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Sample records for tight junction assembly

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

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    Xiao Xiao Tang

    2010-08-01

    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.

  2. Tight junctions and human diseases.

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

    2003-09-01

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

  3. Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4α-induced epithelial polarization

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    Satohisa, Seiro; Chiba, Hideki; Osanai, Makoto; Ohno, Shigeo; Kojima, Takashi; Saito, Tsuyoshi; Sawada, Norimasa

    2005-01-01

    We previously reported that expression of tight-junction molecules occludin, claudin-6 and claudin-7, as well as establishment of epithelial polarity, was triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4α [H. Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada. Hepatocyte nuclear factor (HNF)-4α triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we examined in the present study behavior of tight-junction, adherens-junction and cell polarity proteins and elucidated the molecular mechanism behind HNF-4α-initiated junction formation and epithelial polarization. We herein show that not only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC) accumulate at primordial adherens junctions in undifferentiated F9 cells. In contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular localization in immature cells. Induced expression of HNF-4α led to translocation of these tight-junction and cell polarity proteins to beltlike tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3 or PATJ, were also concentrated on the apical membranes in differentiated cells. These findings indicate that HNF-4α provokes not only expression of tight-junction adhesion molecules, but also modulation of subcellular distribution of junction and cell polarity proteins, resulting in junction formation and epithelial polarization

  4. Effect of cAMP derivates on assembly and maintenance of tight junctions in human umbilical vein endothelial cells

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    Beese Michaela

    2010-09-01

    Full Text Available Abstract Background Endothelial tight and adherens junctions control a variety of physiological processes like adhesion, paracellular transport of solutes or trafficking of activated leukocytes. Formation and maintenance of endothelial junctions largely depend on the microenvironment of the specific vascular bed and on interactions of the endothelium with adjacent cell types. Consequently, primary cultures of endothelial cells often lose their specific junctional pattern and fail to establish tight monolayer in vitro. This is also true for endothelial cells isolated from the vein of human umbilical cords (HUVEC which are widely used as model for endothelial cell-related studies. Results We here compared the effect of cyclic 3'-5'-adenosine monophosphate (cAMP and its derivates on formation and stabilization of tight junctions and on alterations in paracellular permeability in HUVEC. We demonstrated by light and confocal laser microscopy that for shorter time periods the sodium salt of 8-bromoadenosine-cAMP (8-Br-cAMP/Na and for longer incubation periods 8-(4-chlorophenylthio-cAMP (pCPT-cAMP exerted the greatest effects of all compounds tested here on formation of continuous tight junction strands in HUVEC. We further demonstrated that although all compounds induced protein kinase A-dependent expression of the tight junction proteins claudin-5 and occludin only pCPT-cAMP slightly enhanced paracellular barrier functions. Moreover, we showed that pCPT-cAMP and 8-Br-cAMP/Na induced expression and membrane translocation of tricellulin. Conclusions pCPT-cAMP and, to a lesser extend, 8-Br-cAMP/Na improved formation of continuous tight junction strands and decreased paracellular permeability in primary HUVEC. We concluded that under these conditions HUVEC represent a feasible in vitro model to study formation and disassembly of endothelial tight junctions and to characterize tight junction-associated proteins

  5. Regulation of Tight Junctions in Upper Airway Epithelium

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    Takashi Kojima

    2013-01-01

    Full Text Available The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP, which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECs in vitro induces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.

  6. Human zonulin, a potential modulator of intestinal tight junctions.

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    Wang, W; Uzzau, S; Goldblum, S E; Fasano, A

    2000-12-01

    Intercellular tight junctions are dynamic structures involved in vectorial transport of water and electrolytes across the intestinal epithelium. Zonula occludens toxin derived from Vibrio cholerae interacts with a specific intestinal epithelial surface receptor, with subsequent activation of a complex intracellular cascade of events that regulate tight junction permeability. We postulated that this toxin may mimic the effect of a functionally and immunologically related endogenous modulator of intestinal tight junctions. Affinity-purified anti-zonula occludens toxin antibodies and the Ussing chamber assay were used to screen for one or more mammalian zonula occludens toxin analogues in both fetal and adult human intestine. A novel protein, zonulin, was identified that induces tight junction disassembly in non-human primate intestinal epithelia mounted in Ussing chambers. Comparison of amino acids in the active zonula occludens toxin fragment and zonulin permitted the identification of the putative receptor binding domain within the N-terminal region of the two proteins. Zonulin likely plays a pivotal role in tight junction regulation during developmental, physiological, and pathological processes, including tissue morphogenesis, movement of fluid, macromolecules and leukocytes between the intestinal lumen and the interstitium, and inflammatory/autoimmune disorders.

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

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    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.

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

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    Dokladny, Karol; Zuhl, Micah N; Moseley, Pope L

    2016-01-01

    A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or "leaky" intestinal tight junction barrier allows augmented perme...

  9. Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family

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    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.

  10. Tight junction regulates epidermal calcium ion gradient and differentiation

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    Kurasawa, Masumi; Maeda, Tetsuo; Oba, Ai; Yamamoto, Takuya; Sasaki, Hiroyuki

    2011-01-01

    Research highlights: → We disrupted epidermal tight junction barrier in reconstructed epidermis. → It altered Ca 2+ distribution and consequentially differentiation state as well. → Tight junction should affect epidermal homeostasis by maintaining Ca 2+ gradient. -- Abstract: It is well known that calcium ions (Ca 2+ ) induce keratinocyte differentiation. Ca 2+ distributes to form a vertical gradient that peaks at the stratum granulosum. It is thought that the stratum corneum (SC) forms the Ca 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 2+ gradient and epidermal differentiation in reconstructed human epidermis. When the epidermal TJ barrier was disrupted by sodium caprate treatment, Ca 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 2+ gradient.

  11. Zonulin, regulation of tight junctions, and autoimmune diseases.

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    Fasano, Alessio

    2012-07-01

    Recent studies indicate that besides digestion and absorption of nutrients and water and electrolytes homeostasis, another key function of the intestine is to regulate the trafficking of environmental antigens across the host mucosal barrier. Intestinal tight junctions (TJs) create gradients for the optimal absorption and transport of nutrients and control the balance between tolerance and immunity to nonself antigens. To meet diverse physiological challenges, intestinal epithelial TJs must be modified rapidly and in a coordinated fashion by regulatory systems that orchestrate the state of assembly of the TJ multiprotein network. While considerable knowledge exists about TJ ultrastructure, relatively little is known about their physiological and pathophysiological regulation. Our discovery of zonulin, the only known physiologic modulator of intercellular TJs described so far, has increased our understanding of the intricate mechanisms that regulate the intestinal epithelial paracellular pathway and has led us to appreciate that its upregulation in genetically susceptible individuals leads to autoimmune diseases. © 2012 New York Academy of Sciences.

  12. Expression of Tight Junction Protein Claudin-1 in Human Crescentic Glomerulonephritis

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    Ryo Koda

    2014-01-01

    Full Text Available The origin of crescent forming cells in human glomerulonephritis (GN remains unknown. Some animal studies demonstrated that parietal epithelial cells of Bowman’s capsule (PECs were the main component of proliferating cells and PEC-specific tight junction protein claudin-1 was expressed in crescentic lesions. We investigated the expression of claudin-1 in human GN. Immunohistochemistry for claudin-1 was performed on 17 kidney biopsy samples with crescent formation. Colocalization of claudin-1 with intracellular tight junction protein ZO-1 was also evaluated by immunofluorescence double staining. Claudin-1 is expressed mainly at the cell to cell contact site of proliferating cells in cellular crescentic lesions in patients with these forms of human GN. Small numbers of crescent forming cells showed extrajunctional localization of claudin-1. Colocalization of claudin-1 with ZO-1 was found at cell to cell contact sites of adjacent proliferating cells. In control samples, staining of claudin-1 was positive in PECs, but not in podocytes. Our findings suggest that claudin-1 contributes to crescent formation as a component of the tight junction protein complex that includes ZO-1. Co-localization of claudin-1 with ZO-1 implies the formation of functional tight junction complexes in crescentic lesions to prevent the interstitial damage caused by penetration of filtered molecules from Bowman’s space.

  13. Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions.

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    Raleigh, David R; Marchiando, Amanda M; Zhang, Yong; Shen, Le; Sasaki, Hiroyuki; Wang, Yingmin; Long, Manyuan; Turner, Jerrold R

    2010-04-01

    In vitro studies have demonstrated that occludin and tricellulin are important for tight junction barrier function, but in vivo data suggest that loss of these proteins can be overcome. The presence of a heretofore unknown, yet related, protein could explain these observations. Here, we report marvelD3, a novel tight junction protein that, like occludin and tricellulin, contains a conserved four-transmembrane MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain. Phylogenetic tree reconstruction; analysis of RNA and protein tissue distribution; immunofluorescent and electron microscopic examination of subcellular localization; characterization of intracellular trafficking, protein interactions, dynamic behavior, and siRNA knockdown effects; and description of remodeling after in vivo immune activation show that marvelD3, occludin, and tricellulin have distinct but overlapping functions at the tight junction. Although marvelD3 is able to partially compensate for occludin or tricellulin loss, it cannot fully restore function. We conclude that marvelD3, occludin, and tricellulin define the tight junction-associated MARVEL protein family. The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation.

  14. 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. Copyright © 2015. Published by Elsevier B.V.

  15. Strain-dependent augmentation of tight-junction barrier function in human primary epidermal keratinocytes by Lactobacillus and Bifidobacterium lysates.

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    Sultana, Reshma; McBain, Andrew J; O'Neill, Catherine A

    2013-08-01

    In this study, we investigated whether probiotic lysates can modify the tight-junction function of human primary keratinocytes. The keratinocytes were grown on cell culture inserts and treated with lysates from Bifidobacterium longum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, or Lactobacillus rhamnosus GG. With the exception of L. fermentum (which decreased cell viability), all strains markedly enhanced tight-junction barrier function within 24 h, as assessed by measurements of transepithelial electrical resistance (TEER). However, B. longum and L. rhamnosus GG were the most efficacious, producing dose-dependent increases in resistance that were maintained for 4 days. These increases in TEER correlated with elevated expression of tight-junction protein components. Neutralization of Toll-like receptor 2 abolished both the increase in TEER and expression of tight-junction proteins induced by B. longum, but not L. rhamnosus GG. These data suggest that some bacterial strains increase tight-junction function via modulation of protein components but the different pathways involved may vary depending on the bacterial strain.

  16. House Dust Mite Der p 1 Effects on Sinonasal Epithelial Tight Junctions

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    Henriquez, Oswaldo A.; Beste, Kyle Den; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma; Wise, Sarah K.

    2013-01-01

    Background Epithelial permeability is highly dependent upon the integrity of tight junctions, cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer. Methods Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen versus control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of tight junction proteins was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total. Results Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1 exposed cultured sinonasal cells versus controls. Conclusion Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis. PMID:23592402

  17. Conditioned medium from LS 174T goblet cells treated with oxyresveratrol strengthens tight junctions in Caco-2 cells.

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    Hwang, Dahyun; Jo, HyunA; Hwang, Seonwook; Kim, Jeong-Keun; Kim, In-Ho; Lim, Young-Hee

    2017-01-01

    Strengthening of intestinal tight junctions provides an effective barrier from the external environment. Goblet cell-derived trefoil factor 3 (TFF3) increases transepithelial resistance by upregulating the expression of tight junction proteins. Oxyresveratrol (OXY) is a hydroxyl-substituted stilbene found in the roots, leaves, stems, and fruit of many plants and known to have various biological activities. In this study, we investigated the strengthening effect of OXY on intestinal tight junctions through stimulation of TFF production in goblet cells. We prepared conditioned medium from LS 174T goblet cells treated with OXY (GCO-CM) and investigated the effect of GCO-CM on strengthening tight junctions of Caco-2 cells. The mRNA and protein expression levels of major tight junction components (claudin-1, occludin, and ZO-1) were measured by quantitative real-time PCR and western blotting, respectively. Transepithelial electric resistance (TEER) was measured using an ohm/V meter. Monolayer permeability was evaluated by paracellular transport of fluorescein isothiocyanate-dextran. OXY showed a strong antioxidant activity. It significantly increased the expression level of TFF3 in LS 174T goblet cells. GCO-CM prepared by treatment with 2.5, 5, and 10μg/ml OXY did not show cytotoxicity in Caco-2 cells. GCO-CM increased the mRNA and protein expression levels of claudin-1, occludin, and ZO-1. It also significantly increased tight junction integrity and reduced permeability in a dose-dependent manner. OXY stimulates the expression of TFF3 in goblet cells, which might increase the integrity of the intestinal tight junction barrier. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma

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    Anam Naz

    2017-09-01

    Full Text Available Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells.

  19. Functional Molecular Junctions Derived from Double Self-Assembled Monolayers.

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    Seo, Sohyeon; Hwang, Eunhee; Cho, Yunhee; Lee, Junghyun; Lee, Hyoyoung

    2017-09-25

    Information processing using molecular junctions is becoming more important as devices are miniaturized to the nanoscale. Herein, we report functional molecular junctions derived from double self-assembled monolayers (SAMs) intercalated between soft graphene electrodes. Newly assembled molecular junctions are fabricated by placing a molecular SAM/(top) electrode on another molecular SAM/(bottom) electrode by using a contact-assembly technique. Double SAMs can provide tunneling conjugation across the van der Waals gap between the terminals of each monolayer and exhibit new electrical functions. Robust contact-assembled molecular junctions can act as platforms for the development of equivalent contact molecular junctions between top and bottom electrodes, which can be applied independently to different kinds of molecules to enhance either the structural complexity or the assembly properties of molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation

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    Sarah E. Lutz

    2017-11-01

    Full Text Available Lymphocytes cross vascular boundaries via either disrupted tight junctions (TJs or caveolae to induce tissue inflammation. In the CNS, Th17 lymphocytes cross the blood-brain barrier (BBB before Th1 cells; yet this differential crossing is poorly understood. We have used intravital two-photon imaging of the spinal cord in wild-type and caveolae-deficient mice with fluorescently labeled endothelial tight junctions to determine how tight junction remodeling and caveolae regulate CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis (EAE model for multiple sclerosis. We find that dynamic tight junction remodeling occurs early in EAE but does not depend upon caveolar transport. Moreover, Th1, but not Th17, lymphocytes are significantly reduced in the inflamed CNS of mice lacking caveolae. Therefore, tight junction remodeling facilitates Th17 migration across the BBB, whereas caveolae promote Th1 entry into the CNS. Moreover, therapies that target both tight junction degradation and caveolar transcytosis may limit lymphocyte infiltration during inflammation.

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

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    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.

  2. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

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    Li, Zhao; Jin, Zhu-Qiu

    2012-01-01

    Highlights: ► Cardiac tight junctions are present between coronary endothelial cells. ► Ischemic preconditioning preserves the structural and functional integrity of tight junctions. ► Myocardial edema is prevented in hearts subjected to ischemic preconditioning. ► 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 enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in

  3. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

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    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

  4. Intracellular Ca2+ release mediates cationic but not anionic poly(amidoamine) (PAMAM) dendrimer-induced tight junction modulation.

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    Avaritt, Brittany R; Swaan, Peter W

    2014-09-01

    Poly(amidoamine) (PAMAM) dendrimers show great promise for utilization as oral drug delivery vehicles. These polymers are capable of traversing epithelial barriers, and have been shown to translocate by both transcellular and paracellular routes. While many proof-of-concept studies have shown that PAMAM dendrimers improve intestinal transport, little information exists on the mechanisms of paracellular transport, specifically dendrimer-induced tight junction modulation. Using anionic G3.5 and cationic G4 PAMAM dendrimers with known absorption enhancers, we investigated tight junction modulation in Caco-2 monolayers by visualization and mannitol permeability and compared dendrimer-mediated tight junction modulation to that of established permeation enhancers. [(14)C]-Mannitol permeability in the presence and absence of phospholipase C-dependent signaling pathway inhibitors was also examined and indicated that this pathway may mediate dendrimer-induced changes in permeability. Differences between G3.5 and G4 in tight junction protein staining and permeability with inhibitors were evident, suggesting divergent mechanisms were responsible for tight junction modulation. These dissimilarities are further intimated by the intracellular calcium release caused by G4 but not G3.5. Based on our results, it is apparent that the underlying mechanisms of dendrimer permeability are complex, and the complexities are likely a result of the density and sign of the surface charges of PAMAM dendrimers. The results of this study will have implications on the future use of PAMAM dendrimers for oral drug delivery.

  5. You Shall Not Pass – Tight junctions of the Blood Brain Barrier.

    Directory of Open Access Journals (Sweden)

    Hans-Christian eBauer

    2014-12-01

    Full Text Available Tissue barriers restricting the free diffusion of substances between the central nervous system and the systemic circulation are of great medical interest. Excessive leakage of blood-borne molecules into the parenchyma and the concomitant fluctuations in the microenvironment following a transient breakdown of the blood-brain barrier (BBB during ischemic/hypoxic conditions or due to an autoimmune disease are detrimental to the physiology of nervous tissue.On the other hand, the treatment of neurological disorders is often hampered as only minimal amounts of therapeutic agents are able to penetrate a functional BBB or blood cerebrospinal fluid barrier. At the basis of the BBB are, next to an elaborate transporting machinery, intimate cell-cell contacts (tight junctions creating not only a paracellular diffusion constraint but also enabling the vectorial transport across cell monolayers.More recent findings indicate that functional barriers are already established during development, protecting the fetal brain. As an understanding of the biogenesis of TJs might reveal the underlying mechanisms of barrier formation during ontogenic development numerous in vitro systems have been developed to study the assembly and disassembly of TJs. In addition, monitoring the stage-specific expression of TJ proteins during development has brought much insight into the developmental tightening of tissue barriers. Further, over the last two decades a detailed molecular map of tight junctions has emerged.TJs not only represent a cell-cell adhesion structure, but integrate various signaling pathways, thereby directly or indirectly impacting upon processes such as cell proliferation, cytoskeletal rearrangement, and transcriptional control.This review will provide a brief overview on the establishment of the BBB during embryonic development in mammals and a detailed description of the ultrastructure, biogenesis, and molecular composition of epithelial and endothelial

  6. Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2016-05-01

    Full Text Available Since nanoparticles are now widely applied as food additives, in cosmetics and other industries, especially in medical therapy and diagnosis, we ask here whether nanoparticles can cause several adverse effects to human health. In this review, based on research on nanotoxicity, we mainly discuss the negative influence of nanoparticles on blood vessels in several aspects and the potential mechanism for nanoparticles to penetrate endothelial layers of blood vessels, which are the sites of phosphorylation of tight junction proteins (claudins, occludins, and ZO (Zonula occludens proteins, oxidative stress and shear stress. We propose a connection between the presence of nanoparticles and the regulation of the tight junction, which might be the key approach for nanoparticles to penetrate endothelial layers and then have an impact on other tissues and organs.

  7. Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

    Science.gov (United States)

    Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

    2017-01-01

    Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

  8. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

    Science.gov (United States)

    Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

    2017-11-01

    Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

  9. Tight junction protein ZO-2 expression and relative function of ZO-1 and ZO-2 during mouse blastocyst formation

    International Nuclear Information System (INIS)

    Sheth, Bhavwanti; Nowak, Rachael L.; Anderson, Rebecca; Kwong, Wing Yee; Papenbrock, Thomas; Fleming, Tom P.

    2008-01-01

    Apicolateral tight junctions (TJs) between epithelial cells are multiprotein complexes regulating membrane polarity and paracellular transport and also contribute to signalling pathways affecting cell proliferation and gene expression. ZO-2 and other ZO family members form a sub-membranous scaffold for binding TJ constituents. We investigated ZO-2 contribution to TJ biogenesis and function during trophectoderm epithelium differentiation in mouse preimplantation embryos. Our data indicate that ZO-2 is expressed from maternal and embryonic genomes with maternal ZO-2 protein associated with nuclei in zygotes and particularly early cleavage stages. Embryonic ZO-2 assembled at outer blastomere apicolateral junctional sites from the late 16-cell stage. Junctional ZO-2 first co-localised with E-cadherin in a transient complex comprising adherens junction and TJ constituents before segregating to TJs after their separation from the blastocyst stage (32-cell onwards). ZO-2 siRNA microinjection into zygotes or 2-cell embryos resulted in specific knockdown of ZO-2 mRNA and protein within blastocysts. Embryos lacking ZO-2 protein at trophectoderm TJs exhibited delayed blastocoel cavity formation but underwent normal cell proliferation and outgrowth morphogenesis. Quantitative analysis of trophectoderm TJs in ZO-2-deficient embryos revealed increased assembly of ZO-1 but not occludin, indicating ZO protein redundancy as a compensatory mechanism contributing to the mild phenotype observed. In contrast, ZO-1 knockdown, or combined ZO-1 and ZO-2 knockdown, generated a more severe inhibition of blastocoel formation indicating distinct roles for ZO proteins in blastocyst morphogenesis

  10. Role of the Adherens Junction Protein Fascin in the Regulation of Tight Junction Permeability in the Mouse Mammary Gland

    National Research Council Canada - National Science Library

    Beeman, Neal

    2001-01-01

    .... Transduced cells are morphologically normal and produce milk. This gene delivery system was used to express an N-terminally truncated mutant of the tight junction protein occluding in the mammary gland and in cultured cells...

  11. Expression patterns of tight junction components induced by CD24 in an oral epithelial cell-culture model correlated to affected periodontal tissues.

    Science.gov (United States)

    Ye, P; Yu, H; Simonian, M; Hunter, N

    2014-04-01

    Previously we demonstrated uniformly strong expression of CD24 in the epithelial attachment to the tooth and in the migrating epithelium of the periodontitis lesion. Titers of serum antibodies autoreactive with CD24 peptide correlated with reduced severity of periodontal disease. Ligation of CD24 expressed by oral epithelial cells induced formation of tight junctions that limited paracellular diffusion. In this study, we aimed to reveal that the lack of uniform expression of tight junction components in the pocket epithelium of periodontitis lesions is likely to contribute to increased paracellular permeability to bacterial products. This is proposed as a potential driver of the immunopathology of periodontitis. An epithelial culture model with close correspondence for expression patterns for tight junction components in periodontal epithelia was used. Immunohistochemical staining and confocal laser scanning microscopy were used to analyse patterns of expression of gingival epithelial tight junction components. The minimally inflamed gingival attachment was characterized by uniformly strong staining at cell contacts for the tight junction components zona occludens-1, zona occludens-2, occludin, junction adhesion molecule-A, claudin-4 and claudin-15. In contrast, the pocket epithelium of the periodontal lesion showed scattered, uneven staining for these components. This pattern correlated closely with that of unstimulated oral epithelial cells in culture. Following ligation of CD24 expressed by these cells, the pattern of tight junction component expression of the minimally inflamed gingival attachment developed rapidly. There was evidence for non-uniform and focal expression only of tight junction components in the pocket epithelium. In the cell-culture model, ligation of CD24 induced a tight junction expression profile equivalent to that observed for the minimally inflamed gingival attachment. Ligation of CD24 expressed by gingival epithelial cells by lectin

  12. Structural and Functional Changes in the Tight Junctions of Asymptomatic and Serology-negative First-degree Relatives of Patients With Celiac Disease.

    Science.gov (United States)

    Mishra, Asha; Prakash, Shyam; Sreenivas, Vishnubhatla; Das, Taposh K; Ahuja, Vineet; Gupta, Siddhartha D; Makharia, Govind K

    2016-08-01

    Ten to 15% of first-degree relatives (FDRs) of celiac disease (CeD) patients develop CeD. Although intestinal barrier functions (intestinal permeability) are abnormal in the subset of serology-negative FDRs, what leads to the abnormal barrier function is not known. To study the ultrastructure and functions of tight junctions in serology-negative FDRs of CeD patients. The intestinal permeability was measured in 97 asymptomatic and anti-tissue transglutaminase antibody (anti-tTG Ab)-negative FDRs (using the lactulose mannitol ratio) and in 75 controls. The ultrastructure of tight junctions using transmission electron microscopy, and the expression of key tight junction proteins (claudin-2, claudin-3, occludin, JAM-A, and ZO-1) and zonulin using real-time PCR and immunohistochemistry were assessed in anti-tTG Ab-negative, HLA-DQ2/-DQ8-positive FDRs having normal villi and in disease controls. In addition, the serum zonulin level was measured in 172 anti-tTG Ab-negative FDRs and 198 controls. The intestinal permeability was significantly increased in FDRs than in controls. Ultrastructural abnormalities such as dilatation of the tight junction (P=0.004) and loss of the pentalaminar structure (P=0.001) were more common in FDRs than in disease controls. There was significant underexpression of tight junction proteins ZO-1 (P=0.040) and occludin (P=0.041) in FDRs. There was no significant difference in the serum zonulin level between FDRs and controls (P=0.154). Even asymptomatic, anti-tTG-Ab-negative FDRs with a normal villous histology have both ultrastructural and functional abnormalities in tight junctions. These findings are indirect evidence of the presence of tight junction abnormalities before the onset of the disease and may have therapeutic implications.

  13. Oxytocin injections in the postpartal period affect mammary tight junctions in sows

    DEFF Research Database (Denmark)

    Farmer, C.; Lessard, M.; Knight, C. H.

    2017-01-01

    The potential impacts of injecting oxytocin (OXY) to sows in the early postpartum period on the quality of mammary tight junctions, milk composition, and immune status of sows and piglets were studied. Postparturient sows received i.m. injections of either saline (control [CTL]; n = 10) or 75 IU ...

  14. Dioscorin protects tight junction protein expression in A549 human airway epithelium cells from dust mite damage.

    Science.gov (United States)

    Fu, Lin Shien; Ko, Ying Hsien; Lin, Kuo Wei; Hsu, Jeng Yuan; Chu, Jao Jia; Chi, Chin Shiang

    2009-12-01

    In addition to being an allergen, the trypsin activity of dust mite extract also destroys the tight junctions of bronchial epithelium. Such damage can lead to airway leakage, which increases airway exposure to allergens, irritants, and other pathogens. Dioscorin, the storage protein of yam, demonstrates anti-trypsin activity, as well as other potential anti-inflammatory effects. This study investigated the protective role of dioscorin for tight junctions. The immunofluorescence stains of zonula occludens (ZO-1), E-cadherin (EC) and desmoplakin (DP) proteins were compared. A cultured A549 cell line was used as a control and A549 cells were incubated with mite extract 100 mg/mL for 16 h, with or without dioscorin 100 mg/mL pretreatment for 8 h and with dioscorin 100 mg/mL alone for 16 h. Western blot was performed to detect changes in ZO-1, EC, and DP in the treated A549 cell lines. Loss of tight junction protein expression (ZO-1, EC, DP) was demonstrated after 16-h mite extract incubation. The defect could be restored if cells were pretreated with dioscorin for 8 h. In addition, dioscorin did not cause damage to the A549 cell lines in terms of cell survival or morphology. Western blot showed no change in the amount of tight junction protein under various conditions. Dioscorin is a potential protector of airway damage caused by mite extract.

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

    Science.gov (United States)

    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. Copyright © 2015 the American Physiological Society.

  16. Effects of ethanol and acetaldehyde on tight junction integrity: in vitro study in a three dimensional intestinal epithelial cell culture model.

    Directory of Open Access Journals (Sweden)

    Elhaseen Elamin

    Full Text Available BACKGROUND: Intestinal barrier dysfunction and translocation of endotoxins are involved in the pathogenesis of alcoholic liver disease. Exposure to ethanol and its metabolite, acetaldehyde at relatively high concentrations have been shown to disrupt intestinal epithelial tight junctions in the conventional two dimensional cell culture models. The present study investigated quantitatively and qualitatively the effects of ethanol at concentrations detected in the blood after moderate ethanol consumption, of its metabolite acetaldehyde and of the combination of both compounds on intestinal barrier function in a three-dimensional cell culture model. METHODS AND FINDINGS: Caco-2 cells were grown in a basement membrane matrix (Matrigel™ to induce spheroid formation and were then exposed to the compounds at the basolateral side. Morphological differentiation of the spheroids was assessed by immunocytochemistry and transmission electron microscopy. The barrier function was assessed by the flux of FITC-labeled dextran from the basal side into the spheroids' luminal compartment using confocal microscopy. Caco-2 cells grown on Matrigel assembled into fully differentiated and polarized spheroids with a central lumen, closely resembling enterocytes in vivo and provide an excellent model to study epithelial barrier functionality. Exposure to ethanol (10-40 mM or acetaldehyde (25-200 µM for 3 h, dose-dependently and additively increased the paracellular permeability and induced redistribution of ZO-1 and occludin without affecting cell viability or tight junction-encoding gene expression. Furthermore, ethanol and acetaldehyde induced lysine residue and microtubules hyperacetylation. CONCLUSIONS: These results indicate that ethanol at concentrations found in the blood after moderate drinking and acetaldehyde, alone and in combination, can increase the intestinal epithelial permeability. The data also point to the involvement of protein hyperacetylation in

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

    Science.gov (United States)

    Bardet, Claire; Ribes, Sandy; Wu, Yong; Diallo, Mamadou Tidiane; Salmon, Benjamin; Breiderhoff, Tilman; Houillier, Pascal; Müller, Dominik; Chaussain, Catherine

    2017-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Study on the pressure self-adaptive water-tight junction box in underwater vehicle

    Directory of Open Access Journals (Sweden)

    Haocai Huang

    2012-09-01

    Full Text Available Underwater vehicles play a very important role in underwater engineering. Water-tight junction box (WJB is one of the key components in underwater vehicle. This paper puts forward a pressure self-adaptive water-tight junction box (PSAWJB which improves the reliability of the WJB significantly by solving the sealing and pressure problems in conventional WJB design. By redundancy design method, the pressure self-adaptive equalizer (PSAE is designed in such a way that it consists of a piston pressure-adaptive compensator (PPAC and a titanium film pressure-adaptive compensator (TFPAC. According to hydro-mechanical simulations, the operating volume of the PSAE is more than or equal to 11.6 % of the volume of WJB liquid system. Furthermore, the required operating volume of the PSAE also increases as the gas content of oil, hydrostatic pressure or temperature difference increases. The reliability of the PSAWJB is proved by hyperbaric chamber tests.

  20. 3D-fibroblast tissues constructed by a cell-coat technology enhance tight-junction formation of human colon epithelial cells.

    Science.gov (United States)

    Matsusaki, Michiya; Hikimoto, Daichi; Nishiguchi, Akihiro; Kadowaki, Koji; Ohura, Kayoko; Imai, Teruko; Akashi, Mitsuru

    2015-02-13

    Caco-2, human colon carcinoma cell line, has been widely used as a model system for intestinal epithelial permeability because Caco-2 cells express tight-junctions, microvilli, and a number of enzymes and transporters characteristic of enterocytes. However, the functional differentiation and polarization of Caco-2 cells to express sufficient tight-junctions (a barrier) usually takes over 21 days in culture. This may be due to the cell culture environment, for example inflammation induced by plastic petri dishes. Three-dimensional (3D) sufficient cell microenvironments similar to in vivo natural conditions (proteins and cells), will promote rapid differentiation and higher functional expression of tight junctions. Herein we report for the first time an enhancement in tight-junction formation by 3D-cultures of Caco-2 cells on monolayered (1L) and eight layered (8L) normal human dermal fibroblasts (NHDF). Trans epithelial electric resistance (TEER) of Caco-2 cells was enhanced in the 3D-cultures, especially 8L-NHDF tissues, depending on culture times and only 10 days was enough to reach the same TEER value of Caco-2 monolayers after a 21 day incubation. Relative mRNA expression of tight-junction proteins of Caco-2 cells on 3D-cultures showed higher values than those in monolayer structures. Transporter gene expression patterns of Caco-2 cells on 3D-constructs were almost the same as those of Caco-2 monolayers, suggesting that there was no effect of 3D-cultures on transporter protein expression. The expression correlation between carboxylesterase 1 and 2 in 3D-cultures represented similar trends with human small intestines. The results of this study clearly represent a valuable application of 3D-Caco-2 tissues for pharmaceutical applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. 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....

  2. Cellular entry of G3.5 poly (amido amine) dendrimers by clathrin- and dynamin-dependent endocytosis promotes tight junctional opening in intestinal epithelia.

    Science.gov (United States)

    Goldberg, Deborah S; Ghandehari, Hamidreza; Swaan, Peter W

    2010-08-01

    This study investigates the mechanisms of G3.5 poly (amido amine) dendrimer cellular uptake, intracellular trafficking, transepithelial transport and tight junction modulation in Caco-2 cells in the context of oral drug delivery. Chemical inhibitors blocking clathrin-, caveolin- and dynamin-dependent endocytosis pathways were used to investigate the mechanisms of dendrimer cellular uptake and transport across Caco-2 cells using flow cytometry and confocal microscopy. Dendrimer cellular uptake was found to be dynamin-dependent and was reduced by both clathrin and caveolin endocytosis inhibitors, while transepithelial transport was only dependent on dynamin- and clathrin-mediated endocytosis. Dendrimers were quickly trafficked to the lysosomes after 15 min of incubation and showed increased endosomal accumulation at later time points, suggesting saturation of this pathway. Dendrimers were unable to open tight junctions in cell monolayers treated with dynasore, a selective inhibitor of dynamin, confirming that dendrimer internalization promotes tight junction modulation. G3.5 PAMAM dendrimers take advantage of several receptor-mediated endocytosis pathways for cellular entry in Caco-2 cells. Dendrimer internalization by dynamin-dependent mechanisms promotes tight junction opening, suggesting that dendrimers act on intracellular cytoskeletal proteins to modulate tight junctions, thus catalyzing their own transport via the paracellular route.

  3. House dust mite allergen Der p 1 effects on sinonasal epithelial tight junctions.

    Science.gov (United States)

    Henriquez, Oswaldo A; Den Beste, Kyle; Hoddeson, Elizabeth K; Parkos, Charles A; Nusrat, Asma; Wise, Sarah K

    2013-08-01

    Epithelial permeability is highly dependent upon the integrity of tight junctions, which are cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer. Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen vs control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of TJPs was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total. Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1-exposed cultured sinonasal cells vs controls. Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis. © 2013 ARS-AAOA, LLC.

  4. SENP3 grants tight junction integrity and cytoskeleton architecture in mouse Sertoli cells.

    Science.gov (United States)

    Wu, Di; Huang, Chun-Jie; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Liu, Xiao-Ming; Pandupuspitasari, Nuruliarizki Shinta; Brohi, Rahim Dad; Huo, Li-Jun

    2017-08-29

    Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation. SENP3 is predominantly expressed in the nucleus of Sertoli and spermatocyte cells in adult mouse testis, and knockdown of SENP3 compromises tight junction in Sertoli cells by destructing the permeability function with a concomitant decline in trans-epithelial electrical resistance in primary Sertoli cells, which could attribute to the conspicuous dysfunction of tight junction (TJ) proteins (e.g., ZO-1, occludin) at the cell-cell interface due to the inactivation of STAT3. Moreover, SENP3 knockdown disrupts F-actin architecture in Sertoli cells through intervening Rac1/CDC42-N-WASP-Arp2/3 signaling pathway and Profilin-1 abundance. Our study pinpoints SENP3 might be a novel determinant of multiple pathways governing BTB dynamics in testis to support germ cells development in mammals.

  5. Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues.

    Science.gov (United States)

    Zhou, Zejun; Zhang, Lumin; Ding, Miao; Luo, Zhenwu; Yuan, Shao; Bansal, Meena B; Gilkeson, Gary; Lang, Ren; Jiang, Wei

    2017-10-01

    Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Headache under simulated microgravity is related to endocrine, fluid distribution, and tight junction changes.

    Science.gov (United States)

    Feuerecker, Matthias; van Oosterhout, Willebrordus P J; Feuerecker, Benedikt; Matzel, Sandra; Schelling, Gustav; Rehm, Markus; Vein, Alla A; Choukèr, Alexander

    2016-05-01

    Head-down-tilted bed rest (HDTBR) induces headaches similar to headaches during space flights. The objective of this investigation was to study hematological, endocrinological, fluid changes and tight junctions in HDTBR-induced headaches as a proxy for space headache. The randomized crossover HDTBR design by the European Space Agency included 12 healthy, nonheadache male subjects. Before, during, and after confined HDTBR periods, epinephrine (urine), cortisol (saliva), hematological, endothelium markers, and fluid distribution parameters were measured. Headaches were assessed with a validated headache questionnaire. Compared with baseline, HDTBR in all subjects was associated with higher hematocrit, hemoglobin, and epinephrine levels, higher erythrocyte counts, and lower relative plasma volumes (all P zonulin was elevated (vs headache-free subjects in HDTBR days 1, 3, 5; P < 0.05). HDTBR induces hemoconcentration and fluid redistribution in all subjects. During headache episodes, endocrinological changes, fluid distribution, and tight junctions were more pronounced, suggesting an additional role in headache pathophysiology.

  7. Ketamine alleviates bradykinin-induced disruption of the mouse cerebrovascular endothelial cell-constructed tight junction barrier via a calcium-mediated redistribution of occludin polymerization

    International Nuclear Information System (INIS)

    Chen, Jui-Tai; Lin, Yi-Ling; Chen, Ta-Liang; Tai, Yu-Ting; Chen, Cheng-Yu; Chen, Ruei-Ming

    2016-01-01

    Highlights: • Ketamine could suppress bradykinin-induced intracellular calcium mobilization. • Ketamine induced B1R protein and mRNA expressions but did not change B2R protein levels. • Ketamine attenuated bradykinin-induced redistribution of occludin tight junctions. • Ketamine prevented bradykinin-induced breakage of the MCEC-constructed tight junction barrier. - Abstract: Following brain injury, a sequence of mechanisms leads to disruption of the blood-brain barrier (BBB) and subsequent cerebral edema, which is thought to begin with activation of bradykinin. Our previous studies showed that ketamine, a widely used intravenous anesthetic agent, can suppress bradykinin-induced cell dysfunction. This study further aimed to evaluate the protective effects of ketamine against bradykinin-induced disruption of the mouse cerebrovascular endothelial cell (MCEC)-constructed tight junction barrier and the possible mechanisms. Exposure of MCECs to bradykinin increased intracellular calcium (Ca 2+ ) concentrations in a time-dependent manner. However, pretreatment of MCECs with ketamine time- and concentration-dependently lowered the bradykinin-induced calcium influx. As to the mechanisms, although exposure of MCECs to ketamine induced bradykinin R1 receptor protein and mRNA expression, this anesthetic did not change levels of the bradykinin R2 receptor, a major receptor that responds to bradykinin stimulation. Bradykinin increased amounts of soluble occludin in MCECs, but pretreatment with ketamine alleviated this disturbance in occludin polymerization. Consequently, exposure to bradykinin decreased the transendothelial electronic resistance in the MCEC-constructed tight junction barrier. However, pretreatment with ketamine attenuated the bradykinin-induced disruption of the tight junction barrier. Taken together, this study shows that ketamine at a therapeutic concentration can protect against bradykinin-induced breakage of the BBB via suppressing calcium

  8. Splenectomy after partial hepatectomy accelerates liver regeneration in mice by promoting tight junction formation via polarity protein Par 3-aPKC.

    Science.gov (United States)

    Liu, Guoxing; Xie, Chengzhi; Fang, Yu; Qian, Ke; Liu, Qiang; Liu, Gao; Cao, Zhenyu; Du, Huihui; Fu, Jie; Xu, Xundi

    2018-01-01

    Several experimental studies have demonstrated that removal of the spleen accelerates liver regeneration after partial hepatectomy. While the mechanism of splenectomy promotes liver regeneration by the improvement of the formation of tight junction and the establishment of hepatocyte polarity is still unknown. We analyzed the cytokines, genes and proteins expression between 70% partial hepatectomy mice (PHx) and simultaneous 70% partial hepatectomy and splenectomy mice (PHs) at predetermined timed points. Compared with the PHx group mice, splenectomy accelerated hepatocyte proliferation in PHs group. The expression of Zonula occludens-1 (ZO-1) indicated that splenectomy promotes the formation of tight junction during liver regeneration. TNF-α, IL-6, HGF, TSP-1 and TGF-β1 were essential factors for the formation of tight junction and the establishment of hepatocytes polarity in liver regeneration. After splenectomy, Partitioning defective 3 homolog (Par 3) and atypical protein kinase C (aPKC) regulate hepatocyte localization and junctional structures in regeneration liver. Our data suggest that the time course expression of TNF-α, IL-6, HGF, TSP-1, and TGF-β1 and the change of platelets take part in liver regeneration. Combination with splenectomy accelerates liver regeneration by improvement of the tight junction formation which may help to establish hepatocyte polarity via Par 3-aPKC. This may provide a clue for us that splenectomy could accelerate liver regeneration after partial hepatectomy of hepatocellular carcinoma and living donor liver transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Elucidating the principles of the molecular organization of heteropolymeric tight junction strands

    OpenAIRE

    Piontek, Jörg; Fritzsche, Susanne; Cording, Jimmi; Richter, Sandra; Hartwig, Jens; Walter, Maria; Yu, Dan; Turner, Jerrold R.; Gehring, Claudia; Rahn, Hans-Peter; Wolburg, Hartwig; Blasig, Ingolf E.

    2011-01-01

    Paracellular barrier properties of tissues are mainly determined by the composition of claudin hetero-polymers. To analyze the molecular organization of tight junctions (TJ), we investigated the ability of claudins (Cld) to form homo- and heteromers. Cld1, -2, -3, -5, and -12 expressed in cerebral barriers were investigated. TJ-strands were reconstituted by claudin-transfection of HEK293-cells. cis-Interactions and/or spatial proximity were analyzed by fluorescence resonance energy transfer i...

  10. No Change in Bicarbonate Transport but Tight-Junction Formation Is Delayed by Fluoride in a Novel Ameloblast Model

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    Róbert Rácz

    2017-12-01

    Full Text Available We have recently developed a novel in vitro model using HAT-7 rat ameloblast cells to functionally study epithelial ion transport during amelogenesis. Our present aims were to identify key transporters of bicarbonate in HAT-7 cells and also to examine the effects of fluoride exposure on vectorial bicarbonate transport, cell viability, and the development of transepithelial resistance. To obtain monolayers, the HAT-7 cells were cultured on Transwell permeable filters. We monitored transepithelial resistance (TER as an indicator of tight junction formation and polarization. We evaluated intracellular pH changes by microfluorometry using the fluorescent indicator BCECF. Activities of ion transporters were tested by withdrawal of various ions from the bathing medium, by using transporter specific inhibitors, and by activation of transporters with forskolin and ATP. Cell survival was estimated by alamarBlue assay. Changes in gene expression were monitored by qPCR. We identified the activity of several ion transporters, NBCe1, NHE1, NKCC1, and AE2, which are involved in intracellular pH regulation and vectorial bicarbonate and chloride transport. Bicarbonate secretion by HAT-7 cells was not affected by acute fluoride exposure over a wide range of concentrations. However, tight-junction formation was inhibited by 1 mM fluoride, a concentration which did not substantially reduce cell viability, suggesting an effect of fluoride on paracellular permeability and tight-junction formation. Cell viability was only reduced by prolonged exposure to fluoride concentrations greater than 1 mM. In conclusion, cultured HAT-7 cells are functionally polarized and are able to transport bicarbonate ions from the basolateral to the apical fluid spaces. Exposure to 1 mM fluoride has little effect on bicarbonate secretion or cell viability but delays tight-junction formation, suggesting a novel mechanism that may contribute to dental fluorosis.

  11. Effects of topical steroids on tight junction proteins and spongiosis in esophageal epithelia of patients with eosinophilic esophagitis.

    Science.gov (United States)

    Katzka, David A; Tadi, Ravikanth; Smyrk, Thomas C; Katarya, Eesha; Sharma, Anamay; Geno, Deborah M; Camilleri, Michael; Iyer, Prasad G; Alexander, Jeffrey A; Buttar, Navtej S

    2014-11-01

    The allergic response associated with eosinophilic esophagitis (EoE) occurs when food antigens permeate tight junction-mediated epithelial dilated intercellular spaces. We assessed whether levels of tight junction proteins correlate with the dilation of intercellular spaces (spongiosis) and the effects of topical steroids on these parameters. We assessed esophageal biopsy samples from 10 patients with active EoE treated with topical fluticasone, 10 untreated patients, and 10 patients without esophageal disease (controls) for degree of spongiosis. Immunohistochemical assays were used to determine the levels of the tight junction proteins filaggrin, zonula occludens (ZO)-1, ZO-2, ZO-3, and claudin-1. Histology and immunohistochemistry results were assessed blindly, with levels of tight junction proteins and degree of spongiosis rated on scales of 0 to 3. The mean degrees of spongiosis in untreated and treated patients with EoE were 1.3 and 0.4, respectively (P = .016). Esophageal epithelia did not stain significantly for ZO-1 or ZO-2. Filaggrin was observed in a predominant cytoplasmic pattern, compared with the cytoplasmic and membranous patterns of ZO-3 and claudin-1. In biopsy specimens from patients with active EoE, the mean staining intensities for filaggrin, ZO-3, and claudin-1 were 1.6, 1.4, and 0.7, respectively. In biopsy specimens from patients treated with fluticasone, levels of filaggrin, ZO-3, and claudin-1 were 2.8 (P = .002 compared with untreated patients), 1.7 (P = .46 compared with untreated patients), and 1.3 (P = .25 compared with untreated patients), respectively. The correlation between the level of filaggrin and the degree of spongiosis was r = 0.23, and between ZO-3 staining and the degree of spongiosis was r = .016 (P = .001 for filaggrin vs ZO-3 staining). Filaggrin, ZO-3, and claudin-1 (but not ZO-1 or ZO-2) are detected in the esophageal mucosa of patients with EoE treated with steroids and individuals without esophageal disease

  12. Formation of tight junctions between neighboring podocytes is an early ultrastructural feature in experimental crescentic glomerulonephritis

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    Succar L

    2016-11-01

    Full Text Available Lena Succar,1 Ross A Boadle,2 David C Harris,1,3 Gopala K Rangan1,3 1Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, 2Electron Microscopy Laboratory, Institute of Clinical Pathology and Medical Research, Westmead Hospital, 3Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Westmead, Sydney, NSW, Australia Purpose: In crescentic glomerulonephritis (CGN, the development of cellular bridges between podocytes and parietal epithelial cells (PECs triggers glomerular crescent formation. However, the sequential changes in glomerular ultrastructure in CGN are not well defined. This study investigated the time course of glomerular ultrastructure in experimental CGN. Methods: Transmission electron microscopy (TEM was performed using kidney samples from rats with nephrotoxic serum nephritis (NSN from day 1 to day 14. Morphometric analysis was conducted on randomly selected glomeruli captured on TEM digital images. Results: On day 1 of NSN, there was widespread formation of focal contacts between the cell bodies of neighboring podocytes, and tight junctions were evident at the site of cell-to-cell contact. This was confirmed by the increased expression of the tight junction molecule, zonula occludens-1 (ZO-1, which localized to the points of podocyte cell–cell body contact. On day 2, the interpodocyte distance decreased and the glomerular basement membrane thickness increased. Foot process effacement (FPE was segmental on day 3 and diffuse by day 5, accompanied by the formation of podocyte cellular bridges with Bowman’s capsule, as confirmed by a decrease in podocyte-to-PEC distance. Fibrinoid necrosis and cellular crescents were evident in all glomeruli by days 7 and 14. In vitro, the exposure of podocytes to macrophage-conditioned media altered cellular morphology and caused an intracellular redistribution of ZO-1. Conclusion: The formation of tight

  13. Effects of adenine nucleotide and sterol depletion on tight junction structure and function in MDCK cells

    International Nuclear Information System (INIS)

    Ladino, C.A.

    1988-01-01

    The antitumor agent Hadacidin (H), N-formyl-hydroxyamino-acetic acid, reversibly inhibited the multiplication of clone 4 Madin-Darby canine kidney (MDCK) cells at a 4 mM concentration within 24-48 hours. Treated cells were arrested in the S phase of the cell cycle. Accompanying this action was a 16-fold increase in the area occupied b the cells and a refractoriness to trypsin treatment. To test whether this effect was due to an increase in tight junction integrity, electrical resistance (TER) was measured across H-treated monolayers. Addition of H at the onset of junction formation reversibly prevented the development of TER. ATP and cAMP levels were decreased by H, as well as the rate of [ 3 H]-leucine incorporation into protein. When 1 mM dibutyryl-cAMP (d.cAMP) and theophylline were added, H had no effect on cell division or protein synthesis, and TER was partially restored. The addition of 1 mM d.cAMP and 1 mM theophylline to control cultures decreased TER, indicating a biphasic effect on TER development/maintenance. In a separate study, the effect of sterol depletion on tight junctions formation/maintenance in wild-type MDCK cells was investigated

  14. DHT deficiency perturbs the integrity of the rat seminiferous epithelium by disrupting tight and adherens junctions.

    Science.gov (United States)

    Kolasa, Agnieszka; Marchlewicz, Mariola; Wenda-Różewicka, Lidia; Wiszniewska, Barbara

    2011-01-01

    In rats with a DHT deficiency induced by finasteride, morphological changes in the seminiferous epithelium were observed. The structural alterations were manifested by the premature germ cells sloughing into the lumen of seminiferous tubules. The etiology of this disorder could be connected with intercellular junctions disintegration. We showed in the immunohistochemical study the changes in expression of some proteins building tight and adherens junctions. The depression of N-cadherin, β-catenin and occludin immunoexpressions could be the reason for the release of immature germ cells from the seminiferous epithelium. However, the observed increase of the immunohistochemical reaction intensity of vinculin, one of the cadherin/catenin complex regulators, could be insufficient to maintain the proper function of adherens junctions. The hormonal imbalance appears to influence the pattern of expression of junctional proteins in the seminiferous epithelium. It could lead to untimely germ cells sloughing, and ultimately could impair fertility.

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

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    W. Cui

    2010-04-01

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

  16. The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

    Science.gov (United States)

    Hijazi, Assia; Haenlin, Marc; Waltzer, Lucas; Roch, Fernando

    2011-03-15

    Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

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

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    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.

  18. IGF-1 decreases portal vein endotoxin via regulating intestinal tight junctions and plays a role in attenuating portal hypertension of cirrhotic rats.

    Science.gov (United States)

    Zhao, Tian-Yu; Su, Li-Ping; Ma, Chun-Ye; Zhai, Xiao-Han; Duan, Zhi-Jun; Zhu, Ying; Zhao, Gang; Li, Chun-Yan; Wang, Li-Xia; Yang, Dong

    2015-07-08

    Intestinal barrier dysfunction is not only the consequence of liver cirrhosis, but also an active participant in the development of liver cirrhosis. Previous studies showed that external administration of insulin-like growth factor 1 (IGF-1) improved intestinal barrier function in liver cirrhosis. However, the mechanism of IGF-1 on intestinal barrier in liver cirrhosis is not fully elucidated. The present study aims to investigate the mechanisms of IGF-1 improving intestinal barrier function via regulating tight junctions in intestines. We used carbon tetrachloride induced liver cirrhotic rats to investigate the effect of IGF-1 on intestinal claudin-1 and occludin expressions, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, severity of liver fibrosis, portal pressures, enterocytic apoptosis and lipopolysaccharides (LPS) levels in portal vein. The changes of IGF-1 in serum during the development of rat liver cirrhosis were also evaluated. Additionally, we assessed the effect of IGF-1 on claudin-1 and occludin expressions, changes of transepithelial electrical resistance (TEER) and apoptosis in Caco-2 cells to confirm in vivo findings. Serum IGF-1 levels were decreased in the development of rat liver cirrhosis, and external administration of IGF-1 restored serum IGF-1 levels. External administration of IGF-1 reduced serum ALT and AST levels, severity of liver fibrosis, LPS levels in portal vein, enterocytic apoptosis and portal pressure in cirrhotic rats. External administration of IGF-1 increased the expressions of claudin-1 and occludin in enterocytes, and attenuated tight junction dysfunction in intestines of cirrhotic rats. LPS decreased TEER in Caco-2 cell monolayer. LPS also decreased claudin-1 and occludin expressions and increased apoptosis in Caco-2 cells. Furthermore, IGF-1 attenuated the effect of LPS on TEER, claudin-1 expression, occludin expression and apoptosis in Caco-2 cells. Tight junction dysfunction develops during the

  19. Ouabain stimulates a Na+/K+-ATPase-mediated SFK-activated signalling pathway that regulates tight junction function in the mouse blastocyst.

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    Holly Giannatselis

    Full Text Available The Na(+/K(+-ATPase plays a pivotal role during preimplantation development; it establishes a trans-epithelial ionic gradient that facilitates the formation of the fluid-filled blastocyst cavity, crucial for implantation and successful pregnancy. The Na(+/K(+-ATPase is also implicated in regulating tight junctions and cardiotonic steroid (CTS-induced signal transduction via SRC. We investigated the expression of SRC family kinase (SFK members, Src and Yes, during preimplantation development and determined whether SFK activity is required for blastocyst formation. Embryos were collected following super-ovulation of CD1 or MF1 female mice. RT-PCR was used to detect SFK mRNAs encoding Src and Yes throughout preimplantation development. SRC and YES protein were localized throughout preimplantation development. Treatment of mouse morulae with the SFK inhibitors PP2 and SU6656 for 18 hours resulted in a reversible blockade of progression to the blastocyst stage. Blastocysts treated with 10(-3 M ouabain for 2 or 10 minutes and immediately immunostained for phosphorylation at SRC tyr418 displayed reduced phosphorylation while in contrast blastocysts treated with 10(-4 M displayed increased tyr418 fluorescence. SFK inhibition increased and SFK activation reduced trophectoderm tight junction permeability in blastocysts. The results demonstrate that SFKs are expressed during preimplantation development and that SFK activity is required for blastocyst formation and is an important mediator of trophectoderm tight junction permeability.

  20. The role of apical cell-cell junctions and associated cytoskeleton in mechanotransduction.

    Science.gov (United States)

    Sluysmans, Sophie; Vasileva, Ekaterina; Spadaro, Domenica; Shah, Jimit; Rouaud, Florian; Citi, Sandra

    2017-04-01

    Tissues of multicellular organisms are characterised by several types of specialised cell-cell junctions. In vertebrate epithelia and endothelia, tight and adherens junctions (AJ) play critical roles in barrier and adhesion functions, and are connected to the actin and microtubule cytoskeletons. The interaction between junctions and the cytoskeleton is crucial for tissue development and physiology, and is involved in the molecular mechanisms governing cell shape, motility, growth and signalling. The machineries which functionally connect tight and AJ to the cytoskeleton comprise proteins which either bind directly to cytoskeletal filaments, or function as adaptors for regulators of the assembly and function of the cytoskeleton. In the last two decades, specific cytoskeleton-associated junctional molecules have been implicated in mechanotransduction, revealing the existence of multimolecular complexes that can sense mechanical cues and translate them into adaptation to tensile forces and biochemical signals. Here, we summarise the current knowledge about the machineries that link tight and AJ to actin filaments and microtubules, and the molecular basis for mechanotransduction at epithelial and endothelial AJ. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  1. The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Assia Hijazi

    Full Text Available BACKGROUND: Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. METHODOLOGY/PRINCIPAL FINDINGS: In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. CONCLUSION/SIGNIFICANCE: We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

  2. miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition.

    Science.gov (United States)

    Song, Juhyun; Yoon, So Ra; Kim, Oh Yoen

    2017-01-01

    Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor- α ), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

  3. Trends in drug delivery through tissue barriers containing tight junctions.

    Science.gov (United States)

    Tscheik, Christian; Blasig, Ingolf E; Winkler, Lars

    2013-04-01

    A limitation in the uptake of many drugs is the restricted permeation through tissue barriers. There are two general ways to cross barriers formed by cell layers: by transcytosis or by diffusion through the intercellular space. In the latter, tight junctions (TJs) play the decisive role in the regulation of the barrier permeability. Thus, transient modulation of TJs is a potent strategy to improve drug delivery. There have been extensive studies on surfactant-like absorption enhancers. One of the most effective enhancers found is sodium caprate. However, this modulates TJs in an unspecific fashion. A novel approach would be the specific modulation of TJ-associated marvel proteins and claudins, which are the main structural components of the TJs. Recent studies have identified synthetic peptidomimetics and RNA interference techniques to downregulate the expression of targeted TJ proteins. This review summarizes current progress and discusses the impact on TJs' barrier function.

  4. Dendrobium chrysotoxum Lindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

    Science.gov (United States)

    Yu, Zengyang; Gong, Chenyuan; Lu, Bin; Yang, Li; Sheng, Yuchen; Ji, Lili; Wang, Zhengtao

    2015-01-01

    Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. This study aimed to observe the alleviation of the ethanol extract of Dendrobium chrysotoxum Lindl. (DC), a traditional Chinese herbal medicine, on DR and its engaged mechanism. After DC (30 or 300 mg/kg) was orally administrated, the breakdown of blood retinal barrier (BRB) in streptozotocin- (STZ-) induced diabetic rats was attenuated by DC. Decreased retinal mRNA expression of tight junction proteins (including occludin and claudin-1) in diabetic rats was also reversed by DC. Western blot analysis and retinal immunofluorescence staining results further confirmed that DC reversed the decreased expression of occludin and claudin-1 proteins in diabetic rats. DC reduced the increased retinal mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNFα), interleukin- (IL-) 6, and IL-1β in diabetic rats. In addition, DC alleviated the increased 1 and phosphorylated p65, IκB, and IκB kinase (IKK) in diabetic rats. DC also reduced the increased serum levels of TNFα, interferon-γ (IFN-γ), IL-6, IL-1β, IL-8, IL-12, IL-2, IL-3, and IL-10 in diabetic rats. Therefore, DC can alleviate DR by inhibiting retinal inflammation and preventing the decrease of tight junction proteins, such as occludin and claudin-1. PMID:25685822

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

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    Wang Ting

    2012-08-01

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

  6. Claudin-21 Has a Paracellular Channel Role at Tight Junctions

    KAUST Repository

    Tanaka, Hiroo; Yamamoto, Yasuko; Kashihara, Hiroka; Yamazaki, Yuji; Tani, Kazutoshi; Fujiyoshi, Yoshinori; Mineta, Katsuhiko; Takeuchi, Kosei; Tamura, Atsushi; Tsukita, Sachiko

    2016-01-01

    Claudin protein family members, of which there are at least 27 in humans and mice, polymerize to form tight junctions (TJs) between epithelial cells, in a tissue- and developmental stage-specific manner. Claudins have a paracellular barrier function. In addition, certain claudins function as paracellular channels for small ions and/or solutes by forming selective pores at the TJs, although the specific claudins involved and their functional mechanisms are still in question. Here we show for the first time that claudin-21, which is more highly expressed in the embryonic than the postnatal stages, acts as a paracellular channel for small cations, such as Na+, similar to the typical channel-type claudins claudin-2 and -15. Claudin-21 also allows the paracellular passage of larger solutes. Our findings suggest that claudin-21-based TJs allow the passage of small and larger solutes by both paracellular channel-based and some additional mechanisms. © 2016, American Society for Microbiology. All Rights Reserved.

  7. Tight junction proteins contribute to barrier properties in human pleura.

    Science.gov (United States)

    Markov, Alexander G; Voronkova, Maria A; Volgin, George N; Yablonsky, Piotr K; Fromm, Michael; Amasheh, Salah

    2011-03-15

    The permeability of pleural mesothelium helps to control the volume and composition of the liquid lubricating pleural surfaces. Information on pleural barrier function in health and disease, however, is scarce. Tissue specimens of human pleura were mounted in Ussing chambers for measurement of transmesothelial resistance. Expression of tight junction (TJ) proteins was studied by Western blots and immune fluorescence confocal microscopy. Both visceral and parietal pleura showed barrier properties represented by transmesothelial resistance. Occludin, claudin-1, -3, -5, and -7, were detected in visceral pleura. In parietal pleura, the same TJ proteins were detected, except claudin-7. In tissues from patients with pleural inflammation these tightening claudins were decreased and in visceral pleura claudin-2, a paracellular channel former, became apparent. We report that barrier function in human pleura coincides with expression of claudins known to be key determinants of epithelial barrier properties. In inflamed tissue, claudin expression indicates a reduced barrier function. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Claudin-21 Has a Paracellular Channel Role at Tight Junctions

    KAUST Repository

    Tanaka, Hiroo

    2016-01-05

    Claudin protein family members, of which there are at least 27 in humans and mice, polymerize to form tight junctions (TJs) between epithelial cells, in a tissue- and developmental stage-specific manner. Claudins have a paracellular barrier function. In addition, certain claudins function as paracellular channels for small ions and/or solutes by forming selective pores at the TJs, although the specific claudins involved and their functional mechanisms are still in question. Here we show for the first time that claudin-21, which is more highly expressed in the embryonic than the postnatal stages, acts as a paracellular channel for small cations, such as Na+, similar to the typical channel-type claudins claudin-2 and -15. Claudin-21 also allows the paracellular passage of larger solutes. Our findings suggest that claudin-21-based TJs allow the passage of small and larger solutes by both paracellular channel-based and some additional mechanisms. © 2016, American Society for Microbiology. All Rights Reserved.

  9. Horizontal Assembly of Single Nanowire Diode Fabricated by p-n Junction GaN NW Grown by MOCVD

    Directory of Open Access Journals (Sweden)

    Ji-Hyeon Park

    2014-01-01

    Full Text Available Uniaxially p-n junction gallium nitride nanowires have been synthesized via metal-organic chemical vapor deposition method. Nanowires prepared on Si(111 substrates were found to grow perpendicular to the substrate, and the transmission electron microscopy studies demonstrated that the nanowires had singlecrystalline structures with a growth axis. The parallel assembly of the p-n junction nanowire was prepared on a Si substrate with a thermally grown SiO2 layer. The transport studies of horizontal gallium nitride nanowire structures assembled from p- and n-type materials show that these junctions correspond to well-defined p-n junction diodes. The p-n junction devices based on GaN nanowires suspended over the electrodes were fabricated and their electrical properties were investigated. The horizontally assembled gallium nitride nanowire diodes suspended over the electrodes exhibited a substantial increase in conductance under UV light exposure. Apart from the selectivity to different light wavelengths, high responsivity and extremely short response time have also been obtained.

