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Sample records for controls gap junction

  1. 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

  2. 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....

  3. Long-range gap junctional signaling controls oncogene-mediated tumorigenesis in Xenopus laevis embryos

    Directory of Open Access Journals (Sweden)

    Brook T Chernet

    2015-01-01

    Full Text Available In addition to the immediate microenvironment, long-range signaling may be an important component of cancer. Molecular-genetic analyses have implicated gap junctions – key mediators of cell-cell communication – in carcinogenesis. We recently showed that the resting voltage potential of distant cell groups is a key determinant of metastatic transformation and tumor induction. Here, we show in the Xenopus laevis model that gap junctional communication (GJC is a modulator of the long-range bioelectric signaling that regulates tumor formation. Genetic disruption of GJC taking place within tumors, within remote host tissues, or between the host and tumors – significantly lowers the incidence of tumors induced by KRAS mutations. The most pronounced suppression of tumor incidence was observed upon GJC disruption taking place farther away from oncogene-expressing cells, revealing a role for GJC in distant cells in the control of tumor growth. In contrast, enhanced GJC communication through the overexpression of wild-type connexin Cx26 increased tumor incidence. Our data confirm a role for GJC in tumorigenesis, and reveal that this effect is non-local. Based on these results and on published data on movement of ions through GJs, we present a quantitative model linking the GJC coupling and bioelectrical state of cells to the ability of oncogenes to initiate tumorigenesis. When integrated with data on endogenous bioelectric signaling during left-right patterning, the model predicts differential tumor incidence outcomes depending on the spatial configurations of gap junction paths relative to tumor location and major anatomical body axes. Testing these predictions, we found that the strongest influence of GJ modulation on tumor suppression by hyperpolarization occurred along the embryonic left-right axis. Together, these data reveal new, long-range aspects of cancer control by the host’s physiological parameters.

  4. 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

  5. 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.

  6. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)

    LIJUAN CHEN

    2017-12-20

    Dec 20, 2017 ... showed a lower dye diffusion distance of Cx46 V44M cells, which indicates that the gap junction intercellular ... permeability could be affected by alterations of charged residues of .... bled into gap junction plaques is not soluble in 1% Triton ..... regulation of connexin 43 expression by high glucose reduces.

  7. Thalamic gap junctions control local neuronal synchrony and influence macroscopic oscillation amplitude during EEG alpha rhythms

    Directory of Open Access Journals (Sweden)

    Stuart eHughes

    2011-08-01

    Full Text Available Although EEG alpha ( (8-13 Hz rhythms are often considered to reflect an ‘idling’ brain state, numerous studies indicate that they are also related to many aspects of perception. Recently, we outlined a potential cellular substrate by which such aspects of perception might be linked to basic  rhythm mechanisms. This scheme relies on a specialized subset of rhythmically bursting thalamocortical (TC neurons (high-threshold bursting cells in the lateral geniculate nucleus (LGN which are interconnected by gap junctions (GJs. By engaging GABAergic interneurons, that in turn inhibit conventional relay-mode TC neurons, these cells can lead to an effective temporal framing of thalamic relay-mode output. Although the role of GJs is pivotal in this scheme, evidence for their involvement in thalamic  rhythms has thus far mainly derived from experiments in in vitro slice preparations. In addition, direct anatomical evidence of neuronal GJs in the LGN is currently lacking. To address the first of these issues we tested the effects of the GJ inhibitors, carbenoxolone (CBX and 18-glycyrrhetinic acid (18-GA, given directly to the LGN via reverse microdialysis, on spontaneous LGN and EEG  rhythms in behaving cats. We also examined the effect of CBX on  rhythm-related LGN unit activity. Indicative of a role for thalamic GJs in these activities, 18-GA and CBX reversibly suppressed both LGN and EEG  rhythms, with CBX also decreasing neuronal synchrony. To address the second point, we used electron microscopy to obtain definitive ultrastructural evidence for the presence of GJs between neurons in the cat LGN. As interneurons show no phenotypic evidence of GJ coupling (i.e. dye-coupling and spikelets we conclude that these GJs must belong to TC neurons. The potential significance of these findings for relating macroscopic changes in  rhythms to basic cellular processes is discussed.

  8. Spinal Gap Junction Channels in Neuropathic Pain

    OpenAIRE

    Jeon, Young Hoon; Youn, Dong Ho

    2015-01-01

    Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced...

  9. GAP junctional communication in brain secondary organizers.

    Science.gov (United States)

    Bosone, Camilla; Andreu, Abraham; Echevarria, Diego

    2016-06-01

    Gap junctions (GJs) are integral membrane proteins that enable the direct cytoplasmic exchange of ions and low molecular weight metabolites between adjacent cells. They are formed by the apposition of two connexons belonging to adjacent cells. Each connexon is formed by six proteins, named connexins (Cxs). Current evidence suggests that gap junctions play an important part in ensuring normal embryo development. Mutations in connexin genes have been linked to a variety of human diseases, although the precise role and the cell biological mechanisms of their action remain almost unknown. Among the big family of Cxs, several are expressed in nervous tissue but just a few are expressed in the anterior neural tube of vertebrates. Many efforts have been made to elucidate the molecular bases of Cxs cell biology and how they influence the morphogenetic signal activity produced by brain signaling centers. These centers, orchestrated by transcription factors and morphogenes determine the axial patterning of the mammalian brain during its specification and regionalization. The present review revisits the findings of GJ composed by Cx43 and Cx36 in neural tube patterning and discuss Cx43 putative enrollment in the control of Fgf8 signal activity coming from the well known secondary organizer, the isthmic organizer. © 2016 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.

  10. 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.

  11. 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...

  12. 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.

  13. Gap junction diseases of the skin.

    NARCIS (Netherlands)

    Steensel, M.A.M. van

    2004-01-01

    Gap junctions are intercellular channels that allow the passage of water, ions, and small molecules. They are involved in quick, short-range messaging between cells and are found in skin, nervous tissue, heart, and muscle. An increasing number of hereditary skin disorders appear to be caused by

  14. Gap junctions-guards of excitability

    DEFF Research Database (Denmark)

    Stroemlund, Line Waring; Jensen, Christa Funch; Qvortrup, Klaus

    2015-01-01

    Cardiomyocytes are connected by mechanical and electrical junctions located at the intercalated discs (IDs). Although these structures have long been known, it is becoming increasingly clear that their components interact. This review describes the involvement of the ID in electrical disturbances...... of the heart and focuses on the role of the gap junctional protein connexin 43 (Cx43). Current evidence shows that Cx43 plays a crucial role in organizing microtubules at the intercalated disc and thereby regulating the trafficking of the cardiac sodium channel NaV1.5 to the membrane....

  15. Structure modeling and mutational analysis of gap junction beta 2 ...

    African Journals Online (AJOL)

    Yomi

    2012-04-03

    Apr 3, 2012 ... Three dimensional (3 D) structure is very useful for understanding biological functions. Gap junction beta 2 (GJB2), human gene encoding for gap junction beta 2 protein is involved in ... Research in deafness became real.

  16. Gap junction modulation by extracellular signaling molecules: the thymus model

    Directory of Open Access Journals (Sweden)

    Alves L.A.

    2000-01-01

    Full Text Available Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

  17. Terbinafine inhibits gap junctional intercellular communication

    International Nuclear Information System (INIS)

    Lee, Ju Yeun; Yoon, Sei Mee; Choi, Eun Ju; Lee, Jinu

    2016-01-01

    Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca 2+ concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca 2+ concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

  18. Terbinafine inhibits gap junctional intercellular communication

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju Yeun, E-mail: whitewndus@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Yoon, Sei Mee, E-mail: sei_mee@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Department of Integrated OMICS for Biomedical Sciences, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Choi, Eun Ju, E-mail: yureas@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Lee, Jinu, E-mail: jinulee@yonsei.ac.kr [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of)

    2016-09-15

    Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca{sup 2+} concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca{sup 2+} concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

  19. Gap Junctional Intercellular Communication and Breast Cancer Metastasis to Bone

    National Research Council Canada - National Science Library

    Donahue, Henry

    2001-01-01

    .... We found that: 1) expressing the metastasis suppressing gene BRMS1 in diverse cancer cell lines, including breast and melanoma, restores homotypic gap junctional intercellular communication (GJIC); 2...

  20. Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels

    NARCIS (Netherlands)

    Wilders, R.; Jongsma, H. J.

    1992-01-01

    The electrical properties of gap junctions in cell pairs are usually studied by means of the dual voltage clamp method. The voltage across the junctional channels, however, cannot be controlled adequately due to an artificial resistance and a natural resistance, both connected in series with the gap

  1. Terbinafine inhibits gap junctional intercellular communication.

    Science.gov (United States)

    Lee, Ju Yeun; Yoon, Sei Mee; Choi, Eun Ju; Lee, Jinu

    2016-09-15

    Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca(2+) concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Inhibition of hepatocyte gap junctional intercellular communication by tumor promoters

    International Nuclear Information System (INIS)

    Ruch, R.J.

    1988-01-01

    The mechanisms by which tumor promoters enhance neoplasia are poorly understood. One effect common to most tumor promoters is their ability to inhibit the cell-to-cell exchange of small molecules and ions through gap junctions, i.e., gap junctional intercellular communication (IC). IC maybe necessary for normal growth control and the loss of IC may predispose cells to enhanced growth. In the present studies, the effects of liver tumor promoters and other agents on IC between rodent hepatocytes in primary culture has been studied. IC was detected between hepatocytes: (1) autoradiographically following the passage and incorporation of [5- 3 H]uridine nucleotides from pre-labeled donor hepatocytes to non-labeled, adjacent recipient hepatocytes and (2) by fluorescence microscopy after microinjection of fluorescent Lucifer Yellow CH dye into hepatocytes and visualizing dye spread into adjacent hepatocytes

  3. Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels

    OpenAIRE

    Wilders, R.; Jongsma, H.J.

    1992-01-01

    The electrical properties of gap junctions in cell pairs are usually studied by means of the dual voltage clamp method. The voltage across the junctional channels, however, cannot be controlled adequately due to an artificial resistance and a natural resistance, both connected in series with the gap junction. The access resistances to the cell interior of the recording pipettes make up the artificial resistance. The natural resistance consists of the cytoplasmic access resistances to the tigh...

  4. Gap Junctions and Cancer: Communicating for 50 Years’

    Science.gov (United States)

    Aasen, Trond; Mesnil, Marc; Naus, Christian C.; Lampe, Paul D.; Laird, Dale W.

    2017-01-01

    Fifty years ago, tumour cells were found to lack electrical coupling, leading to the hypothesis that loss of direct intercellular communication is commonly associated with cancer onset and progression. Subsequent studies linked this phenomenon to gap junctions composed of connexin proteins. While many studies support the notion that connexins are tumour suppressors, recent evidence suggests that, in some tumour types, they may facilitate specific stages of tumour progression through both junctional and non-junctional signalling pathways. This Timeline article highlights the milestones connecting gap junctions to cancer, and underscores important unanswered questions, controversies and therapeutic opportunities in the field. PMID:27782134

  5. Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

    Science.gov (United States)

    Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

    2004-01-01

    Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

  6. Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Jose L Serrano-Velez

    2014-06-01

    Full Text Available Dye-coupling, whole-mount immunohistochemistry for gap junction channel protein connexin 35 (Cx35, and freeze-fracture replica immunogold labeling (FRIL reveal an abundance of electrical synapses/gap junctions at glutamatergic mixed synapses in the 14th spinal segment that innervates the adult male gonopodium of Western Mosquitofish, Gambusia affinis (Mosquitofish.To study gap junctions’ role in fast motor behavior, we used a minimally-invasive neural-tract-tracing technique to introduce gap junction-permeant or -impermeant dyes into deep muscles controlling the gonopodium of the adult male Mosquitofish, a teleost fish that rapidly transfers (complete in 50 of the 62 gap junctions at mixed synapses are in the 14th spinal segment.Our results support and extend studies showing gap junctions at mixed synapses in spinal cord segments involved in control of genital reflexes in rodents, and they suggest a link between mixed synapses and fast motor behavior. The findings provide a basis for studies of specific roles of spinal neurons in the generation/regulation of sex-specific behavior and for studies of gap junctions’ role in regulating fast motor behavior. Finally, the CoPA IN provides a novel candidate neuron for future studies of gap junctions and neural control of fast motor behaviors.

  7. Gap junction protein connexin-43 interacts directly with microtubules

    NARCIS (Netherlands)

    Giepmans, B N; Verlaan, I; Hengeveld, T; Janssen, H; Calafat, J; Falk, M M; Moolenaar, W H

    2001-01-01

    Gap junctions are specialized cell-cell junctions that mediate intercellular communication. They are composed of connexin proteins, which form transmembrane channels for small molecules [1, 2]. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated

  8. [Inhibition of gap junctional intercellular communication protects astrocytes from hypoxia/reoxygenation injury].

    Science.gov (United States)

    Tong, Xu-Hui; Gu, Yu-Chen; Jiao, Hao; Yu, Li; Dong, Shu-Ying

    2015-01-01

    To investigate the effects of inhibiting gap junctional intercellular communication on hypoxia/reoxygenation injury in astrocytes. Primary cultured cerebral cortical astrocytes of neonate rats were divided into normal control group, hypoxia reoxygenation injury group and 18-α-glycyrrhetinic acid and oleamide (gap junctional intercellular channel inhibitors) group. The gap junction intercellular communication was determined by Parachute assay. The viability of astrocyes was detected by MTT assay. The apoptosis of astrocytes were detected with annexin V/PI and Hoechst 33258 staining. Compared with the normal control group, the gap junctional function of astrocytes was increased significantly in ischemia/reperfusion group (Pastrocytes decreased significantly (Pastrocytes in18-α-glycyrrhetinic acid and oleamide group decreased significantly (Pastrocytes increased significantly (Pastrocytes.

  9. Roles of gap junctions, connexins and pannexins in epilepsy

    Directory of Open Access Journals (Sweden)

    Shanthini eMylvaganam

    2014-05-01

    Full Text Available Enhanced gap junctional communication (GJC between neurons is considered a major factor underlying the neuronal synchrony driving seizure activity. In addition, the hippocampal sharp wave ripple complexes, associated with learning and seizures, are diminished by GJC blocking agents. Although gap junctional blocking drugs inhibit experimental seizures, they all have other nonspecific actions. Besides interneuronal GJC between dendrites, inter-axonal and inter-glial GJC is also considered important for seizure generation. Interestingly, in most studies of cerebral tissue from animal seizure models and from human patients with epilepsy, there is up-regulation of glial, but not neuronal gap junctional mRNA and protein. Significant changes in the expression and post-translational modification of the astrocytic connexin Cx43, and Panx1 were observed in an in vitro Co++ seizure model, further supporting a role for glia in seizure-genesis, although the reasons for this remain unclear. Further suggesting an involvement of astrocytic GJC in epilepsy, is the fact that the expression of astrocytic Cx mRNAs (Cxs 30 and 43 is several fold higher than that of neuronal Cx mRNAs (Cxs 36 and 45, and the number of glial cells outnumber neuronal cells in mammalian hippocampal and cortical tissue. Pannexin expression is also increased in both animal and human epileptic tissues. Specific Cx43 mimetic peptides, Gap 27 and SLS, inhibit the docking of astrocytic connexin Cx43 proteins from forming intercellular gap junctions, diminishing spontaneous seizures. Besides GJs, Cx membrane hemichannels in glia and Panx membrane channels in neurons and glia are also inhibited by gap junctional pharmacological blockers. Although there is no doubt that connexin-based gap junctions and hemichannels, and pannexin-based membrane channels are related to epilepsy, the specific details of how they are involved and how we can modulate their function for therapeutic purposes remain to

  10. A PC microsimulation of a gap acceptance model for turning left at a T-junction

    NARCIS (Netherlands)

    Schaap, Nina; Dijck, T.; van Arem, Bart; Morsink, Peter L.J.

    2009-01-01

    Vehicles are controlled by sub-behavioral models in a microsimulation model, this includes the gap acceptance model where the decision about how to cross a junction is made. The critical gap in these models must serve as a threshold value to accept or reject the space between two successive vehicles

  11. Observation of gap inhomogeneity in superconducting aluminum tunnel junctions

    International Nuclear Information System (INIS)

    Gilmartin, H.R.

    1982-01-01

    Experiments using a novel technique to investigate spatial variations in the superconducting gap parameter of aluminum films driven out of equilibrium by intense tunnel injection are described. The technique features fine spatial and energy resolution of the gap parameter. The experiments employed a finely focused laser spot scanned across the surface of a double tunnel junction sandwich to produce a very weak electrical signal that was analyzed to determine the gap parameter as a function of position in the plane of the device. Technical aspects of the problem are emphasized, since a new technique is presented. An elaborate explanation of the origin and analysis of the laser induced signal is given, as well as a detailed description of the experimental apparatus. Very briefly, the principle of operation is that a large flux of quasiparticles is injected through the lower junction of the sandwich into the middle aluminum film, and the upper junction serves to detect the effects of that injection. The middle film takes on two or more values of the gap parameter under injection, presumably indicating spatial variation. The presence of a small laser spot on a given point on the device perturbs the potential on the detector junction very slightly. That perturbation is measured as a function of bias current to determine the gap parameter of the middle film at that point. The spot is scanned in a raster pattern to produce a picture of the space dependence of the gap parameter

  12. Hyperglycaemia and diabetes impair gap junctional communication among astrocytes.

    Science.gov (United States)

    Gandhi, Gautam K; Ball, Kelly K; Cruz, Nancy F; Dienel, Gerald A

    2010-03-15

    Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15-25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin)-treated rats at 20-24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin) 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs.

  13. Gap Junctions Contribute to Ictal/Interictal Genesis in Human Hypothalamic Hamartomas

    Directory of Open Access Journals (Sweden)

    Jie Wu

    2016-06-01

    Full Text Available Human hypothalamic hamartoma (HH is a rare subcortical lesion associated with treatment-resistant epilepsy. Cellular mechanisms responsible for epileptogenesis are unknown. We hypothesized that neuronal gap junctions contribute to epileptogenesis through synchronous activity within the neuron networks in HH tissue. We studied surgically resected HH tissue with Western-blot analysis, immunohistochemistry, electron microscopy, biocytin microinjection of recorded HH neurons, and microelectrode patch clamp recordings with and without pharmacological blockade of gap junctions. Normal human hypothalamus tissue was used as a control. Western blots showed increased expression of both connexin-36 (Cx36 and connexin-43 (Cx43 in HH tissue compared with normal human mammillary body tissue. Immunohistochemistry demonstrated that Cx36 and Cx43 are expressed in HH tissue, but Cx36 was mainly expressed within neuron clusters while Cx43 was mainly expressed outside of neuron clusters. Gap-junction profiles were observed between small HH neurons with electron microscopy. Biocytin injection into single recorded small HH neurons showed labeling of adjacent neurons, which was not observed in the presence of a neuronal gap-junction blocker, mefloquine. Microelectrode field recordings from freshly resected HH slices demonstrated spontaneous ictal/interictal-like discharges in most slices. Bath-application of gap-junction blockers significantly reduced ictal/interictal-like discharges in a concentration-dependent manner, while not affecting the action-potential firing of small gamma-aminobutyric acid (GABA neurons observed with whole-cell patch-clamp recordings from the same patient's HH tissue. These results suggest that neuronal gap junctions between small GABAergic HH neurons participate in the genesis of epileptic-like discharges. Blockade of gap junctions may be a new therapeutic strategy for controlling seizure activity in HH patients.

  14. Pallidal gap junctions-triggers of synchrony in Parkinson's disease?

    NARCIS (Netherlands)

    Schwab, B.C.; Heida, T.; Zhao, Y.; Gils, S.A. van; Wezel, R.J.A. van

    2014-01-01

    Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a

  15. Pallidal gap junctions - Triggers of synchrony in Parkinson's disease?

    NARCIS (Netherlands)

    Schwab, B.C.; Heida, Tjitske; Zhao, Yan; van Gils, Stephanus A.; van Wezel, Richard Jack Anton

    2014-01-01

    Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a

  16. [Gap junctions: A new therapeutic target in major depressive disorder?].

    Science.gov (United States)

    Sarrouilhe, D; Dejean, C

    2015-11-01

    Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. The psychostimulant modafinil enhances gap junctional communication in cortical astrocytes.

    Science.gov (United States)

    Liu, Xinhe; Petit, Jean-Marie; Ezan, Pascal; Gyger, Joël; Magistretti, Pierre; Giaume, Christian

    2013-12-01

    Sleep-wake cycle is characterized by changes in neuronal network activity. However, for the last decade there is increasing evidence that neuroglial interaction may play a role in the modulation of sleep homeostasis and that astrocytes have a critical impact in this process. Interestingly, astrocytes are organized into communicating networks based on their high expression of connexins, which are the molecular constituents of gap junction channels. Thus, neuroglial interactions should also be considered as the result of the interplay between neuronal and astroglial networks. Here, we investigate the effect of modafinil, a wakefulness-promoting agent, on astrocyte gap junctional communication. We report that in the cortex modafinil injection increases the expression of mRNA and protein of connexin 30 but not those of connexin 43, the other major astroglial connexin. These increases are correlated with an enhancement of intercellular dye coupling in cortical astrocytes, which is abolished when neuronal activity is silenced by tetrodotoxin. Moreover, gamma-hydroxybutyric acid, which at a millimolar concentration induces sleep, has an opposite effect on astroglial gap junctions in an activity-independent manner. These results support the proposition that astroglia may play an important role in complex physiological brain functions, such as sleep regulation, and that neuroglial networking interaction is modified during sleep-wake cycle. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'. Copyright © 2013. Published by Elsevier Ltd.

  18. Gap junctions and inhibitory synapses modulate inspiratory motoneuron synchronization.

    Science.gov (United States)

    Bou-Flores, C; Berger, A J

    2001-04-01

    Interneuronal electrical coupling via gap junctions and chemical synaptic inhibitory transmission are known to have roles in the generation and synchronization of activity in neuronal networks. Uncertainty exists regarding the roles of these two modes of interneuronal communication in the central respiratory rhythm-generating system. To assess their roles, we performed studies on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity observed had two temporal characteristics: the basic respiratory frequency occurring on a long time scale and the synchronous neuronal discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blockers, including 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid, and carbenoxolone, all caused a reduction in respiratory frequency. In contrast, peak integrated phrenic and hypoglossal inspiratory activity was not significantly changed by gap-junction blockade. On a short-time-scale, gap-junction blockade increased the degree of synchronization within an inspiratory burst observed in both nerves. In contrast, opposite results were observed with blockade of GABA(A) and glycine receptors. We found that respiratory frequency increased with receptor blockade, and simultaneous blockade of both receptors consistently resulted in a reduction in short-time-scale synchronized activity observed in phrenic and hypoglossal inspiratory bursts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of respiratory cycle timing and an inspiratory pattern generator that is involved in short-time-scale synchronization. In the neonatal rodent, properties of both components can be regulated by interneuronal

  19. Intracellular trafficking pathways of Cx43 gap junction channels.

    Science.gov (United States)

    Epifantseva, Irina; Shaw, Robin M

    2018-01-01

    Gap Junction (GJ) channels, including the most common Connexin 43 (Cx43), have fundamental roles in excitable tissues by facilitating rapid transmission of action potentials between adjacent cells. For instance, synchronization during each heartbeat is regulated by these ion channels at the cardiomyocyte cell-cell border. Cx43 protein has a short half-life, and rapid synthesis and timely delivery of those proteins to particular subdomains are crucial for the cellular organization of gap junctions and maintenance of intracellular coupling. Impairment in gap junction trafficking contributes to dangerous complications in diseased hearts such as the arrhythmias of sudden cardiac death. Of recent interest are the protein-protein interactions with the Cx43 carboxy-terminus. These interactions have significant impact on the full length Cx43 lifecycle and also contribute to trafficking of Cx43 as well as possibly other functions. We are learning that many of the known non-canonical roles of Cx43 can be attributed to the recently identified six endogenous Cx43 truncated isoforms which are produced by internal translation. In general, alternative translation is a new leading edge for proteome expansion and therapeutic drug development. This review highlights recent mechanisms identified in the trafficking of gap junction channels, involvement of other proteins contributing to the delivery of channels to the cell-cell border, and understanding of possible roles of the newly discovered alternatively translated isoforms in Cx43 biology. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Gap junctions in cells of the immune system: structure, regulation and possible functional roles

    Directory of Open Access Journals (Sweden)

    J.C. Sáez

    2000-04-01

    Full Text Available Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.

  1. Symposia for a Meeting on Ion Channels and Gap Junctions

    CERN Document Server

    Sáez, Juan

    1997-01-01

    Ion channels allow us to see nature in all its magnificence, to hear a Bach suite, to smell the aroma of grandmother's cooking, and, in this regard, they put us in contact with the external world. These ion channels are protein molecules located in the cell membrane. In complex organisms, cells need to communicate in order to know about their metabolic status and to act in a coordinate manner. The latter is also accomplished by a class of ion channels able to pierce the lipid bilayer membranes of two adjacent cells. These intercellular channels are the functional subunits of gap junctions. Accordingly, the book is divided in two parts: the first part is dedicated to ion channels that look to the external world, and the second part is dedicated to gap junctions found at cell interfaces. This book is based on a series of symposia for a meeting on ion channels and gap junctions held in Santiago, Chile, on November 28-30, 1995. The book should be useful to graduate students taking the first steps in this field as...

  2. Conduction gap in graphene strain junctions: direction dependence

    International Nuclear Information System (INIS)

    Nguyen, M Chung; Nguyen, V Hung; Dollfus, P; Nguyen, Huy-Viet

    2014-01-01

    It has been shown in a recent study (Nguyen et al 2014 Nanotechnology 25 165201) that unstrained/strained graphene junctions are promising candidates to improve the performance of graphene transistors which is usually hindered by the gapless nature of graphene. Although the energy bandgap of strained graphene still remains zero, the shift of Dirac points in the k-space due to strain-induced deformation of graphene lattice can lead to the appearance of a finite conduction gap of several hundred meV in strained junctions with a strain of only a few per cent. However, since it depends essentially on the magnitude of the Dirac point shift, this conduction gap strongly depends on the direction of applied strain and the transport direction. In this work, a systematic study of conduction-gap properties with respect to these quantities is presented and the results are carefully analyzed. Our study provides useful information for further investigations to exploit graphene-strained junctions in electronic applications and strain sensors. (paper)

  3. Gap-junction-mediated communication in human periodontal ligament cells.

    Science.gov (United States)

    Kato, R; Ishihara, Y; Kawanabe, N; Sumiyoshi, K; Yoshikawa, Y; Nakamura, M; Imai, Y; Yanagita, T; Fukushima, H; Kamioka, H; Takano-Yamamoto, T; Yamashiro, T

    2013-07-01

    Periodontal tissue homeostasis depends on a complex cellular network that conveys cell-cell communication. Gap junctions (GJs), one of the intercellular communication systems, are found between adjacent human periodontal ligament (hPDL) cells; however, the functional GJ coupling between hPDL cells has not yet been elucidated. In this study, we investigated functional gap-junction-mediated intercellular communication in isolated primary hPDL cells. SEM images indicated that the cells were in contact with each other via dendritic processes, and also showed high anti-connexin43 (Cx43) immunoreactivity on these processes. Gap-junctional intercellular communication (GJIC) among hPDL cells was assessed by fluorescence recovery after a photobleaching (FRAP) analysis, which exhibited dye coupling between hPDL cells, and was remarkably down-regulated when the cells were treated with a GJ blocker. Additionally, we examined GJs under hypoxic stress. The fluorescence recovery and expression levels of Cx43 decreased time-dependently under the hypoxic condition. Exposure to GJ inhibitor or hypoxia increased RANKL expression, and decreased OPG expression. This study shows that GJIC is responsible for hPDL cells and that its activity is reduced under hypoxia. This is consistent with the possible role of hPDL cells in regulating the biochemical reactions in response to changes in the hypoxic environment.

  4. Homeostatic Plasticity Mediated by Rod-Cone Gap Junction Coupling in Retinal Degenerative Dystrophic RCS Rats

    Science.gov (United States)

    Hou, Baoke; Fu, Yan; Weng, Chuanhuang; Liu, Weiping; Zhao, Congjian; Yin, Zheng Qin

    2017-01-01

    Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods. PMID:28473754

  5. Cut-loading: a useful tool for examining the extent of gap junction tracer coupling between retinal neurons.

    Science.gov (United States)

    Choi, Hee Joo; Ribelayga, Christophe P; Mangel, Stuart C

    2012-01-12

    neurons with small somata in intact neural retinal tissue, but it can be difficult to adequately control the illumination conditions during the electrophysiological study of single retinal neurons to avoid light-induced changes in gap junction conductance. Here, we present a straightforward method of determining the extent of gap junction tracer coupling between retinal neurons under different illumination conditions and at different times of the day and night. This cut-loading technique is a modification of scrape loading(9-12), which is based on dye loading and diffusion through open gap junction channels. Scrape loading works well in cultured cells, but not in thick slices such as intact retinas. The cut-loading technique has been used to study photoreceptor coupling in intact fish and mammalian retinas(7, 8,13), and can be used to study coupling between other retinal neurons, as described here.

  6. Gap junction coupling confers isopotentiality on astrocyte syncytium

    Science.gov (United States)

    Ma, Baofeng; Buckalew, Richard; Du, Yixing; Kiyoshi, Conrad M.; Alford, Catherine C.; Wang, Wei; McTigue, Dana D.; Enyeart, John J.; Terman, David; Zhou, Min

    2015-01-01

    Astrocytes are extensively coupled through gap junctions into a syncytium. However, the basic role of this major brain network remains largely unknown. Using electrophysiological and computational modeling methods, we demonstrate that the membrane potential (VM) of an individual astrocyte in a hippocampal syncytium, but not in a single, freshly isolated cell preparation, can be well-maintained at quasi-physiological levels when recorded with reduced or K+ free pipette solutions that alter the K+ equilibrium potential to non-physiological voltages. We show that an astrocyte’s associated syncytium provides powerful electrical coupling, together with ionic coupling at a lesser extent, that equalizes the astrocyte’s VM to levels comparable to its neighbors. Functionally, this minimizes VM depolarization attributable to elevated levels of local extracellular K+ and thereby maintains a sustained driving force for highly efficient K+ uptake. Thus, gap junction coupling functions to achieve isopotentiality in astrocytic networks, whereby a constant extracellular environment can be powerfully maintained for crucial functions of neural circuits. PMID:26435164

  7. Xenobiotic Modulation of Human Mammary Epithelial Cell Gap Junctional Intercellular Communication and Growth

    National Research Council Canada - National Science Library

    Ruch, Randall

    1999-01-01

    .... These agents also inhibit gap junctional intercellular communication (GJIC). This inhibition may contribute to the enhancement of breast epithelial growth and breast cancer formation by xenobiotics...

  8. 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...

  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. 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.

  11. Chlorpromazine reduces the intercellular communication via gap junctions in mammalian cells

    International Nuclear Information System (INIS)

    Orellana, Juan A.; Palacios-Prado, Nicolas; Saez, Juan C.

    2006-01-01

    In the work presented herein, we evaluated the effect of chlorpromazine (CPZ) on gap junctions expressed by two mammalian cell types; Gn-11 cells (cell line derived from mouse LHRH neurons) and rat cortical astrocytes maintained in culture. We also attempted to elucidate possible mechanisms of action of CPZ effects on gap junctions. CPZ, in concentrations comparable with doses used to treat human diseases, was found to reduce the intercellular communication via gap junctions as evaluated with measurements of dye coupling (Lucifer yellow). In both cell types, maximal inhibition of functional gap junctions was reached within about 1 h of treatment with CPZ, an recovery was almost complete at about 5 h after CPZ wash out. In both cell types, CPZ treatment increased the phosphorylation state of connexin43 (Cx43), a gap junction protein subunit. Moreover, CPZ reduced the reactivity of Cx43 (immunofluorescence) at cell interfaces and concomitantly increased its reactivity in intracellular vesicles, suggesting an increased retrieval from and/or reduced insertion into the plasma membrane. CPZ also caused cellular retraction reducing cell-cell contacts in a reversible manner. The reduction in contact area might destabilize existing gap junctions and abrogate formation of new ones. Moreover, the CPZ-induced reduction in gap junctional communication may depend on the connexins (Cxs) forming the junctions. If Cx43 were the only connexin expressed, MAPK-dependent phosphorylation of this connexin would induce closure of gap junction channels

  12. A three-dimensional model of a gap junction

    International Nuclear Information System (INIS)

    Xylouris, K.; Wittum, G.

    2009-01-01

    Gap junctions are effective electric couplings between neurons and form a very important way of communication between them. Since they can be considered as the points on the neuron's membrane on which for example dendrites of different cells become one piece, in three dimensions they can be modelled by observing this property in the created geometry. Thus they can be easily made part in an already existing 3-dimensional model for signal propagation on the neuron's membrane, if the geometries are chosen in such a way respect the blending of the membranes. A small network of two cells was created, which blend in their dendrites and a simulation of the three-dimensional model was carried out which reveals the fast transmission of the signal from one cell to the other.

  13. Methamphetamine compromises gap junctional communication in astrocytes and neurons.

    Science.gov (United States)

    Castellano, Paul; Nwagbo, Chisom; Martinez, Luis R; Eugenin, Eliseo A

    2016-05-01

    Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease. Methamphetamine (meth) is an extremely addictive central nervous system stimulant. Meth reduced gap junctional (GJ) communication by inducing internalization of connexin-43 (Cx43) in astrocytes and reducing expression of Cx36 in neurons by a mechanism involving activation of dopamine receptors (see cartoon). Meth-induced changes in Cx containing channels increased extracellular levels of glutamate and resulted in higher

  14. [Effects of gap junction blocking on the oxygen partial pressure in acupoints of the bladder meridian].

    Science.gov (United States)

    Wang, Qi; Yu, Wei-Chang; Jiang, Hong-Zhi; Chen, Sheng-Li; Zhang, Ming-Min; Kong, E-Sheng; Huang, Guang-Ying

    2010-12-01

    To explore the relation between gap junction and meridian phenomenon. The oxygen partial pressure in acupoints [see text for formula] and in their corresponding non-acupoints of the Bladder Meridian was observed with the needle-type tissue oxygen tension sensor in the gap junction blocking goats by 1-Heptanol injection and the Connexin 43 (Cx43) gene knockout mice. (1) The oxygen partial pressure in acupoints of Bladder Meridian on goats was higher than that in non-acupoints after 1-Heptanol injection with significant differences between them (both P oxygen partial pressure in acupoints of Bladder Meridian on goats increased significantly after injecting 1-Heptanol as compare with that either injecting normal saline or injecting nothing with significant differences between them (all P oxygen partial pressure in acupoints of the Bladder Meridian was significantly higher than that in the non-acupoint controls in Cx43 wild type (WT) mice (all P oxygen partial pressure between acupoints and non-acupoint controls showed no significant differences (all P > 0.05). (4) In acupoints, the oxygen partial pressure in Cx43 WT mice was significantly higher than that in Cx43 HT mice (all P 0.05). Gap junction maybe the essential factor in signal transduction of acupuncture.

  15. Methylmercury inhibits gap junctional intercellular communication in primary cultures of rat proximal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Minoru; Sumi, Yawara [Department of Chemistry, St. Marianna University School of Medicine, Kawasagi (Japan); Kujiraoka, Toru [Department of Physiology, St. Marianna University School of Medicine, Kawasagi (Japan); Hara, Masayuki [Department of Anatomy, St. Marianna University School of Medicine, Kawasagi (Japan); Nakazawa, Hirokazu [Department of Chemistry, Faculty of Sciences, Meisei University (Japan)

    1998-03-01

    Methylmercury (MeHg) causes renal injury in addition to central and peripheral neuropathy. To clarify the mechanism of nephrotoxicity by MeHg, we investigated the effect of this compound on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Twenty minutes after exposure to 30 {mu}M MeHg, gap junctional intercellular communication (GJIC), which was assessed by dye coupling, was markedly inhibited before appearance of cytotoxicity. When the medium containing MeHg was exchanged with MeHg-free medium, dye coupling recovered abruptly. However, the dye-coupling was abolished again 30 min after replacement with control medium, and the cells were damaged. Intracellular calcium concentration, [Ca{sup 2+}]{sub i}, which modulates the function of gap junctions, significantly increased following exposure of the cells to 30 {mu}M MeHg and returned to control level following replacement with MeHg-free medium. These results suggest that the inhibiting effect of MeHg on GJIC is related to the change in [Ca{sup 2+}]{sub i}, and may be involved in the pathogenesis of renal dysfunction. (orig.) With 5 figs., 23 refs.

  16. In vitro study of stem cell communication via gap junctions for fibrocartilage regeneration at entheses.

    Science.gov (United States)

    Nayak, Bibhukalyan Prasad; Goh, James Cho Hong; Toh, Siew Lok; Satpathy, Gyan Ranjan

    2010-03-01

    Entheses are fibrocartilaginous organs that bridge ligament with bone at their interface and add significant insertional strength. To replace a severely damaged ligament, a tissue-engineered graft preinstalled with interfacial fibrocartilage, which is being regenerated from stem cells, appears to be more promising than ligament-alone graft. Such a concept can be realized by a biomimetic approach of establishing a dynamic communication of stem cells with bone cells and/or ligament fibroblasts in vitro. The current study has two objectives. The first objective is to demonstrate functional coculture of bone marrow-derived stem cells (BMSCs) with mature bone cells/ligament fibroblasts as evidenced by gap-junctional communication in vitro. The second objective is to investigate the role of BMSCs in the regeneration of fibrocartilage within the coculture. Rabbit bone/ligament fibroblasts were dual-stained with DiI-Red and calcein (gap-junction permeable dye), and cocultured with unlabeled BMSCs at fixed ratio (1:10). The functional gap junction was demonstrated by the transfer of calcein from donor to recipient cells that was confirmed and quantified by flow cytometry. Type 2 collagen (cartilage extracellular matrix-specific protein) expressed by the mixed cell lines in the cocultures were estimated by real-time reverse transcription PCR and compared with that of the ligament-bone coculture (control). Significant transfer of calcein into BMSCs was observed and flow cytometry analyses showed a gradual increase in the percentage of BMSCs acquiring calcein with time. Cocultures that included BMSCs expressed significantly more type 2 collagen compared with the control. The current study, for the first time, reported the expression of gap-junctional communication of BMSCs with two adherent cell lines of musculoskeletal system in vitro and also confirmed that incorporation of stem cells augments fibrocartilage regeneration. The results open up a path to envisage a composite

  17. 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.

  18. The Control of Junction Flows

    National Research Council Canada - National Science Library

    Smith, Charles

    1997-01-01

    An experimental study of the effects of spatially-limited (i.e. localized) surface suction on unsteady laminar and turbulent junction flows was performed using hydrogen bubble flow visualization and Particle Image Velocimetry (PIV...

  19. Functional roles of the amino terminal domain in determining biophysical properties of Cx50 gap junction channels

    Directory of Open Access Journals (Sweden)

    Li eXin

    2013-12-01

    Full Text Available Communication through gap junction channels is essential for synchronized and coordinated cellular activities. The gap junction channel pore size, its switch control for opening/closing, and the modulations by chemicals can be different depending on the connexin subtypes that compose the channel. Recent structural and functional studies provide compelling evidence that the amino terminal (NT domains of several connexins line the pore of gap junction channels and play an important role in single channel conductance (γj and transjunctional voltage-dependent gating (Vj-gating. This article reviews recent studies conducted on a series of mutations/chimeras in the NT domain of connexin50 (Cx50. Functional examination of the gap junction channels formed by these mutants/chimeras shows the net charge number at the NT domain to be an important factor in γj and in Vj-gating. Furthermore, with an increase in the net negative charge at the NT domain, we observed an increase in the γj, as well as changes in the parameters of the Boltzmann fit of the normalized steady-state conductance and Vj relationship. Our data are consistent with a structural model where the NT domain of Cx50 lines the gap junction pore and plays an important role in sensing Vj and in the subsequent conformational changes leading to gating, as well as in limiting the rate of ion permeation.

  20. Treatment with the gap junction modifier rotigaptide (ZP123) reduces infarct size in rats with chronic myocardial infarction

    DEFF Research Database (Denmark)

    Haugan, Ketil; Marcussen, Niels; Kjølbye, Anne Louise

    2006-01-01

    Treatment with non-selective drugs (eg, long-chain alcohols, halothane) that reduce gap junction intercellular communication (GJIC) is associated with reduced infarct size after myocardial infarction (MI). Therefore, it has been suggested that gap junction intercellular communication stimulating ...

  1. Effects of gap junction blockers on human neocortical synchronization.

    Science.gov (United States)

    Gigout, S; Louvel, J; Kawasaki, H; D'Antuono, M; Armand, V; Kurcewicz, I; Olivier, A; Laschet, J; Turak, B; Devaux, B; Pumain, R; Avoli, M

    2006-06-01

    Field potentials and intracellular recordings were obtained from human neocortical slices to study the role of gap junctions (GJ) in neuronal network synchronization. First, we examined the effects of GJ blockers (i.e., carbenoxolone, octanol, quinine, and quinidine) on the spontaneous synchronous events (duration = 0.2-1.1 s; intervals of occurrence = 3-27 s) generated by neocortical slices obtained from temporal lobe epileptic patients during application of 4-aminopyridine (4AP, 50 muM) and glutamatergic receptor antagonists. The synchronicity of these potentials (recorded at distances up to 5 mm) was decreased by GJ blockers within 20 min of application, while prolonged GJ blockers treatment at higher doses made them disappear with different time courses. Second, we found that slices from patients with focal cortical dysplasia (FCD) could generate in normal medium spontaneous synchronous discharges (duration = 0.4-8 s; intervals of occurrence = 0.5-90 s) that were (i) abolished by NMDA receptor antagonists and (ii) slowed down by carbenoxolone. Finally, octanol or carbenoxolone blocked 4AP-induced ictal-like discharges (duration = up to 35 s) in FCD slices. These data indicate that GJ play a role in synchronizing human neocortical networks and may implement epileptiform activity in FCD.

  2. Local dynamics of gap-junction-coupled interneuron networks

    International Nuclear Information System (INIS)

    Lau, Troy; Zochowski, Michal; Gage, Gregory J; Berke, Joshua D

    2010-01-01

    Interneurons coupled by both electrical gap-junctions (GJs) and chemical GABAergic synapses are major components of forebrain networks. However, their contributions to the generation of specific activity patterns, and their overall contributions to network function, remain poorly understood. Here we demonstrate, using computational methods, that the topological properties of interneuron networks can elicit a wide range of activity dynamics, and either prevent or permit local pattern formation. We systematically varied the topology of GJ and inhibitory chemical synapses within simulated networks, by changing connection types from local to random, and changing the total number of connections. As previously observed we found that randomly coupled GJs lead to globally synchronous activity. In contrast, we found that local GJ connectivity may govern the formation of highly spatially heterogeneous activity states. These states are inherently temporally unstable when the input is uniformly random, but can rapidly stabilize when the network detects correlations or asymmetries in the inputs. We show a correspondence between this feature of network activity and experimental observations of transient stabilization of striatal fast-spiking interneurons (FSIs), in electrophysiological recordings from rats performing a simple decision-making task. We suggest that local GJ coupling enables an active search-and-select function of striatal FSIs, which contributes to the overall role of cortical-basal ganglia circuits in decision-making

  3. 7-Ketocholesterol modulates intercellular communication through gap-junction in bovine lens epithelial cells

    Directory of Open Access Journals (Sweden)

    Pereira Paulo

    2004-06-01

    Full Text Available Abstract Background Connexin43 (Cx43 is an integral membrane protein that forms intercellular channels called gap junctions. Intercellular communication in the eye lens relies on an extensive network of gap junctions essential for the maintenance of lens transparency. The association of Cx43 with cholesterol enriched lipid raft domains was recently demonstrated. The objective of this study is to assess if products of cholesterol oxidation (oxysterols affect gap junction intercellular communication (GJIC. Results Primary cultures of lens epithelial cells (LEC were incubated with 7-ketocholesterol (7-Keto, 25-hydroxycholesterol (25-OH or cholesterol and the subcellular distribution of Cx43 was evaluated by immunofluorescence confocal microscopy. The levels of Cx43 present in gap junction plaques were assessed by its insolubility in Triton X-100 and quantified by western blotting. The stability of Cx43 at the plasma membrane following incubation with oxysterols was evaluated by biotinylation of cell surface proteins. Gap junction intercellular communication was evaluated by transfer of the dye Lucifer yellow. The results obtained showed that 7-keto induces an accumulation of Cx43 at the plasma membrane and an increase in intercellular communication through gap junction. However, incubation with cholesterol or 25-OH did not lead to significant alterations on subcellular distribution of Cx43 nor in intercellular communication. Data further suggests that increased intercellular communication results from increased stability of Cx43 at the plasma membrane, presumably forming functional gap-junctions, as suggested by decreased solubility of Cx43 in 1% Triton X-100. The increased stability of Cx43 at the plasma membrane seems to be specific and not related to disruption of endocytic pathway, as demonstrated by dextran uptake. Conclusions Results demonstrate, for the first time, that 7-keto induces an increase in gap junction intercellular communication

  4. Quantification of gap junctional intercellular communication based on digital image analysis

    DEFF Research Database (Denmark)

    Hofgaard, Johannes P; Mollerup, Sarah; Holstein-Rathlou, Niels-Henrik

    2009-01-01

    Intercellular communication via gap junction channels can be quantified by several methods based on diffusion of fluorescent dyes or metabolites. Given the variation in intercellular coupling of cells, even under untreated control conditions, it is of essence to quantify the coupling between...... and in cells receiving dye by intercellular diffusion. The analysis performed is semiautomatic, and comparison with traditional cell counting shows that this method reliably determines the effect of uncoupling by several interventions. This new method of analysis yields a rapid and objective quantification...

  5. Quantitative analysis of dual whole-cell voltage-clamp determination of gap junctional conductance

    NARCIS (Netherlands)

    van Rijen, H. V.; Wilders, R.; van Ginneken, A. C.; Jongsma, H. J.

    1998-01-01

    The dual whole-cell voltage-clamp technique is used widely for determination of kinetics and conductance of gap junctions. The use of this technique may, however, occasion to considerable errors. We have analysed the errors in steady state junctional conductance measurements under different

  6. ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jorgensen, N R; Geist, S T; Civitelli, R

    1997-01-01

    mechanically induced calcium waves in two rat osteosarcoma cell lines that differ in the gap junction proteins they express, in their ability to pass microinjected dye from cell to cell, and in their expression of P2Y2 (P2U) purinergic receptors. ROS 17/2.8 cells, which express the gap junction protein......Many cells coordinate their activities by transmitting rises in intracellular calcium from cell to cell. In nonexcitable cells, there are currently two models for intercellular calcium wave propagation, both of which involve release of inositol trisphosphate (IP3)- sensitive intracellular calcium...... stores. In one model, IP3 traverses gap junctions and initiates the release of intracellular calcium stores in neighboring cells. Alternatively, calcium waves may be mediated not by gap junctional communication, but rather by autocrine activity of secreted ATP on P2 purinergic receptors. We studied...

  7. Synopsis of the International Gap Junction Conference in Elsinore, Denmark August 5-9, 2007

    DEFF Research Database (Denmark)

    Willecke, Klaus; Nielsen, Morten Schak

    2008-01-01

    This synopsis covers the main results and conclusions from the platform presentations during the International Gap Junction Conference. More detailed information is provided in the mini reviews on controversial scientific issues, short reports of research results and conference abstracts publishe...

  8. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps

    KAUST Repository

    Takaku, Yasuharu

    2014-01-07

    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

  9. Gap junctions and epileptic seizures--two sides of the same coin?

    Directory of Open Access Journals (Sweden)

    Vladislav Volman

    Full Text Available Electrical synapses (gap junctions play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses promotes synchronous activity (and thus is potentially epileptogenic, some recent evidence questions the hypothesis of gap junctions being among purely epileptogenic factors. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before. Here we used a computational modeling approach to address the role of neuronal gap junctions in shaping the stability of a network to perturbations that are often associated with the onset of epileptic seizures. We show that under some circumstances, the addition of gap junctions can increase the dynamical stability of a network and thus suppress the collective electrical activity associated with seizures. This implies that the experimentally observed post-seizure additions of gap junctions could serve to prevent further escalations, suggesting furthermore that they are a consequence of an adaptive response of the neuronal network to the pathological activity. However, if the seizures are strong and persistent, our model predicts the existence of a critical tipping point after which additional gap junctions no longer suppress but strongly facilitate the escalation of epileptic seizures. Our results thus reveal a complex role of electrical coupling in relation to epileptiform events. Which dynamic scenario (seizure suppression or seizure escalation is ultimately adopted by the network depends critically on the strength and duration of seizures, in turn emphasizing the importance of temporal and causal aspects when linking gap junctions with epilepsy.

  10. Chaotic synchronization with gap junction of multi-neurons in external electrical stimulation

    International Nuclear Information System (INIS)

    Deng Bin; Wang Jiang; Fei Xiangyang

    2005-01-01

    The synchronization of n(n 3) neurons coupled with gap junction in external electrical stimulation is investigated. In this paper, the coupled model is established on the basis of nonlinear cable model, and then the relation between coupling strength of the gap junction and the synchronization is discussed in detail. The sufficient condition of complete synchronization is attained from rigorous mathematical derivation. The synchronizations of periodic neurons and chaotic neurons are studied respectively

  11. Inhibition of connexin43 gap junction channels by the endocrine disruptor ioxynil

    International Nuclear Information System (INIS)

    Leithe, Edward; Kjenseth, Ane; Bruun, Jarle; Sirnes, Solveig; Rivedal, Edgar

    2010-01-01

    Gap junctions are intercellular plasma membrane domains containing channels that mediate transport of ions, metabolites and small signaling molecules between adjacent cells. Gap junctions play important roles in a variety of cellular processes, including regulation of cell growth and differentiation, maintenance of tissue homeostasis and embryogenesis. The constituents of gap junction channels are a family of trans-membrane proteins called connexins, of which the best-studied is connexin43. Connexin43 functions as a tumor suppressor protein in various tissue types and is frequently dysregulated in human cancers. The pesticide ioxynil has previously been shown to act as an endocrine disrupting chemical and has multiple effects on the thyroid axis. Furthermore, both ioxynil and its derivative ioxynil octanoate have been reported to induce tumors in animal bioassays. However, the molecular mechanisms underlying the possible tumorigenic effects of these compounds are unknown. In the present study we show that ioxynil and ioxynil octanoate are strong inhibitors of connexin43 gap junction channels. Both compounds induced rapid loss of connexin43 gap junctions at the plasma membrane and increased connexin43 degradation. Ioxynil octanoate, but not ioxynil, was found to be a strong activator of ERK1/2. The compounds also had different effects on the phosphorylation status of connexin43. Taken together, the data show that ioxynil and ioxynil octanoate are potent inhibitors of intercellular communication via gap junctions.

  12. Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

    Directory of Open Access Journals (Sweden)

    Harissios Vliagoftis

    2014-01-01

    Full Text Available Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

  13. Intercellular communication via gap junctions affected by mechanical load in the bovine annulus fibrosus.

    Science.gov (United States)

    Desrochers, Jane; Duncan, Neil A

    2014-01-01

    Cells in the intervertebral disc, as in other connective tissues including tendon, ligament and bone, form interconnected cellular networks that are linked via functional gap junctions. These cellular networks may be necessary to affect a coordinated response to mechanical and environmental stimuli. Using confocal microscopy with fluorescence recovery after photobleaching methods, we explored the in situ strain environment of the outer annulus of an intact bovine disc and the effect of high-level flexion on gap junction signalling. The in situ strain environment in the extracellular matrix of the outer annulus under high flexion load was observed to be non-uniform with the extensive cellular processes remaining crimped sometimes at flexion angles greater than 25°. A significant transient disruption of intercellular communication via functional gap junctions was measured after 10 and 20 min under high flexion load. This study illustrates that in healthy annulus fibrosus tissue, high mechanical loads can impede the functioning of the gap junctions. Future studies will explore more complex loading conditions to determine whether losses in intercellular communication can be permanent and whether gap junctions in aged and degenerated tissues become more susceptible to load. The current research suggests that cellular structures such as gap junctions and intercellular networks, as well as other cell-cell and cell-matrix interconnections, need to be considered in computational models in order to fully understand how macroscale mechanical signals are transmitted across scales to the microscale and ultimately into a cellular biosynthetic response in collagenous tissues.

  14. Inter-band phase fluctuations in macroscopic quantum tunneling of multi-gap superconducting Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Asai, Hidehiro, E-mail: hd-asai@aist.go.jp [Electronics and Photonics Research Institute (ESPRIT), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8568 (Japan); Ota, Yukihiro [CCSE, Japan Atomic Energy Agency, Kashiwa, Chiba 277-8587 (Japan); Kawabata, Shiro [Electronics and Photonics Research Institute (ESPRIT), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8568 (Japan); Nori, Franco [CEMS, RIKEN, Wako-shi, Saitama 351-0198 (Japan); Physics Department, University of Michigan, Ann Arbor, MI 48109-1040 (United States)

    2014-09-15

    Highlights: • We study MQT in Josephson junctions composed of multi-gap superconductors. • We derive a formula of the MQT escape rate for multiple phase differences. • We investigate the effect of inter-band phase fluctuation on MQT. • The MQT escape rate is significantly enhanced by the inter-band phase fluctuation. - Abstract: We theoretically investigate macroscopic quantum tunneling (MQT) in a hetero Josephson junction formed by a conventional single-gap superconductor and a multi-gap superconductor. In such Josephson junctions, phase differences for each tunneling channel are defined, and the fluctuation of the relative phase differences appear which is referred to as Josephson–Leggett’s mode. We take into account the effect of the fluctuation in the tunneling process and calculate the MQT escape rate for various junction parameters. We show that the fluctuation of relative phase differences drastically enhances the escape rate.

  15. Inter-band phase fluctuations in macroscopic quantum tunneling of multi-gap superconducting Josephson junctions

    International Nuclear Information System (INIS)

    Asai, Hidehiro; Ota, Yukihiro; Kawabata, Shiro; Nori, Franco

    2014-01-01

    Highlights: • We study MQT in Josephson junctions composed of multi-gap superconductors. • We derive a formula of the MQT escape rate for multiple phase differences. • We investigate the effect of inter-band phase fluctuation on MQT. • The MQT escape rate is significantly enhanced by the inter-band phase fluctuation. - Abstract: We theoretically investigate macroscopic quantum tunneling (MQT) in a hetero Josephson junction formed by a conventional single-gap superconductor and a multi-gap superconductor. In such Josephson junctions, phase differences for each tunneling channel are defined, and the fluctuation of the relative phase differences appear which is referred to as Josephson–Leggett’s mode. We take into account the effect of the fluctuation in the tunneling process and calculate the MQT escape rate for various junction parameters. We show that the fluctuation of relative phase differences drastically enhances the escape rate

  16. Gemcitabine intercellular diffusion mediated by gap junctions: new implications for cancer therapy

    Directory of Open Access Journals (Sweden)

    Caruso Manuel

    2010-06-01

    Full Text Available Abstract Background Solid tumors are often poorly vascularized, with cells that can be 100 μm away from blood vessels. These distant cells get less oxygen and nutrients and are exposed to lower doses of chemotherapeutic agents. As gap junctions allow the passage of small molecules between cells, we tested the possibility that the chemotherapeutic agent gemcitabine can diffuse through gap junctions in solid tumors. Results We first showed with a dye transfer assay that the glioblastoma and the osteosarcoma cells used in this study have functional gap junctions. These cells were genetically engineered to express the herpes simplex virus thymidine kinase (TK, and induced a "bystander effect" as demonstrated by the killing of TK-negative cells in presence of the nucleoside analogue ganciclovir (GCV. The ability of gemcitabine to induce a similar bystander effect was then tested by mixing cells treated with 3 μM gemcitabine for 24 hours with untreated cells at different ratios. In all cell lines tested, bystander cells were killed with ratios containing as low as 5% treated cells, and this toxic effect was reduced in presence of α-glycyrrhetinic acid (AGA, a specific gap junction inhibitor. We also showed that a 2- or a 24-hour gemcitabine treatment was more efficient to inhibit the growth of spheroids with functional gap junctions as compared to the same treatment made in presence of AGA. Finally, after a 24-hour gemcitabine treatment, the cell viability in spheroids was reduced by 92% as opposed to 51% in presence of AGA. Conclusion These results indicate that gemcitabine-mediated toxicity can diffuse through gap junctions, and they suggest that gemcitabine treatment could be more efficient for treating solid tumors that display gap junctions. The presence of these cellular channels could be used to predict the responsiveness to this nucleoside analogue therapy.

  17. Microwave dependence of subharmonic gap structure in superconducting junctions

    DEFF Research Database (Denmark)

    Sørensen, O. Hoffman; Kofoed, Bent; Pedersen, Niels Falsig

    1974-01-01

    are integers: m=1,2,3,… and n=0,1,2,…. The power dependence of the satellite structure and the microwave-assisted tunneling structure is consistent for all junctions tested with the expression Jn2(m e Vrf / h ν), where Jn(x) is the ordinary Bessel function of order n, Vrf is the amplitude of the induced...

  18. Mechanically controllable break junctions for molecular electronics.

    Science.gov (United States)

    Xiang, Dong; Jeong, Hyunhak; Lee, Takhee; Mayer, Dirk

    2013-09-20

    A mechanically controllable break junction (MCBJ) represents a fundamental technique for the investigation of molecular electronic junctions, especially for the study of the electronic properties of single molecules. With unique advantages, the MCBJ technique has provided substantial insight into charge transport processes in molecules. In this review, the techniques for sample fabrication, operation and the various applications of MCBJs are introduced and the history, challenges and future of MCBJs are discussed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Gap junctional coupling in the vertebrate retina: variations on one theme?

    Science.gov (United States)

    Völgyi, Béla; Kovács-Oller, Tamás; Atlasz, Tamás; Wilhelm, Márta; Gábriel, Róbert

    2013-05-01

    Gap junctions connect cells in the bodies of all multicellular organisms, forming either homologous or heterologous (i.e. established between identical or different cell types, respectively) cell-to-cell contacts by utilizing identical (homotypic) or different (heterotypic) connexin protein subunits. Gap junctions in the nervous system serve electrical signaling between neurons, thus they are also called electrical synapses. Such electrical synapses are particularly abundant in the vertebrate retina where they are specialized to form links between neurons as well as glial cells. In this article, we summarize recent findings on retinal cell-to-cell coupling in different vertebrates and identify general features in the light of the evergrowing body of data. In particular, we describe and discuss tracer coupling patterns, connexin proteins, junctional conductances and modulatory processes. This multispecies comparison serves to point out that most features are remarkably conserved across the vertebrate classes, including (i) the cell types connected via electrical synapses; (ii) the connexin makeup and the conductance of each cell-to-cell contact; (iii) the probable function of each gap junction in retinal circuitry; (iv) the fact that gap junctions underlie both electrical and/or tracer coupling between glial cells. These pan-vertebrate features thus demonstrate that retinal gap junctions have changed little during the over 500 million years of vertebrate evolution. Therefore, the fundamental architecture of electrically coupled retinal circuits seems as old as the retina itself, indicating that gap junctions deeply incorporated in retinal wiring from the very beginning of the eye formation of vertebrates. In addition to hard wiring provided by fast synaptic transmitter-releasing neurons and soft wiring contributed by peptidergic, aminergic and purinergic systems, electrical coupling may serve as the 'skeleton' of lateral processing, enabling important functions such

  20. The extracellular matrix component laminin promotes gap junction formation in the rat anterior pituitary gland.

    Science.gov (United States)

    Horiguchi, Kotaro; Kouki, Tom; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

    2011-03-01

    Folliculo-stellate (FS) cells in the anterior pituitary gland are believed to have multifunctional properties. FS cells connect to each other not only by mechanical means, but also by gap junctional cell-to-cell communication. Using transgenic rats that express green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary gland (S100b-GFP rats), we recently revealed that FS cells in primary culture markedly change their shape, and form numerous interconnections with neighboring FS cells in the presence of laminin, an extracellular matrix (ECM) component of the basement membrane. Morphological and functional changes in cells are believed to be partly modified by matricrine signaling, by which ECM components function as cellular signals. In the present study, we examined whether gap junction formation between FS cells is affected by matricrine cues. A cell sorter was used to isolate FS cells from male S100b-GFP rat anterior pituitary for primary culture. We observed that mRNA and protein levels of connexin 43 in gap junction channels were clearly higher in the presence of laminin. In addition, we confirmed the formation of gap junctions between FS cells in primary culture by electron microscopy. Interestingly, we also observed that FS cells in the presence of laminin displayed well-developed rough endoplasmic reticulum and Golgi apparatus. Our findings suggest that, in anterior pituitary gland, FS cells may facilitate functional roles such as gap junctional cell-to-cell communication by matricrine signaling.

  1. MV controlled spark gap

    International Nuclear Information System (INIS)

    Evdokimovich, V.M.; Evlampiev, S.B.; Korshunov, G.S.; Nikolaev, V.A.; Sviridov, Yu.F.; Khmyrov, V.V.

    1980-01-01

    A megavolt gas-filled trigatron gap with a sectional gas-discharge chamber having a more than three-fold range of operating voltages is described. The discharge chamber consists of ten sections, each 70 mm thick, made of organic glass. The sections are separated one from another by aluminium gradient rings to which ohmic voltage divider is connected. Insulational sections and gradient rings are braced between themselves by means of metal flanges through gaskets made of oil-resistant rubber with the help of fiberglass-laminate pins. The gap has two electrodes 110 mm in diameter. The trigatron ignition assembly uses a dielectric bushing projecting over the main electrode plane. Use has been made of a gas mixture containing 10% of SF 6 and 90% of air making possible to ensure stable gap operation without readjusting in the voltage range from 0.4 to 1.35 MV. The operation time lag in this range is equal to 10 μs at a spread of [ru

  2. Search for a proximity effect induced gap in gold/high Tc junctions

    International Nuclear Information System (INIS)

    Dessau, D.S.; Wells, B.O.; Shen, Z.; Spicer, W.E.; Arko, A.J.; List, R.S.; Olson, C.G.; Eom, C.B.; Mitzi, D.B.; Kapitulnik, A.; Geballe, T.H.

    1991-01-01

    We have used high-resolution photoemission spectroscopy to search for a proximity effect induced superconducting gap in gold overlayers on c-axis single crystals of Bi 2 Sr 2 CaCu 2 O 8 and a-axis thin films of YBa 2 Cu 3 O 7 . These two junction types give us a representative sampling of very well characterized near-ideal interfaces (gold/c-axis Bi 2 Sr 2 CaCu 2 O 8 ) and junctions in which the geometry more strongly favors the existence of the proximity effect but the interfacial quality may not be as ideal (gold/a-axis YBa 2 Cu 3 O 7 ). In neither of these junction types did we observe any evidence for a proximity effect induced gap, and we place an upper limit of approximately 5 meV on its existence in the junctions that we have studied

  3. Protein kinase C-dependent regulation of connexin43 gap junctions and hemichannels

    DEFF Research Database (Denmark)

    Alstrøm, Jette Skov; Stroemlund, Line Waring; Nielsen, Morten Schak

    2015-01-01

    Connexin43 (Cx43) generates intercellular gap junction channels involved in, among others, cardiac and brain function. Gap junctions are formed by the docking of two hemichannels from neighbouring cells. Undocked Cx43 hemichannels can upon different stimuli open towards the extracellular matrix...... and allow transport of molecules such as fluorescent dyes and ATP. A range of phosphorylated amino acids have been detected in the C-terminus of Cx43 and their physiological role has been intensively studied both in the gap junctional form of Cx43 and in its hemichannel configuration. We present the current...... knowledge of protein kinase C (PKC)-dependent regulation of Cx43 and discuss the divergent results....

  4. Feature of the energy gap in YBa2 Cu3 O7 from break junction measurements

    International Nuclear Information System (INIS)

    Ekino, T.; Minami, T.; Fujii, H.

    1995-01-01

    Superconducting energy gap in YBa 2 Cu 3 O 7 have been investigated using break junctions. The tunneling conductance, dI/dV, at T=4.2 K shows no leakage around zero bias, while the gap edge peaks are broadened compared to the simple BCS density of states. These features suggest the spatial distribution of the energy gap or the anisotropic s-wave pairing. The observed largest gap value, determined by the peak-to-peak (p-p) separation in dI/dV, is 140 meV, which corresponds to the 4 δ p-p of an SIS junction. The observed tunneling density of states is fairly well expressed by the probability distribution of the energy gap using the BCS density of states

  5. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo, E-mail: mnuriya@z2.keio.jp

    2014-02-07

    Highlights: • Astrocytes exhibit characteristic changes in [Ca{sup 2+}]{sub i} under OGD. • Astrocytic [Ca{sup 2+}]{sub i} increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca{sup 2+}]{sub i}) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca{sup 2+}]{sub i} oscillations followed by larger and sustained [Ca{sup 2+}]{sub i} increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca{sup 2+}]{sub i} increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca{sup 2+}]{sub i} increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca{sup 2+}]{sub i} increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage

  6. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    International Nuclear Information System (INIS)

    Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo

    2014-01-01

    Highlights: • Astrocytes exhibit characteristic changes in [Ca 2+ ] i under OGD. • Astrocytic [Ca 2+ ] i increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca 2+ ] i ) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca 2+ ] i oscillations followed by larger and sustained [Ca 2+ ] i increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca 2+ ] i increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca 2+ ] i increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca 2+ ] i increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage during the acute phase of ischemia

  7. 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.

  8. Chemopreventive agents attenuate rapid inhibition of gap junctional intercellular communication induced by environmental toxicants

    Czech Academy of Sciences Publication Activity Database

    Babica, Pavel; Čtveráčková, Lucie; Lenčešová, Zuzana; Trosko, J. E.; Upham, B. L.

    2016-01-01

    Roč. 68, č. 5 (2016), s. 827-837 ISSN 0163-5581 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * chemopreventive agents * environmental toxicants Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.447, year: 2016

  9. Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate

    NARCIS (Netherlands)

    van Zeijl, Leonie; Ponsioen, Bas; Giepmans, Ben N G; Ariaens, Aafke; Postma, Friso R; Várnai, Péter; Balla, Tamas; Divecha, Nullin; Jalink, Kees; Moolenaar, Wouter H

    2007-01-01

    Cell-cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell-cell communication is inhibited by depletion of phosphatidylinositol

  10. Gap junction networks can generate both ripple-like and fast ripple-like oscillations

    Science.gov (United States)

    Simon, Anna; Traub, Roger D.; Vladimirov, Nikita; Jenkins, Alistair; Nicholson, Claire; Whittaker, Roger G.; Schofield, Ian; Clowry, Gavin J.; Cunningham, Mark O.; Whittington, Miles A.

    2014-01-01

    Fast ripples (FRs) are network oscillations, defined variously as having frequencies of > 150 to > 250 Hz, with a controversial mechanism. FRs appear to indicate a propensity of cortical tissue to originate seizures. Here, we demonstrate field oscillations, at up to 400 Hz, in spontaneously epileptic human cortical tissue in vitro, and present a network model that could explain FRs themselves, and their relation to ‘ordinary’ (slower) ripples. We performed network simulations with model pyramidal neurons, having axons electrically coupled. Ripples ( 250 Hz, were sustained or interrupted, and had little jitter in the firing of individual axons. The form of model FR was similar to spontaneously occurring FRs in excised human epileptic tissue. In vitro, FRs were suppressed by a gap junction blocker. Our data suggest that a given network can produce ripples, FRs, or both, via gap junctions, and that FRs are favored by clusters of axonal gap junctions. If axonal gap junctions indeed occur in epileptic tissue, and are mediated by connexin 26 (recently shown to mediate coupling between immature neocortical pyramidal cells), then this prediction is testable. PMID:24118191

  11. Opposite effects of the gap junction blocker octanol on focal cerebral ischemia occluded for different durations.

    Science.gov (United States)

    Ding, Wenting; Zhou, Lequan; Liu, Wei; Guan, Li; Li, Xiaoying; Liu, Haimei; Yan, Fuman; Xu, Jinwen; Zeng, Weiyong; Qiu, Min

    2014-06-01

    Protectants and executioners have been demonstrated to be used by gap junctions in focal cerebral ischemia. Certain researchers hypothesized that the opposite role of gap junctions may be associated with the injury extent, which has been demonstrated to be highly correlated with occlusion duration. In order to examine this hypothesis directly, the effects of octanol, a frequently used drug, were examined to investigate the role of gap junctions, in rats following middle cerebral artery occlusion (MCAO) for 30 min/2 h and 24 h reperfusion, respectively. Octanol significantly reduced the infarct volume following 2 h of occlusion concomitant with lower neurological deficits, whereas it enlarged the infarct volume following 30 min of occlusion. Consistently, octanol attenuated the number of transferase dUTP nick-end labeling (TUNEL) positive neurons in the hippocampal CA1 region following 2 h of occlusion, while opposite effects were observed for 30 min of occlusion. Further immunohistochemical studies demonstrated that the expression of B-cell leukemia-2 (Bcl-2, anti-apoptotic protein) was upregulated and that Bcl-2-associated X (Bax, proapoptotic protein) was downregulated following 2 h of occlusion in the octanol group compared with the ischemic group. Conversely, octanol downregulated the expression of the Bcl-2 protein concomitant with increased Bax protein following 30 min of occlusion. These results indicated that the gap junction blocker octanol can protect against ischemic injury following long-term occlusion, however, can aggravate ischemic injury following short-term occlusion.

  12. Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hideyuki eTakeuchi

    2014-09-01

    Full Text Available Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS. Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g. minocycline have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases.

  13. Gap junctions suppress electrical but not [Ca(2+)] heterogeneity in resistance arteries

    DEFF Research Database (Denmark)

    Hald, Bjørn Olav; Welsh, Donald G; von Holstein-Rathlou, Niels-Henrik

    2014-01-01

    arises, a virtual arteriole was developed that introduces variation in the activities of ion-transport proteins between cells. By varying the level of heterogeneity and subpopulations of gap junctions (GJs), the resulting simulations shows that GJs suppress electrical variation but can only reduce...

  14. Interfering amino terminal peptides and functional implications for heteromeric gap junction formation

    Directory of Open Access Journals (Sweden)

    Richard David Veenstra

    2013-05-01

    Full Text Available Connexin43 (Cx43 is widely expressed in many different tissues of the human body. In cells of some organs, Cx43 is co-expressed with other connexins (Cx, including Cx46 and Cx50 in lens, Cx40 in atrium, Purkinje fibers, and the blood vessel wall, Cx45 in heart, and Cx37 in the ovary. Interactions with the co-expressed connexins may have profound functional implications. The abilities of Cx37, Cx45, Cx46, and Cx50 to function in heteromeric gap junction combinations with Cx43 are well documented. Different studies disagree regarding the ability of Cx43 and Cx40 to produce functional heteromeric gap junctions with each other. We review previous studies regarding the heteromeric interactions of Cx43. The possibility of negative functional interactions between the cytoplasmic pore-forming amino terminal (NT domains of these connexins was assessed using pentameric connexin sequence-specific NT domain (iNT peptides applied to cells expressing homomeric Cx40, Cx37, Cx45, Cx46, and Cx50 gap junctions. A Cx43 iNT peptide corresponding to amino acids 9 to 13 (Ac-KLLDK-NH2 specifically inhibited the electrical coupling of Cx40 gap junctions in a transjunctional (Vj voltage-dependent manner without affecting the function of homologous Cx37, Cx46, Cx50, and Cx45 gap junctions. A Cx40 iNT (Ac-EFLEE-OH peptide counteracted the Vj-dependent block of Cx40 gap junctions, whereas a similarly charged Cx50 iNT (Ac-EEVNE-OH peptide did not, suggesting that these NT domain interactions are not solely based on electrostatics. These data are consistent with functional Cx43 heteromeric gap junction formation with Cx37, Cx45, Cx46, and Cx50 and suggest that Cx40 uniquely experiences functional suppressive interactions with a Cx43 NT domain sequence. These findings present unique functional implications about the heteromeric interactions between Cx43 and Cx40 that may influence cardiac conduction in atrial myocardium and the specialized conduction system.

  15. Gold nanoparticle-mediated (GNOME) laser perforation: a new method for a high-throughput analysis of gap junction intercellular coupling.

    Science.gov (United States)

    Begandt, Daniela; Bader, Almke; Antonopoulos, Georgios C; Schomaker, Markus; Kalies, Stefan; Meyer, Heiko; Ripken, Tammo; Ngezahayo, Anaclet

    2015-10-01

    The present report evaluates the advantages of using the gold nanoparticle-mediated laser perforation (GNOME LP) technique as a computer-controlled cell optoperforation to introduce Lucifer yellow (LY) into cells in order to analyze the gap junction coupling in cell monolayers. To permeabilize GM-7373 endothelial cells grown in a 24 multiwell plate with GNOME LP, a laser beam of 88 μm in diameter was applied in the presence of gold nanoparticles and LY. After 10 min to allow dye uptake and diffusion through gap junctions, we observed a LY-positive cell band of 179 ± 8 μm width. The presence of the gap junction channel blocker carbenoxolone during the optoperforation reduced the LY-positive band to 95 ± 6 μm. Additionally, a forskolin-related enhancement of gap junction coupling, recently found using the scrape loading technique, was also observed using GNOME LP. Further, an automatic cell imaging and a subsequent semi-automatic quantification of the images using a java-based ImageJ-plugin were performed in a high-throughput sequence. Moreover, the GNOME LP was used on cells such as RBE4 rat brain endothelial cells, which cannot be mechanically scraped as well as on three-dimensionally cultivated cells, opening the possibility to implement the GNOME LP technique for analysis of gap junction coupling in tissues. We conclude that the GNOME LP technique allows a high-throughput automated analysis of gap junction coupling in cells. Moreover this non-invasive technique could be used on monolayers that do not support mechanical scraping as well as on cells in tissue allowing an in vivo/ex vivo analysis of gap junction coupling.

  16. Ochratoxim A alters cell adhesion and gap junction intercellular communication in MDCK cells

    International Nuclear Information System (INIS)

    Mally, Angela; Decker, Martina; Bekteshi, Michaela; Dekant, Wolfgang

    2006-01-01

    Ochratoxin A (OTA) is one of the most potent renal carcinogens studied to date, but the mechanism of tumor formation by ochratoxin A remains largely unknown. Cell adhesion and cell-cell communication participate in the regulation of signaling pathways involved in cell proliferation and growth control and it is therefore not surprising that modulation of cell-cell signaling has been implicated in cancer development. Several nephrotoxicants and renal carcinogens have been shown to alter cell-cell signaling by interference with gap junction intercell communication (GJIC) and/or cell adhesion, and the aim of this study was to determine if disruption of cell-cell interactions occurs in kidney epithelial cells in response to OTA treatment. MDCK cells were treated with OTA (0-50 μM) for up to 24 h and gap junction function was analyzed using the scrape-load/dye transfer assay. In addition, expression and intracellular localization of Cx43, E-cadherin and β-catenin were determined by immunoblot and immunofluorescence analysis. A clear decrease in the distance of dye transfer was evident following treatment with OTA at concentrations/incubation times which did not affect cell viability. Consistent with the functional inhibition of GJIC, treatment with OTA resulted in a dose-dependent decrease in Cx43 expression. In contrast to Cx43, OTA did not alter total amount of the adherens junction proteins E-cadherin and β-catenin. Moreover, Western blot analysis of Triton X-100 soluble and insoluble protein fractions did not indicate translocation of cell adhesion molecules from the membrane to the cytoplasm. However, a ∼78 kDa fragment of β-catenin was detected in the detergent soluble fraction, indicating proteolytic cleavage of β-catenin. Immunofluorescence analysis also revealed changes in the pattern of both β-catenin and E-cadherin labeling, suggesting that OTA may alter cell-adhesion. Taken together, these data support the hypothesis that disruption of cell

  17. Sustained inhibition of rat myometrial gap junctions and contractions by lindane

    Directory of Open Access Journals (Sweden)

    Grindatti Carmen M

    2003-10-01

    Full Text Available Abstract Background Gap junctions increase in size and abundance coincident with parturition, forming an intercellular communication network that permits the uterus to develop the forceful, coordinated contractions necessary for delivery of the fetus. Lindane, a pesticide used in the human and veterinary treatment of scabies and lice as well as in agricultural applications, inhibits uterine contractions in vitro, inhibits myometrial gap junctions, and has been associated with prolonged gestation length in rats. The aim of the present study was to investigate whether brief exposures to lindane would elicit sustained inhibition of rat uterine contractile activity and myometrial gap junction intercellular communication. Methods To examine effects on uterine contraction, longitudinal uterine strips isolated from late gestation (day 20 rats were exposed to lindane in muscle baths and monitored for changes in spontaneous phasic contractions during and after exposure to lindane. Lucifer yellow dye transfer between myometrial cells in culture was used to monitor gap junction intercellular communication. Results During a 1-h exposure, 10 micro M and 100 micro M lindane decreased peak force and frequency of uterine contraction but 1 micro M lindane did not. After removal of the exposure buffer, contraction force remained significantly depressed in uterine strips exposed to 100 micro M lindane, returning to less than 50% basal levels 5 h after cessation of lindane exposure. In cultured myometrial myocytes, significant sustained inhibition of Lucifer yellow dye transfer was observed 24 h after lindane exposures as brief as 10 min and as low as 0.1 micro M lindane. Conclusion Brief in vitro exposures to lindane have long-term effects on myometrial functions that are necessary for parturition, inhibiting spontaneous phasic contractions in late gestation rat uterus and gap junction intercellular communication in myometrial cell cultures.

  18. Nonlinear gap junctions enable long-distance propagation of pulsating calcium waves in astrocyte networks.

    Directory of Open Access Journals (Sweden)

    Mati Goldberg

    Full Text Available A new paradigm has recently emerged in brain science whereby communications between glial cells and neuron-glia interactions should be considered together with neurons and their networks to understand higher brain functions. In particular, astrocytes, the main type of glial cells in the cortex, have been shown to communicate with neurons and with each other. They are thought to form a gap-junction-coupled syncytium supporting cell-cell communication via propagating Ca(2+ waves. An identified mode of propagation is based on cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP(3 through gap junctions that locally trigger Ca(2+ pulses via IP(3-dependent Ca(2+-induced Ca(2+ release. It is, however, currently unknown whether this intracellular route is able to support the propagation of long-distance regenerative Ca(2+ waves or is restricted to short-distance signaling. Furthermore, the influence of the intracellular signaling dynamics on intercellular propagation remains to be understood. In this work, we propose a model of the gap-junctional route for intercellular Ca(2+ wave propagation in astrocytes. Our model yields two major predictions. First, we show that long-distance regenerative signaling requires nonlinear coupling in the gap junctions. Second, we show that even with nonlinear gap junctions, long-distance regenerative signaling is favored when the internal Ca(2+ dynamics implements frequency modulation-encoding oscillations with pulsating dynamics, while amplitude modulation-encoding dynamics tends to restrict the propagation range. As a result, spatially heterogeneous molecular properties and/or weak couplings are shown to give rise to rich spatiotemporal dynamics that support complex propagation behaviors. These results shed new light on the mechanisms implicated in the propagation of Ca(2+ waves across astrocytes and the precise conditions under which glial cells may participate in information processing in the brain.

  19. Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes.

    Science.gov (United States)

    Xia, Cong-Yuan; Chu, Shi-Feng; Zhang, Shuai; Gao, Yan; Ren, Qian; Lou, Yu-Xia; Luo, Piao; Tian, Man-Tong; Wang, Zhi-Qi; Du, Guo-Hua; Tomioka, Yoshihisa; Yamakuni, Tohru; Zhang, Yi; Wang, Zhen-Zhen; Chen, Nai-Hong

    2017-08-17

    Ginsenoside Rg1 (Rg1), one of the major bioactive ingredients of Panax ginseng C. A. Mey, has neuroprotective effects in animal models of depression, but the mechanism underlying these effects is still largely unknown AIM OF THE STUDY: Gap junction intercellular communication (GJIC) dysfunction is a potentially novel pathogenic mechanism for depression. Thus, we investigated that whether antidepressant-like effects of Rg1 were related to GJIC. Primary rat prefrontal cortical and hippocampal astrocytes cultures were treated with 50μM CORT for 24h to induce gap junction damage. Rg1 (0.1, 1, or 10μM) or fluoxetine (1μM) was added 1h prior to CORT treatment. A scrape loading and dye transfer assay was performed to identify the functional capacity of gap junctions. Western blot was used to detect the expression and phosphorylation of connexin43 (Cx43), the major component of gap junctions. Treatment of primary astrocytes with CORT for 24h inhibited GJIC, decreased total Cx43 expression, and increased the phosphorylation of Cx43 at serine368 in a dose-dependent manner. Pre-treatment with 1μM and 10μM Rg1 significantly improved GJIC in CORT-treated astrocytes from the prefrontal cortex and hippocampus, respectively, and this was accompanied by upregulation of Cx43 expression and downregulation of Cx43 phosphorylation. These findings provide the first evidence indicating that Rg1 can alleviate CORT-induced gap junction dysfunction, which may have clinical significance in the treatment of depression. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  20. 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

  1. Oligomeric structure and functional characterization of Caenorhabditis elegans Innexin-6 gap junction protein.

    Science.gov (United States)

    Oshima, Atsunori; Matsuzawa, Tomohiro; Nishikawa, Kouki; Fujiyoshi, Yoshinori

    2013-04-12

    Innexin is the molecular component of invertebrate gap junctions. Here we successfully expressed and purified Caenorhabditis elegans innexin-6 (INX-6) gap junction channels and characterized the molecular dimensions and channel permeability using electron microscopy (EM) and microinjection of fluorescent dye tracers, respectively. Negative staining and thin-section EM of isolated INX-6 gap junction membranes revealed a loosely packed hexagonal lattice and a greater cross-sectional width than that of connexin26 and connexin43 (Cx43)-GFP. In gel filtration analysis, the elution profile of purified INX-6 channels in dodecyl maltoside solution exhibited a peak at ∼400 kDa that was shifted to ∼800 kDa in octyl glucose neopentyl glycol. We also obtained the class averages of purified INX-6 channels from these peak fractions by single particle analysis. The class average from the ∼800-kDa fraction showed features of the junction form with a longitudinal height of 220 Å, a channel diameter of 110 Å in the absence of detergent micelles, and an extracellular gap space of 60 Å, whereas the class averages from the ∼400-kDa fraction showed diameters of up to 140 Å in the presence of detergent micelles. These findings indicate that the purified INX-6 channels are predominantly hemichannels in dodecyl maltoside and docked junction channels in octyl glucose neopentyl glycol. Dye transfer experiments revealed that the INX-6-GFP-His channels are permeable to 3- and 10-kDa tracers, whereas no significant amounts of these tracers passed through the Cx43-GFP channels. Based on these findings, INX-6 channels have a larger overall structure and greater permeability than connexin channels.

  2. Oligomeric Structure and Functional Characterization of Caenorhabditis elegans Innexin-6 Gap Junction Protein*

    Science.gov (United States)

    Oshima, Atsunori; Matsuzawa, Tomohiro; Nishikawa, Kouki; Fujiyoshi, Yoshinori

    2013-01-01

    Innexin is the molecular component of invertebrate gap junctions. Here we successfully expressed and purified Caenorhabditis elegans innexin-6 (INX-6) gap junction channels and characterized the molecular dimensions and channel permeability using electron microscopy (EM) and microinjection of fluorescent dye tracers, respectively. Negative staining and thin-section EM of isolated INX-6 gap junction membranes revealed a loosely packed hexagonal lattice and a greater cross-sectional width than that of connexin26 and connexin43 (Cx43)-GFP. In gel filtration analysis, the elution profile of purified INX-6 channels in dodecyl maltoside solution exhibited a peak at ∼400 kDa that was shifted to ∼800 kDa in octyl glucose neopentyl glycol. We also obtained the class averages of purified INX-6 channels from these peak fractions by single particle analysis. The class average from the ∼800-kDa fraction showed features of the junction form with a longitudinal height of 220 Å, a channel diameter of 110 Å in the absence of detergent micelles, and an extracellular gap space of 60 Å, whereas the class averages from the ∼400-kDa fraction showed diameters of up to 140 Å in the presence of detergent micelles. These findings indicate that the purified INX-6 channels are predominantly hemichannels in dodecyl maltoside and docked junction channels in octyl glucose neopentyl glycol. Dye transfer experiments revealed that the INX-6-GFP-His channels are permeable to 3- and 10-kDa tracers, whereas no significant amounts of these tracers passed through the Cx43-GFP channels. Based on these findings, INX-6 channels have a larger overall structure and greater permeability than connexin channels. PMID:23460640

  3. Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides.

    Science.gov (United States)

    Dhein, Stefan; Hagen, Anja; Jozwiak, Joanna; Dietze, Anna; Garbade, Jens; Barten, Markus; Kostelka, Martin; Mohr, Friedrich-Wilhelm

    2010-03-01

    Co-ordinated electrical activation of the heart is maintained by intercellular coupling of cardiomyocytes via gap junctional channels located in the intercalated disks. These channels consist of two hexameric hemichannels, docked to each other, provided by either of the adjacent cells. Thus, a complete gap junction channel is made from 12 protein subunits, the connexins. While 21 isoforms of connexins are presently known, cardiomyocytes typically are coupled by Cx43 (most abundant), Cx40 or Cx45. Some years ago, antiarrhythmic peptides were discovered and synthesised, which were shown to increase macroscopic gap junction conductance (electrical coupling) and enhance dye transfer (metabolic coupling). The lead substance of these peptides is AAP10 (H-Gly-Ala-Gly-Hyp-Pro-Tyr-CONH(2)), a peptide with a horseshoe-like spatial structure as became evident from two-dimensional nuclear magnetic resonance studies. A stable D: -amino-acid derivative of AAP10, rotigaptide, as well as a non-peptide analogue, gap-134, has been developed in recent years. Antiarrhythmic peptides act on Cx43 and Cx45 gap junctions but not on Cx40 channels. AAP10 has been shown to enhance intercellular communication in rat, rabbit and human cardiomyocytes. Antiarrhythmic peptides are effective against ventricular tachyarrhythmias, such as late ischaemic (type IB) ventricular fibrillation, CaCl(2) or aconitine-induced arrhythmia. Interestingly, the effect of antiarrhythmic peptides is higher in partially uncoupled cells and was shown to be related to maintained Cx43 phosphorylation, while arrhythmogenic conditions like ischaemia result in Cx43 dephosphorylation and intercellular decoupling. It is still a matter of debate whether these drugs also act against atrial fibrillation. The present review outlines the development of this group of peptides and derivatives, their mode of action and molecular mechanisms, and discusses their possible therapeutic potential.

  4. Do gap junctions regulate synchrony in the parkinsonian basal ganglia?

    NARCIS (Netherlands)

    Schwab, B.C.

    2016-01-01

    Patients with Parkinson’s disease (PD) typically suffer severely from different types of symptoms. Motor symptoms, restricting the patients’ ability to perform controlled movements in daily life, are of special clinical interest and have been related to neural activity in the basal ganglia.

  5. A versatile optical junction using photonic band-gap guidance and self collimation

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Man Mohan; Medhekar, Sarang, E-mail: smedhekarbit@gmail.com [Centre for Applied Physics, Central University of Jharkhand, Ranchi 835205 (India)

    2014-09-29

    We show that it is possible to design two photonic crystal (PC) structures such that an optical beam of desired wavelength gets guided within the line defect of the first structure (photonic band gap guidance) and the same beam gets guided in the second structure by self-collimation. Using two dimensional simulation of a design made of the combination of these two structures, we propose an optical junction that allows for crossing of two optical signals of same wavelength and same polarization with very low crosstalk. Moreover, the junction can be operated at number of frequencies in a wide range. Crossing of multiple beams with very low cross talk is also possible. The proposed junction should be important in future integrated photonic circuits.

  6. Gap Junctions Contribute to the Regulation of Walking-Like Activity in the Adult Mudpuppy (Necturus Maculatus.

    Directory of Open Access Journals (Sweden)

    Igor Lavrov

    Full Text Available Although gap junctions are widely expressed in the developing central nervous system, the role of electrical coupling of neurons and glial cells via gap junctions in the spinal cord in adults is largely unknown. We investigated whether gap junctions are expressed in the mature spinal cord of the mudpuppy and tested the effects of applying gap junction blocker on the walking-like activity induced by NMDA or glutamate in an in vitro mudpuppy preparation. We found that glial and neural cells in the mudpuppy spinal cord expressed different types of connexins that include connexin 32 (Cx32, connexin 36 (Cx36, connexin 37 (Cx37, and connexin 43 (Cx43. Application of a battery of gap junction blockers from three different structural classes (carbenexolone, flufenamic acid, and long chain alcohols substantially and consistently altered the locomotor-like activity in a dose-dependent manner. In contrast, these blockers did not significantly change the amplitude of the dorsal root reflex, indicating that gap junction blockers did not inhibit neuronal excitability nonselectively in the spinal cord. Taken together, these results suggest that gap junctions play a significant modulatory role in the spinal neural networks responsible for the generation of walking-like activity in the adult mudpuppy.

  7. The effects of the Histone Deacetylase (HDAC Inhibitor 4-Phenylbutyrate on gap junction conductance and permeability

    Directory of Open Access Journals (Sweden)

    Joshua eKaufman

    2013-09-01

    Full Text Available Longitudinal resistance is a key factor in determining cardiac action potential propagation. Action potential conduction velocity has been shown to be proportional to the square root of longitudinal resistance. A major determinant of longitudinal resistance in myocardium is the gap junction channel, comprised of connexin proteins. Within the ventricular myocardium connexin 43 (Cx43 is the dominantly expressed connexin. Reduced numbers of gap junction channels will result in an increase in longitudinal resistance creating the possibility of slowed conduction velocity while increased numbers of channels would potentially result in an increase in conduction velocity. We sought to determine if inhibition of histone deacetylase (HDAC by 4-phenylbutyrate (4-PB, a known inhibitor of HDAC resulted in an increase in junctional conductance and permeability, which is not the result of changes in single channel unitary conductance. These experiments were performed using HEK-293 cells and HeLa cells stably transfected with Cx43. Following treatment with increasing concentrations of 4-PB up-regulation of Cx43 was observed via Western blot analysis. Junctional (gj conductance and unitary single channel conductance were measured via whole-cell patch clamp. In addition intercellular transfer of Lucifer Yellow (LY was determined by fluorescence microscopy. The data in this study indicates that 4-PB is able to enhance functional Cx43 gap junction coupling as indicated by LY dye transfer and multichannel and single channel data along with Western blot analysis. As a corollary, pharmacological agents such as 4-PB have the potential, by increasing intercellular coupling, to reduce the effect of ischemia. It remains to be seen whether drugs like 4-PB will be effective in preventing cardiac maladies.

  8. Effect of sound on gap-junction-based intercellular signaling: Calcium waves under acoustic irradiation.

    Science.gov (United States)

    Deymier, P A; Swinteck, N; Runge, K; Deymier-Black, A; Hoying, J B

    2015-01-01

    We present a previously unrecognized effect of sound waves on gap-junction-based intercellular signaling such as in biological tissues composed of endothelial cells. We suggest that sound irradiation may, through temporal and spatial modulation of cell-to-cell conductance, create intercellular calcium waves with unidirectional signal propagation associated with nonconventional topologies. Nonreciprocity in calcium wave propagation induced by sound wave irradiation is demonstrated in the case of a linear and a nonlinear reaction-diffusion model. This demonstration should be applicable to other types of gap-junction-based intercellular signals, and it is thought that it should be of help in interpreting a broad range of biological phenomena associated with the beneficial therapeutic effects of sound irradiation and possibly the harmful effects of sound waves on health.

  9. Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

    Science.gov (United States)

    Todman, M G; Baines, R A; Stebbings, L A; Davies, J A; Bacon, J P

    1999-01-01

    Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.

  10. A unified framework for spiking and gap-junction interactions in distributed neuronal network simulations

    Directory of Open Access Journals (Sweden)

    Jan eHahne

    2015-09-01

    Full Text Available Contemporary simulators for networks of point and few-compartment model neurons come with a plethora of ready-to-use neuron and synapse models and support complex network topologies. Recent technological advancements have broadened the spectrum of application further to the efficient simulation of brain-scale networks on supercomputers. In distributed network simulations the amount of spike data that accrues per millisecond and process is typically low, such that a common optimization strategy is to communicate spikes at relatively long intervals, where the upper limit is given by the shortest synaptic transmission delay in the network. This approach is well-suited for simulations that employ only chemical synapses but it has so far impeded the incorporation of gap-junction models, which require instantaneous neuronal interactions. Here, we present a numerical algorithm based on a waveform-relaxation technique which allows for network simulations with gap junctions in a way that is compatible with the delayed communication strategy. Using a reference implementation in the NEST simulator, we demonstrate that the algorithm and the required data structures can be smoothly integrated with existing code such that they complement the infrastructure for spiking connections. To show that the unified framework for gap-junction and spiking interactions achieves high performance and delivers high accuracy...

  11. 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

  12. Phylogenetic and bioinformatic analysis of gap junction-related proteins, innexins, pannexins and connexins.

    Science.gov (United States)

    Fushiki, Daisuke; Hamada, Yasuo; Yoshimura, Ryoichi; Endo, Yasuhisa

    2010-04-01

    All multi-cellular animals, including hydra, insects and vertebrates, develop gap junctions, which communicate directly with neighboring cells. Gap junctions consist of protein families called connexins in vertebrates and innexins in invertebrates. Connexins and innexins have no homology in their amino acid sequence, but both are thought to have some similar characteristics, such as a tetra-membrane-spanning structure, formation of a channel by hexamer, and transmission of small molecules (e.g. ions) to neighboring cells. Pannexins were recently identified as a homolog of innexins in vertebrate genomes. Although pannexins are thought to share the function of intercellular communication with connexins and innexins, there is little information about the relationship among these three protein families of gap junctions. We phylgenetically and bioinformatically examined these protein families and other tetra-membrane-spanning proteins using a database and three analytical softwares. The clades formed by pannexin families do not belong to the species classification but do to paralogs of each member of pannexins. Amino acid sequences of pannexins are closely related to those of innexins but less to those of connexins. These data suggest that innexins and pannexins have a common origin, but the relationship between innexins/pannexins and connexins is as slight as that of other tetra-membrane-spanning members.

  13. Chemical Synaptic and Gap Junctional Interactions Between Principal Neurons: Partners in Epileptogenesis

    Science.gov (United States)

    Traub, Roger D.; Cunningham, Mark O.; Whittington, Miles A.

    2010-01-01

    Field potential signals, corresponding to electrographic seizures in cortical structures, often contain two components, which sometimes appear to be separable and other times to be superimposed. The first component consists of low-amplitude very fast oscillations (VFO, > 70–80 Hz); the second component consists of larger amplitude transients, lasting tens to hundreds of ms, and variously called population spikes, EEG spikes, or bursts – terms chosen in part because of the cellular correlates of the field events. To first approximation, the two components arise because of distinctive types of cellular interactions: gap junctions for VFO (a model of which is reviewed in the following), and recurrent synaptic excitation and/or inhibition for the transients. With in vitro studies of epileptic human neocortical tissue, it is possible to elicit VFO alone, or VFO superimposed on a large transient, but not a large transient without the VFO. If such observations prove to be general, they would imply that gap junction-mediated interactions are the primary factor in epileptogenesis. It appears to be the case then, that in the setting of seizure initiation (but not necessarily under physiological conditions), the gain of gap junction-mediated circuits can actually be larger than the gain in excitatory synaptic circuits. PMID:21168305

  14. Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

    International Nuclear Information System (INIS)

    Ganesan, Shanthi; Nteeba, Jackson; Keating, Aileen F.

    2015-01-01

    The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) were dosed with sesame oil or DMBA (1 mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function. - Highlights: • Ovarian gap junction proteins are affected by ovarian aging and obesity. • DMBA exposure negatively impacts gap junction proteins. • Altered gap junction proteins may contribute to infertility

  15. Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2015-01-01

    The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) were dosed with sesame oil or DMBA (1 mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function. - Highlights: • Ovarian gap junction proteins are affected by ovarian aging and obesity. • DMBA exposure negatively impacts gap junction proteins. • Altered gap junction proteins may contribute to infertility.

  16. Targeting neuronal gap junctions in mouse retina offers neuroprotection in glaucoma

    Science.gov (United States)

    Kumar, Sandeep; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Viswanathan, Suresh; Bloomfield, Stewart A.

    2017-01-01

    The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma. Further, functional parameters that are negatively affected in glaucoma, including the electroretinogram, visual evoked potential, visual spatial acuity, and contrast sensitivity, were maintained at control levels when Cx36 was ablated. Neuronal GJs may thus represent potential therapeutic targets to prevent the progressive neurodegeneration and visual impairment associated with glaucoma. PMID:28604388

  17. Inhibition of dye-coupling in Patella (mollusca) embryos by microinjection of antiserum against Nephrops (arthropoda) gap junctions

    NARCIS (Netherlands)

    Serras, F.; Buultjens, T.E.J.; Finbow, M.E.

    1988-01-01

    Antiserum raised against Nephrops gap junctions was injected into single cells of the 2-, 4-, 8-, 16-, and 32-cell stage of the Patella vulgata embryos. The pattern of junctional communication by iontophoresis of Lucifer Yellow CH was tested at the 32-cell stage. The results show that the normal

  18. Costimulation of N-methyl-d-aspartate and muscarinic neuronal receptors modulates gap junctional communication in striatal astrocytes

    OpenAIRE

    Rouach, N.; Tencé, M.; Glowinski, J.; Giaume, C.

    2002-01-01

    Cocultures of neurons and astrocytes from the rat striatum were used to determine whether the stimulation of neuronal receptors could affect the level of intercellular communication mediated by gap junctions in astrocytes. The costimulation of N-methyl-D-asparte (NMDA) and muscarinic receptors led to a prominent reduction of astrocyte gap junctional communication (GJC) in coculture. This treatment was not effective in astrocyte cultures, these cells being devoid of NMDA receptors. Both types ...

  19. 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.

  20. Gap junctions and memory: an investigation using a single trial discrimination avoidance task for the neonate chick.

    Science.gov (United States)

    Verwey, L J; Edwards, T M

    2010-02-01

    Gap junctions are important to how the brain functions but are relatively under-investigated with respect to their contribution towards behaviour. In the present study a single trial discrimination avoidance task was used to investigate the effect of the gap junction inhibitor 18-alpha-glycyrrhetinic acid (alphaGA) on retention. Past studies within our research group have implied a potential role for gap junctions during the short-term memory (STM) stage which decays by 15 min post-training. A retention function study comparing 10 microM alphaGA and vehicle given immediately post-training demonstrated a significant main effect for drug with retention loss at all times of test (10-180 min post-training). Given that the most common gap junction in the brain is that forming the astrocytic network it is reasonable to conclude that alphaGA was acting upon these. To confirm this finding and interpretation two additional investigations were undertaken using endothelin-1 (ET-1) and ET-1+tolbutamide. Importantly, a retention function study using 10nM ET-1 replicated the retention loss observed for alphaGA. In order to confirm that ET-1 was acting on astrocytic gap junctions the amnestic action of ET-1 was effectively challenged with increasing concentrations of tolbutamide. The present findings suggest that astrocytic gap junctions are important for memory processing. Copyright 2009 Elsevier Inc. All rights reserved.

  1. Astrocytic Gap Junctional Communication is Reduced in Amyloid-β-Treated Cultured Astrocytes, but not in Alzheimer's Disease Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Nancy F Cruz

    2010-07-01

    Full Text Available Alzheimer's disease is characterized by accumulation of amyloid deposits in brain, progressive cognitive deficits and reduced glucose utilization. Many consequences of the disease are attributed to neuronal dysfunction, but roles of astrocytes in its pathogenesis are not well understood. Astrocytes are extensively coupled via gap junctions, and abnormal trafficking of metabolites and signalling molecules within astrocytic syncytia could alter functional interactions among cells comprising the neurovascular unit. To evaluate the influence of amyloid-β on astrocyte gap junctional communication, cultured astrocytes were treated with monomerized amyloid-β1-40 (1 μmol/l for intervals ranging from 2 h to 5 days, and the areas labelled by test compounds were determined by impaling a single astrocyte with a micropipette and diffusion of material into coupled cells. Amyloid-β-treated astrocytes had rapid, sustained 50-70% reductions in the area labelled by Lucifer Yellow, anionic Alexa Fluor® dyes and energy-related compounds, 6-NBDG (a fluorescent glucose analogue, NADH and NADPH. Amyloid-β treatment also caused a transient increase in oxidative stress. In striking contrast with these results, spreading of Lucifer Yellow within astrocytic networks in brain slices from three regions of 8.5-14-month-old control and transgenic Alzheimer's model mice was variable, labelling 10-2000 cells; there were no statistically significant differences in the number of dye-labelled cells among the groups or with age. Thus amyloid-induced dysfunction of gap junctional communication in cultured astrocytes does not reflect the maintenance of dye transfer through astrocytic syncytial networks in transgenic mice; the pathophysiology of Alzheimer's disease is not appropriately represented by the cell culture system.

  2. Astrocytic gap junctional communication is reduced in amyloid-β-treated cultured astrocytes, but not in Alzheimer's disease transgenic mice.

    Science.gov (United States)

    Cruz, Nancy F; Ball, Kelly K; Dienel, Gerald A

    2010-08-17

    Alzheimer's disease is characterized by accumulation of amyloid deposits in brain, progressive cognitive deficits and reduced glucose utilization. Many consequences of the disease are attributed to neuronal dysfunction, but roles of astrocytes in its pathogenesis are not well understood. Astrocytes are extensively coupled via gap junctions, and abnormal trafficking of metabolites and signalling molecules within astrocytic syncytia could alter functional interactions among cells comprising the neurovascular unit. To evaluate the influence of amyloid-beta on astrocyte gap junctional communication, cultured astrocytes were treated with monomerized amyloid-β(1-40) (1 μmol/l) for intervals ranging from 2 h to 5 days, and the areas labelled by test compounds were determined by impaling a single astrocyte with a micropipette and diffusion of material into coupled cells. Amyloid-β-treated astrocytes had rapid, sustained 50-70% reductions in the area labelled by Lucifer Yellow, anionic Alexa Fluor® dyes and energy-related compounds, 6-NBDG (a fluorescent glucose analogue), NADH and NADPH. Amyloid-β treatment also caused a transient increase in oxidative stress. In striking contrast with these results, spreading of Lucifer Yellow within astrocytic networks in brain slices from three regions of 8.5-14-month-old control and transgenic Alzheimer's model mice was variable, labelling 10-2000 cells; there were no statistically significant differences in the number of dye-labelled cells among the groups or with age. Thus amyloid-induced dysfunction of gap junctional communication in cultured astrocytes does not reflect the maintenance of dye transfer through astrocytic syncytial networks in transgenic mice; the pathophysiology of Alzheimer's disease is not appropriately represented by the cell culture system.

  3. Entrainment, retention, and transport of freely swimming fish in junction gaps between commercial barges operating on the Illinois Waterway

    Science.gov (United States)

    Davis, Jeremiah J.; Jackson, P. Ryan; Engel, Frank; LeRoy, Jessica Z.; Neeley, Rebecca N.; Finney, Samuel T.; Murphy, Elizabeth A.

    2016-01-01

    Large Electric Dispersal Barriers were constructed in the Chicago Sanitary and Ship Canal (CSSC) to prevent the transfer of invasive fish species between the Mississippi River Basin and the Great Lakes Basin while simultaneously allowing the passage of commercial barge traffic. We investigated the potential for entrainment, retention, and transport of freely swimming fish within large gaps (> 50 m3) created at junction points between barges. Modified mark and capture trials were employed to assess fish entrainment, retention, and transport by barge tows. A multi-beam sonar system enabled estimation of fish abundance within barge junction gaps. Barges were also instrumented with acoustic Doppler velocity meters to map the velocity distribution in the water surrounding the barge and in the gap formed at the junction of two barges. Results indicate that the water inside the gap can move upstream with a barge tow at speeds near the barge tow travel speed. Water within 1 m to the side of the barge junction gaps was observed to move upstream with the barge tow. Observed transverse and vertical water velocities suggest pathways by which fish may potentially be entrained into barge junction gaps. Results of mark and capture trials provide direct evidence that small fish can become entrained by barges, retained within junction gaps, and transported over distances of at least 15.5 km. Fish entrained within the barge junction gap were retained in that space as the barge tow transited through locks and the Electric Dispersal Barriers, which would be expected to impede fish movement upstream.

  4. 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.

  5. Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

    International Nuclear Information System (INIS)

    Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue; Panda, Satya P.

    2011-01-01

    Highlights: → Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. → First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. → Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. → Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. → Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b 5 and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.

  6. TC-PTP directly interacts with connexin43 to regulate gap junction intercellular communication

    Science.gov (United States)

    Li, Hanjun; Spagnol, Gaelle; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

    2014-01-01

    ABSTRACT Protein kinases have long been reported to regulate connexins; however, little is known about the involvement of phosphatases in the modulation of intercellular communication through gap junctions and the subsequent downstream effects on cellular processes. Here, we identify an interaction between the T-cell protein tyrosine phosphatase (TC-PTP, officially known as PTPN2) and the carboxyl terminus of connexin43 (Cx43, officially known as GJA1). Two cell lines, normal rat kidney (NRK) cells endogenously expressing Cx43 and an NRK-derived cell line expressing v-Src with temperature-sensitive activity, were used to demonstrate that EGF and v-Src stimulation, respectively, induced TC-PTP to colocalize with Cx43 at the plasma membrane. Cell biology experiments using phospho-specific antibodies and biophysical assays demonstrated that the interaction is direct and that TC-PTP dephosphorylates Cx43 residues Y247 and Y265, but does not affect v-Src. Transfection of TC-PTP also indirectly led to the dephosphorylation of Cx43 S368, by inactivating PKCα and PKCδ, with no effect on the phosphorylation of S279 and S282 (MAPK-dependent phosphorylation sites). Dephosphorylation maintained Cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-Src-mediated phosphorylation of Cx43. Understanding dephosphorylation, along with the well-documented roles of Cx43 phosphorylation, might eventually lead to methods to modulate the regulation of gap junction channels, with potential benefits for human health. PMID:24849651

  7. Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

    Energy Technology Data Exchange (ETDEWEB)

    Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States); Panda, Satya P., E-mail: panda@uthscsa.edu [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States)

    2011-08-05

    Highlights: {yields} Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. {yields} First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. {yields} Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. {yields} Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. {yields} Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b{sub 5} and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.

  8. Intracerebroventricular Injection of Lipopolysaccharide Increases Gene Expression of Connexin32 Gap Junction in Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Mohammad Abbasian

    2013-11-01

    Full Text Available Introduction: Gap junctions are intercellular membrane channels that provide direct cytoplasmic continuity between adjacent cells. This communication can be affected by changes in expression of gap junctional subunits called Connexins (Cx. Changes in the expression and function of connexins are associated with number of brain neurodegenerative diseases. Neuroinflammation is a hallmark of various central nervous system (CNS diseases, like multiple sclerosis, Alzheimer's disease and epilepsy. Neuroinflammation causes change in Connexins expression. Hippocampus, one of the main brain regions with a wide network of Gap junctions between different neural cell types, has particular vulnerability to damage and consequent inflammation. Cx32 – among Connexins– is expressed in hippocampal Olygodandrocytes and some neural subpopulations. Although multiple lines of evidence indicate that there is an association between neuroinflammation and the expression of connexin, the direct effect of neuroinflammation on the expression of connexins has not been well studied. In the present study, the effect of neuroinflammation induced by the Lipopolysaccharide (LPS on Cx32 gene and protein expressions in rat hippocampus is evaluated. Methods: LPS (2.5μg/rat was infused into the rat cerebral ventricles for 14 days. Cx32 mRNA and protein levels were measured by Real Time PCR and Western Blot after 1st, 7th and 14th injection of LPS in the hippocampus. Results: Significant increase in Cx32 mRNA expression was observed after 7th injection of LPS (P<0.001. However, no significant change was observed in Cx32 protein level. Conclusion: LPS seems to modify Cx32 GJ communication in the hippocampus at transcription level but not at translation or post-translation level. In order to have a full view concerning modification of Cx32 GJ communication, effect of LPS on Cx32 channel gating should also be determined.

  9. Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice.

    Science.gov (United States)

    Szilvásy-Szabó, Anett; Varga, Edina; Beliczai, Zsuzsa; Lechan, Ronald M; Fekete, Csaba

    2017-10-15

    Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes. The Cx43-blocker, carbenoxolone, inhibited spreading of LY. The greatest density of Cx43-immunoreactive spots was observed in the cell membrane of α-tanycyte cell bodies. Cx43-immunoreactivity was also present in the membrane of β-tanycyte cell bodies, but in lower density. Processes of both types of tanycytes also contained Cx43-immunoreactivity. At the ultrastructural level, Cx43-immunoreactivity was present in the cell membrane of all types of tanycytes including their ventricular surface, but gap junctions were more frequent among α-tanycytes. Cx43-immunoreactivity was also observed in the cell membrane between contacting tanycyte endfeet processes, and between tanycyte endfeet process and axon varicosities in the external zone of the median eminence and capillaries in the arcuate nucleus and median eminence. These results suggest that gap junctions are present not only among tanycytes, but also between tanycytes and the axons of hypophysiotropic neurons. Cx43 hemichannels may also facilitate the transport between tanycytes and extracellular fluids, including the cerebrospinal fluid, extracellular space of the median eminence and bloodstream. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 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.

  11. Connexin 30 expression and frequency of connexin heterogeneity in astrocyte gap junction plaques increase with age in the rat retina.

    Directory of Open Access Journals (Sweden)

    Hussein Mansour

    Full Text Available We investigated age-associated changes in retinal astrocyte connexins (Cx by assaying Cx numbers, plaque sizes, protein expression levels and heterogeneity of gap junctions utilizing six-marker immunohistochemistry (IHC. We compared Wistar rat retinal wholemounts in animals aged 3 (young adult, 9 (middle-aged and 22 months (aged. We determined that retinal astrocytes have gap junctions composed of Cx26, -30, -43 and -45. Cx30 was consistently elevated at 22 months compared to younger ages both when associated with parenchymal astrocytes and vascular-associated astrocytes. Not only was the absolute number of Cx30 plaques significantly higher (P<0.05 but the size of the plaques was significantly larger at 22 months compared to younger ages (p<0.05. With age, Cx26 increased significantly initially, but returned to basal levels; whereas Cx43 expression remained low and stable with age. Evidence that astrocytes alter connexin compositions of gap junctions was demonstrated by the significant increase in the number of Cx26/Cx45 gap junctions with age. We also found gap junctions comprised of 1, 2, 3 or 4 Cx proteins suggesting that retinal astrocytes use various connexin protein combinations in their gap junctions during development and aging. These data provides new insight into the dynamic and extensive Cx network utilized by retinal astrocytes for communication within both the parenchyma and vasculature for the maintenance of normal retinal physiology with age. This characterisation of the changes in astrocytic gap junctional communication with age in the CNS is crucial to the understanding of physiological aging and age-related neurodegenerative diseases.

  12. Fractional Josephson vortices in two-gap superconductor long Josephson junctions

    Science.gov (United States)

    Kim, Ju

    2014-03-01

    We investigated the phase dynamics of long Josephson junctions (LJJ) with two-gap superconductors in the broken time reversal symmetry state. In this LJJ, spatial phase textures (i-solitons) can be excited due to the presence of two condensates and the interband Joesphson effect between them. The presence of a spatial phase texture in each superconductor layer leads to a spatial variation of the critical current density between the superconductor layers. We find that this spatial dependence of the crtitical current density can self-generate magnetic flux in the insulator layer, resulting in Josephson vortices with fractional flux quanta. Similar to the situation in a YBa2 Cu3O7 - x superconductor film grain boundary, the fractionalization of a Josephson vortex arises as a response to either periodic or random excitation of i-solitions. This suggests that magnetic flux measurements may be used to probe i-soliton excitations in multi-gap superconductor LJJs.

  13. Two-dimensional macroscopic quantum tunneling in multi-gap superconductor Josephson junctions

    International Nuclear Information System (INIS)

    Asai, Hidehiro; Kawabata, Shiro; Ota, Yukihiro; Machida, Masahiko

    2014-01-01

    Low-temperature characters of superconducting devices yield definite probes for different superconducting phenomena. We study the macroscopic quantum tunneling (MQT) in a Josephson junction, composed of a single-gap superconductor and a two-gap superconductor. Since this junction has two kinds to the superconducting phase differences, calculating the MQT escape rate requires the analysis of quantum tunneling in a multi-dimensional configuration space. Our approach is the semi-classical approximation along a 1D curve in a 2D potential- energy landscape, connecting two adjacent potential (local) minimums through a saddle point. We find that this system has two plausible tunneling paths; an in-phase path and an out-of-phase path. The former is characterized by the Josephson-plasma frequency, whereas the latter is by the frequency of the characteristic collective mode in a two-band superconductor, Josephson- Leggett mode. Depending on external bias current and inter-band Josephson-coupling energy, one of them mainly contributes to the MQT. Our numerical calculations show that the difference between the in-phase path and the out-of-phase path is manifest, with respect to the bias- current-dependence of the MQT escape rate. This result suggests that our MQT setting be an indicator of the Josephson-Leggett mode

  14. Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat

    International Nuclear Information System (INIS)

    Mally, Angela; Chipman, James Kevin

    2002-01-01

    Non-genotoxic carcinogens are thought to induce tumour formation by disturbing the balance between cell growth and cell death. Gap junctions (GJ) contribute to the maintenance of tissue homeostasis by allowing the intercellular exchange of growth regulatory signals and potential inhibition of GJ intercellular communication through loss of connexin (Cx) plaques has been shown to be involved in the cancer process. We have investigated the time- and dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap junction plaque expression in relation to proliferation and apoptosis. With the exception of limonene, all non-genotoxic carcinogens significantly reduced the expression of GJ plaques containing Cx32 in their respective target tissue. No dose-dependent, significant effects were seen in non-target organs. Although alteration of Cx32 expression did not appear to correlate with induction of cell proliferation, out data suggest that the interaction of both processes--interference of GJ coupled with a proliferative stimulus (at the carcinogenic dose)--may be important in non-genotoxic carcinogenesis and provide a potential alert for non-genotoxic carcinogens in short-term toxicity tests

  15. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

    Directory of Open Access Journals (Sweden)

    Meeri Eeva-Liisa Mäkinen

    2018-03-01

    Full Text Available The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging and temporal resolution microelectrode array (MEA. We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling.

  16. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

    Science.gov (United States)

    Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

    2018-01-01

    The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893

  17. The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts.

    Science.gov (United States)

    Zhang, Yuan; Tan, Xiaoming; Xue, Lianfang

    2018-01-01

    The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43). The results revealed that exposure of human lung fibroblast cell line to LPS for 24 h increased the apoptosis, and pretreatment of dexmedetomidine and 18α-GA significantly reduced LPS-induced apoptosis. Dexmedetomidine exposure for 1 h inhibited gap junction function mainly via a decrease in Cx43 protein levels in human lung fibroblast cell line. These results demonstrated that the inhibition of gap junction intercellular communication by dexmedetomidine affected the LPS-induced apoptosis through inhibition of gap junction function by reducing Cx43 protein levels. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Two coupled Josephson junctions: dc voltage controlled by biharmonic current

    International Nuclear Information System (INIS)

    Machura, L; Spiechowicz, J; Kostur, M; Łuczka, J

    2012-01-01

    We study transport properties of two Josephson junctions coupled by an external shunt resistance. One of the junctions (say, the first) is driven by an unbiased ac current consisting of two harmonics. The device can rectify the ac current yielding a dc voltage across the first junction. For some values of coupling strength, controlled by an external shunt resistance, a dc voltage across the second junction can be generated. By variation of system parameters such as the relative phase or frequency of two harmonics, one can conveniently manipulate both voltages with high efficiency, e.g. changing the dc voltages across the first and second junctions from positive to negative values and vice versa. (paper)

  19. Perfect GMR effect in gapped graphene-based ferromagnetic normal ferromagnetic junctions

    Institute of Scientific and Technical Information of China (English)

    Hossein Karbaschi; Gholam Reza Rashedi

    2015-01-01

    We investigate the quantum transport property in gapped graphene-based ferromagnetic/normal/ferromagnetic (FG/NG/FG) junctions by using the Dirac–Bogoliubov–de Gennes equation. The graphene is fabricated on SiC and BN substrates separately, so carriers in FG/NG/FG structures are considered as massive relativistic particles. Transmission prob-ability, charge, and spin conductances are studied as a function of exchange energy of ferromagnets (h), size of graphene gap, and thickness of normal graphene region (L) respectively. Using the experimental values of Fermi energy in the normal graphene part (EFN∼400 meV) and energy gap in graphene (260 meV for SiC and 50 meV for BN substrate), it is shown that this structure can be used for both spin-up and spin-down polarized current. The latter case has different behavior of gapped FG/NG/FG from that of gapless FG/NG/FG structures. Also perfect charge giant magnetoresistance is observed in a range of EFN−mv2F

  20. 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.

