Yan, Dong
2016-01-01
Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that UNC-44/ankyrin acts upstream of UNC-33/CRMP in regulation of a potential kinesin VAB-8 to control gap junction dynamics, and loss-of-function in the UNC-44/UNC-33/VAB-8 pathway suppresses the turnover of gap junction channels. Therefore, we first show a signal pathway including ankyrin, CRMP, and kinesin in regulating gap junctions. PMID:27015090
Vedula, Pavan; Cruz, Lissette A; Gutierrez, Natasha; Davis, Justin; Ayee, Brian; Abramczyk, Rachel; Rodriguez, Alexis J
2016-06-30
Quantifying multi-molecular complex assembly in specific cytoplasmic compartments is crucial to understand how cells use assembly/disassembly of these complexes to control function. Currently, biophysical methods like Fluorescence Resonance Energy Transfer and Fluorescence Correlation Spectroscopy provide quantitative measurements of direct protein-protein interactions, while traditional biochemical approaches such as sub-cellular fractionation and immunoprecipitation remain the main approaches used to study multi-protein complex assembly/disassembly dynamics. In this article, we validate and quantify multi-protein adherens junction complex assembly in situ using light microscopy and Fluorescence Covariance Analysis. Utilizing specific fluorescently-labeled protein pairs, we quantified various stages of adherens junction complex assembly, the multiprotein complex regulating epithelial tissue structure and function following de novo cell-cell contact. We demonstrate: minimal cadherin-catenin complex assembly in the perinuclear cytoplasm and subsequent localization to the cell-cell contact zone, assembly of adherens junction complexes, acto-myosin tension-mediated anchoring, and adherens junction maturation following de novo cell-cell contact. Finally applying Fluorescence Covariance Analysis in live cells expressing fluorescently tagged adherens junction complex proteins, we also quantified adherens junction complex assembly dynamics during epithelial monolayer formation.
Ma, Yanlei; Yue, Jiping; Zhang, Yao; Shi, Chenzhang; Odenwald, Matt; Liang, Wenguang G.; Wei, Qing; Goel, Ajay; Gou, Xuewen; Zhang, Jamie; Chen, Shao-Yu; Tang, Wei-Jen; Turner, Jerrold R.; Yang, Feng; Liang, Hong; Qin, Huanlong; Wu, Xiaoyang
2017-01-01
In the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss of ACF7 leads to aberrant microtubule organization, tight junction stabilization and impaired wound closure in vitro. With the mouse genetics approach, we show that ablation of ACF7 inhibits intestinal wound healing and greatly increases susceptibility to experimental colitis in mice. ACF7 level is also correlated with development and progression of ulcerative colitis (UC) in human patients. Together, our results reveal an important molecular mechanism whereby coordinated cytoskeletal dynamics contributes to cell adhesion regulation during intestinal wound repair and the development of IBD. PMID:28541346
Edge mixing dynamics in graphene p–n junctions in the quantum Hall regime
Matsuo, Sadashige; Takeshita, Shunpei; Tanaka, Takahiro; Nakaharai, Shu; Tsukagoshi, Kazuhito; Moriyama, Takahiro; Ono, Teruo; Kobayashi, Kensuke
2015-01-01
Massless Dirac electron systems such as graphene exhibit a distinct half-integer quantum Hall effect, and in the bipolar transport regime co-propagating edge states along the p–n junction are realized. Additionally, these edge states are uniformly mixed at the junction, which makes it a unique structure to partition electrons in these edge states. Although many experimental works have addressed this issue, the microscopic dynamics of electron partition in this peculiar structure remains unclear. Here we performed shot-noise measurements on the junction in the quantum Hall regime as well as at zero magnetic field. We found that, in sharp contrast with the zero-field case, the shot noise in the quantum Hall regime is finite in the bipolar regime, but is strongly suppressed in the unipolar regime. Our observation is consistent with the theoretical prediction and gives microscopic evidence that the edge states are uniquely mixed along the p–n junction. PMID:26337445
Dissipation in microwave quantum circuits with hybrid nanowire Josephson elements
NASA Astrophysics Data System (ADS)
Mugnai, D.; Ranfagni, A.; Agresti, A.