  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. Multi-band tight-binding calculation of electronic transport in Fe/trans-polyacetylene/Fe tunnel junctions

    International Nuclear Information System (INIS)

    Abedi Ravan, B

    2012-01-01

    In this paper, the electronic transport characteristics of Fe/trans-polyacetylene/Fe magnetic tunnel junctions (MTJs) are investigated using multi-band tight-binding calculations within the framework of nonequilibrium Green function theory. A CH 2 radical is added to different positions on the polymer chain and its effects on the tunnelling magnetoresistance of the MTJ are studied. The ferromagnetic electrodes are assumed to be single-band and their tight-binding parameters are chosen in such a way as to simulate the ab initio density functional calculations of the band structure of bcc-Fe along its [001] crystallographic direction. In building the Hamiltonian of the trans-polyacetylene (t-PA) chain, we have assumed an s orbital on the H atoms and one s and three p(p x ,p y ,p z ) orbitals on the C atoms, and the dimerization effects are taken into account. It is found that moving the radical out of the centre of the polymer chain enhances the tunnelling magnetoresistance of the MTJ.

  12. Eye lens membrane junctional microdomains: a comparison between healthy and pathological cases

    Energy Technology Data Exchange (ETDEWEB)

    Buzhynskyy, Nikolay; Scheuring, Simon [Institut Curie, Equipe Inserm Avenir, UMR168-CNRS, 26 Rue d' Ulm, 75248 Paris Cedex 05 (France); Sens, Pierre [ESPCI, CNRS-UMR 7083, 75231 Paris (France); Behar-Cohen, Francine, E-mail: simon.scheuring@curie.fr [UMRS Inserm 872, Universite Paris Descartes, Centre de Recherches des Cordeliers, 15 rue de l' Ecole de Medecine, 75270 Paris Cedex 06 (France)

    2011-08-15

    The eye lens is a transparent tissue constituted of tightly packed fiber cells. To maintain homeostasis and transparency of the lens, the circulation of water, ions and metabolites is required. Junctional microdomains connect the lens cells and ensure both tight cell-to-cell adhesion and intercellular flow of fluids through a microcirculation system. Here, we overview membrane morphology and tissue functional requirements of the mammalian lens. Atomic force microscopy (AFM) has opened up the possibility of visualizing the junctional microdomains at unprecedented submolecular resolution, revealing the supramolecular assembly of lens-specific aquaporin-0 (AQP0) and connexins (Cx). We compare the membrane protein assembly in healthy lenses with senile and diabetes-II cataract cases and novel data of the lens membranes from a congenital cataract. In the healthy case, AQP0s form characteristic square arrays confined by connexons. In the cases of senile and diabetes-II cataract patients, connexons were degraded, leading to malformation of AQP0 arrays and breakdown of the microcirculation system. In the congenital cataract, connexons are present, indicating probable non-membranous grounds for lens opacification. Further, we discuss the energetic aspects of the membrane organization in junctional microdomains. The AFM hence becomes a biomedical nano-imaging tool for the analysis of single-membrane protein supramolecular association in healthy and pathological membranes.

  13. Eye lens membrane junctional microdomains: a comparison between healthy and pathological cases

    Science.gov (United States)

    Buzhynskyy, Nikolay; Sens, Pierre; Behar-Cohen, Francine; Scheuring, Simon

    2011-08-01

    The eye lens is a transparent tissue constituted of tightly packed fiber cells. To maintain homeostasis and transparency of the lens, the circulation of water, ions and metabolites is required. Junctional microdomains connect the lens cells and ensure both tight cell-to-cell adhesion and intercellular flow of fluids through a microcirculation system. Here, we overview membrane morphology and tissue functional requirements of the mammalian lens. Atomic force microscopy (AFM) has opened up the possibility of visualizing the junctional microdomains at unprecedented submolecular resolution, revealing the supramolecular assembly of lens-specific aquaporin-0 (AQP0) and connexins (Cx). We compare the membrane protein assembly in healthy lenses with senile and diabetes-II cataract cases and novel data of the lens membranes from a congenital cataract. In the healthy case, AQP0s form characteristic square arrays confined by connexons. In the cases of senile and diabetes-II cataract patients, connexons were degraded, leading to malformation of AQP0 arrays and breakdown of the microcirculation system. In the congenital cataract, connexons are present, indicating probable non-membranous grounds for lens opacification. Further, we discuss the energetic aspects of the membrane organization in junctional microdomains. The AFM hence becomes a biomedical nano-imaging tool for the analysis of single-membrane protein supramolecular association in healthy and pathological membranes.

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

    International Nuclear Information System (INIS)

    Imamura, Masafumi; Kojima, Takashi; Lan, Mengdong; Son, Seiichi; Murata, Masaki; Osanai, Makoto; Chiba, Hideki; Hirata, Koichi; Sawada, Norimasa

    2007-01-01

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

  15. Air pollution and children: neural and tight junction antibodies and combustion metals, the role of barrier breakdown and brain immunity in neurodegeneration.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Vojdani, Aristo; Blaurock-Busch, Eleonore; Busch, Yvette; Friedle, Albrecht; Franco-Lira, Maricela; Sarathi-Mukherjee, Partha; Martínez-Aguirre, Xavier; Park, Su-Bin; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

    2015-01-01

    Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

  16. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Svoboda, Marek; Bílková, Zuzana; Muthný, Tomáš

    2016-03-01

    The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    Directory of Open Access Journals (Sweden)

    Irna Sufiawati

    Full Text Available Herpes simplex virus (HSV types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD. Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  19. Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells

    Science.gov (United States)

    Chiu, Chun-Ching; Shi, Ya-Fang; Yang, Jiann-Jou; Hsiao, Yuan-Chao; Tzang, Bor-Show; Hsu, Tsai-Ching

    2014-01-01

    As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-α (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-α or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-α, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity. PMID:25268969

  20. Coordination of Septate Junctions Assembly and Completion of Cytokinesis in Proliferative Epithelial Tissues.

    Science.gov (United States)

    Daniel, Emeline; Daudé, Marion; Kolotuev, Irina; Charish, Kristi; Auld, Vanessa; Le Borgne, Roland

    2018-05-07

    How permeability barrier function is maintained when epithelial cells divide is largely unknown. Here, we have investigated how the bicellular septate junctions (BSJs) and tricellular septate junctions (TSJs) are remodeled throughout completion of cytokinesis in Drosophila epithelia. We report that, following cytokinetic ring constriction, the midbody assembles, matures within SJs, and is displaced basally in two phases. In a first slow phase, the neighboring cells remain connected to the dividing cells by means of SJ-containing membrane protrusions pointing to the maturing midbody. Fluorescence recovery after photobleaching (FRAP) experiments revealed that SJs within the membrane protrusions correspond to the old SJs that were present prior to cytokinesis. In contrast, new SJs are assembled below the adherens junctions and spread basally to build a new belt of SJs in a manner analogous to a conveyor belt. Loss of function of a core BSJ component, the Na+/K+-ATPase pump Nervana 2 subunit, revealed that the apical-to-basal spread of BSJs drives the basal displacement of the midbody. In contrast, loss of the TSJ protein Bark beetle indicated that remodeling of TSJs is rate limiting and slowed down midbody migration. In the second phase, once the belt of SJs is assembled, the basal displacement of the midbody is accelerated and ultimately leads to abscission. This last step is temporally uncoupled from the remodeling of SJs. We propose that cytokinesis in epithelia involves the coordinated polarized assembly and remodeling of SJs both in the dividing cell and its neighbors to ensure the maintenance of permeability barrier integrity in proliferative epithelia. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Lecithin-Bound Iodine Prevents Disruption of Tight Junctions of Retinal Pigment Epithelial Cells under Hypoxic Stress

    Directory of Open Access Journals (Sweden)

    Masahiko Sugimoto

    2016-01-01

    Full Text Available Aim. We investigated whether lecithin-bound iodine (LBI can protect the integrity of tight junctions of retinal pigment epithelial cells from hypoxia. Method. Cultured human retinal pigment epithelial (ARPE-19 cells were pretreated with LBI. To mimic hypoxic conditions, cells were incubated with CoCl2. We compared the integrity of the tight junctions (TJs of control to cells with either LBI alone, CoCl2 alone, or LBI + CoCl2. The levels of cytokines in the conditioned media were also determined. Results. Significant decrease in the zonula occludens-1 (ZO-1 intensity in the CoCl2 group compared to the control (5787.7 ± 4126.4 in CoCl2 group versus 29244.6 ± 2981.2 in control; average ± standard deviation. But the decrease was not significant in the LBI + CoCl2 (27189.0 ± 11231.1. The levels of monocyte chemoattractant protein-1 (MCP-1 and Chemokine (C-C Motif Ligand 11 (CCL-11 were significantly higher in the CoCl2 than in the control (340.8 ± 43.3 versus 279.7 ± 68.3 pg/mL for MCP-1, and 15.2 ± 12.9 versus 12.5 ± 6.1 pg/mL for CCL-11. With LBI pretreatment, the levels of both cytokines were decreased to 182.6 ± 23.8 (MCP-1 and 5.46 ± 1.9 pg/mL for CCL-11. Blockade of MCP-1 or CCL-11 also shows similar result representing TJ protection from hypoxic stress. Conclusions. LBI results in a protective action from hypoxia.

  2. 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.

  3. Downregulation of blood-brain barrier phenotype by proinflammatory cytokines involves NADPH oxidase-dependent ROS generation: consequences for interendothelial adherens and tight junctions.

    Directory of Open Access Journals (Sweden)

    Keith D Rochfort

    Full Text Available Blood-brain barrier (BBB dysfunction is an integral feature of neurological disorders and involves the action of multiple proinflammatory cytokines on the microvascular endothelial cells lining cerebral capillaries. There is still however, considerable ambiguity throughout the scientific literature regarding the mechanistic role(s of cytokines in this context, thereby warranting a comprehensive in vitro investigation into how different cytokines may cause dysregulation of adherens and tight junctions leading to BBB permeabilization.The present study employs human brain microvascular endothelial cells (HBMvECs to compare/contrast the effects of TNF-α and IL-6 on BBB characteristics ranging from the expression of interendothelial junction proteins (VE-cadherin, occludin and claudin-5 to endothelial monolayer permeability. The contribution of cytokine-induced NADPH oxidase activation to altered barrier phenotype was also investigated.In response to treatment with either TNF-α or IL-6 (0-100 ng/ml, 0-24 hrs, our studies consistently demonstrated significant dose- and time-dependent decreases in the expression of all interendothelial junction proteins examined, in parallel with dose- and time-dependent increases in ROS generation and HBMvEC permeability. Increased expression and co-association of gp91 and p47, pivotal NADPH oxidase subunits, was also observed in response to either cytokine. Finally, cytokine-dependent effects on junctional protein expression, ROS generation and endothelial permeability could all be attenuated to a comparable extent using a range of antioxidant strategies, which included ROS depleting agents (superoxide dismutase, catalase, N-acetylcysteine, apocynin and targeted NADPH oxidase blockade (gp91 and p47 siRNA, NSC23766.A timely and wide-ranging investigation comparing the permeabilizing actions of TNF-α and IL-6 in HBMvECs is presented, in which we demonstrate how either cytokine can similarly downregulate the

  4. Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain.

    Science.gov (United States)

    Di Pierro, M; Lu, R; Uzzau, S; Wang, W; Margaretten, K; Pazzani, C; Maimone, F; Fasano, A

    2001-06-01

    Zonula occludens toxin (Zot) is an enterotoxin elaborated by Vibrio cholerae that increases intestinal permeability by interacting with a mammalian cell receptor with subsequent activation of intracellular signaling leading to the disassembly of the intercellular tight junctions. Zot localizes in the bacterial outer membrane of V. cholerae with subsequent cleavage and secretion of a carboxyl-terminal fragment in the host intestinal milieu. To identify the Zot domain(s) directly involved in the protein permeating effect, several zot gene deletion mutants were constructed and tested for their biological activity in the Ussing chamber assay and their ability to bind to the target receptor on intestinal epithelial cell cultures. The Zot biologically active domain was localized toward the carboxyl terminus of the protein and coincided with the predicted cleavage product generated by V. cholerae. This domain shared a putative receptor-binding motif with zonulin, the Zot mammalian analogue involved in tight junction modulation. Amino acid comparison between the Zot active fragment and zonulin, combined with site-directed mutagenesis experiments, confirmed the presence of an octapeptide receptor-binding domain toward the amino terminus of the processed Zot.

  5. 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.

  6. The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon.

    Science.gov (United States)

    Cohen, L; Sekler, I; Hershfinkel, M

    2014-06-26

    The intestinal epithelium is a renewable tissue that requires precise balance between proliferation and differentiation, an essential process for the formation of a tightly sealed barrier. Zinc deficiency impairs the integrity of the intestinal epithelial barrier and is associated with ulcerative and diarrheal pathologies, but the mechanisms underlying the role of Zn(2+) are not well understood. Here, we determined a role of the colonocytic Zn(2+) sensing receptor, ZnR/GPR39, in mediating Zn(2+)-dependent signaling and regulating the proliferation and differentiation of colonocytes. Silencing of ZnR/GPR39 expression attenuated Zn(2+)-dependent activation of ERK1/2 and AKT as well as downstream activation of mTOR/p70S6K, pathways that are linked with proliferation. Consistently, ZnR/GPR39 silencing inhibited HT29 and Caco-2 colonocyte proliferation, while not inducing caspase-3 cleavage. Remarkably, in differentiating HT29 colonocytes, silencing of ZnR/GPR39 expression inhibited alkaline phosphatase activity, a marker of differentiation. Furthermore, Caco-2 colonocytes showed elevated expression of ZnR/GPR39 during differentiation, whereas silencing of ZnR/GPR39 decreased monolayer transepithelial electrical resistance, suggesting compromised barrier formation. Indeed, silencing of ZnR/GPR39 or chelation of Zn(2+) by the cell impermeable chelator CaEDTA was followed by impaired expression of the junctional proteins, that is, occludin, zonula-1 (ZO-1) and E-cadherin. Importantly, colon tissues of GPR39 knockout mice also showed a decrease in expression levels of ZO-1 and occludin compared with wildtype mice. Altogether, our results indicate that ZnR/GPR39 has a dual role in promoting proliferation of colonocytes and in controlling their differentiation. The latter is followed by ZnR/GPR39-dependent expression of tight junctional proteins, thereby leading to formation of a sealed intestinal epithelial barrier. Thus, ZnR/GPR39 may be a therapeutic target for promoting

  7. Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System.

    Science.gov (United States)

    Lochhead, Jeffrey J; Ronaldson, Patrick T; Davis, Thomas P

    2017-07-01

    A functional blood-brain barrier (BBB) is necessary to maintain central nervous system (CNS) homeostasis. Many diseases affecting the CNS, however, alter the functional integrity of the BBB. It has been shown that various diseases and physiological stressors can impact the BBB's ability to selectively restrict passage of substances from the blood to the brain. Modifications of the BBB's permeability properties can potentially contribute to the pathophysiology of CNS diseases and result in altered brain delivery of therapeutic agents. Hypoxia and/or inflammation are central components of a number of diseases affecting the CNS. A number of studies indicate hypoxia or inflammatory pain increase BBB paracellular permeability, induce changes in the expression and/or localization of tight junction proteins, and affect CNS drug uptake. In this review, we look at what is currently known with regard to BBB disruption following a hypoxic or inflammatory insult in vivo. Potential mechanisms involved in altering tight junction components at the BBB are also discussed. A more detailed understanding of the mediators involved in changing BBB functional integrity in response to hypoxia or inflammatory pain could potentially lead to new treatments for CNS diseases with hypoxic or inflammatory components. Additionally, greater insight into the mechanisms involved in TJ rearrangement at the BBB may lead to novel strategies to pharmacologically increase delivery of drugs to the CNS.

  8. Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells.

    Science.gov (United States)

    Kojima, Takashi; Takasawa, Akira; Kyuno, Daisuke; Ito, Tatsuya; Yamaguchi, Hiroshi; Hirata, Koichi; Tsujiwaki, Mitsuhiro; Murata, Masaki; Tanaka, Satoshi; Sawada, Norimasa

    2011-10-01

    The novel tight junction protein marvelD3 contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain like occludin and tricellulin. However, little is yet known about the detailed role and regulation of marvelD3 in normal epithelial cells and cancer cells, including pancreatic cancer. In the present study, we investigated marvelD3 expression in well and poorly differentiated human pancreatic cancer cell lines and normal pancreatic duct epithelial cells in which the hTERT gene was introduced into human pancreatic duct epithelial cells in primary culture, and the changes of marvelD3 during Snail-induced epithelial-mesenchymal transition (EMT) under hypoxia, TGF-β treatment and knockdown of FOXA2 in well differentiated pancreatic cancer HPAC cells. MarvelD3 was transcriptionally downregulated in poorly differentiated pancreatic cancer cells and during Snail-induced EMT of pancreatic cancer cells in which Snail was highly expressed and the fence function downregulated, whereas it was maintained in well differentiated human pancreatic cancer cells and normal pancreatic duct epithelial cells. Depletion of marvelD3 by siRNAs in HPAC cells resulted in downregulation of barrier functions indicated as a decrease in transepithelial electric resistance and an increase of permeability to fluorescent dextran tracers, whereas it did not affect fence function of tight junctions. In conclusion, marvelD3 is transcriptionally downregulated in Snail-induced EMT during the progression for the pancreatic cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide

    Directory of Open Access Journals (Sweden)

    Hisako Ibaraki

    2016-09-01

    Full Text Available As a new category of therapeutics for skin diseases including atopic dermatitis (AD, nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery.

  10. Exploring the Tilt-Angle Dependence of electron tunneling across Molecular junction of Self-Assembled Alkanethiols

    DEFF Research Database (Denmark)

    Frederiksen, Thomas; Munuera, C.; Ocal, C.

    2009-01-01

    Electronic transport mechanisms in molecular junctions are investigated by a combination of first-principles calculations and current−voltage measurements of several well-characterized structures. We study self-assembled layers of alkanethiols grown on Au(111) and form tunnel junctions...... for the longer molecular chains. Our calculations confirm the observed trends and explain them as a result of two mechanisms, namely, a previously proposed intermolecular tunneling enhancement as well as a hitherto overlooked tilt-dependent molecular gate effect....

  11. 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.

  12. Time-dependent effects of low-temperature atmospheric-pressure argon plasma on epithelial cell attachment, viability and tight junction formation in vitro

    International Nuclear Information System (INIS)

    Hoentsch, Maxi; Barbara Nebe, J; Von Woedtke, Thomas; Weltmann, Klaus-Dieter

    2012-01-01

    The application of physical plasma to living tissues is expected to promote wound healing by plasma disinfection and stimulation of tissue regeneration. However, the effects of plasma on healthy cells must be studied and understood. In our experiments we used an argon plasma jet (kINPen®09) to gain insights into time-dependent plasma effects on cell attachment, viability and tight junction formation in vitro. Murine epithelial cells mHepR1 were suspended in complete cell culture medium and were irradiated with argon plasma (direct approach) for 30, 60 and 120 s. Suspecting that physical plasma may exert its effect via the medium, cell culture medium alone was first treated with argon plasma (indirect approach) and immediately afterwards, cells were added and also cultured for 24 h. Cell morphology and vitality were verified using light microscopy and an enzyme-linked immunosorbent assay. Already after 30 s of treatment the mHepR1 cells lost their capability to adhere and the cell vitality decreased with increasing treatment time. Interestingly, the same inhibitory effect was observed in the indirect approach. Furthermore, the argon plasma-treated culture medium-induced large openings of the cell's tight junctions, were verified by the zonula occludens protein ZO-1, which we observed for the first time in confluently grown epithelial cells. (paper)

  13. Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

    Science.gov (United States)

    Suzuki, Ryo; Katsuno, Tatsuya; Kishimoto, Yo; Nakamura, Ryosuke; Mizuta, Masanobu; Suehiro, Atsushi; Yamashita, Masaru; Nakamura, Tatsuo; Tateya, Ichiro; Omori, Koichi

    2018-04-01

    The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Animal experiments with controls. Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. NA. Laryngoscope, 128:E150-E156, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  14. 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.

  15. TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture Model of the Corneal Epithelium.

    Science.gov (United States)

    Martínez-Rendón, Jacqueline; Sánchez-Guzmán, Erika; Rueda, Angélica; González, James; Gulias-Cañizo, Rosario; Aquino-Jarquín, Guillermo; Castro-Muñozledo, Federico; García-Villegas, Refugio

    2017-07-01

    TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4 during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells. TRPV4 is a late differentiation feature that is concentrated in the apical membrane of the outmost cell layer of the stratified epithelia. Ca 2+ imaging experiments showed that TRPV4 activation with GSK1016790A produced an influx of calcium that was blunted by the specific TRPV4 blocker RN-1734. We analyzed the involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the development of transepithelial electrical resistance (TER) as an indicator of the tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to establish the TJ. In differentiated epithelia, activation of TRPV4 increases the TER and the accumulation of claudin-4 in cell-cell contacts. Epidermal Growth Factor (EGF) up-regulates the TER of corneal epithelial cultures, and we show here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2, an EGF-activated channel that forms heteromeric complexes with TRPV4, is also concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4-TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the correct establishment of TJ in corneal epithelia and as well as the regulation of both the barrier function of TJ and its ability to respond to EGF. J. Cell. Physiol. 232: 1794-1807, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

    Science.gov (United States)

    Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

    2017-12-01

    Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Effect of Chum Salmon Egg Lectin on Tight Junctions in Caco-2 Cell Monolayers

    Directory of Open Access Journals (Sweden)

    Ryo Nemoto

    2015-05-01

    Full Text Available The effect of a chum salmon egg lectin (CSL3 on tight junction (TJ of Caco-2 cell monolayers was investigated. The lectin opened TJ as indicated by the decrease of the transepithelial electrical resistance (TER value and the increase of the permeation of lucifer yellow, which is transported via the TJ-mediated paracellular pathway. The effects of CSL3 were inhibited by the addition of 10 mM L-rhamnose or D-galactose which were specific sugars for CSL3. The lectin increased the intracellular Ca2+ of Caco-2 cell monolayers, that could be inhibited by the addition of L-rhamnose. The fluorescence immunostaining of β-actin in Caco-2 cell monolayers revealed that the cytoskeleton was changed by the CSL3 treatment, suggesting that CSL3 depolymerized β-actin to cause reversible TJ structural and functional disruption. Although Japanese jack bean lectin and wheat germ lectin showed similar effects in the decrease of the TER values and the increase of the intracellular Ca2+, they could not be inhibited by the same concentrations of simple sugars, such as D-glucose and N-acetyl-D-glucosamine.

  18. Disruption of Intracellular ATP Generation and Tight Junction Protein Expression during the Course of Brain Edema Induced by Subacute Poisoning of 1,2-Dichloroethane

    Directory of Open Access Journals (Sweden)

    Gaoyang Wang

    2018-01-01

    Full Text Available The aim of this study was to explore changes in intracellular ATP generation and tight junction protein expression during the course of brain edema induced by subacute poisoning of 1,2-dichloroethane (1,2-DCE. Mice were exposed to 1.2 g/m3 1,2-DCE for 3.5 h per day for 1, 2, or 3 days, namely group A, B, and C. Na+-K+-ATPase and Ca2+-ATPase activity, ATP and lactic acid content, intracellular free Ca2+ concentration and ZO-1 and occludin expression in the brain were measured. Results of present study disclosed that Ca2+-ATPase activities in group B and C, and Na+/K+-ATPase activity in group C decreased, whereas intracellular free Ca2+ concentrations in group B and C increased significantly compared with control. Moreover, ATP content decreased, whereas lactic acid content increased significantly in group C compared with control. On the other hand, expressions of ZO-1 and occludin at both the protein and gene levels in group B and C decreased significantly compared with control. In conclusion, findings from this study suggest that calcium overload and depressed expression of tight junction associated proteins, such as ZO-1 and occludin might play an important role in the early phase of brain edema formation induced by subacute poisoning of 1,2-DCE.

  19. Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease.

    Science.gov (United States)

    Gweon, Tae-Geun; Park, Jong-Hyung; Kim, Byung-Wook; Choi, Yang Kyu; Kim, Joon Sung; Park, Sung Min; Kim, Chang Whan; Kim, Hyung-Gil; Chung, Jun-Won

    2018-01-15

    The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.

  20. Claudin-11 and occludin are major contributors to Sertoli cell tight junction function, in vitro

    Directory of Open Access Journals (Sweden)

    Mark J McCabe

    2016-01-01

    Full Text Available The Sertoli cell tight junction (TJ is the key component of the blood-testis barrier, where it sequesters developing germ cells undergoing spermatogenesis within the seminiferous tubules. Hormonally regulated claudin-11 is a critical transmembrane protein involved in barrier function and its murine knockout results in infertility. We aimed to assess quantitatively the significance of the contribution of claudin-11 to TJ function, in vitro, using siRNA-mediated gene silencing. We also conducted an analysis of the contribution of occludin, another intrinsic transmembrane protein of the TJ. Silencing of claudin-11 and/or occludin was conducted using siRNA in an immature rat Sertoli cell culture model. Transepithelial electrical resistance was used to assess quantitatively TJ function throughout the culture. Two days after siRNA treatment, cells were fixed for immunocytochemical localization of junction proteins or lyzed for RT-PCR assessment of mRNA expression. Silencing of claudin-11, occludin, or both resulted in significant decreases in TJ function of 55% (P < 0.01, 51% (P < 0.01, and 62% (P < 0.01, respectively. Data were concomitant with significant decreases in mRNA expression and marked reductions in the localization of targeted proteins to the Sertoli cell TJ. We provide quantitative evidence that claudin-11 contributes significantly (P < 0.01 to Sertoli cell TJ function in vitro. Interestingly, occludin, which is hormonally regulated but not implicated in infertility until late adulthood, is also a significant (P < 0.01 contributor to barrier function. Our data are consistent with in vivo studies that clearly demonstrate a role for these proteins in maintaining normal TJ barrier structure and function.

  1. Supramolecular tunneling junctions

    NARCIS (Netherlands)

    Wimbush, K.S.

    2012-01-01

    In this study a variety of supramolecular tunneling junctions were created. The basis of these junctions was a self-assembled monolayer of heptathioether functionalized ß-cyclodextrin (ßCD) formed on an ultra-flat Au surface, i.e., the bottom electrode. This gave a well-defined hexagonally packed

  2. Visualization and quantitative analysis of reconstituted tight junctions using localization microscopy.

    Directory of Open Access Journals (Sweden)

    Rainer Kaufmann

    Full Text Available Tight Junctions (TJ regulate paracellular permeability of tissue barriers. Claudins (Cld form the backbone of TJ-strands. Pore-forming claudins determine the permeability for ions, whereas that for solutes and macromolecules is assumed to be crucially restricted by the strand morphology (i.e., density, branching and continuity. To investigate determinants of the morphology of TJ-strands we established a novel approach using localization microscopy.TJ-strands were reconstituted by stable transfection of HEK293 cells with the barrier-forming Cld3 or Cld5. Strands were investigated at cell-cell contacts by Spectral Position Determination Microscopy (SPDM, a method of localization microscopy using standard fluorophores. Extended TJ-networks of Cld3-YFP and Cld5-YFP were observed. For each network, 200,000 to 1,100,000 individual molecules were detected with a mean localization accuracy of ∼20 nm, yielding a mean structural resolution of ∼50 nm. Compared to conventional fluorescence microscopy, this strongly improved the visualization of strand networks and enabled quantitative morphometric analysis. Two populations of elliptic meshes (mean diameter <100 nm and 300-600 nm, respectively were revealed. For Cld5 the two populations were more separated than for Cld3. Discrimination of non-polymeric molecules and molecules within polymeric strands was achieved. For both subtypes of claudins the mean density of detected molecules was similar and estimated to be ∼24 times higher within the strands than outside the strands.The morphometry and single molecule information provided advances the mechanistic analysis of paracellular barriers. Applying this novel method to different TJ-proteins is expected to significantly improve the understanding of TJ on the molecular level.

  3. A high-grain diet alters the omasal epithelial structure and expression of tight junction proteins in a goat model.

    Science.gov (United States)

    Liu, Jun-Hua; Xu, Ting-Ting; Zhu, Wei-Yun; Mao, Sheng-Yong

    2014-07-01

    The omasal epithelial barrier plays important roles in maintaining nutrient absorption and immune homeostasis in ruminants. However, little information is currently available about the changes in omasal epithelial barrier function at the structural and molecular levels during feeding of a high-grain (HG) diet. Ten male goats were randomly assigned to two groups, fed either a hay diet (0% grain; n = 5) or HG diet (65% grain; n = 5). Changes in omasal epithelial structure and expression of tight junction (TJ) proteins were determined via electron microscopy and Western blot analysis. After 7 weeks on each diet, omasal contents in the HG group showed significantly lower pH (P diet showed profound alterations in omasal epithelial structure and TJ proteins, corresponding to depression of thickness of total epithelia, stratum granulosum, and the sum of the stratum spinosum and stratum basale, marked epithelial cellular damage, erosion of intercellular junctions and down-regulation in expression of the TJ proteins, claudin-4 and occludin. The study demonstrates that feeding a HG diet is associated with omasal epithelial cellular damage and changes in expression of TJ proteins. These research findings provide an insight into the possible significance of diet on the omasal epithelial barrier in ruminants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Intraluminal polyethylene glycol stabilizes tight junctions and improves intestinal preservation in the rat.

    Science.gov (United States)

    Oltean, M; Joshi, M; Björkman, E; Oltean, S; Casselbrant, A; Herlenius, G; Olausson, M

    2012-08-01

    Rapidly progressing mucosal breakdown limits the intestinal preservation time below 10 h. Recent studies indicate that intraluminal solutions containing polyethylene glycol (PEG) alleviate preservation injury of intestines stored in UW-Viaspan. We investigated whether a low-sodium PEG solution is beneficial for intestines stored in histidine-tryptophane-ketoglutarate (HTK) preservation solution. Rat intestines used as control tissue (group 1) were perfused with HTK, groups 2 and 3 received either a customized PEG-3350 (group 2) or an electrolyte solution (group 3) intraluminally before cold storage. Tissue injury, brush-border maltase activity, zonula occludens-1 (ZO-1) and claudin-3 expression in the tight junctions (TJ) were analyzed after 8, 14 and 20 h. We measured epithelial resistance and permeability (Ussing chamber) after 8 and 14 h. Group 2 had superior morphology while maltase activity was similar in all groups. TJ proteins rapidly decreased and decolocalized in groups 1 3; these negative events were delayed in group 2, where colocalization persisted for about 14 h. Intestines in group 2 had higher epithelial resistance and lower permeability than the other groups. These results suggest that a customized PEG solution intraluminally reduces the intestinal preservation injury by improving several major epithelial characteristics without negatively affecting the brush-border enzymes or promoting edema. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. A tight-binding model of the transmission probability through a molecular junction; a single molecule vs. a molecular layer

    International Nuclear Information System (INIS)

    Landau, A.; Nitzan, A.

    2006-01-01

    Full Text: Molecular electronics, one of the major fields of the current effort in nano-science, may be de ed as the study of electronic behaviors, devices and applications that depend on the properties of matter at the molecular scale. If the miniaturization trend of microelectronic devices is to continue, elements such as transistors and contacts will soon shrink to single molecules. The promise of these new technological breakthroughs has been major driving force in this ld. Moreover, the consideration of molecular systems as electronic devices has raised new fundamental questions. In particular, while traditional quantum chemistry deals with electronically closed systems, we now face problems involving molecular systems that are open to their electronic environment, moreover, function in far from equilibrium situations. A generic molecular junction is made of two electrodes connected by a molecular spacer that takes the form of a molecular chain of varying length or a molecular layer of varying thickness. We use a simple nearest-neighbors tight-biding model with the non-equilibrium Green's function (NEGF) method to investigate and compare between a self-assembled monolayer (SAM), finite molecular layer (FML), and single molecule (SM) chemisorption to a surface of a metal substrate. In addition, we examine the difference in the transmission probability through a SAM, FML and SM sandwiched between two metallic electrodes. Dramatic differences are observed between the SM, FML and SAM density of electronic states and transmission functions. In addition, we analyze the effects of changing different physical parameters such as molecule-substrate interaction, molecule-molecule interactions, etc; interesting effects that pertain to the conduction properties of single molecules and molecular layers are observed. Intriguing results are attained when we investigate the commensurability of the SAM with the metallic surface

  6. The tight junction protein Z O-2 has several functional nuclear export signals

    International Nuclear Information System (INIS)

    Gonzalez-Mariscal, Lorenza; Ponce, Arturo; Alarcon, Lourdes; Jaramillo, Blanca Estela

    2006-01-01

    The tight junction (TJ) protein ZO-2 changes its subcellular distribution according to the state of confluency of the culture. Thus in confluent monolayers, it localizes at the TJ region whereas in sparse cultures it concentrates at the nucleus. The canine sequence of ZO-2 displays four putative nuclear export signals (NES), two at the second PDZ domain (NES-0 and NES-1) and the rest at the GK region (NES-2 and NES-3). The functionality of NES-0 and NES-3 was unknown, hence here we have explored it with a nuclear export assay, injecting into the nucleus of MDCK cells peptides corresponding to the ZO-2 NES sequences chemically coupled to ovalbumin. We show that both NES-0 and NES-3 are functional and sensitive to leptomycin B. We also demonstrate that NES-1, previously characterized as a non functional NES, is rendered capable of nuclear export upon the acquisition of a negative charge at its Ser369 residue. Experiments performed injecting at the nucleus WT and mutated ZO-2-GST fusion proteins revealed the need of both NES-0 and NES-1, and NES-2 and NES-3 for attaining an efficient nuclear exit of the respective amino and middle segments of ZO-2. Moreover, the transfection of MDCK cells with full-length ZO-2 revealed that the mutation of any of the NES present in the molecule was sufficient to induce nuclear accumulation of the protein

  7. Protecting intestinal epithelial integrity by galacto-oligosaccharides: Keeping it tight

    NARCIS (Netherlands)

    Akbari, P.

    2016-01-01

    The intestinal barrier serves as a first line of host defense against potentially harmful stressors from the environment ingested with food, and is primarily formed by epithelial cells connected by tight junctions. Oligosaccharides have been identified as components in milk, particularly in

  8. 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.

  9. Molecular anatomy of interendothelial junctions in human blood-brain barrier microvessels.

    Directory of Open Access Journals (Sweden)

    Andrzej W Vorbrodt

    2004-07-01

    Full Text Available Immunogold cytochemical procedure was used to study the localization at the ultrastructural level of interendothelial junction-associated protein molecules in the human brain blood microvessels, representing the anatomic site of the blood-brain barrier (BBB. Ultrathin sections of Lowicryl K4M-embedded biopsy specimens of human cerebral cortex obtained during surgical procedures were exposed to specific antibodies, followed by colloidal gold-labeled secondary antibodies. All tight junction-specific integral membrane (transmembrane proteins--occludin, junctional adhesion molecule (JAM-1, and claudin-5--as well as peripheral zonula occludens protein (ZO-1 were highly expressed. Immunoreactivity of the adherens junction-specific transmembrane protein VE-cadherin was of almost similar intensity. Immunolabeling of the adherens junction-associated peripheral proteins--alpha-catenin, beta-catenin, and p120 catenin--although positive, was evidently less intense. The expression of gamma-catenin (plakoglobin was considered questionable because solitary immunosignals (gold particles appeared in only a few microvascular profiles. Double labeling of some sections made possible to observe strict colocalization of the junctional molecules, such as occludin and ZO-1 or JAM-1 and VE-cadherin, in the interendothelial junctions. We found that in human brain microvessels, the interendothelial junctional complexes contain molecular components specific for both tight and adherens junctions. It is assumed that the data obtained can help us find the immunodetectable junctional molecules that can serve as sensitive markers of normal or abnormal function of the BBB.

  10. Control rod effects on reaction rate distributions in tight pitched PuO2-UO2 fuel assembly

    International Nuclear Information System (INIS)

    Gil, Choong-Sup; Okumura, Keisuke; Ishiguro, Yukio

    1991-11-01

    Investigations were made for the heterogeneity effects caused by insertion or withdrawal of a B 4 C control rod on fine structure of reaction rates distributions in a tight pitched PuO 2 -UO 2 fuel assembly. Analysis was carried out by using the VIM and SRAC codes with the libraries based on JENDL-2 for the hexagonal fuel assembly basically corresponding to the PROTEUS-LWHCR experimental core. The reaction rates are affected more remarkably by the withdrawal of the control rod rather than its insertion. The changes of the reaction rates were decomposed into three terms of spectrum shifts, the changes of effective cross sections with fine groups, and their higher order components. From the analysis, it is concluded that most changes of reaction rates are caused by spectral shifts. The SRAC code with fine group constants can predict the distribution of reaction rates and their ratios with the accuracy of about 5 % except for the values related to Pu-242 capture rate, as compared with the VIM results. To increase the accuracy, it is necessary to generate the effective cross sections of the fuel near control rods with consideration of the heterogeneities in the fuel assembly. (author)

  11. Pronounced Environmental Effects on Injection Currents in EGaIn Tunneling Junctions Comprising Self-Assembled Monolayers.

    Science.gov (United States)

    Carlotti, Marco; Degen, Maarten; Zhang, Yanxi; Chiechi, Ryan C

    2016-09-15

    Large-area tunneling junctions using eutectic Ga-In (EGaIn) as a top contact have proven to be a robust, reproducible, and technologically relevant platform for molecular electronics. Thus far, the majority of studies have focused on saturated molecules with backbones consisting mainly of alkanes in which the frontier orbitals are either highly localized or energetically inaccessible. We show that self-assembled monolayers of wire-like oligophenyleneethynylenes (OPEs), which are fully conjugated, only exhibit length-dependent tunneling behavior in a low-O 2 environment. We attribute this unexpected behavior to the sensitivity of injection current on environment. We conclude that, contrary to previous reports, the self-limiting layer of Ga 2 O 3 strongly influences transport properties and that the effect is related to the wetting behavior of the electrode. This result sheds light on the nature of the electrode-molecule interface and suggests that adhesive forces play a significant role in tunneling charge-transport in large-area molecular junctions.

  12. Cell-cell interactions of isolated and cultured oligodendrocytes: formation of linear occluding junctions and expression of peculiar intramembrane particles.

    Science.gov (United States)

    Massa, P T; Szuchet, S; Mugnaini, E

    1984-12-01

    Oligodendrocytes were isolated from lamb brain. Freshly isolated cells and cultured cells, either 1- to 4-day-old unattached or 1- to 5-week-old attached, were examined by thin section and freeze-fracture electron microscopy. Freeze-fracture of freshly isolated oligodendrocytes showed globular and elongated intramembrane particles similar to those previously described in oligodendrocytes in situ. Enrichment of these particles was seen at sites of inter-oligodendrocyte contact. Numerous gap junctions and scattered linear tight junctional arrays were apparent. Gap junctions were connected to blebs of astrocytic plasma membrane sheared off during isolation, whereas tight junctions were facing extracellular space or blebs of oligodendrocytic plasma membrane. Thin sections of cultured, unattached oligodendrocytes showed rounded cell bodies touching one another at points without forming specialized cell junctions. Cells plated on polylysine-coated aclar dishes attached, emanated numerous, pleomorphic processes, and expressed galactocerebroside and myelin basic protein, characteristic markers for oligodendrocytes. Thin sections showed typical oligodendrocyte ultrastructure but also intermediate filaments not present in unattached cultures. Freeze-fracture showed intramembrane particles similar to but more numerous, and with a different fracture face repartition, than those seen in oligodendrocytes, freshly isolated or in situ. Gap junctions were small and rare. Apposed oligodendrocyte plasma membrane formed linear tight junctions which became more numerous with time in culture. Thus, cultured oligodendrocytes isolated from ovine brains develop and maintain features characteristic of mature oligodendrocytes in situ and can be used to explore formation and maintenance of tight junctions and possibly other classes of cell-cell interactions important in the process of myelination.

  13. Connexin 26-mediated gap junctional intercellular communication suppresses paracellular permeability of human intestinal epithelial cell monolayers

    International Nuclear Information System (INIS)

    Morita, Hidekazu; Katsuno, Tatsuro; Hoshimoto, Aihiro; Hirano, Noriaki; Saito, Yasushi; Suzuki, Yasuo

    2004-01-01

    In some cell types, gap junctional intercellular communication (GJIC) is associated with tight junctions. The present study was performed to determine the roles of GJIC in regulation of the barrier function of tight junctions. Caco-2 human colonic cells were used as a monolayer model, and barrier function was monitored by measuring mannitol permeability and transepithelial electrical resistance (TER). The monolayers were chemically disrupted by treatment with oleic acid and taurocholic acid. Western blotting analyses were performed to evaluate the protein levels of connexins, which are components of gap junctional intercellular channels. Cx26 expression was detected in preconfluent Caco-2 cells, and its level increased gradually after the monolayer reached confluency. These results prompted us to examine whether overexpression of Cx26 affects barrier function. Monolayers of Caco-2 cells stably expressing Cx26 showed significantly lower mannitol permeability and higher TER than mock transfectants when the monolayers were chemically disrupted. The levels of claudin-4, an important component of tight junctions, were significantly increased in the stable Cx26 transfectant. These results suggest that Cx26-mediated GJIC may play a crucial role in enhancing the barrier function of Caco-2 cell monolayers

  14. Edge currents in frustrated Josephson junction ladders

    Science.gov (United States)

    Marques, A. M.; Santos, F. D. R.; Dias, R. G.

    2016-09-01

    We present a numerical study of quasi-1D frustrated Josephson junction ladders with diagonal couplings and open boundary conditions, in the large capacitance limit. We derive a correspondence between the energy of this Josephson junction ladder and the expectation value of the Hamiltonian of an analogous tight-binding model, and show how the overall superconducting state of the chain is equivalent to the minimum energy state of the tight-binding model in the subspace of one-particle states with uniform density. To satisfy the constraint of uniform density, the superconducting state of the ladder is written as a linear combination of the allowed k-states of the tight-binding model with open boundaries. Above a critical value of the parameter t (ratio between the intra-rung and inter-rung Josephson couplings) the ladder spontaneously develops currents at the edges, which spread to the bulk as t is increased until complete coverage is reached. Above a certain value of t, which varies with ladder size (t = 1 for an infinite-sized ladder), the edge currents are destroyed. The value t = 1 corresponds, in the tight-binding model, to the opening of a gap between two bands. We argue that the disappearance of the edge currents with this gap opening is not coincidental, and that this points to a topological origin for these edge current states.

  15. Changes of Tight Junction Protein Claudins in Small Intestine and Kidney Tissues of Mice Fed a DDC Diet.

    Science.gov (United States)

    Abiko, Yukie; Kojima, Takashi; Murata, Masaki; Tsujiwaki, Mitsuhiro; Takeuchi, Masaya; Sawada, Norimasa; Mori, Michio

    2013-12-01

    DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine)-fed mice are widely used as a model for cholestatic liver disease. We examined the expression of tight junction protein claudin subspecies by immunofluorescent histochemistry in small intestine and kidney tissues of mice fed a DDC diet for 12 weeks. In the small intestine, decreases in claudin-3, claudin-7 and claudin-15 were observed in villous epithelial cells corresponding to the severity of histological changes while leaving the abundance of these claudin subspecies unchanged in crypt cells. Nevertheless, the proliferative activity of intestinal crypt cells measured by immunohistochemistry for Ki-67 decreased in the mice fed the DDC diet compared with that of control mice. These results suggest the possibility that DDC feeding affects the barrier function of villous epithelial cells and thus inhibits the proliferative activity of crypt epithelial cells. On the other hand, in the kidney, remarkable changes were found in the subcellular localization of claudin subspecies in a segment-specific manner, although histological changes of renal epithelial cells were quite minimal. These results indicate that immunohistochemistry for claudin subspecies can serve as a useful tool for detecting minute functional alterations of intestinal and renal epithelial cells.

  16. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin.

    Science.gov (United States)

    Fasano, A

    2000-01-01

    The intestinal epithelium represents the largest interface between the external environment and the internal host milieu and constitutes the major barrier through which molecules can either be absorbed or secreted. There is now substantial evidence that tight junctions (tj) play a major role in regulating epithelial permeability by influencing paracellular flow of fluid and solutes. Tj are one of the hallmarks of absorptive and secretory epithelia. Evidence now exists that tj are dynamic rather than static structures and readily adapt to a variety of developmental, physiological, and pathological circumstances. These adaptive mechanisms are still incompletely understood. Activation of PKC either by Zonula occludens toxin (Zot) or by phorbol esters increases paracellular permeability. Alteration of epithelial tj is a recently described property for infectious agents. Clostridium difficile toxin A and B and influenza and vesicular stomatitis viruses have been shown to loosen tj in tissue culture monolayers. Unlike what occurs after the Zot stimulus, these changes appear to be irreversible and are associated with destruction of the tj complex. On the basis of this observation, we postulated that Zot may mimic the effect of a functionally and immunologically related endogenous modulator of epithelial tj. We were able to identify an intestinal Zot analogue, which we named zonulin. It is conceivable that the zonulins participate in the physiological regulation of intercellular tj not only in the small intestine, but also throughout a wide range of extraintestinal epithelia as well as the ubiquitous vascular endothelium, including the blood-brain barrier. Disregulation of this hypothetical zonulin model may contribute to disease states that involve disordered intercellular communication, including developmental and intestinal disorders, tissue inflammation, malignant transformation, and metastasis.

  17. A role for tight junction-associated MARVEL proteins in larval sea lamprey (Petromyzon marinus) osmoregulation.

    Science.gov (United States)

    Kolosov, Dennis; Bui, Phuong; Donini, Andrew; Wilkie, Mike P; Kelly, Scott P

    2017-10-15

    This study reports on tight junction-associated MARVEL proteins of larval sea lamprey ( Petromyzon marinus ) and their potential role in ammocoete osmoregulation. Two occludin isoforms (designated Ocln and Ocln-a) and a tricellulin (Tric) were identified. Transcripts encoding ocln , ocln-a and tric were broadly expressed in larval lamprey, with the greatest abundance of ocln in the gut, liver and kidney, ocln-a in the gill and skin, and tric in the kidney. Ocln and Ocln-a resolved as ∼63 kDa and ∼35 kDa MW proteins, respectively, while Tric resolved as a ∼50 kDa protein. Ocln immunolocalized to the gill vasculature and in gill mucous cells while Ocln-a localized to the gill pouch and gill epithelium. Both Ocln and Ocln-a localized in the nephron, the epidermis and the luminal side of the gut. In branchial tissue, Tric exhibited punctate localization, consistent with its presence at regions of tricellular contact. Following ion-poor water (IPW) acclimation of ammocoetes, serum [Na + ] and [Cl - ] decreased, but not [Ca 2+ ], and carcass moisture content increased. In association, Ocln abundance increased in the skin and kidney, but reduced in the gill of IPW-acclimated ammocoetes while Ocln-a abundance reduced in the kidney only. Tric abundance increased in the gill. Region-specific alterations in ocln , ocln-a and tric mRNA abundance were also observed in the gut. Data support a role for Ocln, Ocln-a and Tric in the osmoregulatory strategies of a basal vertebrate. © 2017. Published by The Company of Biologists Ltd.

  18. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)

    Navya

    2017-03-24

    Mar 24, 2017 ... experiment showed a lower dye diffusion distance of Cx46 V44M cells, ... Studies of connexins show that channel gating and permeability .... have found that connexin assembled into gap junction plaques is not soluble in 1% ..... high glucose reduces gap junction activity in microvascular endothelial cells.

  19. Intraepithelial lymphocytes express junctional molecules in murine small intestine

    International Nuclear Information System (INIS)

    Inagaki-Ohara, Kyoko; Sawaguchi, Akira; Suganuma, Tatsuo; Matsuzaki, Goro; Nawa, Yukifumi

    2005-01-01

    Intestinal intraepithelial lymphocytes (IEL) that reside at basolateral site regulate the proliferation and differentiation of epithelial cells (EC) for providing a first line of host defense in intestine. However, it remains unknown how IEL interact and communicate with EC. Here, we show that IEL express junctional molecules like EC. We identified mRNA expression of the junctional molecules in IEL such as zonula occludens (ZO)-1, occludin and junctional adhesion molecule (JAM) (tight junction), β-catenin and E-cadherin (adherens junction), and connexin26 (gap junction). IEL constitutively expressed occludin and E-cadherin at protein level, while other T cells in the thymus, spleen, liver, mesenteric lymph node, and Peyer's patches did not. γδ IEL showed higher level of these expressions than αβ IEL. The expression of occludin was augmented by anti-CD3 Ab stimulation. These results suggest the possibility of a novel role of IEL concerning epithelial barrier and communication between IEL and EC

  20. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Directory of Open Access Journals (Sweden)

    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  1. Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression.

    Science.gov (United States)

    Wise, Sarah K; Laury, Adrienne M; Katz, Elizabeth H; Den Beste, Kyle A; Parkos, Charles A; Nusrat, Asma

    2014-05-01

    Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a "leaky" epithelial barrier phenotype. We hypothesize that T helper 2 (Th2) cytokines interleukin (IL)-4 and IL-13 modulate epithelial junction proteins, thereby contributing to the leaky epithelial barrier. Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n = 6) and 68.6% (n = 8) of baseline, respectively. Tight junction protein junctional adhesion molecule-A (JAM-A) expression decreased 42.2% with IL-4 exposure (n = 9) and 37.5% with IL-13 exposure (n = 9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n = 9) and 32.9% with IL-13 exposure (n = 9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or zonula occludens-1 (ZO-1) with IL-4 or IL-13 exposure. Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. © 2014 ARS-AAOA, LLC.

  2. TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin.

    Science.gov (United States)

    Kanda, Yusuke; Yamasaki, Youhei; Sasaki-Yamaguchi, Yoshie; Ida-Koga, Noriko; Kamisuki, Shinji; Sugawara, Fumio; Nagumo, Yoko; Usui, Takeo

    2018-02-02

    The delivery of hydrophilic macromolecules runs into difficulties such as penetration of the cell membrane lipid bilayer. Our prior experiment demonstrated that capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. Herein, we screened paracellular permeability enhancers other than capsaicin. As TJ opening by capsaicin is associated with Ca 2+ influx, we first screened the compounds that induce Ca 2+ influx in layered MDCK II cells, and then we determined the compounds' abilities to open TJs. Our results identified several natural compounds with α,β-unsaturated moiety. A structure-activity relationship (SAR) analysis and the results of pretreatment with reducing reagent DTT suggested the importance of α,β-unsaturated moiety. We also examined the underlying mechanisms, and our findings suggest that the actin reorganization seen in capsaicin treatment is important for the reversibility of TJ opening. Furthermore, our analyses revealed that TRPA1 is involved in the Ca 2+ influx and TJ permeability increase not only by an α,β-unsaturated compound but also by capsaicin. Our results indicate that the α,β-unsaturated moiety can be a potent pharmacophore for TJ opening.

  3. Chirality effect in disordered graphene ribbon junctions

    International Nuclear Information System (INIS)

    Long Wen

    2012-01-01

    We investigate the influence of edge chirality on the electronic transport in clean or disordered graphene ribbon junctions. By using the tight-binding model and the Landauer-Büttiker formalism, the junction conductance is obtained. In the clean sample, the zero-magnetic-field junction conductance is strongly chirality-dependent in both unipolar and bipolar ribbons, whereas the high-magnetic-field conductance is either chirality-independent in the unipolar or chirality-dependent in the bipolar ribbon. Furthermore, we study the disordered sample in the presence of magnetic field and find that the junction conductance is always chirality-insensitive for both unipolar and bipolar ribbons with adequate disorders. In addition, the disorder-induced conductance plateaus can exist in all chiral bipolar ribbons provided the disorder strength is moderate. These results suggest that we can neglect the effect of edge chirality in fabricating electronic devices based on the magnetotransport in a disordered graphene ribbon. (paper)

  4. Tight fitting garter springs-MODAR

    Energy Technology Data Exchange (ETDEWEB)

    Kazimer, D. [Bruce Power, Tiverton, Ontario (Canada)

    2011-07-01

    Annulus spacers are used in CANDU reactors to maintain the annular gap between two tubes - an inner pressure tube (PT) and the outer calandria tube (CT). Typically four annulus spacers are used in one fuel channel assembly, each at a specified axial position. Bruce Unit 8 and many other CANDU units were constructed with tight-fitting garter springs (TFGS). The TFGS were not designed to be detected or relocated by the conventional tool, Spacer Location And Repositioning (SLAR) processes. Due to non-optimal 'As Left' construction locations for the Bruce Unit 8 TFGS, PT/CT contact has been predicted to occur well prior to its End of Life (EOL). Bruce Power entered a Project with AECL-CRL to design, manufacture and test and implement a new tooling system that would detect and reposition tight fitting annulus spacers. (author)

  5. Structural and rectifying junction properties of self-assembled ZnO nanoparticles in polystyrene diblock copolymers on (1 0 0)Si substrates

    Science.gov (United States)

    Ali, H. A.; Iliadis, A. A.; Martinez-Miranda, L. J.; Lee, U.

    2006-06-01

    The structural and electronic transport properties of self-assembled ZnO nanoparticles in polystyrene-acrylic acid, [PS] m/[PAA] n, diblock copolymer on p-type (1 0 0)Si substrates are reported for the first time. Four different block repeat unit ratios ( m/ n) of 159/63, 139/17,106/17, and 106/4, were examined in order to correlate the physical parameters (size, density) of the nanoparticles with the copolymer block lengths m and n. We established that the self-assembled ZnO nanoparticle average size increased linearly with minority block length n, while the average density decreased exponentially with majority block length m. Average size varied from 20 nm to 250 nm and average density from 3.5 × 10 7 cm -2 to 1 × 10 10 cm -2, depending on copolymer parameters. X-ray diffraction studies showed the particles to have a wurtzite crystal structure with the (1 0 0) being the dominant orientation. Room temperature current-voltage characteristics measured for an Al/ZnO-nanocomposite/Si structure exhibited rectifying junction properties and indicated the formation of Al/ZnO-nanocomposite Schottky type junction with a barrier height of 0.7 V.

  6. IL-4 and IL-13 Compromise the Sinonasal Epithelial Barrier and Perturb Intercellular Junction Protein Expression

    Science.gov (United States)

    Wise, Sarah K.; Laury, Adrienne M.; Katz, Elizabeth H.; Den Beste, Kyle A.; Parkos, Charles A.; Nusrat, Asma

    2014-01-01

    Introduction Altered expression of epithelial intercellular junction proteins has been observed in sinonasal biopsies from nasal polyps and epithelial layers cultured from nasal polyp patients. These alterations comprise a “leaky” epithelial barrier phenotype. We hypothesize that Th2 cytokines IL-4 and IL-13 modulate epithelial junction proteins thereby contributing to the leaky epithelial barrier. Methods Differentiated primary sinonasal epithelial layers cultured at the air-liquid interface were exposed to IL-4, IL-13, and controls for 24 hours at 37°C. Epithelial resistance measurements were taken every 4 hours during cytokine exposure. Western blot and immunofluorescence staining/confocal microscopy were used to assess changes in a panel of tight and adherens junction proteins. Western blot densitometry was quantified with image analysis. Results IL-4 and IL-13 exposure resulted in a mean decrease in transepithelial resistance at 24 hours to 51.6% (n=6) and 68.6% (n=8) of baseline, respectively. Tight junction protein JAM-A expression decreased 42.2% with IL-4 exposure (n=9) and 37.5% with IL-13 exposure (n=9). Adherens junction protein E-cadherin expression decreased 35.3% with IL-4 exposure (n=9) and 32.9% with IL-13 exposure (n=9). Tight junction protein claudin-2 showed more variability but had a trend toward higher expression with Th2 cytokine exposure. There were no appreciable changes in claudin-1, occludin, or ZO-1 with IL-4 or IL-13 exposure. Conclusion Sinonasal epithelial exposure to Th2 cytokines IL-4 and IL-13 results in alterations in intercellular junction proteins, reflecting increased epithelial permeability. Such changes may explain some of the phenotypic manifestations of Th2-mediated sinonasal disease, such as edema, nasal discharge, and environmental reactivity. PMID:24510479

  7. Charge splitters and charge transport junctions based on guanine quadruplexes

    Science.gov (United States)

    Sha, Ruojie; Xiang, Limin; Liu, Chaoren; Balaeff, Alexander; Zhang, Yuqi; Zhang, Peng; Li, Yueqi; Beratan, David N.; Tao, Nongjian; Seeman, Nadrian C.

    2018-04-01

    Self-assembling circuit elements, such as current splitters or combiners at the molecular scale, require the design of building blocks with three or more terminals. A promising material for such building blocks is DNA, wherein multiple strands can self-assemble into multi-ended junctions, and nucleobase stacks can transport charge over long distances. However, nucleobase stacking is often disrupted at junction points, hindering electric charge transport between the two terminals of the junction. Here, we show that a guanine-quadruplex (G4) motif can be used as a connector element for a multi-ended DNA junction. By attaching specific terminal groups to the motif, we demonstrate that charges can enter the structure from one terminal at one end of a three-way G4 motif, and can exit from one of two terminals at the other end with minimal carrier transport attenuation. Moreover, we study four-way G4 junction structures by performing theoretical calculations to assist in the design and optimization of these connectors.

  8. Gonadotropin suppression in men leads to a reduction in claudin-11 at the Sertoli cell tight junction.

    Science.gov (United States)

    McCabe, M J; Tarulli, G A; Laven-Law, G; Matthiesson, K L; Meachem, S J; McLachlan, R I; Dinger, M E; Stanton, P G

    2016-04-01

    Are Sertoli cell tight junctions (TJs) disrupted in men undergoing hormonal contraception? Localization of the key Sertoli cell TJ protein, claudin-11, was markedly disrupted by 8 weeks of gonadotropin suppression, the degree of which was related to the extent of adluminal germ cell suppression. Sertoli cell TJs are vital components of the blood-testis barrier (BTB) that sequester developing adluminal meiotic germ cells and spermatids from the vascular compartment. Claudin-11 knockout mice are infertile; additionally claudin-11 is spatially disrupted in chronically gonadotropin-suppressed rats coincident with a loss of BTB function, and claudin-11 is disorganized in various human testicular disorders. These data support the Sertoli cell TJ as a potential site of hormonal contraceptive action. BTB proteins were assessed by immunohistochemistry (n = 16 samples) and mRNA (n = 18 samples) expression levels in available archived testis tissue from a previous study of 22 men who had undergone 8 weeks of gonadotropin suppression and for whom meiotic and post-meiotic germ cell numbers were available. The gonadotropin suppression regimens were (i) testosterone enanthate (TE) plus the GnRH antagonist, acyline (A); (ii) TE + the progestin, levonorgestrel, (LNG); (iii) TE + LNG + A or (iv) TE + LNG + the 5α-reductase inhibitor, dutasteride (D). A control group consisted of seven additional men, with three archived samples available for this study. Immunohistochemical localization of claudin-11 (TJ) and other junctional type markers [ZO-1 (cytoplasmic plaque), β-catenin (adherens junction), connexin-43 (gap junction), vinculin (ectoplasmic specialization) and β-actin (cytoskeleton)] and quantitative PCR was conducted using matched frozen testis tissue. Claudin-11 formed a continuous staining pattern at the BTB in control men. Regardless of gonadotropin suppression treatment, claudin-11 localization was markedly disrupted and was broadly associated with the extent of meiotic

  9. Protecting intestinal epithelial integrity by galacto-oligosaccharides: Keeping it tight

    OpenAIRE

    Akbari, P.

    2016-01-01

    The intestinal barrier serves as a first line of host defense against potentially harmful stressors from the environment ingested with food, and is primarily formed by epithelial cells connected by tight junctions. Oligosaccharides have been identified as components in milk, particularly in colostrum, that support the development of intestinal microbiota in the early phase of life and contribute to the maturation of the immune system in infants. Currently, galacto-oligosaccharides (GOS) are u...

  10. OLIFE: Tight Binding Code for Transmission Coefficient Calculation

    Science.gov (United States)

    Mijbil, Zainelabideen Yousif

    2018-05-01

    A new and human friendly transport calculation code has been developed. It requires a simple tight binding Hamiltonian as the only input file and uses a convenient graphical user interface to control calculations. The effect of magnetic field on junction has also been included. Furthermore the transmission coefficient can be calculated between any two points on the scatterer which ensures high flexibility to check the system. Therefore Olife can highly be recommended as an essential tool for pretesting studying and teaching electron transport in molecular devices that saves a lot of time and effort.

  11. Effect of Glucagon-like Peptide 2 on Tight Junction in Jejunal Epithelium of Weaned Pigs though MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Changsong Yu

    2014-05-01

    Full Text Available The glucagon-like peptide 2 (GLP-2 that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets’ intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK signaling pathway in piglets’ intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco’s modified Eagle’s medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1, occludin and claudin-1 were increased (p<0.05. U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05. In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs’ jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.

  12. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

    Science.gov (United States)

    Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

    2008-03-01

    Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

  13. Contact with friction modeling for the study of a bolted junction

    International Nuclear Information System (INIS)

    Lebon, F.; Raous, M.; Boulegues, D.