  1. Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching

    OpenAIRE

    Kuzma-Kuzniarska, Maria; Yapp, Clarence; Pearson-Jones, Thomas W.; Jones, Andrew K.; Hulley, Philippa A.

    2014-01-01

    Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows qu...

  2. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne

    2003-01-01

    The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting...... in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal...... of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx...

  3. ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs

    DEFF Research Database (Denmark)

    Xing, Dezhi; Kjølbye, Anne Louise; Nielsen, Morten S

    2003-01-01

    INTRODUCTION: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. METHODS AND RESULTS: Voltage clamp experiments...... demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation...... AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT....

  4. The beneficial effects of cumulus cells and oocyte-cumulus cell gap junctions depends on oocyte maturation and fertilization methods in mice

    Directory of Open Access Journals (Sweden)

    Cheng-Jie Zhou

    2016-03-01

    Full Text Available Cumulus cells are a group of closely associated granulosa cells that surround and nourish oocytes. Previous studies have shown that cumulus cells contribute to oocyte maturation and fertilization through gap junction communication. However, it is not known how this gap junction signaling affects in vivo versus in vitro maturation of oocytes, and their subsequent fertilization and embryonic development following insemination. Therefore, in our study, we performed mouse oocyte maturation and insemination using in vivo- or in vitro-matured oocyte-cumulus complexes (OCCs, which retain gap junctions between the cumulus cells and the oocytes, in vitro-matured, denuded oocytes co-cultured with cumulus cells (DCs, which lack gap junctions between the cumulus cells and the oocytes, and in vitro-matured, denuded oocytes without cumulus cells (DOs. Using these models, we were able to analyze the effects of gap junction signaling on oocyte maturation, fertilization, and early embryo development. We found that gap junctions were necessary for both in vivo and in vitro oocyte maturation. In addition, for oocytes matured in vivo, the presence of cumulus cells during insemination improved fertilization and blastocyst formation, and this improvement was strengthened by gap junctions. Moreover, for oocytes matured in vitro, the presence of cumulus cells during insemination improved fertilization, but not blastocyst formation, and this improvement was independent of gap junctions. Our results demonstrate, for the first time, that the beneficial effect of gap junction signaling from cumulus cells depends on oocyte maturation and fertilization methods.

  5. Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

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    Neves-dos-Santos Sandra

    2010-01-01

    Full Text Available Abstract Background We investigated the effects of the signaling molecules, cyclic AMP (cAMP and protein-kinase C (PKC, on gap junctional intercellular communication (GJIC between thymic epithelial cells (TEC. Results Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC. Conclusions Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.

  6. Interaction between fractional Josephson vortices in multi-gap superconductor tunnel junctions

    Science.gov (United States)

    Kim, Ju H.

    In a long Josephson junction (LJJ) with two-band superconductors, fractionalization of Josephson vortices (fluxons) can occur in the broken time reversal symmetry state when spatial phase textures (i-solitons) are excited. Excitation of i-solitons in each superconductor layer of the junction, arising due to the presence of two condensates and the interband Josephson effect, leads to spatial variation of the critical current density between the superconductor layers. Similar to the situation in a YBa2 Cu3O7 - x superconductor film grain boundary, this spatial dependence of the crtitical current density can self-generate magnetic flux in the insulator layer, resulting in fractional fluxons with large and small fraction of flux quantum. Similar to fluxons in one-band superconductor LJJ, these fractional fluxons are found to interact with each other. The interaction between large and small fractional fluxons determines the size of a fluxon which includes two (one large and one small) fractional fluxons. We discuss the nature of interaction between fractional fluxons and suggest that i-soliton excitations in multi-gap superconductor LJJs may be probed by using magnetic flux measurements.

  7. Gap junction connexins in female reproductive organs: implications for women's reproductive health.

    Science.gov (United States)

    Winterhager, Elke; Kidder, Gerald M

    2015-01-01

    Connexins comprise a family of ~20 proteins that form intercellular membrane channels (gap junction channels) providing a direct route for metabolites and signalling molecules to pass between cells. This review provides a critical analysis of the evidence for essential roles of individual connexins in female reproductive function, highlighting implications for women's reproductive health. No systematic review has been carried out. Published literature from the past 35 years was surveyed for research related to connexin involvement in development and function of the female reproductive system. Because of the demonstrated utility of genetic manipulation for elucidating connexin functions in various organs, much of the cited information comes from research with genetically modified mice. In some cases, a distinction is drawn between connexin functions clearly related to the formation of gap junction channels and those possibly linked to non-channel roles. Based on work with mice, several connexins are known to be required for female reproductive functions. Loss of connexin43 (CX43) causes an oocyte deficiency, and follicles lacking or expressing less CX43 in granulosa cells exhibit reduced growth, impairing fertility. CX43 is also expressed in human cumulus cells and, in the context of IVF, has been correlated with pregnancy outcome, suggesting that this connexin may be a determinant of oocyte and embryo quality in women. Loss of CX37, which exclusively connects oocytes with granulosa cells in the mouse, caused oocytes to cease growing without acquiring meiotic competence. Blocking of CX26 channels in the uterine epithelium disrupted implantation whereas loss or reduction of CX43 expression in the uterine stroma impaired decidualization and vascularization in mouse and human. Several connexins are important in placentation and, in the human, CX43 is a key regulator of the fusogenic pathway from the cytotrophoblast to the syncytiotrophoblast, ensuring placental growth

  8. Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles.

    Science.gov (United States)

    Shuhaibar, Leia C; Egbert, Jeremy R; Norris, Rachael P; Lampe, Paul D; Nikolaev, Viacheslav O; Thunemann, Martin; Wen, Lai; Feil, Robert; Jaffe, Laurinda A

    2015-04-28

    Meiosis in mammalian oocytes is paused until luteinizing hormone (LH) activates receptors in the mural granulosa cells of the ovarian follicle. Prior work has established the central role of cyclic GMP (cGMP) from the granulosa cells in maintaining meiotic arrest, but it is not clear how binding of LH to receptors that are located up to 10 cell layers away from the oocyte lowers oocyte cGMP and restarts meiosis. Here, by visualizing intercellular trafficking of cGMP in real-time in live follicles from mice expressing a FRET sensor, we show that diffusion of cGMP through gap junctions is responsible not only for maintaining meiotic arrest, but also for rapid transmission of the signal that reinitiates meiosis from the follicle surface to the oocyte. Before LH exposure, the cGMP concentration throughout the follicle is at a uniformly high level of ∼2-4 μM. Then, within 1 min of LH application, cGMP begins to decrease in the peripheral granulosa cells. As a consequence, cGMP from the oocyte diffuses into the sink provided by the large granulosa cell volume, such that by 20 min the cGMP concentration in the follicle is uniformly low, ∼100 nM. The decrease in cGMP in the oocyte relieves the inhibition of the meiotic cell cycle. This direct demonstration that a physiological signal initiated by a stimulus in one region of an intact tissue can travel across many layers of cells via cyclic nucleotide diffusion through gap junctions could provide a general mechanism for diverse cellular processes.

  9. Connexin domains relevant to the chemical gating of gap junction channels

    Directory of Open Access Journals (Sweden)

    C. Peracchia

    1997-05-01

    Full Text Available Most cells exchange ions and small metabolites via gap junction channels. These channels are made of two hemichannels (connexons, each formed by the radial arrangement of six connexin (Cx proteins. Connexins span the bilayer four times (M1-M4 and have both amino- and carboxy-termini (NT, CT at the cytoplasmic side of the membrane, forming two extracellular loops (E1, E2 and one inner (IL loop. The channels are regulated by gates that close with cytosolic acidification (e.g., CO2 treatment or increased calcium concentration, possibly via calmodulin activation. Although gap junction regulation is still unclear, connexin domains involved in gating are being defined. We have recently focused on the CO2 gating sensitivity of Cx32, Cx38 and various mutants and chimeras expressed in Xenopus oocytes and studied by double voltage clamp. Cx32 is weakly sensitive to CO2, whereas Cx38 is highly sensitive. A Cx32 chimera containing the second half of the inner loop (IL2 of Cx38 was as sensitive to CO2 as Cx38, indicating that this domain plays an important role. Deletion of CT by 84% did not affect CO2 sensitivity, but replacement of 5 arginines (R with sparagines (N at the beginning of CT (C1 greatly enhanced the CO2 sensitivity of Cx32. This suggests that whereas most of CT is irrelevant, positive charges of C1 maintain the CO2 sensitivity of Cx32 low. As a hypothesis we have proposed a model that involves charge interaction between negative residues of the beginning of IL1 and positive residues of either C1 or IL2. Open and closed channels would result from IL1-C1 and IL1-IL2 interactions, respectively

  10. Influence of drugs on gap junctions in glioma cell lines and primary astrocytes in vitro

    Directory of Open Access Journals (Sweden)

    Zahra eMoinfar

    2014-05-01

    Full Text Available Gap junctions (GJs are hemichannels on cell membrane. Once they are intercellulary connected to the neighboring cells, they build a functional syncytium which allows rapid transfer of ions and molecules between cells. This characteristic makes GJs a potential modulator in proliferation, migration and development of the cells. So far, several types of GJs are recognized on different brain cells as well as in glioma. Astrocytes, as one of the major cells that maintain neuronal homeostasis, express different types of GJs that let them communicate with neurons, oligodendrocytes and endothelial cells of the blood brain barrier; however, the main GJ in astrocytes is connexin 43. There are different cerebral diseases in which astrocyte GJs might play a role. Several drugs have been reported to modulate gap junctional communication in the brain which can consequently have beneficial or detrimental effects on the course of treatment in certain diseases. However, the exact cellular mechanism behind those pharmaceutical efficacies on GJs is not well-understood. Accordingly, how specific drugs would affect GJs and what some consequent specific brain diseases would be are the interests of the authors of this chapter. We would focus on pharmaceutical effects on GJs on astrocytes in specific diseases where GJs could possibly play a role including: 1 migraine and a novel therapy for migraine with aura, 2 neuroautoimmune diseases and immunomodulatory drugs in the treatment of demyelinating diseases of the central nervous system such as multiple sclerosis, 3 glioma and antineoplastic and anti-inflammatory agents that are used in treating brain tumors and 4 epilepsy and anticonvulsants that are widely used for seizures therapy. All of the above-mentioned therapeutic categories can possibly affect GJs expression of astrocytes and the role is discussed in the upcoming chapter.

  11. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    Science.gov (United States)

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  12. Gap junctions are selectively associated with interlocking ball-and-sockets but not protrusions in the lens.

    Science.gov (United States)

    Biswas, Sondip K; Lee, Jai Eun; Brako, Lawrence; Jiang, Jean X; Lo, Woo-Kuen

    2010-11-09

    Ball-and-sockets and protrusions are specialized interlocking membrane domains between lens fibers of all species studied. Ball-and-sockets and protrusions are similar in their shape, size, and surface morphology, and are traditionally believed to play a key role in maintaining fiber-to-fiber stability. Here, we evaluate the hypothesis that ball-and-sockets and protrusions possess important structural and functional differences during fiber cell differentiation and maturation. Intact lenses of leghorn chickens (E7 days to P62 weeks old) and rhesus monkeys (1.5-20 years old) were studied with SEM, freeze-fracture TEM, freeze-fracture immunogold labeling (FRIL), and filipin cytochemistry for membrane cholesterol detection. SEM showed that ball-and-sockets were distributed along the long and short sides of hexagonal fiber cells, whereas protrusions were located along the cell corners, from superficial to deep cortical regions in both chicken and monkey lenses. Importantly, by freeze-fracture TEM, we discovered the selective association of gap junctions with all ball-and-sockets examined, but not with protrusions, in both species. In the embryonic chicken lens (E18), the abundant distribution of ball-and-socket gap junctions was regularly found in an approximate zone extending at least 300 μm deep from the equatorial surface of the superficial cortical fibers. Many ball-and-socket gap junctions often protruded deeply into neighboring cells. However, in the mature fibers of monkey lenses, several ball-and-sockets exhibited only partial occupancy of gap junctions with disorganized connexons, possibly due to degradation of gap junctions during fiber maturation and aging. FRIL analysis confirmed that both connexin46 (Cx46) and connexin50 (Cx50) antibodies specifically labeled ball-and-socket gap junctions, but not protrusions. Furthermore, filipin cytochemistry revealed that the ball-and-socket gap junctions contained different amounts of cholesterol (i.e., cholesterol

  13. Droplet Traffic Control at a simple T junction

    Science.gov (United States)

    Panizza, Pascal; Engl, Wilfried; Colin, Annie; Ajdari, Armand

    2006-03-01

    A basic yet essential element of every traffic flow control is the effect of a junction where the flow is separated into several streams. How do pedestrians, vehicles or blood cells divide when they reach a junction? How does the outcome depend on their density? Similar fundamental questions hold for much simpler systems: in this paper, we have studied the behaviour of periodic trains of water droplets flowing in oil through a channel as they reach a simple, locally symmetric, T junction. Depending on their dilution, we observe that the droplets are either alternately partitioned between both outlets or sorted exclusively into the shortest one. We show that this surprising behaviour results from the hydrodynamic feed-back of drops in the two outlets on the selection process occurring at the junction. Our results offer a first guide for the design and modelling of droplet traffic in complex branched networks, a necessary step towards parallelized droplet-based ``lab-on-chip'' devices.

  14. Relative Roles of Gap Junction Channels and Cytoplasm in Cell-to-Cell Diffusion of Fluorescent Tracers

    Science.gov (United States)

    Safranyos, Richard G. A.; Caveney, Stanley; Miller, James G.; Petersen, Nils O.

    1987-04-01

    Intercellular (tissue) diffusion of molecules requires cytoplasmic diffusion and diffusion through gap junctional (or cell-to-cell) channels. The rates of tissue and cytoplasmic diffusion of fluorescent tracers, expressed as an effective diffusion coefficient, De, and a cytoplasmic diffusion coefficient, Dcyt, have been measured among the developing epidermal cells of a larval beetle, Tenebrio molitor L., to determine the contribution of the junctional channels to intercellular diffusion. Tracer diffusion was measured by injecting fluorescent tracers into cells and quantitating the rate of subsequent spread into adjacent cells. Cytoplasmic diffusion was determined by fluorescence photobleaching. These experiments show that gap junctional channels constitute approximately 70-80% of the total cell-to-cell resistance to the diffusion of organic tracers at high concentrations in this tissue. At low concentrations, however, the binding of tracer to cytoplasm slows down the cytoplasmic diffusion, which may limit intercellular diffusion.

  15. First-principles spin-transfer torque in CuMnAs |GaP |CuMnAs junctions

    Science.gov (United States)

    Stamenova, Maria; Mohebbi, Razie; Seyed-Yazdi, Jamileh; Rungger, Ivan; Sanvito, Stefano

    2017-02-01

    We demonstrate that an all-antiferromagnetic tunnel junction with current perpendicular to the plane geometry can be used as an efficient spintronic device with potential high-frequency operation. By using state-of-the-art density functional theory combined with quantum transport, we show that the Néel vector of the electrodes can be manipulated by spin-transfer torque. This is staggered over the two different magnetic sublattices and can generate dynamics and switching. At the same time the different magnetization states of the junction can be read by standard tunneling magnetoresistance. Calculations are performed for CuMnAs |GaP |CuMnAs junctions with different surface terminations between the antiferromagnetic CuMnAs electrodes and the insulating GaP spacer. We find that the torque remains staggered regardless of the termination, while the magnetoresistance depends on the microscopic details of the interface.

  16. Interactive effects of inflammatory cytokine and abundant low-molecular-weight PAHs on inhibition of gap junctional intercellular communication, disruption of cell proliferation control, and the AhR-dependent transcription

    Czech Academy of Sciences Publication Activity Database

    Kabátková, Markéta; Svobodová, Jana; Pěnčíková, K.; Mohatad, D.S.; Šmerdová, Lenka; Kozubík, Alois; Machala, M.; Vondráček, Jan

    2015-01-01

    Roč. 232, č. 1 (2015), s. 113-121 ISSN 0378-4274 R&D Projects: GA ČR(CZ) GAP503/11/1227; GA ČR(CZ) GA13-07711S Institutional support: RVO:68081707 Keywords : PAHs * Inflammation * Cell proliferation Subject RIV: BO - Biophysics Impact factor: 3.522, year: 2015

  17. The B[a]P-increased intercellular communication via translocation of connexin-43 into gap junctions reduces apoptosis

    International Nuclear Information System (INIS)

    Tekpli, X.; Rivedal, E.; Gorria, M.; Landvik, N.E.; Rissel, M.; Dimanche-Boitrel, M.-T.; Baffet, G.; Holme, J.A.; Lagadic-Gossmann, D.

    2010-01-01

    Gap junctions are channels in plasma membrane composed of proteins called connexins. These channels are organized in special domains between cells, and provide for direct gap junctional intercellular communication (GJIC), allowing diffusion of signalling molecules < 1 kD. GJIC regulates cell homeostasis and notably the balance between proliferation, cell cycle arrest, cell survival and apoptosis. Here, we have investigated benzo[a]pyrene (B[a]P) effects on GJIC and on the subcellular localization of the major protein of gap junction: connexin-43 (Cx43). Our results showed that B[a]P increased GJIC between mouse hepatoma Hepa1c1c7 cells via translocation of Cx43 from Golgi apparatus and lipid rafts into gap junction plaques. Interestingly, inhibition of GJIC by chlordane or small interference RNA directed against Cx43 enhanced B[a]P-induced apoptosis in Hepa1c1c7 cells. The increased apoptosis caused by inhibition of GJIC appeared to be mediated by ERK/MAPK pathway. It is suggested that B[a]P could induce transfer of cell survival signal or dilute cell death signal via regulation of ERK/MAPK through GJIC.

  18. The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein

    NARCIS (Netherlands)

    Giepmans, B N; Moolenaar, W H

    1998-01-01

    Gap junctions mediate cell-cell communication in almost all tissues and are composed of channel-forming integral membrane proteins, termed connexins [1-3]. Connexin43 (Cx43) is the most widely expressed and the most well-studied member of this family. Cx43-based cell-cell communication is regulated

  19. Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells

    NARCIS (Netherlands)

    Lauf, Undine; Giepmans, Ben N G; Lopez, Patricia; Braconnot, Sebastien; Chen, Shu-Chih; Falk, Matthias M

    2002-01-01

    Certain membrane channels including acetylcholine receptors, gap junction (GJ) channels, and aquaporins arrange into large clusters in the plasma membrane (PM). However, how these channels are recruited to the clusters is unknown. To address this question, we have investigated delivery of GJ channel

  20. Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus

    Directory of Open Access Journals (Sweden)

    Jinmi Koo

    2015-09-01

    Full Text Available BackgroundIn mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN. Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions.MethodsWe examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2 gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC knock-in mice using a real-time bioluminescence measurement system.ResultsAdministration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms.ConclusionThese findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

  1. Lens intracellular hydrostatic pressure is generated by the circulation of sodium and modulated by gap junction coupling

    Science.gov (United States)

    Gao, Junyuan; Sun, Xiurong; Moore, Leon C.; White, Thomas W.; Brink, Peter R.

    2011-01-01

    We recently modeled fluid flow through gap junction channels coupling the pigmented and nonpigmented layers of the ciliary body. The model suggested the channels could transport the secretion of aqueous humor, but flow would be driven by hydrostatic pressure rather than osmosis. The pressure required to drive fluid through a single layer of gap junctions might be just a few mmHg and difficult to measure. In the lens, however, there is a circulation of Na+ that may be coupled to intracellular fluid flow. Based on this hypothesis, the fluid would cross hundreds of layers of gap junctions, and this might require a large hydrostatic gradient. Therefore, we measured hydrostatic pressure as a function of distance from the center of the lens using an intracellular microelectrode-based pressure-sensing system. In wild-type mouse lenses, intracellular pressure varied from ∼330 mmHg at the center to zero at the surface. We have several knockout/knock-in mouse models with differing levels of expression of gap junction channels coupling lens fiber cells. Intracellular hydrostatic pressure in lenses from these mouse models varied inversely with the number of channels. When the lens’ circulation of Na+ was either blocked or reduced, intracellular hydrostatic pressure in central fiber cells was either eliminated or reduced proportionally. These data are consistent with our hypotheses: fluid circulates through the lens; the intracellular leg of fluid circulation is through gap junction channels and is driven by hydrostatic pressure; and the fluid flow is generated by membrane transport of sodium. PMID:21624945

  2. Proinflammatory cytokines downregulate connexin 43-gap junctions via the ubiquitin-proteasome system in rat spinal astrocytes.

    Science.gov (United States)

    Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2015-09-04

    Astrocytic gap junctions formed by connexin 43 (Cx43) are crucial for intercellular communication between spinal cord astrocytes. Various neurological disorders are associated with dysfunctional Cx43-gap junctions. However, the mechanism modulating Cx43-gap junctions in spinal astrocytes under pathological conditions is not entirely clear. A previous study showed that treatment of spinal astrocytes in culture with pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) decreased both Cx43 expression and gap junction intercellular communication (GJIC) via a c-jun N-terminal kinase (JNK)-dependent pathway. The current study further elaborates the intracellular mechanism that decreases Cx43 under an inflammatory condition. Cycloheximide chase analysis revealed that TNF-α (10 ng/ml) alone or in combination with IFN-γ (5 ng/ml) accelerated the degradation of Cx43 protein in cultured spinal astrocytes. The reduction of both Cx43 expression and GJIC induced by a mixture of TNF-α and IFN-γ were blocked by pretreatment with proteasome inhibitors MG132 (0.5 μM) and epoxomicin (25 nM), a mixture of TNF-α and IFN-γ significantly increased proteasome activity and Cx43 ubiquitination. In addition, TNF-α and IFN-γ-induced activation of ubiquitin-proteasome systems was prevented by SP600125, a JNK inhibitor. Together, these results indicate that a JNK-dependent ubiquitin-proteasome system is induced under an inflammatory condition that disrupts astrocytic gap junction expression and function, leading to astrocytic dysfunction and the maintenance of the neuroinflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. PI3K/Akt signaling is involved in the disruption of gap junctional communication caused by v-Src and TNF-α.

    Science.gov (United States)

    Ito, Satoko; Hyodo, Toshinori; Hasegawa, Hitoki; Yuan, Hong; Hamaguchi, Michinari; Senga, Takeshi

    2010-09-17

    Gap junctional communication, which is mediated by the connexin protein family, is essential for the maintenance of normal tissue function and homeostasis. Loss of intercellular communication results in a failure to coordinately regulate cellular functions, and it can facilitate tumorigenesis. Expression of oncogenes and stimulation with cytokines has been shown to suppress intercellular communication; however, the exact mechanism by which intercellular communication is disrupted by these factors remains uncertain. In this report, we show that Akt is essential for the disruption of gap junctional communication in v-Src-transformed cells. In addition, inhibition of Akt restores gap junctional communication after it is suppressed by TNF-α signaling. Furthermore, we demonstrate that the expression of a constitutively active form of Akt1, but not of Akt2 or Akt3, is sufficient to suppress gap junctional communication. Our results clearly define Akt1 as one of the critical regulators of gap junctional communication. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. The antiarrhythmic peptide analog rotigaptide (ZP123) stimulates gap junction intercellular communication in human osteoblasts and prevents decrease in femoral trabecular bone strength in ovariectomized rats

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne

    2005-01-01

    Gap junctions play an important role in bone development and function, but the lack of pharmacological tools has hampered the gap junction research. The antiarrhythmic peptides stimulate gap junction communication between cardiomyocytes, but effects in noncardiac tissue are unknown. The purpose...... of this study was to examine whether antiarrhythmic peptides, which are small peptides increasing gap junctional conductivity, show specific binding to osteoblasts and investigate the effect of the stable analog rotigaptide (ZP123) on gap junctional intercellular communication in vitro and on bone mass...... and strength in vivo. Cell coupling and calcium signaling were assessed in vitro on human, primary, osteoblastic cells. In vivo effects of rotigaptide on bone strength and density were determined 4 wk after ovariectomy in rats treated with either vehicle, sc injection twice daily (300 nmol per kilogram body...

  5. Chaos controlling problems for circuit systems with Josephson junction

    International Nuclear Information System (INIS)

    Gou, X-F; Wang, X; Xie, J-L

    2008-01-01

    The complex dynamical characters of the Josephson junction circuit system are studied and the tunnel effect is considered. The dynamical equation of the system is established. The route from periodic motion to chaos is illustrated using bifurcation diagram. An adscititious coupling controller is constructed to control the chaos

  6. Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.

    Science.gov (United States)

    Rimkute, Lina; Kraujalis, Tadas; Snipas, Mindaugas; Palacios-Prado, Nicolas; Jotautis, Vaidas; Skeberdis, Vytenis A; Bukauskas, Feliksas F

    2018-01-01

    Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pH i ) and cytosolic magnesium ion concentration ([Mg 2+ ] i ), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail. Our experimental results in HeLa cells expressing Cx36 show that changes in both pH i and [Mg 2+ ] i affect junctional conductance (g j ) in an interdependent manner; in other words, intracellular acidification cause increase or decay in g j depending on whether [Mg 2+ ] i is high or low, respectively, and intracellular alkalization cause reduction in g j independently of [Mg 2+ ] i . Our experimental and modelling data support the hypothesis that Cx36 GJ channels contain two separate gating mechanisms, and both are differentially sensitive to changes in pH i and [Mg 2+ ] i . Using recombinant Cx36 we found that two glutamate residues in the N-terminus could be partly responsible for the observed interrelated effect of pH i and [Mg 2+ ] i . Mutation of glutamate at position 8 attenuated the stimulatory effect of intracellular acidification at high [Mg 2+ ] i , while mutation at position 12 and double mutation at both positions reversed stimulatory effect to inhibition. Moreover, Cx36 * E8Q lost the initial increase of g j at low [Mg 2+ ] i and double mutation lost the sensitivity to high [Mg 2+ ] i . These results suggest that E8 and E12 are involved in regulation of Cx36 GJ channels by Mg 2+ and H + ions.

  7. Histone deacetylase inhibition reduces cardiac Connexin43 expression and gap junction communication

    Directory of Open Access Journals (Sweden)

    Qin eXu

    2013-04-01

    Full Text Available Histone deactylase (HDAC inhibitors are being investigated as novel therapies for cancer, inflammation, neurodegeneration, and heart failure. The effects of HDAC inhibitors on the functional expression of cardiac gap junctions (GJ are essentially unknown. The purpose of this study was to determine the effects of trichostatin A (TSA and vorinostat (VOR on functional GJ expression in ventricular cardiomyocytes. The effects of HDAC inhibition on connexin43 (Cx43 expression and functional GJ assembly were examined in primary cultured neonatal mouse ventricular myocytes. TSA and VOR reduced Cx43 mRNA, protein expression, and immunolocalized Cx43 GJ plaque area within ventricular myocyte monolayer cultures in a dose-dependent manner. Chromatin-immunoprecipitation experiments revealed altered protein interactions with the Cx43 promoter. VOR also altered the phosphorylation state of several key regulatory Cx43 phospho-serine sites. Patch clamp analysis revealed reduced electrical coupling between isolated ventricular myocyte pairs, altered transjunctional voltage-dependent inactivation kinetics, and steady state junctional conductance inactivation and recovery relationships. Single GJ channel conductance was reduced to 54 pS only by maximum inhibitory doses of TSA (>= 100 nM. These two hydroxamate pan-HDAC inhibitors exert multiple levels of regulation on ventricular GJ communication by altering Cx43 expression, GJ area, post-translational modifications (e.g. phosphorylation, acetylation, gating, and channel conductance. Although a 50% downregulation of Cx43 GJ communication alone may not be sufficient to slow ventricular conduction or induce arrhythmias, the development of class-selective HDAC inhibitors may help avoid the potential negative cardiovascular effects of pan-HDACI.

  8. Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

    International Nuclear Information System (INIS)

    Choudhary, Mayur; Naczki, Christine; Chen, Wenhong; Barlow, Keith D.; Case, L. Douglas; Metheny-Barlow, Linda J.

    2015-01-01

    Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support

  9. Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity.

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria; Fritz, Teresa; Angle, Amanda; Kielian, Tammy

    2011-01-12

    Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, astrocytes bordering the abscess demonstrated hemichannel activity as evident by enhanced ethidium bromide (EtBr) uptake that could be blocked by several pharmacological inhibitors, including the connexin 43 (Cx43) mimetic peptide Gap26, carbenoxolone, the pannexin1 (Panx1) mimetic peptide (10)Panx1, and probenecid. However, hemichannel opening was transient with astrocytic EtBr uptake observed near the abscess at day 3 but not day 7 after infection. The region-dependent pattern of hemichannel activity at day 3 directly correlated with increases in Cx43, Cx30, Panx1, and glutamate transporter expression (glial L-glutamate transporter and L-glutamate/L-aspartate transporter) along the abscess margins. Changes in astrocyte resting membrane potential and input conductance correlated with the observed changes in GJ communication and hemichannel activity. Collectively, these findings indicate that astrocyte coupling and electrical properties are most dramatically affected near the primary inflammatory site and reveal an opposing relationship between the open states of GJ channels versus hemichannels during acute infection. This relationship may extend to other CNS diseases typified with an inflammatory component.

  10. Jump in current at the gap voltage in a superconducting junction

    International Nuclear Information System (INIS)

    Coombes, J.M.; Carbotte, J.P.

    1986-01-01

    For many materials not previously considered, we have calculated the jump, at the gap voltage, in the quasiparticle current of a tunnel junction. An empirical relationship between the jump and the effective electron-phonon coupling λ-μ/sup */ previously established is confirmed. Further, a new and equally as accurate correlation is found with the strong coupling index T/sub c//ω/sub ln/, where T/sub c/ is the critical temperature and ω/sub ln/ a specific characteristic phonon energy. A simple formula for the jump which includes a strong-coupling correction is derived and found to fit the observed correlation well. Finally, we study the effect on the jump of unusual values of Coulomb pseudopotential μ/sup */. Also a δ-function electron-phonon spectral density α 2 F(ω) is used to help in the understanding of the range of values that is possible for the jump when α 2 F(ω) is not restricted to realistic shapes

  11. Extract from the Zooxanthellate Jellyfish Cotylorhiza tuberculata Modulates Gap Junction Intercellular Communication in Human Cell Cultures

    Directory of Open Access Journals (Sweden)

    Stefano Piraino

    2013-05-01

    Full Text Available On a global scale, jellyfish populations in coastal marine ecosystems exhibit increasing trends of abundance. High-density outbreaks may directly or indirectly affect human economical and recreational activities, as well as public health. As the interest in biology of marine jellyfish grows, a number of jellyfish metabolites with healthy potential, such as anticancer or antioxidant activities, is increasingly reported. In this study, the Mediterranean “fried egg jellyfish” Cotylorhiza tuberculata (Macri, 1778 has been targeted in the search forputative valuable bioactive compounds. A medusa extract was obtained, fractionated, characterized by HPLC, GC-MS and SDS-PAGE and assayed for its biological activity on breast cancer cells (MCF-7 and human epidermal keratinocytes (HEKa. The composition of the jellyfish extract included photosynthetic pigments, valuable ω-3 and ω-6 fatty acids, and polypeptides derived either from jellyfish tissues and their algal symbionts. Extract fractions showed antioxidant activity and the ability to affect cell viability and intercellular communication mediated by gap junctions (GJIC differentially in MCF-7and HEKa cells. A significantly higher cytotoxicity and GJIC enhancement in MCF-7 compared to HEKa cells was recorded. A putative action mechanism for the anticancer bioactivity through the modulation of GJIC has been hypothesized and its nutraceutical and pharmaceutical potential was discussed.

  12. Bipolar cell gap junctions serve major signaling pathways in the human retina.

    Science.gov (United States)

    Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

    2017-08-01

    Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

  13. Barreloid Borders and Neuronal Activity Shape Panglial Gap Junction-Coupled Networks in the Mouse Thalamus.

    Science.gov (United States)

    Claus, Lena; Philippot, Camille; Griemsmann, Stephanie; Timmermann, Aline; Jabs, Ronald; Henneberger, Christian; Kettenmann, Helmut; Steinhäuser, Christian

    2018-01-01

    The ventral posterior nucleus of the thalamus plays an important role in somatosensory information processing. It contains elongated cellular domains called barreloids, which are the structural basis for the somatotopic organization of vibrissae representation. So far, the organization of glial networks in these barreloid structures and its modulation by neuronal activity has not been studied. We have developed a method to visualize thalamic barreloid fields in acute slices. Combining electrophysiology, immunohistochemistry, and electroporation in transgenic mice with cell type-specific fluorescence labeling, we provide the first structure-function analyses of barreloidal glial gap junction networks. We observed coupled networks, which comprised both astrocytes and oligodendrocytes. The spread of tracers or a fluorescent glucose derivative through these networks was dependent on neuronal activity and limited by the barreloid borders, which were formed by uncoupled or weakly coupled oligodendrocytes. Neuronal somata were distributed homogeneously across barreloid fields with their processes running in parallel to the barreloid borders. Many astrocytes and oligodendrocytes were not part of the panglial networks. Thus, oligodendrocytes are the cellular elements limiting the communicating panglial network to a single barreloid, which might be important to ensure proper metabolic support to active neurons located within a particular vibrissae signaling pathway. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication.

    Science.gov (United States)

    Lin, Qingtang; Liu, Zhao; Ling, Feng; Xu, Geng

    2016-02-01

    Gliomas are the most common type of primary brain tumor. Using current standard treatment regimens, the prognosis of patients with gliomas remains poor, which is predominantly due to the resistance of glioma cells to chemotherapy. The organ microenvironment has been implicated in the pathogenesis and survival of tumor cells. Thus, the aim of the present study was to test the hypothesis that astrocytes (the housekeeping cells of the brain microenvironment) may protect glioma cells from chemotherapy and to investigate the underlying mechanism. Immunofluorescent and scanning electron microscopy demonstrated that glioma cells were surrounded and infiltrated by activated astrocytes. In vitro co-culture of glioma cells with astrocytes significantly reduced the cytotoxic effects on glioma cells caused by various chemotherapeutic agents, as demonstrated by fluorescein isothiocyanate-propidium iodide flow cytometry. Transwell experiments indicated that this protective effect was dependent on physical contact and the gap junctional communication (GJC) between astrocytes and glioma cells. Microarray expression profiling further revealed that astrocytes upregulated the expression levels of various critical survival genes in the glioma cells via GJC. The results of the present study indicated that the organ microenvironment may affect the biological behavior of tumor cells and suggest a novel mechanism of resistance in glioma cells, which may be of therapeutic relevance clinically.

  15. Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing.

    Science.gov (United States)

    Zong, Liang; Chen, Jin; Zhu, Yan; Zhao, Hong-Bo

    2017-07-22

    Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low frequency regions, first occurring in the high frequency region and then progressively extending to the middle and low frequency regions with mouse age increased. The speed of hearing loss extending was fast in the basal high frequency region and slow in the apical low frequency region, showing a logarithmic function with mouse age. Before postnatal day 25, there were no significant hearing loss and the reduction of active cochlear amplification in the low frequency region. Hearing loss and the reduction of active cochlear amplification also had frequency difference, severe and large in the high frequency regions. These new data indicate that the effect of gap junction on active cochlear amplification is progressive, but, consistent with our previous report, exists in both high and low frequency regions in adulthood. These new data also suggest that cochlear gap junctions may have an important role in age-related hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Gap junctions composed of connexins 41.8 and 39.4 are essential for colour pattern formation in zebrafish

    Science.gov (United States)

    Irion, Uwe; Frohnhöfer, Hans Georg; Krauss, Jana; Çolak Champollion, Tuǧba; Maischein, Hans-Martin; Geiger-Rudolph, Silke; Weiler, Christian; Nüsslein-Volhard, Christiane

    2014-01-01

    Interactions between all three pigment cell types are required to form the stripe pattern of adult zebrafish (Danio rerio), but their molecular nature is poorly understood. Mutations in leopard (leo), encoding Connexin 41.8 (Cx41.8), a gap junction subunit, cause a phenotypic series of spotted patterns. A new dominant allele, leotK3, leads to a complete loss of the pattern, suggesting a dominant negative impact on another component of gap junctions. In a genetic screen, we identified this component as Cx39.4 (luchs). Loss-of-function alleles demonstrate that luchs is required for stripe formation in zebrafish; however, the fins are almost not affected. Double mutants and chimeras, which show that leo and luchs are only required in xanthophores and melanophores, but not in iridophores, suggest that both connexins form heteromeric gap junctions. The phenotypes indicate that these promote homotypic interactions between melanophores and xanthophores, respectively, and those cells instruct the patterning of the iridophores. DOI: http://dx.doi.org/10.7554/eLife.05125.001 PMID:25535837

  17. Role of Non-Myocyte Gap Junctions and Connexin Hemichannels in Cardiovascular Health and Disease: Novel Therapeutic Targets?

    Science.gov (United States)

    Johnson, Robert D; Camelliti, Patrizia

    2018-03-15

    The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes. Connexins are expressed in both cardiomyocytes and non-myocytes, including cardiac fibroblasts, endothelial cells, and macrophages. Non-myocytes are the largest population of cells in the heart, and therefore it is important to consider what roles connexins, hemichannels, and gap junctions play in these cell types. The aim of this review is to provide insight into connexin-based signalling in non-myocytes during health and disease, and highlight how targeting these proteins could lead to the development of novel therapies. We conclude that connexins in non-myocytes contribute to arrhythmias and adverse ventricular remodelling following myocardial infarction, and are associated with the initiation and development of atherosclerosis. Therefore, therapeutic interventions targeting these connexins represent an exciting new research avenue with great potential.

  18. Diabetes Increases Cryoinjury Size with Associated Effects on Cx43 Gap Junction Function and Phosphorylation in the Mouse Heart.

    Science.gov (United States)

    Palatinus, Joseph A; Gourdie, Robert G

    2016-01-01

    Diabetic patients develop larger myocardial infarctions and have an increased risk of death following a heart attack. The poor response to myocardial injury in the diabetic heart is likely related to the many metabolic derangements from diabetes that create a poor substrate in general for wound healing, response to injury and infection. Studies in rodents have implicated a role for the gap junction protein connexin 43 (Cx43) in regulating the injury response in diabetic skin wounds. In this study, we sought to determine whether diabetes alters Cx43 molecular interactions or intracellular communication in the cryoinjured STZ type I diabetic mouse heart. We found that epicardial cryoinjury size is increased in diabetic mice and this increase is prevented by preinjury insulin administration. Consistent with these findings, we found that intercellular coupling via gap junctions is decreased after insulin administration in diabetic and nondiabetic mice. This decrease in coupling is associated with a concomitant increase in phosphorylation of Cx43 at serine 368, a residue known to decrease channel conductance. Taken together, our results suggest that insulin regulates both gap junction-mediated intercellular communication and injury propagation in the mouse heart.

  19. Articular chondrocyte network mediated by gap junctions: role in metabolic cartilage homeostasis

    Science.gov (United States)

    Mayan, Maria D; Gago-Fuentes, Raquel; Carpintero-Fernandez, Paula; Fernandez-Puente, Patricia; Filgueira-Fernandez, Purificacion; Goyanes, Noa; Valiunas, Virginijus; Brink, Peter R; Goldberg, Gary S; Blanco, Francisco J

    2017-01-01

    Objective This study investigated whether chondrocytes within the cartilage matrix have the capacity to communicate through intercellular connections mediated by voltage-gated gap junction (GJ) channels. Methods Frozen cartilage samples were used for immunofluorescence and immunohistochemistry assays. Samples were embedded in cacodylate buffer before dehydration for scanning electron microscopy. Co-immunoprecipitation experiments and mass spectrometry (MS) were performed to identify proteins that interact with the C-terminal end of Cx43. GJ communication was studied through in situ electroporation, electrophysiology and dye injection experiments. A transwell layered culture system and MS were used to identify and quantify transferred amino acids. Results Microscopic images revealed the presence of multiple cellular projections connecting chondrocytes within the matrix. These projections were between 5 and 150 μm in length. MS data analysis indicated that the C-terminus of Cx43 interacts with several cytoskeletal proteins implicated in Cx trafficking and GJ assembly, including α-tubulin and β-tubulin, actin, and vinculin. Electrophysiology experiments demonstrated that 12-mer oligonucleotides could be transferred between chondrocytes within 12 min after injection. Glucose was homogeneously distributed within 22 and 35 min. No transfer was detected when glucose was electroporated into A549 cells, which have no GJs. Transwell layered culture systems coupled with MS analysis revealed connexins can mediate the transfer of L-lysine and L-arginine between chondrocytes. Conclusions This study reveals that intercellular connections between chondrocytes contain GJs that play a key role in cell-cell communication and a metabolic function by exchange of nutrients including glucose and essential amino acids. A three-dimensional cellular network mediated through GJs might mediate metabolic and physiological homeostasis to maintain cartilage tissue. PMID:24225059

  20. Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells

    International Nuclear Information System (INIS)

    Iwase, Yumiko; Fukata, Hideki; Mori, Chisato

    2006-01-01

    Some estrogenic compounds are reported to cause testicular disorders in humans and/or experimental animals by direct action on Leydig cells. In carcinogenesis and normal development, gap junctional intercellular communication (GJIC) plays an essential role in maintaining homeostasis. In this study, we examine the effects of diethylstilbestrol (DES, a synthetic estrogen), 17β-estradiol (E 2 , a natural estrogen), and genistein (GEN, a phytoestrogen) on GJIC between mouse Leydig TM3 cells using Lucifer yellow microinjection. The three compounds tested produced GJIC inhibition in the TM3 cells after 24 h. Gradually, 10 μM DES began to inhibit GJIC for 24 h and this effect was observed until 72 h. On the other hand, both 20 μM E 2 and 25 μM GEN rapidly inhibited GJIC in 6 h and 2 h, respectively. The effects continued until 24 h, but weakened by 72 h. Furthermore, a combined effect at μM level between DES and E 2 on GJIC inhibition was observed, but not between GEN and E 2 . DES and E 2 showed GJIC inhibition at low dose levels (nearly physiological estrogen levels) after 72 h, but GEN did not. DES-induced GJIC inhibition at 10 pM and 10 μM was completely counteracted by ICI 182,780 (ICl), an estrogen receptor antagonist. On the other hand, the inhibitory effects on GJIC with E 2 (10 pM and 20 μM) and GEN (25 μM) were partially blocked by ICI or calphostin C, a protein kinase C (PKC) inhibitor, and were completely blocked by the combination of ICI and calphostin C. These results demonstrate that DES inhibits GJIC between Leydig cells via the estrogen receptor (ER), and that E 2 and GEN inhibit GJIC via ER and PKC. These estrogenic compounds may have different individual nongenotoxic mechanism including PKC pathway on testicular carcinogenesis or development

  1. Gap junction mediated intercellular metabolite transfer in the cochlea is compromised in connexin30 null mice.

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    Qing Chang

    Full Text Available Connexin26 (Cx26 and connexin30 (Cx30 are two major protein subunits that co-assemble to form gap junctions (GJs in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a

  2. Dysfunction in gap junction intercellular communication induces aberrant behavior of the inner cell mass and frequent collapses of expanded blastocysts in mouse embryos.

    Science.gov (United States)

    Togashi, Kazue; Kumagai, Jin; Sato, Emiko; Shirasawa, Hiromitsu; Shimoda, Yuki; Makino, Kenichi; Sato, Wataru; Kumazawa, Yukiyo; Omori, Yasufumi; Terada, Yukihiro

    2015-06-01

    We investigated the role of gap junctions (GJs) in embryological differentiation, and observed the morphological behavior of the inner cell mass (ICM) by time-lapse movie observation (TLM) with gap junction inhibitors (GJis). ICR mouse embryos were exposed to two types of GJis in CZB medium: oleamide (0 to 50 μM) and 1-heptanol (0 to 10 mM). We compared the rate of blastocyst formation at embryonic day 4.5 (E4.5) with E5.5. We also observed and evaluated the times from the second cleavage to each embryonic developing stage by TLM. We investigated embryonic distribution of DNA, Nanog protein, and Connexin 43 protein with immunofluorescent staining. In the comparison of E4.5 with E5.5, inhibition of gap junction intercellular communication (GJIC) delayed embryonic blastocyst formation. The times from the second cleavage to blastocyst formation were significantly extended in the GJi-treated embryos (control vs with oleamide, 2224 ± 179 min vs 2354 ± 278 min, p = 0.013). Morphological differences were traced in control versus GJi-treated embryos until the hatching stage. Oleamide induced frequent severe collapses of expanded blastocysts (77.4 % versus 26.3 %, p = 0.0001) and aberrant ICM divisions connected to sticky strands (74.3 % versus 5.3 %, p = 0.0001). Immunofluorescent staining indicated Nanog-positive cells were distributed in each divided ICM. GJIC plays an important role in blastocyst formation, collapses of expanded blastocysts, and the ICM construction in mouse embryos.

  3. Stat3 is a positive regulator of gap junctional intercellular communication in cultured, human lung carcinoma cells

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    Geletu Mulu

    2012-12-01

    Full Text Available Abstract Background Neoplastic transformation of cultured cells by a number of oncogenes such as src suppresses gap junctional, intercellular communication (GJIC; however, the role of Src and its effector Signal transducer and activator of transcription-3 (Stat3 upon GJIC in non small cell lung cancer (NSCLC has not been defined. Immunohistochemical analysis revealed high Src activity in NSCLC biopsy samples compared to normal tissues. Here we explored the potential effect of Src and Stat3 upon GJIC, by assessing the levels of tyr418-phosphorylated Src and tyr705-phosphorylated Stat3, respectively, in a panel of NSCLC cell lines. Methods Gap junctional communication was examined by electroporating the fluorescent dye Lucifer yellow into cells grown on a transparent electrode, followed by observation of the migration of the dye to the adjacent, non-electroporated cells under fluorescence illumination. Results An inverse relationship between Src activity levels and GJIC was noted; in five lines with high Src activity GJIC was absent, while two lines with extensive GJIC (QU-DB and SK-LuCi6 had low Src levels, similar to a non-transformed, immortalised lung epithelial cell line. Interestingly, examination of the mechanism indicated that Stat3 inhibition in any of the NSCLC lines expressing high endogenous Src activity levels, or in cells where Src was exogenously transduced, did not restore GJIC. On the contrary, Stat3 downregulation in immortalised lung epithelial cells or in the NSCLC lines displaying extensive GJIC actually suppressed junctional permeability. Conclusions Our findings demonstrate that although Stat3 is generally growth promoting and in an activated form it can act as an oncogene, it is actually required for gap junctional communication both in nontransformed lung epithelial cells and in certain lung cancer lines that retain extensive GJIC.

  4. INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY PERFLUORINATED COMPOUNDS IN RAT LIVER AND DOLPHIN KIDNEY EPITHELIAL CELL LINES IN VITRO AND SPRAGUE-DAWLEY RATS IN VIVO

    Science.gov (United States)

    Abstract Gap Junctional Intercellular Communication (GJIC) is the major pathway of intercellular signal transduction, and is, thus, important for normal cell growth and function. Recent studies have revealed a global distribution of some perfluorinated organic compounds e...

  5. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.

    KAUST Repository

    Ren, Jian; Wang, Xuhui; Wang, Guangchao; Wu, Junhua

    2013-01-01

    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication

  6. High performance as-grown and annealed high band gap tunnel junctions: Te behavior at the interface

    Energy Technology Data Exchange (ETDEWEB)

    Bedair, S. M., E-mail: bedair@ncsu.edu; Harmon, Jeffrey L.; Carlin, C. Zachary; Hashem Sayed, Islam E.; Colter, P. C. [Department of Electrical and Computer Engineering, North Carolina State University, Raleigh, North Carolina 27695 (United States)

    2016-05-16

    The performance of n{sup +}-InGaP(Te)/p{sup +}-AlGaAs(C) high band gap tunnel junctions (TJ) is critical for achieving high efficiency in multijunction photovoltaics. Several limitations for as grown and annealed TJ can be attributed to the Te doping of InGaP and its behavior at the junction interface. Te atoms in InGaP tend to get attached at step edges, resulting in a Te memory effect. In this work, we use the peak tunneling current (J{sub pk}) in this TJ as a diagnostic tool to study the behavior of the Te dopant at the TJ interface. Additionally, we used our understanding of Te behavior at the interface, guided by device modeling, to modify the Te source shut-off procedure and the growth rate. These modifications lead to a record performance for both the as-grown (2000 A/cm{sup 2}) and annealed (1000 A/cm{sup 2}) high band gap tunnel junction.

  7. Role of gap junctional coupling in astrocytic networks in the determination of global ischaemia-induced oxidative stress and hippocampal damage.

    Science.gov (United States)

    Perez Velazquez, Jose L; Kokarovtseva, Larisa; Sarbaziha, Raheleh; Jeyapalan, Zina; Leshchenko, Yevgen

    2006-01-01

    While there is evidence that gap junctions play important roles in the determination of cell injuries, there is not much known about mechanisms by which gap junctional communication may exert these functions. Using a global model of transient ischaemia in rats, we found that pretreatment with the gap junctional blockers carbenoxolone, 18alpha-glycyrrhetinic acid and endothelin, applied via cannulae implanted into the hippocampus in one hemisphere, resulted in decreased numbers of TUNEL-positive neurons, as compared with the contralateral hippocampus that received saline injection. Post-treatment with carbenoxolone for up to 30 min after the stroke injury still resulted in decreased cell death, but post-treatment at 90 min after the ischaemic insult did not result in differences in cell death. However, quinine, an inhibitor of Cx36-mediated gap junctional coupling, did not result in appreciable neuroprotection. Searching for a possible mechanism for the observed protective effects, possible actions of the gap junctional blockers in the electrical activity of the hippocampus during the ischaemic insult were assessed using intracerebral recordings, with no differences observed between the saline-injected and the contralateral drug-injected hippocampus. However, a significant reduction in lipid peroxides, a measure of free radical formation, in the hippocampus treated with carbenoxolone, revealed that the actions of gap junctional coupling during injuries may be causally related to oxidative stress. These observations suggest that coupling in glial networks may be functionally important in determining neuronal vulnerability to oxidative injuries.

  8. On the role of the gap junction protein Cx43 (GJA1 in human cardiac malformations with Fallot-pathology. a study on paediatric cardiac specimen.

    Directory of Open Access Journals (Sweden)

    Aida Salameh

    Full Text Available INTRODUCTION: Gap junction channels are involved in growth and differentiation. Therefore, we wanted to elucidate if the main cardiac gap junction protein connexin43 (GJA1 is altered in patients with Tetralogy of Fallot or double-outlet right ventricle of Fallot-type (62 patients referred to as Fallot compared to other cardiac anomalies (21 patients referred to as non-Fallot. Patients were divided into three age groups: 0-2years, 2-12years and >12years. Myocardial tissue samples were collected during corrective surgery and analysis of cell morphology, GJA1- and N-cadherin (CDH2-distribution, as well as GJA1 protein- and mRNA-expression was carried out. Moreover, GJA1-gene analysis of 16 patients and 20 healthy subjects was performed. RESULTS: Myocardial cell length and width were significantly increased in the oldest age group compared to the younger ones. GJA1 distribution changed significantly during maturation with the ratio of polar/lateral GJA1 increasing from 2.93±0.68 to 8.52±1.41. While in 0-2years old patients ∼6% of the lateral GJA1 was co-localised with CDH2 this decreased with age. Furthermore, the changes in cell morphology and GJA1-distribution were not due to the heart defect itself but were significantly dependent on age. Total GJA1 protein expression decreased during growing-up, whereas GJA1-mRNA remained unchanged. Sequencing of the GJA1-gene revealed only few heterozygous single nucleotide polymorphisms within the Fallot and the healthy control group. CONCLUSION: During maturation significant changes in gap junction remodelling occur which might be necessary for the growing and developing heart. In our study point mutations within the Cx43-gene could not be identified as a cause of the development of TOF.

  9. Gap junctions mediate large-scale Turing structures in a mean-field cortex driven by subcortical noise

    Science.gov (United States)

    Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Wilson, M. T.; Sleigh, J. W.

    2007-07-01

    One of the grand puzzles in neuroscience is establishing the link between cognition and the disparate patterns of spontaneous and task-induced brain activity that can be measured clinically using a wide range of detection modalities such as scalp electrodes and imaging tomography. High-level brain function is not a single-neuron property, yet emerges as a cooperative phenomenon of multiply-interacting populations of neurons. Therefore a fruitful modeling approach is to picture the cerebral cortex as a continuum characterized by parameters that have been averaged over a small volume of cortical tissue. Such mean-field cortical models have been used to investigate gross patterns of brain behavior such as anesthesia, the cycles of natural sleep, memory and erasure in slow-wave sleep, and epilepsy. There is persuasive and accumulating evidence that direct gap-junction connections between inhibitory neurons promote synchronous oscillatory behavior both locally and across distances of some centimeters, but, to date, continuum models have ignored gap-junction connectivity. In this paper we employ simple mean-field arguments to derive an expression for D2 , the diffusive coupling strength arising from gap-junction connections between inhibitory neurons. Using recent neurophysiological measurements reported by Fukuda [J. Neurosci. 26, 3434 (2006)], we estimate an upper limit of D2≈0.6cm2 . We apply a linear stability analysis to a standard mean-field cortical model, augmented with gap-junction diffusion, and find this value for the diffusive coupling strength to be close to the critical value required to destabilize the homogeneous steady state. Computer simulations demonstrate that larger values of D2 cause the noise-driven model cortex to spontaneously crystalize into random mazelike Turing structures: centimeter-scale spatial patterns in which regions of high-firing activity are intermixed with regions of low-firing activity. These structures are consistent with the

  10. Gap features of layered iron-selenium-tellurium compound below and above the superconducting transition temperature by break-junction spectroscopy combined with STS

    Science.gov (United States)

    Ekino, T.; Sugimoto, A.; Gabovich, A. M.

    2018-05-01

    We studied correlations between the superconducting gap features of Te-substituted FeSe observed by scanning tunnelling spectroscopy (STS) and break-junction tunnelling spectroscopy (BJTS). At bias voltages outside the superconducting gap-energy range, the broad gap structure exists, which becomes the normal-state gap above the critical temperature, T c. Such behaviour is consistent with the model of the partially gapped density-wave superconductor involving both superconducting gaps and pseudogaps, which has been applied by us earlier to high-Tc cuprates. The similarity suggests that the parent electronic spectrum features should have much in common for these classes of materials.

  11. AIR GAP CONTROL SYSTEM FOR HYDROGENERATORS

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    I. O. Zaitsev

    2017-01-01

    Full Text Available In this paper, we report of the solving the actual problem of control the air gap in the hydrogenerators. The aim of the study was development of a computerized information-measuring system for measuring the air gap in the hydrogenator, which used two capacitive sensors with parallel coplanar electrodes, and the method of determining the shape of the envelope parameters hydrogenerator rotor poles relative to the center axis of rotation, using the measurement results of the air gap.In practical studies of the sensor circuit it has been shown that its use allows for the informative value of the sensor capacitance conversion function to obtain a high accuracy and resolution measurement with digital linearization of converting function of the sensor with use program utility. To determine the form deviations of the envelope line of the rotor pole from the ideal cylinder, which is one of the main structural defects of the technological errors as results the distortion of the shape of the air gap in the hydrogenator, when the machine was manufacture and assembly. It is proposed to describe the shape of the envelope to use a Fourier transform. Calculation of the coefficients of the Fourier series is performed using the method of least squares as the regression coefficients.Application of this method in processing the measuring data in a computerized information-measuring system the developed with the primary converter with coplanar parallel electrodes allowed attaining the high measurement accuracy and resolution informative in magnitude of the capacity.

  12. Transparent Semiconductor-Superconductor Interface and Induced Gap in an Epitaxial Heterostructure Josephson Junction

    NARCIS (Netherlands)

    Kjaergaard, M.; Suominen, H. J.; Nowak, M.P.; Akhmerov, A.R.; Shabani, J.; Palmstrøm, C. J.; Nichele, F.; Marcus, C.M.

    2017-01-01

    Measurement of multiple Andreev Reflection (MAR) in a Josephson junction made from an InAs quantum well heterostructure with epitaxial aluminum is used to quantify a highly transparent effective semiconductor-superconductor interface with near-unity transmission. The observed temperature

  13. 0-π phase-controllable thermal Josephson junction

    Science.gov (United States)

    Fornieri, Antonio; Timossi, Giuliano; Virtanen, Pauli; Solinas, Paolo; Giazotto, Francesco

    2017-05-01

    Two superconductors coupled by a weak link support an equilibrium Josephson electrical current that depends on the phase difference ϕ between the superconducting condensates. Yet, when a temperature gradient is imposed across the junction, the Josephson effect manifests itself through a coherent component of the heat current that flows opposite to the thermal gradient for |ϕ| heat currents can be inverted by adding a π shift to ϕ. In the static electrical case, this effect has been obtained in a few systems, for example via a ferromagnetic coupling or a non-equilibrium distribution in the weak link. These structures opened new possibilities for superconducting quantum logic and ultralow-power superconducting computers. Here, we report the first experimental realization of a thermal Josephson junction whose phase bias can be controlled from 0 to π. This is obtained thanks to a superconducting quantum interferometer that allows full control of the direction of the coherent energy transfer through the junction. This possibility, in conjunction with the completely superconducting nature of our system, provides temperature modulations with an unprecedented amplitude of ∼100 mK and transfer coefficients exceeding 1 K per flux quantum at 25 mK. Then, this quantum structure represents a fundamental step towards the realization of caloritronic logic components such as thermal transistors, switches and memory devices. These elements, combined with heat interferometers and diodes, would complete the thermal conversion of the most important phase-coherent electronic devices and benefit cryogenic microcircuits requiring energy management, such as quantum computing architectures and radiation sensors.

  14. Role of Myoendothelial Gap Junctions in the Regulation of Human Coronary Artery Smooth Muscle Cell Differentiation by Laminar Shear Stress

    Directory of Open Access Journals (Sweden)

    Zongqi Zhang

    2016-07-01

    Full Text Available Background/Aims: Smooth muscle cells may dedifferentiate into the synthetic phenotype and promote atherosclerosis. Here, we explored the role of myoendothelial gap junctions in phenotypic switching of human coronary artery smooth muscle cells (HCASMCs co-cultured with human coronary artery endothelial cells (HCAECs exposed to shear stress. Methods: HCASMCs and HCAECs were seeded on opposite sides of Transwell inserts, and HCAECs were exposed to laminar shear stress of 12 dyn/cm2 or 5 dyn/cm2. The myoendothelial gap junctions were evaluated by using a multi-photon microscope. Results: In co-culture with HCAECs, HCASMCs exhibited a contractile phenotype, and maintained the expression of differentiation markers MHC and H1-calponin. HCASMCs and HCAECs formed functional intercellular junctions, as evidenced by colocalization of connexin(Cx40 and Cx43 on cellular projections inside the Transwell membrane and biocytin transfer from HCAECs to HCASMCs. Cx40 siRNA and 18-α-GA attenuated protein expression of MHC and H1-calponin in HCASMCs. Shear stress of 5 dyn/cm2 increased Cx43 and decreased Cx40 expression in HCAECs, and partly inhibited biocytin transfer from HCAECs to HCASMCs, which could be completely blocked by Cx43 siRNA or restored by Cx40 DNA transfected into HCAECs. The exposure of HCAECs to shear stress of 5 dyn/cm2 promoted HCASMC phenotypic switching, manifested by morphological changes, decrease in MHC and H1-calponin expression, and increase in platelet-derived growth factor (PDGF-BB release, which was partly rescued by Cx43 siRNA or Cx40 DNA or PDGF receptor signaling inhibitor. Conclusions: The exposure of HCAECs to shear stress of 5 dyn/cm2 caused the dysfunction of Cx40/Cx43 heterotypic myoendothelial gap junctions, which may be replaced by homotypic Cx43/Cx43 channels, and induced HCASMC transition to the synthetic phenotype associated with the activation of PDGF receptor signaling, which may contribute to shear stress

  15. Different mechanisms of modulation of gap junction communication by non-genotoxic carcinogens in rat liver in vivo

    International Nuclear Information System (INIS)

    Cowles, C.; Mally, A.; Chipman, J.K.

    2007-01-01

    This is a comparative study of the mechanisms by which three different rodent non-genotoxic carcinogens modulate connexin-mediated gap junction intercellular communication in male rat liver in vivo. In the case of the peroxisome proliferating agent Wy-14,643, a non-hepatotoxic dose of 50 mg/kg led to a marked loss of inter-hepatocyte dye transfer associated with a loss of both Cx32 and Cx26 protein expression. In contrast, p,p'-dichlorodiphenyltrichloroethane (DDT) at a non-hepatotoxic dose (25 mg/kg) was not found to alter Cx32 or Cx26 expression or to produce a measurable Cx32 serine phosphorylation but did give a small, significant reduction of cell communication. Carbon tetrachloride (CCl 4 ) did not affect cell communication (despite a small significant reduction of Cx32 content) at a non-hepatotoxic dose. Both loss of communication and Cx32 expression was observed only at a dose that caused hepatocyte toxicity as evidenced by increased serum alanine aminotransferase activity. Overall, the findings emphasise that loss of gap junctional communication in vivo can contribute to carcinogenesis by non-genotoxic carcinogens through different primary mechanism. In contrast to Wy-14,643 and DDT, the results with CCl 4 are consistent with a requirement for hepatotoxicity in its carcinogenic action

  16. HDAC inhibition amplifies gap junction communication in neural progenitors: Potential for cell-mediated enzyme prodrug therapy

    International Nuclear Information System (INIS)

    Khan, Zahidul; Akhtar, Monira; Asklund, Thomas; Juliusson, Bengt; Almqvist, Per M.; Ekstroem, Tomas J.

    2007-01-01

    Enzyme prodrug therapy using neural progenitor cells (NPCs) as delivery vehicles has been applied in animal models of gliomas and relies on gap junction communication (GJC) between delivery and target cells. This study investigated the effects of histone deacetylase (HDAC) inhibitors on GJC for the purpose of facilitating transfer of therapeutic molecules from recombinant NPCs. We studied a novel immortalized midbrain cell line, NGC-407 of embryonic human origin having neural precursor characteristics, as a potential delivery vehicle. The expression of gap junction protein connexin 43 (C x 43) was analyzed by western blot and immunocytochemistry. While C x 43 levels were decreased in untreated differentiating NGC-407 cells, the HDAC inhibitor 4-phenylbutyrate (4-PB) increased C x 43 expression along with increased membranous deposition in both proliferating and differentiating cells. Simultaneously, Ser 279/282-phosphorylated form of C x 43 was declined in both culture conditions by 4-PB. The 4-PB effect in NGC-407 cells was verified by using HNSC.100 human neural progenitors and Trichostatin A. Improved functional GJC is of imperative importance for therapeutic strategies involving intercellular transport of low molecular-weight compounds. We show here an enhancement by 4-PB, of the functional GJC among NGC-407 cells, as well as between NGC-407 and human glioma cells, as indicated by increased fluorescent dye transfer

  17. Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline

    Directory of Open Access Journals (Sweden)

    Leif eHertz

    2014-09-01

    Full Text Available Lactate is a versatile metabolite with important roles in modulation of brain glucose utilization rate (CMRglc, diagnosis of brain-injured patients, redox- and receptor-mediated signaling, memory, and alteration of gene transcription. Neurons and astrocytes release and accumulate lactate using equilibrative monocarboxylate transporters that carry out net transmembrane transport of lactate only until intra- and extracellular levels reach equilibrium. Astrocytes have much faster lactate uptake than neurons and shuttle more lactate among gap junction-coupled astrocytes than to nearby neurons. Lactate diffusion within syncytia can provide precursors for oxidative metabolism and glutamate synthesis and facilitate its release from endfeet to perivascular space to stimulate blood flow. Lactate efflux from brain during activation underlies the large underestimation of CMRglc with labeled glucose and fall in CMRO2/CMRglc ratio. Receptor-mediated effects of lactate on locus coeruleus neurons include noradrenaline release in cerebral cortex and c-AMP-mediated stimulation of astrocytic gap junctional coupling, thereby enhancing its dispersal and release from brain. Lactate transport is essential for its multifunctional roles.

  18. Effect of low and staggered gap quantum wells inserted in GaAs tunnel junctions

    Science.gov (United States)

    Louarn, K.; Claveau, Y.; Marigo-Lombart, L.; Fontaine, C.; Arnoult, A.; Piquemal, F.; Bounouh, A.; Cavassilas, N.; Almuneau, G.

    2018-04-01

    In this article, we investigate the impact of the insertion of either a type I InGaAs or a type II InGaAs/GaAsSb quantum well on the performances of MBE-grown GaAs tunnel junctions (TJs). The devices are designed and simulated using a quantum transport model based on the non-equilibrium Green’s function formalism and a 6-band k.p Hamiltonian. We experimentally observe significant improvements of the peak tunneling current density on both heterostructures with a 460-fold increase for a moderately doped GaAs TJ when the InGaAs QW is inserted at the junction interface, and a 3-fold improvement on a highly doped GaAs TJ integrating a type II InGaAs/GaAsSb QW. Thus, the simple insertion of staggered band lineup heterostructures enables us to reach a tunneling current well above the kA cm‑2 range, equivalent to the best achieved results for Si-doped GaAs TJs, implying very interesting potential for TJ-based components, such as multi-junction solar cells, vertical cavity surface emitting lasers and tunnel-field effect transistors.

  19. Visfatin Reduces Gap Junction Mediated Cell-to-Cell Communication in Proximal Tubule-Derived Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2013-11-01

    Full Text Available Background/Aims: In the current study we examined if the adipocytokine, visfatin, alters connexin-mediated intercellular communication in proximal tubule-derived epithelial cells. Methods: The effects of visfatin (10-200ng/mL on cell viability and cytotoxicity in HK2-cells were assessed by MTT, crystal violet and lactate dehydrogenase assays. Western blot analysis was used to confirm expression of Cx26, Cx40 and Cx43. The effect of visfatin (10-200ng/mL on TGF-β1 secretion was confirmed by ELISA, and the effects of both TGF-β1 (2-10ng/mL and visfatin (10-200ng/mL on connexin expression were assessed by western blot. Functional intercellular communication was determined using transfer of Lucifer Yellow and paired-whole cell patch clamp electrophysiology. Results: In low glucose (5mM, visfatin (10-200ng/mL did not affect membrane integrity, cytotoxicity or cell viability at 48hrs, but did evoke a concentration-dependent reduction in Cx26 and Cx43 expression. The expression of Cx40 was unaffected. At 48hrs, visfatin (10-200ng/mL increased the secretion of TGF-β1 and the visfatin-evoked changes in connexin expression were mimicked by exogenous application of the pro-fibrotic cytokine (2-10ng/ml. Visfatin reduced dye transfer between coupled cells and decreased functional conductance, with levels falling by 63% as compared to control. Although input resistance was increased following visfatin treatment by 166%, the change was not significant as compared to control. The effects of visfatin on Cx-expression and cell-coupling were blocked in the presence of a TGF-β1 specific neutralizing antibody. Conclusions: The adipocytokine visfatin selectively evoked a non-toxic reduction in connexin expression in HK2-cells. The loss in gap-junction associated proteins was mirrored by a loss in functional conductance between coupled cells. Visfatin increased TGF-β secretion and the pattern of change for connexins expression was mimicked by exogenous

  20. 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.

  1. 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

  2. Integrating evolutionary game theory into an agent-based model of ductal carcinoma in situ: Role of gap junctions in cancer progression.

    Science.gov (United States)

    Malekian, Negin; Habibi, Jafar; Zangooei, Mohammad Hossein; Aghakhani, Hojjat

    2016-11-01

    There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth. We make an evolutionary game theory component in order to model the signal propagation through gap junctions. The game payoffs are defined as a function of cellular context. Then, the game theory component is integrated into an agent-based model of tumor growth. After that, the integrated model is applied to ductal carcinoma in situ, a type of early stage breast cancer. Different scenarios are explored to observe the impact of the gap junction communication and parameters of the game theory component on cancer progression. We compare these scenarios by using the Wilcoxon signed-rank test. The Wilcoxon signed-rank test succeeds in proving a significant difference between the tumor growth of the model before and after considering the gap junction communication. The Wilcoxon signed-rank test also proves that the tumor growth significantly depends on the oxygen threshold of turning survival signals into apoptosis. In this study, the gap junction communication is modeled by using evolutionary game theory to illustrate its role at early stage cancers such as ductal carcinoma in situ. This work indicates that the gap junction communication and the oxygen threshold of turning survival signals into apoptosis can notably affect cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Application of Stochastic Automata Networks for Creation of Continuous Time Markov Chain Models of Voltage Gating of Gap Junction Channels

    Directory of Open Access Journals (Sweden)

    Mindaugas Snipas

    2015-01-01

    Full Text Available The primary goal of this work was to study advantages of numerical methods used for the creation of continuous time Markov chain models (CTMC of voltage gating of gap junction (GJ channels composed of connexin protein. This task was accomplished by describing gating of GJs using the formalism of the stochastic automata networks (SANs, which allowed for very efficient building and storing of infinitesimal generator of the CTMC that allowed to produce matrices of the models containing a distinct block structure. All of that allowed us to develop efficient numerical methods for a steady-state solution of CTMC models. This allowed us to accelerate CPU time, which is necessary to solve CTMC models, ∼20 times.

  4. Application of Stochastic Automata Networks for Creation of Continuous Time Markov Chain Models of Voltage Gating of Gap Junction Channels

    Science.gov (United States)

    Pranevicius, Henrikas; Pranevicius, Mindaugas; Pranevicius, Osvaldas; Bukauskas, Feliksas F.

    2015-01-01

    The primary goal of this work was to study advantages of numerical methods used for the creation of continuous time Markov chain models (CTMC) of voltage gating of gap junction (GJ) channels composed of connexin protein. This task was accomplished by describing gating of GJs using the formalism of the stochastic automata networks (SANs), which allowed for very efficient building and storing of infinitesimal generator of the CTMC that allowed to produce matrices of the models containing a distinct block structure. All of that allowed us to develop efficient numerical methods for a steady-state solution of CTMC models. This allowed us to accelerate CPU time, which is necessary to solve CTMC models, ∼20 times. PMID:25705700

  5. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury.

    Science.gov (United States)

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H R; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo; Molon, Barbara; Mammano, Fabio

    2015-04-30

    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding "bystander" cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca(2+)-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy.

  6. Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Hui [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Zhuo, Liling [College of Life Science, Zaozhuang University, Zaozhuang, Shandong, 277160 (China); Han, Tao; Hu, Di; Yang, Xiaokang; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Liu, Xuezhong [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Liu, Zongping, E-mail: liuzongping@yzu.edu.cn [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China)

    2015-04-17

    Cadmium (Cd) is known to induce hepatotoxicity, yet the underlying mechanism of how this occurs is not fully understood. In this study, Cd-induced apoptosis was demonstrated in rat liver cells (BRL 3A) with apoptotic nuclear morphological changes and a decrease in cell index (CI) in a time- and concentration-dependent manner. The role of gap junctional intercellular communication (GJIC) and autophagy in Cd-induced apoptosis was investigated. Cd significantly induced GJIC inhibition as well as downregulation of connexin 43 (Cx43). The prototypical gap junction blocker carbenoxolone disodium (CBX) exacerbated the Cd-induced decrease in CI. Cd treatment was also found to cause autophagy, with an increase in mRNA expression of autophagy-related genes Atg-5, Atg-7, Beclin-1, and microtubule-associated protein light chain 3 (LC3) conversion from cytosolic LC3-I to membrane-bound LC3-II. The autophagic inducer rapamycin (RAP) prevented the Cd-induced CI decrease, while the autophagic inhibitor chloroquine (CQ) caused a further reduction in CI. In addition, CBX promoted Cd-induced autophagy, as well as changes in expression of Atg-5, Atg-7, Beclin-1 and LC3. CQ was found to block the Cd-induced decrease in Cx43 and GJIC inhibition, whereas RAP had opposite effect. These results demonstrate that autophagy plays a protective role during Cd-induced apoptosis in BRL 3A cells during 6 h of experiment, while autophagy exacerbates Cd-induced GJIC inhibition which has a negative effect on cellular fate. - Highlights: • GJIC and autophagy is crucial for biological processes. • Cd exposure causes GJIC inhibition and autophagy increase in BRL 3A cells. • Autophagy protects Cd induced BRL 3A cells apoptosis at an early stage. • Autophagy exacerbates Cd-induced GJIC inhibition. • GJIC plays an important role in autophagy induced cell death or survival.

  7. S-diclofenac Protects against Doxorubicin-Induced Cardiomyopathy in Mice via Ameliorating Cardiac Gap Junction Remodeling

    Science.gov (United States)

    Zhang, Huili; Zhang, Alian; Guo, Changfa; Shi, Chunzhi; Zhang, Yang; Liu, Qing; Sparatore, Anna; Wang, Changqian

    2011-01-01

    Hydrogen sulfide (H2S), as a novel gaseous mediator, plays important roles in mammalian cardiovascular tissues. In the present study, we investigated the cardioprotective effect of S-diclofenac (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester), a novel H2S-releasing derivative of diclofenac, in a murine model of doxorubicin-induced cardiomyopathy. After a single dose injection of doxorubicin (15 mg/kg, i.p.), male C57BL/6J mice were given daily treatment of S-diclofenac (25 and 50 µmol/kg, i.p.), diclofenac (25 and 50 µmol/kg, i.p.), NaHS (50 µmol/kg, i.p.), or same volume of vehicle. The cardioprotective effect of S-diclofenac was observed after 14 days. It showed that S-diclofenac, but not diclofenac, dose-dependently inhibited the doxorubicin-induced downregulation of cardiac gap junction proteins (connexin 43 and connexin 45) and thus reversed the remodeling of gap junctions in hearts. It also dose-dependently suppressed doxorubicin-induced activation of JNK in hearts. Furthermore, S-diclofenac produced a dose-dependent anti-inflammatory and anti-oxidative effect in this model. As a result, S-diclofenac significantly attenuated doxorubicin-related cardiac injury and cardiac dysfunction, and improved the survival rate of mice with doxorubicin-induced cardiomyopathy. These effects of S-diclofenac were mimicked in large part by NaHS. Therefore, we propose that H2S released from S-diclofenac in vivo contributes to the protective effect in doxorubicin-induced cardiomyopathy. These data also provide evidence for a critical role of H2S in the pathogenesis of doxorubicin-induced cardiomyopathy. PMID:22039489

  8. Gap junction intercellular communication mediated by connexin43 in astrocytes is essential for their resistance to oxidative stress.

    Science.gov (United States)

    Le, Hoa T; Sin, Wun Chey; Lozinsky, Shannon; Bechberger, John; Vega, José Luis; Guo, Xu Qiu; Sáez, Juan C; Naus, Christian C

    2014-01-17

    Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

  9. Sphingosine-1-Phosphate reduces ischemia/reperfusion injury by phosphorylating the gap junction protein Connexin43

    DEFF Research Database (Denmark)

    Morel, Sandrine; Christoffersen, Christina; Axelsen, Lene N

    2016-01-01

    recruitment seems only indirectly affected. Importantly, short-term S1P treatment at the onset of reperfusion was sufficient to reduce ischemia/reperfusion injury in isolated perfused hearts. Mechanistic in vitro and ex vivo studies revealed that 5 min of S1P treatment induced phosphorylation of the gap...

  10. Velocity barrier-controlled of spin-valley polarized transport in monolayer WSe2 junction

    Science.gov (United States)

    Qiu, Xuejun; Lv, Qiang; Cao, Zhenzhou

    2018-05-01

    In this work, we have theoretically investigated the influence of velocity barrier on the spin-valley polarized transport in monolayer (ML) WSe2 junction with a large spin-orbit coupling (SOC). Both the spin-valley resolved transmission probabilities and conductance are strong dependent on the velocity barrier, as the velocity barrier decreases to 0.06, a spin-valley polarization of exceeding 90% is observed, which is distinct from the ML MoS2 owing to incommensurable SOC. In addition, the spin-valley polarization is further increased above 95% in a ML WSe2 superlattice, in particular, it's found many extraordinary velocity barrier-dependent transport gaps for multiple barrier due to evanescent tunneling. Our results may open an avenue for the velocity barrier-controlled high-efficiency spin and valley polarizations in ML WSe2-based electronic devices.

  11. [Effects of Chinese herbal compound for supplementing qi and activating blood circulation on actin, Cx43 expressions and gap junctional intercellular communication functions of myocardial cells in patients with Coxsackie virus B 3 viral myocarditis].

    Science.gov (United States)

    Zhang, Ming-xue; He, Wei; Gu, Ping

    2010-08-01

    To observe the effect of Chinese herbal compound for supplementing qi and activating blood circulation (CHC) on the gap junctional intercellular communication (GJIC) function of myocardial cells in patients with Coxsackie virus B 3 (CVB3) viral myocarditis. Expressions of actin and connexin43 (Cx43) in myocardial cells of patients arranged in three groups (the normal control group, the viral infected group and the CHC treated group) were detected by immunohistochemical method; the fluorescence photobleaching recovery rate of cells was detected by laser scanning confocal microscope. As compared with the viral infected group, the expressions of actin and Cx43 were increased and the GJIC function was improved in the CHC treated group. CHC could antagonize viral injury on skeleton protein, and repair the structure of gap junction channel to improve the GJIC function of myocardial cells after being attacked by CVB3.

  12. Dynamic Control of Tunneling Conductance in Ferroelectric Tunnel Junctions

    International Nuclear Information System (INIS)

    Zou Ya-Yi; Zhou Yan; Chew Khian-Hooi

    2013-01-01

    We investigate the dynamic characteristics of electric polarization P(t) in a ferroelectric junction under ac applied voltage and stress, and calculate the frequency response and the cut-off frequency f 0 , which provides a reference for the upper limit of the working frequency. Our study might be significant for sensor and memory applications of nanodevices based on ferroelectric junctions

  13. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model

    Czech Academy of Sciences Publication Activity Database

    Sovadinová, I.; Babica, Pavel; Böke, H.; Kumar, E.; Wilke, A.; Park, J.-S.; Trosko, J. E.; Upham, B. L.

    2015-01-01

    Roč. 10, 5 no.e0124454 (2015), s. 1-16 E-ISSN 1932-6203 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * resveratrol * phosphatidylcholine-specific phospholipase C Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

  14. Controlling formation of single-molecule junctions by electrochemical reduction of diazonium terminal groups.

    Science.gov (United States)

    Hines, Thomas; Díez-Pérez, Ismael; Nakamura, Hisao; Shimazaki, Tomomi; Asai, Yoshihiro; Tao, Nongjian

    2013-03-06

    We report controlling the formation of single-molecule junctions by means of electrochemically reducing two axialdiazonium terminal groups on a molecule, thereby producing direct Au-C covalent bonds in situ between the molecule and gold electrodes. We report a yield enhancement in molecular junction formation as the electrochemical potential of both junction electrodes approach the reduction potential of the diazonium terminal groups. Step length analysis shows that the molecular junction is significantly more stable, and can be pulled over a longer distance than a comparable junction created with amine anchoring bonds. The stability of the junction is explained by the calculated lower binding energy associated with the direct Au-C bond compared with the Au-N bond.

  15. Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning

    Directory of Open Access Journals (Sweden)

    Mika Tanaka

    2008-04-01

    Full Text Available Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43, a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre, which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43fl/fl:S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43fl/fl:S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in thier cerebellar slices. In addition, at the behavioral level, Cx43fl/fl:S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.

  16. Chaos synchronization in a Josephson junction system via active sliding mode control

    International Nuclear Information System (INIS)

    Zhao Yang; Wang Wei

    2009-01-01

    In this letter, two types of active siding control methods are proposed and applied to achieve chaotic synchronization in a Josephson junction system. Numerical simulations are used to verify the proposed control techniques.

  17. On the universality of the ''smile''-gap in the density of states of a chaotic Josephson junction

    Energy Technology Data Exchange (ETDEWEB)

    Reutlinger, Johannes; Belzig, Wolfgang [University of Konstanz, Department of Physics (Germany); Nazarov, Yuli [Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft (Netherlands); Glazman, Leonid [Department of Physics, Yale University, New Haven, CT (United States)

    2015-07-01

    The superconducting proximity effect strongly modifies the local density of states in chaotic Josephson junctions. Recently we found that besides the well-known minigap a secondary gap appears just below the superconducting gap edge Δ in the limit of a large Thouless energy E{sub Th} >or similar Δ. To check the universality of this novel gap phenomenon we study the effect of nonideal contacts and show that the ''smile''-gap crucially depends on the transmission eigenvalue distribution. In a next step we use the random matrix method to investigate the ''smile''-gap. This allows us to approach the statistics of Andreev levels, going beyond the quasiclassical Greens function method. It turns out that the hard gap edge softens similar to what is already known from the minigap.

  18. A novel role of dendritic gap junction and mechanisms underlying its interaction with thalamocortical conductance in fast spiking inhibitory neurons

    Directory of Open Access Journals (Sweden)

    Sun Qian-Quan

    2009-10-01

    Full Text Available Abstract Background Little is known about the roles of dendritic gap junctions (GJs of inhibitory interneurons in modulating temporal properties of sensory induced responses in sensory cortices. Electrophysiological dual patch-clamp recording and computational simulation methods were used in combination to examine a novel role of GJs in sensory mediated feed-forward inhibitory responses in barrel cortex layer IV and its underlying mechanisms. Results Under physiological conditions, excitatory post-junctional potentials (EPJPs interact with thalamocortical (TC inputs within an unprecedented few milliseconds (i.e. over 200 Hz to enhance the firing probability and synchrony of coupled fast-spiking (FS cells. Dendritic GJ coupling allows fourfold increase in synchrony and a significant enhancement in spike transmission efficacy in excitatory spiny stellate cells. The model revealed the following novel mechanisms: 1 rapid capacitive current (Icap underlies the activation of voltage-gated sodium channels; 2 there was less than 2 milliseconds in which the Icap underlying TC input and EPJP was coupled effectively; 3 cells with dendritic GJs had larger input conductance and smaller membrane response to weaker inputs; 4 synchrony in inhibitory networks by GJ coupling leads to reduced sporadic lateral inhibition and increased TC transmission efficacy. Conclusion Dendritic GJs of neocortical inhibitory networks can have very powerful effects in modulating the strength and the temporal properties of sensory induced feed-forward inhibitory and excitatory responses at a very high frequency band (>200 Hz. Rapid capacitive currents are identified as main mechanisms underlying interaction between two transient synaptic conductances.

  19. Gate-voltage control of equal-spin Andreev reflection in half-metal/semiconductor/superconductor junctions

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Xiuqiang, E-mail: xianqiangzhe@126.com [National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093 (China); Meng, Hao, E-mail: menghao1982@shu.edu.cn [School of Physics and Telecommunication Engineering, Shanxi University of Technology, Hanzhong 723001 (China)

    2016-04-22

    With the Blonder–Tinkham–Klapwijk (BTK) approach, we investigate conductance spectrum in Ferromagnet/Semiconductor/Superconductor (FM/Sm/SC) double tunnel junctions where strong Rashba spin–orbit interaction (RSOI) is taken into account in semiconductors. For the half-metal limit, we find that the in-gap conductance becomes finite except at zero voltage when inserting a ferromagnetic insulator (FI) at the Sm/SC interface, which means that the appearance of a long-range triplet states in the half-metal. This is because of the emergence of the unconventional equal-spin Andreev reflection (ESAR). When the FI locates at the FM/Sm interface, however, we find the vanishing in-gap conductance due to the absence of the ESAR. Moreover, the non-zero in-gap conductance shows a nonmonotonic dependence on RSOI which can be controlled by applying an external gate voltage. Our results can be used to generate and manipulate the long-range spin triplet correlation in the nascent field of superconducting spintronics. - Highlights: • We study the equal-spin Andreev reflection in half-metal/semiconductor/superconductor (HM/Sm/SC) junctions. • The equal-spin Andreev reflection appearance when inserting a ferromagnetic insulator at the Sm/SC interface. • The finite in-gap conductance is attributed to the emergence of the equal-spin Andreev reflection. • The finite in-gap conductance shows a nonmonotonic dependence on Rashba spin–orbit interaction. • The finite in-gap conductance can be controlled by applying an external gate voltage.

  20. Analysis of trafficking, stability and function of human connexin 26 gap junction channels with deafness-causing mutations in the fourth transmembrane helix.

    Directory of Open Access Journals (Sweden)

    Cinzia Ambrosi

    Full Text Available Human Connexin26 gene mutations cause hearing loss. These hereditary mutations are the leading cause of childhood deafness worldwide. Mutations in gap junction proteins (connexins can impair intercellular communication by eliminating protein synthesis, mis-trafficking, or inducing channels that fail to dock or have aberrant function. We previously identified a new class of mutants that form non-functional gap junction channels and hemichannels (connexons by disrupting packing and inter-helix interactions. Here we analyzed fourteen point mutations in the fourth transmembrane helix of connexin26 (Cx26 that cause non-syndromic hearing loss. Eight mutations caused mis-trafficking (K188R, F191L, V198M, S199F, G200R, I203K, L205P, T208P. Of the remaining six that formed gap junctions in mammalian cells, M195T and A197S formed stable hemichannels after isolation with a baculovirus/Sf9 protein purification system, while C202F, I203T, L205V and N206S formed hemichannels with varying degrees of instability. The function of all six gap junction-forming mutants was further assessed through measurement of dye coupling in mammalian cells and junctional conductance in paired Xenopus oocytes. Dye coupling between cell pairs was reduced by varying degrees for all six mutants. In homotypic oocyte pairings, only A197S induced measurable conductance. In heterotypic pairings with wild-type Cx26, five of the six mutants formed functional gap junction channels, albeit with reduced efficiency. None of the mutants displayed significant alterations in sensitivity to transjunctional voltage or induced conductive hemichannels in single oocytes. Intra-hemichannel interactions between mutant and wild-type proteins were assessed in rescue experiments using baculovirus expression in Sf9 insect cells. Of the four unstable mutations (C202F, I203T, L205V, N206S only C202F and N206S formed stable hemichannels when co-expressed with wild-type Cx26. Stable M195T hemichannels

  1. Visualizing the effect of dynamin inhibition on annular gap vesicle formation and fission.

    Science.gov (United States)

    Nickel, Beth; Boller, Marie; Schneider, Kimberly; Shakespeare, Teresa; Gay, Vernon; Murray, Sandra A

    2013-06-15

    Although gap junction plaque assembly has been extensively studied, mechanisms involved in plaque disassembly are not well understood. Disassembly involves an internalization process in which annular gap junction vesicles are formed. These vesicles undergo fission, but the molecular machinery needed for these fissions has not been described. The mechanoenzyme dynamin has been previously demonstrated to play a role in gap junction plaque internalization. To investigate the role of dynamin in annular gap junction vesicle fission, immunocytochemical, time-lapse and transmission electron microscopy were used to analyze SW-13 adrenocortical cells in culture. Dynamin was demonstrated to colocalize with gap junction plaques and vesicles. Dynamin inhibition, by siRNA knockdown or treatment with the dynamin GTPase inhibitor dynasore, increased the number and size of gap junction 'buds' suspended from the gap junction plaques. Buds, in control populations, were frequently released to form annular gap junction vesicles. In dynamin-inhibited populations, the buds were larger and infrequently released and thus fewer annular gap junction vesicles were formed. In addition, the number of annular gap junction vesicle fissions per hour was reduced in the dynamin-inhibited populations. We believe this to be the first report addressing the details of annular gap junction vesicle fissions and demonstrating a role of dynamin in this process. This information is crucial for elucidating the relationship between gap junctions, membrane regulation and cell behavior.

  2. Heavy-ion-induced bystander killing of human lung cancer cells. Role of gap junctional intercellular communication

    International Nuclear Information System (INIS)

    Harada, Kosaku; Nonaka, Tetsuo; Hamada, Nobuyuki; Sakurai, Hideyuki; Hasegawa, Masatoshi; Kobayashi, Yasuhiko; Nakano, Takashi; Funayama, Tomoo; Kakizaki, Takehiko

    2009-01-01

    The aim of the present study was to clarify the mechanisms of cell death induced by heavy-ion irradiation focusing on the bystander effect in human lung cancer A549 cells. In microbeam irradiation, each of 1, 5, and 25 cells under confluent cell conditions was irradiated with 1, 5, or 10 particles of carbon ions (220 MeV), and then the surviving fraction of the population was measured by a clonogenic assay in order to investigate the bystander effect of heavy-ions. In this experiment, the limited number of cells (0.0001-0.002%, 5-25 cells) under confluent cell conditions irradiated with 5 or 10 carbon ions resulted in an exaggerated 8-14% increase in cell death by clonogenic assay. However, these overshooting responses were not observed under exponentially growing cell conditions. Furthermore, these responses were inhibited in cells treated with an inhibitor of gap junctional intercellular communication (GJIC), whereas they were markedly enhanced by the addition of a stimulator of GJIC. The present results suggest that bystander cell killing by heavy-ions was induced mainly by direct cell-to-cell communication, such as GJIC, which might play important roles in bystander responses. (author)

  3. Firing patterns and synchronization in nonsynaptic epileptiform activity: the effect of gap junctions modulated by potassium accumulation

    International Nuclear Information System (INIS)

    Santos, D O C; Dickman, R; Rodrigues, A M; De Almeida, A C G

    2009-01-01

    Several lines of evidence point to the modification of firing patterns and of synchronization due to gap junctions (GJs) as having a role in the establishment of epileptiform activity (EA). However, previous studies consider GJs as ohmic resistors, ignoring the effects of intense variations in ionic concentration known to occur during seizures. In addition to GJs, extracellular potassium is regarded as a further important factor involved in seizure initiation and sustainment. To analyze how these two mechanisms act together to shape firing and synchronization, we use a detailed computational model for in vitro high-K + and low-Ca 2+ nonsynaptic EA. The model permits us to explore the modulation of electrotonic interactions under ionic concentration changes caused by electrodiffusion in the extracellular space, altered by tortuosity. In addition, we investigate the special case of null GJ current. Increased electrotonic interaction alters bursts and action potential frequencies, favoring synchronization. The particularities of pattern changes depend on the tortuosity and array size. Extracellular potassium accumulation alone modifies firing and synchronization when the GJ coupling is null

  4. Segmental Bayesian estimation of gap-junctional and inhibitory conductance of inferior olive neurons from spike trains with complicated dynamics

    Directory of Open Access Journals (Sweden)

    Huu eHoang

    2015-05-01

    Full Text Available The inverse problem for estimating model parameters from brain spike data is an ill-posed problem because of a huge mismatch in the system complexity between the model and the brain as well as its non-stationary dynamics, and needs a stochastic approach that finds the most likely solution among many possible solutions. In the present study, we developed a segmental Bayesian method to estimate the two parameters of interest, the gap-junctional (gc and inhibitory conductance (gi from inferior olive spike data. Feature vectors were estimated for the spike data in a segment-wise fashion to compensate for the non-stationary firing dynamics. Hierarchical Bayesian estimation was conducted to estimate the gc and gi for every spike segment using a forward model constructed in the principal component analysis (PCA space of the feature vectors, and to merge the segmental estimates into single estimates for every neuron. The segmental Bayesian estimation gave smaller fitting errors than the conventional Bayesian inference, which finds the estimates once across the entire spike data, or the minimum error method, which directly finds the closest match in the PCA space. The segmental Bayesian inference has the potential to overcome the problem of non-stationary dynamics and resolve the ill-posedness of the inverse problem because of the mismatch between the model and the brain under the constraints based, and it is a useful tool to evaluate parameters of interest for neuroscience from experimental spike train data.

  5. Possible Mechanisms of Mercury Toxicity and Cancer Promotion: Involvement of Gap Junction Intercellular Communications and Inflammatory Cytokines

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    Roberto Zefferino

    2017-01-01

    Full Text Available A number of observations indicate that heavy metals are able to alter cellular metabolic pathways through induction of a prooxidative state. Nevertheless, the outcome of heavy metal-mediated effects in the development of human diseases is debated and needs further insights. Cancer is a well-established DNA mutation-linked disease; however, epigenetic events are perhaps more important and harmful than genetic alterations. Unfortunately, we do not have reliable screening methods to assess/validate the epigenetic (promoter effects of a physical or a chemical agent. We propose a mechanism of action whereby mercury acts as a possible promoter carcinogen. In the present contribution, we resume our previous studies on mercury tested at concentrations comparable with its occurrence as environmental pollutant. It is shown that Hg(II elicits a prooxidative state in keratinocytes linked to inhibition of gap junction-mediated intercellular communication and proinflammatory cytokine production. These combined effects may on one hand isolate cells from tissue-specific homeostasis promoting their proliferation and on the other hand tamper the immune system defense/surveillance checkmating the whole organism. Since Hg(II is not a mutagenic/genotoxic compound directly affecting gene expression, in a broader sense, mercury might be an example of an epigenetic tumor promoter or, further expanding this concept, a “metagenetic” effector.

  6. 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.

  7. Conformations of cyclopentasilane stereoisomers control molecular junction conductance

    DEFF Research Database (Denmark)

    Li, Haixing; Garner, Marc Hamilton; Shangguan, Zhichun

    2016-01-01

    ,3-position with methylthiomethyl electrode binding groups using both the scanning tunneling microscope-based break junction technique and density functional theory based ab initio calculations. In contrast with the linear ones, these cyclic silanes yield lower conductance values; calculations reveal...

  8. Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

    International Nuclear Information System (INIS)

    Ma, W.H.; Liu, Y.J.; Wang, W.; Zhang, Y.Z.

    2015-01-01

    Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation

  9. Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

    Energy Technology Data Exchange (ETDEWEB)

    Ma, W.H.; Liu, Y.J.; Wang, W.; Zhang, Y.Z. [The Third Hospital of Hebei Medical University, The Provincial Key Laboratory for Orthopedic Biomechanics of Hebei, Shijiazhuang, Hebei Province (China)

    2015-02-13

    Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation.

  10. Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran

    Directory of Open Access Journals (Sweden)

    Masoud Akbarzadeh Laleh

    2017-01-01

    Full Text Available Background: We aimed to determine the contribution of four DFNB loci and mutation analysis of gap junction beta-2 (GJB2 and GJB4 genes in autosomal recessive nonsyndromic hearing loss (ARNSHL in South of Iran. Materials and Methods: A total of 36 large ARNSHL pedigrees with at least two affected subjects were enrolled in the current study. The GJB2 and GJB4 genes mutations were screened using direct sequencing method. The GJB2 and GJB4 negative families were analyzed for the linkage to DFNB21, DFNB24, DFNB29, and DFNB42 loci by genotyping the corresponding STR markers using polymerase chain reaction-PAGE method. Results: We found a homozygous nonsense mutation W77X and a homozygous missense mutation C169W in 5.55% of studied families in GJB2 and GJB4 genes, respectively. Five heterozygous mutations including V63G, A78T, and R127H in GJB2 gene, and R103C and R227W in GJB4 gene were detected. We identified two novel variations V63G in GJB2 and R227W in GJB4. In silico analysis predicted that both novel variations are deleterious mutations. We did not unveil any linkage between DFNB21, DFNB24, DFNB29, and DFNB42 loci and ARNSHL among studied families. Conclusion: This is the first report of GJB2 and GJB4 mutations from Hormozgan population. According to the previous publications regarding GJB2 and GJB4 mutations, the distribution of the mutations is different from other parts of Iran that should be considered in primary health-care programs. Further investigations are needed to evaluate the contribution of other loci in ARNSHL subjects in South of Iran.

  11. Inhibition of gap junctional intercellular communication by noncoplanar polychlorinated biphenyls: Inhibitory potencies and screening for potential mode(s) of action

    Czech Academy of Sciences Publication Activity Database

    Machala, M.; Bláha, L.; Vondráček, Jan; Trosko, J. E.; Scott, J.; Upham, B. L.

    2003-01-01

    Roč. 76, č. 1 (2003), s. 102-111 ISSN 1096-6080 R&D Projects: GA MZe QC0194; GA ČR GA525/00/D101 Grant - others:National Institute of Health(US) P42 ES04911-07 Institutional research plan: CEZ:AV0Z5004920 Keywords : WB-F344 cell line * gap junction * PCB congeners Subject RIV: BO - Biophysics Impact factor: 3.067, year: 2003

  12. HYS-32, a novel analogue of combretastatin A-4, enhances connexin43 expression and gap junction intercellular communication in rat astrocytes.

    Science.gov (United States)

    Lin, Pei-Chun; Shen, Chien-Chang; Liao, Chih-Kai; Jow, Guey-Mei; Chiu, Chi-Ting; Chung, Tun-Hui; Wu, Jiahn-Chun

    2013-05-01

    HYS-32 [4-(3,4-dimethoxyphenyl)-3-(naphthalen-2-yl)-2(5H)-furanone] is a new analogue of the anti-tumor compound combretastatin A-4 containing a cis-stilbene moiety. In this study, we investigated its effects on Cx43 gap junction intercellular communication (GJIC) and the signaling pathway involved in rat primary astrocytes. Western blot analyses showed that HYS-32 dose- and time-dependently upregulated Cx43 expression. A confocal microscopic study and scrape-loading/dye transfer analyses demonstrated that HYS-32 (5μM) induced microtubule coiling, accumulation of Cx43 in gap junction plaques, and increased GJIC in astrocytes. The HYS-32-induced microtubule coiling and Cx43 accumulation in gap junction plaques was reversed when HYS-32 was removed. Treatment of astrocytes with cycloheximide resulted in time-dependent degradation of by co-treatment with HYS-32 by increasing the half-life of Cx43. Co-treatment with HYS-32 also prevented the LPS-induced downregulation of Cx43 and inhibition of GJIC in astrocytes. HYS-32 induced activation of PKC, ERK, and JNK, and co-treatment with the PKC inhibitor Go6976 or the ERK inhibitor PD98059, but not the JNK inhibitor SP600125, prevented the HYS-32-induced increase in Cx43 expression and GJIC. Go6976 suppressed the HYS-32-induced PKC phosphorylation and increase in phospho-ERK levels, while PD98059 did not prevent the HYS-32-induced increase in phospho-PKC levels, suggesting that PKC is an upstream effector of ERK. In conclusion, our results show that HYS-32 increases the half-life of Cx43 and enhances Cx43 expression and GJIC in astrocytes via a PKC-ERK signaling cascade. These novel biological effects of HYS-32 on astrocyte gap junctions support its potential for therapeutic use as a protective agent for the central nervous system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Keratitis-Ichthyosis-Deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43

    Science.gov (United States)

    García, Isaac E.; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshimi; Olivero, Pablo; Pérez-Acle, Tomás; González, Carlos; Sáez, Juan C.; Contreras, Jorge E.; Martínez, Agustín D.

    2015-01-01

    Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like Keratitis Ichthyosis Deafness syndrome (KID). Because in the human skin Cx26 is co-expressed with other connexins, like Cx43 and Cx30, and since KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channels functions remain unknown. In this study we demonstrate that syndromic mutations at the N-terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) show exacerbated hemichannel activity, but nonfunctional gap junction channels; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca2+ overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin. PMID:25625422

  14. Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine kinase/ganciclovir gene therapy via enhanced gap junctional intercellular communication.

    Directory of Open Access Journals (Sweden)

    Jianyong Xiao

    Full Text Available The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV. This effect is reported to be mediated by gap junctional intercellular communication (GJIC, and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA, a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy.

  15. Role of gap junctions and protein kinase A during the development of oocyte maturational competence in Ayu (Plecoglossus altivelis)

    Science.gov (United States)

    Yamamoto, Y.; Yoshizaki, G.; Takeuchi, T.; Soyano, K.; Patino, R.

    2008-01-01

    Meiotic resumption in teleost oocytes is induced by a maturation-inducing hormone (MIH). The sensitivity of oocytes to MIH, also known as oocyte maturational competence (OMC), is induced by LH via mechanisms that are not fully understood. A previous study of Ayu (Plecoglossus altivelis) showed the presence of functional heterologous gap junctions (GJs) between oocytes and their surrounding granulosa cells. The objectives of this study were to determine the role of ovarian GJs and of protein kinase A (PKA) during the acquisition of OMC. We examined the effects of the specific GJ inhibitor carbenoxolone (CBX) and 18??-glycyrrhetinic acid (??-GA) on the LH-(hCG)-dependent acquisition of OMC and on MIH-(17,20??-dihydroxy-4-pregnen-3-one)-dependent meiotic resumption; measured the cAMP content of ovarian follicles during the hCG-dependent acquisition of OMC; and determined the effects of PK activators and inhibitors on hCG-dependent OMC. Production of follicular cAMP increased during the hCG-dependent acquisition of OMC. Both GJ inhibitors and the PKA inhibitor H8-dihydrochloride, but not the PKC inhibitor GF109203X, suppressed the hCG-dependent acquisition of OMC in a dose-dependent manner. The PKA activator forskolin induced OMC with a similar potency to hCG. Unlike previous observations with teleosts where disruption of heterologous GJ either blocks or stimulates meiotic resumption, treatment with GJ inhibitors did not affect MIH-dependent meiotic resumption in maturationally competent follicles of Ayu. These observations suggest that ovarian GJs are essential for LH-dependent acquisition of OMC but not for MIH-dependent meiotic resumption, and that the stimulation of OMC by LH is mediated by cAMP-dependent PKA. They are also consistent with the view that a precise balance between GJ-mediated signals (positive or negative) and oocyte maturational readiness is required for hormonally regulated meiotic resumption. ?? 2007 Elsevier Inc. All rights reserved.

  16. Oxaliplatin-induced neurotoxicity is mediated through gap junction channels and hemichannels and can be prevented by octanol.

    Science.gov (United States)

    Kagiava, Alexia; Theophilidis, George; Sargiannidou, Irene; Kyriacou, Kyriacos; Kleopa, Kleopas A

    2015-10-01

    Oxaliplatin-induced neurotoxicity (OIN) is a common complication of chemotherapy without effective treatment. In order to clarify the mechanisms of both acute and chronic OIN, we used an ex-vivo mouse sciatic nerve model. Exposure to 25 μM oxaliplatin caused a marked prolongation in the duration of the nerve evoked compound action potential (CAP) by nearly 1200% within 300 min while amplitude remained constant for over 20 h. This oxaliplatin effect was almost completely reversed by the gap junction (GJ) inhibitor octanol in a concentration-dependent manner. Further GJ blockers showed similar effects although with a narrower therapeutic window. To clarify the target molecule we studied sciatic nerves from connexin32 (Cx32) and Cx29 knockout (KO) mice. The oxaliplatin effect and neuroprotection by octanol partially persisted in Cx29 better than in Cx32 KO nerves, suggesting that oxaliplatin affects both, but Cx32 GJ channels more than Cx29 hemichannels. Oxaliplatin also accelerated neurobiotin uptake in HeLa cells expressing the human ortholog of Cx29, Cx31.3, as well as dye transfer between cells expressing the human Cx32, and this effect was blocked by octanol. Oxaliplatin caused no morphological changes initially (up to 3 h of exposure), but prolonged nerve exposure caused juxtaparonodal axonal edema, which was prevented by octanol. Our study indicates that oxaliplatin causes forced opening of Cx32 channels and Cx29 hemichannels in peripheral myelinated fibers leading to disruption of axonal K(+) homeostasis. The GJ blocker octanol prevents OIN at very low concentrations and should be further studied as a neuroprotectant. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Effects of maturation-inducing hormone on heterologous gap junctional coupling in ovarian follicles of Atlantic croaker

    Science.gov (United States)

    Yoshizaki, G.; Patino, R.; Thomas, P.; Bolamba, D.; Chang, Xiaotian

    2001-01-01

    A previous ultrastructural study of heterologous (granulosa cell-oocyte) gap junction (GJ) contacts in ovarian follicles of Atlantic croaker suggested that these contacts disappear late during the process of resumption of oocyte meiosis. This observation suggested that, unlike scenarios proposed for a number of other species, uncoupling of GJ is not necessary for the onset of meiotic resumption in croaker follicles. However, the functionality of heterologous GJ contacts and the temporal association between maturation-inducing hormone (MIH)-induced changes in heterologous coupling and resumption of oocyte meiosis have not been examined in Atlantic croaker. These questions were addressed with a cell-cell coupling assay that is based on the transfer of a GJ marker, Lucifer Yellow, from oocytes to granulosa cells. Follicle-enclosed oocytes injected with Lucifer Yellow allowed transfer of the dye into the follicle cell layer, thus confirming that there is functional heterologous coupling between the oocyte and the granulosa cells. Dye transfer was observed in vitellogenic, full-grown/maturation-incompetent, and full-grown /maturation-competent follicles. Treatment of maturation-competent follicles with MIH caused a time-dependent decline in the number of follicles transferring dye. However, although GJ uncoupling in some of the follicles was observed before germinal vesicle breakdown (GVBD, index of meiotic resumption), about 50% of the follicles maintained the ability to transfer dye even after GVBD had occurred. Further, a known GJ inhibitor (phorbol 12-myristate 13-acetate) blocked heterologous GJ within a time frame similar to that seen with MIH but without inducing any of the morphological changes (including GVBD) associated with follicular maturation. In conclusion, uncoupling of heterologous GJ seems insufficient and unnecessary for the onset of meiotic resumption in ovarian follicles of Atlantic croaker. ?? 2001 Elsevier Science.

  18. Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells

    Directory of Open Access Journals (Sweden)

    Annalucia Carbone

    2018-01-01

    Full Text Available We previously found that human amniotic mesenchymal stem cells (hAMSCs in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ- mediated intercellular communication (GJIC in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43, a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C, and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

  19. Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells.

    Science.gov (United States)

    Carbone, Annalucia; Zefferino, Roberto; Beccia, Elisa; Casavola, Valeria; Castellani, Stefano; Di Gioia, Sante; Giannone, Valentina; Seia, Manuela; Angiolillo, Antonella; Colombo, Carla; Favia, Maria; Conese, Massimo

    2018-01-01

    We previously found that human amniotic mesenchymal stem cells (hAMSCs) in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE) on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ-) mediated intercellular communication (GJIC) in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio) were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43), a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C), and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

  20. Insulator-protected mechanically controlled break junctions for measuring single-molecule conductance in aqueous environments

    OpenAIRE

    Muthusubramanian, N.; Galan, E.; Maity, C.; Eelkema, R.; Grozema, F.C.; van der Zant, H.S.J.

    2016-01-01

    We present a method to fabricate insulated gold mechanically controlled break junctions (MCBJ) by coating the metal with a thin layer of aluminum oxide using plasma enhanced atomic layer deposition. The Al2O3 thickness deposited on the MCBJ devices was varied from 2 to 15 nm to test the suppression of leakage currents in deionized water and phosphate buffered saline. Junctions coated with a 15 nm thick oxide layer yielded atomically sharp electrodes and negligible conductance counts in the ra...

  1. Extending prematuration with cAMP modulators enhances the cumulus contribution to oocyte antioxidant defence and oocyte quality via gap junctions.

    Science.gov (United States)

    Li, H J; Sutton-McDowall, M L; Wang, X; Sugimura, S; Thompson, J G; Gilchrist, R B

    2016-04-01

    Can bovine oocyte antioxidant defence and oocyte quality be improved by extending the duration of pre-in vitro maturation (IVM) with cyclic adenosine mono-phosphate (cAMP) modulators? Lengthening the duration of cAMP-modulated pre-IVM elevates intra-oocyte reduced glutathione (GSH) content and reduces hydrogen peroxide (H2O2) via increased cumulus cell-oocyte gap-junctional communication (GJC), associated with an improvement in subsequent embryo development and quality. Oocytes are susceptible to oxidative stress and the oocyte's most important antioxidant glutathione is supplied, at least in part, by cumulus cells. A temporary inhibition of spontaneous meiotic resumption in oocytes can be achieved by preventing a fall in cAMP, and cyclic AMP-modulated pre-IVM maintains cumulus-oocyte GJC and improves subsequent embryo development. This study consisted of a series of 10 experiments using bovine oocytes in vitro, each with multiple replicates. A range of pre-IVM durations were examined as the key study treatments which were compared with a control. The study was designed to examine if one of the oocyte's major antioxidant defences can be enhanced by pre-IVM with cAMP modulators, and to examine the contribution of cumulus-oocyte GJC on these processes. Immature bovine cumulus-oocyte complexes were treated in vitro without (control) or with the cAMP modulators; 100 µM forskolin (FSK) and 500 µM 3-isobutyl-1-methyxanthine (IBMX), for 0, 2, 4 or 6 h (pre-IVM phase) prior to IVM. Oocyte developmental competence was assessed by embryo development and quality post-IVM/IVF. Cumulus-oocyte GJC, intra-oocyte GSH and H2O2 were quantified at various time points during pre-IVM and IVM, in the presence and the absence of functional inhibitors: carbenoxolone (CBX) to block GJC and buthionine sulfoximide (BSO) to inhibit glutathione synthesis. Pre-IVM with FSK + IBMX increased subsequent blastocyst formation rate and quality compared with standard IVM (P gap junctions between

  2. Mechanotransductive Regulation of Gap-Junction Activity Between MLO-Y4 Osteocyte-Like and MC3T3-E1 Osteoblast-Like Cells in Three-Dimensional Co-Culture.

    Science.gov (United States)

    Juran, C. M.; Blaber, E. A.; Almeida, E. A. C.

    2016-01-01

    Cell and animal studies conducted onboard the International Space Station and formerly on Shuttle flights have provided groundbreaking data illuminating the deleterious biological response of bone to mechanical unloading. However the intercellular communicative mechanisms associated with the regulation of bone synthesis and bone resorption cells are still largely unknown. Connexin-43 (CX43), a gap junction protein, is hypothesized to play a significant role in osteoblast and osteocyte signaling. The purpose of this investigation was to evaluate within a novel three-dimensional microenvironment how the osteocyte-osteoblast gap-junction expression changes when cultures are exposed to exaggerated mechanical load. MLO-Y4 osteocyte-like cells were cultured on a 3D-Biotek polystyrene insert and placed in direct contact with an MC3T3-E1 pre-osteoblast co-cultured monolayer and exposed to 48 h of mechanical stimulation (pulsatile fluid flow (PFF) or monolayer cyclic stretch (MCS)) then evaluated for viability, proliferation, metabolism, and CX43 expression. Mono-cultured MLO-Y4 and MC3T3-E1 control experiments were conducted under PFF and MCS stimulation to observe how strain application stimuli (PFF cell membrane shear or MCS cell focal adhesion/attachment loading) initiates different signaling pathways or downstream regulatory controls. TotalLive cell count, viability and metabolic reduction (Trypan Blue, LIVEDead and Alamar Blue analysis respectively) indicate that mechanical activation of MC3T3-E1 cells inhibits proliferation while maintaining an average 1.04E4 reductioncell metabolic rate, *p0.05 n4. MLO-Y4s in monolayer culture increase in number when exposed to MCS loading but the percent of live cells within the population is low (46.3 total count, *p0.05 n4), these results may indicate an apoptotic signaling cascade. PFF stimulation of the three-dimensional co-cultures elicits a universal increase in CX43 in MLO-Y4 and MC3T3-E1 cells, illustrated by

  3. Nuclear export controls - Closing the gaps

    International Nuclear Information System (INIS)

    Schmidt, Fritz W.

    2005-01-01

    Concerns over a nuclear 'black market' have focused international attention on the effectiveness of nuclear export controls. IAEA Director General Mohamed ElBaradei has stated that the emergence of a multinational illicit network demonstrated the inadequacy of the present export control system, that international cooperation on export controls lay on informal arrangements that were not only not binding but also limited in membership, and that export control information was not systematically shared with the IAEA. This criticism, often heard on the political level, does not really do justice to the work of export control groups. The emergence of a multinational illicit network does not necessarily prove failures in export control systems. Criminal activities, by definition, try to circumvent existing rules and regulations, or they exploit the absence of such rules on State level. To fight such individual cases is not so much a task of regular export control systems, whose function lies primarily in establishing standards and procedures for export controls on State level, but rather the task for intelligence services and their international cooperation. The basis of the export control regime is the Nuclear Non-Proliferation Treaty (NPT). Export controls can - and do - play an important role in fostering this universality goal by demanding the implementation of internationally agreed security standards in recipient countries before export licenses are granted. Drawn from the deliberations in the NPT conferences, the current standards to be demanded as conditions of supply are the following: Safeguards, Physical Protection, National export control provisions. According to the NPT system, export controls require IAEA verification in the recipient country. In addition, export controls enable States to provide information to the IAEA on exports and imports as required by the Additional Protocol. The 2005 NPT Review Conference will be an opportunity to review developments

  4. Competitive behavior of photons contributing to junction voltage jump in narrow band-gap semiconductor multi-quantum-well laser diodes at lasing threshold

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Liefeng, E-mail: fengliefeng@tju.edu.cn, E-mail: lihongru@nankai.edu.cn; Yang, Xiufang; Wang, Cunda; Yao, Dongsheng [Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Faculty of Science, Tianjin University, Tianjin 300072 (China); Li, Yang [Business and Vocational College of Hainan, Haikou 570203 (China); Li, Ding; Hu, Xiaodong [Research Center for Wide Band Gap Semiconductors, State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871 (China); Li, Hongru, E-mail: fengliefeng@tju.edu.cn, E-mail: lihongru@nankai.edu.cn [State Key Laboratory for Medicinal Chemistry and Biology, College of Pharmacy, Nankai University, Tianjin 300071 (China)

    2015-04-15

    The junction behavior of different narrow band-gap multi-quantum-well (MQW) laser diodes (LDs) confirmed that the jump in the junction voltage in the threshold region is a general characteristic of narrow band-gap LDs. The relative change in the 1310 nm LD is the most obvious. To analyze this sudden voltage change, the threshold region is divided into three stages by I{sub th}{sup l} and I{sub th}{sup u}, as shown in Fig. 2; I{sub th}{sup l} is the conventional threshold, and as long as the current is higher than this threshold, lasing exists and the IdV/dI-I plot drops suddenly; I{sub th}{sup u} is the steady lasing point, at which the separation of the quasi-Fermi levels of electron and holes across the active region (V{sub j}) is suddenly pinned. Based on the evolutionary model of dissipative structure theory, the rate equations of the photons in a single-mode LD were deduced in detail at I{sub th}{sup l} and I{sub th}{sup u}. The results proved that the observed behavior of stimulated emission suddenly substituting for spontaneous emission, in a manner similar to biological evolution, must lead to a sudden increase in the injection carriers in the threshold region, which then causes the sudden increase in the junction voltage in this region.

  5. Competitive behavior of photons contributing to junction voltage jump in narrow band-gap semiconductor multi-quantum-well laser diodes at lasing threshold

    International Nuclear Information System (INIS)

    Feng, Liefeng; Yang, Xiufang; Wang, Cunda; Yao, Dongsheng; Li, Yang; Li, Ding; Hu, Xiaodong; Li, Hongru

    2015-01-01

    The junction behavior of different narrow band-gap multi-quantum-well (MQW) laser diodes (LDs) confirmed that the jump in the junction voltage in the threshold region is a general characteristic of narrow band-gap LDs. The relative change in the 1310 nm LD is the most obvious. To analyze this sudden voltage change, the threshold region is divided into three stages by I th l and I th u , as shown in Fig. 2; I th l is the conventional threshold, and as long as the current is higher than this threshold, lasing exists and the IdV/dI-I plot drops suddenly; I th u is the steady lasing point, at which the separation of the quasi-Fermi levels of electron and holes across the active region (V j ) is suddenly pinned. Based on the evolutionary model of dissipative structure theory, the rate equations of the photons in a single-mode LD were deduced in detail at I th l and I th u . The results proved that the observed behavior of stimulated emission suddenly substituting for spontaneous emission, in a manner similar to biological evolution, must lead to a sudden increase in the injection carriers in the threshold region, which then causes the sudden increase in the junction voltage in this region

  6. On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 Hemichannels Expressed in HeLa Cells

    Science.gov (United States)

    Vargas, Anibal A.; Cisterna, Bruno A.; Saavedra-Leiva, Fujiko; Urrutia, Carolina; Cea, Luis A.; Vielma, Alex H.; Gutierrez-Maldonado, Sebastian E.; Martin, Alberto J. M.; Pareja-Barrueto, Claudia; Escalona, Yerko; Schmachtenberg, Oliver; Lagos, Carlos F.; Perez-Acle, Tomas; Sáez, Juan C.

    2017-01-01

    Although connexins (Cxs) are broadly expressed by cells of mammalian organisms, Cx39 has a very restricted pattern of expression and the biophysical properties of Cx39-based channels [hemichannels (HCs) and gap junction channels (GJCs)] remain largely unknown. Here, we used HeLa cells transfected with Cx39 (HeLa-Cx39 cells) in which intercellular electrical coupling was not detected, indicating the absence of GJCs. However, functional HCs were found on the surface of cells exposed to conditions known to increase the open probability of other Cx HCs (e.g., extracellular divalent cationic-free solution (DCFS), extracellular alkaline pH, mechanical stimulus and depolarization to positive membrane potentials). Cx39 HCs were blocked by some traditional Cx HC blockers, but not by others or a pannexin1 channel blocker. HeLa-Cx39 cells showed similar resting membrane potentials (RMPs) to those of parental cells, and exposure to DCFS reduced RMPs in Cx39 transfectants, but not in parental cells. Under these conditions, unitary events of ~75 pS were frequent in HeLa-Cx39 cells and absent in parental cells. Real-time cellular uptake experiments of dyes with different physicochemical features, as well as the application of a machine-learning approach revealed that Cx39 HCs are preferentially permeable to molecules characterized by six categories of descriptors, namely: (1) electronegativity, (2) ionization potential, (3) polarizability, (4) size and geometry, (5) topological flexibility and (6) valence. However, Cx39 HCs opened by mechanical stimulation or alkaline pH were impermeable to Ca2+. Molecular modeling of Cx39-based channels suggest that a constriction present at the intracellular portion of the para helix region co-localizes with an electronegative patch, imposing an energetic and steric barrier, which in the case of GJCs may hinder channel function. Results reported here demonstrate that Cx39 form HCs and add to our understanding of the functional roles of Cx39 HCs

  7. Single molecule dynamics at a mechanically controllable break junction in solution at room temperature.

    Science.gov (United States)

    Konishi, Tatsuya; Kiguchi, Manabu; Takase, Mai; Nagasawa, Fumika; Nabika, Hideki; Ikeda, Katsuyoshi; Uosaki, Kohei; Ueno, Kosei; Misawa, Hiroaki; Murakoshi, Kei

    2013-01-23

    The in situ observation of geometrical and electronic structural dynamics of a single molecule junction is critically important in order to further progress in molecular electronics. Observations of single molecular junctions are difficult, however, because of sensitivity limits. Here, we report surface-enhanced Raman scattering (SERS) of a single 4,4'-bipyridine molecule under conditions of in situ current flow in a nanogap, by using nano-fabricated, mechanically controllable break junction (MCBJ) electrodes. When adsorbed at room temperature on metal nanoelectrodes in solution to form a single molecule junction, statistical analysis showed that nontotally symmetric b(1) and b(2) modes of 4,4'-bipyridine were strongly enhanced relative to observations of the same modes in solid or aqueous solutions. Significant changes in SERS intensity, energy (wavenumber), and selectivity of Raman vibrational bands that are coincident with current fluctuations provide information on distinct states of electronic and geometrical structure of the single molecule junction, even under large thermal fluctuations occurring at room temperature. We observed the dynamics of 4,4'-bipyridine motion between vertical and tilting configurations in the Au nanogap via b(1) and b(2) mode switching. A slight increase in the tilting angle of the molecule was also observed by noting the increase in the energies of Raman modes and the decrease in conductance of the molecular junction.

  8. 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.

  9. Influence of the spatially inhomogeneous gap distribution on the quasiparticle current in c-axis junctions involving d-wave superconductors with charge density waves.

    Science.gov (United States)

    Ekino, T; Gabovich, A M; Suan Li, Mai; Szymczak, H; Voitenko, A I

    2016-11-09

    The quasiparticle tunnel current J(V) between the superconducting ab-planes along the c-axis and the corresponding conductance [Formula: see text] were calculated for symmetric junctions composed of disordered d-wave layered superconductors partially gapped by charge density waves (CDWs). Here, V is the voltage. Both the checkerboard and unidirectional CDWs were considered. It was shown that the spatial spread of the CDW-pairing strength substantially smears the peculiarities of G(V) appropriate to uniform superconductors. The resulting curves G(V) become very similar to those observed for a number of cuprates in intrinsic junctions, e.g. mesas. In particular, the influence of CDWs may explain the peak-dip-hump structures frequently found for high-T c oxides.

  10. Adsorbed states of chlorophenol on Cu(110) and controlled switching of single-molecule junctions

    Energy Technology Data Exchange (ETDEWEB)

    Okuyama, H., E-mail: hokuyama@kuchem.kyoto-u.ac.jp; Kitaguchi, Y.; Hattori, T.; Ueda, Y.; Ferrer, N. G.; Hatta, S.; Aruga, T. [Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan)

    2016-06-28

    A molecular junction of substituted benzene (chlorophenol) is fabricated and controlled by using a scanning tunneling microscope (STM). Prior to the junction formation, the bonding geometry of the molecule on the surface is characterized by STM and electron energy loss spectroscopy (EELS). EELS shows that the OH group of chlorophenol is dissociated on Cu(110) and that the molecule is bonded nearly flat to the surface via an O atom, with the Cl group intact. We demonstrate controlled contact of an STM tip to the “available” Cl group and lift-up of the molecule while it is anchored to the surface via an O atom. The asymmetric bonding motifs of the molecule to the electrodes allow for reversible control of the junction.

  11. Controlling chaos in RCL-shunted Josephson junction by delayed linear feedback

    International Nuclear Information System (INIS)

    Feng Yuling; Shen Ke

    2008-01-01

    The resistively-capacitively-inductively-shunted (RCL-shunted) Josephson junction (RCLSJJ) shows chaotic behaviour under some parameter conditions. Here a scheme for controlling chaos in the RCLSJJ is presented based on the linear feedback theory. Numerical simulations show that this scheme can be effectively used to control chaotic states in this junction into stable periodic states. Moreover, the different stable period states with different period numbers can be obtained by appropriately adjusting the feedback intensity and delay time without any pre-knowledge of this system required

  12. The oligodendroglial precursor cell line Oli-neu represents a cell culture system to examine functional expression of the mouse gap junction gene connexin29 (Cx29

    Directory of Open Access Journals (Sweden)

    Goran Christoph Söhl

    2013-06-01

    Full Text Available The potential gap junction forming mouse connexin29 (Cx29 protein is concomitantly expressed with connexin32 (Cx32 in peripheral myelin forming Schwann cells and together with both Cx32 and connexin47 (Cx47 in oligodendrocytes of the CNS. To study the genomic structure and functional expression of Cx29, either primary cells or cell culture systems might be selected, from which the latter are easier to cultivate. Both structure and expression of Cx29 is still not fully understood. In the mouse sciatic nerve, brain and the oligodendroglial precursor cell line Oli-neu the Cx29 gene is processed in two transcript isoforms both harbouring a unique reading frame. In contrast to Cx32 and Cx47, only Cx29 protein is abundantly expressed in undifferentiated as well as differentiated Oli-neu cells but the absence of Etbr dye transfer after microinjection concealed the function of Cx29 mediated gap junction communication between those cells. Although HeLa cells stably transfected with Cx29 or Cx29-eGFP neither demonstrated any permeability for Lucifer yellow nor for neurobiotin, blocking of Etbr uptake from the media by gap junction blockers does suppose a role of Cx29 in hemi-channel function. Thus, we conclude that, due to its high abundance of Cx29 expression and its reproducible culture conditions, the oligodendroglial precursor cell line Oli-neu might constitute an appropriate cell culture system to study molecular mechanisms or putative extracellular stimuli to functionally open Cx29 channels or hemi-channels.

  13. Star junctions and watermelons of pure or random quantum Ising chains: finite-size properties of the energy gap at criticality

    Science.gov (United States)

    Monthus, Cécile

    2015-06-01

    We consider M  ⩾  2 pure or random quantum Ising chains of N spins when they are coupled via a single star junction at their origins or when they are coupled via two star junctions at the their two ends leading to the watermelon geometry. The energy gap is studied via a sequential self-dual real-space renormalization procedure that can be explicitly solved in terms of Kesten variables containing the initial couplings and and the initial transverse fields. In the pure case at criticality, the gap is found to decay as a power-law {ΔM}\\propto {{N}-z(M)} with the dynamical exponent z(M)=\\frac{M}{2} for the single star junction (the case M   =   2 corresponds to z   =   1 for a single chain with free boundary conditions) and z(M)   =   M  -  1 for the watermelon (the case M   =   2 corresponds to z   =   1 for a single chain with periodic boundary conditions). In the random case at criticality, the gap follows the Infinite Disorder Fixed Point scaling \\ln {ΔM}=-{{N}\\psi}g with the same activated exponent \\psi =\\frac{1}{2} as the single chain corresponding to M   =   2, and where g is an O(1) random positive variable, whose distribution depends upon the number M of chains and upon the geometry (star or watermelon).

  14. Amitriptyline up-regulates connexin43-gap junction in rat cultured cortical astrocytes via activation of the p38 and c-Fos/AP-1 signalling pathway.

    Science.gov (United States)

    Morioka, N; Suekama, K; Zhang, F F; Kajitani, N; Hisaoka-Nakashima, K; Takebayashi, M; Nakata, Y

    2014-06-01

    Intercellular communication via gap junctions, comprised of connexin (Cx) proteins, allow for communication between astrocytes, which in turn is crucial for maintaining CNS homeostasis. The expression of Cx43 is decreased in post-mortem brains from patients with major depression. A potentially novel mechanism of tricyclic antidepressants is to increase the expression and functioning of gap junctions in astrocytes. The effect of amitriptyline on the expression of Cx43 and gap junction intercellular communication (GJIC) in rat primary cultured cortical astrocytes was investigated. We also investigated the role of p38 MAPK intracellular signalling pathway in the amitriptyline-induced expression of Cx43 and GJIC. Treatment with amitriptyline for 48 h significantly up-regulated Cx43 mRNA, protein and GJIC. The up-regulation of Cx43 was not monoamine-related since noradrenaline, 5-HT and dopamine did not induce Cx43 expression and pretreatment with α- and β-adrenoceptor antagonists had no effect. Intracellular signalling involved p38 MAPK, as amitriptyline significantly increased p38 MAPK phosphorylation and Cx43 expression and GJIC were significantly blocked by the p38 inhibitor SB 202190. Furthermore, amitriptyline-induced Cx43 expression and GJIC were markedly reduced by transcription factor AP-1 inhibitors (curcumin and tanshinone IIA). The translocation of c-Fos from the cytosol and the nucleus of cortical astrocytes was increased by amitriptyline, and this response was dependent on p38 activity. These findings indicate a novel mechanism of action of amitriptyline through cortical astrocytes, and further suggest that targeting this mechanism could lead to the development of a new class of antidepressants. © 2014 The British Pharmacological Society.

  15. A two isocenter IMRT technique with a controlled junction dose for long volume targets

    International Nuclear Information System (INIS)

    Zeng, G G; Heaton, R K; Catton, C N; Chung, P W; O'Sullivan, B; Lau, M; Parent, A; Jaffray, D A

    2007-01-01

    Most IMRT techniques have been designed to treat targets smaller than the field size of conventional linac accelerators. In order to overcome the field size restrictions in applying IMRT, we developed a two isocenter IMRT technique to treat long volume targets. The technique exploits an extended dose gradient throughout a junction region of 4-6 cm to minimize the impact of field match errors on a junction dose and manipulates the inverse planning and IMRT segments to fill in the dose gradient and achieve dose uniformity. Techniques for abutting both conventional fields with IMRT ('Static + IMRT') and IMRT fields ('IMRT + IMRT') using two separate isocenters have been developed. Five long volume sarcoma cases have been planned in Pinnacle (Philips, Madison, USA) using Elekta Synergy and Varian 2100EX linacs; two of the cases were clinically treated with this technique. Advantages were demonstrated with well-controlled junction target uniformity and tolerance to setup uncertainties. The junction target dose heterogeneity was controlled at a level of ±5%; for 3 mm setup errors at the field edges, the junction target dose changed less than 5% and the dose sparing to organs at risk (OARs) was maintained. Film measurements confirmed the treatment planning results

  16. The role of engineered materials in superconducting tunnel junction X-ray detectors - Suppression of quasiparticle recombination losses via a phononic band gap

    Science.gov (United States)

    Rippert, Edward D.; Ketterson, John B.; Chen, Jun; Song, Shenian; Lomatch, Susanne; Maglic, Stevan R.; Thomas, Christopher; Cheida, M. A.; Ulmer, Melville P.

    1992-01-01

    An engineered structure is proposed that can alleviate quasi-particle recombination losses via the existence of a phononic band gap that overlaps the 2-Delta energy of phonons produced during recombination of quasi-particles. Attention is given to a 1D Kronig-Penny model for phonons normally incident to the layers of a multilayered superconducting tunnel junction as an idealized example. A device with a high density of Bragg resonances is identified as desirable; both Nb/Si and NbN/SiN superlattices have been produced, with the latter having generally superior performance.

  17. Efficacy of dexmedetomidine for the control of junctional ectopic tachycardia after repair of tetralogy of Fallot

    Directory of Open Access Journals (Sweden)

    Randhir S Rajput

    2014-01-01

    Full Text Available Background: Junctional ectopic tachycardia occurs frequently after congenital cardiac surgery and can be a cause of increased morbidity and mortality. Dexmedetomidine (DEX is an a2 adrenoreceptor agonist, has properties of controlling tachyarrhythmia by regulating the sympatho-adrenal system. Objective: To evaluate the efficacy of DEX for control of junctional ectopic tachycardia after repair of Tetralogy of Fallot (TOF. Materials and Methods: Two hundred and twenty pediatric cardiac patients with TOFs were enrolled in a prospective randomized control study. Patients underwent correction surgery. They were divided into two groups, i.e., Group 1 (DEX and Group 2 (control. Heart rate, rhythm, mean arterial pressure (MAP were recorded after the anesthetic induction (T1, after termination of bypass (T2, after 04 hours (T3, and 08 hours after transferring the patient to intensive care unit (ICU; T4. Results: Heart rate was comparable between two groups before starting the drug but statistically significant after bypass until 08 hours after transferring the patient to ICU. Junctional ectopic tachycardia occurred more in Group-2 (20% as compared to Group-1 (9.09%; P = 0.022. Junctional ectopic tachycardia occurs early in Group-2 (0.14 ± 0.527 hours as compared to Group 1 (0.31 ± 1.29 hours; P = 0.042. The duration of junctional ectopic tachycardia was more prolonged in Group-2 (1.63 ± 3.64 hours as compared to Group-1 (0.382 ± 1.60 hours; P = 0.012. The time to withdraw from mechanical ventilation and ICU stay of Group 1 patient was less than of Group 2 patients (P = <0.001. Conclusion: DEX had a therapeutic role in the prevention of junctional ectopic tachycardia in patients undergoing repair for TOF.

  18. Closing the gap between glia and neuroblast proliferation.

    Science.gov (United States)

    Limmer, Stefanie; Klämbt, Christian

    2014-08-11

    Reporting in this issue of Developmental Cell, Spéder and Brand (2014) show that gap junctions are required in blood-brain barrier glial cells to reactivate proliferation of quiescent neuroblasts. Gap junctions allow synchronous Ca(2+) waves and control insulin-like protein Dipl6 expression and secretion to trigger neuroblast division. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Controllable asymmetric transmission via gap-tunable acoustic metasurface

    Science.gov (United States)

    Liu, Bingyi; Jiang, Yongyuan

    2018-04-01

    In this work, we utilize the acoustic gradient metasurface (AGM) of a bilayer configuration to realize the controllable asymmetric transmission. Relying on the adjustable gap between the two composing layers, the metasurface could switch from symmetric transmission to asymmetric transmission at a certain gap value. The underlying mechanism is attributed to the interference between the forward diffracted waves scattered by the surface bound waves at two air-AGM interfaces, which is apparently influenced by the interlayer distance. We further utilize the hybrid acoustic elements to construct the desired gradient metasurface with a tunable gap and validate the controllable asymmetric transmission with full-wave simulations. Our work provides the solution for actively controlling the transmission property of an acoustic element, which shows potential application in acoustic communication as a dynamic tunable acoustic diode.

  20. Controlling the thermoelectric effect by mechanical manipulation of the electron's quantum phase in atomic junctions.

    Science.gov (United States)

    Aiba, Akira; Demir, Firuz; Kaneko, Satoshi; Fujii, Shintaro; Nishino, Tomoaki; Tsukagoshi, Kazuhito; Saffarzadeh, Alireza; Kirczenow, George; Kiguchi, Manabu

    2017-08-11

    The thermoelectric voltage developed across an atomic metal junction (i.e., a nanostructure in which one or a few atoms connect two metal electrodes) in response to a temperature difference between the electrodes, results from the quantum interference of electrons that pass through the junction multiple times after being scattered by the surrounding defects. Here we report successfully tuning this quantum interference and thus controlling the magnitude and sign of the thermoelectric voltage by applying a mechanical force that deforms the junction. The observed switching of the thermoelectric voltage is reversible and can be cycled many times. Our ab initio and semi-empirical calculations elucidate the detailed mechanism by which the quantum interference is tuned. We show that the applied strain alters the quantum phases of electrons passing through the narrowest part of the junction and hence modifies the electronic quantum interference in the device. Tuning the quantum interference causes the energies of electronic transport resonances to shift, which affects the thermoelectric voltage. These experimental and theoretical studies reveal that Au atomic junctions can be made to exhibit both positive and negative thermoelectric voltages on demand, and demonstrate the importance and tunability of the quantum interference effect in the atomic-scale metal nanostructures.

  1. Insulator-protected mechanically controlled break junctions for measuring single-molecule conductance in aqueous environments

    NARCIS (Netherlands)

    Muthusubramanian, N.; Galan, E.; Maity, C.; Eelkema, R.; Grozema, F.C.; van der Zant, H.S.J.

    2016-01-01

    We present a method to fabricate insulated gold mechanically controlled break junctions (MCBJ) by coating the metal with a thin layer of aluminum oxide using plasma enhanced atomic layer deposition. The Al2O3 thickness deposited on the MCBJ devices was varied from 2 to 15 nm

  2. Modulation and Control of Charge Transport Through Single-Molecule Junctions.

    Science.gov (United States)

    Wang, Kun; Xu, Bingqian

    2017-02-01

    The ability to modulate and control charge transport though single-molecule junction devices is crucial to achieving the ultimate goal of molecular electronics: constructing real-world-applicable electronic components from single molecules. This review aims to highlight the progress made in single-molecule electronics, emphasizing the development of molecular junction electronics in recent years. Among many techniques that attempt to wire a molecule to metallic electrodes, the single-molecule break junction (SMBJ) technique is one of the most reliable and tunable experimental platforms for achieving metal-molecule-metal configurations. It also provides great freedom to tune charge transport through the junction. Soon after the SMBJ technique was introduced, it was extensively used to measure the conductances of individual molecules; however, different conductances were obtained for the same molecule, and it proved difficult to interpret this wide distribution of experimental data. This phenomenon was later found to be mainly due to a lack of precise experimental control and advanced data analysis methods. In recent years, researchers have directed considerable effort into advancing the SMBJ technique by gaining a deeper physical understanding of charge transport through single molecules and thus enhancing its potential applicability in functional molecular-scale electronic devices, such as molecular diodes and molecular transistors. In parallel with that research, novel data analysis methods and approaches that enable the discovery of hidden yet important features in the data are being developed. This review discusses various aspects of molecular junction electronics, from the initial goal of molecular electronics, the development of experimental techniques for creating single-molecule junctions and determining single-molecule conductance, to the characterization of functional current-voltage features and the investigation of physical properties other than charge

  3. Chaos synchronization in RCL-shunted Josephson junction via active control

    International Nuclear Information System (INIS)

    Ucar, Ahmet; Lonngren, Karl E.; Bai, E.-W.

    2007-01-01

    This paper investigates the synchronization of coupled RCL-shunted Josephson junction that is of interest in high-frequency applications. A nonlinear controller is developed in order to achieve the desired behavior. The synchronization is obtained using the slave-master technique and the controller ensures that the states of the controlled chaotic slave system exponentially synchronize with the state of the master system. Numerical simulations are illustrate and verify the proposed method

  4. Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis.

    Science.gov (United States)

    Trosko, James E

    2016-06-15

    The first anaerobic organism extracted energy for survival and reproduction from its source of nutrients, with the genetic means to ensure protection of its individual genome but also its species survival. While it had a means to communicate with its community via simple secreted molecules ("quorum sensing"), the eventual shift to an aerobic environment led to multi-cellular metazoan organisms, with evolutionary-selected genes to form extracellular matrices, stem cells, stem cell niches, and a family of gap junction or "connexin" genes. These germinal and somatic stem cells responded to extracellular signals that triggered intra-cellular signaling to regulate specific genes out of the total genome. These extra-cellular induced intra-cellular signals also modulated gap junctional intercellular communication (GJIC) in order to regulate the new cellular functions of symmetrical and asymmetrical cell division, cell differentiation, modes of cell death, and senescence. Within the hierarchical and cybernetic concepts, differentiated by neurons organized in the brain of the Homo sapiens, the conscious mind led to language, abstract ideas, technology, myth-making, scientific reasoning, and moral decision-making, i.e., the creation of culture. Over thousands of years, this has created the current collision between biological and cultural evolution, leading to the global "metabolic disease" crisis.

  5. Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis

    Directory of Open Access Journals (Sweden)

    James E. Trosko

    2016-06-01

    Full Text Available The first anaerobic organism extracted energy for survival and reproduction from its source of nutrients, with the genetic means to ensure protection of its individual genome but also its species survival. While it had a means to communicate with its community via simple secreted molecules (“quorum sensing”, the eventual shift to an aerobic environment led to multi-cellular metazoan organisms, with evolutionary-selected genes to form extracellular matrices, stem cells, stem cell niches, and a family of gap junction or “connexin” genes. These germinal and somatic stem cells responded to extracellular signals that triggered intra-cellular signaling to regulate specific genes out of the total genome. These extra-cellular induced intra-cellular signals also modulated gap junctional intercellular communication (GJIC in order to regulate the new cellular functions of symmetrical and asymmetrical cell division, cell differentiation, modes of cell death, and senescence. Within the hierarchical and cybernetic concepts, differentiated by neurons organized in the brain of the Homo sapiens, the conscious mind led to language, abstract ideas, technology, myth-making, scientific reasoning, and moral decision–making, i.e., the creation of culture. Over thousands of years, this has created the current collision between biological and cultural evolution, leading to the global “metabolic disease” crisis.

  6. Rescue of Notch signaling in cells incapable of GDP-L-fucose synthesis by gap junction transfer of GDP-L-fucose in Drosophila.

    Science.gov (United States)

    Ayukawa, Tomonori; Matsumoto, Kenjiroo; Ishikawa, Hiroyuki O; Ishio, Akira; Yamakawa, Tomoko; Aoyama, Naoki; Suzuki, Takuya; Matsuno, Kenji

    2012-09-18

    Notch (N) is a transmembrane receptor that mediates cell-cell interactions to determine many cell-fate decisions. N contains EGF-like repeats, many of which have an O-fucose glycan modification that regulates N-ligand binding. This modification requires GDP-L-fucose as a donor of fucose. The GDP-L-fucose biosynthetic pathways are well understood, including the de novo pathway, which depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase/4-reductase (Gmer). However, the potential for intercellularly supplied GDP-L-fucose and the molecular basis of such transportation have not been explored in depth. To address these points, we studied the genetic effects of mutating Gmd and Gmer on fucose modifications in Drosophila. We found that these mutants functioned cell-nonautonomously, and that GDP-L-fucose was supplied intercellularly through gap junctions composed of Innexin-2. GDP-L-fucose was not supplied through body fluids from different isolated organs, indicating that the intercellular distribution of GDP-L-fucose is restricted within a given organ. Moreover, the gap junction-mediated supply of GDP-L-fucose was sufficient to support the fucosylation of N-glycans and the O-fucosylation of the N EGF-like repeats. Our results indicate that intercellular delivery is a metabolic pathway for nucleotide sugars in live animals under certain circumstances.

  7. Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry

    Directory of Open Access Journals (Sweden)

    Guoqiang Zhong

    2017-05-01

    Full Text Available In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45, and Cx30.2 is a requirement for proper development and function. Gap junctions formed by these connexins have distinct permeability and gating mechanisms. Since a single cell can express more than one connexin isoform, the formation of hetero-multimeric gap junction channels provides a tissue with an enormous repertoire of combinations to modulate intercellular communication. To study further the perm-selectivity and gating properties of channels containing Cx43 and Cx45, we studied two monoheteromeric combinations in which a HeLa cell co-transfected with Cx43 and Cx45 was paired with a cell expressing only one of these connexins. Macroscopic measurements of total conductance between cell pairs indicated a drastic reduction in total conductance for mono-heteromeric channels. In terms of Vj dependent gating, Cx43 homomeric connexons facing heteromeric connexons only responded weakly to voltage negativity. Cx45 homomeric connexons exhibited no change in Vj gating when facing heteromeric connexons. The distributions of unitary conductances (γj for both mono-heteromeric channels were smaller than predicted, and both showed low permeability to the fluorescent dyes Lucifer yellow and Rhodamine123. For both mono-heteromeric channels, we observed flux asymmetry regardless of dye charge: flux was higher in the direction of the heteromeric connexon for MhetCx45 and in the direction of the homomeric Cx43 connexon for MhetCx43. Thus, our data suggest that co-expression of Cx45 and Cx43 induces the formation of heteromeric connexons with greatly reduced permeability and unitary conductance. Furthermore, it increases the asymmetry for voltage gating for opposing connexons, and it favors asymmetric flux of molecules across the junction that depends primarily on the size (not the charge of the crossing molecules.

  8. Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry

    Science.gov (United States)

    Zhong, Guoqiang; Akoum, Nazem; Appadurai, Daniel A.; Hayrapetyan, Volodya; Ahmed, Osman; Martinez, Agustin D.; Beyer, Eric C.; Moreno, Alonso P.

    2017-01-01

    In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45, and Cx30.2) is a requirement for proper development and function. Gap junctions formed by these connexins have distinct permeability and gating mechanisms. Since a single cell can express more than one connexin isoform, the formation of hetero-multimeric gap junction channels provides a tissue with an enormous repertoire of combinations to modulate intercellular communication. To study further the perm-selectivity and gating properties of channels containing Cx43 and Cx45, we studied two monoheteromeric combinations in which a HeLa cell co-transfected with Cx43 and Cx45 was paired with a cell expressing only one of these connexins. Macroscopic measurements of total conductance between cell pairs indicated a drastic reduction in total conductance for mono-heteromeric channels. In terms of Vj dependent gating, Cx43 homomeric connexons facing heteromeric connexons only responded weakly to voltage negativity. Cx45 homomeric connexons exhibited no change in Vj gating when facing heteromeric connexons. The distributions of unitary conductances (γj) for both mono-heteromeric channels were smaller than predicted, and both showed low permeability to the fluorescent dyes Lucifer yellow and Rhodamine123. For both mono-heteromeric channels, we observed flux asymmetry regardless of dye charge: flux was higher in the direction of the heteromeric connexon for MhetCx45 and in the direction of the homomeric Cx43 connexon for MhetCx43. Thus, our data suggest that co-expression of Cx45 and Cx43 induces the formation of heteromeric connexons with greatly reduced permeability and unitary conductance. Furthermore, it increases the asymmetry for voltage gating for opposing connexons, and it favors asymmetric flux of molecules across the junction that depends primarily on the size (not the charge) of the crossing molecules. PMID:28611680

  9. All-electric-controlled spin current switching in single-molecule magnet-tunnel junctions

    Science.gov (United States)

    Zhang, Zheng-Zhong; Shen, Rui; Sheng, Li; Wang, Rui-Qiang; Wang, Bai-Gen; Xing, Ding-Yu

    2011-04-01

    A single-molecule magnet (SMM) coupled to two normal metallic electrodes can both switch spin-up and spin-down electronic currents within two different windows of SMM gate voltage. Such spin current switching in the SMM tunnel junction arises from spin-selected single electron resonant tunneling via the lowest unoccupied molecular orbit of the SMM. Since it is not magnetically controlled but all-electrically controlled, the proposed spin current switching effect may have potential applications in future spintronics.

  10. Magnetic-field-controlled negative differential conductance in scanning tunneling spectroscopy of graphene npn junction resonators

    Science.gov (United States)

    Li, Si-Yu; Liu, Haiwen; Qiao, Jia-Bin; Jiang, Hua; He, Lin

    2018-03-01

    Negative differential conductance (NDC), characterized by the decreasing current with increasing voltage, has attracted continuous attention for its various novel applications. The NDC typically exists in a certain range of bias voltages for a selected system and controlling the regions of NDC in curves of current versus voltage (I -V ) is experimentally challenging. Here, we demonstrate a magnetic-field-controlled NDC in scanning tunneling spectroscopy of graphene npn junction resonators. The magnetic field not only can switch on and off the NDC, but also can continuously tune the regions of the NDC in the I -V curves. In the graphene npn junction resonators, magnetic fields generate sharp and pronounced Landau-level peaks with the help of the Klein tunneling of massless Dirac fermions. A tip of scanning tunneling microscope induces a relatively shift of the Landau levels in graphene beneath the tip. Tunneling between the misaligned Landau levels results in the magnetic-field-controlled NDC.

  11. Tuning of optical and electrical properties of wide band gap Fe:SnO{sub 2}/Li:NiO p-n junctions using 80 MeV oxygen ion beam

    Energy Technology Data Exchange (ETDEWEB)

    Mistry, Bhaumik V.; Joshi, U.S. [Gujarat University, Department of Physics, School of Sciences, Ahmedabad (India); Avasthi, D.K. [Inter University Accelerator Centre, New Delhi (India)

    2016-12-15

    Electrical and optical properties of pristine and swift heavy ion (SHI) irradiated p-n junction diode have been investigated for advanced electronics application. Fe:SnO{sub 2}/Li:NiO p-n junction was fabricated by using pulsed laser deposition on c-sapphire substrate. The optical band gaps of Fe:SnO{sub 2} and Li:NiO films were obtained to be 3.88 and 3.37 eV, respectively. The current-voltage characteristics of the oxide-based p-n junction showed a rectifying behaviour with turn-on voltage of 0.95 V. The oxide-based p-n junction diode was irradiated to 80 MeV O{sup +6} ions with 1 x 10{sup 12} ions/cm{sup 2} fluence. Decrease in grain size due to SHI irradiation is confirmed by the grazing angle X-ray diffraction and atomic force microscopy. In comparison with the pristine p-n junction diode, O{sup +6} ion irradiated p-n junction diode shows the increase of surface roughness and decrease of percentage transmittance in visible region. For irradiated p-n junction diode, current-voltage curve has still rectifying behaviour but exhibits lower turn-on voltage than that of virgin p-n junction diode. (orig.)

  12. Controlling the trajectories of bubble trains at a microfluidic junction

    Science.gov (United States)

    Parthiban, Pravien; Khan, Saif

    2011-11-01

    The increasing number of applications facilitated by digital microfluidic flows has resulted in a sustained interest in not only understanding the diverse, interesting and often complex dynamics associated with such flows in microchannel networks but also in developing facile strategies to control them. We find that there are readily accessible flow speeds wherein resistance to flow in microchannels decreases with an increase in the number of confined bubbles present, and exploit this intriguing phenomenon to sort all bubble of a train exclusively into one of the arms of a nominally symmetric microfluidic loop. We also demonstrate how the arm into which the train filters into can be chosen by applying a temporary external stimulus by means of an additional flow of the continuous liquid into one the arms of the loop. Furthermore, we show how by tuning the magnitude and period of this temporary stimulus we can switch controllably, the traffic of bubbles between both arms of the loop even when the loop is asymmetric. The results of this work should aid in developing viable methods to regulate traffic of digital flows in microfluidic networks.

  13. Controlling single-molecule junction conductance by molecular interactions

    Science.gov (United States)

    Kitaguchi, Y.; Habuka, S.; Okuyama, H.; Hatta, S.; Aruga, T.; Frederiksen, T.; Paulsson, M.; Ueba, H.

    2015-01-01

    For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment. PMID:26135251

  14. Redox-controlled memristive switching in the junctions employing Ti reactive electrodes

    Directory of Open Access Journals (Sweden)

    Haitao Li

    2011-09-01

    Full Text Available We have proposed a kind of memristive device based on the junctions employing Ti as the reactive electrodes. The role of electrically-derived redox of Ti in such memristive switching is shown. The structural and chemical evidence of the electrically-derived oxidation is presented by TEM and XPS experiment, respectively. Due to the redox of the top electrode Ti and the consequent drift of oxygen vacancies, the device shows two distinct resistance states under a sweeping voltage loading. ON state is controlled by tunneling process, while OFF state is controlled by Schottky emission conductive mechanism. The failure behaviors of such memristive junctions are also discussed. In the light of the redox principle, we demonstrate that the devices could be recovered by loading a long electrical reduction treatment.

  15. New technology for the control of narrow-gap semiconductors

    International Nuclear Information System (INIS)

    Antoniou, I.; Bozhevolnov, V.; Melnikov, Yu.; Yafyasov, A.

    2003-01-01

    We present the results of the year work in the frame of the EU ESPRIT Project 28890 NTCONGS 'New technology for the control of narrow-gap semiconductors'. This work has involved both theoretical and experimental study, as well as the development of new specific equipment, towards the creation of a new generation of nanoelectronic devices able to operate at 77 K and even at room temperature

  16. Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways

    Directory of Open Access Journals (Sweden)

    Aiqing Zhang

    2015-06-01

    Full Text Available Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC proliferation from a new point of view considering Connexin 43 (Cx43. Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR. Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT, and the intracellular calcium concentrations ([Ca2+]i were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P0.05. Our data also showed that the mineralcorticoid receptor (MR antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca2+]i (PConclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways.

  17. Gap junctions and hydrogen peroxide are involved in endothelium-derived hyperpolarising responses to bradykinin in omental arteries and veins isolated from pregnant women.

    Science.gov (United States)

    Hammond, Stephanie; Mathewson, Alastair M; Baker, Philip N; Mayhew, Terry M; Dunn, William R

    2011-10-01

    Altered endothelial function may underlie human cardiovascular diseases, including hypertension, diabetes and pre-eclampsia. While much is known about endothelial function in small arteries, very little is known about endothelial responses in small veins isolated from humans. Therefore, we assessed endothelium-dependent responses in omental arteries and veins isolated from healthy pregnant women, focussing on endothelium-dependent hyperpolarising (EDH) mechanisms. Human omental arteries and veins were obtained from women undergoing elective caesarean sections and examined using pressure myography. In pressurised vessels, the effects of proposed inhibitors of EDH production/function were examined on responses to bradykinin. The expression of connexins Cx37, 40 and 43 was assessed using immunohistochemistry. Bradykinin caused vasodilatation in human pressurised omental arteries and veins. In both vessels, responses to bradykinin were partially blocked in the presence of the gap junction uncoupler, carbenoxolone, and reduced further with the addition of catalase, which acts to degrade H(2)O(2). The effect of catalase alone was more pronounced in venous preparations. All three connexins were expressed in both arteries and veins, with a similar distribution pattern, where Cx37 and Cx40 were located mainly in the endothelium and Cx43 located mostly in the media. These data show that, in human omental vessels, an EDH mechanism is produced in response to bradykinin that involves gap junction communication and the production of H(2)O(2). These mechanisms may be involved in the haemodynamic alterations that take place during pregnancy, and any aberration in their function could contribute to raised blood pressure in hypertensive disorders of pregnancy, such as pre-eclampsia. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Insulator-protected mechanically controlled break junctions for measuring single-molecule conductance in aqueous environments

    Energy Technology Data Exchange (ETDEWEB)

    Muthusubramanian, N.; Zant, H. S. J. van der [Kavli Institute of Nanoscience, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft (Netherlands); Galan, E.; Maity, C.; Eelkema, R.; Grozema, F. C. [Department of Chemical Engineering, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft (Netherlands)

    2016-07-04

    We present a method to fabricate insulated gold mechanically controlled break junctions (MCBJ) by coating the metal with a thin layer of aluminum oxide using plasma enhanced atomic layer deposition. The Al{sub 2}O{sub 3} thickness deposited on the MCBJ devices was varied from 2 to 15 nm to test the suppression of leakage currents in deionized water and phosphate buffered saline. Junctions coated with a 15 nm thick oxide layer yielded atomically sharp electrodes and negligible conductance counts in the range of 1 to 10{sup −4} G{sub 0} (1 G{sub 0} = 77 μS), where single-molecule conductances are commonly observed. The insulated devices were used to measure the conductance of an amphiphilic oligophenylene ethynylene derivative in deionized water.

  19. Electrical control of memristance and magnetoresistance in oxide magnetic tunnel junctions

    KAUST Repository

    Zhang, Kun

    2015-01-01

    Electric-field control of magnetic and transport properties of magnetic tunnel junctions has promising applications in spintronics. Here, we experimentally demonstrate a reversible electrical manipulation of memristance, magnetoresistance, and exchange bias in Co/CoO–ZnO/Co magnetic tunnel junctions, which enables the realization of four nonvolatile resistance states. Moreover, greatly enhanced tunneling magnetoresistance of 68% was observed due to the enhanced spin polarization of the bottom Co/CoO interface. The ab initio calculations further indicate that the spin polarization of the Co/CoO interface is as high as 73% near the Fermi level and plenty of oxygen vacancies can induce metal–insulator transition of the CoO1−v layer. Thus, the electrical manipulation mechanism on the memristance, magnetoresistance and exchange bias can be attributed to the electric-field-driven migration of oxygen ions/vacancies between very thin CoO and ZnO layers.

  20. Insulator-protected mechanically controlled break junctions for measuring single-molecule conductance in aqueous environments

    Science.gov (United States)

    Muthusubramanian, N.; Galan, E.; Maity, C.; Eelkema, R.; Grozema, F. C.; van der Zant, H. S. J.

    2016-07-01

    We present a method to fabricate insulated gold mechanically controlled break junctions (MCBJ) by coating the metal with a thin layer of aluminum oxide using plasma enhanced atomic layer deposition. The Al2O3 thickness deposited on the MCBJ devices was varied from 2 to 15 nm to test the suppression of leakage currents in deionized water and phosphate buffered saline. Junctions coated with a 15 nm thick oxide layer yielded atomically sharp electrodes and negligible conductance counts in the range of 1 to 10-4 G0 (1 G0 = 77 μS), where single-molecule conductances are commonly observed. The insulated devices were used to measure the conductance of an amphiphilic oligophenylene ethynylene derivative in deionized water.

  1. A device for automatic photoelectric control of the analytical gap for emission spectrographs

    Science.gov (United States)

    Dietrich, John A.; Cooley, Elmo F.; Curry, Kenneth J.

    1977-01-01

    A photoelectric device has been built that automatically controls the analytical gap between electrodes during excitation period. The control device allows for precise control of the analytical gap during the arcing process of samples, resulting in better precision of analysis.

  2. Inhibition of Connexin 26/43 and Extracellular-Regulated Kinase Protein Plays a Critical Role in Melatonin Facilitated Gap Junctional Intercellular Communication in Hydrogen Peroxide-Treated HaCaT Keratinocyte Cells

    Directory of Open Access Journals (Sweden)

    Hyo-Jung Lee

    2012-01-01

    Full Text Available Though melatonin was known to regulate gap junctional intercellular communication (GJIC in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H2O2- treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2 mM and hydrogen peroxide (H2O2 at 300 μM showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS in H2O2-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H2O2-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26 and connexin 43 (Cx43 at mRNA and protein levels, but not that of connexin 30 (Cx30 in H2O2-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs more than p38 MAPK or JNK in H2O2-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H2O2-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 μM and vitamin C (10 μg/mL significantly reduced ROS production in H2O2-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H2O2-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent.

  3. 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

  4. Silver nanoparticles increase connexin43-mediated gap junctional intercellular communication in HaCaT cells through activation of reactive oxygen species and mitogen-activated protein kinase signal pathway

    DEFF Research Database (Denmark)

    Qin, Yu; Han, Limin; Yang, Di

    2018-01-01

    Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms to ...

  5. Measurement and control of detailed electronic properties in a single molecule break junction.

    Science.gov (United States)

    Wang, Kun; Hamill, Joseph; Zhou, Jianfeng; Guo, Cunlan; Xu, Bingqian

    2014-01-01

    The lack of detailed experimental controls has been one of the major obstacles hindering progress in molecular electronics. While large fluctuations have been occurring in the experimental data, specific details, related mechanisms, and data analysis techniques are in high demand to promote our physical understanding at the single-molecule level. A series of modulations we recently developed, based on traditional scanning probe microscopy break junctions (SPMBJs), have helped to discover significant properties in detail which are hidden in the contact interfaces of a single-molecule break junction (SMBJ). For example, in the past we have shown that the correlated force and conductance changes under the saw tooth modulation and stretch-hold mode of PZT movement revealed inherent differences in the contact geometries of a molecular junction. In this paper, using a bias-modulated SPMBJ and utilizing emerging data analysis techniques, we report on the measurement of the altered alignment of the HOMO of benzene molecules with changing the anchoring group which coupled the molecule to metal electrodes. Further calculations based on Landauer fitting and transition voltage spectroscopy (TVS) demonstrated the effects of modulated bias on the location of the frontier molecular orbitals. Understanding the alignment of the molecular orbitals with the Fermi level of the electrodes is essential for understanding the behaviour of SMBJs and for the future design of more complex devices. With these modulations and analysis techniques, fruitful information has been found about the nature of the metal-molecule junction, providing us insightful clues towards the next step for in-depth study.

  6. GAP junctional intercellular communication confers an enhanced bystander effect as well as a protective effect in HSV-TK/gancyclovir mediated cytotoxicity

    International Nuclear Information System (INIS)

    Wygoda, Marc R.; Rehemtulla, Alnawaz; Davis, Mary A.; Lawrence, Theodore S.

    1996-01-01

    Purpose/Objective: The 'Bystander Effect' is the phenomenon by which cells which are not transduced with the Herpes Simplex Virus - Thymidine Kinase (HSV-TK) gene are killed by the guanosine analog Gancyclovir (GCV) when they are nearby HSV-TK positive cells. Since currently available gene transfer technologies have a low efficiency (typically less than 10% of cells are transduced), a better understanding of the mechanism underlying the bystander effect is crucial for the success of the HSV-TK/GCV enzyme prodrug gene therapy approach. Gap junctions, which are specialized cell membrane channels allowing the passage of molecules < 1000 daltons in size directly from cell to cell, have been proposed as a possible mediator of the bystander effect. In particular, gap junctions could permit the transfer of toxic metabolites from the HSV-TK positive cells to the bystander cells. Our aim was to assess the role of gap junctional intercellular communication (GJIC) in the bystander effect. Materials and Methods: Co-culture of an HSV-TK transduced rat liver epithelial cell line (WB-TK), with either its communication competent parental cell line (WB), or an isogenic cell line differing by its communication incompetence (aB1). The ratios of effector cells (WB-TK) to bystander cells (WB or aB1), were (100(0)), (50(50)), (5(95)), or(0(100)) . These various mixed populations were exposed for 24 hours to 10μM GCV and thereafter placed at clonal density into selective media, allowing for growth of either the bystander (TK negative) cells or the effector (TK-positive) cells. Results: 1) When the effector/bystander ratio was (50(50)) the surviving fraction of the bystander cells was 3.5% and 37% for the WB and aB1, respectively. When the effector/bystander ratio was (5(95)), the surviving fraction was 51% and 65% for the WB and aB1, respectively. Either cell line (WB or aB1) cultured alone was unaffected by GCV. These results demonstrate that the bystander effect is much higher when

  7. Controlling the formation process and atomic structures of single pyrazine molecular junction by tuning the strength of the metal-molecule interaction.

    Science.gov (United States)

    Kaneko, Satoshi; Takahashi, Ryoji; Fujii, Shintaro; Nishino, Tomoaki; Kiguchi, Manabu

    2017-04-12

    The formation process and atomic structures were investigated for single pyrazine molecular junctions sandwiched by three different Au, Ag, and Cu electrodes using a mechanically controllable break junction technique in ultrahigh vacuum conditions at 300 K. We demonstrated that the formation process of the single-molecule junction crucially depended on the choice of the metal electrodes. While single-molecule junction showing two distinct conductance states were found for the Au electrodes, only the single conductance state was evident for the Ag electrodes, and there was no junction formation for the Cu electrodes. These results suggested that metal-molecule interaction dominates the formation process and probability of the single-molecule junction. In addition to the metal-molecule interaction, temperature affected the formation process of the single-molecule junction. The single pyrazine molecular junction formed between Au electrodes exhibited significant temperature dependence where the junction-formation probability was about 8% at 300 K, while there was no junction-formation at 100 K. Instead of the junction formation, an Au atomic wire was formed at the low temperature. This study provides insight into the tuning of the junction-forming process for single-molecule junctions, which is needed to construct device structures on a single molecule scale.

  8. Synchronization of chaos in RCL-shunted Josephson junction using a simple adaptive controller

    International Nuclear Information System (INIS)

    Guo, R; Vincent, U E; Idowu, B A

    2009-01-01

    In this paper, a simple adaptive control is proposed for the synchronization of chaotic dynamics of resistive-capacitive-inductive-shunted Josephson junctions (RCLSJ). The synchronization problem is investigated based on a drive-response system configuration consisting of two identical RCLSJ with and without identical system parameters. In addition, the synchronization when the system parameters are unknown is considered based on adaptive parameter control estimation. Sufficient conditions for global asymptotic synchronization are given and numerical simulations are employed to demonstrate the efficiency of the adaptive control scheme. In the presence of noise, we also show that the synchronization is robust and discuss the implication of our adaptive control technique in rapid single flux quantum (RSFQ) devices.

  9. Clinical outcome of increased flexion gap after total knee arthroplasty. Can controlled gap imbalance improve knee flexion?

    Science.gov (United States)

    Ismailidis, P; Kuster, M S; Jost, B; Giesinger, K; Behrend, H

    2017-06-01

    Increased range of motion (ROM) while maintaining joint stability is the goal of modern total knee arthroplasty (TKA). A biomechanical study has shown that small increases in flexion gap result in decreased tibiofemoral force beyond 90° flexion. The purpose of this paper was to investigate clinical implications of controlled increased flexion gap. Four hundred and four TKAs were allocated into one of two groups and analysed retrospectively. In the first group (n = 352), flexion gap exceeded extension gap by 2.5 mm, while in the second group (n = 52) flexion gap was equal to the extension gap. The procedures were performed from 2008 to 2012. The patients were reviewed 12 months postoperatively. Objective clinical results were assessed for ROM, mediolateral and sagittal stability. Patient-reported outcome measures were the WOMAC score and the Forgotten Joint Score (FJS-12). After categorizing postoperative flexion into three groups (poor < 90°, satisfactory 91°-119°, good ≥ 120°) significantly more patients in group 1 achieved satisfactory or good ROM (p = 0.006). Group 1 also showed a significantly higher mean FJS-12 (group 1: 73, group 2: 61, p = 0.02). The mean WOMAC score was 11 in the first and 14 in the second group (n.s.). Increase in flexion gap did not influence knee stability. The clinical relevance of this study is that a controlled flexion gap increase of 2.5 mm may have a positive effect on postoperative flexion and patient satisfaction after TKA. Neither knee stability in the coronal and sagittal planes nor complications were influenced by a controlled increase in flexion gap. III.

  10. Inhibition of gap-junctional intercellular communication and activation of mitogen-activated protein kinases by cyanobacterial extracts--indications of novel tumor-promoting cyanotoxins?

    Science.gov (United States)

    Bláha, Ludĕk; Babica, Pavel; Hilscherová, Klára; Upham, Brad L

    2010-01-01

    Toxicity and liver tumor promotion of cyanotoxins microcystins have been extensively studied. However, recent studies document that other metabolites present in the complex cyanobacterial water blooms may also have adverse health effects. In this study we used rat liver epithelial stem-like cells (WB-F344) to examine the effects of cyanobacterial extracts on two established markers of tumor promotion, inhibition of gap-junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) - ERK1/2. Extracts of cyanobacteria (laboratory cultures of Microcystis aeruginosa and Aphanizomenon flos-aquae and water blooms dominated by these species) inhibited GJIC and activated MAPKs in a dose-dependent manner (effective concentrations ranging 0.5-5mgd.w./mL). Effects were independent of the microcystin content and the strongest responses were elicited by the extracts of Aphanizomenon sp. Neither pure microcystin-LR nor cylindrospermopsin inhibited GJIC or activated MAPKs. Modulations of GJIC and MAPKs appeared to be specific to cyanobacterial extracts since extracts from green alga Chlamydomonas reinhardtii, heterotrophic bacterium Klebsiella terrigena, and isolated bacterial lipopolysaccharides had no comparable effects. Our study provides the first evidence on the existence of unknown cyanobacterial toxic metabolites that affect in vitro biomarkers of tumor promotion, i.e. inhibition of GJIC and activation of MAPKs.

  11. Antiproliferative Action of Conjugated Linoleic Acid on Human MCF-7 Breast Cancer Cells Mediated by Enhancement of Gap Junctional Intercellular Communication through Inactivation of NF-κB

    Directory of Open Access Journals (Sweden)

    Md. Abdur Rakib

    2013-01-01

    Full Text Available The major conjugated linoleic acid (CLA isomers, c9,t11-CLA and t10,c12-CLA, have anticancer effects; however, the exact mechanisms underlying these effects are unknown. Evidence suggests that reversal of reduced gap junctional intercellular communication (GJIC in cancer cells inhibits cell growth and induces cell death. Hence, we determined that CLA isomers enhance GJIC in human MCF-7 breast cancer cells and investigated the underlying molecular mechanisms. The CLA isomers significantly enhanced GJIC of MCF-7 cells at 40 μM concentration, whereas CLA inhibited cell growth and induced caspase-dependent apoptosis. CLA increased connexin43 (Cx43 expression both at the transcriptional and translational levels. CLA inhibited nuclear factor-κB (NF-κB activity and enhanced reactive oxygen species (ROS generation. No significant difference was observed in the efficacy of c9,t11-CLA and t10,c12-CLA. These results suggest that the anticancer effect of CLA is associated with upregulation of GJIC mediated by enhanced Cx43 expression through inactivation of NF-κB and generation of ROS in MCF-7 cells.

  12. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.

    KAUST Repository

    Ren, Jian

    2013-04-01

    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication (GJIC) remain obscure. We found that 17β estradiol (E2) up-regulated Cx43, and enhanced GJIC in osteocyte-like MLO-Y4 cells in fluorescence recovery after photobleaching (FRAP) assay. Combination of E2 pre-treatment and oscillating fluid flow (OFF) further enhanced Cx43 expression and mitogen-activated protein kinase (MAPK) phosphorylation, comparing to E2 or OFF treatment alone. Both blocking of classical estrogen receptors (ERα/β) by fulvestrant and ERα knockdown by small interfering RNA inhibited E2-mediated Cx43 increase, while a GPR30-specific agonist G-1 failed to promote Cx43 expression. Our results suggest that the presence of E2 enhanced Cx43-based GJIC mainly via ERα/β pathway, and sensitized osteocytes to mechanical loading. © 2012 Elsevier Inc. All rights reserved.

  13. Point correlation dimension can reveal functional changes caused by gap junction blockers in the 4-aminopyridine in vivo rat epilepsy model

    Energy Technology Data Exchange (ETDEWEB)

    Jardanhazy, Anett [Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725 (Hungary); Molnar, Mark [Department of Psychophysiology, Institute for Psychology of the Hungarian Academy of Sciences, P.O. Box 398, Budapest H-1394 (Hungary)], E-mail: molnar@cogpsyphy.hu; Jardanhazy, Tamas [Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725 (Hungary)], E-mail: jt@nepsy.szote.u-szeged.hu

    2009-04-15

    The contribution of gap junction (GJ) blockers to seizure initiation was reexamined by means of an analysis on nonlinear dynamics with point correlation dimension (PD2i) at as well as around the primary focus, and mirror focus in an already active 4-aminopyridine-induced in vivo epilepsy model. From the data base of the ECoGs of anesthetized adult rats treated with quinine, a selective blocker of Cx36, and in combination with an additional broad-spectrum GJ blocker, carbenoxolone, 14 cases of each condition were reexamined with a stationarity insensitive nonlinear PD2i method. The blockade of the Cx36 channels decreased the usual drop of the point correlation dimension at the beginning of the seizures, and this was enhanced by the additional use of the global blocker carbenoxolone. The so-called characteristic DC shift just prior to seizure onset denotes a low dimensional seizure event and the recognizable seizures display very variable, rapidly changing dynamics, as revealed by the PD2i analysis. This nonlinear PD2i analysis demonstrated that the different GJ blockers in the already active epileptic model helped seizure initiation, but exerted inhibitory effects on the seizure onset itself, acting differently on the local components of the network organization generating seizure discharges, possibly changing the coupling strengths and time delays in the GJ-s.

  14. Point correlation dimension can reveal functional changes caused by gap junction blockers in the 4-aminopyridine in vivo rat epilepsy model

    International Nuclear Information System (INIS)

    Jardanhazy, Anett; Molnar, Mark; Jardanhazy, Tamas

    2009-01-01

    The contribution of gap junction (GJ) blockers to seizure initiation was reexamined by means of an analysis on nonlinear dynamics with point correlation dimension (PD2i) at as well as around the primary focus, and mirror focus in an already active 4-aminopyridine-induced in vivo epilepsy model. From the data base of the ECoGs of anesthetized adult rats treated with quinine, a selective blocker of Cx36, and in combination with an additional broad-spectrum GJ blocker, carbenoxolone, 14 cases of each condition were reexamined with a stationarity insensitive nonlinear PD2i method. The blockade of the Cx36 channels decreased the usual drop of the point correlation dimension at the beginning of the seizures, and this was enhanced by the additional use of the global blocker carbenoxolone. The so-called characteristic DC shift just prior to seizure onset denotes a low dimensional seizure event and the recognizable seizures display very variable, rapidly changing dynamics, as revealed by the PD2i analysis. This nonlinear PD2i analysis demonstrated that the different GJ blockers in the already active epileptic model helped seizure initiation, but exerted inhibitory effects on the seizure onset itself, acting differently on the local components of the network organization generating seizure discharges, possibly changing the coupling strengths and time delays in the GJ-s.

  15. Inhibition of gap junctional Intercellular communication in WB-F344 rat liver epithelial cells by triphenyltin chloride through MAPK and PI3-kinase pathways

    Directory of Open Access Journals (Sweden)

    Tsai Ming-Che

    2010-06-01

    Full Text Available Abstract Background Organotin compounds (OTCs have been widely used as stabilizers in the production of plastic, agricultural pesticides, antifoulant plaints and wood preservation. The toxicity of triphenyltin (TPT compounds was known for their embryotoxic, neurotoxic, genotoxic and immunotoxic effects in mammals. The carcinogenicity of TPT was not well understood and few studies had discussed the effects of OTCs on gap junctional intercellular communication (GJIC of cells. Method In the present study, the effects of triphenyltin chloride (TPTC on GJIC in WB-F344 rat liver epithelial cells were evaluated, using the scrape-loading dye transfer technique. Results TPTC inhibited GJIC after a 30-min exposure in a concentration- and time-dependent manner. Pre-incubation of cells with the protein kinase C (PKC inhibitor did not modify the response, but the specific MEK 1 inhibitor PD98059 and PI3K inhibitor LY294002 decreased substantially the inhibition of GJIC by TPTC. After WB-F344 cells were exposed to TPTC, phosphorylation of Cx43 increased as seen in Western blot analysis. Conclusions These results show that TPTC inhibits GJIC in WB-F344 rat liver epithelial cells by altering the Cx43 protein expression through both MAPK and PI3-kinase pathways.

  16. Human strongyloidiasis: identifying knowledge gaps, with emphasis on environmental control

    Directory of Open Access Journals (Sweden)

    Taylor MJ

    2014-08-01

    Full Text Available Michael J Taylor, Tara A Garrard, Francis J O'Donahoo, Kirstin E Ross Health and Environment, School of the Environment, Flinders University, Adelaide, SA, Australia Abstract: Strongyloides is a human parasitic nematode that is poorly understood outside a clinical context. This article identifies gaps within the literature, with particular emphasis on gaps that are hindering environmental control of Strongyloides. The prevalence and distribution of Strongyloides is unclear. An estimate of 100–370 million people infected worldwide has been proposed; however, inaccuracy of diagnosis, unreliability of prevalence mapping, and the fact that strongyloidiasis remains a neglected disease suggest that the higher figure of more than 300 million cases is likely to be a more accurate estimate. The complexity of Strongyloides life cycle means that laboratory cultures cannot be maintained outside of a host. This currently limits the range of laboratory-based research, which is vital to controlling Strongyloides through environmental alteration or treatment. Successful clinical treatment with antihelminthic drugs has meant that controlling Strongyloides through environmental control, rather than clinical intervention, has been largely overlooked. These control measures may encompass alteration of the soil environment through physical means, such as desiccation or removal of nutrients, or through chemical or biological agents. Repeated antihelminthic treatment of individuals with recurrent strongyloidiasis has not been observed to result in the selection of resistant strains; however, this has not been explicitly demonstrated, and relying on such assumptions in the long-term may prove to be shortsighted. It is ultimately naive to assume that continued administration of antihelminthics will be without any negative long-term effects. In Australia, strongyloidiasis primarily affects Indigenous communities, including communities from arid central Australia. This

  17. Long-range neural and gap junction protein-mediated cues control polarity during planarian regeneration

    NARCIS (Netherlands)

    Morokuma, Junji; Oviedo, Nestor J.; Walentek, Peter; Kema, Ido P.; Gu, Man Bock; Ahn, Joo-Myung; Hwang, Jung Shan; Gojobori, Takashi; Levin, Michael

    2010-01-01

    Having the ability to coordinate the behavior of stem cells to induce regeneration of specific large-scale structures would have far-reaching consequences in the treatment of degenerative diseases, acute injury, and aging. Thus, identifying and learning to manipulate the sequential steps that

  18. The need for control of magnetic parameters for energy efficient performance of magnetic tunnel junctions

    Science.gov (United States)

    Farhat, I. A. H.; Gale, E.; Alpha, C.; Isakovic, A. F.

    2017-07-01

    Optimizing energy performance of Magnetic Tunnel Junctions (MTJs) is the key for embedding Spin Transfer Torque-Random Access Memory (STT-RAM) in low power circuits. Due to the complex interdependencies of the parameters and variables of the device operating energy, it is important to analyse parameters with most effective control of MTJ power. The impact of threshold current density, Jco , on the energy and the impact of HK on Jco are studied analytically, following the expressions that stem from Landau-Lifshitz-Gilbert-Slonczewski (LLGS-STT) model. In addition, the impact of other magnetic material parameters, such as Ms , and geometric parameters such as tfree and λ is discussed. Device modelling study was conducted to analyse the impact at the circuit level. Nano-magnetism simulation based on NMAGTM package was conducted to analyse the impact of controlling HK on the switching dynamics of the film.

  19. Controlled thermoelectric response of a tunable Rashba coupled metal-insulator-superconductor junction

    Science.gov (United States)

    Kapri, Priyadarshini; Adhikary, Priyanka; Sinha, Shubham; Basu, Saurabh

    2018-05-01

    Thermoelectric effect for metal, insulator and the superconductor junctions has been studied with Rashba spin-orbit coupling (RSOC) being present at the interfaces via modified Blonder-Tinkham-Klapwijk (BTK) theory. We find that the thermopower, as a function of an effective barrier potential that characterizes the intermediate insulating layer, displays an oscillatory behavior. Interesting interplay between the strength of RSOC and the effective barrier potential has been carried out in details in this regard. For specific ranges of the effective barrier potential, RSOC enhances the thermopower, while the reverse happens for other values. Moreover it is found that the effective barrier potential plays a crucial role in determining the thermopower spectrum. For a tunable Rashba coupling, the thermopower of the junction can be controlled with precision, which may useful for the thermoelectric applications, at low temperatures. Further the efficiency of the system is obtained for different pairing correlations of the superconducting lead where we find that the system with a d-wave symmetry is more efficient as compared to a s-wave correlation, in some selective regions of effective barrier potential. It is found that for some selective regions of effective barrier potential, the efficiency of the system increases with RSOC and the opposite happens for other values.

  20. Electrochemical gate-controlled electron transport of redox-active single perylene bisimide molecular junctions

    International Nuclear Information System (INIS)

    Li, C; Mishchenko, A; Li, Z; Pobelov, I; Wandlowski, Th; Li, X Q; Wuerthner, F; Bagrets, A; Evers, F

    2008-01-01

    We report a scanning tunneling microscopy (STM) experiment in an electrochemical environment which studies a prototype molecular switch. The target molecules were perylene tetracarboxylic acid bisimides modified with pyridine (P-PBI) and methylthiol (T-PBI) linker groups and with bulky tert-butyl-phenoxy substituents in the bay area. At a fixed bias voltage, we can control the transport current through a symmetric molecular wire Au|P-PBI(T-PBI)|Au by variation of the electrochemical 'gate' potential. The current increases by up to two orders of magnitude. The conductances of the P-PBI junctions are typically a factor 3 larger than those of T-PBI. A theoretical analysis explains this effect as a consequence of shifting the lowest unoccupied perylene level (LUMO) in or out of the bias window when tuning the electrochemical gate potential VG. The difference in on/off ratios reflects the variation of hybridization of the LUMO with the electrode states with the anchor groups. I T -E S(T) curves of asymmetric molecular junctions formed between a bare Au STM tip and a T-PBI (P-PBI) modified Au(111) electrode in an aqueous electrolyte exhibit a pronounced maximum in the tunneling current at -0.740, which is close to the formal potential of the surface-confined molecules. The experimental data were explained by a sequential two-step electron transfer process

  1. Role of solvent environments in single molecule conductance used insulator-modified mechanically controlled break junctions

    Science.gov (United States)

    Muthusubramanian, Nandini; Maity, Chandan; Galan Garcia, Elena; Eelkema, Rienk; Grozema, Ferdinand; van der Zant, Herre; Kavli Institute of Nanoscience Collaboration; Department of Chemical Engineering Collaboration

    We present a method for studying the effects of polar solvents on charge transport through organic/biological single molecules by developing solvent-compatible mechanically controlled break junctions of gold coated with a thin layer of aluminium oxide using plasma enhanced atomic layer deposition (ALD). The optimal oxide thickness was experimentally determined to be 15 nm deposited at ALD operating temperature of 300°C which yielded atomically sharp electrodes and reproducible single-barrier tunnelling behaviour across a wide conductance range between 1 G0 and 10-7 G0. The insulator protected MCBJ devices were found to be effective in various solvents such as deionized water, phosphate buffered saline, methanol, acetonitrile and dichlorobenzene. The yield of molecular junctions using such insulated electrodes was tested by developing a chemical protocol for synthesizing an amphipathic form of oligo-phenylene ethynylene (OPE3-PEO) with thioacetate anchoring groups. This work has further applications in studying effects of solvation, dipole orientation and other thermodynamic interactions on charge transport. Eu Marie Curie Initial Training Network (ITN). MOLECULAR-SCALE ELECTRONICS: ``MOLESCO'' Project Number 606728.

  2. Impact of 7,12-dimethylbenz[a]anthracene exposure on connexin gap junction proteins in cultured rat ovaries

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2014-01-15

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles in a concentration-dependent manner. The impact of DMBA on connexin (CX) proteins that mediate communication between follicular cell types along with pro-apoptotic factors p53 and Bax were investigated. Postnatal day (PND) 4 Fisher 344 rat ovaries were cultured for 4 days in vehicle medium (1% DMSO) followed by a single exposure to vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and cultured for 4 or 8 days. RT-PCR was performed to quantify Cx37, Cx43, p53 and Bax mRNA level. Western blotting and immunofluorescence staining were performed to determine CX37 or CX43 level and/or localization. Cx37 mRNA and protein increased (P < 0.05) at 4 days of 12.5 nM DMBA exposure. Relative to vehicle control-treated ovaries, mRNA encoding Cx43 decreased (P < 0.05) but CX43 protein increased (P < 0.05) at 4 days by both DMBA exposures. mRNA expression of pro-apoptotic p53 was decreased (P < 0.05) but no changes in Bax expression were observed after 4 days of DMBA exposures. In contrast, after 8 days, DMBA decreased Cx37 and Cx43 mRNA and protein but increased both p53 and Bax mRNA levels. CX43 protein was located between granulosa cells, while CX37 was located at the oocyte cell surface of all follicle stages. These findings support that DMBA exposure impacts ovarian Cx37 and Cx43 mRNA and protein prior to both observed changes in pro-apoptotic p53 and Bax and follicle loss. It is possible that such interference in follicular cell communication is detrimental to follicle viability, and may play a role in DMBA-induced follicular atresia. - Highlights: • DMBA increases Cx37 and Cx43 expression prior to follicle loss. • During follicle loss both Cx37 and Cx43 expressions are reduced. • CX43 protein is absent in follicle remnants lacking an oocyte.

  3. Changes in homologous and heterologous gap junction contacts during maturation-inducing hormone-dependent meiotic resumption in ovarian follicles of Atlantic croaker

    Science.gov (United States)

    Bolamba, D.; Patino, R.; Yoshizaki, G.; Thomas, P.

    2003-01-01

    Homologous (granulosa cell-granulosa cell) gap junction (GJ) contacts increase in ovarian follicles of Atlantic croaker (Micropogonias undulatus) during the early (first) stage of maturation, but their profile during the second stage [i.e., during maturation-inducing hormone (MIH)-mediated meiotic resumption] is unknown. The profile of homologous GJ contacts during the second stage of maturation in croaker follicles was examined in this study and compared to that of heterologous (granulosa cell-oocyte) GJ, for which changes have been previously documented. Follicles were incubated with human chorionic gonadotropin to induce maturational competence (first stage), and then with MIH to induce meiotic resumption. The follicles were collected for examination immediately before and after different durations of MIH exposure until the oocyte had reached the stage of germinal vesicle breakdown (GVBD; index of meiotic resumption). Ultrathin sections were observed by transmission electron microscopy, and homologous and heterologous GJ contacts were quantified along a 100-??m segment of granulosa cell-zona radiata complex per follicle (three follicles/time/fish, n=3 fish). Relatively high numbers of both types of GJ were observed before and after the first few hours of MIH exposure (up to the stage of oil droplet coalescence). GJ numbers declined during partial yolk globule coalescence (at or near GVBD) and were just under 50% of starting values after the completion of GVBD (P<0.05). These results confirm earlier observations that GVBD temporally correlates with declining heterologous GJ contacts, and for the first time in teleosts show that there is a parallel decline in homologous GJ. The significance of the changes in homologous and heterologous GJ is uncertain and deserves further study. ?? 2003 Elsevier Science (USA). All rights reserved.

  4. Fast electric control of the droplet size in a microfluidic T-junction droplet generator

    Science.gov (United States)

    Shojaeian, Mostafa; Hardt, Steffen

    2018-05-01

    The effect of DC electric fields on the generation of droplets of water and xanthan gum solutions in sunflower oil at a microfluidic T-junction is experimentally studied. The electric field leads to a significant reduction of the droplet diameter, by about a factor of 2 in the case of water droplets. The droplet size can be tuned by varying the electric field strength, an effect that can be employed to produce a stream of droplets with a tailor-made size sequence. Compared to the case of purely hydrodynamic droplet production without electric fields, the electric control has about the same effect on the droplet size if the electric stress at the liquid/liquid interface is the same as the hydrodynamic stress.

  5. A parabolic model to control quantum interference in T-shaped molecular junctions

    DEFF Research Database (Denmark)

    Nozaki, Daijiro; Sevincli, Haldun; Avdoshenko, Stanislav M.

    2013-01-01

    Quantum interference (QI) effects in molecular devices have drawn increasing attention over the past years due to their unique features observed in the conductance spectrum. For the further development of single molecular devices exploiting QI effects, it is of great theoretical and practical...... interest to develop simple methods controlling the emergence and the positions of QI effects like anti-resonances or Fano line shapes in conductance spectra. In this work, starting from a well-known generic molecular junction with a side group (T-shaped molecule), we propose a simple graphical method...... to visualize the conditions for the appearance of quantum interference, Fano resonances or anti-resonances, in the conductance spectrum. By introducing a simple graphical representation (parabolic diagram), we can easily visualize the relation between the electronic parameters and the positions of normal...

  6. Optically controlled electroresistance and electrically controlled photovoltage in ferroelectric tunnel junctions

    KAUST Repository

    Jin Hu, Wei; Wang, Zhihong; Yu, Weili; Wu, Tao

    2016-01-01

    Ferroelectric tunnel junctions (FTJs) have recently attracted considerable interest as a promising candidate for applications in the next-generation non-volatile memory technology. In this work, using an ultrathin (3 nm) ferroelectric Sm0.1Bi0.9FeO3 layer as the tunnelling barrier and a semiconducting Nb-doped SrTiO3 single crystal as the bottom electrode, we achieve a tunnelling electroresistance as large as 105. Furthermore, the FTJ memory states could be modulated by light illumination, which is accompanied by a hysteretic photovoltaic effect. These complimentary effects are attributed to the bias- and light-induced modulation of the tunnel barrier, both in height and width, at the semiconductor/ferroelectric interface. Overall, the highly tunable tunnelling electroresistance and the correlated photovoltaic functionalities provide a new route for producing and non-destructively sensing multiple non-volatile electronic states in such FTJs.

  7. Optically controlled electroresistance and electrically controlled photovoltage in ferroelectric tunnel junctions

    KAUST Repository

    Jin Hu, Wei

    2016-02-29

    Ferroelectric tunnel junctions (FTJs) have recently attracted considerable interest as a promising candidate for applications in the next-generation non-volatile memory technology. In this work, using an ultrathin (3 nm) ferroelectric Sm0.1Bi0.9FeO3 layer as the tunnelling barrier and a semiconducting Nb-doped SrTiO3 single crystal as the bottom electrode, we achieve a tunnelling electroresistance as large as 105. Furthermore, the FTJ memory states could be modulated by light illumination, which is accompanied by a hysteretic photovoltaic effect. These complimentary effects are attributed to the bias- and light-induced modulation of the tunnel barrier, both in height and width, at the semiconductor/ferroelectric interface. Overall, the highly tunable tunnelling electroresistance and the correlated photovoltaic functionalities provide a new route for producing and non-destructively sensing multiple non-volatile electronic states in such FTJs.

  8. Functional connectivity profile of the human inferior frontal junction: involvement in a cognitive control network

    Directory of Open Access Journals (Sweden)

    Sundermann Benedikt

    2012-10-01

    Full Text Available Abstract Background The human inferior frontal junction area (IFJ is critically involved in three main component processes of cognitive control (working memory, task switching and inhibitory control. As it overlaps with several areas in established anatomical labeling schemes, it is considered to be underreported as a functionally distinct location in the neuroimaging literature. While recent studies explicitly focused on the IFJ's anatomical organization and functional role as a single brain area, it is usually not explicitly denominated in studies on cognitive networks. However based on few analyses in small datasets constrained by specific a priori assumptions on its functional specialization, the IFJ has been postulated to be part of a cognitive control network. Goal of this meta-analysis was to establish the IFJ’s connectivity profile on a high formal level of evidence by aggregating published implicit knowledge about its co-activations. We applied meta-analytical connectivity modeling (MACM based on the activation likelihood estimation (ALE method without specific assumptions regarding functional specialization on 180 (reporting left IFJ activity and 131 (right IFJ published functional neuroimaging experiments derived from the BrainMap database. This method is based on coordinates in stereotaxic space, not on anatomical descriptors. Results The IFJ is significantly co-activated with areas in the dorsolateral and ventrolateral prefrontal cortex, anterior insula, medial frontal gyrus / pre-SMA, posterior parietal cortex, occipitotemporal junction / cerebellum, thalamus and putamen as well as language and motor areas. Results are corroborated by an independent resting-state fMRI analysis. Conclusions These results support the assumption that the IFJ is part of a previously described cognitive control network. They also highlight the involvement of subcortical structures in this system. A direct line is drawn from works on the functional

  9. A new singularity in the coherent coupling in Al/GaAs/Al SNS junctions at the bias voltage corresponding to the superconducting energy gap

    DEFF Research Database (Denmark)

    Taboryski, Rafael Jozef; Kutchinsky, Jonatan; Kuhn, Oliver

    1998-01-01

    Particularly high transmittivity superconductor-semiconductor barriers formed by MBE growth have been used to form short Josephson planar type Superconductor-Normal-metal-Superconductor (SNS) Josephson junctions with lengths down to 1 mu m. In these junctions the quasiparticles move diffusively...... across the normal region and carry along the phase information given to them by Andreev reflections at both SN boundaries. In order to probe the importance of the coherent transport of quasiparticles in the normal region, we formed one of the superconducting electrodes of the junction as an open loop i...

  10. Magnetic and electric control of spin- and valley-polarized transport across tunnel junctions on monolayer WSe2

    Science.gov (United States)

    Tahir, M.; Krstajić, P. M.; Vasilopoulos, P.

    2017-06-01

    The recent experimental realization of high-quality WSe2 leads to the possibility of an efficient manipulation of its spin and valley degrees of freedom. Its electronic properties comprise a huge spin-orbit coupling, a direct band gap, and a strong anisotropic lifting of the degeneracy of the valley degree of freedom in a magnetic field. We evaluate its band structure and study ballistic electron transport through single and double junctions (or barriers) on monolayer WSe2 in the presence of spin Ms and valley Mv Zeeman fields and of an electric potential U . The conductance versus the field Ms or Mv decreases in a fluctuating manner. For a single junction, the spin Ps and valley Pv polarizations rise with M =Mv=2 Ms , reach a value of more than 55 % , and become perfect above U ≈45 meV while for a double junction this change can occur for U ≥50 meV and M ≥5 meV. In certain regions of the (M ,U ) plane Pv becomes perfect. The conductance gc, its spin-up and spin-down components, and both polarizations oscillate with the barrier width d . The ability to isolate various carrier degrees of freedom in WSe2 may render it a promising candidate for new spintronic and valleytronic devices.

  11. A prospective controlled study of sleep respiratory events in patients with craniovertebral junction malformation.

    Science.gov (United States)

    Botelho, Ricardo Vieira; Bittencourt, Lia Rita Azeredo; Rotta, José Marcos; Tufik, Sergio

    2003-12-01

    Craniovertebral junction malformation (CVJM) or Chiari malformation in adults, with or without syringomyelia and basilar invagination, produces neuronal dysfunction of the brainstem, cerebellum, cranial nerves, and upper spinal cord. The respiratory center and some of its afferent and efferent components can be altered in these diseases. The authors studied patients with and without CVJM to determine whether this physical feature contributed to sleep disturbances. Respiratory manifestations during sleep were studied prospectively, by using whole-night polysomnography, in 32 symptomatic patients (CVJM group) and 16 healthy volunteers (control group). Patients with CVJM presented with more sleep disturbances (reports of snoring and apnea) than those in the control group. The apnea/hypopnea index values were higher in patients with CVJMs than in the control group (13 +/- 15 compared with 3 +/- 6; p = 0.007) and the rate of central sleep apneas was higher in the CVJM than in the control group (22 +/- 30 compared with 4 +/- 8%; p = 0.009). The apnea/hypopnea index was highest in the subgroup with basilar invagination than in the other subgroups. The central apneic episodes were more frequent in the patients with basilar invagination (35 +/- 40%; p = 0.001) and in those with syringomyelia (17.6 +/- 24.6%; p = 0.003) than in the control group (4 +/- 8%). Patients with symptomatic CVJM, especially those with basilar invagination, presented with more sleep respiratory compromise than did those in the control group. The incidence of sleep apnea/hypopnea syndrome is significantly higher in patients with CVJM.

  12. Engineering of Fermi level by nin diamond junction for control of charge states of NV centers

    Science.gov (United States)

    Murai, T.; Makino, T.; Kato, H.; Shimizu, M.; Murooka, T.; Herbschleb, E. D.; Doi, Y.; Morishita, H.; Fujiwara, M.; Hatano, M.; Yamasaki, S.; Mizuochi, N.

    2018-03-01

    The charge-state control of nitrogen-vacancy (NV) centers in diamond is very important toward its applications because the NV centers undergo stochastic charge-state transitions between the negative charge state (NV-) and the neutral charge state (NV0) of the NV center upon illumination. In this letter, engineering of the Fermi level by a nin diamond junction was demonstrated for the control of the charge state of the NV centers in the intrinsic (i) layer region. By changing the size (d) of the i-layer region between the phosphorus-doped n-type layer regions (nin) from 2 μm to 10 μm, we realized the gradual change in the NV- charge-state population in the i-layer region from 60% to 80% under 532 nm excitation, which can be attributed to the band bending in the i-layer region. Also, we quantitatively simulated the changes in the Fermi level in the i-layer region depending on d with various concentrations of impurities in the i-layer region.

  13. Accurate tool height control by bearing gap adjustment

    NARCIS (Netherlands)

    Wielen, van der A.M.; Schellekens, P.H.J.; Jaartsveld, F.T.M.

    2002-01-01

    Face turning of optical surfaces on precision lathes needs high precision tool height adjustment, which may be a difficult and time-consuming task. In this paper we present a new tool adjustment mechanism based on varying the bearing gap height of the hydrostatic bearings present in precision lathe

  14. Supervised learning from human performance at the computationally hard problem of optimal traffic signal control on a network of junctions.

    Science.gov (United States)

    Box, Simon

    2014-12-01

    Optimal switching of traffic lights on a network of junctions is a computationally intractable problem. In this research, road traffic networks containing signallized junctions are simulated. A computer game interface is used to enable a human 'player' to control the traffic light settings on the junctions within the simulation. A supervised learning approach, based on simple neural network classifiers can be used to capture human player's strategies in the game and thus develop a human-trained machine control (HuTMaC) system that approaches human levels of performance. Experiments conducted within the simulation compare the performance of HuTMaC to two well-established traffic-responsive control systems that are widely deployed in the developed world and also to a temporal difference learning-based control method. In all experiments, HuTMaC outperforms the other control methods in terms of average delay and variance over delay. The conclusion is that these results add weight to the suggestion that HuTMaC may be a viable alternative, or supplemental method, to approximate optimization for some practical engineering control problems where the optimal strategy is computationally intractable.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-01

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

  16. 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.

  17. Electrochemical control of a DNA Holliday Junction nanoswitch by Mg2+ ions.

    Science.gov (United States)

    Ferapontova, E E; Mountford, C P; Crain, J; Buck, A H; Dickinson, P; Beattie, J S; Ghazal, P; Terry, J G; Walton, A J; Mount, A R

    2008-11-15

    The molecular conformation of a synthetic branched, 4-way DNA Holliday junction (HJ) was electrochemically switched between the open and closed (stacked) conformers. Switching was achieved by electrochemically induced quantitative release of Mg(2+) ions from the oxidised poly(N-methylpyrrole) film (PPy), which contained polyacrylate as an immobile counter anion and Mg(2+) ions as charge compensating mobile cations. This increase in the Mg(2+) concentration screened the electrostatic repulsion between the widely separated arms in the open HJ configuration, inducing switching to the closed conformation. Upon electrochemical reduction of PPy, entrapment of Mg(2+) ions back into the PPy film induced the reverse HJ switching from the closed to open state. The conformational transition was monitored using fluorescence resonance energy transfer (FRET) between donor and acceptor dyes each located at the terminus of one of the arms. The demonstrated electrochemical control of the conformation of the used probe-target HJ complex, previously reported as a highly sequence specific nanodevice for detecting of unlabelled target [Buck, A.H., Campbell, C.J., Dickinson, P., Mountford, C.P., Stoquert, H.C., Terry, J.G., Evans, S.A.G., Keane, L., Su, T.J., Mount, A.R., Walton, A.J., Beattie, J.S., Crain, J., Ghazal, P., 2007. Anal. Chem., 79, 4724-4728], allows the development of electronically addressable DNA nanodevices and label-free gene detection assays.

  18. Multiferroic tunnel junctions and ferroelectric control of magnetic state at interface (invited)

    KAUST Repository

    Yin, Y. W.

    2015-03-03

    As semiconductor devices reach ever smaller dimensions, the challenge of power dissipation and quantum effect place a serious limit on the future device scaling. Recently, a multiferroic tunnel junction (MFTJ) with a ferroelectric barrier sandwiched between two ferromagnetic electrodes has drawn enormous interest due to its potential applications not only in multi-level data storage but also in electric field controlled spintronics and nanoferronics. Here, we present our investigations on four-level resistance states, giant tunneling electroresistance (TER) due to interfacial magnetoelectric coupling, and ferroelectric control of spin polarized tunneling in MFTJs. Coexistence of large tunneling magnetoresistance and TER has been observed in manganite/(Ba, Sr)TiO3/manganite MFTJs at low temperatures and room temperature four-resistance state devices were also obtained. To enhance the TER for potential logic operation with a magnetic memory, La0.7Sr0.3MnO3/BaTiO3/La0.5Ca0.5MnO3 /La0.7Sr0.3MnO3 MFTJs were designed by utilizing a bilayer tunneling barrier in which BaTiO3 is ferroelectric and La0.5Ca0.5MnO3 is close to ferromagnetic metal to antiferromagnetic insulator phase transition. The phase transition occurs when the ferroelectric polarization is reversed, resulting in an increase of TER by two orders of magnitude. Tunneling magnetoresistance can also be controlled by the ferroelectric polarization reversal, indicating strong magnetoelectric coupling at the interface.

  19. Electrical control of memristance and magnetoresistance in oxide magnetic tunnel junctions

    KAUST Repository

    Zhang, Kun; Cao, Yan-ling; Fang, Yue-wen; Li, Qiang; Zhang, Jie; Duan, Chun-gang; Yan, Shi-shen; Tian, Yu-feng; Huang, Rong; Zheng, Rong-kun; Kang, Shi-shou; Chen, Yan-xue; Liu, Guo-lei; Mei, Liang-mo

    2015-01-01

    , and exchange bias in Co/CoO–ZnO/Co magnetic tunnel junctions, which enables the realization of four nonvolatile resistance states. Moreover, greatly enhanced tunneling magnetoresistance of 68% was observed due to the enhanced spin polarization of the bottom Co/Co

  20. Electrically controlled band gap and topological phase transition in two-dimensional multilayer germanane

    International Nuclear Information System (INIS)

    Qi, Jingshan; Li, Xiao; Qian, Xiaofeng

    2016-01-01

    Electrically controlled band gap and topological electronic states are important for the next-generation topological quantum devices. In this letter, we study the electric field control of band gap and topological phase transitions in multilayer germanane. We find that although the monolayer and multilayer germananes are normal insulators, a vertical electric field can significantly reduce the band gap of multilayer germananes owing to the giant Stark effect. The decrease of band gap eventually leads to band inversion, transforming them into topological insulators with nontrivial Z_2 invariant. The electrically controlled topological phase transition in multilayer germananes provides a potential route to manipulate topologically protected edge states and design topological quantum devices. This strategy should be generally applicable to a broad range of materials, including other two-dimensional materials and ultrathin films with controlled growth.

  1. Active Power Controls from Wind Power: Bridging the Gaps

    Energy Technology Data Exchange (ETDEWEB)

    Ela, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Gevorgian, V. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Fleming, P. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Zhang, Y. C. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Singh, M. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Muljadi, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Scholbrook, A. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Aho, J. [Univ. of Colorado, Boulder, CO (United States); Buckspan, A. [Univ. of Colorado, Boulder, CO (United States); Pao, L. [Univ. of Colorado, Boulder, CO (United States); Singhvi, V. [Electric Power Research Inst. (EPRI), Palo Alto, CA (United States); Tuohy, A. [Electric Power Research Inst. (EPRI), Palo Alto, CA (United States); Pourbeik, P. [Electric Power Research Inst. (EPRI), Palo Alto, CA (United States); Brooks, D. [Electric Power Research Inst. (EPRI), Palo Alto, CA (United States); Bhatt, N. [Electric Power Research Inst. (EPRI), Palo Alto, CA (United States)

    2014-01-01

    This paper details a comprehensive study undertaken by the National Renewable Energy Laboratory, Electric Power Research Institute, and the University of Colorado to understand how the contribution of wind power providing active power control (APC) can benefit the total power system economics, increase revenue streams, improve the reliability and security of the power system, and provide superior and efficient response while reducing any structural and loading impacts that may reduce the life of the wind turbine or its components. The study includes power system simulations, control simulations, and actual field tests using turbines at NREL's National Wind Technology Center (NWTC). The study focuses on synthetic inertial control, primary frequency control, and automatic generation control, and analyzes timeframes ranging from milliseconds to minutes to the lifetime of wind turbines, locational scope ranging from components of turbines to large wind plants to entire synchronous interconnections, and additional topics ranging from economics to power system engineering to control design.

  2. Knowledge Gaps Impacting the Development of Bovine Viral Diarrhea Virus Control Programs in the United States

    Science.gov (United States)

    This paper identifies knowledge gaps that impact on the design of programs to control and or eradicate bovine viral diarrhea viruses (BVDV) in the United States. Currently there are several voluntary regional BVDV control programs in place. These control programs are aimed at the removal of animals ...

  3. Knowledge gaps that hamper prevention and control of Mycobacterium avium subspecies paratuberculosis infection

    DEFF Research Database (Denmark)

    Barkema, H W; Orsel, K; Nielsen, S S

    2018-01-01

    In the last decades, many regional and country-wide control programmes for Johne's disease (JD) were developed due to associated economic losses, or because of a possible association with Crohn's disease. These control programmes were often not successful, partly because management protocols were...... programmes are typically evaluated in a limited number of herds and the duration of the study is less than 5 year, making it difficult to adequately assess the efficacy of control programmes. In this manuscript, we identify the most important gaps in knowledge hampering JD prevention and control programmes......, including vaccination and diagnostics. Secondly, we discuss directions that research should take to address those knowledge gaps....

  4. 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

  5. Heterogenous treatment of water gaps and control rods in core calculations

    International Nuclear Information System (INIS)

    Lindahl, S.Oe.

    1984-08-01

    The conventional fuel assembly homogenization process introduces errors in the gross power distribution of the order of 10%. A method to mitigate the homogenization error is proposed. The gaps in between the fuel pin domains, containing water, control rod blades, fuel channel shroud, etc, are described by their transmission and reflection properties while the fuel pin regions are represented by conventional, homogenized cross sections. A nodal equation, incorporating the gap transmission and reflection functions, is set up in a general form. By numerical testing on 2D core problems it is shown that the explicit gap treatment is capable of reducing the homogenization error by an order of magnitude. (author)

  6. 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.

  7. Inter-vehicle gap statistics on signal-controlled crossroads

    International Nuclear Information System (INIS)

    Krbalek, Milan

    2008-01-01

    We investigate a microscopical structure in a chain of cars waiting at a red signal on signal-controlled crossroads. A one-dimensional space-continuous thermodynamical model leading to an excellent agreement with the data measured is presented. Moreover, we demonstrate that an inter-vehicle spacing distribution disclosed in relevant traffic data agrees with the thermal-balance distribution of particles in the thermodynamical traffic gas (discussed in [1]) with a high inverse temperature (corresponding to a strong traffic congestion). Therefore, as we affirm, such a system of stationary cars can be understood as a specific state of the traffic sample operating inside a congested traffic stream

  8. Voltage control of a magnetic switching field for magnetic tunnel junctions with low resistance and perpendicular magnetic anisotropy

    Science.gov (United States)

    Tezuka, N.; Oikawa, S.; Matsuura, M.; Sugimoto, S.; Nishimura, K.; Irisawa, T.; Nagamine, Y.; Tsunekawa, K.

    2018-05-01

    The authors investigated the voltage control of a magnetic anisotropy field for perpendicular-magnetic tunnel junctions (p-MTJs) with low and high resistance-area (RA) products and for synthetic antiferromagnetic free and pinned layers. It was found that the sample with low RA products was more sensitive to the applied bias voltage than the sample with high RA products. The bias voltage effect was less pronounced for our sample with the synthetic antiferromagnetic layer for high RA products compared to the MTJs with single free and pinned layers.

  9. 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.

  10. Stability and controllability of InGaAs/GaAsP wire-on-well (WoW) structure for multi-junction solar cells

    Science.gov (United States)

    Cho, Hirofumi; Toprasertpong, Kasidit; Sodabanlu, Hassanet; Watanabe, Kentaroh; Sugiyama, Masakazu; Nakano, Yoshiaki

    2017-04-01

    Wire on Well (WoW) structure embedded in a matrix is naturally formed by growing InxGa1-xAs/GaAs1-yPy strained multiple quantum wells (MQW) on vicinal substrates and employing triethylgallium (TEGa) as a precursor in low-temperature MOVPE. The structure is useful for the subcell in current-matched mult-junction solar cells with lattice-matched materials because of its ability of band-gap tuning. In this research, high density and uniform In0.30Ga0.70As/GaAs0.6P0.4 WoW was obtained up to 200 stacks and its structure was analyzed by X-ray diffraction reciprocal space mapping, atomic force microscopy and scanning transmission electron microscopy. The structure of the wire can be controlled by changing the equivalent layer thicknesses of In0.30Ga0.70As and GaAs0.6P0.4. The photoluminescence peak from the WoW shifted according to the size of InGaAs wires and the intensity was dependent on the accumulation of lattice-mismatch stress.

  11. Dual-probe near-field fiber head with gap servo control for data storage applications.

    Science.gov (United States)

    Fang, Jen-Yu; Tien, Chung-Hao; Shieh, Han-Ping D

    2007-10-29

    We present a novel fiber-based near-field optical head consisting of a straw-shaped writing probe and a flat gap sensing probe. The straw-shaped probe with a C-aperture on the end face exhibits enhanced transmission by a factor of 3 orders of magnitude over a conventional fiber probe due to a hybrid effect that excites both propagation modes and surface plasmon waves. In the gap sensing probe, the spacing between the probe and the disk surface functions as an external cavity. The high sensitivity of the output power to the change in the gap width is used as a feedback control signal. We characterize and design the straw-shaped writing probe and the flat gap sensing probe. The dual-probe system is installed on a conventional biaxial actuator to demonstrate the capability of flying over a disk surface with nanometer position precision.

  12. Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression

    Science.gov (United States)

    Verd, Berta; Crombach, Anton

    2017-01-01

    Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory

  13. Bi-Sn alloy catalyst for simultaneous morphology and doping control of silicon nanowires in radial junction solar cells

    International Nuclear Information System (INIS)

    Yu, Zhongwei; Lu, Jiawen; Qian, Shengyi; Xu, Jun; Xu, Ling; Wang, Junzhuan; Shi, Yi; Chen, Kunji; Misra, Soumyadeep; Roca i Cabarrocas, Pere; Yu, Linwei

    2015-01-01

    Low-melting point metals such as bismuth (Bi) and tin (Sn) are ideal choices for mediating a low temperature growth of silicon nanowires (SiNWs) for radial junction thin film solar cells. The incorporation of Bi catalyst atoms leads to sufficient n-type doping in the SiNWs core that exempts the use of hazardous dopant gases, while an easy morphology control with pure Bi catalyst has never been demonstrated so far. We here propose a Bi-Sn alloy catalyst strategy to achieve both a beneficial catalyst-doping and an ideal SiNW morphology control. In addition to a potential of further growth temperature reduction, we show that the alloy catalyst can remain quite stable during a vapor-liquid-solid growth, while providing still sufficient n-type catalyst-doping to the SiNWs. Radial junction solar cells constructed over the alloy-catalyzed SiNWs have demonstrated a strongly enhanced photocurrent generation, thanks to optimized nanowire morphology, and largely improved performance compared to the reference samples based on the pure Bi or Sn-catalyzed SiNWs

  14. Control of Nanofilament Structure and Observations of Quantum Point Contact Behavior in Ni/NiO Nanowire Junctions

    Science.gov (United States)

    Oliver, Sean; Fairfield, Jessamyn; Lee, Sunghun; Bellew, Allen; Stone, Iris; Ruppalt, Laura; Boland, John; Vora, Patrick

    Resistive switching is ideal for use in non-volatile memory where information is stored in a metallic or insulating state. Nanowire junctions formed at the intersection of two Ni/NiO core/shell nanowires have emerged as a leading candidate structure where resistive switching occurs due to the formation and destruction of conducting filaments. However, significant knowledge gaps remain regarding the conduction mechanisms as measurements are typically only performed at room temperature. Here, we combine temperature-dependent current-voltage (IV) measurements from 15 - 300 K with magnetoresistance studies and achieve new insight into the nature of the conducting filaments. We identify a novel semiconducting state that behaves as a quantum point contact and find evidence for a possible electric-field driven phase transition. The insulating state exhibits unexpectedly complex IV characteristics that highlight the disordered nature of the ruptured filament while we find clear signs of anisotropic magnetoresistance in the metallic state. Our results expose previously unobserved behaviors in nanowire resistive switching devices and pave the way for future applications where both electrical and magnetic switching can be achieved in a single device. This work was supported by ONR Grant N-00014-15-1-2357.

  15. Electrical transport characteristics of Bi2Sr2CaCu2O8+δstacked junctions with control of the carrier density

    International Nuclear Information System (INIS)

    Inomata, Kunihiro; Kawae, Takeshi; Kim, Sang-Jae; Nakajima, Kensuke; Yamashita, Tsutomu; Sato, Shigeo; Nakajima, Koji; Hatano, Takeshi

    2003-01-01

    The control of the critical current density (J c ) and the junction resistance (R N ) along the c-axis of intrinsic Josephson junctions (IJJs) on a high-T c superconductor is very important for applying the IJJs to electronic devices. For controlling these junction parameters, we have clarified the relationship of J c , R N and the carrier density in Bi 2 Sr 2 CaCu 2 O 8+δ whiskers by changing the carrier density with an annealing process. We determined the electrical transport characteristics of the IJJs. As a result, the J c increased, and the R N decreased systematically when the carrier density increased. The values of J c and R N could be controlled by a change in the carrier density

  16. 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.

  17. Task-dependent and distinct roles of the temporoparietal junction and inferior frontal cortex in the control of imitation.

    Science.gov (United States)

    Hogeveen, Jeremy; Obhi, Sukhvinder S; Banissy, Michael J; Santiesteban, Idalmis; Press, Clare; Catmur, Caroline; Bird, Geoffrey

    2015-07-01

    The control of neurological networks supporting social cognition is crucially important for social interaction. In particular, the control of imitation is directly linked to interaction quality, with impairments associated with disorders characterized by social difficulties. Previous work suggests inferior frontal cortex (IFC) and the temporoparietal junction (TPJ) are involved in controlling imitation, but the functional roles of these areas remain unclear. Here, transcranial direct current stimulation (tDCS) was used to enhance cortical excitability at IFC and the TPJ prior to the completion of three tasks: (i) a naturalistic social interaction during which increased imitation is known to improve rapport, (ii) a choice reaction time task in which imitation needs to be inhibited for successful performance and (iii) a non-imitative control task. Relative to sham stimulation, stimulating IFC improved the context-dependent control of imitation-participants imitated more during the social interaction and less during the imitation inhibition task. In contrast, stimulating the TPJ reduced imitation in the inhibition task without affecting imitation during social interaction. Neither stimulation site affected the non-imitative control task. These data support a model in which IFC modulates imitation directly according to task demands, whereas TPJ controls task-appropriate shifts in attention toward representation of the self or the other, indirectly impacting upon imitation. © The Author (2014). Published by Oxford University Press.

  18. Upper airway dimensions in patients with craniocervical junction malformations with and without sleep apnea. A pilot case-control study

    Directory of Open Access Journals (Sweden)

    Ramon Barbalho Guerreiro

    2015-04-01

    Full Text Available Objective Patients with craniocervical junction malformations (CCJM tend to suffer more frequently from sleep respiratory disturbances, which are more frequent and severe in patients with basilar invagination. Here we evaluate if patients with CCJM and sleep respiratory disorders (SRD present smaller airway dimensions than patients without SRD. Method Patients with CCCM with and without sleep respiratory disturbances were evaluated clinically by Bindal's score, modified Mallampati classification, full-night polysomnography and upper airway cone beam tomography. Results Eleven patients had sleep respiratory disorders (SRD, and nine patients performed control group without SRD. CCJM patients with SRD were predominantly female, older, had higher BMI, were more likely to have Mallampati grades 3 and 4 and had statistically significant smaller anteroposterior diameter of the upper airway than patients without SRD. Conclusion Patients with CCJM and sleep respiratory disturbances have higher BMI, higher Mallampati score and smaller anterior posterior diameter of the upper airway.

  19. Local control of T3 carcinomas after accelerated fractionation: a look at the 'gap'

    International Nuclear Information System (INIS)

    Wang, C.C.; Efird, Jimmy; Nakfoor, Bruce; Martins, Patricia

    1996-01-01

    Purpose: To study the effects of midcourse treatment break or gaps related to the local control of T3 carcinoma of the oropharynx and larynx following accelerated hyperfractionated radiation therapy. Methods and Materials: All patients were treated at the Massachusetts General Hospital from 1979 through 1994 with treatment consisting of 1.6 Gy per fraction, two fractions a day for the treatment of T3 carcinoma of the oropharynx and larynx. They were entered in the head and neck data base. Their treatment dates, treatment breaks, and doses vs. local control were analyzed and compared. A p-value of 0.05 was considered statistically significant. Results: A total of 162 patients were available for review. Due to the acute severe mucosal effects, most of the patients required a midcourse pause or 'break' after a dose of 38.4-48 Gy before treatment could be resumed and completed. The data indicate that (a) prolongation of the treatment gap for more than 14 days, (b) total treatment course longer than 45 days, (c) total dose less than 67 Gy, and (d) male gender adversely affected local control. In spite of the gaps, the female patients with advanced carcinomas enjoyed the benefits of improved local control after the accelerated hyperfractionated radiation therapy. Conclusions: Accelerated hyperfractionation radiation therapy using 1.6 Gy per fraction/twice-a-day (b.i.d.) for a total dose of 70.4 Gy in 6 weeks is effective in achieving high local control of T3 squamous cell carcinoma of the oropharynx and larynx. The midcourse treatment gap should be as short as possible with the projected total dose and time. Should the gaps be unduly prolonged due to various circumstances, further increase in the total dose, for example, 72-75 Gy, and/or increase of the fraction sizes, for example, 1.8-2.0 Gy/f b.i.d. after the gap may be necessary to compensate for the adverse effects of the tumor regeneration from the prolonged gap

  20. Enhanced voltage-controlled magnetic anisotropy in magnetic tunnel junctions with an MgO/PZT/MgO tunnel barrier

    Science.gov (United States)

    Chien, Diana; Li, Xiang; Wong, Kin; Zurbuchen, Mark A.; Robbennolt, Shauna; Yu, Guoqiang; Tolbert, Sarah; Kioussis, Nicholas; Khalili Amiri, Pedram; Wang, Kang L.; Chang, Jane P.

    2016-03-01

    Compared with current-controlled magnetization switching in a perpendicular magnetic tunnel junction (MTJ), electric field- or voltage-induced magnetization switching reduces the writing energy of the memory cell, which also results in increased memory density. In this work, an ultra-thin PZT film with high dielectric constant was integrated into the tunneling oxide layer to enhance the voltage-controlled magnetic anisotropy (VCMA) effect. The growth of MTJ stacks with an MgO/PZT/MgO tunnel barrier was performed using a combination of sputtering and atomic layer deposition techniques. The fabricated MTJs with the MgO/PZT/MgO barrier demonstrate a VCMA coefficient, which is ˜40% higher (19.8 ± 1.3 fJ/V m) than the control sample MTJs with an MgO barrier (14.3 ± 2.7 fJ/V m). The MTJs with the MgO/PZT/MgO barrier also possess a sizeable tunneling magnetoresistance (TMR) of more than 50% at room temperature, comparable to the control MTJs with an MgO barrier. The TMR and enhanced VCMA effect demonstrated simultaneously in this work make the MgO/PZT/MgO barrier-based MTJs potential candidates for future voltage-controlled, ultralow-power, and high-density magnetic random access memory devices.

  1. Controlled heat flux measurement across a closing nanoscale gap and its comparison to theory

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Y.; Ghafari, A.; Budaev, B. V.; Bogy, D. B., E-mail: dbogy@berkeley.edu [Department of mechanical Engineering, Computer Mechanics Lab, University of California, Berkeley, California 94720 (United States)

    2016-05-23

    We present here a controlled measurement of heat flux across a closing gap that is initially less than 10 nm wide between two solid surfaces at different temperatures. The measured heat transfer is compared with our published theoretical analyses of this phenomenon that show thermal radiation dominates the heat transfer for gaps wider than about 1–2 nm, but phonon conduction dominates between 1 and 2 nm and contact. The experiments employ a thermal actuator mounted on a rocking base block for coarse positioning that supplies Joule heating to an embedded element to cause thermal expansion of a localized region for less than 10 nm spacing control, together with an embedded near-surface resistive temperature sensor to measure its temperature change due to the heat flux across the gap. The measured results are in general agreement with the theoretical predictions, and they also agree with common sense expectations. This paper not only shows nano-scale heat transfer measurement across a closing gap, it also lends additional strong support to the validity of the referenced theoretical developments. The proposed experimental approach can provide support to design of future devices for nano-scale heat transfer measurement.

  2. Positioning the 5'-flap junction in the active site controls the rate of flap endonuclease-1-catalyzed DNA cleavage

    KAUST Repository

    Song, Bo

    2018-02-09

    Flap endonucleases catalyze cleavage of single-stranded DNA flaps formed during replication, repair and recombination, and are therefore essential for genome processing and stability. Recent crystal structures of DNA-bound human flap endonuclease (hFEN1) offer new insights into how conformational changes in the DNA and hFEN1 may facilitate the reaction mechanism. For example, previous biochemical studies of DNA conformation performed under non-catalytic conditions with Ca2+ have suggested that base unpairing at the 5\\'-flap:template junction is an important step in the reaction, but the new structural data suggest otherwise. To clarify the role of DNA changes in the kinetic mechanism, we measured a series of transient steps - from substrate binding to product release - during the hFEN1-catalyzed reaction in the presence of Mg2+. We found that while hFEN1 binds and bends DNA at a fast, diffusion-limited rate, much slower Mg2+-dependent conformational changes in DNA around the active site are subsequently necessary and rate-limiting for 5\\'-flap cleavage. These changes are reported overall by fluorescence of 2-aminopurine at the 5\\'-flap:template junction, indicating that local DNA distortion (e.g., disruption of base stacking observed in structures), associated with positioning the 5\\'-flap scissile phosphodiester bond in the hFEN1 active site, controls catalysis. hFEN1 residues with distinct roles in the catalytic mechanism, including those binding metal ions (Asp-34, Asp-181), steering the 5\\'-flap through the active site and binding the scissile phosphate (Lys-93, Arg-100), and stacking against the base 5\\' to the scissile phosphate (Tyr-40), all contribute to these rate-limiting conformational changes, ensuring efficient and specific cleavage of 5\\'-flaps.

  3. Positioning the 5'-flap junction in the active site controls the rate of flap endonuclease-1-catalyzed DNA cleavage

    KAUST Repository

    Song, Bo; Hamdan, Samir; Hingorani, Manju M

    2018-01-01

    Flap endonucleases catalyze cleavage of single-stranded DNA flaps formed during replication, repair and recombination, and are therefore essential for genome processing and stability. Recent crystal structures of DNA-bound human flap endonuclease (hFEN1) offer new insights into how conformational changes in the DNA and hFEN1 may facilitate the reaction mechanism. For example, previous biochemical studies of DNA conformation performed under non-catalytic conditions with Ca2+ have suggested that base unpairing at the 5'-flap:template junction is an important step in the reaction, but the new structural data suggest otherwise. To clarify the role of DNA changes in the kinetic mechanism, we measured a series of transient steps - from substrate binding to product release - during the hFEN1-catalyzed reaction in the presence of Mg2+. We found that while hFEN1 binds and bends DNA at a fast, diffusion-limited rate, much slower Mg2+-dependent conformational changes in DNA around the active site are subsequently necessary and rate-limiting for 5'-flap cleavage. These changes are reported overall by fluorescence of 2-aminopurine at the 5'-flap:template junction, indicating that local DNA distortion (e.g., disruption of base stacking observed in structures), associated with positioning the 5'-flap scissile phosphodiester bond in the hFEN1 active site, controls catalysis. hFEN1 residues with distinct roles in the catalytic mechanism, including those binding metal ions (Asp-34, Asp-181), steering the 5'-flap through the active site and binding the scissile phosphate (Lys-93, Arg-100), and stacking against the base 5' to the scissile phosphate (Tyr-40), all contribute to these rate-limiting conformational changes, ensuring efficient and specific cleavage of 5'-flaps.

  4. Diesel/CNG Mixture Autoignition Control Using Fuel Composition and Injection Gap

    Directory of Open Access Journals (Sweden)

    Firmansyah

    2017-10-01

    Full Text Available Combustion phasing is the main obstacle to the development of controlled auto-ignition based (CAI engines to achieve low emissions and low fuel consumption operation. Fuel combinations with substantial differences in reactivity, such as diesel/compressed natural gas (CNG, show desirable combustion outputs and demonstrate great possibility in controlling the combustion. This paper discusses a control method for diesel/CNG mixture combustion with a variation of fuel composition and fuel stratification levels. The experiments were carried out in a constant volume combustion chamber with both fuels directly injected into the chamber. The mixture composition was varied from 0 to 100% CNG/diesel at lambda 1 while the fuel stratification level was controlled by the injection phasing between the two fuels, with gaps between injections ranging from 0 to 20 ms. The results demonstrated the suppressing effect of CNG on the diesel combustion, especially at the early combustion stages. However, CNG significantly enhanced the combustion performance of the diesel in the later stages. Injection gaps, on the other hand, showed particular behavior depending on mixture composition. Injection gaps show less effect on combustion phasing but a significant effect on the combustion output for higher diesel percentage (≥70%, while it is contradictive for lower diesel percentage (<70%.

  5. Modulation of gap junctional intercellular communication between human smooth muscle cells by leukocyte-derived growth factors and cytokines in relation to atherogenesis

    NARCIS (Netherlands)

    Mensink, A.

    1997-01-01


    In this thesis, the effect of leukocyte-derived growth factors and cytokines on GJIC between SMC was investigated. GJIC is regarded as an important mechanism in the control of cell growth, cell differentiation and tissue homeostasis. Disturbance of SMC growth control is regarded to be a

  6. A15 Nb-Sn tunnel junction fabrication and properties

    International Nuclear Information System (INIS)

    Rudman, D.A.; Hellman, F.; Hammond, R.H.; Beasley, M.R.

    1984-01-01

    We have investigated the deposition conditions necessary to produce optimized films of A15 Nb-Sn (19--26 at. % Sn) by electron-beam codeposition. Reliable high-quality superconducting tunnel junctions can be made on this material by using an oxidized-amorphous silicon overlayer as the tunneling barrier and lead as the counter-electrode. These junctions have been used both as a tool for materials diagnosis and as a probe of the superconducting properties (critical temperature and gap) of the films. Careful control of the substrate temperature during the growth of the films has proved critical to obtain homogeneous samples. When the substrate temperature is properly stabilized, stoichiometric Nb 3 Sn is found to be relatively insensitive to the deposition temperature and conditions. In contrast, the properties of the off-stoichiometry (Sn-poor) material depend strongly on the deposition temperature. For this Sn-poor material the ratio 2Δ/kT/sub c/ at a given composition increases with increasing deposition temperature. This change appears to be due to an increase in the gap at the surface of the material (as measured by tunneling) relative to the critical temperature of the bulk. All the tunnel junctions exhibit some persistent nonidealities in their current-voltage characteristics that are qualitatively insensitive to composition or deposition conditions. In particular, the junctions show excess conduction below the sum of the energy gaps (with onset at the counter-electrode gap) and a broadened current rise at the sum gap. The detailed origins of these problems are not yet understood

  7. Controllable Synthesis of Band Gap-Tunable and Monolayer Transition Metal Dichalcogenide Alloys

    Directory of Open Access Journals (Sweden)

    Sheng-Han eSu

    2014-07-01

    Full Text Available The electronic and optical properties of transition metal dichalcogenide (TMD materials are directly governed by their energy gap; thus, the band gap engineering has become an important topic recently. Theoretical and some experimental results have indicated that these monolayer TMD alloys exhibit direct-gap properties and remain stable at room temperature, making them attractive for optoelectronic applications. Here we systematically compared the two approaches of forming MoS2xSe2(1-x monolayer alloys: selenization of MoS2 and sulfurization of MoSe2. The optical energy gap of as-grown CVD MoS2 can be continuously modulated from 1.86 eV (667 nm to 1.57 eV (790 nm controllable by the reaction temperature. Spectroscopic and microscopic evidences show that the Mo-S bonds can be replaced by the Mo-Se bonds in a random and homogeneous manner. By contrast, the replacement of Mo-Se by Mo-S does not randomly occur in the MoSe2 lattice, where the reaction preferentially occurs along the crystalline orientation of MoSe2 and thus the MoSe2/MoS2 biphases are easily observed in the alloys, which makes the optical band gap of these alloys distinctly different. Therefore, the selenization of metal disulfide is preferred and the proposed synthetic strategy opens up a simple route to control the atomic structure as well as optical properties of monolayer TMD alloys.

  8. A novel micromachined shadow mask system with self-alignment and gap control capability

    International Nuclear Information System (INIS)

    Hong, Jung Moo; Zou Jun

    2008-01-01

    We present a novel micromachined shadow mask system, which is capable of accurate self-alignment and mask-substrate gap control. The shadow mask system consists of a silicon shadow mask and a silicon carrier wafer with pyramidal cavities fabricated with bulk micromachining. Self-alignment and gap control of the shadow mask and the fabrication substrate can readily be achieved by using matching pairs of pyramidal cavities and steel spheres placed between. The layer-to-layer alignment accuracy of the new shadow mask system has been experimentally characterized and verified using both optical and atomic force microscopic measurements. As an application of this new shadow mask system, an organic thin-film transistor (OTFT) using pentacene as the semiconductor layer has been successfully fabricated and tested

  9. Disruption of gap junctional intercellular communication by antibiotic gentamicin is associated with aberrant localization of occludin, N-cadherin, connexin 43, and vimentin in SerW3 Sertoli cells in vitro.

    Science.gov (United States)

    Bekheet, Souad H M; Stahlmann, Ralf

    2009-09-01

    Spermatogenesis is a very complex process by which male germ cells differentiate into mature spermatozoa. The sophisticated communication network that controls spermatogenesis can be derailed so that dysfunction of one cell type propagates to all types as a cascade. This accounts for the particular vulnerability of the testis to environmental factors such as drugs and xenobiotics. Sertoli cells play an important role in protecting developing germ cells by forming a physiological barrier, limiting exposure to potentially toxic substrates, or conversely, facilitating uptake of xenobiotics within the testis. In this study, cells from the rat Sertoli line (SerW3) were incubated for 3, 6 and 9 subsequent days in serum free DMEM (SFDM) composed of DMEM supplemented with three different concentrations of antibiotic gentamicin (10, 30, and 100 μg). The effect of the three different concentrations of this antibiotic was determined on Sertoli cell-cell interaction through impaired expression of their constitutive tight junction proteins as early targets for different toxicants in vitro by immunochemistry analysis. The Sertoli SerW3 cell line illustrated the cytotoxicity of GS, as the intercellular junction proteins such as occludin, N-cadherin, connexin 43, and vimentin were delocalized from the membrane to the cytoplasmic compartment during exposure to the antibiotic. This study underlines the potential deleterious effects of the routine use of antibiotics during continuous cell culture.

  10. 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.

  11. Parenting, self-control, and the gender gap in heavy drinking: the case of Russia.

    Science.gov (United States)

    Botchkovar, Ekaterina V; Broidy, Lisa

    2013-03-01

    Drawing on Gottfredson and Hirschi's theory linking parenting to deviant behavior via development of self-control, the authors assess the association between parenting styles, self-control ability, and frequent alcohol use separately for males and females. The authors' findings from a random sample of 440 Russian respondents provide mixed support for self-control theory. Contrary to the theory, but in line with extant research, the authors failed to uncover significant gender differences in childhood upbringing or establish a strong link between parenting techniques and self-control. Furthermore, whereas parental upbringing appears to increase the likelihood of frequent drinking among men, self-control does not mediate this relationship but rather acts as an independent predictor of men's alcohol abuse. Finally, the relatively modest contribution of self-control differences to the gender gap in frequent drinking suggests that higher alcohol consumption among men likely stems from alternative, possibly context-embedded factors.

  12. 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.

  13. Age, education, and the gender gap in the sense of control.

    Science.gov (United States)

    Slagsvold, Britt; Sørensen, Annemette

    2008-01-01

    High sense of control is related to benefits in many aspects of life, and education is known to be strongly related to sense of control. In this article we explore why women tend to feel a lower sense of control than men, and why the sense of control tends to be lower among the elderly than among younger people. In particular we explore the role played by education in explaining age- and gender differences in sense of control. The analysis is based on data from the first wave of the Norwegian NorLAG study, with a representative sample of adults aged 40-79 in 30 municipalities. We find that education accounts for some of the age and gender differences in sense of control, but the mediating effects of education are rather modest. We find an increasing gender gap in sense of control with age, and this increasing gap is completely explained by differences in education. Gender differences in sense of control is explained completely by four factors, which are related to resources and power; physical health, education, living with a partner, and leadership experience. Age differences in sense of control are only partially explained. Education, physical health and employment status cuts the age effect on sense of control to half. The effect of education on sense of control is partly mediated through what we suggest are tangible benefits of education, namely health, employment, and leadership experience. Education also influences individuals through socialization mechanisms. We view agentive orientation as a psychological benefit of education, and measure this characteristic with Bem's (1981) sex-role scale on masculinity. Agentive orientation completely explains the remaining effect of education on sense of control.

  14. Control of low-frequency noise for piping systems via the design of coupled band gap of acoustic metamaterials

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanfei [College of Power Engineering, Naval University of Engineering, Wuhan, 430033 (China); Shen, Huijie, E-mail: shj588@163.com [College of Power Engineering, Naval University of Engineering, Wuhan, 430033 (China); Zhang, Linke [School of Energy and Power Engineering, Wuhan University of Technology, Wuhan, 430063 (China); Su, Yongsheng, E-mail: suyongsheng1981@163.com [College of Power Engineering, Naval University of Engineering, Wuhan, 430033 (China); Yu, Dianlong [Key Laboratory of Science and Technology on Integrated Logistics Support, National University of Defense Technology, Changsha 410073 (China)

    2016-07-01

    Acoustic wave propagation and sound transmission in a metamaterial-based piping system with Helmholtz resonator (HR) attached periodically are studied. A transfer matrix method is developed to conduct the investigation. Calculational results show that the introduction of periodic HRs in the piping system could generate a band gap (BG) near the resonant frequency of the HR, such that the bandwidth and the attenuation effect of HR improved notably. Bragg type gaps are also exist in the system due to the systematic periodicity. By plotting the BG as functions of HR parameters, the effect of resonator parameters on the BG behavior, including bandwidth, location and attenuation performance, etc., is examined. It is found that Bragg-type gap would interplay with the resonant-type gap under some special situations, thereby giving rise to a super-wide coupled gap. Further, explicit formulation for BG exact coupling is extracted and some key parameters on modulating the width and the attenuation coefficient of coupled gaps are investigated. The coupled gap can be located to any frequency range as one concerned, thus rendering the low-frequency noise control feasible in a broad band range. - Highlights: • A metamaterial-type pipe system with Bragg and resonant acoustic gaps. • A low-frequency acoustic coupled gap. • Exact coupling condition for Bragg and resonant gaps. • Effects of resonant parameters on coupled gaps.

  15. Gap Balancing Sacrifices Joint-Line Maintenance to Improve Gap Symmetry: 5-Year Follow-Up of a Randomized Controlled Trial.

    Science.gov (United States)

    Babazadeh, Sina; Dowsey, Michelle M; Vasimalla, Michael G; Stoney, James D; Choong, Peter F M

    2018-01-01

    Gap balancing (GB) has been noted to sacrifice joint-line maintenance to improve gap symmetry. This study aims to determine whether this change affects function or quality of life in the midterm. A prospective blinded randomized controlled trial was completed with 103 patients randomized to measured resection (n = 52) or GB (n = 51). Primary outcome measured was femoral component rotation. Secondary outcomes measured were joint-line change, gap symmetry, and function and quality-of-life outcomes. At 5 years, 83 of 103 patients (85%) were assessed. There was no significant difference between groups in terms of functional or quality of life outcomes. A subgroup analysis revealed that there was no significant association between those with asymmetrical flexion and/or extension or medial and/or lateral gaps during knee replacement and subsequent functional outcomes. No significant difference was detected with those with an elevated joint line and postoperative function. In the midterm, the resultant change in joint-line and maintained gap symmetry noted with GB does not result in significant change to function or quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Surface origin and control of resonance Raman scattering and surface band gap in indium nitride

    International Nuclear Information System (INIS)

    Alarcón-Lladó, Esther; Brazzini, Tommaso; Ager, Joel W

    2016-01-01

    Resonance Raman scattering measurements were performed on indium nitride thin films under conditions where the surface electron concentration was controlled by an electrolyte gate. As the surface condition is tuned from electron depletion to accumulation, the spectral feature at the expected position of the ( E 1 , A 1 ) longitudinal optical (LO) near 590 cm −1 shifts to lower frequency. The shift is reversibly controlled with the applied gate potential, which clearly demonstrates the surface origin of this feature. The result is interpreted within the framework of a Martin double resonance, where the surface functions as a planar defect, allowing the scattering of long wavevector phonons. The allowed wavevector range, and hence the frequency, is modulated by the electron accumulation due to band gap narrowing. A surface band gap reduction of over 500 meV is estimated for the conditions of maximum electron accumulation. Under conditions of electron depletion, the full InN bandgap ( E g   =  0.65 eV) is expected at the surface. The drastic change in the surface band gap is expected to influence the transport properties of devices which utilize the surface electron accumulation layer. (paper)

  17. Surface origin and control of resonance Raman scattering and surface band gap in indium nitride

    Science.gov (United States)

    Alarcón-Lladó, Esther; Brazzini, Tommaso; Ager, Joel W.

    2016-06-01

    Resonance Raman scattering measurements were performed on indium nitride thin films under conditions where the surface electron concentration was controlled by an electrolyte gate. As the surface condition is tuned from electron depletion to accumulation, the spectral feature at the expected position of the (E 1, A 1) longitudinal optical (LO) near 590 cm-1 shifts to lower frequency. The shift is reversibly controlled with the applied gate potential, which clearly demonstrates the surface origin of this feature. The result is interpreted within the framework of a Martin double resonance, where the surface functions as a planar defect, allowing the scattering of long wavevector phonons. The allowed wavevector range, and hence the frequency, is modulated by the electron accumulation due to band gap narrowing. A surface band gap reduction of over 500 meV is estimated for the conditions of maximum electron accumulation. Under conditions of electron depletion, the full InN bandgap (E g  =  0.65 eV) is expected at the surface. The drastic change in the surface band gap is expected to influence the transport properties of devices which utilize the surface electron accumulation layer.

  18. A perisynaptic ménage à trois between Dlg, DLin-7, and Metro controls proper organization of Drosophila synaptic junctions.

    Science.gov (United States)

    Bachmann, André; Kobler, Oliver; Kittel, Robert J; Wichmann, Carolin; Sierralta, Jimena; Sigrist, Stephan J; Gundelfinger, Eckart D; Knust, Elisabeth; Thomas, Ulrich

    2010-04-28

    Structural plasticity of synaptic junctions is a prerequisite to achieve and modulate connectivity within nervous systems, e.g., during learning and memory formation. It demands adequate backup systems that allow remodeling while retaining sufficient stability to prevent unwanted synaptic disintegration. The strength of submembranous scaffold complexes, which are fundamental to the architecture of synaptic junctions, likely constitutes a crucial determinant of synaptic stability. Postsynaptic density protein-95 (PSD-95)/ Discs-large (Dlg)-like membrane-associated guanylate kinases (DLG-MAGUKs) are principal scaffold proteins at both vertebrate and invertebrate synapses. At Drosophila larval glutamatergic neuromuscular junctions (NMJs) DlgA and DlgS97 exert pleiotropic functions, probably reflecting a few known and a number of yet-unknown binding partners. In this study we have identified Metro, a novel p55/MPP-like Drosophila MAGUK as a major binding partner of perisynaptic DlgS97 at larval NMJs. Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7. In a remarkably interdependent manner, Metro and DLin-7 act downstream of DlgS97 to control NMJ expansion and proper establishment of synaptic boutons. Using quantitative 3D-imaging we further demonstrate that the complex controls the size of postsynaptic glutamate receptor fields. Our findings accentuate the importance of perisynaptic scaffold complexes for synaptic stabilization and organization.

  19. Multiferroic tunnel junctions and ferroelectric control of magnetic state at interface (invited)

    KAUST Repository

    Yin, Y. W.; Raju, M.; Hu, Weijin; Burton, J. D.; Kim, Y.-M.; Borisevich, A. Y.; Pennycook, S. J.; Yang, S. M.; Noh, T. W.; Gruverman, A.; Li, X. G.; Zhang, Z. D.; Tsymbal, E. Y.; Li, Qi

    2015-01-01

    between two ferromagnetic electrodes has drawn enormous interest due to its potential applications not only in multi-level data storage but also in electric field controlled spintronics and nanoferronics. Here, we present our investigations on four

  20. Valley and spin resonant tunneling current in ferromagnetic/nonmagnetic/ferromagnetic silicene junction

    Directory of Open Access Journals (Sweden)

    Yaser Hajati

    2016-02-01

    Full Text Available We study the transport properties in a ferromagnetic/nonmagnetic/ferromagnetic (FNF silicene junction in which an electrostatic gate potential, U, is attached to the nonmagnetic region. We show that the electrostatic gate potential U is a useful probe to control the band structure, quasi-bound states in the nonmagnetic barrier as well as the transport properties of the FNF silicene junction. In particular, by introducing the electrostatic gate potential, both the spin and valley conductances of the junction show an oscillatory behavior. The amplitude and frequency of such oscillations can be controlled by U. As an important result, we found that by increasing U, the second characteristic of the Klein tunneling is satisfied as a result of the quasiparticles chirality which can penetrate through a potential barrier. Moreover, it is found that for special values of U, the junction shows a gap in the spin and valley-resolve conductance and the amplitude of this gap is only controlled by the on-site potential difference, Δz. Our findings of high controllability of the spin and valley transport in such a FNF silicene junction may improve the performance of nano-electronics and spintronics devices.

  1. Controlled switching of single-molecule junctions by mechanical motion of a phenyl ring

    Directory of Open Access Journals (Sweden)

    Yuya Kitaguchi

    2015-10-01

    Full Text Available Mechanical methods for single-molecule control have potential for wide application in nanodevices and machines. Here we demonstrate the operation of a single-molecule switch made functional by the motion of a phenyl ring, analogous to the lever in a conventional toggle switch. The switch can be actuated by dual triggers, either by a voltage pulse or by displacement of the electrode, and electronic manipulation of the ring by chemical substitution enables rational control of the on-state conductance. Owing to its simple mechanics, structural robustness, and chemical accessibility, we propose that phenyl rings are promising components in mechanical molecular devices.

  2. Dynamic Tunneling Junctions at the Atomic Intersection of Two Twisted Graphene Edges.

    Science.gov (United States)

    Bellunato, Amedeo; Vrbica, Sasha D; Sabater, Carlos; de Vos, Erik W; Fermin, Remko; Kanneworff, Kirsten N; Galli, Federica; van Ruitenbeek, Jan M; Schneider, Grégory F

    2018-04-11

    The investigation of the transport properties of single molecules by flowing tunneling currents across extremely narrow gaps is relevant for challenges as diverse as the development of molecular electronics and sequencing of DNA. The achievement of well-defined electrode architectures remains a technical challenge, especially due to the necessity of high precision fabrication processes and the chemical instability of most bulk metals. Here, we illustrate a continuously adjustable tunneling junction between the edges of two twisted graphene sheets. The unique property of the graphene electrodes is that the sheets are rigidly supported all the way to the atomic edge. By analyzing the tunneling current characteristics, we also demonstrate that the spacing across the gap junction can be controllably adjusted. Finally, we demonstrate the transition from the tunneling regime to contact and the formation of an atomic-sized junction between the two edges of graphene.

  3. The role of the inferior frontal junction area in cognitive control

    NARCIS (Netherlands)

    Brass, M.; Derrfuss, J.; Forstmann, B.U.; Cramon, D.Y. von

    2005-01-01

    Cognitive control processes refer to our ability to coordinate thoughts and actions in accordance with internal goals. In the fronto-lateral cortex such processes have been primarily related to mid-dorsolateral prefrontal cortex (mid-DLPFC). However, recent brain-imaging and meta-analytic studies

  4. Formation of interlayer gap and control of interlayer burr in dry drilling of stacked aluminum alloy plates

    Directory of Open Access Journals (Sweden)

    Tian Wei

    2016-02-01

    Full Text Available In aircraft assembly, interlayer burr formation in dry drilling of stacked metal materials is a common problem. Traditional manual deburring operation seriously affects the assembly quality and assembly efficiency, is time-consuming and costly, and is not conducive to aircraft automatic assembly based on industrial robot. In this paper, the formation of drilling exit burr and the influence of interlayer gap on interlayer burr formation were studied, and the mechanism of interlayer gap formation in drilling stacked aluminum alloy plates was investigated, a simplified mathematical model of interlayer gap based on the theory of plates and shells and finite element method was established. The relationship between interlayer gap and interlayer burr, as well as the effect of feed rate and pressing force on interlayer burr height and interlayer gap was discussed. The result shows that theoretical interlayer gap has a positive correlation with interlayer burr height and preloading pressing force is an effective method to control interlayer burr formation.

  5. Controlled fabrication of nano-scale double barrier magnetic tunnel junctions using focused ion beam milling method

    International Nuclear Information System (INIS)

    Wei, H.X.; Wang, T.X.; Zeng, Z.M.; Zhang, X.Q.; Zhao, J.; Han, X.F.

    2006-01-01

    The controlled fabrication method for nano-scale double barrier magnetic tunnel junctions (DBMTJs) with the layer structure of Ta(5)/Cu(10)/Ni 79 Fe 21 (5)/Ir 22 Mn 78 (12)/Co 6 Fe 2 B 2 (4)/Al(1) -oxide/Co 6 Fe 2 B 2 (6)/Al (1)-oxide/Co 6 Fe 2 B 2 (4)/Ir 22 Mn 78 (12)/Ni 79 Fe 21 (5)/Ta(5) (thickness unit: nm) was used. This method involved depositing thin multi-layer stacks by sputtering system, and depositing a Pt nano-pillar using a focused ion beam which acted both as a top contact and as an etching mask. The advantages of this process over the traditional process using e-beam and optical lithography in that it involve only few processing steps, e.g. it does not involve any lift-off steps. In order to evaluate the nanofabrication techniques, the DBMTJs with the dimensions of 200 nmx400 nm, 200 nmx200 nm nano-scale were prepared and their R-H, I-V characteristics were measured.

  6. Correlations of differentially expressed gap junction connexins Cx26, Cx30, Cx32, Cx43 and Cx46 with breast cancer progression and prognosis.

    Directory of Open Access Journals (Sweden)

    Ivett Teleki

    Full Text Available Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers.Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally representing all tumor grades, using immunofluorescence and multilayer, multichannel digital microscopy. Prognostic correlations were plotted in Kaplan-Meier curves and tested using the log-rank test and cox-regression analysis in univariate and multivariate models.The expression of GJA1/Cx43, GJA3/Cx46 and GJB2/Cx26 and, for the first time, GJA6/Cx30 and GJB1/Cx32 was revealed both in normal human mammary glands and breast carcinomas. Within their subfamilies these connexins can form homo- and heterocellular epithelial channels. In cancer, the array datasets cross-validated each other's prognostic results. In line with the significant correlations found at mRNA level, elevated Cx43 protein levels were linked with significantly improved breast cancer outcome, offering Cx43 protein detection as an independent prognostic marker stronger than vascular invasion or necrosis. As a contrary, elevated Cx30 mRNA and protein levels were associated with a reduced disease outcome offering Cx30 protein detection as an independent prognostic marker outperforming mitotic index and necrosis. Elevated versus low Cx43 protein levels allowed the stratification of grade 2 tumors into good and poor relapse free survival subgroups, respectively. Also, elevated versus low Cx30 levels stratified grade 3 patients into poor and good overall survival subgroups, respectively.Differential expression of Cx43 and Cx

  7. Identifying knowledge gaps for gene drive research to control invasive animal species: The next CRISPR step

    Directory of Open Access Journals (Sweden)

    Dorian Moro

    2018-01-01

    Full Text Available Invasive animals have been linked to the extinctions of native wildlife, and to significant agricultural financial losses or impacts. Current approaches to control invasive species require ongoing resources and management over large geographic scales, and often result in the short-term suppression of populations. New and innovative approaches are warranted. Recently, the RNA guided gene drive system based on CRISPR/Cas9 is being proposed as a potential gene editing tool that could be used by wildlife managers as a non-lethal addition or alternative to help reduce pest animal populations. While regulatory control and social acceptance are crucial issues that must be addressed, there is an opportunity now to identify the knowledge and research gaps that exist for some important invasive species. Here we systematically determine the knowledge gaps for pest species for which gene drives could potentially be applied. We apply a conceptual ecological risk framework within the gene drive context within an Australian environment to identify key requirements for undertaking work on seven exemplar invasive species in Australia. This framework allows an evaluation of the potential research on an invasive species of interest and within a gene drive and risk context. We consider the currently available biological, genetic and ecological information for the house mouse, European red fox, feral cat, European rabbit, cane toad, black rat and European starling to evaluate knowledge gaps and identify candidate species for future research. We discuss these findings in the context of future thematic areas of research worth pursuing in preparation for a more formal assessment of the use of gene drives as a novel strategy for the control of these and other invasive species. Keywords: Invasive species, Gene drive, CRISPR, Pest management, Islands

  8. Lyme disease ecology in a changing world: Consensus, uncertainty and critical gaps for improving control

    Science.gov (United States)

    Kilpatrick, A. Marm; Dobson, Andrew D.M.; Levi, Taal; Salkeld, Daniel J.; Swei, Andrea; Ginsberg, Howard; Kjemtrup, Anne; Padgett, Kerry A.; Jensen, Per A.; Fish, Durland; Ogden, Nick H.; Diuk-Wasser, Maria A.

    2017-01-01

    Lyme disease is the most common tick-borne disease in temperate regions of North America, Europe and Asia, and the number of reported cases has increased in many regions as landscapes have been altered. Although there has been extensive work on the ecology and epidemiology of this disease in both Europe and North America, substantial uncertainty exists about fundamental aspects that determine spatial and temporal variation in both disease risk and human incidence, which hamper effective and efficient prevention and control. Here we describe areas of consensus that can be built on, identify areas of uncertainty and outline research needed to fill these gaps to facilitate predictive models of disease risk and the development of novel disease control strategies. Key areas of uncertainty include: (i) the precise influence of deer abundance on tick abundance, (ii) how tick populations are regulated, (iii) assembly of host communities and tick-feeding patterns across different habitats, (iv) reservoir competence of host species, and (v) pathogenicity for humans of different genotypes of Borrelia burgdorferi. Filling these knowledge gaps will improve Lyme disease prevention and control and provide general insights into the drivers and dynamics of this emblematic multi-host–vector-borne zoonotic disease.

  9. A Simple Method for Decreasing the Liquid Junction Potential in a Flow-through-Type Differential pH Sensor Probe Consisting of pH-FETs by Exerting Spatiotemporal Control of the Liquid Junction

    Science.gov (United States)

    Yamada, Akira; Mohri, Satoshi; Nakamura, Michihiro; Naruse, Keiji

    2015-01-01

    The liquid junction potential (LJP), the phenomenon that occurs when two electrolyte solutions of different composition come into contact, prevents accurate measurements in potentiometry. The effect of the LJP is usually remarkable in measurements of diluted solutions with low buffering capacities or low ion concentrations. Our group has constructed a simple method to eliminate the LJP by exerting spatiotemporal control of a liquid junction (LJ) formed between two solutions, a sample solution and a baseline solution (BLS), in a flow-through-type differential pH sensor probe. The method was contrived based on microfluidics. The sensor probe is a differential measurement system composed of two ion-sensitive field-effect transistors (ISFETs) and one Ag/AgCl electrode. With our new method, the border region of the sample solution and BLS is vibrated in order to mix solutions and suppress the overshoot after the sample solution is suctioned into the sensor probe. Compared to the conventional method without vibration, our method shortened the settling time from over two min to 15 s and reduced the measurement error by 86% to within 0.060 pH. This new method will be useful for improving the response characteristics and decreasing the measurement error of many apparatuses that use LJs. PMID:25835300

  10. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)

    Navya

    2017-03-24

    Mar 24, 2017 ... ... applied to analyze the expression and subcellular localization of recombinant ... Cx46. The fluorescent localization assay revealed the plaque formation ... composed of six trans-membrane protein subunits called connexins ...

  11. 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

  12. Bridging the gap between the linear and nonlinear predictive control: Adaptations fo refficient building climate control

    Czech Academy of Sciences Publication Activity Database

    Pčolka, M.; Žáčeková, E.; Robinett, R.; Čelikovský, Sergej; Šebek, M.

    2016-01-01

    Roč. 53, č. 1 (2016), s. 124-138 ISSN 0967-0661 R&D Projects: GA ČR GA13-20433S Institutional support: RVO:67985556 Keywords : Model predictive control * Identification for control * Building climatecontrol Subject RIV: BC - Control Systems Theory Impact factor: 2.602, year: 2016 http://library.utia.cas.cz/separaty/2016/TR/celikovsky-0460306.pdf

  13. 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.

  14. Band gap control in a line-defect magnonic crystal waveguide

    Energy Technology Data Exchange (ETDEWEB)

    Morozova, M. A., E-mail: mamorozovama@yandex.ru; Grishin, S. V.; Sadovnikov, A. V.; Romanenko, D. V.; Sharaevskii, Yu. P.; Nikitov, S. A. [Laboratory ' Metamaterials,' Saratov State University, Astrakhanskaya 83, Saratov 410012 (Russian Federation)

    2015-12-14

    We report on the experimental observation of the spin wave spectrum control in a line-defect magnonic crystal (MC) waveguide. We demonstrate the possibility to control the forbidden frequency band (band gap) for spin waves tuning the line-defect width. In particular, this frequency may be greater or lower than the one of 1D MC waveguide without line-defect. By means of space-resolved Brillouin light scattering technique, we study the localization of magnetization amplitude in the line-defect area. We show that the length of this localization region depends on the line-defect width. These results agree well with theoretical calculations of spin wave spectrum using the proposed model of two coupled magnonic crystal waveguides. The proposed simple geometry of MC with line-defect can be used as a logic and multiplexing block for application in the novel field of magnonic devices.

  15. Mind the gaps in research on the control of gastrointestinal nematodes of farmed ruminants and pigs

    DEFF Research Database (Denmark)

    Charlier, J; Thamsborg, S M; Bartley, D J

    2018-01-01

    , to support the development of roadmaps and strategic research agendas by governments, industry and policymakers. These priorities were derived from the DISCONTOOLS gap analysis for nematodes and follow-up discussions within the recently formed Livestock Helminth Research Alliance (LiHRA). In the face......Gastrointestinal (GI) nematode control has an important role to play in increasing livestock production from a limited natural resource base and to improve animal health and welfare. In this synthetic review, we identify key research priorities for GI nematode control in farmed ruminants and pigs......-use and farm husbandry changes. More emphasis needs to be placed on the upfront evaluation of the economic value of these innovations as well as the socio-psychological aspects to prioritize research and facilitate uptake of innovations in practice. Finally, targeted regulatory guidance is needed to create...

  16. The effects of in-vehicle tasks and time-gap selection while reclaiming control from adaptive cruise control (ACC) with bus simulator.

    Science.gov (United States)

    Lin, Tsang-Wei; Hwang, Sheue-Ling; Su, Jau-Ming; Chen, Wan-Hui

    2008-05-01

    This research aimed to find out the effects of in-vehicle distractions and time-gap settings with a fix-based bus driving simulator in a following scenario. Professional bus drivers were recruited to perform in-vehicle tasks while driving with adaptive cruise control (ACC) of changeable time-gap settings in freeway traffic. Thirty subjects were divided equally into three groups for different in-vehicle task modes (between subjects), including no task distraction, hands-free, and manual modes. Further, time-gap settings for the experimental ACC were: shorter than 1.0 s, 1.0-1.5 s, 1.5-2.0 s, and longer than 2.0 s (within subjects). Longitudinal (mean headway, forward collision rate, and response time) and lateral control (mean lateral lane position and its standard deviation) performance was assessed. In the results, longitudinal control performance was worsened by both shorter time-gaps and heavier in-vehicle tasks. But the interaction indicated that the harm by heavier in-vehicle distraction could be improved by longer time-gaps. As for the lateral control, it would only be negatively affected by shorter time-gap settings. This research indicates the effects of time-gaps and in-vehicle distraction, as well as the interaction. Proper time-gap selection under different in-vehicle distractions can help avoid accidents and keep safe.

  17. Active control of annular flow-induced vibration of axisymmetric elastic beam by the local gap width control

    International Nuclear Information System (INIS)

    Takada, Shoji; Shintani, Atsuhiko; Ito, Tomohiro; Fujita, Katsuhisa

    2011-01-01

    Flow-induced vibration may occur in the structures such as elastic beams subjected to annular flow in the narrow passage. Once the flow-induced vibration occurs, vibration amplitude becomes larger, consequently it causes a lot of troubles such as fatigue or failure in mechanical structures. In this paper, for the purpose to avoid these troubles, the active control of vibration of an axisymmetric elastic beam subjected to annular flow is investigated. An air-pressured actuator is attached on the surface of the circular cylinder for the vibrational control. As the shape of the actuator changes by control, the gap width in narrow passage changes, which causes the change of the fluid pressure. Therefore, the vibration of the fluid-structure coupled system can be suppressed. The fluid-structure coupled equation based on the Euler-Bernoulli type of partial differential equation and the Navier-Stokes equations is analytically derived including control terms. By applying the optimal control law to the coupled system, the unstable behavior is stabilized. The stability of the coupled system is investigated by eigenvalue analyses of controlled coupled equations. Numerical simulations are performed to investigate the efficiency of the proposed control method. (author)

  18. Motion control of a large gap magnetic suspension system for microrobotic manipulation

    Energy Technology Data Exchange (ETDEWEB)

    Craig, David; Khamesee, Mir Behrad [Department of Mechanical and Mechatronics Engineering, University of Waterloo, Ontario, N2L 3G1 (Canada)

    2007-06-07

    Magnetic suspension systems have shown a great deal of promise in the field of microrobotics. This paper discusses the performance of a new large gap magnetic suspension system developed by the researchers. The magnetic drive unit consists of six electromagnets attached to a soft iron pole piece and yoke. Levitation of an 11.19 g microrobot prototype is demonstrated for step, ramp and periodic input trajectories using PID control. The working envelope of the microrobot is 30 x 22 x 20 mm{sup 3}, with an RMS error on the order of 18 {mu}m in the vertical direction and 8 {mu}m in the horizontal direction. It is demonstrated that the levitated microrobot is able to track the desired trajectory precisely and that the system has potential application for micromanipulation.

  19. Motion control of a large gap magnetic suspension system for microrobotic manipulation

    International Nuclear Information System (INIS)

    Craig, David; Khamesee, Mir Behrad

    2007-01-01

    Magnetic suspension systems have shown a great deal of promise in the field of microrobotics. This paper discusses the performance of a new large gap magnetic suspension system developed by the researchers. The magnetic drive unit consists of six electromagnets attached to a soft iron pole piece and yoke. Levitation of an 11.19 g microrobot prototype is demonstrated for step, ramp and periodic input trajectories using PID control. The working envelope of the microrobot is 30 x 22 x 20 mm 3 , with an RMS error on the order of 18 μm in the vertical direction and 8 μm in the horizontal direction. It is demonstrated that the levitated microrobot is able to track the desired trajectory precisely and that the system has potential application for micromanipulation

  20. Optimal design and control of solar driven air gap membrane distillation desalination systems

    International Nuclear Information System (INIS)

    Chen, Yih-Hang; Li, Yu-Wei; Chang, Hsuan

    2012-01-01

    Highlights: ► Air gap membrane distillation unit was used in the desalination plants. ► Aspen Custom Molder was used to simulate each unit of desalination plants. ► Design parameters were investigated to obtain the minimum total annual cost. ► The control structure was proposed to operate desalination plants all day long. -- Abstract: A solar heated membrane distillation desalination system is constructed of solar collectors and membrane distillation devices for increasing pure water productivity. This technically and economically feasible system is designed to use indirect solar heat to drive membrane distillation processes to overcome the unstable supply of solar radiation from sunrise to sunset. The solar heated membrane distillation desalination system in the present study consisted of hot water storage devices, heat exchangers, air gap membrane distillation units, and solar collectors. Aspen Custom Molder (ACM) software was used to model and simulate each unit and establish the cost function of a desalination plant. From Design degree of freedom (DOF) analysis, ten design parameters were investigated to obtain the minimum total annual cost (TAC) with fixed pure water production rate. For a given solar energy density profile of typical summer weather, the minimal TAC per 1 m 3 pure water production can be found at 500 W/m 2 by varying the solar energy intensity. Therefore, we proposed two modes for controlling the optimal design condition of the desalination plant; day and night. In order to widen the operability range of the plant, the sensitivity analysis was used to retrofit the original design point to lower the effluent temperature from the solar collector by increasing the hot water recycled stream. The simulation results show that the pure water production can be maintained at a very stable level whether in sunny or cloudy weather.

  1. True photonic band-gap mode-control in VCSEL structures

    DEFF Research Database (Denmark)

    Romstad, F.; Madsen, M.; Birkedal, Dan

    2003-01-01

    Photonic band-gap mode confinement in novel nano-structured large area VCSEL structures is confirmed by the amplified spontaneous emission spectrum. Both guide and anti-guide VCSEL structures are experimentally characterised to verify the photonic band-gap effect.......Photonic band-gap mode confinement in novel nano-structured large area VCSEL structures is confirmed by the amplified spontaneous emission spectrum. Both guide and anti-guide VCSEL structures are experimentally characterised to verify the photonic band-gap effect....

  2. 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

  3. Bridging ImmunoGenomic Data Analysis Workflow Gaps (BIGDAWG): An integrated case-control analysis pipeline.

    Science.gov (United States)

    Pappas, Derek J; Marin, Wesley; Hollenbach, Jill A; Mack, Steven J

    2016-03-01

    Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG) is an integrated data-analysis pipeline designed for the standardized analysis of highly-polymorphic genetic data, specifically for the HLA and KIR genetic systems. Most modern genetic analysis programs are designed for the analysis of single nucleotide polymorphisms, but the highly polymorphic nature of HLA and KIR data require specialized methods of data analysis. BIGDAWG performs case-control data analyses of highly polymorphic genotype data characteristic of the HLA and KIR loci. BIGDAWG performs tests for Hardy-Weinberg equilibrium, calculates allele frequencies and bins low-frequency alleles for k×2 and 2×2 chi-squared tests, and calculates odds ratios, confidence intervals and p-values for each allele. When multi-locus genotype data are available, BIGDAWG estimates user-specified haplotypes and performs the same binning and statistical calculations for each haplotype. For the HLA loci, BIGDAWG performs the same analyses at the individual amino-acid level. Finally, BIGDAWG generates figures and tables for each of these comparisons. BIGDAWG obviates the error-prone reformatting needed to traffic data between multiple programs, and streamlines and standardizes the data-analysis process for case-control studies of highly polymorphic data. BIGDAWG has been implemented as the bigdawg R package and as a free web application at bigdawg.immunogenomics.org. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  4. Gap analysis of Mycoplasma bovis disease, diagnosis and control: An aid to identify future development requirements.

    Science.gov (United States)

    Calcutt, M J; Lysnyansky, I; Sachse, K; Fox, L K; Nicholas, R A J; Ayling, R D

    2018-05-01

    There is a worldwide problem of disease caused by Mycoplasma (M.) bovis in cattle; it has a significant detrimental economic and animal welfare impact on cattle rearing. Infection can manifest as a plethora of clinical signs including mastitis, pneumonia, arthritis, keratoconjunctivitis, otitis media and genital disorders that may result in infertility and abortion. Current diagnosis and control information are reviewed and analysed to identify gaps in knowledge of the causative organism in respect of the disease pathology, diagnosis and control methods. The main considerations are as follows: no vaccines are commercially available; antimicrobial resistance is increasing; diagnostic and antimicrobial sensitivity testing needs to be improved; and a pen-side test would facilitate more rapid diagnosis and implementation of treatment with antimicrobials. More data on host susceptibility, stress factors, immune response and infectious dose levels are required. The impact of asymptomatic carriers, M. bovis survival in the environment and the role of wildlife in transmitting the disease also needs investigation. To facilitate development of vaccines, further analysis of more M. bovis genomes, its pathogenic mechanisms, including variable surface proteins, is required, along with reproducible disease models. © 2018 Blackwell Verlag GmbH.

  5. [Biopsy and endoscopic prospective study of the prevalence of intestinal metaplasia in the gastroesophageal junction in controls and in patients with gastroesophageal reflux].

    Science.gov (United States)

    Csendes, A; Smok, G; Sagastume, H; Rojas, J

    1998-02-01

    The classic diagnosis of Barret esophagus is based on the finding of three of more cm of distal esophagus covered by specialized columnar epithelium. However, at the present time, it is based on the presence of intestinal metaplasia in the junction of squamous-columnar mucosae. To assess the prevalence of Barret esophagus using endoscopic and pathological criteria in healthy subjects and in individuals with gastroesophageal reflux. One hundred thirty nine controls and 372 patients with symptoms of gastroesophageal reflux subjected to an upper gastrointestinal endoscopy were studied. Patients with Barret esophagus were classified as having a "mini Barret" when the pathological presence of intestinal metaplasia was the only finding. A "short Barret esophagus" was diagnosed when less than 3 cm were covered with fingerings of mucosal substitutions and "extensive Barret esophagus" when more than 3 cm of esophageal mucosa were substituted. Two percent of controls, 12.4% of patients with gastroesophageal reflux without esophagitis and 11.7% of such patients with esophagitis had intestinal metaplasia in the gastroesophageal junction. Patients with Barret esophagus were older than the rest of patients. "Short Barret esophagus" is six times more frequent than "extensive Barret esophagus". Esophageal erosions, peptic ulcers and stenosis were more frequent in patients with extensive Barret esophagus. The prevalence of dysplasia was similar in all types of Barret esophagus. Intestinal metaplasia was very infrequent in control patients. In subjects with gastroesophageal reflux, classic endoscopic diagnosis may miss up to 80% of patients with Barret esophagus. Thus, gastroesophageal junction biopsies must be obtained in all patients with symptoms of gastroesophageal reflux.

  6. In-process monitoring and adaptive control for gap in micro butt welding with pulsed YAG laser

    International Nuclear Information System (INIS)

    Kawahito, Yousuke; Kito, Masayuki; Katayama, Seiji

    2007-01-01

    A gap is one of the most important issues to be solved in laser welding of a micro butt joint, because the gap results in welding defects such as underfilling or a non-bonded joint. In-process monitoring and adaptive control has been expected as one of the useful procedures for the stable production of sound laser welds without defects. The objective of this research is to evaluate the availability of in-process monitoring and adaptive control in micro butt welding of pure titanium rods with a pulsed neodymium : yttrium aluminium garnet (Nd : YAG) laser beam of a 150 μm spot diameter. It was revealed that a 45 μm narrow gap was detected by the remarkable jump in a reflected light intensity due to the formation of the molten pool which could bridge the gap. Heat radiation signal levels increased in proportion to the sizes of molten pools or penetration depths for the respective laser powers. As for adaptive control, the laser peak power was controlled on the basis of the reflected light or the heat radiation signals to stably produce a sound deeply penetrated weld reduced underfilling. In the case of a 100 μm gap, the underfilling was greatly reduced by half smaller than those made with a conventional rectangular pulse shape in seam welding as well as spot welding with a pulsed Nd : YAG laser beam. Consequently, the adaptive control of the laser peak power on the basis of in-process monitoring could reduce the harmful effects due to a gap in micro butt laser welding with a pulsed laser beam

  7. Control of zoonoses in emergency situations: lessons learned during recent outbreaks (gaps and weaknesses of current zoonoses control programmes

    Directory of Open Access Journals (Sweden)

    Darem Tabbaa

    2008-12-01

    Full Text Available In emergency situations, domestic animals and wildlife are, like people, exposed to infectious diseases and environmental contaminants in the air, soil, water and food. They can suffer from acute and/or chronic diseases from such exposure. Often animals serve as disease reservoirs or early warning systems for the community in regard to the spread of zoonotic diseases. Over 100 years of experience have shown that animal and human health are closely related. During the past few years, emergent disease episodes have increased; nearly all have involved zoonotic agents. As there is no way to predict when or where the next important new zoonotic pathogen will emerge or what its ultimate importance might be, investigation at the first sign of emergence of a new zoonotic disease is particularly important. Today, in many emerging situations, different activities involving zoonotic disease control are at risk because of failed investigative infrastructures or financial constraints. Considering that zoonotic diseases have their own characteristics, their prevention and control require unique strategies, based more on fundamental and applied research than on traditional approaches. Such strategies require cooperation and coordination between animal and public health sectors and the involvement of other disciplines and experts such as epidemiologists, entomologists, environmentalists and climatologists. Lessons learned from the avian influenza pandemic threat, the Crimean-Congo haemorrhagic fever and rabies outbreaks are presented and the gaps and weakness of current control programmes are discussed.

  8. Modeling the Daly Gap: The Influence of Latent Heat Production in Controlling Magma Extraction and Eruption

    Science.gov (United States)

    Nelson, B. K.; Ghiorso, M. S.; Bachmann, O.; Dufek, J.

    2011-12-01

    A century-old issue in volcanology is the origin of the gap in chemical compositions observed in magmatic series on ocean islands and arcs - the "Daly Gap". If the gap forms during differentiation from a mafic parent, models that predict the dynamics of magma extraction as a function of chemical composition must simulate a process that results in volumetrically biased, bimodal compositions of erupted magmas. The probability of magma extraction is controlled by magma dynamical processes, which have a complex response to magmatic heat evolution. Heat loss from the magmatic system is far from a simple, monotonic function of time. It is modified by the crystallization sequence, chamber margin heat flux, and is buffered by latent heat production. We use chemical and thermal calculations of MELTS (Ghiorso & Sack, 1995) as input to the physical model of QUANTUM (Dufek & Bachmann, 2010) to predict crystallinity windows of most probable magma extraction. We modeled two case studies: volcanism on Tenerife, Canary Islands, and the Campanian Ignimbrite (CI) of Campi Flegrei, Italy. Both preserve a basanitic to phonolitic lineage and have comparable total alkali concentrations; however, CI has high and Tenerife has low K2O/Na2O. Modeled thermal histories of differentiation for the two sequences contrast strongly. In Tenerife, the rate of latent heat production is almost always greater than sensible heat production, with spikes in the ratio of latent to sensible heats of up to 40 associated with the appearance of Fe-Ti oxides at near 50% crystallization. This punctuated heat production must cause magma temperature change to stall or slow in time. The extended time spent at ≈50% crystallinity, associated with dynamical processes that enhance melt extraction near 50% crystallinity, suggests the magma composition at this interval should be common. In Tenerife, the modeled composition coincides with that of the first peak in the bimodal frequency-composition distribution. In our

  9. UV and visible light photocatalytic activity of Au/TiO2 nanoforests with Anatase/Rutile phase junctions and controlled Au locations.

    Science.gov (United States)

    Yu, Yang; Wen, Wei; Qian, Xin-Yue; Liu, Jia-Bin; Wu, Jin-Ming

    2017-01-24

    To magnify anatase/rutile phase junction effects through appropriate Au decorations, a facile solution-based approach was developed to synthesize Au/TiO 2 nanoforests with controlled Au locations. The nanoforests cons®isted of anatase nanowires surrounded by radially grown rutile branches, on which Au nanoparticles were deposited with preferred locations controlled by simply altering the order of the fabrication step. The Au-decoration increased the photocatalytic activity under the illumination of either UV or visible light, because of the beneficial effects of either electron trapping or localized surface plasmon resonance (LSPR). Gold nanoparticles located preferably at the interface of anatase/rutile led to a further enhanced photocatalytic activity. The appropriate distributions of Au nanoparticles magnify the beneficial effects arising from the anatase/rutile phase junctions when illuminated by UV light. Under the visible light illumination, the LSPR effect followed by the consecutive electron transfer explains the enhanced photocatalysis. This study provides a facile route to control locations of gold nanoparticles in one-dimensional nanostructured arrays of multiple-phases semiconductors for achieving a further increased photocatalytic activity.

  10. Control strategies for reducing consumption and pollutant emission on isolated junctions: field results; Enjeux de la regulation aux carrefours pour reduire la consommation et la polution: resultats experimentaux

    Energy Technology Data Exchange (ETDEWEB)

    Midenet, S.; Boillot, F.; Pierrelee, J.C. [Institut National de Recherche sur les Transports et leur Securite, INRETS, Lab. Genie des Reseaux de Transports et Informatique Avancee, GRETIA, 94 - Arcueil (France)

    2000-07-01

    We present experimental results dealing with traffic light control strategies for reducing CO{sub 2} emission and fuel consumption on isolated intersection. The experimental site, located near Paris, is a 400 meter area centred on an isolated junction that has been equipped with video sensors (for queue lengths and other spatial traffic measurements). A complete control device enables to actually control the junction traffic lights from our INRETS laboratory. A model has been designed to estimate emission and consumption mean costs based on video traffic measurements. The model's coefficients have been calibrated with real life kinematics profiles and corresponding instantaneous emission measurements, provided by INRETS-LTE; we ended up with coefficients for diesel, catalyst gasoline and non-catalyst gasoline passenger cars. An 8 months experimental period in 1998-1999 led to constitute a large database of one-hour traffic measurement samples, that cover the usual traffic condition ranges for each strategy applied on field. The consumption and emission costs for each strategy, along with comparative benefits have been computed on this basis. We show that the CRONOS adaptive real-time strategy based on waiting time minimization leads to important benefits on the part of the cost that is related to stops and waiting time: 14 % on average for CO{sub 2} emission. This benefit remains significant on the total cost (around 4 % for CO{sub 2}) and noticeable whatever the traffic conditions. (authors)

  11. In vitro early changes in intercellular junctions by treatment with a chemical carcinogen.

    Science.gov (United States)

    Tachikawa, T; Kohno, Y; Matsui, Y; Yoshiki, S

    1986-06-01

    To examine early intercellular junction changes caused by treatment with 9,10-dimethyl-1,2-benzanthracene (DMBA), rat lingual epithelium was cultivated in isolation and observed by electrophysiological, freeze-fracture and whole-mount electron microscopy. Electrophysiological measurements showed a transient decrease in membrane potential of -10.2 mV 6 h after the treatment. It returned to almost the same level as that of the control group 1 day later. Six hours after treatment, input resistance decreased rapidly to 5.3 M omega but increased to 18.0 M omega 12 h after treatment. Transient reduction of input resistance and membrane potential occurred prior to the decrease in the coupling ratio 6 h after treatment with DMBA. In freeze-fracture replicas, the number of gap junctions decreased by approximately 45% of the control value 6 h after treatment with DMBA. At 12 h and thereafter, the number and area of gap junctions subsequently decreased by 60-80% of the control value. Alterations in the number and area of desmosomes were similar to those of the gap junctions. The formation of epithelial cytoskeletons, partially devoid of the 2-4 and 5-8 nm filaments was also observed. A decrease in the density of filament networks beneath the plasma membranes was especially apparent. Treatment with a carcinogen brought about morphological cellular changes as early as 6 h after treatment, and such early changes might trigger metabolic cellular abnormalities. Affected cells appear to move away from normal cells in a process of repeated destruction and revision of intercellular junctions, and cytoskeletons.

  12. Local correlations for flap gap oscillatory blowing active flow control technology

    Directory of Open Access Journals (Sweden)

    Cătălin NAE

    2010-09-01

    Full Text Available Active technology for oscillatory blowing in the flap gap has been tested at INCAS subsonic wind tunnel in order to evaluate this technology for usage in high lift systems with active flow control. The main goal for this investigation was to validate TRL level 4 for this technology and to extend towards flight testing. CFD analysis was performed in order to identify local correlations with experimental data and to better formulate a design criteria so that a maximum increase in lift is possible under given geometrical constraints. Reference to a proposed metric for noise evaluation is also given. This includes basic 2D flow cases and also 2.5D configurations. In 2.5D test cases this work has been extended so that the proposed system may be selected as a mature technology in the JTI Clean Sky, Smart Fixed Wing Aircraft ITD. Complex post-processing of the experimental and CFD data was mainly oriented towards system efficiency and TRL evaluation for this active technology.

  13. Interplay of Chiral and Helical States in a Quantum Spin Hall Insulator Lateral Junction

    Science.gov (United States)

    Calvo, M. R.; de Juan, F.; Ilan, R.; Fox, E. J.; Bestwick, A. J.; Mühlbauer, M.; Wang, J.; Ames, C.; Leubner, P.; Brüne, C.; Zhang, S. C.; Buhmann, H.; Molenkamp, L. W.; Goldhaber-Gordon, D.

    2017-12-01

    We study the electronic transport across an electrostatically gated lateral junction in a HgTe quantum well, a canonical 2D topological insulator, with and without an applied magnetic field. We control the carrier density inside and outside a junction region independently and hence tune the number and nature of 1D edge modes propagating in each of those regions. Outside the bulk gap, the magnetic field drives the system to the quantum Hall regime, and chiral states propagate at the edge. In this regime, we observe fractional plateaus that reflect the equilibration between 1D chiral modes across the junction. As the carrier density approaches zero in the central region and at moderate fields, we observe oscillations in the resistance that we attribute to Fabry-Perot interference in the helical states, enabled by the broken time reversal symmetry. At higher fields, those oscillations disappear, in agreement with the expected absence of helical states when band inversion is lifted.

  14. Traction force dynamics predict gap formation in activated endothelium

    Energy Technology Data Exchange (ETDEWEB)

    Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van; Hordijk, Peter L., E-mail: p.hordijk@vumc.nl

    2016-09-10

    In many pathological conditions the endothelium becomes activated and dysfunctional, resulting in hyperpermeability and plasma leakage. No specific therapies are available yet to control endothelial barrier function, which is regulated by inter-endothelial junctions and the generation of acto-myosin-based contractile forces in the context of cell-cell and cell-matrix interactions. However, the spatiotemporal distribution and stimulus-induced reorganization of these integral forces remain largely unknown. Traction force microscopy of human endothelial monolayers was used to visualize contractile forces in resting cells and during thrombin-induced hyperpermeability. Simultaneously, information about endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F-actin) were captured. This revealed a heterogeneous distribution of traction forces, with nuclear areas showing lower and cell-cell junctions higher traction forces than the whole-monolayer average. Moreover, junctional forces were asymmetrically distributed among neighboring cells. Force vector orientation analysis showed a good correlation with the alignment of F-actin and revealed contractile forces in newly formed filopodia and lamellipodia-like protrusions within the monolayer. Finally, unstable areas, showing high force fluctuations within the monolayer were prone to form inter-endothelial gaps upon stimulation with thrombin. To conclude, contractile traction forces are heterogeneously distributed within endothelial monolayers and force instability, rather than force magnitude, predicts the stimulus-induced formation of intercellular gaps. - Highlights: • Endothelial monolayers exert dynamic- and heterogeneous traction forces. • High traction forces correlate with junctional areas and the F-actin cytoskeleton. • Newly formed inter-endothelial gaps are characterized by opposing traction forces. • Force stability is a key feature controlling endothelial permeability.

  15. Traction force dynamics predict gap formation in activated endothelium

    International Nuclear Information System (INIS)

    Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van; Hordijk, Peter L.

    2016-01-01

    In many pathological conditions the endothelium becomes activated and dysfunctional, resulting in hyperpermeability and plasma leakage. No specific therapies are available yet to control endothelial barrier function, which is regulated by inter-endothelial junctions and the generation of acto-myosin-based contractile forces in the context of cell-cell and cell-matrix interactions. However, the spatiotemporal distribution and stimulus-induced reorganization of these integral forces remain largely unknown. Traction force microscopy of human endothelial monolayers was used to visualize contractile forces in resting cells and during thrombin-induced hyperpermeability. Simultaneously, information about endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F-actin) were captured. This revealed a heterogeneous distribution of traction forces, with nuclear areas showing lower and cell-cell junctions higher traction forces than the whole-monolayer average. Moreover, junctional forces were asymmetrically distributed among neighboring cells. Force vector orientation analysis showed a good correlation with the alignment of F-actin and revealed contractile forces in newly formed filopodia and lamellipodia-like protrusions within the monolayer. Finally, unstable areas, showing high force fluctuations within the monolayer were prone to form inter-endothelial gaps upon stimulation with thrombin. To conclude, contractile traction forces are heterogeneously distributed within endothelial monolayers and force instability, rather than force magnitude, predicts the stimulus-induced formation of intercellular gaps. - Highlights: • Endothelial monolayers exert dynamic- and heterogeneous traction forces. • High traction forces correlate with junctional areas and the F-actin cytoskeleton. • Newly formed inter-endothelial gaps are characterized by opposing traction forces. • Force stability is a key feature controlling endothelial permeability.

  16. Update on Mycoplasma hyopneumoniae infections in pigs: Knowledge gaps for improved disease control.

    Science.gov (United States)

    Maes, D; Sibila, M; Kuhnert, P; Segalés, J; Haesebrouck, F; Pieters, M

    2017-08-23

    Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary pathogen of enzootic pneumonia, a chronic respiratory disease in pigs. Infections occur worldwide and cause major economic losses to the pig industry. The present paper reviews the current knowledge on M. hyopneumoniae infections, with emphasis on identification and analysis of knowledge gaps for optimizing control of the disease. Close contact between infected and susceptible pigs is the main route of M. hyopneumoniae transmission. Management and housing conditions predisposing for infection or disease are known, but further research is needed to better understand M. hyopneumoniae transmission patterns in modern pig production systems, and to assess the importance of the breeding population for downstream disease control. The organism is primarily found on the mucosal surface of the trachea, bronchi and bronchioles. Different adhesins and lipoproteins are involved in the adherence process. However, a clear picture of the virulence and pathogenicity of M. hyopneumoniae is still missing. The role of glycerol metabolism, myoinositol metabolism and the Mycoplasma Ig binding protein-Mycoplasma Ig protease system should be further investigated for their contribution to virulence. The destruction of the mucociliary apparatus, together with modulating the immune response, enhances the susceptibility of infected pigs to secondary pathogens. Clinical signs and severity of lesions depend on different factors, such as management, environmental conditions and likely also M. hyopneumoniae strain. The potential impact of strain variability on disease severity is not well defined. Diagnostics could be improved by developing tests that may detect virulent strains, by improving sampling in live animals and by designing ELISAs allowing discrimination between infected and vaccinated pigs. The currently available vaccines are often cost-efficient, but the ongoing research on developing new vaccines that confer protective

  17. The Connection between Environmental Attitude-Behavior Gap and Other Individual Inconsistencies: A Call for Strengthening Self-Control

    Science.gov (United States)

    Redondo, Ignacio; Puelles, María

    2017-01-01

    What is going on with environmental education, which is currently unable to promote pro-environmental behaviors as effectively as it promotes pro-environmental attitudes? A tentative answer is that the environmental attitude-behavior gap observed in some individuals is just one manifestation of their lack of self-control for maintaining…

  18. SIGNAL CONTROLLED JUNCTIONS CALCULATIONS IN TRAFFIC-CAPACITY ASSESSMENT - AIMSUN, OMNITRANS, WEBSTER AND TP 10/2010 RESULTS COMPARISON

    Directory of Open Access Journals (Sweden)

    Ľubomír ČERNICKÝ

    2016-03-01

    Full Text Available Every increase in traffic volume on road network in towns can lead to overcrowding of road network. This results in undesirable external costs such as traffic congestions, which cause high loses in time during transportation, increased fuel consumption and thus higher production of greenhouse gases and noise. This all ultimately reduces the attractiveness of the area. The increase of traffic volume and therefrom derived traffic problems are needed to be solved during traffic-capacity assessment of every larger investment. The software can help to assess increased traffic in solved area and thus help authorities to make a right decision during approving of the investment plan. This article is focused on comparison of two software – Aimsun and OmniTrans, and calculations according to Webster and technical regulations for assessing junction capacity in the Slovak Republic. The packages outputs are also compared to the measured data at the assessed junction in this article. The analysis showed that outputs of various tools differ, generally all packages showed higher delays compared to measured data at the main road and lower delays compared to measured data at the side roads.

  19. An update on minding the gap in cancer.

    Science.gov (United States)

    Mesnil, Marc; Aasen, Trond; Boucher, Jonathan; Chépied, Amandine; Cronier, Laurent; Defamie, Norah; Kameritsch, Petra; Laird, Dale W; Lampe, Paul D; Lathia, Justin D; Leithe, Edward; Mehta, Parmender P; Monvoisin, Arnaud; Pogoda, Kristin; Sin, Wun-Chey; Tabernero, Arantxa; Yamasaki, Hiroshi; Yeh, Elizabeth S; Dagli, Maria Lucia Zaidan; Naus, Christian C

    2018-01-01

    This article is a report of the "International Colloquium on Gap junctions: 50Years of Impact on Cancer" that was held 8-9 September 2016, at the Amphitheater "Pôle Biologie Santé" of the University of Poitiers (Poitiers, France). The colloquium was organized by M Mesnil (Université de Poitiers, Poitiers, France) and C Naus (University of British Columbia, Vancouver, Canada) to celebrate the 50th anniversary of the seminal work published in 1966 by Loewenstein and Kanno [Intercellular communication and the control of tissue growth: lack of communication between cancer cells, Nature, 116 (1966) 1248-1249] which initiated studies on the involvement of gap junctions in carcinogenesis. During the colloquium, 15 participants presented reviews or research updates in the field which are summarized below. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. 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...

  1. 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).

  2. 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

  3. GAP Analysis Program (GAP)

    Data.gov (United States)

    Kansas Data Access and Support Center — The Kansas GAP Analysis Land Cover database depicts 43 land cover classes for the state of Kansas. The database was generated using a two-stage hybrid classification...

  4. 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 ...

  5. Minding the gap: Frequency of indels in mtDNA control region sequence data and influence on population genetic analyses

    Science.gov (United States)

    Pearce, J.M.

    2006-01-01

    Insertions and deletions (indels) result in sequences of various lengths when homologous gene regions are compared among individuals or species. Although indels are typically phylogenetically informative, occurrence and incorporation of these characters as gaps in intraspecific population genetic data sets are rarely discussed. Moreover, the impact of gaps on estimates of fixation indices, such as FST, has not been reviewed. Here, I summarize the occurrence and population genetic signal of indels among 60 published studies that involved alignments of multiple sequences from the mitochondrial DNA (mtDNA) control region of vertebrate taxa. Among 30 studies observing indels, an average of 12% of both variable and parsimony-informative sites were composed of these sites. There was no consistent trend between levels of population differentiation and the number of gap characters in a data block. Across all studies, the average influence on estimates of ??ST was small, explaining only an additional 1.8% of among population variance (range 0.0-8.0%). Studies most likely to observe an increase in ??ST with the inclusion of gap characters were those with control region DNA appears small, dependent upon total number of variable sites in the data block, and related to species-specific characteristics and the spatial distribution of mtDNA lineages that contain indels. ?? 2006 Blackwell Publishing Ltd.

  6. 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.)

  7. 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

  8. The research gap in chronic paediatric pain: A systematic review of randomised controlled trials.

    Science.gov (United States)

    Boulkedid, R; Abdou, A Y; Desselas, E; Monégat, M; de Leeuw, T G; Avez-Couturier, J; Dugue, S; Mareau, C; Charron, B; Alberti, C; Kaguelidou, F

    2018-02-01

    Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants

  9. Strategy and gaps for modeling, simulation, and control of hybrid systems

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Garcia, Humberto E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hovsapian, Rob [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mesina, George L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bragg-Sitton, Shannon M. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Boardman, Richard D. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-04-01

    The purpose of this report is to establish a strategy for modeling and simulation of candidate hybrid energy systems. Modeling and simulation is necessary to design, evaluate, and optimize the system technical and economic performance. Accordingly, this report first establishes the simulation requirements to analysis candidate hybrid systems. Simulation fidelity levels are established based on the temporal scale, real and synthetic data availability or needs, solution accuracy, and output parameters needed to evaluate case-specific figures of merit. Accordingly, the associated computational and co-simulation resources needed are established; including physical models when needed, code assembly and integrated solutions platforms, mathematical solvers, and data processing. This report first attempts to describe the figures of merit, systems requirements, and constraints that are necessary and sufficient to characterize the grid and hybrid systems behavior and market interactions. Loss of Load Probability (LOLP) and effective cost of Effective Cost of Energy (ECE), as opposed to the standard Levelized Cost of Electricty (LCOE), are introduced as technical and economical indices for integrated energy system evaluations. Financial assessment methods are subsequently introduced for evaluation of non-traditional, hybrid energy systems. Algorithms for coupled and iterative evaluation of the technical and economic performance are subsequently discussed. This report further defines modeling objectives, computational tools, solution approaches, and real-time data collection and processing (in some cases using real test units) that will be required to model, co-simulate, and optimize; (a) an energy system components (e.g., power generation unit, chemical process, electricity management unit), (b) system domains (e.g., thermal, electrical or chemical energy generation, conversion, and transport), and (c) systems control modules. Co-simulation of complex, tightly coupled

  10. Controlling emission and propagation of light with photonic band gap crystals

    NARCIS (Netherlands)

    Yeganegi Dastgerdi, Elahe

    2014-01-01

    In certain three-dimensional crystals, a frequency range exist for all polarizations for which light is not allowed to propagate in any direction, called the 3D photonic band gap: a frequency range where the density of vacuum fluctuations vanishes in an ideal infinitely large and perfect system. The

  11. An Evolutionary Robotics Approach to the Control of Plant Growth and Motion: Modeling Plants and Crossing the Reality Gap

    DEFF Research Database (Denmark)

    Wahby, Mostafa; Hofstadler, Daniel Nicolas; Heinrich, Mary Katherine

    2016-01-01

    approach where task performance is determined by monitoring the plant's reaction. First, we do initial plant experiments with simple, predetermined controllers. Then we use image sampling data as a model of the dynamics of the plant tip xy position. Second, we use this approach to evolve robot controllers...... in simulation. The task is to make the plant approach three predetermined, distinct points in an xy-plane. Finally, we test the evolved controllers in real plant experiments and find that we cross the reality gap successfully. We shortly describe how we have extended from plant tip to many points on the plant...

  12. Evaluating the effects of moving to a low maintenance ARD control strategy at the Victoria Junction coal tailings site

    Energy Technology Data Exchange (ETDEWEB)

    Ziemkiewicz, P.F. [Morgantown, WV (United States); Peckham, D.; Kehoe, A. [Enterprise Cape Breton Corp., Sydney, NS (Canada)

    2010-07-01

    The Victoria Junction Coal Preparation site located near Sydney, Nova Scotia has been a major source of acid rock drainage (ARD) to waterways and surrounding wetlands. A polymer cap placed on the pile in 2005 resulted in a rapid improvement in waterway and wetland health. An earlier water treatment system (WTS) remained in operation until an evaluation was conducted to determine if the WTS was needed to maintain water quality in the region. This paper described the acid base loading model used to develop a close-out plan for the WTS. A mass balance model was used to isolate and compare the effects of the WTS and the capping system. The effect of shutting down the WTS was monitored for 8 moths. The model used flow and net acidity rates to calculate loadings. Net acidity represented the mass of pure base expressed as a calcium carbonate equivalent needed to neutralize acid loads. Acidity was calculated base on pH and metal concentrations. Alkalinity was determined by titration. A comparison with analytical studies of collected water samples showed that the mass balance model underestimated the alkalinity produced at the site. Results of the study showed that the site is now a net alkalinity generator. 5 refs., 1 tab., 1 fig.

  13. Separate development of the maxilla and mandible is controlled by regional signaling of the maxillomandibular junction during avian development.

    Science.gov (United States)

    Tak, Hye-Jin; Park, Tae-Jin; Piao, Zhenngu; Lee, Sang-Hwy

    2017-01-01

    Syngnathia is a congenital craniofacial disorder characterized by bony or soft tissue fusion of upper and lower jaws. Previous studies suggested some causative signals, such as Foxc1 or Bmp4, cause the disruption of maxillomandibular identity, but their location and the interactive signals involved remain unexplored. We wanted to examine the embryonic origin of syngnathia based on the assumption that it may be located at the separation between the maxillary and mandibular processes. This region, known as the maxillomandibular junction (MMJ), is involved in segregation of cranial neural crest-derived mesenchyme into the presumptive upper and lower jaws. Here we investigated the role of Fgf, Bmp, and retinoid signaling during development of MMJ in chicken embryos. By changing the levels of these signals with bead implants, we induced syngnathia with microstomia on the treated side, which showed increased Barx1 and neural cell adhesion molecule (NCAM) expression. Redistribution of proliferating cells was also observed at the proximal region to maxillary and mandibular arch around MMJ. We propose that interactive molecular signaling by Fgfs, Bmps, and retinoids around MMJ is required for normal separation of the maxilla and mandible, as well as the proper positioning of beak commissure during early facial morphogenesis. Developmental Dynamics 246:28-40, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Magnetic resonance imaging of ligaments and membranes in the craniocervical junction in whiplash-associated injury and in healthy control subjects

    International Nuclear Information System (INIS)

    Dullerud, Reidar; Gjertsen, Oeivind; Server, Andres

    2010-01-01

    Background: The pathogenesis and imaging findings in whiplash-associated injury (WAD) are poorly understood and remain debatable. Purpose: To assess the ligaments and membranes in the craniocervical junction with magnetic resonance imaging (MRI) in patients with WAD and to compare them with healthy control subjects. Material and Methods: Twenty-eight patients with WAD were selected at random from a total number of 180 examined with MRI using 2-mm proton density (PD)-weighted images in three orthogonal planes at 1.5T. The patients were compared with 27 healthy control subjects without neck trauma. Results: High signal intensity of the alar and transverse ligaments was quite common and was reported at an average of about 50% both among patients and control subjects. The incidence of abnormalities of the tectorial and posterior atlanto-occipital membranes was low in both groups. No statistically significant difference between control subjects and patients with WAD was revealed for any of the structures assessed. Additional fat-suppressed images seemed to reduce the number of reported anomalies. Conclusion: Due to lack of significant differences between patients with WAD and healthy control subjects, it is not recommended that MRI with the current technique and classification system be used in the routine workup of patients with WAD

  15. Magnetic resonance imaging of ligaments and membranes in the craniocervical junction in whiplash-associated injury and in healthy control subjects

    Energy Technology Data Exchange (ETDEWEB)

    Dullerud, Reidar; Gjertsen, Oeivind; Server, Andres (Dept. of Neuroradiology, Ullevaal Univ. Hospital, Oslo (Norway)), e-mail: redu@lds.no

    2010-03-15

    Background: The pathogenesis and imaging findings in whiplash-associated injury (WAD) are poorly understood and remain debatable. Purpose: To assess the ligaments and membranes in the craniocervical junction with magnetic resonance imaging (MRI) in patients with WAD and to compare them with healthy control subjects. Material and Methods: Twenty-eight patients with WAD were selected at random from a total number of 180 examined with MRI using 2-mm proton density (PD)-weighted images in three orthogonal planes at 1.5T. The patients were compared with 27 healthy control subjects without neck trauma. Results: High signal intensity of the alar and transverse ligaments was quite common and was reported at an average of about 50% both among patients and control subjects. The incidence of abnormalities of the tectorial and posterior atlanto-occipital membranes was low in both groups. No statistically significant difference between control subjects and patients with WAD was revealed for any of the structures assessed. Additional fat-suppressed images seemed to reduce the number of reported anomalies. Conclusion: Due to lack of significant differences between patients with WAD and healthy control subjects, it is not recommended that MRI with the current technique and classification system be used in the routine workup of patients with WAD

  16. Doping and band gap control at poly(vinylidene fluoride)/graphene interface

    Science.gov (United States)

    Cai, Jia; Wang, Jian-Lu; Gao, Heng; Tian, Bobo; Gong, Shi-Jing; Duan, Chun-Gang; Chu, Jun-Hao

    2018-05-01

    Using the density-functional first-principles calculations, we investigate the electronic structures of poly(vinylidene fluoride) PVDF/graphene composite systems. The n- and p-doping of graphene can be flexibly switched by reversing the ferroelectric polarization of PVDF, without scarifying the intrinsic π-electron band dispersions of graphene that are usually undermined by chemical doping. The doping degree is also dependent on the thickness of PVDF layers, which will get saturated when PVDF is thick enough. In PVDF/bilayer graphene (BLG) heterostructure, the doping degree directly determines the local energy gap of the charged BLG. The sandwich structure of PVDF/BLG/PVDF can further enhance the local energy gap as well as keep the electric neutrality of BLG, which will be of great application potentials in graphene-based nanoelectronics.

  17. 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

  18. 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)

  19. Stratigraphic controls on saltwater intrusion in the Dominguez Gap area of coastal Los Angeles

    Science.gov (United States)

    Edwards, B.D.; Ehman, K.D.; Ponti, D.J.; Reichard, E.G.; Tinsley, J.C.; Rosenbauer, R.J.; Land, M.

    2009-01-01

    The Los Angeles Basin is a densely populated coastal area that significantly depends on groundwater. A part of this groundwater supply is at risk from saltwater intrusion-the impetus for this study. High-resolution seismic-reflection data collected from the Los Angeles-Long Beach Harbor Complex have been combined with borehole geophysical and descriptive geological data from four nearby ??400-m-deep continuously cored wells and with borehole geophysical data from adjacent water and oil wells to characterize the Pliocene to Holocene stratigraphy of the Dominguez Gap coastal aquifer system. The new data are shown as a north-south, two- dimensional, sequence-stratigraphic model that is compared to existing lithostratigraphic models of the Los Angeles Basin in an attempt to better understand pathways of saltwater intrusion into coastal aquifers. Intrusion of saltwater into the coastal aquifer system generally is attributed to over-pumping that caused the hydraulic gradient to reverse during the mid-1920s. Local water managers have used the existing lithostratigraphic model to site closely spaced injection wells of freshwater (barrier projects) attempting to hydraulically control the saltwater intrusion. Improved understanding of the stratigraphic relationships can guide modifications to barrier design that will allow more efficient operation. Allostratigraphic nomenclature is used to define a new sequence-stratigraphic model for the area because the existing lithostratigraphic correlations that have been used to define aquifer systems are shown not to be time-correlative. The youngest sequence, the Holocene Dominguez sequence, contains the Gaspur aquifer at its base. The Gaspur aquifer is intruded with saltwater and consists of essentially flat-lying gravelly sands deposited by the ancestral Los Angeles River as broad channels that occupied a paleovalley incised into the coastal plain during the last glacio-eustatic highstand. The underlying sequences are deformed into

  20. 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

  1. Evolved Control of Natural Plants: Crossing the Reality Gap for User-Defined Steering of Growth and Motion

    DEFF Research Database (Denmark)

    Hofstadler, Daniel Nicolas; Wahby, Mostafa; Heinrich, Mary Katherine

    2017-01-01

    Mixing societies of natural and artificial systems can provide interesting and potentially fruitful research targets. Here we mix robotic setups and natural plants in order to steer the motion behavior of plants while growing. The robotic setup uses a camera to observe the plant and uses a pair...... of light sources to trigger phototropic response, steering the plant to user-defined targets. An evolutionary robotic approach is used to design a controller for the setup. Initially, preliminary experiments are performed with a simple predetermined controller and a growing bean plant. The plant behavior......-evolved controller in the real setup controlling a natural bean plant. The results demonstrate a successful crossing of the reality gap in the setup. The success of the approach allows for future extensions to more complex tasks including control of the shape of plants and pattern formation in multiple plant setups....

  2. To assess control measures for tobacco consumption in Zambia between 2014 and 2017. What are the gaps?

    Directory of Open Access Journals (Sweden)

    Davies Kalunga

    2018-03-01

    Full Text Available Background Cigarette smoking is a leading cause of global morbidity and mortality, in developing countries interest in smoking prevalence has been growing since 1999. Many factors are known to influence smoking prevalence and trends in prevalence, from individual level factors such as education level, to country-level factors such as national economic development and implementation of tobacco control policies, therefore there is need to assess the control measures for tobacco smoking in Zambia between 2014 and 2017and determine the gaps in policy implementation in tobacco consumption in Zambia. Methods This was a retrospective study using policy documents from central statistical office. Results The following gaps were identified in which there was no legislation: concerning Institutions and mechanisms to provide for a funding mechanism, Public education requiring mass public education campaigns to change public attitudes regarding tobacco and tobacco control, Advertising, promotion and sponsorship as a comprehensive ban involves a ban on all forms of direct and indirect advertisements, promotion and sponsorship, Price and tax measures as an effective means of reducing tobacco consumption, especially among young people. Monitoring- No known data or no recent data or data that are not both recent and representative (WHO report on the global tobacco epidemic, 2017. Conclusions The absence of legislation in these areas of institutions and mechanisms, public education, advertising, promotion and sponsorship and the price and tax measures have far reaching consequences in tobacco control in Zambia.

  3. 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

  4. Have the auditors closed the expectation gap concerning evaluation of internal control?

    DEFF Research Database (Denmark)

    Birkholm, Peter; Holm, Claus

    internal controls intended for management directors, it provides a framework which explicitly deals with the interests of all parties involved (including auditors, board of directors and regulating bodies). The auditors took this into account by updating the particular auditing standard on internal control....... Realized discrepancies are identified and related to the necessary features of an integrated framework. The necessary features include (1) the definition of internal controls, (2) the components of internal control, (3) the criteria for evaluating internal control as stated by the auditors (4) the criteria...... for evaluating internal controls as stated by management, and (5) the integration of internal control evaluations from management and auditors. The paper provides evidence from an in-depth contents analysis comparing SAS No. 55 from 1988 with the COSO-report from 1992 and SAS No. 78 from 1995. The analysis...

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

    Science.gov (United States)

    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.

  6. DISCONTOOLS: a database to identify research gaps on vaccines, pharmaceuticals and diagnostics for the control of infectious diseases of animals.

    Science.gov (United States)

    O'Brien, Declan; Scudamore, Jim; Charlier, Johannes; Delavergne, Morgane

    2017-01-03

    The public and private sector in the EU spend around €800 million per year on animal health and welfare related research. An objective process to identify critical gaps in knowledge and available control tools should aid the prioritisation of research in order to speed up the development of new or improved diagnostics, vaccines and pharmaceuticals and reduce the burden of animal diseases. Here, we describe the construction of a database based on expert consultation for 52 infectious diseases of animals. For each disease, an expert group produced a disease and product analysis document that formed the basis for gap analysis and prioritisation. The prioritisation model was based on a closed scoring system, employing identical weights for six evaluation criteria (disease knowledge; impact on animal health and welfare; impact on public health; impact on wider society; impact on trade; control tools). The diseases were classified into three groups: epizootic diseases, food-producing animal complexes or zoonotic diseases. The highly ranked diseases in the prioritisation model comprised mostly zoonotic and epizootic diseases with important gaps identified in vaccine development and pharmaceuticals, respectively. The most important outcome is the identification of key research needs by disease. The rankings and research needs by disease are provided on a public website ( www.discontools.eu ) which is currently being updated based on new expert consultations. As such, it can become a reference point for funders of research including the European Commission, member states, foundations, trusts along with private industry to prioritise research. This will deliver benefits in terms of animal health and welfare but also public health, societal benefits and a safe and secure food supply.

  7. Enhanced Andreev reflection in gapped graphene

    Science.gov (United States)

    Majidi, Leyla; Zareyan, Malek

    2012-08-01

    We theoretically demonstrate unusual features of superconducting proximity effect in gapped graphene that presents a pseudospin symmetry-broken ferromagnet with a net pseudomagnetization. We find that the presence of a band gap makes the Andreev conductance of graphene superconductor/pseudoferromagnet (S/PF) junction to behave similar to that of a graphene ferromagnet-superconductor junction. The energy gap ΔN can enhance the pseudospin inverted Andreev conductance of S/PF junction to reach a limiting maximum value for ΔN≫μ, which depending on the bias voltage can be larger than the value for the corresponding junction with no energy gap. We further demonstrate a damped-oscillatory behavior for the local density of states of the PF region of S/PF junction and a long-range crossed Andreev reflection process in PF/S/PF structure with antiparallel alignment of pseudomagnetizations of PFs, which confirm that, in this respect, the gapped normal graphene behaves like a ferromagnetic graphene.

  8. Pentacene-based photodiode with Schottky junction

    International Nuclear Information System (INIS)

    Lee, Jiyoul; Hwang, D.K.; Park, C.H.; Kim, S.S.; Im, Seongil

    2004-01-01

    We have fabricated a metal/organic semiconductor Schottky photodiode based on Al/pentacene junction. Since the energy band gap of thin solid pentacene was determined to be 1.82 eV, as characterized by direct absorption spectroscopy, we measured spectral photoresponses on our Schottky photodiode in the monochromatic light illumination range of 325-650 nm applying a reverse bias of -2 V. The main features of photo-response spectra were found to shift from those of direct absorption spectra toward higher photon energies. It is because the direct absorption spectra mainly show exciton level peaks rather than the true highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gaps while the photo-response spectra clearly represents the true HOMO-LUMO gap. Our photo-response spectra reveal 1.97 eV as the HOMO-LUMO gap

  9. An optically controlled SiC lateral power transistor based on SiC/SiCGe super junction structure

    International Nuclear Information System (INIS)

    Pu Hongbin; Cao Lin; Ren Jie; Chen Zhiming; Nan Yagong

    2010-01-01

    An optically controlled SiC/SiCGe lateral power transistor based on superjunction structure has been proposed, in which n-SiCGe/p-SiC superjunction structure is employed to improve device figure of merit. Performance of the novel optically controlled power transistor was simulated using Silvaco Atlas tools, which has shown that the device has a very good response to the visible light and the near infrared light. The optoelectronic responsivities of the device at 0.5 μm and 0.7 μm are 330 mA/W and 76.2 mA/W at 2 V based voltage, respectively. (semiconductor devices)

  10. An optically controlled SiC lateral power transistor based on SiC/SiCGe super junction structure

    Energy Technology Data Exchange (ETDEWEB)

    Pu Hongbin; Cao Lin; Ren Jie; Chen Zhiming; Nan Yagong, E-mail: puhongbin@xaut.edu.c [Xi' an University of Technology, Xi' an 710048 (China)

    2010-04-15

    An optically controlled SiC/SiCGe lateral power transistor based on superjunction structure has been proposed, in which n-SiCGe/p-SiC superjunction structure is employed to improve device figure of merit. Performance of the novel optically controlled power transistor was simulated using Silvaco Atlas tools, which has shown that the device has a very good response to the visible light and the near infrared light. The optoelectronic responsivities of the device at 0.5 {mu}m and 0.7 {mu}m are 330 mA/W and 76.2 mA/W at 2 V based voltage, respectively. (semiconductor devices)

  11. Knowledge gaps that hamper prevention and control of Mycobacterium avium subspecies paratuberculosis infection

    NARCIS (Netherlands)

    Barkema, H.W.; Orsel, K.; Nielsen, S.; Koets, Ad; Rutten, V.P.M.G.; Bannantine, J.P.; Keefe, G.P.; Kelton, D.F.; Wells, S.J.; Whittington, R.J.; Mackintosh, C.G.; Manning, E.J.; Weber, M.F.; Heuer, C.; Forde, T.L.; Ritter, C.; Roche, S.; Corbett, C.S.; Wolf, R.; Griebel, P.J.; Kastelic, J.P.; Buck, De J.

    2017-01-01

    In the last decades, many regional and country-wide control programmes for Johne's disease (JD) were developed due to associated economic losses, or because of a possible association with Crohn's disease. These control programmes were often not successful, partly because management protocols were

  12. O tabagismo está associado com a remodelação de junções comunicantes no coração de ratos: explicação do paradoxo dos fumantes? Smoking is associated with remodeling of gap junction in the rat heart: smoker's paradox explanation?

    Directory of Open Access Journals (Sweden)

    Rosangela Novo

    2013-03-01

    reperfusion. OBJECTIVE: Thus, this study aimed to analyze the effects of exposure to tobacco smoke on intensity, distribution or phosphorylation of connexin 43 in the rat heart. METHODS: Wistar rats weighing 100 g were randomly allocated into 2 groups: 1 Control (n = 25; 2 Exposed to tobacco smoke (ETS, n = 23. After 5 weeks, left ventricular morphometric analysis, immunohisthochemistry and western blotting for connexin 43 (Cx43 were performed. RESULTS: Collagen volume fraction, cross-sectional areas, and ventricular weight were not statistically different between control and ETS. ETS showed lower stain intensity of Cx43 at intercalated disks (Control: 2.32 ± 0.19; ETS: 1.73 ± 0.18; p = 0.04. The distribution of CX43 at intercalated disks did not differ between the groups (Control: 3.73 ± 0.12; ETS: 3.20 ± 0.17; p = 0.18. ETS rats showed higher levels of dephosphorylated form of Cx43 (Control: 0.45 ± 0.11; ETS: 0.90 ± 0.11; p = 0.03. On the other hand, total Cx43 did not differ between control and ETS groups (Control: 0.75 ± 0.19; ETS: 0.93 ± 0.27; p = 0.58. CONCLUSION: Exposure to tobacco smoke resulted in cardiac gap junction remodeling, characterized by alterations in the quantity and phosphorylation of the Cx43, in rats hearts. This finding could explain the smoker's paradox observed in some studies.

  13. 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.)

  14. How to control spin-Seebeck current in a metal-quantum dot-magnetic insulator junction

    Science.gov (United States)

    Fu, Hua-Hua; Gu, Lei; Wu, Ruqian

    The control of the spin-Seebeck current is still a challenging task for the development of spin caloritronic devices. Here, we construct a spin-Seebeck device by inserting a quantum dot (QD) between the metal lead and magnetic insulator. Using the slave-particle approach and noncrossing approximation, we find that the spin-Seebeck effect increases significantly when the energy level of the QD locates near the Fermi level of the metal lead due to the enhancement of spin flipping and occurrences of quantum resonance. Since this can be easily realized by applying a gate voltage in experiments, the spin-Seebeck device proposed here can also work as a thermovoltaic transistor. Moreover, the optimal correlation strength and the energy level position of the QD are discussed to maximize the spin-Seebeck current as required for applications in controllable spin caloritronic devices.

  15. The RhoGAP Stard13 controls insulin secretion through F-actin remodeling

    Directory of Open Access Journals (Sweden)

    Heike Naumann

    2018-02-01

    Full Text Available Objective: Actin cytoskeleton remodeling is necessary for glucose-stimulated insulin secretion in pancreatic β-cells. A mechanistic understanding of actin dynamics in the islet is paramount to a better comprehension of β-cell dysfunction in diabetes. Here, we investigate the Rho GTPase regulator Stard13 and its role in F-actin cytoskeleton organization and islet function in adult mice. Methods: We used Lifeact-EGFP transgenic animals to visualize actin cytoskeleton organization and dynamics in vivo in the mouse islets. Furthermore, we applied this model to study actin cytoskeleton and insulin secretion in mutant mice deleted for Stard13 selectively in pancreatic cells. We isolated transgenic islets for 3D-imaging and perifusion studies to measure insulin secretion dynamics. In parallel, we performed histological and morphometric analyses of the pancreas and used in vivo approaches to study glucose metabolism in the mouse. Results: In this study, we provide the first genetic evidence that Stard13 regulates insulin secretion in response to glucose. Postnatally, Stard13 expression became restricted to the mouse pancreatic islets. We showed that Stard13 deletion results in a marked increase in actin polymerization in islet cells, which is accompanied by severe reduction of insulin secretion in perifusion experiments. Consistently, Stard13-deleted mice displayed impaired glucose tolerance and reduced glucose-stimulated insulin secretion. Conclusions: Taken together, our results suggest a previously unappreciated role for the RhoGAP protein Stard13 in the interplay between actin cytoskeletal remodeling and insulin secretion. Keywords: F-actin, Insulin secretion, Islet, Pancreas, Lifeact, Stard13

  16. Bridging the gap: adapting advanced display technologies for use in hybrid control rooms

    International Nuclear Information System (INIS)

    Jokstad, Håkon; Boring, Ronald

    2015-01-01

    The Institute for Energy Technology (IFE), runs the OECD Halden Reactor Project (HRP), featuring a state-of-the-art research simulator facility in Halden, Norway, called HAMMLAB. HAMMLAB serves two main purposes: the study of human behaviour in interaction with complex process systems; and the development, test and evaluation of prototype control centres and their individual systems. By studying operator performance in HAMMLAB and integrating the knowledge gained into new designs, the HRP contributes to improving operational safety, reliability, efficiency and productivity. The U.S. Department of Energy's (DOE) Light Water Reactor Sustainability (LWRS) Program has contracted IFE to assist DOE national laboratory staff at Idaho National Laboratory (INL) in adapting HAMMLAB design concepts for the purpose of control room modernization at nuclear power plants in the U.S. In support of this effort, the DOE has built a simulator research facility at INL called the Human Systems Simulation Laboratory (HSSL). The HSSL is centered on control room modernization, in which industry provided plant instrumentation and controls are modified for upgrade opportunities. The HSSL houses the LWRS simulator, which is a reconfigurable full-scale and full-scope control room simulator. Consisting of 45 large touchscreens on 15 panels, the LWRS simulator is currently using this glass top technology to digitally represent and replicate the functionality of the analog I&C systems in existing control rooms. The LWRS simulator is reconfigurable in that different plant training simulator models obtained from the utilities can be run on the panels, and the panels can be physically moved and arranged to mimic the layout of those control rooms. The glass top technology and reconfigurability capabilities allow the LWRS simulator to be the research platform that is necessary to design, prototype, and validate human-system interface (HSI) technologies that can replace existing analog I&C. IFE

  17. Bridging the gap: adapting advanced display technologies for use in hybrid control rooms

    Energy Technology Data Exchange (ETDEWEB)

    Jokstad, Håkon [Inst. for Energy Technology, Halden (Norway); Boring, Ronald [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-02-01

    The Institute for Energy Technology (IFE), runs the OECD Halden Reactor Project (HRP), featuring a state-of-the-art research simulator facility in Halden, Norway, called HAMMLAB. HAMMLAB serves two main purposes: the study of human behaviour in interaction with complex process systems; and the development, test and evaluation of prototype control centres and their individual systems. By studying operator performance in HAMMLAB and integrating the knowledge gained into new designs, the HRP contributes to improving operational safety, reliability, efficiency and productivity. The U.S. Department of Energy’s (DOE) Light Water Reactor Sustainability (LWRS) Program has contracted IFE to assist DOE national laboratory staff at Idaho National Laboratory (INL) in adapting HAMMLAB design concepts for the purpose of control room modernization at nuclear power plants in the U.S. In support of this effort, the DOE has built a simulator research facility at INL called the Human Systems Simulation Laboratory (HSSL). The HSSL is centered on control room modernization, in which industry provided plant instrumentation and controls are modified for upgrade opportunities. The HSSL houses the LWRS simulator, which is a reconfigurable full-scale and full-scope control room simulator. Consisting of 45 large touchscreens on 15 panels, the LWRS simulator is currently using this glass top technology to digitally represent and replicate the functionality of the analog I&C systems in existing control rooms. The LWRS simulator is reconfigurable in that different plant training simulator models obtained from the utilities can be run on the panels, and the panels can be physically moved and arranged to mimic the layout of those control rooms. The glass top technology and reconfigurability capabilities allow the LWRS simulator to be the research platform that is necessary to design, prototype, and validate human-system interface (HSI) technologies that can replace existing analog I&C. IFE has

  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. Centralized Gap Clearance Control for Maglev Based Steel-Plate Conveyance System

    Directory of Open Access Journals (Sweden)

    GUNEY, O. F.

    2017-08-01

    Full Text Available The conveyance of steel-plates is one of the potential uses of the magnetic levitation technology in industry. However, the electromagnetic levitation systems inherently show nonlinear feature and are unstable without an active control. Well-known U-shaped or E-shaped electromagnets cannot provide redundant levitation with multiple degrees of freedom. In this paper, to achieve the full redundant levitation of the steel plate, a quadruple configuration of U shaped electromagnets has been proposed. To resolve the issue of instability and attain more robust levitation, a centralized control algorithm based on a modified PID controller (I PD is designed for each degree of freedom by using the Manabe canonical polynomial technique. The model of the system is carried out using electromechanical energy conversion princi¬ples and verified by 3-D FEM analysis. An experimental bench is built up to test the system performance under trajectory tracking and external disturbance excitation. The results confirm the effectiveness of the proposed system and the control approach to obtain a full redundant levitation even in case of disturbances. The paper demonstrates the feasibility of the con¬veyance of steel plates by using the quadruple configuration of U-shaped electromagnets and shows the merits of I-PD controller both in stabilization and increased robust levitation.

  20. Proximity effect and Andreev reflection in single-C{sub 60} junctions

    Energy Technology Data Exchange (ETDEWEB)

    Brand, Jonathan; Neel, Nicolas; Kroeger, Joerg [Institut fuer Physik, Technische Universitaet Ilmenau, D-98693 Ilmenau (Germany)

    2016-07-01

    Single C{sub 60} molecules deposited on an ultrathin oxide film on Nb(110) were investigated using a low-temperature scanning tunnelling microscope. Spectroscopy of the differential conductance (dI/dV) in the tunnelling range indicates proximity-induced superconductivity in junctions comprising the oxide layer as well as single C{sub 60} molecules. Andreev reflection is enhanced upon controlled fabrication of tip-surface contacts. With decreasing electrode separation the Bardeen-Cooper-Schrieffer energy gap gradually evolves into a zero-bias peak in dI/dV spectra reflecting the spectroscopic signature of Andreev reflection. The current-voltage characteristics of the tunnelling and contact junctions are well described by the Blonder-Tinkham-Klapwijk theory. Our spectroscopic data evidence the influence of the electrodes' atomic-scale structure on electron transport across normal metal-superconductor interfaces.

  1. How big is the physical activity intention-behaviour gap? A meta-analysis using the action control framework.

    Science.gov (United States)

    Rhodes, Ryan E; de Bruijn, Gert-Jan

    2013-05-01

    The physical activity (PA) intention-behaviour gap is a topic of considerable contemporary research, given that most of our models used to understand physical activity suggest that intention is the proximal antecedent of behavioural enactment. The purpose of this study was to quantify the intention-PA gap at public health guidelines with a meta-analysis of the action control framework. Systematic review and meta-analysis. Literature searches were conducted in July 2012 among five key search engines. This search yielded a total of 2,865 potentially relevant records; of these, 10 studies fulfilled the full eligibility criteria (N = 3,899). Random-effects meta-analysis procedures with correction for sampling bias were employed in the analysis for estimates of non-intenders who subsequently did not engage in physical activity (21%), non-intenders who subsequently performed physical activity (2%), intenders who were not successful at following through with their PA (36%), and successful intenders (42%). The overall intention-PA gap was 46%. These results emphasize the weakness in early intention models for understanding PA and suggest this would be a problem during intervention. Contemporary research that is validating and exploring additional constructs (e.g., self-regulation, automaticity) that augment intention or improving the measurement of motivation seems warranted. What is already known on this subject? Intention is considered the proximal antecedent of behaviour in many popular models. Intention is also an established correlate of physical activity behaviour, yet discordance is considerable in experimental research. What does this study add? This meta-analysis of studies that have assessed concordance/discordance of physical activity intention and behaviour at public health guidelines shows the intention-behaviour gap at 48% and the discordance is from intenders who do not act. The results demonstrate that discordance is not just from extreme levels of

  2. Gaps and barriers in the control of blood glucose in people with type 2 diabetes.

    Science.gov (United States)

    Blonde, Lawrence; Aschner, Pablo; Bailey, Clifford; Ji, Linong; Leiter, Lawrence A; Matthaei, Stephan

    2017-05-01

    Glycaemic control is suboptimal in a large proportion of people with type 2 diabetes who are consequently at an increased and avoidable risk of potentially severe complications. We sought to explore attitudes and practices among healthcare professionals that may contribute to suboptimal glycaemic control through a review of recent relevant publications in the scientific literature. An electronic search of the PubMed database was performed to identify relevant publications from January 2011 to July 2015. The electronic search was complemented by a manual search of abstracts from key diabetes conferences in 2014/2015 available online. Recently published data indicate that glycaemic control is suboptimal in a substantial proportion (typically 40%-60%) of people with diabetes. This is the case across geographic regions and in both low- and higher-income countries. Therapeutic inertia appears to be an important contributor to poor glycaemic control in up to half of people with type 2 diabetes. In particular, prescribers are often willing to tolerate extended periods of 'mild' hyperglycaemia as well as having low expectations for their patients. There are often delays of 3 years or longer in initiating or intensifying glucose-lowering therapy when needed. Many people with type 2 diabetes are failed by current management, with approximately half not achieving or maintaining appropriate target blood glucose levels, leaving these patients at increased and avoidable risk of serious complications. Review criteria: The methodology of this review article is detailed in the 'Methods' section.

  3. Situational analysis of tuberculosis control programs in the Eastern Mediterranean Region: Gaps and solutions

    Directory of Open Access Journals (Sweden)

    Samiha Baghdadi

    2016-01-01

    Conclusion: The year 2015 marks a transition from the MDGs to the Sustainable Development Goals and from the Stop TB Strategy to the End TB Strategy. The region will move into three main directions: complete pending tasks, mitigate the impact of the complex emergencies on TB control, and move toward TB elimination.

  4. 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.

  5. The control gap : the role of budgets, accounting information and (non-) decisions in hospital settings

    OpenAIRE

    Nyland, Kari; Pettersen, Inger Johanne

    2004-01-01

    This paper investigates the link between budgets, accounting information and the decisionmaking processes at both strategic and operational levels in a large Norwegian hospital, as this hospital now is facing the New Public Management reforms which are introduced in Norway. The study has examined the use of budget and accounting information in the management control process. The empirical data are based on interviews with key actors in the decision-making process at all management levels in t...

  6. A risk perception gap? Comparing expert, producer and consumer prioritization of food hazard controls.

    Science.gov (United States)

    Hartmann, Christina; Hübner, Philipp; Siegrist, Michael

    2018-06-01

    Using a survey approach, the study examined how experts (i.e. food control representatives), producers (i.e. food industry representatives) and consumers prioritized control activities for 28 hazards related to food and other everyday items. The investigated hazards encompassed a wide range of safety issues, including health risks, consumer deception and poor food hygiene behaviour. The participants included 41 experts, 138 producers and 243 consumers from the German- and French-speaking parts of Switzerland. Based on detailed descriptions of the hazards, they were asked to rank these on a score sheet in terms of the perceived importance of monitoring by food control authorities. A between-group comparison of average rankings showed that consumers and experts differed significantly in relation to 17 of the 28 hazards. While the experts assigned higher priority to hazards related to everyday items such as nitrosamine in mascara and chromium VI in leather products, producers and consumers tended to prioritize products related to plant treatment and genetic modification of food and feeds. Producer and consumer rankings of the hazards were highly correlated (r = .96, p < .001). Rankings were also similar among participants from the two cultural regions (i.e. German and French-speaking parts of Switzerland). Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Understanding tobacco control policy at the national level: bridging the gap between public policy and tobacco control advocacy

    Directory of Open Access Journals (Sweden)

    Marc C. Willemsen

    2018-03-01

    Full Text Available Background While some countries have advanced tobacco control policies, other countries struggle to adopt and implement FCTC's measures. This presentation uncovers the main factors that explain such variations, taking insights from public policy and political science as a starting point for a case study. Methods A case study of tobacco control policy making in the Netherlands, covering the period from the 1960s until the present. The study consisted of a systematic search and analysis of documents and proceedings of parliamentary debates on tobacco policy, supplemented with 22 interviews with key informants from the government, health organisations, politicians, and the tobacco industry. In addition, documents from the Truth Tobacco Industry Documents database, pertaining to the influence of the tobacco industry on Dutch policy making, were analysed. Results The Dutch government started relatively late to regulate tobacco. The choices in tobacco control policy making at the national level and the tempo in which they are made are explained by the interaction of the five main elements of the tobacco control policy making process: Relatively stable context factors (constitutional structures, 'rules of the policy making game', national cultural values Relatively dynamic context factors (regime changes, EU regulation and FCTC guidelines, changing social norms, public support Transfer of ideas (availability and interpretation of scientific evidence Pro and anti-tobacco control networks and coalitions (their organisational and lobby strength Agenda-setting (changes in problem definition, issue framing, media advocacy Conclusions Despite worldwide convergence of tobacco control policies, accelerated by the ratification of the FCTC treaty by most nations, governments develop approaches to tobacco control in line with cultural values, ideological preferences and specific national institutional arrangements. There is no one-size-fits-all approach. The

  8. Membrane junctions in xenopus eggs: their distribution suggests a role in calcium regulation

    OpenAIRE

    Gardiner, DM; Grey, RD

    1983-01-01

    We have observed the presence of membrane junctions formed between the plasma membrane and cortical endoplasmic reticulum of mature, unactivated eggs of xenopus laevis. The parallel, paired membranes of the junction are separated by a 10-mn gap within which electron-dense material is present. This material occurs in patches with an average center-to-center distance of approximately 30 nm. These junctions are rare in immature (but fully grown) oocytes (approximately 2 percent of the plasma mem...

  9. Gaps in tobacco control research in accordance with WHO FCTC guidelines: a systematic literature review in Thailand

    Directory of Open Access Journals (Sweden)

    Sarunya Benjakul

    2018-03-01

    Full Text Available Background Evidence-based policy is a term often applied in various field of public health including tobacco control policy. Strengthening evidence -based tobacco control policy development should also base on reliable evidence, in particular research approach. The coverage of tobacco control research under WHO FCTC guidelines is crucial issues. Methods A systematic literature review was conducted for identifying the gaps in tobacco control research. The search for relevant publications was done by the search engine. The key inclusion and exclusion criteria were defined, focusing on published original article conducting in Thai context, both English and Thai language in the past 5 years. The quality of articles was assessed. The text of articles was analyzed based on WHO FCTC articles, at totally 15 articles as well as the 2 nd National Strategic Plan for Tobacco Control 2015 - 2019. Results The initial search resulted in 1,048 abstracts. After applying the inclusion and exclusion criteria for two rounds, 176 original articles were selected for the review. In the article reviewed, the most of WHO FCTC articles applying into the research conceptual framework was article 20 (63.1% with the purpose of gain new knowledge on tobacco harms and effects on health and cross sectional survey design for surveillance tobacco use among various groups. The rest of articles were focused on research related WHO FCTC article 12 (31.0% and article 14 (19.3%. Three articles did not conducted as a research framework, articles 5.3, 9 - 10 and 19. However, those resulted were implemented in specific area, setting and target groups that's not applicable for scaling up. Conclusions The successful transformation of research results to effective tobacco control policy under WHO FCTC depends on various issuers, especially time-based for conducting the research that sufficient to prove the project outcome and appropriate budget for comprehensive research design, coverage

  10. Mind the gap: a flow instability controlled by particle-surface distance

    Science.gov (United States)

    Driscoll, Michelle; Delmotte, Blaise; Youssef, Mena; Sacanna, Stefano; Donev, Aleksandar; Chaikin, Paul

    2016-11-01

    Does a rotating particle always spin in place? Not if that particle is near a surface: rolling leads to translational motion, as well as very strong flows around the particle, even quite far away. These large advective flows strongly couple the motion of neighboring particles, giving rise to strong collective effects in groups of rolling particles. Using a model experimental system, weakly magnetic colloids driven by a rotating magnetic field, we observe that driving a compact group of microrollers leads to a new kind of flow instability. First, an initially uniformly-distributed strip of particles evolves into a shock structure, and then it becomes unstable, emitting fingers with a well-defined wavelength. Using 3D large-scale simulations in tandem with our experiments, we find that the instability wavelength is controlled not by the driving torque or the fluid viscosity, but a geometric parameter: the microroller's distance above the container floor. Furthermore, we find that the instability dynamics can be reproduced using only one ingredient: hydrodynamic interactions near a no-slip boundary.

  11. Band gap control using electric field of photonic gel cells fabricated with block copolymer and hydrogel.

    Science.gov (United States)

    Lee, Sung Nam; Baek, Young Bin; Shin, Dong Myung

    2014-08-01

    Optical and electrical characteristics of the devices using photonic gel film and hydrogel electrolyte were studied. Poly(styrene-b-2-vinylpyridine) (PS-b-P2VP) lamellar film with alternating hydrophobic block and hydrophilic polyelectrolyte block polymers (52 kg/mol-b-57 kg/mol) were prepared for the photonic gel. Poly(isobutylene-co-maleic acid) sodium salts were prepared for the hydrogel. This hydrogel fiber is common water swelling material and it owned ions for a device has conductivity. Photonic gel and hydrogel was spin coating onto Indium-tin-oxide (ITO) glass for make electric fields. The reflectance maximum wavelength of photonic crystal device shifted from 538 nm and reached to 557 nm, 585 nm and 604 nm during 30 min voltage applying time. The bandwidth variation was very limited. Loss of electrolyte was much less with hydrogel compared to the pure water. We can control color of hydrogel used photonic device by electric field with reasonable time range under moderate electric field by applying 2 V between two facing electrodes.

  12. Characterization of double-loop four-Josephson-junction flux qubit

    International Nuclear Information System (INIS)

    Shimazu, Y.; Saito, Y.; Wada, Z.

    2009-01-01

    An advantage of a double-loop four-Josephson-junction (4-JJ) flux qubit is the tunability of the energy gap at a symmetry point, i.e., the point at which the double-well potential of the qubit is symmetric. The energy gap is controlled via the magnetic flux in a DC superconducting quantum interference device (DC-SQUID) loop incorporated in a 4-JJ qubit. We investigate the locus of the symmetry point in the plane of two control fluxes of the qubit, taking into account the asymmetry in the DC-SQUID, which is inevitable in practical cases. The observed positions of the qubit steps are in reasonable agreement with the calculated locus of the symmetry point. We estimate the asymmetry parameter of the DC-SQUID from this analysis.

  13. 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

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

    DEFF Research Database (Denmark)

    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...

  15. Study of the electronic properties of organic molecules within a metal-molecule-metal junction

    International Nuclear Information System (INIS)

    Lambert, Mathieu

    2003-01-01

    This ph-D thesis is about electronic transport through organic molecules inserted in a metal molecule-metal junction. We describe first a simple process to prepare sub-3 nm gaps by controllable breakage (under an electrical stress) of gold wires lithographed on a SiO 2 Si substrate at low temperature (4.2 K). We show that the involved mechanism is thermally assisted electromigration. We observe that current-voltage (I-V) characteristics of resulting electrodes are stable up to ∼5 V. which gives access to the well-known Fowler-Nordheim regime in the I-V, allowing an accurate characterisation of the gap size. The average gap is found lo be between 1.5 nm in width and 2.5 eV in height. Molecules and nanoparticles have then been inserted in the junction in the case of nanoparticles for example. The resulting IV clearly shows the suppression of electrical current at low bias known as Coulomb blockade. Characteristic of single-electron tunnelling through nanometer-sized structures, finally we fabricated a single-electron tunneling device based on Au nanoparticles connected to the electrodes via terthiophene (T3) molecule. We use the silicon substrate, separated from the planar structure by a silicon oxide of 200 nm, as an electrostatic gate and observed clear current modulation with possible signature of the transport properties of the terthiophene molecules. (author) [fr

  16. Thermally controlled mid-IR band-gap engineering in all-glass chalcogenide microstructured fibers: a numerical study

    DEFF Research Database (Denmark)

    Barh, Ajanta; Varshney, Ravi K.; Pal, Bishnu P.

    2017-01-01

    Presence of photonic band-gap (PBG) in an all-glass low refractive index (RI) contrast chalcogenide (Ch) microstructured optical fibers (MOFs) is investigated numerically. The effect of external temperature on the position of band-gap is explored to realize potential fiber-based wavelength filters....... Then the temperature sensitivity of band-gaps is investigated to design fiber-based mid-IR wavelength filters/sensors....

  17. Trauma hemostasis and oxygenation research position paper on remote damage control resuscitation: definitions, current practice, and knowledge gaps.

    Science.gov (United States)

    Jenkins, Donald H; Rappold, Joseph F; Badloe, John F; Berséus, Olle; Blackbourne, Lorne; Brohi, Karim H; Butler, Frank K; Cap, Andrew P; Cohen, Mitchell Jay; Davenport, Ross; DePasquale, Marc; Doughty, Heidi; Glassberg, Elon; Hervig, Tor; Hooper, Timothy J; Kozar, Rosemary; Maegele, Marc; Moore, Ernest E; Murdock, Alan; Ness, Paul M; Pati, Shibani; Rasmussen, Todd; Sailliol, Anne; Schreiber, Martin A; Sunde, Geir Arne; van de Watering, Leo M G; Ward, Kevin R; Weiskopf, Richard B; White, Nathan J; Strandenes, Geir; Spinella, Philip C

    2014-05-01

    The Trauma Hemostasis and Oxygenation Research Network held its third annual Remote Damage Control Resuscitation Symposium in June 2013 in Bergen, Norway. The Trauma Hemostasis and Oxygenation Research Network is a multidisciplinary group of investigators with a common interest in improving outcomes and safety in patients with severe traumatic injury. The network's mission is to reduce the risk of morbidity and mortality from traumatic hemorrhagic shock, in the prehospital phase of resuscitation through research, education, and training. The concept of remote damage control resuscitation is in its infancy, and there is a significant amount of work that needs to be done to improve outcomes for patients with life-threatening bleeding secondary to injury. The prehospital phase of resuscitation is critical in these patients. If shock and coagulopathy can be rapidly identified and minimized before hospital admission, this will very likely reduce morbidity and mortality. This position statement begins to standardize the terms used, provides an acceptable range of therapeutic options, and identifies the major knowledge gaps in the field.

  18. Majorana splitting from critical currents in Josephson junctions

    Science.gov (United States)

    Cayao, Jorge; San-Jose, Pablo; Black-Schaffer, Annica M.; Aguado, Ramón; Prada, Elsa

    2017-11-01

    A semiconducting nanowire with strong Rashba spin-orbit coupling and coupled to a superconductor can be tuned by an external Zeeman field into a topological phase with Majorana zero modes. Here we theoretically investigate how this exotic topological superconductor phase manifests in Josephson junctions based on such proximitized nanowires. In particular, we focus on critical currents in the short junction limit (LN≪ξ , where LN is the junction length and ξ is the superconducting coherence length) and show that they contain important information about nontrivial topology and Majoranas. This includes signatures of the gap inversion at the topological transition and a unique oscillatory pattern that originates from Majorana interference. Interestingly, this pattern can be modified by tuning the transmission across the junction, thus providing complementary evidence of Majoranas and their energy splittings beyond standard tunnel spectroscopy experiments, while offering further tunability by virtue of the Josephson effect.

  19. Niobium nitride Josephson tunnel junctions with magnesium oxide barriers

    International Nuclear Information System (INIS)

    Shoji, A.; Aoyagi, M.; Kosaka, S.; Shinoki, F.; Hayakawa, H.

    1985-01-01

    Niobium nitride-niobium nitride Josephson tunnel junctions have been fabricated using amorphous magnesium oxide (a-MgO) films as barriers. These junctions have excellent tunneling characteristics. For example, a large gap voltage (V/sub g/ = 5.1 mV), a large product of the maximum critical current and the normal tunneling resistance (I/sub c/R/sub n/ = 3.25 mV), and a small subgap leakage current (V/sub m/ = 45 mV, measured at 3 mV) have been obtained for a NbN/a-MgO/NbN junction. The critical current of this junction remains finite up to 14.5 K

  20. Resistance switch employing a simple metal nanogap junction

    International Nuclear Information System (INIS)

    Naitoh, Yasuhisa; Horikawa, Masayo; Abe, Hidekazu; Shimizu, Tetsuo

    2006-01-01

    In recent years, several researchers have reported the occurrence of reversible resistance switching effects in simple metal nanogap junctions. A large negative resistance is observed in the I-V characteristics of such a junction when high-bias voltages are applied. This phenomenon is characteristic behaviour on the nanometre scale; it only occurs for gap widths slightly under 13 nm. Furthermore, such a junction exhibits a non-volatile resistance hysteresis when the bias voltage is reduced very rapidly from a high level to around 0 V, and when the bias voltage is reduced slowly. This non-volatile resistance change occurs as a result of changes in the gap width between the metal electrodes, brought about by the applied bias voltage

  1. Josephson junctions in high-T/sub c/ superconductors

    Science.gov (United States)

    Falco, C.M.; Lee, T.W.

    1981-01-14

    The invention includes a high T/sub c/ Josephson sperconducting junction as well as the method and apparatus which provides the junction by application of a closely controlled and monitored electrical discharge to a microbridge region connecting two portions of a superconducting film.

  2. Fast temporal fluctuations in single-molecule junctions.

    Science.gov (United States)

    Ochs, Roif; Secker, Daniel; Elbing, Mark; Mayor, Marcel; Weber, Heiko B

    2006-01-01

    The noise within the electrical current through single-molecule junctions is studied cryogenic temperature. The organic sample molecules were contacted with the mechanically controlled break-junction technique. The noise spectra refer to a where only few Lorentzian fluctuators occur in the conductance. The frequency dependence shows qualitative variations from sample to sample.

  3. Gap Resolution

    Energy Technology Data Exchange (ETDEWEB)

    2017-04-25

    Gap Resolution is a software package that was developed to improve Newbler genome assemblies by automating the closure of sequence gaps caused by repetitive regions in the DNA. This is done by performing the follow steps:1) Identify and distribute the data for each gap in sub-projects. 2) Assemble the data associated with each sub-project using a secondary assembler, such as Newbler or PGA. 3) Determine if any gaps are closed after reassembly, and either design fakes (consensus of closed gap) for those that closed or lab experiments for those that require additional data. The software requires as input a genome assembly produce by the Newbler assembler provided by Roche and 454 data containing paired-end reads.

  4. 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.

  5. Quantum Junction Solar Cells

    KAUST Repository

    Tang, Jiang; Liu, Huan; Zhitomirsky, David; Hoogland, Sjoerd; Wang, Xihua; Furukawa, Melissa; Levina, Larissa; Sargent, Edward H.

    2012-01-01

    -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

  6. Multiband model for tunneling in MgB2 junctions

    NARCIS (Netherlands)

    Brinkman, Alexander; Golubov, Alexandre Avraamovitch; Rogalla, Horst; Dolgov, O.V.; Kortus, J.; Kong, Y.; Jepsen, O.; Andersen, O.K.

    2002-01-01

    A theoretical model for quasiparticle and Josephson tunneling in multiband superconductors is developed and applied to MgB2-based junctions. The gap functions in different bands in MgB2 are obtained from an extended Eliashberg formalism, using the results of band structure calculations. The

  7. Experimental demonstration of line-width modulation in plasmonic lithography using a solid immersion lens-based active nano-gap control

    International Nuclear Information System (INIS)

    Lee, Won-Sup; Kim, Taeseob; Choi, Guk-Jong; Lim, Geon; Joe, Hang-Eun; Gang, Myeong-Gu; Min, Byung-Kwon; Park, No-Cheol; Moon, Hyungbae; Kim, Do-Hyung; Park, Young-Pil

    2015-01-01

    Plasmonic lithography has been used in nanofabrication because of its utility beyond the diffraction limit. The resolution of plasmonic lithography depends on the nano-gap between the nanoaperture and the photoresist surface—changing the gap distance can modulate the line-width of the pattern. In this letter, we demonstrate solid-immersion lens based active non-contact plasmonic lithography, applying a range of gap conditions to modulate the line-width of the pattern. Using a solid-immersion lens-based near-field control system, the nano-gap between the exit surface of the nanoaperture and the media can be actively modulated and maintained to within a few nanometers. The line-widths of the recorded patterns using 15- and 5-nm gaps were 47 and 19.5 nm, respectively, which matched closely the calculated full-width at half-maximum. From these results, we conclude that changing the nano-gap within a solid-immersion lens-based plasmonic head results in varying line-width patterns

  8. 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)

  9. Magnetic resonance imaging zygapophyseal joint space changes (gapping) in low back pain patients following spinal manipulation and side-posture positioning: a randomized controlled mechanisms trial with blinding.

    Science.gov (United States)

    Cramer, Gregory D; Cambron, Jerrilyn; Cantu, Joe A; Dexheimer, Jennifer M; Pocius, Judith D; Gregerson, Douglas; Fergus, Michael; McKinnis, Ray; Grieve, Thomas J

    2013-05-01

    The purpose of this study was to quantify lumbar zygapophyseal (Z) joint space separation (gapping) in low back pain (LBP) subjects after spinal manipulative therapy (SMT) or side-posture positioning (SPP). This was a controlled mechanisms trial with randomization and blinding. Acute LBP subjects (N = 112; four n = 28 magnetic resonance imaging [MRI] protocol groups) had 2 MRI appointments (initial enrollment and after 2 weeks of chiropractic treatment, receiving 2 MRI scans of the L4/L5 and L5/S1 Z joints at each MRI appointment. After the first MRI scan of each appointment, subjects were randomized (initial enrollment appointment) or assigned (after 2 weeks of chiropractic treatment appointment) into SPP (nonmanipulation), SMT (manipulation), or control MRI protocol groups. After SPP or SMT, a second MRI was taken. The central anterior-posterior joint space was measured. Difference between most painful side anterior-posterior measurements taken postintervention and preintervention was the Z joint "gapping difference." Gapping differences were compared (analysis of variance) among protocol groups. Secondary measures of pain (visual analog scale, verbal numeric pain rating scale) and function (Bournemouth questionnaire) were assessed. Gapping differences were significant at the first (adjusted, P = .009; SPP, 0.66 ± 0.48 mm; SMT, 0.23 ± 0.86; control, 0.18 ± 0.71) and second (adjusted, P = .0005; SPP, 0.65 ± 0.92 mm; SMT, 0.89 ± 0.71; control, 0.35 ± 0.32) MRI appointments. Verbal numeric pain rating scale differences were significant at first MRI appointment (P = .04) with SMT showing the greatest improvement. Visual analog scale and Bournemouth questionnaire improved after 2 weeks of care in all groups (both P posture positioning showed greatest gapping at baseline. After 2 weeks, SMT resulted in greatest gapping. Side-posture positioning appeared to have additive therapeutic benefit to SMT. Copyright © 2013 National University of Health Sciences

  10. Ultra-low switching energy and scaling in electric-field-controlled nanoscale magnetic tunnel junctions with high resistance-area product

    Energy Technology Data Exchange (ETDEWEB)

    Grezes, C.; Alzate, J. G.; Cai, X.; Wang, K. L. [Department of Electrical Engineering, University of California, Los Angeles, California 90095 (United States); Ebrahimi, F.; Khalili Amiri, P. [Department of Electrical Engineering, University of California, Los Angeles, California 90095 (United States); Inston, Inc., Los Angeles, California 90024 (United States); Katine, J. A. [HGST, Inc., San Jose, California 95135 (United States); Langer, J.; Ocker, B. [Singulus Technologies AG, Kahl am Main 63796 (Germany)

    2016-01-04

    We report electric-field-induced switching with write energies down to 6 fJ/bit for switching times of 0.5 ns, in nanoscale perpendicular magnetic tunnel junctions (MTJs) with high resistance-area product and diameters down to 50 nm. The ultra-low switching energy is made possible by a thick MgO barrier that ensures negligible spin-transfer torque contributions, along with a reduction of the Ohmic dissipation. We find that the switching voltage and time are insensitive to the junction diameter for high-resistance MTJs, a result accounted for by a macrospin model of purely voltage-induced switching. The measured performance enables integration with same-size CMOS transistors in compact memory and logic integrated circuits.

  11. Membrane junctions in Xenopus eggs: their distribution suggests a role in calcium regulation.

    Science.gov (United States)

    Gardiner, D M; Grey, R D

    1983-04-01

    We have observed the presence of membrane junctions formed between the plasma membrane and cortical endoplasmic reticulum of mature, unactivated eggs of xenopus laevis. The parallel, paired membranes of the junction are separated by a 10-mn gap within which electron-dense material is present. This material occurs in patches with an average center-to-center distance of approximately 30 nm. These junctions are rare in immature (but fully grown) oocytes (approximately 2 percent of the plasma membrane is associated with junctions) and increase dramatically during progesterone-induced maturation. Junctions in the mature, unactivated egg are two to three times more abundant in the animal hemisphere (25-30 percent of the plasma membrane associated with junction) as compared with the vegetal hemisphere (10-15 percent). Junction density decreases rapidly to values characteristic of immature oocytes in response to egg activation. The plasma membrane-ER junctions of xenopus eggs are strikingly similar in structure to membrane junctions in muscle cells thought to be essential in the triggering of intracellular calcium release from the sarcoplasmic reticulum. In addition, the junctions' distinctive, animal-vegetal polarity of distribution, their dramatic appearance during maturation, and their disapperance during activation are correlated with previously documented patterns of calcium-mediated events in anuran eggs. We discuss several lines of evidence supporting the hypothesis that these junctions in xenopus eggs are sites that transduce extracellular events into intracellular calcium release during fertilization and activation of development.

  12. The role of remote closure in the perception of occlusion at junctions and illusory contours.

    Science.gov (United States)

    Gillam, Barbara J; Grove, Philip M; Layden, Jessica

    2010-01-01

    Abstract. Perceived occlusion at T-junctions or illusory contours at implicit T-junctions are often modelled by using edge information without surface context. We explored the effect of closure on perceived occlusion at T-junctions. Two vertical lines separated by a gap each had six abutting horizontal lines on opposite sides forming T-junctions. These lines were either closed or not closed into pairs at the stem ends of the Ts. In experiment 1, closed T-junction stems gave a much stronger sense of occlusion at the vertical lines than unclosed ones, even though closure information was remote from the putative occlusion and local T-junction information remained constant. When the outer two T-junctions were converted to L-junctions, perceived occlusion considerably diminished. The effect of closure on illusory-contour strength for stimuli like those of experiment 1 but with the vertical lines omitted was explored in experiment 2. The two sets of horizontal lines, separated by a gap, were either closed or not closed into pairs at their outer ends. Illusory-contour strength along the vertical alignments was much greater for closed pairs. Line terminations on both sides of the gap enhanced illusory-contour strength, but whether they were collinear or not had little effect.

  13. Mythic gaps

    Directory of Open Access Journals (Sweden)

    William Hansen

    2014-11-01

    Full Text Available Different kinds of omissions sometimes occur, or are perceived to occur, in traditional narratives and in tradition-inspired literature. A familiar instance is when a narrator realizes that he or she does not fully remember the story that he or she has begun to tell, and so leaves out part of it, which for listeners may possibly result in an unintelligible narrative. But many instances of narrative gap are not so obvious. From straightforward, objective gaps one can distinguish less-obvious subjective gaps: in many cases narrators do not leave out anything crucial or truly relevant from their exposition, and yet readers perceive gaps and take steps to fill them. The present paper considers four examples of subjective gaps drawn from ancient Greek literature (the Pandora myth, ancient Roman literature (the Pygmalion legend, ancient Hebrew literature (the Joseph legend, and early Christian literature (the Jesus legend. I consider the quite varied ways in which interpreters expand the inherited texts of these stories, such as by devising names, manufacturing motives, creating backstories, and in general filling in biographical ellipses. Finally, I suggest an explanation for the phenomenon of subjective gaps, arguing that, despite their variety, they have a single cause.

  14. Josephson junctions array resonators

    Energy Technology Data Exchange (ETDEWEB)

    Gargiulo, Oscar; Muppalla, Phani; Mirzaei, Iman; Kirchmair, Gerhard [Institute for Quantum Optics and Quantum Information, Innsbruck (Austria)

    2016-07-01

    We present an experimental analysis of the self- and cross-Kerr effect of extended plasma resonances in Josephson junction chains. The chain consists of 1600 individual junctions and we can measure quality factors in excess of 10000. The Kerr effect manifests itself as a frequency shift that depends linearly on the number of photons in a resonant mode. By changing the input power we are able to measure this frequency shift on a single mode (self-kerr). By changing the input power on another mode while measuring the same one, we are able to evaluate the cross-kerr effect. We can measure the cross-Kerr effect by probing the resonance frequency of one mode while exciting another mode of the array with a microwave drive.

  15. 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.

  16. Tunneling Spectroscopy of the Energy Gap in MgB2 Under Magnetic Fields

    International Nuclear Information System (INIS)

    Ekino, T.; Takasaki, T.; Fujii, H.; Muranaka, T.; Akimitsu, J.

    2003-01-01

    Effects of magnetic field on the multiple-gap structure in the superconductor MgB 2 have been studied by break junctions. With increasing the field, the gap value decreases with filling up of the states inside of the gap. The gap-closing field B c correlates with the gap size. The extrapolated B c value for the larger gap is almost consistent with the upper critical field of this compound. (author)

  17. The impact of gap duration on local control in anal canal carcinoma treated by split-course radiotherapy and concomitant chemotherapy

    International Nuclear Information System (INIS)

    Weber, Damien C.; Kurtz, John M.; Allal, Abdelkarim S.

    2001-01-01

    Purpose: To investigate the potential benefit of reducing the intersequence gap in patients with anal cancer treated with split-course chemoradiotherapy. Methods: The study group consisted of 90 patients with anal squamous carcinoma treated between 1981 and 1998, using concomitant chemotherapy (CT) and radiation (RT). Median age was 65 years (range 41-87). RT was delivered in a split course, with a median gap of 37.5 days (range 4-97) between sequences. First (pelvic) sequence delivered a median dose of 40 Gy (range 36-50.4), using AP/PA megavoltage photon beams. Boost treatment (median dose 20 Gy, range 13-26) consisted of either Iridium-192 implantation (49 patients) or external beam RT (41 patients). CT consisted of 1-2 cycles of a 5-day continuous infusion of 5-fluorouracil and bolus mitomycin C, usually administered during the first week of each RT course. Median follow-up was 76.2 months. Univariate and multivariate analyses were performed to determine the factors associated with locoregional control (LRC). Results: Five-year actuarial LRC was 72.5%. Factors associated with poorer LRC (univariate) were: age ≤65, male gender, and gap >37.5 days. Number of CT cycles (1 vs. 2 or more), boost technique (brachytherapy vs. external), and T-stage were not significantly associated with LRC. In multivariate analysis, only age (p=0.01), and gap (p=0.02) retained their significance. In patients older than 65 years, LRC was 92.3% and 75% for shorter and longer gaps, respectively. In younger patients, the corresponding values for LRC were 73.7% and 50%. Conclusion: In anal cancers, split-course RT with >50 Gy dose delivery is difficult to avoid because of acute toxicity. The present analysis suggests that shortening the gap contributes to optimizing LRC. Gaps longer than 5 weeks correlated with poorer LRC, with especially unsatisfactory results observed in younger patients

  18. Many-junction photovoltaic device performance under non-uniform high-concentration illumination

    Science.gov (United States)

    Valdivia, Christopher E.; Wilkins, Matthew M.; Chahal, Sanmeet S.; Proulx, Francine; Provost, Philippe-Olivier; Masson, Denis P.; Fafard, Simon; Hinzer, Karin

    2017-09-01

    A parameterized 3D distributed circuit model was developed to calculate the performance of III-V solar cells and photonic power converters (PPC) with a variable number of epitaxial vertically-stacked pn junctions. PPC devices are designed with many pn junctions to realize higher voltages and to operate under non-uniform illumination profiles from a laser or LED. Performance impacts of non-uniform illumination were greatly reduced with increasing number of junctions, with simulations comparing PPC devices with 3 to 20 junctions. Experimental results using Azastra Opto's 12- and 20-junction PPC illuminated by an 845 nm diode laser show high performance even with a small gap between the PPC and optical fiber output, until the local tunnel junction limit is reached.

  19. Association of visceral adiposity with oesophageal and junctional adenocarcinomas.

    LENUS (Irish Health Repository)

    Beddy, P

    2012-02-01

    BACKGROUND: Obesity is associated with an increased incidence of oesophageal and oesophagogastric junction adenocarcinoma, in particular Siewert types I and II. This study compared abdominal fat composition in patients with oesophageal\\/junctional adenocarcinoma with that in patients with oesophageal squamous cell carcinoma and gastric adenocarcinoma, and in controls. METHOD: In total, 194 patients (110 with oesophageal\\/junctional adenocarcinoma, 38 with gastric adenocarcinoma and 46 with oesophageal squamous cell carcinoma) and 90 matched control subjects were recruited. The abdominal fat area was assessed using computed tomography (CT), and the total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were calculated. RESULTS: Patients with oesophageal\\/junctional adenocarcinoma had significantly higher TFA and VFA values compared with controls (both P < 0.001), patients with gastric adenocarcinoma (P = 0.013 and P = 0.006 respectively) and patients with oesophageal squamous cell carcinoma (both P < 0.001). For junctional tumours, the highest TFA and VFA values were seen in patients with Siewert type I tumours (respectively P = 0.041 and P = 0.033 versus type III; P = 0.332 and P = 0.152 versus type II). CONCLUSION: Patients with oesophageal\\/junctional adenocarcinoma, in particular oesophageal and Siewert type I junctional tumours, have greater CT-defined visceral adiposity than patients with gastric adenocarcinoma or oesophageal squamous cell carcinoma, or controls.

  20. Intraepithelial lymphocytes express junctional molecules in murine small intestine