2017-04-01
Recent experiments on hybrid Josephson junctions have made the argument a topical subject. However, a quantity which remains still unknown is the tunneling (or response) time, which is strictly connected to the role that dissipation plays in the dynamics of the complete system. A simple way for evaluating dissipation in microwave circuits, previously developed for describing the dynamics of conventional Josephson junctions, is now presented as suitable for application even to non-conventional junctions. The method is based on a stochastic model, as derived from the telegrapher's equation, and is particularly devoted to the case of junctions loaded by real transmission lines. When the load is constituted by lumped-constant circuits, a connection with the stochastic model is also maintained. The theoretical model demonstrated its ability to analyze both classically-allowed and forbidden processes, and has found a wide field of applicability, namely in all cases in which dissipative effects cannot be ignored.
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
NASA Technical Reports Server (NTRS)
Neudeck, Philip G.; Fazi, Christian
1999-01-01
This paper outlines the dynamic reverse-breakdown characteristics of low-voltage (<250 V) small-area <5 x 10(exp -4) sq cm 4H-SiC p(sup +)n diodes subjected to nonadiabatic breakdown-bias pulsewidths ranging from 0.1 to 20 microseconds. 4H-SiC diodes with and without elementary screw dislocations exhibited positive temperature coefficient of breakdown voltage and high junction failure power densities approximately five times larger than the average failure power density of reliable silicon pn rectifiers. This result indicates that highly reliable low-voltage SiC rectifiers may be attainable despite the presence of elementary screw dislocations. However, the impact of elementary screw dislocations on other more useful 4H-SiC power device structures, such as high-voltage (>1 kV) pn junction and Schottky rectifiers, and bipolar gain devices (thyristors, IGBT's, etc.) remains to be investigated.
First-principles spin-transfer torque in CuMnAs |GaP |CuMnAs junctions
NASA Astrophysics Data System (ADS)
Stamenova, Maria; Mohebbi, Razie; Seyed-Yazdi, Jamileh; Rungger, Ivan; Sanvito, Stefano
2017-02-01
We demonstrate that an all-antiferromagnetic tunnel junction with current perpendicular to the plane geometry can be used as an efficient spintronic device with potential high-frequency operation. By using state-of-the-art density functional theory combined with quantum transport, we show that the Néel vector of the electrodes can be manipulated by spin-transfer torque. This is staggered over the two different magnetic sublattices and can generate dynamics and switching. At the same time the different magnetization states of the junction can be read by standard tunneling magnetoresistance. Calculations are performed for CuMnAs |GaP |CuMnAs junctions with different surface terminations between the antiferromagnetic CuMnAs electrodes and the insulating GaP spacer. We find that the torque remains staggered regardless of the termination, while the magnetoresistance depends on the microscopic details of the interface.
Dynamic Tunneling Junctions at the Atomic Intersection of Two Twisted Graphene Edges.
Bellunato, Amedeo; Vrbica, Sasha D; Sabater, Carlos; de Vos, Erik W; Fermin, Remko; Kanneworff, Kirsten N; Galli, Federica; van Ruitenbeek, Jan M; Schneider, Grégory F
2018-04-11
The investigation of the transport properties of single molecules by flowing tunneling currents across extremely narrow gaps is relevant for challenges as diverse as the development of molecular electronics and sequencing of DNA. The achievement of well-defined electrode architectures remains a technical challenge, especially due to the necessity of high precision fabrication processes and the chemical instability of most bulk metals. Here, we illustrate a continuously adjustable tunneling junction between the edges of two twisted graphene sheets. The unique property of the graphene electrodes is that the sheets are rigidly supported all the way to the atomic edge. By analyzing the tunneling current characteristics, we also demonstrate that the spacing across the gap junction can be controllably adjusted. Finally, we demonstrate the transition from the tunneling regime to contact and the formation of an atomic-sized junction between the two edges of graphene.
Dynamic Tunneling Junctions at the Atomic Intersection of Two Twisted Graphene Edges
2018-01-01
The investigation of the transport properties of single molecules by flowing tunneling currents across extremely narrow gaps is relevant for challenges as diverse as the development of molecular electronics and sequencing of DNA. The achievement of well-defined electrode architectures remains a technical challenge, especially due to the necessity of high precision fabrication processes and the chemical instability of most bulk metals. Here, we illustrate a continuously adjustable tunneling junction between the edges of two twisted graphene sheets. The unique property of the graphene electrodes is that the sheets are rigidly supported all the way to the atomic edge. By analyzing the tunneling current characteristics, we also demonstrate that the spacing across the gap junction can be controllably adjusted. Finally, we demonstrate the transition from the tunneling regime to contact and the formation of an atomic-sized junction between the two edges of graphene. PMID:29513997
The role of the baryon junction in relativistic heavy-ion collisions
NASA Astrophysics Data System (ADS)
Vance, Stephen Earl
The non-perturbative nature of the conserved baryon number of nuclei is investigated by studying the role of the baryon junction in relativistic heavy-ion collisions. The junction, J, of a baryon originates in the Standard Model of Strong Interactions (QCD) and is the vertex which connects the color flux (Wilson) lines flowing from the three valence quarks. In high energy interactions, the baryon junction can play a dynamical role through the Regge exchange of junction states. We show that the junction exchange provides a natural mechanism for the transport of baryon number into the central rapidity region and has the remarkable ability to produce valence hyperons, including W- baryons. This mechanism is used to describe the observed baryon stopping and associated hyperon production in nucleus-nucleus collisions at the CERN SPS. We also show that junction - antijunction excitations or JJ loops provide a new mechanism for baryon pair production and lead to enhanced hyperon and antihyperon production. The combination of these two mechanisms is able to explain part of the anomalous hyperon production observed in Pb + Pb collisions at the SPS. Using the junction initial state dynamics, final state strangeness exchange interactions are shown to further enhance hyperon production and are proposed as an explanation of the remaining anomalous hyperon production. With larger phase space (higher energy) accessible at the newly constructed BNL RHIC facility, we propose that the observation of valence W- baryons in pp collisions will be a decisive observable to confirm the junction exchange picture of baryon number transport. In addition, we note that novel rapidity correlations between baryons and antibaryons of completely different quark flavors, like D++(uuu) and W+( ss s) , are predicted by the JJ loop mechanism. For numerical calculations of multiparticle observables associated with these junction mechanisms, we developed the HIJING/BB¯ nuclear event generator. HIJING/BB¯ was then coupled to the General Cascade Program (GCP) to study the role of the final state flavor changing interactions.
Verma, Suzie; Han, Siew Ping; Michael, Magdalene; Gomez, Guillermo A.; Yang, Zhe; Teasdale, Rohan D.; Ratheesh, Aparna; Kovacs, Eva M.; Ali, Radiya G.; Yap, Alpha S.
2012-01-01
The epithelial zonula adherens (ZA) is a specialized adhesive junction where actin dynamics and myosin-driven contractility coincide. The junctional cytoskeleton is enriched in myosin II, which generates contractile force to support junctional tension. It is also enriched in dynamic actin filaments, which are replenished by ongoing actin assembly. In this study we sought to pursue the relationship between actin assembly and junctional contractility. We demonstrate that WAVE2–Arp2/3 is a major nucleator of actin assembly at the ZA and likely acts in response to junctional Rac signaling. Furthermore, WAVE2–Arp2/3 is necessary for junctional integrity and contractile tension at the ZA. Maneuvers that disrupt the function of either WAVE2 or Arp2/3 reduced junctional tension and compromised the ability of cells to buffer side-to-side forces acting on the ZA. WAVE2–Arp2/3 disruption depleted junctions of both myosin IIA and IIB, suggesting that dynamic actin assembly may support junctional tension by facilitating the local recruitment of myosin. PMID:23051739
Verma, Suzie; Han, Siew Ping; Michael, Magdalene; Gomez, Guillermo A; Yang, Zhe; Teasdale, Rohan D; Ratheesh, Aparna; Kovacs, Eva M; Ali, Radiya G; Yap, Alpha S
2012-12-01
The epithelial zonula adherens (ZA) is a specialized adhesive junction where actin dynamics and myosin-driven contractility coincide. The junctional cytoskeleton is enriched in myosin II, which generates contractile force to support junctional tension. It is also enriched in dynamic actin filaments, which are replenished by ongoing actin assembly. In this study we sought to pursue the relationship between actin assembly and junctional contractility. We demonstrate that WAVE2-Arp2/3 is a major nucleator of actin assembly at the ZA and likely acts in response to junctional Rac signaling. Furthermore, WAVE2-Arp2/3 is necessary for junctional integrity and contractile tension at the ZA. Maneuvers that disrupt the function of either WAVE2 or Arp2/3 reduced junctional tension and compromised the ability of cells to buffer side-to-side forces acting on the ZA. WAVE2-Arp2/3 disruption depleted junctions of both myosin IIA and IIB, suggesting that dynamic actin assembly may support junctional tension by facilitating the local recruitment of myosin.
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.
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
Contour junctions defined by dynamic image deformations enhance perceptual transparency.
Kawabe, Takahiro; Nishida, Shin'ya
2017-11-01
The majority of work on the perception of transparency has focused on static images with luminance-defined contour junctions, but recent work has shown that dynamic image sequences with dynamic image deformations also provide information about transparency. The present study demonstrates that when part of a static image is dynamically deformed, contour junctions at which deforming and nondeforming contours are connected facilitate the deformation-based perception of a transparent layer. We found that the impression of a transparent layer was stronger when a dynamically deforming area was adjacent to static nondeforming areas than when presented alone. When contour junctions were not formed at the dynamic-static boundaries, however, the impression of a transparent layer was not facilitated by the presence of static surrounding areas. The effect of the deformation-defined junctions was attenuated when the spatial pattern of luminance contrast at the junctions was inconsistent with the perceived transparency related to luminance contrast, while the effect did not change when the spatial luminance pattern was consistent with it. In addition, the results showed that contour completions across the junctions were required for the perception of a transparent layer. These results indicate that deformation-defined junctions that involve contour completion between deforming and nondeforming regions enhance the perception of a transparent layer, and that the deformation-based perceptual transparency can be promoted by the simultaneous presence of appropriately configured luminance and contrast-other features that can also by themselves produce the sensation of perceiving transparency.
Klinke, David J.; Horvath, Nicholas; Cuppett, Vanessa; Wu, Yueting; Deng, Wentao; Kanj, Rania
2015-01-01
The integrity of epithelial tissue architecture is maintained through adherens junctions that are created through extracellular homotypic protein–protein interactions between cadherin molecules. Cadherins also provide an intracellular scaffold for the formation of a multiprotein complex that contains signaling proteins, including β-catenin. Environmental factors and controlled tissue reorganization disrupt adherens junctions by cleaving the extracellular binding domain and initiating a series of transcriptional events that aim to restore tissue homeostasis. However, it remains unclear how alterations in cell adhesion coordinate transcriptional events, including those mediated by β-catenin in this pathway. Here were used quantitative single-cell and population-level in vitro assays to quantify the endogenous pathway dynamics after the proteolytic disruption of the adherens junctions. Using prior knowledge of isolated elements of the overall network, we interpreted these data using in silico model-based inference to identify the topology of the regulatory network. Collectively the data suggest that the regulatory network contains interlocked network motifs consisting of a positive feedback loop, which is used to restore the integrity of adherens junctions, and a negative feedback loop, which is used to limit β-catenin–induced gene expression. PMID:26224311
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
Effect of single-strand break on branch migration and folding dynamics of Holliday junctions.