    1987-01-01

    Many structural analysis problems are concerned by contact phenomena. A good knowledge of the contact displacements and the contact forces between the different parts of the structure is generally essential in structure assembling. The special boundary behaviour has a strong influence on the distribution of the stresses in the whole structure and on his total fiability. The contact behaviour is strongly non linear because of the non penetration conditions on the one hand, and because of the friction on the other. On such problems the real contact zone and the contact forces are unknown 'a priori' and have to be determined during the resolution. The non-penetration is characterized by unilateral conditions and the friction is described by a constitutive law (Coulomb friction law). The application presented here concerns the assembling of the three parts of a bolted junction using a pressing ring. There are three contact zones in this program. A good description of the contact phenomena is essential to ensure tightness. Our methods are based on projection techniques coupled with overrelaxed Gauss-Seidel methods including condensation procedures (reduction of the number of variables). Non linear programming methods and iterative procedures on special boundary conditions are also used. (orig./HP)

  14. Decaffeinated coffee consumption induces expression of tight junction proteins in high fat diet fed rats

    Directory of Open Access Journals (Sweden)

    Mazzone G

    2016-09-01

    Full Text Available Background: Recent evidence indicates that gut microbiota plays a key role in the development of NAFLD through the gut-liver axis. An altered gut permeability induced by alterations of tight junction (TJ proteins allows the passage of bacteria and substances leading to liver inflammation, hepatocyte damage and fibrosis. This study aims to evaluate the influence of decaffeinated coffee on gut permeability in a rat model of fat liver damage induced by a high fat diet (HFD. Methods: Twelve male Wistar rats were assigned to 3 groups. The first group received HFD for 5 months and drank water. The second group received HFD for 5 months and drank water added with 1.2mL decaffeinated coffee/day starting from the 4th month. The third group received standard diet (SD and drank water. Protein and mRNA expression levels of Toll-Like Receptor- 4 (TLR-4, Occludin and Zonula occludens-1 (ZO-1 were assessed in rat intestines. Results: A significant reduction of Occludin and ZO-1 was observed in HFD fed rats (0.97±0.05 vs 0.15±0.08 p˂0.01, and 0.97±0.05 vs 0.57±0.14 p˂0.001 respectively. This reduction was reverted in HFD+COFFEE rats (0.15±0.08 vs 0.83±0.27 p˂0.01 and 0.57±0.14 vs 0.85±0.12 p˂0.01 respectively. The TLR-4 expression up-regulated by HFD was partially reduced by coffee administration. Conclusions: HFD impairs the intestinal TJ barrier integrity. Coffee increases the expression of TJ proteins, reverting the altered gut permeability and reducing TLR-4 expression.

  15. Phase transition in one Josephson junction with a side-coupled magnetic impurity

    Science.gov (United States)

    Zhi, Li-Ming; Wang, Xiao-Qi; Jiang, Cui; Yi, Guang-Yu; Gong, Wei-Jiang

    2018-04-01

    This work focuses on one Josephson junction with a side-coupled magnetic impurity. And then, the Josephson phase transition is theoretically investigated, with the help of the exact diagonalization approach. It is found that even in the absence of intradot Coulomb interaction, the magnetic impurity can efficiently induce the phenomenon of Josephson phase transition, which is tightly related to the spin correlation manners (i.e., ferromagnetic or antiferromagnetic) between the impurity and the junction. Moreover, the impurity plays different roles when it couples to the dot and superconductor, respectively. This work can be helpful in describing the influence of one magnetic impurity on the supercurrent through the Josephson junction.

  16. Baicalin Protects against TNF-α-Induced Injury by Down-Regulating miR-191a That Targets the Tight Junction Protein ZO-1 in IEC-6 Cells.

    Science.gov (United States)

    Wang, Li; Zhang, Ren; Chen, Jian; Wu, Qihui; Kuang, Zaoyuan

    2017-04-01

    Tumor necrosis factor-alpha (TNF-α) plays an important role in the developing process of inflammatory bowel disease. Tight junction protein zonula occludens-1 (ZO-1), one of epithelial junctional proteins, maintains the permeability of intestinal barrier. The objective of this study was to investigate the mechanism of the protective effect of baicalin on TNF-α-induced injury and ZO-1 expression in intestinal epithelial cells (IECs). We found that baicalin pretreatment significantly improved cell viability and cell migration following TNF-α stimulation. miR-191a inhibitor increased the protective effect of baicalin on cell motility injured by TNF-α. In addition, miR-191a down-regulated the mRNA and protein level of its target gene ZO-1. TNF-α stimulation increased miR-191a expression, leading to the decline of ZO-1 mRNA and protein. Moreover, pretreatment with baicalin reversed TNF-α induced decrease of ZO-1 and increase of miR-191a, miR-191a inhibitor significantly enhanced ZO-1 protein expression restored by baicalin. These results indicate that baicalin exerts a protective effect on IEC-6 (rat small intestinal epithelial cells) cells against TNF-α-induced injury, which is at least partly via inhibiting the expression of miR-191a, thus increasing ZO-1 mRNA and protein levels.

  17. Spin-transfer torque in spin filter tunnel junctions

    KAUST Repository

    Ortiz Pauyac, Christian

    2014-12-08

    Spin-transfer torque in a class of magnetic tunnel junctions with noncollinear magnetizations, referred to as spin filter tunnel junctions, is studied within the tight-binding model using the nonequilibrium Green\\'s function technique within Keldysh formalism. These junctions consist of one ferromagnet (FM) adjacent to a magnetic insulator (MI) or two FM separated by a MI. We find that the presence of the magnetic insulator dramatically enhances the magnitude of the spin-torque components compared to conventional magnetic tunnel junctions. The fieldlike torque is driven by the spin-dependent reflection at the MI/FM interface, which results in a small reduction of its amplitude when an insulating spacer (S) is inserted to decouple MI and FM layers. Meanwhile, the dampinglike torque is dominated by the tunneling electrons that experience the lowest barrier height. We propose a device of the form FM/(S)/MI/(S)/FM that takes advantage of these characteristics and allows for tuning the spin-torque magnitudes over a wide range just by rotation of the magnetization of the insulating layer.

  18. Spin-transfer torque in spin filter tunnel junctions

    KAUST Repository

    Ortiz Pauyac, Christian; Kalitsov, Alan; Manchon, Aurelien; Chshiev, Mairbek

    2014-01-01

    Spin-transfer torque in a class of magnetic tunnel junctions with noncollinear magnetizations, referred to as spin filter tunnel junctions, is studied within the tight-binding model using the nonequilibrium Green's function technique within Keldysh formalism. These junctions consist of one ferromagnet (FM) adjacent to a magnetic insulator (MI) or two FM separated by a MI. We find that the presence of the magnetic insulator dramatically enhances the magnitude of the spin-torque components compared to conventional magnetic tunnel junctions. The fieldlike torque is driven by the spin-dependent reflection at the MI/FM interface, which results in a small reduction of its amplitude when an insulating spacer (S) is inserted to decouple MI and FM layers. Meanwhile, the dampinglike torque is dominated by the tunneling electrons that experience the lowest barrier height. We propose a device of the form FM/(S)/MI/(S)/FM that takes advantage of these characteristics and allows for tuning the spin-torque magnitudes over a wide range just by rotation of the magnetization of the insulating layer.

  19. Supramolecular Systems and Chemical Reactions in Single-Molecule Break Junctions.

    Science.gov (United States)

    Li, Xiaohui; Hu, Duan; Tan, Zhibing; Bai, Jie; Xiao, Zongyuan; Yang, Yang; Shi, Jia; Hong, Wenjing

    2017-04-01

    The major challenges of molecular electronics are the understanding and manipulation of the electron transport through the single-molecule junction. With the single-molecule break junction techniques, including scanning tunneling microscope break junction technique and mechanically controllable break junction technique, the charge transport through various single-molecule and supramolecular junctions has been studied during the dynamic fabrication and continuous characterization of molecular junctions. This review starts from the charge transport characterization of supramolecular junctions through a variety of noncovalent interactions, such as hydrogen bond, π-π interaction, and electrostatic force. We further review the recent progress in constructing highly conductive molecular junctions via chemical reactions, the response of molecular junctions to external stimuli, as well as the application of break junction techniques in controlling and monitoring chemical reactions in situ. We suggest that beyond the measurement of single molecular conductance, the single-molecule break junction techniques provide a promising access to study molecular assembly and chemical reactions at the single-molecule scale.

  20. ProbeZT: Simulation of transport coefficients of molecular electronic junctions under environmental effects using Büttiker's probes

    Science.gov (United States)

    Korol, Roman; Kilgour, Michael; Segal, Dvira

    2018-03-01

    We present our in-house quantum transport package, ProbeZT. This program provides linear response coefficients: electrical and electronic thermal conductances, as well as the thermopower of molecular junctions in which electrons interact with the surrounding thermal environment. Calculations are performed based on the Büttiker probe method, which introduces decoherence, energy exchange and dissipation effects phenomenologically using virtual electrode terminals called probes. The program can realize different types of probes, each introducing various environmental effects, including elastic and inelastic scattering of electrons. The molecular system is described by an arbitrary tight-binding Hamiltonian, allowing the study of different geometries beyond simple one-dimensional wires. Applications of the program to study the thermoelectric performance of molecular junctions are illustrated. The program also has a built-in functionality to simulate electron transport in double-stranded DNA molecules based on a tight-binding (ladder) description of the junction.

  1. 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

  2. Scutellaria barbata attenuates diabetic retinopathy by preventing retinal inflammation and the decreased expression of tight junction protein

    Directory of Open Access Journals (Sweden)

    Xi-Yu Mei

    2017-06-01

    Full Text Available AIM: To observe the attenuation of ethanol extract of Herba Scutellaria barbata (SE against diabetic retinopathy (DR and its engaged mechanism. METHODS: C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ, 55 mg/kg for 5 consecutive days to induce diabetes. The diabetic mice were orally given with SE (100, 200 mg/kg for 1mo at 1mo after STZ injection. Blood-retinal barrier (BRB breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction (RT-PCR, Western blot and immunofluorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA was used to detect serum contents of tumor necrosis factor-α (TNF-α and interleukin (IL-1β. RESULTS: SE (100, 200 mg/kg reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction (TJ proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-α and IL-1β. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 (ICAM-1. SE reduced the increased phosphorylation of nuclear factor kappa B (NFκB p65 and its subsequent nuclear translocation in retinas from STZ-induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 (Iba1 demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION: SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19.

  3. Gas separation membrane module assembly

    Science.gov (United States)

    Wynn, Nicholas P [Palo Alto, CA; Fulton, Donald A [Fairfield, CA

    2009-03-31

    A gas-separation membrane module assembly and a gas-separation process using the assembly. The assembly includes a set of tubes, each containing gas-separation membranes, arranged within a housing. The housing contains a tube sheet that divides the space within the housing into two gas-tight spaces. A permeate collection system within the housing gathers permeate gas from the tubes for discharge from the housing.

  4. Immunohistochemical quantification of expression of a tight junction protein, claudin-7, in human lung cancer samples using digital image analysis method.

    Science.gov (United States)

    Lu, Zhe; Liu, Yi; Xu, Junfeng; Yin, Hongping; Yuan, Haiying; Gu, Jinjing; Chen, Yan-Hua; Shi, Liyun; Chen, Dan; Xie, Bin

    2018-03-01

    Tight junction proteins are correlated with cancer development. As the pivotal proteins in epithelial cells, altered expression and distribution of different claudins have been reported in a wide variety of human malignancies. We have previously reported that claudin-7 was strongly expressed in benign bronchial epithelial cells at the cell-cell junction while expression of claudin-7 was either altered with discontinued weak expression or completely absent in lung cancers. Based on these results, we continued working on the expression pattern of claudin-7 and its relationship with lung cancer development. We herein proposed a new Digital Image Classification, Fragmentation index, Morphological analysis (DICFM) method for differentiating the normal lung tissues and lung cancer tissues based on the claudin-7 immunohistochemical staining. Seventy-seven lung cancer samples were obtained from the Second Affiliated Hospital of Zhejiang University and claudin-7 immunohistochemical staining was performed. Based on C++ and Open Source Computer Vision Library (OpenCV, version 2.4.4), the DICFM processing module was developed. Intensity and fragmentation of claudin-7 expression, as well as the morphological parameters of nuclei were calculated. Evaluation of results was performed using Receiver Operator Characteristic (ROC) analysis. Agreement between these computational results and the results obtained by two pathologists was demonstrated. The intensity of claudin-7 expression was significantly decreased while the fragmentation was significantly increased in the lung cancer tissues compared to the normal lung tissues and the intensity was strongly positively associated with the differentiation of lung cancer cells. Moreover, the perimeters of the nuclei of lung cancer cells were significantly greater than that of the normal lung cells, while the parameters of area and circularity revealed no statistical significance. Taken together, our DICFM approach may be applied as an

  5. Influence of Th2 Cytokines on the Cornified Envelope, Tight Junction Proteins, and ß-Defensins in Filaggrin-Deficient Skin Equivalents.

    Science.gov (United States)

    Hönzke, Stefan; Wallmeyer, Leonie; Ostrowski, Anja; Radbruch, Moritz; Mundhenk, Lars; Schäfer-Korting, Monika; Hedtrich, Sarah

    2016-03-01

    Atopic dermatitis is a chronic skin condition with complex etiology. It is characterized by skin barrier defects and T helper type 2 (Th2)-polarized inflammation. Although mutations in the filaggrin gene are known to be prominent genetic risk factors for the development of atopic dermatitis, the interdependency between these and an altered cytokine milieu is not fully understood. In this study, we evaluated the direct effects of filaggrin deficiency on the cornified envelope, tight junction proteins, and innate immune response, and report the effects of Th2 cytokines in normal and filaggrin-deficient skin equivalents. Supplementation with IL-4 and IL-13 led to distinct histologic changes and significantly increased skin surface pH, both of which were enhanced in filaggrin knockdown skin equivalents. We detected a compensatory up-regulation of involucrin and occludin in filaggrin-deficient skin that was dramatically disturbed when simultaneous inflammation occurred. Furthermore, we found that a lack of filaggrin triggered an up-regulation of human ?-defensin 2 via an unknown mechanism, which was abolished by Th2 cytokine supplementation. Taken together, these results indicate that defects in the epidermal barrier, skin permeability, and cutaneous innate immune response are not primarily linked to filaggrin deficiency but are rather secondarily induced by Th2 inflammation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats.

    Science.gov (United States)

    Watts, Tammara; Berti, Irene; Sapone, Anna; Gerarduzzi, Tania; Not, Tarcisio; Zielke, Ronald; Fasano, Alessio

    2005-02-22

    Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased intestinal permeability plays a role in the pathogenesis of T1D. In the BB diabetic-prone rat model of T1D, intestinal intraluminal zonulin levels were elevated 35-fold compared to control BB diabetic-resistant rats. Zonulin up-regulation was coincident with decreased small intestinal transepithelial electrical resistance, and was followed by the production of autoantibodies against pancreatic beta cells, which preceded the onset of clinically evident T1D by approximately 25 days. In those diabetic prone rats that did not progress to diabetes, both intraluminal zonulin and transepithelial electrical resistance were similar to those detected in diabetic-resistant animal controls. Blockade of the zonulin receptor reduced the cumulative incidence of T1D by 70%, despite the persistence of intraluminal zonulin up-regulation. Moreover, treatment responders did not seroconvert to islet cell antibodies. Combined together, these findings suggest that the zonulin-induced loss in small intestinal barrier function is involved in the pathogenesis of T1D in the BB diabetic-prone animal model.

  7. Leak tight sealants and joint details for concrete structure in RAPP

    International Nuclear Information System (INIS)

    Singha Roy, P.K.; Baste, M.S.

    1975-01-01

    Leak tightness may pertain to either air or water and in extreme cases each will require separate consideration based on general basic requirements. Leak-tight sealants against air pressure are required in the construction joints and around penetrations in the concrete containment structures. The containment structures should be able to withstand the maximum anticipated design pressure during the incident of a MCA with only minimal leakage (0.1% of bldg. volume per day in RAPP) which is mostly through these joints. Apart from proper joint design and preparation the sealant itself must have superb adhesion to the concrete surface and integrify throughout its service life to prevent any rupture or micro-cracks at any section of the joint. Leak tightness pertains to water tightness as well. A critical water-tight joint at the bottom dome of the prestressed concrete dousing tank at its junction with the 36 inches dia dousing water pipes constructed in RAPP-2, which should be able to withstand the water pressure, continuous submergence in the water of the tank and the longitudinal and lateral movement of the water pipes during opening and closure of the dousing valves, has been made and hydrostatically tested when not even the slight sweating was found. The construction and materials of the above joints and the sealant along with the properties and performance observed during testing/use are described. As the sealant used is an imported poly-sulphide caulking compound suggestions have also been made, which may be kept in mind while developing an Indian substitute. (author)

  8. The status of intercellular junctions in established lens epithelial cell lines.

    Science.gov (United States)

    Dave, Alpana; Craig, Jamie E; Sharma, Shiwani

    2012-01-01

    Cataract is the major cause of vision-related disability worldwide. Mutations in the crystallin genes are the most common known cause of inherited congenital cataract. Mutations in the genes associated with intercellular contacts, such as Nance-Horan Syndrome (NHS) and Ephrin type A receptor-2 (EPHA2), are other recognized causes of congenital cataract. The EPHA2 gene has been also associated with age-related cataract, suggesting that intercellular junctions are important in not only lens development, but also in maintaining lens transparency. The purpose of this study was to analyze the expression and localization of the key cell junction and cytoskeletal proteins, and of NHS and EPHA2, in established lens epithelial cell lines to determine their suitability as model epithelial systems for the functional investigation of genes involved in intercellular contacts and implicated in cataract. The expression and subcellular localization of occludin and zona occludens protein-1 (ZO-1), which are associated with tight junctions; E-cadherin, which is associated with adherence junctions; and the cytoskeletal actin were analyzed in monolayers of a human lens epithelial cell line (SRA 01/04) and a mouse lens epithelial cell line (αTN4). In addition, the expression and subcellular localization of the NHS and EPHA2 proteins were analyzed in these cell lines. Protein or mRNA expression was respectively determined by western blotting or reverse transcription-polymerase chain reaction (RT-PCR), and localization was determined by immunofluorescence labeling. Human SRA 01/04 and mouse αTN4 lens epithelial cells expressed either the proteins of interest or their encoding mRNA. Occludin, ZO-1, and NHS proteins localized to the cellular periphery, whereas E-cadherin, actin, and EPHA2 localized in the cytoplasm in these cell lines. The human SRA 01/04 and mouse αTN4 lens epithelial cells express the key junctional proteins. The localization patterns of these proteins suggest that

  9. Immunosuppressant MPA Modulates Tight Junction through Epigenetic Activation of MLCK/MLC-2 Pathway via p38MAPK

    Directory of Open Access Journals (Sweden)

    Niamat Khan

    2015-12-01

    Full Text Available Background: Mycophenolic acid (MPA is an important immunosuppressive drug (ISD prescribed to prevent graft rejection in the organ transplanted patients, however, its use is also associated with adverse side effects like sporadic gastrointestinal (GI disturbances. Recently, we reported the MPA induced tight junctions (TJs deregulation which involves MLCK/MLC-2 pathway. Here, we investigated the global histone acetylation as well as gene-specific chromatin signature of several genes associated with TJs regulation in Caco-2 cells after MPA treatment.Results: The epigenetic analysis shows that MPA treatment increases the global histone acetylation levels as well as the enrichment for transcriptional active histone modification mark (H3K4me3 at promoter regions of p38MAPK, ATF-2, MLCK, and MLC-2. In contrast, the promoter region of occludin was enriched for transcriptional repressive histone modification mark (H3K27me3 after MPA treatment. In line with the chromatin status, MPA treatment increased the expression of p38MAPK, ATF-2, MLCK, and MLC-2 both at transcriptional and translational level, while occludin expression was negatively influenced. Interestingly, the MPA induced gene expression changes and functional properties of Caco-2 cells could be blocked by the inhibition of p38MAPK using a chemical inhibitor (SB203580.Conclusions: Collectively, our results highlight that MPA disrupts the structure of TJs via p38MAPK-dependent activation of MLCK/MLC-2 pathway that results in decreased integrity of Caco-2 monolayer. These results led us to suggest that p38MAPK-mediated lose integrity of epithelial monolayer could be the possible cause of GI disturbance (barrier dysfunction in the intestine, leading to leaky style diarrhea observed in the organ-transplanted patients treated with MPA.

  10. Understanding the length dependence of molecular junction thermopower

    DEFF Research Database (Denmark)

    Karlström, Sven Olov Harald; Strange, Mikkel; Solomon, Gemma

    2014-01-01

    Thermopower of molecular junctions is sensitive to details in the junction and may increase, decrease, or saturate with increasing chain length, depending on the system. Using McConnell's theory for exponentially suppressed transport together with a simple and easily interpretable tight binding...... model, we show how these different behaviors depend on the molecular backbone and its binding to the contacts. We distinguish between resonances from binding groups or undercoordinated electrode atoms, and those from the periodic backbone. It is demonstrated that while the former gives a length......-independent contribution to the thermopower, possibly changing its sign, the latter determines its length dependence. This means that the question of which orbitals from the periodic chain that dominate the transport should not be inferred from the sign of the thermopower but from its length dependence. We find...

  11. Effect of ionising radiation exposure on structure and permeability of epithelial junctions in rat ileum

    International Nuclear Information System (INIS)

    Lebrum, F.; Dublineau, I.; Grison, S.; Strup, C.; Griffiths, N.M.

    2002-01-01

    Exposure of the digestive tract to ionising radiation results in both morphological and functional alterations of the small intestine. However little is known about the effect of irradiation on the junctions playing a major role in the maintenance of epithelial barrier integrity. Thus the aim of this study was to investigate, in rat ileum, the effect of radiation exposure on the permeability of the epithelial barrier in parallel with the localization of certain inter- and intra-cellular proteins of tight and adherent junctions

  12. Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.

    Science.gov (United States)

    Liu, Xiaobai; Wang, Zhenhua; Wang, Ping; Yu, Bo; Liu, Yunhui; Xue, Yixue

    2013-07-21

    It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

  13. 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.

  14. Subchannel analysis of 37-rod tight-lattice bundle experiments for reduced-moderation water reactor

    International Nuclear Information System (INIS)

    Nakatsuka, Toru; Tamai, Hidesada; Akimoto, Hajime

    2005-01-01

    R and D project to investigate thermal-hydraulic performance of tight-lattice fuel bundles for Reduced-Moderation Water Reactor (RMWR) started at Japan Atomic Energy Research Institute (JAERI) in collaboration with utilities, reactor vendors and universities from 2002. The RMWR realizes a high conversion ratio larger than 0.1 for sustainable energy supply through plutonium multiple recycling based on the well-experienced LWR technologies. The reactor core comprises tight-lattice fuel assemblies with gap clearance of around 1.0 mm to reduce the water volume ratio to achieve the high conversion ratio. A problem of utmost importance from a thermal-hydraulic point of view is the coolability of the tight-lattice assembly with such a small gap width. JAERI has been carrying out experimental study to investigate the system parameter effects on the thermal-hydraulic performance and to confirm the feasibility of the core. In the present study, the subchannel analysis code NASCA was applied to 37-rod tight-lattice bundle experiments. The NASCA can give good predictions of critical power for the gap width of 1.3 mm while the prediction accuracy decreases for the gap width of 1.0 mm. To improve the prediction accuracy, the code will be modified to take the effect of film thickness distribution around fuel rods on boiling transition. (author)

  15. Less-tight versus tight control of hypertension in pregnancy.

    Science.gov (United States)

    Magee, Laura A; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E; Menzies, Jennifer; Sanchez, Johanna; Singer, Joel; Gafni, Amiram; Gruslin, Andrée; Helewa, Michael; Hutton, Eileen; Lee, Shoo K; Lee, Terry; Logan, Alexander G; Ganzevoort, Wessel; Welch, Ross; Thornton, Jim G; Moutquin, Jean-Marie

    2015-01-29

    The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear. We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational hypertension, office diastolic blood pressure of 90 to 105 mm Hg (or 85 to 105 mm Hg if the woman was taking antihypertensive medications), and a live fetus. Women were randomly assigned to less-tight control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days. The secondary outcome was serious maternal complications occurring up to 6 weeks post partum or until hospital discharge, whichever was later. Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-outcome rates were similar among 493 women assigned to less-tight control and 488 women assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7% and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4). Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-control group and 27.5% of the women in the tight-control group (Phypertension. (Funded by the Canadian Institutes of Health Research; CHIPS Current Controlled Trials number, ISRCTN71416914; ClinicalTrials.gov number, NCT01192412.).

  16. Test-beds for molecular electronics: metal-molecules-metal junctions based on Hg electrodes.

    Science.gov (United States)

    Simeone, Felice Carlo; Rampi, Maria Anita

    2010-01-01

    Junctions based on mesoscopic Hg electrodes are used to characterize the electrical properties of the organic molecules organized in self-assembled monolayers (SAMs). The junctions M-SAM//SAM-Hg are formed by one electrode based on metals (M) such as Hg, Ag, Au, covered by a SAM, and by a second electrode always formed by a Hg drop carrying also a SAM. The electrodes, brought together by using a micromanipulator, sandwich SAMs of different nature at the contact area (approximately = 0.7 microm2). The high versatility of the system allows a series of both electrical and electrochemical junctions to be assembled and characterized: (i) The compliant nature of the Hg electrodes allows incorporation into the junction and measurement of the electrical behavior of a large number of molecular systems and correlation of their electronic structure to the electrical behavior; (ii) by functionalizing both electrodes with SAMs exposing different functional groups, X and Y, it is possible to compare the rate of electron transfer through different X...Y molecular interactions; (iii) when the junction incorporates one of the electrode formed by a semitransparent film of Au, it allows electrical measurements under irradiation of the sandwiched SAMs. In this case the junction behaves as a photoswitch; iv) incorporation of redox centres with low lying, easily reachable energy levels, provides electron stations as indicated by the hopping mechanism dominating the current flow; (v) electrochemical junctions incorporating redox centres by both covalent and electrostatic interactions permit control of the potential of the electrodes with respect to that of the redox state by means of an external reference electrode. Both these junctions show an electrical behavior similar to that of conventional diodes, even though the mechanism generating the current flow is different. These systems, demonstrating high mechanical stability and reproducibility, easy assembly, and a wide variety of

  17. Sample preconcentration utilizing nanofractures generated by junction gap breakdown assisted by self-assembled monolayer of gold nanoparticles.

    Directory of Open Access Journals (Sweden)

    Chun-Ping Jen

    Full Text Available The preconcentration of proteins with low concentrations can be used to increase the sensitivity and accuracy of detection. A nonlinear electrokinetic flow is induced in a nanofluidic channel due to the overlap of electrical double layers, resulting in the fast accumulation of proteins, referred to as the exclusion-enrichment effect. The proposed chip for protein preconcentration was fabricated using simple standard soft lithography with a polydimethylsiloxane replica. This study extends our previous paper, in which gold nanoparticles were manually deposited onto the surface of a protein preconcentrator. In the present work, nanofractures were formed by utilizing the self-assembly of gold-nanoparticle-assisted electric breakdown. This reliable method for nanofracture formation, involving self-assembled monolayers of nanoparticles at the junction gap between microchannels, also decreases the required electric breakdown voltage. The experimental results reveal that a high concentration factor of 1.5×10(4 for a protein sample with an extremely low concentration of 1 nM was achieved in 30 min by using the proposed chip, which is faster than our previously proposed chip at the same conditions. Moreover, an immunoassay of bovine serum albumin (BSA and anti-BSA was carried out to demonstrate the applicability of the proposed chip.

  18. Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function.

    Science.gov (United States)

    Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina

    2016-02-01

    A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Rectified tunneling current response of bio-functionalized metal-bridge-metal junctions.

    Science.gov (United States)

    Liu, Yaqing; Offenhäusser, Andreas; Mayer, Dirk

    2010-01-15

    Biomolecular bridged nanostructures allow direct electrical addressing of electroactive biomolecules, which is of interest for the development of bioelectronic and biosensing hybrid junctions. In the present paper, the electroactive biomolecule microperoxidase-11 (MP-11) was integrated into metal-bridge-metal (MBM) junctions assembled from a scanning tunneling microscope (STM) setup. Before immobilization of MP-11, the Au working electrode was first modified by a self-assembled monolayer of 1-undecanethiol (UDT). A symmetric and potential independent response of current-bias voltage (I(t)/V(b)) was observed for the Au (substrate)/UDT/Au (tip) junction. However, the I(t)/V(b) characteristics became potential dependent and asymmetrical after binding of MP-11 between the electrodes of the junction. The rectification ratio of the asymmetric current response varies with gate electrode modulation. A resonant tunneling process between metal electrode and MP-11 enhances the tunneling current and is responsible for the observed rectification. Our investigations demonstrated that functional building blocks of proteins can be reassembled into new conceptual devices with operation modes deviating from their native function, which could prove highly useful in the design of future biosensors and bioelectronic devices. Copyright 2009 Elsevier B.V. All rights reserved.

  20. The Mammalian Cell Cycle Regulates Parvovirus Nuclear Capsid Assembly

    Science.gov (United States)

    Riolobos, Laura; Domínguez, Carlos; Kann, Michael; Almendral, José M.

    2015-01-01

    It is unknown whether the mammalian cell cycle could impact the assembly of viruses maturing in the nucleus. We addressed this question using MVM, a reference member of the icosahedral ssDNA nuclear parvoviruses, which requires cell proliferation to infect by mechanisms partly understood. Constitutively expressed MVM capsid subunits (VPs) accumulated in the cytoplasm of mouse and human fibroblasts synchronized at G0, G1, and G1/S transition. Upon arrest release, VPs translocated to the nucleus as cells entered S phase, at efficiencies relying on cell origin and arrest method, and immediately assembled into capsids. In synchronously infected cells, the consecutive virus life cycle steps (gene expression, proteins nuclear translocation, capsid assembly, genome replication and encapsidation) proceeded tightly coupled to cell cycle progression from G0/G1 through S into G2 phase. However, a DNA synthesis stress caused by thymidine irreversibly disrupted virus life cycle, as VPs became increasingly retained in the cytoplasm hours post-stress, forming empty capsids in mouse fibroblasts, thereby impairing encapsidation of the nuclear viral DNA replicative intermediates. Synchronously infected cells subjected to density-arrest signals while traversing early S phase also blocked VPs transport, resulting in a similar misplaced cytoplasmic capsid assembly in mouse fibroblasts. In contrast, thymidine and density arrest signals deregulating virus assembly neither perturbed nuclear translocation of the NS1 protein nor viral genome replication occurring under S/G2 cycle arrest. An underlying mechanism of cell cycle control was identified in the nuclear translocation of phosphorylated VPs trimeric assembly intermediates, which accessed a non-conserved route distinct from the importin α2/β1 and transportin pathways. The exquisite cell cycle-dependence of parvovirus nuclear capsid assembly conforms a novel paradigm of time and functional coupling between cellular and virus life

  1. Prime tight frames

    DEFF Research Database (Denmark)

    Lemvig, Jakob; Miller, Christopher; Okoudjou, Kasso A.

    2014-01-01

    to suggest effective analysis and synthesis computation strategies for such frames. Finally, we describe all prime frames constructed from the spectral tetris method, and, as a byproduct, we obtain a characterization of when the spectral tetris construction works for redundancies below two.......We introduce a class of finite tight frames called prime tight frames and prove some of their elementary properties. In particular, we show that any finite tight frame can be written as a union of prime tight frames. We then characterize all prime harmonic tight frames and use thischaracterization...

  2. Fabrication of TiO{sub 2} hierarchical architecture assembled by nanowires with anatase/TiO{sub 2}(B) phase-junctions for efficient photocatalytic hydrogen production

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Yong; Ouyang, Feng, E-mail: ouyangfh@hit.edu.cn

    2017-05-01

    Highlights: • H-titanate nanowires hierarchical architectures (TNH) were prepared by a hydrothermal method. • Calcinations of TNH leads to the formation of anatase/TiO{sub 2}(B) phase-junctions. • The hierarchical architecture offered enhanced light harvesting and large specific surface area. • The 1D nanowires and anatase/TiO{sub 2}(B) phase-junctions both can enhance the separation of photoinduced electron-hole. • The products calcined at the optimum conditions (450 °C) exhibited a maximum hydrogenproduction rate of 7808 μmol g{sup −1} h{sup −1}. - Abstract: TiO{sub 2} hierarchical architecture assembled by nanowires with anatase/TiO{sub 2}(B) phase-junctions was prepared by a hydrothermal process followed by calcinations. The optimum calcination treatment (450 °C) not only led to the formation of anatase/TiO{sub 2}(B) phase-junctions, but also kept the morphology of 1D nanowire and hierarchical architecture well. The T-450 load 0.5 wt% Pt cocatalysts showed the best photocatalytic hydrogen production activity, with a maximum hydrogen production rate of 7808 μmol g{sup −1} h{sup −1}. The high photocatalytic activity is ascribed to the combined effects of the following three factors: (1) the hierarchical architecture exhibits better light harvesting; (2) the larger specific surface area provides more surface active sites for the photocatalytic reaction; (3) the 1D nanowires and anatase/TiO{sub 2}(B) phase-junctions both can enhance the separation of photoinduced electron-hole pairs and inhibit their recombination.

  3. Assembly tool design

    International Nuclear Information System (INIS)

    Kanamori, Naokazu; Nakahira, Masataka; Ohkawa, Yoshinao; Tada, Eisuke; Seki, Masahiro

    1996-06-01

    The reactor core of the International Thermonuclear Experimental Reactor (ITER) is assembled with a number of large and asymmetric components within a tight tolerance in order to assure the structural integrity for various loads and to provide the tritium confinement. In addition, the assembly procedure should be compatible with remote operation since the core structures will be activated by 14-MeV neutrons once it starts operation and thus personal access will be prohibited. Accordingly, the assembly procedure and tool design are quite essential and should be designed from the beginning to facilitate remote operation. According to the ITER Design Task Agreement, the Japan Atomic Energy Research Institute (JAERI) has performed design study to develop the assembly procedures and associated tool design for the ITER tokamak assembly. This report describes outlines of the assembly tools and the remaining issues obtained in this design study. (author)

  4. Protective Effect of 1,25-Dihydroxy Vitamin D3 on Pepsin-Trypsin-Resistant Gliadin-Induced Tight Junction Injuries.

    Science.gov (United States)

    Dong, Shouquan; Singh, Tikka Prabhjot; Wei, Xin; Yao, Huang; Wang, Hongling

    2018-01-01

    Tight junction (TJ) injuries induced by pepsin-trypsin-resistant gliadin (PT-G) play an important role in the pathogenesis of celiac disease. Previously, 1,25-dihydroxy vitamin D3 (VD3) was reported to be a TJ regulator that attenuates lipopolysaccharide- and alcohol-induced TJ injuries. However, whether VD3 can attenuate PT-G-induced TJ injuries is unknown. The aim of this study was to evaluate the effects of VD3 on PT-G-induced TJ injuries. Caco-2 monolayers were used as in vitro models. After being cultured for 21 days, the monolayers were treated with PT-G plus different concentrations of VD3. Then, the changes in trans-epithelial electrical resistance and FITC-dextran 4000 (FD-4) flux were determined to evaluate the monolayer barrier function. TJ protein levels were measured to assess TJ injury severity, and myeloid differentiation factor 88 (MyD88) expression and zonulin release levels were determined to estimate zonulin release signaling pathway activity. Additionally, a gluten-sensitized mouse model was established as an in vivo model. After the mice were treated with VD3 for 7 days, we measured serum FD-4 concentrations, TJ protein levels, MyD88 expression, and zonulin release levels to confirm the effect of VD3. Both in vitro and in vivo, VD3 significantly attenuated the TJ injury-related increase in intestinal mucosa barrier permeability. Moreover, VD3 treatment up-regulated TJ protein expression levels and significantly decreased MyD88 expression and zonulin release levels. VD3 has protective effects against PT-G-induced TJ injuries both in vitro and in vivo, which may correlate with the disturbance of the MyD88-dependent zonulin release signaling pathway.

  5. Faucet: streaming de novo assembly graph construction.

    Science.gov (United States)

    Rozov, Roye; Goldshlager, Gil; Halperin, Eran; Shamir, Ron

    2018-01-01

    We present Faucet, a two-pass streaming algorithm for assembly graph construction. Faucet builds an assembly graph incrementally as each read is processed. Thus, reads need not be stored locally, as they can be processed while downloading data and then discarded. We demonstrate this functionality by performing streaming graph assembly of publicly available data, and observe that the ratio of disk use to raw data size decreases as coverage is increased. Faucet pairs the de Bruijn graph obtained from the reads with additional meta-data derived from them. We show these metadata-coverage counts collected at junction k-mers and connections bridging between junction pairs-contain most salient information needed for assembly, and demonstrate they enable cleaning of metagenome assembly graphs, greatly improving contiguity while maintaining accuracy. We compared Fauceted resource use and assembly quality to state of the art metagenome assemblers, as well as leading resource-efficient genome assemblers. Faucet used orders of magnitude less time and disk space than the specialized metagenome assemblers MetaSPAdes and Megahit, while also improving on their memory use; this broadly matched performance of other assemblers optimizing resource efficiency-namely, Minia and LightAssembler. However, on metagenomes tested, Faucet,o outputs had 14-110% higher mean NGA50 lengths compared with Minia, and 2- to 11-fold higher mean NGA50 lengths compared with LightAssembler, the only other streaming assembler available. Faucet is available at https://github.com/Shamir-Lab/Faucet. rshamir@tau.ac.il or eranhalperin@gmail.com. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press.

  6. [Effect of eicosapentaenoic acid on mRNA expression of tight junction protein ZO-1 in intestinal epithelial cells after Escherichia coli LF82 infection].

    Science.gov (United States)

    Hao, Li-Jun; Lin, Yan; Zhang, Wei; Tian, Jiao; Wang, Ya; Chen, Peng-De; Hu, Chong-Kang; Zeng, Ling-Chao; Yang, Jie; Wang, Bao-Xi; Jiang, Xun

    2017-06-01

    To investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection. The Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant. After EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (PE.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (PE.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (PE.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated

  7. Virus interaction with the apical junctional complex.

    Science.gov (United States)

    Gonzalez-Mariscal, Lorenza; Garay, Erika; Lechuga, Susana

    2009-01-01

    In order to infect pathogens must breach the epithelial barriers that separate the organism from the external environment or that cover the internal cavities and ducts of the body. Epithelia seal the passage through the paracellular pathway with the apical junctional complex integrated by tight and adherens junctions. In this review we describe how viruses like coxsackie, swine vesicular disease virus, adenovirus, reovirus, feline calcivirus, herpes viruses 1 and 2, pseudorabies, bovine herpes virus 1, poliovirus and hepatitis C use as cellular receptors integral proteins present at the AJC of epithelial cells. Interaction with these proteins contributes in a significant manner in defining the particular tropism of each virus. Besides these proteins, viruses exhibit a wide range of cellular co-receptors among which proteins present in the basolateral cell surface like integrins are often found. Therefore targeting proteins of the AJC constitutes a strategy that might allow viruses to bypass the physical barrier that blocks their access to receptors expressed on the basolateral surface of epithelial cells.

  8. Construction of van der Waals magnetic tunnel junction using ferromagnetic layered dichalcogenide

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Miho; Moriya, Rai, E-mail: moriyar@iis.u-tokyo.ac.jp; Yabuki, Naoto; Masubuchi, Satoru [Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8505 (Japan); Ueno, Keiji [Department of Chemistry, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570 (Japan); Machida, Tomoki, E-mail: tmachida@iis.u-tokyo.ac.jp [Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8505 (Japan); Institute for Nano Quantum Information Electronics, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8505 (Japan)

    2015-09-07

    We investigate the micromechanical exfoliation and van der Waals (vdW) assembly of ferromagnetic layered dichalcogenide Fe{sub 0.25}TaS{sub 2}. The vdW interlayer coupling at the Fe-intercalated plane of Fe{sub 0.25}TaS{sub 2} allows exfoliation of flakes. A vdW junction between the cleaved crystal surfaces is constructed by dry transfer method. We observe tunnel magnetoresistance in the resulting junction under an external magnetic field applied perpendicular to the plane, demonstrating spin-polarized tunneling between the ferromagnetic layered material and the vdW junction.

  9. Thermoelectric generator with hinged assembly for fins

    International Nuclear Information System (INIS)

    Purdy, D.L.; Shapiro, Z.M.; Hursen, T.F.; Maurer, G.W.

    1976-01-01

    A cylindrical casing has a central shielded capsule of radioisotope fuel. A plurality of thermonuclear modules are axially arranged with their hot junctions resiliently pressed toward the shield and with their cold junctions adjacent a transition member having fins radiating heat to the environment. For each module, the assembly of transition member and fins is hinged to the casing for swinging to permit access to and removal of such module. A ceramic plate having gold layers on opposite faces prevents diffusion bonding of the hot junction to the shield

  10. Fabrication and characterization of graphene/molecule/graphene vertical junctions with aryl alkane monolayers

    Science.gov (United States)

    Jeong, Inho; Song, Hyunwook

    2017-11-01

    In this study, we fabricated and characterized graphene/molecule/graphene (GMG) vertical junctions with aryl alkane monolayers. The constituent molecules were chemically self-assembled via electrophilic diazonium reactions into a monolayer on the graphene bottom electrode, while the other end physically contacted the graphene top electrode. A full understanding of the transport properties of molecular junctions is a key step in the realization of molecular-scale electronic devices and requires detailed microscopic characterization of the junction's active region. Using a multiprobe approach combining a variety of transport techniques, we elucidated the transport mechanisms and electronic structure of the GMG junctions, including temperature- and length-variable transport measurements, and transition voltage spectroscopy. These results provide criteria to establish a valid molecular junction and to determine the most probable transport characteristics of the GMG junctions.

  11. Rectification of Current Responds to Incorporation of Fullerenes into Mixed-Monolayers of Alkanethiolates in Tunneling Junctions

    NARCIS (Netherlands)

    Qiu, Li; Zhang, Yanxi; Krijger, Theodorus; Qiu, Xinkai; van 't Hof, Patrick; Hummelen, Jan; Chiechi, Ryan

    2016-01-01

    This paper describes the rectification of current through molecular junctions comprising self-assembled monolayers of decanethiolate through the incorporation of C60 fullerene moieties bearing undecanethiol groups in junctions using eutectic Ga–In (EGaIn) and Au conducting probe AFM (CP-AFM)

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

    Science.gov (United States)

    Lechuga, Susana; Ivanov, Andrei I

    2017-07-01

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

  13. Garlic (Allium sativum) feeding impairs Sertoli cell junctional proteins in male Wistar rat testis: microscopy study.

    Science.gov (United States)

    Hammami, I; Nahdi, A; Atig, F; El May, A; El May, M V

    2016-12-01

    Sertoli cell junctions, such as adhesion junction (AJ), gap junction (GJ) and tight junction (TJ), are important for maintaining spermatogenesis. In previous studies, we showed the inhibitory effect of crude garlic (Allium sativum, As) on spermatogenesis and steroidogenesis. The aim of this work was to complete our investigation on the impact of this plant, especially on Sertoli cell junctional proteins (SCJPs). During 1 month, 24 male rats were divided into groups: group control (0% of As) and treated groups fed 5%, 10% and 15% of As. Light and electron microscopy observations were performed to localise junctional proteins: connexin-43, Zona Occluding-1 and N-cadherin (immunohistochemistry) and to describe junctions. We showed that the specific cells involved in the localisation of the SCJP were similar in both control and treated groups, but with different immunoreactivity intensity between them. The electron microscopy observation focused on TJs between Sertoli cells, constituting the blood-testis barrier, showed ultrastructural changes such as fragmentation of TJs between adjacent Sertoli cell membranes and dilatation of rough endoplasmic reticulum saccules giving an aspect of scale to these junctions. We concluded that crude garlic consumption during 1 month induces perturbations on Sertoli cell junctions. These alterations can explain apoptosis in testicular germ cells previously showed. © 2016 Blackwell Verlag GmbH.

  14. Ultrathin reduced graphene oxide films as transparent top-contacts for light switchable solid-state molecular junctions

    DEFF Research Database (Denmark)

    Li, Tao; Jevric, Martyn; Hauptmann, Jonas Rahlf

    2013-01-01

    A new type of solid-state molecular junction is introduced, which employs reduced graphene oxide as a transparent top contact that permits a self-assembled molecular monolayer to be photoswitched in situ, while simultaneously enabling charge-transport measurements across the molecules. The electr......A new type of solid-state molecular junction is introduced, which employs reduced graphene oxide as a transparent top contact that permits a self-assembled molecular monolayer to be photoswitched in situ, while simultaneously enabling charge-transport measurements across the molecules...

  15. 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.

  16. Fuel assembly leak tightness control on WWER-1000 reactor

    International Nuclear Information System (INIS)

    Ivanova, R.; Gerchev, N.; Mateev, A.

    2001-01-01

    The main index for integrity of the fuel rods cladding is the specific activity value of the primary coolant. This value determines the safe operation of the reactor. The limit for safe operation of WWER-1000 reactor is the value of the total activity of Iodine isotopes in the primary coolant 5.0x10 -3 Ci/l. The paper briefly describes the methodology for performing a fuel tightness test (sipping test) and shows the results from these tests performed during the period 1987 -1999 in units 5 and 6 at the Kozloduy NPP. An additional index related to the safe operation is defined to characterize the fuel cladding integrity Fuel Reliability Index (FRI). The FRI is defined as value of the average activity of 131 I in the primary coolant, corrected with a part of precipitated 235 U migration and fixed to the general permanent purification frequency. Two criteria (quantitative and statistic) are determined to qualify the fuel cladding integrity. The results from sipping tests show good reliability of the fuel irradiated in unit 5 and 6 at the Kozloduy NPP

  17. Less-Tight versus Tight Control of Hypertension in Pregnancy

    NARCIS (Netherlands)

    Magee, Laura A.; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E.; Menzies, Jennifer; Sanchez, Johanna; Singer, Joel; Gafni, Amiram; Gruslin, Andrée; Helewa, Michael; Hutton, Eileen; Lee, Shoo K.; Lee, Terry; Logan, Alexander G.; Ganzevoort, Wessel; Welch, Ross; Thornton, Jim G.; Moutquin, Jean-Marie

    2015-01-01

    BACKGROUND The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear. METHODS We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational

  18. Modular Nuclease-Responsive DNA Three-Way Junction-Based Dynamic Assembly of a DNA Device and Its Sensing Application.

    Science.gov (United States)

    Zhu, Jing; Wang, Lei; Xu, Xiaowen; Wei, Haiping; Jiang, Wei

    2016-04-05

    Here, we explored a modular strategy for rational design of nuclease-responsive three-way junctions (TWJs) and fabricated a dynamic DNA device in a "plug-and-play" fashion. First, inactivated TWJs were designed, which contained three functional domains: the inaccessible toehold and branch migration domains, the specific sites of nucleases, and the auxiliary complementary sequence. The actions of different nucleases on their specific sites in TWJs caused the close proximity of the same toehold and branch migration domains, resulting in the activation of the TWJs and the formation of a universal trigger for the subsequent dynamic assembly. Second, two hairpins (H1 and H2) were introduced, which could coexist in a metastable state, initially to act as the components for the dynamic assembly. Once the trigger initiated the opening of H1 via TWJs-driven strand displacement, the cascade hybridization of hairpins immediately switched on, resulting in the formation of the concatemers of H1/H2 complex appending numerous integrated G-quadruplexes, which were used to obtain label-free signal readout. The inherent modularity of this design allowed us to fabricate a flexible DNA dynamic device and detect multiple nucleases through altering the recognition pattern slightly. Taking uracil-DNA glycosylase and CpG methyltransferase M.SssI as models, we successfully realized the butt joint between the uracil-DNA glycosylase and M.SssI recognition events and the dynamic assembly process. Furthermore, we achieved ultrasensitive assay of nuclease activity and the inhibitor screening. The DNA device proposed here will offer an adaptive and flexible tool for clinical diagnosis and anticancer drug discovery.

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

    International Nuclear Information System (INIS)

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

    2017-01-01

    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 (40 μM, 12 h) 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 (5–10 mM, 1 h) 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. Characterization of the Tetraspan Junctional Complex (4JC) superfamily.

    Science.gov (United States)

    Chou, Amy; Lee, Andre; Hendargo, Kevin J; Reddy, Vamsee S; Shlykov, Maksim A; Kuppusamykrishnan, Harikrishnan; Medrano-Soto, Arturo; Saier, Milton H

    2017-03-01

    Connexins or innexins form gap junctions, while claudins and occludins form tight junctions. In this study, statistical data, derived using novel software, indicate that these four junctional protein families and eleven other families of channel and channel auxiliary proteins are related by common descent and comprise the Tetraspan (4 TMS) Junctional Complex (4JC) Superfamily. These proteins all share similar 4 transmembrane α-helical (TMS) topologies. Evidence is presented that they arose via an intragenic duplication event, whereby a 2 TMS-encoding genetic element duplicated tandemly to give 4 TMS proteins. In cases where high resolution structural data were available, the conclusion of homology was supported by conducting structural comparisons. Phylogenetic trees reveal the probable relationships of these 15 families to each other. Long homologues containing fusions to other recognizable domains as well as internally duplicated or fused domains are reported. Large "fusion" proteins containing 4JC domains proved to fall predominantly into family-specific patterns as follows: (1) the 4JC domain was N-terminal; (2) the 4JC domain was C-terminal; (3) the 4JC domain was duplicated or occasionally triplicated and (4) mixed fusion types were present. Our observations provide insight into the evolutionary origins and subfunctions of these proteins as well as guides concerning their structural and functional relationships. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Oscillating Magnetoresistance in Graphene p-n Junctions at Intermediate Magnetic Fields.

    Science.gov (United States)

    Overweg, Hiske; Eggimann, Hannah; Liu, Ming-Hao; Varlet, Anastasia; Eich, Marius; Simonet, Pauline; Lee, Yongjin; Watanabe, Kenji; Taniguchi, Takashi; Richter, Klaus; Fal'ko, Vladimir I; Ensslin, Klaus; Ihn, Thomas

    2017-05-10

    We report on the observation of magnetoresistance oscillations in graphene p-n junctions. The oscillations have been observed for six samples, consisting of single-layer and bilayer graphene, and persist up to temperatures of 30 K, where standard Shubnikov-de Haas oscillations are no longer discernible. The oscillatory magnetoresistance can be reproduced by tight-binding simulations. We attribute this phenomenon to the modulated densities of states in the n- and p-regions.

  2. Self-limited plasmonic welding of silver nanowire junctions

    KAUST Repository

    Garnett, Erik C.

    2012-02-05

    Nanoscience provides many strategies to construct high-performance materials and devices, including solar cells, thermoelectrics, sensors, transistors, and transparent electrodes. Bottom-up fabrication facilitates large-scale chemical synthesis without the need for patterning and etching processes that waste material and create surface defects. However, assembly and contacting procedures still require further development. Here, we demonstrate a light-induced plasmonic nanowelding technique to assemble metallic nanowires into large interconnected networks. The small gaps that form naturally at nanowire junctions enable effective light concentration and heating at the point where the wires need to be joined together. The extreme sensitivity of the heating efficiency on the junction geometry causes the welding process to self-limit when a physical connection between the wires is made. The localized nature of the heating prevents damage to low-thermal-budget substrates such as plastics and polymer solar cells. This work opens new avenues to control light, heat and mass transport at the nanoscale. © 2012 Macmillan Publishers Limited. All rights reserved.

  3. 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

  4. Automated Array Assembly, Phase 2. Quarterly technical progress report, April-June 1979

    Energy Technology Data Exchange (ETDEWEB)

    Carbajal, B.G.

    1979-07-01

    The Automated Array Assembly Task, Phase 2 of the Low Cost Solar Array (LSA) Project is a process development task. This contract provides for the fabrication of modules from large area Tandem Junction Cells (TJC). The key activities in this contract effort are (a) Large Area TJC including cell design, process verification and cell fabrication and (b) Tandem Junction Module (TJM) including definition of the cell-module interfaces, substrate fabrication, interconnect fabrication and module assembly. The overall goal is to advance solar cell module process technology to meet the 1986 goal of a production capability of 500 megawatts per year at a cost of less than $500 per peak kilowatt. This contract will focus on the Tandem Junction Module process. During this quarter, effort was focused on design and process verification. The large area TJC design was completed and the design verification was completed. Process variation experiments led to refinements in the baseline TJC process. Formed steel substrates were porcelainized. Cell array assembly techniques using infrared soldering are being checked out. Dummy cell arrays up to 5 cell by 5 cell have been assembled using all backside contacts.

  5. The distribution of work performed on a NIS junction

    DEFF Research Database (Denmark)

    Santos, Jaime Eduardo Vieira da Silva Moutinho; Ribeiro, Pedro; Kirchner, Stefan

    2016-01-01

    We propose an experimental setup to measure the work performed in a normal-metal/insulator/superconducting (NIS) junction, subjected to a voltage change and in contact with a thermal bath. We compute the performed work and argue that the associated heat release can be measured experimentally. Our...... results are based on an equivalence between the dynamics of the NIS junction and that of an assembly of two-level systems subjected to a circularly polarised field, for which we can determine the work-characteristic function exactly. The average work dissipated by the NIS junction, as well as its...... fluctuations, are determined. From the work characteristic function, we also compute the work probability-distribution and show that it does not have a Gaussian character. Our results allow for a direct experimental test of the Crooks–Tasaki fluctuation relation....

  6. The distribution of work performed on a NIS junction

    International Nuclear Information System (INIS)

    Santos, Jaime E; Ribeiro, Pedro; Kirchner, Stefan

    2016-01-01

    We propose an experimental setup to measure the work performed in a normal-metal/insulator/superconducting (NIS) junction, subjected to a voltage change and in contact with a thermal bath. We compute the performed work and argue that the associated heat release can be measured experimentally. Our results are based on an equivalence between the dynamics of the NIS junction and that of an assembly of two-level systems subjected to a circularly polarised field, for which we can determine the work-characteristic function exactly. The average work dissipated by the NIS junction, as well as its fluctuations, are determined. From the work characteristic function, we also compute the work probability-distribution and show that it does not have a Gaussian character. Our results allow for a direct experimental test of the Crooks–Tasaki fluctuation relation. (paper)

  7. DNA Self-Assembly: From Chirality to Evolution

    Directory of Open Access Journals (Sweden)

    Youri Timsit

    2013-04-01

    Full Text Available Transient or long-term DNA self-assembly participates in essential genetic functions. The present review focuses on tight DNA-DNA interactions that have recently been found to play important roles in both controlling DNA higher-order structures and their topology. Due to their chirality, double helices are tightly packed into stable right-handed crossovers. Simple packing rules that are imposed by DNA geometry and sequence dictate the overall architecture of higher order DNA structures. Close DNA-DNA interactions also provide the missing link between local interactions and DNA topology, thus explaining how type II DNA topoisomerases may sense locally the global topology. Finally this paper proposes that through its influence on DNA self-assembled structures, DNA chirality played a critical role during the early steps of evolution.

  8. Molecular series-tunneling junctions.

    Science.gov (United States)

    Liao, Kung-Ching; Hsu, Liang-Yan; Bowers, Carleen M; Rabitz, Herschel; Whitesides, George M

    2015-05-13

    Charge transport through junctions consisting of insulating molecular units is a quantum phenomenon that cannot be described adequately by classical circuit laws. This paper explores tunneling current densities in self-assembled monolayer (SAM)-based junctions with the structure Ag(TS)/O2C-R1-R2-H//Ga2O3/EGaIn, where Ag(TS) is template-stripped silver and EGaIn is the eutectic alloy of gallium and indium; R1 and R2 refer to two classes of insulating molecular units-(CH2)n and (C6H4)m-that are connected in series and have different tunneling decay constants in the Simmons equation. These junctions can be analyzed as a form of series-tunneling junctions based on the observation that permuting the order of R1 and R2 in the junction does not alter the overall rate of charge transport. By using the Ag/O2C interface, this system decouples the highest occupied molecular orbital (HOMO, which is localized on the carboxylate group) from strong interactions with the R1 and R2 units. The differences in rates of tunneling are thus determined by the electronic structure of the groups R1 and R2; these differences are not influenced by the order of R1 and R2 in the SAM. In an electrical potential model that rationalizes this observation, R1 and R2 contribute independently to the height of the barrier. This model explicitly assumes that contributions to rates of tunneling from the Ag(TS)/O2C and H//Ga2O3 interfaces are constant across the series examined. The current density of these series-tunneling junctions can be described by J(V) = J0(V) exp(-β1d1 - β2d2), where J(V) is the current density (A/cm(2)) at applied voltage V and βi and di are the parameters describing the attenuation of the tunneling current through a rectangular tunneling barrier, with width d and a height related to the attenuation factor β.

  9. The Performance of Calcium Silicate Board Partition Fireproof Drywall Assembly with Junction Box under Fire

    Directory of Open Access Journals (Sweden)

    Yinuo Wang

    2015-01-01

    Full Text Available This study uses a metal stud partition fireproof drywall measuring 83 mm in thickness as a test specimen to explore the impact of an embedded junction box on the firefighting performance of the wall through one time of standard fire test on a 300 cm × 300 cm area and five times of standard fire test on a 120 cm × 120 cm area. The results show that the quality of calcium silicate board plays a big role in the fireproof effectiveness. The embedded junction box located on the backside of the fire can reduce the effectiveness of the wall, especially the area above the socket. The thickness of rock wool may increase the performance, but in a limited rate. External junction box may not impact the fireproofing performance of the wall but it still possesses some safety risks. An embedded junction box measuring 101 × 55 mm could already damage the fire compartment, and in reality there may be more complicated situations that should be noted and improved.

  10. Methamphetamine transiently increases the blood-brain barrier permeability in the hippocampus: role of tight junction proteins and matrix metalloproteinase-9.

    Science.gov (United States)

    Martins, Tânia; Baptista, Sofia; Gonçalves, Joana; Leal, Ermelindo; Milhazes, Nuno; Borges, Fernanda; Ribeiro, Carlos F; Quintela, Oscar; Lendoiro, Elena; López-Rivadulla, Manuel; Ambrósio, António F; Silva, Ana P

    2011-09-09

    Methamphetamine (METH) is a powerful stimulant drug of abuse that has steadily gained popularity worldwide. It is known that METH is highly neurotoxic and causes irreversible damage of brain cells leading to neurological and psychiatric abnormalities. Recent studies suggested that METH-induced neurotoxicity might also result from its ability to compromise blood-brain barrier (BBB) function. Due to the crucial role of BBB in the maintenance of brain homeostasis and protection against toxic molecules and pathogenic organisms, its dysfunction could have severe consequences. In this study, we investigated the effect of an acute high dose of METH (30mg/kg) on BBB permeability after different time points and in different brain regions. For that, young adult mice were sacrificed 1h, 24h or 72h post-METH administration. METH increased BBB permeability, but this effect was detected only at 24h after administration, being therefore a transitory effect. Interestingly, we also found that the hippocampus was the most susceptible brain region to METH, comparing to frontal cortex and striatum. Moreover, in an attempt to identify the key players in METH-induced BBB dysfunction we further investigated potential alterations in tight junction (TJ) proteins and matrix metalloproteinase-9 (MMP-9). METH was able to decrease the protein levels of zonula occludens (ZO)-1, claudin-5 and occludin in the hippocampus 24h post-injection, and increased the activity and immunoreactivity of MMP-9. The pre-treatment with BB-94 (30mg/kg), a matrix metalloproteinase inhibitor, prevented the METH-induced increase in MMP-9 immunoreactivity in the hippocampus. Overall, the present data demonstrate that METH transiently increases the BBB permeability in the hippocampus, which can be explained by alterations on TJ proteins and MMP-9. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma.

    Science.gov (United States)

    Babkair, Hamzah; Yamazaki, Manabu; Uddin, Md Shihab; Maruyama, Satoshi; Abé, Tatsuya; Essa, Ahmed; Sumita, Yoshimasa; Ahsan, Md Shahidul; Swelam, Wael; Cheng, Jun; Saku, Takashi

    2016-11-01

    We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction (TJ) molecules in oral carcinoma in situ (CIS) and squamous cell carcinoma (SCC). To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS. We used immunofluorescence, Western blotting, reverse-transcription polymerase chain reaction, and RNA interference to evaluate the functions of CLDN-1 and ZO-1 in cultured oral SCC cells. TJ molecules were not detected in normal oral epithelial tissues but were expressed in SCC/CIS cells. ZO-1 was localized within the nucleus of proliferating cells. When CLDN-1 expression was inhibited by transfecting cells with specific small interference RNAs, SCC cells dissociated, and their ability to proliferate and invade Matrigel was inhibited. In contrast, although RNA interference-mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Simulations of signal amplification and oscillations using a SNS junction

    International Nuclear Information System (INIS)

    Luiz, A.M.; Soares, V.; Nicolsky, R.

    1998-01-01

    A superconducting - normal metal - superconducting junction (SNS junction) may exhibit a low voltage negative differential resistance (LVNDR) effect over part of its current voltage characteristic (CVC). As the LVNDR effect is stable against a bias voltage at this CVC range, it should be possible to combine a SNS junction with conventional electronic circuits to obtain electronic devices such as mixers, amplifiers and oscillators. Making use of this remarkable effect, we show that an amplifier may be feasible by assembling a simple voltage divider made up of a SNS junction in series with a resistor. The amplifier circuit includes an adjustable DC voltage supply (the bias voltage) and an AC signal source with a given voltage. The SNS junction is connected in series with a resistor R. Choosing values of the load resistance R approximately equal to the module of the negative differential resistance (dV/dI), at the bias voltage, we may obtain large gains in this amplifier device. In order to get an oscillator, the SNS junction should be connected to a RLC tank circuit with a bias voltage adjusted in the range of the LVNDR region of its CVC. A power output of the order of one microwatt may be easily obtained. (orig.)

  13. 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

    Directory of Open Access Journals (Sweden)

    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

  14. Cardiotonic steroid ouabain stimulates expression of blood-testis barrier proteins claudin-1 and -11 and formation of tight junctions in Sertoli cells.

    Science.gov (United States)

    Dietze, Raimund; Shihan, Mazen; Stammler, Angelika; Konrad, Lutz; Scheiner-Bobis, Georgios

    2015-04-15

    The interaction of ouabain with the sodium pump induces signalling cascades resembling those triggered by hormone/receptor interactions. In the rat Sertoli cell line 93RS2, ouabain at low concentrations stimulates the c-Src/c-Raf/Erk1/2 signalling cascade via its interaction with the α4 isoform of the sodium pump expressed in these cells, leading to the activation of the transcription factor CREB. As a result of this signalling sequence, ouabain stimulates expression of claudin-1 and claudin-11, which are also controlled by a CRE promoter. Both of these proteins are known to be essential constituents of tight junctions (TJ) between Sertoli cells, and as a result of the ouabain-induced signalling TJ formation between neighbouring Sertoli cells is significantly enhanced by the steroid. Thus, ouabain-treated cell monolayers display higher transepithelial resistance and reduced free diffusion of FITC-coupled dextran in tracer diffusion assays. Taking into consideration that the formation of TJ is indispensable for the maintenance of the blood-testis barrier (BTB) and therefore for male fertility, the actions of ouabain described here and the fact that this and other related cardiotonic steroids (CTS) are produced endogenously suggest a direct influence of ouabain/sodium pump interactions on the maintenance of the BTB and thereby an effect on male fertility. Since claudin-1 and claudin-11 are also present in other blood-tissue barriers, one can speculate that ouabain and perhaps other CTS influence the dynamics of these barriers as well. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Scaffolding proteins in the development and maintenance of the epidermal permeability barrier.

    Science.gov (United States)

    Crawford, Melissa; Dagnino, Lina

    2017-10-02

    The skin of mammals and other terrestrial vertebrates protects the organism against the external environment, preventing heat, water and electrolyte loss, as well as entry of chemicals and pathogens. Impairments in the epidermal permeability barrier function are associated with the genesis and/or progression of a variety of pathological conditions, including genetic inflammatory diseases, microbial and viral infections, and photodamage induced by UV radiation. In mammals, the outside-in epidermal permeability barrier is provided by the joint action of the outermost cornified layer, together with assembled tight junctions in granular keratinocytes found in the layers underneath. Tight junctions serve as both outside-in and inside-out barriers, and impede paracellular movements of ions, water, macromolecules and microorganisms. At the molecular level, tight junctions consist of integral membrane proteins that form an extracellular seal between adjacent cells, and associate with cytoplasmic scaffold proteins that serve as links with the actin cytoskeleton. In this review, we address the roles that scaffold proteins play specifically in the establishment and maintenance of the epidermal permeability barrier, and how various pathologies alter or impair their functions.

  16. Expression pattern of adhesion molecules in junctional epithelium differs from that in other gingival epithelia.

    Science.gov (United States)

    Hatakeyama, S; Yaegashi, T; Oikawa, Y; Fujiwara, H; Mikami, T; Takeda, Y; Satoh, M

    2006-08-01

    The gingival epithelium is the physiologically important interface between the bacterially colonized gingival sulcus and periodontal soft and mineralized connective tissues, requiring protection from exposure to bacteria and their products. However, of the three epithelia comprising the gingival epithelium, the junctional epithelium has much wider intercellular spaces than the sulcular epithelium and oral gingival epithelium. Hence, the aim of the present study was to characterize the cell adhesion structure in the junctional epithelium compared with the other two epithelia. Gingival epithelia excised at therapeutic flap surgery from patients with periodontitis were examined for expression of adhesion molecules by immunofluorescence. In the oral gingival epithelium and sulcular epithelium, but not in the junctional epithelium, desmoglein 1 and 2 in cell-cell contact sites were more abundant in the upper than the suprabasal layers. E-cadherin, the main transmembranous molecule of adherens junctions, was present in spinous layers of the oral gingival epithelium and sulcular epithelium, but was scarce in the junctional epithelium. In contrast, desmoglein 3 and P-cadherin were present in all layers of the junctional epithelium as well as the oral gingival epithelium and sulcular epithelium. Connexin 43 was clearly localized to spinous layers of the oral gingival epithelium, sulcular epithelium and parts of the junctional epithelium. Claudin-1 and occludin were expressed in the cell membranes of a few superficial layers of the oral gingival epithelium. These findings indicated that the junctional epithelium contains only a few desmosomes, composed of only desmoglein 3; adherens junctions are probably absent because of defective E-cadherin. Thus, the anchoring junctions connecting junctional epithelium cells are lax, causing widened intercellular spaces. In contrast, the oral gingival epithelium, which has a few tight junctions, functions as a barrier.

  17. Self-Assembly of Hierarchical DNA Nanotube Architectures with Well-Defined Geometries.

    Science.gov (United States)

    Jorgenson, Tyler D; Mohammed, Abdul M; Agrawal, Deepak K; Schulman, Rebecca

    2017-02-28

    An essential motif for the assembly of biological materials such as actin at the scale of hundreds of nanometers and beyond is a network of one-dimensional fibers with well-defined geometry. Here, we demonstrate the programmed organization of DNA filaments into micron-scale architectures where component filaments are oriented at preprogrammed angles. We assemble L-, T-, and Y-shaped DNA origami junctions that nucleate two or three micron length DNA nanotubes at high yields. The angles between the nanotubes mirror the angles between the templates on the junctions, demonstrating that nanoscale structures can control precisely how micron-scale architectures form. The ability to precisely program filament orientation could allow the assembly of complex filament architectures in two and three dimensions, including circuit structures, bundles, and extended materials.

  18. Charge Transport Phenomena in Peptide Molecular Junctions

    International Nuclear Information System (INIS)

    Luchini, A.; Petricoin, E.F.; Geho, D.H.; Liotta, L.A.; Long, D.P.; Vaisman, I.I.

    2008-01-01

    Inelastic electron tunneling spectroscopy (IETS) is a valuable in situ spectroscopic analysis technique that provides a direct portrait of the electron transport properties of a molecular species. In the past, IETS has been applied to small molecules. Using self-assembled nano electronic junctions, IETS was performed for the first time on a large polypeptide protein peptide in the phosphorylated and native form, yielding interpretable spectra. A reproducible 10-fold shift of the I/V characteristics of the peptide was observed upon phosphorylation. Phosphorylation can be utilized as a site-specific modification to alter peptide structure and thereby influence electron transport in peptide molecular junctions. It is envisioned that kinases and phosphatases may be used to create tunable systems for molecular electronics applications, such as biosensors and memory devices.

  19. 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).

  20. Azobenzenes as light-controlled molecular electronic switches in nanoscale metal-molecule-metal junctions.

    Science.gov (United States)

    Mativetsky, Jeffrey M; Pace, Giuseppina; Elbing, Mark; Rampi, Maria A; Mayor, Marcel; Samorì, Paolo

    2008-07-23

    Conductance switching associated with the photoisomerization of azobenzene-based (Azo) molecules was observed in nanoscopic metal-molecule-metal junctions. The junctions were formed by using a conducting atomic force microscope (C-AFM) approach, where a metallic AFM tip was used to electrically contact a gold-supported Azo self-assembled monolayer. The measured 30-fold increase in conductance is consistent with the expected decrease in tunneling barrier length resulting from the conformational change of the Azo molecule.

  1. Tight closure and vanishing theorems

    International Nuclear Information System (INIS)

    Smith, K.E.

    2001-01-01

    Tight closure has become a thriving branch of commutative algebra since it was first introduced by Mel Hochster and Craig Huneke in 1986. Over the past few years, it has become increasingly clear that tight closure has deep connections with complex algebraic geometry as well, especially with those areas of algebraic geometry where vanishing theorems play a starring role. The purpose of these lectures is to introduce tight closure and to explain some of these connections with algebraic geometry. Tight closure is basically a technique for harnessing the power of the Frobenius map. The use of the Frobenius map to prove theorems about complex algebraic varieties is a familiar technique in algebraic geometry, so it should perhaps come as no surprise that tight closure is applicable to algebraic geometry. On the other hand, it seems that so far we are only seeing the tip of a large and very beautiful iceberg in terms of tight closure's interpretation and applications to algebraic geometry. Interestingly, although tight closure is a 'characteristic p' tool, many of the problems where tight closure has proved useful have also yielded to analytic (L2) techniques. Despite some striking parallels, there had been no specific result directly linking tight closure and L∼ techniques. Recently, however, the equivalence of an ideal central to the theory of tight closure was shown to be equivalent to a certain 'multiplier ideal' first defined using L2 methods. Presumably, deeper connections will continue to emerge. There are two main types of problems for which tight closure has been helpful: in identifying nice structure and in establishing uniform behavior. The original algebraic applications of tight closure include, for example, a quick proof of the Hochster-Roberts theorem on the Cohen-Macaulayness of rings of invariants, and also a refined version of the Brianqon-Skoda theorem on the uniform behaviour of integral closures of powers of ideals. More recent, geometric

  2. 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

  3. 21-Benzylidene Digoxin: A Proapoptotic Cardenolide of Cancer Cells That Up-Regulates Na,K-ATPase and Epithelial Tight Junctions

    Science.gov (United States)

    Rocha, Sayonarah C.; Pessoa, Marco T. C.; Neves, Luiza D. R.; Alves, Silmara L. G.; Silva, Luciana M.; Santos, Herica L.; Oliveira, Soraya M. F.; Taranto, Alex G.; Comar, Moacyr; Gomes, Isabella V.; Santos, Fabio V.; Paixão, Natasha; Quintas, Luis E. M.; Noël, François; Pereira, Antonio F.; Tessis, Ana C. S. C.; Gomes, Natalia L. S.; Moreira, Otacilio C.; Rincon-Heredia, Ruth; Varotti, Fernando P.; Blanco, Gustavo; Villar, Jose A. F. P.; Contreras, Rubén G.; Barbosa, Leandro A.

    2014-01-01

    Cardiotonic steroids are used to treat heart failure and arrhythmia and have promising anticancer effects. The prototypic cardiotonic steroid ouabain may also be a hormone that modulates epithelial cell adhesion. Cardiotonic steroids consist of a steroid nucleus and a lactone ring, and their biological effects depend on the binding to their receptor, Na,K-ATPase, through which, they inhibit Na+ and K+ ion transport and activate of several intracellular signaling pathways. In this study, we added a styrene group to the lactone ring of the cardiotonic steroid digoxin, to obtain 21-benzylidene digoxin (21-BD), and investigated the effects of this synthetic cardiotonic steroid in different cell models. Molecular modeling indicates that 21-BD binds to its target Na,K-ATPase with low affinity, adopting a different pharmacophoric conformation when bound to its receptor than digoxin. Accordingly, 21-DB, at relatively high µM amounts inhibits the activity of Na,K-ATPase α1, but not α2 and α3 isoforms. In addition, 21-BD targets other proteins outside the Na,K-ATPase, inhibiting the multidrug exporter Pdr5p. When used on whole cells at low µM concentrations, 21-BD produces several effects, including: 1) up-regulation of Na,K-ATPase expression and activity in HeLa and RKO cancer cells, which is not found for digoxin, 2) cell specific changes in cell viability, reducing it in HeLa and RKO cancer cells, but increasing it in normal epithelial MDCK cells, which is different from the response to digoxin, and 3) changes in cell-cell interaction, altering the molecular composition of tight junctions and elevating transepithelial electrical resistance of MDCK monolayers, an effect previously found for ouabain. These results indicate that modification of the lactone ring of digoxin provides new properties to the compound, and shows that the structural change introduced could be used for the design of cardiotonic steroid with novel functions. PMID:25290152

  4. Zinc ions regulate opening of tight junction favouring efflux of macromolecules via the GSK3β/snail-mediated pathway.

    Science.gov (United States)

    Xiao, Ruyue; Yuan, Lan; He, Weijiang; Yang, Xiaoda

    2018-01-24

    Zinc is an essential trace element presenting in particularly high concentration in the brain. In some regions, e.g. lateral amygdala, subiculum and hippocampus, rapidly-exchangeable zinc may transiently reach even up to 600 μM. To explore the possible roles of high-concentration Zn 2+ in regulating the blood-brain barrier (BBB), we investigated the effects of Zn 2+ on the functions and structures of the tight junction (TJ) with an in vitro model of a Madin-Darby canine kidney (MDCK) cell monolayer. The experimental results indicated that high concentrations (>200 μM) of Zn 2+ can affect the TJ integrity in a polarized manner. Basolateral addition of Zn 2+ led to reversible TJ opening with pore paths of r ∼ 2 nm or more depending on Zn 2+ concentration. The efflux/influx ratios of different sized probes were found to be ∼4.6 for FD4 (M W 4000) and ∼1.8 for Eu-DTPA (M W 560), suggesting that the Zn 2+ -induced paracelluar channels favour efflux especially for macromolecules. Further mechanistic studies revealed that the elevated intracellular Zn 2+ taken from the basolateral side can increase phosphorylation of glycogen synthase kinase (GSK) 3β, primarily due to the inhibition of calcineurin (CaN), thus resulting in the elevation of the snail transcriptional repressors. Subsequently, Zn 2+ can cause the down-regulation of claudin-1, breakage of occludin and ZO-1 rings, and collapse of basolateral F-actin structures. These overall factors result in the formation of a trumpet-like paracellular channel, which allows asymmetric solute permeation. The ERK1/2 and JNK1/2 pathways may also be involved in the Zn 2+ -induced TJ opening process, while the activation of matrix metalloproteinase was not observed. Our results may suggest a potential role of zinc in regulation of BBB permeability associated with brain clearance of metabolites through the glymphatic system.

  5. Electron Transport through Porphyrin Molecular Junctions

    Science.gov (United States)

    Zhou, Qi

    The goal of this work is to study the properties that would affect the electron transport through a porphyrin molecular junction. This work contributes to the field of electron transport in molecular junctions in the following 3 aspects. First of all, by carrying out experiments comparing the conductance of the iron (III) porphyrin (protected) and the free base porphyrin (protected), it is confirmed that the molecular energy level broadening and shifting occurs for porphyrin molecules when coupled with the metal electrodes, and this level broadening and shifting plays an important role in the electron transport through molecular junctions. Secondly, by carrying out an in-situ deprotection of the acetyl-protected free base porphyrin molecules, it is found out that the presence of acetyl groups reduces the conductance. Thirdly, by incorporating the Matrix-assisted laser desorption/ionization (MALDI) spectrum and the in-situ deprotection prior to formation of molecular junctions, it allows a more precise understanding of the molecules involved in the formation of molecular junctions, and therefore allows an accurate analysis of the conductance histogram. The molecules are prepared by self-assembly and the junctions are formed using a Scanning Tunneling Microscopy (STM) molecular break junction technique. The porphyrin molecules are characterized by MALDI in solution before self-assembly to a gold/mica substrate. The self-assembled monolayers (SAMs) of porphyrins on gold are characterized by Ultraviolet-visible (UV-Vis) reflection spectroscopy to confirm that the molecules are attached to the substrate. The SAMs are then characterized by Angle-Resolved X-ray photoelectron spectroscopy (ARXPS) to determine the thickness and the average molecular orientation of the molecular layer. The electron transport is measured by conductance-displacement (G-S) experiments under a given bias (-0.4V). The conductance value of a single molecule is identified by a statistical analysis

  6. An EMMPRIN–γ-catenin–Nm23 complex drives ATP production and actomyosin contractility at endothelial junctions

    Science.gov (United States)

    Moreno, Vanessa; Gonzalo, Pilar; Gómez-Escudero, Jesús; Pollán, Ángela; Acín-Pérez, Rebeca; Breckenridge, Mark; Yáñez-Mó, María; Barreiro, Olga; Orsenigo, Fabrizio; Kadomatsu, Kenji; Chen, Christopher S.; Enríquez, José A.; Dejana, Elisabetta; Sánchez-Madrid, Francisco; Arroyo, Alicia G.

    2014-01-01

    ABSTRACT Cell–cell adhesions are important sites through which cells experience and resist forces. In endothelial cells, these forces regulate junction dynamics and determine endothelial barrier strength. We identify the Ig superfamily member EMMPRIN (also known as basigin) as a coordinator of forces at endothelial junctions. EMMPRIN localization at junctions correlates with endothelial junction strength in different mouse vascular beds. Accordingly, EMMPRIN-deficient mice show altered junctions and increased junction permeability. Lack of EMMPRIN alters the localization and function of VE-cadherin (also known as cadherin-5) by decreasing both actomyosin contractility and tugging forces at endothelial cell junctions. EMMPRIN ensures proper actomyosin-driven maturation of competent endothelial junctions by forming a molecular complex with γ-catenin (also known as junction plakoglobin) and Nm23 (also known as NME1), a nucleoside diphosphate kinase, thereby locally providing ATP to fuel the actomyosin machinery. These results provide a novel mechanism for the regulation of actomyosin contractility at endothelial junctions and might have broader implications in biological contexts such as angiogenesis, collective migration and tissue morphogenesis by coupling compartmentalized energy production to junction assembly. PMID:24994937

  7. An EMMPRIN-γ-catenin-Nm23 complex drives ATP production and actomyosin contractility at endothelial junctions.

    Science.gov (United States)

    Moreno, Vanessa; Gonzalo, Pilar; Gómez-Escudero, Jesús; Pollán, Ángela; Acín-Pérez, Rebeca; Breckenridge, Mark; Yáñez-Mó, María; Barreiro, Olga; Orsenigo, Fabrizio; Kadomatsu, Kenji; Chen, Christopher S; Enríquez, José A; Dejana, Elisabetta; Sánchez-Madrid, Francisco; Arroyo, Alicia G

    2014-09-01

    Cell-cell adhesions are important sites through which cells experience and resist forces. In endothelial cells, these forces regulate junction dynamics and determine endothelial barrier strength. We identify the Ig superfamily member EMMPRIN (also known as basigin) as a coordinator of forces at endothelial junctions. EMMPRIN localization at junctions correlates with endothelial junction strength in different mouse vascular beds. Accordingly, EMMPRIN-deficient mice show altered junctions and increased junction permeability. Lack of EMMPRIN alters the localization and function of VE-cadherin (also known as cadherin-5) by decreasing both actomyosin contractility and tugging forces at endothelial cell junctions. EMMPRIN ensures proper actomyosin-driven maturation of competent endothelial junctions by forming a molecular complex with γ-catenin (also known as junction plakoglobin) and Nm23 (also known as NME1), a nucleoside diphosphate kinase, thereby locally providing ATP to fuel the actomyosin machinery. These results provide a novel mechanism for the regulation of actomyosin contractility at endothelial junctions and might have broader implications in biological contexts such as angiogenesis, collective migration and tissue morphogenesis by coupling compartmentalized energy production to junction assembly. © 2014. Published by The Company of Biologists Ltd.

  8. Junctional transfer in cultured vascular endothelium: II. Dye and nucleotide transfer

    International Nuclear Information System (INIS)

    Larson, D.M.; Sheridan, J.D.

    1985-01-01

    Vascular endothelial cultures, derived from large vessels, retain many of the characteristics of their in vivo counterparts. However, the observed reduction in size and complexity of intercellular gap and tight junctions in these cultured cells suggests that important functions, thought to be mediated by these structures, may be altered in vitro. In continuing studies on intercellular communication in vessel wall cells, the authors have quantitated the extent of junctional transfer of small molecular tracers (the fluorescent dye Lucifer Yellow CH and tritiated uridine nucleotides) in confluent cultures of calf aortic (BAEC) and umbilical vein (BVEC) endothelium. Both BAEC and BVEC show extensive (and quantitatively equivalent) dye and nucleotide transfer. As an analogue of intimal endothelium, the authors have also tested dye transfer in freshly isolated sheets of endothelium. Transfer in BAEC and BVEC sheets was more rapid, extensive and homogeneous than in the cultured cells, implying a reduction in molecular coupling as endothelium adapts to culture conditions. In addition, they have documented heterocellular nucleotide transfer between cultured endothelium and vascular smooth muscle cells, of particular interest considering the prevalence of ''myo-endothelial'' junctions in vivo. These data yield further information on junctional transfer in cultured vascular endothelium and have broad implications for the functional integration of the vessel wall in the physiology and pathophysiology of the vasculature

  9. Self-Assembly Assisted Fabrication of Dextran-Based Nanohydrogels with Reduction-Cleavable Junctions for Applications as Efficient Drug Delivery Systems

    Science.gov (United States)

    Wang, Hao; Dai, Tingting; Zhou, Shuyan; Huang, Xiaoxiao; Li, Songying; Sun, Kang; Zhou, Guangdong; Dou, Hongjing

    2017-01-01

    In order to overcome the key challenge in improving both fabrication efficiency and their drug delivery capability of anti-cancer drug delivery systems (ACDDS), here polyacrylic acid (PAA) grafted dextran (Dex) nanohydrogels (NGs) with covalent crosslinked structure bearing redox sensitive disulfide crosslinking junctions (Dex-SS-PAA) were synthesized efficiently through a one-step self-assembly assisted methodology (SAA). The Dex-SS-PAA were subsequently conjugated with doxorubicin through an acid-labile hydrazone bond (Dex-SS-PAA-DOX). The in vitro drug release behavior, anti-cancer effects in vivo, and biosafety of the as-prepared acid- and redox-dual responsive biodegradable NGs were systematically investigated. The results revealed that the Dex-SS-PAA-DOX exhibited pH- and redox-controlled drug release, greatly reduced the toxicity of free DOX, while exhibiting a strong ability to inhibit the growth of MDA-MB-231 tumors. Our study demonstrated that the Dex-SS-PAA-DOX NGs are very promising candidates as ACDDS for anti-cancer therapeutics.

  10. New phenomena observed during fuel assemblies testing

    International Nuclear Information System (INIS)

    Tzotcheva, V.

    2001-01-01

    The paper presents a new attempt to explain inexplicable increase of specific activity for some of the fuel assemblies during the fuel tightness testing procedures on Kozloduy NPP. A brief description of established procedure for fuel tightness control is presented in the paper. Special emphasis is given on a hypothesis that explains the fact of existence of deviation in Iodine activity more than usual, which have no reasonable interpretation. The reasons for uniform high Iodine activity for reloaded assemblies, that have kept in the open measuring can for a long time (1-3 hours), is found to be the process of Iodine dissolving in the water and the accelerated process of natural degassing. A proposal to use the 134 Cs and 137 Cs as stand-alone criteria for more precise results is made in respect to increase the reliability of fuel reloading and storage procedures

  11. ZO-1 and ZO-2 are required for extra-embryonic endoderm integrity, primitive ectoderm survival and normal cavitation in embryoid bodies derived from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Dominic C Y Phua

    Full Text Available The Zonula Occludens proteins ZO-1 and ZO-2 are cell-cell junction-associated adaptor proteins that are essential for the structural and regulatory functions of tight junctions in epithelial cells and their absence leads to early embryonic lethality in mouse models. Here, we use the embryoid body, an in vitro peri-implantation mouse embryogenesis model, to elucidate and dissect the roles ZO-1 and ZO-2 play in epithelial morphogenesis and de novo tight junction assembly. Through the generation of individual or combined ZO-1 and ZO-2 null embryoid bodies, we show that their dual deletion prevents tight junction formation, resulting in the disorganization and compromised barrier function of embryoid body epithelial layers. The disorganization is associated with poor microvilli development, fragmented basement membrane deposition and impaired cavity formation, all of which are key epithelial tissue morphogenetic processes. Expression of Podocalyxin, which positively regulates the formation of microvilli and the apical membrane, is repressed in embryoid bodies lacking both ZO-1 and ZO-2 and this correlates with an aberrant submembranous localization of Ezrin. The null embryoid bodies thus give an insight into how the two ZO proteins influence early mouse embryogenesis and possible mechanisms underlying the embryonic lethal phenotype.

  12. Method of transporting fuel assemblies

    International Nuclear Information System (INIS)

    Okada, Katsutoshi.

    1979-01-01

    Purpose: To enable safety transportation of fuel assemblies for FBR type reactors by surrounding each of fuel elements in a wrapper tube by a rubbery, hollow cylindrical container and by sealing medium such as air to the inside of the container. Method: A fuel element is contained in a hollow cylindrical rubber-like tube. The fuel element has an upper end plug, a lower end plug and a wire spirally wound around the outer periphery. Upon transportation of the fuel assemblies, each of the fuel elements is covered with the container and arranged in the wrapper tube and then the fuel assemblies are assembled. Then, medium such as air is sealed for each of the fuel elements by way of an opening and then the opening is tightly closed. Before loading the transported fuel assemblies in the reactor, the medium is discharged through the opening and the container is completely extracted and removed from the inside of the wrapper tube. (Seki, T.)

  13. Experimental Air-Tightness Analysis in Mediterranean Buildings after Windows Retrofit

    Directory of Open Access Journals (Sweden)

    Francesca Romana d’Ambrosio Alfano

    2016-09-01

    Full Text Available Energy saving and Indoor Air Quality (IAQ in buildings are strongly affected by air leakages. Several studies reveal that the energy loss owing to leaky windows can account for up to 40% of the total building energy demand. Furthermore, at the design stage, the possible infiltration of outdoor air through windows is not taken into account when determining the nominal outdoor airflow rate of the ventilation system. This practice may result in an oversizing of the ventilation system and consequent energy waste. Thus, the air-tightness class of a wall assembly should be assessed for each window component considering the type of material, the presence of the seal, the type of closure, the sealing and the maintenance condition. In this paper, the authors present the experimental results of air-tightness measurements carried out using the fan pressurization method in three residential buildings located in the Mediterranean region before and after a window retrofit. Two different window retrofits were investigated: the application of rubber seals on window frames and the substitution of existing windows with new certified high performance windows. The effectiveness of such retrofits was estimated also in terms of energy saving. Test results demonstrated a high variability of the building air tightness after window retrofits, despite the fact that air tight–certified windows were used.

  14. Managing the complexity of communication: regulation of gap junctions by post-translational modification

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Callø, Kirstine; von Holstein-Rathlou, Niels-Henrik

    2013-01-01

    Gap junctions are comprised of connexins that form cell-to-cell channels which couple neighboring cells to accommodate the exchange of information. The need for communication does, however, change over time and therefore must be tightly controlled. Although the regulation of connexin protein...... probability, single channel conductance or selectivity. The most extensively investigated post translational modifications are phosphorylations, which have been documented in all mammalian connexins. Besides phosphorylations, some connexins are known to be ubiquitinated, SUMOylated, nitrosylated, hydroxylated...

  15. Transforming growth factor beta 1 modulates extracellular matrix organization and cell-cell junctional complex formation during in vitro angiogenesis.

    Science.gov (United States)

    Merwin, J R; Anderson, J M; Kocher, O; Van Itallie, C M; Madri, J A

    1990-01-01

    Transforming growth factor-beta 1 (TGF-beta 1) is angiogenic in vivo. In two-dimensional (2-D) culture systems microvascular endothelial cell proliferation is inhibited up to 80% by TGF-beta 1; however, in three-dimensional (3-D) collagen gels TGF-beta 1 is found to have no effect on proliferation while eliciting the formation of calcium and magnesium dependent tube-like structures mimicking angiogenesis. DNA analyses performed on 3-D cell cultures reveal no significant difference in the amount of DNA or cell number in control versus TGF-beta 1 treated cultures. In 2-D cultures TGF-beta 1 is known to increase cellular fibronectin accumulation; however, in 3-D cultures no difference is seen between control and TGF-beta 1 treated cells as established by ELISA testing for type IV collagen, fibronectin, and laminin. In 3-D cultures there is increased synthesis and secretion of type V collagen in both control and TGF-beta 1 treated cultures over 2-D cultures. Even though an equal amount of type V collagen is seen in both 3-D conditions, there is a reorganization of the protein with concentration along an organizing basal lamina in TGF-beta 1 treated cultures. EM morphological analyses on 3-D cultures illustrate quiescent, control cells lacking cell contacts. In contrast, TGF-beta 1 treated cells show increased pseudopod formation, cell-cell contact, and organized basal lamina-like material closely apposed to the "abluminal" plasma membranes. TGF-beta 1 treated cells also appear to form junctional complexes between adjoining cells. Immunofluorescence using specific antibodies to the tight junction protein ZO-1 results in staining at apparent cell-cell junctions in the 3-D cultures. Northern blots of freshly isolated microvascular endothelium, 2-D and 3-D cultures, using cDNA and cRNA probes specific for the ZO-1 tight junction protein, reveal the presence of the 7.8 kb mRNA. Western blots of rat epididymal fat pad endothelial cells (RFC) monolayer lysates probed with

  16. Humidity dependence of molecular tunnel junctions with an AlOx/COOH- interface

    Science.gov (United States)

    Zhang, Xiaohang; McGill, Stephen; Xiong, Peng

    2006-03-01

    We have studied the electron transport in planar tunneling junctions with aluminum oxide and an organic self-assembled monolayer (SAM) as the tunnel barrier. The structure of the junctions is Al/AlOx/SAM/(Au, Pb) with a junction area of ˜ 0.4mm^2. The organic molecules investigated include mercaptohexadecanoic acid (MHA), hexadecanoic acid (HDA), and octadecyltrichlorosilane (OTS); all of which form ordered SAMs on top of aluminum oxide. The use of a superconducting electrode (Al) enables us to determine unambiguously that these are high-quality tunnel junctions. For junctions incorporating MHA, the transport behavior is found to be strongly humidity dependent. The resistance of these junctions drops more than 50% when placed in dry nitrogen and recovers when returned into the ambient. The same drop also occurs when the sample is placed into a vacuum, and backfilling the vacuum with either dry N2 or O2 has negligible effect on the resistance. For comparison, junctions with HDA show the same humidity dependence, while OTS samples do not. Since both MHA and HDA have carboxylic groups and OTS does not, the results suggest that water molecules at the AlOx/COOH- interface play the central role in the observed behavior. Inelastic tunneling spectroscopy (IETS) has also been performed to understand the role of water. This work was supported by a FSU Research Foundation PEG grant.

  17. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients.

    Science.gov (United States)

    Sugita, Kazunari; Steer, Catherine A; Martinez-Gonzalez, Itziar; Altunbulakli, Can; Morita, Hideaki; Castro-Giner, Francesc; Kubo, Terufumi; Wawrzyniak, Paulina; Rückert, Beate; Sudo, Katsuko; Nakae, Susumu; Matsumoto, Kenji; O'Mahony, Liam; Akdis, Mübeccel; Takei, Fumio; Akdis, Cezmi A

    2018-01-01

    Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously. We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice. Cocultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial electrical resistance, paracellular flux, and TJ mRNA and protein expressions. The effect of ILC2s on TJs was examined by using a murine model of IL-33-induced airway inflammation in wild-type, recombination-activating gene 2 (Rag2) -/- , Rag2 -/- Il2rg -/- , and Rora sg/sg mice undergoing bone marrow transplantation to analyze the in vivo relevance of barrier disruption by ILC2s. ILC2s significantly impaired the epithelial barrier, as demonstrated by reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability in air-liquid interface cultures of human bronchial epithelial cells. This was in parallel to decreased mRNAs and disrupted protein expression of TJ proteins and was restored by neutralization of IL-13. Intranasal administration of recombinant IL-33 to wild-type and Rag2 -/- mice lacking T and B cells triggered TJ disruption, whereas Rag2 -/- Il2rg -/- and Rora sg/sg mice undergoing bone marrow transplantation that lack ILC2s did not show any barrier leakiness. Direct nasal administration of IL-13 was sufficient to induce deficiency in the TJ barrier in the bronchial epithelium of mice in vivo. These data highlight an essential mechanism in asthma pathogenesis by demonstrating that ILC2s are responsible for bronchial epithelial TJ barrier leakiness through IL-13. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

  18. Vinculin but not alpha-actinin is a target of PKC phosphorylation during junctional assembly induced by calcium

    DEFF Research Database (Denmark)

    Perez-Moreno, M; Avila, A; Islas, S

    1998-01-01

    and alpha-actinin, two actin binding proteins of the adherent junctions. We found that during the junctional sealing induced by Ca2+, both proteins move towards the cell periphery and, while there is a significant increase in the phosphorylation of vinculin, alpha-actinin remains unchanged. The increased...

  19. Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF-κB, TOR and Nrf2 signaling molecules in the gills of fish: Preventive role of arginine

    International Nuclear Information System (INIS)

    Wang, Biao; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Kuang, Sheng-Yao; Jiang, Jun; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Liu, Yang

    2015-01-01

    Highlights: • Cu exposure induced oxidative stress via disruption of antioxidant system. • Cu exposure disrupted TJ mRNA expression through regulation of cytokines in fish. • Cu induced gill apoptosis partly via intrinsic pathway but not extrinsic pathway. • Cu exposure can regulate Nrf2, NF-κB and TOR signaling molecules in fish. • Arginine can effectively prevent Cu-induced fish gill damage. - Abstract: This study explored the possible preventive effects of dietary arginine on copper (Cu)-induced tight junction mRNA expression changes, apoptosis and antioxidant responses in the gills of young grass carp (Ctenopharyngodon idella). The results indicated that exposure to 0.7 mg/L (11.01 μmol/L) Cu for 96 h induced the production of reactive oxygen species (ROS), thereby increasing protein oxidation, lipid peroxidation and DNA damage in the gills of fish. However, these oxidative effects were prevented by arginine supplementation. Arginine also prevented the toxic effects of Cu on the activities of copper/zinc superoxide dismutase (SOD1), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and the glutathione (GSH) content (P < 0.05). However, Cu induced an adaptive increase in the activity of catalase (CAT), and arginine supplementation further increased CAT activity (P < 0.05). Moreover, Cu induced increases in the relative mRNA expressions of SOD1, CAT, GPx, GST, caspase-3, caspase-9, NF-E2-related factor 2 (Nrf2), Kelch-like-ECH-associated protein 1a (Keap1a), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), transforming growth factor-β (TGF-β) and nuclear transcription factor-κB p65 (NF-κB p65) in the gills of grass carp (P < 0.05). In contrast, the relative mRNA expression levels of occludin, zonula occludens-1 (ZO-1), claudin b, claudin 3, claudin 12, target of rapamycin (TOR) and inhibitor factor κBα (IκBα) in the gills were decreased by Cu (P < 0.05). However, pre

  20. Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF-κB, TOR and Nrf2 signaling molecules in the gills of fish: Preventive role of arginine

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Biao [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Feng, Lin; Jiang, Wei-Dan [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Wu, Pei [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Kuang, Sheng-Yao [Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan (China); Jiang, Jun [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Tang, Ling; Tang, Wu-Neng [Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan (China); Zhang, Yong-An [Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Liu, Yang, E-mail: kyckgk@hotmail.com [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); and others

    2015-01-15

    Highlights: • Cu exposure induced oxidative stress via disruption of antioxidant system. • Cu exposure disrupted TJ mRNA expression through regulation of cytokines in fish. • Cu induced gill apoptosis partly via intrinsic pathway but not extrinsic pathway. • Cu exposure can regulate Nrf2, NF-κB and TOR signaling molecules in fish. • Arginine can effectively prevent Cu-induced fish gill damage. - Abstract: This study explored the possible preventive effects of dietary arginine on copper (Cu)-induced tight junction mRNA expression changes, apoptosis and antioxidant responses in the gills of young grass carp (Ctenopharyngodon idella). The results indicated that exposure to 0.7 mg/L (11.01 μmol/L) Cu for 96 h induced the production of reactive oxygen species (ROS), thereby increasing protein oxidation, lipid peroxidation and DNA damage in the gills of fish. However, these oxidative effects were prevented by arginine supplementation. Arginine also prevented the toxic effects of Cu on the activities of copper/zinc superoxide dismutase (SOD1), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and the glutathione (GSH) content (P < 0.05). However, Cu induced an adaptive increase in the activity of catalase (CAT), and arginine supplementation further increased CAT activity (P < 0.05). Moreover, Cu induced increases in the relative mRNA expressions of SOD1, CAT, GPx, GST, caspase-3, caspase-9, NF-E2-related factor 2 (Nrf2), Kelch-like-ECH-associated protein 1a (Keap1a), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), transforming growth factor-β (TGF-β) and nuclear transcription factor-κB p65 (NF-κB p65) in the gills of grass carp (P < 0.05). In contrast, the relative mRNA expression levels of occludin, zonula occludens-1 (ZO-1), claudin b, claudin 3, claudin 12, target of rapamycin (TOR) and inhibitor factor κBα (IκBα) in the gills were decreased by Cu (P < 0.05). However, pre

  1. Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation

    International Nuclear Information System (INIS)

    Wu, Hai-Lu; Gao, Xin; Jiang, Zong-Dan; Duan, Zhao-Tao; Wang, Shu-Kui; He, Bang-Shun; Zhang, Zhen-Yu; Xie, Hong-Guang

    2013-01-01

    Highlights: ► Clopidogrel suppressed GES-1 cell viability in a concentration- and time-dependent manner. ► Clopidogrel significantly increased dextran permeability, reduced occludin and ZO-1 expression, and induced cell apoptosis. ► Clopidogrel activated p38 MAPK signaling pathway. ► Activation of p38 activity was involved in clopidogrel-induced increase in gastric epithelial cells permeability and disruption of TJ. -- Abstract: Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined. This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved. After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0.5–2.5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy. Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot. In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested. Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation. Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric

  2. An Evaluation of Test and Physical Uncertainty of Measuring Vibration in Wooden Junctions

    DEFF Research Database (Denmark)

    Dickow, Kristoffer Ahrens; Kirkegaard, Poul Henning; Andersen, Lars Vabbersgaard

    2012-01-01

    In the present paper a study of test and material uncertainty in modal analysis of certain wooden junctions is presented. The main structure considered here is a T-junction made from a particleboard plate connected to a spruce beam of rectangular cross section. The size of the plate is 1.2 m by 0.......6 m. The T-junctions represent cut-outs of actual full size floor assemblies. The aim of the experiments is to investigate the underlying uncertainties of both the test method as well as variation in material and craftmanship. For this purpose, ten nominally identical junctions are tested and compared...... to each other in terms of modal parameters such as natural frequencies, modeshapes and damping. Considerations regarding the measurement procedure and test setup are discussed. The results indicate a large variation of the response at modes where the coupling of torsion in the beam to bending of the plate...

  3. Expanding to teleoperation of a tight modular workshop for dismantling radioactive components

    International Nuclear Information System (INIS)

    Gasc, B.

    1990-01-01

    The CEA (French Nuclear Energy Commission) in connection with TECHNICATOME developed a tight modular workshop for the dismantling of AT1 plant facilities in LA HAGUE. This workshop constructed of reusable stainless steel panels assembled by bolting provides a tight and decontaminable working zone compatible with any building configuration. This being the case, the operators bearing ventilated suits may work under the best safety conditions on alpha-contaminated materials. For the purpose of expanding the working capacities of this workshop it was decided to develop special components for teleoperation from the outside as in a conventional cell. To meet this objective which is within the scope of the contract signed with the CEC, the following components were developed and constructed: - manipulator holder panel, - swivelling hatch panel, - wall equipment sealed transfer device and, - modular biological protection. The design, construction and tests of these new components led to their qualification and further incorporation in the list of components of the modular workshop liable to be used for teleoperation procedures

  4. Rol de las uniones estrechas del epitelio intestinal en la patogenia de la enfermedad de Crohn

    Directory of Open Access Journals (Sweden)

    Dionisio Díaz

    2015-11-01

    In his review the molecular composition, structure, interactions and function of the tight junctions are briefly described, and recent evidence on the relationship between the dysfunction of the tight junctions and Crohn’s disease is commented. The role of microbiota in the regulation of tight junctions and the participation of tight junctions deregulation in the development of cancer associated to Crohn’s disease are also detailed. Finally, recent findings about the employment of tight junctions as targets for the development of new drugs are described.

  5. Energy scales in YBaCuO grain boundary biepitaxial Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Tafuri, F., E-mail: tafuri@na.infn.it [Dip. Ingegneria dell' Informazione, Seconda Universita di Napoli, 81031 Aversa (CE) (Italy); CNR-SPIN, UOS Napoli, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); Dip. Scienze Fisiche, Universita di Napoli Federico II, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); Stornaiuolo, D. [DPMC, University of Geneva, 24 Quai Ernest-Ansermet, 1211 Geneva 4 (Switzerland); CNR-SPIN, UOS Napoli, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); Lucignano, P. [CNR-ISC, sede di Tor Vergata, Via del Fosso del Cavaliere 100, 00133 Roma (Italy); Dip. Scienze Fisiche, Universita di Napoli Federico II, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); Galletti, L. [Dip. Scienze Fisiche, Universita di Napoli Federico II, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); Longobardi, L. [Dip. Ingegneria dell' Informazione, Seconda Universita di Napoli, 81031 Aversa (CE) (Italy); Massarotti, D. [Dip. Scienze Fisiche, Universita di Napoli Federico II, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); CNR-SPIN, UOS Napoli, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); Montemurro, D. [NEST and Scuola Normale Superiore, Piazza San Silvestro 12, I-56127 Pisa (Italy); Papari, G. [INPAC - Institute for Nanoscale Physics and Chemistry, Nanoscale Superconductivity and Magnetism Pulsed Fields Group, K.U. Leuven, Celestijnenlaan 200 D, B-3001 Leuven (Belgium); Dip. Scienze Fisiche, Universita di Napoli Federico II, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); Barone, A.; Tagliacozzo, A. [Dip. Scienze Fisiche, Universita di Napoli Federico II, Monte S. Angelo via Cinthia, 80126 Napoli (Italy); CNR-SPIN, UOS Napoli, Monte S. Angelo via Cinthia, 80126 Napoli (Italy)

    2012-09-15

    Self-assembled nanoscale channels may naturally arise in the growth process of grain boundaries (GBs) in high critical temperature superconductor (HTS) systems, and deeply influence the transport properties of the GB Josephson junctions (JJs). By isolating nano-channels in YBCO biepitaxial JJs and studying their properties, we sort out specific fingerprints of the mesoscopic nature of the contacts. The size of the channels combined to the characteristic properties of HTS favors a special regime of the proximity effect, where normal state coherence prevails on the superconducting coherence in the barrier region. Resistance oscillations from the current-voltage characteristic encode mesoscopic information on the junction and more specifically on the minigap induced in the barrier. Thouless energy emerges as a characteristic energy of these types of Josephson junctions. Possible implications on the understanding of coherent transport of quasiparticles in HTS and of the dissipation mechanisms are discussed, along with elements to take into account when designing HTS nanostructures.

  6. The sequence d(CGGCGGCCGC) self-assembles into a two dimensional rhombic DNA lattice

    International Nuclear Information System (INIS)

    Venkadesh, S.; Mandal, P.K.; Gautham, N.

    2011-01-01

    Highlights: → This is the first crystal structure of a four-way junction with sticky ends. → Four junction structures bind to each other and form a rhombic cavity. → Each rhombus binds to others to form 'infinite' 2D tiles. → This is an example of bottom-up fabrication of a DNA nano-lattice. -- Abstract: We report here the crystal structure of the partially self-complementary decameric sequence d(CGGCGGCCGC), which self assembles to form a four-way junction with sticky ends. Each junction binds to four others through Watson-Crick base pairing at the sticky ends to form a rhombic structure. The rhombuses bind to each other and form two dimensional tiles. The tiles stack to form the crystal. The crystal diffracted in the space group P1 to a resolution of 2.5 A. The junction has the anti-parallel stacked-X conformation like other junction structures, though the formation of the rhombic net noticeably alters the details of the junction geometry.

  7. Linker-dependent Junction Formation Probability in Single-Molecule Junctions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Pil Sun; Kim, Taekyeong [HankukUniversity of Foreign Studies, Yongin (Korea, Republic of)

    2015-01-15

    We compare the junction formation probabilities of single-molecule junctions with different linker molecules by using a scanning tunneling microscope-based break-junction technique. We found that the junction formation probability varies as SH > SMe > NH2 for the benzene backbone molecule with different types of anchoring groups, through quantitative statistical analysis. These results are attributed to different bonding forces according to the linker groups formed with Au atoms in the electrodes, which is consistent with previous works. Our work allows a better understanding of the contact chemistry in the metal.molecule junction for future molecular electronic devices.

  8. The spontaneous formation of single-molecule junctions via terminal alkynes

    International Nuclear Information System (INIS)

    Pla-Vilanova, Pepita; Aragonès, Albert C; Sanz, Fausto; Darwish, Nadim; Diez-Perez, Ismael; Ciampi, Simone

    2015-01-01

    Herein, we report the spontaneous formation of single-molecule junctions via terminal alkyne contact groups. Self-assembled monolayers that form spontaneously from diluted solutions of 1, 4-diethynylbenzene (DEB) were used to build single-molecule contacts and assessed using the scanning tunneling microscopy-break junction technique (STM-BJ). The STM-BJ technique in both its dynamic and static approaches was used to characterize the lifetime (stability) and the conductivity of a single-DEB wire. It is demonstrated that single-molecule junctions form spontaneously with terminal alkynes and require no electrochemical control or chemical deprotonation. The alkyne anchoring group was compared against typical contact groups exploited in single-molecule studies, i.e. amine (benzenediamine) and thiol (benzendithiol) contact groups. The alkyne contact showed a conductance magnitude comparable to that observed with amine and thiol groups. The lifetime of the junctions formed from alkynes were only slightly less than that of thiols and greater than that observed for amines. These findings are important as (a) they extend the repertoire of chemical contacts used in single-molecule measurements to 1-alkynes, which are synthetically accessible and stable and (b) alkynes have a remarkable affinity toward silicon surfaces, hence opening the door for the study of single-molecule transport on a semiconducting electronic platform. (fast track communication)

  9. Automated Array Assembly, Phase 2. Final technical progress report, 1979

    Energy Technology Data Exchange (ETDEWEB)

    Carbajal, B.G.

    1979-11-01

    The 1979 phase of this Automated Array Assembly, Phase 2 contract was devoted solely to the tasks of scaling up the Tandem Junction Cell (TJC) from 2 cm x 2 cm to 6.2 cm x 6.2 cm and the assembly of several modules using these large-area TJCs. The scale-up of the TJC was based on using the existing process and doing the necessary design activities to increase the cell area to an acceptably large area. The design was carried out using available device models. The design was verified and sample large-area TJCs were fabricated. Mechanical and process problems occurred causing a schedule slippage that resulted in contract expiration before enough large-area TCs were fabricated to populate the sample Tandem Junction Modules (TJMs). A TJM design was carried out in which the module interconnects served to augment the current collecting buses on the cell. The module was made up of a 5 x 6 TJC matrix mounted on a porcelainized steel substrate with a glass cover. The TJC matrix was series-parallel connected using copper clad Invar interconnects soldered to the TJC metallization. Sample cell matrices were assembled using dummy cells. No sample TJMs were assembled due to a shortage of large-area TJCs and contract expiration.

  10. Lightweight IMM Multi-Junction Photovoltaic Flexible Blanket Assembly, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — DSS's recently completed successful NASA SBIR Phase 1 program has established a TRL 3/4 classification for an innovative IMM PV Integrated Modular Blanket Assembly...

  11. Are tight gas resources overstated?

    Energy Technology Data Exchange (ETDEWEB)

    Roche, P.

    2004-11-01

    According to conventional wisdom, North America's tight gas resources are continuous, regional accumulations of water-free methane, trapped in low-permeability rock, and involving very little exploration risk. Backing up conventional wisdom, EnCana Corporation is investing heavily in technology-intensive and capital-intensive tight gas plays in Western Canada and the Rocky Mountain regions of the United States. On the other hand, a recent study in the Greater Green River Basin of southwestern Wyoming says that tight gas resources have been significantly overestimated, by as much as three to five times too high, and the risks of exploration are every bit as high as those for conventional exploration. This study essentially dismisses the whole idea of tight gas, or basin-centred gas as a myth, the authors being firmly convinced that tight gas formations should be viewed as conventional hydrocarbon systems, with the usual risks of exploration. This paper discusses the controversy created by this recent study and the implications for natural gas reserves on a basin and individual company level, and the risks associated with exploration. The views of EnCana Corporation, being the company most heavily involved in tight gas and coalbed methane, and those of John Masters, co-founder of Canadian Hunter Exploration Ltd., and discoverer of the blockbuster Elsmworth tight gas deposit in northeastern Alberta in the mid-1970s, are explained in considerable detail, in an effort to dismiss the doubters. EnCana officials and Masters argue that the points raised by the authors of the Greater Green River study do not hold water: Tight gas or basin gas is a distinct hydrocarbon formation, characterized by low permeability, therefore it is to be expected that the gas will take longer to come out of the ground. Neither is the role of water in basin-centred gas systems the major problem as claimed by the doubters. They also characterize it as imprudent to claim to know what the

  12. Classification of the NPP core and fuel assembly states by the pattern recoguition method

    International Nuclear Information System (INIS)

    Egorov, Yu.A.; Ivanov, E.A.; Kazakov, S.V.; Tolstykh, V.D.

    1981-01-01

    The patern recognition methods used for solving the problems of analysis of radiohazard states of fuel assemblies (FA) and uranium-graphite reactor core as a whole are considered. The problem under consideration is formulated as the problem of studying the deformation of signal space for the system of fuel can tightness control on the background of fuel assembly character space as characteristics, reflecting the FA living conditions in a core power, coolant flow rate, coolant steam content and pipeline length up to the detector of the system of fuel can tightness control are chosen. The analysis of deformation of the fuel can tightness control system signal space is completed by its division into two spaces: the background signal space and the valid signal space. For solving the problem the method of basic components and variational approach have been used. The conclusion is drawn that as the extent of FA failure and valid signals of by-channel system of fuel can tightness control are in one-to-one correspondence it is advantageous to solve the problem of FA state classification in the space of valid signals [ru

  13. 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.

  14. Feasibility study on thermal-hydraulic performance in tight-lattice rod bundles for reduced-moderation water reactors

    International Nuclear Information System (INIS)

    Ohnuki, A.; Kureta, M.; Liu, W.; Tamai, H.; Akimoto, H.

    2004-01-01

    Research and development project for investigating thermal-hydraulic performance in tight-lattice rod bundles for Reduced-Moderation Water Reactor (RMWR) started at Japan Atomic Energy Research Institute (JAERI) in 2002. The RMWR can attain the favorable characteristics such as effective utilization of uranium resources, multiple recycling of plutonium, high burn-up and long operation cycle, based on matured light-water reactor technologies. MOX fuel assemblies with tight lattice arrangement are used to increase the conversion ratio by reducing the moderation of neutron. Increasing the in-core void fraction also contributes to the reduction of neutron moderation. The confirmation of thermal-hydraulic feasibility is one of the most important issues for the RMWR because of the tight-lattice configuration. The project has mainly consisted of a large-scale thermal-hydraulic test and development of analytical methods named modeling engineering. In the large-scale test, 37-rod bundle experiments can be performed. Steady-state critical power experiments have been achieved in the test facility and the experimental data reveal the feasibility of RMWR

  15. The Assembly of the LHC Short Straight Sections (SSS) at CERN Project Status and Lessons Learned

    CERN Document Server

    Parma, Vittorio; Dos Santos de Campos, Paulo M; Feitor, Rogerio C; Gandel, Makcim; López, R; Schmidlkofer, Martin; Slits, Ivo

    2005-01-01

    The series production of the LHC SSS has started in the beginning of 2004 and is foreseen to last until end 2006. The production consists in the assembly of 474 cold masses housing superconducting quadrupoles and corrector magnets within their cryostats. 87 cold mass variants, resulting from various combinations of main quadrupole and corrector magnets, have to be assembled in 55 cryostat types, depending on the specific cryogenic and electrical powering schemes required by the collider topology. The assembly activity features the execution of more than 5 km of leak-tight welding of stainless steel and aluminium cryogenic lines, designed for 20-bar pressure, according to high qualification standards and undergoing severe QA inspections. Some 2500 leak detection tests, using He mass spectrometry, are required to check the tightness of the cryogenic circuits. Extensive electrical control work, to check the integrity of the magnet instrumentation and electrical circuits throughout the assembly of the SSS, is als...

  16. Keratinocytes express fibrillin and assemble microfibrils: implications for dermal matrix organization.

    Science.gov (United States)

    Haynes, S L; Shuttleworth, C A; Kielty, C M

    1997-07-01

    Fibrillin-containing microfibrils are key architectural structures of the upper dermis and integral components of the dermal elastic fibre network. Microfibril bundles intercalate into the dermal-epithelial junction and provide an elastic connection between the dermal elastic fibre network and the epidermis. Immunohistochemical studies have suggested that they are laid down both at the dermal-epithelial junction and in the deep dermis. While dermal fibroblasts are responsible for deposition of the elastin and microfibrillar components that comprise the elastic fibres of the deep dermis, the cellular origin of the microfibril bundles that extrude from the dermal-epithelial junction is not well defined. We have used fresh tissues, freshly isolated epidermis and primary human and porcine keratinocyte cultures to investigate the possibility that keratinocytes are responsible for deposition of these microfibrils. We have shown that keratinocytes in vivo and in vitro synthesize both fibrillin-1 and fibrillin-2, and assemble beaded microfibrils concurrently with expression of basement membrane collagen. These observations suggest that keratinocytes co-ordinate the secretion, deposition and assembly of these distinct structural elements of the dermal matrix, and have important implications for skin remodelling.

  17. Effect of film roughness in Fe/MgO/Fe magnetic tunnel junctions: model calculations

    Energy Technology Data Exchange (ETDEWEB)

    Edalati Boostan, Saeideh; Heiliger, Christian [I. Physikalisches Institut, Justus Liebig University Giessen, D-35392 (Germany); Moradi, Hosein [Department of Physics,Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of)

    2011-07-01

    We calculate how interface roughness affects the tunneling magnetoresistance (TMR) in Fe/MgO/Fe (100) junctions. The used method is based on a single-band tight-binding (SBTB) approximation employing the Green's function formalism. We investigate the influence of disorder at the TMR ratio. Thereby, the disorder is modeled by considering different occupation probabilities of Fe and MgO at interface sites. We calculate the current densities for parallel and anti-parallel configurations for different disorders. The results show that the roughness decreases the TMR that match well with experimental observations.

  18. Fabrication-process-induced variations of Nb/Al/AlOx/Nb Josephson junctions in superconductor integrated circuits

    International Nuclear Information System (INIS)

    Tolpygo, Sergey K; Amparo, Denis

    2010-01-01

    Currently, superconductor digital integrated circuits fabricated at HYPRES, Inc. can operate at clock frequencies approaching 40 GHz. The circuits present multilayered structures containing tens of thousands of Nb/Al/AlO x /Nb Josephson junctions (JJs) of various sizes interconnected by four Nb wiring layers, resistors, and other circuit elements. In order to be fully operational, the integrated circuits should be fabricated such that the critical currents of the JJs are within the tight design margins and the proper relationships between the critical currents of JJs of different sizes are preserved. We present experimental data and discuss mechanisms of process-induced variations of the critical current and energy gap of Nb/Al/AlO x /Nb JJs in integrated circuits. We demonstrate that the Josephson critical current may depend on the type and area of circuit elements connected to the junction, on the circuit pattern, and on the step in the fabrication process at which the connection is made. In particular, we discuss the influence of (a) the junction base electrode connection to the ground plane, (b) the junction counter electrode connection to the ground plane, and (c) the counter electrode connection to the Ti/Au or Ti/Pd/Au contact pads by Nb wiring. We show that the process-induced changes of the properties of Nb/Al/AlO x /Nb junctions are caused by migration of impurity atoms (hydrogen) between the different layers comprising the integrated circuits.

  19. Pronounced Environmental Effects on Injection Currents in EGaln Tunneling Junctions Comprising Self-Assembled Monolayers

    NARCIS (Netherlands)

    Carlotti, Marco; Degen, Maarten; Zhang, Yanxi; Chiechi, Ryan C.

    2016-01-01

    Large-area tunneling junctions using eutectic Ga-In (EGaIn) as a top contact have proven to be a robust, reproducible, and technologically relevant platform for molecular electronics. Thus far, the majority of studies have focused on saturated molecules with backbones consisting mainly of alkanes in

  20. The effects of electromagnetic pulse on the protein levels of tight junction associated-proteins in the cerebral cortex, hippocampus, heart, lung, and testis of rats.

    Science.gov (United States)

    Qiu, LianBo; Chen, Chen; Ding, GuiRong; Zhou, Yan; Zhang, MengYao

    2011-08-01

    To investigate changes in the expression of tight junction (TJ) proteins in the cerebral cortex, hippocampus, heart, lung, and testes of rats after exposure to electromagnetic pulse (EMP). Eighteen adult male Sprague-Dawley rats were divided into sham and exposure groups. The exposure groups received EMP at 200 kV/m for 200 pulses with a repetition rate of 1 Hz. The expression of TJ proteins (ZO-1, occludin, actin) in the several organs was examined by western blotting. ZO-1 levels in the cerebral cortex decreased 1 h and 3 h after EMP exposure compared with sham group (P<0.05). No significant difference was observed for occludin and actin. ZO-1 levels in the hippocampus increased 1 h and 3 h post-exposure (P<0.05), and occludin decreased after 3 h (P<0.05); however, actin was unaffected. ZO-1 levels in the heart increased 3 h post-exposure (P<0.05), occludin decreased 3 h post-exposure (P<0.05), and actin increased 1 h and 3 h post-exposure (P<0.05). ZO-1, occludin and actin levels in the lung decreased compared with those in the sham group (P<0.05). ZO-1 and occludin levels in the testes decreased 1 h and 3 h post-exposure (P<0.05), but actin showed no significant change. Exposure to EMP altered the expression levels of TJ proteins, particularly ZO-1, in the organs of adult male rats, which may induce changes in barrier structure and function. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

  1. 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.

  2. Evidence for differential changes of junctional complex proteins in murine neurocysticercosis dependent upon CNS vasculature.

    Science.gov (United States)

    Alvarez, Jorge I; Teale, Judy M

    2007-09-12

    The delicate balance required to maintain homeostasis of the central nervous system (CNS) is controlled by the blood-brain barrier (BBB). Upon injury, the BBB is disrupted compromising the CNS. BBB disruption has been represented as a uniform event. However, our group has shown in a murine model of neurocysticercosis (NCC) that BBB disruption varies depending upon the anatomical site/vascular bed analyzed. In this study further understanding of the mechanisms of BBB disruption was explored in blood vessels located in leptomeninges (pial vessels) and brain parenchyma (parenchymal vessels) by examining the expression of junctional complex proteins in murine brain infected with Mesocestoides corti. Both pial and parenchymal vessels from mock infected animals showed significant colocalization of junctional proteins and displayed an organized architecture. Upon infection, the patterned organization was disrupted and in some cases, particular tight junction and adherens junction proteins were undetectable or appeared to be undergoing proteolysis. The extent and timing of these changes differed between both types of vessels (pial vessel disruption within days versus weeks for parenchymal vessels). To approach potential mechanisms, the expression and activity of matrix metalloproteinase-9 (MMP-9) were evaluated by in situ zymography. The results indicated an increase in MMP-9 activity at sites of BBB disruption exhibiting leukocyte infiltration. Moreover, the timing of MMP activity in pial and parenchymal vessels correlated with the timing of permeability disruption. Thus, breakdown of the BBB is a mutable process despite the similar structure of the junctional complex between pial and parenchymal vessels and involvement of MMP activity.

  3. Structural and thermodynamic analysis of modified nucleosides in self-assembled DNA cross-tiles.

    Science.gov (United States)

    Hakker, Lauren; Marchi, Alexandria N; Harris, Kimberly A; LaBean, Thomas H; Agris, Paul F

    2014-01-01

    DNA Holliday junctions are important natural strand-exchange structures that form during homologous recombination. Immobile four-arm junctions, analogs to Holliday junctions, have been designed to self-assemble into cross-tile structures by maximizing Watson-Crick base pairing and fixed crossover points. The cross-tiles, self-assembled from base pair recognition between designed single-stranded DNAs, form higher order lattice structures through cohesion of self-associating sticky ends. These cross-tiles have 16 unpaired nucleosides in the central loop at the junction of the four duplex stems. The importance of the centralized unpaired nucleosides to the structure's thermodynamic stability and self-assembly is unknown. Cross-tile DNA nanostructures were designed and constructed from nine single-stranded DNAs with four shell strands, four arms, and a central loop containing 16 unpaired bases. The 16 unpaired bases were either 2'-deoxyribothymidines, 2'-O-methylribouridines, or abasic 1',2'-dideoxyribonucleosides. Thermodynamic profiles and structural base-stacking contributions were assessed using UV absorption spectroscopy during thermal denaturation and circular dichroism spectroscopy, respectively, and the resulting structures were observed by atomic force microscopy. There were surprisingly significant changes in the thermodynamic and structural properties of lattice formation as a result of altering only the 16 unpaired, centralized nucleosides. The 16 unpaired 2'-O-methyluridines were stabilizing and produced uniform tubular structures. In contrast, the abasic nucleosides were destabilizing producing a mixture of structures. These results strongly indicate the importance of a small number of centrally located unpaired nucleosides within the structures. Since minor modifications lead to palpable changes in lattice formation, DNA cross-tiles present an easily manipulated structure convenient for applications in biomedical and biosensing devices.

