gap junction intercellular communication and benzene toxicity.

    Science.gov (United States)

    Rivedal, Edgar; Witz, Gisela; Leithe, Edward

    2010-03-19

    Aberrant regulation of gap junction intercellular communication (GJIC) has been linked to several human diseases, including cancer and abnormal hematopoietic development. Benzene exposure has been shown to cause hematotoxicity and leukemia, but the underlying mechanisms involved remain unclear. We have observed that several metabolites of benzene have the ability to block gap junction intercellular communication. The ring-opened trans,trans-muconaldehyde (MUC) was found to be the most potent inhibitor of gap junction channels. MUC was found to induce cross-linking of the gap junction protein connexin43, which seemed to be responsible for the induced inhibition of GJIC. Glutaraldehyde, which has a similar molecular structure as MUC, was found to possess similar effects on gap junctions as MUC, while the mono-aldehyde formaldehyde shows lower potency, both as a connexin cross-linker, and as an inhibitor of GJIC. Both glutaraldehyde and formaldehyde have previously been associated with induction of leukemia and disturbance of hematopoiesis. Taken together, the data support a possible link between the effect of MUC on gap junctions, and the toxic effects of benzene. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  18. Gap junctions: structure and function (Review).

    Science.gov (United States)

    Evans, W Howard; Martin, Patricia E M

    2002-01-01

    Gap junctions are plasma membrane spatial microdomains constructed of assemblies of channel proteins called connexins in vertebrates and innexins in invertebrates. The channels provide direct intercellular communication pathways allowing rapid exchange of ions and metabolites up to approximately 1 kD in size. Approximately 20 connexins are identified in the human or mouse genome, and orthologues are increasingly characterized in other vertebrates. Most cell types express multiple connexin isoforms, making likely the construction of a spectrum of heteromeric hemichannels and heterotypic gap junctions that could provide a structural basis for the charge and size selectivity of these intercellular channels. The precise nature of the potential signalling information traversing junctions in physiologically defined situations remains elusive, but extensive progress has been made in elucidating how connexins are assembled into gap junctions. Also, participation of gap junction hemichannels in the propagation of calcium waves via an extracellular purinergic pathway is emerging. Connexin mutations have been identified in a number of genetically inherited channel communication-opathies. These are detected in connexin 32 in Charcot Marie Tooth-X linked disease, in connexins 26 and 30 in deafness and skin diseases, and in connexins 46 and 50 in hereditary cataracts. Biochemical approaches indicate that many of the mutated connexins are mistargeted to gap junctions and/or fail to oligomerize correctly into hemichannels. Genetic ablation approaches are helping to map out a connexin code and point to specific connexins being required for cell growth and differentiation as well as underwriting basic intercellular communication.

  19. Predictive modelling of ferroelectric tunnel junctions

    Science.gov (United States)

    Velev, Julian P.; Burton, John D.; Zhuravlev, Mikhail Ye; Tsymbal, Evgeny Y.

    2016-05-01

    Ferroelectric tunnel junctions combine the phenomena of quantum-mechanical tunnelling and switchable spontaneous polarisation of a nanometre-thick ferroelectric film into novel device functionality. Switching the ferroelectric barrier polarisation direction produces a sizable change in resistance of the junction—a phenomenon known as the tunnelling electroresistance effect. From a fundamental perspective, ferroelectric tunnel junctions and their version with ferromagnetic electrodes, i.e., multiferroic tunnel junctions, are testbeds for studying the underlying mechanisms of tunnelling electroresistance as well as the interplay between electric and magnetic degrees of freedom and their effect on transport. From a practical perspective, ferroelectric tunnel junctions hold promise for disruptive device applications. In a very short time, they have traversed the path from basic model predictions to prototypes for novel non-volatile ferroelectric random access memories with non-destructive readout. This remarkable progress is to a large extent driven by a productive cycle of predictive modelling and innovative experimental effort. In this review article, we outline the development of the ferroelectric tunnel junction concept and the role of theoretical modelling in guiding experimental work. We discuss a wide range of physical phenomena that control the functional properties of ferroelectric tunnel junctions and summarise the state-of-the-art achievements in the field.

  20. Nitric oxide turnover in permeable river sediment

    DEFF Research Database (Denmark)

    Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M

    2014-01-01

    We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed...