High-efficiency thermal switch based on topological Josephson junctions

NASA Astrophysics Data System (ADS)

Sothmann, Björn; Giazotto, Francesco; Hankiewicz, Ewelina M.

2017-02-01

We propose theoretically a thermal switch operating by the magnetic-flux controlled diffraction of phase-coherent heat currents in a thermally biased Josephson junction based on a two-dimensional topological insulator. For short junctions, the system shows a sharp switching behavior while for long junctions the switching is smooth. Physically, the switching arises from the Doppler shift of the superconducting condensate due to screening currents induced by a magnetic flux. We suggest a possible experimental realization that exhibits a relative temperature change of 40% between the on and off state for realistic parameters. This is a factor of two larger than in recently realized thermal modulators based on conventional superconducting tunnel junctions.

Endothelial connexin 32 regulates tissue factor expression induced by inflammatory stimulation and direct cell-cell interaction with activated cells.

PubMed

Okamoto, Takayuki; Akita, Nobuyuki; Hayashi, Tatsuya; Shimaoka, Motomu; Suzuki, Koji

2014-10-01

Endothelial cell (EC) interacts with adjacent EC through gap junction, and abnormal expression or function of Cxs is associated with cardiovascular diseases. In patients with endothelial dysfunction, the up-regulation of tissue factor (TF) expression promotes the pathogenic activation of blood coagulation, however the relationship between gap junctions and TF expression in ECs remains uncharacterized. ECs express the gap junction (GJ) proteins connexin32 (Cx32), Cx37, Cx40 and Cx43. We investigated the role of endothelial gap junctions, particularly Cx32, in modulating TF expression during vascular inflammation. Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor-α (TNF-α) and TF activity was assessed in the presence of GJ blockers and an inhibitory anti-Cx32 monoclonal antibody. Treatment with GJ blockers and anti-Cx32 monoclonal antibody enhanced the TNF-α-induced TF activity and mRNA expression in HUVECs. TNF-α-activated effector HUVECs or mouse MS-1 cells were co-cultured with non-stimulated acceptor HUVECs and TF expression in acceptor HUVECs was detected. Effector EC induced TF expression in adjacent acceptor HUVECs through direct cell-cell interaction. Cell-cell interaction induced TF expression was reduced by anti-intercellular adhesion molecule-1 (ICAM1) monoclonal antibody. Soluble ICAM1-Fc fusion protein promotes TF expression. GJ blockers and anti-Cx32 monoclonal antibody enhanced TF expression induced by cell-cell interaction and ICAM1-Fc treatment. Blockade of endothelial Cx32 increased TF expression induced by TNF-α stimulation and cell-cell interaction which was at least partly dependent upon ICAM1. These results suggest that direct Cx32-mediated interaction modulates TF expression in ECs during vascular inflammation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Imaging charge carriers in potential-induced degradation defects of c-Si solar cells by scanning capacitance microscopy

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

Jiang, C. -S.; Xiao, C.; Moutinho, H. R.

We report on nm-resolution imaging of charge-carrier distribution around local potential-induced degradation (PID) shunting defects using scanning capacitance microscopy. We imaged on cross sections of heavily field-degraded module areas, cored out and selected by mm-scale photoluminescence imaging. We found localized areas with abnormal carrier behavior induced by the PID defects: the apparent n-type carrier extends vertically into the absorber to ~1-2 um from the cell surface, and laterally in similar lengths; in defect-free areas, the n-type carrier extends ~0.5 um, which is consistent with the junction depth. For comparison, we also investigated areas of the same module exhibiting the leastmore » PID stress, and we found no such heavily damaged junction area. Instead, we found slightly abnormal carrier behavior, where the carrier-type inversion in the absorber did not occur, but the p-type carrier concentration changed slightly in a much smaller lateral length of ~300 nm. These nano-electrical findings may indicate a possible mechanism that the existing extended defects, which may not be significantly harmful to cell performance, can be changed by PID to heavily damaged junction areas.« less

Imaging charge carriers in potential-induced degradation defects of c-Si solar cells by scanning capacitance microscopy

DOE PAGES

Jiang, C. -S.; Xiao, C.; Moutinho, H. R.; ...

2018-02-13

We report on nm-resolution imaging of charge-carrier distribution around local potential-induced degradation (PID) shunting defects using scanning capacitance microscopy. We imaged on cross sections of heavily field-degraded module areas, cored out and selected by mm-scale photoluminescence imaging. We found localized areas with abnormal carrier behavior induced by the PID defects: the apparent n-type carrier extends vertically into the absorber to ~1-2 um from the cell surface, and laterally in similar lengths; in defect-free areas, the n-type carrier extends ~0.5 um, which is consistent with the junction depth. For comparison, we also investigated areas of the same module exhibiting the leastmore » PID stress, and we found no such heavily damaged junction area. Instead, we found slightly abnormal carrier behavior, where the carrier-type inversion in the absorber did not occur, but the p-type carrier concentration changed slightly in a much smaller lateral length of ~300 nm. These nano-electrical findings may indicate a possible mechanism that the existing extended defects, which may not be significantly harmful to cell performance, can be changed by PID to heavily damaged junction areas.« less

Reactive tunnel junctions in electrically driven plasmonic nanorod metamaterials

NASA Astrophysics Data System (ADS)

Wang, Pan; Krasavin, Alexey V.; Nasir, Mazhar E.; Dickson, Wayne; Zayats, Anatoly V.

2018-02-01

Non-equilibrium hot carriers formed near the interfaces of semiconductors or metals play a crucial role in chemical catalysis and optoelectronic processes. In addition to optical illumination, an efficient way to generate hot carriers is by excitation with tunnelling electrons. Here, we show that the generation of hot electrons makes the nanoscale tunnel junctions highly reactive and facilitates strongly confined chemical reactions that can, in turn, modulate the tunnelling processes. We designed a device containing an array of electrically driven plasmonic nanorods with up to 1011 tunnel junctions per square centimetre, which demonstrates hot-electron activation of oxidation and reduction reactions in the junctions, induced by the presence of O2 and H2 molecules, respectively. The kinetics of the reactions can be monitored in situ following the radiative decay of tunnelling-induced surface plasmons. This electrically driven plasmonic nanorod metamaterial platform can be useful for the development of nanoscale chemical and optoelectronic devices based on electron tunnelling.

Flexible substrate based 2D ZnO (n)/graphene (p) rectifying junction as enhanced broadband photodetector using strain modulation

NASA Astrophysics Data System (ADS)

Sahatiya, Parikshit; Jones, S. Solomon; Thanga Gomathi, P.; Badhulika, Sushmee

2017-06-01

Strain modulation is considered to be an effective way to modulate the electronic structure and carrier behavior in flexible semiconductors heterojunctions. In this work, 2D Graphene (Gr)/ZnO junction was successfully fabricated on flexible eraser substrate using simple, low-cost solution processed hydrothermal method and has been utilized for broadband photodetection in the UV to visible range at room temperature. Optimization in terms of process parameters were done to obtain 2D ZnO over 2D graphene which shows decrease in bandgap and broad absorption range from UV to visible. Under compressive strain piezopotential induced by the atoms displacements in 2D ZnO, 87% enhanced photosensing for UV light was observed under 30% strain. This excellent performance improvement can be attributed to piezopotential induced under compressive strain in 2D ZnO which results in lowering of conduction band energy and raising the schottky barrier height thereby facilitating electron-hole pair separation in 2D Gr/ZnO junction. Detailed mechanism studies in terms of density of surface states and energy band diagram is presented to understand the proposed phenomena. Results provide an excellent approach for improving the optoelectronic performance of 2D Gr/ZnO interface which can also be applied to similar semiconductor heterojunctions.

p - n Junction Dynamics Induced in a Graphene Channel by Ferroelectric-Domain Motion in the Substrate

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

Kurchak, Anatolii I.; Eliseev, Eugene A.; Kalinin, Sergei V.

The p - n junction dynamics induced in a graphene channel by stripe-domain nucleation, motion, and reversal in a ferroelectric substrate is explored using a self-consistent approach based on Landau-Ginzburg-Devonshire phenomenology combined with classical electrostatics. Relatively low gate voltages are required to induce the hysteresis of ferroelectric polarization and graphene charge in response to the periodic gate voltage. Pronounced nonlinear hysteresis of graphene conductance with a wide memory window corresponds to high amplitudes of gate voltage. Also, we reveal the extrinsic size effect in the dependence of the graphene-channel conductivity on its length. We predict that the top-gate–dielectric-layer–graphene-channel–ferroelectric-substrate nanostructure consideredmore » here can be a promising candidate for the fabrication of the next generation of modulators and rectifiers based on the graphene p - n junctions.« less

Smad ubiquitination regulatory factor-2 controls gap junction intercellular communication by modulating endocytosis and degradation of connexin43.

PubMed

Fykerud, Tone Aase; Kjenseth, Ane; Schink, Kay Oliver; Sirnes, Solveig; Bruun, Jarle; Omori, Yasufumi; Brech, Andreas; Rivedal, Edgar; Leithe, Edward

2012-09-01

Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junction channels are made of a family of integral membrane proteins called connexins, of which the best-studied member is connexin43. Gap junctions are dynamic plasma membrane domains, and connexin43 has a high turnover rate in most tissue types. However, the mechanisms involved in the regulation of connexin43 endocytosis and transport to lysosomes are still poorly understood. Here, we demonstrate by live-cell imaging analysis that treatment of cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) induces endocytosis of subdomains of connexin43 gap junctions. The internalized, connexin43-enriched vesicles were found to fuse with early endosomes, which was followed by transport of connexin43 to the lumen of early endosomes. The HECT E3 ubiquitin ligase smad ubiquitination regulatory factor-2 (Smurf2) was found to be recruited to connexin43 gap junctions in response to TPA treatment. Depletion of Smurf2 by small interfering RNA resulted in enhanced levels of connexin43 gap junctions between adjacent cells and increased gap junction intercellular communication. Smurf2 depletion also counteracted the TPA-induced endocytosis and degradation of connexin43. Collectively, these data identify Smurf2 as a novel regulator of connexin43 gap junctions.

Behavioral data of thin-film single junction amorphous silicon (a-Si) photovoltaic modules under outdoor long term exposure

PubMed Central

Kichou, Sofiane; Silvestre, Santiago; Nofuentes, Gustavo; Torres-Ramírez, Miguel; Chouder, Aissa; Guasch, Daniel

2016-01-01

Four years׳ behavioral data of thin-film single junction amorphous silicon (a-Si) photovoltaic (PV) modules installed in a relatively dry and sunny inland site with a Continental-Mediterranean climate (in the city of Jaén, Spain) are presented in this article. The shared data contributes to clarify how the Light Induced Degradation (LID) impacts the output power generated by the PV array, especially in the first days of exposure under outdoor conditions. Furthermore, a valuable methodology is provided in this data article permitting the assessment of the degradation rate and the stabilization period of the PV modules. Further discussions and interpretations concerning the data shared in this article can be found in the research paper “Characterization of degradation and evaluation of model parameters of amorphous silicon photovoltaic modules under outdoor long term exposure” (Kichou et al., 2016) [1]. PMID:26977439

Morphological adaptation and protein modulation of myotendinous junction following moderate aerobic training.

PubMed

Curzi, Davide; Baldassarri, Valentina; De Matteis, Rita; Salamanna, Francesca; Bolotta, Alessandra; Frizziero, Antonio; Fini, Milena; Marini, Marina; Falcieri, Elisabetta

2015-04-01

Myotendinous junction is the muscle-tendon interface through which the contractile force can be transferred from myofibrils to the tendon extracellular matrix. At the ultrastructural level, aerobic training can modify the distal myotendinous junction of rat gastrocnemius, increasing the contact area between tissues. The aim of this work is to investigate the correlation between morphological changes and protein modulation of the myotendinous junction following moderate training. For this reason, talin, vinculin and type IV collagen amount and spatial distribution were investigated by immunohistochemistry and confocal microscopy. The images were then digitally analyzed by evaluating fluorescence intensity. Morphometric analysis revealed a significant increased thickening of muscle basal lamina in the trained group (53.1 ± 0.4 nm) with respect to the control group (43.9 ± 0.3 nm), and morphological observation showed the presence of an electron-dense area in the exercised muscles, close to the myotendinous junction. Protein concentrations appeared significantly increased in the trained group (talin +22.2%; vinculin +22.8% and type IV collagen +11.8%) with respect to the control group. Therefore, our findings suggest that moderate aerobic training induces/causes morphological changes at the myotendinous junction, correlated to the synthesis of structural proteins of the muscular basal lamina and of the cytoskeleton.

Laser-assisted electron tunneling in a STM junction

NASA Astrophysics Data System (ADS)

Chang, Shunhua Thomas

2000-10-01

Since its introduction in 1981, the Nobel prize-winning scanning tunneling microscope (STM) has been developed into a powerful yet conceptually simple instrument, replacing traditional scanning and transmission electron microscopes (SEM/TEM) in many of the microscopic surface phenomenon studies. The strength of the STM stems from the sensitive tunneling current-potential barrier width relationship of the electron tunneling process, and has been used to re-examine the frequency-mixing and harmonic generation properties of an non-linear metal- oxide-metal (MOM) tunneling junction. In this research, electron-tunneling events under polarized laser radiation at 514.5-nm argon and 10.6-μm carbon dioxide laser wavelengths were investigated. The objective is to understand the underlying interactive mechanisms between the tunneling junction and the external laser excitation. A commercial scanning tunneling microscope head and controller were incorporated into the experimental setup. Operation characteristics and the electrical properties of the STM junction were determined. Tunneling current and distance responses with respect to different laser polarization, modulation frequency, incident power, and tunneling distance were also conducted. From the experimental results it is shown that thermal expansion effect was the dominant source of response for laser modulation frequency up to about 100 kHz, in quantitative agreement with theoretical calculations. Different laser polarizations as the experiments demonstrated did not contribute significantly to the STM response in the investigated frequency range. The electric field induced by the laser beam was calculated to be one to two order of magnitudes lower than the field required to initiate field emission where the tunneling junction I- V curve is most non-linear. Also, the electrical coupling of the incident laser at the STM junction was determined to be non-critical at visible laser wavelength, and the reflected laser energy from the sample re-entering the junction was shown to be weak and did not influence the ongoing electron tunneling process. In conclusion, the thermal expansion of the physical tunneling junction was found to be responsible to the tunneling current modulation in a laser - STM setup for laser modulation frequencies in the lower frequency range.

Activity-Induced Synaptic Structural Modifications by an Activator of Integrin Signaling at the Drosophila Neuromuscular Junction.

PubMed

Lee, Joo Yeun; Geng, Junhua; Lee, Juhyun; Wang, Andrew R; Chang, Karen T

2017-03-22

Activity-induced synaptic structural modification is crucial for neural development and synaptic plasticity, but the molecular players involved in this process are not well defined. Here, we report that a protein named Shriveled (Shv) regulates synaptic growth and activity-dependent synaptic remodeling at the Drosophila neuromuscular junction. Depletion of Shv causes synaptic overgrowth and an accumulation of immature boutons. We find that Shv physically and genetically interacts with βPS integrin. Furthermore, Shv is secreted during intense, but not mild, neuronal activity to acutely activate integrin signaling, induce synaptic bouton enlargement, and increase postsynaptic glutamate receptor abundance. Consequently, loss of Shv prevents activity-induced synapse maturation and abolishes post-tetanic potentiation, a form of synaptic plasticity. Our data identify Shv as a novel trans-synaptic signal secreted upon intense neuronal activity to promote synapse remodeling through integrin receptor signaling. SIGNIFICANCE STATEMENT The ability of neurons to rapidly modify synaptic structure in response to neuronal activity, a process called activity-induced structural remodeling, is crucial for neuronal development and complex brain functions. The molecular players that are important for this fundamental biological process are not well understood. Here we show that the Shriveled (Shv) protein is required during development to maintain normal synaptic growth. We further demonstrate that Shv is selectively released during intense neuronal activity, but not mild neuronal activity, to acutely activate integrin signaling and trigger structural modifications at the Drosophila neuromuscular junction. This work identifies Shv as a key modulator of activity-induced structural remodeling and suggests that neurons use distinct molecular cues to differentially modulate synaptic growth and remodeling to meet synaptic demand. Copyright © 2017 the authors 0270-6474/17/373246-18$15.00/0.

New insights into the fundamental role of topological constraints as a determinant of two-way junction conformation

PubMed Central

Mustoe, Anthony M.; Bailor, Maximillian H.; Teixeira, Robert M.; Brooks, Charles L.; Al-Hashimi, Hashim M.

2012-01-01

Recent studies have shown that topological constraints encoded at the RNA secondary structure level involving basic steric and stereochemical forces can significantly restrict the orientations sampled by helices across two-way RNA junctions. Here, we formulate these topological constraints in greater quantitative detail and use this topological framework to rationalize long-standing but poorly understood observations regarding the basic behavior of RNA two-way junctions. Notably, we show that the asymmetric nature of the A-form helix and the finite length of a bulge provide a physical basis for the experimentally observed directionality and bulge-length amplitude dependence of bulge induced inter-helical bends. We also find that the topologically allowed space can be modulated by variations in sequence, particularly with the addition of non-canonical GU base pairs at the junction, and, surprisingly, by the length of the 5′ and 3′ helices. A survey of two-way RNA junctions in the protein data bank confirms that junction residues have a strong preference to adopt looped-in, non-canonically base-paired conformations, providing a route for extending our bulge-directed framework to internal loop motifs and implying a simplified link between secondary and tertiary structure. Finally, our results uncover a new simple mechanism for coupling junction-induced topological constraints with tertiary interactions. PMID:21937512

Electric field-induced ferromagnetic resonance in a CoFeB/MgO magnetic tunnel junction under dc bias voltages

NASA Astrophysics Data System (ADS)

Kanai, Shun; Gajek, Martin; Worledge, D. C.; Matsukura, Fumihiro; Ohno, Hideo

2014-12-01

We measure homodyne-detected ferromagnetic resonance (FMR) induced by the electric-field effect in a CoFeB/MgO/CoFeB magnetic tunnel junction (MTJ) with perpendicular magnetic easy axis under dc bias voltages up to 0.1 V. From the bias dependence of the resonant frequency, we find that the first order perpendicular magnetic anisotropy is modulated by the applied electric field, whereas the second order component is virtually independent of the electric field. The lineshapes of the FMR spectra are bias dependent, which are explained by the combination of electric-field effect and reflection of the bias voltage from the MTJ.

The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction.

PubMed

Obis, Teresa; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Priego, Mercedes; Simon, Anna; Garcia, Neus; Santafe, Manel M; Lanuza, Maria A; Tomàs, Josep

2015-12-01

Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction. We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3',5'-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion. Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction.

Formation of a PKCζ/β-catenin complex in endothelial cells promotes angiopoietin-1–induced collective directional migration and angiogenic sprouting

PubMed Central

Oubaha, Malika; Lin, Michelle I.; Margaron, Yoran; Filion, Dominic; Price, Emily N.; Zon, Leonard I.; Côté, Jean-François

2012-01-01

Angiogenic sprouting requires that cell-cell contacts be maintained during migration of endothelial cells. Angiopoietin-1 (Ang-1) and vascular endothelial growth factor act oppositely on endothelial cell junctions. We found that Ang-1 promotes collective and directional migration and, in contrast to VEGF, induces the formation of a complex formed of atypical protein kinase C (PKC)-ζ and β-catenin at cell-cell junctions and at the leading edge of migrating endothelial cells. This complex brings Par3, Par6, and adherens junction proteins at the front of migrating cells to locally activate Rac1 in response to Ang-1. The colocalization of PKCζ and β-catenin at leading edge along with PKCζ-dependent stabilization of cell-cell contacts promotes directed and collective endothelial cell migration. Consistent with these results, down-regulation of PKCζ in endothelial cells alters Ang-1–induced sprouting in vitro and knockdown in developing zebrafish results in intersegmental vessel defects caused by a perturbed directionality of tip cells and by loss of cell contacts between tip and stalk cells. These results reveal that PKCζ and β-catenin function in a complex at adherens junctions and at the leading edge of migrating endothelial cells to modulate collective and directional migration during angiogenesis. PMID:22936663

Implanted neural progenitor cells regulate glial reaction to brain injury and establish gap junctions with host glial cells.

PubMed

Talaverón, Rocío; Matarredona, Esperanza R; de la Cruz, Rosa R; Macías, David; Gálvez, Victoria; Pastor, Angel M

2014-04-01

Transplantation of neural stem/progenitor cells (NPCs) in the lesioned brain is able to restore morphological and physiological alterations induced by different injuries. The local microenvironment created at the site of grafting and the communication between grafted and host cells are crucial in the beneficial effects attributed to the NPC implants. We have previously described that NPC transplantation in an animal model of central axotomy restores firing properties and synaptic coverage of lesioned neurons and modulates their trophic factor content. In this study, we aim to explore anatomical relationships between implanted NPCs and host glia that might account for the implant-induced neuroprotective effects. Postnatal rat subventricular zone NPCs were isolated and grafted in adult rats after transection of the medial longitudinal fascicle. Brains were removed and analyzed eight weeks later. Immunohistochemistry for different glial markers revealed that NPC-grafted animals displayed significantly greater microglial activation than animals that received only vehicle injections. Implanted NPCs were located in close apposition to activated microglia and reactive astrocytes. The gap junction protein connexin43 was present in NPCs and glial cells at the lesion site and was often found interposed within adjacent implanted and glial cells. Gap junctions were identified between implanted NPCs and host astrocytes and less frequently between NPCs and microglia. Our results show that implanted NPCs modulate the glial reaction to lesion and establish the possibility of communication through gap junctions between grafted and host glial cells which might be involved in the restorative effects of NPC implants. Copyright © 2014 Wiley Periodicals, Inc.

Distinct photoresponse in graphene induced by laser irradiation and interfacial gating.

NASA Astrophysics Data System (ADS)

Wang, Wenhui; Guo, Xitao; Nan, Haiyan; Ni, Zhenhua; Spectroscopy; Optoelectronics Group Team

Graphene-based photodetectors have recently received much attention due to its unique optical and electronic properties. The photoresponse modulation plays a crucial role in the study of photocurrent generation mechanism and optoelectronic applications. Here, the tunable p-p +-p junctions of graphene were fabricated through simple laser irradiation process. Distinct photoresponse was observed at the graphene (G)-laser irradiation graphene (LIG) junction. Detailed investigation suggests that the photo-thermoelectric effect, instead of the photovoltaic effect, dominates the photocurrent generation at the G-LIG junction. On the other hand, the localized interface states, existing at the silicon dioxide/lightly doped Si interface, would induce an interfacial gating mechanism, which will enhance the photoresponsivity to 1000 A/W. More important, the photoresponse time of our device has been pushed to 400ns. The current device structure does not need a complicated fabrication process and is fully compatible with silicon technology. This work will open up a route to graphene-based high-performance optoelectronic devices. This work was supported by Southeast University.

Elucidating PID Degradation Mechanisms and In Situ Dark I–V Monitoring for Modeling Degradation Rate in CdTe Thin-Film Modules

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

Hacke, Peter; Spataru, Sergiu; Johnston, Steve

A progression of potential-induced degradation (PID) mechanisms are observed in CdTe modules, including shunting/junction degradation and two different manifestations of series resistance depending on the stress level and water ingress. The dark I-V method for in-situ characterization of Pmax based on superposition was adapted for the thin-film modules undergoing PID in view of the degradation mechanisms observed. An exponential model based on module temperature and relative humidity was fit to the PID rate for multiple stress levels in chamber tests and validated by predicting the observed degradation of the module type in the field.

Biasing, operation and parasitic current limitation in single device equivalent to CMOS, and other semiconductor systems

DOEpatents

Welch, James D.

2003-09-23

Disclosed are semiconductor devices including at least one junction which is rectifying whether the semiconductor is caused to be N or P-type, by the presence of applied gate voltage field induced carriers in essentially intrinsic, essentially homogeneously simultaneously containing both N and P-type metallurgical dopants at substantially equal doping levels, essentially homogeneously simultaneously containing both N and P-type metallurgical dopants at different doping levels, and containing a single metallurgical doping type, and functional combinations thereof. In particular, inverting and non-inverting gate voltage channel induced semiconductor single devices with operating characteristics similar to conventional multiple device CMOS systems, which can be operated as modulators, are disclosed as are a non-latching SCR and an approach to blocking parasitic currents utilizing material(s) which form rectifying junctions with both N and P-type semiconductor whether metallurigically or field induced.

Modulation of circular current and associated magnetic field in a molecular junction: A new approach

NASA Astrophysics Data System (ADS)

Patra, Moumita; Maiti, Santanu K.

2017-03-01

A new proposal is given to control local magnetic field in a molecular junction. In presence of finite bias a net circular current is established in the molecular ring which induces a magnetic field at its centre. Allowing a direct coupling between two electrodes, due to their close proximity, and changing its strength we can regulate circular current as well as magnetic field for a wide range, without disturbing any other physical parameters. We strongly believe that our proposal is quite robust compared to existing approaches of controlling local magnetic field and can be verified experimentally.

Progress in piezo-phototronic effect modulated photovoltaics.

PubMed

Que, Miaoling; Zhou, Ranran; Wang, Xiandi; Yuan, Zuqing; Hu, Guofeng; Pan, Caofeng

2016-11-02

Wurtzite structured materials, like ZnO, GaN, CdS, and InN, simultaneously possess semiconductor and piezoelectric properties. The inner-crystal piezopotential induced by external strain can effectively tune/control the carrier generation, transport and separation/combination processes at the metal-semiconductor contact or p-n junction, which is called the piezo-phototronic effect. This effect can efficiently enhance the performance of photovoltaic devices based on piezoelectric semiconductor materials by utilizing the piezo-polarization charges at the junction induced by straining, which can modulate the energy band of the piezoelectric material and then accelerate or prevent the separation process of the photon-generated electrons and vacancies. This paper introduces the fundamental physics principles of the piezo-phototronic effect, and reviews recent progress in piezo-phototronic effect enhanced solar cells, including solar cells based on semiconductor nanowire, organic/inorganic materials, quantum dots, and perovskite. The piezo-phototronic effect is suggested as a suitable basis for the development of an innovative method to enhance the performance of solar cells based on piezoelectric semiconductors by applied extrinsic strains, which might be appropriate for fundamental research and potential applications in various areas of optoelectronics.

Progress in piezo-phototronic effect modulated photovoltaics

NASA Astrophysics Data System (ADS)

Que, Miaoling; Zhou, Ranran; Wang, Xiandi; Yuan, Zuqing; Hu, Guofeng; Pan, Caofeng

2016-11-01

Wurtzite structured materials, like ZnO, GaN, CdS, and InN, simultaneously possess semiconductor and piezoelectric properties. The inner-crystal piezopotential induced by external strain can effectively tune/control the carrier generation, transport and separation/combination processes at the metal-semiconductor contact or p-n junction, which is called the piezo-phototronic effect. This effect can efficiently enhance the performance of photovoltaic devices based on piezoelectric semiconductor materials by utilizing the piezo-polarization charges at the junction induced by straining, which can modulate the energy band of the piezoelectric material and then accelerate or prevent the separation process of the photon-generated electrons and vacancies. This paper introduces the fundamental physics principles of the piezo-phototronic effect, and reviews recent progress in piezo-phototronic effect enhanced solar cells, including solar cells based on semiconductor nanowire, organic/inorganic materials, quantum dots, and perovskite. The piezo-phototronic effect is suggested as a suitable basis for the development of an innovative method to enhance the performance of solar cells based on piezoelectric semiconductors by applied extrinsic strains, which might be appropriate for fundamental research and potential applications in various areas of optoelectronics.

Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating

PubMed Central

Kraujalis, Tadas; Maciunas, Kestutis

2017-01-01

We combined the Hodgkin–Huxley equations and a 36-state model of gap junction channel gating to simulate electrical signal transfer through electrical synapses. Differently from most previous studies, our model can account for dynamic modulation of junctional conductance during the spread of electrical signal between coupled neurons. The model of electrical synapse is based on electrical properties of the gap junction channel encompassing two fast and two slow gates triggered by the transjunctional voltage. We quantified the influence of a difference in input resistances of electrically coupled neurons and instantaneous conductance–voltage rectification of gap junctions on an asymmetry of cell-to-cell signaling. We demonstrated that such asymmetry strongly depends on junctional conductance and can lead to the unidirectional transfer of action potentials. The simulation results also revealed that voltage spikes, which develop between neighboring cells during the spread of action potentials, can induce a rapid decay of junctional conductance, thus demonstrating spiking activity-dependent short-term plasticity of electrical synapses. This conclusion was supported by experimental data obtained in HeLa cells transfected with connexin45, which is among connexin isoforms expressed in neurons. Moreover, the model allowed us to replicate the kinetics of junctional conductance under different levels of intracellular concentration of free magnesium ([Mg2+]i), which was experimentally recorded in cells expressing connexin36, a major neuronal connexin. We demonstrated that such [Mg2+]i-dependent long-term plasticity of the electrical synapse can be adequately reproduced through the changes of slow gate parameters of the 36-state model. This suggests that some types of chemical modulation of gap junctions can be executed through the underlying mechanisms of voltage gating. Overall, the developed model accounts for direction-dependent asymmetry, as well as for short- and long-term plasticity of electrical synapses. Our modeling results demonstrate that such complex behavior of the electrical synapse is important in shaping the response of coupled neurons. PMID:28384220

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

PubMed Central

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

2014-01-01

Abstract. Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows quantitative measurement of gap junction function in living cells. It is based on diffusion-dependent redistribution of a gap junction-permeable fluorescent dye. Using FRAP, we showed that human tenocytes form functional gap junctions in monolayer and three-dimensional (3-D) collagen I culture. Fluorescently labeled tenocytes following photobleaching rapidly reacquired the fluorescent dye from neighboring cells, while HeLa cells, which do not communicate by gap junctions, remained bleached. Furthermore, both 18 β-glycyrrhetinic acid and carbenoxolone, standard inhibitors of gap junction activity, impaired fluorescence recovery in tendon cells. In both monolayer and 3-D cultures, intercellular communication in isolated cells was significantly decreased when compared with cells forming many cell-to-cell contacts. In this study, we used FRAP as a tool to quantify and experimentally manipulate the function of gap junctions in human tenocytes in both two-dimensional (2-D) and 3-D cultures. PMID:24390370

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

PubMed

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

2012-01-12

In addition to chemical synaptic transmission, neurons that are connected by gap junctions can also communicate rapidly via electrical synaptic transmission. Increasing evidence indicates that gap junctions not only permit electrical current flow and synchronous activity between interconnected or coupled cells, but that the strength or effectiveness of electrical communication between coupled cells can be modulated to a great extent(1,2). In addition, the large internal diameter (~1.2 nm) of many gap junction channels permits not only electric current flow, but also the diffusion of intracellular signaling molecules and small metabolites between interconnected cells, so that gap junctions may also mediate metabolic and chemical communication. The strength of gap junctional communication between neurons and its modulation by neurotransmitters and other factors can be studied by simultaneously electrically recording from coupled cells and by determining the extent of diffusion of tracer molecules, which are gap junction permeable, but not membrane permeable, following iontophoretic injection into single cells. However, these procedures can be extremely difficult to perform on neurons with small somata in intact neural tissue. Numerous studies on electrical synapses and the modulation of electrical communication have been conducted in the vertebrate retina, since each of the five retinal neuron types is electrically connected by gap junctions(3,4). Increasing evidence has shown that the circadian (24-hour) clock in the retina and changes in light stimulation regulate gap junction coupling(3-8). For example, recent work has demonstrated that the retinal circadian clock decreases gap junction coupling between rod and cone photoreceptor cells during the day by increasing dopamine D2 receptor activation, and dramatically increases rod-cone coupling at night by reducing D2 receptor activation(7,8). However, not only are these studies extremely difficult to perform on 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.

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

PubMed

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.

Optically controlled electroresistance and electrically controlled photovoltage in ferroelectric tunnel junctions

PubMed Central

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

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. PMID:26924259

Modulation of spin transfer torque amplitude in double barrier magnetic tunnel junctions

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

Clément, P.-Y.; Baraduc, C., E-mail: claire.baraduc@cea.fr; Chshiev, M.

2015-09-07

Magnetization switching induced by spin transfer torque is used to write magnetic memories (Magnetic Random Access Memory, MRAM) but can be detrimental to the reading process. It would be quite convenient therefore to modulate the efficiency of spin transfer torque. A solution is adding an extra degree of freedom by using double barrier magnetic tunnel junctions with two spin-polarizers, with controllable relative magnetic alignment. We demonstrate, for these structures, that the amplitude of in-plane spin transfer torque on the middle free layer can be efficiently tuned via the magnetic configuration of the electrodes. Using the proposed design could thus pavemore » the way towards more reliable read/write schemes for MRAM. Moreover, our results suggest an intriguing effect associated with the out-of-plane (field-like) spin transfer torque, which has to be further investigated.« less

Electronic thermometry in tunable tunnel junction

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

Maksymovych, Petro

A tunable tunnel junction thermometry circuit includes a variable width tunnel junction between a test object and a probe. The junction width is varied and a change in thermovoltage across the junction with respect to the change in distance across the junction is determined. Also, a change in biased current with respect to a change in distance across the junction is determined. A temperature gradient across the junction is determined based on a mathematical relationship between the temperature gradient, the change in thermovoltage with respect to distance and the change in biased current with respect to distance. Thermovoltage may bemore » measured by nullifying a thermoelectric tunneling current with an applied voltage supply level. A piezoelectric actuator may modulate the probe, and thus the junction width, to vary thermovoltage and biased current across the junction. Lock-in amplifiers measure the derivatives of the thermovoltage and biased current modulated by varying junction width.« less

Light-induced new memory states in electronic resistive switching of NiO/NSTO junction

NASA Astrophysics Data System (ADS)

Wei, Ling; Li, G. Q.; Zhang, W. F.

2016-02-01

n-type and p-type NiO films were prepared on SrTiO3:Nb (NSTO) by controlling oxygen pressures during the process of pulsed laser deposition. The results of current-voltage (I-V) characteristics and photocurrent investigation indicate that the junction shows a typical electronic bipolar resistive switching (RS) behavior and the optical injection can add new resistance states. Photocurrents can obviously be modulated by different resistance states of NiO/NSTO junction. The linear fitting results of I-V curves reveal that the low resistance state follows Ohmic behavior and the high resistance state follows Schottky-emission mechanism. The depletion widths under forward and reverse bias in the dark and with the illumination were estimated respectively. Combined with the energy band structure, the mechanism of RS and photoresponse in the NiO/NSTO junction can be attributed to the variance of interfacial barrier during electrical and optical injection. These results pave the way for the application of the NiO/NSTO junction in the multilevel storage of optical-electrical devices.

Giant Electroresistance in Edge Metal-Insulator-Metal Tunnel Junctions Induced by Ferroelectric Fringe Fields

PubMed Central

Jung, Sungchul; Jeon, Youngeun; Jin, Hanbyul; Lee, Jung-Yong; Ko, Jae-Hyeon; Kim, Nam; Eom, Daejin; Park, Kibog

2016-01-01

An enormous amount of research activities has been devoted to developing new types of non-volatile memory devices as the potential replacements of current flash memory devices. Theoretical device modeling was performed to demonstrate that a huge change of tunnel resistance in an Edge Metal-Insulator-Metal (EMIM) junction of metal crossbar structure can be induced by the modulation of electric fringe field, associated with the polarization reversal of an underlying ferroelectric layer. It is demonstrated that single three-terminal EMIM/Ferroelectric structure could form an active memory cell without any additional selection devices. This new structure can open up a way of fabricating all-thin-film-based, high-density, high-speed, and low-power non-volatile memory devices that are stackable to realize 3D memory architecture. PMID:27476475

Nonlinear Gap Junctions Enable Long-Distance Propagation of Pulsating Calcium Waves in Astrocyte Networks

PubMed Central

Goldberg, Mati; De Pittà, Maurizio; Volman, Vladislav; Berry, Hugues; Ben-Jacob, Eshel

2010-01-01

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 Ca2+ waves. An identified mode of propagation is based on cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP3) through gap junctions that locally trigger Ca2+ pulses via IP3-dependent Ca2+-induced Ca2+ release. It is, however, currently unknown whether this intracellular route is able to support the propagation of long-distance regenerative Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ waves across astrocytes and the precise conditions under which glial cells may participate in information processing in the brain. PMID:20865153

Voltage-Driven Conformational Switching with Distinct Raman Signature in a Single-Molecule Junction.

PubMed

Bi, Hai; Palma, Carlos-Andres; Gong, Yuxiang; Hasch, Peter; Elbing, Mark; Mayor, Marcel; Reichert, Joachim; Barth, Johannes V

2018-04-11

Precisely controlling well-defined, stable single-molecule junctions represents a pillar of single-molecule electronics. Early attempts to establish computing with molecular switching arrays were partly challenged by limitations in the direct chemical characterization of metal-molecule-metal junctions. While cryogenic scanning probe studies have advanced the mechanistic understanding of current- and voltage-induced conformational switching, metal-molecule-metal conformations are still largely inferred from indirect evidence. Hence, the development of robust, chemically sensitive techniques is instrumental for advancement in the field. Here we probe the conformation of a two-state molecular switch with vibrational spectroscopy, while simultaneously operating it by means of the applied voltage. Our study emphasizes measurements of single-molecule Raman spectra in a room-temperature stable single-molecule switch presenting a signal modulation of nearly 2 orders of magnitude.

Presence of claudins mRNA in the brain. Selective modulation of expression by kindling epilepsy.

PubMed

Lamas, Mónica; González-Mariscal, Lorenza; Gutiérrez, Rafael

2002-08-15

In the central nervous system, the junctional types that establish and maintain tissue architecture include gap junctions, for cytoplasmic connectivity, and tight junctions, for paracellular and/or cell polarity barriers. Connexins are the integral membrane proteins of gap junctions, whereas occludin and members of the multigene family of claudins form tight junctions. In the brain, there are no transendothelial pathways, as continuous tight junctions are present between the endothelial cells. Thus, they provide a continuous cellular barrier between the blood and the insterstitial fluid. However, several brain pathologies, including epilepsy, are known to alter the permeability of the blood-brain barrier and to cause edema. Therefore, since claudins, as constitutive proteins of tight junctions are likely candidates for modulation under pathological states, we explored their normal pattern of expression in the brain and its modulation by seizures. We found that several members of this family are normally expressed in the hippocampus and cortex. Interestingly, claudin-7 is expressed in the hippocampus but not in the cortex. On the other hand, the expression of claudin-8 is selectively down-regulated in the hippocampus as kindling evolves. These results link for the first time the modulation of expression of a tight junction protein to abnormal neuronal synchronization that could probably be reflected in permeability changes of the blood-brain barrier or edema.

Modulation of Intestinal Paracellular Transport by Bacterial Pathogens.

PubMed

Roxas, Jennifer Lising; Viswanathan, V K

2018-03-25

The passive and regulated movement of ions, solutes, and water via spaces between cells of the epithelial monolayer plays a critical role in the normal intestinal functioning. This paracellular pathway displays a high level of structural and functional specialization, with the membrane-spanning complexes of the tight junctions, adherens junctions, and desmosomes ensuring its integrity. Tight junction proteins, like occludin, tricellulin, and the claudin family isoforms, play prominent roles as barriers to unrestricted paracellular transport. The past decade has witnessed major advances in our understanding of the architecture and function of epithelial tight junctions. While it has been long appreciated that microbes, notably bacterial and viral pathogens, target and disrupt junctional complexes and alter paracellular permeability, the precise mechanisms remain to be defined. Notably, renewed efforts will be required to interpret the available data on pathogen-mediated barrier disruption in the context of the most recent findings on tight junction structure and function. While much of the focus has been on pathogen-induced dysregulation of junctional complexes, commensal microbiota and their products may influence paracellular permeability and contribute to the normal physiology of the gut. Finally, microbes and their products have become important tools in exploring host systems, including the junctional properties of epithelial cells. © 2018 American Physiological Society. Compr Physiol 8:823-842, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

PN-type carrier-induced filter with modulatable extinction ratio.

PubMed

Fang, Qing; Tu, Xiaoguang; Song, Junfeng; Jia, Lianxi; Luo, Xianshu; Yang, Yan; Yu, Mingbin; Lo, Guoqiang

2014-12-01

We demonstrate the first PN-type carrier-induced silicon waveguide Bragg grating filter on a SOI wafer. The optical extinction ratio of this kind of filter can be efficiently modulated under both reverse and forward biases. The carrier-induced Bragg grating based on a PN junction is fabricated on the silicon waveguide using litho compensation technology. The measured optical bandwidth and the extinction ratio of the filter are 0.45 nm and 19 dB, respectively. The optical extinction ratio modulation under the reverse bias is more than 11.5 dB and it is more than 10 dB under the forward bias. Only 1-dB optical transmission loss is realized in this Bragg grating under a reverse bias. The shifting rates of the central wavelength under forward and reverse biases are ~-1.25 nm/V and 0.01 nm/V, respectively. The 3-dB modulation bandwidth of this filter is 5.1 GHz at a bias of -10 V.

Optimal Normal Tissue Sparing in Craniospinal Axis Irradiation Using IMRT With Daily Intrafractionally Modulated Junction(s)

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

Kusters, Johannes M.A.M.; Louwe, Rob J.W.; Kollenburg, Peter G.M. van

2011-12-01

Purpose: To develop a treatment technique for craniospinal irradiation using intensity-modulated radiotherapy (IMRT) with improved dose homogeneity at the field junction(s), increased target volume conformity, and minimized dose to the organs at risk (OARs). Methods and Materials: Five patients with high-risk medulloblastoma underwent CT simulation in supine position. For each patient, an IMRT plan with daily intrafractionally modulated junction(s) was generated, as well as a treatment plan based on conventional three-dimensional planning (3DCRT). A dose of 39.6 Gy in 22 daily fractions of 1.8 Gy was prescribed. Dose-volume parameters for target volumes and OARs were compared for the two techniques.more » Results: The maximum dose with IMRT was <107% in all patients. V{sub <95} and V{sub >107} were <1 cm{sup 3} for IMRT compared with 3-9 cm{sup 3} for the craniospinal and 26-43 cm{sup 3} for the spinal-spinal junction with 3DCRT. These observations corresponded with a lower homogeneity index and a higher conformity index for the spinal planning target volume with IMRT. IMRT provided considerable sparing of acute and late reacting tissues. V{sub 75} for the esophagus, gastroesophageal junction, and intestine was 81%, 81%, and 22% with 3DCRT versus 5%, 0%, and 1% with IMRT, respectively. V{sub 75} for the heart and thyroid was 42% and 32% vs. 0% with IMRT. Conclusion: IMRT with daily intrafractionally modulated junction results in a superior target coverage and junction homogeneity compared with 3DCRT. A significant dose reduction can be obtained for acute as well as late-reacting tissues.« less

Ferroelectric-Domain-Patterning-Controlled Schottky Junction State in Monolayer MoS 2

DOE PAGES

Xiao, Zhiyong; Song, Jingfeng; Ferry, David K.; ...

2017-06-08

Here, we exploit scanning probe controlled domain patterning in a ferroelectric top-layer to induce nonvolatile modulation of the conduction characteristic of monolayer MoS 2 between a transistor and a junction state. In the presence of a domain wall, MoS 2 exhibits rectified I-V that is well described by the thermionic emission model. The induced Schottky barrier height Φ eff Β varies from 0.38 eV to 0.57 eV and is tunabe by a SiO 2 global back-gate, while the tuning range of Φ eff Β the barrier height depends sensitively on the conduction band tail trapping states. Our work points tomore » a new route to achieve programmable functionalities in van der Waals materials and sheds light on the critical performance limiting factors in these hybrid systems.« less

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

Harvey, Steven P.; Aguiar, Jeffery A.; Hacke, Peter

Here, we investigated potential-induced degradation (PID) in silicon mini-modules that were subjected to accelerated stressing to induce PID conditions. Shunted areas on the cells were identified with photoluminescence and dark lock-in thermography (DLIT) imaging. The identical shunted areas were then analyzed via time-of-flight secondary-ion mass spectrometry (TOFSIMS) imaging, 3-D tomography, and high-resolution transmission electron microscopy. The TOF-SIMS imaging indicates a high concentration of sodium in the shunted areas, and 3-D tomography reveals that the sodium extends more than 2 um from the surface below shunted regions. Transmission electron microscopy investigation reveals that a stacking fault is present at an areamore » identified as shunted by DLIT imaging. After the removal of surface sodium, tomography reveals persistent sodium present around the junction depth of 300 nm and a drastic difference in sodium content at the junction when comparing shunted and nonshunted regions.« less

Ferroelectric-Domain-Patterning-Controlled Schottky Junction State in Monolayer MoS 2

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

Xiao, Zhiyong; Song, Jingfeng; Ferry, David K.

Here, we exploit scanning probe controlled domain patterning in a ferroelectric top-layer to induce nonvolatile modulation of the conduction characteristic of monolayer MoS 2 between a transistor and a junction state. In the presence of a domain wall, MoS 2 exhibits rectified I-V that is well described by the thermionic emission model. The induced Schottky barrier height Φ eff Β varies from 0.38 eV to 0.57 eV and is tunabe by a SiO 2 global back-gate, while the tuning range of Φ eff Β the barrier height depends sensitively on the conduction band tail trapping states. Our work points tomore » a new route to achieve programmable functionalities in van der Waals materials and sheds light on the critical performance limiting factors in these hybrid systems.« less

Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium.

PubMed

Samak, Geetha; Chaudhry, Kamaljit K; Gangwar, Ruchika; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

2015-02-01

Disruption of intestinal epithelial tight junctions is an important event in the pathogenesis of ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis in mice with symptoms similar to ulcerative colitis. However, the mechanism of DSS-induced colitis is unknown. We investigated the mechanism of DSS-induced disruption of intestinal epithelial tight junctions and barrier dysfunction in Caco-2 cell monolayers in vitro and mouse colon in vivo. DSS treatment resulted in disruption of tight junctions, adherens junctions and actin cytoskeleton leading to barrier dysfunction in Caco-2 cell monolayers. DSS induced a rapid activation of c-Jun N-terminal kinase (JNK), and the inhibition or knockdown of JNK2 attenuated DSS-induced tight junction disruption and barrier dysfunction. In mice, DSS administration for 4 days caused redistribution of tight junction and adherens junction proteins from the epithelial junctions, which was blocked by JNK inhibitor. In Caco-2 cell monolayers, DSS increased intracellular Ca(2+) concentration, and depletion of intracellular Ca(2+) by 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM) or thapsigargin attenuated DSS-induced JNK activation, tight junction disruption and barrier dysfunction. Knockdown of apoptosis signal-regulated kinase 1 (Ask1) or MKK7 blocked DSS-induced tight junction disruption and barrier dysfunction. DSS activated c-Src by a Ca2+ and JNK-dependent mechanism. Inhibition of Src kinase activity or knockdown of c-Src blocked DSS-induced tight junction disruption and barrier dysfunction. DSS increased tyrosine phosphorylation of occludin, zonula occludens-1 (ZO-1), E-cadherin and β-catenin. SP600125 abrogated DSS-induced tyrosine phosphorylation of junctional proteins. Recombinant JNK2 induced threonine phosphorylation and auto-phosphorylation of c-Src. The present study demonstrates that Ca(2+)/Ask1/MKK7/JNK2/cSrc signalling cascade mediates DSS-induced tight junction disruption and barrier dysfunction.

Nonadiabatic effect on the quantum heat flux control.

PubMed

Uchiyama, Chikako

2014-05-01

We provide a general formula of quantum transfer that includes the nonadiabatic effect under periodic environmental modulation by using full counting statistics in Hilbert-Schmidt space. Applying the formula to an anharmonic junction model that interacts with two bosonic environments within the Markovian approximation, we find that the quantum transfer is divided into the adiabatic (dynamical and geometrical phases) and nonadiabatic contributions. This extension shows the dependence of quantum transfer on the initial condition of the anharmonic junction just before the modulation, as well as the characteristic environmental parameters such as interaction strength and cut-off frequency of spectral density. We show that the nonadiabatic contribution represents the reminiscent effect of past modulation including the transition from the initial condition of the anharmonic junction to a steady state determined by the very beginning of the modulation. This enables us to tune the frequency range of modulation, whereby we can obtain the quantum flux corresponding to the geometrical phase by setting the initial condition of the anharmonic junction.

Thermoelectric generator with hinged assembly for fins

DOEpatents

Purdy, David L.; Shapiro, Zalman M.; Hursen, Thomas F.; Maurer, Gerould W.

1976-11-02

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

Ac electronic tunneling at optical frequencies

NASA Technical Reports Server (NTRS)

Faris, S. M.; Fan, B.; Gustafson, T. K.

1974-01-01

Rectification characteristics of non-superconducting metal-barrier-metal junctions deduced from electronic tunneling have been observed experimentally for optical frequency irradiation of the junction. The results provide verification of optical frequency Fermi level modulation and electronic tunneling current modulation.

Gap Junctions and Connexin Hemichannels Underpin Haemostasis and Thrombosis

PubMed Central

Vaiyapuri, Sakthivel; Jones, Chris I.; Sasikumar, Parvathy; Moraes, Leonardo A.; Munger, Stephanie J.; Wright, Joy R.; Ali, Marfoua S.; Sage, Tanya; Kaiser, William J.; Tucker, Katherine L.; Stain, Christopher J.; Bye, Alexander P.; Jones, Sarah; Oviedo-Orta, Ernesto; Simon, Alexander M.; Mahaut-Smith, Martyn P.; Gibbins, Jonathan M.

2012-01-01

Background Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have now examined the role of connexins in platelets, blood cells that circulate in isolation, but upon tissue injury adhere to each other and the vessel wall to prevent blood loss and facilitate wound repair. Methods and Results We report the presence of connexins in platelets, notably connexin37, and that the formation of gap junctions within platelet thrombi is required for the control of clot retraction. Inhibition of connexin function modulated a range of platelet functional responses prior to platelet-platelet contact, and reduced laser induced thrombosis in vivo in mice. Deletion of the Cx37 gene (Gja4) in transgenic mice reduced platelet aggregation, fibrinogen binding, granule secretion and clot retraction indicating an important role for Cx37 hemichannels and gap junctions in platelet thrombus function. Conclusions Together, these data demonstrate that platelet gap junctions and hemichannels underpin the control of haemostasis and thrombosis and represent potential therapeutic targets. PMID:22528526

Intestinal barrier: A gentlemen’s agreement between microbiota and immunity

PubMed Central

Caricilli, Andrea Moro; Castoldi, Angela; Câmara, Niels Olsen Saraiva

2014-01-01

Our body is colonized by more than a hundred trillion commensals, represented by viruses, bacteria and fungi. This complex interaction has shown that the microbiome system contributes to the host’s adaptation to its environment, providing genes and functionality that give flexibility of diet and modulate the immune system in order not to reject these symbionts. In the intestine, specifically, the microbiota helps developing organ structures, participates of the metabolism of nutrients and induces immunity. Certain components of the microbiota have been shown to trigger inflammatory responses, whereas others, anti-inflammatory responses. The diversity and the composition of the microbiota, thus, play a key role in the maintenance of intestinal homeostasis and explain partially the link between intestinal microbiota changes and gut-related disorders in humans. Tight junction proteins are key molecules for determination of the paracellular permeability. In the context of intestinal inflammatory diseases, the intestinal barrier is compromised, and decreased expression and differential distribution of tight junction proteins is observed. It is still unclear what is the nature of the luminal or mucosal factors that affect the tight junction proteins function, but the modulation of the immune cells found in the intestinal lamina propria is hypothesized as having a role in this modulation. In this review, we provide an overview of the current understanding of the interaction of the gut microbiota with the immune system in the development and maintenance of the intestinal barrier. PMID:24891972

Congestion relaxation due to density-dependent junction rules in TASEP network

NASA Astrophysics Data System (ADS)

Tannai, Takahiro; Nishinari, Katsuhiro

2017-09-01

We now consider a small network module of Totally Asymmetric Simple Exclusion Process with branching and aggregation points, and rules of junctions dependent on the densities of segments of the network module. We also focus on the interaction among junctions which are branching and aggregation. The interaction among junctions with density-dependent rules possesses more complexity than those with density-independent rules studied in the previous papers. In conclusion, we confirm the result that density-dependent rules enable vehicles to move more effectively than the density-independent rules.

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

PubMed Central

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

Modulation of the Pyrococcus abyssi NucS Endonuclease Activity by Replication Clamp at Functional and Structural Levels*

PubMed Central

Creze, Christophe; Ligabue, Alessio; Laurent, Sébastien; Lestini, Roxane; Laptenok, Sergey P.; Khun, Joelle; Vos, Marten H.; Czjzek, Mirjam; Myllykallio, Hannu; Flament, Didier

2012-01-01

Pyrococcus abyssi NucS is the founding member of a new family of structure-specific DNA endonucleases that interact with the replication clamp proliferating cell nuclear antigen (PCNA). Using a combination of small angle x-ray scattering and surface plasmon resonance analyses, we demonstrate the formation of a stable complex in solution, in which one molecule of the PabNucS homodimer binds to the outside surface of the PabPCNA homotrimer. Using fluorescent labels, PCNA is shown to increase the binding affinity of NucS toward single-strand/double-strand junctions on 5′ and 3′ flaps, as well as to modulate the cleavage specificity on the branched DNA structures. Our results indicate that the presence of a single major contact between the PabNucS and PabPCNA proteins, together with the complex-induced DNA bending, facilitate conformational flexibility required for specific cleavage at the single-strand/double-strand DNA junction. PMID:22431731

Modulation of the Pyrococcus abyssi NucS endonuclease activity by replication clamp at functional and structural levels.

PubMed

Creze, Christophe; Ligabue, Alessio; Laurent, Sébastien; Lestini, Roxane; Laptenok, Sergey P; Khun, Joelle; Vos, Marten H; Czjzek, Mirjam; Myllykallio, Hannu; Flament, Didier

2012-05-04

Pyrococcus abyssi NucS is the founding member of a new family of structure-specific DNA endonucleases that interact with the replication clamp proliferating cell nuclear antigen (PCNA). Using a combination of small angle x-ray scattering and surface plasmon resonance analyses, we demonstrate the formation of a stable complex in solution, in which one molecule of the PabNucS homodimer binds to the outside surface of the PabPCNA homotrimer. Using fluorescent labels, PCNA is shown to increase the binding affinity of NucS toward single-strand/double-strand junctions on 5' and 3' flaps, as well as to modulate the cleavage specificity on the branched DNA structures. Our results indicate that the presence of a single major contact between the PabNucS and PabPCNA proteins, together with the complex-induced DNA bending, facilitate conformational flexibility required for specific cleavage at the single-strand/double-strand DNA junction.

Coherent Charge Transport in Ballistic InSb Nanowire Josephson Junctions

PubMed Central

Li, S.; Kang, N.; Fan, D. X.; Wang, L. B.; Huang, Y. Q.; Caroff, P.; Xu, H. Q.

2016-01-01

Hybrid InSb nanowire-superconductor devices are promising for investigating Majorana modes and topological quantum computation in solid-state devices. An experimental realisation of ballistic, phase-coherent superconductor-nanowire hybrid devices is a necessary step towards engineering topological superconducting electronics. Here, we report on a low-temperature transport study of Josephson junction devices fabricated from InSb nanowires grown by molecular-beam epitaxy and provide a clear evidence for phase-coherent, ballistic charge transport through the nanowires in the junctions. We demonstrate that our devices show gate-tunable proximity-induced supercurrent and clear signatures of multiple Andreev reflections in the differential conductance, indicating phase-coherent transport within the junctions. We also observe periodic modulations of the critical current that can be associated with the Fabry-Pérot interference in the nanowires in the ballistic transport regime. Our work shows that the InSb nanowires grown by molecular-beam epitaxy are of excellent material quality and hybrid superconducting devices made from these nanowires are highly desirable for investigation of the novel physics in topological states of matter and for applications in topological quantum electronics. PMID:27102689

Calcium Channels and Oxidative Stress Mediate a Synergistic Disruption of Tight Junctions by Ethanol and Acetaldehyde in Caco-2 Cell Monolayers.

PubMed

Samak, Geetha; Gangwar, Ruchika; Meena, Avtar S; Rao, Roshan G; Shukla, Pradeep K; Manda, Bhargavi; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

2016-12-13

Ethanol is metabolized into acetaldehyde in most tissues. In this study, we investigated the synergistic effect of ethanol and acetaldehyde on the tight junction integrity in Caco-2 cell monolayers. Expression of alcohol dehydrogenase sensitized Caco-2 cells to ethanol-induced tight junction disruption and barrier dysfunction, whereas aldehyde dehydrogenase attenuated acetaldehyde-induced tight junction disruption. Ethanol up to 150 mM did not affect tight junction integrity or barrier function, but it dose-dependently increased acetaldehyde-mediated tight junction disruption and barrier dysfunction. Src kinase and MLCK inhibitors blocked this synergistic effect of ethanol and acetaldehyde on tight junction. Ethanol and acetaldehyde caused a rapid and synergistic elevation of intracellular calcium. Calcium depletion by BAPTA or Ca 2+ -free medium blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. Diltiazem and selective knockdown of TRPV6 or Ca V 1.3 channels, by shRNA blocked ethanol and acetaldehyde-induced tight junction disruption and barrier dysfunction. Ethanol and acetaldehyde induced a rapid and synergistic increase in reactive oxygen species by a calcium-dependent mechanism. N-acetyl-L-cysteine and cyclosporine A, blocked ethanol and acetaldehyde-induced barrier dysfunction and tight junction disruption. These results demonstrate that ethanol and acetaldehyde synergistically disrupt tight junctions by a mechanism involving calcium, oxidative stress, Src kinase and MLCK.

R&D issues in scale-up and manufacturing of amorphous silicon tandem modules

NASA Astrophysics Data System (ADS)

Arya, R. R.; Carlson, D. E.; Chen, L. F.; Ganguly, G.; He, M.; Lin, G.; Middya, R.; Wood, G.; Newton, J.; Bennett, M.; Jackson, F.; Willing, F.

1999-03-01

R & D on amorphous silicon based tandem junction devices has improved the throughtput, the material utilization, and the performance of devices on commercial tin oxide coated glass. The tandem junction technology has been scaled-up to produce 8.6 Ft2 monolithically integrated modules in manufacturing at the TF1 plant. Optimization of performance and stability of these modules is ongoing.

A scanning tunneling microscope break junction method with continuous bias modulation.

PubMed

Beall, Edward; Yin, Xing; Waldeck, David H; Wierzbinski, Emil

2015-09-28

Single molecule conductance measurements on 1,8-octanedithiol were performed using the scanning tunneling microscope break junction method with an externally controlled modulation of the bias voltage. Application of an AC voltage is shown to improve the signal to noise ratio of low current (low conductance) measurements as compared to the DC bias method. The experimental results show that the current response of the molecule(s) trapped in the junction and the solvent media to the bias modulation can be qualitatively different. A model RC circuit which accommodates both the molecule and the solvent is proposed to analyze the data and extract a conductance for the molecule.

Poly(ADP-ribose) polymerase-1 regulates microglia mediated decrease of endothelial tight junction integrity.

PubMed

Mehrabadi, Abbas Rezaeian; Korolainen, Minna A; Odero, Gary; Miller, Donald W; Kauppinen, Tiina M

2017-09-01

Alzheimer's disease pathology includes, beside neuronal damage, reactive gliosis and reduced blood-brain barrier (BBB) integrity. Microglia are intimately associated with the BBB and upon AD pathology, pro-inflammatory responses of microglia could contribute to BBB damage. To study whether microglia can directly affect BBB integrity, the effects of amyloid beta (Aβ) -stimulated primary murine microglia on co-cultured mouse brain endothelial cells (bEnd3) and murine astrocyte cultures were assessed. We also assessed whether microglial phenotype modulation via poly(ADP-ribose) polymerase-1 (PARP-1) inhibition/ablation can reverse microglial impact on these BBB forming cells. Unstimulated microglia promoted expression of tight junction proteins (TJPs), zonula ocluden-1 (ZO-1) and occludin in co-cultured endothelia cells, whereas Aβ-stimulated microglia reduced endothelial expression of ZO-1 and occludin. Astrocytes co-cultured with microglia showed elevated glial fibrillary acidic protein (GFAP) expression, which was further increased if microglia had been stimulated with Aβ. Aβ induced microglial release of nitric oxide (NO) and tumour necrosis factor alpha (TNFα), which resulted in reduced endothelial expression of TJPs and increased paracellular permeability. Microglial PARP-1 inhibition attenuated these Aβ-induced events. These findings demonstrate that PARP-1 mediated microglial responses (NO and TNFα) can directly reduce BBB integrity by promoting TJP degradation, increasing endothelial cell permeability and inducing astrogliosis. PARP-1 as a modulator of microglial phenotype can prevent microglial BBB damaging events, and thus is a potential therapeutic target. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gap junctions modulate glioma invasion by direct transfer of microRNA.

PubMed

Hong, Xiaoting; Sin, Wun Chey; Harris, Andrew L; Naus, Christian C

2015-06-20

The invasiveness of high-grade glioma is the primary reason for poor survival following treatment. Interaction between glioma cells and surrounding astrocytes are crucial to invasion. We investigated the role of gap junction mediated miRNA transfer in this context. By manipulating gap junctions with a gap junction inhibitor, siRNAs, and a dominant negative connexin mutant, we showed that functional glioma-glioma gap junctions suppress glioma invasion while glioma-astrocyte and astrocyte-astrocyte gap junctions promote it in an in vitro transwell invasion assay. After demonstrating that glioma-astrocyte gap junctions are permeable to microRNA, we compared the microRNA profiles of astrocytes before and after co-culture with glioma cells, identifying specific microRNAs as candidates for transfer through gap junctions from glioma cells to astrocytes. Further analysis showed that transfer of miR-5096 from glioma cells to astrocytes is through gap junctions; this transfer is responsible, in part, for the pro-invasive effect. Our results establish a role for glioma-astrocyte gap junction mediated microRNA signaling in modulation of glioma invasive behavior, and that gap junction coupling among astrocytes magnifies the pro-invasive signaling. Our findings reveal the potential for therapeutic interventions based on abolishing alteration of stromal cells by tumor cells via manipulation of microRNA and gap junction channel activity.

Gap junctions modulate glioma invasion by direct transfer of microRNA

PubMed Central

Hong, Xiaoting; Sin, Wun Chey; Harris, Andrew L.; Naus, Christian C.

2015-01-01

The invasiveness of high-grade glioma is the primary reason for poor survival following treatment. Interaction between glioma cells and surrounding astrocytes are crucial to invasion. We investigated the role of gap junction mediated miRNA transfer in this context. By manipulating gap junctions with a gap junction inhibitor, siRNAs, and a dominant negative connexin mutant, we showed that functional glioma-glioma gap junctions suppress glioma invasion while glioma-astrocyte and astrocyte-astrocyte gap junctions promote it in an in vitro transwell invasion assay. After demonstrating that glioma-astrocyte gap junctions are permeable to microRNA, we compared the microRNA profiles of astrocytes before and after co-culture with glioma cells, identifying specific microRNAs as candidates for transfer through gap junctions from glioma cells to astrocytes. Further analysis showed that transfer of miR-5096 from glioma cells to astrocytes is through gap junctions; this transfer is responsible, in part, for the pro-invasive effect. Our results establish a role for glioma-astrocyte gap junction mediated microRNA signaling in modulation of glioma invasive behavior, and that gap junction coupling among astrocytes magnifies the pro-invasive signaling. Our findings reveal the potential for therapeutic interventions based on abolishing alteration of stromal cells by tumor cells via manipulation of microRNA and gap junction channel activity. PMID:25978028

Tonic regulation of vascular permeability

PubMed Central

Curry, Fitz-Roy E.; Adamson, Roger H.

2014-01-01

Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signaling pathways regulated by S1P and intracellular cAMP. These pathways modulate the adherens junction, continuity of tight junction strands, and the balance of synthesis and degradation of glycocalyx components. We evaluate recent evidence that baseline permeability is maintained by constant activity of mechanisms involving the small GTPases Rap1 and Rac1. In the basal state, the barrier is compromised when activities of the small GTPases are reduced by low S1P supply or delivery. With inflammatory stimulus, increased permeability can be understood in part as the action of signaling to reduce Rap1 and Rac1 activation. With the hypothesis that microvessel permeability and selectivity under both normal and inflammatory conditions are regulated by mechanisms that are continuously active it follows that when S1P or intracellular cAMP are elevated at the time of inflammatory stimulus, they can buffer changes induced by inflammatory agents and maintain normal barrier stability. When endothelium is exposed to inflammatory conditions and subsequently exposed to elevated S1P or intracellular cAMP, the same processes restore the functional barrier by first reestablishing the adherens junction, then modulating tight junctions and glycocalyx. In more extreme inflammatory conditions, loss of the inhibitory actions of Rac1 dependent mechanisms may promote expression of more inflammatory endothelial phenotypes by contributing to the up-regulation of RhoA dependent contractile mechanisms and the sustained loss of surface glycocalyx allowing access of inflammatory cells to the endothelium. PMID:23374222

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

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

Hadley, Austin; Ding, George X., E-mail: george.ding@vanderbilt.edu

2014-01-01

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

Josephson junction microwave modulators for qubit control

NASA Astrophysics Data System (ADS)

Naaman, O.; Strong, J. A.; Ferguson, D. G.; Egan, J.; Bailey, N.; Hinkey, R. T.

2017-02-01

We demonstrate Josephson junction based double-balanced mixer and phase shifter circuits operating at 6-10 GHz and integrate these components to implement both a monolithic amplitude/phase vector modulator and an I/Q quadrature mixer. The devices are actuated by flux signals, dissipate no power on chip, exhibit input saturation powers in excess of 1 nW, and provide cryogenic microwave modulation solutions for integrated control of superconducting qubits.

Photon-assisted quantum transport in quantum point contacts

NASA Astrophysics Data System (ADS)

Hu, Qing

1993-02-01

We have studied the feasibility of photon-assisted quantum transport in semiconductor quantum point contacts or electron waveguides. Due to photon-induced intersubband transitions, it is expected that the drain/source conductance of the quantum point contacts can be modulated by far-infrared (f not less than 300 GHz) radiation, which is similar to the photon-assisted tunneling in superconducting tunnel junctions. An antenna/gate electrodes structure will be used to couple far-infrared photons into quantum point contacts of submicron dimensions. A calculation of the photon-induced drain/source current as a function of the far-infrared radiation power is also presented.

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

PubMed

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

2016-02-01

The intercellular junctions restrict the free passage of hydrophilic compounds through the paracellular clefts. Reversible opening of the tight junctions of biological barriers is investigated as one of the ways to increase drug delivery to the systemic circulation or the central nervous system. Six peptides, ADT-6, HAV-6, C-CPE, 7-mer (FDFWITP, PN-78), AT-1002, and PN-159, acting on different integral membrane and linker junctional proteins were tested on Caco-2 intestinal epithelial cell line and a coculture model of the blood-brain barrier. All peptides tested in nontoxic concentrations showed a reversible tight junctions modulating effect and were effective to open the paracellular pathway for the marker molecules fluorescein and albumin. The change in the structure of cell-cell junctions was verified by immunostaining for occludin, claudin-4,-5, ZO-1, β-catenin, and E-cadherin. Expression levels of occludin and claudins were measured in both models. We could demonstrate a selectivity of C-CPE, ADT-6, and HAV-6 peptides for epithelial cells and 7-mer and AT-1002 peptides for brain endothelial cells. PN-159 was the most effective modulator of junctional permeability in both models possibly acting via claudin-1 and -5. Our results indicate that these peptides can be effectively and selectively used as potential pharmaceutical excipients to improve drug delivery across biological barriers. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

An induced junction photovoltaic cell

NASA Technical Reports Server (NTRS)

Call, R. L.

1974-01-01

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

Direct endothelial junction restoration results in significant tumor vascular normalization and metastasis inhibition in mice

PubMed Central

Agrawal, Vijayendra; Maharjan, Sony; Kim, Kyeojin; Kim, Nam-Jung; Son, Jimin; Lee, Keunho; Choi, Hyun-Jung; Rho, Seung-Sik; Ahn, Sunjoo; Won, Moo-Ho; Ha, Sang-Jun; Koh, Gou Young; Kim, Young-Myeong; Suh, Young-Ger; Kwon, Young-Guen

2014-01-01

Tumor blood vessels are leaky and immature, which causes inadequate blood supply to tumor tissues resulting in hypoxic microenvironment and promotes metastasis. Here we have explored tumor vessel modulating activity of Sac-1004, a recently developed molecule in our lab, which directly potentiates VE-cadherin-mediated endothelial cell junction. Sac-1004 could enhance vascular junction integrity in tumor vessels and thereby inhibit vascular leakage and enhance vascular perfusion. Improved perfusion enabled Sac-1004 to have synergistic anti-tumor effect on cisplatin-mediated apoptosis of tumor cells. Interestingly, characteristics of normalized blood vessels namely reduced hypoxia, improved pericyte coverage and decreased basement membrane thickness were readily observed in tumors treated with Sac-1004. Remarkably, Sac-1004 was also able to inhibit lung and lymph node metastasis in MMTV and B16BL6 tumor models. This was in correlation with a reduction in epithelial-to-mesenchymal transition of tumor cells with considerable diminution in expression of related transcription factors. Moreover, cancer stem cell population dropped substantially in Sac-1004 treated tumor tissues. Taken together, our results showed that direct restoration of vascular junction could be a significant strategy to induce normalization of tumor blood vessels and reduce metastasis. PMID:24811731

R&D issues in scale-up and manufacturing of amorphous silicon tandem modules

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

Arya, R.R.; Carlson, D.E.; Chen, L.F.

1999-03-01

R & D on amorphous silicon based tandem junction devices has improved the throughtput, the material utilization, and the performance of devices on commercial tin oxide coated glass. The tandem junction technology has been scaled-up to produce 8.6&hthinsp;Ft{sup 2} monolithically integrated modules in manufacturing at the TF1 plant. Optimization of performance and stability of these modules is ongoing. {copyright} {ital 1999 American Institute of Physics.}

Anomalous spin-dependent tunneling statistics in Fe/MgO/Fe junctions induced by disorder at the interface

NASA Astrophysics Data System (ADS)

Yan, Jiawei; Wang, Shizhuo; Xia, Ke; Ke, Youqi

2018-01-01

We present first-principles analysis of interfacial disorder effects on spin-dependent tunneling statistics in thin Fe/MgO/Fe magnetic tunnel junctions. We find that interfacial disorder scattering can significantly modulate the tunneling statistics in the minority spin of the parallel configuration (PC) while all other spin channels remain dominated by the Poissonian process. For the minority-spin channel of PC, interfacial disorder scattering favors the formation of resonant tunneling channels by lifting the limitation of symmetry conservation at low concentration, presenting an important sub-Poissonian process in PC, but is destructive to the open channels at high concentration. We find that the important modulation of tunneling statistics is independent of the type of interfacial disorder. A bimodal distribution function of transmission with disorder dependence is introduced and fits very well our first-principles results. The increase of MgO thickness can quickly change the tunneling from a sub-Poissonian to Poissonian dominated process in the minority spin of PC with disorder. Our results provide a sensitive detection method of an ultralow concentration of interfacial defects.

Rac1 and Cdc42 Differentially Modulate Cigarette Smoke–Induced Airway Cell Migration through p120-Catenin–Dependent and –Independent Pathways

PubMed Central

Zhang, Lili; Gallup, Marianne; Zlock, Lorna; Finkbeiner, Walter E.; McNamara, Nancy A.

2014-01-01

The adherens junction protein p120-catenin (p120ctn) shuttles between E-cadherin–bound and cytoplasmic pools to regulate E-cadherin/catenin complex stability and cell migration, respectively. When released from the adherens junction, p120ctn promotes cell migration through modulation of the Rho GTPases Rac1, Cdc42, and RhoA. Accordingly, the down-regulation and cytoplasmic mislocalization of p120ctn has been reported in all subtypes of lung cancers and is associated with grave prognosis. Previously, we reported that cigarette smoke induced cytoplasmic translocation of p120ctn and cell migration, but the underlying mechanism was unclear. Using primary human bronchial epithelial cells exposed to smoke-concentrated medium (Smk), we observed the translocation of Rac1 and Cdc42, but not RhoA, to the leading edge of polarized and migrating human bronchial epithelial cells. Rac1 and Cdc42 were robustly activated by smoke, whereas RhoA was inhibited. Accordingly, siRNA knockdown of Rac1 or Cdc42 completely abolished Smk-induced cell migration, whereas knockdown of RhoA had no effect. p120ctn/Rac1 double knockdown completely abolished Smk-induced cell migration, whereas p120ctn/Cdc42 double knockdown did not. These data suggested that Rac1 and Cdc42 coactivation was essential to smoke-promoted cell migration in the presence of p120ctn, whereas migration proceeded via Rac1 alone in the absence of p120ctn. Thus, Rac1 may provide an omnipotent therapeutic target in reversing cell migration during the early (intact p120ctn) and late (loss of p120ctn) stages of lung carcinogenesis. PMID:23562274

Glutamine Supplementation Attenuates Ethanol-Induced Disruption of Apical Junctional Complexes in Colonic Epithelium and Ameliorates Gut Barrier Dysfunction and Fatty Liver in Mice

PubMed Central

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

2015-01-01

Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of glutamine in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed Gln-free diet and absent in mice fed Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury. PMID:26365579

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

PubMed

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

2010-08-01

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

VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the α-catenin-vinculin module.

PubMed

Oldenburg, Joppe; van der Krogt, Gerard; Twiss, Floor; Bongaarts, Annika; Habani, Yasmin; Slotman, Johan A; Houtsmuller, Adriaan; Huveneers, Stephan; de Rooij, Johan

2015-11-27

Mechanical forces are integrated at cadherin-based adhesion complexes to regulate morphology and strength of cell-cell junctions and organization of associated F-actin. A central mechanosensor at the cadherin complex is α-catenin, whose stretching recruits vinculin to regulate adhesion strength. The identity of the F-actin regulating signals that are also activated by mechanical forces at cadherin-based junctions has remained elusive. Here we identify the actin-regulators VASP, zyxin and TES as members of punctate, tensile cadherin-based junctions called Focal Adherens Junctions (FAJ) and show that they display mechanosensitive recruitment similar to that of vinculin. However, this recruitment is not altered by destroying or over-activating the α-catenin/vinculin module. Structured Illumination Microscopy (SIM) indicates that these tension sensitive proteins concentrate at locations within FAJs that are distinct from the core cadherin complex proteins. Furthermore, localization studies using mutated versions of VASP and zyxin indicate that these two proteins require binding to each other in order to localize to the FAJs. We conclude that there are multiple force sensitive modules present at the FAJ that are activated at distinct locations along the cadherin-F-actin axis and regulate specific aspects of junction dynamics.

VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the α-catenin-vinculin module

PubMed Central

Oldenburg, Joppe; van der Krogt, Gerard; Twiss, Floor; Bongaarts, Annika; Habani, Yasmin; Slotman, Johan A.; Houtsmuller, Adriaan; Huveneers, Stephan; de Rooij, Johan

2015-01-01

Mechanical forces are integrated at cadherin-based adhesion complexes to regulate morphology and strength of cell-cell junctions and organization of associated F-actin. A central mechanosensor at the cadherin complex is α-catenin, whose stretching recruits vinculin to regulate adhesion strength. The identity of the F-actin regulating signals that are also activated by mechanical forces at cadherin-based junctions has remained elusive. Here we identify the actin-regulators VASP, zyxin and TES as members of punctate, tensile cadherin-based junctions called Focal Adherens Junctions (FAJ) and show that they display mechanosensitive recruitment similar to that of vinculin. However, this recruitment is not altered by destroying or over-activating the α-catenin/vinculin module. Structured Illumination Microscopy (SIM) indicates that these tension sensitive proteins concentrate at locations within FAJs that are distinct from the core cadherin complex proteins. Furthermore, localization studies using mutated versions of VASP and zyxin indicate that these two proteins require binding to each other in order to localize to the FAJs. We conclude that there are multiple force sensitive modules present at the FAJ that are activated at distinct locations along the cadherin-F-actin axis and regulate specific aspects of junction dynamics. PMID:26611125

Calcium-Mediated Oxidative Stress: a Common Mechanism in Tight Junction Disruption by Different Types of Cellular Stress

PubMed Central

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

2017-01-01

The role of reactive oxygen species (ROS) in osmotic stress, dextran sulfate sodium (DSS) and cyclic stretch-induced tight junction disruption was investigated in Caco-2 cell monolayers in vitro, and restraint stress-induced barrier dysfunction in mouse colon in vivo. Live cell imaging showed that osmotic stress, cyclic stretch and DSS triggered rapid production of ROS in Caco-2 cell monolayers, which was blocked by depletion of intracellular Ca2+ by BAPTA. Knockdown of CaV1.3 or TRPV6 channels blocked osmotic stress and DSS-induced ROS production and attenuated tight junction disruption and barrier dysfunction. N-acetyl L-cysteine (NAC) and L-nitroarginine methyl ester (L-NAME) blocked stress-induced tight junction disruption and barrier dysfunction. NAC and L-NAME also blocked stress-induced activation of JNK and c-Src. ROS was co-localized with the mitochondrial marker in stressed cells. Cyclosporin A blocked osmotic stress and DSS-induced ROS production, barrier dysfunction, tight junction disruption and JNK activation. Mitochondria-targeted Mito-TEMPO blocked osmotic stress and DSS-induced barrier dysfunction and tight junction disruption. Chronic restraint stress in mice resulted in the elevation of intracellular Ca2+, activation of JNK and c-Src, and disruption of tight junction in the colonic epithelium. Furthermore, corticosterone administration induced JNK and c-Src activation, tight junction disruption and protein thiol oxidation in colonic mucosa. This study demonstrates that oxidative stress is a common signal in the mechanism of tight junction disruption in the intestinal epithelium by different types of cellular stress in vitro and bio behavioral stress in vivo. PMID:28057718

When proteome meets genome: the alpha helix and the beta strand of proteins are eschewed by mRNA splice junctions and may define the minimal indivisible modules of protein architecture

PubMed Central

Barik, Sailen

2008-01-01

The significance of the intron-exon structure of genes is a mystery. As eukaryotic proteins are made up of modular functional domains, each exon was suspected to encode some form of module; however, the definition of a module remained vague. Comparison of pre-mRNA splice junctions with the three-dimensional architecture of its protein product from different eukaryotes revealed that the junctions were far less likely to occur inside the α-helices and β-strands of proteins than within the more flexible linker regions (‘turns’ and ‘loops’) connecting them. The splice junctions were equally distributed in the different types of linkers and throughout the linker sequence, although a slight preference for the central region of the linker was observed. The avoidance of the α-helix and the β-strand by splice junctions suggests the existence of a selection pressure against their disruption, perhaps underscoring the investment made by nature in building these intricate secondary structures. A corollary is that the helix and the strand are the smallest integral architectural units of a protein and represent the minimal modules in the evolution of protein structure. These results should find use in comparative genomics, designing of cloning strategies, and in the mutual verification of genome sequences with protein structures. PMID:15381847

When proteome meets genome: the alpha helix and the beta strand of proteins are eschewed by mRNA splice junctions and may define the minimal indivisible modules of protein architecture.

PubMed

Barik, Sailen

2004-09-01

The significance of the intron-exon structure of genes is a mystery. As eukaryotic proteins are made up of modular functional domains, each exon was suspected to encode some form of module; however, the definition of a module remained vague. Comparison of pre-mRNA splice junctions with the three-dimensional architecture of its protein product from different eukaryotes revealed that the junctions were far less likely to occur inside the alpha-helices and beta-strands of proteins than within the more flexible linker regions ('turns' and 'loops') connecting them. The splice junctions were equally distributed in the different types of linkers and throughout the linker sequence, although a slight preference for the central region of the linker was observed. The avoidance of the alpha-helix and the beta-strand by splice junctions suggests the existence of a selection pressure against their disruption, perhaps underscoring the investment made by nature in building these intricate secondary structures. A corollary is that the helix and the strand are the smallest integral architectural units of a protein and represent the minimal modules in the evolution of protein structure. These results should find use in comparative genomics, designing of cloning strategies, and in the mutual verification of genome sequences with protein structures.

Modulation of Brain Hemichannels and Gap Junction Channels by Pro-Inflammatory Agents and Their Possible Role in Neurodegeneration

PubMed Central

Sáez, Pablo J.; Shoji, Kenji F.; Schalper, Kurt A.; Palacios–Prado, Nicolás; Velarde, Victoria; Giaume, Christian; Bennett, Michael V.L.; Sáez, Juan C.

2009-01-01

Abstract In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e.g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process. Antiox. Redox Signal. 11, 369–399. PMID:18816186

Non-invasive optical modulation of local vascular permeability

NASA Astrophysics Data System (ADS)

Choi, Myunghwan; Choi, Chulhee

2011-03-01

For a systemically administered drug to act, it first needs to cross the vascular wall. This step represents a bottleneck for drug development, especially in the brain or retina, where tight junctions between endothelial cells form physiological barriers. Here, we demonstrate that femtosecond pulsed laser irradiation focused on the blood vessel wall induces transient permeabilization of plasma. Nonlinear absorption of the pulsed laser enabled the noninvasive modulation of vascular permeability with high spatial selectivity in three dimensions. By combining this method with systemic injection, we could locally deliver molecular probes in various tissues, such as brain cortex, meninges, ear, striated muscle, and bone. We suggest this method as a novel delivery tool for molecular probes or drugs.

Neisseria gonorrhoeae infects the human endocervix by activating non-muscle myosin II-mediated epithelial exfoliation

PubMed Central

Yu, Qian; Lin, Brian; Qiu, Jessica; Stein, Daniel C.

2017-01-01

Colonization and disruption of the epithelium is a major infection mechanism of mucosal pathogens. The epithelium counteracts infection by exfoliating damaged cells while maintaining the mucosal barrier function. The sexually transmitted bacterium Neisseria gonorrhoeae (GC) infects the female reproductive tract primarily from the endocervix, causing gonorrhea. However, the mechanism by which GC overcome the mucosal barrier remains elusive. Using a new human tissue model, we demonstrate that GC can penetrate into the human endocervix by inducing the exfoliation of columnar epithelial cells. We found that GC colonization causes endocervical epithelial cells to shed. The shedding results from the disassembly of the apical junctions that seal the epithelial barrier. Apical junction disruption and epithelial exfoliation increase GC penetration into the endocervical epithelium without reducing bacterial adherence to and invasion into epithelial cells. Both epithelial exfoliation and junction disruption require the activation and accumulation of non-muscle myosin II (NMII) at the apical surface and GC adherent sites. GC inoculation activates NMII by elevating the levels of the cytoplasmic Ca2+ and NMII regulatory light chain phosphorylation. Piliation of GC promotes, but the expression of a GC opacity-associated protein variant, OpaH that binds to the host surface proteins CEACAMs, inhibits GC-induced NMII activation and reorganization and Ca2+ flux. The inhibitory effects of OpaH lead to reductions in junction disruption, epithelial exfoliation, and GC penetration. Therefore, GC phase variation can modulate infection in the human endocervix by manipulating the activity of NMII and epithelial exfoliation. PMID:28406994

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

PubMed

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.

Operation and biasing for single device equivalent to CMOS

DOEpatents

Welch, James D.

2001-01-01

Disclosed are semiconductor devices including at least one junction which is rectifying whether the semiconductor is caused to be N or P-type, by the presence of field induced carriers. In particular, inverting and non-inverting gate voltage channel induced semiconductor single devices with operating characteristics similar to conventional multiple device CMOS systems, which can be operated as modulators, are disclosed as are a non-latching SCR and an approach to blocking parasitic currents. Operation of the gate voltage channel induced semiconductor single devices with operating characteristics similar to multiple device CMOS systems under typical bias schemes is described, and simple demonstrative five mask fabrication procedures for the inverting and non-inverting gate voltage channel induced semiconductor single devices with operating characteristics similar to multiple device CMOS systems are also presented.

Plant-derived triterpene celastrol ameliorates oxygen glucose deprivation-induced disruption of endothelial barrier assembly via inducing tight junction proteins.

PubMed

Luo, Dan; Zhao, Jia; Rong, Jianhui

2016-12-01

The integrity and functions of blood-brain barrier (BBB) are regulated by the expression and organization of tight junction proteins. The present study was designed to explore whether plant-derived triterpenoid celastrol could regulate tight junction integrity in murine brain endothelial bEnd3 cells. We disrupted the tight junctions between endothelial bEnd3 cells by oxygen glucose deprivation (OGD). We investigated the effects of celastrol on the permeability of endothelial monolayers by measuring transepithelial electrical resistance (TEER). To clarify the tight junction composition, we analyzed the expression of tight junction proteins by RT-PCR and Western blotting techniques. We found that celastrol recovered OGD-induced TEER loss in a concentration-dependent manner. Celastrol induced occludin, claudin-5 and zonula occludens-1 (ZO-1) in endothelial cells. As a result, celastrol effectively maintained tight junction integrity and inhibited macrophage migration through endothelial monolayers against OGD challenge. Further mechanistic studies revealed that celastrol induced the expression of occludin and ZO-1) via activating MAPKs and PI3K/Akt/mTOR pathway. We also observed that celastrol regulated claudin-5 expression through different mechanisms. The present study demonstrated that celastrol effectively protected tight junction integrity against OGD-induced damage. Thus, celastrol could be a drug candidate for the treatment of BBB dysfunction in various diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

Modulation of Sonic hedgehog-induced mouse embryonic stem cell behaviors through E-cadherin expression and Integrin β1-dependent F-actin formation.

PubMed

Oh, Ji Young; Suh, Han Na; Choi, Gee Euhn; Lee, Hyun Jik; Jung, Young Hyun; Ko, So Hee; Kim, Jun Sung; Chae, Chang Woo; Lee, Chang-Kyu; Han, Ho Jae

2018-06-22

Sonic hedgehog pathway (Shh) plays a central role in maintaining stem cell function and behavior in various processes related to self-renewal and tissue regeneration. However, the therapeutic effect of Shh on mouse embryonic stem cells (mESCs) has not yet been clearly described. Thus, we investigated the effect of Shh on the regulation of mESC behaviors as well as the effect of Shh-pretreated mESCs in skin wound healing. The present study investigated the underlying mechanisms of Shh signaling pathway in growth and motility of mESCs using western blot analysis, cell proliferation assay, and cell migration assay. In addition, the effect of Shh-pretreated mESCs in skin wound healing was determined using mouse excisional wound splinting model. Shh induced adherens junction disruption through proteolysis by activating matrix metallopeptidases. In addition, the release of β-catenin from adherens junctions mediated by Shh led to cell cycle-dependent mESC proliferation. Shh-mediated Gli1 expression led to integrin β1 upregulation, followed by FAK and Src phosphorylation. Furthermore, among the Rho-GTPases, Rac1 and Cdc42 were activated in a Shh-dependent manner while F-actin expression was suppressed by Rac1 and Cdc42 siRNA transfection. Consistent with the in vitro results, skin wound healing assay revealed that Shh-treated mESCs induced angiogenesis and skin wound repair compared to that in Shh-treated mESCs transfected with integrin β1 siRNA in vivo. Our results imply that Shh induces adherens junction disruption and integrin β1-dependent F-actin formation involving FAK/Src and Rac1/Cdc42 signaling pathways in mESCs. This article is protected by copyright. All rights reserved.

Claudins and the Modulation of Tight Junction Permeability

PubMed Central

Günzel, Dorothee

2013-01-01

Claudins are tight junction membrane proteins that are expressed in epithelia and endothelia and form paracellular barriers and pores that determine tight junction permeability. This review summarizes our current knowledge of this large protein family and discusses recent advances in our understanding of their structure and physiological functions. PMID:23589827

Electrolyte-gated transistors based on conducting polymer nanowire junction arrays.

PubMed

Alam, Maksudul M; Wang, Jun; Guo, Yaoyao; Lee, Stephanie P; Tseng, Hsian-Rong

2005-07-07

In this study, we describe the electrolyte gating and doping effects of transistors based on conducting polymer nanowire electrode junction arrays in buffered aqueous media. Conducting polymer nanowires including polyaniline, polypyrrole, and poly(ethylenedioxythiophene) were investigated. In the presence of a positive gate bias, the device exhibits a large on/off current ratio of 978 for polyaniline nanowire-based transistors; these values vary according to the acidity of the gate medium. We attribute these efficient electrolyte gating and doping effects to the electrochemically fabricated nanostructures of conducting polymer nanowires. This study demonstrates that two-terminal devices can be easily converted into three-terminal transistors by simply immersing the device into an electrolyte solution along with a gate electrode. Here, the field-induced modulation can be applied for signal amplification to enhance the device performance.

Lipopolysaccharide regulation of intestinal tight junction permeability is mediated by TLR-4 signal transduction pathway activation of FAK and MyD88

PubMed Central

Guo, Shuhong; Nighot, Meghali; Al-Sadi, Rana; Alhmoud, Tarik; Nighot, Prashant; Ma, Thomas Y.

2015-01-01

Gut-derived bacterial lipopolysaccharides (LPS) play an essential role in inducing intestinal and systemic inflammatory responses and have been implicated as a pathogenic factor of necrotizing enterocolitis (NEC) and inflammatory bowel disease (IBD). The defective intestinal tight junction (TJ) barrier has been shown to be an important factor contributing to the development of intestinal inflammation. LPS, at physiological concentrations, cause an increase in intestinal tight junction permeability (TJP) via a TLR-4 dependent process; however the intracellular mechanisms that mediate LPS regulation of intestinal TJP remain unclear. The aim of this study was to investigate the adaptor proteins and the signaling interactions that mediate LPS modulation of intestinal TJ barrier using an in-vitro and in-vivo model system. LPS caused a TLR-4 dependent activation of membrane-associated adaptor protein FAK in Caco-2 monolayers. LPS caused an activation of both MyD88-dependent and –independent pathways. SiRNA silencing of MyD88 prevented LPS-induced increase in TJP. LPS caused a MyD88-dependent activation of IRAK4. TLR-4, FAK and MyD88 were co-localized. SiRNA silencing of TLR-4 inhibited TLR-4 associated FAK activation; and FAK knockdown prevented MyD88 activation. In-vivo studies also confirmed that LPS-induced increase in mouse intestinal permeability was associated with FAK and MyD88 activation; knockdown of intestinal epithelial FAK prevented LPS-induced increase in intestinal permeability. Additionally, high dose LPS-induced intestinal inflammation was also dependent on TLR-4/FAK/MyD88 signal-transduction axis. Our data show for the first time that LPS-induced increase in intestinal TJP and intestinal inflammation was regulated by TLR-4 dependent activation of FAK-MyD88-IRAK4 signaling pathway. PMID:26466961

Gap junction blockage promotes cadmium-induced apoptosis in BRL 3A derived from Buffalo rat liver cells.

PubMed

Hu, Di; Zou, Hui; Han, Tao; Xie, Junze; Dai, Nannan; Zhuo, Liling; Gu, Jianhong; Bian, Jianchun; Yuan, Yan; Liu, Xuezhong; Liu, Zongping

2016-03-01

Gap junctions mediate direct communication between cells; however, toxicological cascade triggered by nonessential metals can abrogate cellular signaling mediated by gap junctions. Although cadmium (Cd) is known to induce apoptosis in organs and tissues, the mechanisms that underlie gap junction activity in Cd-induced apoptosis in BRL 3A rat liver cells has yet to be established. In this study, we showed that Cd treatment decreased the cell index (a measure of cellular electrical impedance) in BRL 3A cells. Mechanistically, we found that Cd exposure decreased expression of connexin 43 (Cx43), increased expression of p-Cx43 and elevated intracellular free Ca(2+) concentration, corresponding to a decrease in gap junctional intercellular communication. Gap junction blockage pretreatment with 18β-glycyrrhizic acid (GA) promoted Cd-induced apoptosis, involving changes in expression of Bax, Bcl-2, caspase-3 and the mitochondrial transmembrane electrical potential (Δψm). Additionally, GA was found to enhance ERK and p38 activation during Cd-induced activation of mitogen-activated protein kinases, but had no significant effect on JNK activation. Our results indicated the apoptosis-related proteins and the ERK and p38 signaling pathways may participate in gap junction blockage promoting Cd-induced apoptosis in BRL 3A cells.

MicroRNA-205 targets tight junction-related proteins during urothelial cellular differentiation.

PubMed

Chung, Pei-Jung Katy; Chi, Lang-Ming; Chen, Chien-Lun; Liang, Chih-Lung; Lin, Chung-Tzu; Chang, Yu-Xun; Chen, Chun-Hsien; Chang, Yu-Sun

2014-09-01

The mammalian bladder urothelium classified as basal, intermediate, and terminally differentiated umbrella cells offers one of the most effective permeability barrier functions known to exist in nature because of the formation of apical uroplakin plaques and tight junctions. To improve our understanding of urothelial differentiation, we analyzed the microRNA (miRNA) expression profiles of mouse urinary tissues and by TaqMan miRNA analysis of microdissected urothelial layers and in situ miRNA-specific hybridization to determine the dependence of these miRNAs on the differentiation stage. Our in situ hybridization studies revealed that miR-205 was enriched in the undifferentiated basal and intermediate cell layers. We then used a quantitative proteomics approach to identify miR-205 target genes in primary cultured urothelial cells subjected to antagomir-mediated knockdown of specific miRNAs. Twenty-four genes were reproducibly regulated by miR-205; eleven of them were annotated as cell junction- and tight junction-related molecules. Western blot analysis demonstrated that antagomir-induced silencing of miR-205 in primary cultured urothelial cells elevated the expression levels of Tjp1, Cgnl1, and Cdc42. Ectopic expression of miR-205 in MDCK cells inhibited the expression of tight junction proteins and the formation of tight junctions. miR-205- knockdown urothelial cells showed alterations in keratin synthesis and increases of uroplakin Ia and Ib, which are the urothelial differentiation products. These results suggest that miR-205 may contribute a role in regulation of urothelial differentiation by modulating the expression of tight junction-related molecules. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

World Encircling Tectonic Vortex Street - Geostreams Revisited: The Southern Ring Current EM Plasma-Tectonic Coupling in the Western Pacific Rim

NASA Astrophysics Data System (ADS)

Leybourne, Bruce; Smoot, Christian; Longhinos, Biju

2014-05-01

Interplanetary Magnetic Field (IMF) coupling to south polar magnetic ring currents transfers induction energy to the Southern Geostream ringing Antarctica and underlying its encircling mid-ocean ridge structure. Magnetic reconnection between the southward interplanetary magnetic field and the magnetic field of the earth is the primary energy transfer mechanism between the solar wind and the magnetosphere. Induced telluric currents focused within joule spikes along Geostreams heat the southern Pacific. Alignment of the Australian Antarctic Discordance to other tectonic vortexes along the Western Pacific Rim, provide electrical connections to Earths core that modulate global telluric currents. The Banda Sea Triple Junction, a mantle vortex north of Australia, and the Lake Baikal Continental Rift vortex in the northern hemisphere modulate atmospheric Jetstream patterns gravitationally linked to internal density oscillations induced by these telluric currents. These telluric currents are driven by solar magnetic power, rotation and orbital dynamics. A solar rotation 40 day power spectrum in polarity controls north-south migration of earthquakes along the Western Pacific Rim and manifest as the Madden Julian Oscillation a well-documented climate cycle. Solar plasma turbulence cycles related to Hale flares trigger El Nino Southern Oscillations (ENSO's), while solar magnetic field strength frequencies dominate global warming and cooling trends indexed to the Pacific Decadal Oscillation. These Pacific climate anomalies are solar-electro-tectonically modulated via coupling to tropical geostream vortex streets. Particularly the section along the Central Pacific Megatrend connecting the Banda Sea Triple Junction (up welling mantle vortex) north of Australia with the Easter Island & Juan Fernandez twin rotating micro-plates (twin down welling mantle vortexes) along the East Pacific Rise modulating ENSO. Solar eruptions also enhance the equatorial ring current located approximately at the boundary of the plasmasphere and the outer magnetosphere. Induction power of geo-magnetic storms, are linked to ring current strength, and depend on the speed of solar eruptions, along with the dynamic pressure, strength and orientation of the IMF.

The relationship of choline acetyltransferase activity at the neuromuscular junction to changes in muscle mass and function

PubMed Central

Diamond, Ivan; Franklin, Gary M.; Milfay, Dale

1974-01-01

1. The role of muscle mass and function in the regulation of choline acetyltransferase activity at the neuromuscular junction has been investigated in the rat. 2. Choline acetyltransferase (ChAc) is located in presynaptic nerve terminals and is a specific enzymatic marker of cholinergic innervation in muscle. 3. ChAc activity increased co-ordinately with developmental growth of the soleus muscle. However, another form of muscle growth, work hypertrophy, did not produce an increase in ChAc. 4. Growth arrest of muscle by hypophysectomy did not alter the normal development of ChAc activity, and cortisone-induced muscle atrophy did not reduce ChAc activity in the soleus or plantaris. 5. Tenotomy-induced muscle atrophy provoked a significant fall in ChAc in the soleus and plantaris. 6. The tonic soleus had significantly greater ChAc activity than the phasic plantaris. 7. These observations suggest that muscle mass per se does not influence the development and regulation of ChAc in muscle but that the quality of muscle contraction may modulate enzyme activity. PMID:4818500

Silicon modulators with optimized vertical PN junctions for high-modulation-efficiency and low-loss in the O-band

NASA Astrophysics Data System (ADS)

Ang, Thomas Y. L.; Png, Ching Eng; Lim, Soon Thor; Ong, Jun Rong

2018-02-01

Silicon modulators based on the carrier depletion mechanism are extensively used in recent years for high-speed data transmission. Lateral PN junctions are the most common electro-optical phase shifters for silicon Mach-Zehnder modulators (MZMs) due to its ease of fabrication. They have a relatively high DC VπLπ of around 2.5 V.cm in the Oband. An alternative approach is to design and optimize vertical PN junctions for lower DC VπLπ, which is currently lacking in the literature for silicon MZMs that operates using carrier depletion mechanism in the O-band. In this work, we look into the design and optimization of silicon phase shifters based on vertical PN junctions for high-modulationefficiency with VπLπ <= 1 V.cm, while meeting the stringent low loss budget of <= 1 dB/mm for data communication in the O-band. This is achieved by varying the offsets of the vertical PN junction with respect to different doping concentrations (2e17/cm3 - 3e18/cm3 ) near the depletion region. Different types of doping schemes are explored and optimized. Our optimized vertical PN junction designs are predicted to give low DC VπLπ of 0.26-0.5 V.cm for low DC reverse bias of >= -2V and low propagation loss of <= 1dB/mm, resulting in α.VπLπ = 1.7 for the best designs, which to the best of our knowledge, is the lowest α.VπLπ at the O-band to date. Electrical and optical modeling are based on our in-house proprietary software that is able to perform both optical and electrical simulations without loss of data fidelity.

Porcine circovirus 2 (PCV2) increases the expression of endothelial adhesion/junction molecules.

PubMed

Marks, Fernanda S; Almeida, Laura L; Driemeier, David; Canal, Cláudio; Barcellos, David E S N; Guimarães, Jorge A; Reck, José

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus disease, a complex multisystem syndrome in domestic pigs. Despite the significant economic losses caused by porcine circovirus disease, the mechanisms of pathogenesis underlying the clinical findings remain largely unclear. As various reports have highlighted the potential key role of vascular lesions in the pathogenesis of porcine circovirus disease, the aim of this work was to investigate effects of PCV2 infection on vascular endothelial cells, focusing on cell viability and expression of adhesion/junction molecules. PCV2 infection reduced endothelial cell viability, while viral infection did not affected the viability of several other classical cell lines. Also, PCV2 infection in endothelial cells displayed a dual/biphasic effect: initially, infection increased ICAM-1 expression, which can favor leukocyte recruitment and emigration to tissues and possibly inducing characteristic porcine circovirus disease inflammatory lesions; then, secondarily, infection caused an increase in zonula occludens 1 tight junction protein (ZO-1) expression, which in turn can result in difficulties for cell traffic across the endothelium and a potential impairment the immune response in peripheral tissues. These virus-induced endothelial changes could directly impact the inflammatory process of porcine circovirus disease and associated vascular/immune system disturbances. Data suggest that, among the wide range of effects induced by PCV2 on the host, endothelial modulation can be a pivotal process which can help to explain PCV2 pathogenesis in some porcine circovirus disease presentations. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Spinal astrocyte gap junctions contribute to oxaliplatin-induced mechanical hypersensitivity.

PubMed

Yoon, Seo-Yeon; Robinson, Caleb R; Zhang, Haijun; Dougherty, Patrick M

2013-02-01

Spinal glial cells contribute to the development of many types of inflammatory and neuropathic pain. Here the contribution of spinal astrocytes and astrocyte gap junctions to oxaliplatin-induced mechanical hypersensitivity was explored. The expression of glial fibrillary acidic protein (GFAP) in spinal dorsal horn was significantly increased at day 7 but recovered at day 14 after oxaliplatin treatment, suggesting a transient activation of spinal astrocytes by chemotherapy. Astrocyte-specific gap junction protein connexin 43 (Cx43) was significantly increased in dorsal horn at both day 7 and day 14 following chemotherapy, but neuronal (connexin 36 [Cx36]) and oligodendrocyte (connexin 32 [Cx32]) gap junction proteins did not show any change. Blockade of astrocyte gap junction with carbenoxolone (CBX) prevented oxaliplatin-induced mechanical hypersensitivity in a dose-dependent manner and the increase of spinal GFAP expression, but had no effect once the mechanical hypersensitivity induced by oxaliplatin had fully developed. These results suggest that oxaliplatin chemotherapy induces the activation of spinal astrocytes and this is accompanied by increased expression of astrocyte-astrocyte gap junction connections via Cx43. These alterations in spinal astrocytes appear to contribute to the induction but not the maintenance of oxaliplatin-induced mechanical hypersensitivity. Combined, these results suggest that targeting spinal astrocyte/astrocyte-specific gap junction could be a new therapeutic strategy to prevent oxaliplatin-induced neuropathy. Spinal astrocytes but not microglia were recently shown to be recruited in paclitaxel-related chemoneuropathy. Here, spinal astrocyte gap junctions are shown to play an important role in the induction of oxaliplatin neuropathy. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Internal Electric Field Modulation in Molecular Electronic Devices by Atmosphere and Mobile Ions.

PubMed

Chandra Mondal, Prakash; Tefashe, Ushula M; McCreery, Richard L

2018-06-13

The internal potential profile and electric field are major factors controlling the electronic behavior of molecular electronic junctions consisting of ∼1-10 nm thick layers of molecules oriented in parallel between conducting contacts. The potential profile is assumed linear in the simplest cases, but can be affected by internal dipoles, charge polarization, and electronic coupling between the contacts and the molecular layer. Electrochemical processes in solutions or the solid state are entirely dependent on modification of the electric field by electrolyte ions, which screen the electrodes and form the ionic double layers that are fundamental to electrode kinetics and widespread applications. The current report investigates the effects of mobile ions on nominally solid-state molecular junctions containing aromatic molecules covalently bonded between flat, conducting carbon surfaces, focusing on changes in device conductance when ions are introduced into an otherwise conventional junction design. Small changes in conductance were observed when a polar molecule, acetonitrile, was present in the junction, and a large decrease of conductance was observed when both acetonitrile (ACN) and lithium ions (Li + ) were present. Transient experiments revealed that conductance changes occur on a microsecond-millisecond time scale, and are accompanied by significant alteration of device impedance and temperature dependence. A single molecular junction containing lithium benzoate could be reversibly transformed from symmetric current-voltage behavior to a rectifier by repetitive bias scans. The results are consistent with field-induced reorientation of acetonitrile molecules and Li + ion motion, which screen the electrodes and modify the internal potential profile and provide a potentially useful means to dynamically alter junction electronic behavior.

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

NASA Technical Reports Server (NTRS)

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.

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

PubMed

Smith, I M; Baker, A; Arneborg, N; Jespersen, L

2015-11-01

The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast-mediated epithelial cell barrier protection from Salmonella invasion, thus encouraging future efforts aimed at confirming the observed effects in vivo and driving further strain development towards novel yeast probiotics. © 2015 The Society for Applied Microbiology.

Progress in amorphous silicon based large-area multijunction modules

NASA Astrophysics Data System (ADS)

Carlson, D. E.; Arya, R. R.; Bennett, M.; Chen, L.-F.; Jansen, K.; Li, Y.-M.; Maley, N.; Morris, J.; Newton, J.; Oswald, R. S.; Rajan, K.; Vezzetti, D.; Willing, F.; Yang, L.

1996-01-01

Solarex, a business unit of Amoco/Enron Solar, is scaling up its a-Si:H/a-SiGe:H tandem device technology for the production of 8 ft2 modules. The current R&D effort is focused on improving the performance, reliability and cost-effectiveness of the tandem junction technology by systematically optimizing the materials and interfaces in small-area single- and tandem junction cells. Average initial conversion efficiencies of 8.8% at 85% yield have been obtained in pilot production runs with 4 ft2 tandem modules.

Modulation of Excitability in the Temporoparietal Junction Relieves Virtual Reality Sickness.

PubMed

Takeuchi, Naoyuki; Mori, Takayuki; Suzukamo, Yoshimi; Izumi, Shin-Ichi

2018-06-01

Virtual reality (VR) immersion often provokes subjective discomfort and postural instability, so called VR sickness. The neural mechanism of VR sickness is speculated to be related to visual-vestibular information mismatch and/or postural instability. However, the approaches proposed to relieve VR sickness through modulation of brain activity are poorly understood. Using transcranial direct current stimulation (tDCS), we aimed to investigate whether VR sickness could be relieved by the modulation of cortical excitability in the temporoparietal junction (TPJ), which is known to be involved in processing of both vestibular and visual information. Twenty healthy subjects received tDCS over right TPJ before VR immersion. The order of the three types of tDCS (anodal, cathodal, and sham) was counterbalanced across subjects. We evaluated the subjective symptoms, heart rate, and center of pressure at baseline, after tDCS, and after VR immersion. VR immersion using head-mounted displays provoked subjective discomfort and postural instability. However, anodal tDCS over right TPJ ameliorated subjective disorientation symptoms and postural instability induced by VR immersion compared with sham condition. The amelioration of VR sickness by anodal tDCS over the right TPJ might result from relief of the sensory conflict and/or facilitation of vestibular function. Our result not only has potential clinical implications for the neuromodulation approach of VR sickness but also implies a causal role of the TPJ in VR sickness.

Tight junctions and the modulation of barrier function in disease

PubMed Central

2008-01-01

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease. PMID:18415116

Polarization and resistive switching behavior of ferroelectric tunnel junctions with transition metal dichalcogenides

NASA Astrophysics Data System (ADS)

Li, Tao; Lipatov, Alexey; Sharma, Pankaj; Lee, Hyungwoo; Eom, Chang-Beom; Sinitskii, Alexander; Gruverman, Alexei; Alexei Gruverman Team; Alexander Sinitskii Team; Chang-Beom Eom Team

Transition metal dichalcogenides (TMDs) are emerging 2-dimensional (2D) materials of the MX2 type, where M is a transition metal atom (Mo, W, Ti, Sn, Zr, etc.) and X is a chalcogen atom (S, Se, or Te.). Comparing to graphene, TMDs have a sizable band gap and can be metal, half-metal, semiconductor or superconductor. Their band structures can be tuned by external bias voltage, mechanical force, or light illumination. Their rich physical properties make TMDs potential candidates for a variety of applications in nanoelectronics and optoelectronics. Ferroelectric tunnel junctions (FTJs) are actively studied as a next-generation of non-volatile memory elements. An FTJ comprises a ferroelectric tunnel barrier sandwiched between two electrodes. In this work, we investigate the resistive switching behavior of MoS2/BaTiO3-based FTJs. The ON/OFF ratio can be modulated via electric or mechanical control of the switched polarization fraction opening a possibility of tunable electroresistance effect. Effect of optical illumination on the polarization reversal dynamics has been observed and analyzed based on the polarization-induced modulation of the MoS2 layered electronic properties.

Monolithic interconnected module with a tunnel junction for enhanced electrical and optical performance

DOEpatents

Murray, Christopher S.; Wilt, David M.

2000-01-01

An improved thermophotovoltaic (TPV) n/p/n device is provided. Monolithic Interconnected Modules (MIMS), semiconductor devices converting infrared radiation to electricity, have been developed with improved electrical and optical performance. The structure is an n-type emitter on a p-type base with an n-type lateral conduction layer. The incorporation of a tunnel junction and the reduction in the amount of p-type material used results in negligible parasitic absorption, decreased series resistance, increased voltage and increased active area. The novel use of a tunnel junction results in the potential for a TPV device with efficiency greater than 24%.

Estrogen Modulates Expression of Tight Junction Proteins in Rat Vagina

PubMed Central

Oh, Kyung-Jin; Ahn, Kyuyoun

2016-01-01

Background. The objectives of this study were to investigate the localization of tight junctions and the modulation of zonula occludens- (ZO-) 1, occludin and claudin-1 expression by estrogen in castrated female rat vagina. Female Sprague-Dawley rats (230–240 g, n = 45) were divided into three groups and subjected to a sham operation (control group, n = 15), bilateral ovariectomy (Ovx group, n = 15), or bilateral ovariectomy followed by daily subcutaneous injection of 17β-estradiol (50 μg/kg/day, Ovx + Est group, n = 15). The cellular localization and expression of ZO-1, occludin, and claudin-1 were determined in each group by immunohistochemistry and western blot. Results. Expression of ZO-1 was diffuse in all groups, with the highest intensity in the superficial epithelium in the control group. Occludin was localized in the intermediate and basal epithelium. Claudin-1 was most intense in the superficial layer of the vaginal epithelium in the control group. Expression of ZO-1, occludin, and claudin-1 was significantly decreased after ovariectomy and was restored to the level of the control after estrogen replacement. Conclusions. Tight junctions are distinctly localized in rat vagina, and estrogen modulates the expression of tight junctions. Further researches are needed to clarify the functional role of tight junctions in vaginal lubrication. PMID:27127786

Estrogen Modulates Expression of Tight Junction Proteins in Rat Vagina.

PubMed

Oh, Kyung-Jin; Lee, Hyun-Suk; Ahn, Kyuyoun; Park, Kwangsung

2016-01-01

Background. The objectives of this study were to investigate the localization of tight junctions and the modulation of zonula occludens- (ZO-) 1, occludin and claudin-1 expression by estrogen in castrated female rat vagina. Female Sprague-Dawley rats (230-240 g, n = 45) were divided into three groups and subjected to a sham operation (control group, n = 15), bilateral ovariectomy (Ovx group, n = 15), or bilateral ovariectomy followed by daily subcutaneous injection of 17β-estradiol (50 μg/kg/day, Ovx + Est group, n = 15). The cellular localization and expression of ZO-1, occludin, and claudin-1 were determined in each group by immunohistochemistry and western blot. Results. Expression of ZO-1 was diffuse in all groups, with the highest intensity in the superficial epithelium in the control group. Occludin was localized in the intermediate and basal epithelium. Claudin-1 was most intense in the superficial layer of the vaginal epithelium in the control group. Expression of ZO-1, occludin, and claudin-1 was significantly decreased after ovariectomy and was restored to the level of the control after estrogen replacement. Conclusions. Tight junctions are distinctly localized in rat vagina, and estrogen modulates the expression of tight junctions. Further researches are needed to clarify the functional role of tight junctions in vaginal lubrication.

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

PubMed

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

2017-11-01

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

Pulse-voltammetric glucose detection at gold junction electrodes.

PubMed

Rassaei, Liza; Marken, Frank

2010-09-01

A novel glucose sensing concept based on the localized change or "modulation" in pH within a symmetric gold-gold junction electrode is proposed. A paired gold-gold junction electrode (average gap size ca. 500 nm) is prepared by simultaneous bipotentiostatic electrodeposition of gold onto two closely spaced platinum disk electrodes. For glucose detection in neutral aqueous solution, the potential of the "pH-modulator" electrode is set to -1.5 V vs saturated calomel reference electrode (SCE) to locally increase the pH, and simultaneously, either cyclic voltammetry or square wave voltammetry experiments are conducted at the sensor electrode. A considerable improvement in the sensor electrode response is observed when a normal pulse voltammetry sequence is applied to the modulator electrode (to generate "hydroxide pulses") and the glucose sensor electrode is operated with fixed bias at +0.5 V vs SCE (to eliminate capacitive charging currents). Preliminary data suggest good linearity for the glucose response in the medically relevant 1-10 mM concentration range (corresponding to 0.18-1.8 g L(-1)). Future electroanalytical applications of multidimensional pulse voltammetry in junction electrodes are discussed.

Modulation-doped growth of mosaic graphene with single-crystalline p–n junctions for efficient photocurrent generation

PubMed Central

Yan, Kai; Wu, Di; Peng, Hailin; Jin, Li; Fu, Qiang; Bao, Xinhe; Liu, Zhongfan

2012-01-01

Device applications of graphene such as ultrafast transistors and photodetectors benefit from the combination of both high-quality p- and n-doped components prepared in a large-scale manner with spatial control and seamless connection. Here we develop a well-controlled chemical vapour deposition process for direct growth of mosaic graphene. Mosaic graphene is produced in large-area monolayers with spatially modulated, stable and uniform doping, and shows considerably high room temperature carrier mobility of ~5,000 cm2 V−1 s−1 in intrinsic portion and ~2,500 cm2 V−1 s−1 in nitrogen-doped portion. The unchanged crystalline registry during modulation doping indicates the single-crystalline nature of p–n junctions. Efficient hot carrier-assisted photocurrent was generated by laser excitation at the junction under ambient conditions. This study provides a facile avenue for large-scale synthesis of single-crystalline graphene p–n junctions, allowing for batch fabrication and integration of high-efficiency optoelectronic and electronic devices within the atomically thin film. PMID:23232410

Connexin-dependent gap junction enhancement is involved in the synergistic effect of sorafenib and all-trans retinoic acid on HCC growth inhibition.

PubMed

Yang, Yan; Qin, Shu-Kui; Wu, Qiong; Wang, Zi-Shu; Zheng, Rong-Sheng; Tong, Xu-Hui; Liu, Hao; Tao, Liang; He, Xian-Di

2014-02-01

Increasing gap junction activity in tumor cells provides a target by which to enhance antineoplastic therapies. Previously, several naturally occurring agents, including all-trans retinoic acid (ATRA) have been demonstrated to increase gap junctional intercellular communication (GJIC) in a number of types of cancer cells. In the present study, we investigated in vitro whether ATRA modulates the response of human hepatocellular carcinoma (HCC) cells to sorafenib, the only proven oral drug for advanced HCC, and the underlying mechanisms. HepG2 and SMMC-7721 cells were treated with sorafenib and/or ATRA, and cell proliferation and apoptosis were analyzed; the role of GJIC was also explored. We found that ATRA, at non-toxic concentrations, enhanced sorafenib-induced growth inhibition in both HCC cell lines, and this effect was abolished by two GJIC inhibitors, 18-α-GA and oleamide. Whereas lower concentrations of sorafenib (5 µM) or ATRA (0.1 or 10 µM) alone modestly induced GJIC activity, the combination of sorafenib plus ATRA resulted in a strong enhancement of GJIC. However, the action paradigm differed in the HepG2 and SMMC-7721 cells, with the dominant effect of GJIC dependent on the cell-specific connexin increase in protein amounts and relocalization. RT-PCR assay further revealed a transcriptional modification of the key structural connexin in the two cell lines. Thus, a connexin-dependent gap junction enhancement may play a central role in ATRA plus sorafenib synergy in inhibiting HCC cell growth. Since both agents are available for human use, the combination treatment represents a future profitable strategy for the treatment of advanced HCC.

Vasopressin modulates social recognition-related activity in the left temporoparietal junction in humans.

PubMed

Zink, C F; Kempf, L; Hakimi, S; Rainey, C A; Stein, J L; Meyer-Lindenberg, A

2011-04-04

The neuropeptide vasopressin is a key molecular mediator of social behavior in animals and humans, implicated in anxiety and autism. Social recognition, the ability to assess the familiarity of others, is essential for appropriate social interactions and enhanced by vasopressin; however, the neural mechanisms mediating this effect in humans are unknown. Using functional magnetic resonance imaging (fMRI) and an implicit social recognition matching task, we employed a double-blinded procedure in which 20 healthy male volunteers self-administered 40 UI of vasopressin or placebo intranasally, 45 min before performing the matching task in the scanner. In a random-effects fMRI analysis, we show that vasopressin induces a regionally specific alteration in a key node of the theory of mind network, the left temporoparietal junction, identifying a neurobiological mechanism for prosocial neuropeptide effects in humans that suggests novel treatment strategies.

Cellular level robotic surgery: Nanodissection of intermediate filaments in live keratinocytes.

PubMed

Yang, Ruiguo; Song, Bo; Sun, Zhiyong; Lai, King Wai Chiu; Fung, Carmen Kar Man; Patterson, Kevin C; Seiffert-Sinha, Kristina; Sinha, Animesh A; Xi, Ning

2015-01-01

We present the nanosurgery on the cytoskeleton of live cells using AFM based nanorobotics to achieve adhesiolysis and mimic the effect of pathophysiological modulation of intercellular adhesion. Nanosurgery successfully severs the intermediate filament bundles and disrupts cell-cell adhesion similar to the desmosomal protein disassembly in autoimmune disease, or the cationic modulation of desmosome formation. Our nanomechanical analysis revealed that adhesion loss results in a decrease in cellular stiffness in both cases of biochemical modulation of the desmosome junctions and mechanical disruption of intercellular adhesion, supporting the notion that intercellular adhesion through intermediate filaments anchors the cell structure as focal adhesion does and that intermediate filaments are integral components in cell mechanical integrity. The surgical process could potentially help reveal the mechanism of autoimmune pathology-induced cell-cell adhesion loss as well as its related pathways that lead to cell apoptosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Simvastatin-induced up-regulation of gap junctions composed of connexin 43 sensitize Leydig tumor cells to etoposide: an involvement of PKC pathway.

PubMed

Wang, Lingzhi; Fu, Yanni; Peng, Jianxin; Wu, Dengpan; Yu, Meiling; Xu, Chengfang; Wang, Qin; Tao, Liang

2013-10-04

Some of lipophilic statins have been reported to enhance toxicities induced by antineoplastic agents but the underling mechanism is unclear. The authors investigated the involvement of Cx43-mediated gap junction intercellular communication (GJIC) in the effect of simvastatin on the cellular toxicity induced by etoposide in this study. The results showed that a major component of the cytotoxicity of therapeutic levels of etoposide is mediated by gap junctions composed of connexin 43(Cx43) and simvastatin at the dosage which does not induce cytotoxicity enhances etoposide toxicity by increasing gap junction coupling. The augmentative effect of simvastatin on GJIC was related to the inhibition of PKC-mediated Cx43 phosphorylation at ser368 and subsequent enhancement of Cx43 membrane location induced by the agent. The present study suggests the possibility that upregulation of gap junctions may be utilized to increase the efficacy of anticancer chemotherapies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Micrometer size polarization independent depletion-type photonic modulator in Silicon On Insulator

NASA Astrophysics Data System (ADS)

Gardes, F. Y.; Tsakmakidis, K. L.; Thomson, D.; Reed, G. T.; Mashanovich, G. Z.; Hess, O.; Avitabile, D.

2007-04-01

The trend in silicon photonics, in the last few years has been to reduce waveguide size to obtain maximum gain in the real estate of devices as well as to increase the performance of active devices. Using different methods for the modulation, optical modulators in silicon have seen their bandwidth increased to reach multi GHz frequencies. In order to simplify fabrication, one requirement for a waveguide, as well as for a modulator, is to retain polarisation independence in any state of operation and to be as small as possible. In this paper we provide a way to obtain polarization independence and improve the efficiency of an optical modulator using a V-shaped pn junction base on the natural etch angle of silicon, 54.7 deg. This modulator is compared to a flat junction depletion type modulator of the same size and doping concentration.

Testing of dual-junction SCARLET modules and cells plus lessons learned

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

Eskenazi, M.I.; Murphy, D.M.; Ralph, E.L.

1997-12-31

Key simulator test methods and results for Solar Concentrator Array with Refractive Linear Element Technology (SCARLET) cells, modules, and module strings are presented from the NASA/JPL New Millennium DS1 program. Important observations and lessons learned are discussed. These findings include: (1) a significant efficiency increase for shunted low performing 1 sun cells at SCARLET`s {approximately}7 sun concentration, (2) a decrease in temperature coefficient under SCARLET concentration, and (3) the importance of active germanium (third junction) screening during GaInP{sub 2}/GaAs/Ge cell production especially when red reflecting covers are used.

TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways.

PubMed

Tacheau, Charlotte; Fontaine, Juliette; Loy, Jennifer; Mauviel, Alain; Verrecchia, Franck

2008-12-01

One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression.

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

PubMed

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.

Spacer type mediated tunable spin crossover (SCO) characteristics of pyrene decorated 2,6-bis(pyrazol-1-yl)pyridine (bpp) based Fe(ii) molecular spintronic modules.

PubMed

Kumar, Kuppusamy Senthil; Šalitroš, Ivan; Moreno-Pineda, Eufemio; Ruben, Mario

2017-08-14

A simple "isomer-like" variation of the spacer group in a set of Fe(ii) spin crossover (SCO) complexes designed to probe spin state dependence of electrical conductivity in graphene-based molecular spintronic junctions led to the observation of remarkable variations in the thermal- and light-induced magnetic characteristics, paving a simple route for the design of functional SCO complexes with different temperature switching regimes based on a 2,6-bis(pyrazol-1-yl)pyridine ligand skeleton.

Synaptopodin couples epithelial contractility to α-actinin-4–dependent junction maturation

PubMed Central

Kannan, Nivetha

2015-01-01

The epithelial junction experiences mechanical force exerted by endogenous actomyosin activities and from interactions with neighboring cells. We hypothesize that tension generated at cell–cell adhesive contacts contributes to the maturation and assembly of the junctional complex. To test our hypothesis, we used a hydraulic apparatus that can apply mechanical force to intercellular junction in a confluent monolayer of cells. We found that mechanical force induces α-actinin-4 and actin accumulation at the cell junction in a time- and tension-dependent manner during junction development. Intercellular tension also induces α-actinin-4–dependent recruitment of vinculin to the cell junction. In addition, we have identified a tension-sensitive upstream regulator of α-actinin-4 as synaptopodin. Synaptopodin forms a complex containing α-actinin-4 and β-catenin and interacts with myosin II, indicating that it can physically link adhesion molecules to the cellular contractile apparatus. Synaptopodin depletion prevents junctional accumulation of α-actinin-4, vinculin, and actin. Knockdown of synaptopodin and α-actinin-4 decreases the strength of cell–cell adhesion, reduces the monolayer permeability barrier, and compromises cellular contractility. Our findings underscore the complexity of junction development and implicate a control process via tension-induced sequential incorporation of junctional components. PMID:26504173

Fluorescence recovery after photobleaching reveals regulation and distribution of connexin36 gap junction coupling within mouse islets of Langerhans

PubMed Central

Farnsworth, Nikki L; Hemmati, Alireza; Pozzoli, Marina; Benninger, Richard K P

2014-01-01

The pancreatic islets are central to the maintenance of glucose homeostasis through insulin secretion. Glucose-stimulated insulin secretion is tightly linked to electrical activity in β cells within the islet. Gap junctions, composed of connexin36 (Cx36), form intercellular channels between β cells, synchronizing electrical activity and insulin secretion. Loss of gap junction coupling leads to altered insulin secretion dynamics and disrupted glucose homeostasis. Gap junction coupling is known to be disrupted in mouse models of pre-diabetes. Although approaches to measure gap junction coupling have been devised, they either lack cell specificity, suitable quantification of coupling or spatial resolution, or are invasive. The purpose of this study was to develop fluorescence recovery after photobleaching (FRAP) as a technique to accurately and robustly measure gap junction coupling in the islet. The cationic dye Rhodamine 123 was used with FRAP to quantify dye diffusion between islet β cells as a measure of Cx36 gap junction coupling. Measurements in islets with reduced Cx36 verified the accuracy of this technique in distinguishing between distinct levels of gap junction coupling. Analysis of individual cells revealed that the distribution of coupling across the islet is highly heterogeneous. Analysis of several modulators of gap junction coupling revealed glucose- and cAMP-dependent modulation of gap junction coupling in islets. Finally, FRAP was used to determine cell population specific coupling, where no functional gap junction coupling was observed between α cells and β cells in the islet. The results of this study show FRAP to be a robust technique which provides the cellular resolution to quantify the distribution and regulation of Cx36 gap junction coupling in specific cell populations within the islet. Future studies utilizing this technique may elucidate the role of gap junction coupling in the progression of diabetes and identify mechanisms of gap junction regulation for potential therapies. PMID:25172942

Fluorescence recovery after photobleaching reveals regulation and distribution of connexin36 gap junction coupling within mouse islets of Langerhans.

PubMed

Farnsworth, Nikki L; Hemmati, Alireza; Pozzoli, Marina; Benninger, Richard K P

2014-10-15

The pancreatic islets are central to the maintenance of glucose homeostasis through insulin secretion. Glucose‐stimulated insulin secretion is tightly linked to electrical activity in β cells within the islet. Gap junctions, composed of connexin36 (Cx36), form intercellular channels between β cells, synchronizing electrical activity and insulin secretion. Loss of gap junction coupling leads to altered insulin secretion dynamics and disrupted glucose homeostasis. Gap junction coupling is known to be disrupted in mouse models of pre‐diabetes. Although approaches to measure gap junction coupling have been devised, they either lack cell specificity, suitable quantification of coupling or spatial resolution, or are invasive. The purpose of this study was to develop fluorescence recovery after photobleaching (FRAP) as a technique to accurately and robustly measure gap junction coupling in the islet. The cationic dye Rhodamine 123 was used with FRAP to quantify dye diffusion between islet β cells as a measure of Cx36 gap junction coupling. Measurements in islets with reduced Cx36 verified the accuracy of this technique in distinguishing between distinct levels of gap junction coupling. Analysis of individual cells revealed that the distribution of coupling across the islet is highly heterogeneous. Analysis of several modulators of gap junction coupling revealed glucose‐ and cAMP‐dependent modulation of gap junction coupling in islets. Finally, FRAP was used to determine cell population specific coupling, where no functional gap junction coupling was observed between α cells and β cells in the islet. The results of this study show FRAP to be a robust technique which provides the cellular resolution to quantify the distribution and regulation of Cx36 gap junction coupling in specific cell populations within the islet. Future studies utilizing this technique may elucidate the role of gap junction coupling in the progression of diabetes and identify mechanisms of gap junction regulation for potential therapies.

Simulation and parametric analysis of graphene p-n junctions with two rectangular top gates and a single back gate

NASA Astrophysics Data System (ADS)

Nikiforidis, Ioannis; Karafyllidis, Ioannis G.; Dimitrakis, Panagiotis

2018-02-01

Graphene p-n junctions could be the building blocks of future nanoelectronic circuits. While the conductance modulation of graphene p-n junctions formed in devices with one bottom and one top gate have received much attention, there is comparatively little work done on devices with two top gates. Here, we employ tight-bind Hamiltonians and non-equilibrium Green function method to compute in a systematic way the dependence of the conductance of graphene p-n junctions, formed in a device with two top gates, on the device parameters. We present our results in a compact and systematic way, so that the effect of each parameter is clearly shown. Our results show that the device conductance can be effectively modulated, and that graphene devices with two top gates may be used as basic elements in future carbon-based nanoelectronic circuits.

Mammalian target of rapamycin complex (mTOR) pathway modulates blood-testis barrier (BTB) function through F-actin organization and gap junction

PubMed Central

Li, Nan; Cheng, C. Yan

2016-01-01

mTOR (mammalian target of rapamycin) is one of the most important signaling molecules in mammalian cells which regulates an array of cellular events, ranging from cell metabolism to cell proliferation. Based on the association of mTOR with the core component proteins, such as Raptor or Rictor, mTOR can become the mTORC1 (mammalian target of rapamycin complex 1) or mTORC2, respectively. Studies have shown that during the epithelial cycle of spermatogenesis, mTORC1 promotes remodeling and restructuring of the blood-testis barrier (BTB) in vitro and in vivo, making the Sertoli cell tight junction (TJ)-permeability barrier “leaky”; whereas mTORC2 promotes BTB integrity, making the Sertoli cell TJ-barrier “tighter”. These contrasting effects, coupled with the spatiotemporal expression of the core signaling proteins at the BTB that confer the respective functions of mTORC1 vs. mTORC2 thus provide a unique mechanism to modulate BTB dynamics, allowing or disallowing the transport of biomolecules and also preleptotene spermatocytes across the immunological barrier. More importantly, studies have shown that these changes to BTB dynamics conferred by mTORC1 and mTORC2 are mediated by changes in the organization of the actin microfilament networks at the BTB, and involve gap junction (GJ) intercellular communication. Since GJ has recently been shown to be crucial to reboot spermatogenesis and meiosis following toxicant-induced aspermatogenesis, these findings thus provide new insightful information regarding the integration of mTOR and GJ to regulate spermatogenesis. PMID:26957088

Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system.

PubMed

Zeniya, Satoshi; Kuwahara, Hiroya; Daizo, Kaiichi; Watari, Akihiro; Kondoh, Masuo; Yoshida-Tanaka, Kie; Kaburagi, Hidetoshi; Asada, Ken; Nagata, Tetsuya; Nagahama, Masahiro; Yagi, Kiyohito; Yokota, Takanori

2018-05-17

Within the field of RNA therapeutics, antisense oligonucleotide-based therapeutics are a potentially powerful means of treating intractable diseases. However, if these therapeutics are used for the treatment of neurological disorders, safe yet efficient methods of delivering antisense oligonucleotides across the blood-brain barrier to the central nervous system must be developed. Here, we examined the use of angubindin-1, a binder to the tricellular tight junction, to modulate paracellular transport between brain microvascular endothelial cells in the blood-brain barrier for the delivery of antisense oligonucleotides to the central nervous system. This proof-of-concept study demonstrated that intravenously injected angubindin-1 increased the permeability of the blood-brain barrier and enabled transient delivery of subsequently administered antisense oligonucleotides into the mouse brain and spinal cord, leading to silencing of a target RNA without any overt adverse effects. We also found that two bicellular tight junction modulators did not produce such a silencing effect, suggesting that the tricellular tight junction is likely a better target for the delivery of antisense oligonucleotides than the bicellular tight junction. Our delivery strategy of modulating the tricellular tight junction in the blood-brain barrier via angubindin-1 provides a novel avenue of research for the development of antisense oligonucleotide-based therapeutics for the treatment of neurological disorders. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Robust integration schemes for junction-based modulators in a 200mm CMOS compatible silicon photonic platform (Conference Presentation)

NASA Astrophysics Data System (ADS)

Szelag, Bertrand; Abraham, Alexis; Brision, Stéphane; Gindre, Paul; Blampey, Benjamin; Myko, André; Olivier, Segolene; Kopp, Christophe

2017-05-01

Silicon photonic is becoming a reality for next generation communication system addressing the increasing needs of HPC (High Performance Computing) systems and datacenters. CMOS compatible photonic platforms are developed in many foundries integrating passive and active devices. The use of existing and qualified microelectronics process guarantees cost efficient and mature photonic technologies. Meanwhile, photonic devices have their own fabrication constraints, not similar to those of cmos devices, which can affect their performances. In this paper, we are addressing the integration of PN junction Mach Zehnder modulator in a 200mm CMOS compatible photonic platform. Implantation based device characteristics are impacted by many process variations among which screening layer thickness, dopant diffusion, implantation mask overlay. CMOS devices are generally quite robust with respect to these processes thanks to dedicated design rules. For photonic devices, the situation is different since, most of the time, doped areas must be carefully located within waveguides and CMOS solutions like self-alignment to the gate cannot be applied. In this work, we present different robust integration solutions for junction-based modulators. A simulation setup has been built in order to optimize of the process conditions. It consist in a Mathlab interface coupling process and device electro-optic simulators in order to run many iterations. Illustrations of modulator characteristic variations with process parameters are done using this simulation setup. Parameters under study are, for instance, X and Y direction lithography shifts, screening oxide and slab thicknesses. A robust process and design approach leading to a pn junction Mach Zehnder modulator insensitive to lithography misalignment is then proposed. Simulation results are compared with experimental datas. Indeed, various modulators have been fabricated with different process conditions and integration schemes. Extensive electro-optic characterization of these components will be presented.

Blockade of brain stem gap junctions increases phrenic burst frequency and reduces phrenic burst synchronization in adult rat.

PubMed

Solomon, Irene C; Chon, Ki H; Rodriguez, Melissa N

2003-01-01

Recent investigations have examined the influence of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in vitro using transverse medullary slice and en bloc brain stem-spinal cord preparations obtained from neonatal (1-5 days postnatal) mice. Gap junction proteins, however, have been identified in both neurons and glia in brain stem regions implicated in respiratory control in both neonatal and adult rodents. Here, we used an in vitro arterially perfused rat preparation to examine the role of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents. We recorded rhythmic inspiratory motor activity from one or both phrenic nerves before and during pharmacological blockade (i.e., uncoupling) of brain stem gap junctions using carbenoxolone (100 microM), 18alpha-glycyrrhetinic acid (25-100 microM), 18beta-glycyrrhetinic acid (25-100 microM), octanol (200-300 microM), or heptanol (200 microM). During perfusion with a gap junction uncoupling agent, we observed an increase in the frequency of phrenic bursts (~95% above baseline frequency; P < 0.001) and a decrease in peak amplitude of integrated phrenic nerve discharge (P < 0.001). The increase in frequency of phrenic bursts resulted from a decrease in both T(I) (P < 0.01) and T(E) (P < 0.01). In addition, the pattern of phrenic nerve discharge shifted from an augmenting discharge pattern to a "bell-shaped" or square-wave discharge pattern in most experiments. Spectral analyses using a fast Fourier transform (FFT) algorithm revealed a reduction in the peak power of both the 40- to 50-Hz peak (corresponding to the MFO) and 90- to 110-Hz peak (corresponding to the HFO) although spurious higher frequency activity (> or =130 Hz) was observed, suggesting an overall loss or reduction in inspiratory-phase synchronization. Although additional experiments are required to identify the specific brain stem regions and cell types (i.e., neurons, glia) mediating the observed modulations in phrenic motor output, these findings suggest that gap junction communication modulates generation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents in vitro.

Performance tradeoff between lateral and interdigitated doping patterns for high speed carrier-depletion based silicon modulators.

PubMed

Yu, Hui; Pantouvaki, Marianna; Van Campenhout, Joris; Korn, Dietmar; Komorowska, Katarzyna; Dumon, Pieter; Li, Yanlu; Verheyen, Peter; Absil, Philippe; Alloatti, Luca; Hillerkuss, David; Leuthold, Juerg; Baets, Roel; Bogaerts, Wim

2012-06-04

Carrier-depletion based silicon modulators with lateral and interdigitated PN junctions are compared systematically on the same fabrication platform. The interdigitated diode is shown to outperform the lateral diode in achieving a low VπLπ of 0.62 V∙cm with comparable propagation loss at the expense of a higher depletion capacitance. The low VπLπ of the interdigitated PN junction is employed to demonstrate 10 Gbit/s modulation with 7.5 dB extinction ration from a 500 µm long device whose static insertion loss is 2.8 dB. In addition, up to 40 Gbit/s modulation is demonstrated for a 3 mm long device comprising a lateral diode and a co-designed traveling wave electrode.

Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity

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

Zhou, Yuan; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093; Wang, Hui

2015-08-15

Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through themore » regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system. - Highlights: • miRNAs were altered in Sertoli cells exposed to MC-LR. • Alerted genes were involved in different cell functions including the cell morphology. • MC-LR adversely affected Sertoli cell junction formation through the regulating miRNAs.« less

Participation of satellite glial cells of the dorsal root ganglia in acute nociception.

PubMed

Lemes, Júlia Borges Paes; de Campos Lima, Tais; Santos, Débora Oliveira; Neves, Amanda Ferreira; de Oliveira, Fernando Silva; Parada, Carlos Almicar; da Cruz Lotufo, Celina Monteiro

2018-05-29

At dorsal root ganglia, neurons and satellite glial cells (SGC) can communicate through ATP release and P2X7 receptor activation. SGCs are also interconnected by gap junctions and have been previously implicated in modulating inflammatory and chronic pain.We now present evidence that SGCs are also involved in processing acute nociception in rat dorsal root ganglia. Using primary dorsal root ganglia cultures we observed that calcium transients induced in neurons by capsaicin administration were followed by satellite glial cells activation. Only satellite glial cells response was reduced by administration of the P2X7 receptor antagonist A740003. In vivo, acute nociception induced by intraplantar injection of capsaicin in rats was inhibited by A740003 or by the gap junction blocker carbenoxolone administered at the dorsal root ganglia (L5 level). Both drugs also reduced the second phase of the formalin test. These results suggest that communication between neurons and satellite glial cells is not only involved in inflammatory or pathological pain, but also in the transmission of the nociceptive signal, possibly in situations involving C-fiber activation. Copyright © 2018 Elsevier B.V. All rights reserved.

A mechanism enhancing macromolecule transport through paracellular spaces induced by Poly-L-Arginine: Poly-L-Arginine induces the internalization of tight junction proteins via clathrin-mediated endocytosis.

PubMed

Yamaki, Tsutomu; Kamiya, Yusuke; Ohtake, Kazuo; Uchida, Masaki; Seki, Toshinobu; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

2014-09-01

Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we investigated the mechanism of disappearance of TJ proteins from cell-cell junctions after the application of PLA to Caco-2 cell monolayers. The membrane conductance (Gt), FITC-dextran (FD-4) permeability, and localization of TJ proteins were examined after the treatment of Caco-2 cell monolayers with PLA in the presence of various endocytosis inhibitors. In addition, the localization of endosome marker proteins was also observed. Clathrin-mediated endocytosis inhibitors suppressed the increase in Gt and Papp of FD-4 induced by PLA, and also significantly suppressed the disappearance of TJ proteins induced by PLA. Furthermore, occludin, one of the TJ proteins, colocalized with early endosome and recycling endosomes after the internalization of occludin induced by PLA, and then was recycled to the cell-cell junctions. PLA induced the transient internalization of TJ proteins in cell-cell junctions via clathrin-mediated endocytosis, subsequently increasing the permeability of the Caco-2 cell monolayer to FD-4 via a paracellular route.

Low-molecular-weight hyaluronan (LMW-HA) accelerates lymph node metastasis of melanoma cells by inducing disruption of lymphatic intercellular adhesion.

PubMed

Du, Yan; Cao, Manlin; Liu, Yiwen; He, Yiqing; Yang, Cuixia; Wu, Man; Zhang, Guoliang; Gao, Feng

2016-01-01

Endothelial integrity defects initiate lymphatic metastasis of tumor cells. Low-molecular-weight hyaluronan (LMW-HA) derived from plasma and interstitial fluid was reported to be associated with tumor lymphatic metastasis. In addition, LMW-HA was proved to disrupt lymphatic vessel endothelium integrity, thus promoting lymphatic metastasis of tumor cells. Until now, there are few reports on how LMW-HA modulates lymphatic endothelial cells adhesion junctions and affects cancer cells metastasizing into lymph vessels. The aim of our study is to unravel the novel mechanism of LMW-HA in mediating tumor lymphatic metastasis. Here, we employed a melanoma metastasis model to investigate whether LMW-HA facilitates tumor cells transferring from foci to remote lymph nodes by disrupting the lymphatic endothelial integrity. Our data indicate that LMW-HA significantly induces metastasis of melanoma cells to lymph nodes and accelerates interstitial-lymphatic flow in vivo . Further experiments show that increased migration of melanoma cells across human dermal lymphatic endothelial cell (HDLEC) monolayers is accompanied by impaired lymphatic endothelial barrier function and increased permeability. The mechanism study reveals that VE-cadherin-β-catenin pathway and relevant signals are involved in modulating the interactions between endothelial cells and that a significant inhibition of lymphatic endothelium disruption is observed when antibodies to the LMW-HA receptor (LYVE-1) are present. Thus, our findings demonstrate a disruptive effect of LMW-HA on lymphatic endothelium continuity which leads to a promotion on melanoma lymphatic metastasis and also suggest a cellular signaling mechanism associated with VE-cadherin-mediated lymphatic intercellular junctions.

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

PubMed

DiGuilio, K M; Valenzano, M C; Rybakovsky, E; Mullin, J M

2018-01-05

Elevation of the transcription factor HIF-1 is a prominent mediator of not only processes that accompany hypoxia, but also the tumor microenvironment and tissue regeneration. This study uses mediators of "chemical hypoxia" to ask the question whether HIF-1α elevation in a healthy epithelial cell layer leads to leakiness in its tight junctional seals. Transepithelial electrical resistance and transepithelial diffusion of 14 C-D-mannitol and other radiolabeled probes are used as indicators of transepithelial barrier function of CaCo-2 BBe human gastrointestinal epithelial cell layers cultured on permeable supports. Western immunoblot analyses of integral tight junctional proteins (occludin and claudins) are used as further indicators of barrier function change. Cobalt, an inhibitor of the prolyl hydroxylase enzymes governing HIF-1α breakdown in the cell, induces transepithelial leakiness in CaCo-2 BBe cell layers in a time and concentration-dependent manner. This increased leakiness is accompanied by significant changes in certain specific integral tight junctional (TJ) proteins such as a decreased level of occludin and increased level of claudin-5. Similar results regarding barrier function compromise also occur with other chemical inhibitors of HIF-1α breakdown, namely ciclopiroxolamine (CPX) and dimethyloxalylglycine (DMOG). The increased leak is manifested by both decreased transepithelial electrical resistance (R t ) and increased paracellular diffusion of D-mannitol (J m ). The induced transepithelial leak shows significant size selectivity, consistent with induced effects on TJ permeability. Less-differentiated cell layers were significantly more affected than well-differentiated cell layers regarding induced transepithelial leak. A genetically modified CaCo-2 variant with reduced levels of HIF-1β, showed reduced transepithelial leak in response to cobalt exposure, further indicating that elevation of HIF-1α levels induced by agents of "chemical hypoxia" is responsible for the compromised barrier function of the CaCo-2 BBe cell layers. Exposure to inducers of chemical hypoxia elevated HIF-1α levels and increased transepithelial leak. The degree of epithelial differentiation has significant effects on this action, possibly explaining the varying effects of HIF-1 modulation in epithelial and endothelial barrier function in different physiological and pathophysiological conditions.

Doping enhanced barrier lowering in graphene-silicon junctions

NASA Astrophysics Data System (ADS)

Zhang, Xintong; Zhang, Lining; Chan, Mansun

2016-06-01

Rectifying properties of graphene-semiconductor junctions depend on the Schottky barrier height. We report an enhanced barrier lowering in graphene-Si junction and its essential doping dependence in this paper. The electric field due to ionized charge in n-type Si induces the same type doping in graphene and contributes another Schottky barrier lowering factor on top of the image-force-induced lowering (IFIL). We confirm this graphene-doping-induced lowering (GDIL) based on well reproductions of the measured reverse current of our fabricated graphene-Si junctions by the thermionic emission theory. Excellent matching between the theoretical predictions and the junction data of the doping-concentration dependent barrier lowering serves as another evidence of the GDIL. While both GDIL and IFIL are enhanced with the Si doping, GDIL exceeds IFIL with a threshold doping depending on the as-prepared graphene itself.

Optimizing performance of silicon-based p-n junction photodetectors by the piezo-phototronic effect.

PubMed

Wang, Zhaona; Yu, Ruomeng; Wen, Xiaonan; Liu, Ying; Pan, Caofeng; Wu, Wenzhuo; Wang, Zhong Lin

2014-12-23

Silicon-based p-n junction photodetectors (PDs) play an essential role in optoelectronic applications for photosensing due to their outstanding compatibility with well-developed integrated circuit technology. The piezo-phototronic effect, a three-way coupling effect among semiconductor properties, piezoelectric polarizations, and photon excitation, has been demonstrated as an effective approach to tune/modulate the generation, separation, and recombination of photogenerated electron-hole pairs during optoelectronic processes in piezoelectric-semiconductor materials. Here, we utilize the strain-induced piezo-polarization charges in a piezoelectric n-ZnO layer to modulate the optoelectronic process initiated in a p-Si layer and thus optimize the performances of p-Si/ZnO NWs hybridized photodetectors for visible sensing via tuning the transport property of charge carriers across the Si/ZnO heterojunction interface. The maximum photoresponsivity R of 7.1 A/W and fastest rising time of 101 ms were obtained from these PDs when applying an external compressive strain of -0.10‰ on the ZnO NWs, corresponding to relative enhancement of 177% in R and shortening to 87% in response time, respectively. These results indicate a promising method to enhance/optimize the performances of non-piezoelectric semiconductor material (e.g., Si) based optoelectronic devices by the piezo-phototronic effect.

Effect of quantum well position on the distortion characteristics of transistor laser

NASA Astrophysics Data System (ADS)

Piramasubramanian, S.; Ganesh Madhan, M.; Radha, V.; Shajithaparveen, S. M. S.; Nivetha, G.

2018-05-01

The effect of quantum well position on the modulation and distortion characteristics of a 1300 nm transistor laser is analyzed in this paper. Standard three level rate equations are numerically solved to study this characteristics. Modulation depth, second order harmonic and third order intermodulation distortion of the transistor laser are evaluated for different quantum well positions for a 900 MHz RF signal modulation. From the DC analysis, it is observed that optical power is maximum, when the quantum well is positioned near base-emitter interface. The threshold current of the device is found to increase with increasing the distance between the quantum well and the base-emitter junction. A maximum modulation depth of 0.81 is predicted, when the quantum well is placed at 10 nm from the base-emitter junction, under RF modulation. The magnitude of harmonic and intermodulation distortion are found to decrease with increasing current and with an increase in quantum well distance from the emitter base junction. A minimum second harmonic distortion magnitude of -25.96 dBc is predicted for quantum well position (230 nm) near to the base-collector interface for 900 MHz modulation frequency at a bias current of 20 Ibth. Similarly, a minimum third order intermodulation distortion of -38.2 dBc is obtained for the same position and similar biasing conditions.

Inductance analysis of superconducting quantum interference devices with 3D nano-bridge junctions

NASA Astrophysics Data System (ADS)

Wang, Hao; Yang, Ruoting; Li, Guanqun; Wu, Long; Liu, Xiaoyu; Chen, Lei; Ren, Jie; Wang, Zhen

2018-05-01

Superconducting quantum interference devices (SQUIDs) with 3D nano-bridge junctions can be miniaturized into nano-SQUIDs that are able to sense a few spins in a large magnetic field. Among all device parameters, the inductance is key to the performance of SQUIDs with 3D nano-bridge junctions. Here, we measured the critical-current magnetic flux modulation curves of 12 devices with three design types using a current strip-line directly coupled to the SQUID loop. A best flux modulation depth of 71% was achieved for our 3D Nb SQUID. From the modulation curves, we extracted the inductance values of the current stripe-line in each design and compared them with the corresponding simulation results of InductEX. In this way, London penetration depths of 110 and 420 nm were determined for our Nb (niobium) and NbN (niobium nitride) films, respectively. Furthermore, we showed that inductances of 11 and 119 pH for Nb and NbN 3D nano-bridge junctions, respectively, dominated the total inductance of our SQUID loops which are 23 pH for Nb and 255 pH for NbN. A screening parameter being equal to one suggests optimal critical currents of 89.6 and 8.1 μA for Nb and NbN SQUIDs, respectively. Additionally, intrinsic flux noise of 110 ± 40 nΦ0/(Hz)1/2 is calculated for the Nb SQUIDs with 3D nano-bridge junctions by Langevin simulation.

Angiotensin receptors and β-catenin regulate brain endothelial integrity in malaria

PubMed Central

Basu-Roy, Upal; Ty, Maureen; Alique, Matilde; Fernandez-Arias, Cristina; Movila, Alexandru; Gomes, Pollyanna; Edagha, Innocent; Wassmer, Samuel C.; Walther, Thomas

2016-01-01

Cerebral malaria is characterized by cytoadhesion of Plasmodium falciparum–infected red blood cells (Pf-iRBCs) to endothelial cells in the brain, disruption of the blood-brain barrier, and cerebral microhemorrhages. No available antimalarial drugs specifically target the endothelial disruptions underlying this complication, which is responsible for the majority of malaria-associated deaths. Here, we have demonstrated that ruptured Pf-iRBCs induce activation of β-catenin, leading to disruption of inter–endothelial cell junctions in human brain microvascular endothelial cells (HBMECs). Inhibition of β-catenin–induced TCF/LEF transcription in the nucleus of HBMECs prevented the disruption of endothelial junctions, confirming that β-catenin is a key mediator of P. falciparum adverse effects on endothelial integrity. Blockade of the angiotensin II type 1 receptor (AT1) or stimulation of the type 2 receptor (AT2) abrogated Pf-iRBC–induced activation of β-catenin and prevented the disruption of HBMEC monolayers. In a mouse model of cerebral malaria, modulation of angiotensin II receptors produced similar effects, leading to protection against cerebral malaria, reduced cerebral hemorrhages, and increased survival. In contrast, AT2-deficient mice were more susceptible to cerebral malaria. The interrelation of the β-catenin and the angiotensin II signaling pathways opens immediate host-targeted therapeutic possibilities for cerebral malaria and other diseases in which brain endothelial integrity is compromised. PMID:27643439

Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

NASA Astrophysics Data System (ADS)

Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

2014-02-01

The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

Involvement of connexin 43 phosphorylation and gap junctional communication between smooth muscle cells in vasopressin-induced ROCK-dependent vasoconstriction after hemorrhagic shock.

PubMed

Yang, Guangming; Peng, Xiaoyong; Wu, Yue; Li, Tao; Liu, Liangming

2017-10-01

We examined the roles played by gap junctions (GJs) and the GJ channel protein connexin 43 (Cx43) in arginine vasopressin (AVP)-induced vasoconstriction after hemorrhagic shock and their relationship to Rho kinase (ROCK) and protein kinase C (PKC). The results showed that AVP induced an endothelium-independent contraction in rat superior mesenteric arteries (SMAs). Blocking the GJs significantly decreased the contractile response of SMAs and vascular smooth muscle cells (VSMCs) to AVP after shock and hypoxia. The selective Cx43-mimetic peptide inhibited the vascular contractile effect of AVP after shock and hypoxia. AVP restored hypoxia-induced decrease of Cx43 phosphorylation at Ser 262 and gap junctional communication in VSMCs. Activation of RhoA with U-46619 increased the contractile effect of AVP. This effect was antagonized by the ROCK inhibitor Y27632 and the Cx43-mimetic peptide. In contrast, neither an agonist nor an inhibitor of PKC had significant effects on AVP-induced contraction after hemorrhagic shock. In addition, silencing of Cx43 with siRNA blocked the AVP-induced increase of ROCK activity in hypoxic VSMCs. In conclusion, AVP-mediated vascular contractile effects are endothelium and myoendothelial gap junction independent. Gap junctions between VSMCs, gap junctional communication, and Cx43 phosphorylation at Ser 262 play important roles in the vascular effects of AVP. RhoA/ROCK, but not PKC, is involved in this process. Copyright © 2017 the American Physiological Society.

Ultrastructural demonstration of Cx43 gap junctions in induced pluripotent stem cells from human cord blood.

PubMed

Beckmann, Anja; Schubert, Madline; Hainz, Nadine; Haase, Alexandra; Martin, Ulrich; Tschernig, Thomas; Meier, Carola

2016-11-01

Gap junction proteins are essential for direct intercellular communication but also influence cellular differentiation and migration. The expression of various connexin gap junction proteins has been demonstrated in embryonic stem cells, with Cx43 being the most intensely studied. As Cx43 is the most prominent gap junction protein in the heart, cardiomyocyte-differentiated stem cells have been studied intensely. To date, however, little is known about the expression and the subcellular distribution of Cx43 in undifferentiated stem cells or about the structural arrangement of channels. We, therefore, here investigate expression of Cx43 in undifferentiated human cord-blood-derived induced pluripotent stem cells (hCBiPS2). For this purpose, we carried out quantitative real-time PCR and immunohistochemistry. For analysis of Cx43 ultrastructure and protein assembly, we performed freeze-fracture replica immunogold labeling (FRIL). Cx43 expression was detected at mRNA and protein level in hCBIPS2 cells. For the first time, ultrastructural data are presented on gap junction morphology in induced pluripotent stem (iPS) cells from cord blood: Our FRIL and electron microscopical analysis revealed the occurrence of gap junction plaques in undifferentiated iPS cells. In addition, these gap junctions were shown to contain the gap junction protein Cx43.

Photovoltaic module kit including connector assembly for non-penetrating array installation

DOEpatents

Botkin, Jonathan; Graves, Simon; Danning, Matt; Culligan, Matthew

2013-12-31

A PV module kit for non-penetrating rooftop installation, including a plurality of PV modules and a plurality of connectors. Each of the PV modules includes a PV laminate and a frame forming a mounting region assembled thereto. The connectors include a male connector having a male fastener extending from a head, and a female connector having a female fastener assempbled within a head. The heads are entirely formed of plastic. The kit provides a mounted array state including a junction at which the mounting regions of at least two of the PV modules are aligned and interconnected by engagement of the male connector with the female connector. The so-formed junction is substantially electrically insulated. The plurality of connectors can further include a spacer connector including a head forming a bore sized slidably receive the male fastener, with all of the connector heads being identical.

Photovoltaic module kit including connector assembly for non-penetrating array installation

DOEpatents

Botkin, Jonathan [El Cerrito, CA; Graves, Simon [Berkeley, CA; Danning, Matt [Oakland, CA; Culligan, Matthew [Berkeley, CA

2011-11-22

A PV module kit for non-penetrating rooftop installation, including a plurality of PV modules and a plurality of connectors. Each of the PV modules includes a PV laminate and a frame forming a mounting region assembled thereto. The connectors include a male connector having a male fastener extending from a head, and a female connector having a female fastener assembled within a head. The heads are entirely formed of plastic. The kit provides a mounted array state including a junction at which the mounting region of at least two of the PV modules are aligned and interconnected by engagement of the male connector with the female connector. The so-formed junction is substantially electrically insulated. The plurality of connectors can further include a spacer connector including a head forming a bore sized to slidably receive the male fastener, with all of the connector heads being identical.

Photovoltaic module kit including connector assembly for non-penetrating array installation

DOEpatents

Botkin, Jonathan; Graves, Simon; Danning, Matt; Culligan, Matthew

2012-10-23

A PV module kit for non-penetrating rooftop installation, including a plurality of PV modules and a plurality of connectors. Each of the PV modules includes a PV laminate and a frame forming a mounting region assembled thereto. The connectors include a male connector having a male fastener extending from a head, and a female connector having a female fastener assembled within a head. The heads are entirely formed of plastic. The kit provides a mounted array state including a junction at which the mounting region of at least two of the PV modules are aligned and interconnected by engagement of the male connector with the female connector. The so-formed junction is substantially electrically insulated. The plurality of connectors can further include a spacer connector including a head forming a bore sized to slidably receive the male fastener, with all of the connector heads being identical.

Low-Cost CdTe/Silicon Tandem Solar Cells

DOE PAGES

Tamboli, Adele C.; Bobela, David C.; Kanevce, Ana; ...

2017-09-06

Achieving higher photovoltaic efficiency in single-junction devices is becoming increasingly difficult, but tandem modules offer the possibility of significant efficiency improvements. By device modeling we show that four-terminal CdTe/Si tandem solar modules offer the prospect of 25%-30% module efficiency, and technoeconomic analysis predicts that these efficiency gains can be realized at costs per Watt that are competitive with CdTe and Si single junction alternatives. The cost per Watt of the modeled tandems is lower than crystalline silicon, but slightly higher than CdTe alone. But, these higher power modules reduce area-related balance of system costs, providing increased value especially in area-constrainedmore » applications. This avenue for high-efficiency photovoltaics enables improved performance on a near-term timeframe, as well as a path to further reduced levelized cost of electricity as module and cell processes continue to advance.« less

Low-Cost CdTe/Silicon Tandem Solar Cells

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

Tamboli, Adele C.; Bobela, David C.; Kanevce, Ana

Achieving higher photovoltaic efficiency in single-junction devices is becoming increasingly difficult, but tandem modules offer the possibility of significant efficiency improvements. By device modeling we show that four-terminal CdTe/Si tandem solar modules offer the prospect of 25%-30% module efficiency, and technoeconomic analysis predicts that these efficiency gains can be realized at costs per Watt that are competitive with CdTe and Si single junction alternatives. The cost per Watt of the modeled tandems is lower than crystalline silicon, but slightly higher than CdTe alone. But, these higher power modules reduce area-related balance of system costs, providing increased value especially in area-constrainedmore » applications. This avenue for high-efficiency photovoltaics enables improved performance on a near-term timeframe, as well as a path to further reduced levelized cost of electricity as module and cell processes continue to advance.« less

Using the intrinsic properties of silicon micro-ring modulators for characterization of RF termination

NASA Astrophysics Data System (ADS)

Wang, Zhao; Knights, Andrew P.

2017-02-01

We describe a direct experimental method to determine the effective driving voltage (Vpp) applied to a silicon photonic modulator possessing an impedance mismatch between the unterminated capacitive load and input source. This method thus permits subsequent estimation of the power consumption of an imperfectly terminated device as well as a deduction of load impedance for optimization of termination design. The capacitive load in this paper is a silicon micro-ring modulator with an integrated p-n junction acting as a phase shifter. The RF reflection under high-speed drive is directly determined from observation of the eye-diagram following measurement of the power transfer function for various junction bias.

Degradation of connexins and gap junctions

PubMed Central

Falk, Matthias M.; Kells, Rachael M.; Berthoud, Viviana M.

2014-01-01

Connexin proteins are short-lived within the cell, whether present in the secretory pathway or in gap junction plaques. Their levels can be modulated by their rate of degradation. Connexins, at different stages of assembly, are degraded through the proteasomal, endo-/lysosomal, and phago-/lysosomal pathways. In this review, we summarize the current knowledge about connexin and gap junction degradation including the signals and protein-protein interactions that participate in their targeting for degradation. PMID:24486527

Chronic administration of dietary grape seed extract increases colonic expression of gut tight junction protein occludin and reduces fecal calprotectin: a secondary analysis of healthy Wistar Furth rats.

PubMed

Goodrich, Katheryn M; Fundaro, Gabrielle; Griffin, Laura E; Grant, Ar'quette; Hulver, Matthew W; Ponder, Monica A; Neilson, Andrew P

2012-10-01

Animal studies have demonstrated the potential of grape seed extract (GSE) to prevent metabolic syndrome, obesity, and type 2 diabetes. Recently, metabolic endotoxemia induced by bacterial endotoxins produced in the colon has emerged as a possible factor in the etiology of metabolic syndrome. Improving colonic barrier function may control endotoxemia by reducing endotoxin uptake. However, the impact of GSE on colonic barrier integrity and endotoxin uptake has not been evaluated. We performed a secondary analysis of samples collected from a chronic GSE feeding study with pharmacokinetic end points to examine potential modulation of biomarkers of colonic integrity and endotoxin uptake. We hypothesized that a secondary analysis would indicate that chronic GSE administration increases colonic expression of intestinal tight junction proteins and reduces circulating endotoxin levels, even in the absence of an obesity-promoting stimulus. Wistar Furth rats were administered drinking water containing 0.1% GSE for 21 days. Grape seed extract significantly increased the expression of gut junction protein occludin in the proximal colon and reduced fecal levels of the neutrophil protein calprotectin, compared with control. Grape seed extract did not significantly reduce serum or fecal endotoxin levels compared with control, although the variability in serum levels was widely increased by GSE. These data suggest that the improvement of gut barrier integrity and potential modulation of endotoxemia warrant investigation as a possible mechanism by which GSE prevents metabolic syndrome and associated diseases. Further investigation of this mechanism in high-fat feeding metabolic syndrome and obesity models is therefore justified. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2013-01-01

Summary The urinary bladder is a common site of bacterial infection with a majority of cases attributed to uropathogenic Escherichia coli. Sequels of urinary tract infections (UTIs) include the loss of urothelial barrier function and subsequent clinical morbidity secondary to the permeation of urine potassium, urea and ammonia into the subepithelium. To date there has been limited research describing the mechanism by which this urothelial permeability defect develops. The present study models acute uropathogenic E. coli infection in vitro using intact canine bladder mucosa mounted in Ussing chambers to determine whether infection induces primarily a transcellular or paracellular permeability defect. The Ussing chamber sustains tissue viability while physically separating submucosal and lumen influences, so this model is ideal for quantitative measurement of transepithelial electrical resistance (TER) to assess alterations of urothelial barrier function. Using this model, changes in both tissue ultrastructure and TER indicated that uropathogenic E. coli infection promotes a paracellular permeability defect associated with the failure of umbrella cell tight junction formation and umbrella cell sloughing. In addition, bacterial interaction with the urothelium promoted secretion of cytokines from the urinary bladder with bioactivity capable of modulating epithelial barrier function including tumour necrosis factor-α, interleukin (IL)-6 and IL-15. IL-15 secretion by the infected bladder mucosa is a novel finding and, because IL-15 plays key roles in reconstitution of tight junction function in damaged intestine, this study points to a potential role for IL-15 in UTI-induced urothelial injury. PMID:22014415

Ferroelectricity-induced resistive switching in Pb(Zr0.52Ti0.48)O3/Pr0.7Ca0.3MnO3/Nb-doped SrTiO3 epitaxial heterostructure

NASA Astrophysics Data System (ADS)

Md. Sadaf, Sharif; Mostafa Bourim, El; Liu, Xinjun; Hasan Choudhury, Sakeb; Kim, Dong-Wook; Hwang, Hyunsang

2012-03-01

We investigated the effect of a ferroelectric Pb(Zr0.52Ti0.48)O3 (PZT) thin film on the generation of resistive switching in a stacked Pr0.7Ca0.3MnO3 (PCMO)/Nb-doped SrTiO3 (Nb:STO) heterostructure forming a p-n junction. To promote the ferroelectric effect, the thin PZT active layer was deposited on an epitaxially grown p-type PCMO film on a lattice-matched n-type Nb:STO single crystal. It was concluded that the observed resistive switching behavior in the all-perovskite Pt/PZT/PCMO/Nb:STO heterostructure was related to the modulation of PCMO/Nb:STO p-n junction's depletion width, which was caused either by the PZT ferroelectric polarization field effect, the electrochemical drift of oxygen ions under an electric field, or both simultaneously.

Serotonin passes through myoendothelial gap junctions to promote pulmonary arterial smooth muscle cell differentiation.

PubMed

Gairhe, Salina; Bauer, Natalie N; Gebb, Sarah A; McMurtry, Ivan F

2012-11-01

Myoendothelial gap junctional signaling mediates pulmonary arterial endothelial cell (PAEC)-induced activation of latent TGF-β and differentiation of cocultured pulmonary arterial smooth muscle cells (PASMCs), but the nature of the signal passing from PAECs to PASMCs through the gap junctions is unknown. Because PAECs but not PASMCs synthesize serotonin, and serotonin can pass through gap junctions, we hypothesized that the monoamine is the intercellular signal. We aimed to determine whether PAEC-derived serotonin mediates PAEC-induced myoendothelial gap junction-dependent activation of TGF-β signaling and differentiation of PASMCs. Rat PAECs and PASMCs were monocultured or cocultured with (touch) or without (no-touch) direct cell-cell contact. In all cases, tryptophan hydroxylase 1 (Tph1) transcripts were expressed predominantly in PAECs. Serotonin was detected by immunostaining in both PAECs and PASMCs in PAEC/PASMC touch coculture but was not found in PASMCs in either PAEC/PASMC no-touch coculture or in PASMC/PASMC touch coculture. Furthermore, inhibition of gap junctions but not of the serotonin transporter in PAEC/PASMC touch coculture prevented serotonin transfer from PAECs to PASMCs. Inhibition of serotonin synthesis pharmacologically or by small interfering RNAs to Tph1 in PAECs inhibited the PAEC-induced activation of TGF-β signaling and differentiation of PASMCs. We concluded that serotonin synthesized by PAECs is transferred through myoendothelial gap junctions into PASMCs, where it activates TGF-β signaling and induces a more differentiated phenotype. This finding suggests a novel role of gap junction-mediated intercellular serotonin signaling in regulation of PASMC phenotype.

The Role of Gap Junction Communication and Oxidative Stress in the Propagation of Toxic Effects among High-Dose α-Particle-Irradiated Human Cells

PubMed Central

Autsavapromporn, Narongchai; de Toledo, Sonia M.; Little, John B.; Jay-Gerin, Jean-Paul; Harris, Andrew L.; Azzam, Edouard I.

2011-01-01

We investigated the roles of gap junction communication and oxidative stress in modulating potentially lethal damage repair in human fibroblast cultures exposed to doses of α particles or γ rays that targeted all cells in the cultures. As expected, α particles were more effective than γ rays at inducing cell killing; further, holding γ-irradiated cells in the confluent state for several hours after irradiation promoted increased survival and decreased chromosomal damage. However, maintaining α-particle-irradiated cells in the confluent state for various times prior to subculture resulted in increased rather than decreased lethality and was associated with persistent DNA damage and increased protein oxidation and lipid peroxidation. Inhibiting gap junction communication with 18-α-glycyrrhetinic acid or by knockdown of connexin43, a constitutive protein of junctional channels in these cells, protected against the toxic effects in α-particle-irradiated cell cultures during confluent holding. Upregulation of antioxidant defense by ectopic overexpression of glutathione peroxidase protected against cell killing by α particles when cells were analyzed shortly after exposure. However, it did not attenuate the decrease in survival during confluent holding. Together, these findings indicate that the damaging effect of α particles results in oxidative stress, and the toxic effects in the hours after irradiation are amplified by intercellular communication, but the communicated molecule(s) is unlikely to be a substrate of glutathione peroxidase. PMID:21388278

Cell line specific modulation of connexin43 expression after exposure to ionizing radiation.

PubMed

Banaz-Yaşar, Ferya; Tischka, Rabea; Iliakis, George; Winterhager, Elke; Gellhaus, Alexandra

2005-01-01

Gap junctional intercellular communication plays a significant role in mediating radiation-induced bystander effects. However, the level of Cx43 itself is influenced by ionizing radiation, which could modify the bystander effect. Here we have investigated several cell lines for the modulation of Cx43 expression 24 h after irradiation with 5 Gy X-rays. The mouse endothelial cell line bEnd3 revealed a significantly elevated level of Cx43 already 15 min after exposure to X-rays, whereas human hybrid endothelial cells (EA.hy926) exhibited a transient downregulation of Cx43 mRNA. No obvious changes in the communication properties of the different cell lines could be observed after irradiation. The communication-deficient malignant human trophoblast cell line Jeg3 stably transfected with Cx43 did not reveal any induction of endogenous nor alteration in the exogenous Cx43 transcript level upon exposure to 5 Gy. Taken together, our data show a cell line specific modulation of Cx43 expression after exposure to X-rays.

MicroRNA-1 Downregulation Increases Connexin 43 Displacement and Induces Ventricular Tachyarrhythmias in Rodent Hypertrophic Hearts

PubMed Central

Curcio, Antonio; Torella, Daniele; Iaconetti, Claudio; Pasceri, Eugenia; Sabatino, Jolanda; Sorrentino, Sabato; Giampà, Salvatore; Micieli, Mariella; Polimeni, Alberto; Henning, Beverley J.; Leone, Angelo; Catalucci, Daniele; Ellison, Georgina M.; Condorelli, Gianluigi; Indolfi, Ciro

2013-01-01

Downregulation of the muscle-specific microRNA-1 (miR-1) mediates the induction of pathologic cardiac hypertrophy. Dysfunction of the gap junction protein connexin 43 (Cx43), an established miR-1 target, during cardiac hypertrophy leads to ventricular tachyarrhythmias (VT). However, it is still unknown whether miR-1 and Cx43 are interconnected in the pro-arrhythmic context of hypertrophy. Thus, in this study we investigated whether a reduction in the extent of cardiac hypertrophy could limit the pathological electrical remodeling of Cx43 and the onset of VT by modulating miR-1 levels. Wistar male rats underwent mechanical constriction of the ascending aorta to induce pathologic left ventricular hypertrophy (LVH) and afterwards were randomly assigned to receive 10mg/kg valsartan, VAL (LVH+VAL) delivered in the drinking water or placebo (LVH) for 12 weeks. Sham surgery was performed for control groups. Programmed ventricular stimulation reproducibly induced VT in LVH compared to LVH+VAL group. When compared to sham controls, rats from LVH group showed a significant decrease of miR-1 and an increase of Cx43 expression and its ERK1/2-dependent phosphorylation, which displaces Cx43 from the gap junction. Interestingly, VAL administration to rats with aortic banding significantly reduced cardiac hypertrophy and prevented miR-1 down-regulation and Cx43 up-regulation and phosphorylation. Gain- and loss-of-function experiments in neonatal cardiomyocytes (NCMs) in vitro confirmed that Cx43 is a direct target of miR-1. Accordingly, in vitro angiotensin II stimulation reduced miR-1 levels and increased Cx43 expression and phosphorylation compared to un-stimulated NCMs. Finally, in vivo miR-1 cardiac overexpression by an adenoviral vector intra-myocardial injection reduced Cx43 expression and phosphorylation in mice with isoproterenol-induced LVH. In conclusion, miR-1 regulates Cx43 expression and activity in hypertrophic cardiomyocytes in vitro and in vivo. Treatment of pressure overload-induced myocyte hypertrophy reduces the risk of life-threatening VT by normalizing miR-1 expression levels with the consequent stabilization of Cx43 expression and activity within the gap junction. PMID:23922949

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

PubMed

Xu, Liming; Dan, Mo; Shao, Anliang; Cheng, Xiang; Zhang, Cuiping; Yokel, Robert A; Takemura, Taro; Hanagata, Nobutaka; Niwa, Masami; Watanabe, Daisuke

2015-01-01

Silver nanoparticles (Ag-NPs) can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood-brain barrier (BBB) and the underlying mechanism(s) of action on the BBB and the brain are not well understood. To investigate Ag-NP suspension (Ag-NPS)-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM). Global gene expression of astrocytes was measured using a DNA microarray. A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200 Ω·cm(2). After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the tight junction (TJ) protein ZO-1 was decreased. Discontinuous TJs were also observed between microvascular endothelial cells. After Ag-NPS exposure, severe mitochondrial shrinkage, vacuolations, endoplasmic reticulum expansion, and Ag-NPs were observed in astrocytes by TEM. Global gene expression analysis showed that three genes were upregulated and 20 genes were downregulated in astrocytes treated with Ag-NPS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the 23 genes were associated with metabolic processes, biosynthetic processes, response to stimuli, cell death, the MAPK pathway, and so on. No GO term and KEGG pathways were changed in the released-ion or polystyrene-NP groups. Ag-NPS inhibited the antioxidant defense of the astrocytes by increasing thioredoxin interacting protein, which inhibits the Trx system, and decreasing Nr4a1 and Dusp1. Meanwhile, Ag-NPS induced inflammation and apoptosis through modulation of the MAPK pathway or B-cell lymphoma-2 expression or mTOR activity in astrocytes. These results draw our attention to the importance of Ag-NP-induced toxicity on the neurovascular unit and provide a better understanding of its toxicological mechanisms on astrocytes.

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

PubMed

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

2011-12-01

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

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.

PubMed

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.

Large resistance change on magnetic tunnel junction based molecular spintronics devices

NASA Astrophysics Data System (ADS)

Tyagi, Pawan; Friebe, Edward

2018-05-01

Molecular bridges covalently bonded to two ferromagnetic electrodes can transform ferromagnetic materials and produce intriguing spin transport characteristics. This paper discusses the impact of molecule induced strong coupling on the spin transport. To study molecular coupling effect the octametallic molecular cluster (OMC) was bridged between two ferromagnetic electrodes of a magnetic tunnel junction (Ta/Co/NiFe/AlOx/NiFe/Ta) along the exposed side edges. OMCs induced strong inter-ferromagnetic electrode coupling to yield drastic changes in transport properties of the magnetic tunnel junction testbed at the room temperature. These OMCs also transformed the magnetic properties of magnetic tunnel junctions. SQUID and ferromagnetic resonance studies provided insightful data to explain transport studies on the magnetic tunnel junction based molecular spintronics devices.

The Sleep-inducing Lipid Oleamide Deconvolutes Gap Junction Communication and Calcium Wave Transmission in Glial Cells

PubMed Central

Guan, Xiaojun; Cravatt, Benjamin F.; Ehring, George R.; Hall, James E.; Boger, Dale L.; Lerner, Richard A.; Gilula, Norton B.

1997-01-01

Oleamide is a sleep-inducing lipid originally isolated from the cerebrospinal fluid of sleep-deprived cats. Oleamide was found to potently and selectively inactivate gap junction–mediated communication between rat glial cells. In contrast, oleamide had no effect on mechanically stimulated calcium wave transmission in this same cell type. Other chemical compounds traditionally used as inhibitors of gap junctional communication, like heptanol and 18β-glycyrrhetinic acid, blocked not only gap junctional communication but also intercellular calcium signaling. Given the central role for intercellular small molecule and electrical signaling in central nervous system function, oleamide- induced inactivation of glial cell gap junction channels may serve to regulate communication between brain cells, and in doing so, may influence higher order neuronal events like sleep induction. PMID:9412472

PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia.

PubMed

Gu, Y; Groome, L J; Alexander, J S; Wang, Y

2012-10-01

PAR-2 is a G-protein coupled protease receptor whose activation in endothelial cells (ECs) is associated with increased solute permeability. VE-cadherin is an endothelial-specific junction protein, which exhibits a disorganized distribution at cell junction during inflammation and is a useful indicator of endothelial barrier dysfunction. In the present study, we tested the hypothesis that PAR-2 activation mediates placenta-derived chymotrypsin-like protease (CLP)-induced endothelial junction disturbance and permeability in preeclampsia (PE). PAR-2 and VE-cadherin were examined by immunofluorescent staining. Specific CLP induced PAR-2 activation and altered VE-cadherin distribution was assessed following depletion of protease chymotrypsin in the placental conditioned medium and after PAR-2 siRNA. VE-cadherin assembly was determined by treating cells with protease chymotrypsin and/or the specific PAR-2 agonist SLIGKV-NH2. Our results showed: 1) placental conditioned medium not only disturbed VE-cadherin distribution at cell junctions but also activated PAR-2 in ECs; 2) PAR-2 siRNA blocked the placental conditioned medium induced PAR-2 upregulation and disorganization of VE-cadherin at cell junctions; 3) PAR-2 agonist induced PAR-2 activation and VE-cadherin reorganization were dose-dependent; and 4) PAR-2 agonist could stimulate ERK1/2 activation. These results strongly suggest that proteases produced by the placenta elicit endothelial barrier dysfunction via a PAR-2 signaling regulatory mechanism in PE. Copyright © 2012 Elsevier Ltd. All rights reserved.

PAR-2 triggers placenta-derived protease-induced altered VE-cadherin reorganization at endothelial junctions in preeclampsia

PubMed Central

Gu, Yang; Groome, Lynn J.; Alexander, J. Steven; Wang, Yuping

2014-01-01

PAR-2 is a G-protein coupled protease receptor whose activation in endothelial cells (ECs) is associated with increased solute permeability. VE-cadherin is an endothelial specific junction protein, which exhibits a disorganized distribution at cell junction during inflammation and is a useful indicator of endothelial barrier dysfunction. In the present study, we tested the hypothesis that PAR-2 activation mediates placenta-derived chymotrypsin-like protease (CLP)-induced endothelial junction disturbance and permeability in preeclampsia (PE). PAR-2 and VE-cadherin were examined by immunofluorescent staining. Specific CLP-induced PAR-2 activation and altered VE-cadherin distribution was assessed following depletion of protease chymotrypsin in the placental conditioned medium and after PAR-2 siRNA. VE-cadherin assembly was determined by treating cells with protease chymotrypsin and/or the specific PAR-2 agonist SLIGKV-NH2. Our results showed: 1) placental conditioned medium not only disturbed VE-cadherin distribution at cell junctions but also activated PAR-2 in ECs; 2) PAR-2 siRNA blocked the placental conditioned medium induced PAR-2 upregulation and disorganization of VE-cadherin at cell junctions; 3) PAR-2 agonist induced PAR-2 activation and VE-cadherin reorganization were dose-dependent; and 4) PAR-2 agonist could stimulate ERK1/2 activation. These results strongly suggest that proteases produced by the placenta elicit endothelial barrier dysfunction via a PAR-2 signaling regulatory mechanism in PE. PMID:22840244

Lipopolysaccharide effects on the proliferation of NRK52E cells via alternations in gap-junction function.

PubMed

Hei, Ziqing; Zhang, Ailan; Wei, Jing; Gan, Xiaoliang; Wang, Yanling; Luo, Gangjian; Li, Xiaoyun

2012-07-01

Gap junctions regulate proper kidney function by facilitating intercellular communication, vascular conduction, and tubular purinergic signaling. However, no clear relationship has been described between gap-junction function and acute kidney injury induced by the endotoxin lipopolysaccharide (LPS). Normal rat kidney epithelial cells (NRK52E cells) were seeded at high and low densities to promote or impede gap-junction formation, respectively, and establish distinctive levels of intercellular communication in culture. Cells were then challenged with LPS at various concentrations (10-1,000 ng/mL). LPS-induced formation and function of gap junctions were assessed by measuring changes in cell proliferation and colony-forming rates, fluorescent dye transmission to adjacent cells, expression levels of connexin43, and repositioning of confluent cells in response to the gap junction inhibitor oleamide or agonist retinoic acid. The cell proliferation rate and colony-forming rate of high- and low-density NRK52E cells were decreased upon LPS challenge, in a dose-dependent manner. The colony-forming rate of confluent high-density cells was significantly lower than that of low-density cells. Oleamide treatment raised the LPS-induced colony-forming rate of high-density cells, whereas retinoic acid decreased the rate. Neither oleamide nor retinoic acid significantly affected the LPS-induced colony-forming rate of low-density cells. Fluorescence transmission of high-density cells was reduced by LPS challenge, in a dose-dependent manner, but inclusion of retinoic acid increased the LPS-induced transmission of fluorescence. LPS challenge of either high- or low-density NRK52E cells resulted in down-regulated connexin43 expression. Gap-junction function plays an important role in concentration-dependent cytotoxic effect of LPS on normal rat kidney cells in vitro.

RAPID COMMUNICATION: DC superconducting quantum interference devices fabricated using bicrystal grain boundary junctions in Co-doped BaFe2As2 epitaxial films

NASA Astrophysics Data System (ADS)

Katase, Takayoshi; Ishimaru, Yoshihiro; Tsukamoto, Akira; Hiramatsu, Hidenori; Kamiya, Toshio; Tanabe, Keiichi; Hosono, Hideo

2010-08-01

DC superconducting quantum interference devices (dc-SQUIDs) were fabricated in Co-doped BaFe2As2 epitaxial films on (La, Sr)(Al, Ta)O3 bicrystal substrates with 30° misorientation angles. The 18 × 8 µm2 SQUID loop with an estimated inductance of 13 pH contained two 3 µm wide grain boundary junctions. The voltage-flux characteristics clearly exhibited periodic modulations with ΔV = 1.4 µV at 14 K, while the intrinsic flux noise of dc-SQUIDs was 7.8 × 10 - 5 Φ0 Hz - 1/2 above 20 Hz. The rather high flux noise is mainly attributed to the small voltage modulation depth which results from the superconductor-normal-metal-superconductor junction nature of the bicrystal grain boundary.

MoS2 Heterojunctions by Thickness Modulation

PubMed Central

Tosun, Mahmut; Fu, Deyi; Desai, Sujay B.; Ko, Changhyun; Seuk Kang, Jeong; Lien, Der-Hsien; Najmzadeh, Mohammad; Tongay, Sefaattin; Wu, Junqiao; Javey, Ali

2015-01-01

In this work, we report lateral heterojunction formation in as-exfoliated MoS2 flakes by thickness modulation. Kelvin probe force microscopy is used to map the surface potential at the monolayer-multilayer heterojunction, and consequently the conduction band offset is extracted. Scanning photocurrent microscopy is performed to investigate the spatial photocurrent response along the length of the device including the source and the drain contacts as well as the monolayer-multilayer junction. The peak photocurrent is measured at the monolayer-multilayer interface, which is attributed to the formation of a type-I heterojunction. The work presents experimental and theoretical understanding of the band alignment and photoresponse of thickness modulated MoS2 junctions with important implications for exploring novel optoelectronic devices. PMID:26121940

MoS 2 Heterojunctions by Thickness Modulation

DOE PAGES

Tosun, Mahmut; Fu, Deyi; Desai, Sujay B.; ...

2015-06-30

In this work, we report lateral heterojunction formation in as-exfoliated MoS 2 flakes by thickness modulation. Kelvin probe force microscopy is used to map the surface potential at the monolayer-multilayer heterojunction, and consequently the conduction band offset is extracted. Scanning photocurrent microscopy is performed to investigate the spatial photocurrent response along the length of the device including the source and the drain contacts as well as the monolayer-multilayer junction. The peak photocurrent is measured at the monolayer-multilayer interface, which is attributed to the formation of a type-I heterojunction. Finally, the work presents experimental and theoretical understanding of the band alignmentmore » and photoresponse of thickness modulated MoS 2 junctions with important implications for exploring novel optoelectronic devices.« less

Process research of non-CZ silicon material

NASA Technical Reports Server (NTRS)

Campbell, R. B.

1984-01-01

Advanced processing techniques for non-CZ silicon sheet material that might improve the cost effectiveness of photovoltaic module production were investigated. Specifically, the simultaneous diffusion of liquid boron and liquid phosphorus organometallic precursors into n-type dendritic silicon web was examined. The simultaneous junction formation method for solar cells was compared with the sequential junction formation method. The electrical resistivity of the n-n and p-n junctions was discussed. Further research activities for this program along with a program documentation schedule are given.

TLR2 mediates gap junctional intercellular communication through connexin-43 in intestinal epithelial barrier injury.

PubMed

Ey, Birgit; Eyking, Annette; Gerken, Guido; Podolsky, Daniel K; Cario, Elke

2009-08-14

Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser368 to prevent spontaneous chronic colitis in MDR1alpha-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair.

TLR2 Mediates Gap Junctional Intercellular Communication through Connexin-43 in Intestinal Epithelial Barrier Injury*

PubMed Central

Ey, Birgit; Eyking, Annette; Gerken, Guido; Podolsky, Daniel K.; Cario, Elke

2009-01-01

Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser368 to prevent spontaneous chronic colitis in MDR1α-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair. PMID:19528242

Neisseria gonorrhoeae breaches the apical junction of polarized epithelial cells for transmigration by activating EGFR

PubMed Central

Edwards, Vonetta L.; Wang, Liang-Chun; Dawson, Valerie; Stein, Daniel C.; Song, Wenxia

2017-01-01

Summary Neisseria gonorrhoeae initiates infection at the apical surface of columnar endocervical epithelial cells in the female reproductive tract. These cells provide a physical barrier against pathogens by forming continuous apical junctional complexes between neighbouring cells. This study examines the interaction of gonococci (GC) with polarized epithelial cells. We show that viable GC preferentially localize at the apical side of the cell–cell junction in polarized endometrial and colonic epithelial cells, HEC-1-B and T84. In GC-infected cells, continuous apical junctional complexes are disrupted, and the junction-associated protein β-catenin is redistributed from the apical junction to the cytoplasm and to GC adherent sites; however, overall cellular levels remain unchanged. This redistribution of junctional proteins is associated with a decrease in the ‘fence’ function of the apical junction but not its ‘gate’ function. Disruption of the apical junction by removing calcium increases GC transmigration across the epithelial monolayer. GC inoculation induces the phosphorylation of both epidermal growth factor receptor (EGFR) and β-catenin, while inhibition of EGFR kinase activity significantly reduces both GC-induced β-catenin redistribution and GC transmigration. Therefore, the gonococcus is capable of weakening the apical junction and polarity of epithelial cells by activating EGFR, which facilitates GC transmigration across the epithelium. PMID:23279089

Chaos and multi-scroll attractors in RCL-shunted junction coupled Jerk circuit connected by memristor

PubMed Central

Zhou, Ping; Ahmad, Bashir; Ren, Guodong; Wang, Chunni

2018-01-01

In this paper, a new four-variable dynamical system is proposed to set chaotic circuit composed of memristor and Josephson junction, and the dependence of chaotic behaviors on nonlinearity is investigated. A magnetic flux-controlled memristor is used to couple with the RCL-shunted junction circuit, and the dynamical behaviors can be modulated by changing the coupling intensity between the memristor and the RCL-shunted junction. Bifurcation diagram and Lyapunov exponent are calculated to confirm the emergence of chaos in the improved dynamical system. The outputs and dynamical behaviors can be controlled by the initial setting and external stimulus as well. As a result, chaos can be suppressed and spiking occurs in the sampled outputs under negative feedback, while applying positive feedback type via memristor can be effective to trigger chaos. Furthermore, it is found that the number of multi-attractors in the Jerk circuit can be modulated when memristor coupling is applied on the circuit. These results indicate that memristor coupling can be effective to control chaotic circuits and it is also useful to reproduce dynamical behaviors for neuronal activities. PMID:29342178

Chaos and multi-scroll attractors in RCL-shunted junction coupled Jerk circuit connected by memristor.

PubMed

Ma, Jun; Zhou, Ping; Ahmad, Bashir; Ren, Guodong; Wang, Chunni

2018-01-01

In this paper, a new four-variable dynamical system is proposed to set chaotic circuit composed of memristor and Josephson junction, and the dependence of chaotic behaviors on nonlinearity is investigated. A magnetic flux-controlled memristor is used to couple with the RCL-shunted junction circuit, and the dynamical behaviors can be modulated by changing the coupling intensity between the memristor and the RCL-shunted junction. Bifurcation diagram and Lyapunov exponent are calculated to confirm the emergence of chaos in the improved dynamical system. The outputs and dynamical behaviors can be controlled by the initial setting and external stimulus as well. As a result, chaos can be suppressed and spiking occurs in the sampled outputs under negative feedback, while applying positive feedback type via memristor can be effective to trigger chaos. Furthermore, it is found that the number of multi-attractors in the Jerk circuit can be modulated when memristor coupling is applied on the circuit. These results indicate that memristor coupling can be effective to control chaotic circuits and it is also useful to reproduce dynamical behaviors for neuronal activities.

Spinal gap junctions: potential involvement in pain facilitation.

PubMed

Spataro, Leah E; Sloane, Evan M; Milligan, Erin D; Wieseler-Frank, Julie; Schoeniger, Diana; Jekich, Brian M; Barrientos, Ruth M; Maier, Steven F; Watkins, Linda R

2004-09-01

Glia are now recognized as important contributors in pathological pain creation and maintenance. Spinal cord glia exhibit extensive gap junctional connectivity, raising the possibility that glia are involved in the contralateral spread of excitation resulting in mirror image pain. In the present experiments, the gap junction decoupler carbenoxolone was administered intrathecally after induction of neuropathic pain in response to sciatic nerve inflammation (sciatic inflammatory neuropathy) or partial nerve injury (chronic constriction injury). In both neuropathic pain models, a low dose of carbenoxolone reversed mirror image mechanical allodynia, while leaving ipsilateral mechanical allodynia unaffected. Ipsilateral thermal hyperalgesia was briefly attenuated. Critically, blockade of mechanical allodynia and thermal hyperalgesia was not observed in response to intrathecal glycyrrhizic acid, a compound similar to carbenoxolone in all respects but it does not decouple gap junctions. Thus, blockade of mechanical allodynia and thermal hyperalgesia by carbenoxolone does appear to reflect an effect on gap junctions. Examination of carbenoxolone's effects on intrathecal human immunodeficiency virus type 1 gp120 showed that blockade of pain facilitation might result, at least in part, via suppression of interleukin-1 and, in turn, interleukin-6. These data provide the first suggestion that spread of excitation via gap junctions might contribute importantly to inflammatory and traumatic neuropathic pain. The current studies provide evidence for involvement of gap junctions in spinal cord pain facilitation. Intrathecal carbenoxolone, a gap junction decoupler, reversed neuropathy-induced mirror image pain and intrathecal gp120-induced allodynia. In addition, it decreased gp120-induced proinflammatory cytokines. This suggests gap junction activation might lead to proinflammatory cytokine release by distantly activated glia.

Theory of coherent quantum phase slips in Josephson junction chains with periodic spatial modulations

NASA Astrophysics Data System (ADS)

Svetogorov, Aleksandr E.; Taguchi, Masahiko; Tokura, Yasuhiro; Basko, Denis M.; Hekking, Frank W. J.

2018-03-01

We study coherent quantum phase slips which lift the ground state degeneracy in a Josephson junction ring, pierced by a magnetic flux of the magnitude equal to half of a flux quantum. The quantum phase-slip amplitude is sensitive to the normal mode structure of superconducting phase oscillations in the ring (Mooij-Schön modes). These, in turn, are affected by spatial inhomogeneities in the ring. We analyze the case of weak periodic modulations of the system parameters and calculate the corresponding modification of the quantum phase-slip amplitude.

Spin-dependent Seebeck effects in a graphene superlattice p-n junction with different shapes

NASA Astrophysics Data System (ADS)

Zhou, Benhu; Zhou, Benliang; Yao, Yagang; Zhou, Guanghui; Hu, Ming

2017-10-01

We theoretically calculate the spin-dependent transmission probability and spin Seebeck coefficient for a zigzag-edge graphene nanoribbon p-n junction with periodically attached stubs under a perpendicular magnetic field and a ferromagnetic insulator. By using the nonequilibrium Green’s function method combining with the tight-binding Hamiltonian, it is demonstrated that the spin-dependent transmission probability and spin Seebeck coefficient for two types of superlattices can be modulated by the potential drop, the magnetization strength, the number of periods of the superlattice, the strength of the perpendicular magnetic field, and the Anderson disorder strength. Interestingly, a metal to semiconductor transition occurs as the number of the superlattice for a crossed superlattice p-n junction increases, and its spin Seebeck coefficient is much larger than that for the T-shaped one around the zero Fermi energy. Furthermore, the spin Seebeck coefficient for crossed systems can be much pronounced and their maximum absolute value can reach 528 μV K-1 by choosing optimized parameters. Besides, the spin Seebeck coefficient for crossed p-n junction is strongly enhanced around the zero Fermi energy for a weak magnetic field. Our results provide theoretical references for modulating the thermoelectric properties of a graphene superlattice p-n junction by tuning its geometric structure and physical parameters.

Photovoltaic module bypass diode encapsulation

NASA Technical Reports Server (NTRS)

Shepard, N. J., Jr.

1983-01-01

The design and processing techniques necessary to incorporate bypass diodes within the module encapsulant are presented. The Semicon PN junction diode cells were selected. Diode junction to heat spreader thermal resistance measurements, performed on a variety of mounted diode chip types and sizes, have yielded values which are consistently below 1 deg C per watt, but show some instability when thermally cycled over the temperature range from -40 to 150 deg C. Three representative experimental modules, each incorporating integral bypass diode/heat spreader assemblies of various sizes, were designed. Thermal testing of these modules enabled the formulation of a recommended heat spreader plate sizing relationship. The production cost of three encapsulated bypass diode/heat spreader assemblies were compared with similarly rated externally mounted packaged diodes. It is concluded that, when proper designed and installed, these bypass diode devices will improve the overall reliability of a terrestrial array over a 20 year design lifetime.

Large resistance change on magnetic tunnel junction based molecular spintronics devices

DOE PAGES

Tyagi, Pawan; Friebe, Edward

2018-01-12

Here, molecular bridges covalently bonded to two ferromagnetic electrodes can transform ferromagnetic materials and produce intriguing spin transport characteristics. This paper discusses the impact of molecule induced strong coupling on the spin transport. To study molecular coupling effect the octametallic molecular cluster (OMC) was bridged between two ferromagnetic electrodes of a magnetic tunnel junction (Ta/Co/NiFe/AlOx/NiFe/Ta) along the exposed side edges. OMCs induced strong inter-ferromagnetic electrode coupling to yield drastic changes in transport properties of the magnetic tunnel junction testbed at the room temperature. These OMCs also transformed the magnetic properties of magnetic tunnel junctions. SQUID and ferromagnetic resonance studies providedmore » insightful data to explain transport studies on the magnetic tunnel junction based molecular spintronics devices.« less

Large resistance change on magnetic tunnel junction based molecular spintronics devices

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

Tyagi, Pawan; Friebe, Edward

Here, molecular bridges covalently bonded to two ferromagnetic electrodes can transform ferromagnetic materials and produce intriguing spin transport characteristics. This paper discusses the impact of molecule induced strong coupling on the spin transport. To study molecular coupling effect the octametallic molecular cluster (OMC) was bridged between two ferromagnetic electrodes of a magnetic tunnel junction (Ta/Co/NiFe/AlOx/NiFe/Ta) along the exposed side edges. OMCs induced strong inter-ferromagnetic electrode coupling to yield drastic changes in transport properties of the magnetic tunnel junction testbed at the room temperature. These OMCs also transformed the magnetic properties of magnetic tunnel junctions. SQUID and ferromagnetic resonance studies providedmore » insightful data to explain transport studies on the magnetic tunnel junction based molecular spintronics devices.« less

Multiple p-n junction subwavelength gratings for transmission-mode electro-optic modulators

PubMed Central

Lee, Ki Young; Yoon, Jae Woong; Song, Seok Ho; Magnusson, Robert

2017-01-01

We propose a free-space electro-optic transmission modulator based on multiple p-n-junction semiconductor subwavelength gratings. The proposed device operates with a high-Q guided-mode resonance undergoing electro-optic resonance shift due to direct electrical control. Using rigorous electrical and optical modeling methods, we theoretically demonstrate a modulation depth of 84%, on-state efficiency 85%, and on-off extinction ratio of 19 dB at 1,550 nm wavelength under electrical control signals within a favorably low bias voltage range from −4 V to +1 V. This functionality operates in the transmission mode and sustainable in the high-speed operation regime up to a 10-GHz-scale modulation bandwidth in principle. The theoretical performance prediction is remarkably advantageous over plasmonic tunable metasurfaces in the power-efficiency and absolute modulation-depth aspects. Therefore, further experimental study is of great interest for creating practical-level metasurface components in various application areas. PMID:28417962

Ring modulators with enhanced efficiency based on standing-wave operation on a field-matched, interdigitated p-n junction.

PubMed

Pavanello, Fabio; Zeng, Xiaoge; Wade, Mark T; Popović, Miloš A

2016-11-28

We propose ring modulators based on interdigitated p-n junctions that exploit standing rather than traveling-wave resonant modes to improve modulation efficiency, insertion loss and speed. Matching the longitudinal nodes and antinodes of a standing-wave mode with high (contacts) and low (depletion regions) carrier density regions, respectively, simultaneously lowers loss and increases sensitivity significantly. This approach permits further to relax optical constraints on contacts placement and can lead to lower device capacitance. Such structures are well-matched to fabrication in advanced microelectronics CMOS processes. Device architectures that exploit this concept are presented along with their benefits and drawbacks. A temporal coupled mode theory model is used to investigate the static and dynamic response. We show that modulation efficiencies or loss Q factors up to 2 times higher than in previous traveling-wave geometries can be achieved leading to much larger extinction ratios. Finally, we discuss more complex doping geometries that can improve carrier dynamics for higher modulation speeds in this context.

Id-1 promotes TGF-{beta}1-induced cell motility through HSP27 activation and disassembly of adherens junction in prostate epithelial cells

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

Di Kaijun; Wong, Y.C.; Wang Xianghong

Id-1 (inhibitor of differentiation or DNA binding-1) has been positively associated with cell proliferation, cell cycle progression, and invasiveness during tumorigenesis. In addition, Id-1 has been shown to modulate cellular sensitivity to TGF-{beta}1 (transforming growth factor {beta}1). Here we demonstrate a novel role of Id-1 in promoting TGF-{beta}1-induced cell motility in a non-malignant prostate epithelial cell line, NPTX. We found that Id-1 promoted F-actin stress fiber formation in response to TGF-{beta}1, which was associated with increased cell-substrate adhesion and cell migration in NPTX cells. In addition, this positive effect of Id-1 on TGF-{beta}1-induced cell motility was mediated through activation ofmore » MEK-ERK signaling pathway and subsequent phosphorylation of HSP27 (heat shock protein 27). Furthermore, Id-1 disrupted the adherens junction complex in TGF-{beta}1-treated cells through down-regulation of E-cadherin, redistribution of {beta}-catenin, along with up-regulation of N-cadherin. These lines of evidence reveal a novel tumorigenic role of Id-1 through reorganization of actin cytoskeleton and disassembly of cell-cell adhesion in response to TGF-{beta}1 in human prostate epithelial cells, and suggest that intracellular Id-1 levels might be a determining factor for switching TGF-{beta}1 from a growth inhibitor to a tumor promoter during prostate carcinogenesis.« less

Protein kinase C activation modulates reversible increase in cortical blood-brain barrier permeability and tight junction protein expression during hypoxia and posthypoxic reoxygenation.

PubMed

Willis, Colin L; Meske, Diana S; Davis, Thomas P

2010-11-01

Hypoxia (Hx) is a component of many disease states including stroke. Ischemic stroke occurs when there is a restriction of cerebral blood flow and oxygen to part of the brain. During the ischemic, and subsequent reperfusion phase of stroke, blood-brain barrier (BBB) integrity is lost with tight junction (TJ) protein disruption. However, the mechanisms of Hx and reoxygenation (HR)-induced loss of BBB integrity are not fully understood. We examined the role of protein kinase C (PKC) isozymes in modifying TJ protein expression in a rat model of global Hx. The Hx (6% O(2)) induced increased hippocampal and cortical vascular permeability to 4 and 10 kDa dextran fluorescein isothiocyanate (FITC) and endogenous rat-IgG. Cortical microvessels revealed morphologic changes in nPKC-θ distribution, increased nPKC-θ and aPKC-ζ protein expression, and activation by phosphorylation of nPKC-θ (Thr538) and aPKC-ζ (Thr410) residues after Hx treatment. Claudin-5, occludin, and ZO-1 showed disrupted organization at endothelial cell margins, whereas Western blot analysis showed increased TJ protein expression after Hx. The PKC inhibition with chelerythrine chloride (5 mg/kg intraperitoneally) attenuated Hx-induced hippocampal vascular permeability and claudin-5, PKC (θ and ζ) expression, and phosphorylation. This study supports the hypothesis that nPKC-θ and aPKC-ζ signaling mediates TJ protein disruption resulting in increased BBB permeability.

IGF2BP3 modulates the interaction of invasion-associated transcripts with RISC

PubMed Central

Ennajdaoui, Hanane; Howard, Jonathan M.; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J.; Uren, Philip J.; Dargyte, Marija; Katzman, Sol; Draper, Jolene M.; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C.; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D.; Toloue, Masoud M.; Blencowe, Benjamin J.; Penalva, Luiz O.F.; Sanford, Jeremy R.

2016-01-01

Summary Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy. But its role(s) in pathogenesis remain enigmatic. Here, we interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches we identify 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and miRNA binding sites. IGF2BP3 promotes association of the RNA induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. PMID:27210763

Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation

PubMed Central

Li, Xiling; Goel, Pragya; Chen, Catherine; Angajala, Varun; Chen, Xun

2018-01-01

Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic homeostatic plasticity (PHP) stabilizes neurotransmission at the Drosophila neuromuscular junction, where a retrograde enhancement of presynaptic neurotransmitter release compensates for diminished postsynaptic receptor functionality. To test the specificity of PHP induction and expression, we have developed a genetic manipulation to reduce postsynaptic receptor expression at one of the two muscles innervated by a single motor neuron. We find that PHP can be induced and expressed at a subset of synapses, over both acute and chronic time scales, without influencing transmission at adjacent release sites. Further, homeostatic modulations to CaMKII, vesicle pools, and functional release sites are compartmentalized and do not spread to neighboring pre- or post-synaptic structures. Thus, both PHP induction and expression mechanisms are locally transmitted and restricted to specific synaptic compartments. PMID:29620520

Contractile actin cables induced by Bacillus anthracis lethal toxin depend on the histone acetylation machinery.

PubMed

Rolando, Monica; Stefani, Caroline; Doye, Anne; Acosta, Maria I; Visvikis, Orane; Yevick, Hannah G; Buchrieser, Carmen; Mettouchi, Amel; Bassereau, Patricia; Lemichez, Emmanuel

2015-10-01

It remains a challenge to decode the molecular basis of the long-term actin cytoskeleton rearrangements that are governed by the reprogramming of gene expression. Bacillus anthracis lethal toxin (LT) inhibits mitogen-activated protein kinase (MAPK) signaling, thereby modulating gene expression, with major consequences for actin cytoskeleton organization and the loss of endothelial barrier function. Using a laser ablation approach, we characterized the contractile and tensile mechanical properties of LT-induced stress fibers. These actin cables resist pulling forces that are transmitted at cell-matrix interfaces and at cell-cell discontinuous adherens junctions. We report that treating the cells with trichostatin A (TSA), a broad range inhibitor of histone deacetylases (HDACs), or with MS-275, which targets HDAC1, 2 and 3, induces stress fibers. LT decreased the cellular levels of HDAC1, 2 and 3 and reduced the global HDAC activity in the nucleus. Both the LT and TSA treatments induced Rnd3 expression, which is required for the LT-mediated induction of actin stress fibers. Furthermore, we reveal that treating the LT-intoxicated cells with garcinol, an inhibitor of histone acetyl-transferases (HATs), disrupts the stress fibers and limits the monolayer barrier dysfunctions. These data demonstrate the importance of modulating the flux of protein acetylation in order to control actin cytoskeleton organization and the endothelial cell monolayer barrier. © 2015 Wiley Periodicals, Inc.

Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels

PubMed Central

Xu, Jian Hui; Liu, Xing Zhen; Pan, Wei; Zou, Da Jin

2017-01-01

Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high-fat diet-mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels. Alterations in the gut microbiota induced by berberine resulted in a significant reduction in bacterial lipopolysaccharide levels in portal plasma. Levels of inflammatory and oxidative stress markers, as well as the mRNA expression levels of macrophage infiltration markers in visceral adipose tissue, were also reduced by berberine. Inhibition of the inflammatory response was associated with a reduction in intestinal permeability and an increase in the expression of tight junction proteins. In addition, berberine was reported to restore aberrant levels of gut hormones in the portal plasma, such as glucagon-like peptide-1 and −2, peptide YY, glucose-dependent insulinotropic polypeptide and pancreatic polypeptide. The present findings indicated that berberine, through modulating gut microbiota, restored the gut barrier, reduced metabolic endotoxemia and systemic inflammation, and improved gut peptide levels in high-fat diet-fed rats. The present study suggests that berberine may be an effective therapeutic strategy for the treatment of obesity and insulin resistance. PMID:28447763

Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels.

PubMed

Xu, Jian Hui; Liu, Xing Zhen; Pan, Wei; Zou, Da Jin

2017-05-01

Systemic inflammation, which can be induced by metabolic endotoxemia, and corresponding high‑fat diet‑mediated metabolic disorders are associated with gut microbiota. In the present study reverse transcription-polymerase chain reaction, immunofluorescence, pyrosequencing, ELISA and Oil Red O staining were performed to assess whether berberine can protect against diet-induced obesity, through modulating the gut microbiota and consequently improving metabolic endotoxemia and gastrointestinal hormone levels. Alterations in the gut microbiota induced by berberine resulted in a significant reduction in bacterial lipopolysaccharide levels in portal plasma. Levels of inflammatory and oxidative stress markers, as well as the mRNA expression levels of macrophage infiltration markers in visceral adipose tissue, were also reduced by berberine. Inhibition of the inflammatory response was associated with a reduction in intestinal permeability and an increase in the expression of tight junction proteins. In addition, berberine was reported to restore aberrant levels of gut hormones in the portal plasma, such as glucagon‑like peptide‑1 and ‑2, peptide YY, glucose‑dependent insulinotropic polypeptide and pancreatic polypeptide. The present findings indicated that berberine, through modulating gut microbiota, restored the gut barrier, reduced metabolic endotoxemia and systemic inflammation, and improved gut peptide levels in high‑fat diet‑fed rats. The present study suggests that berberine may be an effective therapeutic strategy for the treatment of obesity and insulin resistance.

Analysis of Ares Crew Launch Vehicle Transonic Alternating Flow Phenomenon

NASA Technical Reports Server (NTRS)

Sekula, Martin K.; Piatak, David J.; Rausch, Russ D.

2012-01-01

A transonic wind tunnel test of the Ares I-X Rigid Buffet Model (RBM) identified a Mach number regime where unusually large buffet loads are present. A subsequent investigation identified the cause of these loads to be an alternating flow phenomenon at the Crew Module-Service Module junction. The conical design of the Ares I-X Crew Module and the cylindrical design of the Service Module exposes the vehicle to unsteady pressure loads due to the sudden transition between a subsonic separated and a supersonic attached flow about the cone-cylinder junction as the local flow randomly fluctuates back and forth between the two flow states. These fluctuations produce a square-wave like pattern in the pressure time histories resulting in large amplitude, impulsive buffet loads. Subsequent testing of the Ares I RBM found much lower buffet loads since the evolved Ares I design includes an ogive fairing that covers the Crew Module-Service Module junction, thereby making the vehicle less susceptible to the onset of alternating flow. An analysis of the alternating flow separation and attachment phenomenon indicates that the phenomenon is most severe at low angles of attack and exacerbated by the presence of vehicle protuberances. A launch vehicle may experience either a single or, at most, a few impulsive loads since it is constantly accelerating during ascent rather than dwelling at constant flow conditions in a wind tunnel. A comparison of a windtunnel- test-data-derived impulsive load to flight-test-data-derived load indicates a significant over-prediction in the magnitude and duration of the buffet load. I. Introduction One

Tunneling modulation of a quantum-well transistor laser

NASA Astrophysics Data System (ADS)

Feng, M.; Qiu, J.; Wang, C. Y.; Holonyak, N.

2016-11-01

Different than the Bardeen and Brattain transistor (1947) with the current gain depending on the ratio of the base carrier spontaneous recombination lifetime to the emitter-collector transit time, the Feng and Holonyak transistor laser current gain depends upon the base electron-hole (e-h) stimulated recombination, the base dielectric relaxation transport, and the collector stimulated tunneling. For the n-p-n transistor laser tunneling operation, the electron-hole pairs are generated at the collector junction under the influence of intra-cavity photon-assisted tunneling, with electrons drifting to the collector and holes drifting to the base. The excess charge in the base lowers the emitter junction energy barrier, allowing emitter electron injection into the base and satisfying charge neutrality via base dielectric relaxation transport (˜femtoseconds). The excess electrons near the collector junction undergo stimulated recombination at the base quantum-well or transport to the collector, thus supporting tunneling current amplification and optical modulation of the transistor laser.

Integral bypass diodes in an amorphous silicon alloy photovoltaic module

NASA Technical Reports Server (NTRS)

Hanak, J. J.; Flaisher, H.

1991-01-01

Thin-film, tandem-junction, amorphous silicon (a-Si) photovoltaic modules were constructed in which a part of the a-Si alloy cell material is used to form bypass protection diodes. This integral design circumvents the need for incorporating external, conventional diodes, thus simplifying the manufacturing process and reducing module weight.

Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation

PubMed Central

Dhein, S; Rothe, S; Busch, A; Rojas Gomez, DM; Boldt, A; Reutemann, A; Seidel, T; Salameh, A; Pfannmüller, B; Rastan, A; Kostelka, M; Mohr, FW

2011-01-01

BACKGROUND AND PURPOSE We investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF). EXPERIMENTAL APPROACH Left atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 ± 9.1 mg·day−1) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi-electrode mapping. KEY RESULTS Both Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43-expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF-induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol. CONCLUSIONS AND IMPLICATIONS AF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti-arrythmic drugs. PMID:21542828

On Field-Effect Photovoltaics: Gate Enhancement of the Power Conversion Efficiency in a Nanotube/Silicon-Nanowire Solar Cell.

PubMed

Petterson, Maureen K; Lemaitre, Maxime G; Shen, Yu; Wadhwa, Pooja; Hou, Jie; Vasilyeva, Svetlana V; Kravchenko, Ivan I; Rinzler, Andrew G

2015-09-30

Recent years have seen a resurgence of interest in crystalline silicon Schottky junction solar cells distinguished by the use of low density of electronic states (DOS) nanocarbons (nanotubes, graphene) as the metal contacting the Si. Recently, unprecedented modulation of the power conversion efficiency in a single material system has been demonstrated in such cells by the use of electronic gating. The gate field induced Fermi level shift in the low-DOS carbon serves to enhance the junction built-in potential, while a gate field induced inversion layer at the Si surface, in regions remote from the junction, keeps the photocarriers well separated there, avoiding recombination at surface traps and defects (a key loss mechanism). Here, we extend these results into the third dimension of a vertical Si nanowire array solar cell. A single wall carbon nanotube layer engineered to contact virtually each n-Si nanowire tip extracts the minority carriers, while an ionic liquid electrolytic gate drives the nanowire body into inversion. The enhanced light absorption of the vertical forest cell, at 100 mW/cm(2) AM1.5G illumination, results in a short-circuit current density of 35 mA/cm(2) and associated power conversion efficiency of 15%. These results highlight the use of local fields as opposed to surface passivation as a means of avoiding front surface recombination. A deleterious electrochemical reaction of the silicon due to the electrolyte gating is shown to be caused by oxygen/water entrained in the ionic liquid electrolyte. While encapsulation can avoid the issue, a nonencapsulation-based approach is also implemented.

Connexin 30 expression inhibits growth of human malignant gliomas but protects them against radiation therapy

PubMed Central

Artesi, Maria; Kroonen, Jerome; Bredel, Markus; Nguyen-Khac, Minh; Deprez, Manuel; Schoysman, Laurent; Poulet, Christophe; Chakravarti, Arnab; Kim, Hyunsoo; Scholtens, Denise; Seute, Tatjana; Rogister, Bernard; Bours, Vincent; Robe, Pierre A.

2015-01-01

Background Glioblastomas remain ominous tumors that almost invariably escape treatment. Connexins are a family of transmembrane, gap junction-forming proteins, some members of which were reported to act as tumor suppressors and to modulate cellular metabolism in response to cytotoxic stress. Methods We analyzed the copy number and expression of the connexin (Cx)30 gene gap junction beta-6 (GJB6), as well as of its protein immunoreactivity in several public and proprietary repositories of glioblastomas, and their influence on patient survival. We evaluated the effect of the expression of this gap junction protein on the growth, DNA repair and energy metabolism, and treatment resistance of these tumors. Results The GJB6 gene was deleted in 25.8% of 751 analyzed tumors and mutated in 15.8% of 158 tumors. Cx30 immunoreactivity was absent in 28.9% of 145 tumors. Restoration of Cx30 expression in human glioblastoma cells reduced their growth in vitro and as xenografts in the striatum of immunodeficient mice. Cx30 immunoreactivity was, however, found to adversely affect survival in 2 independent retrospective cohorts of glioblastoma patients. Cx30 was found in clonogenic assays to protect glioblastoma cells against radiation-induced mortality and to decrease radiation-induced DNA damage. This radioprotection correlated with a heat shock protein 90–dependent mitochondrial translocation of Cx30 following radiation and an improved ATP production following this genotoxic stress. Conclusion These results underline the complex relationship between potential tumor suppressors and treatment resistance in glioblastomas and single out GJB6/Cx30 as a potential biomarker and target for therapeutic intervention in these tumors. PMID:25155356

On Field-Effect Photovoltaics: Gate Enhancement of the Power Conversion Efficiency in a Nanotube/Silicon-Nanowire Solar Cell

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

Petterson, Maureen K.; Lemaitre, Maxime G.; Shen, Yu

Recent years have seen a resurgence of interest in crystalline silicon Schottky junction solar cells distinguished by the use of low density of electronic states (DOS) nanocarbons (nanotubes, graphene) as the metal contacting the Si. Recently, unprecedented modulation of the power conversion efficiency in a single material system has been demonstrated in such cells by the use of electronic gating. The gate field induced Fermi level shift in the low-DOS carbon serves to enhance the junction built-in potential, while a gate field induced inversion layer at the Si surface, in regions remote from the junction, keeps the photocarriers well separatedmore » there, avoiding recombination at surface traps and defects (a key loss mechanism). Here, we extend these results into the third dimension of a vertical Si nanowire array solar cell. A single wall carbon nanotube layer engineered to contact virtually each n-Si nanowire tip extracts the minority carriers, while an ionic liquid electrolytic gate drives the nanowire body into inversion. The enhanced light absorption of the vertical forest cell, at 100 mW/cm 2 AM1.5G illumination, results in a short-circuit current density of 35 mA/cm 2 and associated power conversion efficiency of 15%. These results highlight the use of local fields as opposed to surface passivation as a means of avoiding front surface recombination. Finally, a deleterious electrochemical reaction of the silicon due to the electrolyte gating is shown to be caused by oxygen/water entrained in the ionic liquid electrolyte. While encapsulation can avoid the issue, a nonencapsulation-based approach is also implemented.« less

On Field-Effect Photovoltaics: Gate Enhancement of the Power Conversion Efficiency in a Nanotube/Silicon-Nanowire Solar Cell

DOE PAGES

Petterson, Maureen K.; Lemaitre, Maxime G.; Shen, Yu; ...

2015-09-09

Recent years have seen a resurgence of interest in crystalline silicon Schottky junction solar cells distinguished by the use of low density of electronic states (DOS) nanocarbons (nanotubes, graphene) as the metal contacting the Si. Recently, unprecedented modulation of the power conversion efficiency in a single material system has been demonstrated in such cells by the use of electronic gating. The gate field induced Fermi level shift in the low-DOS carbon serves to enhance the junction built-in potential, while a gate field induced inversion layer at the Si surface, in regions remote from the junction, keeps the photocarriers well separatedmore » there, avoiding recombination at surface traps and defects (a key loss mechanism). Here, we extend these results into the third dimension of a vertical Si nanowire array solar cell. A single wall carbon nanotube layer engineered to contact virtually each n-Si nanowire tip extracts the minority carriers, while an ionic liquid electrolytic gate drives the nanowire body into inversion. The enhanced light absorption of the vertical forest cell, at 100 mW/cm 2 AM1.5G illumination, results in a short-circuit current density of 35 mA/cm 2 and associated power conversion efficiency of 15%. These results highlight the use of local fields as opposed to surface passivation as a means of avoiding front surface recombination. Finally, a deleterious electrochemical reaction of the silicon due to the electrolyte gating is shown to be caused by oxygen/water entrained in the ionic liquid electrolyte. While encapsulation can avoid the issue, a nonencapsulation-based approach is also implemented.« less

A High Temperature Silicon Carbide mosfet Power Module With Integrated Silicon-On-Insulator-Based Gate Drive

DOE PAGES

Wang, Zhiqiang; Shi, Xiaojie; Tolbert, Leon M.; ...

2014-04-30

Here we present a board-level integrated silicon carbide (SiC) MOSFET power module for high temperature and high power density application. Specifically, a silicon-on-insulator (SOI)-based gate driver capable of operating at 200°C ambient temperature is designed and fabricated. The sourcing and sinking current capability of the gate driver are tested under various ambient temperatures. Also, a 1200 V/100 A SiC MOSFET phase-leg power module is developed utilizing high temperature packaging technologies. The static characteristics, switching performance, and short-circuit behavior of the fabricated power module are fully evaluated at different temperatures. Moreover, a buck converter prototype composed of the SOI gate drivermore » and SiC power module is built for high temperature continuous operation. The converter is operated at different switching frequencies up to 100 kHz, with its junction temperature monitored by a thermosensitive electrical parameter and compared with thermal simulation results. The experimental results from the continuous operation demonstrate the high temperature capability of the power module at a junction temperature greater than 225°C.« less

30% CPV Module Milestone

NASA Astrophysics Data System (ADS)

Gordon, Robert; Kinsey, Geoff; Nayaak, Adi; Garboushian, Vahan

2010-10-01

Concentrating Photovoltaics has held out the promise of low cost solar electricity for now several decades. Steady progress towards this goal in the 80's and 90's gradually produced more efficient and reliable systems. System efficiency is regarded as the largest factor in lowering the electricity cost and the relatively recent advent of the terrestrial multi-junction solar cell has pressed this race forward dramatically. CPV systems are now exhibiting impressive AC field efficiencies of 25% and more, approximately twice that of the best flat plate systems available today. Amonix inc. has just tested their latest generation multi-junction module design, achieving over 31% DC efficiency at near PVUSA test conditions. Inculcating this design into their next MegaModule is forthcoming, but the expected AC system field efficiency should be significantly higher than current 25% levels.

Adrenocortical Gap Junctions and Their Functions

PubMed Central

Bell, Cheryl L.; Murray, Sandra A.

2016-01-01

Adrenal cortical steroidogenesis and proliferation are thought to be modulated by gap junction-mediated direct cell–cell communication of regulatory molecules between cells. Such communication is regulated by the number of gap junction channels between contacting cells, the rate at which information flows between these channels, and the rate of channel turnover. Knowledge of the factors regulating gap junction-mediated communication and the turnover process are critical to an understanding of adrenal cortical cell functions, including development, hormonal response to adrenocorticotropin, and neoplastic dedifferentiation. Here, we review what is known about gap junctions in the adrenal gland, with particular attention to their role in adrenocortical cell steroidogenesis and proliferation. Information and insight gained from electrophysiological, molecular biological, and imaging (immunocytochemical, freeze fracture, transmission electron microscopic, and live cell) techniques will be provided. PMID:27445985

Negative tunnel magnetoresistance and spin transport in ferromagnetic graphene junctions.

PubMed

Zou, Jianfei; Jin, Guojun; Ma, Yu-Qiang

2009-03-25

We study the tunnel magnetoresistance (TMR) and spin transport in ferromagnetic graphene junctions composed of ferromagnetic graphene (FG) and normal graphene (NG) layers. It is found that the TMR in the FG/NG/FG junction oscillates from positive to negative values with respect to the chemical potential adjusted by the gate voltage in the barrier region when the Fermi level is low enough. Particularly, the conventionally defined TMR in the FG/FG/FG junction oscillates periodically from a positive to negative value with increasing the barrier height at any Fermi level. The spin polarization of the current through the FG/FG/FG junction also has an oscillating behavior with increasing barrier height, whose oscillating amplitude can be modulated by the exchange splitting in the ferromagnetic graphene.

Cell polarity proteins and spermatogenesis.

PubMed

Gao, Ying; Xiao, Xiang; Lui, Wing-Yee; Lee, Will M; Mruk, Dolores; Cheng, C Yan

2016-11-01

When the cross-section of a seminiferous tubule from an adult rat testes is examined microscopically, Sertoli cells and germ cells in the seminiferous epithelium are notably polarized cells. For instance, Sertoli cell nuclei are found near the basement membrane. On the other hand, tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific actin-rich anchoring junction), gap junction (GJ) and desmosome that constitute the blood-testis barrier (BTB) are also located near the basement membrane. The BTB, in turn, divides the epithelium into the basal and the adluminal (apical) compartments. Within the epithelium, undifferentiated spermatogonia and preleptotene spermatocytes restrictively reside in the basal compartment whereas spermatocytes and post-meiotic spermatids reside in the adluminal compartment. Furthermore, the heads of elongating/elongated spermatids point toward the basement membrane with their elongating tails toward the tubule lumen. However, the involvement of polarity proteins in this unique cellular organization, in particular the underlying molecular mechanism(s) by which polarity proteins confer cellular polarity in the seminiferous epithelium is virtually unknown until recent years. Herein, we discuss latest findings regarding the role of different polarity protein complexes or modules and how these protein complexes are working in concert to modulate Sertoli cell and spermatid polarity. These findings also illustrate polarity proteins exert their effects through the actin-based cytoskeleton mediated by actin binding and regulatory proteins, which in turn modulate adhesion protein complexes at the cell-cell interface since TJ, basal ES and GJ utilize F-actin for attachment. We also propose a hypothetical model which illustrates the antagonistic effects of these polarity proteins. This in turn provides a unique mechanism to modulate junction remodeling in the testis to support germ cell transport across the epithelium in particular the BTB during the epithelial cycle of spermatogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gap junction plasticity as a mechanism to regulate network-wide oscillations

PubMed Central

Nicola, Wilten; Clopath, Claudia

2018-01-01

Cortical oscillations are thought to be involved in many cognitive functions and processes. Several mechanisms have been proposed to regulate oscillations. One prominent but understudied mechanism is gap junction coupling. Gap junctions are ubiquitous in cortex between GABAergic interneurons. Moreover, recent experiments indicate their strength can be modified in an activity-dependent manner, similar to chemical synapses. We hypothesized that activity-dependent gap junction plasticity acts as a mechanism to regulate oscillations in the cortex. We developed a computational model of gap junction plasticity in a recurrent cortical network based on recent experimental findings. We showed that gap junction plasticity can serve as a homeostatic mechanism for oscillations by maintaining a tight balance between two network states: asynchronous irregular activity and synchronized oscillations. This homeostatic mechanism allows for robust communication between neuronal assemblies through two different mechanisms: transient oscillations and frequency modulation. This implies a direct functional role for gap junction plasticity in information transmission in cortex. PMID:29529034

Curli modulates adherence of Escherichia coli O157 to bovine recto-anal junction squamous epithelial cells

USDA-ARS?s Scientific Manuscript database

Our recent studies have shown that Intimin and the Locus of Enterocyte Effacement-encoded proteins do not play a role in Escherichia coli O157 (O157) adherence to the bovine recto-anal junction squamous epithelial cells (RSE) cells. Hence, to define factors that play a contributory role, we investi...

JAM-C regulates tight junctions and integrin-mediated cell adhesion and migration.

PubMed

Mandicourt, Guillaume; Iden, Sandra; Ebnet, Klaus; Aurrand-Lions, Michel; Imhof, Beat A

2007-01-19

Junctional Adhesion Molecules (JAMs) have been described as major components of tight junctions in endothelial and epithelial cells. Tight junctions are crucial for the establishment and maintenance of cell polarity. During tumor development, they are remodeled, enabling neoplastic cells to escape from constraints imposed by intercellular junctions and to adopt a migratory behavior. Using a carcinoma cell line we tested whether JAM-C could affect tight junctions and migratory properties of tumor cells. We show that transfection of JAM-C improves the tight junctional barrier in tumor cells devoid of JAM-C expression. This is dependent on serine 281 in the cytoplasmic tail of JAM-C because serine mutation into alanine abolishes the specific localization of JAM-C in tight junctions and establishment of cell polarity. More importantly, the same mutation stimulates integrin-mediated cell migration and adhesion via the modulation of beta1 and beta3 integrin activation. These results highlight an unexpected function for JAM-C in controlling epithelial cell conversion from a static, polarized state to a pro-migratory phenotype.

78 FR 4192 - Petition for Exemption From the Vehicle Theft Prevention Standard; Ford Motor Company

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-18

... Smart Power Distribution Junction Box (SPDJB), the PEPS/RFA module, the power train control module and a... listed in Sec. 543.6(a)(3): promoting activation; attracting attention to the efforts of unauthorized...

Modulated wave formation in myocardial cells under electromagnetic radiation

NASA Astrophysics Data System (ADS)

Takembo, Clovis N.; Mvogo, A.; Ekobena Fouda, H. P.; Kofané, T. C.

2018-06-01

We exclusively analyze the onset and condition of formation of modulated waves in a diffusive FitzHugh-Nagumo model for myocardial cell excitations. The cells are connected through gap junction coupling. An additive magnetic flux variable is used to describe the effect of electromagnetic induction, while electromagnetic radiation is imposed on the magnetic flux variable as a periodic forcing. We used the discrete multiple scale expansion and obtained, from the model equations, a single differential-difference amplitude nonlinear equation. We performed the linear stability analysis of this equation and found that instability features are importantly influenced by the induced electromagnetic gain. We present the unstable and stable regions of modulational instability (MI). The resulting analytic predictions are confirmed by numerical experiments of the generic equations. The results reveal that due to MI, an initial steady state that consisted of a plane wave with low amplitude evolves into a modulated localized wave patterns, soliton-like in shape, with features of synchronization. Furthermore, the formation of periodic pulse train with breathing motion presents a disappearing pattern in the presence of electromagnetic radiation. This could provide guidance and better understanding of sudden heart failure exposed to heavily electromagnetic radiation.

Too Hot for Photon-Assisted Transport: Hot-Electrons Dominate Conductance Enhancement in Illuminated Single-Molecule Junctions.

PubMed

Fung, E-Dean; Adak, Olgun; Lovat, Giacomo; Scarabelli, Diego; Venkataraman, Latha

2017-02-08

We investigate light-induced conductance enhancement in single-molecule junctions via photon-assisted transport and hot-electron transport. Using 4,4'-bipyridine bound to Au electrodes as a prototypical single-molecule junction, we report a 20-40% enhancement in conductance under illumination with 980 nm wavelength radiation. We probe the effects of subtle changes in the transmission function on light-enhanced current and show that discrete variations in the binding geometry result in a 10% change in enhancement. Importantly, we prove theoretically that the steady-state behavior of photon-assisted transport and hot-electron transport is identical but that hot-electron transport is the dominant mechanism for optically induced conductance enhancement in single-molecule junctions when the wavelength used is absorbed by the electrodes and the hot-electron relaxation time is long. We confirm this experimentally by performing polarization-dependent conductance measurements of illuminated 4,4'-bipyridine junctions. Finally, we perform lock-in type measurements of optical current and conclude that currents due to laser-induced thermal expansion mask optical currents. This work provides a robust experimental framework for studying mechanisms of light-enhanced transport in single-molecule junctions and offers tools for tuning the performance of organic optoelectronic devices by analyzing detailed transport properties of the molecules involved.

Neural coding using telegraphic switching of magnetic tunnel junction

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

Suh, Dong Ik; Bae, Gi Yoon; Oh, Heong Sik

2015-05-07

In this work, we present a synaptic transmission representing neural coding with spike trains by using a magnetic tunnel junction (MTJ). Telegraphic switching generates an artificial neural signal with both the applied magnetic field and the spin-transfer torque that act as conflicting inputs for modulating the number of spikes in spike trains. The spiking probability is observed to be weighted with modulation between 27.6% and 99.8% by varying the amplitude of the voltage input or the external magnetic field. With a combination of the reverse coding scheme and the synaptic characteristic of MTJ, an artificial function for the synaptic transmissionmore » is achieved.« less

Nondestructive determination of the depth of planar p-n junctions by scanning electron microscopy

NASA Technical Reports Server (NTRS)

Chi, J.-Y.; Gatos, H. C.

1977-01-01

A method was developed for measuring nondestructively the depth of planar p-n junctions in simple devices as well as in integrated-circuit structures with the electron-beam induced current (EBIC) by scanning parallel to the junction in a scanning electron microscope (SEM). The results were found to be in good agreement with those obtained by the commonly used destructive method of lapping at an angle to the junction and staining to reveal the junction.

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

PubMed Central

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

2011-01-01

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

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

PubMed Central

Trosko, James E.

2016-01-01

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. PMID:27314399

Charge transport and ac response under light illumination in gate-modulated DNA molecular junctions.

PubMed

Zhang, Yan; Zhu, Wen-Huan; Ding, Guo-Hui; Dong, Bing; Wang, Xue-Feng

2015-05-22

Using a two-strand tight-binding model and within nonequilibrium Green's function approach, we study charge transport through DNA sequences (GC)NGC and (GC)1(TA)NTA (GC)3 sandwiched between two Pt electrodes. We show that at low temperature DNA sequence (GC)NGC exhibits coherent charge carrier transport at very small bias, since the highest occupied molecular orbital in the GC base pair can be aligned with the Fermi energy of the metallic electrodes by a gate voltage. A weak distance dependent conductance is found in DNA sequence (GC)1(TA)NTA (GC)3 with large NTA. Different from the mechanism of thermally induced hopping of charges proposed by the previous experiments, we find that this phenomenon is dominated by quantum tunnelling through discrete quantum well states in the TA base pairs. In addition, ac response of this DNA junction under light illumination is also investigated. The suppression of ac conductances of the left and right lead of DNA sequences at some particular frequencies is attributed to the excitation of electrons in the DNA to the lead Fermi surface by ac potential, or the excitation of electrons in deep DNA energy levels to partially occupied energy levels in the transport window. Therefore, measuring ac response of DNA junctions can reveal a wealth of information about the intrinsic dynamics of DNA molecules.

Novel signal inversion of laser beam induced current for femtosecond-laser-drilling-induced junction on vacancy-doped p-type HgCdTe

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

Qiu, W. C.; Wang, R.; Xu, Z. J.

2014-05-28

In this paper, experimental results of temperature-dependent signal inversion of laser beam induced current (LBIC) for femtosecond-laser-drilling-induced junction on vacancy-doped p-type HgCdTe are reported. LBIC characterization shows that the traps induced by femtosecond laser drilling are sensitive to temperature. Theoretical models for trap-related p-n junction transformation are proposed and demonstrated using numerical simulations. The simulations are in good agreement with the experimental results. The effects of traps and mixed conduction are possibly the main reasons that result in the novel signal inversion of LBIC microscope at room temperature. The research results provide a theoretical guide for practical applications of large-scalemore » array HgCdTe infrared photovoltaic detectors formed by femtosecond laser drilling, which may act as a potential new method for fabricating HgCdTe photodiodes.« less

Gap Junction Coupling and Calcium Waves in the Pancreatic Islet

PubMed Central

Benninger, Richard K. P.; Zhang, Min; Head, W. Steven; Satin, Leslie S.; Piston, David W.

2008-01-01

The pancreatic islet is a highly coupled, multicellular system that exhibits complex spatiotemporal electrical activity in response to elevated glucose levels. The emergent properties of islets, which differ from those arising in isolated islet cells, are believed to arise in part by gap junctional coupling, but the mechanisms through which this coupling occurs are poorly understood. To uncover these mechanisms, we have used both high-speed imaging and theoretical modeling of the electrical activity in pancreatic islets under a reduction in the gap junction mediated electrical coupling. Utilizing islets from a gap junction protein connexin 36 knockout mouse model together with chemical inhibitors, we can modulate the electrical coupling in the islet in a precise manner and quantify this modulation by electrophysiology measurements. We find that after a reduction in electrical coupling, calcium waves are slowed as well as disrupted, and the number of cells showing synchronous calcium oscillations is reduced. This behavior can be reproduced by computational modeling of a heterogeneous population of β-cells with heterogeneous levels of electrical coupling. The resulting quantitative agreement between the data and analytical models of islet connectivity, using only a single free parameter, reveals the mechanistic underpinnings of the multicellular behavior of the islet. PMID:18805925

Role of connexin43 hemichannels in mechanical stress-induced ATP release in human periodontal ligament cells.

PubMed

Luckprom, P; Kanjanamekanant, K; Pavasant, P

2011-10-01

Our previous studies showed that mechanical stress could induce ATP release in human periodontal ligament (HPDL) cells. By signaling through P2 purinergic receptors, ATP increased the expression and the synthesis of osteopontin and RANKL. In this study, the mechanism of stress-induced ATP release was investigated. Continuous compressive forces were applied on cultured HPDL cells. The ATP released was measured using luciferin-luciferase bioluminescence. The expression of gap-junction proteins was examined using RT-PCR and western blot analysis. The opening of hemichannels was demonstrated by cellular uptake of a fluorescent dye, 5(6)-carboxyfluorescein, which is known to penetrate hemichannels. Intracellular signal transduction was investigated using inhibitors and antagonists. Mechanical stress induced the release of ATP into the culture medium, which was attenuated by carbenoxolone, a nonspecific gap-junction inhibitor. Addition of meclofenamic acid sodium salt, a connexin43 inhibitor, inhibited ATP release by mechanical stress. Knockdown of connexin43 expression by small interfering RNA reduced the amount of ATP released by mechanical stress, suggesting the role of connexin43 hemichannels. In addition, intracellular Ca(2+) blockers could also inhibit mechanical stress-induced ATP release and the opening of the gap junction. Our study demonstrated the involvement of gap-junction hemichannels, especially connexin43, in the stress-induced ATP-release mechanism. Furthermore, this mechanism may be regulated by the intracellular Ca(2+) signaling pathway. These results suggest an important role of gap-junction hemichannels in the function and behavior of HPDL cells. © 2011 John Wiley & Sons A/S.

Temperature-sensitive junction transformations for mid-wavelength HgCdTe photovoltaic infrared detector arrays by laser beam induced current microscope

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

Qiu, Weicheng; National Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083; Hu, Weida, E-mail: wdhu@mail.sitp.ac.cn

2014-11-10

In this paper, we report on the disappearance of the photosensitive area extension effect and the unusual temperature dependence of junction transformation for mid-wavelength, n-on-p HgCdTe photovoltaic infrared detector arrays. The n-type region is formed by B{sup +} ion implantation on Hg-vacancy-doped p-type HgCdTe. Junction transformations under different temperatures are visually captured by a laser beam induced current microscope. A physical model of temperature dependence on junction transformation is proposed and demonstrated by using numerical simulations. It is shown that Hg-interstitial diffusion and temperature activated defects jointly lead to the p-n junction transformation dependence on temperature, and the weaker mixedmore » conduction compared with long-wavelength HgCdTe photodiode contributes to the disappearance of the photosensitive area extension effect in mid-wavelength HgCdTe infrared detector arrays.« less

Magnetically-driven colossal supercurrent enhancement in InAs nanowire Josephson junctions

PubMed Central

Tiira, J.; Strambini, E.; Amado, M.; Roddaro, S.; San-Jose, P.; Aguado, R.; Bergeret, F. S.; Ercolani, D.; Sorba, L.; Giazotto, F.

2017-01-01

The Josephson effect is a fundamental quantum phenomenon where a dissipationless supercurrent is introduced in a weak link between two superconducting electrodes by Andreev reflections. The physical details and topology of the junction drastically modify the properties of the supercurrent and a strong enhancement of the critical supercurrent is expected to occur when the topology of the junction allows an emergence of Majorana bound states. Here we report charge transport measurements in mesoscopic Josephson junctions formed by InAs nanowires and Ti/Al superconducting leads. Our main observation is a colossal enhancement of the critical supercurrent induced by an external magnetic field applied perpendicular to the substrate. This striking and anomalous supercurrent enhancement cannot be described by any known conventional phenomenon of Josephson junctions. We consider these results in the context of topological superconductivity, and show that the observed critical supercurrent enhancement is compatible with a magnetic field-induced topological transition. PMID:28401951

Automated array assembly, phase 2

NASA Technical Reports Server (NTRS)

Carbajal, B. G.

1979-01-01

Tasks of scaling up the tandem junction cell (TJC) from 2 cm x 2 cm to 6.2 cm and the assembly of several modules using these large area TJC's are described. The scale-up of the TJC was based on using the existing process and doing the necessary design activities to increase the cell area to an acceptably large area. The design was carried out using available device models. The design was verified and sample large area TJCs were fabricated. Mechanical and process problems occurred causing a schedule slippage that resulted in contract expiration before enough large-area TJCs were fabricated to populate the sample tandem junction modules (TJM). A TJM design was carried out in which the module interconnects served to augment the current collecting buses on the cell. No sample TJMs were assembled due to a shortage of large-area TJCs.

ORIENTATION REQUIREMENT TO DETECT MAGNETIC FIELD-INDUCTED ALTERATION OF GAP JUNCTION COMMUNICATION IN EPITHELIAL CELLS

EPA Science Inventory

ORIENTATION REQUIREMENT TO DETECT MAGNETIC FIELD-INDUCED ALTERATION OF GAP JUNCTION COMMUNICATION IN EPITHELIAL CELLS.
OBJECTIVE: We have shown that functional gap junction communication as measured by Lucifer yellow dye transfer (DT) in Clone-9 rat liver epithelial cells, c...

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

PubMed Central

Xu, Liming; Dan, Mo; Shao, Anliang; Cheng, Xiang; Zhang, Cuiping; Yokel, Robert A; Takemura, Taro; Hanagata, Nobutaka; Niwa, Masami; Watanabe, Daisuke

2015-01-01

Background Silver nanoparticles (Ag-NPs) can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood–brain barrier (BBB) and the underlying mechanism(s) of action on the BBB and the brain are not well understood. Method To investigate Ag-NP suspension (Ag-NPS)-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM). Global gene expression of astrocytes was measured using a DNA microarray. Results A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200 Ω·cm2. After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the tight junction (TJ) protein ZO-1 was decreased. Discontinuous TJs were also observed between microvascular endothelial cells. After Ag-NPS exposure, severe mitochondrial shrinkage, vacuolations, endoplasmic reticulum expansion, and Ag-NPs were observed in astrocytes by TEM. Global gene expression analysis showed that three genes were upregulated and 20 genes were downregulated in astrocytes treated with Ag-NPS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the 23 genes were associated with metabolic processes, biosynthetic processes, response to stimuli, cell death, the MAPK pathway, and so on. No GO term and KEGG pathways were changed in the released-ion or polystyrene-NP groups. Ag-NPS inhibited the antioxidant defense of the astrocytes by increasing thioredoxin interacting protein, which inhibits the Trx system, and decreasing Nr4a1 and Dusp1. Meanwhile, Ag-NPS induced inflammation and apoptosis through modulation of the MAPK pathway or B-cell lymphoma-2 expression or mTOR activity in astrocytes. Conclusion These results draw our attention to the importance of Ag-NP-induced toxicity on the neurovascular unit and provide a better understanding of its toxicological mechanisms on astrocytes. PMID:26491287

Inhibition of gap junction intercellular communication is involved in silica nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial pathway.

PubMed

Du, Zhong-Jun; Cui, Guan-Qun; Zhang, Juan; Liu, Xiao-Mei; Zhang, Zhi-Hu; Jia, Qiang; Ng, Jack C; Peng, Cheng; Bo, Cun-Xiang; Shao, Hua

2017-01-01

Gap junction intercellular communication (GJIC) between cardiomyocytes is essential for synchronous heart contraction and relies on connexin-containing channels. Connexin 43 (Cx43) is a major component involved in GJIC in heart tissue, and its abnormal expression is closely associated with various cardiac diseases. Silica nanoparticles (SNPs) are known to induce cardiovascular toxicity. However, the mechanisms through which GJIC plays a role in cardiomyocytes apoptosis induced by SNPs remain unknown. The aim of the present study is to determine whether SNPs-decreased GJIC promotes apoptosis in rat cardiomyocytes cell line (H9c2 cells) via the mitochondrial pathway using CCK-8 Kit, scrape-loading dye transfer technique, Annexin V/PI double-staining assays, and Western blot analysis. The results showed that SNPs elicited cytotoxicity in H9c2 cells in a time- and concentration-dependent manner. SNPs also reduced GJIC in H9c2 cells in a concentration-dependent manner through downregulation of Cx43 and upregulation of P-Cx43. Inhibition of gap junctions by gap junction blocker carbenoxolone disodium resulted in decreased survival and increased apoptosis, whereas enhancement of the gap junctions by retinoic acid led to enhanced survival but decreased apoptosis. Furthermore, SNPs-induced apoptosis through the disrupted functional gap junction was correlated with abnormal expressions of the proteins involved in the mitochondrial pathway-related apoptosis such as Bcl-2/Bax, cytochrome C, Caspase-9, and Caspase-3. Taken together, our results provide the first evidence that SNPs-decreased GJIC promotes apoptosis in cardiomyocytes via the mitochondrial pathway. In addition, downregulation of GJIC by SNPs in cardiomyocytes is mediated through downregulation of Cx43 and upregulation of P-Cx43. These results suggest that in rat cardiomyocytes cell line, GJIC plays a protective role in SNPs-induced apoptosis and that GJIC may be one of the targets for SNPs-induced biological effects.

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

PubMed Central

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

2013-01-01

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

'Special K' and a Loss of Cell-To-Cell Adhesion in Proximal Tubule-Derived Epithelial Cells: Modulation of the Adherens Junction Complex by Ketamine

PubMed Central

Hills, Claire E.; Jin, Tianrong; Siamantouras, Eleftherios; Liu, Issac K-K; Jefferson, Kieran P.; Squires, Paul E.

2013-01-01

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention. PMID:24009666

Temperature and current coefficients of lasing wavelength in tunable diode laser spectroscopy.

PubMed

Fukuda, M; Mishima, T; Nakayama, N; Masuda, T

2010-08-01

The factors determining temperature and current coefficients of lasing wavelength are investigated and discussed under monitoring CO(2)-gas absorption spectra. The diffusion rate of Joule heating at the active layer to the surrounding region is observed by monitoring the change in the junction voltage, which is a function of temperature and the wavelength (frequency) deviation under sinusoidal current modulation. Based on the experimental results, the time interval of monitoring the wavelength after changing the ambient temperature or injected current (scanning rate) has to be constant at least to eliminate the monitoring error induced by the deviation of lasing wavelength, though the temperature and current coefficients of lasing wavelength differ with the rate.

Effect of complement and its regulation on myasthenia gravis pathogenesis

PubMed Central

Kusner, Linda L; Kaminski, Henry J; Soltys, Jindrich

2015-01-01

Myasthenia gravis (MG) is primarily caused by antibodies directed towards the skeletal muscle acetylcholine receptor, leading to muscle weakness. Although these antibodies may induce compromise of neuromuscular transmission by blocking acetylcholine receptor function or antigenic modulation, the predominant mechanism of injury to the neuromuscular junction is complement-mediated lysis of the postsynaptic membrane. The vast majority of data to support the role of complement derives from experimentally acquired MG (EAMG). In this article, we review studies that demonstrate the central role of complement in EAMG and MG pathogenesis along with the emerging role of complement in T- and B-cell function, as well as the potential for complement inhibitor-based therapy to treat human MG. PMID:20477586

Visualization of anomalous Ettingshausen effect in a ferromagnetic film: Direct evidence of different symmetry from spin Peltier effect

NASA Astrophysics Data System (ADS)

Seki, T.; Iguchi, R.; Takanashi, K.; Uchida, K.

2018-04-01

Spatial distribution of temperature modulation due to the anomalous Ettingshausen effect (AEE) is visualized in a ferromagnetic FePt thin film with in-plane and out-of-plane magnetizations using the lock-in thermography technique. Comparing the AEE of FePt with the spin Peltier effect (SPE) of a Pt/yttrium iron garnet junction provides direct evidence of different symmetries of AEE and SPE. Our experiments and numerical calculations reveal that the distribution of heat sources induced by AEE strongly depends on the direction of magnetization, leading to the remarkable different temperature profiles in the FePt thin film between the in-plane and perpendicularly magnetized configurations.

Subgap transport in silicene-based superconducting hybrid structures

NASA Astrophysics Data System (ADS)

Li, Hai

2016-08-01

We investigate the influences of exchange field and perpendicular electric field on the subgap transport in silicene-based ferromagnetic/superconducting (FS) and ferromagnetic/superconducting/ferromagnetic (FSF) junctions. Owing to the unique buckling structure of silicene, the Andreev reflection and subgap conductance can be effectively modulated by a perpendicular electric field. It is revealed that the subgap conductance in the FS junction can be distinctly enhanced by an exchange field. Remarkably, resorting to the tunable band gap of silicene, an exclusive crossed Andreev reflection (CAR) process in the FSF junction can be realized within a wide range of related parameters. Moreover, in the FSF junction the exclusive CAR and exclusive elastic cotunneling processes can be switched by reversing the magnetization direction in one of the ferromagnetic regions.

Design and Photovoltaic Properties of Graphene/Silicon Solar Cell

NASA Astrophysics Data System (ADS)

Xu, Dikai; Yu, Xuegong; Yang, Lifei; Yang, Deren

2018-04-01

Graphene/silicon (Gr/Si) Schottky junction solar cells have attracted widespread attention for the fabrication of high-efficiency and low-cost solar cells. However, their performance is still limited by the working principles of Schottky junctions. Modulating the working mechanism of the solar cells into a quasi p-n junction has advantages, including higher open-circuit voltage (V OC) and less carrier recombination. In this study, Gr/Si quasi p-n junction solar cells were formed by inserting a tunneling Al2O3 interlayer in-between graphene and silicon, which led to obtain the PCE up to 8.48% without antireflection or chemical doping techniques. Our findings could pave a new way for the development of Gr/Si solar cells.

Filtering microfluidic bubble trains at a symmetric junction.

PubMed

Parthiban, Pravien; Khan, Saif A

2012-02-07

We report how a nominally symmetric microfluidic junction can be used to sort all bubbles of an incoming train exclusively into one of its arms. The existence of this "filter" regime is unexpected, given that the junction is symmetric. We analyze this behavior by quantifying how bubbles modulate the hydrodynamic resistance in microchannels and show how speeding up a bubble train whilst preserving its spatial periodicity can lead to filtering at a nominally symmetric junction. We further show how such an asymmetric traffic of bubble trains can be triggered in symmetric geometries by identifying conditions wherein the resistance to flow decreases with an increase in the number of bubbles in the microchannel and derive an exact criterion to predict the same.

Tuning Chemical Potential Difference across Alternately Doped Graphene p-n Junctions for High-Efficiency Photodetection.

PubMed

Lin, Li; Xu, Xiang; Yin, Jianbo; Sun, Jingyu; Tan, Zhenjun; Koh, Ai Leen; Wang, Huan; Peng, Hailin; Chen, Yulin; Liu, Zhongfan

2016-07-13

Being atomically thin, graphene-based p-n junctions hold great promise for applications in ultrasmall high-efficiency photodetectors. It is well-known that the efficiency of such photodetectors can be improved by optimizing the chemical potential difference of the graphene p-n junction. However, to date, such tuning has been limited to a few hundred millielectronvolts. To improve this critical parameter, here we report that using a temperature-controlled chemical vapor deposition process, we successfully achieved modulation-doped growth of an alternately nitrogen- and boron-doped graphene p-n junction with a tunable chemical potential difference up to 1 eV. Furthermore, such p-n junction structure can be prepared on a large scale with stable, uniform, and substitutional doping and exhibits a single-crystalline nature. This work provides a feasible method for synthesizing low-cost, large-scale, high efficiency graphene p-n junctions, thus facilitating their applications in optoelectronic and energy conversion devices.

Thermo-electric modular structure and method of making same

DOEpatents

Freedman, N.S.; Horsting, C.W.; Lawrence, W.F.; Carrona, J.J.

1974-01-29

A method is presented for making a thermoelectric module wtth the aid of an insulating wafer having opposite metallized surfaces, a pair of similar equalizing sheets of metal, a hot-junction strap of metal, a thermoelectric element having hot- and cold-junction surfaces, and a radiator sheet of metal. The method comprises the following steps: brazing said equalizer sheets to said opposite metallized surfaces, respectively, of said insulating wafer with pure copper in a non-oxidizing ambient; brazing one surface of said hot-junction strap to one of the surfaces of said equalizing sheet with a nickel-gold alloy in a non- oxidizing ambient; and diffusion bonding said hot-junction surface of said thermoelectric element to the other surface of said hot-junction strap and said radiator sheet to said cold-junction surface of said thermoelectric element, said diffusion bonding being carried out in a non-oxidizing ambient, under compressive loading, at a temperature of about 550 deg C., and for about one-half hour. (Official Gazette)

Animal models of myasthenia gravis: utility and limitations

PubMed Central

Mantegazza, Renato; Cordiglieri, Chiara; Consonni, Alessandra; Baggi, Fulvio

2016-01-01

Myasthenia gravis (MG) is a chronic autoimmune disease caused by the immune attack of the neuromuscular junction. Antibodies directed against the acetylcholine receptor (AChR) induce receptor degradation, complement cascade activation, and postsynaptic membrane destruction, resulting in functional reduction in AChR availability. Besides anti-AChR antibodies, other autoantibodies are known to play pathogenic roles in MG. The experimental autoimmune MG (EAMG) models have been of great help over the years in understanding the pathophysiological role of specific autoantibodies and T helper lymphocytes and in suggesting new therapies for prevention and modulation of the ongoing disease. EAMG can be induced in mice and rats of susceptible strains that show clinical symptoms mimicking the human disease. EAMG models are helpful for studying both the muscle and the immune compartments to evaluate new treatment perspectives. In this review, we concentrate on recent findings on EAMG models, focusing on their utility and limitations. PMID:27019601

One-pot growth of two-dimensional lateral heterostructures via sequential edge-epitaxy

NASA Astrophysics Data System (ADS)

Sahoo, Prasana K.; Memaran, Shahriar; Xin, Yan; Balicas, Luis; Gutiérrez, Humberto R.

2018-01-01

Two-dimensional heterojunctions of transition-metal dichalcogenides have great potential for application in low-power, high-performance and flexible electro-optical devices, such as tunnelling transistors, light-emitting diodes, photodetectors and photovoltaic cells. Although complex heterostructures have been fabricated via the van der Waals stacking of different two-dimensional materials, the in situ fabrication of high-quality lateral heterostructures with multiple junctions remains a challenge. Transition-metal-dichalcogenide lateral heterostructures have been synthesized via single-step, two-step or multi-step growth processes. However, these methods lack the flexibility to control, in situ, the growth of individual domains. In situ synthesis of multi-junction lateral heterostructures does not require multiple exchanges of sources or reactors, a limitation in previous approaches as it exposes the edges to ambient contamination, compromises the homogeneity of domain size in periodic structures, and results in long processing times. Here we report a one-pot synthetic approach, using a single heterogeneous solid source, for the continuous fabrication of lateral multi-junction heterostructures consisting of monolayers of transition-metal dichalcogenides. The sequential formation of heterojunctions is achieved solely by changing the composition of the reactive gas environment in the presence of water vapour. This enables selective control of the water-induced oxidation and volatilization of each transition-metal precursor, as well as its nucleation on the substrate, leading to sequential edge-epitaxy of distinct transition-metal dichalcogenides. Photoluminescence maps confirm the sequential spatial modulation of the bandgap, and atomic-resolution images reveal defect-free lateral connectivity between the different transition-metal-dichalcogenide domains within a single crystal structure. Electrical transport measurements revealed diode-like responses across the junctions. Our new approach offers greater flexibility and control than previous methods for continuous growth of transition-metal-dichalcogenide-based multi-junction lateral heterostructures. These findings could be extended to other families of two-dimensional materials, and establish a foundation for the development of complex and atomically thin in-plane superlattices, devices and integrated circuits.

Measurement of Beta Particles Induced Electron-Hole Pairs Recombination in Depletion Region of GaAs PN Junction

NASA Astrophysics Data System (ADS)

Chen, Hai-Yang; Jiang, Lan; Li, Da-Rang

2011-05-01

PN junctions and schottky diodes are widely employed as electron-hole pair collectors in electron beam induced current (EBIC) techniques and betavoltaic batteries, in which the recombination in depletion regions is ignored. We measured the beta particles induced electron-hole pairs recombination in the depletion region of a GaAs P+PN+ junction, based on comparisons between measured short currents and ideal values. The results show that only 20% electron-hole pairs in the depletion can be collected, causing the short current. This indicates an electron-hole pair diffusion length of 0.2μm in the depletion region. Hence, it is necessary to evaluate the recombination in the EBIC techniques and betavoltaic design.

Polarization-induced Zener tunnel diodes in GaN/InGaN/GaN heterojunctions

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

Yan, Xiaodong; Li, Wenjun; Islam, S. M.

By the insertion of thin In{sub x}Ga{sub 1−x}N layers into Nitrogen-polar GaN p-n junctions, polarization-induced Zener tunnel junctions are studied. The reverse-bias interband Zener tunneling current is found to be weakly temperature dependent, as opposed to the strongly temperature-dependent forward bias current. This indicates tunneling as the primary reverse-bias current transport mechanism. The Indium composition in the InGaN layer is systematically varied to demonstrate the increase in the interband tunneling current. Comparing the experimentally measured tunneling currents to a model helps identify the specific challenges in potentially taking such junctions towards nitride-based polarization-induced tunneling field-effect transistors.

Strong Depletion in Hybrid Perovskite p-n Junctions Induced by Local Electronic Doping.

PubMed

Ou, Qingdong; Zhang, Yupeng; Wang, Ziyu; Yuwono, Jodie A; Wang, Rongbin; Dai, Zhigao; Li, Wei; Zheng, Changxi; Xu, Zai-Quan; Qi, Xiang; Duhm, Steffen; Medhekar, Nikhil V; Zhang, Han; Bao, Qiaoliang

2018-04-01

A semiconductor p-n junction typically has a doping-induced carrier depletion region, where the doping level positively correlates with the built-in potential and negatively correlates with the depletion layer width. In conventional bulk and atomically thin junctions, this correlation challenges the synergy of the internal field and its spatial extent in carrier generation/transport. Organic-inorganic hybrid perovskites, a class of crystalline ionic semiconductors, are promising alternatives because of their direct badgap, long diffusion length, and large dielectric constant. Here, strong depletion in a lateral p-n junction induced by local electronic doping at the surface of individual CH 3 NH 3 PbI 3 perovskite nanosheets is reported. Unlike conventional surface doping with a weak van der Waals adsorption, covalent bonding and hydrogen bonding between a MoO 3 dopant and the perovskite are theoretically predicted and experimentally verified. The strong hybridization-induced electronic coupling leads to an enhanced built-in electric field. The large electric permittivity arising from the ionic polarizability further contributes to the formation of an unusually broad depletion region up to 10 µm in the junction. Under visible optical excitation without electrical bias, the lateral diode demonstrates unprecedented photovoltaic conversion with an external quantum efficiency of 3.93% and a photodetection responsivity of 1.42 A W -1 . © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Economic competitiveness of III-V on silicon tandem one-sun photovoltaic solar modules in favorable future scenarios

DOE PAGES

Bobela, David C.; Gedvilas, Lynn; Woodhouse, Michael; ...

2016-09-05

Here, tandem modules combining a III-V top cell with a Si bottom cell offer the potential to increase the solar energy conversion efficiency of one-sun photovoltaic modules beyond 25%, while fully utilizing the global investment that has been made in Si photovoltaics manufacturing. At present, the cost of III-V cells is far too high for this approach to be competitive for one-sun terrestrial power applications. We investigated the system-level economic benefits of both GaAs/Si and InGaP/Si tandem modules in favorable future scenarios where the cost of III-V cells is substantially reduced, perhaps to less than the cost of Si cells.more » We found, somewhat unexpectedly, that these tandems can reduce installed system cost only when the area-related balance-of-system cost is high, such as for area-constrained residential rooftop systems in the USA. When area-related balance-of-system cost is lower, such as for utility-scale systems, the tandem module offers no benefit. This is because a system using tandem modules is more expensive than one using single-junction Si modules when III-V cells are expensive, and a system using tandem modules is more expensive than one using single-junction III-V modules when III-V cells are inexpensive.« less

Economic competitiveness of III-V on silicon tandem one-sun photovoltaic solar modules in favorable future scenarios

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

Bobela, David C.; Gedvilas, Lynn; Woodhouse, Michael

Here, tandem modules combining a III-V top cell with a Si bottom cell offer the potential to increase the solar energy conversion efficiency of one-sun photovoltaic modules beyond 25%, while fully utilizing the global investment that has been made in Si photovoltaics manufacturing. At present, the cost of III-V cells is far too high for this approach to be competitive for one-sun terrestrial power applications. We investigated the system-level economic benefits of both GaAs/Si and InGaP/Si tandem modules in favorable future scenarios where the cost of III-V cells is substantially reduced, perhaps to less than the cost of Si cells.more » We found, somewhat unexpectedly, that these tandems can reduce installed system cost only when the area-related balance-of-system cost is high, such as for area-constrained residential rooftop systems in the USA. When area-related balance-of-system cost is lower, such as for utility-scale systems, the tandem module offers no benefit. This is because a system using tandem modules is more expensive than one using single-junction Si modules when III-V cells are expensive, and a system using tandem modules is more expensive than one using single-junction III-V modules when III-V cells are inexpensive.« less

Coulomb blockade in a single tunnel junction directly connected to a multiwalled carbon nanotube

NASA Astrophysics Data System (ADS)

Haruyama, Junji; Takesue, Izumi; Sato, Yuki

2000-10-01

We report on Coulomb blockade in a single tunnel junction directly connected to a multiwalled carbon nanotube (MWNT) by utilizing a nanoporous alumina film. The MWNT exhibits a weak localization effect with strong spin flip scattering. Experimental results and analysis suggest that a high-impedance external environment caused by the weak localization in the MWNT can yield Coulomb blockade, in accordance with phase correlation theory in a single junction system. It is also revealed that the Coulomb blockade is very sensitive to phase modulation in the MWNT, which also acts as a high-impedance transmission line.

Quarter-Rate Superconducting Modulator for Improved High Resolution Analog-to-Digital Converter

DTIC Science & Technology

2006-08-01

third pulse to Output B2, and the fourth to Output C2. The fifth pulse goes to Output B1 and the pattern continues. The inductances LQA , LQB, LQC...inductance LQA . Junction JL1A is now biased with the loop phase being equal to – π. In the bottom left demultiplexer, junctions JR1B and JL2B are

Hybrid thermoelectric solar collector design and analysis

NASA Technical Reports Server (NTRS)

Roberts, A. S., Jr.; Shaheen, K. E.

1982-01-01

A flat-plate solar collector is conceived where energy cascades through thermoelectric power modules generating direct-current electricity. The intent of this work was to choose a collector configuration and to perform a steady-state thermal performance assessment. A set of energy balance equations were written and solved numerically for the purpose of optimizing collector thermal and electrical performance. The collector design involves finned columns of thermoelectric modules imbedded in the absorber plate (hot junction) over a parallel array of vertical tubes. The thermoelectric power output is limited by the small hot-junction/cold-junction temperature difference which can be maintained under steady-state conditions. The electric power per unit tube pass area is found to have a maximum as a function of a geometric parameter, while electric power is maximized with respect to an electric resistance ratio. Although the electric power efficiency is small, results indicate that there is sufficient electric power production to drive a coolant circulator, suggesting the potential for a stand-alone system.

Decursin inhibits VEGF-mediated inner blood-retinal barrier breakdown by suppression of VEGFR-2 activation.

PubMed

Kim, Jin Hyoung; Kim, Jeong Hun; Lee, You Mie; Ahn, Eun-Mi; Kim, Kyu-Won; Yu, Young Suk

2009-09-01

The blood-retinal barrier (BRB) is essential for the normal structural and functional integrity of the retina, whose breakdown could cause the serious vision loss. Vascular endothelial growth factor (VEGF), as a permeable factor, induces alteration of tight junction proteins to result in BRB breakdown. Herein, we demonstrated that decursin inhibits VEGF-mediated inner BRB breakdown through suppression of VEGFR-2 signaling pathway. In retinal endothelial cells, decursin inhibited VEGF-mediated hyperpermeability. Decursin prevented VEGF-mediated loss of tight junction proteins including zonula occludens-1 (ZO-1), ZO-2, and occludin in retinal endothelial cells, which was also supported by restoration of tight junction proteins in intercellular junction. In addition, decursin significantly inhibited VEGF-mediated vascular leakage from retinal vessels, which was accompanied by prevention of loss of tight junction proteins in retinal vessels. Decursin significantly suppressed VEGF-induced VEGFR-2 phosphrylation that consequently led to inhibition of extracellular signal-regulated kinase (ERK) 1/2 activation. Moreover, decursin induced no cytotoxicity to retinal endothelial cells and no retinal toxicity under therapeutic concentrations. Therefore, our results suggest that decursin prevents VEGF-mediated BRB breakdown through blocking of loss of tight junction proteins, which might be regulated by suppression of VEGFR-2 activation. As a novel inhibitor to BRB breakdown, decursin could be applied to variable retinopathies with BRB breakdown.

Gap Junction Inhibition Prevents Drug-induced Liver Toxicity and Fulminant Hepatic Failure

PubMed Central

Patel, Suraj J; Milwid, Jack M; King, Kevin R; Bohr, Stefan; Iracheta, Arvin; Li, Matthew; Vitalo, Antonia; Parekkadan, Biju; Jindal, Rohit; Yarmush, Martin L

2013-01-01

Drug-induced liver injury (DILI) limits the development and utilization of numerous therapeutic compounds, and consequently presents major challenges to the pharmaceutical industry and clinical medicine1, 2. Acetaminophen (APAP) containing compounds are among the most frequently prescribed drugs, and also the most common cause of DILI3. Here we describe a pharmacological strategy that targets gap junction communication to prevent amplification of fulminant hepatic failure and APAP-induced hepatotoxicity. We report that connexin 32 (Cx32), a key hepatic gap junction protein, is an essential mediator of DILI by showing that mice deficient in Cx32 are protected against liver damage, acute inflammation, and death. We identified a small molecule inhibitor of Cx32 as a novel hepatoprotectant that achieves the same result in wildtype mice when coadministered with known hepatotoxic drugs. These findings demonstrate that gap junction inhibition is an effective therapy for limiting DILI, and suggest a novel pharmaceutical strategy to improve drug safety. PMID:22252509

CRTC2 and Nedd4 ligase involvement in FSH and TGFβ1 upregulation of connexin43 gap junction.

PubMed

Fang, Wei-Ling; Lai, Si-Yi; Lai, Wei-An; Lee, Ming-Ting; Liao, Ching-Fong; Ke, Ferng-Chun; Hwang, Jiuan-Jiuan

2015-12-01

The major mission of the ovarian follicle is the timely production of the mature fertilizable oocyte, and this is achieved by gonadotropin-regulated, gap junction-mediated cell-cell communication between the oocyte and surrounding nurturing granulosa cells. We have demonstrated that FSH and transforming growth factor beta 1 (TGFβ1) stimulate Gja1 gene-encoded connexin43 (Cx43) gap junction formation/function in rat ovarian granulosa cells is important for their induction of steroidogenesis; additionally, cAMP-protein kinase A (PKA)- and calcium-calcineurin-sensitive cAMP response element-binding (CREB) coactivator CRTC2 plays a crucial role during steroidogenesis. This study was to explore the potential molecular mechanism whereby FSH and TGFβ1 regulate Cx43 synthesis and degradation, particularly the involvement of CRTC2 and ubiquitin ligase Nedd4. Primary culture of granulosa cells from ovarian antral follicles of gonadotropin-primed immature rats was used. At 48 h post-treatment, FSH plus TGFβ1 increased Cx43 level and gap junction function in a PKA- and calcineurin-dependent manner, and TGFβ1 acting through its type I receptor modulated FSH action. Chromatin-immunoprecipitation analysis reveals FSH induced an early-phase (45 min) and FSH+TGFβ1 further elicited a late-phase (24 h) increase in CRTC2, CREB and CBP binding to the Gja1 promoter. Additionally, FSH+TGFβ1 increased the half-life of hyper-phosphorylated Cx43 (Cx43-P2). Also, the proteasome inhibitor MG132 prevented the brefeldin A (blocker of protein transport through Golgi)-reduced Cx43-P2 level and membrane Cx43 gap junction plaque. This is associated with FSH+TGFβ1-attenuated Cx43 interaction with Nedd4 and Cx43 ubiquitination. In all, this study uncovers that FSH and TGFβ1 upregulation of Cx43 gap junctions in ovarian granulosa cells critically involves enhancing CRTC2/CREB/CBP-mediated Cx43 expression and attenuating ubiquitin ligase Nedd4-mediated proteosomal degradation of Cx43 protein. © 2015 Society for Endocrinology.

Ferromagnetic resonance with long Josephson junction

NASA Astrophysics Data System (ADS)

Golovchanskiy, I. A.; Abramov, N. N.; Stolyarov, V. S.; Emelyanova, O. V.; Golubov, A. A.; Ustinov, A. V.; Ryazanov, V. V.

2017-05-01

In this work we propose a hybrid device based on a long Josephson junction (JJ) coupled inductively to an external ferromagnetic (FM) layer. The long JJ in a zero-field operation mode induces a localized AC magnetic field in the FM layer and enables a synchronized magnetostatic standing wave. The magnetostatic wave induces additional dissipation for soliton propagation in the junction and also enables a phase locking (resonant soliton synchronization) at a frequency of natural ferromagnetic resonance. The later manifests itself as an additional constant voltage step on the current-voltage characteristics at the corresponding voltage. The proposed device allows to study magnetization dynamics of individual micro-scaled FM samples using just DC technique, and also it provides additional phase locking frequency in the junction, determined exclusively by characteristics of the ferromagnet.

Modulation of VEGF-induced retinal vascular permeability by peroxisome proliferator-activated receptor-β/δ.

PubMed

Suarez, Sandra; McCollum, Gary W; Bretz, Colin A; Yang, Rong; Capozzi, Megan E; Penn, John S

2014-11-18

Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability contributes to diabetic macular edema (DME), a serious vision-threatening condition. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) antagonist/reverse agonist, GSK0660, inhibits VEGF-induced human retinal microvascular endothelial cell (HRMEC) proliferation, tubulogenesis, and oxygen-induced retinal vasculopathy in newborn rats. These VEGF-induced HRMEC behaviors and VEGF-induced disruption of endothelial cell junctional complexes may well share molecular signaling events. Thus, we sought to examine the role of PPARβ/δ in VEGF-induced retinal hyperpermeability. Transendothelial electrical resistance (TEER) measurements were performed on HRMEC monolayers to assess permeability. Claudin-1/Claudin-5 localization in HRMEC monolayers was determined by immunocytochemistry. Extracellular signal-regulated protein kinases 1 and 2 (Erk 1/2) phosphorylation, VEGF receptor 1 (VEGFR1) and R2 were assayed by Western blot analysis. Expression of VEGFR1 and R2 was measured by quantitative RT-PCR. Last, retinal vascular permeability was assayed in vivo by Evans blue extravasation. Human retinal microvascular endothelial cell monolayers treated with VEGF for 24 hours showed decreased TEER values that were completely reversed by the highest concentration of GSK0660 (10 μM) and PPARβ/δ-directed siRNA (20 μM). In HRMEC treated with VEGF, GSK0660 stabilized tight-junctions as evidenced by Claudin-1 staining, reduced phosphorylation of Erk1/2, and reduced VEGFR1/2 expression. Peroxisome proliferator-activated receptor β/δ siRNA had a similar effect on VEGFR expression and Claudin-1, supporting the specificity of GSK0660 in our experiments. Last, GSK0660 significantly inhibited VEGF-induced retinal vascular permeability and reduced retinal VEGFR1and R2 levels in C57BL/6 mice. These data suggest a protective effect for PPARβ/δ antagonism against VEGF-induced vascular permeability, possibly through reduced VEGFR expression. Therefore, antagonism/reverse agonism of PPARβ/δ siRNA may represent a novel therapeutic methodology against retinal hyperpermeability and is worthy of future investigation. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Modulation of VEGF-Induced Retinal Vascular Permeability by Peroxisome Proliferator-Activated Receptor-β/δ

PubMed Central

Suarez, Sandra; McCollum, Gary W.; Bretz, Colin A.; Yang, Rong; Capozzi, Megan E.; Penn, John S.

2014-01-01

Purpose. Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability contributes to diabetic macular edema (DME), a serious vision-threatening condition. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) antagonist/reverse agonist, GSK0660, inhibits VEGF-induced human retinal microvascular endothelial cell (HRMEC) proliferation, tubulogenesis, and oxygen-induced retinal vasculopathy in newborn rats. These VEGF-induced HRMEC behaviors and VEGF-induced disruption of endothelial cell junctional complexes may well share molecular signaling events. Thus, we sought to examine the role of PPARβ/δ in VEGF-induced retinal hyperpermeability. Methods. Transendothelial electrical resistance (TEER) measurements were performed on HRMEC monolayers to assess permeability. Claudin-1/Claudin-5 localization in HRMEC monolayers was determined by immunocytochemistry. Extracellular signal-regulated protein kinases 1 and 2 (Erk 1/2) phosphorylation, VEGF receptor 1 (VEGFR1) and R2 were assayed by Western blot analysis. Expression of VEGFR1 and R2 was measured by quantitative RT-PCR. Last, retinal vascular permeability was assayed in vivo by Evans blue extravasation. Results. Human retinal microvascular endothelial cell monolayers treated with VEGF for 24 hours showed decreased TEER values that were completely reversed by the highest concentration of GSK0660 (10 μM) and PPARβ/δ-directed siRNA (20 μM). In HRMEC treated with VEGF, GSK0660 stabilized tight-junctions as evidenced by Claudin-1 staining, reduced phosphorylation of Erk1/2, and reduced VEGFR1/2 expression. Peroxisome proliferator-activated receptor β/δ siRNA had a similar effect on VEGFR expression and Claudin-1, supporting the specificity of GSK0660 in our experiments. Last, GSK0660 significantly inhibited VEGF-induced retinal vascular permeability and reduced retinal VEGFR1and R2 levels in C57BL/6 mice. Conclusions. These data suggest a protective effect for PPARβ/δ antagonism against VEGF-induced vascular permeability, possibly through reduced VEGFR expression. Therefore, antagonism/reverse agonism of PPARβ/δ siRNA may represent a novel therapeutic methodology against retinal hyperpermeability and is worthy of future investigation. PMID:25406289

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

Repins, Ingrid; Jordan, Dirk; Bosco, Nick

The proposed new IEC standard will address the test temperature requirements in IEC 61215 (module design), IEC 61730 (module safety), IEC 62790 (junction box safety) and IEC 62852 (connectors), and will provide guidelines to modify temperature limits in four existing standards to better describe module performance in hotter climates. This workshop includes four presentations: Special Testing for Modules Deployed in Hot Use Environments - Are We Doing This in a Low-Cost Way?, Experimental Evidence, Why the highest temperatures are the most stressful to PV modules during thermal cycling, and Safety Aspects for Modules Deployed in Hot Use Environments.

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

NASA Astrophysics Data System (ADS)

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.

Modulation of Quantum Tunneling via a Vertical Two-Dimensional Black Phosphorus and Molybdenum Disulfide p-n Junction.

PubMed

Liu, Xiaochi; Qu, Deshun; Li, Hua-Min; Moon, Inyong; Ahmed, Faisal; Kim, Changsik; Lee, Myeongjin; Choi, Yongsuk; Cho, Jeong Ho; Hone, James C; Yoo, Won Jong

2017-09-26

Diverse diode characteristics were observed in two-dimensional (2D) black phosphorus (BP) and molybdenum disulfide (MoS 2 ) heterojunctions. The characteristics of a backward rectifying diode, a Zener diode, and a forward rectifying diode were obtained from the heterojunction through thickness modulation of the BP flake or back gate modulation. Moreover, a tunnel diode with a precursor to negative differential resistance can be realized by applying dual gating with a solid polymer electrolyte layer as a top gate dielectric material. Interestingly, a steep subthreshold swing of 55 mV/dec was achieved in a top-gated 2D BP-MoS 2 junction. Our simple device architecture and chemical doping-free processing guaranteed the device quality. This work helps us understand the fundamentals of tunneling in 2D semiconductor heterostructures and shows great potential in future applications in integrated low-power circuits.

Investigation of silicide-induced-dopant-activation for steep tunnel junction in tunnel field effect transistor (TFET)

NASA Astrophysics Data System (ADS)

Kim, Sihyun; Kwon, Dae Woong; Park, Euyhwan; Lee, Junil; Lee, Roongbin; Lee, Jong-Ho; Park, Byung-Gook

2018-02-01

Numerous researches for making steep tunnel junction within tunnel field-effect transistor (TFET) have been conducted. One of the ways to make an abrupt junction is source/drain silicidation, which uses the phenomenon often called silicide-induced-dopant-segregation. It is revealed that the silicide process not only helps dopants to pile up adjacent to the metal-silicon alloy, also induces the dopant activation, thereby making it possible to avoid additional high temperature process. In this report, the availability of dopant activation induced by metal silicide process was thoroughly investigated by diode measurement and device simulation. Metal-silicon (MS) diodes having p+ and n+ silicon formed on the p- substrate exhibit the characteristics of ohmic and pn diodes respectively, for both the samples with and without high temperature annealing. The device simulation for TFETs with dopant-segregated source was also conducted, which verified enhanced DC performance.

Computational Analysis of Stresses Acting on Intermodular Junctions in Thoracic Aortic Endografts

PubMed Central

Prasad, Anamika; To, Lillian K.; Gorrepati, Madhu L.; Zarins, Christopher K.; Figueroa, C. Alberto

2011-01-01

Purpose: To evaluate the biomechanical and hemodynamic forces acting on the intermodular junctions of a multi-component thoracic endograft and elucidate their influence on the development of type III endoleak due to disconnection of stent-graft segments. Methods: Three-dimensional computer models of the thoracic aorta and a 4-component thoracic endograft were constructed using postoperative (baseline) and follow-up computed tomography (CT) data from a 69-year-old patient who developed type III endoleak 4 years after stent-graft placement. Computational fluid dynamics (CFD) techniques were used to quantitate the displacement forces acting on the device. The contact stresses between the different modules of the graft were then quantified using computational solid mechanics (CSM) techniques. Lastly, the intermodular junction frictional stability was evaluated using a Coulomb model. Results: The CFD analysis revealed that curvature and length are key determinants of the displacement forces experienced by each endograft and that the first 2 modules were exposed to displacement forces acting in opposite directions in both the lateral and longitudinal axes. The CSM analysis revealed that the highest concentration of stresses occurred at the junction between the first and second modules of the device. Furthermore, the frictional analysis demonstrated that most of the surface area (53%) of this junction had unstable contact. The predicted critical zone of intermodular stress concentration and frictional instability matched the location of the type III endoleak observed in the 4-year follow-up CT image. Conclusion: The region of larger intermodular stresses and highest frictional instability correlated with the zone where a type III endoleak developed 4 years after thoracic stent-graft placement. Computational techniques can be helpful in evaluating the risk of endograft migration and potential for modular disconnection and may be useful in improving device placement strategies and endograft design. PMID:21861748

Tunneling studies of compositionally modulated PB/Fe films

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

Wawro, A.; Witek, A.; Majewski, J.

1988-01-01

Preliminary results of preparation and investigation of compositionally modulated Pb/Fe films are reported. These films have been used as electrodes in Al/Al/sub 2/O/sub 3//{kappa}(Pb/Fe) tunnel junctions and the tunnelling characteristics I-V, dV/dI and d/sup 2/V/d/I/sup 2/ vs V have been studied in dependence on the modulation period.

Inverted Three-Junction Tandem Thermophotovoltaic Modules

NASA Technical Reports Server (NTRS)

Wojtczuk, Steven

2012-01-01

An InGaAs-based three-junction (3J) tandem thermophotovoltaic (TPV) cell has been investigated to utilize more of the blackbody spectrum (from a 1,100 C general purpose heat source GPHS) efficiently. The tandem consists of three vertically stacked subcells, a 0.74-eV InGaAs cell, a 0.6- eV InGaAs cell, and a 0.55-eV InGaAs cell, as well as two interconnecting tunnel junctions. A greater than 20% TPV system efficiency was achieved by another group with a 1,040 C blackbody using a single-bandgap 0.6- eV InGaAs cell MIM (monolithic interconnected module) (30 lateral junctions) that delivered about 12 V/30 or 0.4 V/junction. It is expected that a three-bandgap tandem MIM will eventually have about 3 this voltage (1.15 V) and about half the current. A 4 A/cm2 would be generated by a single-bandgap 0.6-V InGaAs MIM, as opposed to the 2 A/cm2 available from the same spectrum when split among the three series-connected junctions in the tandem stack. This would then be about a 50% increase (3xVoc, 0.5xIsc) in output power if the proposed tandem replaced the single- bandgap MIM. The advantage of the innovation, if successful, would be a 50% increase in power conversion efficiency from radioisotope heat sources using existing thermophotovoltaics. Up to 50% more power would be generated for radioisotope GPHS deep space missions. This type of InGaAs multijunction stack could be used with terrestrial concentrator solar cells to increase efficiency from 41 to 45% or more.

Crack propagation in teeth: a comparison of perimortem and postmortem behavior of dental materials and cracks.

PubMed

Hughes, Cris E; White, Crystal A

2009-03-01

This study presents a new method for understanding postmortem heat-induced crack propagation patterns in teeth. The results demonstrate that patterns of postmortem heat-induced crack propagation differ from perimortem and antemortem trauma-induced crack propagation patterns. Dental material of the postmortem tooth undergoes dehydration leading to a shrinking and more brittle dentin material and a weaker dentin-enamel junction. Dentin intertubule tensile stresses are amplified by the presence of the pulp cavity, and initiates crack propagation from the internal dentin, through the dentin-enamel junction and lastly the enamel. In contrast, in vivo perimortem and antemortem trauma-induced crack propagation initiates cracking from the external surface of the enamel toward the dentin-enamel junction where the majority of the energy of the crack is dissipated, eliminating the crack's progress into the dentin. These unique patterns of crack propagation can be used to differentiate postmortem taphonomy-induced damage from antemortem and perimortem trauma in teeth.

A junction-level optoelectronic characterization of etching-induced damage for third-generation HgCdTe infrared focal-plane array photodetectors

NASA Astrophysics Data System (ADS)

Wang, Peng; Wang, Yueming; Wu, Mingzai; Ye, Zhenhua

2018-06-01

Third-generation HgCdTe-based infrared focal plane arrays require high aspect ratio trenches with admissible etch induced damage at the surface and sidewalls for effectively isolating the pixels. In this paper, the high-density inductively coupled plasma enhanced reaction ion etching technique has been used for micro-mesa delineation of HgCdTe for third-generation infrared focal-plane array detectors. A nondestructive junction-level optoelectronic characterization method called laser beam induced current (LBIC) is used to evaluate the lateral junction extent of HgCdTe etch-induced damage scanning electron microscopy. It is found that the LBIC profiles exhibit evident double peaks and valleys phenomena. The lateral extent of etch induced mesa damage of ∼2.4 μm is obtained by comparing the LBIC profile and the scanning electron microscopy image of etched sample. This finding will guide us to nondestructively identify the distributions of the etching damages in large scale HgCdTe micro-mesa.

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.

PubMed

Kabátková, Markéta; Svobodová, Jana; Pěnčíková, Kateřina; Mohatad, Dilshad Shaik; Šmerdová, Lenka; Kozubík, Alois; Machala, Miroslav; Vondráček, Jan

2015-01-05

Polycyclic aromatic hydrocarbons (PAHs) with lower molecular weight exhibit lesser genotoxicity and carcinogenicity than highly carcinogenic PAHs with a higher number of benzene rings. Nevertheless, they elicit specific effects linked with tumor promotion, such as acute inhibition of gap junctional intercellular communication (GJIC). Although inflammatory reaction may alter bioactivation and toxicity of carcinogenic PAHs, little is known about the impact of pro-inflammatory cytokines on toxic effects of the low-molecular-weight PAHs. Here, we investigated the impact of a pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), on the effects associated with tumor promotion and with induction of the aryl hydrocarbon receptor (AhR)-dependent gene expression in rat liver epithelial cells. We found that a prolonged incubation with TNF-α induced a down-regulation of GJIC, associated with reduced expression of connexin 43 (Cx43), a major connexin isoform found in liver epithelial cells. The Cx43 down-regulation was partly mediated by the activity of the mitogen-activated protein (MAP) p38 kinase. Independently of GJIC modulation, or p38 activation, TNF-α potentiated the AhR-dependent proliferative effect of a model low-molecular-weight PAH, fluoranthene, on contact-inhibited cells. In contrast, this pro-inflammatory cytokine repressed the fluoranthene-induced expression of a majority of model AhR gene targets, such as Cyp1a1, Ahrr or Tiparp. The results of the present study indicate that inflammatory reaction may differentially modulate various toxic effects of low-molecular-weight PAHs; the exposure to pro-inflammatory cytokines may both strengthen (inhibition of GJIC, disruption of contact inhibition) and repress (expression of a majority of AhR-dependent genes) their impact on toxic endpoints associated with carcinogenesis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Spin and charge thermopower effects in the ferromagnetic graphene junction

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

Vahedi, Javad, E-mail: javahedi@gmail.com; Center for Theoretical Physics of Complex Systems, Institute for Basic Science; Barimani, Fattaneh

2016-08-28

Using wave function matching approach and employing the Landauer-Buttiker formula, a ferromagnetic graphene junction with temperature gradient across the system is studied. We calculate the thermally induced charge and spin current as well as the thermoelectric voltage (Seebeck effect) in the linear and nonlinear regimes. Our calculation revealed that due to the electron-hole symmetry, the charge Seebeck coefficient is, for an undoped magnetic graphene, an odd function of chemical potential while the spin Seebeck coefficient is an even function regardless of the temperature gradient and junction length. We have also found with an accurate tuning external parameter, namely, the exchangemore » filed and gate voltage, the temperature gradient across the junction drives a pure spin current without accompanying the charge current. Another important characteristic of thermoelectric transport, thermally induced current in the nonlinear regime, is examined. It would be our main finding that with increasing thermal gradient applied to the junction the spin and charge thermovoltages decrease and even become zero for non zero temperature bias.« less

Gap state charge induced spin-dependent negative differential resistance in tunnel junctions

NASA Astrophysics Data System (ADS)

Jiang, Jun; Zhang, X.-G.; Han, X. F.

2016-04-01

We propose and demonstrate through first-principles calculation a new spin-dependent negative differential resistance (NDR) mechanism in magnetic tunnel junctions (MTJ) with cubic cation disordered crystals (CCDC) AlO x or Mg1-x Al x O as barrier materials. The CCDC is a class of insulators whose band gap can be changed by cation doping. The gap becomes arched in an ultrathin layer due to the space charge formed from metal-induced gap states. With an appropriate combination of an arched gap and a bias voltage, NDR can be produced in either spin channel. This mechanism is applicable to 2D and 3D ultrathin junctions with a sufficiently small band gap that forms a large space charge. It provides a new way of controlling the spin-dependent transport in spintronic devices by an electric field. A generalized Simmons formula for tunneling current through junction with an arched gap is derived to show the general conditions under which ultrathin junctions may exhibit NDR.

Gap junction blockade induces apoptosis in human endometrial stromal cells.

PubMed

Yu, Jie; Berga, Sarah L; Zou, Wei; Sun, He-Ying; Johnston-MacAnanny, Erika; Yalcinkaya, Tamer; Sidell, Neil; Bagchi, Indrani C; Bagchi, Milan K; Taylor, Robert N

2014-07-01

One of the most dynamic adult human tissues is the endometrium. Through coordinated, cyclical proliferation, differentiation, leukocyte recruitment, apoptosis, and desquamation, the uterine lining is expanded and shed monthly, unless pregnancy is established. Errors in these steps potentially cause endometrial dysfunction, abnormal uterine bleeding, failed embryonic implantation, infertility, or endometrial carcinoma. Our prior studies showed that gap junctions comprised of Gap junction alpha-1 (GJA1) protein, also known as connexin 43 (CX43), subunits are critical to endometrial stromal cell differentiation. The current studies were undertaken to explore the mechanism of endometrial dysfunction when gap junction intercellular communication (GJIC) is disrupted. Gap junction blockade by two distinct GJIC inhibitors, 18α-glycyrrhetinic acid (AGA) and octanol (OcOH), suppressed proliferation and induced apoptosis in endometrial stromal cells, as manifested by reduced biomarkers of cell viability, increased TUNEL staining, caspase-3 activation, sub-G1 chromosomal DNA complement, as well as shortened telomere length. Unexpectedly, we also observed that the chemical inhibitors blocked CX43 gene expression. Moreover, when endometrial stromal cells were induced to undergo hormonal decidualization, following a 7-day exposure to 10 nM 17β-estradiol + 100 nM progesterone + 0.5 mM dibutyryl cAMP, characteristic epithelioid changes in cell shape and secretion of prolactin were blunted in the presence of AGA or OcOH, recapitulating effects of RNA interference of CX43. Our findings indicate that endometrial stromal cell proliferation and maintenance of decidualized endometrial function are GJIC-dependent, and that disruption of gap junctions induces endometrial stromal cell apoptosis. These observations may have important implications for several common clinical endometrial pathologies. © 2014 Wiley Periodicals, Inc.

Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart.

PubMed

Martins-Marques, Tania; Anjo, Sandra Isabel; Pereira, Paulo; Manadas, Bruno; Girão, Henrique

2015-11-01

The coordinated and synchronized cardiac muscle contraction relies on an efficient gap junction-mediated intercellular communication (GJIC) between cardiomyocytes, which involves the rapid anisotropic impulse propagation through connexin (Cx)-containing channels, namely of Cx43, the most abundant Cx in the heart. Expectedly, disturbing mechanisms that affect channel activity, localization and turnover of Cx43 have been implicated in several cardiomyopathies, such as myocardial ischemia. Besides gap junction-mediated intercellular communication, Cx43 has been associated with channel-independent functions, including modulation of cell adhesion, differentiation, proliferation and gene transcription. It has been suggested that the role played by Cx43 is dictated by the nature of the proteins that interact with Cx43. Therefore, the characterization of the Cx43-interacting network and its dynamics is vital to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication, but also to unveil novel and unanticipated biological functions of Cx43. In the present report, we applied a quantitative SWATH-MS approach to characterize the Cx43 interactome in rat hearts subjected to ischemia and ischemia-reperfusion. Our results demonstrate that, in the heart, Cx43 interacts with proteins related with various biological processes such as metabolism, signaling and trafficking. The interaction of Cx43 with proteins involved in gene transcription strengthens the emerging concept that Cx43 has a role in gene expression regulation. Importantly, our data shows that the interactome of Cx43 (Connexome) is differentially modulated in diseased hearts. Overall, the characterization of Cx43-interacting network may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Data are available via ProteomeXchange with identifier PXD002331. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

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

2014-04-01

Previously we demonstrated uniformly strong expression of CD24 in the epithelial attachment to the tooth and in the migrating epithelium of the periodontitis lesion. Titers of serum antibodies autoreactive with CD24 peptide correlated with reduced severity of periodontal disease. Ligation of CD24 expressed by oral epithelial cells induced formation of tight junctions that limited paracellular diffusion. In this study, we aimed to reveal that the lack of uniform expression of tight junction components in the pocket epithelium of periodontitis lesions is likely to contribute to increased paracellular permeability to bacterial products. This is proposed as a potential driver of the immunopathology of periodontitis. An epithelial culture model with close correspondence for expression patterns for tight junction components in periodontal epithelia was used. Immunohistochemical staining and confocal laser scanning microscopy were used to analyse patterns of expression of gingival epithelial tight junction components. The minimally inflamed gingival attachment was characterized by uniformly strong staining at cell contacts for the tight junction components zona occludens-1, zona occludens-2, occludin, junction adhesion molecule-A, claudin-4 and claudin-15. In contrast, the pocket epithelium of the periodontal lesion showed scattered, uneven staining for these components. This pattern correlated closely with that of unstimulated oral epithelial cells in culture. Following ligation of CD24 expressed by these cells, the pattern of tight junction component expression of the minimally inflamed gingival attachment developed rapidly. There was evidence for non-uniform and focal expression only of tight junction components in the pocket epithelium. In the cell-culture model, ligation of CD24 induced a tight junction expression profile equivalent to that observed for the minimally inflamed gingival attachment. Ligation of CD24 expressed by gingival epithelial cells by lectin-like receptors of commensal oral streptococci could mediate the phenotype of health, whereas pathogenic organisms associated with periodontal disease might not signal effectively through CD24. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Controlled finite momentum pairing and spatially varying order parameter in proximitized HgTe quantum wells

NASA Astrophysics Data System (ADS)

Hart, Sean; Ren, Hechen; Kosowsky, Michael; Ben-Shach, Gilad; Leubner, Philipp; Bruene, Christoph; Buhmann, Hartmut; Molenkamp, Laurens; Halperin, Bertrand; Yacoby, Amir

Conventional s-wave superconductivity arises from singlet pairing of electrons with opposite Fermi momenta, forming Cooper pairs with zero net momentum. Recent studies have focused on coupling s-wave superconductors to systems with an unusual configuration of electronic spin and momentum at the Fermi surface, where the nature of the paired state can be modified and the system may even undergo a topological phase transition. Here we present measurements on Josephson junctions based on HgTe quantum wells coupled to aluminum or niobium superconductors, and subject to a magnetic field in the plane of the quantum well. We observe that the in-plane magnetic field modulates the Fraunhofer interference pattern, and that this modulation depends both on electron density and on the direction of the in-plane field with respect to the junction. However, the orientation of the junction with respect to the underlying crystal lattice does not impact the measurements. These findings suggest that spin-orbit coupling plays a role in the observed behavior, and that measurements of Josephson junctions in the presence of an in-plane field can elucidate the Fermi surface properties of the weak link material. NSF DMR-1206016; STC Center for Integrated Quantum Materials under NSF Grant No. DMR-1231319; NSF GRFP under Grant DGE1144152, Microsoft Corporation Project Q.

Array of Josephson junctions with a nonsinusoidal current-phase relation as a model of the resistive transition of unconventional superconductors

NASA Astrophysics Data System (ADS)

Carbone, Anna; Gilli, Marco; Mazzetti, Piero; Ponta, Linda

2010-12-01

An array of resistively and capacitively shunted Josephson junctions with nonsinusoidal current-phase relation is considered for modeling the transition in high-Tc superconductors. The emergence of higher harmonics, besides the simple sinusoid Ic sin ϕ, is expected for dominant d-wave symmetry of the Cooper pairs, random distribution of potential drops, dirty grains, or nonstationary conditions. We show that additional cosine and sine terms act, respectively, by modulating the global resistance and by changing the Josephson coupling of the mixed superconductive-normal states. First, the approach is applied to simulate the transition in disordered granular superconductors with the weak-links characterized by nonsinusoidal current-phase relation. In granular superconductors, the emergence of higher-order harmonics affects the slope of the transition. Then, arrays of intrinsic Josephson junctions, naturally formed by the CuO2 planes in cuprates, are considered. The critical temperature suppression, observed at values of hole doping close to p =1/8, is investigated. Such suppression, related to the sign change and modulation of the Josephson coupling across the array, is quantified in terms of the intensities of the first and second sinusoids of the current-phase relation. Applications are envisaged for the design and control of quantum devices based on stacks of intrinsic Josephson junctions.

IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.

PubMed

Ennajdaoui, Hanane; Howard, Jonathan M; Sterne-Weiler, Timothy; Jahanbani, Fereshteh; Coyne, Doyle J; Uren, Philip J; Dargyte, Marija; Katzman, Sol; Draper, Jolene M; Wallace, Andrew; Cazarez, Oscar; Burns, Suzanne C; Qiao, Mei; Hinck, Lindsay; Smith, Andrew D; Toloue, Masoud M; Blencowe, Benjamin J; Penalva, Luiz O F; Sanford, Jeremy R

2016-05-31

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy, but its role(s) in pathogenesis remains enigmatic. We interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches, we have identified 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation, and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and microRNA (miRNA) binding sites. IGF2BP3 promotes association of the RNA-induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Statistical evidence of strain induced breaking of metallic point contacts

NASA Astrophysics Data System (ADS)

Alwan, Monzer; Candoni, Nadine; Dumas, Philippe; Klein, Hubert R.

2013-06-01

A scanning tunneling microscopy in break junction regime and a mechanically controllable break junction are used to acquire thousands of conductance-elongation curves by stretching until breaking and re-connecting Au junctions. From a robust statistical analysis performed on large sets of experiments, parameters such as lifetime, elongation and occurrence probabilities are extracted. The analysis of results obtained for different stretching speeds of the electrodes indicates that the breaking mechanism of di- and mono-atomic junction is identical, and that the junctions undergo atomic rearrangement during their stretching and at the moment of breaking.

Adenosine receptors regulate gap junction coupling of the human cerebral microvascular endothelial cells hCMEC/D3 by Ca2+ influx through cyclic nucleotide‐gated channels

PubMed Central

Bader, Almke; Bintig, Willem; Begandt, Daniela; Klett, Anne; Siller, Ina G.; Gregor, Carola; Schaarschmidt, Frank; Weksler, Babette; Romero, Ignacio; Couraud, Pierre‐Olivier; Hell, Stefan W.

2017-01-01

Key points Gap junction channels are essential for the formation and regulation of physiological units in tissues by allowing the lateral cell‐to‐cell diffusion of ions, metabolites and second messengers.Stimulation of the adenosine receptor subtype A2B increases the gap junction coupling in the human blood–brain barrier endothelial cell line hCMEC/D3.Although the increased gap junction coupling is cAMP‐dependent, neither the protein kinase A nor the exchange protein directly activated by cAMP were involved in this increase.We found that cAMP activates cyclic nucleotide‐gated (CNG) channels and thereby induces a Ca2+ influx, which leads to the increase in gap junction coupling.The report identifies CNG channels as a possible physiological link between adenosine receptors and the regulation of gap junction channels in endothelial cells of the blood–brain barrier. Abstract The human cerebral microvascular endothelial cell line hCMEC/D3 was used to characterize the physiological link between adenosine receptors and the gap junction coupling in endothelial cells of the blood–brain barrier. Expressed adenosine receptor subtypes and connexin (Cx) isoforms were identified by RT‐PCR. Scrape loading/dye transfer was used to evaluate the impact of the A2A and A2B adenosine receptor subtype agonist 2‐phenylaminoadenosine (2‐PAA) on the gap junction coupling. We found that 2‐PAA stimulated cAMP synthesis and enhanced gap junction coupling in a concentration‐dependent manner. This enhancement was accompanied by an increase in gap junction plaques formed by Cx43. Inhibition of protein kinase A did not affect the 2‐PAA‐related enhancement of gap junction coupling. In contrast, the cyclic nucleotide‐gated (CNG) channel inhibitor l‐cis‐diltiazem, as well as the chelation of intracellular Ca2+ with BAPTA, or the absence of external Ca2+, suppressed the 2‐PAA‐related enhancement of gap junction coupling. Moreover, we observed a 2‐PAA‐dependent activation of CNG channels by a combination of electrophysiology and pharmacology. In conclusion, the stimulation of adenosine receptors in hCMEC/D3 cells induces a Ca2+ influx by opening CNG channels in a cAMP‐dependent manner. Ca2+ in turn induces the formation of new gap junction plaques and a consecutive sustained enhancement of gap junction coupling. The report identifies CNG channels as a physiological link that integrates gap junction coupling into the adenosine receptor‐dependent signalling of endothelial cells of the blood–brain barrier. PMID:28075020

Adenosine receptors regulate gap junction coupling of the human cerebral microvascular endothelial cells hCMEC/D3 by Ca2+ influx through cyclic nucleotide-gated channels.

PubMed

Bader, Almke; Bintig, Willem; Begandt, Daniela; Klett, Anne; Siller, Ina G; Gregor, Carola; Schaarschmidt, Frank; Weksler, Babette; Romero, Ignacio; Couraud, Pierre-Olivier; Hell, Stefan W; Ngezahayo, Anaclet

2017-04-15

Gap junction channels are essential for the formation and regulation of physiological units in tissues by allowing the lateral cell-to-cell diffusion of ions, metabolites and second messengers. Stimulation of the adenosine receptor subtype A 2B increases the gap junction coupling in the human blood-brain barrier endothelial cell line hCMEC/D3. Although the increased gap junction coupling is cAMP-dependent, neither the protein kinase A nor the exchange protein directly activated by cAMP were involved in this increase. We found that cAMP activates cyclic nucleotide-gated (CNG) channels and thereby induces a Ca 2+ influx, which leads to the increase in gap junction coupling. The report identifies CNG channels as a possible physiological link between adenosine receptors and the regulation of gap junction channels in endothelial cells of the blood-brain barrier. The human cerebral microvascular endothelial cell line hCMEC/D3 was used to characterize the physiological link between adenosine receptors and the gap junction coupling in endothelial cells of the blood-brain barrier. Expressed adenosine receptor subtypes and connexin (Cx) isoforms were identified by RT-PCR. Scrape loading/dye transfer was used to evaluate the impact of the A 2A and A 2B adenosine receptor subtype agonist 2-phenylaminoadenosine (2-PAA) on the gap junction coupling. We found that 2-PAA stimulated cAMP synthesis and enhanced gap junction coupling in a concentration-dependent manner. This enhancement was accompanied by an increase in gap junction plaques formed by Cx43. Inhibition of protein kinase A did not affect the 2-PAA-related enhancement of gap junction coupling. In contrast, the cyclic nucleotide-gated (CNG) channel inhibitor l-cis-diltiazem, as well as the chelation of intracellular Ca 2+ with BAPTA, or the absence of external Ca 2+ , suppressed the 2-PAA-related enhancement of gap junction coupling. Moreover, we observed a 2-PAA-dependent activation of CNG channels by a combination of electrophysiology and pharmacology. In conclusion, the stimulation of adenosine receptors in hCMEC/D3 cells induces a Ca 2+ influx by opening CNG channels in a cAMP-dependent manner. Ca 2+ in turn induces the formation of new gap junction plaques and a consecutive sustained enhancement of gap junction coupling. The report identifies CNG channels as a physiological link that integrates gap junction coupling into the adenosine receptor-dependent signalling of endothelial cells of the blood-brain barrier. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Pharmaceutical Activation or Genetic Absence of ClC-2 Alters Tight Junctions During Experimental Colitis.

PubMed

Jin, Younggeon; Pridgen, Tiffany A; Blikslager, Anthony T

2015-12-01

We have previously reported that the ClC-2 chloride channel has an important role in regulation of tight junction barrier function during experimental colitis, and the pharmaceutical ClC-2 activator lubiprostone initiates intestinal barrier repair in ischemic-injured intestine. Thus, we hypothesized that pharmaceutical ClC-2 activation would have a protective and therapeutic effect in murine models of colitis, which would be absent in ClC-2 mice. We administered lubiprostone to wild-type or ClC-2 mice with dextran sulfate sodium (DSS) or 2, 4, 5-trinitrobenzene sulfonic acid-induced colitis. We determined the severity of colitis and assessed intestinal permeability. Selected tight junction proteins were analyzed by Western blotting and immunofluorescence/confocal microscopy, whereas proliferative and differentiated cells were examined with special staining and immunohistochemistry. Oral preventive or therapeutic administration of lubiprostone significantly reduced the severity of colitis and reduced intestinal permeability in both DSS and trinitrobenzene sulfonic acid-induced colitis. Preventive treatment with lubiprostone induced significant recovery of the expression and distribution of selected sealing tight junction proteins in mice with DSS-induced colitis. In addition, lubiprostone reduced crypt proliferation and increased the number of differentiated epithelial cells. Alternatively, when lubiprostone was administered to ClC-2 mice, the protective effect against DSS colitis was limited. This study suggests a central role for ClC-2 in restoration of barrier function and tight junction architecture in experimental murine colitis, which can be therapeutically targeted with lubiprostone.

Epithelial-mesenchymal transition abolishes the susceptibility of polarized epithelial cell lines to measles virus.

PubMed

Shirogane, Yuta; Takeda, Makoto; Tahara, Maino; Ikegame, Satoshi; Nakamura, Takanori; Yanagi, Yusuke

2010-07-02

Measles virus (MV), an enveloped negative-strand RNA virus, remains a major cause of morbidity and mortality in developing countries. MV predominantly infects immune cells by using signaling lymphocyte activation molecule (SLAM; also called CD150) as a receptor, but it also infects polarized epithelial cells, forming tight junctions in a SLAM-independent manner. Although the ability of MV to infect polarized epithelial cells is thought to be important for its transmission, the epithelial cell receptor for MV has not been identified. A transcriptional repressor, Snail, induces epithelial-mesenchymal transition (EMT), in which epithelial cells lose epithelial cell phenotypes, such as adherens and tight junctions. In this study, EMT was induced by expressing Snail in a lung adenocarcinoma cell line, II-18, which is highly susceptible to wild-type MV. Snail-expressing II-18 cells lost adherens and tight junctions. Microarray analysis confirmed the induction of EMT in II-18 cells and suggested a novel function of Snail in protein degradation and distribution. Importantly, wild-type MV no longer entered EMT-induced II-18 cells, suggesting that the epithelial cell receptor is down-regulated by the induction of EMT. Other polarized cell lines, NCI-H358 and HT-29, also lost susceptibility to wild-type MV when EMT was induced. However, the complete formation of tight junctions rather reduced MV entry into HT-29 cells. Taken together, these data suggest that the unidentified epithelial cell receptor for MV is involved in the formation of epithelial intercellular junctions.

Experimental Evidence for Quantum Interference and Vibrationally Induced Decoherence in Single-Molecule Junctions

NASA Astrophysics Data System (ADS)

Ballmann, Stefan; Härtle, Rainer; Coto, Pedro B.; Elbing, Mark; Mayor, Marcel; Bryce, Martin R.; Thoss, Michael; Weber, Heiko B.

2012-08-01

We analyze quantum interference and decoherence effects in single-molecule junctions both experimentally and theoretically by means of the mechanically controlled break junction technique and density-functional theory. We consider the case where interference is provided by overlapping quasidegenerate states. Decoherence mechanisms arising from electronic-vibrational coupling strongly affect the electrical current flowing through a single-molecule contact and can be controlled by temperature variation. Our findings underline the universal relevance of vibrations for understanding charge transport through molecular junctions.

Experimental evidence for quantum interference and vibrationally induced decoherence in single-molecule junctions.

PubMed

Ballmann, Stefan; Härtle, Rainer; Coto, Pedro B; Elbing, Mark; Mayor, Marcel; Bryce, Martin R; Thoss, Michael; Weber, Heiko B

2012-08-03

We analyze quantum interference and decoherence effects in single-molecule junctions both experimentally and theoretically by means of the mechanically controlled break junction technique and density-functional theory. We consider the case where interference is provided by overlapping quasidegenerate states. Decoherence mechanisms arising from electronic-vibrational coupling strongly affect the electrical current flowing through a single-molecule contact and can be controlled by temperature variation. Our findings underline the universal relevance of vibrations for understanding charge transport through molecular junctions.

Gap-junction blocker carbenoxolone differentially enhances NMDA-induced cell death in hippocampal neurons and astrocytes in co-culture.

PubMed

Zündorf, Gregor; Kahlert, Stefan; Reiser, Georg

2007-07-01

The beneficial or detrimental role of gap junction communication in the pathophysiology of brain injury is still controversial. We used co-cultures of hippocampal astrocytes and neurons, where we identified homocellular astrocyte-astrocyte and heterocellular astrocyte-neuron coupling by fluorescence recovery after photobleaching, which was decreased by the gap junction blocker carbenoxolone (CBX). In these cultures, we determined the cell type-specific effects of CBX on the excitotoxic damage caused by N-methyl-D-aspartate (NMDA). We determined in both astrocytes and neurons the influence of CBX, alone or together with NMDA challenge, on cytotoxicity using propidium iodide labeling. CBX alone was not cytotoxic, but CBX treatment differentially accelerated the NMDA-induced cell death in both astrocytes and neurons. In addition, we measured mitochondrial potential using rhodamine 123, membrane potential using the oxonol dye bis(1,3-diethylthiobarbituric acid)trimethine oxonol, cytosolic Ca(2+) level using fura-2, and formation of reactive oxygen species (ROS) using dihydroethidium. CBX alone induced neither an intracellular Ca(2+) rise nor a membrane depolarization. However, CBX elicited a mitochondrial depolarization in both astrocytes and neurons and increased the ROS formation in neurons. In contrast, NMDA caused a membrane depolarization in neurons, coinciding with intracellular Ca(2+) rise, but neither mitochondrial depolarization nor ROS production seem to be involved in NMDA-mediated cytotoxicity. Pre-treatment with CBX accelerated the NMDA-induced membrane depolarization and prevented the repolarization of neurons after the NMDA challenge. We hypothesize that these effects are possibly mediated via blockage of gap junctions, and might be involved in the mechanism of CBX-induced acceleration of excitotoxic cell death, whereas the CBX-induced mitochondrial depolarization and ROS formation are not responsible for the increase in cytotoxicity. We conclude that both in astrocytes and neurons gap junctions provide protection against NMDA-induced cytotoxicity.

Protein kinase C isoforms at the neuromuscular junction: localization and specific roles in neurotransmission and development.

PubMed

Lanuza, Maria A; Santafe, Manel M; Garcia, Neus; Besalduch, Núria; Tomàs, Marta; Obis, Teresa; Priego, Mercedes; Nelson, Phillip G; Tomàs, Josep

2014-01-01

The protein kinase C family (PKC) regulates a variety of neural functions including neurotransmitter release. The selective activation of a wide range of PKC isoforms in different cells and domains is likely to contribute to the functional diversity of PKC phosphorylating activity. In this review, we describe the isoform localization, phosphorylation function, regulation and signalling of the PKC family at the neuromuscular junction. Data show the involvement of the PKC family in several important functions at the neuromuscular junction and in particular in the maturation of the synapse and the modulation of neurotransmission in the adult. © 2013 Anatomical Society.

Polarity Proteins as Regulators of Cell Junction Complexes: Implications for Breast Cancer

PubMed Central

Bazzoun, Dana; Lelièvre, Sophie; Talhouk, Rabih

2013-01-01

The epithelium of multicellular organisms possesses a well-defined architecture, referred to as polarity that coordinates the regulation of essential cell features. Polarity proteins are intimately linked to the protein complexes that make the tight, adherens and gap junctions; they contribute to the proper localization and assembly of these cell-cell junctions within cells and consequently to functional tissue organization. The establishment of cell-cell junctions and polarity are both implicated in the regulation of epithelial modifications in normal and cancer situations. Uncovering the mechanisms through which cell-cell junctions and epithelial polarization are established and how their interaction with the microenvironment direct cell and tissue organization has opened new venues for the development of cancer therapies. In this review, we focus on the breast epithelium to highlight how polarity and cell-cell junction proteins interact together in normal and cancerous contexts to regulate major cellular mechanisms such as migration. The impact of these proteins on epigenetic mechanisms responsible for resetting cells towards oncogenesis is discussed in light of increasing evidence that tissue polarity modulates chromatin function. Finally, we give an overview of recent breast cancer therapies that target proteins involved in cell-cell junctions. PMID:23458609

Spatio-temporal regulation of connexin43 phosphorylation and gap junction dynamics.

PubMed

Solan, Joell L; Lampe, Paul D

2018-01-01

Gap junctions are specialized membrane domains containing tens to thousands of intercellular channels. These channels permit exchange of small molecules (<1000Da) including ions, amino acids, nucleotides, metabolites and secondary messengers (e.g., calcium, glucose, cAMP, cGMP, IP 3 ) between cells. The common reductionist view of these structures is that they are composed entirely of integral membrane proteins encoded by the 21 member connexin human gene family. However, it is clear that the normal physiological function of this structure requires interaction and regulation by a variety of proteins, especially kinases. Phosphorylation is capable of directly modulating connexin channel function but the most dramatic effects on gap junction activity occur via the organization of the gap junction structures themselves. This is a direct result of the short half-life of the primary gap junction protein, connexin, which requires them to be constantly assembled, remodeled and turned over. The biological consequences of this remodeling are well illustrated during cardiac ischemia, a process wherein gap junctions are disassembled and remodeled resulting in arrhythmia and ultimately heart failure. 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.

Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.

PubMed

Miyata, Ryo; Nomura, Kazuaki; Kakuki, Takuya; Takano, Ken-Ichi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi

2015-04-01

The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.

Gate-controlled current and inelastic electron tunneling spectrum of benzene: a self-consistent study.

PubMed

Liang, Y Y; Chen, H; Mizuseki, H; Kawazoe, Y

2011-04-14

We use density functional theory based nonequilibrium Green's function to self-consistently study the current through the 1,4-benzenedithiol (BDT). The elastic and inelastic tunneling properties through this Au-BDT-Au molecular junction are simulated, respectively. For the elastic tunneling case, it is found that the current through the tilted molecule can be modulated effectively by the external gate field, which is perpendicular to the phenyl ring. The gate voltage amplification comes from the modulation of the interaction between the electrodes and the molecules in the junctions. For the inelastic case, the electron tunneling scattered by the molecular vibrational modes is considered within the self-consistent Born approximation scheme, and the inelastic electron tunneling spectrum is calculated.

Triptycene: A Nucleic Acid Three-Way Junction Binder Scaffold

NASA Astrophysics Data System (ADS)

Yoon, Ina

Nucleic acids play a critical role in many biological processes such as gene regulation and replication. The development of small molecules that modulate nucleic acids with sequence or structure specificity would provide new strategies for regulating disease states at the nucleic acid level. However, this remains challenging mainly because of the nonspecific interactions between nucleic acids and small molecules. Three-way junctions are critical structural elements of nucleic acids. They are present in many important targets such as trinucleotide repeat junctions related to Huntington's disease, a temperature sensor sigma32 in E. coli, Dengue virus, and HIV. Triptycene-derived small molecules have been shown to bind to nucleic acid three-way junctions, resulting from their shape complementary. To develop a better understanding of designing molecules for targeting different junctions, a rapid screening of triptycene-based small molecules is needed. We envisioned that the installation of a linker at C9 position of the bicyclic core would allow for a rapid solid phase diversification. To achieve this aim, we synthesized 9-substituted triptycene scaffolds by using two different synthetic routes. The first synthetic route installed the linker from the amidation reaction between carboxylic acid at C9 position of the triptycene and an amine linker, beta-alanine ethyl ester. This new 9-substituted triptycene scaffold was then attached to a 2-chlorotrityl chloride resin for solid-phase diversification. This enabled a rapid diversification and an easy purification of mono-, di-, and tri-peptide triptycene derivatives. The binding affinities of these compounds were investigated towards a (CAG)˙(CTG) trinucleotide repeat junction. In the modified second synthetic route, we utilized a combined Heck coupling/benzyne Diels-Alder strategy. This improved synthetic strategy reduced the number of steps and total reaction times, increased the overall yield, improved solubilities of intermediates, and provided a new regioisomer that was not observed in the previous synthesis. Through this investigation, we discovered new high-affinity lead compounds towards a d(CAG)·(CTG) trinucleotide repeat junction. In addition, we turned our attention to sigma 32 mRNA, which contains a RNA three-way junction in E. coli. We demonstrated that triptycene-based small molecules can modulate the heat shock response in E. coli..

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

PubMed Central

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

2016-01-01

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. PMID:27436542

Gate-dependent asymmetric transport characteristics in pentacene barristors with graphene electrodes.

PubMed

Hwang, Wang-Taek; Min, Misook; Jeong, Hyunhak; Kim, Dongku; Jang, Jingon; Yoo, Daekyung; Jang, Yeonsik; Kim, Jun-Woo; Yoon, Jiyoung; Chung, Seungjun; Yi, Gyu-Chul; Lee, Hyoyoung; Wang, Gunuk; Lee, Takhee

2016-11-25

We investigated the electrical characteristics and the charge transport mechanism of pentacene vertical hetero-structures with graphene electrodes. The devices are composed of vertical stacks of silicon, silicon dioxide, graphene, pentacene, and gold. These vertical heterojunctions exhibited distinct transport characteristics depending on the applied bias direction, which originates from different electrode contacts (graphene and gold contacts) to the pentacene layer. These asymmetric contacts cause a current rectification and current modulation induced by the gate field-dependent bias direction. We observed a change in the charge injection barrier during variable-temperature current-voltage characterization, and we also observed that two distinct charge transport channels (thermionic emission and Poole-Frenkel effect) worked in the junctions, which was dependent on the bias magnitude.

Molecular wires acting as quantum heat ratchets.

PubMed

Zhan, Fei; Li, Nianbei; Kohler, Sigmund; Hänggi, Peter

2009-12-01

We explore heat transfer in molecular junctions between two leads in the absence of a finite net thermal bias. The application of an unbiased time-periodic temperature modulation of the leads entails a dynamical breaking of reflection symmetry, such that a directed heat current may emerge (ratchet effect). In particular, we consider two cases of adiabatically slow driving, namely, (i) periodic temperature modulation of only one lead and (ii) temperature modulation of both leads with an ac driving that contains a second harmonic, thus, generating harmonic mixing. Both scenarios yield sizable directed heat currents, which should be detectable with present techniques. Adding a static thermal bias allows one to compute the heat current-thermal load characteristics, which includes the ratchet effect of negative thermal bias with positive-valued heat flow against the thermal bias, up to the thermal stop load. The ratchet heat flow in turn generates also an electric current. An applied electric stop voltage, yielding effective zero electric current flow, then mimics a solely heat-ratchet-induced thermopower ("ratchet Seebeck effect"), although no net thermal bias is acting. Moreover, we find that the relative phase between the two harmonics in scenario (ii) enables steering the net heat current into a direction of choice.

pH during non-synaptic epileptiform activity-computational simulations.

PubMed

Rodrigues, Antônio Márcio; Santos, Luiz Eduardo Canton; Covolan, Luciene; Hamani, Clement; de Almeida, Antônio-Carlos Guimarães

2015-09-02

The excitability of neuronal networks is strongly modulated by changes in pH. The origin of these changes, however, is still under debate. The high complexity of neural systems justifies the use of computational simulation to investigate mechanisms that are possibly involved. Simulated neuronal activity includes non-synaptic epileptiform events (NEA) induced in hippocampal slices perfused with high-K(+) and zero-Ca(2+), therefore in the absence of the synaptic circuitry. A network of functional units composes the NEA model. Each functional unit represents one interface of neuronal/extracellular space/glial segments. Each interface contains transmembrane ionic transports, such as ionic channels, cotransporters, exchangers and pumps. Neuronal interconnections are mediated by gap-junctions, electric field effects and extracellular ionic fluctuations modulated by extracellular electrodiffusion. Mechanisms investigated are those that change intracellular and extracellular ionic concentrations and are able to affect [H(+)]. Our simulations suggest that the intense fluctuations in intra and extracellular concentrations of Na(+), K(+) and Cl(-) that accompany NEA are able to affect the combined action of the Na(+)/H(+) exchanger (NHE), [HCO(-)(3)]/Cl(-) exchanger (HCE), H(+) pump and the catalytic activity of intra and extracellular carbonic anhydrase. Cellular volume changes and extracellular electrodiffusion are responsible for modulating pH.

Power degradation and reliability study of high-power laser bars at quasi-CW operation

NASA Astrophysics Data System (ADS)

Zhang, Haoyu; Fan, Yong; Liu, Hui; Wang, Jingwei; Zah, Chungen; Liu, Xingsheng

2017-02-01

The solid state laser relies on the laser diode (LD) pumping array. Typically for high peak power quasi-CW (QCW) operation, both energy output per pulse and long term reliability are critical. With the improved bonding technique, specially Indium-free bonded diode laser bars, most of the device failures were caused by failure within laser diode itself (wearout failure), which are induced from dark line defect (DLD), bulk failure, point defect generation, facet mirror damage and etc. Measuring the reliability of LD under QCW condition will take a rather long time. Alternatively, an accelerating model could be a quicker way to estimate the LD life time under QCW operation. In this report, diode laser bars were mounted on micro channel cooler (MCC) and operated under QCW condition with different current densities and junction temperature (Tj ). The junction temperature is varied by modulating pulse width and repetition frequency. The major concern here is the power degradation due to the facet failure. Reliability models of QCW and its corresponding failures are studied. In conclusion, QCW accelerated life-time model is discussed, with a few variable parameters. The model is compared with CW model to find their relationship.

Role of CoFeB thickness in electric field controlled sub-100 nm sized magnetic tunnel junctions

NASA Astrophysics Data System (ADS)

Lourembam, James; Huang, Jiancheng; Lim, Sze Ter; Gerard, Ernult Franck

2018-05-01

We report a comprehensive study on the role of the free layer thickness (tF) in electric-field controlled nanoscale perpendicular magnetic tunnel junctions (MTJs), comprising of free layer structure Ta/Co40Fe40B20/MgO, by using dc magnetoresistance and ultra-short magnetization switching measurements. Focusing on MTJs that exhibits positive effective device anisotropy (Keff), we observe that both the voltage-controlled magnetic anisotropy (ξ) and voltage modulation of coercivity show strong dependence on tF. We found that ξ varies dramatically and unexpectedly from ˜-3 fJ/V-m to ˜-41 fJ/V-m with increasing tF. We discuss the possibilities of electric-field tuning of the effective surface anisotropy term, KS as well as an additional interfacial magnetoelastic anisotropy term, K3 that scales with 1 /tF2. Voltage pulse induced 180° magnetization reversal is also demonstrated in our MTJs. Unipolar switching and oscillatory function of switching probability vs. pulse duration can be observed at higher tF, and agrees well with the two key device parameters — Keff and ξ.

How to probe transverse magnetic anisotropy of a single-molecule magnet by electronic transport?

NASA Astrophysics Data System (ADS)

Misiorny, M.; Burzuri, E.; Gaudenzi, R.; Park, K.; Leijnse, M.; Wegewijs, M.; Paaske, J.; Cornia, A.; van der Zant, H.

We propose an approach for in-situ determination of the transverse magnetic anisotropy (TMA) of an individual molecule by electronic transport measurements, see Phys. Rev. B 91, 035442 (2015). We study a Fe4 single-molecule magnet (SMM) captured in a gateable junction, a unique tool for addressing the spin in different redox states of a molecule. We show that, due to mixing of the spin eigenstates of the SMM, the TMA significantly manifests itself in transport. We predict and experimentally observe the pronounced intensity modulation of the Coulomb peak amplitude with the magnetic field in the linear-response transport regime, from which the TMA parameter E can be estimated. Importantly, the method proposed here does not rely on the small induced tunnelling effects and, hence, works well at temperatures and electron tunnel broadenings by far exceeding the tunnel splittings and even E itself. We deduce that the TMA for a single Fe4 molecule captured in a junction is substantially larger than the bulk value. Work supported by the Polish Ministry of Science and Education as `Iuventus Plus' project (IP2014 030973) in years 2015-2016.

EMMPRIN Modulates Epithelial Barrier Function through a MMP–Mediated Occludin Cleavage

PubMed Central

Huet, Eric; Vallée, Benoit; Delbé, Jean; Mourah, Samia; Prulière-Escabasse, Virginie; Tremouilleres, Magali; Kadomatsu, Kenji; Doan, Serge; Baudouin, Christophe; Menashi, Suzanne; Gabison, Eric E.

2011-01-01

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. PMID:21777561

What can Andreev bound states tell us about superconductors?

PubMed

Millo, Oded; Koren, Gad

2018-08-06

Zero-energy Andreev bound states, which manifest themselves in the tunnelling spectra as zero-bias conductance peaks (ZBCPs), are abundant at interfaces between superconductors and other materials and on the nodal surface of high-temperature superconductors. In this review, we focus on the information such excitations can provide on the properties of superconductor systems. First, a general introduction to the physics of Andreev bound states in superconductor/normal metal interfaces is given with a particular emphasis on why they appear at zero energy in d -wave superconductors. Then, specific spectroscopic tunnelling studies of thin films, bilayers and junctions are described, focusing on the corresponding ZBCP features. Scanning tunnelling spectroscopy (STS) studies show that the ZBCPs on the c -axis YBa 2 Cu 3 O 7- δ (YBCO) films are correlated with the surface morphology and appear only in proximity to (110) facets. STS on c -axis La 1.88 Sr 0.12 CuO 4 (LSCO) films exhibiting the 1/8 anomaly shows spatially modulated peaks near zero bias associated with the anti-phase ordering of the d -wave order parameter predicted at this doping level. ZBCPs were also found in micrometre-size edge junctions of YBCO/SrRuO 3 /YBCO, where SrRuO 3 is ferromagnetic. Here, the results are consistent with a crossed Andreev reflection effect (CARE) at the narrow domain walls of the SrRuO 3 ZBCPs measured in STS studies of manganite/cuprate bilayers could not be attributed to CARE because the manganite's domain wall is much larger than the coherence length in YBCO, and instead are attributed to proximity-induced triplet-pairing superconductivity with non-conventional symmetry. And finally, ZBCPs found in junctions of non-intentionally doped topological insulator films of Bi 2 Se 3 and the s -wave superconductor NbN are attributed to proximity-induced p x  + ip y triplet order parameter in the topological material.This article is part of the theme issue 'Andreev bound states'. © 2018 The Author(s).

Electro-refractive photonic device

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

Zortman, William A.; Watts, Michael R.

2015-06-09

The various technologies presented herein relate to phase shifting light to facilitate any of light switching, modulation, amplification, etc. Structures are presented where a second layer is juxtaposed between a first layer and a third layer with respective doping facilitating formation of p-n junctions at the interface between the first layer and the second layer, and between the second layer and the third layer. Application of a bias causes a carrier concentration change to occur at the p-n junctions which causes a shift in the effective refractive index per incremental change in an applied bias voltage. The effective refractive indexmore » enhancement can occur in both reverse bias and forward bias. The structure can be incorporated into a waveguide, an optical resonator, a vertical junction device, a horizontal junction device, a Mach-Zehnder interferometer, a tuneable optical filter, etc.« less

Electrical isolation of component cells in monolithically interconnected modules

DOEpatents

Wanlass, Mark W.

2001-01-01

A monolithically interconnected photovoltaic module having cells which are electrically connected which comprises a substrate, a plurality of cells formed over the substrate, each cell including a primary absorber layer having a light receiving surface and a p-region, formed with a p-type dopant, and an n-region formed with an n-type dopant adjacent the p-region to form a single pn-junction, and a cell isolation diode layer having a p-region, formed with a p-type dopant, and an n-region formed with an n-type dopant adjacent the p-region to form a single pn-junction, the diode layer intervening the substrate and the absorber layer wherein the absorber and diode interfacial regions of a same conductivity type orientation, the diode layer having a reverse-breakdown voltage sufficient to prevent inter-cell shunting, and each cell electrically isolated from adjacent cells with a vertical trench trough the pn-junction of the diode layer, interconnects disposed in the trenches contacting the absorber regions of adjacent cells which are doped an opposite conductivity type, and electrical contacts.

Mode of action of claudin peptidomimetics in the transient opening of cellular tight junction barriers.

PubMed

Staat, Christian; Coisne, Caroline; Dabrowski, Sebastian; Stamatovic, Svetlana M; Andjelkovic, Anuska V; Wolburg, Hartwig; Engelhardt, Britta; Blasig, Ingolf E

2015-06-01

In epithelial/endothelial barriers, claudins form tight junctions, seal the paracellular cleft, and limit the uptake of solutes and drugs. The peptidomimetic C1C2 from the C-terminal half of claudin-1's first extracellular loop increases drug delivery through epithelial claudin-1 barriers. However, its molecular and structural mode of action remains unknown. In the present study, >100 μM C1C2 caused paracellular opening of various barriers with different claudin compositions, ranging from epithelial to endothelial cells, preferentially modulating claudin-1 and claudin-5. After 6 h incubation, C1C2 reversibly increased the permeability to molecules of different sizes; this was accompanied by redistribution of claudins and occludin from junctions to cytosol. Internalization of C1C2 in epithelial cells depended on claudin-1 expression and clathrin pathway, whereby most C1C2 was retained in recyclosomes >2 h. In freeze-fracture electron microscopy, C1C2 changed claudin-1 tight junction strands to a more parallel arrangement and claudin-5 strands from E-face to P-face association - drastic and novel effects. In conclusion, C1C2 is largely recycled in the presence of a claudin, which explains the delayed onset of barrier and junction loss, the high peptide concentration required and the long-lasting effect. Epithelial/endothelial barriers are specifically modulated via claudin-1/claudin-5, which can be targeted to improve drug delivery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Four-state non-volatile memory in a multiferroic spin filter tunnel junction

NASA Astrophysics Data System (ADS)

Ruan, Jieji; Li, Chen; Yuan, Zhoushen; Wang, Peng; Li, Aidong; Wu, Di

2016-12-01

We report a spin filter type multiferroic tunnel junction with a ferromagnetic/ferroelectric bilayer barrier. Memory functions of a spin filter magnetic tunnel junction and a ferroelectric tunnel junction are combined in this single device, producing four non-volatile resistive states that can be read out in a non-destructive manner. This concept is demonstrated in a LaNiO3/Pr0.8Ca0.2MnO3/BaTiO3/La0.7Sr0.3MnO3 all-oxide tunnel junction. The ferromagnetic insulator Pr0.8Ca0.2MnO3 serves as the spin filter and the ferromagnetic metal La0.7Sr0.3MnO3 is the spin analyzer. The ferroelectric polarization reversal in the BaTiO3 barrier switches the tunneling barrier height to produce a tunneling electroresistance. The ferroelectric switching also modulates the spin polarization and the spin filtering efficiency in Pr0.8Ca0.2MnO3.

Cyclooxygenase-2 Deficiency Leads to Intestinal Barrier Dysfunction and Increased Mortality During Polymicrobial Sepsis 1

PubMed Central

Fredenburgh, Laura E.; Velandia, Margarita M. Suarez; Ma, Jun; Olszak, Torsten; Cernadas, Manuela; Englert, Joshua A.; Chung, Su Wol; Liu, Xiaoli; Begay, Cynthia; Padera, Robert F.; Blumberg, Richard S.; Walsh, Stephen R.; Baron, Rebecca M.; Perrella, Mark A.

2011-01-01

Sepsis remains the leading cause of death in critically ill patients despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase-2 (COX-2) is highly upregulated in the intestine during sepsis and we hypothesized that it may be critical in the maintenance of intestinal epithelial barrier function during peritonitis-induced polymicrobial sepsis. COX-2−/− and COX-2+/+ BALB/c mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398, PGD2, or vehicle and stimulated with cytokines. COX-2−/− mice developed exaggerated bacteremia and increased mortality compared with COX-2+/+ mice following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia following CLP. Absence of COX-2 significantly increased epithelial permeability of the ileum and reduced expression of the tight junction proteins zonula occludens-1 (ZO-1), occludin, and claudin-1 in the ileum following CLP. Furthermore, PGD2 attenuated cytokine-induced hyperpermeability and ZO-1 downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence of COX-2 is associated with enhanced intestinal epithelial permeability and leads to exaggerated bacterial translocation and increased mortality during peritonitis-induced sepsis. Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis. PMID:21967897

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells

PubMed Central

Babica, Pavel; Zurabian, Rimma; Kumar, Esha R.; Chopra, Rajus; Mianecki, Maxwell J.; Park, Joon-Suk; Jaša, Libor; Trosko, James E.; Upham, Brad L.

2016-01-01

Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors. PMID:27413106

EEG slow-wave coherence changes in propofol-induced general anesthesia: experiment and theory

PubMed Central

Wang, Kaier; Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Wilson, Marcus T.; Sleigh, Jamie W.

2014-01-01

The electroencephalogram (EEG) patterns recorded during general anesthetic-induced coma are closely similar to those seen during slow-wave sleep, the deepest stage of natural sleep; both states show patterns dominated by large amplitude slow waves. Slow oscillations are believed to be important for memory consolidation during natural sleep. Tracking the emergence of slow-wave oscillations during transition to unconsciousness may help us to identify drug-induced alterations of the underlying brain state, and provide insight into the mechanisms of general anesthesia. Although cellular-based mechanisms have been proposed, the origin of the slow oscillation has not yet been unambiguously established. A recent theoretical study by Steyn-Ross et al. (2013) proposes that the slow oscillation is a network, rather than cellular phenomenon. Modeling anesthesia as a moderate reduction in gap-junction interneuronal coupling, they predict an unconscious state signposted by emergent low-frequency oscillations with chaotic dynamics in space and time. They suggest that anesthetic slow-waves arise from a competitive interaction between symmetry-breaking instabilities in space (Turing) and time (Hopf), modulated by gap-junction coupling strength. A significant prediction of their model is that EEG phase coherence will decrease as the cortex transits from Turing–Hopf balance (wake) to Hopf-dominated chaotic slow-waves (unconsciousness). Here, we investigate changes in phase coherence during induction of general anesthesia. After examining 128-channel EEG traces recorded from five volunteers undergoing propofol anesthesia, we report a significant drop in sub-delta band (0.05–1.5 Hz) slow-wave coherence between frontal, occipital, and frontal–occipital electrode pairs, with the most pronounced wake-vs.-unconscious coherence changes occurring at the frontal cortex. PMID:25400558

HGF Gene Modification in Mesenchymal Stem Cells Reduces Radiation-Induced Intestinal Injury by Modulating Immunity.

PubMed

Wang, Hua; Sun, Rui-Ting; Li, Yang; Yang, Yue-Feng; Xiao, Feng-Jun; Zhang, Yi-Kun; Wang, Shao-Xia; Sun, Hui-Yan; Zhang, Qun-Wei; Wu, Chu-Tse; Wang, Li-Sheng

2015-01-01

Effective therapeutic strategies to address intestinal complications after radiation exposure are currently lacking. Mesenchymal stem cells (MSCs), which display the ability to repair the injured intestine, have been considered as delivery vehicles for repair genes. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF)-gene-modified MSCs on radiation-induced intestinal injury (RIII). Female 6- to 8-week-old mice were radiated locally at the abdomen with a single 13-Gy dose of radiation and then treated with saline control, Ad-HGF or Ad-Null-modified MSCs therapy. The transient engraftment of human MSCs was detected via real-time PCR and immunostaining. The therapeutic effects of non- and HGF-modified MSCs were evaluated via FACS to determine the lymphocyte immunophenotypes; via ELISA to measure cytokine expression; via immunostaining to determine tight junction protein expression; via PCNA staining to examine intestinal epithelial cell proliferation; and via TUNEL staining to detect intestinal epithelial cell apoptosis. The histopathological recovery of the radiation-injured intestine was significantly enhanced following non- or HGF-modified MSCs treatment. Importantly, the radiation-induced immunophenotypic disorders of the mesenteric lymph nodes and Peyer's patches were attenuated in both MSCs-treated groups. Treatment with HGF-modified MSCs reduced the expression and secretion of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ), increased the expression of the anti-inflammatory cytokine IL-10 and the tight junction protein ZO-1, and promoted the proliferation and reduced the apoptosis of intestinal epithelial cells. Treatment of RIII with HGF-gene-modified MSCs reduces local inflammation and promotes the recovery of small intestinal histopathology in a mouse model. These findings might provide an effective therapeutic strategy for RIII.

Basic concepts for the design of high-efficiency single-junction and multibandgap solar cells

NASA Technical Reports Server (NTRS)

Fan, J. C. C.

1985-01-01

Concepts for obtaining practical solar-cell modules with one-sun efficiencies up to 30 percent at air mass 1 are now well understood. Such high-efficiency modules utilize multibandgap structures. To achieve module efficiencies significantly above 30 percent, it is necessary to employ different concepts such as spectral compression and broad-band detection. A detailed description of concepts for the design of high-efficiency multibandgap solar cells is given.

Bioelectrical coupling in multicellular domains regulated by gap junctions: A conceptual approach.

PubMed

Cervera, Javier; Pietak, Alexis; Levin, Michael; Mafe, Salvador

2018-04-21

We review the basic concepts involved in bioelectrically-coupled multicellular domains, focusing on the role of membrane potentials (V mem ). In the first model, single-cell V mem is modulated by two generic polarizing and depolarizing ion channels, while intercellular coupling is implemented via voltage-gated gap junctions. Biochemical and bioelectrical signals are integrated via a feedback loop between V mem and the transcription and translation of a protein forming an ion channel. The effective rate constants depend on the single-cell V mem because these potentials modulate the local concentrations of signaling molecules and ions. This electrochemically-based idealization of the complex biophysical problem suggests that the spatio-temporal map of single-cell potentials can influence downstream patterning processes by means of the voltage-gated gap junction interconnectivity, much as in the case of electronic devices where the control of electric potentials and currents allows the local modulation of the circuitry to achieve full functionality. An alternative theoretical approach, the BioElectrical Tissue Simulation Engine (BETSE), is also presented. The BETSE modeling environment utilizes finite volume techniques to simulate bioelectric states from the perspective of ion concentrations and fluxes. This model has been successfully applied to make predictions and explain experimental observations in a variety of embryonic, regenerative, and oncogenic contexts. Copyright © 2018 Elsevier B.V. All rights reserved.

A spot laser modulated resistance switching effect observed on n-type Mn-doped ZnO/SiO2/Si structure.

PubMed

Lu, Jing; Tu, Xinglong; Yin, Guilin; Wang, Hui; He, Dannong

2017-11-09

In this work, a spot laser modulated resistance switching (RS) effect is firstly observed on n-type Mn-doped ZnO/SiO 2 /Si structure by growing n-type Mn-doped ZnO film on Si wafer covered with a 1.2 nm native SiO 2 , which has a resistivity in the range of 50-80 Ω∙cm. The I-V curve obtained in dark condition evidences the structure a rectifying junction, which is further confirmed by placing external bias. Compared to the resistance state modulated by electric field only in dark (without illumination), the switching voltage driving the resistance state of the structure from one state to the other, shows clear shift under a spot laser illumination. Remarkably, the switching voltage shift shows a dual dependence on the illumination position and power of the spot laser. We ascribe this dual dependence to the electric filed produced by the redistribution of photo-generated carriers, which enhance the internal barrier of the hetero-junction. A complete theoretical analysis based on junction current and diffusion equation is presented. The dependence of the switching voltage on spot laser illumination makes the n-type Mn-doped ZnO/SiO 2 /Si structure sensitive to light, which thus allows for the integration of an extra functionality in the ZnO-based photoelectric device.

Poster - Thur Eve - 57: Craniospinal irradiation with jagged-junction IMRT approach without beam edge matching for field junctions.

PubMed

Cao, F; Ramaseshan, R; Corns, R; Harrop, S; Nuraney, N; Steiner, P; Aldridge, S; Liu, M; Carolan, H; Agranovich, A; Karva, A

2012-07-01

Craniospinal irradiation were traditionally treated the central nervous system using two or three adjacent field sets. A intensity-modulated radiotherapy (IMRT) plan (Jagged-Junction IMRT) which overcomes problems associated with field junctions and beam edge matching, improves planning and treatment setup efficiencies with homogenous target dose distribution was developed. Jagged-Junction IMRT was retrospectively planned on three patients with prescription of 36 Gy in 20 fractions and compared to conventional treatment plans. Planning target volume (PTV) included the whole brain and spinal canal to the S3 vertebral level. The plan employed three field sets, each with a unique isocentre. One field set with seven fields treated the cranium. Two field sets treated the spine, each set using three fields. Fields from adjacent sets were overlapped and the optimization process smoothly integrated the dose inside the overlapped junction. For the Jagged-Junction IMRT plans vs conventional technique, average homogeneity index equaled 0.08±0.01 vs 0.12±0.02, and conformity number equaled 0.79±0.01 vs 0.47±0.12. The 95% isodose surface covered (99.5±0.3)% of the PTV vs (98.1±2.0)%. Both Jagged-Junction IMRT plans and the conventional plans had good sparing of the organs at risk. Jagged-Junction IMRT planning provided good dose homogeneity and conformity to the target while maintaining a low dose to the organs at risk. Jagged-Junction IMRT optimization smoothly distributed dose in the junction between field sets. Since there was no beam matching, this treatment technique is less likely to produce hot or cold spots at the junction in contrast to conventional techniques. © 2012 American Association of Physicists in Medicine.

Size dependence of spin-torque induced magnetic switching in CoFeB-based perpendicular magnetization tunnel junctions (invited)

NASA Astrophysics Data System (ADS)

Sun, J. Z.; Trouilloud, P. L.; Gajek, M. J.; Nowak, J.; Robertazzi, R. P.; Hu, G.; Abraham, D. W.; Gaidis, M. C.; Brown, S. L.; O'Sullivan, E. J.; Gallagher, W. J.; Worledge, D. C.

2012-04-01

CoFeB-based magnetic tunnel junctions with perpendicular magnetic anisotropy are used as a model system for studies of size dependence in spin-torque-induced magnetic switching. For integrated solid-state memory applications, it is important to understand the magnetic and electrical characteristics of these magnetic tunnel junctions as they scale with tunnel junction size. Size-dependent magnetic anisotropy energy, switching voltage, apparent damping, and anisotropy field are systematically compared for devices with different materials and fabrication treatments. Results reveal the presence of sub-volume thermal fluctuation and reversal, with a characteristic length-scale of the order of approximately 40 nm, depending on the strength of the perpendicular magnetic anisotropy and exchange stiffness. To have the best spin-torque switching efficiency and best stability against thermal activation, it is desirable to optimize the perpendicular anisotropy strength with the junction size for intended use. It also is important to ensure strong exchange-stiffness across the magnetic thin film. These combine to give an exchange length that is comparable or larger than the lateral device size for efficient spin-torque switching.

Role of Gap Junctions in Early Brain Injury Following Subarachnoid Hemorrhage

PubMed Central

Ayer, Robert; Chen, Wanqiu; Sugawara, Takashi; Suzuki, Hidenori; Zhang, John H.

2010-01-01

Gap junction inhibition has been demonstrated to reverse the vascular contraction that follows experimental subarachnoid hemorrhage. This study hypothesizes that the use of established gap junction inhibitors: octonal and carbenoxolone, to interrupt cell to cell communication will provide neuroprotection against early brain injury after SAH. The filament perforation model of SAH was performed in male Sprague–Dawley rats weighing between 300 and 380g. Octanol (260.46mg or 781.38 mg/kg), carbenoxolone (100 mg/kg), or vehicles were given via intraperitoneal injection 1 hour after SAH. Neurologic deficits and cerebral apoptosis were assessed 24 and 72 hours after SAH. In addition, Western blot analysis was performed to confirm the in vivo inhibition of CNS gap junctions. The administration of octanol and carbenoxolone both failed to attenuate the neurological deficits induced by SAH, and they did not reduce neuronal apoptosis. Additionally, carbenoloxone increased post SAH mortality and exacerbated SAH induced apoptosis. Despites previous studies that show gap junction inhibitors reverse vasospasm following experimental SAH, they failed to improve clinical outcomes or provide neuroprotection in this study. PMID:20018179

Majorana ϕ0-junction in a disordered spin-orbit coupling nanowire with tilted magnetic field

NASA Astrophysics Data System (ADS)

Huang, Hong; Liang, Qi-Feng; Yao, Dao-Xin; Wang, Zhi

2017-12-01

Majorana Josephson junctions in nanowire systems exhibit a pseudo-4π period current-phase relation in the clean limit. In this work, we study how this current-phase relation responds to a tilted magnetic field in a disordered Majorana Josephson junction within the Bogoliubov-de Gennes approach. We show that the tilted magnetic field induces a ϕ0 phase shift to the current-phase relation. Most importantly, we find that this ϕ0-junction behavior is robust even in the presence of disorders.

Magnetization induced by odd-frequency spin-triplet Cooper pairs in a Josephson junction with metallic trilayers

NASA Astrophysics Data System (ADS)

Hikino, S.; Yunoki, S.

2015-07-01

We theoretically study the magnetization inside a normal metal induced in an s -wave superconductor/ferromagnetic metal/normal metal/ferromagnetic metal/s -wave superconductor (S /F 1 /N /F 2 /S ) Josephson junction. Using the quasiclassical Green's function method, we show that the magnetization becomes finite inside the N . The origin of this magnetization is due to odd-frequency spin-triplet Cooper pairs formed by electrons of equal and opposite spins, which are induced by the proximity effect in the S /F 1 /N /F 2 /S junction. We find that the magnetization M (d ,θ ) in the N can be decomposed into two parts, M (d ,θ ) =MI(d ) +MII(d ,θ ) , where θ is the superconducting phase difference between the two S s and d is the thickness of N . The θ -independent magnetization MI(d ) exists generally in S /F junctions, while MII(d ,θ ) carries all θ dependence and represents the fingerprint of the phase coherence between the two S s in Josephson junctions. The θ dependence thus allows us to control the magnetization in the N by tuning θ for a fixed d . We show that the θ -independent magnetization MI(d ) weakly decreases with increasing d , while the θ -dependent magnetization MII(d ,θ ) rapidly decays with d . Moreover, we find that the time-averaged magnetization exhibits a discontinuous peak at each resonance dc voltage Vn=n ℏ ωS/2 e (n : integer) when dc voltage V as well as ac voltage vac(t ) with frequency ωS are both applied to the S /F 1 /N /F 2 /S junction. This is because MII(d ,θ ) oscillates generally in time t (ac magnetization) with d θ /d t =2 e [V +vac(t ) ]/ℏ and thus =0 , but can be converted into the time-independent dc magnetization for the dc voltage at Vn. We also discuss that the magnetization induced in the N can be measurably large in realistic systems. Therefore, the measurement of the induced magnetization serves as an alternative way to detect the phase coherence between the two S s in Josephson junctions. Our results also provide a basic concept for tunable magnetization in superconducting spintronics devices.

Axial p-n junction and space charge limited current in single GaN nanowire.

PubMed

Fang, Zhihua; Donatini, Fabrice; Daudin, Bruno; Pernot, Julien

2018-01-05

The electrical characterizations of individual basic GaN nanostructures, such as axial nanowire (NW) p-n junctions, are becoming indispensable and crucial for the fully controlled realization of GaN NW based devices. In this study, electron beam induced current (EBIC) measurements were performed on two single axial GaN p-n junction NWs grown by plasma-assisted molecular beam epitaxy. I-V characteristics revealed that both ohmic and space charge limited current (SCLC) regimes occur in GaN p-n junction NW. Thanks to an improved contact process, both the electric field induced by the p-n junction and the SCLC in the p-part of GaN NW were disclosed and delineated by EBIC signals under different biases. Analyzing the EBIC profiles in the vicinity of the p-n junction under 0 V and reverse bias, we deduced a depletion width in the range of 116-125 nm. Following our previous work, the acceptor N a doping level was estimated to be 2-3 × 10 17 at cm -3 assuming a donor level N d of 2-3 × 10 18 at cm -3 . The hole diffusion length in n-GaN was determined to be 75 nm for NW #1 and 43 nm for NW #2, demonstrating a low surface recombination velocity at the m-plane facet of n-GaN NW. Under forward bias, EBIC imaging visualized the electric field induced by the SCLC close to p-side contact, in agreement with unusual SCLC previously reported in GaN NWs.

Axial p-n junction and space charge limited current in single GaN nanowire

NASA Astrophysics Data System (ADS)

Fang, Zhihua; Donatini, Fabrice; Daudin, Bruno; Pernot, Julien

2018-01-01

The electrical characterizations of individual basic GaN nanostructures, such as axial nanowire (NW) p-n junctions, are becoming indispensable and crucial for the fully controlled realization of GaN NW based devices. In this study, electron beam induced current (EBIC) measurements were performed on two single axial GaN p-n junction NWs grown by plasma-assisted molecular beam epitaxy. I-V characteristics revealed that both ohmic and space charge limited current (SCLC) regimes occur in GaN p-n junction NW. Thanks to an improved contact process, both the electric field induced by the p-n junction and the SCLC in the p-part of GaN NW were disclosed and delineated by EBIC signals under different biases. Analyzing the EBIC profiles in the vicinity of the p-n junction under 0 V and reverse bias, we deduced a depletion width in the range of 116-125 nm. Following our previous work, the acceptor N a doping level was estimated to be 2-3 × 1017 at cm-3 assuming a donor level N d of 2-3 × 1018 at cm-3. The hole diffusion length in n-GaN was determined to be 75 nm for NW #1 and 43 nm for NW #2, demonstrating a low surface recombination velocity at the m-plane facet of n-GaN NW. Under forward bias, EBIC imaging visualized the electric field induced by the SCLC close to p-side contact, in agreement with unusual SCLC previously reported in GaN NWs.

External noise-induced transitions in a current-biased Josephson junction

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

Huang, Qiongwei; Xue, Changfeng, E-mail: cfxue@163.com; Tang, Jiashi

We investigate noise-induced transitions in a current-biased and weakly damped Josephson junction in the presence of multiplicative noise. By using the stochastic averaging procedure, the averaged amplitude equation describing dynamic evolution near a constant phase difference is derived. Numerical results show that a stochastic Hopf bifurcation between an absorbing and an oscillatory state occurs. This means the external controllable noise triggers a transition into the non-zero junction voltage state. With the increase of noise intensity, the stationary probability distribution peak shifts and is characterised by increased width and reduced height. And the different transition rates are shown for large andmore » small bias currents.« less

big bang gene modulates gut immune tolerance in Drosophila.

PubMed

Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

2013-02-19

Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

Connexin43 synthesis, phosphorylation, and degradation in regulation of transient inhibition of gap junction intercellular communication by the phorbol ester TPA in rat liver epithelial cells.

PubMed

Rivedal, Edgar; Leithe, Edward

2005-01-15

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces transient inhibition of gap junction intercellular communication (GJIC) in several cell types. The initial block in GJIC has been attributed to protein kinase C (PKC) mediated phosphorylation of connexin gap junction proteins, including connexin43 (Cx43). Restoration of GJIC, associated with normalization of the Cx43 phosphorylation status, has been ascribed to different events, including dephosphorylation of Cx43 and de novo synthesis of Cx43 or other, non-gap junctional, proteins. The data presented suggest that restoration of GJIC during continuous TPA exposure in normal and transformed rat liver epithelial cells is dependent on synthesis of Cx43 protein, as well as the transport of already synthesized Cx43 from intracellular pools to the plasma membrane. Reactivation of inactivated Cx43 by dephosphorylation does not appear to be involved in the recovery of GJIC. Both PKC and MAP kinase is involved in TPA-induced degradation of Cx43 and inhibition of GJIC. We show that coincubation of TPA with the protein synthesis inhibitor cycloheximide or the transcription inhibitor actinomycin D results in synergistic enhancement of the level of activated ERK1/2. Together, the present data highlight Cx43 degradation and synthesis as critical determinants in TPA-induced modifications of cell-cell communication via gap junctions.

Penetration depth of MgB2 measured using Josephson junctions and SQUIDs

NASA Astrophysics Data System (ADS)

Cunnane, Daniel; Zhuang, Chenggang; Chen, Ke; Xi, X. X.; Yong, Jie; Lemberger, T. R.

2013-02-01

The penetration depth of MgB2 was measured using two methods of different mechanisms. The first method used MgB2 Josephson junctions and the magnetic field dependence of the junction critical current. The second method deduced the penetration depth from the inductance of a MgB2 microstrip used to modulate the voltage of a MgB2 DC SQUID. The two methods showed a consistent value of the low-temperature penetration depth for MgB2 to be about 40 nm. Both the small penetration depth value and its temperature dependence are in agreement with a microscopic theory for MgB2 in the clean limit.

Bypass diode integration

NASA Technical Reports Server (NTRS)

Shepard, N. F., Jr.

1981-01-01

Protective bypass diodes and mounting configurations which are applicable for use with photovoltaic modules having power dissipation requirements in the 5 to 50 watt range were investigated. Using PN silicon and Schottky diode characterization data on packaged diodes and diode chips, typical diodes were selected as representative for each range of current carrying capacity, an appropriate heat dissipating mounting concept along with its environmental enclosure was defined, and a thermal analysis relating junction temperature as a function of power dissipation was performed. In addition, the heat dissipating mounting device dimensions were varied to determine the effect on junction temperature. The results of the analysis are presented as a set of curves indicating junction temperature as a function of power dissipation for each diode package.

Dietary glucosylceramide enhances tight junction function in skin epidermis via induction of claudin-1.

PubMed

Kawada, Chinatsu; Hasegawa, Tatsuya; Watanabe, Mutsuto; Nomura, Yoshihiro

2013-01-01

Dietary glucosylceramide increased the expression of claudin-1 in UVB-irradiated mouse epidermis. Sphingosine and phytosphingosine, metabolites of glucosylceramide, increased trans-epithelial electrical resistance, and phytosphingosine increased claudin-1 mRNA expression in cultured keratinocytes. Our results indicate that the skin barrier improvement induced by dietary glucosylceramide might be due to enhancement of tight junction function, mediated by increased expression of claudin-1 induced by sphingoid metabolites.

Imprint control of BaTiO 3 thin films via chemically induced surface polarization pinning

DOE PAGES

Lee, Hyungwoo; Kim, Tae Heon; Patzner, Jacob J.; ...

2016-02-22

Surface-adsorbed polar molecules can significantly alter the ferroelectric properties of oxide thin films. Thus, fundamental understanding and controlling the effect of surface adsorbates are crucial for the implementation of ferroelectric thin film devices, such as ferroelectric tunnel junctions. Herein, we report an imprint control of BaTiO 3 (BTO) thin films by chemically induced surface polarization pinning in the top few atomic layers of the water-exposed BTO films. Our studies based on synchrotron X-ray scattering and coherent Bragg rod analysis demonstrate that the chemically induced surface polarization is not switchable but reduces the polarization imprint and improves the bistability of ferroelectricmore » phase in BTO tunnel junctions. Here, we conclude that the chemical treatment of ferroelectric thin films with polar molecules may serve as a simple yet powerful strategy to enhance functional properties of ferroelectric tunnel junctions for their practical applications.« less

Hybrid photovoltaic and thermoelectric module for high concentration solar system

NASA Astrophysics Data System (ADS)

Tamaki, Ryo; Toyoda, Takeshi; Tamura, Yoichi; Matoba, Akinari; Minamikawa, Toshiharu; Tokuda, Masayuki; Masui, Megumi; Okada, Yoshitaka

2017-09-01

A photovoltaic (PV) and thermoelectric (TE) hybrid module was developed for application to high concentration solar systems. The waste heat from the solar cells under concentrated light illumination was utilized to generate additional electricity by assembling TE devices below the multi-junction solar cells (MJSCs). Considering the high operating temperature of the PV and TE hybrid module compared with conventional concentrator PV modules, the TE device could compensate a part of the MJSC efficiency degradation at high temperature. The performance investigation clarified the feasibility of the hybrid PV and TE module under highly concentrated sunlight illumination.

Giant electroresistance of super-tetragonal BiFeO3-based ferroelectric tunnel junctions.

PubMed

Yamada, Hiroyuki; Garcia, Vincent; Fusil, Stéphane; Boyn, Sören; Marinova, Maya; Gloter, Alexandre; Xavier, Stéphane; Grollier, Julie; Jacquet, Eric; Carrétéro, Cécile; Deranlot, Cyrile; Bibes, Manuel; Barthélémy, Agnès

2013-06-25

Ferroelectric tunnel junctions enable a nondestructive readout of the ferroelectric state via a change of resistance induced by switching the ferroelectric polarization. We fabricated submicrometer solid-state ferroelectric tunnel junctions based on a recently discovered polymorph of BiFeO3 with giant axial ratio ("T-phase"). Applying voltage pulses to the junctions leads to the highest resistance changes (OFF/ON ratio >10,000) ever reported with ferroelectric tunnel junctions. Along with the good retention properties, this giant effect reinforces the interest in nonvolatile memories based on ferroelectric tunnel junctions. We also show that the changes in resistance scale with the nucleation and growth of ferroelectric domains in the ultrathin BiFeO3 (imaged by piezoresponse force microscopy), thereby suggesting potential as multilevel memory cells and memristors.

Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

PubMed

Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

2016-09-02

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Heme Oxygenase-1 Protects Corexit 9500A-Induced Respiratory Epithelial Injury across Species

PubMed Central

Oliva, Octavio M.; Karki, Suman; Surolia, Ranu; Wang, Zheng; Watson, R. Douglas; Thannickal, Victor J.; Powell, Mickie; Watts, Stephen; Kulkarni, Tejaswini; Batra, Hitesh; Bolisetty, Subhashini; Agarwal, Anupam; Antony, Veena B.

2015-01-01

The effects of Corexit 9500A (CE) on respiratory epithelial surfaces of terrestrial mammals and marine animals are largely unknown. This study investigated the role of CE-induced heme oxygenase-1 (HO-1), a cytoprotective enzyme with anti-apoptotic and antioxidant activity, in human bronchial airway epithelium and the gills of exposed aquatic animals. We evaluated CE-mediated alterations in human airway epithelial cells, mice lungs and gills from zebrafish and blue crabs. Our results demonstrated that CE induced an increase in gill epithelial edema and human epithelial monolayer permeability, suggesting an acute injury caused by CE exposure. CE induced the expression of HO-1 as well as C-reactive protein (CRP) and NADPH oxidase 4 (NOX4), which are associated with ROS production. Importantly, CE induced caspase-3 activation and subsequent apoptosis of epithelial cells. The expression of the intercellular junctional proteins, such as tight junction proteins occludin, zonula occludens (ZO-1), ZO-2 and adherens junctional proteins E-cadherin and Focal Adhesion Kinase (FAK), were remarkably inhibited by CE, suggesting that these proteins are involved in CE-induced increased permeability and subsequent apoptosis. The cytoskeletal protein F-actin was also disrupted by CE. Treatment with carbon monoxide releasing molecule-2 (CORM-2) significantly inhibited CE-induced ROS production, while the addition of HO-1 inhibitor, significantly increased CE-induced ROS production and apoptosis, suggesting a protective role of HO-1 or its reaction product, CO, in CE-induced apoptosis. Using HO-1 knockout mice, we further demonstrated that HO-1 protected against CE-induced inflammation and cellular apoptosis and corrected CE-mediated inhibition of E-cadherin and FAK. These observations suggest that CE activates CRP and NOX4-mediated ROS production, alters permeability by inhibition of junctional proteins, and leads to caspase-3 dependent apoptosis of epithelial cells, while HO-1 and its reaction products protect against oxidative stress and apoptosis. PMID:25835394

Single-contact tunneling thermometry

DOEpatents

Maksymovych, Petro

2016-02-23

A single-contact tunneling thermometry circuit includes a tunnel junction formed between two objects. Junction temperature gradient information is determined based on a mathematical relationship between a target alternating voltage applied across the junction and the junction temperature gradient. Total voltage measured across the junction indicates the magnitude of the target alternating voltage. A thermal gradient is induced across the junction. A reference thermovoltage is measured when zero alternating voltage is applied across the junction. An increasing alternating voltage is applied while measuring a thermovoltage component and a DC rectification voltage component created by the applied alternating voltage. The target alternating voltage is reached when the thermovoltage is nullified or doubled by the DC rectification voltage depending on the sign of the reference thermovoltage. Thermoelectric current and current measurements may be utilized in place of the thermovoltage and voltage measurements. The system may be automated with a feedback loop.

Propofol inhibits gap junctions by attenuating sevoflurane-induced cytotoxicity against rat liver cells in vitro.

PubMed

Huang, Fei; Li, Shangrong; Gan, Xiaoliang; Wang, Ren; Chen, Zhonggang

2014-04-01

Liver abnormalities are seen in a small proportion of patients following anaesthesia with sevoflurane. To investigate whether the cytotoxicity of sevoflurane against rat liver cells was mediated by gap junction intercellular communications, and the effect of propofol on sevoflurane-induced cytotoxicity. Experimental study. The study was carried out in the central laboratory of The Third Affiliated Hospital, Sun Yat-sen University. BRL-3A rat liver cells. Immortal rat liver cells BRL-3A were grown at low and high density. Colony-forming assays were performed to determine clonogenic growth of these cells. To investigate the effect of oleamide and propofol on gap junction function, we measured fluorescence transmission between cells using parachute dye-coupling assays. Immunoblotting assays were performed to determine connexin32 and connexin43 expression. Our colony formation assays revealed that, in low-density culture, sevoflurane caused no apparent inhibition of clonogenic growth of BRL-3A cells. In high-density culture, 2.2 to 4.4% sevoflurane markedly inhibited clonogenic growth of BRL-3A cells with 67.6 (0.34)% and 61.2 (0.17)% of the cells being viable, respectively (P = 0.003 vs. low-density culture), suggesting cell density dependency of sevoflurane-induced cytotoxicity. Our colony formation assays revealed that propofol markedly attenuated the suppression by sevoflurane of the clonogenic growth of BRL-3A cells (viability: propofol and sevoflurane, 91.5 (0.014)% vs. sevoflurane, 56.6 (0.019)%; P <0.01). Blocking gap junctions with 10 μmol l oleamide significantly attenuated 4.4% sevoflurane-induced suppression with a viability of 83.6 ± 0.138% (oleamide and sevoflurane vs. sevoflurane, P < 0.01). Immunoblotting assays further showed that propofol (3.2 μg ml) markedly reduced CX32 levels and significantly inhibited gap junctional intercellular communications as revealed by parachute dye-coupling assays. Values are mean (SD). This study provides the first direct evidence that sevoflurane-induced cytotoxicity, which is mediated through gap junctions, is attenuated by propofol, possibly by its action on Cx32 homomeric or heteromeric complexes.

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

Yin, Qingqiao; Xia, Yuanyu, E-mail: xiayuanyu.wh@gmail.com; Wang, Guan

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression inmore » HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.« less

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

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

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

2007-05-15

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

Effect of d-wave pairing symmetry in transport properties of silicene-based superconductor junction

NASA Astrophysics Data System (ADS)

Vosoughi-nia, S.; Rashedi, G.; hajati, Y.

2018-06-01

We theoretically study the tunneling conductance of a normal/d-wave superconductor silicene junction using Blonder-Tinkham-Klapwijk (BTK) formalism. We discuss how the conductance spectra are affected by changing the chemical potential (μN) in the normal silicene region. It is obtained that the amplitude of the spin/valley-dependent Andreev reflection (AR) and charge conductance (G) of the junction can be strongly modulated by the orientation angle of superconductive gap (β) and perpendicular electric field (Ez). We demonstrate that the charge conductance exhibits an oscillatory behavior as a function of β by a period of π/2. Remarkably, variation of μN strongly modifies the amplitude of the oscillations and periodically there are transport gaps in the G - β oscillations for a range of μN. These findings suggest that one may experimentally tune the transport properties of the junction through changing β, Ez and μN.

Purification of complex samples: Implementation of a modular and reconfigurable droplet-based microfluidic platform with cascaded deterministic lateral displacement separation modules

PubMed Central

Pudda, Catherine; Boizot, François; Verplanck, Nicolas; Revol-Cavalier, Frédéric; Berthier, Jean; Thuaire, Aurélie

2018-01-01

Particle separation in microfluidic devices is a common problematic for sample preparation in biology. Deterministic lateral displacement (DLD) is efficiently implemented as a size-based fractionation technique to separate two populations of particles around a specific size. However, real biological samples contain components of many different sizes and a single DLD separation step is not sufficient to purify these complex samples. When connecting several DLD modules in series, pressure balancing at the DLD outlets of each step becomes critical to ensure an optimal separation efficiency. A generic microfluidic platform is presented in this paper to optimize pressure balancing, when DLD separation is connected either to another DLD module or to a different microfluidic function. This is made possible by generating droplets at T-junctions connected to the DLD outlets. Droplets act as pressure controllers, which perform at the same time the encapsulation of DLD sorted particles and the balance of output pressures. The optimized pressures to apply on DLD modules and on T-junctions are determined by a general model that ensures the equilibrium of the entire platform. The proposed separation platform is completely modular and reconfigurable since the same predictive model applies to any cascaded DLD modules of the droplet-based cartridge. PMID:29768490

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

Rivedal, Edgar; Leithe, Edward

Benzene is used at large volumes in many different human activities. Hematotoxicity and cancer-causation as a result of benzene exposure was recognized many years ago, but the mechanisms involved remain unclear. Aberrant regulation of gap junction intercellular communication (GJIC) has been linked to both cancer induction and interference with normal hematopoietic development. We have previously suggested that inhibition of GJIC may play a role in benzene toxicity since benzene metabolites were found to block GJIC, the ring-opened trans,trans-muconaldehyde (MUC) being the most potent metabolite. In the present work we have studied the molecular mechanisms underlying the MUC-induced inhibition of gapmore » junctional communication. We show that MUC induces cross-linking of the gap junction protein connexin43 and that this is likely to be responsible for the induced inhibition of GJIC, as well as the loss of connexin43 observed in Western blots. We also show that glutaraldehyde possesses similar effects as MUC, and we compare the effects to that of formaldehyde. The fact that glutaraldehyde and formaldehyde have been associated with induction of leukemia as well as disturbance of hematopoiesis, strengthens the possible link between the effect of MUC on gap junctions, and the toxic effects of benzene.« less

Functional maturation of motor nerve terminals in the avian iris: ultrastructure, transmitter metabolism and synaptic reliability

PubMed Central

Pilar, Guillermo; Tuttle, Jeremy; Vaca, Ken

1981-01-01

1. The transformation of easily fatigued embryonic neuromuscular junctions into highly reliable mature terminals was examined by studying functional and morphological changes during development of the avian iris. The mature ability to follow repetitive electrical nerve stimulation was correlated with the rate of acetylcholine (ACh) synthesis and choline uptake, and with the fine structure of the nerve terminals and the post-synaptic elements. 2. The terminals of the ciliary nerve of the chick initially form functional synaptic contacts with the iris muscle at embryonic St. 34-40. At the onset of this period, no Na+-dependent high affinity choline uptake can be demonstrated, and the low level of ACh synthesis present is sensitive to Na+ removal. At St. 36 [3H]ACh synthesis begins to increase, the increment being Na+-dependent. 3. ACh synthesis in the embryonic iris was insensitive to a conditioning [K+]o depolarization even as late as St. 43. Just before hatching, depolarization elicits some augmentation in synthesis, but by 2 days ex ovo this release-induced response has increased by an order of magnitude. 4. Concurrently with the acquisition of the ability to respond to depolarization with accelerated synthesis, neuromuscular transmission in the iris becomes reliable and secure during stimulation at 20 Hz. Embryonic junctions rapidly block during such stimulation, and the failure is shown to be presynaptic in origin, resulting most probably from failure to sustain adequate levels of transmitter release. 5. Ultrastructural examination of the developing ciliary terminals revealed few synaptic vesicles at early stages, and a dearth of other specializations. The sequence of development from these small structurally undistinguished endings to large en plaque junctions completely filled with vesicles was reconstructed and compared to other neuromuscular junctions. Morphological maturation appears progressive with little evidence of discontinuity signalling functional status, but it is only after the terminals enlarge and become closely packed with vesicles that mature synaptic reliability is found. 6. The temporal correlation between responsiveness of transmitter synthesis to depolarization and reliable neuromuscular transmission suggests that modulation of neurotransmitter metabolism in response to demand signals the achievement of junctional maturity. ImagesABPlate 2Plate 3Plate 4 PMID:6279822

Conductance modulation in Weyl semimetals with tilted energy dispersion without a band gap

NASA Astrophysics Data System (ADS)

Yesilyurt, Can; Siu, Zhuo Bin; Tan, Seng Ghee; Liang, Gengchiau; Jalil, Mansoor B. A.

2017-06-01

We investigate the tunneling conductance of Weyl semimetal with tilted energy dispersion by considering electron transmission through a p-n-p junction with one-dimensional electric and magnetic barriers. In the presence of both electric and magnetic barriers, we found that a large conductance gap can be produced with the aid of tilted energy dispersion without a band gap. The origin of this effect is the shift of the electron wave-vector at barrier boundaries caused by (i) the pseudo-magnetic field induced by electrical potential, i.e., a newly discovered feature that is only possible in the materials possessing tilted energy dispersion, (ii) the real magnetic field induced by a ferromagnetic layer deposited on the top of the system. We use a realistic barrier structure applicable in current nanotechnology and analyze the temperature dependence of the tunneling conductance. The new approach presented here may resolve a major problem of possible transistor applications in topological semimetals, i.e., the absence of normal backscattering and gapless band structure.

Current-voltage characteristics and increase in the quantum efficiency of three-terminal gate and avalanche-based silicon LEDs.

PubMed

Xu, Kaikai

2013-09-20

In this paper, the emission of visible light by a monolithically integrated silicon p-n junction under reverse-bias is discussed. The modulation of light intensity is achieved using an insulated-gate terminal on the surface of the p-n junction. By varying the gate voltage, the breakdown voltage of the p-n junction will be adjustable so that the reverse current I(sub) flowing through the p-n junction at a fixed reverse-bias voltage is changed. It is observed that the light, which is emitted from the defects located at the p-n junction, depends closely on the reverse current I(sub). In regard to the phenomenon of electroluminescence, the relationship between the optical emission power and the reverse current I(sub) is linear. On the other hand, it is observed that both the quantum efficiency and the power conversion efficiency are able to have obvious enhancement, although the reverse-bias of the p-n junction is reduced and the corresponding reverse-current is much lower. Moreover, the successful fabrication on monolithic silicon light source on the bulk silicon by means of standard silicon complementary metal-oxide-semiconductor process technology is presented.

SU-F-T-522: Dosimetric Study of Junction Dose in Double Isocenter Flatten and Flatten Filter Free IMRT and VMAT Plan Delivery

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

Samuvel, K; Yadav, G; Bhushan, M

2016-06-15

Purpose: To quantify the dosimetric accuracy of junction dose in double isocenter flattened and flatten filter free(FFF) intensity modulated radiation therapy(IMRT) and volumetric modulated arc therapy(VMAT) plan delivery using pelvis phantom. Methods: Five large field pelvis patients were selected for this study. Double isocenter IMRT and VMAT treatment plans were generated in Eclipse Treatment planning System (V.11.0) using 6MV FB and FFF beams. For all the plans same distance 17.0cm was kept between one isocenter to another isocenter. IMRT Plans were made with 7 coplanar fields and VMAT plans were made with full double arcs. Dose calculation was performed usingmore » AAA algorithms with dose grid size of 0.25 cm. Verification plans were calculated on Scanditronix Wellhofer pelvis slab phantom. Measurement point was selected and calculated, where two isocenter plan fields are overlapping, this measurement point was kept at distance 8.5cm from both isocenter. The plans were delivered using Varian TrueBeamTM machine on pelvis slab phantom. Point dose measurements was carried out using CC13 ion chamber volume of 0.13cm3. Results: The measured junction point dose are compared with TPS calculated dose. The mean difference observed was 4.5%, 6.0%, 4.0% and 7.0% for IMRT-FB,IMRT-FFF, VMAT-FB and VMAT-FFF respectively. The measured dose results shows closer agreement with calculated dose in Flatten beam planning in both IMRT and VMAT, whereas in FFF beam plan dose difference are more compared with flatten beam plan. Conclusion: Dosimetry accuracy of Large Field junction dose difference was found less in Flatten beam compared with FFF beam plan delivery. Even though more dosimetric studies are required to analyse junction dose for FFF beam planning using multiple point dose measurements and fluence map verification in field junction area.« less

Enhanced Contacts for Inverted Metamorphic Multi-Junction Solar Cells Using Carbon Nanotube Metal Matrix Composites

DTIC Science & Technology

2018-01-18

to a variety solar energy markets. For instance, micro-cracks have been shown to cause decreased power output in single- and multi-crystalline Si PV ...fingers in silicon wafer solar cells and PV modules," Solar Energy Materials and Solar Cells, vol. 108, pp. 78-81, 1// 2013. [4] T. H. Reijenga and H...AFRL-RV-PS- AFRL-RV-PS- TR-2017-0125 TR-2017-0125 ENHANCED CONTACTS FOR INVERTED METAMORPHIC MULTI-JUNCTION SOLAR CELLS USING CARBON NANOTUBE METAL

Tight junctions in cancer metastasis.

PubMed

Martin, Tracey A; Mason, Malcolm D; Jiang, Wen G

2011-01-01

Tight Junctions (TJ) are well known to function as a control for the paracellular diffusion of ions and certain molecules, it has however, become evident that the TJ has a vital role in maintaining cell to cell integrity. Loss of cohesion of the TJ structure can lead to invasion and ultimately to the metastasis of cancer cells. This review will discuss how modulation of expression of TJ molecules results in key changes in TJ barrier function leading to the progression of cancer and progression of metastasis.

Spin wave scattering and interference in ferromagnetic cross

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

Nanayakkara, Kasuni; Kozhanov, Alexander; Center for Nano Optics, Georgia State University, Atlanta, Georgia 30303

2015-10-28

Magnetostatic spin wave scattering and interference across a CoTaZr ferromagnetic spin wave waveguide cross junction were investigated experimentally and by micromagnetic simulations. It is observed that the phase of the scattered waves is dependent on the wavelength, geometry of the junction, and scattering direction. It is found that destructive and constructive interference of the spin waves generates switching characteristics modulated by the input phase of the spin waves. Micromagnetic simulations are used to analyze experimental data and simulate the spin wave scattering and interference.

Controlling charge transport mechanisms in molecular junctions: Distilling thermally induced hopping from coherent-resonant conduction.

PubMed

Kim, Hyehwang; Segal, Dvira

2017-04-28

The electrical conductance of molecular junctions may depend strongly on the temperature and weakly on molecular length, under two distinct mechanisms: phase-coherent resonant conduction, with charges proceeding via delocalized molecular orbitals, and incoherent thermally assisted multi-step hopping. While in the case of coherent conduction, the temperature dependence arises from the broadening of the Fermi distribution in the metal electrodes, in the latter case it corresponds to electron-vibration interaction effects on the junction. With the objective to distill the thermally activated hopping component, thus exposing intrinsic electron-vibration interaction phenomena on the junction, we suggest the design of molecular junctions with "spacers," extended anchoring groups that act to filter out phase-coherent resonant electrons. Specifically, we study the electrical conductance of fixed-gap and variable-gap junctions that include a tunneling block, with spacers at the boundaries. Using numerical simulations and analytical considerations, we demonstrate that in our design, resonant conduction is suppressed. As a result, the electrical conductance is dominated by two (rather than three) mechanisms: superexchange (deep tunneling) and multi-step thermally induced hopping. We further exemplify our analysis on DNA junctions with an A:T block serving as a tunneling barrier. Here, we show that the electrical conductance is insensitive to the number of G:C base-pairs at the boundaries. This indicates that the tunneling-to-hopping crossover revealed in such sequences truly corresponds to the properties of the A:T barrier.

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

Ohkuni, Tsuyoshi; Department of Pathology, Sapporo Medical University School of Medicine, Sapporo; Kojima, Takashi, E-mail: ktakashi@sapmed.ac.jp

Human nasal epithelium is an important physical barrier and innate immune defense protecting against inhaled substances and pathogens. Toll-like receptor (TLR) signaling, which plays a key role in the innate immune response, has not been well characterized in human nasal epithelial cells (HNECs), including the epithelial tight junctional barrier. In the present study, mRNAs of TLR1-10 were detected in hTERT-transfected HNECs, which can be used as an indispensable and stable model of normal HNECs, similar to primary cultured HNECs. To investigate the changes of tight junction proteins and the signal transduction pathways via TLRs in HNECs in vitro, hTERT-transfected HNECsmore » were treated with TLR2 ligand P{sub 3}CSK{sub 4}, TLR3 ligand poly(I:C), TLR4 ligand LPS, TLR7/8 ligand CL097, TLR8 ligand ssRNA40/LyoVec, and TLR9 ligand ODN2006. In hTERT-transfected HNECs, treatment with poly(I:C) significantly reduced expression of the tight junction protein JAM-A and induced secretion of proinflammatory cytokines IL-8 and TNF-{alpha}. Both the reduction of JAM-A expression and the induction of secretion of IL-8 and TNF-{alpha} after treatment with poly(I:C) were modulated by distinct signal transduction pathways via EGFR, PI3K, and p38 MAPK and finally regulated by a TLR3-mediated NF-{kappa}B pathway. The control of TLR3-mediated signaling pathways in HNECs may be important not only in infection by viral dsRNA but also in autoimmune diseases caused by endogenous dsRNA released from necrotic cells.« less

Planar-type ferromagnetic tunnel junctions fabricated by SPM local oxidation

NASA Astrophysics Data System (ADS)

Tomoda, Y.; Kayashima, S.; Ogino, T.; Motoyama, M.; Takemura, Y.; Shirakashi, J.

Nanometer-scale oxide wires were fabricated by local oxidation nanolithography using scanning probe microscope (SPM). This technique was applied to the fabrication of planar-type Ni/Ni oxide/Ni ferromagnetic tunnel junctions. In order to induce magnetic shape anisotropy, asymmetrical channel structure was patterned by conventional photolithography and wet etching processes. The magnetoresistance (MR) characteristics were clearly shown in the planar-type Ni/Ni oxide/Ni ferromagnetic tunnel junctions. MR ratio of above 100% was obtained at 17 K. This result suggests that the local oxidation nanolithography using SPM is useful for the application to planar-type ferromagnetic tunnel junctions.

Occludin confers adhesiveness when expressed in fibroblasts.

PubMed

Van Itallie, C M; Anderson, J M

1997-05-01

Occludin is an integral membrane protein specifically associated with tight junctions. Previous studies suggest it is likely to function in forming the intercellular seal. In the present study, we expressed occludin under an inducible promotor in occludin-null fibroblasts to determine whether this protein confers intercellular adhesion. When human occludin is stably expressed in NRK and Rat-1 fibroblasts, which lack endogenous occludin and tight junctions but do have well developed ZO-1-containing adherens-like junctions, occludin colocalizes with ZO-1 to points of cell-cell contact. In contrast, L-cell fibroblasts which lack cadherin-based adherens junctions, target neither ZO-1 nor occludin to sites of cell contact. Occludin-induced adhesion was next quantified using a suspended cell assay. In NRK and Rat-1 cells, occludin expression induces adhesion in the absence of calcium, thus independent of cadherin-cadherin contacts. In contrast, L-cells are nonadhesive in this assay and show no increase in adhesion after induction of occludin expression. Binding of an antibody to the first of the putative extracellular loops of occludin confirmed that this sequence was exposed on the cell surface, and synthetic peptides containing the amino acid sequence of this loop inhibit adhesion induced by occludin expression. These results suggest that the extracellular surface of occludin is directly involved in cell-cell adhesion and the ability to confer adhesiveness correlates with the ability to colocalize with its cytoplasmic binding protein, ZO-1.

Thin-film amorphous silicon alloy research partnership. Phase 2, Annual technical progress report, 2 February 1996--1 February 1997

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

Guha, S

This is Phase II of a 3-phase, 3-year program. It is intended to expand, enhance, and accelerate knowledge and capabilities for developing high-performance, two-terminal multijunction amorphous Si alloy modules. We discuss investigations on back reflectors to improve cell performance and investigate uniformity in performance over a 1-sq.-ft. area. We present results on component cell performance, both in the initial and in the light-degraded states, deposited over a 1-sq.-ft. area. The uniformity in deposited is investigated by studying the performance of subcells deposited over the entire area. We also present results on the performance of triple- junction cells and modules. Themore » modules use grid-lines and encapsulants compatible with our production technology. We discuss the novel laser-processing technique that has bee developed at United Solar to improve energy-conversion efficiency and reduce manufacturing costs. We discuss in detail the optimization of the processing steps, and the performance of a laser-processed, triple- junction device of 12.6 cm{sup 2} area is presented. We also present experimental results on investigations of module reliability.« less

Voltage-Controlled Switching and Thermal Effects in VO2 Nano-Gap Junctions

DTIC Science & Technology

2014-06-09

Voltage-controlled switching and thermal effects in VO2 nano-gap junctions Arash Joushaghani,1 Junho Jeong,1 Suzanne Paradis,2 David Alain,2 J...2014) Voltage-controlled switching in lateral VO2 nano-gap junctions with different gap lengths and thermal properties was investigated. The effect of...indicate that the VO2 phase transition was likely initiated electroni- cally, which was sometimes followed by a secondary thermally-induced transition

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

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

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

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) weremore » 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.« less

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

PubMed Central

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

2015-01-01

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

TNF-α Signals Through PKCζ/NF-κB to Alter the Tight Junction Complex and Increase Retinal Endothelial Cell Permeability

PubMed Central

Aveleira, Célia A.; Lin, Cheng-Mao; Abcouwer, Steven F.; Ambrósio, António F.; Antonetti, David A.

2010-01-01

OBJECTIVE Tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) are elevated in the vitreous of diabetic patients and in retinas of diabetic rats associated with increased retinal vascular permeability. However, the molecular mechanisms underlying retinal vascular permeability induced by these cytokines are poorly understood. In this study, the effects of IL-1β and TNF-α on retinal endothelial cell permeability were compared and the molecular mechanisms by which TNF-α increases cell permeability were elucidated. RESEARCH DESIGN AND METHODS Cytokine-induced retinal vascular permeability was measured in bovine retinal endothelial cells (BRECs) and rat retinas. Western blotting, quantitative real-time PCR, and immunocytochemistry were performed to determine tight junction protein expression and localization. RESULTS IL-1β and TNF-α increased BREC permeability, and TNF-α was more potent. TNF-α decreased the protein and mRNA content of the tight junction proteins ZO-1 and claudin-5 and altered the cellular localization of these tight junction proteins. Dexamethasone prevented TNF-α–induced cell permeability through glucocorticoid receptor transactivation and nuclear factor-kappaB (NF-κB) transrepression. Preventing NF-κB activation with an inhibitor κB kinase (IKK) chemical inhibitor or adenoviral overexpression of inhibitor κB alpha (IκBα) reduced TNF-α–stimulated permeability. Finally, inhibiting protein kinase C zeta (PKCζ) using both a peptide and a novel chemical inhibitor reduced NF-κB activation and completely prevented the alterations in the tight junction complex and cell permeability induced by TNF-α in cell culture and rat retinas. CONCLUSIONS These results suggest that PKCζ may provide a specific therapeutic target for the prevention of vascular permeability in retinal diseases characterized by elevated TNF-α, including diabetic retinopathy. PMID:20693346

Resistive switching and voltage induced modulation of tunneling magnetoresistance in nanosized perpendicular organic spin valves

NASA Astrophysics Data System (ADS)

Göckeritz, Robert; Homonnay, Nico; Müller, Alexander; Fuhrmann, Bodo; Schmidt, Georg

2016-04-01

Nanoscale multifunctional perpendicular organic spin valves have been fabricated. The devices based on an La0.7Sr0.3MnO3/Alq3/Co trilayer show resistive switching of up to 4-5 orders of magnitude and magnetoresistance as high as -70% the latter even changing sign when voltage pulses are applied. This combination of phenomena is typically observed in multiferroic tunnel junctions where it is attributed to magnetoelectric coupling between a ferromagnet and a ferroelectric material. Modeling indicates that here the switching originates from a modification of the La0.7Sr0.3MnO3 surface. This modification influences the tunneling of charge carriers and thus both the electrical resistance and the tunneling magnetoresistance which occurs at pinholes in the organic layer.

Generation of high-power terahertz radiation by nonlinear photon-assisted tunneling transport in plasmonic metamaterials

NASA Astrophysics Data System (ADS)

Chen, Pai-Yen; Salas, Rodolfo; Farhat, Mohamed

2017-12-01

We propose an optoelectronic terahertz oscillator based on the quantum tunneling effect in a plasmonic metamaterial, utilizing a nanostructured metal-insulator-metal (MIM) tunneling junction. The collective resonant response of meta-atoms can achieve >90% optical absorption and strongly localized optical fields within the MIM plasmonic nanojunction. By properly tailoring the radiation aperture, the nonlinear quantum conductance induced by the metamaterial-enhanced, photon-assisted tunneling may produce miliwatt-level terahertz radiation through the optical beating (or heterodyne down conversion) of two lasers with a slight frequency offset. We envisage that the interplay between photon-assisted tunneling and plasmon coupling within the MIM metamaterial/diode may substantially enhance the modulated terahertz photocurrent, and may therefore realize a practical high-power, room-temperature source in applications of terahertz electronics.

Interplay of Bias-Driven Charging and the Vibrational Stark Effect in Molecular Junctions

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

Li, Yajing; Zolotavin, Pavlo; Doak, Peter

We observe large, reversible, bias driven changes in the vibrational energies of PCBM based on simultaneous transport and surface-enhanced Raman spectroscopy (SERS) measurements on PCBM-gold junctions. A combination of linear and quadratic shifts in vibrational energies with voltage is analyzed and compared with similar measurements involving C-60-gold junctions. A theoretical model based on density functional theory (DFT) calculations suggests that both a vibrational Stark effect and bias-induced charging of the junction contribute to the shifts in vibrational energies. In the PCBM case, a linear vibrational Stark effect is observed due to the permanent electric dipole moment of PCBM. The vibrationalmore » Stark shifts shown here for PCBM junctions are comparable to or larger than the charging effects that dominate in C-60 junctions.« less

Interplay of Bias-Driven Charging and the Vibrational Stark Effect in Molecular Junctions

DOE PAGES

Li, Yajing; Zolotavin, Pavlo; Doak, Peter; ...

2016-01-27

We observe large, reversible, bias driven changes in the vibrational energies of PCBM based on simultaneous transport and surface-enhanced Raman spectroscopy (SERS) measurements on PCBM-gold junctions. A combination of linear and quadratic shifts in vibrational energies with voltage is analyzed and compared with similar measurements involving C-60-gold junctions. A theoretical model based on density functional theory (DFT) calculations suggests that both a vibrational Stark effect and bias-induced charging of the junction contribute to the shifts in vibrational energies. In the PCBM case, a linear vibrational Stark effect is observed due to the permanent electric dipole moment of PCBM. The vibrationalmore » Stark shifts shown here for PCBM junctions are comparable to or larger than the charging effects that dominate in C-60 junctions.« less

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

PubMed

Nagasawa, Kunihiko; Chiba, Hideki; Fujita, Hiroki; Kojima, Takashi; Saito, Tsuyoshi; Endo, Toshiaki; Sawada, Norimasa

2006-07-01

Gap-junction plaques are often observed with tight-junction strands of vascular endothelial cells but the molecular interaction and functional relationships between these two junctions remain obscure. We herein show that gap-junction proteins connexin40 (Cx40) and Cx43 are colocalized and coprecipitated with tight-junction molecules occludin, claudin-5, and ZO-1 in porcine blood-brain barrier (BBB) endothelial cells. Gap junction blockers 18beta-glycyrrhetinic acid (18beta-GA) and oleamide (OA) did not influence expression of Cx40, Cx43, occludin, claudin-5, junctional adhesion molecule (JAM)-A, JAM-B, JAM-C, or ZO-1, or their subcellular localization in the porcine BBB endothelial cells. In contrast, these gap-junction blocking agents inhibited the barrier function of tight junctions in cells, determined by measurement of transendothelial electrical resistance and paracellular flux of mannitol and inulin. 18beta-GA also significantly reduced the barrier property in rat lung endothelial (RLE) cells expressing doxycycline-induced claudin-1, but did not change the interaction between Cx43 and either claudin-1 or ZO-1, nor their expression levels or subcellular distribution. These findings suggest that Cx40- and/or Cx43-based gap junctions might be required to maintain the endothelial barrier function without altering the expression and localization of the tight-junction components analyzed. Copyright 2006 Wiley-Liss, Inc.

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

PubMed Central

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

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

PubMed

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.

Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application

PubMed Central

Pilarczyk, Götz; Nesnidal, Ines; Gunkel, Manuel; Bach, Margund; Bestvater, Felix; Hausmann, Michael

2017-01-01

In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin-1β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ-irradiation or alternatively neuregulin-1β application mobilized ErbB receptors in a nucleograde fashion—a process attenuated by trastuzumab antibody application. This was accompanied by increased receptor density, indicating packing into transport units. Factors mobilizing ErbB receptors also mobilized plasma membrane resident gap junction channels. The time course of ErbB receptor activation and gap junction mobilization recapitulates the time course of non-homologous end-joining DNA repair. We explain our findings under terms of DNA injury-induced membrane receptor tyrosine kinase activation and retrograde trafficking. In addition, we interpret the phenomenon of retrograde co-trafficking of gap junction connexons stimulated by ErbB receptor activation. PMID:28208769

Inversion layer solar cell fabrication and evaluation. [measurement of response of inversion layer solar cell to light of different wavelengths

NASA Technical Reports Server (NTRS)

Call, R. L.

1973-01-01

Silicon solar cells operating with induced junctions rather than diffused junctions have been fabricated and tested. Induced junctions were created by forming an inversion layer near the surface of the silicon by supplying a sheet of positive charge above the surface. This charged layer was supplied through three mechanisms: (1) applying a positive potential to a transparent electrode separated from the silicon surface by a dielectric, (2) contaminating the oxide layer with positive ions, and (3) forming donor surface states that leave a positive charge on the surface. A movable semi-infinite shadow delineated the extent of sensitivity of the cell due to the inversion region. Measurements of the response of the inversion layer cell to light of different wavelengths indicated it to be more sensitive to the shorter wavelengths of the sun's spectrum than conventional cells. The greater sensitivity occurs because of the shallow junction and the strong electric field at the surface.

Molecular cell biology and physiology of solute transport

PubMed Central

Caplan, Michael J.; Seo-Mayer, Patricia; Zhang, Li

2010-01-01

Purpose of review An enormous body of research has been focused on exploring the mechanisms through which epithelial cells establish their characteristic polarity. It is clear that under normal circumstances cell–cell contacts mediated by the calcium-dependent adhesion proteins of the intercellular adhesion junctions are required to initiate complete polarization. Furthermore, formation of the tight, or occluding, junctions that limit paracellular permeability has long been thought to help to establish polarity by preventing the diffusion of membrane proteins between the two plasmalemmal domains. This review will discuss several selected kinases and protein complexes and highlight their relevance to transporting epithelial cell polarization. Recent findings Recent work has shed new light on the roles of junctional complexes in establishing and maintaining epithelial cell polarity. In addition, work from several laboratories, suggests that the formation of these junctions is tied to processes that regulate cellular energy metabolism. Summary Junctional complexes and energy sensing kinases constitute a novel class of machinery whose capacity to generate and modulate epithelial cell polarity is likely to have wide ranging and important physiological ramifications. PMID:18695392

Electrostatically tunable lateral MoTe2 p-n junction for use in high-performance optoelectronics.

PubMed

Wang, Zhenxing; Wang, Feng; Yin, Lei; Huang, Yun; Xu, Kai; Wang, Fengmei; Zhan, Xueying; He, Jun

2016-07-21

Because of their ultimate thickness, layered structure and high flexibility, pn junctions based on layered two-dimensional semiconductors have been attracting increasing attention recently. In this study, for the first time, we fabricated lateral pn junctions (LPNJs) based on ultrathin MoTe2 by introducing two separated electrostatic back gates, and investigated their electronic and photovoltaic performance. Pn, np, nn, and pp junctions can be easily realized by modulating the conductive channel type using gate voltages with different polarities. Strong rectification effects were observed in the pn and np junctions and the rectification ratio reached ∼5 × 10(4). Importantly, we find a unique phenomenon that the parameters for MoTe2 LPNJs experience abrupt changes during the transition from p to n or n to p. Furthermore, a high performance photovoltaic device with a filling factor of above 51% and electrical conversion efficiency (η) of around 0.5% is achieved. Our findings are of importance to comprehensively understand the electronic and optoelectronic properties of MoTe2 and may further open up novel electronic and optoelectronic device applications.

Studies of silicon p-n junction solar cells

NASA Technical Reports Server (NTRS)

Neugroschel, A.; Lindholm, F. A.

1979-01-01

To provide theoretical support for investigating different ways to obtain high open-circuit voltages in p-n junction silicon solar cells, an analytical treatment of heavily doped transparent-emitter devices is presented that includes the effects of bandgap narrowing, Fermi-Dirac statistics, a doping concentration gradient, and a finite surface recombination velocity at the emitter surface. Topics covered include: (1) experimental determination of bandgap narrowing in the emitter of silicon p-n junction devices; (2) heavily doped transparent regions in junction solar cells, diodes, and transistors; (3) high-low-emitter solar cell; (4) determination of lifetimes and recombination currents in p-n junction solar cells; (5) MOS and oxide-charged-induced BSF solar cells; and (6) design of high efficiency solar cells for space and terrestrial applications.

Currents Induced by Injected Charge in Junction Detectors

PubMed Central

Gaubas, Eugenijus; Ceponis, Tomas; Kalesinskas, Vidas

2013-01-01

The problem of drifting charge-induced currents is considered in order to predict the pulsed operational characteristics in photo- and particle-detectors with a junction controlled active area. The direct analysis of the field changes induced by drifting charge in the abrupt junction devices with a plane-parallel geometry of finite area electrodes is presented. The problem is solved using the one-dimensional approach. The models of the formation of the induced pulsed currents have been analyzed for the regimes of partial and full depletion. The obtained solutions for the current density contain expressions of a velocity field dependence on the applied voltage, location of the injected surface charge domain and carrier capture parameters. The drift component of this current coincides with Ramo's expression. It has been illustrated, that the synchronous action of carrier drift, trapping, generation and diffusion can lead to a vast variety of possible current pulse waveforms. Experimental illustrations of the current pulse variations determined by either the rather small or large carrier density within the photo-injected charge domain are presented, based on a study of Si detectors. PMID:24036586

Chaotic Dynamics of a Josephson Junction with a Ratchet Potential and Current-Modulating Damping

NASA Astrophysics Data System (ADS)

Li, Fei; Li, Wenwu; Xu, Lan

2018-06-01

The chaotic dynamics of a Josephson junction with a ratchet potential and current-modulating damping are studied. Under the first-order approximation, we construct the general solution of the first-order equation whose boundedness condition contains the famous Melnikov chaotic criterion. Based on the general solution, the incomputability and unpredictability of the system's chaotic behavior are discussed. For the case beyond perturbation conditions, the evolution of stroboscopic Poincaré sections shows that the system undergoes a quasi-periodic transition to chaos with an increasing intensity of the rf-current. Through a suitable feedback controlling strategy, the chaos can be effectively suppressed and the intensity of the controller can vary in a large range. It is also found that the current between the two separated superconductors increases monotonously in some specific parameter spaces.

Chaotic Dynamics of a Josephson Junction with a Ratchet Potential and Current-Modulating Damping

NASA Astrophysics Data System (ADS)

Li, Fei; Li, Wenwu; Xu, Lan

2018-04-01

The chaotic dynamics of a Josephson junction with a ratchet potential and current-modulating damping are studied. Under the first-order approximation, we construct the general solution of the first-order equation whose boundedness condition contains the famous Melnikov chaotic criterion. Based on the general solution, the incomputability and unpredictability of the system's chaotic behavior are discussed. For the case beyond perturbation conditions, the evolution of stroboscopic Poincaré sections shows that the system undergoes a quasi-periodic transition to chaos with an increasing intensity of the rf-current. Through a suitable feedback controlling strategy, the chaos can be effectively suppressed and the intensity of the controller can vary in a large range. It is also found that the current between the two separated superconductors increases monotonously in some specific parameter spaces.

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

PubMed

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

2015-05-01

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

Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation*

PubMed Central

Yamada, Aya; Futagi, Masaharu; Fukumoto, Emiko; Saito, Kan; Yoshizaki, Keigo; Ishikawa, Masaki; Arakaki, Makiko; Hino, Ryoko; Sugawara, Yu; Ishikawa, Momoko; Naruse, Masahiro; Miyazaki, Kanako; Nakamura, Takashi; Fukumoto, Satoshi

2016-01-01

Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43−/− salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43−/− samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43−/− phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis. PMID:26565022

Anticonvulsant effects of mefloquine on generalized tonic-clonic seizures induced by two acute models in rats.

PubMed

Franco-Pérez, Javier; Ballesteros-Zebadúa, Paola; Manjarrez-Marmolejo, Joaquín

2015-03-01

Mefloquine can cross the blood-brain barrier and block the gap junction intercellular communication in the brain. Enhanced electrical coupling mediated by gap junctions is an underlying mechanism involved in the generation and maintenance of seizures. For this reason, the aim of this study was to analyze the effects of the systemic administration of mefloquine on tonic-clonic seizures induced by two acute models such as pentylenetetrazole and maximal electroshock. All the control rats presented generalized tonic-clonic seizures after the administration of pentylenetetrazole. However, the incidence of seizures induced by pentylenetetrazole significantly decreased in the groups administered systematically with 40 and 80 mg/kg of mefloquine. In the control group, none of the rats survived after the generalized tonic-clonic seizures induced by pentylenetetrazole, but survival was improved by mefloquine. Besides, mefloquine significantly modified the total spectral power as well as the duration, amplitude and frequency of the epileptiform activity induced by pentylenetetrazole. For the maximal electroshock model, mefloquine did not change the occurrence of tonic hindlimb extension. However, this gap junction blocker significantly decreased the duration of the tonic hindlimb extension induced by the acute electroshock. These data suggest that mefloquine at low doses might be eliciting some anticonvulsant effects when is systemically administered to rats.

Distal gap junctions and active dendrites can tune network dynamics.

PubMed

Saraga, Fernanda; Ng, Leo; Skinner, Frances K

2006-03-01

Gap junctions allow direct electrical communication between CNS neurons. From theoretical and modeling studies, it is well known that although gap junctions can act to synchronize network output, they can also give rise to many other dynamic patterns including antiphase and other phase-locked states. The particular network pattern that arises depends on cellular, intrinsic properties that affect firing frequencies as well as the strength and location of the gap junctions. Interneurons or GABAergic neurons in hippocampus are diverse in their cellular characteristics and have been shown to have active dendrites. Furthermore, parvalbumin-positive GABAergic neurons, also known as basket cells, can contact one another via gap junctions on their distal dendrites. Using two-cell network models, we explore how distal electrical connections affect network output. We build multi-compartment models of hippocampal basket cells using NEURON and endow them with varying amounts of active dendrites. Two-cell networks of these model cells as well as reduced versions are explored. The relationship between intrinsic frequency and the level of active dendrites allows us to define three regions based on what sort of network dynamics occur with distal gap junction coupling. Weak coupling theory is used to predict the delineation of these regions as well as examination of phase response curves and distal dendritic polarization levels. We find that a nonmonotonic dependence of network dynamic characteristics (phase lags) on gap junction conductance occurs. This suggests that distal electrical coupling and active dendrite levels can control how sensitive network dynamics are to gap junction modulation. With the extended geometry, gap junctions located at more distal locations must have larger conductances for pure synchrony to occur. Furthermore, based on simulations with heterogeneous networks, it may be that one requires active dendrites if phase-locking is to occur in networks formed with distal gap junctions.

Interaction of Ddc1 and RPA with single-stranded/double-stranded DNA junctions in yeast whole cell extracts: Proteolytic degradation of the large subunit of replication protein A in ddc1Δ strains.

PubMed

Sukhanova, Maria V; D'Herin, Claudine; Boiteux, Serge; Lavrik, Olga I

2014-10-01

To characterize proteins that interact with single-stranded/double-stranded (ss/ds) DNA junctions in whole cell free extracts of Saccharomyces cerevisiae, we used [(32)P]-labeled photoreactive partial DNA duplexes containing a 3'-ss/ds-junction (3'-junction) or a 5'-ss/ds-junction (5'-junction). Identification of labeled proteins was achieved by MALDI-TOF mass spectrometry peptide mass fingerprinting and genetic analysis. In wild-type extract, one of the components of the Ddc1-Rad17-Mec3 complex, Ddc1, was found to be preferentially photocrosslinked at a 3'-junction. On the other hand, RPAp70, the large subunit of the replication protein A (RPA), was the predominant crosslinking product at a 5'-junction. Interestingly, ddc1Δ extracts did not display photocrosslinking of RPAp70 at a 5'-junction. The results show that RPAp70 crosslinked to DNA with a 5'-junction is subject to limited proteolysis in ddc1Δ extracts, whereas it is stable in WT, rad17Δ, mec3Δ and mec1Δ extracts. The degradation of the RPAp70-DNA adduct in ddc1Δ extract is strongly reduced in the presence of the proteasome inhibitor MG 132. We also addressed the question of the stability of free RPA, using anti-RPA antibodies. The results show that RPAp70 is also subject to proteolysis without photocrosslinking to DNA upon incubation in ddc1Δ extract. The data point to a novel property of Ddc1, modulating the turnover of DNA binding proteins such as RPAp70 by the proteasome. Copyright © 2014 Elsevier B.V. All rights reserved.

Formation of functional gap junctions in amniotic fluid-derived stem cells induced by transmembrane co-culture with neonatal rat cardiomyocytes

PubMed Central

Connell, Jennifer Petsche; Augustini, Emily; Moise, Kenneth J; Johnson, Anthony; Jacot, Jeffrey G

2013-01-01

Amniotic fluid-derived stem cells (AFSC) have been reported to differentiate into cardiomyocyte-like cells and form gap junctions when directly mixed and cultured with neonatal rat ventricular myocytes (NRVM). This study investigated whether or not culture of AFSC on the opposite side of a Transwell membrane from NRVM, allowing for contact and communication without confounding factors such as cell fusion, could direct cardiac differentiation and enhance gap junction formation. Results were compared to shared media (Transwell), conditioned media and monoculture media controls. After a 2-week culture period, AFSC did not express cardiac myosin heavy chain or troponin T in any co-culture group. Protein expression of cardiac calsequestrin 2 was up-regulated in direct transmembrane co-cultures and media control cultures compared to the other experimental groups, but all groups were up-regulated compared with undifferentiated AFSC cultures. Gap junction communication, assessed with a scrape-loading dye transfer assay, was significantly increased in direct transmembrane co-cultures compared to all other conditions. Gap junction communication corresponded with increased connexin 43 gene expression and decreased phosphorylation of connexin 43. Our results suggest that direct transmembrane co-culture does not induce cardiomyocyte differentiation of AFSC, though calsequestrin expression is increased. However, direct transmembrane co-culture does enhance connexin-43-mediated gap junction communication between AFSC. PMID:23634988

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

PubMed Central

Fox, Philip D.; Haberkorn, Christopher J.; Akin, Elizabeth J.; Seel, Peter J.; Krapf, Diego; Tamkun, Michael M.

2015-01-01

ABSTRACT Junctions between cortical endoplasmic reticulum (cER) and the plasma membrane are a subtle but ubiquitous feature in mammalian cells; however, very little is known about the functions and molecular interactions that are associated with neuronal ER–plasma-membrane junctions. Here, we report that Kv2.1 (also known as KCNB1), the primary delayed-rectifier K+ channel in the mammalian brain, induces the formation of ER–plasma-membrane junctions. Kv2.1 localizes to dense, cell-surface clusters that contain non-conducting channels, indicating that they have a function that is unrelated to membrane-potential regulation. Accordingly, Kv2.1 clusters function as membrane-trafficking hubs, providing platforms for delivery and retrieval of multiple membrane proteins. Using both total internal reflection fluorescence and electron microscopy we demonstrate that the clustered Kv2.1 plays a direct structural role in the induction of stable ER–plasma-membrane junctions in both transfected HEK 293 cells and cultured hippocampal neurons. Glutamate exposure results in a loss of Kv2.1 clusters in neurons and subsequent retraction of the cER from the plasma membrane. We propose Kv2.1-induced ER–plasma-membrane junctions represent a new macromolecular plasma-membrane complex that is sensitive to excitotoxic insult and functions as a scaffolding site for both membrane trafficking and Ca2+ signaling. PMID:25908859

Induced formation and maturation of acetylcholine receptor clusters in a defined 3D bio-artificial muscle.

PubMed

Wang, Lin; Shansky, Janet; Vandenburgh, Herman

2013-12-01

Dysfunction of the neuromuscular junction is involved in a wide range of muscular diseases. The development of neuromuscular junction through which skeletal muscle is innervated requires the functional modulation of acetylcholine receptor (AchR) clustering on myofibers. However, studies on AchR clustering in vitro are mostly done on monolayer muscle cell culture, which lacks a three-dimensional (3D) structure, a prominent limitation of the two-dimensional (2D) system. To enable a better understanding on the structure-function correlation underlying skeletal muscle innervation, a muscle system with a well-defined geometry mimicking the in vivo muscular setting is needed. Here, we report a 3D bio-artificial muscle (BAM) bioengineered from green fluorescent protein-transduced C3H murine myoblasts as a novel in vitro tissue-based model for muscle innervation studies. Our cell biological and molecular analysis showed that this BAM is structurally similar to in vivo muscle tissue and can reach the perinatal differentiation stage, higher than does 2D culture. Effective clustering and morphological maturation of AchRs on BAMs induced by agrin and laminin indicate the functional activity and plasticity of this BAM system toward innervation. Taken together, our results show that the BAM provides a favorable 3D environment that at least partially recapitulates real physiological skeletal muscle with regard to innervation. With a convenience of fabrication and manipulation, this 3D in vitro system offers a novel model for studying mechanisms underlying skeletal muscle innervation and testing therapeutic strategies for relevant nervous and muscular diseases.

EMMPRIN modulates epithelial barrier function through a MMP-mediated occludin cleavage: implications in dry eye disease.

PubMed

Huet, Eric; Vallée, Benoit; Delbé, Jean; Mourah, Samia; Prulière-Escabasse, Virginie; Tremouilleres, Magali; Kadomatsu, Kenji; Doan, Serge; Baudouin, Christophe; Menashi, Suzanne; Gabison, Eric E

2011-09-01

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Electron-Beam-Induced Current | Materials Science | NREL

Science.gov Websites

Electron-Beam-Induced Current Electron-Beam-Induced Current Photo of a GaAsP-on-Si solar cell. EBIC measure electron-beam-induced current (EBIC). In presence of an electrostatic field (p-n junction

The canonical WNT2 pathway and FSH interact to regulate gap junction assembly in mouse granulosa cells.

PubMed

Wang, Hong-Xing; Gillio-Meina, Carolina; Chen, Shuli; Gong, Xiang-Qun; Li, Tony Y; Bai, Donglin; Kidder, Gerald M

2013-08-01

WNTs are extracellular signaling molecules that exert their actions through receptors of the frizzled (FZD) family. Previous work indicated that WNT2 regulates cell proliferation in mouse granulosa cells acting through CTNNB1 (beta-catenin), a key component in canonical WNT signaling. In other cells, WNT signaling has been shown to regulate expression of connexin43 (CX43), a gap junction protein, as well as gap junction assembly. Since previous work demonstrated that CX43 is also essential in ovarian follicle development, the objective of this study was to determine if WNT2 regulates CX43 expression and/or gap-junctional intercellular communication (GJIC) in granulosa cells. WNT2 knockdown via siRNA markedly reduced CX43 expression and GJIC. CX43 expression, the extent of CX43-containing gap junction membrane, and GJIC were also reduced by CTNNB1 transient knockdown. CTNNB1 is mainly localized to the membranes between granulosa cells but disappeared from this location after WNT2 knockdown. Furthermore, CTNNB1 knockdown interfered with the ability of follicle-stimulating hormone (FSH) to promote the mobilization of CX43 into gap junctions. We propose that the WNT2/CTNNB1 pathway regulates CX43 expression and GJIC in granulosa cells by modulating CTNNB1 stability and localization in adherens junctions, and that this is essential for FSH stimulation of GJIC.

Task modulations of racial bias in neural responses to others' suffering.

PubMed

Sheng, Feng; Liu, Qiang; Li, Hong; Fang, Fang; Han, Shihui

2014-03-01

Recent event related brain potential research observed a greater frontal activity to pain expressions of racial in-group than out-group members and such racial bias in neural responses to others' suffering was modulated by task demands that emphasize race identity or painful feeling. However, as pain expressions activate multiple brain regions in the pain matrix, it remains unclear which part of the neural circuit in response to others' suffering undergoes modulations by task demands. We scanned Chinese adults, using functional MRI, while they categorized Asian and Caucasian faces with pain or neutral expressions in terms of race or identified painful feelings of each individual face. We found that pain vs. neutral expressions of Asian but not Caucasian faces activated the anterior cingulate (ACC) and anterior insular (AI) activity during race judgments. However, pain compared to race judgments increased ACC and AI activity to pain expressions of Caucasian but not Asian faces. Moreover, race judgments induced increased activity in the dorsal medial prefrontal cortex whereas pain judgments increased activity in the bilateral temporoparietal junction. The results suggest that task demands emphasizing an individual's painful feeling increase ACC/AI activities to pain expressions of racial out-group members and reduce the racial bias in empathic neural responses. © 2013.

An extensive investigation of work function modulated trapezoidal recessed channel MOSFET

NASA Astrophysics Data System (ADS)

Lenka, Annada Shankar; Mishra, Sikha; Mishra, Satyaranjan; Bhanja, Urmila; Mishra, Guru Prasad

2017-11-01

The concept of silicon on insulator (SOI) and grooved gate help to lessen the short channel effects (SCEs). Again the work function modulation along the metal gate gives a better drain current due to the uniform electric field along the channel. So all these concepts are combined and used in the proposed MOSFET structure for more improved performance. In this work, trapezoidal recessed channel silicon on insulator (TRC-SOI) MOSFET and work function modulated trapezoidal recessed channel silicon on insulator (WFM-TRC-SOI) MOSFET are compared with DC and RF parameters and later linearity of both the devices is tested. An analytical model is formulated by using a 2-D Poisson's equation and develops a compact equation for threshold voltage using minimum surface potential. In this work we analyze the effect of negative junction depth and the corner angle on various device parameters such as minimum surface potential, sub-threshold slope (SS), drain induced barrier lowering (DIBL) and threshold voltage. The analysis interprets that the switching performance of WFM-TRC-SOI MOSFET surpasses TRC-SOI MOSFET in terms of high Ion/Ioff ratio and also the proposed structure can minimize the short channel effects (SCEs) in RF application. The validity of proposed model has been verified with simulation result performed on Sentaurus TCAD device simulator.

Solid State Research.

DTIC Science & Technology

1982-11-15

Optics Y-Junction and Mach-Zehnder Interferometric Modulator Using Four -Port Scattering Matrix 7 1.3 Heterodyne and Direct Detection at 10 om with High...and of the Mach-Zehnder interferometric modulator have been analyzed using the four -port scattering i- matrix. The interferometric properties of the Y...USING FOUR -PORT SCATTERING MATRIX The scattering matrix formalism for a lossless four -port device has been used to describe the performance of the

Thermoelectric module

DOEpatents

Kortier, William E.; Mueller, John J.; Eggers, Philip E.

1980-07-08

A thermoelectric module containing lead telluride as the thermoelectric mrial is encapsulated as tightly as possible in a stainless steel canister to provide minimum void volume in the canister. The lead telluride thermoelectric elements are pressure-contacted to a tungsten hot strap and metallurgically bonded at the cold junction to iron shoes with a barrier layer of tin telluride between the iron shoe and the p-type lead telluride element.

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

Alloatti, L., E-mail: luca.alloatti@gmail.com; Cheian, D.; Ram, R. J.

A microring depletion modulator is demonstrated with T-shaped lateral p-n junctions used to realize efficient modulation while maximizing the RC limited bandwidth. The device having a 3 dB bandwidth of 13 GHz has been fabricated in a standard 45 nm microelectronics CMOS process. The cavity has a linewidth of 17 GHz and an average wavelength-shift of 9 pm/V in reverse-bias conditions.

Role of heteromeric gap junctions in the cytotoxicity of cisplatin.

PubMed

Tong, Xuhui; Dong, Shuying; Yu, Meiling; Wang, Qin; Tao, Liang

2013-08-09

In several systems, the presence of gap junctions made of a single connexin has been shown to enhance the cytotoxicity of cisplatin. However, most gap junction channels in vivo appear to be heteromeric (composed of more than one connexin isoform). Here we explore in HeLa cells the cytotoxicity to cisplatin that is enhanced by heteromeric gap junctions composed of Cx26 and Cx32, which have been shown to be more selective among biological permeants than the corresponding homomeric channels. We found that survival and subsequent proliferation of cells exposed to cisplatin were substantially reduced when gap junctions were present than when there were no gap junctions. Functional inhibition of gap junctions by oleamide enhanced survival/proliferation, and enhancement of gap junctions by retinoic acid decreased survival/proliferation. These effects occurred only in high density cultures, and the treatments were without effect when there was no opportunity for gap junction formation. The presence of functional gap junctions enhanced apoptosis as reflected in markers of both early-stage and late-stage apoptosis. Furthermore, analysis of caspases 3, 8 and 9 showed that functional gap junctions specifically induced apoptosis by the mitochondrial pathway. These results demonstrate that heteromeric Cx26/Cx32 gap junctions increase the cytotoxicity of cisplatin by induction of apoptosis via the mitochondrial pathway. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Process Development for Automated Solar Cell and Module Production. Task 4: Automated Array Assembly

NASA Technical Reports Server (NTRS)

1979-01-01

A baseline sequence for the manufacture of solar cell modules was specified. Starting with silicon wafers, the process goes through damage etching, texture etching, junction formation, plasma edge etch, aluminum back surface field formation, and screen printed metallization to produce finished solar cells. The cells were then series connected on a ribbon and bonded into a finished glass tedlar module. A number of steps required additional developmental effort to verify technical and economic feasibility. These steps include texture etching, plasma edge etch, aluminum back surface field formation, array layup and interconnect, and module edge sealing and framing.

Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence

PubMed Central

Bull, Cecilia; Freitas, Kelen CC; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

2014-01-01

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that NAcore astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior. PMID:24903651

Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence.

PubMed

Bull, Cecilia; Freitas, Kelen C C; Zou, Shiping; Poland, Ryan S; Syed, Wahab A; Urban, Daniel J; Minter, Sabrina C; Shelton, Keith L; Hauser, Kurt F; Negus, S Stevens; Knapp, Pamela E; Bowers, M Scott

2014-11-01

Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine whether nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core (NAcore) during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased NAcore astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 weeks abstinence was increased following microinjection of gap-junction hemichannel blockers into the NAcore at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 weeks abstinence was unaffected by NAcore gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in NAcore astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 weeks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that NAcore astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior.

Energy conditions and junction conditions

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

Marolf, Donald; Yaida, Sho; Mathematics Department, UCSB, Santa Barbara, California 93106

2005-08-15

We consider the familiar junction conditions described by Israel for thin timelike walls in Einstein-Hilbert gravity. One such condition requires the induced metric to be continuous across the wall. Now, there are many spacetimes with sources confined to a thin wall for which this condition is violated and the Israel formalism does not apply. However, we explore the conjecture that the induced metric is in fact continuous for any thin wall which models spacetimes containing only positive energy matter. Thus, the usual junction conditions would hold for all positive energy spacetimes. This conjecture is proven in various special cases, includingmore » the case of static spacetimes with spherical or planar symmetry as well as settings without symmetry which may be sufficiently well approximated by smooth spacetimes with well-behaved null geodesic congruences.« less

Ultra-low switching energy and scaling in electric-field-controlled nanoscale magnetic tunnel junctions with high resistance-area product

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

Grezes, C.; Alzate, J. G.; Cai, X.

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 memorymore » and logic integrated circuits.« less

On-chip integration of suspended InGaN/GaN multiple-quantum-well devices with versatile functionalities.

PubMed

Cai, Wei; Yang, Yongchao; Gao, Xumin; Yuan, Jialei; Yuan, Wei; Zhu, Hongbo; Wang, Yongjin

2016-03-21

We propose, fabricate and demonstrate on-chip photonic integration of suspended InGaN/GaN multiple quantum wells (MQWs) devices on the GaN-on-silicon platform. Both silicon removal and back wafer etching are conducted to obtain membrane-type devices, and suspended waveguides are used for the connection between p-n junction InGaN/GaN MQWs devices. As an in-plane data transmission system, the middle p-n junction InGaN/GaN MQWs device is used as a light emitting diode (LED) to deliver signals by modulating the intensity of the emitted light, and the other two devices act as photodetectors (PDs) to sense the light guided by the suspended waveguide and convert the photons into electrons, achieving 1 × 2 in-plane information transmission via visible light. Correspondingly, the three devices can function as independent PDs to realize multiple receivers for free space visible light communication. Further, the on-chip photonic platform can be used as an active electro-optical sensing system when the middle device acts as a PD and the other two devices serve as LEDs. The experimental results show that the auxiliary LED sources can enhance the amplitude of the induced photocurrent.

Electrical detection of the biological interaction of a charged peptide via gallium arsenide junction-field-effect transistors

PubMed Central

Lee, Kangho; Nair, Pradeep R.; Alam, Muhammad A.; Janes, David B.; Wampler, Heeyeon P.; Zemlyanov, Dmitry Y.; Ivanisevic, Albena

2008-01-01

GaAs junction-field-effect transistors (JFETs) are utilized to achieve label-free detection of biological interaction between a probe transactivating transcriptional activator (TAT) peptide and the target trans-activation-responsive (TAR) RNA. The TAT peptide is a short sequence derived from the human immunodeficiency virus-type 1 TAT protein. The GaAs JFETs are modified with a mixed adlayer of 1-octadecanethiol (ODT) and TAT peptide, with the ODT passivating the GaAs surface from polar ions in physiological solutions and the TAT peptide providing selective binding sites for TAR RNA. The devices modified with the mixed adlayer exhibit a negative pinch-off voltage (VP) shift, which is attributed to the fixed positive charges from the arginine-rich regions in the TAT peptide. Immersing the modified devices into a TAR RNA solution results in a large positive VP shift (>1 V) and a steeper subthreshold slope (∼80 mV∕decade), whereas “dummy” RNA induced a small positive VP shift (∼0.3 V) without a significant change in subthreshold slopes (∼330 mV∕decade). The observed modulation of device characteristics is analyzed with analytical modeling and two-dimensional numerical device simulations to investigate the electronic interactions between the GaAs JFETs and biological molecules. PMID:19484151

Highly strain-sensitive magnetostrictive tunnel magnetoresistance junctions

NASA Astrophysics Data System (ADS)

Tavassolizadeh, Ali; Hayes, Patrick; Rott, Karsten; Reiss, Günter; Quandt, Eckhard; Meyners, Dirk

2015-06-01

Tunnel magnetoresistance (TMR) junctions with CoFeB/MgO/CoFeB layers are promising for strain sensing applications due to their high TMR effect and magnetostrictive sense layer (CoFeB). TMR junctions available even in submicron dimensions can serve as strain sensors for microelectromechanical systems devices. Upon stress application, the magnetization configuration of such junctions changes due to the inverse magnetostriction effect resulting in strain-sensitive tunnel resistance. Here, strain sensitivity of round-shaped junctions with diameters of 11.3 μm, 19.2 μm, 30.5 μm, and 41.8 μm were investigated on macroscopic cantilevers using a four-point bending apparatus. This investigation mainly focuses on changes in hard-axis TMR loops caused by the stress-induced anisotropy. A macrospin model is proposed, supported by micromagnetic simulations, which describes the complete rotation of the sense layer magnetization within TMR loops of junctions, exposed to high stress. Below 0.2‰ tensile strain, a representative junction with 30.5 μm diameter exhibits a very large gauge factor of 2150. For such high gauge factor a bias field H = - 3.2 kA / m is applied in an angle equal to 3 π / 2 toward the pinned magnetization of the reference layer. The strain sensitivity strongly depends on the bias field. Applying stress along π / 4 against the induced magnetocrystalline anisotropy, both compressive and tensile strain can be identified by a unique sensor. More importantly, a configuration with a gauge factor of 400 at zero bias field is developed which results in a straightforward and compact measuring setup.

Induced unconventional superconductivity on the surface states of Bi2Te3 topological insulator.

PubMed

Charpentier, Sophie; Galletti, Luca; Kunakova, Gunta; Arpaia, Riccardo; Song, Yuxin; Baghdadi, Reza; Wang, Shu Min; Kalaboukhov, Alexei; Olsson, Eva; Tafuri, Francesco; Golubev, Dmitry; Linder, Jacob; Bauch, Thilo; Lombardi, Floriana

2017-12-08

Topological superconductivity is central to a variety of novel phenomena involving the interplay between topologically ordered phases and broken-symmetry states. The key ingredient is an unconventional order parameter, with an orbital component containing a chiral p x  + ip y wave term. Here we present phase-sensitive measurements, based on the quantum interference in nanoscale Josephson junctions, realized by using Bi 2 Te 3 topological insulator. We demonstrate that the induced superconductivity is unconventional and consistent with a sign-changing order parameter, such as a chiral p x  + ip y component. The magnetic field pattern of the junctions shows a dip at zero externally applied magnetic field, which is an incontrovertible signature of the simultaneous existence of 0 and π coupling within the junction, inherent to a non trivial order parameter phase. The nano-textured morphology of the Bi 2 Te 3 flakes, and the dramatic role played by thermal strain are the surprising key factors for the display of an unconventional induced order parameter.

Current-induced SQUID behavior of superconducting Nb nano-rings

NASA Astrophysics Data System (ADS)

Sharon, Omri J.; Shaulov, Avner; Berger, Jorge; Sharoni, Amos; Yeshurun, Yosef

2016-06-01

The critical temperature in a superconducting ring changes periodically with the magnetic flux threading it, giving rise to the well-known Little-Parks magnetoresistance oscillations. Periodic changes of the critical current in a superconducting quantum interference device (SQUID), consisting of two Josephson junctions in a ring, lead to a different type of magnetoresistance oscillations utilized in detecting extremely small changes in magnetic fields. Here we demonstrate current-induced switching between Little-Parks and SQUID magnetoresistance oscillations in a superconducting nano-ring without Josephson junctions. Our measurements in Nb nano-rings show that as the bias current increases, the parabolic Little-Parks magnetoresistance oscillations become sinusoidal and eventually transform into oscillations typical of a SQUID. We associate this phenomenon with the flux-induced non-uniformity of the order parameter along a superconducting nano-ring, arising from the superconducting leads (‘arms’) attached to it. Current enhanced phase slip rates at the points with minimal order parameter create effective Josephson junctions in the ring, switching it into a SQUID.

BDNF-TrkB Signaling Coupled to nPKCε and cPKCβI Modulate the Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at the Neuromuscular Junction

PubMed Central

Simó, Anna; Just-Borràs, Laia; Cilleros-Mañé, Víctor; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A.; Tomàs, Josep

2018-01-01

Munc18-1, a neuron-specific member of the Sec1/Munc18 family, is involved in neurotransmitter release by binding tightly to syntaxin. Munc18-1 is phosphorylated by PKC on Ser-306 and Ser-313 in vitro which reduces the amount of Munc18-1 able to bind syntaxin. We have previously identified that PKC is involved in neurotransmitter release when continuous electrical stimulation imposes a moderate activity on the NMJ and that muscle contraction through TrkB has an important impact on presynaptic PKC isoforms levels, specifically cPKCβI and nPKCε. Therefore, the present study was designed to understand how Munc18-1 phosphorylation is affected by (1) synaptic activity at the neuromuscular junction, (2) nPKCε and cPKCβI isoforms activity, (3) muscle contraction per se, and (4) the BDNF/TrkB signaling in a neuromuscular activity-dependent manner. We performed immunohistochemistry and confocal techniques to evidence the presynaptic location of Munc18-1 in the rat diaphragm muscle. To study synaptic activity, we stimulated the phrenic nerve (1 Hz, 30 min) with or without contraction (abolished by μ-conotoxin GIIIB). Specific inhibitory reagents were used to block nPKCε and cPKCβI activity and to modulate the tropomyosin receptor kinase B (TrkB). Main results obtained from Western blot experiments showed that phosphorylation of Munc18-1 at Ser-313 increases in response to a signaling mechanism initiated by synaptic activity and directly mediated by nPKCε. Otherwise, cPKCβI and TrkB activities work together to prevent this synaptic activity–induced Munc18-1 phosphorylation by a negative regulation of cPKCβI over nPKCε. Therefore, a balance between the activities of these PKC isoforms could be a relevant cue in the regulation of the exocytotic apparatus. The results also demonstrate that muscle contraction prevents the synaptic activity–induced Munc18-1 phosphorylation through a mechanism that opposes the TrkB/cPKCβI/nPKCε signaling. PMID:29946239

BDNF-TrkB Signaling Coupled to nPKCε and cPKCβI Modulate the Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at the Neuromuscular Junction.

PubMed

Simó, Anna; Just-Borràs, Laia; Cilleros-Mañé, Víctor; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A; Tomàs, Josep

2018-01-01

Munc18-1, a neuron-specific member of the Sec1/Munc18 family, is involved in neurotransmitter release by binding tightly to syntaxin. Munc18-1 is phosphorylated by PKC on Ser-306 and Ser-313 in vitro which reduces the amount of Munc18-1 able to bind syntaxin. We have previously identified that PKC is involved in neurotransmitter release when continuous electrical stimulation imposes a moderate activity on the NMJ and that muscle contraction through TrkB has an important impact on presynaptic PKC isoforms levels, specifically cPKCβI and nPKCε. Therefore, the present study was designed to understand how Munc18-1 phosphorylation is affected by (1) synaptic activity at the neuromuscular junction, (2) nPKCε and cPKCβI isoforms activity, (3) muscle contraction per se , and (4) the BDNF/TrkB signaling in a neuromuscular activity-dependent manner. We performed immunohistochemistry and confocal techniques to evidence the presynaptic location of Munc18-1 in the rat diaphragm muscle. To study synaptic activity, we stimulated the phrenic nerve (1 Hz, 30 min) with or without contraction (abolished by μ-conotoxin GIIIB). Specific inhibitory reagents were used to block nPKCε and cPKCβI activity and to modulate the tropomyosin receptor kinase B (TrkB). Main results obtained from Western blot experiments showed that phosphorylation of Munc18-1 at Ser-313 increases in response to a signaling mechanism initiated by synaptic activity and directly mediated by nPKCε. Otherwise, cPKCβI and TrkB activities work together to prevent this synaptic activity-induced Munc18-1 phosphorylation by a negative regulation of cPKCβI over nPKCε. Therefore, a balance between the activities of these PKC isoforms could be a relevant cue in the regulation of the exocytotic apparatus. The results also demonstrate that muscle contraction prevents the synaptic activity-induced Munc18-1 phosphorylation through a mechanism that opposes the TrkB/cPKCβI/nPKCε signaling.

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

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

Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.

Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2)more » after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP2A/MMP-2 induced PCB153-induced dysfunction of occludin. • Disrupted lipid rafts modulated PCB153-induced increase of permeability. • Lipid rafts act as a signaling platform for PCB153-induced dysfunction of occludin.« less

Economic viability of thin-film tandem solar modules in the United States

NASA Astrophysics Data System (ADS)

Sofia, Sarah E.; Mailoa, Jonathan P.; Weiss, Dirk N.; Stanbery, Billy J.; Buonassisi, Tonio; Peters, I. Marius

2018-05-01

Tandem solar cells are more efficient but more expensive per unit area than established single-junction (SJ) solar cells. To understand when specific tandem architectures should be utilized, we evaluate the cost-effectiveness of different II-VI-based thin-film tandem solar cells and compare them to the SJ subcells. Levelized cost of electricity (LCOE) and energy yield are calculated for four technologies: industrial cadmium telluride and copper indium gallium selenide, and their hypothetical two-terminal (series-connected subcells) and four-terminal (electrically independent subcells) tandems, assuming record SJ quality subcells. Different climatic conditions and scales (residential and utility scale) are considered. We show that, for US residential systems with current balance-of-system costs, the four-terminal tandem has the lowest LCOE because of its superior energy yield, even though it has the highest US per watt (US W-1) module cost. For utility-scale systems, the lowest LCOE architecture is the cadmium telluride single junction, the lowest US W-1 module. The two-terminal tandem requires decreased subcell absorber costs to reach competitiveness over the four-terminal one.

Transport and Junction Physics of Semiconductor-Metal Eutectic Composites

DTIC Science & Technology

1988-06-01

eutectic junction and includes the method for making contacts as well as current-voltage (I-V), capacitance- voltage (C-V), and electron-beam-induced current...junction was performed with another RTA at 8000C to 9000C for 10 s. This technique also worked well to provide the necessary ohmic contact. The necessary...solid state diffusion of Ta and Si. The diode is well behaved, with an ideality factor n = 1.10 ± 0.05. Deviation from the straight line forward

Gap Junction Intercellular Communication: A Review of a Potential Platform to Modulate Craniofacial Tissue Engineering

PubMed Central

Rossello, Ricardo A.; Kohn, David H.

2009-01-01

Defects in craniofacial tissues, resulting from trauma, congenital abnormalities, oncologic resection or progressive deforming diseases, may result in aesthetic deformity, pain and reduced function. Restoring the structure, function and aesthetics of craniofacial tissues represents a substantial clinical problem in need of new solutions. More biologically-interactive biomaterials could potentially improve the treatment of craniofacial defects, and an understanding of developmental processes may help identify strategies and materials that can be used in tissue engineering. One such strategy that can potentially advance tissue engineering is cell–cell communication. Gap junction intercellular communication is the most direct way of achieving such signaling. Gap junction communication through connexin-mediated junctions, in particular connexin 43 (Cx43), plays a major role bone development. Given the important role of Cx43 in controlling development and differentiation, especially in bone cells, controlling the expression of Cx43 may provide control over cell-to-cell communication and may help overcome some of the challenges in craniofacial tissue engineering. Following a review of gap junctions in bone cells, the ability to enhance cell–cell communication and osteogenic differentiation via control of gap junctions is discussed, as is the potential utility of this approach in craniofacial tissue engineering. PMID:18481782

Gap junctions between CA3 pyramidal cells contribute to network synchronization in neonatal hippocampus.

PubMed

Molchanova, Svetlana M; Huupponen, Johanna; Lauri, Sari E; Taira, Tomi

2016-08-01

Direct electrical coupling between neurons through gap junctions is prominent during development, when synaptic connectivity is scarce, providing the additional intercellular connectivity. However, functional studies of gap junctions are hampered by the unspecificity of pharmacological tools available. Here we have investigated gap-junctional coupling between CA3 pyramidal cells in neonatal hippocampus and its contribution to early network activity. Four different gap junction inhibitors, including the general blocker carbenoxolone, decreased the frequency of network activity bursts in CA3 area of hippocampus of P3-6 rats, suggesting the involvement of electrical connections in the generation of spontaneous network activity. In CA3 pyramidal cells, spikelets evoked by local stimulation of stratum oriens, were inhibited by carbenoxolone, but not by inhibitors of glutamatergic and GABAergic synaptic transmission, signifying the presence of electrical connectivity through axo-axonic gap junctions. Carbenoxolone also decreased the success rate of firing antidromic action potentials in response to stimulation, and changed the pattern of spontaneous action potential firing of CA3 pyramidal cells. Altogether, these data suggest that electrical coupling of CA3 pyramidal cells contribute to the generation of the early network events in neonatal hippocampus by modulating their firing pattern and synchronization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alterations in gap junction connexin43/connexin45 ratio mediate a transition from quiescence to excitation in a mathematical model of the myometrium

PubMed Central

Sheldon, Rachel E.; Mashayamombe, Chipo; Shi, Shao-Qing; Garfield, Robert E.; Shmygol, Anatoly; Blanks, Andrew M.; van den Berg, Hugo A.

2014-01-01

The smooth muscle cells of the uterus contract in unison during delivery. These cells achieve coordinated activity via electrical connections called gap junctions which consist of aggregated connexin proteins such as connexin43 and connexin45. The density of gap junctions governs the excitability of the myometrium (among other factors). An increase in gap junction density occurs immediately prior to parturition. We extend a mathematical model of the myometrium by incorporating the voltage-dependence of gap junctions that has been demonstrated in the experimental literature. Two functional subtypes exist, corresponding to systems with predominantly connexin43 and predominantly connexin45, respectively. Our simulation results indicate that the gap junction protein connexin45 acts as a negative modulator of uterine excitability, and hence, activity. A network with a higher proportion of connexin45 relative to connexin43 is unable to excite every cell. Connexin45 has much more rapid gating kinetics than connexin43 which we show limits the maximum duration of a local burst of activity. We propose that this effect regulates the degree of synchronous excitation attained during a contraction. Our results support the hypothesis that as labour approaches, connexin45 is downregulated to allow action potentials to spread more readily through the myometrium. PMID:25401181

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

PubMed Central

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

2017-01-01

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

Single gate p-n junctions in graphene-ferroelectric devices

NASA Astrophysics Data System (ADS)

Hinnefeld, J. Henry; Xu, Ruijuan; Rogers, Steven; Pandya, Shishir; Shim, Moonsub; Martin, Lane W.; Mason, Nadya

2016-05-01

Graphene's linear dispersion relation and the attendant implications for bipolar electronics applications have motivated a range of experimental efforts aimed at producing p-n junctions in graphene. Here we report electrical transport measurements of graphene p-n junctions formed via simple modifications to a PbZr0.2Ti0.8O3 substrate, combined with a self-assembled layer of ambient environmental dopants. We show that the substrate configuration controls the local doping region, and that the p-n junction behavior can be controlled with a single gate. Finally, we show that the ferroelectric substrate induces a hysteresis in the environmental doping which can be utilized to activate and deactivate the doping, yielding an "on-demand" p-n junction in graphene controlled by a single, universal backgate.

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

PubMed

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.

Optical pulse generation in a transistor laser via intra-cavity photon-assisted tunneling and excess base carrier redistribution

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

Feng, M.; Iverson, E. W.; Wang, C. Y.

2015-11-02

For a direct-gap semiconductor (e.g., a p-n junction), photon-assisted tunneling is known to exhibit a high nonlinear absorption. In a transistor laser, as discussed here, the coherent photons generated at the quantum well interact with the collector junction field and “assist” electron tunneling from base to collector, thus resulting in the nonlinear modulation of the laser and the realization of optical pulse generation. 1 and 2 GHz optical pulses are demonstrated in the transistor laser using collector voltage control.

Differential protein modulation by ketoprofen and ibuprofen underlines different cellular response by gastric epithelium.

PubMed

Brandolini, Laura; d'Angelo, Michele; Antonosante, Andrea; Villa, Sara; Cristiano, Loredana; Castelli, Vanessa; Benedetti, Elisabetta; Catanesi, Mariano; Aramini, Andrea; Luini, Alberto; Parashuraman, Seetharaman; Mayo, Emilia; Giordano, Antonio; Cimini, Annamaria; Allegretti, Marcello

2018-03-01

Ketoprofen L-lysine salt (KLS), is widely used due to its analgesic efficacy and tolerability, and L-lysine was reported to increase the solubility and the gastric tolerance of ketoprofen. In a recent report, L-lysine salification has been shown to exert a gastroprotective effect due to its specific ability to counteract the NSAIDs-induced oxidative stress and up-regulate gastroprotective proteins. In order to derive further insights into the safety and efficacy profile of KLS, in this study we additionally compared the effect of lysine and arginine, another amino acid counterion commonly used for NSAIDs salification, in control and in ethanol challenged human gastric mucosa model. KLS is widely used for the control of post-surgical pain and for the management of pain and fever in inflammatory conditions in children and adults. It is generally well tolerated in pediatric patients, and data from three studies in >900 children indicate that oral administration is well tolerated when administered for up to 3 weeks after surgery. Since only few studies have so far investigated the effect of ketoprofen on gastric mucosa maintenance and adaptive mechanisms, in the second part of the study we applied the cMap approach to compare ketoprofen-induced and ibuprofen-induced gene expression profiles in order to explore compound-specific targeted biological pathways. Among the several genes exclusively modulated by ketoprofen, our attention was particularly focused on genes involved in the maintenance of gastric mucosa barrier integrity (cell junctions, morphology, and viability). The hypothesis was further validated by Real-time PCR. © 2017 Wiley Periodicals, Inc.

CSReport: A New Computational Tool Designed for Automatic Analysis of Class Switch Recombination Junctions Sequenced by High-Throughput Sequencing.

PubMed

Boyer, François; Boutouil, Hend; Dalloul, Iman; Dalloul, Zeinab; Cook-Moreau, Jeanne; Aldigier, Jean-Claude; Carrion, Claire; Herve, Bastien; Scaon, Erwan; Cogné, Michel; Péron, Sophie

2017-05-15

B cells ensure humoral immune responses due to the production of Ag-specific memory B cells and Ab-secreting plasma cells. In secondary lymphoid organs, Ag-driven B cell activation induces terminal maturation and Ig isotype class switch (class switch recombination [CSR]). CSR creates a virtually unique IgH locus in every B cell clone by intrachromosomal recombination between two switch (S) regions upstream of each C region gene. Amount and structural features of CSR junctions reveal valuable information about the CSR mechanism, and analysis of CSR junctions is useful in basic and clinical research studies of B cell functions. To provide an automated tool able to analyze large data sets of CSR junction sequences produced by high-throughput sequencing (HTS), we designed CSReport, a software program dedicated to support analysis of CSR recombination junctions sequenced with a HTS-based protocol (Ion Torrent technology). CSReport was assessed using simulated data sets of CSR junctions and then used for analysis of Sμ-Sα and Sμ-Sγ1 junctions from CH12F3 cells and primary murine B cells, respectively. CSReport identifies junction segment breakpoints on reference sequences and junction structure (blunt-ended junctions or junctions with insertions or microhomology). Besides the ability to analyze unprecedentedly large libraries of junction sequences, CSReport will provide a unified framework for CSR junction studies. Our results show that CSReport is an accurate tool for analysis of sequences from our HTS-based protocol for CSR junctions, thereby facilitating and accelerating their study. Copyright © 2017 by The American Association of Immunologists, Inc.

Redox-mediated regulation of connexin proteins; focus on nitric oxide.

PubMed

García, Isaac E; Sánchez, Helmuth A; Martínez, Agustín D; Retamal, Mauricio A

2018-01-01

Connexins are membrane proteins that form hemichannels and gap junction channels at the plasma membrane. Through these channels connexins participate in autocrine and paracrine intercellular communication. Connexin-based channels are tightly regulated by membrane potential, phosphorylation, pH, redox potential, and divalent cations, among others, and the imbalance of this regulation have been linked to many acquired and genetic diseases. Concerning the redox potential regulation, the nitric oxide (NO) has been described as a modulator of the hemichannels and gap junction channels properties. However, how NO regulates these channels is not well understood. In this mini-review, we summarize the current knowledge about the effects of redox potential focused in NO on the trafficking, formation and functional properties of hemichannels and gap junction channels. Copyright © 2017 Elsevier B.V. All rights reserved.

Switchable diode effect in oxygen vacancy-modulated SrTiO3 single crystal

NASA Astrophysics Data System (ADS)

Pan, Xinqiang; Shuai, Yao; Wu, Chuangui; Luo, Wenbo; Sun, Xiangyu; Zeng, Huizhong; Bai, Xiaoyuan; Gong, Chaoguan; Jian, Ke; Zhang, Lu; Guo, Hongliang; Tian, Benlang; Zhang, Wanli

2017-09-01

SrTiO3 (STO) single crystal wafer was annealed in vacuum, and co-planar metal-insulator-metal structure of Pt/Ti/STO/Ti/Pt were formed by sputtering Pt/Ti electrodes onto the surface of STO after annealing. The forming-free resistive switching behavior with self-compliance property was observed in the sample. The sample showed switchable diode effect, which is explained by a simple model that redistribution of oxygen vacancies (OVs) under the external electric field results in the formation of n-n+ junction or n+-n junction (n donated n-type semiconductor; n+ donated heavily doped n-type semiconductor). The self-compliance property is also interpreted by the formation of n-n+/n+-n junction caused by the migration of the OVs under the electric field.

Classical heat transport in anharmonic molecular junctions: exact solutions.

PubMed

Liu, Sha; Agarwalla, Bijay Kumar; Wang, Jian-Sheng; Li, Baowen

2013-02-01

We study full counting statistics for classical heat transport through anharmonic or nonlinear molecular junctions formed by interacting oscillators. An analytical result of the steady-state heat flux for an overdamped anharmonic junction with arbitrary temperature bias is obtained. It is found that the thermal conductance can be expressed in terms of a temperature-dependent effective force constant. The role of anharmonicity is identified. We also give the general formula for the second cumulant of heat in steady state, as well as the average geometric heat flux when two system parameters are modulated adiabatically. We present an anharmonic example for which all cumulants for heat can be obtained exactly. For a bounded single oscillator model with mass we found that the cumulants are independent of the nonlinear potential.

Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network

PubMed Central

Sun, Shuguo; Irvine, Kenneth D.

2016-01-01

The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell-cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated, and to define their respective contributions in vivo. PMID:27268910

Collective Calcium Signaling of Defective Multicellular Networks

NASA Astrophysics Data System (ADS)

Potter, Garrett; Sun, Bo

2015-03-01

A communicating multicellular network processes environmental cues into collective cellular dynamics. We have previously demonstrated that, when excited by extracellular ATP, fibroblast monolayers generate correlated calcium dynamics modulated by both the stimuli and gap junction communication between the cells. However, just as a well-connected neural network may be compromised by abnormal neurons, a tissue monolayer can also be defective with cancer cells, which typically have down regulated gap junctions. To understand the collective cellular dynamics in a defective multicellular network we have studied the calcium signaling of co-cultured breast cancer cells and fibroblast cells in various concentrations of ATP delivered through microfluidic devices. Our results demonstrate that cancer cells respond faster, generate singular spikes, and are more synchronous across all stimuli concentrations. Additionally, fibroblast cells exhibit persistent calcium oscillations that increase in regularity with greater stimuli. To interpret these results we quantitatively analyzed the immunostaining of purigenic receptors and gap junction channels. The results confirm our hypothesis that collective dynamics are mainly determined by the availability of gap junction communications.

Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer

PubMed Central

Jin, Xin; Valiente, Manuel; Er, Ekrem Emrah; Lopez-Soto, Alejandro; Jacob, Leni; Patwa, Ruzeen; Shah, Hardik; Xu, Ke; Cross, Justin R.; Massagué, Joan

2016-01-01

SUMMARY Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in promoting brain metastasis. Breast and lung cancer cells express protocadherin 7 (PCDH7) to favor the assembly of carcinoma-astrocyte gap junctions composed of connexin 43 (Cx43). Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells employ these channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and production of inflammatory cytokines IFNα and TNFα. As paracrine signals, these factors activate the STAT1 and NF-κB pathways in brain metastatic cells, which support tumour growth and chemoresistance. The orally bioavailable modulators of gap junctions meclofenamate and tonabersat break this paracrine loop, and we provide proof-of-principle for the applicability of this therapeutic strategy to treat established brain metastasis. PMID:27225120

Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer.

PubMed

Chen, Qing; Boire, Adrienne; Jin, Xin; Valiente, Manuel; Er, Ekrem Emrah; Lopez-Soto, Alejandro; Jacob, Leni; Patwa, Ruzeen; Shah, Hardik; Xu, Ke; Cross, Justin R; Massagué, Joan

2016-05-26

Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in promoting brain metastasis. We show that human and mouse breast and lung cancer cells express protocadherin 7 (PCDH7), which promotes the assembly of carcinoma-astrocyte gap junctions composed of connexin 43 (Cx43). Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells use these channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and production of inflammatory cytokines such as interferon-α (IFNα) and tumour necrosis factor (TNF). As paracrine signals, these factors activate the STAT1 and NF-κB pathways in brain metastatic cells, thereby supporting tumour growth and chemoresistance. The orally bioavailable modulators of gap junctions meclofenamate and tonabersat break this paracrine loop, and we provide proof-of-principle that these drugs could be used to treat established brain metastasis.

Impact of semiconducting electrodes on the electroresistance of ferroelectric tunnel junctions

NASA Astrophysics Data System (ADS)

Asa, M.; Bertacco, R.

2018-02-01

Ferroelectric tunnel junctions are promising candidates for the realization of energy-efficient digital memories and analog memcomputing devices. In this work, we investigate the impact of a semiconducting layer in series to the junction on the sign of electroresistance. To this scope, we compare tunnel junctions fabricated out of Pt/BaTiO3/La1/3Sr2/3MnO3 (LSMO) and Pt/BaTiO3/Nb:SrTiO3 (Nb:STO) heterostructures, displaying an opposite sign of the electroresistance. By capacitance-voltage profiling, we observe a behavior typical of Metal-Oxide-Semiconductor tunnel devices in both cases but compatible with the opposite sign of charge carriers in the semiconducting layer. While Nb:STO displays the expected n-type semiconducting character, metallic LSMO develops an interfacial p-type semiconducting layer. The different types of carriers at the semiconducting interfaces and the modulation of the depleted region by the ferroelectric charge have a deep impact on electroresistance, possibly accounting for the different sign observed in the two systems.

Traction force dynamics predict gap formation in activated endothelium

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

Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van

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 heterogeneousmore » 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.« less

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

PubMed

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

2016-12-02

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

Local GABAergic signaling within sensory ganglia controls peripheral nociceptive transmission

PubMed Central

Du, Xiaona; Hao, Han; Yang, Yuehui; Huang, Sha; Wang, Caixue; Gigout, Sylvain; Ramli, Rosmaliza; Li, Xinmeng; Jaworska, Ewa; Edwards, Ian; Yanagawa, Yuchio; Qi, Jinlong; Guan, Bingcai; Jaffe, David B.; Zhang, Hailin

2017-01-01

The integration of somatosensory information is generally assumed to be a function of the central nervous system (CNS). Here we describe fully functional GABAergic communication within rodent peripheral sensory ganglia and show that it can modulate transmission of pain-related signals from the peripheral sensory nerves to the CNS. We found that sensory neurons express major proteins necessary for GABA synthesis and release and that sensory neurons released GABA in response to depolarization. In vivo focal infusion of GABA or GABA reuptake inhibitor to sensory ganglia dramatically reduced acute peripherally induced nociception and alleviated neuropathic and inflammatory pain. In addition, focal application of GABA receptor antagonists to sensory ganglia triggered or exacerbated peripherally induced nociception. We also demonstrated that chemogenetic or optogenetic depolarization of GABAergic dorsal root ganglion neurons in vivo reduced acute and chronic peripherally induced nociception. Mechanistically, GABA depolarized the majority of sensory neuron somata, yet produced a net inhibitory effect on the nociceptive transmission due to the filtering effect at nociceptive fiber T-junctions. Our findings indicate that peripheral somatosensory ganglia represent a hitherto underappreciated site of somatosensory signal integration and offer a potential target for therapeutic intervention. PMID:28375159

Spin Transport in Electric-Barrier-Modulated Ferromagnetic/Normal/Ferromagnetic Monolayer Zigzag MoS2 Nanoribbon Junction

NASA Astrophysics Data System (ADS)

Xia, Y.-Y.; Yuan, R.-Y.; Yang, Q.-J.; Sun, Q.; Zheng, J.; Guo, Y.

In this paper, with the three-band tight-binding model and non-equilibrium Green’s function technique, we investigate spin transport in electric-barrier-modulated Ferromagnetic/Normal/Ferromagnetic (F/N/F) monolayer (ML) zigzag MoS2 nanoribbon junction. The results demonstrate that once the double electric barriers structure emerges, the oscillations of spin conductances become violent, especially for spin-down conductance, the numbers of resonant peaks increase obviously, thus we can obtain 100% spin polarization in the low energy region. It is also found that with the intensity of the exchange field enhancement, the resonant peaks of spin-up and spin-down conductances move in the opposite direction in a certain energy region. As a consequence, the spin-down conductance can be filtered out completely. The findings here indicate that the present structure may be considered as a good candidate for spin filter.

Cell chip temperature measurements in different operation regimes of HCPV modules

NASA Astrophysics Data System (ADS)

Rumyantsev, V. D.; Chekalin, A. V.; Davidyuk, N. Yu.; Malevskiy, D. A.; Pokrovskiy, P. V.; Sadchikov, N. A.; Pan'chak, A. N.

2013-09-01

A new method has been developed for accurate measurements of the solar cell temperature in maximum power point (MPP) operation regime in comparison with that in open circuit (OC) regime (TMPP and TOC). For this, an electronic circuit has been elaborated for fast variation of the cell load conditions and for voltage measurements, so that VOC values could serve as an indicator of TMPP at the first moment after the load disconnection. The method was verified in indoor investigations of the single-junction AlGaAs/GaAs cells under CW laser irradiation, where different modifications of the heat spreaders were involved. PV modules of the "SMALFOC" design (Small-size concentrators; Multijunction cells; "All-glass" structure; Lamination technology; Fresnel Optics for Concentration) with triple-junction InGaP/GaAs/Ge cells were examined outdoors to evaluate temperature regimes of their operation.

Josephson-like spin current in junctions composed of antiferromagnets and ferromagnets

NASA Astrophysics Data System (ADS)

Moor, A.; Volkov, A. F.; Efetov, K. B.

2012-01-01

We study Josephson-like junctions formed by materials with antiferromagnetic (AF) order parameters. As an antiferromagnet, we consider a two-band material in which a spin density wave (SDW) arises. This could be Fe-based pnictides in the temperature interval Tc≤T≤TN, where Tc and TN are the critical temperatures for the superconducting and antiferromagnetic transitions, respectively. The spin current jSp in AF/F/AF junctions with a ballistic ferromagnetic layer and in tunnel AF/I/AF junctions is calculated. It depends on the angle between the magnetization vectors in the AF leads in the same way as the Josephson current depends on the phase difference of the superconducting order parameters in S/I/S tunnel junctions. It turns out that in AF/F/AF junctions, two components of the SDW order parameter are induced in the F layer. One of them oscillates in space with a short period ξF,b˜ℏv/H, while the other decays monotonously from the interfaces over a long distance of the order ξN,b=ℏv/2πT (where v, H, and T are the Fermi velocity, the exchange energy, and the temperature, respectively; the subindex “b” denotes the ballistic case). This is a clear analogy with the case of Josephson S/F/S junctions with a nonhomogeneous magnetization where short- and long-range condensate components are induced in the F layer. However, in contrast to the charge Josephson current in S/F/S junctions, the spin current in AF/F/AF junctions is not constant in space, but oscillates in the ballistic F layer. We also calculate the dependence of jSp on the deviation from the ideal nesting in the AF/I/AF junctions. The spin current is maximal in the insulating phase of the AF and decreases in the metallic phase. It turns to zero at the Neel point when the amplitude of the SDW is zero and changes sign for certain values of the detuning parameter.

Solid State Research

DTIC Science & Technology

1985-02-15

Wave Mach-Zehnder Interferometric Modulator with Center-Tapped Electrode. The Two Y Junctions have 2° Full Branching Angles, and the Direction of...and < 110> Directions 20 3-6 Nomarski Micrographs of Seeded 50-/um Ge-on-Insulator Islands After ZMR and Defect Etching 21 3-7 Scanning Electron...achieved to date in this long- wavelength region. A LiNb03 guided-wave interferometric modulator has been demonstrated at A. = 3.39 /um with a

Catheter ablation of junctional ectopic tachycardia in children, with preservation of atrioventricular conduction.

PubMed

Emmel, M; Sreeram, N; Brockmeier, K

2005-04-01

Idiopathic junctional ectopic tachycardia is a rare arrhythmia in children. Several studies have demonstrated that drug therapy is often ineffective and sometimes the only achieved effect is rate control. Early presentation and frequent recurrence are associated with adverse outcome. Three consecutive children, aged 9, 7 and 12 years respectively, underwent radiofrequency catheter ablation for junctional ectopic tachycardia, after having failed antiarrhythmic drug therapy. The entire His bundle was plotted out and marked, using the Localisa navigation system. The arrhythmia was readily and repeatedly inducible using intravenous isoprenaline infusion and the site of earliest retrograde conduction during tachycardia could be assessed. Ablations were performed in sinus rhythm, empirically targeting the site of earliest retrograde conduction during tachycardia. This approach was successful in abolishing tachyarrhythmia in the first two patients, in whom the successful ablation site was located superoparaseptally. In the third patient, junctional ectopic tachycardia was inducible, despite abolishing retrograde atrial activation, in a septal location on the tricuspid valve annulus. Further ablations in the superoparaseptal region, closer to the His bundle, were successful in rendering tachyarrhythmia noninducible. Over a median follow-up of 10 months, none of the patients has had recurrence of arrhythmia, despite discontinuing all antiarrhythmic medications. Radio frequency catheter ablation of junctional ectopic tachycardia is feasible with preservation of atrioventricular conduction.

Large-area triple-junction a-Si alloy production scaleup. Annual subcontract report, 17 March 1993--18 March 1994

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

Oswald, R.; Morris, J.

1994-11-01

The objective of this subcontract over its three-year duration is to advance Solarex`s photovoltaic manufacturing technologies, reduce its a-Si:H module production costs, increase module performance and expand the Solarex commercial production capacity. Solarex shall meet these objectives by improving the deposition and quality of the transparent front contact, by optimizing the laser patterning process, scaling-up the semiconductor deposition process, improving the back contact deposition, scaling-up and improving the encapsulation and testing of its a-Si:H modules. In the Phase 2 portion of this subcontract, Solarex focused on improving deposition of the front contact, investigating alternate feed stocks for the front contact,more » maximizing throughput and area utilization for all laser scribes, optimizing a-Si:H deposition equipment to achieve uniform deposition over large-areas, optimizing the triple-junction module fabrication process, evaluating the materials to deposit the rear contact, and optimizing the combination of isolation scribe and encapsulant to pass the wet high potential test. Progress is reported on the following: Front contact development; Laser scribe process development; Amorphous silicon based semiconductor deposition; Rear contact deposition process; Frit/bus/wire/frame; Materials handling; and Environmental test, yield and performance analysis.« less

Trial-Run of a Junction-Box Attachment Test for Use in Photovoltaic Module Qualification: Preprint

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

Miller, D. C.; Deibert, S. L.; Wohlgemuth, J. H.

Engineering robust adhesion of the junction box (j-box) is a hurdle typically encountered by photovoltaic module manufacturers during product development and manufacturing process control. There are historical incidences of adverse effects (e.g., fires) caused when the j-box/adhesive/module system has failed in the field. The addition of a weight to the j-box during the 'damp-heat,' 'thermal-cycle,' or 'creep' tests within the IEC qualification protocol is proposed to verify the basic robustness of the adhesion system. The details of the proposed test are described, in addition to a trial-run of the test procedure. The described experiments examine four moisture-cured silicones, four foammore » tapes, and a hot-melt adhesive used in conjunction with glass, KPE, THV, and TPE substrates. For the purpose of validating the experiment, j-boxes were adhered to a substrate, loaded with a prescribed weight, and then subjected to aging. The replicate mock-modules were aged in an environmental chamber (at 85 degrees C/85% relative humidity for 1000 hours; then 100 degrees C/<10% relative humidity for 200 hours) or fielded in Golden (CO), Miami (FL), and Phoenix (AZ) for one year. Attachment strength tests, including pluck and shear test geometries, were also performed on smaller component specimens.« less

Trial Run of a Junction-Box Attachment Test for Use in Photovoltaic Module Qualification (Presentation)

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

Miller, D.; Deibert, S.; Wohlgemuth, J.

Engineering robust adhesion of the junction-box (j-box) is a hurdle typically encountered by photovoltaic (PV) module manufacturers during product development and manufacturing process control. There are historical incidences of adverse effects (e.g., fires), caused when the j-box/adhesive/module system has failed in the field. The addition of a weight to the j-box during the 'damp-heat', 'thermal-cycle', or 'creep' tests within the IEC qualification protocol is proposed to verify the basic robustness of the adhesion system. The details of the proposed test are described, in addition to a trial run of the test procedure. The described experiments examine 4 moisture-cured silicones, 4more » foam tapes, and a hot-melt adhesive used in conjunction with glass, KPE, THV, and TPE substrates. For the purpose of validating the experiment, j-boxes were adhered to a substrate, loaded with a prescribed weight, and then subjected to aging. The replicate mock-modules were aged in an environmental chamber (at 85 deg C/85% relative humidity for 1000 hours; then 100 degrees C/<10% relative humidity for 200 hours) or fielded in Golden, Miami, and Phoenix for 1 year. Attachment strength tests, including pluck and shear test geometries, were also performed on smaller component specimens.« less

Autism and psychosis expressions diametrically modulate the right temporoparietal junction.

PubMed

Abu-Akel, Ahmad M; Apperly, Ian A; Wood, Stephen J; Hansen, Peter C

2017-10-01

The mentalizing network is atypically activated in autism and schizophrenia spectrum disorders. While these disorders are considered diagnostically independent, expressions of both can co-occur in the same individual. We examined the concurrent effect of autism traits and psychosis proneness on the activity of the mentalizing network in 24 neurotypical adults while performing a social competitive game. Activations were observed in the paracingulate cortex and the right temporoparietal junction (rTPJ). Autism traits and psychosis proneness did not modulate activity within the paracingulate or the dorsal component of the rTPJ. However, diametric modulations of autism traits and psychosis proneness were observed in the posterior (rvpTPJ) and anterior (rvaTPJ) subdivisions of the ventral rTPJ, which respectively constitute core regions within the mentalizing and attention-reorienting networks. Within the rvpTPJ, increasing autism tendencies decreased activity, and increasing psychosis proneness increased activity. This effect was reversed within the rvaTPJ. We suggest that this results from an interaction between regions responsible for higher level social cognitive processing (rvpTPJ) and regions responsible for domain-general attentional processes (rvaTPJ). The observed diametric modulation of autism tendencies and psychosis proneness of neuronal activity within the mentalizing network highlights the importance of assessing both autism and psychosis expressions within the individual.

Improvement of modulation bandwidth in electroabsorption-modulated laser by utilizing the resonance property in bonding wire.

PubMed

Kwon, Oh Kee; Han, Young Tak; Baek, Yong Soon; Chung, Yun C

2012-05-21

We present and demonstrate a simple and cost-effective technique for improving the modulation bandwidth of electroabsorption-modulated laser (EML). This technique utilizes the RF resonance caused by the EML chip (i.e., junction capacitance) and bonding wire (i.e, wire inductance). We analyze the effects of the lengths of the bonding wires on the frequency responses of EML by using an equivalent circuit model. To verify this analysis, we package a lumped EML chip on the sub-mount and measure its frequency responses. The results show that, by using the proposed technique, we can increase the modulation bandwidth of EML from ~16 GHz to ~28 GHz.

PASTA: splice junction identification from RNA-Sequencing data

PubMed Central

2013-01-01

Background Next generation transcriptome sequencing (RNA-Seq) is emerging as a powerful experimental tool for the study of alternative splicing and its regulation, but requires ad-hoc analysis methods and tools. PASTA (Patterned Alignments for Splicing and Transcriptome Analysis) is a splice junction detection algorithm specifically designed for RNA-Seq data, relying on a highly accurate alignment strategy and on a combination of heuristic and statistical methods to identify exon-intron junctions with high accuracy. Results Comparisons against TopHat and other splice junction prediction software on real and simulated datasets show that PASTA exhibits high specificity and sensitivity, especially at lower coverage levels. Moreover, PASTA is highly configurable and flexible, and can therefore be applied in a wide range of analysis scenarios: it is able to handle both single-end and paired-end reads, it does not rely on the presence of canonical splicing signals, and it uses organism-specific regression models to accurately identify junctions. Conclusions PASTA is a highly efficient and sensitive tool to identify splicing junctions from RNA-Seq data. Compared to similar programs, it has the ability to identify a higher number of real splicing junctions, and provides highly annotated output files containing detailed information about their location and characteristics. Accurate junction data in turn facilitates the reconstruction of the splicing isoforms and the analysis of their expression levels, which will be performed by the remaining modules of the PASTA pipeline, still under development. Use of PASTA can therefore enable the large-scale investigation of transcription and alternative splicing. PMID:23557086

Membrane junctions in Xenopus eggs: their distribution suggests a role in calcium regulation.

PubMed

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.

Automated Array Assembly, Phase 2

NASA Technical Reports Server (NTRS)

Carbajal, B. G.

1979-01-01

The Automated Array Assembly Task, Phase 2 of the Low Cost Silicon Solar Array Project is a process development task. The contract provides for the fabrication of modules from large area tandem junction cells (TJC). During this quarter, effort was focused on the design of a large area, approximately 36 sq cm, TJC and process verification runs. The large area TJC design was optimized for minimum I squared R power losses. In the TJM activity, the cell-module interfaces were defined, module substrates were formed and heat treated and clad metal interconnect strips were fabricated.

Tuning Light Emission of a Pressure-Sensitive Silicon/ZnO Nanowires Heterostructure Matrix through Piezo-phototronic Effects.

PubMed

Chen, Mengxiao; Pan, Caofeng; Zhang, Taiping; Li, Xiaoyi; Liang, Renrong; Wang, Zhong Lin

2016-06-28

Based on white light emission at silicon (Si)/ZnO hetrerojunction, a pressure-sensitive Si/ZnO nanowires heterostructure matrix light emitting diode (LED) array is developed. The light emission intensity of a single heterostructure LED is tuned by external strain: when the applied stress keeps increasing, the emission intensity first increases and then decreases with a maximum value at a compressive strain of 0.15-0.2%. This result is attributed to the piezo-phototronic effect, which can efficiently modulate the LED emission intensity by utilizing the strain-induced piezo-polarization charges. It could tune the energy band diagrams at the junction area and regulate the optoelectronic processes such as charge carriers generation, separation, recombination, and transport. This study achieves tuning silicon based devices through piezo-phototronic effect.

Muscle Contraction Regulates BDNF/TrkB Signaling to Modulate Synaptic Function through Presynaptic cPKCα and cPKCβI.

PubMed

Hurtado, Erica; Cilleros, Víctor; Nadal, Laura; Simó, Anna; Obis, Teresa; Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Halievski, Katherine; Jordan, Cynthia L; Lanuza, Maria A; Tomàs, Josep

2017-01-01

The neurotrophin brain-derived neurotrophic factor (BDNF) acts via tropomyosin-related kinase B receptor (TrkB) to regulate synapse maintenance and function in the neuromuscular system. The potentiation of acetylcholine (ACh) release by BDNF requires TrkB phosphorylation and Protein Kinase C (PKC) activation. BDNF is secreted in an activity-dependent manner but it is not known if pre- and/or postsynaptic activities enhance BDNF expression in vivo at the neuromuscular junction (NMJ). Here, we investigated whether nerve and muscle cell activities regulate presynaptic conventional PKC (cPKCα and βI) via BDNF/TrkB signaling to modulate synaptic strength at the NMJ. To differentiate the effects of presynaptic activity from that of muscle contraction, we stimulated the phrenic nerve of rat diaphragms (1 Hz, 30 min) with or without contraction (abolished by μ-conotoxin GIIIB). Then, we performed ELISA, Western blotting, qRT-PCR, immunofluorescence and electrophysiological techniques. We found that nerve-induced muscle contraction: (1) increases the levels of mature BDNF protein without affecting pro-BDNF protein or BDNF mRNA levels; (2) downregulates TrkB.T1 without affecting TrkB.FL or p75 neurotrophin receptor (p75) levels; (3) increases presynaptic cPKCα and cPKCβI protein level through TrkB signaling; and (4) enhances phosphorylation of cPKCα and cPKCβI. Furthermore, we demonstrate that cPKCβI, which is exclusively located in the motor nerve terminals, increases activity-induced acetylcholine release. Together, these results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cPKCβI) to modulate synaptic function. These results indicate that a decrease in neuromuscular activity, as occurs in several neuromuscular disorders, could affect the BDNF/TrkB/PKC pathway that links pre- and postsynaptic activity to maintain neuromuscular function.

Muscle Contraction Regulates BDNF/TrkB Signaling to Modulate Synaptic Function through Presynaptic cPKCα and cPKCβI

PubMed Central

Hurtado, Erica; Cilleros, Víctor; Nadal, Laura; Simó, Anna; Obis, Teresa; Garcia, Neus; Santafé, Manel M.; Tomàs, Marta; Halievski, Katherine; Jordan, Cynthia L.; Lanuza, Maria A.; Tomàs, Josep

2017-01-01

The neurotrophin brain-derived neurotrophic factor (BDNF) acts via tropomyosin-related kinase B receptor (TrkB) to regulate synapse maintenance and function in the neuromuscular system. The potentiation of acetylcholine (ACh) release by BDNF requires TrkB phosphorylation and Protein Kinase C (PKC) activation. BDNF is secreted in an activity-dependent manner but it is not known if pre- and/or postsynaptic activities enhance BDNF expression in vivo at the neuromuscular junction (NMJ). Here, we investigated whether nerve and muscle cell activities regulate presynaptic conventional PKC (cPKCα and βI) via BDNF/TrkB signaling to modulate synaptic strength at the NMJ. To differentiate the effects of presynaptic activity from that of muscle contraction, we stimulated the phrenic nerve of rat diaphragms (1 Hz, 30 min) with or without contraction (abolished by μ-conotoxin GIIIB). Then, we performed ELISA, Western blotting, qRT-PCR, immunofluorescence and electrophysiological techniques. We found that nerve-induced muscle contraction: (1) increases the levels of mature BDNF protein without affecting pro-BDNF protein or BDNF mRNA levels; (2) downregulates TrkB.T1 without affecting TrkB.FL or p75 neurotrophin receptor (p75) levels; (3) increases presynaptic cPKCα and cPKCβI protein level through TrkB signaling; and (4) enhances phosphorylation of cPKCα and cPKCβI. Furthermore, we demonstrate that cPKCβI, which is exclusively located in the motor nerve terminals, increases activity-induced acetylcholine release. Together, these results show that nerve-induced muscle contraction is a key regulator of BDNF/TrkB signaling pathway, retrogradely activating presynaptic cPKC isoforms (in particular cPKCβI) to modulate synaptic function. These results indicate that a decrease in neuromuscular activity, as occurs in several neuromuscular disorders, could affect the BDNF/TrkB/PKC pathway that links pre- and postsynaptic activity to maintain neuromuscular function. PMID:28572757

Glutamine enhances tight junction protein expression and modulates corticotropin-releasing factor signaling in the jejunum of weanling piglets.

PubMed

Wang, Hao; Zhang, Chen; Wu, Guoyao; Sun, Yuli; Wang, Bin; He, Beibei; Dai, Zhaolai; Wu, Zhenlong

2015-01-01

Dysfunction of tight junction integrity is associated with decreased nutrient absorption and numerous gastrointestinal diseases in humans and piglets. Although l-glutamine has been reported to enhance intestinal-mucosal mass and barrier function under stressful conditions, in vivo data to support a functional role for l-glutamine on intestinal tight junction protein (TJP) expression in weanling mammals are limited. This study tested the hypothesis that glutamine regulates expression of TJPs and stress-related corticotropin-releasing factor (CRF) signaling in the jejunum of weanling piglets. Piglets were reared by sows or weaned at 21 d of age to a corn and soybean meal-based diet that was or was not supplemented with 1% l-glutamine for 7 d. Growth performance, intestinal permeability, TJP abundance, and CRF expression were examined. Weaning caused increases (P < 0.05) in intestinal permeability by 40% and in CRF concentrations by 4.7 times in association with villus atrophy (P < 0.05). Western blot analysis showed reductions (P < 0.05) in jejunal expression of occludin, claudin-1, zonula occludens (ZO) 2, and ZO-3, but no changes in the abundance of claudin-3, claudin-4, or ZO-1 in weanling piglets compared with age-matched suckling controls. Glutamine supplementation improved (P < 0.05) intestinal permeability and villus height, while reducing (P < 0.05) jejunal mRNA and protein levels for CRF and attenuating (P < 0.05) weanling-induced decreases in occludin, claudin-1, ZO-2, and ZO-3 protein abundances. Collectively, our results support an important role for l-glutamine in regulating expression of TJPs and CRF in the jejunum of weanling piglets. © 2015 American Society for Nutrition.

Hard-hard coupling assisted anomalous magnetoresistance effect in amine-ended single-molecule magnetic junction

NASA Astrophysics Data System (ADS)

Tang, Y.-H.; Lin, C.-J.; Chiang, K.-R.

2017-06-01

We proposed a single-molecule magnetic junction (SMMJ), composed of a dissociated amine-ended benzene sandwiched between two Co tip-like nanowires. To better simulate the break junction technique for real SMMJs, the first-principles calculation associated with the hard-hard coupling between a amine-linker and Co tip-atom is carried out for SMMJs with mechanical strain and under an external bias. We predict an anomalous magnetoresistance (MR) effect, including strain-induced sign reversal and bias-induced enhancement of the MR value, which is in sharp contrast to the normal MR effect in conventional magnetic tunnel junctions. The underlying mechanism is the interplay between four spin-polarized currents in parallel and anti-parallel magnetic configurations, originated from the pronounced spin-up transmission feature in the parallel case and spiky transmission peaks in other three spin-polarized channels. These intriguing findings may open a new arena in which magnetotransport and hard-hard coupling are closely coupled in SMMJs and can be dually controlled either via mechanical strain or by an external bias.

Transforming growth factor β-induced epithelial to mesenchymal transition requires the Ste20-like kinase SLK independently of its catalytic activity

PubMed Central

Conway, Jillian; Al-Zahrani, Khalid N.; Pryce, Benjamin R.; Abou-Hamad, John; Sabourin, Luc A.

2017-01-01

Invasion can be stimulated in vitro using the soluble ligand transforming growth factor-β (TGFβ) to induce a process called epithelial-to-mesenchymal transition (EMT) characterized by cell-cell junction breakdown and an invasive phenotype. We have previously demonstrated a role for Ste20-like kinase SLK cell migration and invasion. Here we show that SLK depletion in NMuMG mammary epithelial cells significantly impairs their TGFβ-induced migration and invasion. Immunofluorescence studies show that a fraction of SLK localizes to E-cadherin-positive adherens junction and that SLK impairs the breakdown of cell-cell contacts. We find that SLK-depleted cultures express significantly lower levels of vimentin protein as well as Snai1 and E-cadherin mRNA levels following TGF-β treatment. Surprisingly, our data show that SLK depletion does not affect the activation and nuclear translocation of Smad3. Furthermore, we show that expression of a dominant negative kinase does not impair tight junction breakdown and rescues Snai1 mRNA expression levels. Together these data suggest that SLK plays a novel role in TGFβ-induced EMT, independent of Smads, in a kinase activity-independent manner. PMID:29228724

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

PubMed

Ambrosi, Cinzia; Walker, Amy E; Depriest, Adam D; Cone, Angela C; Lu, Connie; Badger, John; Skerrett, I Martha; Sosinsky, Gina E

2013-01-01

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 displayed an increased tendency to aggregate. Thus, mutations in TM4 cause a range of phenotypes of dysfunctional gap junction channels that are discussed within the context of the X-ray crystallographic structure.

Photoinduced currents in metal-barrier-metal junctions

NASA Technical Reports Server (NTRS)

Guedes, M. P.; Gustafson, T. K.; Heiblum, M.; Siu, D. P.; Slayman, C. W.; Whinnery, J. R.; Yasuoka, Y.

1978-01-01

The fabrication and application of metal-barrier-metal tunneling junctions for radiative interactions are discussed. Particular attention is given to the photolithographic fabrication of small area devices and the coupling to such devices via surface plasmon waves which play an important role at infrared and optical frequencies. It has been shown that the junction electron tunneling currents can be strongly coupled to surface plasmon junction modes, and spontaneous and stimulated emission of the latter are possible as well as nonlinear interactions. Finally, results demonstrating the photo-excitation of electrons with subsequent tunneling induced by ultraviolet radiation are presented. It is estimated that quantum efficiencies of the order of 5% and higher are possible in the ultraviolet region.

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

PubMed

Liu, Yaqing; Offenhäusser, Andreas; Mayer, Dirk

2010-01-15

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

Giant tunnelling electroresistance in metal/ferroelectric/semiconductor tunnel junctions by engineering the Schottky barrier

PubMed Central

Xi, Zhongnan; Ruan, Jieji; Li, Chen; Zheng, Chunyan; Wen, Zheng; Dai, Jiyan; Li, Aidong; Wu, Di

2017-01-01

Recently, ferroelectric tunnel junctions have attracted much attention due to their potential applications in non-destructive readout non-volatile memories. Using a semiconductor electrode has been proven effective to enhance the tunnelling electroresistance in ferroelectric tunnel junctions. Here we report a systematic investigation on electroresistance of Pt/BaTiO3/Nb:SrTiO3 metal/ferroelectric/semiconductor tunnel junctions by engineering the Schottky barrier on Nb:SrTiO3 surface via varying BaTiO3 thickness and Nb doping concentration. The optimum ON/OFF ratio as great as 6.0 × 106, comparable to that of commercial Flash memories, is achieved in a device with 0.1 wt% Nb concentration and a 4-unit-cell-thick BaTiO3 barrier. With this thinnest BaTiO3 barrier, which shows a negligible resistance to the tunnelling current but is still ferroelectric, the device is reduced to a polarization-modulated metal/semiconductor Schottky junction that exhibits a more efficient control on the tunnelling resistance to produce the giant electroresistance observed. These results may facilitate the design of high performance non-volatile resistive memories. PMID:28513590

Giant tunnelling electroresistance in metal/ferroelectric/semiconductor tunnel junctions by engineering the Schottky barrier

NASA Astrophysics Data System (ADS)

Xi, Zhongnan; Ruan, Jieji; Li, Chen; Zheng, Chunyan; Wen, Zheng; Dai, Jiyan; Li, Aidong; Wu, Di

2017-05-01

Recently, ferroelectric tunnel junctions have attracted much attention due to their potential applications in non-destructive readout non-volatile memories. Using a semiconductor electrode has been proven effective to enhance the tunnelling electroresistance in ferroelectric tunnel junctions. Here we report a systematic investigation on electroresistance of Pt/BaTiO3/Nb:SrTiO3 metal/ferroelectric/semiconductor tunnel junctions by engineering the Schottky barrier on Nb:SrTiO3 surface via varying BaTiO3 thickness and Nb doping concentration. The optimum ON/OFF ratio as great as 6.0 × 106, comparable to that of commercial Flash memories, is achieved in a device with 0.1 wt% Nb concentration and a 4-unit-cell-thick BaTiO3 barrier. With this thinnest BaTiO3 barrier, which shows a negligible resistance to the tunnelling current but is still ferroelectric, the device is reduced to a polarization-modulated metal/semiconductor Schottky junction that exhibits a more efficient control on the tunnelling resistance to produce the giant electroresistance observed. These results may facilitate the design of high performance non-volatile resistive memories.

Tunneling anisotropic magnetoresistance driven by magnetic phase transition.

PubMed

Chen, X Z; Feng, J F; Wang, Z C; Zhang, J; Zhong, X Y; Song, C; Jin, L; Zhang, B; Li, F; Jiang, M; Tan, Y Z; Zhou, X J; Shi, G Y; Zhou, X F; Han, X D; Mao, S C; Chen, Y H; Han, X F; Pan, F

2017-09-06

The independent control of two magnetic electrodes and spin-coherent transport in magnetic tunnel junctions are strictly required for tunneling magnetoresistance, while junctions with only one ferromagnetic electrode exhibit tunneling anisotropic magnetoresistance dependent on the anisotropic density of states with no room temperature performance so far. Here, we report an alternative approach to obtaining tunneling anisotropic magnetoresistance in α'-FeRh-based junctions driven by the magnetic phase transition of α'-FeRh and resultantly large variation of the density of states in the vicinity of MgO tunneling barrier, referred to as phase transition tunneling anisotropic magnetoresistance. The junctions with only one α'-FeRh magnetic electrode show a magnetoresistance ratio up to 20% at room temperature. Both the polarity and magnitude of the phase transition tunneling anisotropic magnetoresistance can be modulated by interfacial engineering at the α'-FeRh/MgO interface. Besides the fundamental significance, our finding might add a different dimension to magnetic random access memory and antiferromagnet spintronics.Tunneling anisotropic magnetoresistance is promising for next generation memory devices but limited by the low efficiency and functioning temperature. Here the authors achieved 20% tunneling anisotropic magnetoresistance at room temperature in magnetic tunnel junctions with one α'-FeRh magnetic electrode.

Single gate p-n junctions in graphene-ferroelectric devices

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

Hinnefeld, J. Henry; Mason, Nadya, E-mail: nadya@illinois.edu; Xu, Ruijuan

Graphene's linear dispersion relation and the attendant implications for bipolar electronics applications have motivated a range of experimental efforts aimed at producing p-n junctions in graphene. Here we report electrical transport measurements of graphene p-n junctions formed via simple modifications to a PbZr{sub 0.2}Ti{sub 0.8}O{sub 3} substrate, combined with a self-assembled layer of ambient environmental dopants. We show that the substrate configuration controls the local doping region, and that the p-n junction behavior can be controlled with a single gate. Finally, we show that the ferroelectric substrate induces a hysteresis in the environmental doping which can be utilized to activatemore » and deactivate the doping, yielding an “on-demand” p-n junction in graphene controlled by a single, universal backgate.« less

Assessing Urinary Tract Junction Obstruction Defects by Methylene Blue Dye Injection.

PubMed

Yun, Kangsun

2017-10-12

Urinary tract junction obstruction defects are congenital anomalies inducing hydronephrosis and hydroureter. Murine urinary tract junction obstruction defects can be assessed by tracking methylene blue dye flow within the urinary system. Methylene blue dye is injected into the renal pelvis of perinatal embryonic kidneys and dye flow is monitored from the renal pelvis of the kidney through the ureter and into the bladder lumen after applying hydrostatic pressure. Dye accumulation will be evident in the bladder lumen of the normal perinatal urinary tract, but will be constrained between the renal pelvis and the end point of an abnormal ureter, if urinary tract obstructions occur. This method facilitates the confirmation of urinary tract junction obstructions and visualization of hydronephrosis and hydroureter. This manuscript describes a protocol for methylene blue dye injection into the renal pelvis to confirm urinary tract junction obstructions.

Single-sideband modulator for frequency domain multiplexing of superconducting qubit readout

NASA Astrophysics Data System (ADS)

Chapman, Benjamin J.; Rosenthal, Eric I.; Kerckhoff, Joseph; Vale, Leila R.; Hilton, Gene C.; Lehnert, K. W.

2017-04-01

We introduce and experimentally characterize a superconducting single-sideband modulator compatible with cryogenic microwave circuits and propose its use for frequency domain multiplexing of superconducting qubit readout. The monolithic double-balanced modulators that comprise the device are formed with purely reactive elements (capacitors and Josephson junction inductors) and require no microwave-frequency control tones. Microwave signals in the 4 to 8 GHz band, with power up to -85 dBm, are converted up or down in frequency by as much as 120 MHz. Spurious harmonics in the device can be suppressed by up to 25 dB for select probe and modulation frequencies.

Modulation linearization of a frequency-modulated voltage controlled oscillator, part 3

NASA Technical Reports Server (NTRS)

Honnell, M. A.

1975-01-01

An analysis is presented for the voltage versus frequency characteristics of a varactor modulated VHF voltage controlled oscillator in which the frequency deviation is linearized by using the nonlinear characteristics of a field effect transistor as a signal amplifier. The equations developed are used to calculate the oscillator output frequency in terms of pertinent circuit parameters. It is shown that the nonlinearity exponent of the FET has a pronounced influence on frequency deviation linearity, whereas the junction exponent of the varactor controls total frequency deviation for a given input signal. A design example for a 250 MHz frequency modulated oscillator is presented.

An Inhibitory Innervation at the Gastroduodenal Junction

PubMed Central

Anuras, Sinn; Cooke, Allan R.; Christensen, James

1974-01-01

Transverse muscle strips, 2-mm wide, were cut serially from the gastroduodenal junction in opossums, cats, dogs, and man. Electrical field stimulation with trains of rectangular current pulses of 0.5 ms in all opossums, all cats, some dogs, and the one human specimen induced relaxation in strips from the thickened circular muscle proximal to the mucosal junction. In some opossums weak relaxations also occurred in the first few strips below the mucosal junction. All other strips contracted or showed no response. This relaxation in opossums was abolished by tetrodotoxin but was not affected by antagonists to adrenergic and cholinergic transmission, nor by tripelennamine, methysergide, pentagastrin, secretin, cerulein, or cholecystokinin. Optimal frequency for stimulus-relaxation was 12 Hz. Chronaxie was 0.85 ms. The junctional strips also showed greater resistances to stretch than those remote from the junction. With apparent species variations, the junctional muscle possesses a nonadrenergic inhibitory innervation which is either absent or unexpressed in adjacent muscle of stomach and duodenum. This suggests the existence of a distinctive inhibitory neural control mechanism for pyloric muscle. Images PMID:4152775

Finger millet arabinoxylan protects mice from high-fat diet induced lipid derangements, inflammation, endotoxemia and gut bacterial dysbiosis.

PubMed

Sarma, Siddhartha Mahadeva; Singh, Dhirendra Pratap; Singh, Paramdeep; Khare, Pragyanshu; Mangal, Priyanka; Singh, Shashank; Bijalwan, Vandana; Kaur, Jaspreet; Mantri, Shrikant; Boparai, Ravneet Kaur; Mazumder, Koushik; Bishnoi, Mahendra; Bhutani, Kamlesh Kumar; Kondepudi, Kanthi Kiran

2018-01-01

Arabinoxylan (AX), a non-starch polysaccharide extracted from cereals such as wheat, rice and millets, is known to impart various health promoting effects. Our earlier study suggested that finger millet (FM) could ameliorate high fat diet (HFD)-induced metabolic derangements. The present study is aimed to evaluate the effect of FM-AX supplementation, a key bioactive from finger millet, on HFD-induced metabolic and gut bacterial derangements. Male Swiss albino mice were fed with normal chow diet (NPD) or HFD (60%kcal from fat) for 10 weeks. FM-AX was orally supplemented at doses of 0.5 and 1.0g/kg bodyweight on every alternate day for 10 weeks. Glucose tolerance, serum hormones, hepatic lipid accumulation and inflammation, white adipose tissue marker gene expression, adipocyte size and inflammation; metagenomic alterations in cecal bacteria; cecal short chain fatty acids and colonic tight junction gene expressions were studied. FM-AX supplementation prevented HFD-induced weight gain, alerted glucose tolerance and serum lipid profile, hepatic lipid accumulation and inflammation. Hepatic and white adipose tissue gene expressions were beneficially modulated. Further, AX supplementation prevented metagenomic alterations in cecum; improved ileal and colonic health and overall prevented metabolic endotoxemia. Present work suggests that AX from finger millet can be developed as a nutraceutical for the management of HFD- induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Bisphenol A affects placental layers morphology and angiogenesis during early pregnancy phase in mice.

PubMed

Tait, Sabrina; Tassinari, Roberta; Maranghi, Francesca; Mantovani, Alberto

2015-11-01

Bisphenol A (BPA) is a widespread endocrine disrupter mainly used in food contact plastics. Much evidence supports the adverse effects of BPA, particularly on susceptible groups such as pregnant women. The present study considered placental development - relevant for pregnancy outcomes and fetal nutrition/programming - as a potential target of BPA. Pregnant CD-1 mice were administered per os with vehicle, 0.5 (BPA05) or 50 mg kg(-1) (BPA50) body weight day(-1) of BPA, from gestational day (GD) 1 to GD11. At GD12, BPA50 induced significant degeneration and necrosis of giant cells, increased vacuolization in the junctional zone in the absence of glycogen accumulation and reduction of the spongiotrophoblast layer. In addition, BPA05 induced glycogen depletion as well as significant nuclear accumulation of β-catenin in trophoblasts of labyrinthine and spongiotrophoblast layers, supporting the activation of the Wnt/β-catenin pathway. Transcriptomic analysis indicated that BPA05 promoted and BPA50 inhibited blood vessel development and branching; morphologically, maternal vessels were narrower in BPA05 placentas, whereas embryonic and maternal vessels were irregularly dilated in the labyrinth of BPA50 placentas. Quantitative polymerase chain reaction evidenced an estrogen receptor β induction by BPA50, which did not correspond to downstream genes activation; indeed, the transcription factor binding sites analysis supported the AhR/Arnt complex as regulator of BPA50-modulated genes. Conversely, Creb appeared as the main transcription factor regulating BPA05-modulated genes. Embryonic structures (head, forelimb) showed divergent perturbations upon BPA05 or BPA50 exposure, potentially related to unbalanced embryonic nutrition and/or to modulation of genes involved in embryo development. Our findings support placenta as an important target of BPA, even at environmentally relevant dose levels. Copyright © 2015 John Wiley & Sons, Ltd.

The role of apoptosis in LDL transport through cultured endothelial cell monolayers

PubMed Central

Cancel, Limary M.; Tarbell, John M.

2009-01-01

We have previously shown that leaky junctions associated with dying or dividing cells are the dominant pathway for LDL transport under convective conditions, accounting for more than 90% of the transport [1]. To explore the role of apoptosis in the leaky junction pathway, TNFα and cycloheximide (TNFα/CHX) were used to induce an elevated rate of apoptosis in cultured bovine aortic endothelial cell (BAEC) monolayers and the convective fluxes of LDL and water were measured. Treatment with TNFα/CHX induced a 18.3-fold increase in apoptosis and a 4.4-fold increase in LDL permeability. Increases in apoptosis and permeability were attenuated by treatment with the caspase inhibitor Z-VAD-FMK. Water flux increased by 2.7-fold after treatment with TNFα/CHX, and this increase was not attenuated by treatment with Z-VAD-FMK. Immunostaining of the tight junction protein ZO-1 showed that TNFα/CHX treatment disrupts the tight junction in addition to inducing apoptosis. This disruption is present even when Z-VAD-FMK is used to inhibit apoptosis, and likely accounts for the increase in water flux. We found a strong correlation between the rate of apoptosis and the permeability of BAEC monolayers to LDL. These results demonstrate the potential of manipulating endothelial monolayer permeability by altering the rate of apoptosis pharmacollogicaly. This has implications for the treatment of atherosclerosis. PMID:19709659

Communication-dependent mineralization of osteoblasts via gap junctions.

PubMed

Hashida, Yukihiko; Nakahama, Ken-ichi; Shimizu, Kaori; Akiyama, Masako; Harada, Kiyoshi; Morita, Ikuo

2014-04-01

Connexin43 (Cx43) is a major gap junction (GJ) protein in bone and plays a critical role in osteoblast differentiation. Several studies show that osteoblast differentiation is delayed by Cx43 ablation. However, the precise mechanism underlying the role of Cx43 in osteoblast differentiation is not fully understood. Firstly, we analyzed the phenotype of a conditional knockout mouse, which was generated by mating of an osterix promoter-driven Cre expressing mouse with a Cx43-floxed mouse. As expected, delayed ossification was observed. Secondly, we demonstrated that the cell communication via gap junctions played an important role in osteoblast differentiation using a tamoxifen-inducible knockout system in vitro. Genetic ablation of Cx43 resulted in both the disruption of cell-communications and the attenuation of osteoblast mineralization induced by BMP-2, but not by ascorbic acid. Moreover, restoring full-length Cx43 (382aa) expression rescued the impairment of osteoblast cell-communication and osteoblast mineralization; however, the expression of the Cx43 N-terminal mutant (382aaG2V) did not rescue either of them. Comparing the gene expression profiles, the genes directly regulated by BMP-2 were attenuated by Cx43 gene ablation. These results suggested that the cell-communication mediated by gap junctions was indispensable for normal differentiation of osteoblast induced by BMP-2. Copyright © 2013 Elsevier Inc. All rights reserved.

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells.

PubMed

Babica, Pavel; Zurabian, Rimma; Kumar, Esha R; Chopra, Rajus; Mianecki, Maxwell J; Park, Joon-Suk; Jaša, Libor; Trosko, James E; Upham, Brad L

2016-09-01

Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Functional role of connexin43 gap junction channels in adult mouse heart assessed by inducible gene deletion.

PubMed

Eckardt, D; Theis, M; Degen, J; Ott, T; van Rijen, H V M; Kirchhoff, S; Kim, J-S; de Bakker, J M T; Willecke, K

2004-01-01

The gap junction protein Connexin43 (Cx43) is expressed in various cell types during embryonic development and in adult mice. Cx43 null mice (Cx43-/-) die perinatally due to cardiac malformation. In order to define the major functional role of Cx43 gap junction channels in adult mice and to circumvent perinatal death as well as direct or indirect compensation of Cx43 deficiency during development, we established a novel conditional Cx43 mouse mutant. To ablate Cx43 in adult mice in all cells that express Cx43 at a certain time, we targeted the 4-hydroxytamoxifen inducible Cre recombinase, Cre-ER(T), into the endogenous Cx43 locus. This approach left only one Cx43 coding region to be deleted upon induction of Cre-ER(T) activity. Highly efficient inducible ablation of Cx43 was shown in an embryonic stem cell test system and in adult mice. Although Cx43 protein was decreased in different tissues after induction of Cre-ER(T)-mediated recombination, cardiac abnormalities most likely account for death of those mice. Surface and telemetric ECG recordings revealed significant delay of ventricular activation and death during periods of bradyarrhythmia preceded by tachycardias. This novel approach of inducible ablation of Cx43 highlights the functional importance of normal activation of ventricular cardiomyocytes mediated by Cx43 gap junction channels in adult mouse heart to prevent initiation of fatal arrhythmias. The new mouse model should be useful for further analyses of molecular changes initiated by acute loss of Cx43 expression in various cell types.

SU-E-T-283: Dose Perturbations Near Heterogeneity Junctions for Modulated-Scanning Protons

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

Deng, Y; Li, Y; Sheng, Y

2015-06-15

Purpose: To compare calculated and measured doses near heterogeneity junctions of tissue-substitute materials for modulated-scanning protons. Methods: Three heterogeneous phantoms were configured using slabs of various plastics to simulate lung, fat, soft-tissue (polystyrene), and bone with known relative linear stopping powers (RLSPs). Each phantom consisted of soft-tissue and a single heterogeneity of a 5 or 10 cm thickness of a non-soft-tissue material. CT images were loaded into a Syngo treatment planning system and each material contoured and assigned its RLSP. Planning target volumes (PTVs) were drawn such that a beam would partially traverse the heterogeneity and partially only soft-tissue. Lateralmore » profiles were measured using EDR2 films at a minimum of six depths between the phantom surface and the depth corresponding to the beam range. Absolute doses were measured inside and distal to the PTV in all phantoms using either a parallel plate or thimble chamber. Additional dose measurements were made between two lung slabs. Results: Profiles measured by film generally agreed with calculations except for depths distal to lung and fat junctions. Measured lateral penumbras for depths at the distal junction of lung were found to be wider than calculated ones. Compared with calculated doses, measured doses in the PTVs were 5.19% and 2.51% lower for lung and fat respectively but for bone were 0.2% higher. Measured doses for depths distal to the PTV were up to 29.65% and 10.58% higher for lung and fat, respectively but 6.30% lower for bone. Conclusion: The low measured doses in the PTVs for lung and fat might be due to underestimation of lateral scattering of protons. The higher measured doses distal to the PTV for the lung and fat are a Result of a shortened calculated beam range whereas the higher dose distal to the bone junction is within uncertainties.« less

Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior.

PubMed

Li, Haiyan; He, Jin; Yu, Hongfei; Green, Colin R; Chang, Jiang

2016-04-01

It is well known that gap junctions play an important role in wound healing, and bioactive glass (BG) has been shown to help healing when applied as a wound dressing. However, the effects of BG on gap junctional communication between cells involved in wound healing is not well understood. We hypothesized that BG may be able to affect gap junction mediated cell behavior to enhance wound healing. Therefore, we set out to investigate the effects of BG on gap junction related behavior of endothelial cells in order to elucidate the mechanisms through which BG is operating. In in vitro studies, BG ion extracts prevented death of human umbilical vein endothelial cells (HUVEC) following hypoxia in a dose dependent manner, possibly through connexin hemichannel modulation. In addition, BG showed stimulatory effects on gap junction communication between HUVECs and upregulated connexin43 (Cx43) expression. Furthermore, BG prompted expression of vascular endothelial growth factor and basic fibroblast growth factor as well as their receptors, and vascular endothelial cadherin in HUVECs, all of which are beneficial for vascularization. In vivo wound healing results showed that the wound closure of full-thickness excisional wounds of rats was accelerated by BG with reduced inflammation during initial stages of healing and stimulated angiogenesis during the proliferation stage. Therefore, BG can stimulate wound healing through affecting gap junctions and gap junction related endothelial cell behaviors, including prevention of endothelial cell death following hypoxia, stimulation of gap junction communication and upregulation of critical vascular growth factors, which contributes to the enhancement of angiogenesis in the wound bed and finally to accelerate wound healing. Although many studies have reported that BG stimulates angiogenesis and wound healing, this work reveals the relationship between BG and gap junction connexin 43 mediated endothelial cell behavior and elucidates one of the possible mechanisms through which BG stimulates wound healing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells.

PubMed

Appelt-Menzel, Antje; Cubukova, Alevtina; Günther, Katharina; Edenhofer, Frank; Piontek, Jörg; Krause, Gerd; Stüber, Tanja; Walles, Heike; Neuhaus, Winfried; Metzger, Marco

2017-04-11

In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm 2 and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Shear stress and the endothelial transport barrier.

PubMed

Tarbell, John M

2010-07-15

The shear stress of flowing blood on the surfaces of endothelial cells that provide the barrier to transport of solutes and water between blood and the underlying tissue modulates the permeability to solutes and the hydraulic conductivity. This review begins with a discussion of transport pathways across the endothelium and then considers the experimental evidence from both in vivo and in vitro studies that shows an influence of shear stress on endothelial transport properties after both acute (minutes to hours) and chronic (hours to days) changes in shear stress. Next, the effects of shear stress on individual transport pathways (tight junctions, adherens junctions, vesicles and leaky junctions) are described, and this information is integrated with the transport experiments to suggest mechanisms controlling both acute and chronic responses of transport properties to shear stress. The review ends with a summary of future research challenges.

Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network.

PubMed

Sun, Shuguo; Irvine, Kenneth D

2016-09-01

The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell-cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated and to define their respective contributions in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

Schweitzer, Kelly S; Hatoum, Hadi; Brown, Mary Beth; Gupta, Mehak; Justice, Matthew J; Beteck, Besem; Van Demark, Mary; Gu, Yuan; Presson, Robert G; Hubbard, Walter C; Petrache, Irina

2011-12-01

The epithelial and endothelial cells lining the alveolus form a barrier essential for the preservation of the lung respiratory function, which is, however, vulnerable to excessive oxidative, inflammatory, and apoptotic insults. Whereas profound breaches in this barrier function cause pulmonary edema, more subtle changes may contribute to inflammation. The mechanisms by which cigarette smoke (CS) exposure induce lung inflammation are not fully understood, but an early alteration in the epithelial barrier function has been documented. We sought to investigate the occurrence and mechanisms by which soluble components of mainstream CS disrupt the lung endothelial cell barrier function. Using cultured primary rat microvascular cell monolayers, we report that CS induces endothelial cell barrier disruption in a dose- and time-dependent manner of similar magnitude to that of the epithelial cell barrier. CS exposure triggered a mechanism of neutral sphingomyelinase-mediated ceramide upregulation and p38 MAPK and JNK activation that were oxidative stress dependent and that, along with Rho kinase activation, mediated the endothelial barrier dysfunction. The morphological changes in endothelial cell monolayers induced by CS included actin cytoskeletal rearrangement, junctional protein zonula occludens-1 loss, and intercellular gap formation, which were abolished by the glutathione modulator N-acetylcysteine and ameliorated by neutral sphingomyelinase inhibition. The direct application of ceramide recapitulated the effects of CS, by disrupting both endothelial and epithelial cells barrier, by a mechanism that was redox and apoptosis independent and required Rho kinase activation. Furthermore, ceramide induced dose-dependent alterations of alveolar microcirculatory barrier in vivo, measured by two-photon excitation microscopy in the intact rat. In conclusion, soluble components of CS have direct endothelial barrier-disruptive effects that could be ameliorated by glutathione modulators or by inhibitors of neutral sphingomyelinase, p38 MAPK, JNK, and Rho kinase. Amelioration of endothelial permeability may alleviate lung and systemic vascular dysfunction associated with smoking-related chronic obstructive lung diseases.

Gap Junction Modulation of Low-Frequency Oscillations in the Cerebellar Granule Cell Layer.

PubMed

Robinson, Jennifer Claire; Chapman, C Andrew; Courtemanche, Richard

2017-08-01

Local field potential (LFP) oscillations in the granule cell layer (GCL) of the cerebellar cortex have been identified previously in the awake rat and monkey during immobility. These low-frequency oscillations are thought to be generated through local circuit interactions between Golgi cells and granule cells within the GCL. Golgi cells display rhythmic firing and pacemaking properties, and also are electrically coupled through gap junctions within the GCL. Here, we tested if gap junctions in the rat cerebellar cortex contribute to the generation of LFP oscillations in the GCL. We recorded LFP oscillations under urethane anesthesia, and examined the effects of local infusion of gap junction blockers on 5-15 Hz oscillations. Local infusion of the gap junction blockers carbenoxolone and mefloquine resulted in significant decreases in the power of oscillations over a 30-min period, but the power of oscillations was unchanged in control experiments following vehicle injections. In addition, infusion of gap junction blockers had no significant effect on multi-unit activity, suggesting that the attenuation of low-frequency oscillations was likely due to reductions in electrical coupling rather than a decreased excitability within the granule cell layer. Our results indicate that electrical coupling among the Golgi cell networks in the cerebellar cortex contributes to the local circuit mechanisms that promote the occurrence of GCL LFP slow oscillations in the anesthetized rat.

UNC-1 regulates gap junctions important to locomotion in C. elegans.

PubMed

Chen, Bojun; Liu, Qiang; Ge, Qian; Xie, Jia; Wang, Zhao-Wen

2007-08-07

In C. elegans, loss-of-function (lf) mutations of the stomatin-like protein (SLP) UNC-1 and the innexin UNC-9 inhibit locomotion [1, 2] and modulate sensitivity to volatile anesthetics [3, 4]. It was unknown why unc-1(lf) and unc-9(lf) mutants have similar phenotypes. We tested the hypothesis that UNC-1 is a regulator of gap junctions formed by UNC-9. Analyses of junctional currents between body-wall muscle cells showed that electrical coupling was inhibited to a similar degree in unc-1(lf), unc-9(lf), and unc-1(lf);unc-9(lf) double mutants, suggesting that UNC-1 and UNC-9 function together. Expression of Punc-1::DsRED2 and Punc-9::GFP transcriptional fusions suggests that unc-1 and unc-9 are coexpressed in neurons and body-wall muscle cells. Immunohistochemistry showed that UNC-1 and UNC-9 colocalized at intercellular junctions and that unc-1(lf) did not alter UNC-9 expression or subcellular localization. Bimolecular fluorescence complementation (BiFC) assays suggest that UNC-1 and UNC-9 are physically very close at intercellular junctions. Targeted rescue experiments suggest that UNC-9 and UNC-1 function predominantly in neurons to control locomotion. Thus, in addition to the recently reported function of regulating mechanosensitive ion channels [5, 6], SLPs might have a novel function of regulating gap junctions.

Superluminescence from an optically pumped molecular tunneling junction by injection of plasmon induced hot electrons

PubMed Central

Braun, Kai; Wang, Xiao; Kern, Andreas M; Adler, Hilmar; Peisert, Heiko; Chassé, Thomas; Zhang, Dai

2015-01-01

Summary Here, we demonstrate a bias-driven superluminescent point light-source based on an optically pumped molecular junction (gold substrate/self-assembled molecular monolayer/gold tip) of a scanning tunneling microscope, operating at ambient conditions and providing almost three orders of magnitude higher electron-to-photon conversion efficiency than electroluminescence induced by inelastic tunneling without optical pumping. A positive, steadily increasing bias voltage induces a step-like rise of the Stokes shifted optical signal emitted from the junction. This emission is strongly attenuated by reversing the applied bias voltage. At high bias voltage, the emission intensity depends non-linearly on the optical pump power. The enhanced emission can be modelled by rate equations taking into account hole injection from the tip (anode) into the highest occupied orbital of the closest substrate-bound molecule (lower level) and radiative recombination with an electron from above the Fermi level (upper level), hence feeding photons back by stimulated emission resonant with the gap mode. The system reflects many essential features of a superluminescent light emitting diode. PMID:26171286

Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation.

PubMed

Yamada, Aya; Futagi, Masaharu; Fukumoto, Emiko; Saito, Kan; Yoshizaki, Keigo; Ishikawa, Masaki; Arakaki, Makiko; Hino, Ryoko; Sugawara, Yu; Ishikawa, Momoko; Naruse, Masahiro; Miyazaki, Kanako; Nakamura, Takashi; Fukumoto, Satoshi

2016-01-08

Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43(-/-) salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43(-/-) samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43(-/-) phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

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

Chopjitt, Peechanika; Pientong, Chamsai; Sunthamala, Nuchsupha

HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E andmore » E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. - Highlights: • E6D25E HPV16 specifically modulates protein profile of human keratinocytes. • E6D25E HPV16 modulates protein profile which involves in TLR signalling and transformation of squamocolumnar junction cells. • E6D25E oncoprotein may correlate to impair of immune response against viral infection and cells transformation.« less

S-nitrosation of β-catenin and p120 catenin: a novel regulatory mechanism in endothelial hyperpermeability

PubMed Central

Marín, N.; Zamorano, P.; Carrasco, R.; Mujica, P.; González, FG.; Quezada, C.; Meininger, CJ.; Boric, MP.; Durán, WN.; Sánchez, FA.

2014-01-01

Rationale Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of eNOS to cytosol and stimulation of eNOS-derived NO signaling cascade. The mechanisms by which NO signaling regulates permeability at adherens junctions are still incompletely understood. Objective We explored the hypothesis that PAF stimulates hyperpermeability via S-nitrosation (SNO) of adherens junction proteins. Methods and Results We measured PAF-stimulated S-nitrosation of β-catenin and p120-catenin (p120) in three cell lines: ECV-eNOSGFP, EAhy926 (derived from human umbilical vein) and CVEC (derived from bovine heart endothelium) and in the mouse cremaster muscle in vivo. SNO correlated with diminished abundance of β-catenin and p120 at the adherens junction and with hyperpermeability. TNF-α increased NO production and caused similar increase in S-nitrosation as PAF. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S-nitrosation of β-catenin and p120 and significantly diminished association between these proteins in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Inhibitors of NO production and of S-nitrosation blocked PAF-induced S-nitrosation and hyperpermeability whereas inhibition of the cGMP pathway had no effect. Mass spectrometry analysis of purified p120 identified cysteine 579 as the main S-nitrosated residue in the region that putatively interacts with VE-cadherin. Conclusions Our results demonstrate that agonist-induced SNO contributes to junctional membrane protein changes that enhance endothelial permeability. PMID:22777005

Design and characterization of the first peptidomimetic molecule that prevents acidification-induced closure of cardiac gap junctions

PubMed Central

Verma, Vandana; Larsen, Bjarne Due; Coombs, Wanda; Lin, Xianming; Sarrou, Eliana; Taffet, Steven M.; Delmar, Mario

2010-01-01

Background Gap junctions are potential targets for pharmacological intervention. We have previously developed a series of peptide sequences that prevent closure of Cx43 channels, bind to cardiac Cx43 and prevent acidification-induced uncoupling of cardiac gap junctions. Objective We aimed to identify and validate the minimum core active structure in peptides containing an RR-N/Q-Y motif. Based on that information, we sought to generate a peptidomimetic molecule that acts on the chemical regulation of Cx43 channels. Methods Experiments were based on a combination of biochemical, spectroscopic and electrophysiological techniques, as well as molecular modeling of active pharmacophores with Cx43 activity. Results Molecular modeling analysis indicated that the functional elements of the side chains in the motif RRXY form a triangular structure. Experimental data revealed that compounds containing such a structure bind to Cx43 and prevent Cx43 chemical gating. These results provided us with the first platform for drug design targeted to the carboxyl terminal of Cx43. Using that platform, we designed and validated a peptidomimetic compound (ZP2519; molecular weight 619 Da) that prevented octanol-induced uncoupling of Cx43 channels, and pH gating of cardiac gap junctions. Conclusion Structure-based drug design can be applied to the development of pharmacophores that act directly on Cx43. Small molecules containing these pharmacophores can serve as tools to determine the role of gap junction regulation in the control of cardiac rhythm. Future studies will determine whether these compounds can function as pharmacological agents for the treatment of a selected subset of cardiac arrhythmias. PMID:20601149

Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability.

PubMed

Cani, P D; Possemiers, S; Van de Wiele, T; Guiot, Y; Everard, A; Rottier, O; Geurts, L; Naslain, D; Neyrinck, A; Lambert, D M; Muccioli, G G; Delzenne, N M

2009-08-01

Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.

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

PubMed Central

Liu, Hao-Yu; Roos, Stefan; Jonsson, Hans; Ahl, David; Dicksved, Johan; Lindberg, Jan Erik; Lundh, Torbjörn

2015-01-01

Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic, Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on cytoprotective HSP expression and gut barrier function, were investigated in a porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells polarized on a permeable filter exhibited villus-like cell phenotype with development of apical microvilli. Western blot analysis detected HSP expression in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG did not. For HSP72, only the supernatant of L. reuteri induced the expression, which was comparable to the heat shock treatment, which indicated that HSP72 expression was more stimulus specific. The protective effect of lactobacilli was further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC) challenge. ETEC caused intestinal barrier destruction, as reflected by loss of cell–cell contact, reduced IPEC-J2 cell viability and transepithelial electrical resistance, and disruption of tight junction protein zonula occludens-1. In contrast, the L. reuteri treatment substantially counteracted these detrimental effects and preserved the barrier function. L. johnsonii and LGG also achieved barrier protection, partly by directly inhibiting ETEC attachment. Together, the results indicate that specific strains of Lactobacillus can enhance gut barrier function through cytoprotective HSP induction and fortify the cell protection against ETEC challenge through tight junction protein modulation and direct interaction with pathogens. PMID:25847917

Semiconductor solar cells: Recent progress in terrestrial applications

NASA Astrophysics Data System (ADS)

Avrutin, V.; Izyumskaya, N.; Morkoç, H.

2011-04-01

In the last decade, the photovoltaic industry grew at a rate exceeding 30% per year. Currently, solar-cell modules based on single-crystal and large-grain polycrystalline silicon wafers comprise more than 80% of the market. Bulk Si photovoltaics, which benefit from the highly advanced growth and fabrication processes developed for microelectronics industry, is a mature technology. The light-to-electric power conversion efficiency of the best modules offered on the market is over 20%. While there is still room for improvement, the device performance is approaching the thermodynamic limit of ˜28% for single-junction Si solar cells. The major challenge that the bulk Si solar cells face is, however, the cost reduction. The potential for price reduction of electrical power generated by wafer-based Si modules is limited by the cost of bulk Si wafers, making the electrical power cost substantially higher than that generated by combustion of fossil fuels. One major strategy to bring down the cost of electricity generated by photovoltaic modules is thin-film solar cells, whose production does not require expensive semiconductor substrates and very high temperatures and thus allows decreasing the cost per unit area while retaining a reasonable efficiency. Thin-film solar cells based on amorphous, microcrystalline, and polycrystalline Si as well as cadmium telluride and copper indium diselenide compound semiconductors have already proved their commercial viability and their market share is increasing rapidly. Another avenue to reduce the cost of photovoltaic electricity is to increase the cell efficiency beyond the Shockley-Queisser limit. A variety of concepts proposed along this avenue forms the basis of the so-called third generation photovoltaics technologies. Among these approaches, high-efficiency multi-junction solar cells based on III-V compound semiconductors, which initially found uses in space applications, are now being developed for terrestrial applications. In this article, we discuss the progress, outstanding problems, and environmental issues associated with bulk Si, thin-film, and high-efficiency multi-junction solar cells.

Low-current-density spin-transfer switching in Gd{sub 22}Fe{sub 78}-MgO magnetic tunnel junction

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

Kinjo, Hidekazu, E-mail: kinjou.h-lk@nhk.or.jp; Machida, Kenji; Aoshima, Ken-ichi

2014-05-28

Magnetization switching of a relatively thick (9 nm) Gd-Fe free layer was achieved with a low spin injection current density of 1.0 × 10{sup 6} A/cm{sup 2} using MgO based magnetic tunnel junction devices, fabricated for light modulators. At about 560 × 560 nm{sup 2} in size, the devices exhibited a tunneling magnetoresistance ratio of 7%. This low-current switching is mainly attributed to thermally assisted spin-transfer switching in consequence of its thermal magnetic behavior arising from Joule heating.

An EBIC equation for solar cells. [Electron Beam Induced Current

NASA Technical Reports Server (NTRS)

Luke, K. L.; Von Roos, O.

1983-01-01

When an electron beam of a scanning electron microscope (SEM) impinges on an N-P junction, the generation of electron-hole pairs by impact ionization causes a characteristic short circuit current I(sc) to flow. The I(sc), i.e., EBIC (electron beam induced current) depends strongly on the configuration used to investigate the cell's response. In this paper the case where the plane of the junction is perpendicular to the surface is considered. An EBIC equation amenable to numerical computations is derived as a function of cell thickness, source depth, surface recombination velocity, diffusion length, and distance of the junction to the beam-cell interaction point for a cell with an ohmic contact at its back surface. It is shown that the EBIC equation presented here is more general and easier to use than those previously reported. The effects of source depth, ohmic contact, and diffusion length on the normalized EBIC characteristic are discussed.

The Effect of Metal-Semiconductor Contact on the Transient Photovoltaic Characteristic of HgCdTe PV Detector

PubMed Central

Cui, Haoyang; Xu, Yongpeng; Yang, Junjie; Tang, Naiyun; Tang, Zhong

2013-01-01

The transient photovoltaic (PV) characteristic of HgCdTe PV array is studied using an ultrafast laser. The photoresponse shows an apparent negative valley first, then it evolves into a positive peak. By employing a combined theoretical model of pn junction and Schottky potential, this photo-response polarity changing curves can be interpreted well. An obvious decreasing of ratio of negative valley to positive peak can be realized by limiting the illumination area of the array electrode. This shows that the photoelectric effect of Schottky barrier at metal-semiconductor (M/S) interface is suppressed, which will verify the correctness of the model. The characteristic parameters of transient photo-response induced from p-n junction and Schottky potential are extracted by fitting the response curve utilizing this model. It shows that the negative PV response induced by the Schottky barrier decreases the positive photovoltage generated by the pn junction. PMID:24194676

Modeling Bloch oscillations in nanoscale Josephson junctions.

PubMed

Vora, Heli; Kautz, R L; Nam, S W; Aumentado, J

2017-08-01

Bloch oscillations in nanoscale Josephson junctions with a Coulomb charging energy comparable to the Josephson coupling energy are explored within the context of a model previously considered by Geigenmüller and Schön that includes Zener tunneling and treats quasiparticle tunneling as an explicit shot-noise process. The dynamics of the junction quasicharge are investigated numerically using both Monte Carlo and ensemble approaches to calculate voltage-current characteristics in the presence of microwaves. We examine in detail the origin of harmonic and subharmonic Bloch steps at dc biases I = ( n/m )2 ef induced by microwaves of frequency f and consider the optimum parameters for the observation of harmonic ( m = 1) steps. We also demonstrate that the GS model allows a detailed semiquantitative fit to experimental voltage-current characteristics previously obtained at the Chalmers University of Technology, confirming and strengthening the interpretation of the observed microwave-induced steps in terms of Bloch oscillations.

Modeling Bloch oscillations in nanoscale Josephson junctions

PubMed Central

Vora, Heli; Kautz, R. L.; Nam, S. W.; Aumentado, J.

2018-01-01

Bloch oscillations in nanoscale Josephson junctions with a Coulomb charging energy comparable to the Josephson coupling energy are explored within the context of a model previously considered by Geigenmüller and Schön that includes Zener tunneling and treats quasiparticle tunneling as an explicit shot-noise process. The dynamics of the junction quasicharge are investigated numerically using both Monte Carlo and ensemble approaches to calculate voltage-current characteristics in the presence of microwaves. We examine in detail the origin of harmonic and subharmonic Bloch steps at dc biases I = (n/m)2ef induced by microwaves of frequency f and consider the optimum parameters for the observation of harmonic (m = 1) steps. We also demonstrate that the GS model allows a detailed semiquantitative fit to experimental voltage-current characteristics previously obtained at the Chalmers University of Technology, confirming and strengthening the interpretation of the observed microwave-induced steps in terms of Bloch oscillations. PMID:29577106

The effect of metal-semiconductor contact on the transient photovoltaic characteristic of HgCdTe PV detector.

PubMed

Cui, Haoyang; Xu, Yongpeng; Yang, Junjie; Tang, Naiyun; Tang, Zhong

2013-01-01

The transient photovoltaic (PV) characteristic of HgCdTe PV array is studied using an ultrafast laser. The photoresponse shows an apparent negative valley first, then it evolves into a positive peak. By employing a combined theoretical model of pn junction and Schottky potential, this photo-response polarity changing curves can be interpreted well. An obvious decreasing of ratio of negative valley to positive peak can be realized by limiting the illumination area of the array electrode. This shows that the photoelectric effect of Schottky barrier at metal-semiconductor (M/S) interface is suppressed, which will verify the correctness of the model. The characteristic parameters of transient photo-response induced from p-n junction and Schottky potential are extracted by fitting the response curve utilizing this model. It shows that the negative PV response induced by the Schottky barrier decreases the positive photovoltage generated by the pn junction.

Distribution of cardiac sodium channels in clusters potentiates ephaptic interactions in the intercalated disc.

PubMed

Hichri, Echrak; Abriel, Hugues; Kucera, Jan P

2018-02-15

It has been proposed that ephaptic conduction, relying on interactions between the sodium (Na + ) current and the extracellular potential in intercalated discs, might contribute to cardiac conduction when gap junctional coupling is reduced, but this mechanism is still controversial. In intercalated discs, Na + channels form clusters near gap junction plaques, but the functional significance of these clusters has never been evaluated. In HEK cells expressing cardiac Na + channels, we show that restricting the extracellular space modulates the Na + current, as predicted by corresponding simulations accounting for ephaptic effects. In a high-resolution model of the intercalated disc, clusters of Na + channels that face each other across the intercellular cleft facilitate ephaptic impulse transmission when gap junctional coupling is reduced. Thus, our simulations reveal a functional role for the clustering of Na + channels in intercalated discs, and suggest that rearrangement of these clusters in disease may influence cardiac conduction. It has been proposed that ephaptic interactions in intercalated discs, mediated by extracellular potentials, contribute to cardiac impulse propagation when gap junctional coupling is reduced. However, experiments demonstrating ephaptic effects on the cardiac Na + current (I Na ) are scarce. Furthermore, Na + channels form clusters around gap junction plaques, but the electrophysiological significance of these clusters has never been investigated. In patch clamp experiments with HEK cells stably expressing human Na v 1.5 channels, we examined how restricting the extracellular space modulates I Na elicited by an activation protocol. In parallel, we developed a high-resolution computer model of the intercalated disc to investigate how the distribution of Na + channels influences ephaptic interactions. Approaching the HEK cells to a non-conducting obstacle always increased peak I Na at step potentials near the threshold of I Na activation and decreased peak I Na at step potentials far above threshold (7 cells, P = 0.0156, Wilcoxon signed rank test). These effects were consistent with corresponding control simulations with a uniform Na + channel distribution. In the intercalated disc computer model, redistributing the Na + channels into a central cluster of the disc potentiated ephaptic effects. Moreover, ephaptic impulse transmission from one cell to another was facilitated by clusters of Na + channels facing each other across the intercellular cleft when gap junctional coupling was reduced. In conclusion, our proof-of-principle experiments demonstrate that confining the extracellular space modulates cardiac I Na , and our simulations reveal the functional role of the aggregation of Na + channels in the perinexus. These findings highlight novel concepts in the physiology of cardiac excitation. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Design optimization of GaAs betavoltaic batteries

NASA Astrophysics Data System (ADS)

Chen, Haiyanag; Jiang, Lan; Chen, Xuyuan

2011-06-01

GaAs junctions are designed and fabricated for betavoltaic batteries. The design is optimized according to the characteristics of GaAs interface states and the diffusion length in the depletion region of GaAs carriers. Under an illumination of 10 mCi cm-2 63Ni, the open circuit voltage of the optimized batteries is about ~0.3 V. It is found that the GaAs interface states induce depletion layers on P-type GaAs surfaces. The depletion layer along the P+PN+ junction edge isolates the perimeter surface from the bulk junction, which tends to significantly reduce the battery dark current and leads to a high open circuit voltage. The short circuit current density of the optimized junction is about 28 nA cm-2, which indicates a carrier diffusion length of less than 1 µm. The overall results show that multi-layer P+PN+ junctions are the preferred structures for GaAs betavoltaic battery design.

Chirality effect in disordered graphene ribbon junctions

NASA Astrophysics Data System (ADS)

Long, Wen

2012-05-01

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

Significance of Reflux Abolition at the Saphenofemoral Junction in Connection with Stripping and Ablative Methods

PubMed Central

Recek, Cestmir

2015-01-01

Saphenous reflux interferes with the physiological decrease in pressure and induces ambulatory venous hypertension. Elimination of reflux is achieved by flush ligation at the incompetent saphenofemoral junction and stripping of the great saphenous vein, which is the basis of the conventional surgical therapy. Endovenous ablative methods substitute stripping by thermal of chemical destruction of the saphenous trunk; they usually refrain from saphenofemoral junction ligation. Short-term and medium-term results up to 5 years, achieved after endovenous ablation without high ligation, are comparable with those after conventional surgery, which questioned the necessity to ligate the incompetent saphenofemoral junction. Nevertheless, clinical symptoms caused by recurrent reflux occur as a rule not earlier than 8 to 10 years after efficient abolition of reflux. Consequently, randomized studies with long-term follow-ups exceeding 10 years are necessary for trustworthy assessment whether it is justified to abstain from saphenofemoral junction ligation. PMID:26648666

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

PubMed Central

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

2014-01-01

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

Mixed Electrical–Chemical Synapses in Adult Rat Hippocampus are Primarily Glutamatergic and Coupled by Connexin-36

PubMed Central

Hamzei-Sichani, Farid; Davidson, Kimberly G. V.; Yasumura, Thomas; Janssen, William G. M.; Wearne, Susan L.; Hof, Patrick R.; Traub, Roger D.; Gutiérrez, Rafael; Ottersen, Ole P.; Rash, John E.

2012-01-01

Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for “mixed” (electrical/chemical) synapses on both principal cells and interneurons in adult rat hippocampus. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber (MF) terminals on thorny excrescences of CA3 pyramidal neurons (CA3pyr), apparently forming glutamatergic mixed synapses. Lucifer Yellow injected into weakly fixed CA3pyr was detected in MF axons that contacted four injected CA3pyr, supporting gap junction-mediated coupling between those two types of principal cells. Freeze-fracture replica immunogold labeling revealed diverse sizes and morphologies of connexin-36-containing gap junctions throughout hippocampus. Of 20 immunogold-labeled gap junctions, seven were large (328–1140 connexons), three of which were consistent with electrical synapses between interneurons; but nine were at axon terminal synapses, three of which were immediately adjacent to distinctive glutamate receptor-containing postsynaptic densities, forming mixed glutamatergic synapses. Four others were adjacent to small clusters of immunogold-labeled 10-nm E-face intramembrane particles, apparently representing extrasynaptic glutamate receptor particles. Gap junctions also were on spines in stratum lucidum, stratum oriens, dentate gyrus, and hilus, on both interneurons and unidentified neurons. In addition, one putative GABAergic mixed synapse was found in thin-section images of a CA3pyr, but none were found by immunogold labeling, suggesting the rarity of GABAergic mixed synapses. Cx36-containing gap junctions throughout hippocampus suggest the possibility of reciprocal modulation of electrical and chemical signals in diverse hippocampal neurons. PMID:22615687

Degeneration and regeneration of neuromuscular junction architecture in rat skeletal muscle fibers damaged by bupivacaine hydrochloride.

PubMed

Nishizawa, Tomie; Tamaki, Hiroyuki; Kasuga, Norikatsu; Takekura, Hiroaki

2003-01-01

We evaluated the degeneration and regeneration of neuromuscular junctions (NMJs) on the extensor digitorum longus muscle of Fischer 344 rats between 4 h and 3 weeks after bupivacaine hydrochloride (BPVC) injection, which induces muscle fiber necrosis, using histochemical staining by acetylcholine esterase (AchE)-silver and electron microscopy. Degeneration of muscle fibers and NMJs was observed 4 h after BPVC injection. One week after BPVC injection, some terminal axons were almost completely retracted, and the level of basal lamina-associated AchE in some NMJ regions had gradually disappeared. At that time, the depression contained a few, mostly pit-like or elongated oval invaginations: the incipient junctional folds and some NMJs did not have any secondary junctional fold. By 2 weeks after the BPVC injection, secondary junctional folds began to develop: however, the number of secondary junctional folds was clearly less than that in normal NMJs. At 3 weeks when regeneration of muscle fibers was well advanced, the staining for AchE at the end-plates became stronger and better-defined. The volume density of mitochondria in the terminal area of the terminal significantly decreased upon BPVC-induced destruction of the NMJ, and the density reached the lowest value 24 h after BPVC injection. Significant changes in the ultrastructural features of the architecture of NMJs occurred in skeletal muscle fibers damaged by BPVC during both the degeneration and regeneration processes. The changes in the ultrastructural and morphological features of the NMJ architecture during the regeneration of degenerated muscle fibers resembled those that occur during the differentiation of normal muscle fibers.

Ferroelectric-field-effect-enhanced electroresistance in metal/ferroelectric/semiconductor tunnel junctions

NASA Astrophysics Data System (ADS)

Wen, Zheng; Li, Chen; Wu, Di; Li, Aidong; Ming, Naiben

2013-07-01

Ferroelectric tunnel junctions (FTJs), composed of two metal electrodes separated by an ultrathin ferroelectric barrier, have attracted much attention as promising candidates for non-volatile resistive memories. Theoretical and experimental works have revealed that the tunnelling resistance switching in FTJs originates mainly from a ferroelectric modulation on the barrier height. However, in these devices, modulation on the barrier width is very limited, although the tunnelling transmittance depends on it exponentially as well. Here we propose a novel tunnelling heterostructure by replacing one of the metal electrodes in a normal FTJ with a heavily doped semiconductor. In these metal/ferroelectric/semiconductor FTJs, not only the height but also the width of the barrier can be electrically modulated as a result of a ferroelectric field effect, leading to a greatly enhanced tunnelling electroresistance. This idea is implemented in Pt/BaTiO3/Nb:SrTiO3 heterostructures, in which an ON/OFF conductance ratio above 104, about one to two orders greater than those reported in normal FTJs, can be achieved at room temperature. The giant tunnelling electroresistance, reliable switching reproducibility and long data retention observed in these metal/ferroelectric/semiconductor FTJs suggest their great potential in non-destructive readout non-volatile memories.

Visual short-term memory load suppresses temporo-parietal junction activity and induces inattentional blindness.

PubMed

Todd, J Jay; Fougnie, Daryl; Marois, René

2005-12-01

The right temporo-parietal junction (TPJ) is critical for stimulus-driven attention and visual awareness. Here we show that as the visual short-term memory (VSTM) load of a task increases, activity in this region is increasingly suppressed. Correspondingly, increasing VSTM load impairs the ability of subjects to consciously detect the presence of a novel, unexpected object in the visual field. These results not only demonstrate that VSTM load suppresses TPJ activity and induces inattentional blindness, but also offer a plausible neural mechanism for this perceptual deficit: suppression of the stimulus-driven attentional network.

Strain-assisted current-induced magnetization reversal in magnetic tunnel junctions: A micromagnetic study with phase-field microelasticity

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

Huang, H. B., E-mail: houbinghuang@gmail.com; Department of Physics, University of Science and Technology Beijing, Beijing 100083; Hu, J. M.

2014-09-22

Effect of substrate misfit strain on current-induced in-plane magnetization reversal in CoFeB-MgO based magnetic tunnel junctions is investigated by combining micromagnetic simulations with phase-field microelasticity theory. It is found that the critical current density for in-plane magnetization reversal decreases dramatically with an increasing substrate strain, since the effective elastic field can drag the magnetization to one of the four in-plane diagonal directions. A potential strain-assisted multilevel bit spin transfer magnetization switching device using substrate misfit strain is also proposed.

Ionophore and Biometal Modulation of P-glycoprotein Expression and Function in Human Brain Microvascular Endothelial Cells.

PubMed

McInerney, Mitchell P; Volitakis, Irene; Bush, Ashley I; Banks, William A; Short, Jennifer L; Nicolazzo, Joseph A

2018-03-05

Biometals such as zinc and copper have been shown to affect tight junction expression and subsequently blood-brain barrier (BBB) integrity. Whether these biometals also influence the expression and function of BBB transporters such as P-glycoprotein (P-gp) however is currently unknown. Using the immortalised human cerebral microvascular endothelial (hCMEC/D3) cell line, an in-cell western assay (alongside western blotting) assessed relative P-gp expression after treatment with the metal ionophore clioquinol and biometals zinc and copper. The fluorescent P-gp substrate rhodamine-123 was employed to observe functional modulation, and inductively coupled plasma mass spectrometry (ICP-MS) provided information on biometal trafficking. A 24-h treatment with clioquinol, zinc and copper (0.5, 0.5 and 0.1 μM) induced a significant upregulation of P-gp (1.7-fold) assessed by in-cell western and this was confirmed with western blotting (1.8-fold increase). This same treatment resulted in a 23% decrease in rhodamine-123 accumulation over a 1 h incubation. ICP-MS demonstrated that while t8his combination treatment had no effect on intracellular zinc concentrations, the treatment significantly enhanced bioavailable copper (4.6-fold). Enhanced delivery of copper to human brain microvascular endothelial cells is associated with enhanced expression and function of the important efflux pump P-gp, which may provide therapeutic opportunities for P-gp modulation.

Ultralow drive voltage silicon traveling-wave modulator.

PubMed

Baehr-Jones, Tom; Ding, Ran; Liu, Yang; Ayazi, Ali; Pinguet, Thierry; Harris, Nicholas C; Streshinsky, Matt; Lee, Poshen; Zhang, Yi; Lim, Andy Eu-Jin; Liow, Tsung-Yang; Teo, Selin Hwee-Gee; Lo, Guo-Qiang; Hochberg, Michael

2012-05-21

There has been great interest in the silicon platform as a material system for integrated photonics. A key challenge is the development of a low-power, low drive voltage, broadband modulator. Drive voltages at or below 1 Vpp are desirable for compatibility with CMOS processes. Here we demonstrate a CMOS-compatible broadband traveling-wave modulator based on a reverse-biased pn junction. We demonstrate operation with a drive voltage of 0.63 Vpp at 20 Gb/s, a significant improvement in the state of the art, with an RF energy consumption of only 200 fJ/bit.

Computational Aeroelastic Analysis of Ares Crew Launch Vehicle Bi-Modal Loading

NASA Technical Reports Server (NTRS)

Massey, Steven J.; Chwalowski, Pawel

2010-01-01

A Reynolds averaged Navier-Stokes analysis, with and without dynamic aeroelastic effects, is presented for the Ares I-X launch vehicle at transonic Mach numbers and flight Reynolds numbers for two grid resolutions and two angles of attack. The purpose of the study is to quantify the force and moment increment imparted by the sudden transition from fully separated flow around the crew module - service module junction to that of the bi-modal flow state in which only part of the flow reattaches. The bi-modal flow phenomenon is of interest to the guidance, navigation and control community because it causes a discontinuous jump in forces and moments. Computations with a rigid structure at zero zero angle of attack indicate significant increases in normal force and pitching moment. Dynamic aeroelastic computations indicate the bi-modal flow state is insensitive to vehicle flexibility due to the resulting deflections imparting only very small changes in local angle of attack. At an angle of attack of 2.5deg, the magnitude of the pitching moment increment resulting from the bi-modal state nearly triples, while occurring at a slightly lower Mach number. Significant grid induced variations between the solutions indicate that further grid refinement is warranted.

Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury.

PubMed

Cho, Young-Eun; Yu, Li-Rong; Abdelmegeed, Mohamed A; Yoo, Seong-Ho; Song, Byoung-Joon

2018-07-01

Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherens junction (AJ) proteins in binge alcohol-induced gut leakiness. The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses. Binge alcohol exposure caused apoptosis of gut enterocytes with elevated serum endotoxin and liver injury. The levels of intestinal CYP2E1, iNOS, nitrated proteins and apoptosis-related marker proteins were significantly elevated in binge alcohol-exposed rodents. Differential, quantitative mass-spectral analyses of the TJ-enriched fractions of intestinal epithelial layers revealed that several TJ, AJ and desmosome proteins were decreased in binge alcohol-exposed rats compared to controls. Consistently, the levels of TJ proteins (claudin-1, claudin-4, occludin and zonula occludens-1), AJ proteins (β-catenin and E-cadherin) and desmosome plakoglobin were very low in binge alcohol-exposed rats, wild-type mice, and autopsied human ileums but not in Cyp2e1-null mice. Additionally, pretreatment with specific inhibitors of CYP2E1 and iNOS prevented disorganization and/or degradation of TJ proteins in alcohol-exposed T84 colonic cells. Furthermore, immunoprecipitation followed by immunoblot confirmed that intestinal TJ and AJ proteins were nitrated and degraded via ubiquitin-dependent proteolysis, resulting in their decreased levels. These results demonstrated for the first time the critical roles of CYP2E1, apoptosis of enterocytes, and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins, in promoting binge alcohol-induced gut leakiness and endotoxemia, contributing to inflammatory liver disease. Binge alcohol exposure causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury. Our results demonstrated for the first time the critical roles of apoptosis of enterocytes and nitration followed by ubiquitin-dependent proteolytic degradation of the junctional complex proteins in promoting this gut leakiness and endotoxemia. These results provide insight into the molecular mechanisms of alcohol-induced inflammatory liver disease. Published by Elsevier B.V.

ROCK inhibitor primes human induced pluripotent stem cells to selectively differentiate towards mesendodermal lineage via epithelial-mesenchymal transition-like modulation.

PubMed

Maldonado, Maricela; Luu, Rebeccah J; Ramos, Michael E P; Nam, Jin

2016-09-01

Robust control of human induced pluripotent stem cell (hIPSC) differentiation is essential to realize its patient-tailored therapeutic potential. Here, we demonstrate a novel application of Y-27632, a small molecule Rho-associated protein kinase (ROCK) inhibitor, to significantly influence the differentiation of hIPSCs in a lineage-specific manner. The application of Y-27632 to hIPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration and time-dependent manner. Such changes in cell and colony morphology were associated with decreased expression of E-cadherin, a cell-cell junctional protein, proportional to the increased exposure to Y-27632. Interestingly, gene and protein expression of pluripotency markers such as NANOG and OCT4 were not downregulated by an exposure to Y-27632 up to 36h. Simultaneously, epithelial-to-mesenchymal (EMT) transition markers were upregulated with an exposure to Y-27632. These EMT-like changes in the cells with longer exposure to Y-27632 resulted in a significant increase in the subsequent differentiation efficiency towards mesendodermal lineage. In contrast, an inhibitory effect was observed when cells were subjected to ectodermal differentiation after prolonged exposure to Y-27632. Collectively, these results present a novel method for priming hIPSCs to modulate their differentiation potential with a simple application of Y-27632. Copyright © 2016 Helmholtz Zentrum München. Published by Elsevier B.V. All rights reserved.

In tight junctions, claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization.

PubMed

Cording, Jimmi; Berg, Johanna; Käding, Nadja; Bellmann, Christian; Tscheik, Christian; Westphal, Julie K; Milatz, Susanne; Günzel, Dorothee; Wolburg, Hartwig; Piontek, Jörg; Huber, Otmar; Blasig, Ingolf Ernst

2013-01-15

Tight junctions seal the paracellular cleft of epithelia and endothelia, form vital barriers between tissue compartments and consist of tight-junction-associated marvel proteins (TAMPs) and claudins. The function of TAMPs and the interaction with claudins are not understood. We therefore investigated the binding between the TAMPs occludin, tricellulin, and marvelD3 and their interaction with claudins in living tight-junction-free human embryonic kidney-293 cells. In contrast to claudins and occludin, tricellulin and marvelD3 showed no enrichment at cell-cell contacts indicating lack of homophilic trans-interaction between two opposing cell membranes. However, occludin, marvelD3 and tricellulin exhibited homophilic cis-interactions, along one plasma membrane, as measured by fluorescence resonance energy transfer. MarvelD3 also cis-interacted with occludin and tricellulin heterophilically. Classic claudins, such as claudin-1 to -5 may show cis-oligomerization with TAMPs, whereas the non-classic claudin-11 did not. Claudin-1 and -5 improved enrichment of occludin and tricellulin at cell-cell contacts. The low mobile claudin-1 reduced the membrane mobility of the highly mobile occludin and tricellulin, as studied by fluorescence recovery after photobleaching. Co-transfection of claudin-1 with TAMPs led to changes of the tight junction strand network of this claudin to a more physiological morphology, depicted by freeze-fracture electron microscopy. The results demonstrate multilateral interactions between the tight junction proteins, in which claudins determine the function of TAMPs and vice versa, and provide deeper insights into the tight junction assembly.

Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease.

PubMed

Burke, Shoshana; Nagajyothi, Fnu; Thi, Mia M; Hanani, Menachem; Scherer, Philipp E; Tanowitz, Herbert B; Spray, David C

2014-11-01

Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions. Copyright © 2014. Published by Elsevier Masson SAS.

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

PubMed

Lavrov, Igor; Fox, Lyle; Shen, Jun; Han, Yingchun; Cheng, Jianguo

2016-01-01

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.

Selective binding of meiosis-specific yeast Hop1 protein to the holliday junctions distorts the DNA structure and its implications for junction migration and resolution.

PubMed

Tripathi, Pankaj; Anuradha, S; Ghosal, Gargi; Muniyappa, K

2006-12-08

Saccharomyces cerevisiae HOP1, which encodes a component of synaptonemal complex (SC), plays an important role in both gene conversion and crossing over between homologs, as well as enforces meiotic recombination checkpoint control over the progression of recombination intermediates. In hop1Delta mutants, meiosis-specific double-strand breaks (DSBs) are reduced to 10% of the wild-type level, and at aberrantly late times, these DSBs are processed into inter-sister recombination intermediates. However, the underlying mechanism by which Hop1 protein regulates these nuclear events remains obscure. Here we show that Hop1 protein interacts selectively with the Holliday junction, changes its global conformation and blocks the dissolution of the junction by a RecQ helicase. The Holliday junction-Hop1 protein complexes are significantly more stable at higher ionic strengths and molar excess of unlabeled competitor DNA than complexes containing other recombination intermediates. Structural analysis of the Holliday junction using 2-aminopurine fluorescence emission, DNase I footprinting and KMnO4 probing provide compelling evidence that Hop1 protein binding induces significant distortion at the center of the Holliday junction. We propose that Hop1 protein might coordinate the physical monitoring of meiotic recombination intermediates with the process of branch migration of Holliday junction.

Measure synchronization in a spin-orbit-coupled bosonic Josephson junction

NASA Astrophysics Data System (ADS)

Wang, Wen-Yuan; Liu, Jie; Fu, Li-Bin

2015-11-01

We present measure synchronization (MS) in a bosonic Josephson junction with spin-orbit coupling. The two atomic hyperfine states are coupled by a Raman dressing scheme, and they are regarded as two orientations of a pseudo-spin-1 /2 system. A feature specific to a spin-orbit-coupled (SOC) bosonic Josephson junction is that the transition from non-MS to MS dynamics can be modulated by Raman laser intensity, even in the absence of interspin atomic interaction. A phase diagram of non-MS and MS dynamics as functions of Raman laser intensity and Josephson tunneling amplitude is presented. Taking into account interspin atomic interactions, the system exhibits MS breaking dynamics resulting from the competition between intraspin and interspin atomic interactions. When interspin atomic interactions dominate in the competition, the system always exhibits MS dynamics. For interspin interaction weaker than intraspin interaction, a window for non-MS dynamics is present. Since SOC Bose-Einstein condensates provide a powerful platform for studies on physical problems in various fields, the study of MS dynamics is valuable in researching the collective coherent dynamical behavior in a spin-orbit-coupled bosonic Josephson junction.