  4. 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

  5. Interface-Engineered Charge-Transport Properties in Benzenedithiol Molecular Electronic Junctions via Chemically p-Doped Graphene Electrodes.

    Science.gov (United States)

    Jang, Yeonsik; Kwon, Sung-Joo; Shin, Jaeho; Jeong, Hyunhak; Hwang, Wang-Taek; Kim, Junwoo; Koo, Jeongmin; Ko, Taeg Yeoung; Ryu, Sunmin; Wang, Gunuk; Lee, Tae-Woo; Lee, Takhee

    2017-12-06

    In this study, we fabricated and characterized vertical molecular junctions consisting of self-assembled monolayers of benzenedithiol (BDT) with a p-doped multilayer graphene electrode. The p-type doping of a graphene film was performed by treating pristine graphene (work function of ∼4.40 eV) with trifluoromethanesulfonic (TFMS) acid, producing a significantly increased work function (∼5.23 eV). The p-doped graphene-electrode molecular junctions statistically showed an order of magnitude higher current density and a lower charge injection barrier height than those of the pristine graphene-electrode molecular junctions, as a result of interface engineering. This enhancement is due to the increased work function of the TFMS-treated p-doped graphene electrode in the highest occupied molecular orbital-mediated tunneling molecular junctions. The validity of these results was proven by a theoretical analysis based on a coherent transport model that considers asymmetric couplings at the electrode-molecule interfaces.

  6. The rate of charge tunneling is insensitive to polar terminal groups in self-assembled monolayers in Ag(TS)S(CH2)(n)M(CH2)(m)T//Ga2O3/EGaIn junctions.

    Science.gov (United States)

    Yoon, Hyo Jae; Bowers, Carleen M; Baghbanzadeh, Mostafa; Whitesides, George M

    2014-01-08

    This paper describes a physical-organic study of the effect of uncharged, polar, functional groups on the rate of charge transport by tunneling across self-assembled monolayer (SAM)-based large-area junctions of the form Ag(TS)S(CH2)(n)M(CH2)(m)T//Ga2O3/EGaIn. Here Ag(TS) is a template-stripped silver substrate, -M- and -T are "middle" and "terminal" functional groups, and EGaIn is eutectic gallium-indium alloy. Twelve uncharged polar groups (-T = CN, CO2CH3, CF3, OCH3, N(CH3)2, CON(CH3)2, SCH3, SO2CH3, Br, P(O)(OEt)2, NHCOCH3, OSi(OCH3)3), having permanent dipole moments in the range 0.5 < μ < 4.5, were incorporated into the SAM. A comparison of the electrical characteristics of these junctions with those of junctions formed from n-alkanethiolates led to the conclusion that the rates of charge tunneling are insensitive to the replacement of terminal alkyl groups with the terminal polar groups in this set. The current densities measured in this work suggest that the tunneling decay parameter and injection current for SAMs terminated in nonpolar n-alkyl groups, and polar groups selected from common polar organic groups, are statistically indistinguishable.

  7. PWR fuel assembly

    International Nuclear Information System (INIS)

    Yamada, Yuji.

    1995-01-01

    A lower end plug is secured to a lower end of a thimble tube. A bolt-like thimble screw is screw-coupled and fastened to a female screw disposed to the end plug by way of a bushing screw-coupled to a lower nozzle. Then, the thimble screw and the lower nozzle are welded to secure the thimble tube and the lower nozzle. The lower portion of the bushing extends near the lower surface of the lower nozzle. The extended portion is provided with a recess to which a bolt head of the thimble screw is tightly inserted and a seating-face portion against which a seating-face of the bolt head abuts. Then, the extended portion of the bushing and the lower nozzle are spot-welded on the side of the lower surface of the nozzle, to prevent rotation of the bushing. This can easily prevent the rotation of the bushing after adjustment, to simplify the assembling of the fuel assembly. (I.N.)

  8. 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.

    Directory of Open Access Journals (Sweden)

    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.

  9. US production of natural gas from tight reservoirs

    International Nuclear Information System (INIS)

    1993-01-01

    For the purposes of this report, tight gas reservoirs are defined as those that meet the Federal Energy Regulatory Commission's (FERC) definition of tight. They are generally characterized by an average reservoir rock permeability to gas of 0.1 millidarcy or less and, absent artificial stimulation of production, by production rates that do not exceed 5 barrels of oil per day and certain specified daily volumes of gas which increase with the depth of the reservoir. All of the statistics presented in this report pertain to wells that have been classified, from 1978 through 1991, as tight according to the FERC; i.e., they are ''legally tight'' reservoirs. Additional production from ''geologically tight'' reservoirs that have not been classified tight according to the FERC rules has been excluded. This category includes all producing wells drilled into legally designated tight gas reservoirs prior to 1978 and all producing wells drilled into physically tight gas reservoirs that have not been designated legally tight. Therefore, all gas production referenced herein is eligible for the Section 29 tax credit. Although the qualification period for the credit expired at the end of 1992, wells that were spudded (began to be drilled) between 1978 and May 1988, and from November 5, 1990, through year end 1992, are eligible for the tax credit for a subsequent period of 10 years. This report updates the EIA's tight gas production information through 1991 and considers further the history and effect on tight gas production of the Federal Government's regulatory and tax policy actions. It also provides some high points of the geologic background needed to understand the nature and location of low-permeability reservoirs

  10. Connexin43 hemichannels contributes to the disassembly of cell junctions through modulation of intracellular oxidative status

    Directory of Open Access Journals (Sweden)

    Yuan Chi

    2016-10-01

    Full Text Available Connexin (Cx hemichannels regulate many cellular processes with little information available regarding their mechanisms. Given that many pathological factors that activate hemichannels also disrupts the integrity of cellular junctions, we speculated a potential participation of hemichannels in the regulation of cell junctions. Here we tested this hypothesis. Exposure of renal tubular epithelial cells to Ca2+-free medium led to disassembly of tight and adherens junctions, as indicated by the reduced level of ZO-1 and cadherin, disorganization of F-actin, and severe drop in transepithelial electric resistance. These changes were preceded by an activation of Cx43 hemichannels, as revealed by extracellular efflux of ATP and intracellular influx of Lucifer Yellow. Inhibition of hemichannels with chemical inhibitors or Cx43 siRNA greatly attenuated the disassembly of cell junctions. Further analysis using fetal fibroblasts derived from Cx43 wide-type (Cx43+/+, heterozygous (Cx43+/- and knockout (Cx43-/- littermates showed that Cx43-positive cells (Cx43+/+ exhibited more dramatic changes in cell shape, F-actin, and cadherin in response to Ca2+ depletion, as compared to Cx43-null cells (Cx43-/-. Consistently, these cells had higher level of protein carbonyl modification and phosphorylation, and much stronger activation of P38 and JNK. Hemichannel opening led to extracellular loss of the major antioxidant glutathione (GSH. Supplement of cells with exogenous GSH or inhibition of oxidative sensitive kinases largely prevented the above-mentioned changes. Taken together, our study indicates that Cx43 hemichannels promote the disassembly of cell junctions through regulation of intracellular oxidative status.

  11. Improvement of intestinal absorption of forsythoside A in weeping forsythia extract by various absorption enhancers based on tight junctions.

    Science.gov (United States)

    Zhou, Wei; Qin, Kun Ming; Shan, Jin Jun; Ju, Wen Zheng; Liu, Shi Jia; Cai, Bao Chang; Di, Liu Qing

    2012-12-15

    Forsythoside A (FTA), one of the main active ingredients in weeping forsythia extract, possesses strong antibacterial, antioxidant and antiviral effects, and its content was about 8% of totally, higher largely than that of other ingredients, but the absolute bioavailability orally was approximately 0.5%, which is significant low influencing clinical efficacies of its oral preparations. In the present study, in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo pharmacokinetics study were performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test, measurement of total amount of protein and the activity of LDH and morphology observation, respectively. The pharmacological effects such as antioxidant activity improvement by absorption enhancers were verified by PC12 cell damage inhibition rate after H₂O₂ insults. The observations from in vitro Caco-2 cell showed that the absorption of FTA in weeping forsythia extract could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/ml was safe for the Caco-2 cells, but water-soluble chitosan at different concentrations was all safe for these cells. The observations from single-pass intestinal perfusion in situ model showed that duodenum, jejunum, ileum and colon showed significantly concentration-dependent increase in P(eff)-value, and that P(eff)-value in the ileum and colon groups, where sodium caprate was added, was higher than that of duodenum and jejunum groups, but P(eff)-value in the jejunum group was higher than that of duodenum, ileum and colon groups where water-soluble chitosan was added. Intestinal mucosal toxicity studies showed no

  12. Four-junction superconducting circuit

    Science.gov (United States)

    Qiu, Yueyin; Xiong, Wei; He, Xiao-Ling; Li, Tie-Fu; You, J. Q.

    2016-01-01

    We develop a theory for the quantum circuit consisting of a superconducting loop interrupted by four Josephson junctions and pierced by a magnetic flux (either static or time-dependent). In addition to the similarity with the typical three-junction flux qubit in the double-well regime, we demonstrate the difference of the four-junction circuit from its three-junction analogue, including its advantages over the latter. Moreover, the four-junction circuit in the single-well regime is also investigated. Our theory provides a tool to explore the physical properties of this four-junction superconducting circuit. PMID:27356619

  13. Impact of Anchoring Groups on Ballistic Transport: Single Molecule vs Monolayer Junctions

    Science.gov (United States)

    2015-01-01

    Tuning the transport properties of molecular junctions by chemically modifying the molecular structure is one of the key challenges for advancing the field of molecular electronics. In the present contribution, we investigate current–voltage characteristics of differently linked metal–molecule–metal systems that comprise either a single molecule or a molecular assembly. This is achieved by employing density functional theory in conjunction with a Green’s function approach. We show that the conductance of a molecular system with a specific anchoring group is fundamentally different depending on whether a single molecule or a continuous monolayer forms the junction. This is a consequence of collective electrostatic effects that arise from dipolar elements contained in the monolayer and from interfacial charge rearrangements. As a consequence of these collective effects, the “ideal” choice for an anchoring group is clearly different for monolayer and single molecule devices. A particularly striking effect is observed for pyridine-docked systems. These are subject to Fermi-level pinning at high molecular packing densities, causing an abrupt increase of the junction current already at small voltages. PMID:26401191

  14. Magnetic field oscillations of the critical current in long ballistic graphene Josephson junctions

    Science.gov (United States)

    Rakyta, Péter; Kormányos, Andor; Cserti, József

    2016-06-01

    We study the Josephson current in long ballistic superconductor-monolayer graphene-superconductor junctions. As a first step, we have developed an efficient computational approach to calculate the Josephson current in tight-binding systems. This approach can be particularly useful in the long-junction limit, which has hitherto attracted less theoretical interest but has recently become experimentally relevant. We use this computational approach to study the dependence of the critical current on the junction geometry, doping level, and an applied perpendicular magnetic field B . In zero magnetic field we find a good qualitative agreement with the recent experiment of M. Ben Shalom et al. [Nat. Phys. 12, 318 (2016), 10.1038/nphys3592] for the length dependence of the critical current. For highly doped samples our numerical calculations show a broad agreement with the results of the quasiclassical formalism. In this case the critical current exhibits Fraunhofer-like oscillations as a function of B . However, for lower doping levels, where the cyclotron orbit becomes comparable to the characteristic geometrical length scales of the system, deviations from the results of the quasiclassical formalism appear. We argue that due to the exceptional tunability and long mean free path of graphene systems a new regime can be explored where geometrical and dynamical effects are equally important to understand the magnetic field dependence of the critical current.

  15. Hermetic compartments leak-tightness enhancement

    International Nuclear Information System (INIS)

    Murani, J.

    2000-01-01

    In connection with the enhancement of the nuclear safety of the Jaslovske Bohunice V-1 NPP actions for the increase of the leak tightness are performed. The reconstruction has been done in the following directions: hermetic compartments leak tightness enhancement; air lock installation; installation of air lock in SP 4 vent system; integrated leakage rate test to hermetic compartments with leak detection. After 'major' leaks on the hermetic boundary components had been eliminated, since 1994 works on a higher qualitative level began. The essence of the works consists in the detection and identification of leaks in the structural component of the hermetic boundary during the planned refueling outages. The results of the Small Reconstruction and gradual enhancement of leak tightness are presented

  16. Effect of various absorption enhancers based on tight junctions on the intestinal absorption of forsythoside A in Shuang-Huang-Lian, application to its antivirus activity.

    Science.gov (United States)

    Zhou, Wei; Zhu, Xuan Xuan; Yin, Ai Ling; Cai, Bao Chang; Wang, Hai Dan; Di, Liuqing; Shan, Jin Jun

    2014-01-01

    Forsythoside A (FTA), one of the main active ingredients in Shuang-Huang-Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously. In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control. Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL.

  17. Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma alter tight junction structure and function in the rat parotid gland Par-C10 cell line.

    Science.gov (United States)

    Baker, Olga J; Camden, Jean M; Redman, Robert S; Jones, Jonathan E; Seye, Cheikh I; Erb, Laurie; Weisman, Gary A

    2008-11-01

    Sjögren's syndrome (SS) is an autoimmune disorder characterized by inflammation and dysfunction of salivary glands, resulting in impaired secretory function. The production of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) is elevated in exocrine glands of patients with SS, although little is known about the effects of these cytokines on salivary epithelial cell functions necessary for saliva secretion, including tight junction (TJ) integrity and the establishment of transepithelial ion gradients. The present study demonstrates that chronic exposure of polarized rat parotid gland (Par-C10) epithelial cell monolayers to TNF-alpha and IFN-gamma decreases transepithelial resistance (TER) and anion secretion, as measured by changes in short-circuit current (I(sc)) induced by carbachol, a muscarinic cholinergic receptor agonist, or UTP, a P2Y(2) nucleotide receptor agonist. In contrast, TNF-alpha and IFN-gamma had no effect on agonist-induced increases in the intracellular calcium concentration [Ca(2+)](i) in Par-C10 cells. Furthermore, treatment of Par-C10 cell monolayers with TNF-alpha and IFN-gamma increased paracellular permeability to normally impermeant proteins, altered cell and TJ morphology, and downregulated the expression of the TJ protein, claudin-1, but not other TJ proteins expressed in Par-C10 cells. The decreases in TER, agonist-induced transepithelial anion secretion, and claudin-1 expression caused by TNF-alpha, but not IFN-gamma, were reversible by incubation of Par-C10 cell monolayers with cytokine-free medium for 24 h, indicating that IFN-gamma causes irreversible inhibition of cellular activities associated with fluid secretion in salivary glands. Our results suggest that cytokine production is an important contributor to secretory dysfunction in SS by disrupting TJ integrity of salivary epithelium.

  18. Preparation of large-area molecular junctions with metallic conducting Langmuir–Blodgett films

    Energy Technology Data Exchange (ETDEWEB)

    Mochizuki, Kengo [Division of Marine Technology, Tokyo University of Marine Science and Technology, 2-1-6 Etchujima Koto-ku, Tokyo 135-8533 (Japan); Ohnuki, Hitoshi, E-mail: ohnuki@kaiyodai.ac.jp [Division of Marine Technology, Tokyo University of Marine Science and Technology, 2-1-6 Etchujima Koto-ku, Tokyo 135-8533 (Japan); Shimizu, Daisuke [Division of Marine Technology, Tokyo University of Marine Science and Technology, 2-1-6 Etchujima Koto-ku, Tokyo 135-8533 (Japan); Imakubo, Tatsuro [Department of Materials and Technology, Nagaoka University of Technology, 1603-1 Kamitomioka, Nagaoka, Niigata 940-2188 (Japan); Tsuya, Daiju [National Institute for Materials Science,1-2-1 Sengen, Tsukuba, Ibaraki 305-0047 (Japan); Izumi, Mitsuru [Division of Marine Technology, Tokyo University of Marine Science and Technology, 2-1-6 Etchujima Koto-ku, Tokyo 135-8533 (Japan)

    2014-03-03

    Metallic conducting Langmuir–Blodgett (LB) films were used as soft electrodes to fabricate molecular junctions with self-assembled monolayers (SAMs) of alkanethiols (CH{sub 3}(CH{sub 2}){sub n−1}SH) on an Au surface. Alkanethiols can form highly ordered, stable dielectric SAMs on metal surfaces over large areas. However, it is difficult to establish electrical contacts on such SAMs, which has limited their application. In this work, we used metallic conducting LB films composed of bis(ethylenedioxy)tetrathiafulvalene and stearic acid as a soft electrode onto alkanethiol SAMs (C{sub n}-SAM, n = 12, 14, 16, 18) to prepare Au/SAM/metal junctions of relatively large size (∼ 15.6 × 10{sup 3} μm{sup 2}). The current density–voltage (J–V) characteristics across the junctions exhibited rectifying behavior with a ratio R of ∼ 5 (R = |J(V)|/|J(− V)| at ± 1 V). The lower transfer rate corresponding to the electron transport from Au to the LB films exhibited nonlinear J–V characteristics, while the higher transfer rate of electrons from the LB film to Au showed linear J–V characteristics. Kelvin probe force microscopy revealed that the work function of the metallic LB films was smaller than that of Au. The observed rectification behavior is probably caused by different electron transport mechanisms between the two current directions. - Highlights: • Metallic Langmuir–Blodgett (LB) films were used as soft electrodes. • Molecular junctions of metal–alkanethiol–LB films were fabricated. • The current–voltage curve across the junctions exhibited rectifying behavior. • This is the first observation for alkanethiol monolayer junctions. • The work function difference between the electrodes induces the rectification.

  19. 7-Ketocholesterol modulates intercellular communication through gap-junction in bovine lens epithelial cells

    Directory of Open Access Journals (Sweden)

    Pereira Paulo

    2004-06-01

    , that is most likely due to an increased stability of protein at the plasma membrane and to increased abundance of Cx43 assembled in gap junction plaques.

  20. Operational indices of WWER-1000 fuel assemblies and their improvements

    Energy Technology Data Exchange (ETDEWEB)

    Vasilchenko, I; Demin, E [Opytno-Konstruktorskoe Byuro Gidropress, Podol` sk (Russian Federation)

    1994-12-31

    The most general design features of WWER-1000 fuel assembly are discussed. The following advantages of design are stated as well as their operational confirmation and occurrences: (1) `packing` density (tight-lattice) of fuel rods within the fuel assemblies; (2) simple handling of fuel assemblies and its small vulnerability; (3) good conditions for coolant mixing; (4) protection of the absorber rods against coolant effect; (5) adaptability to manufacture that provides stable quality. The main operational indices gathered during a ten-year period (1982-1992) at 17 WWER-1000 units in Russia and Ukraine are outlined. Provisions for emergency protection reliability are described. Future directions to improve fuel economy and control rod operability are discussed. 1 fig.

  1. Operational indices of WWER-1000 fuel assemblies and their improvements

    International Nuclear Information System (INIS)

    Vasilchenko, I.; Demin, E.

    1994-01-01

    The most general design features of WWER-1000 fuel assembly are discussed. The following advantages of design are stated as well as their operational confirmation and occurrences: 1) 'packing' density (tight-lattice) of fuel rods within the fuel assemblies; 2) simple handling of fuel assemblies and its small vulnerability; 3) good conditions for coolant mixing; 4) protection of the absorber rods against coolant effect; 5) adaptability to manufacture that provides stable quality. The main operational indices gathered during a ten-year period (1982-1992) at 17 WWER-1000 units in Russia and Ukraine are outlined. Provisions for emergency protection reliability are described. Future directions to improve fuel economy and control rod operability are discussed. 1 fig

  2. Assembly of Drift Tubes (DT) Chambers at CIEMAT (Madrid)

    CERN Multimedia

    Jesus Puerta-Pelayo

    2003-01-01

    The construction of muon drift tube chambers (DT) has been carried out in four different european institutes: Aachen (Germany), CIEMAT-Madrid (Spain), Legnaro and Turin (Italy), all of them following similar procedures and quality tests. Each chamber is composed by three or two independent units called superlayers, with four layers of staggered drift cells each. The assembly of a superlayer is a succesive glueing of aluminium plates and I-beams with electrodes previously attached, forming a rectangular and gas-tight volume. These pictures illustrate the various processes of material preparation, construction, equipment and assembly of full chambers at CIEMAT (Madrid).

  3. Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue

    Directory of Open Access Journals (Sweden)

    Mehta Bhavya C

    2005-10-01

    the in vitro culture of arachnoidal cells grown from human AG tissue. We demonstrated that these cells in vitro continue to express some of the cytoskeletal and junctional proteins characterized previously in human AG tissue, such as proteins involved in the formation of gap junctions, desmosomes, epithelial specific adherens junctions, as well as tight junctions. These junctional proteins in particular may be important in allowing these arachnoidal cells to regulate CSF outflow.

  4. Cytoplasmic Actin: Purification and Single Molecule Assembly Assays

    Science.gov (United States)

    Hansen, Scott D.; Zuchero, J. Bradley; Mullins, R. Dyche

    2014-01-01

    The actin cytoskeleton is essential to all eukaryotic cells. In addition to playing important structural roles, assembly of actin into filaments powers diverse cellular processes, including cell motility, cytokinesis, and endocytosis. Actin polymerization is tightly regulated by its numerous cofactors, which control spatial and temporal assembly of actin as well as the physical properties of these filaments. Development of an in vitro model of actin polymerization from purified components has allowed for great advances in determining the effects of these proteins on the actin cytoskeleton. Here we describe how to use the pyrene actin assembly assay to determine the effect of a protein on the kinetics of actin assembly, either directly or as mediated by proteins such as nucleation or capping factors. Secondly, we show how fluorescently labeled phalloidin can be used to visualize the filaments that are created in vitro to give insight into how proteins regulate actin filament structure. Finally, we describe a method for visualizing dynamic assembly and disassembly of single actin filaments and fluorescently labeled actin binding proteins using total internal reflection fluorescence (TIRF) microscopy. PMID:23868587

  5. Container for spent fuel assembly

    International Nuclear Information System (INIS)

    Sawai, Takeshi.

    1996-01-01

    The container of the present invention comprises a container main body having a body portion which can contain spent fuel assemblies and a lid, and heat pipes having an evaporation portion disposed along the outer surface of the spent fuel assemblies to be contained and a condensation portion exposed to the outside of the container main body. Further, the heat pipe is formed spirally at the evaporation portions so as to surround the outer circumference of the spent fuel assemblies, branched into a plurality of portions at the condensation portion, each of the branched portion of the condensation portion being exposed to the outside of the container main body, and is tightly in contact with the periphery of the slit portions disposed to the container main body. Then, since released after heat is transferred to the outside of the container main body from the evaporation portion of the heat pipe along the outer surface of the spent fuel assemblies by way of the condensation portion of the heat pipes exposed to the outside of the container main body, the efficiency of the heat transfer is extremely improved to enhance the effect of removing heat of spent fuel assemblies. Further, cooling effect is enhanced by the spiral form of the evaporation portion and the branched condensation portion. (N.H.)

  6. Channel selective tunnelling through a nanographene assembly

    International Nuclear Information System (INIS)

    Wong, H S; Durkan, C; Feng, X; Müllen, K; Chandrasekhar, N

    2012-01-01

    We report selective tunnelling through a nanographene intermolecular tunnel junction achieved via scanning tunnelling microscope tip functionalization with hexa-peri-hexabenzocoronene (HBC) molecules. This leads to an offset in the alignment between the energy levels of the tip and the molecular assembly, resulting in the imaging of a variety of distinct charge density patterns in the HBC assembly, not attainable using a bare metallic tip. Different tunnelling channels can be selected by the application of an electric field in the tunnelling junction, which changes the condition of the HBC on the tip. Density functional theory-based calculations relate the imaged HBC patterns to the calculated molecular orbitals at certain energy levels. These patterns bear a close resemblance to the π-orbital states of the HBC molecule calculated at the relevant energy levels, mainly below the Fermi energy of HBC. This correlation demonstrates the ability of an HBC functionalized tip as regards accessing an energy range that is restricted to the usual operating bias range around the Fermi energy with a normal metallic tip at room temperature. Apart from relating to molecular orbitals, some patterns could also be described in association with the Clar aromatic sextet formula. Our observations may help pave the way towards the possibility of controlling charge transport between organic interfaces. (paper)

  7. Ballistic Graphene Josephson Junctions from the Short to the Long Junction Regimes.

    Science.gov (United States)

    Borzenets, I V; Amet, F; Ke, C T; Draelos, A W; Wei, M T; Seredinski, A; Watanabe, K; Taniguchi, T; Bomze, Y; Yamamoto, M; Tarucha, S; Finkelstein, G

    2016-12-02

    We investigate the critical current I_{C} of ballistic Josephson junctions made of encapsulated graphene-boron-nitride heterostructures. We observe a crossover from the short to the long junction regimes as the length of the device increases. In long ballistic junctions, I_{C} is found to scale as ∝exp(-k_{B}T/δE). The extracted energies δE are independent of the carrier density and proportional to the level spacing of the ballistic cavity. As T→0 the critical current of a long (or short) junction saturates at a level determined by the product of δE (or Δ) and the number of the junction's transversal modes.

  8. Equivalent Josephson junctions

    International Nuclear Information System (INIS)

    Boyadzhiev, T.L.; ); Semerdzhieva, E.G.; Shukrinov, Yu.M.; Fiziko-Tekhnicheskij Inst., Dushanbe

    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 possible 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 flux [ru

  9. Gap junction protein connexin43 exacerbates lung vascular permeability.

    Directory of Open Access Journals (Sweden)

    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. Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation.

    Science.gov (United States)

    Revenu, Céline; Streichan, Sebastian; Donà, Erika; Lecaudey, Virginie; Hufnagel, Lars; Gilmour, Darren

    2014-03-01

    The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process.

  11. Junction and circuit fabrication

    International Nuclear Information System (INIS)

    Jackel, L.D.

    1980-01-01

    Great strides have been made in Josephson junction fabrication in the four years since the first IC SQUID meeting. Advances in lithography have allowed the production of devices with planar dimensions as small as a few hundred angstroms. Improved technology has provided ultra-high sensitivity SQUIDS, high-efficiency low-noise mixers, and complex integrated circuits. This review highlights some of the new fabrication procedures. The review consists of three parts. Part 1 is a short summary of the requirements on junctions for various applications. Part 2 reviews intergrated circuit fabrication, including tunnel junction logic circuits made at IBM and Bell Labs, and microbridge radiation sources made at SUNY at Stony Brook. Part 3 describes new junction fabrication techniques, the major emphasis of this review. This part includes a discussion of small oxide-barrier tunnel junctions, semiconductor barrier junctions, and microbridge junctions. Part 3 concludes by considering very fine lithography and limitations to miniaturization. (orig.)

  12. Fabrication of BiOBr nanosheets@TiO{sub 2} nanobelts p–n junction photocatalysts for enhanced visible-light activity

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Huang, Xiang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); School of Science, Tibet University, Lhasa 850000 (China); Tan, Xin [School of Science, Tibet University, Lhasa 850000 (China); Yu, Tao, E-mail: yutao@tju.edu.cn [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072 (China); Li, Xiangli [School of Environmental Science and Engineering, Tianjin University, Tianjin 300072 (China); Yang, Libin [College of Chemical Engineering and Materials Science, Tianjin University of Science & Technology, Tianjin Key Laboratory of Marine Resources and Chemistry, Tianjin 300457 (China); Wang, Shucong [School of Environmental Science and Engineering, Tianjin University, Tianjin 300072 (China)

    2016-03-01

    Graphical abstract: - Highlights: • BiOBr nanosheets@TiO{sub 2} nanobelts p–n junction photocatalysts have been synthesized. • The p–n junction photocatalysts improved water splitting and dye degradation activity. • BiOBr amount in the BiOBr@TiO{sub 2} photocatalysts was investigated. - Abstract: The construction of p–n junction structure is a smart strategy for improving the photocatalytic activity, since p–n junctions can inhibit the recombination of photo-induced charges. Herein, BiOBr nanosheets@TiO{sub 2} nanobelts p–n junction photocatalysts were prepared by assembling BiOBr nanosheets on the surface of TiO{sub 2} nanobelts via a hydrothermal route followed by a co-precipitation process. BiOBr@TiO{sub 2} p–n junction photocatalysts exhibited enhanced photocatalytic activity in photocatalytic H{sub 2} production over water splitting and photodegradation of Rhodamine B (RhB) under visible light irradiation. Mott–Schottky plots confirmed the formation of p–n junctions in the interface of BiOBr and TiO{sub 2}. The enhanced photocatalytic performance can be ascribed to the 1D nanostructure and the formation of p–n junctions. This work shows a potential application of low cost BiOBr as a substitute for noble metals in photocatalytic H{sub 2} production under visible light irradiation.

  13. Ouabain Increases Gap Junctional Communication in Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Arturo Ponce

    2014-11-01

    Full Text Available Background/Aims: The finding that endogenous ouabain acts as a hormone prompted efforts to elucidate its physiological function. In previous studies, we have shown that 10 nM ouabain (i.e., a concentration within the physiological range modulates cell-cell contacts such as tight junctions and apical/basolateral polarity. In this study, we examined whether 10 nM ouabain affects another important cell-cell feature: gap junction communication (GJC. Methods: We employed two different approaches: 1 analysis of the cell-to-cell diffusion of neurobiotin injected into a particular MDCK cell (epithelial cells from dog kidneys in a confluent monolayer by counting the number of neighboring cells reached by the probe and 2 measurement of the electrical capacitance. Results: We found that 10 nM ouabain increase GJC by 475% within 1 hour. The Na+-K+-ATPase acts as a receptor of ouabain. In previous works we have shown that ouabain activates c-Src and ERK1/2 in 1 hour; in the present study we show that the inhibition of these proteins block the effect of ouabain on GJC. This increase in GJC does not require synthesis of new protein components, because the inhibitors cycloheximide and actinomycin D did not affect this phenomenon. Using silencing assays we also demonstrate that this ouabain-induced enhancement of GJC involves connexins 32 and 43. Conclusion: Ouabain 10 nM increases GJC in MDCK cells.

  14. Micro-Masonry: Construction of 3D Structures by Mesoscale Self-Assembly

    Science.gov (United States)

    Fernandez, Javier G.; Khademhosseini, Ali

    2010-01-01

    A general method for construction of three dimensional structures by directed assembly of microscale polymeric sub-units is presented. Shape-controlled microgels are directed to assemble into different shapes by limiting their movement onto a molded substrate. The capillary forces, resulting from the presence of a liquid polymer, assemble the microgels in close contact with the rest of the units and with the free surface, the latter imposing the final geometry of the resulting construct. The result is a freestanding structure composed of one or multiple layers of sub-units assembled in a tightly packed conformation. The applicability of the technique for the construction of scaffolds with cell-laden sub-units is demonstrated. In addition, scaffolds formed by the sequential aggregation of sub-units are produced. PMID:20440697

  15. Tight connection between fission gas discharge channels

    International Nuclear Information System (INIS)

    Jung, W.; Peehs, M.; Rau, P.; Krug, W.; Stechemesser, H.

    1978-01-01

    The invention is concerned with the tight connection between the fission gas discharge channel, leading away from the support plate of a gas-cooled reactor, and the top of the fuel element suspended from this support plate. The closure is designed to be gas-tight for the suspended as well as for the released fuel element. The tight connection has got an annular body resting on the core support plate in the mouth region of the fission gas discharge channel. This body is connected with the fission gas discharge channel in the fuel element top fitting via a gas-tight part and supported by a compression spring. Care is taken for sealing if the fuel element is removal. (RW) [de

  16. 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.

  17. Analytic expression for the giant fieldlike spin torque in spin-filter magnetic tunnel junctions

    Science.gov (United States)

    Tang, Y.-H.; Huang, Z.-W.; Huang, B.-H.

    2017-08-01

    We propose analytic expressions for fieldlike, T⊥, and spin-transfer, T∥, spin torque components in the spin-filter-based magnetic tunnel junction (SFMTJ), by using the single-band tight-binding model with the nonequilibrium Keldysh formalism. In consideration of multireflection processes between noncollinear magnetization of the spin-filter (SF) barrier and the ferromagnetic (FM) electrode, the central spin-selective SF barrier plays an active role in the striking discovery T⊥≫T∥ , which can be further identified by the unusual barrier thickness dependence of giant T⊥. Our general expressions reveal the sinusoidal angular dependence of both spin torque components, even in the presence of the SF barrier.

  18. Tightly Secure Signatures From Lossy Identification Schemes

    OpenAIRE

    Abdalla , Michel; Fouque , Pierre-Alain; Lyubashevsky , Vadim; Tibouchi , Mehdi

    2015-01-01

    International audience; In this paper, we present three digital signature schemes with tight security reductions in the random oracle model. Our first signature scheme is a particularly efficient version of the short exponent discrete log-based scheme of Girault et al. (J Cryptol 19(4):463–487, 2006). Our scheme has a tight reduction to the decisional short discrete logarithm problem, while still maintaining the non-tight reduction to the computational version of the problem upon which the or...

  19. Design report of the disposal canister for twelve fuel assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Raiko, H. [VTT Energy, Espoo (Finland); Salo, J.P. [Posiva Oy, Helsinki (Finland)

    1999-05-01

    The report provides a summary of the design of the canister for final disposal of spent nuclear fuel. The canister structure consists of a cylindrical massive nodular graphite cast iron insert covered by a 50 mm thick copper overlay. The capacity of the canister is 12 assemblies of BWR or VVER 440 fuel. The canister shall be tight with a high probability for about 100 000 years. The good and long lasting tightness requires: (1) The good initial tightness that is achieved by high quality requirements and extensive quality control, (2) The good corrosion resistance, which is obtained by the overpack of oxygen free copper, and (3) Mechanical strength of the canister, that is ensured by analyses (the following loads are considered: hydrostatic pressure, even and uneven swelling pressure of bentonite, thermal effects, and elevated hydrostatic pressure during glaciation. The allowed stresses and strains are set in such a way that reasonable engineering safety factors are obtained in all assessed design base loading cases). The canister shall limit the radiation dose rate outside the canister to minimise the radiolysis of the water in the vicinity of the canister. The canister insert shall keep the fuel assemblies in a subcritical configuration even if the void in the canister is filled with water due to postulated leakage. The design basis of the canister is set, the performed analyses are summarised and the results are assessed and discussed in the report. (orig.) 35 refs.

  20. Design report of the disposal canister for twelve fuel assemblies

    International Nuclear Information System (INIS)

    Raiko, H.; Salo, J.P.

    1999-05-01

    The report provides a summary of the design of the canister for final disposal of spent nuclear fuel. The canister structure consists of a cylindrical massive nodular graphite cast iron insert covered by a 50 mm thick copper overlay. The capacity of the canister is 12 assemblies of BWR or VVER 440 fuel. The canister shall be tight with a high probability for about 100 000 years. The good and long lasting tightness requires: (1) The good initial tightness that is achieved by high quality requirements and extensive quality control, (2) The good corrosion resistance, which is obtained by the overpack of oxygen free copper, and (3) Mechanical strength of the canister, that is ensured by analyses (the following loads are considered: hydrostatic pressure, even and uneven swelling pressure of bentonite, thermal effects, and elevated hydrostatic pressure during glaciation. The allowed stresses and strains are set in such a way that reasonable engineering safety factors are obtained in all assessed design base loading cases). The canister shall limit the radiation dose rate outside the canister to minimise the radiolysis of the water in the vicinity of the canister. The canister insert shall keep the fuel assemblies in a subcritical configuration even if the void in the canister is filled with water due to postulated leakage. The design basis of the canister is set, the performed analyses are summarised and the results are assessed and discussed in the report. (orig.)

  1. Macroscopic quantum tunneling in Josephson tunnel junctions and Coulomb blockade in single small tunnel junctions

    International Nuclear Information System (INIS)

    Cleland, A.N.

    1991-04-01

    Experiments investigating the process of macroscopic quantum tunneling in a moderately-damped, resistively shunted, Josephson junction are described, followed by a discussion of experiments performed on very small capacitance normal-metal tunnel junctions. The experiments on the resistively-shunted Josephson junction were designed to investigate a quantum process, that of the tunneling of the Josephson phase variable under a potential barrier, in a system in which dissipation plays a major role in the dynamics of motion. All the parameters of the junction were measured using the classical phenomena of thermal activation and resonant activation. Theoretical predictions are compared with the experimental results, showing good agreement with no adjustable parameters; the tunneling rate in the moderately damped (Q ∼ 1) junction is seen to be reduced by a factor of 300 from that predicted for an undamped junction. The phase is seen to be a good quantum-mechanical variable. The experiments on small capacitance tunnel junctions extend the measurements on the larger-area Josephson junctions from the region in which the phase variable has a fairly well-defined value, i.e. its wavefunction has a narrow width, to the region where its value is almost completely unknown. The charge on the junction becomes well-defined and is predicted to quantize the current through the junction, giving rise to the Coulomb blockade at low bias. I present the first clear observation of the Coulomb blockade in single junctions. The electrical environment of the tunnel junction, however, strongly affects the behavior of the junction: higher resistance leads are observed to greatly sharpen the Coulomb blockade over that seen with lower resistance leads. I present theoretical descriptions of how the environment influences the junctions; comparisons with the experimental results are in reasonable agreement

  2. Experimental analysis of the strength of silver-alumina junction elaborated at solid state bonding

    International Nuclear Information System (INIS)

    Serier, B.; Bachir Bouiadjra, B.; Belhouari, M.; Treheux, D.

    2011-01-01

    Highlights: → The adhesion strength is closely related to the plastic deformation of the metal joint. → It is possible to transform a system with weak energy of adhesion into a system with strong energy. → The adhesion strength depends on Silver diffusion in the ceramic grains boundaries. -- Abstract: The mechanisms of ceramics-metal assemblies, particularly silver and alumina, can be better understood by studying the strength of their adhesion. These two materials are a priori non-reactive, their thermodynamic work of adhesion is low and the difference between their thermal coefficients of expansion in very considerable. In this study, the strength of silver-alumina junctions elaborated at solid state by thermo-compression is tested by an indirect tensile test and shearing one. The effects of several parameters such as: the pressure of bonding, the time of bonding, the temperature, and the oxygen dissolve in metal solid solution on the strength of the junction are analyzed. The obtained results show that the resistance of the junction is affected by all this parameters and it is essential to optimize these different parameters in order to increase the durability of the junction. It was also shown that the diffusion of the silver in alumina could be the cause of the damage of alumina near the interface.

  3. Tightness Entropic Uncertainty Relation in Quantum Markovian-Davies Environment

    Science.gov (United States)

    Zhang, Jun; Liu, Liang; Han, Yan

    2018-05-01

    In this paper, we investigate the tightness of entropic uncertainty relation in the absence (presence) of the quantum memory which the memory particle being weakly coupled to a decohering Davies-type Markovian environment. The results show that the tightness of the quantum uncertainty relation can be controlled by the energy relaxation time F, the dephasing time G and the rescaled temperature p, the perfect tightness can be arrived by dephasing and energy relaxation satisfying F = 2G and p = 1/2. In addition, the tightness of the memory-assisted entropic uncertainty relation and the entropic uncertainty relation can be influenced mainly by the purity. While in memory-assisted model, the purity and quantum correlation can also influence the tightness actively while the quantum entanglement can influence the tightness slightly.

  4. Josephson junction arrays

    International Nuclear Information System (INIS)

    Bindslev Hansen, J.; Lindelof, P.E.

    1985-01-01

    In this review we intend to cover recent work involving arrays of Josephson junctions. The work on such arrays falls naturally into three main areas of interest: 1. Technical applications of Josephson junction arrays for high-frequency devices. 2. Experimental studies of 2-D model systems (Kosterlitz-Thouless phase transition, commensurate-incommensurate transition in frustrated (flux) lattices). 3. Investigations of phenomena associated with non-equilibrium superconductivity in and around Josephson junctions (with high current density). (orig./BUD)

  5. Transient suppression of gap junctional intercellular communication after exposure to 100-nanosecond pulsed electric fields.

    Science.gov (United States)

    Steuer, Anna; Schmidt, Anke; Labohá, Petra; Babica, Pavel; Kolb, Juergen F

    2016-12-01

    Gap junctional intercellular communication (GJIC) is an important mechanism that is involved and affected in many diseases and injuries. So far, the effect of nanosecond pulsed electric fields (nsPEFs) on the communication between cells was not investigated. An in vitro approach is presented with rat liver epithelial WB-F344 cells grown and exposed in a monolayer. In order to observe sub-lethal effects, cells were exposed to pulsed electric fields with a duration of 100ns and amplitudes between 10 and 20kV/cm. GJIC strongly decreased within 15min after treatment but recovered within 24h. Gene expression of Cx43 was significantly decreased and associated with a reduced total amount of Cx43 protein. In addition, MAP kinases p38 and Erk1/2, involved in Cx43 phosphorylation, were activated and Cx43 became hyperphosphorylated. Immunofluorescent staining of Cx43 displayed the disassembly of gap junctions. Further, a reorganization of the actin cytoskeleton was observed whereas tight junction protein ZO-1 was not significantly affected. All effects were field- and time-dependent and most pronounced within 30 to 60min after treatment. A better understanding of a possible manipulation of GJIC by nsPEFs might eventually offer a possibility to develop and improve treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. EAST machine assembly and its measurement system

    International Nuclear Information System (INIS)

    Wu, S.T.

    2005-01-01

    The EAST (HT-7U) superconducting tokamak consists of a superconducting poloidal field magnet system, a toroidal field magnet system, a vacuum vessel and in-vessel components, thermal shields and a cryostat vessel. The main parts of the machine have been delivered to ASIPP (Institute of Plasma Physics, Chinese Academy of Sciences) successionally from 2003. For its complicated constitution and precise requirement, a reasonable assembly procedure and measurement technique should be defined carefully. Before the assembly procedure, a reference frame has been set up with reference fiducial targets on the wall of the test hall by an industrial measurement system. After the torus of TF coils is formed, a new reference frame will be set up from the position of the TF torus. The vacuum vessel with all inner parts will be installed with reference of the new reference frame. The big size and mass of components, special configuration of the superconducting machine with tight installation tolerances of the HT-7U (EAST) machine result in complicated assembly procedure. The procedure had begun with the installation of the support frame and the base of cryostat vessel last year. In this paper, the requirements of the assembly precise for some key components of the machine are described. The reference frame for the assembly and maintenance is explained. The assembly procedure is introduced

  7. Electronic thermometry in tunable tunnel junction

    Science.gov (United States)

    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.

  8. Interrogating the architecture of protein assemblies and protein interaction networks by cross-linking mass spectrometry

    NARCIS (Netherlands)

    Liu, Fan; Heck, Albert J R

    2015-01-01

    Proteins are involved in almost all processes of the living cell. They are organized through extensive networks of interaction, by tightly bound macromolecular assemblies or more transiently via signaling nodes. Therefore, revealing the architecture of protein complexes and protein interaction

  9. Dynamics of Josephson junction arrays

    International Nuclear Information System (INIS)

    Hadley, P.

    1989-01-01

    The dynamics of Josephson junction arrays is a topic that lies at the intersection of the fields of nonlinear dynamics and Josephson junction technology. The series arrays considered here consist of several rapidly oscillating Josephson junctions where each junction is coupled equally to every other junction. The purpose of this study is to understand phaselocking and other cooperative dynamics of this system. Previously, little was known about high dimensional nonlinear systems of this sort. Numerical simulations are used to study the dynamics of these arrays. Three distinct types of periodic solutions to the array equations were observed as well as period doubled and chaotic solutions. One of the periodic solutions is the symmetric, in-phase solution where all of the junctions oscillate identically. The other two periodic solutions are symmetry-broken solutions where all of the junction do not oscillate identically. The symmetry-broken solutions are highly degenerate. As many as (N - 1) stable solutions can coexist for an array of N junctions. Understanding the stability of these several solutions and the transitions among them is vital to the design of useful devices

  10. Controllable assembly of silver nanoparticles induced by femtosecond laser direct writing

    International Nuclear Information System (INIS)

    Wang, Huan; Liu, Sen; Zhang, Yong-Lai; Wang, Jian-Nan; Wang, Lei; Xia, Hong; Chen, Qi-Dai; Sun, Hong-Bo; Ding, Hong

    2015-01-01

    We report controllable assembly of silver nanoparticles (Ag NPs) for patterning of silver microstructures. The assembly is induced by femtosecond laser direct writing (FsLDW). A tightly focused femtosecond laser beam is capable of trapping and driving Ag NPs to form desired micropatterns with a high resolution of ∼190 nm. Taking advantage of the ‘direct writing’ feature, three microelectrodes have been integrated with a microfluidic chip; two silver-based microdevices including a microheater and a catalytic reactor have been fabricated inside a microfluidic channel for chip functionalization. The FsLDW-induced programmable assembly of Ag NPs may open up a new way to the designable patterning of silver microstructures toward flexible fabrication and integration of functional devices. (focus issue paper)

  11. Inverted-conical light guide for crosstalk reduction in tightly-packed scintillator matrix and MAPMT assembly

    DEFF Research Database (Denmark)

    Chang, Y.-Y.; Chen, P.; Huang, J.-J.

    2015-01-01

    In this paper we present the Inverted-Conical light guide designed for optical crosstalk reduction in the scintillator-MAPMT assemblies. The research was motivated by the 30% crosstalk observed in UFFO X-ray telescope, UBAT, during the preliminary calibration with MAPMTs of 64 2.88 × 2.88 mm2...... pixels and identically gridded YSO crystal matrices. We began the study with the energy and crosstalk calibrations of the detector, then we constructed a GEANT4 simulation with the customized metallic film model as the MAPMT photocathode. The simulation reproduced more than 70% of the crosstalk...... and explained it as a consequence of the total reflection produced by the photocathode. The result indicated that the crosstalk mechanism could be a common case in most of the contact-assembled scintillation detectors. The concept of the Inverted-Conical light guide was to suppress the total reflection...

  12. Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters

    Science.gov (United States)

    Stains, Joseph P.; Lecanda, Fernando; Screen, Joanne; Towler, Dwight A.; Civitelli, Roberto

    2003-01-01

    Loss-of-function mutations of gap junction proteins, connexins, represent a mechanism of disease in a variety of tissues. We have shown that recessive (gene deletion) or dominant (connexin45 overexpression) disruption of connexin43 function results in osteoblast dysfunction and abnormal expression of osteoblast genes, including down-regulation of osteocalcin transcription. To elucidate the molecular mechanisms of gap junction-sensitive transcriptional regulation, we systematically analyzed the rat osteocalcin promoter for sensitivity to gap junctional intercellular communication. We identified an Sp1/Sp3 containing complex that assembles on a minimal element in the -70 to -57 region of the osteocalcin promoter in a gap junction-dependent manner. This CT-rich connexin-response element is necessary and sufficient to confer gap junction sensitivity to the osteocalcin proximal promoter. Repression of osteocalcin transcription occurs as a result of displacement of the stimulatory Sp1 by the inhibitory Sp3 on the promoter when gap junctional communication is perturbed. Modulation of Sp1/Sp3 recruitment also occurs on the collagen Ialpha1 promoter and translates into gap junction-sensitive transcriptional control of collagen Ialpha1 gene expression. Thus, regulation of Sp1/Sp3 recruitment to the promoter may represent a potential general mechanism for transcriptional control of target genes by signals passing through gap junctions.

  13. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  14. Assembly and method for testing the integrity of stuffing tubes

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, E.F.

    1996-12-31

    A stuffing tube integrity checking assembly includes first and second annular seals, with each seal adapted to be positioned about a stuffing tube penetration component. An annular inflation bladder is provided, the bladder having a slot extending longitudinally there along and including a separator for sealing the slot. A first valve is in fluid communication with the bladder for introducing pressurized fluid to the space defined by the bladder when mounted about the tube. First and second releasible clamps are provided. Each clamp assembly is positioned about the bladder for securing the bladder to one of the seals for thereby establishing a fluid-tight chamber about the tube.

  15. A single-gradient junction technique to replace multiple-junction shifts for craniospinal irradiation treatment

    International Nuclear Information System (INIS)

    Hadley, Austin; Ding, George X.

    2014-01-01

    Craniospinal irradiation (CSI) requires abutting fields at the cervical spine. Junction shifts are conventionally used to prevent setup error–induced overdosage/underdosage from occurring at the same location. This study compared the dosimetric differences at the cranial-spinal junction between a single-gradient junction technique and conventional multiple-junction shifts and evaluated the effect of setup errors on the dose distributions between both techniques for a treatment course and single fraction. Conventionally, 2 lateral brain fields and a posterior spine field(s) are used for CSI with weekly 1-cm junction shifts. We retrospectively replanned 4 CSI patients using a single-gradient junction between the lateral brain fields and the posterior spine field. The fields were extended to allow a minimum 3-cm field overlap. The dose gradient at the junction was achieved using dose painting and intensity-modulated radiation therapy planning. The effect of positioning setup errors on the dose distributions for both techniques was simulated by applying shifts of ± 3 and 5 mm. The resulting cervical spine doses across the field junction for both techniques were calculated and compared. Dose profiles were obtained for both a single fraction and entire treatment course to include the effects of the conventional weekly junction shifts. Compared with the conventional technique, the gradient-dose technique resulted in higher dose uniformity and conformity to the target volumes, lower organ at risk (OAR) mean and maximum doses, and diminished hot spots from systematic positioning errors over the course of treatment. Single-fraction hot and cold spots were improved for the gradient-dose technique. The single-gradient junction technique provides improved conformity, dose uniformity, diminished hot spots, lower OAR mean and maximum dose, and one plan for the entire treatment course, which reduces the potential human error associated with conventional 4-shifted plans

  16. 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.

  17. Alterations of Intercellular Junctions in Peritoneal Mesothelial Cells from Patients Undergoing Dialysis: Effect of Retinoic Acid

    Science.gov (United States)

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

    2015-01-01

    ♦ Background: 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. ♦ Methods: 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. ♦ Results: 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. ♦ Conclusions: 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. PMID:24584604

  18. Cotunneling enhancement of magnetoresistance in double magnetic tunnel junctions with embedded superparamagnetic NiFe nanoparticles

    International Nuclear Information System (INIS)

    Dempsey, K.J.; Arena, D.; Hindmarch, A.T.; Wei, H.X.; Qin, Q.H.; Wen, Z.C.; Wang, W.X.; Vallejo-Fernandez, G.; Han, X.F.; Marrows, C.H.

    2010-01-01

    Temperature and bias voltage-dependent transport characteristics are presented for double magnetic tunnel junctions (DMTJs) with self-assembled NiFe nanoparticles embedded between insulating alumina barriers. The junctions with embedded nanoparticles are compared to junctions with a single barrier of comparable size and growth conditions. The embedded particles are characterized using x-ray absorption spectroscopy, transmission electron microscopy, and magnetometry techniques, showing that they are unoxidized and remain superparamagnetic to liquid helium temperatures. The tunneling magnetoresistance (TMR) for the DMTJs is lower than the control samples, however, for the DMTJs an enhancement in TMR is seen in the Coulomb blockade region. Fitting the transport data in this region supports the theory that cotunneling is the dominant electron transport process within the Coulomb blockade region, sequential tunneling being suppressed. We therefore see an enhanced TMR attributed to the change in the tunneling process due to the interplay of the Coulomb blockade and spin-dependent tunneling through superparamagnetic nanoparticles, and develop a simple model to quantify the effect, based on the fact that our nanoparticles will appear blocked when measured on femtosecond tunneling time scales.

  19. Unsteady Reynolds averaged Navier-Stokes: toward accurate predictions in fuel-bundles and T-junctions

    International Nuclear Information System (INIS)

    Merzari, E.; Ninokata, H.; Baglietto, E.

    2008-01-01

    Traditional steady-state simulation and turbulence modelling are not always reliable. Even in simple flows, the results can be not accurate when particular conditions occur. Examples are buoyancy, flow oscillations, and turbulent mixing. Often, unsteady simulations are necessary, but they tend to be computationally not affordable. The Unsteady Reynolds Averaged Navier-Stokes (URANS) approach holds promise to be less computational expensive than Large Eddy Simulation (LES) or Direct Numerical Simulation (DNS), reaching a considerable degree of accuracy. Moreover, URANS methodologies do not need complex boundary formulations for the inlet and the outlet like LES or DNS. The Test cases for this methodology will be Fuel Bundles and T-junctions. Tight-Fuel Rod-Bundles present large scale coherent structures than cannot be taken into account by a simple steady-state simulation. T-junctions where a hot fluid and a cold fluid mix present temperature fluctuations and therefore thermal fatigue. For both cases the capacity of the methodology to reproduce the flow field are assessed and it is evaluated that URANS holds promise to be the industrial standard in nuclear engineering applications that do not involve buoyancy. The codes employed are STAR-CD 3.26 and 4.06. (author)

  20. Macroscopic quantum tunneling in Josephson tunnel junctions and Coulomb blockade in single small tunnel junctions

    International Nuclear Information System (INIS)

    Cleland, A.N.

    1991-01-01

    Experiments investigated the process of macroscopic quantum tunneling in a moderately-damped, resistively shunted, Josephson junction are described, followed by a discussion of experiments performed on very-small-capacitance normal-metal tunnel junctions. The experiments on the resistively-shunted Josephson junction were designed to investigate a quantum process, that of the tunneling of the Josephson-phase variable under a potential barrier, in a system in which dissipation plays a major role in the dynamics of motion. All the parameters of the junction were measured using the classical phenomena of thermal activation and resonant activation. Theoretical predictions are compared with the experimental results, showing good agreement with no adjustable parameters. The experiments on small-capacitance tunnel junctions extend the measurements on the large-area Josephson junctions from the region in which the phase variable has a fairly well-defined value, i.e. its wave function has a narrow width, to the region where its value is almost completely unknown. The charge on the junction becomes well-defined and is predicted to quantize the current through the junction, giving rise to the Coulomb blockade at low bias

  1. Examination of leakage aspects through concrete - steel interfaces at and around containment penetration assemblies

    International Nuclear Information System (INIS)

    Chakrabarti, S.K.; Sai, A.S.R.; Basu, P.C.

    1994-01-01

    Penetration assemblies are parts required to be provided in the containment wall/dome to permit piping, mechanical devices, equipments, electrical cables, personnel movements etc. Integrity of arrangements with respect to leak tightness at or around these penetration assemblies, is of utmost importance for achieving safe functioning of containment. Considering the feasibilities in controlling leakages along different possible paths, it has been found necessary to examine in detail the leakage possibilities at concrete - steel interfaces at and around penetration assemblies. The present paper addresses this issue with respect to the important related aspects like constructional details, testing conditions, normal operating conditions, and the accidental situation associated with containment structures. (author)

  2. Increasing gap junctional coupling: a tool for dissecting the role of gap junctions

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Haugan, Ketil; Stahlhut, Martin

    2007-01-01

    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...

  3. Charge solitons and their dynamical mass in one-dimensional arrays of Josephson junctions

    International Nuclear Information System (INIS)

    Homfeld, Jens; Protopopov, Ivan; Rachel, Stephan; Shnirman, Alexander

    2011-01-01

    We investigate charge transport in one-dimensional arrays of Josephson junctions. In the interesting regime of ''small charge solitons'' (polarons), ΛE J >E C >E J , where Λ is the (electrostatic) screening length, the charge dynamics are strongly influenced by the polaronic effects (i.e., by dressing of a Cooper pair by charge dipoles). In particular, the soliton's mass in this regime scales approximately as E J -2 . We employ two theoretical techniques: the many-body tight-binding approach and the mean-field approach, and the results of the two approaches agree in the regime of ''small charge solitons.'' Renormalization of the soliton's mass could be observed; for example, as enhancement of the persistent current in a ring-shaped array.

  4. Charge Transport Processes in Molecular Junctions

    Science.gov (United States)

    Smith, Christopher Eugene

    Molecular electronics (ME) has evolved into a rich area of exploration that combines the fields of chemistry, materials, electronic engineering and computational modeling to explore the physics behind electronic conduction at the molecular level. Through studying charge transport properties of single molecules and nanoscale molecular materials the field has gained the potential to bring about new avenues for the miniaturization of electrical components where quantum phenomena are utilized to achieve solid state molecular device functionality. Molecular junctions are platforms that enable these studies and consist of a single molecule or a small group of molecules directly connected to electrodes. The work presented in this thesis has built upon the current understanding of the mechanisms of charge transport in ordered junctions using self-assembled monolayer (SAM) molecular thin films. Donor and acceptor compounds were synthesized and incorporated into SAMs grown on metal substrates then the transport properties were measured with conducting probe atomic force microscopy (CP-AFM). In addition to experimentally measured current-voltage (I-V) curves, the transport properties were addressed computationally and modeled theoretically. The key objectives of this project were to 1) investigate the impact of molecular structure on hole and electron charge transport, 2) understand the nature of the charge carriers and their structure-transport properties through long (chemically gated to modulate the transport. These results help advance our understanding of transport behavior in semiconducting molecular thin films, and open opportunities to engineer improved electronic functionality into molecular devices.

  5. Junction detection and pathway selection

    Science.gov (United States)

    Peck, Alex N.; Lim, Willie Y.; Breul, Harry T.

    1992-02-01

    The ability to detect junctions and make choices among the possible pathways is important for autonomous navigation. In our script-based navigation approach where a journey is specified as a script of high-level instructions, actions are frequently referenced to junctions, e.g., `turn left at the intersection.' In order for the robot to carry out these kind of instructions, it must be able (1) to detect an intersection (i.e., an intersection of pathways), (2) know that there are several possible pathways it can take, and (3) pick the pathway consistent with the high level instruction. In this paper we describe our implementation of the ability to detect junctions in an indoor environment, such as corners, T-junctions and intersections, using sonar. Our approach uses a combination of partial scan of the local environment and recognition of sonar signatures of certain features of the junctions. In the case where the environment is known, we use additional sensor information (such as compass bearings) to help recognize the specific junction. In general, once a junction is detected and its type known, the number of possible pathways can be deduced and the correct pathway selected. Then the appropriate behavior for negotiating the junction is activated.

  6. Colloidal polymers with controlled sequence and branching constructed from magnetic field assembled nanoparticles.

    Science.gov (United States)

    Bannwarth, Markus B; Utech, Stefanie; Ebert, Sandro; Weitz, David A; Crespy, Daniel; Landfester, Katharina

    2015-03-24

    The assembly of nanoparticles into polymer-like architectures is challenging and usually requires highly defined colloidal building blocks. Here, we show that the broad size-distribution of a simple dispersion of magnetic nanocolloids can be exploited to obtain various polymer-like architectures. The particles are assembled under an external magnetic field and permanently linked by thermal sintering. The remarkable variety of polymer-analogue architectures that arises from this simple process ranges from statistical and block copolymer-like sequencing to branched chains and networks. This library of architectures can be realized by controlling the sequencing of the particles and the junction points via a size-dependent self-assembly of the single building blocks.

  7. Steam and electroheating remediation of tight soils

    Energy Technology Data Exchange (ETDEWEB)

    Balshaw-Biddle, K.; Oubre, C.L.; Ward, C.H. [eds.; Dablow, J.F. III; Pearce, J.A.; Johnson, P.C.

    2000-07-01

    In the past few decades the need for soil remediation has become urgent, even more necessary--innovative, cost effective methods. Steam and Electroheating Remediation of Tight Soils presents the results of a field study testing the cleanup of semi-volatile fuels from tight soils using combination of hydraulic fracturing and soil heating technologies.

  8. Gap junctions at the dendritic cell-T cell interface are key elements for antigen-dependent T cell activation.

    Science.gov (United States)

    Elgueta, Raul; Tobar, Jaime A; Shoji, Kenji F; De Calisto, Jaime; Kalergis, Alexis M; Bono, Maria R; Rosemblatt, Mario; Sáez, Juan C

    2009-07-01

    The acquired immune response begins with Ag presentation by dendritic cells (DCs) to naive T cells in a heterocellular cell-cell contact-dependent process. Although both DCs and T cells are known to express connexin43, a gap junction protein subunit, the role of connexin43 on the initiation of T cell responses remains to be elucidated. In the present work, we report the formation of gap junctions between DCs and T cells and their role on T cell activation during Ag presentation by DCs. In cocultures of DCs and T cells, Lucifer yellow microinjected into DCs is transferred to adjacent transgenic CD4(+) T cells, only if the specific antigenic peptide was present at least during the first 24 h of cocultures. This dye transfer was sensitive to gap junction blockers, such as oleamide, and small peptides containing the extracellular loop sequences of conexin. Furthermore, in this system, gap junction blockers drastically reduced T cell activation as reflected by lower proliferation, CD69 expression, and IL-2 secretion. This lower T cell activation produced by gap junction blockers was not due to a lower expression of CD80, CD86, CD40, and MHC-II on DCs. Furthermore, gap junction blocker did not affect polyclonal activation of T cell induced with anti-CD3 plus anti-CD28 Abs in the absence of DCs. These results strongly suggest that functional gap junctions assemble at the interface between DCs and T cells during Ag presentation and that they play an essential role in T cell activation.

  9. SV40 Assembly In Vivo and In Vitro

    Directory of Open Access Journals (Sweden)

    Ariella Oppenheim

    2008-01-01

    Full Text Available The Simian virus 40 (SV40 capsid is a T = 7d icosahedral lattice ∼45 nm in diameter surrounding the ∼5 kb circular minichromosome. The outer shell is composed of 360 monomers of the major capsid protein VP1, tightly bound in 72 pentamers. VP1 is a jellyroll β-barrel, with extending N- and C-terminal arms. The N-terminal arms bind DNA and face the interior of the capsid. The flexible C-arms tie together the 72 pentamers in three distinct kinds of interactions, thus facilitating the formation of a T = 7 icosahedron from identical pentameric building blocks. Assembly in vivo was shown to occur by addition of capsomers around the DNA. We apply a combination of biochemical and genetic approaches to study SV40 assembly. Our in vivo and in vitro studies suggest the following model: one or two capsomers bind at a high affinity to ses, the viral DNA encapsidation signal, forming the nucleation centre for assembly. Next, multiple capsomers attach concomitantly, at lower affinity, around the minichromosome. This increases their local concentration facilitating rapid, cooperative assembly reaction. Formation of the icosahedron proceeds either by gradual addition of single pentamers to the growing shell or by concerted assembly of pentamer clusters.

  10. Advances of study on thermal-hydraulic performance in tight-lattice rod bundles for reduced-moderation water reactors

    International Nuclear Information System (INIS)

    Akira Ohnuki; Kazuyuki Takase; Masatoshi Kureta; Hiroyuki Yoshida; Hidesada Tamai; Wei Liu; Toru Nakatsuka; Hajime Akimoto

    2005-01-01

    R and D project to investigate thermal-hydraulic performance in tight-lattice rod bundles for Reduced-Moderation Water Reactor (RMWR) is started at Japan Atomic Energy Research Institute in collaboration with power company, reactor vendors, universities since 2002. The RMWR can attain the favorable characteristics such as effective utilization of uranium resources, multiple recycling of plutonium, high burn-up and long operation cycle, based on matured LWR technologies. MOX fuel assemblies with tight lattice arrangement are used to increase the conversion ratio by reducing the moderation of neutron. Increasing the in-core void fraction also contributes to the reduction of neutron moderation. The confirmation of thermal-hydraulic feasibility is one of the most important R and D items for the RMWR because of the tight-lattice configuration. In this paper, we will show the R and D plan and describe some advances on experimental and analytical studies. The experimental study is performed mainly using large-scale (37-rod bundle) test facility and the analytical one aims to develop a predictable technology for geometry effects such as gap between rods, grid spacer configuration etc. using advanced 3-D two-phase flow simulation methods. Steady-state and transient critical power experiments are conducted with the test facility (Gap width between rods: 1.0 mm) and the experimental data reveal the feasibility of RMWR. (authors)

  11. Critical experiments supporting underwater storage of tightly packed configurations of spent fuel pins. Technical progress report, January 1-March 31, 1981

    International Nuclear Information System (INIS)

    Hoovler, G.S.; Baldwin, M.N.

    1981-04-01

    Critical experiments are in progress on arrays of 2 1/2% enriched UO 2 fuel pins simulating underwater pin storage of spent power reactor fuel. Pin storage refers to a spent fuel storage concept in which the fuel assemblies are dismantled and the fuel pins are tightly packed into specially designed canisters. These experiments are providing benchmark data with which to validate nuclear codes used to design spent fuel pin storage racks

  12. An introduction to finite tight frames

    CERN Document Server

    Waldron, Shayne F D

    2018-01-01

    This textbook is an introduction to the theory and applications of finite tight frames, an area that has developed rapidly in the last decade. Stimulating much of this growth are the applications of finite frames to diverse fields such as signal processing, quantum information theory, multivariate orthogonal polynomials, and remote sensing. Key features and topics: * First book entirely devoted to finite frames * Extensive exercises and MATLAB examples for classroom use * Important examples, such as harmonic and Heisenberg frames, are presented in preliminary chapters, encouraging readers to explore and develop an intuitive feeling for tight frames * Later chapters delve into general theory details and recent research results * Many illustrations showing the special aspects of the geometry of finite frames * Provides an overview of the field of finite tight frames * Discusses future research directions in the field Featuring exercises and MATLAB examples in each chapter, the book is well suited as a textbook ...

  13. Phase diagrams of particles with dissimilar patches: X-junctions and Y-junctions

    International Nuclear Information System (INIS)

    Tavares, J M; Teixeira, P I C

    2012-01-01

    We use Wertheim’s first-order perturbation theory to investigate the phase behaviour and the structure of coexisting fluid phases for a model of patchy particles with dissimilar patches (two patches of type A and f B patches of type B). A patch of type α = {A,B} can bond to a patch of type β = {A,B} in a volume v αβ , thereby decreasing the internal energy by ε αβ . We analyse the range of model parameters where AB bonds, or Y-junctions, are energetically disfavoured (ε AB AA /2) but entropically favoured (v AB ≫ v αα ), and BB bonds, or X-junctions, are energetically favoured (ε BB > 0). We show that, for low values of ε BB /ε AA , the phase diagram has three different regions: (i) close to the critical temperature a low-density liquid composed of long chains and rich in Y-junctions coexists with a vapour of chains; (ii) at intermediate temperatures there is coexistence between a vapour of short chains and a liquid of very long chains with X- and Y-junctions; (iii) at low temperatures an ideal gas coexists with a high-density liquid with all possible AA and BB bonds formed. It is also shown that in region (i) the liquid binodal is reentrant (its density decreases with decreasing temperature) for the lower values of ε BB /ε AA . The existence of these three regions is a consequence of the competition between the formation of X- and Y-junctions: X-junctions are energetically favoured and thus dominate at low temperatures, whereas Y-junctions are entropically favoured and dominate at higher temperatures. (paper)

  14. Tight or sick building syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Thirumalaikolundusubramanian, P; Shanmuganadan, S [Madurai Kamaraj Univ. (India). Dept. of Geography; Uma, A [Madurai Medical Coll. (India). Dept. of Medicine and Microbiology

    1991-01-01

    Modern buildings are designed with the usual heating, air-conditioning and ventilation equipment. In most of these buildings, air is continuously recirculated and, as a result, workers suffer from tight or sick building syndrome. This syndrome is discussed with reference to symptoms of air contamination, ventilation system standards and research needs. The most common symptoms of tight building syndrome are eye, nose and throat irritation, headache, fatigue, sneezing, difficulty in wearing contact lenses, chest tightness, nausea, dizziness and dermatitis. Symptoms experienced by 50 doctors and 50 paramedical personnel working in an air-conditioned intensive care unit and operating theatres of the Government Rajaji Hospital, Madurai in India were studied by means of a questionnaire survey. In the present study, respiratory and ocular symptoms were observed more in those working in operating theatres and were believed to be due to excessive use of formaldehyde used for sterilization. Various suggestions were made to prevent sick building syndrome. Moreover, the physicians treating sick individuals should be aware of the symptoms caused by indoor air pollutants as sufferers invariably require a change of environment rather than drugs. (orig.).

  15. Magnetoanisotropic spin-triplet Andreev reflection in ferromagnet-Ising superconductor junctions

    Science.gov (United States)

    Lv, Peng; Zhou, Yan-Feng; Yang, Ning-Xuan; Sun, Qing-Feng

    2018-04-01

    We theoretically study the electronic transport through a ferromagnet-Ising superconductor junction. A tight-binding Hamiltonian describing the Ising superconductor is presented. Then by combining the nonequilibrium Green's function method, the expressions of Andreev reflection coefficient and conductance are obtained. A strong magnetoanisotropic spin-triplet Andreev reflection is shown, and the magnetoanisotropic period is π instead of 2 π as in the conventional magnetoanisotropic system. We demonstrate a significant increase of the spin-triplet Andreev reflection for the single-band Ising superconductor. Furthermore, the dependence of the Andreev reflection on the incident energy and incident angle are also investigated. A complete Andreev reflection can occur when the incident energy is equal to the superconducting gap, regardless of the Fermi energy (spin polarization) of the ferromagnet. For the suitable oblique incidence, the spin-triplet Andreev reflection can be strongly enhanced. In addition, the conductance spectroscopies of both zero bias and finite bias are studied, and the influence of gate voltage, exchange energy, and spin-orbit coupling on the conductance spectroscopy are discussed in detail. The conductance exhibits a strong magnetoanisotropy with period π as the Andreev reflection coefficient. When the magnetization direction is parallel to the junction plane, a large conductance peak always emerges at the superconducting gap. This work offers a comprehensive and systematic study of the spin-triplet Andreev reflection and has an underlying application of π -periodic spin valve in spintronics.

  16. Common features of a vortex structure in long exponentially shaped Josephson junctions and Josephson junctions with inhomogeneities

    International Nuclear Information System (INIS)

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

    2007-01-01

    We study the vortex structure in three different models of the long Josephson junction: the exponentially shaped Josephson junction and the Josephson junctions with the resistor and the shunt inhomogeneities in the barrier layer. For these three models the critical curves 'critical current-magnetic field' are numerically constructed. We develop the idea of the equivalence of the exponentially shaped Josephson junction and the rectangular junction with the distributed inhomogeneity and demonstrate that at some parameters of the shunt and the resistor inhomogeneities in the ends of the junction the corresponding critical curves are very close to the exponentially shaped one

  17. Accurate DNA assembly and genome engineering with optimized uracil excision cloning

    DEFF Research Database (Denmark)

    Cavaleiro, Mafalda; Kim, Se Hyeuk; Seppala, Susanna

    2015-01-01

    Simple and reliable DNA editing by uracil excision (a.k.a. USER cloning) has been described by several research groups, but the optimal design of cohesive DNA ends for multigene assembly remains elusive. Here, we use two model constructs based on expression of gfp and a four-gene pathway that pro......Simple and reliable DNA editing by uracil excision (a.k.a. USER cloning) has been described by several research groups, but the optimal design of cohesive DNA ends for multigene assembly remains elusive. Here, we use two model constructs based on expression of gfp and a four-gene pathway...... that produces β-carotene to optimize assembly junctions and the uracil excision protocol. By combining uracil excision cloning with a genomic integration technology, we demonstrate that up to six DNA fragments can be assembled in a one-tube reaction for direct genome integration with high accuracy, greatly...... facilitating the advanced engineering of robust cell factories....

  18. Quantum transport through mesoscopic disordered interfaces, junctions, and multilayers

    International Nuclear Information System (INIS)

    Nikolic, Branislav K.

    2002-01-01

    This study explores perpendicular transport through macroscopically inhomogeneous three-dimensional disordered conductors using mesoscopic methods (the real-space Green function technique in a two-probe measuring geometry). The nanoscale samples (containing ∼ 1000 atoms) are modelled by a tight-binding Hamiltonian on a simple cubic lattice where disorder is introduced in the on-site potential energy. I compute the transport properties of: disordered metallic junctions formed by concatenating two homogeneous samples with different kinds of microscopic disorder, a single strongly disordered interface, and multilayers composed of such interfaces and homogeneous layers characterized by different strengths of the same type of microscopic disorder. This allows us to: contrast the resistor model (semiclassical) approach with a fully quantum description of dirty mesoscopic multilayers; study the transmission properties of dirty interfaces (where the Schep-Bauer distribution of transmission eigenvalues is confirmed for a single interface, as well as for a stack of such interfaces that is thinner than the localization length); and elucidate the effect of coupling to ideal leads ('measuring apparatus') on the conductance of both bulk conductors and dirty interfaces. When a multilayer contains a ballistic layer in between two interfaces, its disorder-averaged conductance oscillates as a function of the Fermi energy. I also address some fundamental issues in quantum transport theory - the relationship between the Kubo formula in the exact state representation and the 'mesoscopic Kubo formula' (which gives the exact zero-temperature conductance of a finite-size sample attached to two semi-infinite ideal leads) is thoroughly re-examined by comparing their outcomes for both the junctions and homogeneous samples. (author)

  19. Comparison of de novo assembly statistics of Cucumis sativus L.

    Science.gov (United States)

    Wojcieszek, Michał; Kuśmirek, Wiktor; Pawełkowicz, Magdalena; PlÄ der, Wojciech; Nowak, Robert M.

    2017-08-01

    Genome sequencing is the core of genomic research. With the development of NGS and lowering the cost of procedure there is another tight gap - genome assembly. Developing the proper tool for this task is essential as quality of genome has important impact on further research. Here we present comparison of several de Bruijn assemblers tested on C. sativus genomic reads. The assessment shows that newly developed software - dnaasm provides better results in terms of quantity and quality. The number of generated sequences is lower by 5 - 33% with even two fold higher N50. Quality check showed reliable results were generated by dnaasm. This provides us with very strong base for future genomic analysis.

  20. Flexible 2D layered material junctions

    Science.gov (United States)

    Balabai, R.; Solomenko, A.

    2018-03-01

    Within the framework of the methods of the electron density functional and the ab initio pseudopotential, we have obtained the valence electron density spatial distribution, the densities of electron states, the widths of band gaps, the charges on combined regions, and the Coulomb potentials for graphene-based flexible 2D layered junctions, using author program complex. It is determined that the bending of the 2D layered junctions on the angle α leads to changes in the electronic properties of these junctions. In the graphene/graphane junction, there is clear charge redistribution with different signs in the regions of junctions. The presence in the heterojunctions of charge regions with different signs leads to the formation of potential barriers. The greatest potential jump is in the graphene/fluorographene junction. The greatest value of the band gap width is in the graphene/graphane junction.

  1. Interactions Between HIV-1 Gag and Viral RNA Genome Enhance Virion Assembly

    DEFF Research Database (Denmark)

    Dilley, Kari A; Nikolaitchik, Olga A; Galli, Andrea

    2017-01-01

    between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA:Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged......Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious virus-like particles and the viral RNA is dispensable...... in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle...

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

    Science.gov (United States)

    Vetrano, Stefania; Danese, Silvio

    2009-05-01

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

  3. Electrical Resistance of Ag-TS-S(CH2)(n-1)CH3//Ga2O3/EGaln Tunneling Junctions

    NARCIS (Netherlands)

    Cademartiri, Ludovico; Thuo, Martin M.; Nijhuis, Christian A.; Reus, William F.; Tricard, Simon; Barber, Jabulani R.; Sodhi, Rana N. S.; Brodersen, Peter; Kim, Choongik; Chiechi, Ryan C.; Whitesides, George M.

    2012-01-01

    Tunneling junctions having the structure Ag-TS-S(CH2)(n-1)CH3//Ga2O3/EGaIn allow physical-organic studies of charge transport across self-assembled monolayers (SAMs). In ambient conditions, the surface of the liquid metal electrode (EGaIn, 75.5 wt % Ga, 24.5 wt % In, mp 15.7 degrees C) oxidizes and

  4. System for determining the local power in the fuel assembly of a nuclear reactor

    International Nuclear Information System (INIS)

    Rolstad, Erik; Korpas, T.-H.; Leyse, R.H.; Smith, R.D.

    1979-01-01

    System for determining the local power in the fuel assembly of a nuclear reactor which includes a rod conducting the heat and electricity, along which axial areas act as a gamma radiation thermometer. Each area includes a thermal bridge, a cold source and a pair of junctions acting as thermocouples so placed that they measure the temperature difference between the thermal bridge and the cold source. The power created by the fuel assembly near each area acting as gamma thermometer is found from this difference in temperature [fr

  5. Heterocellular interaction enhances recruitment of α and β-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells

    International Nuclear Information System (INIS)

    Talhouk, Rabih S.; Mroue, Rana; Mokalled, Mayssa; Abi-Mosleh, Lina; Nehme, Ralda; Ismail, Ayman; Khalil, Antoine; Zaatari, Mira; El-Sabban, Marwan E.

    2008-01-01

    Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation (β-casein expression) was evaluated. Heterocellular interaction is critical for β-casein expression, independent of exogenous basement membrane or cell anchoring substrata. Functional differentiation of SCp2, co-cultured with SCg6, is more sensitive to GJ inhibition relative to homocellular SCp2 cultures differentiated by exogenous basement membrane. Connexin (Cx)32 and Cx43 levels were not regulated across culture conditions; however, GJ functionality was enhanced under differentiation-permissive conditions. Immunoprecipitation studies demonstrated association of junctional complex components (α-catenin, β-catenin and ZO-2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although β-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and β-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear β-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of β-catenin in GJ complexes

  6. 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......Double Holliday junctions (dHJS) are important intermediates of homologous recombination. The separate junctions can each be cleaved by DNA structure-selective endonucleases known as Holliday junction resolvases. Alternatively, double Holliday junctions can be processed by a reaction known......) 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....

  7. Dielectric response of molecules in empirical tight-binding theory

    Science.gov (United States)

    Boykin, Timothy B.; Vogl, P.

    2002-01-01

    In this paper we generalize our previous approach to electromagnetic interactions within empirical tight-binding theory to encompass molecular solids and isolated molecules. In order to guarantee physically meaningful results, we rederive the expressions for relevant observables using commutation relations appropriate to the finite tight-binding Hilbert space. In carrying out this generalization, we examine in detail the consequences of various prescriptions for the position and momentum operators in tight binding. We show that attempting to fit parameters of the momentum matrix directly generally results in a momentum operator which is incompatible with the underlying tight-binding model, while adding extra position parameters results in numerous difficulties, including the loss of gauge invariance. We have applied our scheme, which we term the Peierls-coupling tight-binding method, to the optical dielectric function of the molecular solid PPP, showing that this approach successfully predicts its known optical properties even in the limit of isolated molecules.

  8. 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.

  9. Self-assembly of regioregular poly (3,3‴-didodecylquarterthiophene) in chloroform and study of its junction properties

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Manish Kumar; Kumar, Ashish; Prakash, Rajiv, E-mail: rprakash.mst@iitbhu.ac.in

    2017-03-15

    Graphical abstract: rr-PQT-12 films formed by spin coating before and after ageing (at 25 °C) showing the effect of fiber growth and significant change in charge transfer property. - Highlights: • Self-assembly of rr-PQT-12 into fiber form in chloroform marginal solvent at RT. • As assembled dispersion is processed for the fabrication of organic devices. • Processed fiber shows improvement in charge transport over its pristine one. - Abstract: This article deals with the study of self-assembly of regioregular poly (3,3‴-didodecylquarterthiophene), rr-PQT-12 into fiber form in chloroform by ageing process. Time dependent fiber growth mechanism is monitored by UV–vis absorption and confirmed by atomic force microscopy technique. It is observed that isolated rr-PQT-12 undergoes self-assembled fibril growth along π-π interaction direction and 45 min is sufficient for such assemblies in case of 0.125% w/v of rr-PQT-12 polymer in chloroform. Further the self-assembled fibril polymer is used in fabrication of Schottky diode. It exhibits ten times enhancement in forward current density (with one-fold higher mobility) and high rectification ratio compared to the isolated rr-PQT-12 due to the segmental electronic traps filling within stacking region. Our study provides a facile method of ordering of PQT-12 isolated chains in chloroform solvent and an effective way for improvement of performance of organic polymers based devices through such self-assembly.

  10. Simulation and development of a multi-leg homogeniser concentrating assembly for concentrated photovoltaic (CPV) system with electrical rating analysis

    KAUST Repository

    Burhan, Muhammad

    2016-03-09

    Concentrated photovoltaic (CPV) system utilizing multi-junction solar cells, is the main focus for current research, offering highest efficiency among all photovoltaic systems. The main aspect of CPV system is the design and performance of concentrating assembly, as it determines the performance of whole CPV system. However, the conventional design of CPV concentrating assembly dedicates one concentrator for each solar cell, in which single concentrator is capable to concentrate solar radiation onto single solar cell. This paper proposes a novel concentrating assembly for CPV system, which is designed to concentrate solar radiation onto four multi-junction solar cells with a single set of concentrators. The proposed design not only can reduce the number of concentrators and assembly efforts for CPV systems, but also achieved an acceptance angle of 1°. In this paper, the proposed multi-leg homogeniser CPV concentrating assembly is designed, developed, experimentally tested and verified through ray tracing simulation. The paper also discuss the development of mini, precise and accurate but cost effective two axis solar tracker for CPV system, which can be installed at any location even at rooftop of residential buildings, unlike conventional large scale CPV systems. Moreover, through the electrical rating analysis of the developed CPV system, its performance can be accurately estimated in any region. © 2016 Elsevier Ltd. All rights reserved.

  11. Simulation and development of a multi-leg homogeniser concentrating assembly for concentrated photovoltaic (CPV) system with electrical rating analysis

    KAUST Repository

    Burhan, Muhammad; Chua, Kian Jon Ernest; Ng, Kim Choon

    2016-01-01

    Concentrated photovoltaic (CPV) system utilizing multi-junction solar cells, is the main focus for current research, offering highest efficiency among all photovoltaic systems. The main aspect of CPV system is the design and performance of concentrating assembly, as it determines the performance of whole CPV system. However, the conventional design of CPV concentrating assembly dedicates one concentrator for each solar cell, in which single concentrator is capable to concentrate solar radiation onto single solar cell. This paper proposes a novel concentrating assembly for CPV system, which is designed to concentrate solar radiation onto four multi-junction solar cells with a single set of concentrators. The proposed design not only can reduce the number of concentrators and assembly efforts for CPV systems, but also achieved an acceptance angle of 1°. In this paper, the proposed multi-leg homogeniser CPV concentrating assembly is designed, developed, experimentally tested and verified through ray tracing simulation. The paper also discuss the development of mini, precise and accurate but cost effective two axis solar tracker for CPV system, which can be installed at any location even at rooftop of residential buildings, unlike conventional large scale CPV systems. Moreover, through the electrical rating analysis of the developed CPV system, its performance can be accurately estimated in any region. © 2016 Elsevier Ltd. All rights reserved.

  12. Principles of building and assembly technology of containment from steel structural blocks for WWER 1000 nuclear power plant

    International Nuclear Information System (INIS)

    Eichstedt, J.; Friedrich, F.

    1983-01-01

    This technology is being developed in cooperation between the USSR and the GDR. The cylindrical part of the containment consists of prefabricated double-sided steel blocks with inner reinforcement. The steel plates in a thickness of 20 mm provide casing and secure tightness. Blocks with one steel wall are used for the construction of the cupola. The outer slabs are assembled subsequently. The methods of assembly, concreting and quality assurance are described. (Ha)

  13. Van der Waals MoS2/VO2 heterostructure junction with tunable rectifier behavior and efficient photoresponse.

    Science.gov (United States)

    Oliva, Nicoló; Casu, Emanuele Andrea; Yan, Chen; Krammer, Anna; Rosca, Teodor; Magrez, Arnaud; Stolichnov, Igor; Schueler, Andreas; Martin, Olivier J F; Ionescu, Adrian Mihai

    2017-10-27

    Junctions between n-type semiconductors of different electron affinity show rectification if the junction is abrupt enough. With the advent of 2D materials, we are able to realize thin van der Waals (vdW) heterostructures based on a large diversity of materials. In parallel, strongly correlated functional oxides have emerged, having the ability to show reversible insulator-to-metal (IMT) phase transition by collapsing their electronic bandgap under a certain external stimulus. Here, we report for the first time the electronic and optoelectronic characterization of ultra-thin n-n heterojunctions fabricated using deterministic assembly of multilayer molybdenum disulphide (MoS 2 ) on a phase transition material, vanadium dioxide (VO 2 ). The vdW MoS 2 /VO 2 heterojunction combines the excellent blocking capability of an n-n junction with a high conductivity in on-state, and it can be turned into a Schottky rectifier at high applied voltage or at temperatures higher than 68 °C, exploiting the metal state of VO 2 . We report tunable diode-like current rectification with a good diode ideality factor of 1.75 and excellent conductance swing of 120 mV/dec. Finally, we demonstrate unique tunable photosensitivity and excellent junction photoresponse in the 500/650 nm wavelength range.

  14. On-wire lithography-generated molecule-based transport junctions: a new testbed for molecular electronics.

    Science.gov (United States)

    Chen, Xiaodong; Jeon, You-Moon; Jang, Jae-Won; Qin, Lidong; Huo, Fengwei; Wei, Wei; Mirkin, Chad A

    2008-07-02

    On-wire lithography (OWL) fabricated nanogaps are used as a new testbed to construct molecular transport junctions (MTJs) through the assembly of thiolated molecular wires across a nanogap formed between two Au electrodes. In addition, we show that one can use OWL to rapidly characterize a MTJ and optimize gap size for two molecular wires of different dimensions. Finally, we have used this new testbed to identify unusual temperature-dependent transport mechanisms for alpha,omega-dithiol terminated oligo(phenylene ethynylene).

  15. Photovoltaic enhancement of Si solar cells by assembled carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    Y.F.Zhang; Y.F.Wang; N.Chen; Y.Y.Wang; Y.Z.Zhang; Z.H.Zhou; L.M.Wei

    2010-01-01

    Photovoltaic conversion was enhanced by directly assemble of a network of single-walled carbon nanotubes(SWNTs) onto the surface of n-p junction silicon solar cells. When the density of SWNTs increased from 50 to 400 tubes μm-2, an enhancement of 3.92% in energy conversion efficiency was typically obtained. The effect of the SWNTs network is proposed for trapping incident photons and assisting electronic transportation at the interface of silicon solar cells.

  16. 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...

  17. Mechanical Mounting and Adhesive Junction for Large Quartz Optics Operatng at Cryogenic Temperature

    Science.gov (United States)

    Pellizzari, M.; Mosciarello, P.

    2012-07-01

    Gaia is a global space astrometry mission, with the goal to make the largest, most precise three-dimensional map of our Galaxy. Gaia contains two optical telescopes: in front of their Focal Plane Assembly -FPA- two narrow quartz prisms are mounted for spectrophotometer science: the Blue and Red Photometer Prisms -BPP and RPP-. They are framed in a SiC structure by means of brackets and adhesive junctions between metal parts and quartz optical elements. SELEX GALILEO developed this project as subcontractor of Astrium France. The assembly has to withstand thermoelastic loads due to CTE mismatch at an operative temperature of 120 K. The mechanical mountings design to reduce the stresses due to thermal loads on the adhesive joint is described and the results of the bonding qualification process as well as the flight hardware bonding results are reported.

  18. Gap junctions and motor behavior

    DEFF Research Database (Denmark)

    Kiehn, Ole; Tresch, Matthew C.

    2002-01-01

    The production of any motor behavior requires coordinated activity in motor neurons and premotor networks. In vertebrates, this coordination is often assumed to take place through chemical synapses. Here we review recent data suggesting that electrical gap-junction coupling plays an important role...... in coordinating and generating motor outputs in embryonic and early postnatal life. Considering the recent demonstration of a prevalent expression of gap-junction proteins and gap-junction structures in the adult mammalian spinal cord, we suggest that neuronal gap-junction coupling might also contribute...... to the production of motor behavior in adult mammals....

  19. Ferromagnetic Josephson Junctions for Cryogenic Memory

    Science.gov (United States)

    Niedzielski, Bethany M.; Gingrich, Eric C.; Khasawneh, Mazin A.; Loloee, Reza; Pratt, William P., Jr.; Birge, Norman O.

    2015-03-01

    Josephson junctions containing ferromagnetic materials are of interest for both scientific and technological purposes. In principle, either the amplitude of the critical current or superconducting phase shift across the junction can be controlled by the relative magnetization directions of the ferromagnetic layers in the junction. Our approach concentrates on phase control utilizing two junctions in a SQUID geometry. We will report on efforts to control the phase of junctions carrying either spin-singlet or spin-triplet supercurrent for cryogenic memory applications. Supported by Northorp Grumman Corporation and by IARPA under SPAWAR Contract N66001-12-C-2017.

  20. Electronic noise of superconducting tunnel junction detectors

    International Nuclear Information System (INIS)

    Jochum, J.; Kraus, H.; Gutsche, M.; Kemmather, B.; Feilitzsch, F. v.; Moessbauer, R.L.

    1994-01-01

    The optimal signal to noise ratio for detectors based on superconducting tunnel junctions is calculated and compared for the cases of a detector consisting of one single tunnel junction, as well as of series and of parallel connections of such tunnel junctions. The influence of 1 / f noise and its dependence on the dynamical resistance of tunnel junctions is discussed quantitatively. A single tunnel junction yields the minimum equivalent noise charge. Such a tunnel junction exhibits the best signal to noise ratio if the signal charge is independent of detector size. In case, signal charge increases with detector size, a parallel or a series connection of tunnel junctions would provide the optimum signal to noise ratio. The equivalent noise charge and the respective signal to noise ratio are deduced as functions of tunnel junction parameters such as tunneling time, quasiparticle lifetime, etc. (orig.)

  1. Fabrication of nanostructure via self-assembly of nanowires within the AAO template

    Directory of Open Access Journals (Sweden)

    Brust Mathias

    2006-01-01

    Full Text Available AbstractThe novel nanostructures are fabricated by the spatial chemical modification of nanowires within the anodic aluminum oxide (AAO template. To make the nanowires better dispersion in the aqueous solution, the copper is first deposited to fill the dendrite structure at the bottom of template. During the process of self-assembly, the dithiol compound was used as the connector between the nanowires and nanoparticles by a self-assembly method. The nanostructures of the nano cigars and structure which is containing particles junction are characterized by transmission electron microscopy (TEM. These kinds of novel nanostructure will be the building blocks for nanoelectronic and nanophotonic devices.

  2. Atomic-scaled characterization of graphene PN junctions

    Science.gov (United States)

    Zhou, Xiaodong; Wang, Dennis; Dadgar, Ali; Agnihotri, Pratik; Lee, Ji Ung; Reuter, Mark C.; Ross, Frances M.; Pasupathy, Abhay N.

    Graphene p-n junctions are essential devices for studying relativistic Klein tunneling and the Veselago lensing effect in graphene. We have successfully fabricated graphene p-n junctions using both lithographically pre-patterned substrates and the stacking of vertical heterostructures. We then use our 4-probe STM system to characterize the junctions. The ability to carry out scanning electron microscopy (SEM) in our STM instrument is essential for us to locate and measure the junction interface. We obtain both the topography and dI/dV spectra at the junction area, from which we track the shift of the graphene chemical potential with position across the junction interface. This allows us to directly measure the spatial width and roughness of the junction and its potential barrier height. We will compare the junction properties of devices fabricated by the aforementioned two methods and discuss their effects on the performance as a Veselago lens.

  3. Improved Density Functional Tight Binding Potentials for Metalloid Aluminum Clusters

    Science.gov (United States)

    2016-06-01

    unlimited IMPROVED DENSITY-FUNCTIONAL TIGHT BINDING POTENTIALS FOR METALLOID ALUMINUM CLUSTERS by Joon H. Kim June 2016 Thesis Advisor...DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE IMPROVED DENSITY-FUNCTIONAL TIGHT BINDING POTENTIALS FOR METALLOID ALUMINUM CLUSTERS 5. FUNDING...repulsive potentials for use in density-functional tight binding (DFTB) simulations of low-valence aluminum metalloid clusters . These systems are under

  4. Determination of Residual Forces in Mechanisms Assembled by Edge-Form Rolling

    Directory of Open Access Journals (Sweden)

    K. Turgut Gürsel

    2011-03-01

    Full Text Available Steering and suspension systems are components that supply driving safety in vehicles. For a correct working the mechanisms of these systems consist of many ball-joints that have different functions. Generally the ball-joints are assembled to systems in press-fit without any gaps, but even with residual forces. On the other hand excessive tightness causes high moments, which requires additional processes of manufacturing. But low tightness also creates gaps in joints. None of these conditions are desired. Manufacturing a ball-race that has long-life, low-friction and provides required working angles in every road condition, can be designed after long test processes and sample productions including lots of improvements. An important element of steering systems in vehicles is suspension ball-race that can be manufactured by assembling with plastic deformation after designing the ball-joint. In this study, during the manufacturing of the suspension ball-race supplying the motion transmission, the edge-form rolling process that is a subsection of rolling process of manufacturing methods based on plastic deformation was examined. Effects of pressure forces occurring after edge-form rolling in bearing systems at different values were studied by changing operation pressure of edge form rolling by means of specific numerical simulations.

  5. 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

  6. Superconducting flux qubits with π-junctions

    International Nuclear Information System (INIS)

    Shcherbakova, Anastasia

    2014-01-01

    In this thesis, we present a fabrication technology of Al/AlO x /Al Josephson junctions on Nb pads. The described technology gives the possibility of combining a variety of Nb-based superconducting circuits, like pi-junction phase-shifters with sub-micron Al/AlO x /Al junctions. Using this approach, we fabricated hybrid Nb/Al flux qubits with and without the SFS-junctions and studied dispersive magnetic field response of these qubits as well as their spectroscopy characteristics.

  7. Resonance Transport of Graphene Nanoribbon T-Shaped Junctions

    International Nuclear Information System (INIS)

    Xiao-Lan, Kong; Yong-Jian, Xiong

    2010-01-01

    We investigate the transport properties of T-shaped junctions composed of armchair graphene nanoribbons of different widths. Three types of junction geometries are considered. The junction conductance strongly depends on the atomic features of the junction geometry. When the shoulders of the junction have zigzag type edges, sharp conductance resonances usually appear in the low energy region around the Dirac point, and a conductance gap emerges. When the shoulders of the junction have armchair type edges, the conductance resonance behavior is weakened significantly, and the metal-metal-metal junction structures show semimetallic behaviors. The contact resistance also changes notably due to the various interface geometries of the junction

  8. Josephson junctions with ferromagnetic interlayer

    International Nuclear Information System (INIS)

    Wild, Georg Hermann

    2012-01-01

    We report on the fabrication of superconductor/insulator/ferromagnetic metal/superconductor (Nb/AlO x /Pd 0.82 Ni 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 π-coupling is observed for a thickness d F =6 nm of the ferromagnetic Pd 0.82 Ni 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 0.82 Ni 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.

  9. 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.

  10. Rectification of current responds to incorporation of fullerenes into mixed-monolayers of alkanethiolates in tunneling junctions.

    Science.gov (United States)

    Qiu, Li; Zhang, Yanxi; Krijger, Theodorus L; Qiu, Xinkai; Hof, Patrick Van't; Hummelen, Jan C; Chiechi, Ryan C

    2017-03-01

    This paper describes the rectification of current through molecular junctions comprising self-assembled monolayers of decanethiolate through the incorporation of C 60 fullerene moieties bearing undecanethiol groups in junctions using eutectic Ga-In (EGaIn) and Au conducting probe AFM (CP-AFM) top-contacts. The degree of rectification increases with increasing exposure of the decanethiolate monolayers to the fullerene moieties, going through a maximum after 24 h. We ascribe this observation to the resulting mixed-monolayer achieving an optimal packing density of fullerene cages sitting above the alkane monolayer. Thus, the degree of rectification is controlled by the amount of fullerene present in the mixed-monolayer. The voltage dependence of R varies with the composition of the top-contact and the force applied to the junction and the energy of the lowest unoccupied π-state determined from photoelectron spectroscopy is consistent with the direction of rectification. The maximum value of rectification R = | J (+)/ J (-)| = 940 at ±1 V or 617 at ±0.95 V is in agreement with previous studies on pure monolayers relating the degree of rectification to the volume of the head-group on which the frontier orbitals are localized.

  11. Electron optics with ballistic graphene junctions

    Science.gov (United States)

    Chen, Shaowen

    Electrons transmitted across a ballistic semiconductor junction undergo refraction, analogous to light rays across an optical boundary. A pn junction theoretically provides the equivalent of a negative index medium, enabling novel electron optics such as negative refraction and perfect (Veselago) lensing. In graphene, the linear dispersion and zero-gap bandstructure admit highly transparent pn junctions by simple electrostatic gating, which cannot be achieved in conventional semiconductors. Robust demonstration of these effects, however, has not been forthcoming. Here we employ transverse magnetic focusing to probe propagation across an electrostatically defined graphene junction. We find perfect agreement with the predicted Snell's law for electrons, including observation of both positive and negative refraction. Resonant transmission across the pn junction provides a direct measurement of the angle dependent transmission coefficient, and we demonstrate good agreement with theory. Comparing experimental data with simulation reveals the crucial role played by the effective junction width, providing guidance for future device design. Efforts toward sharper pn junction and possibility of zero field Veselago lensing will also be discussed. This work is supported by the Semiconductor Research Corporations NRI Center for Institute for Nanoelectronics Discovery and Exploration (INDEX).

  12. Peltier cooling in molecular junctions

    Science.gov (United States)

    Cui, Longji; Miao, Ruijiao; Wang, Kun; Thompson, Dakotah; Zotti, Linda Angela; Cuevas, Juan Carlos; Meyhofer, Edgar; Reddy, Pramod

    2018-02-01

    The study of thermoelectricity in molecular junctions is of fundamental interest for the development of various technologies including cooling (refrigeration) and heat-to-electricity conversion1-4. Recent experimental progress in probing the thermopower (Seebeck effect) of molecular junctions5-9 has enabled studies of the relationship between thermoelectricity and molecular structure10,11. However, observations of Peltier cooling in molecular junctions—a critical step for establishing molecular-based refrigeration—have remained inaccessible. Here, we report direct experimental observations of Peltier cooling in molecular junctions. By integrating conducting-probe atomic force microscopy12,13 with custom-fabricated picowatt-resolution calorimetric microdevices, we created an experimental platform that enables the unified characterization of electrical, thermoelectric and energy dissipation characteristics of molecular junctions. Using this platform, we studied gold junctions with prototypical molecules (Au-biphenyl-4,4'-dithiol-Au, Au-terphenyl-4,4''-dithiol-Au and Au-4,4'-bipyridine-Au) and revealed the relationship between heating or cooling and charge transmission characteristics. Our experimental conclusions are supported by self-energy-corrected density functional theory calculations. We expect these advances to stimulate studies of both thermal and thermoelectric transport in molecular junctions where the possibility of extraordinarily efficient energy conversion has been theoretically predicted2-4,14.

  13. The media of sociology: tight or loose translations?

    Science.gov (United States)

    Guggenheim, Michael

    2015-06-01

    Sociologists have increasingly come to recognize that the discipline has unduly privileged textual representations, but efforts to incorporate visual and other media are still only in their beginning. This paper develops an analysis of the ways objects of knowledge are translated into other media, in order to understand the visual practices of sociology and to point out unused possibilities. I argue that the discourse on visual sociology, by assuming that photographs are less objective than text, is based on an asymmetric media-determinism and on a misleading notion of objectivity. Instead, I suggest to analyse media with the concept of translations. I introduce several kinds of translations, most centrally the distinction between tight and loose ones. I show that many sciences, such as biology, focus on tight translations, using a variety of media and manipulating both research objects and representations. Sociology, in contrast, uses both tight and loose translations, but uses the latter only for texts. For visuals, sociology restricts itself to what I call 'the documentary': focusing on mechanical recording technologies without manipulating either the object of research or the representation. I conclude by discussing three rare examples of what is largely excluded in sociology: visual loose translations, visual tight translations based on non-mechanical recording technologies, and visual tight translations based on mechanical recording technologies that include the manipulation of both object and representation. © London School of Economics and Political Science 2015.

  14. 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 depe...

  15. Engineering feasibility of tight aspect ratio Tokamak (spherical torus) reactors

    International Nuclear Information System (INIS)

    Peng, Y-K.M.; Hicks, J.B.

    1990-01-01

    Engineering solutions are identified and analyzed for key high-power-density components of tight aspect ratio tokamak reactors (spherical torus reactors). The potentially extreme divertor heat loads can be reduced to about 3 MW/m 2 in expanded divertors using coils inside the demountable toroidal field coils. Given the long and narrow divertor channels, gaseous divertor targets become possible, which eliminate sputtering and increase the divertor life. The unshielded centre conductor post (CCP) of the toroidal field coil can be made of a single dispersion strengthened copper conductor cooled by high-velocity pressurized water to maintain acceptable copper temperature and strength. Damage and activation of the CCP at a neutron fluence of 10 MW-a/m 2 are also tolerable. Annual replacement of the centre post, the divertor assemblies and the blanket can be accomplished with vertical access for all torus components, which are modularized to reduce size and weight. The technical requirements of these solutions are shown to be comparable with, if not less demanding than, those estimated for conventional tokamak reactors. (author)

  16. Disease: H01301 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ve syndrome with severe hemorrhagic destruction of the brain as a cardinal feature. A mutation in JAM3 that encodes tight-junction... B, Al-Gazali L, Walsh CA ... TITLE ... A homozygous mutation in the tight-junction

  17. Geodynamical simulation of the RRF triple junction

    Science.gov (United States)

    Wang, Z.; Wei, D.; Liu, M.; Shi, Y.; Wang, S.

    2017-12-01

    Triple junction is the point at which three plate boundaries meet. Three plates at the triple junction form a complex geological tectonics, which is a natural laboratory to study the interactions of plates. This work studies a special triple junction, the oceanic transform fault intersects the collinear ridges with different-spreading rates, which is free of influence of ridge-transform faults and nearby hotspots. First, we build 3-D numerical model of this triple junction used to calculate the stead-state velocity and temperature fields resulting from advective and conductive heat transfer. We discuss in detail the influence of the velocity and temperature fields of the triple junction from viscosity, spreading rate of the ridge. The two sides of the oceanic transform fault are different sensitivities to the two factors. And, the influence of the velocity mainly occurs within 200km of the triple junction. Then, we modify the model by adding a ridge-transform fault to above model and directly use the velocity structure of the Macquarie triple junction. The simulation results show that the temperature at both sides of the oceanic transform fault decreases gradually from the triple junction, but the temperature difference between the two sides is a constant about 200°. And, there is little effect of upwelling velocity away from the triple junction 100km. The model results are compared with observational data. The heat flux and thermal topography along the oceanic transform fault of this model are consistent with the observed data of the Macquarie triple junction. The earthquakes are strike slip distributed along the oceanic transform fault. Their depths are also consistent with the zone of maximum shear stress. This work can help us to understand the interactions of plates of triple junctions and help us with the foundation for the future study of triple junctions.

  18. 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....

  19. Dynamics of the Josephson multi-junction system with junctions characterized by non-sinusoidal current - phase relationship

    International Nuclear Information System (INIS)

    Abal'osheva, I.; Lewandowski, S.J.

    2004-01-01

    It is shown that the inclusion of junctions characterized by non-sinusoidal current - phase relationship in the systems composed of multiple Josephson junctions - results in the appearance of additional system phase states. Numerical simulations and stability considerations confirm that those phase states can be realized in practice. Moreover, spontaneous formation of the grain boundary junctions in high-T c superconductors with non-trivial current-phase relations due to the d-wave symmetry of the order parameter is probable. Switching between the phase states of multiple grain boundary junction systems can lead to additional 1/f noise in high-T c superconductors. (author)

  20. Theoretical and experimental investigations on synchronization in many-junction arrays of HTSC Josephson junctions. Final report

    International Nuclear Information System (INIS)

    Seidel, P.; Heinz, E.; Pfuch, A.; Machalett, F.; Krech, W.; Basler, M.

    1996-06-01

    Different many-junction arrays of Josephson junctions were studied theoretically to analyse the mechanisms of synchronization, the influence of internal and external parameters and the maximal allowed spread of parameters for the single junctions. Concepts to realize arrays using standard high-T c superconductor technology were created, e.g. the new arrangement of multijunction superconducting loops (MSL). First experimental results show the relevance of this concept. Intrinsic one-dimensional arrays in thin film technology were prepared as mesas out of Bi or Tl 2212 films. to characterize HTSC Josephson junctions methods based on the analysis of microwave-induced steps were developed. (orig.) [de

  1. Single P-N junction tandem photovoltaic device

    Science.gov (United States)

    Walukiewicz, Wladyslaw [Kensington, CA; Ager, III, Joel W.; Yu, Kin Man [Lafayette, CA

    2011-10-18

    A single P-N junction solar cell is provided having two depletion regions for charge separation while allowing the electrons and holes to recombine such that the voltages associated with both depletion regions of the solar cell will add together. The single p-n junction solar cell includes an alloy of either InGaN or InAlN formed on one side of the P-N junction with Si formed on the other side in order to produce characteristics of a two junction (2J) tandem solar cell through only a single P-N junction. A single P-N junction solar cell having tandem solar cell characteristics will achieve power conversion efficiencies exceeding 30%.

  2. Inverted-conical light guide for crosstalk reduction in tightly-packed scintillator matrix and MAPMT assembly

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-Y., E-mail: gixd@hep1.phys.ntu.edu.tw [Department of Physics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Chen, C.R. [National Space Organization (NSPO), 8F., No. 9, Prosperity 1 s Rd., Hsinchu Science Park, Hsinchu 30078, Taiwan, ROC (China); Chen, P.; Huang, J.-J. [Department of Physics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Huang, M.A. [Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Department of Energy Engineering, National United University, 1, Lienda, Miaoli 36003, Taiwan, ROC (China); Liu, T.-C. [Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Nam, J.W. [Department of Physics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Wang, M.-Z., E-mail: mzwang@hep1.phys.ntu.edu.tw [Department of Physics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, 1 Roosevelt Rd., Taipei 10617, Taiwan, ROC (China); Bogomolov, V. [Skobeltsyn Institute of Nuclear Physics of Lomonosov Moscow State University, Leninskie Gory 119234 (Russian Federation); Physics Department of Lomonosov Moscow State University, Leninskie Gory 119234 (Russian Federation); Brandt, S.; Budtz-Jørgensen, C. [National Space Institute, Astrophysics, Technical University of Denmark, DK-2800 Kongens, Lyngby (Denmark); and others

    2015-01-21

    In this paper we present the Inverted-Conical light guide designed for optical crosstalk reduction in the scintillator-MAPMT assemblies. The research was motivated by the 30% crosstalk observed in UFFO X-ray telescope, UBAT, during the preliminary calibration with MAPMTs of 64 2.88×2.88 mm{sup 2} pixels and identically gridded YSO crystal matrices. We began the study with the energy and crosstalk calibrations of the detector, then we constructed a GEANT4 simulation with the customized metallic film model as the MAPMT photocathode. The simulation reproduced more than 70% of the crosstalk and explained it as a consequence of the total reflection produced by the photocathode. The result indicated that the crosstalk mechanism could be a common case in most of the contact-assembled scintillation detectors. The concept of the Inverted-Conical light guide was to suppress the total reflection by contracting the incident angle of the scintillation. We optimized the design in the simulation and fabricated a test sample. The test sample reduced 52% crosstalk with a loss of 6% signal yield. The idea of the Inverted-Conical light guide can be adapted by scintillation detectors multi-pixel, imaging-purpose scintillation detectors such as the ultra-fast GRB observatory UFFO-UBAT, whose performances are sensitive to responding time, image resolution, and geometrical modifications.

  3. Inverted-conical light guide for crosstalk reduction in tightly-packed scintillator matrix and MAPMT assembly

    International Nuclear Information System (INIS)

    Chang, Y.-Y.; Chen, C.R.; Chen, P.; Huang, J.-J.; Huang, M.A.; Liu, T.-C.; Nam, J.W.; Wang, M.-Z.; Bogomolov, V.; Brandt, S.; Budtz-Jørgensen, C.

    2015-01-01

    In this paper we present the Inverted-Conical light guide designed for optical crosstalk reduction in the scintillator-MAPMT assemblies. The research was motivated by the 30% crosstalk observed in UFFO X-ray telescope, UBAT, during the preliminary calibration with MAPMTs of 64 2.88×2.88 mm 2 pixels and identically gridded YSO crystal matrices. We began the study with the energy and crosstalk calibrations of the detector, then we constructed a GEANT4 simulation with the customized metallic film model as the MAPMT photocathode. The simulation reproduced more than 70% of the crosstalk and explained it as a consequence of the total reflection produced by the photocathode. The result indicated that the crosstalk mechanism could be a common case in most of the contact-assembled scintillation detectors. The concept of the Inverted-Conical light guide was to suppress the total reflection by contracting the incident angle of the scintillation. We optimized the design in the simulation and fabricated a test sample. The test sample reduced 52% crosstalk with a loss of 6% signal yield. The idea of the Inverted-Conical light guide can be adapted by scintillation detectors multi-pixel, imaging-purpose scintillation detectors such as the ultra-fast GRB observatory UFFO-UBAT, whose performances are sensitive to responding time, image resolution, and geometrical modifications

  4. Protein: FBA7 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available FBA7 claudin-zona occluden Tjp1 Zo1 Tight junction protein ZO-1 Tight junction protein 1, Zona occludens pr...otein 1, Zonula occludens protein 1 10090 Mus musculus 21872 P39447 2RRM P39447 21431884 ...

  5. The anatomical locus of T-junction processing.

    Science.gov (United States)

    Schirillo, James A

    2009-07-01

    Inhomogeneous surrounds can produce either asymmetrical or symmetrical increment/decrement induction by orienting T-junctions to selectively group a test patch with surrounding regions [Melfi, T., & Schirillo, J. (2000). T-junctions in inhomogeneous surrounds. Vision Research, 40, 3735-3741]. The current experiments aimed to determine where T-junctions are processed by presenting each eye with a different image so that T-junctions exist only in the fused percept. Only minor differences were found between retinal and cortical versus cortical-only conditions, indicating that T-junctions are processed cortically.

  6. Proximity effects and Josephson currents in ferromagnet. Spin-triplet superconductors junctions

    International Nuclear Information System (INIS)

    Terrade, Damien

    2015-01-01

    Spin-triplet superconductivity, first attached to the description of 3 He, is now generally considered to also occur in heavy-fermions compounds and in perovskite ruthenium oxide Sr 2 RuO 4 . The latter material is especially interesting since many experiments show strong evidences for a unitary chiral spin-triplet state. Moreover, the recent fabrication of thin heterostructures made of ferromagnetic SrRuO 3 on the top of Sr 2 RuO 4 strongly encourages new theoretical studies on the interplay between spin-triplet superconductor and ferromagnet in similar fashion to spin-singlet superconductors. Using an extended tight-binding Hamiltonian to model the superconductor, we discuss in this thesis the specific proximity effects of such interface by solving self-consistently the Bogoliubov-De Gennes equations on two- and three-dimensional lattices in the ballistic limit. We obtain the spatial profile of the superconducting order parameters at the interface as well as the spin-polarisation and the current across the Josephson junctions. In contrast to heterostructures made of spin-singlet superconductor, we show that the physical properties at the interface are not only controlled by the strength of the magnetization inside the ferromagnet but also by its orientation due to the existence of a finite pair spin projection of the spin-triplet Cooper pairs. We analyse in the first part the spin-polarisation and the Gibbs free energy at the three-dimensional ferromagnet-chiral spin-triplet superconductor interface. Then, the second part of the thesis is dedicated to the study of the Josephson junctions made of a chiral spin-triplet superconductor and a ferromagnetic barrier. More precisely, we analyse the existence of 0-π state transitions in two- and three-dimensional junctions with respect to the strength and the orientation of the magnetization. Finally, we study the proximity effects at the interface of helical spin-triplet superconductors. They differ from the chiral

  7. Three-dimensional measurement of a tightly focused laser beam

    Directory of Open Access Journals (Sweden)

    Xiangsheng Xie

    2013-02-01

    Full Text Available The spatial structure of a tightly focused light field is measured with a double knife-edge scanning method. The measurement method is based on the use of a high-quality double knife-edge fabricated from a right-angled silicon fragment mounted on a photodetector. The reconstruction of the three-dimensional structures of tightly focused spots is carried out with both uniform and partially obstructed linearly polarized incident light beams. The optical field distribution is found to deviate substantially from the input beam profile in the tightly focused region, which is in good agreement with the results of numerical simulations.

  8. 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

  9. Activation of the Small GTPase Rap1 Inhibits Choroidal Neovascularization by Regulating Cell Junctions and ROS Generation in Rats.

    Science.gov (United States)

    Li, Jiajia; Zhang, Rong; Wang, Caixia; Wang, Xin; Xu, Man; Ma, Jingxue; Shang, Qingli

    2018-03-30

    Choroidal neovascularization (CNV) is a common vision-threatening complication associated with many  fundus diseases. The retinal pigment epithelial (RPE) cell junction barrier has critical functions in preventing CNV, and oxidative stress can cause compromise of barrier integrity and induce angiogenesis. Rap1, a small guanosine triphosphatase (GTPase), is involved in regulating endothelial and epithelial cell junctions. In this work, we explored the function and mechanism of Rap1 in CNV in vivo. A laser-induced rat CNV model was developed. Rap1 was activated through intravitreal injection of the Rap1 activator 8CPT-2'-O-Me-cAMP (8CPT). At 14 days after laser treatment, CNV size in RPE/choroid flat mounts was measured by fluorescein isothiocyanate-dextran staining. Expression of vascular endothelial growth factor (VEGF) and cell junction proteins in RPE/choroid tissues were analyzed by western blots and quantitative real-time PCR assays. Reactive oxygen species (ROS) in RPE cells were detectedbydichloro-dihydro-fluorescein diacetate assays. The antioxidant apocynin was intraperitoneally injected into rats. Activating Rap1 by 8CPT significantly reduced CNV size and VEGF expression in the rat CNV model. Rap1 activation enhanced protein and mRNA levels of ZO-1 and occludin, two tight junction proteins in the RPE barrier. In addition, reducing ROS generation by injection of apocynin, a NADPH oxidase inhibitor, inhibited CNV formation. Rap1 activation reduced ROS generation and expression of NADPH oxidase 4. Rap1 activation inhibits CNV through regulating barrier integrity and ROS generation of RPE in vivo, and selectively activating Rap1 may be a way to reduce vision loss from CNV.

  10. Cellular Interaction of Integrin α3β1 with Laminin 5 Promotes Gap Junctional Communication

    Science.gov (United States)

    Lampe, Paul D.; Nguyen, Beth P.; Gil, Susana; Usui, Marcia; Olerud, John; Takada, Yoshikazu; Carter, William G.

    1998-01-01

    Wounding of skin activates epidermal cell migration over exposed dermal collagen and fibronectin and over laminin 5 secreted into the provisional basement membrane. Gap junctional intercellular communication (GJIC) has been proposed to integrate the individual motile cells into a synchronized colony. We found that outgrowths of human keratinocytes in wounds or epibole cultures display parallel changes in the expression of laminin 5, integrin α3β1, E-cadherin, and the gap junctional protein connexin 43. Adhesion of keratinocytes on laminin 5, collagen, and fibronectin was found to differentially regulate GJIC. When keratinocytes were adhered on laminin 5, both structural (assembly of connexin 43 in gap junctions) and functional (dye transfer) assays showed a two- to threefold increase compared with collagen and five- to eightfold over fibronectin. Based on studies with immobilized integrin antibody and integrin-transfected Chinese hamster ovary cells, the interaction of integrin α3β1 with laminin 5 was sufficient to promote GJIC. Mapping of intermediate steps in the pathway linking α3β1–laminin 5 interactions to GJIC indicated that protein trafficking and Rho signaling were both required. We suggest that adhesion of epithelial cells to laminin 5 in the basement membrane via α3β1 promotes GJIC that integrates individual cells into synchronized epiboles. PMID:9852164

  11. Modulation of Intestinal Paracellular Transport by Bacterial Pathogens.

    Science.gov (United States)

    Roxas, Jennifer Lising; Viswanathan, V K

    2018-03-25

    The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport. The past decade has witnessed major advances in our understanding of the architecture and function of epithelial tight junctions. While it has been long appreciated that microbes, notably bacterial and viral pathogens, target and disrupt junctional complexes and alter paracellular permeability, the precise mechanisms remain to be defined. Notably, renewed efforts will be required to interpret the available data on pathogen-mediated barrier disruption in the context of the most recent findings on tight junction structure and function. While much of the focus has been on pathogen-induced dysregulation of junctional complexes, commensal microbiota and their products may influence paracellular permeability and contribute to the normal physiology of the gut. Finally, microbes and their products have become important tools in exploring host systems, including the junctional properties of epithelial cells. © 2018 American Physiological Society. Compr Physiol 8:823-842, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

  12. Western tight gas sands advanced logging workshop proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, J B; Carroll, Jr, H B [eds.

    1982-04-01

    An advanced logging research program is one major aspect of the Western Tight Sands Program. Purpose of this workshop is to help BETC define critical logging needs for tight gas sands and to allow free interchange of ideas on all aspects of the current logging research program. Sixteen papers and abstracts are included together with discussions. Separate abstracts have been prepared for the 12 papers. (DLC)

  13. Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.

    Science.gov (United States)

    Su, Tsung-Wei; Yang, Chao-Yu; Kao, Wen-Pin; Kuo, Bai-Jiun; Lin, Shan-Meng; Lin, Jung-Yaw; Lo, Yu-Chih; Lin, Su-Chang

    2017-03-07

    Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Effect of junction configurations on microdroplet formation in a T-junction microchannel

    Science.gov (United States)

    Lih, F. L.; Miao, J. M.

    2015-03-01

    This study investigates the dynamic formation process of water microdroplets in a silicon oil flow in a T-junction microchannel. Segmented water microdroplets are formed at the junction when the water flow is perpendicularly injected into the silicon oil flow in a straight rectangular microchannel. This study further presents the effects of the water flow inlet geometry on hydrodynamic characteristics of water microdroplet formation. A numerical multiphase volume of fluid (VOF) scheme is coupled to solve the unsteady three-dimensional laminar Navier-Stokes equations to depict the droplet formation phenomena at the junction. Predicted results on the length and generated frequency of the microdroplets agree well with experimental results in a T-junction microchannel with straight and flat inlets (the base model) for both fluid flows. Empirical correlations are reported between the volumetric flow ratio and the dimensionless microdroplet length or dimensionless frequency of droplet generation at a fixed capillary number of 4.7 · 10-3. The results of this study indicate a reduction in the droplet length of approximately 21% if the straight inlet for the water flow is modified to a downstream sudden contraction inlet for the water flow.

  15. The Effects of Glucagon-like Peptide-2 on the Tight Junction and Barrier Function in IPEC-J2 Cells through Phosphatidylinositol 3-kinase–Protein Kinase B–Mammalian Target of Rapamycin Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Changsong Yu

    2016-05-01

    Full Text Available Glucagon-like peptide-2 (GLP-2 is important for intestinal barrier function and regulation of tight junction (TJ proteins, but the intracellular mechanisms of action remain undefined. The purpose of this research was to determine the protective effect of GLP-2 mediated TJ and transepithelial electrical resistance (TER in lipopolysaccharide (LPS stressed IPEC-J2 cells and to test the hypothesis that GLP-2 regulate TJ and TER through the phosphatidylinositol 3-kinase (PI3K-protein kinase B (Akt-mammalian target of rapamycin (mTOR signaling pathway in IPEC-J2 cells. Wortmannin and LY294002 are specific inhibitors of PI3K. The results showed that 100 μg/mL LPS stress decreased TER and TJ proteins occludin, claudin-1 and zonula occludens protein 1 (ZO-1 mRNA, proteins expressions (p<0.01 respectively. GLP-2 (100 nmol/L promote TER and TJ proteins occludin, claudin-1, and zo-1 mRNA, proteins expressions in LPS stressed and normal IPEC-J2 cells (p<0.01 respectively. In normal cells, both wortmannin and LY294002, PI3K inhibitors, prevented the mRNA and protein expressions of Akt and mTOR increase induced by GLP-2 (p<0.01 following with the significant decreasing of occludin, claudin-1, ZO-1 mRNA and proteins expressions and TER (p<0.01. In conclusion, these results indicated that GLP-2 can promote TJ’s expression and TER in LPS stressed and normal IPEC-J2 cells and GLP-2 could regulate TJ and TER through the PI3K/Akt/mTOR pathway.

  16. Poster - Thur Eve - 57: Craniospinal irradiation with jagged-junction IMRT approach without beam edge matching for field junctions.

    Science.gov (United States)

    Cao, F; Ramaseshan, R; Corns, R; Harrop, S; Nuraney, N; Steiner, P; Aldridge, S; Liu, M; Carolan, H; Agranovich, A; Karva, A

    2012-07-01

    Craniospinal irradiation were traditionally treated the central nervous system using two or three adjacent field sets. A intensity-modulated radiotherapy (IMRT) plan (Jagged-Junction IMRT) which overcomes problems associated with field junctions and beam edge matching, improves planning and treatment setup efficiencies with homogenous target dose distribution was developed. Jagged-Junction IMRT was retrospectively planned on three patients with prescription of 36 Gy in 20 fractions and compared to conventional treatment plans. Planning target volume (PTV) included the whole brain and spinal canal to the S3 vertebral level. The plan employed three field sets, each with a unique isocentre. One field set with seven fields treated the cranium. Two field sets treated the spine, each set using three fields. Fields from adjacent sets were overlapped and the optimization process smoothly integrated the dose inside the overlapped junction. For the Jagged-Junction IMRT plans vs conventional technique, average homogeneity index equaled 0.08±0.01 vs 0.12±0.02, and conformity number equaled 0.79±0.01 vs 0.47±0.12. The 95% isodose surface covered (99.5±0.3)% of the PTV vs (98.1±2.0)%. Both Jagged-Junction IMRT plans and the conventional plans had good sparing of the organs at risk. Jagged-Junction IMRT planning provided good dose homogeneity and conformity to the target while maintaining a low dose to the organs at risk. Jagged-Junction IMRT optimization smoothly distributed dose in the junction between field sets. Since there was no beam matching, this treatment technique is less likely to produce hot or cold spots at the junction in contrast to conventional techniques. © 2012 American Association of Physicists in Medicine.

  17. Simulation and development of a multi-leg homogeniser concentrating assembly for concentrated photovoltaic (CPV) system with electrical rating analysis

    International Nuclear Information System (INIS)

    Burhan, Muhammad; Chua, Kian Jon Ernest; Ng, Kim Choon

    2016-01-01

    Highlights: • Novel multi-leg homogeniser concentrating assembly is developed for CPV system. • Single set of concentrator, concentrates sunlight on 4 MJCs with 1° acceptance angle. • The system performance is analyzed through experiment and ray tracing simulation. • Mini two axis solar tracker, with high tracking accuracy, is developed and tested. • Electrical rating analysis accurately estimates CPV system performance in any region. - Abstract: Concentrated photovoltaic (CPV) system utilizing multi-junction solar cells, is the main focus for current research, offering highest efficiency among all photovoltaic systems. The main aspect of CPV system is the design and performance of concentrating assembly, as it determines the performance of whole CPV system. However, the conventional design of CPV concentrating assembly dedicates one concentrator for each solar cell, in which single concentrator is capable to concentrate solar radiation onto single solar cell. This paper proposes a novel concentrating assembly for CPV system, which is designed to concentrate solar radiation onto four multi-junction solar cells with a single set of concentrators. The proposed design not only can reduce the number of concentrators and assembly efforts for CPV systems, but also achieved an acceptance angle of 1°. In this paper, the proposed multi-leg homogeniser CPV concentrating assembly is designed, developed, experimentally tested and verified through ray tracing simulation. The paper also discuss the development of mini, precise and accurate but cost effective two axis solar tracker for CPV system, which can be installed at any location even at rooftop of residential buildings, unlike conventional large scale CPV systems. Moreover, through the electrical rating analysis of the developed CPV system, its performance can be accurately estimated in any region.

  18. Comparative testing of women's tights, which are realized in the Ukrainian market

    OpenAIRE

    Мартосенко, Марина Григорьевна; Браилко, Анна Сергеевна

    2015-01-01

    Assortment of women's tights represented on the Ukrainian market is diverse: medical and corrective tights, classic thin and warm, simple and exclusive, ornamental and sports, for pregnant women and moisturizing effect. The size, density, pattern, material composition, visual appearance, matching fashion trends, colors, pricing policy – all these are criteria for the selection of women's tights.With such huge and diverse range of women's tights in the Ukrainian market, the problem of quality ...

  19. Valley dependent transport in graphene L junction

    Science.gov (United States)

    Chan, K. S.

    2018-05-01

    We studied the valley dependent transport in graphene L junctions connecting an armchair lead and a zigzag lead. The junction can be used in valleytronic devices and circuits. Electrons injected from the armchair lead into the junction is not valley polarized, but they can become valley polarized in the zigzag lead. There are Fermi energies, where the current in the zigzag lead is highly valley polarized and the junction is an efficient generator of valley polarized current. The features of the valley polarized current depend sensitively on the widths of the two leads, as well as the number of dimers in the armchair lead, because this number has a sensitive effect on the band structure of the armchair lead. When an external potential is applied to the junction, the energy range with high valley polarization is enlarged enhancing its function as a generator of highly valley polarized current. The scaling behavior found in other graphene devices is also found in L junctions, which means that the results presented here can be extended to junctions with larger dimensions after appropriate scaling of the energy.

  20. Method of manufacturing Josephson junction integrated circuits

    International Nuclear Information System (INIS)

    Jillie, D.W. Jr.; Smith, L.N.

    1985-01-01

    Josephson junction integrated circuits of the current injection type and magnetically controlled type utilize a superconductive layer that forms both Josephson junction electrode for the Josephson junction devices on the integrated circuit as well as a ground plane for the integrated circuit. Large area Josephson junctions are utilized for effecting contact to lower superconductive layers and islands are formed in superconductive layers to provide isolation between the groudplane function and the Josephson junction electrode function as well as to effect crossovers. A superconductor-barrier-superconductor trilayer patterned by local anodization is also utilized with additional layers formed thereover. Methods of manufacturing the embodiments of the invention are disclosed

  1. delta-biased Josephson tunnel junctions

    DEFF Research Database (Denmark)

    Monaco, R.; Mygind, Jesper; Koshelet, V.

    2010-01-01

    Abstract: The behavior of a long Josephson tunnel junction drastically depends on the distribution of the dc bias current. We investigate the case in which the bias current is fed in the central point of a one-dimensional junction. Such junction configuration has been recently used to detect...... the persistent currents circulating in a superconducting loop. Analytical and numerical results indicate that the presence of fractional vortices leads to remarkable differences from the conventional case of uniformly distributed dc bias current. The theoretical findings are supported by detailed measurements...

  2. Air tightness measurements in older Danish single-family houses

    DEFF Research Database (Denmark)

    Mortensen, Lone Hedegaard; Bergsøe, Niels Christian

    2017-01-01

    of the building envelope of older buildings despite the fact that the air tightness has a major influence on the energy use. In connection with renovation of the Danish building stock, the coming years will see increased focus on the air tightness of the building envelope like in other countries. This paper...

  3. Junction depth measurement using carrier illumination

    International Nuclear Information System (INIS)

    Borden, Peter

    2001-01-01

    Carrier Illumination [trade mark] (CI) is a new method recently developed to meet the need for a non-destructive, high throughput junction depth measurement on patterned wafers. A laser beam creates a quasi-static excess carrier profile in the semiconductor underlying the activated junction. The excess carrier profile is fairly constant below the junction, and drops rapidly in the junction, creating a steep index of refraction gradient at the junction edge. Interference with light reflected from this index gradient provides a signal that is analyzed to determine the junction depth. The paper summarizes evaluation of performance in full NMOS and PMOS process flows, on both bare and patterned wafers. The aims have been to validate (1) performance in the presence of underlying layers typically found at the source/drain (S/D) process steps and (2) measurement on patterned wafers. Correlation of CI measurements to SIMS and transistor drive current are shown. The data were obtained from NMOS structures using As S/D and LDD implants. Correlations to SRP, SIMS and sheet resistance are shown for PMOS structures using B 11 LDD implants. Gage capability measurements are also presented

  4. The assembly and use of continuous flow systems for chemical synthesis.

    Science.gov (United States)

    Britton, Joshua; Jamison, Timothy F

    2017-11-01

    The adoption of and opportunities in continuous flow synthesis ('flow chemistry') have increased significantly over the past several years. Continuous flow systems provide improved reaction safety and accelerated reaction kinetics, and have synthesised several active pharmaceutical ingredients in automated reconfigurable systems. Although continuous flow platforms are commercially available, systems constructed 'in-lab' provide researchers with a flexible, versatile, and cost-effective alternative. Herein, we describe the assembly and use of a modular continuous flow apparatus from readily available and affordable parts in as little as 30 min. Once assembled, the synthesis of a sulfonamide by reacting 4-chlorobenzenesulfonyl chloride with dibenzylamine in a single reactor coil with an in-line quench is presented. This example reaction offers the opportunity to learn several important skills including reactor construction, charging of a back-pressure regulator, assembly of stainless-steel syringes, assembly of a continuous flow system with multiple junctions, and yield determination. From our extensive experience of single-step and multistep continuous flow synthesis, we also describe solutions to commonly encountered technical problems such as precipitation of solids ('clogging') and reactor failure. Following this protocol, a nonspecialist can assemble a continuous flow system from reactor coils, syringes, pumps, in-line liquid-liquid separators, drying columns, back-pressure regulators, static mixers, and packed-bed reactors.

  5. NbN tunnel junctions

    International Nuclear Information System (INIS)

    Villegier, J.C.; Vieux-Rochaz, L.; Goniche, M.; Renard, P.; Vabre, M.

    1984-09-01

    All-niobium nitride Josephon junctions have been prepared successfully using a new processing called SNOP: Selective Niobium (nitride) Overlap Process. Such a process involves the ''trilayer'' deposition on the whole wafer before selective patterning of the electrodes by optically controlled dry reactive ion etching. Only two photomask levels are need to define an ''overlap'' or a ''cross-type'' junction with a good accuracy. The properties of the niobium nitride films deposited by DC-magnetron sputtering and the surface oxide growth are analysed. The most critical point to obtain high quality and high gap value junctions resides in the early stage of the NbN counterelectrode growth. Some possibilities to overcome such a handicap exist even if the fabrication needs substrate temperatures below 250 0 C

  6. Hamstring tightness and Scheuermann's disease a pilot study.

    Science.gov (United States)

    Fisk, J W; Baigent, M L

    1981-06-01

    The lateral radiographs of the dorsal spines of 20 patients presenting with mainly low back pain are studied. These patients had clinically evident loss of flexion in the low dorsal spine and very tight hamstring muscles. 85% of them showed definite evidence of previous Scheuermann's Disease. The possibility that tight hamstrings may be an important factor in the aetiology of this disease is discussed, and a further large scale study is proposed.

  7. Hysteresis development in superconducting Josephson junctions

    International Nuclear Information System (INIS)

    Refai, T.F.; Shehata, L.N.

    1988-09-01

    The resistively and capacitive shunted junction model is used to investigate hysteresis development in superconducting Josephson junctions. Two empirical formulas that relate the hysteresis width and the quasi-particle diffusion length in terms of the junctions electrical parameters, temperature and frequency are obtained. The obtained formulas provide a simple tool to investigate the full potentials of the hysteresis phenomena. (author). 9 refs, 3 figs

  8. DNA nanotechnology: a future perspective

    Science.gov (United States)

    2013-01-01

    In addition to its genetic function, DNA is one of the most distinct and smart self-assembling nanomaterials. DNA nanotechnology exploits the predictable self-assembly of DNA oligonucleotides to design and assemble innovative and highly discrete nanostructures. Highly ordered DNA motifs are capable of providing an ultra-fine framework for the next generation of nanofabrications. The majority of these applications are based upon the complementarity of DNA base pairing: adenine with thymine, and guanine with cytosine. DNA provides an intelligent route for the creation of nanoarchitectures with programmable and predictable patterns. DNA strands twist along one helix for a number of bases before switching to the other helix by passing through a crossover junction. The association of two crossovers keeps the helices parallel and holds them tightly together, allowing the assembly of bigger structures. Because of the DNA molecule's unique and novel characteristics, it can easily be applied in a vast variety of multidisciplinary research areas like biomedicine, computer science, nano/optoelectronics, and bionanotechnology. PMID:23497147

  9. Fabrication of Josephson Junction without shadow evaporation

    Science.gov (United States)

    Wu, Xian; Ku, Hsiangsheng; Long, Junling; Pappas, David

    We developed a new method of fabricating Josephson Junction (Al/AlOX/Al) without shadow evaporation. Statistics from room temperature junction resistance and measurement of qubits are presented. Unlike the traditional ``Dolan Bridge'' technique, this method requires two individual lithographies and straight evaporations of Al. Argon RF plasma is used to remove native AlOX after the first evaporation, followed by oxidation and second Al evaporation. Junction resistance measured at room temperature shows linear dependence on Pox (oxidation pressure), √{tox} (oxidation time), and inverse proportional to junction area. We have seen 100% yield of qubits made with this method. This method is promising because it eliminates angle dependence during Junction fabrication, facilitates large scale qubits fabrication.

  10. Quantum synchronization effects in intrinsic Josephson junctions

    International Nuclear Information System (INIS)

    Machida, M.; Kano, T.; Yamada, S.; Okumura, M.; Imamura, T.; Koyama, T.

    2008-01-01

    We investigate quantum dynamics of the superconducting phase in intrinsic Josephson junctions of layered high-T c superconductors motivated by a recent experimental observation for the switching rate enhancement in the low temperature quantum regime. We pay attention to only the capacitive coupling between neighboring junctions and perform large-scale simulations for the Schroedinger equation derived from the Hamiltonian considering the capacitive coupling alone. The simulation focuses on an issue whether the switching of a junction induces those of the other junctions or not. The results reveal that the superconducting phase dynamics show synchronous behavior with increasing the quantum character, e.g., decreasing the junction plane area and effectively the temperature. This is qualitatively consistent with the experimental result

  11. Heated junction thermocouple level measurement apparatus

    International Nuclear Information System (INIS)

    Bevilacqua, F.; Burger, J.M.

    1984-01-01

    A liquid level sensing apparatus senses the level of liquid surrounding the apparatus. A plurality of axially spaced sensors are enclosed in a separator tube. The separator tube tends to collapse the level of a two-phase fluid within the separator tube into essentially a liquid phase and a gaseous phase where the collapsed level bears a relationship to the coolant inventory outside the separator tube. The level of the liquid phase is sensed by level sensing apparatus. The separator tube contains inlet-outlet ports near the top and bottom thereof to equalize the liquid level inside and outside the separator tube when the level fluctuates or the water within the separator tube flashes to steam. Each sensor is comprised of a heater, a heated thermocouple junction and an unheated thermocouple junction within an elongated heat conductive housing. The heated portion of housing is enclosed in a splash guard with inlet-outlet ports near the top and bottom to equalize the liquid level inside and outside the splash guardand to eliminate the spurious indications of liquid level change which may arise if water droplets contact the housing in the region of the heater. To prevent steam bubbles entrained in a two-phase fluid cross flow from entering the lateral inlet-outlet ports of the separator tube, the separator tube is enclosed in support tube which may in turn be enclosed in an otherwise unused control element assembly shroud. The lateral inlet-outlet ports of separator tube are axially offset from lateral inlet-outlet ports of support tube at least where support tube is subjected to cross flow. The shroud is open on the bottom and has lateral inlet-outlet ports to facilitate liquid level fluctuations to equalize inside and outside shroud

  12. Unconventional Tight Reservoirs Characterization with Nuclear Magnetic Resonance

    Science.gov (United States)

    Santiago, C. J. S.; Solatpour, R.; Kantzas, A.

    2017-12-01

    The increase in tight reservoir exploitation projects causes producing many papers each year on new, modern, and modified methods and techniques on estimating characteristics of these reservoirs. The most ambiguous of all basic reservoir property estimations deals with permeability. One of the logging methods that is advertised to predict permeability but is always met by skepticism is Nuclear Magnetic Resonance (NMR). The ability of NMR to differentiate between bound and movable fluids and providing porosity increased the capability of NMR as a permeability prediction technique. This leads to a multitude of publications and the motivation of a review paper on this subject by Babadagli et al. (2002). The first part of this presentation is dedicated to an extensive review of the existing correlation models for NMR based estimates of tight reservoir permeability to update this topic. On the second part, the collected literature information is used to analyze new experimental data. The data are collected from tight reservoirs from Canada, the Middle East, and China. A case study is created to apply NMR measurement in the prediction of reservoir characterization parameters such as porosity, permeability, cut-offs, irreducible saturations etc. Moreover, permeability correlations are utilized to predict permeability. NMR experiments were conducted on water saturated cores. NMR T2 relaxation times were measured. NMR porosity, the geometric mean relaxation time (T2gm), Irreducible Bulk Volume (BVI), and Movable Bulk Volume (BVM) were calculated. The correlation coefficients were computed based on multiple regression analysis. Results are cross plots of NMR permeability versus the independently measured Klinkenberg corrected permeability. More complicated equations are discussed. Error analysis of models is presented and compared. This presentation is beneficial in understanding existing tight reservoir permeability models. The results can be used as a guide for choosing

  13. Entropy Flow Through Near-Critical Quantum Junctions

    Science.gov (United States)

    Friedan, Daniel

    2017-05-01

    This is the continuation of Friedan (J Stat Phys, 2017. doi: 10.1007/s10955-017-1752-8). Elementary formulas are derived for the flow of entropy through a circuit junction in a near-critical quantum circuit close to equilibrium, based on the structure of the energy-momentum tensor at the junction. The entropic admittance of a near-critical junction in a bulk-critical circuit is expressed in terms of commutators of the chiral entropy currents. The entropic admittance at low frequency, divided by the frequency, gives the change of the junction entropy with temperature—the entropic "capacitance". As an example, and as a check on the formalism, the entropic admittance is calculated explicitly for junctions in bulk-critical quantum Ising circuits (free fermions, massless in the bulk), in terms of the reflection matrix of the junction. The half-bit of information capacity per end of critical Ising wire is re-derived by integrating the entropic "capacitance" with respect to temperature, from T=0 to T=∞.

  14. Ballistic Josephson junctions based on CVD graphene

    Science.gov (United States)

    Li, Tianyi; Gallop, John; Hao, Ling; Romans, Edward

    2018-04-01

    Josephson junctions with graphene as the weak link between superconductors have been intensely studied in recent years, with respect to both fundamental physics and potential applications. However, most of the previous work was based on mechanically exfoliated graphene, which is not compatible with wafer-scale production. To overcome this limitation, we have used graphene grown by chemical vapour deposition (CVD) as the weak link of Josephson junctions. We demonstrate that very short, wide CVD-graphene-based Josephson junctions with Nb electrodes can work without any undesirable hysteresis in their electrical characteristics from 1.5 K down to a base temperature of 320 mK, and their gate-tuneable critical current shows an ideal Fraunhofer-like interference pattern in a perpendicular magnetic field. Furthermore, for our shortest junctions (50 nm in length), we find that the normal state resistance oscillates with the gate voltage, consistent with the junctions being in the ballistic regime, a feature not previously observed in CVD-graphene-based Josephson junctions.

  15. Uterine inactivation of muscle segment homeobox (Msx) genes alters epithelial cell junction proteins during embryo implantation.

    Science.gov (United States)

    Sun, Xiaofei; Park, Craig B; Deng, Wenbo; Potter, S Steven; Dey, Sudhansu K

    2016-04-01

    Embryo implantation requires that the uterus differentiate into the receptive state. Failure to attain uterine receptivity will impede blastocyst attachment and result in a compromised pregnancy. The molecular mechanism by which the uterus transitions from the prereceptive to the receptive stage is complex, involving an intricate interplay of various molecules. We recently found that mice with uterine deletion ofMsxgenes (Msx1(d/d)/Msx2(d/d)) are infertile because of implantation failure associated with heightened apicobasal polarity of luminal epithelial cells during the receptive period. However, information on Msx's roles in regulating epithelial polarity remains limited. To gain further insight, we analyzed cell-type-specific gene expression by RNA sequencing of separated luminal epithelial and stromal cells by laser capture microdissection fromMsx1(d/d)/Msx2(d/d)and floxed mouse uteri on d 4 of pseudopregnancy. We found that claudin-1, a tight junction protein, and small proline-rich (Sprr2) protein, a major component of cornified envelopes in keratinized epidermis, were substantially up-regulated inMsx1(d/d)/Msx2(d/d)uterine epithelia. These factors also exhibited unique epithelial expression patterns at the implantation chamber (crypt) inMsx1(f/f)/Msx2(f/f)females; the patterns were lost inMsx1(d/d)/Msx2(d/d)epithelia on d 5, suggesting important roles during implantation. The results suggest thatMsxgenes play important roles during uterine receptivity including modulation of epithelial junctional activity.-Sun, X., Park, C. B., Deng, W., Potter, S. S., Dey, S. K. Uterine inactivation of muscle segment homeobox (Msx) genes alters epithelial cell junction proteins during embryo implantation. © FASEB.

  16. Overlap junctions for high coherence superconducting qubits

    Science.gov (United States)

    Wu, X.; Long, J. L.; Ku, H. S.; Lake, R. E.; Bal, M.; Pappas, D. P.

    2017-07-01

    Fabrication of sub-micron Josephson junctions is demonstrated using standard processing techniques for high-coherence, superconducting qubits. These junctions are made in two separate lithography steps with normal-angle evaporation. Most significantly, this work demonstrates that it is possible to achieve high coherence with junctions formed on aluminum surfaces cleaned in situ by Ar plasma before junction oxidation. This method eliminates the angle-dependent shadow masks typically used for small junctions. Therefore, this is conducive to the implementation of typical methods for improving margins and yield using conventional CMOS processing. The current method uses electron-beam lithography and an additive process to define the top and bottom electrodes. Extension of this work to optical lithography and subtractive processes is discussed.

  17. Surface-Enhanced Raman Scattering in Molecular Junctions.

    Science.gov (United States)

    Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu

    2017-08-18

    Surface-enhanced Raman scattering (SERS) is a surface-sensitive vibrational spectroscopy that allows Raman spectroscopy on a single molecular scale. Here, we present a review of SERS from molecular junctions, in which a single molecule or molecules are made to have contact from the top to the bottom of metal surfaces. The molecular junctions are nice platforms for SERS as well as transport measurement. Electronic characterization based on the transport measurements of molecular junctions has been extensively studied for the development of miniaturized electronic devices. Simultaneous SERS and transport measurement of the molecular junctions allow both structural (geometrical) and electronic information on the single molecule scale. The improvement of SERS measurement on molecular junctions open the door toward new nanoscience and nanotechnology in molecular electronics.

  18. Primary Tunnel Junction Thermometry

    International Nuclear Information System (INIS)

    Pekola, Jukka P.; Holmqvist, Tommy; Meschke, Matthias

    2008-01-01

    We describe the concept and experimental demonstration of primary thermometry based on a four-probe measurement of a single tunnel junction embedded within four arrays of junctions. We show that in this configuration random sample specific and environment-related errors can be avoided. This method relates temperature directly to Boltzmann constant, which will form the basis of the definition of temperature and realization of official temperature scales in the future

  19. Ginzburg–Landau theory of mesoscopic multi-band Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Romeo, F.; De Luca, R., E-mail: rdeluca@unisa.it

    2017-05-15

    Highlights: • We generalize, in the realm of the Ginzburg–Landau theory, the de Gennes matching-matrix method for the interface order parameters to describe the superconducting properties of multi-band mesoscopic Josephson junctions. • The results are in agreement with a microscopic treatment of nanobridge junctions. • Thermal stability of the nanobridge junction is discussed in connection with recent experiments on iron-based grain-boundary junctions. - Abstract: A Ginzburg–Landau theory for multi-band mesoscopic Josephson junctions has been developed. The theory, obtained by generalizing the de Gennes matching-matrix method for the interface order parameters, allows the study of the phase dynamics of various types of mesoscopic Josephson junctions. As a relevant application, we studied mesoscopic double-band junctions also in the presence of a superconducting nanobridge interstitial layer. The results are in agreement with a microscopic treatment of the same system. Furthermore, thermal stability of the nanobridge junction is discussed in connection with recent experiments on iron-based grain-boundary junctions.

  20. Tritium safety study using Caisson Assembly (CATS) at TPL/JAEA

    International Nuclear Information System (INIS)

    Hayashi, T.; Kobayashi, K.; Iwai, Y.; Isobe, K.; Nakamura, H.; Kawamura, Y.; Shu, W.; Suzuki, T.; Yamada, M.; Yamanishi, T.

    2008-01-01

    Tritium confinement is required as the most important safety Junction for a fusion reactor. In order to demonstrate the confinement performance experimentally, an unique equipment, called CATS: Caisson Assembly for Tritium Safety study, was installed in Tritium Process Laboratory of Japan Atomic Energy Agency and operated for about 10 years. Tritium confinement and migration data in CATS have been accumulated and dynamic simulation code was accumulated using these data. Contamination and decontamination behavior on various materials and new safety equipment functions have been investigated under collaborations with a lot of laboratories and universities. (authors)

  1. The influence of junction conformation on RNA cleavage by the hairpin ribozyme in its natural junction form.

    Science.gov (United States)

    Thomson, J B; Lilley, D M

    1999-01-01

    In the natural form of the hairpin ribozyme the two loop-carrying duplexes that comprise the majority of essential bases for activity form two adjacent helical arms of a four-way RNA junction. In the present work we have manipulated the sequence around the junction in a way known to perturb the global folding properties. We find that replacement of the junction by a different sequence that has the same conformational properties as the natural sequence gives closely similar reaction rate and Arrhenius activation energy for the substrate cleavage reaction. By comparison, rotation of the natural sequence in order to alter the three-dimensional folding of the ribozyme leads to a tenfold reduction in the kinetics of cleavage. Replacement with the U1 four-way junction that is resistant to rotation into the antiparallel structure required to allow interaction between the loops also gives a tenfold reduction in cleavage rate. The results indicate that the conformation of the junction has a major influence on the catalytic activity of the ribozyme. The results are all consistent with a role for the junction in the provision of a framework by which the loops are presented for interaction in order to create the active form of the ribozyme. PMID:10024170

  2. Design of thin InGaAsN(Sb) n-i-p junctions for use in four-junction concentrating photovoltaic devices

    Science.gov (United States)

    Wilkins, Matthew M.; Gupta, James; Jaouad, Abdelatif; Bouzazi, Boussairi; Fafard, Simon; Boucherif, Abderraouf; Valdivia, Christopher E.; Arès, Richard; Aimez, Vincent; Schriemer, Henry P.; Hinzer, Karin

    2017-04-01

    Four-junction solar cells for space and terrestrial applications require a junction with a band gap of ˜1 eV for optimal performance. InGaAsN or InGaAsN(Sb) dilute nitride junctions have been demonstrated for this purpose, but in achieving the 14 mA/cm2 short-circuit current needed to match typical GaInP and GaAs junctions, the open-circuit voltage (VOC) and fill factor of these junctions are compromised. In multijunction devices incorporating materials with short diffusion lengths, we study the use of thin junctions to minimize sensitivity to varying material quality and ensure adequate transmission into lower junctions. An n-i-p device with 0.65-μm absorber thickness has sufficient short-circuit current, however, it relies less heavily on field-aided collection than a device with a 1-μm absorber. Our standard cell fabrication process, which includes a rapid thermal anneal of the contacts, yields a significant improvement in diffusion length and device performance. By optimizing a four-junction cell around a smaller 1-sun short-circuit current of 12.5 mA/cm2, we produced an InGaAsN(Sb) junction with open-circuit voltage of 0.44 V at 1000 suns (1 sun=100 mW/cm2), diode ideality factor of 1.4, and sufficient light transmission to allow >12.5 mA/cm2 in all four subcells.

  3. Harmonic synchronization in resistively coupled Josephson junctions

    International Nuclear Information System (INIS)

    Blackburn, J.A.; Gronbech-Jensen, N.; Smith, H.J.T.

    1994-01-01

    The oscillations of two resistively coupled Josephson junctions biased only by a single dc current source are shown to lock harmonically in a 1:2 mode over a significant range of bias current, even when the junctions are identical. The dependence of this locking on both junction and coupling parameters is examined, and it is found that, for this particular two-junction configuration, 1:1 locking can never occur, and also that a minimum coupling coefficient is needed to support harmonic locking. Some issues related to subharmonic locking are also discussed

  4. Differences between tight and loose cultures : A 33-nation study

    NARCIS (Netherlands)

    Gelfand, M.J.; Raver, R.L.; Nishii, L.; Leslie, L.M.; Lun, J.; Lim, B.C.; Van de Vliert, E.

    2011-01-01

    With data from 33 nations, we illustrate the differences between cultures that are tight (have many strong norms and a low tolerance of deviant behavior) versus loose (have weak social norms and a high tolerance of deviant behavior). Tightness-looseness is part of a complex, loosely integrated

  5. Belching, regurgitation, chest tightness and dyspnea: not gastroesophageal reflux disease but asthma.

    Science.gov (United States)

    Zhang, Jing-Xi; Zhan, Xian-Bao; Bai, Chong; Li, Qiang

    2015-02-07

    Belching is a common symptom of gastroesophageal reflux disease. If the symptoms are not relieved after anti-reflux treatment, another etiology should be considered. Here, we report a case of a 43-year-old man who presented with belching, regurgitation, chest tightness and dyspnea for 18 mo, which became gradually more severe. Gastroscopic examination suggested superficial gastritis. Twenty-four-hour esophageal pH monitoring showed that the Demeester score was 11.4, in the normal range. High-resolution manometry showed that integrated relaxation pressure and intrabolus pressure were higher than normal (20 mmHg and 22.4 mmHg, respectively), indicating gastroesophageal junction outflow tract obstruction. Pulmonary function test showed severe obstructive ventilation dysfunction [forced expiratory volume in 1 second (FEV1)/forced vital capacity 32%, FEV1 was 1.21 L, occupying 35% predicted value after salbuterol inhalation], and positive bronchial dilation test (∆FEV1 260 mL, ∆FEV1% 27%). Skin prick test showed Dermatophagoides farinae (++), house dust mite (++++), and shrimp protein (++). Fractional exhaled nitric oxide measurement was 76 ppb. All the symptoms were alleviated completely and pulmonary function increased after combination therapy with corticosteroids and long-acting β2-agonist. Bronchial asthma was eventually diagnosed by laboratory tests and the effect of anti-asthmatic treatment, therefore, physicians, especially the Gastrointestinal physicians, should pay attention to the belching symptoms of asthma.

  6. Josephson junctions of multiple superconducting wires

    Science.gov (United States)

    Deb, Oindrila; Sengupta, K.; Sen, Diptiman

    2018-05-01

    We study the spectrum of Andreev bound states and Josephson currents across a junction of N superconducting wires which may have s - or p -wave pairing symmetries and develop a scattering matrix based formalism which allows us to address transport across such junctions. For N ≥3 , it is well known that Berry curvature terms contribute to the Josephson currents; we chart out situations where such terms can have relatively large effects. For a system of three s -wave or three p -wave superconductors, we provide analytic expressions for the Andreev bound-state energies and study the Josephson currents in response to a constant voltage applied across one of the wires; we find that the integrated transconductance at zero temperature is quantized to integer multiples of 4 e2/h , where e is the electron charge and h =2 π ℏ is Planck's constant. For a sinusoidal current with frequency ω applied across one of the wires in the junction, we find that Shapiro plateaus appear in the time-averaged voltage across that wire for any rational fractional multiple (in contrast to only integer multiples in junctions of two wires) of 2 e /(ℏ ω ) . We also use our formalism to study junctions of two p -wave and one s -wave wires. We find that the corresponding Andreev bound-state energies depend on the spin of the Bogoliubov quasiparticles; this produces a net magnetic moment in such junctions. The time variation of these magnetic moments may be controlled by an external voltage applied across the junction. We discuss experiments which may test our theory.

  7. Theory of spin-dependent tunnelling in magnetic junctions

    International Nuclear Information System (INIS)

    Mathon, J.

    2002-01-01

    Rigorous theory of the tunnelling magnetoresistance (TMR) based on the real-space Kubo formula and fully realistic tight-binding bands fitted to an ab initio band structure is described. It is first applied to calculate the TMR of two Co electrodes separated by a vacuum gap. The calculated TMR ratio reaches ∼65% in the tunnelling regime but can be as high as 280% in the metallic regime when the vacuum gap is of the order of the Co interatomic distance (abrupt domain wall). It is also shown that the spin polarization P of the tunnelling current is negative in the metallic regime but becomes positive P∼35% in the tunnelling regime. Calculation of the TMR of an epitaxial Fe/MgO/Fe(001) junction is also described. The calculated optimistic TMR ratio is in excess of 1000% for an MgO barrier of ∼20 atomic planes and the spin polarization of the tunnelling current is positive for all MgO thicknesses. It is also found that spin-dependent tunnelling in an Fe/MgO/Fe(001) junction is not entirely determined by states at the Γ point (k parallel = 0) even for MgO thicknesses as large as ∼20 atomic planes. Finally, it is demonstrated that the TMR ratio calculated from the Kubo formula remains non-zero when one of the Co electrodes is covered with a copper layer. It is shown that non-zero TMR is due to quantum well states in the Cu layer which do not participate in transport. Since these only occur in the down-spin channel, their loss from transport creates a spin asymmetry of electrons tunnelling from a Cu interlayer, i.e. non-zero TMR. Numerical modelling is used to show that diffuse scattering from a random distribution of impurities in the barrier may cause quantum well states to evolve into propagating states, in which case the spin asymmetry of the non-magnetic layer is lost and with it the TMR. (author)

  8. Molecular Diffusion through Cyanobacterial Septal Junctions.

    Science.gov (United States)

    Nieves-Morión, Mercedes; Mullineaux, Conrad W; Flores, Enrique

    2017-01-03

    Heterocyst-forming cyanobacteria grow as filaments in which intercellular molecular exchange takes place. During the differentiation of N 2 -fixing heterocysts, regulators are transferred between cells. In the diazotrophic filament, vegetative cells that fix CO 2 through oxygenic photosynthesis provide the heterocysts with reduced carbon and heterocysts provide the vegetative cells with fixed nitrogen. Intercellular molecular transfer has been traced with fluorescent markers, including calcein, 5-carboxyfluorescein, and the sucrose analogue esculin, which are observed to move down their concentration gradient. In this work, we used fluorescence recovery after photobleaching (FRAP) assays in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 to measure the temperature dependence of intercellular transfer of fluorescent markers. We find that the transfer rate constants are directly proportional to the absolute temperature. This indicates that the "septal junctions" (formerly known as "microplasmodesmata") linking the cells in the filament allow molecular exchange by simple diffusion, without any activated intermediate state. This constitutes a novel mechanism for molecular transfer across the bacterial cytoplasmic membrane, in addition to previously characterized mechanisms for active transport and facilitated diffusion. Cyanobacterial septal junctions are functionally analogous to the gap junctions of metazoans. Although bacteria are frequently considered just as unicellular organisms, there are bacteria that behave as true multicellular organisms. The heterocyst-forming cyanobacteria grow as filaments in which cells communicate. Intercellular molecular exchange is thought to be mediated by septal junctions. Here, we show that intercellular transfer of fluorescent markers in the cyanobacterial filament has the physical properties of simple diffusion. Thus, cyanobacterial septal junctions are functionally analogous to metazoan gap junctions

  9. Spectrometric assembly for portable installations

    International Nuclear Information System (INIS)

    Kluger, A.; Popescu, C.

    1997-01-01

    The components of the portable spectrometric assembly are: - the detecting probe with Na I(Tl) crystal and air-tight case of industrial type; - a microcomputer; - a unit of analogical processing of the signal from the detecting probe; - a single-channel analyzer with adjustable threshold; - commands and display module; - a source of high voltage; - an electrical supply battery. The device uses the method of gamma photons detection in energetic windows. Through theoretical and experimental studies carried out during the prototype development phase, the superiority of this method has been proved as compared with the installations which make use of the classical principle of photon integral detection. The achieved prototype has a basic program enabling the setting of all working parameters (measuring time, discriminating thresholds, discriminators operating conditions, etc.). Through the included interface RS232 it is possible to transmit the data to a more powerful computer in order to continually process the results. The spectrometric assembly, realized on the basis of micro-computers, can be used in a wide range of applications: measurement of thickness and erosion of walls and tubes, measurement of level in closed containers, of soil density, etc. The adjustment for specific application is performed only through a program modification. (authors)

  10. Tight Money, Real Interest Rates, and Inflation in Sub-Saharan Africa

    OpenAIRE

    Edward F. Buffie

    2003-01-01

    The consequences of tight monetary policy are analyzed in an optimizing currency-substitution model of a small, open economy that operates under an open capital account and a flexible exchange rate. There is a reasonably good fit between the dynamics generated by the model and the stylized facts in the tight-money episodes that occurred in Kenya in 1993 and Nigeria in 1989-91. The study's results shed light on two issues: why tight money has provoked stupendous increases in inflation and the ...

  11. Josephson tunnel junctions in niobium films

    International Nuclear Information System (INIS)

    Wiik, Tapio.

    1976-12-01

    A method of fabricating stable Josephson tunnel junctions with reproducible characteristics is described. The junctions have a sandwich structure consisting of a vacuum evaporated niobium film, a niobium oxide layer produced by the glow discharge method and a lead film deposited by vacuum evaporation. Difficulties in producing thin-film Josephson junctions are discussed. Experimental results suggest that the lower critical field of the niobium film is the most essential parameter when evaluating the quality of these junctions. The dependence of the lower critical field on the film thickness and on the Ginzburg-Landau parameter of the film is studied analytically. Comparison with the properties of the evaporated films and with the previous calculations for bulk specimens shows that the presented model is applicable for most of the prepared samples. (author)

  12. Josephson junctions with ferromagnetic alloy interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Himmel, Nico

    2015-07-23

    Josephson junctions are used as active devices in superconducting electronics and quantum information technology. Outstanding properties are their distinct non-linear electrical characteristics and a usually sinusoidal relation between the current and the superconducting phase difference across the junction. In general the insertion of ferromagnetic material in the barrier of a Josephson junction is associated with a suppression of superconducting correlations. But also new phenomena can arise which may allow new circuit layouts and enhance the performance of applications. This thesis presents a systematic investigation for two concepts to fabricate Josephson junctions with a rather uncommon negative critical current. Such devices exhibit an intrinsic phase slip of π between the electrodes, so they are also known as π junctions. Both studies go well beyond existing experiments and in one system a π junction is shown for the first time. All the thin film junctions are based on superconducting Nb electrodes. In a first approach, barriers made from Si and Fe were investigated with respect to the realisation of π junctions by spin-flip processes. The distribution of Fe in the Si matrix was varied from pure layers to disperse compounds. The systematic fabrication of alloy barriers was facilitated by the development of a novel timing-based combinatorial sputtering technique for planetary deposition systems. An orthogonal gradient approach allowed to create binary layer libraries with independent variations of thickness and composition. Second, Nb vertical stroke AlO{sub x} vertical stroke Nb vertical stroke Ni{sub 60}Cu{sub 40} vertical stroke Nb (SIsFS) double barrier junctions were experimentally studied for the occurrence of proximity effect induced order parameter oscillations. Detailed dependencies of the critical current density on the thickness of s-layer and F-layer were acquired and show a remarkable agreement to existing theoretical predictions. Especially

  13. Josephson junctions with ferromagnetic alloy interlayer

    International Nuclear Information System (INIS)

    Himmel, Nico

    2015-01-01

    Josephson junctions are used as active devices in superconducting electronics and quantum information technology. Outstanding properties are their distinct non-linear electrical characteristics and a usually sinusoidal relation between the current and the superconducting phase difference across the junction. In general the insertion of ferromagnetic material in the barrier of a Josephson junction is associated with a suppression of superconducting correlations. But also new phenomena can arise which may allow new circuit layouts and enhance the performance of applications. This thesis presents a systematic investigation for two concepts to fabricate Josephson junctions with a rather uncommon negative critical current. Such devices exhibit an intrinsic phase slip of π between the electrodes, so they are also known as π junctions. Both studies go well beyond existing experiments and in one system a π junction is shown for the first time. All the thin film junctions are based on superconducting Nb electrodes. In a first approach, barriers made from Si and Fe were investigated with respect to the realisation of π junctions by spin-flip processes. The distribution of Fe in the Si matrix was varied from pure layers to disperse compounds. The systematic fabrication of alloy barriers was facilitated by the development of a novel timing-based combinatorial sputtering technique for planetary deposition systems. An orthogonal gradient approach allowed to create binary layer libraries with independent variations of thickness and composition. Second, Nb vertical stroke AlO x vertical stroke Nb vertical stroke Ni 60 Cu 40 vertical stroke Nb (SIsFS) double barrier junctions were experimentally studied for the occurrence of proximity effect induced order parameter oscillations. Detailed dependencies of the critical current density on the thickness of s-layer and F-layer were acquired and show a remarkable agreement to existing theoretical predictions. Especially a variation of

  14. Self-assembly of a double-helical complex of sodium.

    Science.gov (United States)

    Bell, T W; Jousselin, H

    1994-02-03

    Spontaneous self-organization of helical and multiple-helical molecular structures occurs on several levels in living organisms. Key examples are alpha-helical polypeptides, double-helical nucleic acids and helical protein structures, including F-actin, microtubules and the protein sheath of the tobacco mosaic virus. Although the self-assembly of double-helical transition-metal complexes bears some resemblance to the molecular organization of double-stranded DNA, selection between monohelical, double-helical and triple-helical structures is determined largely by the size and geometrical preference of the tightly bound metal. Here we present an example of double-helical assembly induced by the weaker and non-directional interactions of an alkali-metal ion with an organic ligand that is pre-organized into a coil. We have characterized the resulting complex by two-dimensional NMR and fast-atom-bombardment mass spectrometry. These results provide a step toward the creation of molecular tubes or ion channels consisting of intertwined coils.

  15. Performance of single-junction and dual-junction InGaP/GaAs solar cells under low concentration ratios

    International Nuclear Information System (INIS)

    Khan, Aurangzeb; Yamaguchi, Masafumi; Takamoto, Tatsuya

    2004-01-01

    A study of the performance of single-junction InGaP/GaAs and dual-junction InGaP/GaAs tandem cells under low concentration ratios (up to 15 suns), before and after 1 MeV electron irradiation is presented. Analysis of the tunnel junction parameters under different concentrated light illuminations reveals that the peak current (J P ) and valley current (J V ) densities should be greater than the short-circuit current density (J sc ) for better performance. The tunnel junction behavior against light intensity improved after irradiation. This led to the suggestion that the peak current density (J P ) and valley current density (J V ) of the tunnel junction were enhanced after irradiation or the peak current was shifted to higher concentration. The recovery of the radiation damage under concentrated light illumination conditions suggests that the performance of the InGaP/GaAs tandem solar cell can be enhanced even under low concentration ratios

  16. 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)

  17. The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex.

    Science.gov (United States)

    Gay, Darren C; Wagner, Drew T; Meinke, Jessica L; Zogzas, Charles E; Gay, Glen R; Keatinge-Clay, Adrian T

    2016-03-01

    Polyketides such as the clinically-valuable antibacterial agent mupirocin are constructed by architecturally-sophisticated assembly lines known as trans-acyltransferase polyketide synthases. Organelle-sized megacomplexes composed of several copies of trans-acyltransferase polyketide synthase assembly lines have been observed by others through transmission electron microscopy to be located at the Bacillus subtilis plasma membrane, where the synthesis and export of the antibacterial polyketide bacillaene takes place. In this work we analyze ten crystal structures of trans-acyltransferase polyketide synthases ketosynthase domains, seven of which are reported here for the first time, to characterize a motif capable of zippering assembly lines into a megacomplex. While each of the three-helix LINKS (Laterally-INteracting Ketosynthase Sequence) motifs is observed to similarly dock with a spatially-reversed copy of itself through hydrophobic and ionic interactions, the amino acid sequences of this motif are not conserved. Such a code is appropriate for mediating homotypic contacts between assembly lines to ensure the ordered self-assembly of a noncovalent, yet tightly-knit, enzymatic network. LINKS-mediated lateral interactions would also have the effect of bolstering the vertical association of the polypeptides that comprise a polyketide synthase assembly line. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Superluminescence from an optically pumped molecular tunneling junction by injection of plasmon induced hot electrons

    Directory of Open Access Journals (Sweden)

    Kai Braun

    2015-05-01

    Full Text Available Here, we demonstrate a bias-driven superluminescent point light-source based on an optically pumped molecular junction (gold substrate/self-assembled molecular monolayer/gold tip of a scanning tunneling microscope, operating at ambient conditions and providing almost three orders of magnitude higher electron-to-photon conversion efficiency than electroluminescence induced by inelastic tunneling without optical pumping. A positive, steadily increasing bias voltage induces a step-like rise of the Stokes shifted optical signal emitted from the junction. This emission is strongly attenuated by reversing the applied bias voltage. At high bias voltage, the emission intensity depends non-linearly on the optical pump power. The enhanced emission can be modelled by rate equations taking into account hole injection from the tip (anode into the highest occupied orbital of the closest substrate-bound molecule (lower level and radiative recombination with an electron from above the Fermi level (upper level, hence feeding photons back by stimulated emission resonant with the gap mode. The system reflects many essential features of a superluminescent light emitting diode.

  19. Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease

    Directory of Open Access Journals (Sweden)

    Mahesh Mohan

    2016-10-01

    Full Text Available The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD, gluten-free diet (GFD, barley gluten-derived diet (BOMI and reduced gluten barley-derived diet (RGB. It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p < 0.05 following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity of gut microbiome in GS macaques started to change (p = 0.011 towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b were upregulated (p < 0.05 in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911, Prevotella stercorea (NR_041364 and Streptococcus luteciae (AJ297218 that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes

  20. Curved Josephson junction

    International Nuclear Information System (INIS)

    Dobrowolski, Tomasz

    2012-01-01

    The constant curvature one and quasi-one dimensional Josephson junction is considered. On the base of Maxwell equations, the sine–Gordon equation that describes an influence of curvature on the kink motion was obtained. It is showed that the method of geometrical reduction of the sine–Gordon model from three to lower dimensional manifold leads to an identical form of the sine–Gordon equation. - Highlights: ► The research on dynamics of the phase in a curved Josephson junction is performed. ► The geometrical reduction is applied to the sine–Gordon model. ► The results of geometrical reduction and the fundamental research are compared.

  1. Josephson tunnel junctions with ferromagnetic interlayer

    International Nuclear Information System (INIS)

    Weides, M.P.

    2006-01-01

    Superconductivity and ferromagnetism are well-known physical properties of solid states that have been widely studied and long thought about as antagonistic phenomena due to difference in spin ordering. It turns out that the combination of both superconductor and ferromagnet leads to a very rich and interesting physics. One particular example, the phase oscillations of the superconducting order parameter inside the ferromagnet, will play a major role for the devices discussed in this work. In this thesis, I present Josephson junctions with a thin Al 2 O 3 tunnel barrier and a ferromagnetic interlayer, i.e. superconductor-insulator-ferromagnet-superconductor (SIFS) stacks. The fabrication of junctions was optimized regarding the insulation of electrodes and the homogeneity of the current transport. The junctions were either in the 0 or π coupled ground state, depending on the thickness of the ferromagnetic layer and on temperature. The influence of ferromagnetic layer thickness on the transport properties and the coupling (0, π) of SIFS tunnel junctions was studied. Furthermore, using a stepped ferromagnetic layer with well-chosen thicknesses, I obtained the so-called 0-π Josephson junction. At a certain temperature this 0-π junction can be made perfectly symmetric. In this case the ground state corresponds to a vortex of supercurrent creating a magnetic flux which is a fraction of the magnetic flux quantum Φ 0 . Such structures allow to study the physics of fractional vortices and to build various electronic circuits based on them. The SIFS junctions presented here have an exponentially vanishing damping at T → 0. The SIFS technology developed within the framework of this work may be used to construct classical and quantum devices such as oscillators, memory cells and qubits. (orig.)

  2. Josephson tunnel junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Weides, M.P.

    2006-07-01

    Superconductivity and ferromagnetism are well-known physical properties of solid states that have been widely studied and long thought about as antagonistic phenomena due to difference in spin ordering. It turns out that the combination of both superconductor and ferromagnet leads to a very rich and interesting physics. One particular example, the phase oscillations of the superconducting order parameter inside the ferromagnet, will play a major role for the devices discussed in this work. In this thesis, I present Josephson junctions with a thin Al{sub 2}O{sub 3} tunnel barrier and a ferromagnetic interlayer, i.e. superconductor-insulator-ferromagnet-superconductor (SIFS) stacks. The fabrication of junctions was optimized regarding the insulation of electrodes and the homogeneity of the current transport. The junctions were either in the 0 or {pi} coupled ground state, depending on the thickness of the ferromagnetic layer and on temperature. The influence of ferromagnetic layer thickness on the transport properties and the coupling (0, {pi}) of SIFS tunnel junctions was studied. Furthermore, using a stepped ferromagnetic layer with well-chosen thicknesses, I obtained the so-called 0-{pi} Josephson junction. At a certain temperature this 0-{pi} junction can be made perfectly symmetric. In this case the ground state corresponds to a vortex of supercurrent creating a magnetic flux which is a fraction of the magnetic flux quantum {phi}{sub 0}. Such structures allow to study the physics of fractional vortices and to build various electronic circuits based on them. The SIFS junctions presented here have an exponentially vanishing damping at T {yields} 0. The SIFS technology developed within the framework of this work may be used to construct classical and quantum devices such as oscillators, memory cells and qubits. (orig.)

  3. Pannexin-1 channels show distinct morphology and no gap junction characteristics in mammalian cells.

    Science.gov (United States)

    Beckmann, Anja; Grissmer, Alexander; Krause, Elmar; Tschernig, Thomas; Meier, Carola

    2016-03-01

    Pannexins (Panx) are proteins with a similar membrane topology to connexins, the integral membrane protein of gap junctions. Panx1 channels are generally of major importance in a large number of system and cellular processes and their function has been thoroughly characterized. In contrast, little is known about channel structure and subcellular distribution. We therefore determine the subcellular localization of Panx1 channels in cultured cells and aim at the identification of channel morphology in vitro. Using freeze-fracture replica immunolabeling on EYFP-Panx1-overexpressing HEK 293 cells, large particles were identified in plasma membranes, which were immunogold-labeled using either GFP or Panx1 antibodies. There was no labeling or particles in the nuclear membranes of these cells, pointing to plasma membrane localization of Panx1-EYFP channels. The assembly of particles was irregular, this being in contrast to the regular pattern of gap junctions. The fact that no counterparts were identified on apposing cells, which would have been indicative of intercellular signaling, supported the idea of Panx1 channels within one membrane. Control cells (transfected with EYFP only, non-transfected) were devoid of both particles and immunogold labeling. Altogether, this study provides the first demonstration of Panx1 channel morphology and assembly in intact cells. The identification of Panx1 channels as large particles within the plasma membrane provides the knowledge required to enable recognition of Panx1 channels in tissues in future studies. Thus, these results open up new avenues for the detailed analysis of the subcellular localization of Panx1 and of its nearest neighbors such as purinergic receptors in vivo.

  4. Mechanically Stacked Dual-Junction and Triple-Junction III-V/Si-IBC Cells with Efficiencies Exceeding 31.5% and 35.4%: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Schnabel, Manuel [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Tamboli, Adele C [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Warren, Emily L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Schulte-Huxel, Henning [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Klein, Talysa [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Van Hest, Marinus F [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Geisz, John F [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Stradins, Paul [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Steiner, Myles A [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Rienaecker, Michael [Institute for Solar Energy Research Hamelin (ISFH); Merkle, Agnes [Institute for Solar Energy Research Hamelin (ISFH); Kajari-Schroeder, S. [Institute for Solar Energy Research Hamelin (ISFH); Niepelt, Raphael [Institute for Solar Energy Research Hamelin (ISFH); Schmidt, Jan [Institute for Solar Energy Research Hamelin (ISFH); Leibniz Universitat Hannover; Brendel, Rolf [Institute for Solar Energy Research Hamelin (ISFH); Leibniz Universitat Hannover; Peibst, Robby [Institute for Solar Energy Research Hamelin (ISFH); Leibniz Universitat Hannover

    2017-10-02

    Despite steady advancements in the efficiency of crystalline Silicon (c-Si) photovoltaics (PV) within the last decades, the theoretical efficiency limit of 29.4 percent depicts an insurmountable barrier for silicon-based single-junction solar cells. Combining the Si cell with a second absorber material on top in a dual junction tandem or triple junction solar cell is an attractive option to surpass this limit significantly. We demonstrate a mechanically stacked GaInP/Si dual-junction cell with an in-house measured efficiency of 31.5 percent and a GaInP/GaAs/Si triple-junction cell with a certified efficiency of 35.4 percent.

  5. Immunocytochemical localization of claudin 1 in the maturation ameloblasts of rat incisors

    Directory of Open Access Journals (Sweden)

    Sumio eNishikawa

    2010-11-01

    Full Text Available Claudin 1 is a tight junction transmembrane protein. Its localization in the maturation ameloblasts of rat incisors was examined by immunofluorescence microscopy. Distal junction area of ruffle-ended ameloblasts (RA and the Golgi apparatus of a sub-population of smooth-ended ameloblasts (SA and RAs stained positive with anti-claudin 1 antibodies. Since it has been shown that ameloblasts repeatedly alternate between an SA and an RA morphology during enamel maturation, the presence of claudin 1 in the Golgi cisterns may indicate the presence of tight junction precursors before transportation to the junctional area.

  6. Electromagnetic waves in single- and multi-Josephson junctions

    International Nuclear Information System (INIS)

    Matsumoto, Hideki; Koyama, Tomio; Machida, Masahiko

    2008-01-01

    The terahertz wave emission from the intrinsic Josephson junctions is one of recent topics in high T c superconductors. We investigate, by numerical simulation, properties of the electromagnetic waves excited by a constant bias current in the single- and multi-Josephson junctions. Nonlinear equations of phase-differences are solved numerically by treating the effects of the outside electromagnetic fields as dynamical boundary conditions. It is shown that the emitted power of the electromagnetic wave can become large near certain retrapping points of the I-V characteristics. An instability of the inside phase oscillation is related to large amplitude of the oscillatory waves. In the single- (or homogeneous mutli-) Josephson junctions, electromagnetic oscillations can occur either in a form of standing waves (shorter junctions) or by formation of vortex-antivortex pairs (longer junctions). How these two effects affects the behavior of electromagnetic waves in the intrinsic Josephson junctions is discussed

  7. Tunable Nitride Josephson Junctions.

    Energy Technology Data Exchange (ETDEWEB)

    Missert, Nancy A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Henry, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lewis, Rupert M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Howell, Stephen W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolfley, Steven L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Brunke, Lyle Brent [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolak, Matthaeus [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-12-01

    We have developed an ambient temperature, SiO2/Si wafer - scale process for Josephson junctions based on Nb electrodes and Ta x N barriers with tunable electronic properties. The films are fabricated by magnetron sputtering. The electronic properties of the TaxN barriers are controlled by adjusting the nitrogen flow during sputtering. This technology offers a scalable alternative to the more traditional junctions based on AlOx barriers for low - power, high - performance computing.

  8. Scattering theory of superconductive tunneling in quantum junctions

    International Nuclear Information System (INIS)

    Shumeiko, V.S.; Bratus', E.N.

    1997-01-01

    A consistent theory of superconductive tunneling in single-mode junctions within a scattering formulation of Bogolyubov-de Gennes quantum mechanics is presented. The dc Josephson effect and dc quasiparticle transport in the voltage-biased junctions are considered. Elastic quasiparticle scattering by the junction determines the equilibrium Josephson current. The origin of Andreev bound states in tunnel junctions and their role in equilibrium Josephson transport are discussed. In contrast, quasiparticle tunneling in voltage-biased junctions is determined by inelastic scattering. A general expression for inelastic scattering amplitudes is derived and the quasiparticle current is calculated at all voltages with emphasis on a discussion of the properties of sub gap tunnel current and the nature of subharmonic gap structure

  9. Short chain molecular junctions: Charge transport versus dipole moment

    International Nuclear Information System (INIS)

    Ikram, I. Mohamed; Rabinal, M.K.

    2015-01-01

    Graphical abstract: - Highlights: • The role of dipole moment of organic molecules on molecular junctions has been studied. • Molecular junctions constituted using propargyl molecules of different dipole moments. • The electronic properties of the molecules were calculated using Gaussian software. • Junctions show varying rectification due to their varying dipole moment and orientation. - Abstract: The investigation of the influence of dipole moment of short chain organic molecules having three carbon atoms varying in end group on silicon surface was carried on. Here, we use three different molecules of propargyl series varying in dipole moment and its orientation to constitute molecular junctions. The charge transport mechanism in metal–molecules–semiconductor (MMS) junction obtained from current–voltage (I–V) characteristics shows the rectification behavior for two junctions whereas the other junction shows a weak rectification. The electronic properties of the molecules were calculated using Gaussian software package. The observed rectification behavior of these junctions is examined and found to be accounted to the orientation of dipole moment and electron cloud density distribution inside the molecules

  10. Some chaotic features of intrinsically coupled Josephson junctions

    International Nuclear Information System (INIS)

    Kolahchi, M.R.; Shukrinov, Yu.M.; Hamdipour, M.; Botha, A.E.; Suzuki, M.

    2013-01-01

    Highlights: ► Intrinsically coupled Josephson junctions model a high-T c superconductor. ► Intrinsically coupled Josephson junctions can act as a chaotic nonlinear system. ► Chaos could be due to resonance overlap. ► Avoiding parameters that lead to chaos is important for the design of resonators. -- Abstract: We look for chaos in an intrinsically coupled system of Josephson junctions. This study has direct applications for the high-T c resonators which require coherence amongst the junctions

  11. 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

  12. Advanced Hydraulic Fracturing Technology for Unconventional Tight Gas Reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Stephen Holditch; A. Daniel Hill; D. Zhu

    2007-06-19

    The objectives of this project are to develop and test new techniques for creating extensive, conductive hydraulic fractures in unconventional tight gas reservoirs by statistically assessing the productivity achieved in hundreds of field treatments with a variety of current fracturing practices ranging from 'water fracs' to conventional gel fracture treatments; by laboratory measurements of the conductivity created with high rate proppant fracturing using an entirely new conductivity test - the 'dynamic fracture conductivity test'; and by developing design models to implement the optimal fracture treatments determined from the field assessment and the laboratory measurements. One of the tasks of this project is to create an 'advisor' or expert system for completion, production and stimulation of tight gas reservoirs. A central part of this study is an extensive survey of the productivity of hundreds of tight gas wells that have been hydraulically fractured. We have been doing an extensive literature search of the SPE eLibrary, DOE, Gas Technology Institute (GTI), Bureau of Economic Geology and IHS Energy, for publicly available technical reports about procedures of drilling, completion and production of the tight gas wells. We have downloaded numerous papers and read and summarized the information to build a database that will contain field treatment data, organized by geographic location, and hydraulic fracture treatment design data, organized by the treatment type. We have conducted experimental study on 'dynamic fracture conductivity' created when proppant slurries are pumped into hydraulic fractures in tight gas sands. Unlike conventional fracture conductivity tests in which proppant is loaded into the fracture artificially; we pump proppant/frac fluid slurries into a fracture cell, dynamically placing the proppant just as it occurs in the field. From such tests, we expect to gain new insights into some of the critical

  13. Strain and spin-orbit effects in self-assembled quantum dots

    International Nuclear Information System (INIS)

    Zielinski, M.; Jaskolski, W.; Aizpurua, J.; Bryant, G.W.

    2005-01-01

    The Effects of strain and spin-orbit interaction in self-assembled lien-shaped InAs/GaAs quantum dots are investigated. Calculations are performed with empirical tight-binding theory supplemented by the valence force field method to account for effects of strain caused by lattice mismatch at the InAs-GaAs interface. It is shown that both effects influence strongly the electron and hole energy structure: splitting of the energy levels, the number of bound states, density distributions, and transition rates. We show that piezoelectric effects are almost negligible in quantum dots of the size investigated. (author)

  14. Planar Josephson tunnel junctions in a transverse magnetic field

    DEFF Research Database (Denmark)

    Monacoa, R.; Aarøe, Morten; Mygind, Jesper

    2007-01-01

    demagnetization effects imposed by the tunnel barrier and electrodes geometry are important. Measurements of the junction critical current versus magnetic field in planar Nb-based high-quality junctions with different geometry, size, and critical current density show that it is advantageous to use a transverse......Traditionally, since the discovery of the Josephson effect in 1962, the magnetic diffraction pattern of planar Josephson tunnel junctions has been recorded with the field applied in the plane of the junction. Here we discuss the static junction properties in a transverse magnetic field where...

  15. Particle detection with superconducting tunnel junctions

    International Nuclear Information System (INIS)

    Jany, P.

    1990-08-01

    At the Institute of Experimental Nuclear Physics of the University of Karlsruhe (TH) and at the Institute for Nuclear Physics of the Kernforschungszentrum Karlsruhe we started to produce superconducting tunnel junctions and to investigate them for their suitability as particle detectors. The required facilities for the production of tunnel junctions and the experimental equipments to carry out experiments with them were erected. Experiments are presented in which radiations of different kinds of particles could successfully be measured with the tunnel junctions produced. At first we succeeded in detectioning light pulses of a laser. In experiments with alpha-particles of an energy of 4,6 MeV the alpha-particles were detected with an energy resolution of 1,1%, and it was shown in specific experiments that the phonons originating from the deposition of energy by an alpha-particle in the substrate can be detected with superconducting tunnel junctions at the surface. On that occasion it turned out that the signals could be separated with respect to their point of origin (tunnel junction, contact leads, substrate). Finally X-rays with an energy of 6 keV were detected with an energy resolution of 8% in a test arrangement that makes use of the so-called trapping effect to read out a larger absorber volume. (orig.) [de

  16. Tightness of M-estimators for multiple linear regression in time series

    DEFF Research Database (Denmark)

    Johansen, Søren; Nielsen, Bent

    We show tightness of a general M-estimator for multiple linear regression in time series. The positive criterion function for the M-estimator is assumed lower semi-continuous and sufficiently large for large argument: Particular cases are the Huber-skip and quantile regression. Tightness requires...

  17. Effect of solar-cell junction geometry on open-circuit voltage

    Science.gov (United States)

    Weizer, V. G.; Godlewski, M. P.

    1985-01-01

    Simple analytical models have been found that adequately describe the voltage behavior of both the stripe junction and dot junction grating cells as a function of junction area. While the voltage in the former case is found to be insensitive to junction area reduction, significant voltage increases are shown to be possible for the dot junction cell. With regard to cells in which the junction area has been increased in a quest for better performance, it was found that (1) texturation does not affect the average saturation current density J0, indicating that the texturation process is equivalent to a simple extension of junction area by a factor of square root of 3 and (2) the vertical junction cell geometry produces a sizable decrease in J0 that, unfortunately, is more than offset by the effects of attendant areal increases.

  18. Local thermal-hydraulic behaviour in tight 7-rod bundles

    International Nuclear Information System (INIS)

    Cheng, X.; Yu, Y.Q.

    2009-01-01

    Advanced water-cooled reactor concepts with tight lattices have been proposed worldwide to improve the fuel utilization and the economic competitiveness. In the present work, experimental investigations were performed on thermal-hydraulic behaviour in tight hexagonal 7-rod bundles under both single-phase and two-phase conditions. Freon-12 was used as working fluid due to its convenient operating parameters. Tests were carried out under both single-phase and two-phase flow conditions. Rod surface temperatures are measured at a fixed axial elevation and in various circumferential positions. Test data with different radial power distributions are analyzed. Measured surface temperatures of unheated rods are used for the assessment of and comparison with numerical codes. In addition, numerical simulation using sub-channel analysis code MATRA and the computational fluid dynamics (CFD) code ANSYS-10 is carried out to understand the experimental data and to assess the validity of these codes in the prediction of flow and heat transfer behaviour in tight rod bundle geometries. Numerical results are compared with experimental data. A good agreement between the measured temperatures on the unheated rod surface and the CFD calculation is obtained. Both sub-channel analysis and CFD calculation indicates that the turbulent mixing in the tight rod bundle is significantly stronger than that computed with a well established correlation.

  19. Advance of Mechanically Controllable Break Junction for Molecular Electronics.

    Science.gov (United States)

    Wang, Lu; Wang, Ling; Zhang, Lei; Xiang, Dong

    2017-06-01

    Molecular electronics stands for the ultimate size of functional elements, keeping up with an unstoppable trend over the past few decades. As a vital component of molecular electronics, single molecular junctions have attracted significant attention from research groups all over the world. Due to its pronounced superiority, the mechanically controllable break junctions (MCBJ) technique has been widely applied to characterize the dynamic performance of single molecular junctions. This review presents a system analysis for single-molecule junctions and offers an overview of four test-beds for single-molecule junctions, thus offering more insight into the mechanisms of electron transport. We mainly focus on the development of state-of-the-art mechanically controlled break junctions. The three-terminal gated MCBJ approaches are introduced to manipulate the electron transport of molecules, and MCBJs are combined with characterization techniques. Additionally, applications of MCBJs and remarkable properties of single molecules are addressed. Finally, the challenges and perspective for the mechanically controllable break junctions technique are provided.

  20. 热应激对奶山羊瘤胃黏膜紧密连接蛋白表达的影响%Effects of Heat Stress on Expressions of Tight Junction Proteins in Ruminal Mucosa of Dairy Goats

    Institute of Scientific and Technical Information of China (English)

    马燕芬; 杜瑞平; 高民

    2014-01-01

    本试验旨在研究热应激对奶山羊瘤胃黏膜紧密连接蛋白表达的影响。将8只体况良好,体重、年龄、胎次和产奶量相近,处于泌乳中后期的奶山羊随机分为对照组和热应激组,每组4只羊。饲养环境采取人工控温控湿。试验期45 d,在试验30和45 d时,采集瘤胃背囊和腹囊组织,分别采用免疫组化法、实时定量PCR法和蛋白质免疫印迹法检测其闭合蛋白( claudin )、闭锁小带蛋白1( ZO-1)蛋白的结构分布、基因mRNA表达量和蛋白表达量。结果表明:与对照组相比,热应激组(30 d)背囊和腹囊中claudin、ZO-1蛋白的信号强度和表达量均有所下降,而热应激组(45 d)下降更为严重。与对照组相比,热应激组(30 d)背囊和腹囊中claudin、ZO-1基因mRNA表达量均显著下降(P<0.05),而热应激组(45 d)则显著低于热应激组(30 d)(P<0.05)。结果提示,热应激对瘤胃黏膜的结构和完整性的破坏与瘤胃黏膜紧密连接蛋白表达量下降有关。%This study was conducted to study the effects of heat stress ( HS) on expressions of tight junction proteins in ruminal mucosa of dairy goats. Eight healthy dietary goats with similar body weight, age, parity and milk yield at mid to late-locating period were randomly divided into control group and heat stress ( HS ) group with 4 goats in each group. Environmental temperature and humidity during feeding period were artifi-cially controlled. The experiment lasted for 45 days. Knapsack and abdominal sac samples were collected at 30 and 45 days of experiment to determine protein structural distribution, gene mRNA expression levels and pro-tein expression levels of claudin and zonula occluden 1 ( ZO-1 ) using the methods of immunohistochemisty, real-time quantitative PCR and West-bloting, respectively. The results showed as follows: compared with the control group, expression levels and signal intensity of claudin and ZO-1 proteins in knapsack and abdominal in HS

  1. Nanomanipulation and Lithography: The Building (and Modeling) of Carbon Nanotube Magnetic Tunnel Junctions

    Science.gov (United States)

    Louie, Richard Nam

    2002-12-01

    sizes, through the re-writing of a critical code segment that gives a hundredfold improvement in speed. Furthermore, the tight-binding model calculations are now generalized to include all types of nanotubes, not merely armchair tubes. On the experimental side, innovative junction fabrication procedures are investigated, including diamond-tip scanning probe lithography and e-beam lithography. Programs are written for the Nanometer Pattern Generation System to effect the creation of many junctions at once, to increase the chances of a CNT connecting two FM electrodes. As it is not prudent to rely solely on luck, the capability for tube nanomanipulation with an unprecedented level of control is also shown, and a procedure for controlled deposition upon chemically functionalized lithographic patterns is discussed. All of the techniques demonstrated can be used to create a magnetic tunnel junction to be refrigerated for extensive magnetoconductance studies.

  2. Microwave phase locking of Josephson-junction fluxon oscillators

    DEFF Research Database (Denmark)

    Salerno, M.; Samuelsen, Mogens Rugholm; Filatrella, G.

    1990-01-01

    Application of the classic McLaughlin-Scott soliton perturbation theory to a Josephson-junction fluxon subjected to a microwave field that interacts with the fluxon only at the junction boundaries reduces the problem of phase locking of the fluxon oscillation to the study of a two-dimensional fun......Application of the classic McLaughlin-Scott soliton perturbation theory to a Josephson-junction fluxon subjected to a microwave field that interacts with the fluxon only at the junction boundaries reduces the problem of phase locking of the fluxon oscillation to the study of a two...

  3. The critical current of point symmetric Josephson tunnel junctions

    International Nuclear Information System (INIS)

    Monaco, Roberto

    2016-01-01

    Highlights: • We disclose some geometrical properties of the critical current field dependence that apply to a large class of Josephson junctions characterized by a point symmetric shape. • The developed theory is valid for any orientation of the applied magnetic field, therefore it allows the determine the consequences of field misalignment in the experimental setups. • We also address that the threshold curves of Josephson tunnel junctions with complex shapes can be expressed as a linear combination of the threshold curves of junctions with simpler point symmetric shapes. - Abstract: The physics of Josephson tunnel junctions drastically depends on their geometrical configurations. The shape of the junction determines the specific form of the magnetic-field dependence of its Josephson current. Here we address the magnetic diffraction patterns of specially shaped planar Josephson tunnel junctions in the presence of an in-plane magnetic field of arbitrary orientations. We focus on a wide ensemble of junctions whose shape is invariant under point reflection. We analyze the implications of this type of isometry and derive the threshold curves of junctions whose shape is the union or the relative complement of two point symmetric plane figures.

  4. 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.

  5. Soliton excitations in Josephson tunnel junctions

    DEFF Research Database (Denmark)

    Lomdahl, P. S.; Sørensen, O. H.; Christiansen, Peter Leth

    1982-01-01

    A detailed numerical study of a sine-Gordon model of the Josephson tunnel junction is compared with experimental measurements on junctions with different L / λJ ratios. The soliton picture is found to apply well on both relatively long (L / λJ=6) and intermediate (L / λJ=2) junctions. We find good...... agreement for the current-voltage characteristics, power output, and for the shape and height of the zero-field steps (ZFS). Two distinct modes of soliton oscillations are observed: (i) a bunched or congealed mode giving rise to the fundamental frequency f1 on all ZFS's and (ii) a "symmetric" mode which...... on the Nth ZFS yields the frequency Nf1 Coexistence of two adjacent frequencies is found on the third ZFS of the longer junction (L / λJ=6) in a narrow range of bias current as also found in the experiments. Small asymmetries in the experimental environment, a weak magnetic field, e.g., is introduced via...

  6. Constructing carbon nanotube junctions by Ar ion beam irradiation

    International Nuclear Information System (INIS)

    Ishaq, Ahmad; Ni Zhichun; Yan Long; Gong Jinlong; Zhu Dezhang

    2010-01-01

    Carbon nanotubes (CNTs) irradiated by Ar ion beams at elevated temperature were studied. The irradiation-induced defects in CNTs are greatly reduced by elevated temperature. Moreover, the two types of CNT junctions, the crossing junction and the parallel junction, were formed. And the CNT networks may be fabricated by the two types of CNT junctions. The formation process and the corresponding mechanism of CNT networks are discussed.

  7. Field modulation of the critical current in magnetic Josephson junctions

    International Nuclear Information System (INIS)

    Blamire, M G; Smiet, C B; Banerjee, N; Robinson, J W A

    2013-01-01

    The dependence of the critical current of a simple Josephson junction on the applied magnetic field is well known and, for a rectangular junction, gives rise to the classic ‘Fraunhofer’ modulation with periodic zeros at the fields that introduce a flux quantum into the junction region. Much recent work has been performed on Josephson junctions that contain magnetic layers. The magnetization of such layers introduces additional flux into the junction and, for large junction areas or strong magnetic materials, can significantly distort the modulation of the critical current and strongly suppress the maximum critical current. The growing interest in junctions that induce odd-frequency triplet pairing in a ferromagnet, and the need to make quantitative comparisons with theory, mean that a full understanding of the role of magnetic barriers in controlling the critical current is necessary. This paper analyses the effect of magnetism and various magnetic configurations on Josephson critical currents; the overall treatment applies to junctions of general shape, but the specific cases of square and rectangular junctions are considered. (paper)

  8. Shunted-Josephson-junction model. II. The nonautonomous case

    DEFF Research Database (Denmark)

    Belykh, V. N.; Pedersen, Niels Falsig; Sørensen, O. H.

    1977-01-01

    The shunted-Josephson-junction model with a monochromatic ac current drive is discussed employing the qualitative methods of the theory of nonlinear oscillations. As in the preceding paper dealing with the autonomous junction, the model includes a phase-dependent conductance and a shunt capacitance....... The mathematical discussion makes use of the phase-space representation of the solutions to the differential equation. The behavior of the trajectories in phase space is described for different characteristic regions in parameter space and the associated features of the junction IV curve to be expected are pointed...... out. The main objective is to provide a qualitative understanding of the junction behavior, to clarify which kinds of properties may be derived from the shunted-junction model, and to specify the relative arrangement of the important domains in the parameter-space decomposition....

  9. Observation of supercurrent in graphene-based Josephson junction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Libin; Li, Sen; Kang, Ning [Key Laboratory for the Physics and Chemistry of Nanodevices and Department of Electronics, Peking University, Beijing 100871 (China); Xu, Chuan; Ren, Wencai [Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China)

    2015-07-01

    Josephson junctions with a normal metal region sandwiched between two superconductors (S) are known as superconductor- normal-superconductor (SNS) structures. It has attracted significant attention especially when changing the normal metal with graphene, which allow for high tunability with the gate voltage and to study the proximity effect of the massless Dirac fermions. Here we report our work on graphene-based Josephson junction with a new two dimensional superconductor crystal, which grown directly on graphene, as superconducting electrodes. At low temperature, we observer proximity effect induced supercurrent flowing through the junction. The temperature and the magnetic field dependences of the critical current characteristics of the junction are also studied. The critical current exhibits a Fraunhofer-type diffraction pattern against magnetic field. Our experiments provided a new route of fabrication of graphene-based Josephson junction.

  10. Josephson junction arrays and superconducting wire networks

    International Nuclear Information System (INIS)

    Lobb, C.J.

    1992-01-01

    Techniques used to fabricate integrated circuits make it possible to construct superconducting networks containing as many as 10 6 wires or Josephson junctions. Such networks undergo phase transitions from resistive high-temperature states to ordered low-resistance low-temperature states. The nature of the phase transition depends strongly on controllable parameters such as the strength of the superconductivity in each wire or junction and the external magnetic field. This paper will review the physics of these phase transitions, starting with the simplest zero-magnetic field case. This leads to a Kosterlitz-Thouless transition when the junctions or wires are weak, and a simple mean-field fransition when the junctions or wires are strong. Rich behavior, resulting from frustration, occurs in the presence of a magnetic field. (orig.)

  11. Phenomenological approach to bistable behavior of Josephson junctions

    International Nuclear Information System (INIS)

    Nishi, K.; Nara, S.; Hamanaka, K.

    1985-01-01

    The interaction of unbiased Josephson junction with external electromagnetic field in the presence of externally applied uniform magnetic field is theoretically examined by means of phenomenological treatment. It is proposed that an irradiated junction with suitably chosen parameters shows a bistable behavior of voltage across the junction as a function of the radiation intensity

  12. Experimental study on reflooding in advanced tight lattice PWR

    International Nuclear Information System (INIS)

    Hori, K.; Kodama, J.; Teramae, T.

    2000-01-01

    This paper is related to the experimental study on the feasibility of core cooling by re-flooding in a large break loss of coolant accident (LOCA) for the advanced tight lattice pressurized water reactor (PWR). The tight lattice core design should be adopted to improve the conversion ratio. Major one of the key questions of such tight lattice core is the cooling capability under the re-flood condition in a large break LOCA. Forced feed bottom re-flooding experiments have been performed by use of a 4x4 triangular array rod bundle. The rod gap is 0.5 mm, 1.0 mm, or 1.5 mm. The measured peak temperature is below around 1273 K even in case of 1.0/0.5 mm rod gap. And, the evaluation based on the experimental results of rod temperatures and core pressure drop also shows that the core cooling under re-flooding condition is feasible. (author)

  13. Synthesis and characterization of Mn.sup.2+./sup. doped ZnS nanocrystals self-assembled in a tight mesoporous structure

    Czech Academy of Sciences Publication Activity Database

    Nistor, S.V.; Nistor, L.C.; Stefan, M.; Mateescu, C.D.; Birjega, R.; Solovieva, Natalia; Nikl, Martin

    2009-01-01

    Roč. 46, 1-2 (2009), s. 306-311 ISSN 0749-6036 Institutional research plan: CEZ:AV0Z10100521 Keywords : nanocrystalline ZnS:Mn * mesoporous structure * self-assembly * photoluminescence Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.910, year: 2009

  14. Multiplication in Silicon p-n Junctions

    DEFF Research Database (Denmark)

    Moll, John L.

    1965-01-01

    Multiplication values were measured in the collector junctions of silicon p-n-p and n-p-n transistors before and after bombardment by 1016 neutrons/cm2. Within experimental error there was no change either in junction fields, as deduced from capacitance measurements, or in multiplication values i...

  15. Anchored PKA as a gatekeeper for gap junctions.

    Science.gov (United States)

    Pidoux, Guillaume; Taskén, Kjetil

    2015-01-01

    Anchored protein kinase A (PKA) bound to A Kinase Anchoring Protein (AKAP) mediates effects of localized increases in cAMP in defined subcellular microdomains and retains the specificity in cAMP-PKA signaling to distinct extracellular stimuli. Gap junctions are pores between adjacent cells constituted by connexin proteins that provide means of communication and transfer of small molecules. While the PKA signaling is known to promote human trophoblast cell fusion, the gap junction communication through connexin 43 (Cx43) is a prerequisite for this process. We recently demonstrated that trophoblast fusion is regulated by ezrin, a known AKAP, which binds to Cx43 and delivers PKA in the vicinity gap junctions. We found that disruption of the ezrin-Cx43 interaction abolished PKA-dependent phosphorylation of Cx43 as well as gap junction communication and subsequently cell fusion. We propose that the PKA-ezrin-Cx43 macromolecular complex regulating gap junction communication constitutes a general mechanism to control opening of Cx43 gap junctions by phosphorylation in response to cAMP signaling in various cell types.

  16. Heat Transport in Graphene Ferromagnet-Insulator-Superconductor Junctions

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-Wei

    2011-01-01

    We study heat transport in a graphene ferromagnet-insulator-superconducting junction. It is found that the thermal conductance of the graphene ferromagnet-insulator-superconductor (FIS) junction is an oscillatory function of the barrier strength x in the thin-barrier limit. The gate potential U0 decreases the amplitude of thermal conductance oscillation. Both the amplitude and phase of the thermal conductance oscillation varies with the exchange energy Eh. The thermal conductance of a graphene FIS junction displays the usual exponential dependence on temperature, reflecting the s-wave symmetry of superconducting graphene.%@@ We study heat transport in a graphene ferromagnet-insulator-superconducting junction.It is found that the thermal conductance of the graphene ferromagnet-insulator-superconductor(FIS)junction is an oscillatory function of the barrier strength X in the thin-barrier limit.The gate potential Uo decreases the amplitude of thermal conductance oscillation.Both the amplitude and phase of the thermal conductance oscillation varies with the exchange energy Eh.The thermal conductance of a graphene FIS junction displays the usual exponential dependence on temperature, reflecting the s-wave symmetry of superconducting graphene.

  17. Transferable tight-binding model for strained group IV and III-V materials and heterostructures

    Science.gov (United States)

    Tan, Yaohua; Povolotskyi, Michael; Kubis, Tillmann; Boykin, Timothy B.; Klimeck, Gerhard

    2016-07-01

    It is critical to capture the effect due to strain and material interface for device level transistor modeling. We introduce a transferable s p3d5s* tight-binding model with nearest-neighbor interactions for arbitrarily strained group IV and III-V materials. The tight-binding model is parametrized with respect to hybrid functional (HSE06) calculations for varieties of strained systems. The tight-binding calculations of ultrasmall superlattices formed by group IV and group III-V materials show good agreement with the corresponding HSE06 calculations. The application of the tight-binding model to superlattices demonstrates that the transferable tight-binding model with nearest-neighbor interactions can be obtained for group IV and III-V materials.

  18. Terahertz Responses of Intrinsic Josephson Junctions in High TC Superconductors

    International Nuclear Information System (INIS)

    Wang, H. B.; Wu, P. H.; Yamashita, T.

    2001-01-01

    High frequency responses of intrinsic Josephson junctions up to 2.5THz, including the observation of Shapiro steps under various conditions, are reported and discussed in this Letter. The sample was an array of intrinsic Josephson junctions singled out from inside a high T C superconducting Bi 2 Sr 2 CaCu 2 O 8+x single crystal, with a bow-tie antenna integrated to it. The number of junctions in the array was controllable, the junctions were homogeneous, the distribution of applied irradiation among the junctions was even, and the junctions could synchronously respond to high frequency irradiation

  19. Ferritin Assembly in Enterocytes of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Abraham Rosas-Arellano

    2016-02-01

    Full Text Available Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH and Ferritin 2 Light Chain Homolog (Fer2LCH are further stabilized by disulfide-bridge in the 24-subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH-Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated.

  20. Long Josephson Junction Stack Coupled to a Cavity

    DEFF Research Database (Denmark)

    Madsen, Søren Peder; Pedersen, Niels Falsig; Groenbech-Jensen, N.

    2007-01-01

    A stack of inductively coupled long Josephson junctions are modeled as a system of coupled sine-Gordon equations. One boundary of the stack is coupled electrically to a resonant cavity. With one fluxon in each Josephson junction, the inter-junction fluxon forces are repulsive. We look at a possible...... transition, induced by the cavity, to a bunched state....

  1. Structural Origins of Conductance Fluctuations in Gold–Thiolate Molecular Transport Junctions

    KAUST Repository

    French, William R.

    2013-03-21

    We report detailed atomistic simulations combined with high-fidelity conductance calculations to probe the structural origins of conductance fluctuations in thermally evolving Au-benzene-1,4-dithiolate-Au junctions. We compare the behavior of structurally ideal junctions (where the electrodes are modeled as flat surfaces) to structurally realistic, experimentally representative junctions resulting from break-junction simulations. The enhanced mobility of metal atoms in structurally realistic junctions results in significant changes to the magnitude and origin of the conductance fluctuations. Fluctuations are larger by a factor of 2-3 in realistic junctions compared to ideal junctions. Moreover, in junctions with highly deformed electrodes, the conductance fluctuations arise primarily from changes in the Au geometry, in contrast to results for junctions with nondeformed electrodes, where the conductance fluctuations are dominated by changes in the molecule geometry. These results provide important guidance to experimentalists developing strategies to control molecular conductance, and also to theoreticians invoking simplified structural models of junctions to predict their behavior. © 2013 American Chemical Society.

  2. Structural Origins of Conductance Fluctuations in Gold–Thiolate Molecular Transport Junctions

    KAUST Repository

    French, William R.; Iacovella, Christopher R.; Rungger, Ivan; Souza, Amaury Melo; Sanvito, Stefano; Cummings, Peter T.

    2013-01-01

    We report detailed atomistic simulations combined with high-fidelity conductance calculations to probe the structural origins of conductance fluctuations in thermally evolving Au-benzene-1,4-dithiolate-Au junctions. We compare the behavior of structurally ideal junctions (where the electrodes are modeled as flat surfaces) to structurally realistic, experimentally representative junctions resulting from break-junction simulations. The enhanced mobility of metal atoms in structurally realistic junctions results in significant changes to the magnitude and origin of the conductance fluctuations. Fluctuations are larger by a factor of 2-3 in realistic junctions compared to ideal junctions. Moreover, in junctions with highly deformed electrodes, the conductance fluctuations arise primarily from changes in the Au geometry, in contrast to results for junctions with nondeformed electrodes, where the conductance fluctuations are dominated by changes in the molecule geometry. These results provide important guidance to experimentalists developing strategies to control molecular conductance, and also to theoreticians invoking simplified structural models of junctions to predict their behavior. © 2013 American Chemical Society.

  3. Silicon fiber with p-n junction

    International Nuclear Information System (INIS)

    Homa, D.; Cito, A.; Pickrell, G.; Hill, C.; Scott, B.

    2014-01-01

    In this study, we fabricated a p-n junction in a fiber with a phosphorous doped silicon core and fused silica cladding. The fibers were fabricated via a hybrid process of the core-suction and melt-draw techniques and maintained overall diameters ranging from 200 to 900 μm and core diameters of 20–800 μm. The p-n junction was formed by doping the fiber with boron and confirmed via the current-voltage characteristic. The demonstration of a p-n junction in a melt-drawn silicon core fiber paves the way for the seamless integration of optical and electronic devices in fibers.

  4. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease.

    Science.gov (United States)

    Fasano, A; Not, T; Wang, W; Uzzau, S; Berti, I; Tommasini, A; Goldblum, S E

    2000-04-29

    We identified zonulin, a novel human protein analogue to the Vibrio cholerae derived Zonula occludens toxin, which induces tight junction disassembly and a subsequent increase in intestinal permeability in non-human primate intestinal epithelia. Zonulin expression was raised in intestinal tissues during the acute phase of coeliac disease, a clinical condition in which tight junctions are opened and permeability is increased.

  5. Tightness of voter model interfaces

    Czech Academy of Sciences Publication Activity Database

    Sturm, A.; Swart, Jan M.

    2008-01-01

    Roč. 13, - (2008), s. 165-174 ISSN 1083-589X R&D Projects: GA ČR GA201/06/1323; GA ČR GA201/07/0237 Institutional research plan: CEZ:AV0Z10750506 Keywords : long range voter model * swapping voter model * interface tightness * exclusion process Subject RIV: BD - Theory of Information Impact factor: 0.392, year: 2008 http://www.emis.de/journals/EJP-ECP/_ejpecp/index.html

  6. Quasiparticle current in superconductor-semiconductor-superconductor junctions

    International Nuclear Information System (INIS)

    Tartakovskij, A.V.; Fistul', M.V.

    1988-01-01

    It is shown that the quasiparticle current in a superconductor-semiconductor-superconductor junction may significantly increase as a result of resonant passage of the quasiparticle along particular trajectories from periodically situated localized centers. A prediction of the theory is that with increasing junction resistance there should be a change from an excessive current to a insufficient current on the current-voltage characteristics (at high voltages). The effect of transparency of the boundaries on resonance tunneling in such junctions is also investigated

  7. Tight turns

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    The Italian National Institute for Nuclear Physics (INFN) has successfully tested the first model of a new fast-ramping curved dipole magnet. This is great news for CERN, which sees the advance as holding potential for the future of the SPS.   The first model of a new fast-ramping curved dipole magnet being prepared for cryogenic testing at the LASA laboratory (INFN Milano, Italy). On 16 July INFN introduced an innovative dipole magnet. With a length of some 4 metres, it can produce a 4.5 Tesla magnetic field and achieve a tighter bend than ever before (the bending radius has been squeezed to a remarkable 66.7 metres). This new magnet was designed in the first instance for GSI’s SIS300 synchrotron (in Germany), which will require 60 dipoles of this type. "Achieving such a tight bend demanded a major R&D effort," stressed Pasquale Fabbricatore, the spokesman of the INFN collaboration responsible for the magnet’s development. "We had to not o...

  8. Transport properties of molecular junctions

    CERN Document Server

    Zimbovskaya, Natalya A

    2013-01-01

    A comprehensive overview of the physical mechanisms that control electron transport and the characteristics of metal-molecule-metal (MMM) junctions is presented. As far as possible, methods and formalisms presented elsewhere to analyze electron transport through molecules are avoided. This title introduces basic concepts—a description of the electron transport through molecular junctions—and briefly describes relevant experimental methods. Theoretical methods commonly used to analyze the electron transport through molecules are presented. Various effects that manifest in the electron transport through MMMs, as well as the basics of density-functional theory and its applications to electronic structure calculations in molecules are presented. Nanoelectronic applications of molecular junctions and similar systems are discussed as well. Molecular electronics is a diverse and rapidly growing field. Transport Properties of Molecular Junctions presents an up-to-date survey of the field suitable for researchers ...

  9. Impact of Air Tightness on the Evaluation of Building Energy Performance in Lithuania

    Directory of Open Access Journals (Sweden)

    Jolanta Šadauskienė

    2014-08-01

    Full Text Available In order to fulfil the European Energy Performance of Buildings Directive (EPBD requirements for the reduction of energy consumption, European national requirements have been created for building envelope thermal properties and calculation methodology to determine if building energy efficiency is created. This is however not true in all methodologies. The necessity of building air tightness appears only for new A class buildings, and there are no requirements for air tightness for other building classes. Therefore, the aim of this work is to improve the methodology for the calculation of energy efficiency of buildings, while taking into account the air tightness of the buildings. In order to achieve this aim, the sum energy consumption of investigated buildings was calculated, energy efficiency classes were determined, air tightness of the buildings was measured, and reasons for insufficient air tightness were analyzed. Investigation results show that the average value of air tightness of A energy efficiency class buildings is 0.6 h−1. The results of other investigated buildings, corresponding to B and C energy efficiency classes, show insufficient air tightness (the average n50 value is 6 h−1; herewith, energy consumption for heating is higher than calculated, according to the energy efficiency methodology. This paper provides an energy performance evaluation scheme, under which performed evaluation of energy performance of buildings ensures high quality construction work, building durability, and the reliability of heat-loss calculations.

  10. Spatial inhomogeneous barrier heights at graphene/semiconductor Schottky junctions

    Science.gov (United States)

    Tomer, Dushyant

    Graphene, a semimetal with linear energy dispersion, forms Schottky junction when interfaced with a semiconductor. This dissertation presents temperature dependent current-voltage and scanning tunneling microscopy/spectroscopy (STM/S) measurements performed on graphene Schottky junctions formed with both three and two dimensional semiconductors. To fabricate Schottky junctions, we transfer chemical vapor deposited monolayer graphene onto Si- and C-face SiC, Si, GaAs and MoS2 semiconducting substrates using polymer assisted chemical method. We observe three main type of intrinsic spatial inhomogeneities, graphene ripples, ridges and semiconductor steps in STM imaging that can exist at graphene/semiconductor junctions. Tunneling spectroscopy measurements reveal fluctuations in graphene Dirac point position, which is directly related to the Schottky barrier height. We find a direct correlation of Dirac point variation with the topographic undulations of graphene ripples at the graphene/SiC junction. However, no such correlation is established at graphene/Si and Graphene/GaAs junctions and Dirac point variations are attributed to surface states and trapped charges at the interface. In addition to graphene ripples and ridges, we also observe atomic scale moire patterns at graphene/MoS2 junction due to van der Waals interaction at the interface. Periodic topographic modulations due to moire pattern do not lead to local variation in graphene Dirac point, indicating that moire pattern does not contribute to fluctuations in electronic properties of the heterojunction. We perform temperature dependent current-voltage measurements to investigate the impact of topographic inhomogeneities on electrical properties of the Schottky junctions. We observe temperature dependence in junction parameters, such as Schottky barrier height and ideality factor, for all types of Schottky junctions in forward bias measurements. Standard thermionic emission theory which assumes a perfect

  11. Understanding the Function of Tuberous Sclerosis Complex Genes in Neural Development: Roles in Synapse Assembly and Axon Guidance

    Science.gov (United States)

    2012-02-01

    physiological levels (Jan and Jan, 1976; Gramates and Budnik, 1999; Ruiz-Canada and Budnik, 2006; Schuster, 2006). The Drosophila...Gherbesi N, Thomas U, Gundelfinger E, Gramates LS, et al. 2007. Postsynaptic membrane addition depends on the discs-large-interacting t-SNARE gtaxin. J...Neurosci 27:1033–1044. Gramates LS, Budnik V. 1999. Assembly and maturation of the Drosophila larval neuromuscular junction. Int Rev Neurobiol 43

  12. Gas leak tightness of SiC/SiC composites at elevated temperature

    Energy Technology Data Exchange (ETDEWEB)

    Hayasaka, Daisuke, E-mail: hayasaka@oasis.muroran-it.ac.jp [OASIS, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Graduate School of Engineering, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Park, Joon-Soo. [OASIS, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Kishimoto, Hirotatsu [OASIS, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Graduate School of Engineering, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Kohyama, Akira [OASIS, Muroran Institute of Technology, Muroran, Hokkaido (Japan)

    2016-11-01

    Highlights: • NITE-SiC/SiC has extremely densified microstructure compared with other SiC/SiC composite like CVI. • Excellent helium and hydrogen gas-leak tightness of SiC/SiC composites by DEMO-NITE method from prototype industrialization production line was presented. • The excellence against stainless steel and Zircaloy at elevated temperature, together with generic excellent properties of SiC will be inevitable for innovative blanket and divertors for DEMO- and power- fusion reactors. - Abstract: SiC/SiC composite materials are attractive candidates for high heat flux components and blanket of fusion reactor, mainly due to their high temperature properties, radiation damage tolerance and low induced radioactivity. One of the challenges for SiC/SiC application in fusion reactors is to satisfy sufficient gas leak tightness of hydrogen and helium isotopes. Although many efforts have been carried-out, SiC/SiC composites by conventional processes have not been successful to satisfy the requirements, except SiC/SiC composites by NITE-methods. Toward the early realization of SiC/SiC components into fusion reactor systems process development of NITE-process has been continued. Followed to the brief introduction of recently developed DEMO-NITE process, baseline properties and hydrogen and helium gas leak tightness is presented. SiC/SiC claddings with 10 mm in diameter and 1 mm in wall thickness are tested by gas leak tightness system developed. The leak tightness measurements are done room temperature to 400 °C. Excellent gas leak tightness equivalent or superior to Zircaloy claddings for light water fission reactors is confirmed. The excellent gas leak tightness suggests nearly perfect suppression of large gas leak path in DEMO-NITE SiC/SiC.

  13. Construction of a Holliday Junction in Small Circular DNA Molecules for Stable Motifs and Two-Dimensional Lattices.

    Science.gov (United States)

    Guo, Xin; Wang, Xue-Mei; Wei, Shuai; Xiao, Shou-Jun

    2018-04-12

    Design rules for DNA nanotechnology have been mostly learnt from using linear single-stranded (ss) DNA as the source material. For example, the core structure of a typical DAO (double crossover, antiparallel, odd half-turns) tile for assembling 2D lattices is constructed from only two linear ss-oligonucleotide scaffold strands, similar to two ropes making a square knot. Herein, a new type of coupled DAO (cDAO) tile and 2D lattices of small circular ss-oligonucleotides as scaffold strands and linear ss-oligonucleotides as staple strands are reported. A cDAO tile of cDAO-c64nt (c64nt: circular 64 nucleotides), shaped as a solid parallelogram, is constructed with a Holliday junction (HJ) at the center and two HJs at both poles of a c64nt; similarly, cDAO-c84nt, shaped as a crossed quadrilateral composed of two congruent triangles, is formed with a HJ at the center and four three-way junctions at the corners of a c84nt. Perfect 2D lattices were assembled from cDAO tiles: infinite nanostructures of nanoribbons, nanotubes, and nanorings, and finite nanostructures. The structural relationship between the visible lattices imaged by AFM and the corresponding invisible secondary and tertiary molecular structures of HJs, inclination angle of hydrogen bonds against the double-helix axis, and the chirality of the tile can be interpreted very well. This work could shed new light on DNA nanotechnology with unique circular tiles. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Development of a transverse mixing model for large scale impulsion phenomenon in tight lattice

    International Nuclear Information System (INIS)

    Liu, Xiaojing; Ren, Shuo; Cheng, Xu

    2017-01-01

    Highlights: • Experiment data of Krauss is used to validate the feasibility of CFD simulation method. • CFD simulation is performed to simulate the large scale impulsion phenomenon for tight-lattice bundle. • A mixing model to simulate the large scale impulsion phenomenon is proposed based on CFD result fitting. • The new developed mixing model has been added in the subchannel code. - Abstract: Tight-lattice is widely adopted in the innovative reactor fuel bundles design since it can increase the conversion ratio and improve the heat transfer between fuel bundles and coolant. It has been noticed that a large scale impulsion of cross-velocity exists in the gap region, which plays an important role on the transverse mixing flow and heat transfer. Although many experiments and numerical simulation have been carried out to study the impulsion of velocity, a model to describe the wave length, amplitude and frequency of mixing coefficient is still missing. This research work takes advantage of the CFD method to simulate the experiment of Krauss and to compare experiment data and simulation result in order to demonstrate the feasibility of simulation method and turbulence model. Then, based on this verified method and model, several simulations are performed with different Reynolds number and different Pitch-to-Diameter ratio. By fitting the CFD results achieved, a mixing model to simulate the large scale impulsion phenomenon is proposed and adopted in the current subchannel code. The new mixing model is applied to some fuel assembly analysis by subchannel calculation, it can be noticed that the new developed mixing model can reduce the hot channel factor and contribute to a uniform distribution of outlet temperature.

  15. Systematic study of shallow junction formation on germanium substrates

    DEFF Research Database (Denmark)

    Hellings, Geert; Rosseel, Erik; Clarysse, Trudo

    2011-01-01

    Published results on Ge junctions are benchmarked systematically using RS–XJ plots. The electrical activation level required to meet the ITRS targets is calculated. Additionally, new results are presented on shallow furnace-annealed B junctions and shallow laser-annealed As junctions. Co-implanting...

  16. Growth and self-assembly of BaTiO3 nanocubes for resistive switching memory cells

    International Nuclear Information System (INIS)

    Chu, Dewei; Lin, Xi; Younis, Adnan; Li, Chang Ming; Dang, Feng; Li, Sean

    2014-01-01

    In this work, the self-assembled BaTiO 3 nanocubes based resistive switching memory capacitors are fabricated with hydrothermal and drop-coating approaches. The device exhibits excellent bipolar resistance switching characteristics with ON/OFF ratio of 58–70, better reliability and stability over various polycrystalline BaTiO 3 nanostructures. It is believed that the inter cube junctions is responsible for such a switching behaviour and it can be described by the filament model. The effect of film thickness on switching ratio (ON/OFF) was also investigated in details. - Graphical abstract: This work describes a novel resistive switching memory cell based on self-assembled BaTiO 3 nanocubes. - Highlights: • BaTiO 3 nanocubes were prepared by one step facile hydrothermal method. • Self-assembled BaTiO 3 nanocubes thin films were obtained by drop-coating approach. • The BaTiO 3 nanocubes show excellent resistive switching properties for memory applications

  17. Microwave emulations and tight-binding calculations of transport in polyacetylene

    Energy Technology Data Exchange (ETDEWEB)

    Stegmann, Thomas, E-mail: stegmann@icf.unam.mx [Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n, 62210 Cuernavaca (Mexico); Franco-Villafañe, John A., E-mail: jofravil@fis.unam.mx [Instituto de Física, Benemérita Universidad Autónoma de Puebla, Apartado Postal J-48, 72570 Puebla (Mexico); Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n, 62210 Cuernavaca (Mexico); Ortiz, Yenni P. [Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n, 62210 Cuernavaca (Mexico); Kuhl, Ulrich [Université de Nice – Sophia Antipolis, Laboratoire de la Physique de la Matière Condensée, CNRS, Parc Valrose, 06108 Nice (France); Mortessagne, Fabrice, E-mail: fabrice.mortessagne@unice.fr [Université de Nice – Sophia Antipolis, Laboratoire de la Physique de la Matière Condensée, CNRS, Parc Valrose, 06108 Nice (France); Seligman, Thomas H. [Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n, 62210 Cuernavaca (Mexico); Centro Internacional de Ciencias, 62210 Cuernavaca (Mexico)

    2017-01-05

    A novel approach to investigate the electron transport of cis- and trans-polyacetylene chains in the single-electron approximation is presented by using microwave emulation measurements and tight-binding calculations. In the emulation we take into account the different electronic couplings due to the double bonds leading to coupled dimer chains. The relative coupling constants are adjusted by DFT calculations. For sufficiently long chains a transport band gap is observed if the double bonds are present, whereas for identical couplings no band gap opens. The band gap can be observed also in relatively short chains, if additional edge atoms are absent, which cause strong resonance peaks within the band gap. The experimental results are in agreement with our tight-binding calculations using the nonequilibrium Green's function method. The tight-binding calculations show that it is crucial to include third nearest neighbor couplings to obtain the gap in the cis-polyacetylene. - Highlights: • Electronic transport in individual polyacetylene chains is studied. • Microwave emulation experiments and tight-binding calculations agree well. • In long chains a band-gap opens due the dimerization of the chain. • In short chains edge atoms cause strong resonance peaks in the center of the band-gap.

  18. Microwave emulations and tight-binding calculations of transport in polyacetylene

    International Nuclear Information System (INIS)

    Stegmann, Thomas; Franco-Villafañe, John A.; Ortiz, Yenni P.; Kuhl, Ulrich; Mortessagne, Fabrice; Seligman, Thomas H.

    2017-01-01

    A novel approach to investigate the electron transport of cis- and trans-polyacetylene chains in the single-electron approximation is presented by using microwave emulation measurements and tight-binding calculations. In the emulation we take into account the different electronic couplings due to the double bonds leading to coupled dimer chains. The relative coupling constants are adjusted by DFT calculations. For sufficiently long chains a transport band gap is observed if the double bonds are present, whereas for identical couplings no band gap opens. The band gap can be observed also in relatively short chains, if additional edge atoms are absent, which cause strong resonance peaks within the band gap. The experimental results are in agreement with our tight-binding calculations using the nonequilibrium Green's function method. The tight-binding calculations show that it is crucial to include third nearest neighbor couplings to obtain the gap in the cis-polyacetylene. - Highlights: • Electronic transport in individual polyacetylene chains is studied. • Microwave emulation experiments and tight-binding calculations agree well. • In long chains a band-gap opens due the dimerization of the chain. • In short chains edge atoms cause strong resonance peaks in the center of the band-gap.

  19. Junction Potentials Bias Measurements of Ion Exchange Membrane Permselectivity.

    Science.gov (United States)

    Kingsbury, Ryan S; Flotron, Sophie; Zhu, Shan; Call, Douglas F; Coronell, Orlando

    2018-04-17

    Ion exchange membranes (IEMs) are versatile materials relevant to a variety of water and waste treatment, energy production, and industrial separation processes. The defining characteristic of IEMs is their ability to selectively allow positive or negative ions to permeate, which is referred to as permselectivity. Measured values of permselectivity that equal unity (corresponding to a perfectly selective membrane) or exceed unity (theoretically impossible) have been reported for cation exchange membranes (CEMs). Such nonphysical results call into question our ability to correctly measure this crucial membrane property. Because weighing errors, temperature, and measurement uncertainty have been shown to not explain these anomalous permselectivity results, we hypothesized that a possible explanation are junction potentials that occur at the tips of reference electrodes. In this work, we tested this hypothesis by comparing permselectivity values obtained from bare Ag/AgCl wire electrodes (which have no junction) to values obtained from single-junction reference electrodes containing two different electrolytes. We show that permselectivity values obtained using reference electrodes with junctions were greater than unity for CEMs. In contrast, electrodes without junctions always produced permselectivities lower than unity. Electrodes with junctions also resulted in artificially low permselectivity values for AEMs compared to electrodes without junctions. Thus, we conclude that junctions in reference electrodes introduce two biases into results in the IEM literature: (i) permselectivity values larger than unity for CEMs and (ii) lower permselectivity values for AEMs compared to those for CEMs. These biases can be avoided by using electrodes without a junction.

  20. On simulation of local fluxes in molecular junctions

    Science.gov (United States)

    Cabra, Gabriel; Jensen, Anders; Galperin, Michael

    2018-05-01

    We present a pedagogical review of the current density simulation in molecular junction models indicating its advantages and deficiencies in analysis of local junction transport characteristics. In particular, we argue that current density is a universal tool which provides more information than traditionally simulated bond currents, especially when discussing inelastic processes. However, current density simulations are sensitive to the choice of basis and electronic structure method. We note that while discussing the local current conservation in junctions, one has to account for the source term caused by the open character of the system and intra-molecular interactions. Our considerations are illustrated with numerical simulations of a benzenedithiol molecular junction.

  1. Shunted-Josephson-junction model. I. The autonomous case

    DEFF Research Database (Denmark)

    Belykh, V. N.; Pedersen, Niels Falsig; Sørensen, O. H.

    1977-01-01

    The shunted-Josephson-junction model: the parallel combination of a capacitance, a phase-dependent conductance, and an ideal junction element biased by a constant current, is discussed for arbitrary values of the junction parameters. The main objective is to provide a qualitative understanding...... current-voltage curves are presented. The case with a time-dependent monochromatic bias current is treated in a similar fashion in the companion paper....

  2. Joint diseases: from connexins to gap junctions.

    Science.gov (United States)

    Donahue, Henry J; Qu, Roy W; Genetos, Damian C

    2017-12-19

    Connexons form the basis of hemichannels and gap junctions. They are composed of six tetraspan proteins called connexins. Connexons can function as individual hemichannels, releasing cytosolic factors (such as ATP) into the pericellular environment. Alternatively, two hemichannel connexons from neighbouring cells can come together to form gap junctions, membrane-spanning channels that facilitate cell-cell communication by enabling signalling molecules of approximately 1 kDa to pass from one cell to an adjacent cell. Connexins are expressed in joint tissues including bone, cartilage, skeletal muscle and the synovium. Indicative of their importance as gap junction components, connexins are also known as gap junction proteins, but individual connexin proteins are gaining recognition for their channel-independent roles, which include scaffolding and signalling functions. Considerable evidence indicates that connexons contribute to the function of bone and muscle, but less is known about the function of connexons in other joint tissues. However, the implication that connexins and gap junctional channels might be involved in joint disease, including age-related bone loss, osteoarthritis and rheumatoid arthritis, emphasizes the need for further research into these areas and highlights the therapeutic potential of connexins.

  3. Electrochemically assisted mechanically controllable break junction studies on the stacking configurations of oligo(phenylene ethynylene)s molecular junctions

    International Nuclear Information System (INIS)

    Zheng, Jue-Ting; Yan, Run-Wen; Tian, Jing-Hua; Liu, Jun-Yang; Pei, Lin-Qi; Wu, De-Yin; Dai, Ke; Yang, Yang; Jin, Shan

    2016-01-01

    Highlights: • I-V characteristics of a series of oligo(phenylene ethynylene)s molecular junctions were measured. • Conductance values were found to be dependent on molecular length and substituent group. • The measured low conductance values were explained by theoretical calculations. • EC-MCBJ is feasible to fabricate and characterize molecular junctions. - Abstract: We demonstrate an electrochemically assisted mechanically controllable break junction (EC-MCBJ) approach for current-voltage characteristic (I-V curve) measurements of metal/molecule/metal junctions. A series of oligo(phenylene ethynylene)s compounds (OPEs), including those involving electron withdrawing substituent group and different backbone lengths, had been successfully designed, synthesized, and placed onto the fabricated nanogap to form molecular junctions. The observed evolution in the measured conductances of OPEs indicates that there is a dependence of conductance on molecular length and substituent group. Compared with those extracted from conductance histogram construction, the conductances of OPEs measured from I-V curves are considerably lower. Based on the transmission spectra of OPEs that calculated by density functional theory (DFT) combined with non-equilibrium Green’s function (NEGF) method, this difference was attributed to our distinct experimental operation, which may give rise to a stacking configuration of two OPE molecules.

  4. LDA+U and tight-binding electronic structure of InN nanowires

    Science.gov (United States)

    Molina-Sánchez, A.; García-Cristóbal, A.; Cantarero, A.; Terentjevs, A.; Cicero, G.

    2010-10-01

    In this paper we employ a combined ab initio and tight-binding approach to obtain the electronic and optical properties of hydrogenated Indium nitride (InN) nanowires. We first discuss InN band structure for the wurtzite structure calculated at the LDA+U level and use this information to extract the parameters needed for an empirical tight-binging implementation. These parameters are then employed to calculate the electronic and optical properties of InN nanowires in a diameter range that would not be affordable by ab initio techniques. The reliability of the large nanowires results is assessed by explicitly comparing the electronic structure of a small diameter wire studied both at LDA+U and tight-binding level.

  5. ALTERNATIVE MATERIALS FOR RAMP-EDGE SNS JUNCTIONS

    International Nuclear Information System (INIS)

    Jia, Q.; Fan, Y.; Gim, Y.

    1999-01-01

    We report on the processing optimization and fabrication of ramp-edge high-temperature superconducting junctions by using alternative materials for both superconductor electrodes and normal-metal barrier. By using Ag-doped YBa 2 Cu 3 O 7-x (Ag:YBCO) as electrodes and a cation-modified compound of (Pr y Gd 0.6-y )Ca 0.4 Ba 1.6 La 0.4 Cu 3 O 7 (y = 0.4, 0.5, and 0.6) as a normal-metal barrier, high-temperature superconducting Josephson junctions have been fabricated in a ramp-edge superconductor/normal-metal/superconductor (SNS) configuration. By using Ag:YBCO as electrodes, we have found that the processing controllability /reproducibility and the stability of the SNS junctions are improved substantially. The junctions fabricated with these alternative materials show well-defined RSJ-like current vs voltage characteristics at liquid nitrogen temperature

  6. Electron-beam damaged high-temperature superconductor Josephson junctions

    International Nuclear Information System (INIS)

    Pauza, A.J.; Booij, W.E.; Herrmann, K.; Moore, D.F.; Blamire, M.G.; Rudman, D.A.; Vale, L.R.

    1997-01-01

    Results are presented on the fabrication and characterization of high critical temperature Josephson junctions in thin films of YBa 2 Cu 3 O 7-δ produced by the process of focused electron-beam irradiation using 350 keV electrons. The junctions so produced have uniform spatial current densities, can be described in terms of the resistive shunted junction model, and their current densities can be tailored for a given operating temperature. The physical properties of the damaged barrier can be described as a superconducting material of either reduced or zero critical temperature (T c ), which has a length of ∼15nm. The T c reduction is caused primarily by oxygen Frenkel defects in the Cu - O planes. The large beam currents used in the fabrication of the junctions mean that the extent of the barrier is limited by the incident electron-beam diameter, rather than by scattering within the film. The properties of the barrier can be calculated using a superconductor/normal/superconductor (SNS) junction model with no boundary resistance. From the SNS model, we can predict the scaling of the critical current resistance (I c R n ) product and gain insight into the factors controlling the junction properties, T c , and reproducibility. From the measured I c R n scaling data, we can predict the I c R n product of a junction at a given operating temperature with a given current density. I c R n products of ∼2mV can be achieved at 4.2 K. The reproducibility of several junctions in a number of samples can be characterized by the ratio of the maximum-to-minimum critical currents on the same substrate of less than 1.4. Stability over several months has been demonstrated at room and refrigerator temperatures (297 and 281 K) for junctions that have been initially over damaged and then annealed at temperatures ∼380K. (Abstract Truncated)

  7. Active stretching for lower extremity muscle tightness in pediatric patients with lumbar spondylolysis.

    Science.gov (United States)

    Sato, Masahiro; Mase, Yasuyoshi; Sairyo, Koichi

    2017-01-01

    It was reported that hamstring muscle tightness may increase mechanical loading on the lumbar spine. Therefore, we attempt to decrease tightness in the leg muscles in pediatric patients. Forty-six pediatric patients with spondylolysis underwent rehabilitation. We applied active stretching to the hamstrings, quadriceps, and triceps surae. Tightness in each muscle was graded as good, fair, or poor. We educated each patient on how to perform active stretching at home. They were re-evaluated for muscle tightness 2 months later. Tightness at baseline and after 2 months was as follows: for the hamstrings, good in 3 patients, fair in 9, and poor in 34 and significant improved after 2 months (p<0.05), with improvement by least 1 grade seen in 86% of patients with fair or poor at baseline; for the quadriceps, 7, 3, and 30 patients had good, fair and poor, with significant improvements in 72% (p<0.05). For the triceps surae, 6, 3 and 10 patients had good, fair and poor, which improved significantly (p<0.05). Home-based active stretching was effective for relieving muscle tightness in the leg in a pediatric population. Adolescent athletes should perform such exercise to maintain flexibility and prevent lumbar disorders. J. Med. Invest. 64: 136-139, February, 2017.

  8. Performance Improvement of Receivers Based on Ultra-Tight Integration in GNSS-Challenged Environments

    Directory of Open Access Journals (Sweden)

    Feng Qin

    2013-12-01

    Full Text Available Ultra-tight integration was first proposed by Abbott in 2003 with the purpose of integrating a global navigation satellite system (GNSS and an inertial navigation system (INS. This technology can improve the tracking performances of a receiver by reconfiguring the tracking loops in GNSS-challenged environments. In this paper, the models of all error sources known to date in the phase lock loops (PLLs of a standard receiver and an ultra-tightly integrated GNSS/INS receiver are built, respectively. Based on these models, the tracking performances of the two receivers are compared to verify the improvement due to the ultra-tight integration. Meanwhile, the PLL error distributions of the two receivers are also depicted to analyze the error changes of the tracking loops. These results show that the tracking error is significantly reduced in the ultra-tightly integrated GNSS/INS receiver since the receiver’s dynamics are estimated and compensated by an INS. Moreover, the mathematical relationship between the tracking performances of the ultra-tightly integrated GNSS/INS receiver and the quality of the selected inertial measurement unit (IMU is derived from the error models and proved by the error comparisons of four ultra-tightly integrated GNSS/INS receivers aided by different grade IMUs.

  9. 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...... may explain the experimentally measured linewidth broadening of Josephson oscillations at mm and submm wave frequencies in high-Tc superconducting junctions. Experimental results are discussed in terms of bound states existing at surfaces of d-wave superconducting electrodes....

  10. Cdt1 revisited: complex and tight regulation during the cell cycle and consequences of deregulation in mammalian cells

    Directory of Open Access Journals (Sweden)

    Fujita Masatoshi

    2006-10-01

    Full Text Available Abstract In eukaryotic cells, replication of genomic DNA initiates from multiple replication origins distributed on multiple chromosomes. To ensure that each origin is activated precisely only once during each S phase, a system has evolved which features periodic assembly and disassembly of essential pre-replication complexes (pre-RCs at replication origins. The pre-RC assembly reaction involves the loading of a presumptive replicative helicase, the MCM2-7 complexes, onto chromatin by the origin recognition complex (ORC and two essential factors, CDC6 and Cdt1. The eukaryotic cell cycle is driven by the periodic activation and inactivation of cyclin-dependent kinases (Cdks and assembly of pre-RCs can only occur during the low Cdk activity period from late mitosis through G1 phase, with inappropriate re-assembly suppressed during S, G2, and M phases. It was originally suggested that inhibition of Cdt1 function after S phase in vertebrate cells is due to geminin binding and that Cdt1 hyperfunction resulting from Cdt1-geminin imbalance induces re-replication. However, recent progress has revealed that Cdt1 activity is more strictly regulated by two other mechanisms in addition to geminin: (1 functional and SCFSkp2-mediated proteolytic regulation through phosphorylation by Cdks; and (2 replication-coupled proteolysis mediated by the Cullin4-DDB1Cdt2 ubiquitin ligase and PCNA, an eukaryotic sliding clamp stimulating replicative DNA polymerases. The tight regulation implies that Cdt1 control is especially critical for the regulation of DNA replication in mammalian cells. Indeed, Cdt1 overexpression evokes chromosomal damage even without re-replication. Furthermore, deregulated Cdt1 induces chromosomal instability in normal human cells. Since Cdt1 is overexpressed in cancer cells, this could be a new molecular mechanism leading to carcinogenesis. In this review, recent insights into Cdt1 function and regulation in mammalian cells are discussed.

  11. Affordance-based individuation of junctions in Open Street Map

    Directory of Open Access Journals (Sweden)

    Simon Scheider

    2012-06-01

    Full Text Available We propose an algorithm that can be used to identify automatically the subset of street segments of a road network map that corresponds to a junction. The main idea is to use turn-compliant locomotion affordances, i.e., restricted patterns of supported movement, in order to specify junctions independently of their data representation, and in order to motivate tractable individuation and classification strategies. We argue that common approaches based solely on geometry or topology of the street segment graph are useful but insufficient proxies. They miss certain turn restrictions essential to junctions. From a computational viewpoint, the main challenge of affordance-based individuation of junctions lies in its complex recursive definition. In this paper, we show how Open Street Map data can be interpreted into locomotion affordances, and how the recursive junction definition can be translated into a deterministic algorithm. We evaluate this algorithm by applying it to small map excerpts in order to delineate the contained junctions.

  12. STIM proteins and the endoplasmic reticulum-plasma membrane junctions.

    Science.gov (United States)

    Carrasco, Silvia; Meyer, Tobias

    2011-01-01

    Eukaryotic organelles can interact with each other through stable junctions where the two membranes are kept in close apposition. The junction that connects the endoplasmic reticulum to the plasma membrane (ER-PM junction) is unique in providing a direct communication link between the ER and the PM. In a recently discovered signaling process, STIM (stromal-interacting molecule) proteins sense a drop in ER Ca(2+) levels and directly activate Orai PM Ca(2+) channels across the junction space. In an inverse process, a voltage-gated PM Ca(2+) channel can directly open ER ryanodine-receptor Ca(2+) channels in striated-muscle cells. Although ER-PM junctions were first described 50 years ago, their broad importance in Ca(2+) signaling, as well as in the regulation of cholesterol and phosphatidylinositol lipid transfer, has only recently been realized. Here, we discuss research from different fields to provide a broad perspective on the structures and unique roles of ER-PM junctions in controlling signaling and metabolic processes.

  13. Morphological variation of the kidney secondary to junctional parenchyma on ultrasound

    International Nuclear Information System (INIS)

    Lee, Ji Yoon; Park, Byeong Ho; Nam, Kyeong Jin; Choi, Jong Cheol; Koo, Bong Sig; Kim, Jou Yeoun; Ahn, Seung Eon; Lee, Yung Il

    1996-01-01

    To evaluate the prevalance of morphological variation of the kidney secondary to junctional parenchyma, as well as to analyze the ultrasonographic features of junctional parenchyma. Two hundred and eighty two kidneys of 141 patient without clinical or radiologic evidence of renal disease were prospectively analysed using ultrasound. In all patients, ultrasonograms were obtained in sagittal, coronal and transaxial planes. The kidney was considered to have morphological variation if the ultrasonogram demonstrated junctional parenchymal defect of line ; those showing such variation were classified as one of three types : continuous, discontinuous, or junctional parenchymal line or defect without junctional parenchyma. The prevalance and ultrasonographic features of the kidneys were evaluated. Morphological variation was noted in 71 cases(25%). the continuous type accounted for 54% of these, the discontinuous type for 38%, and junctional parenchymal defect or line without junctional parenchyma for 8%. In all cases, junctional parenchyma was located approximately at the junction of the upper and middle third of the kidney, and had the same echogenecity as the renal cortex. An understanding of the morphological variation of the kidney resulting from junctional renal parenchyma would be helpful in differentiating pseudotumor from true renal neoplasm

  14. Production of Natural Gas and Fluid Flow in Tight Sand Reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Maria Cecilia Bravo

    2006-06-30

    This document reports progress of this research effort in identifying relationships and defining dependencies between macroscopic reservoir parameters strongly affected by microscopic flow dynamics and production well performance in tight gas sand reservoirs. These dependencies are investigated by identifying the main transport mechanisms at the pore scale that should affect fluids flow at the reservoir scale. A critical review of commercial reservoir simulators, used to predict tight sand gas reservoir, revealed that many are poor when used to model fluid flow through tight reservoirs. Conventional simulators ignore altogether or model incorrectly certain phenomena such as, Knudsen diffusion, electro-kinetic effects, ordinary diffusion mechanisms and water vaporization. We studied the effect of Knudsen's number in Klinkenberg's equation and evaluated the effect of different flow regimes on Klinkenberg's parameter b. We developed a model capable of explaining the pressure dependence of this parameter that has been experimentally observed, but not explained in the conventional formalisms. We demonstrated the relevance of this, so far ignored effect, in tight sands reservoir modeling. A 2-D numerical simulator based on equations that capture the above mentioned phenomena was developed. Dynamic implications of new equations are comprehensively discussed in our work and their relative contribution to the flow rate is evaluated. We performed several simulation sensitivity studies that evidenced that, in general terms, our formalism should be implemented in order to get more reliable tight sands gas reservoirs' predictions.

  15. Visualizing supercurrents in 0-{pi} ferromagnetic Josephson tunnel junctions

    Energy Technology Data Exchange (ETDEWEB)

    Goldobin, Edward; Guerlich, Christian; Gaber, Tobias; Koelle, Dieter; Kleiner, Reinhold [Physikalisches Institut and Center for Collective Quantum Phenomena, Universitaet Tuebingen (Germany); Weides, Martin; Kohlstedt, Hermann [Institute of Solid State Physics, Reserch Center Juelich (Germany)

    2009-07-01

    So-called 0 and {pi} Josephson junctions can be treated as having positive and negative critical currents. This implies that the same phase shift applied to a Josephson junction causes counterflow of supercurrents in 0 and in {pi} junctions connected in parallel provided they are short in comparison with Josephson penetration depth {lambda}{sub J}. We have fabricated several 0, {pi}, 0-{pi}, 0-{pi}-0 and 20 x (0-{pi}-) planar superconductor-insulator-ferromagnet-superconductor Josephson junctions and studied the spatial supercurrent density distribution j{sub s}(x,y) across the junction area using low temperature scanning electron microscopy. At zero magnetic field we clearly see counterflow of the supercurrents in 0 and {pi} regions. The picture also changes consistently in the applied magnetic field.

  16. Fabrication of magnetic tunnel junctions with epitaxial and textured ferromagnetic layers

    Science.gov (United States)

    Chang, Y. Austin; Yang, Jianhua Joshua

    2008-11-11

    This invention relates to magnetic tunnel junctions and methods for making the magnetic tunnel junctions. The magnetic tunnel junctions include a tunnel barrier oxide layer sandwiched between two ferromagnetic layers both of which are epitaxial or textured with respect to the underlying substrate upon which the magnetic tunnel junctions are grown. The magnetic tunnel junctions provide improved magnetic properties, sharper interfaces and few defects.

  17. Spin, Vibrations and Radiation in Superconducting Junctions

    NARCIS (Netherlands)

    Padurariu, C.

    2013-01-01

    This thesis presents the theoretical study of superconducting transport in several devices based on superconducting junctions. The important feature of these devices is that the transport properties of the junction are modified by the interaction with another physical system integrated in the

  18. Contraption and Prediction of Exhalation Tight Brownstone in Exhalation Cistern

    OpenAIRE

    XhingZhiwang, -; Xuchao, -

    2012-01-01

    The reservoir connate water saturation is high and gas wells generally produce water which seriously affects the productivity of gas wells in Xujiahe tight sandstone gas reservoirs in Sichuan Basin. Take the sixth formation for example, there are 39 wells producing water unequally in the 42 commissioning wells, and the excessive water production leads to the production of the gas well declining rapidly. Studying of the mechanism of water production in tight sandstone gas reservoirs and predic...

  19. Study on water leak-tightness of small leaks on a 1 inch cylinder valve

    International Nuclear Information System (INIS)

    Miyazawa, T.; Kasai, Y.; Inabe, N.; Aritomi, M.

    2002-01-01

    Practical thresholds for water leak-tightness of small leaks were determined by experimentation. Measurements for small leak samples were taken of air leakage rates and water leakage rates for identical leak samples in order to identify parameters that influence water leak-tightness threshold. Four types of leaks were evaluated: a fine wire inserted in an O-ring seal, a glass capillary tube, a stainless steel orifice, and a scratched valve stem on a 1 inch UF 6 cylinder valve. Experimental results demonstrated that the key parameter for water leak-tightness is the opening size of the leak hole. The maximum allowable hole size to achieve water leak-tightness ranged from 10 to 20 μm in diameter in this study. Experimental results with 1 inch UF 6 cylinder valve samples demonstrated that the acceptance criteria for preshipment leakage test, 1x10 -3 ref-cm 3 .s -1 , as prescribed in ANSI N14.5 is an appropriate value from the point of view of water leak-tightness for enriched UF 6 packages. The mechanism of water leak-tightness is plugging by tiny particles existing in water. The water used in experiments in this study contained far fewer particles than in water assumed to be encountered under accident conditions of transport. Therefore, the water leak-tightness threshold determined in this study is a conservative value in a practical evaluation. (author)

  20. Tricellulin, occludin and claudin-3 expression in salmon intestine and kidney during salinity adaptation

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Madsen, Steffen

    2012-01-01

    Molecular regulation of tight junctions in osmoregulatory epithelia of euryhaline fishes must be extensive during ontogeny and acclimation to salinity changes. In this study, five tight junction proteins were examined in Atlantic salmon (Salmo salar): tight junction associated tricellulin, occludin...... and claudin-3 isoforms (a, b, c). A survey of tissue distribution in freshwater (FW) salmon showed that tricellulin expression was highest in the intestine. Occludin was detected in tissues with importance for epithelial transport and the order of expression was gill>intestine>kidney. The three claudin-3...... isoforms were expressed at highest level in kidney tissue. Transfer of juvenile FW salmon to seawater (SW) elevated intestinal tricellulin and occludin mRNA, and these transcripts were also elevated at the time of best SW-tolerance during the course of smoltification. In the kidney, expression...