Palets, Dmytro; Lushnikov, Alexander Y; Karymov, Mikhail A; Lyubchenko, Yuri L
2010-09-22
The Holliday junction (HJ), or four-way junction, is a central intermediate state of DNA for homologous genetic recombination and other genetic processes such as replication and repair. Branch migration is the process by which the exchange of homologous DNA regions occurs, and it can be spontaneous or driven by proteins. Unfolding of the HJ is required for branch migration. Our previous single-molecule fluorescence studies led to a model according to which branch migration is a stepwise process consisting of consecutive migration and folding steps. Folding of the HJ in one of the folded conformations terminates the branch migration phase. At the same time, in the unfolded state HJ rapidly migrates over entire homology region of the HJ in one hop. This process can be affected by irregularities in the DNA double helical structure, so mismatches almost terminate a spontaneous branch migration. Single-stranded breaks or nicks are the most ubiquitous defects in the DNA helix; however, to date, their effect on the HJ branch migration has not been studied. In addition, although nicked HJs are specific substrates for a number of enzymes involved in DNA recombination and repair, the role of this substrate specificity remains unclear. Our main goal in this work was to study the effect of nicks on the efficiency of HJ branch migration and the dynamics of the HJ. To accomplish this goal, we applied two single-molecule methods: atomic force microscopy and fluorescence resonance energy transfer. The atomic force microscopy data show that the nick does not prevent branch migration, but it does decrease the probability that the HJ will pass the DNA lesion. The single-molecule fluorescence resonance energy transfer approaches were instrumental in detailing the effects of nicks. These studies reveal a dramatic change of the HJ dynamics. The nick changes the structure and conformational dynamics of the junctions, leading to conformations with geometries that are different from those for the intact HJ. On the basis of these data, we propose a model of branch migration in which the propensity of the junction to unfold decreases the lifetimes of folded states, thereby increasing the frequency of junction fluctuations between the folded states. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Switching Dynamics of an Underdamped Josephson Junction Coupled to a Microwave Cavity
NASA Astrophysics Data System (ADS)
Oelsner, G.; Il'ichev, E.
2018-05-01
Current-biased Josephson junctions are promising candidates for the detection of single photons in the microwave frequency domain. With modern fabrication technologies, the switching properties of the junction can be adjusted to achieve quantum limited sensitivity. Namely, the width of the switching current distribution can be reduced well below the current amplitude produced by a single photon trapped inside a superconducting cavity. However, for an effective detection a strong junction cavity coupling is required, providing nonlinear system dynamics. We compare experimental findings for our prototype device with a theoretical analysis aimed to describe the switching dynamics of junctions under microwave irradiation. Measurements are found in qualitative agreement with our simulations.
Multifluxon dynamics in driven Josephson junctions
NASA Astrophysics Data System (ADS)
Lawrence, Albert; Kim, Nung Soo; McDaniel, James; Jack, Michael
1985-06-01
The dynamics of fluxons in a long Josephson junction driven by time-varying nonuniform bias currents are described by a generalization of the sine-Gordon equation. This equation has solitary wave solutions which correspond to current vortices or quantized packets of magnetic flux in the junction. As with the sine-Gordon equation, multifluxon solutions may be demonstrated for the long Josephson junction. Our numerical calculations show that several fluxons may be launched or annihilated at the end of a junction. We also show multiple steady state conditions which correspond to one or more flux quanta trapped in the junction.
Distal gap junctions and active dendrites can tune network dynamics.
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.
A supine cranio-spinal irradiation technique using moving field junctions
NASA Astrophysics Data System (ADS)
Mani, Karthick Raj; Sapru, Shantanu; Maria Das, K. J.; Basu, Ayan
2016-12-01
Aim: To demonstrate a simple technique of cranio-spinal irradiation (CSI) in supine position using inter fraction moving field junctions to feather out any potential hot and cold spots. Materials and Methods: Fifteen patients diagnosed with medulloblastoma were treated during the period February 2011 to June 2015 were included in this study. Out of fifteen patients in the study nine were male and 6 were female with a median age of 13.4 years (range 5-27 years). All the patients were positioned supine on CT simulation, immobilized using thermoplastic mask and aligned using room based laser system. Two parallel opposed lateral fields for the whole brain using an asymmetrical jaw with isocenter at C2 vertebral body. A posterior field also placed to cover the cervical and dorsal field using the same isocenter at C2. The second isocenter was placed at lumbar vertebral region to cover the remaining dorsal, lumbar and sacral region using an inter-fraction moving junction. Field-in-field and enhanced dynamic wedge used to homogeneous dose distribution when required. Results and Discussion: In this study, we found that only two patients failed in the primary site, no radiation myelitis or recurrences in the filed junctions were reported in these fifteen patients with a median follow-up of 36.4 months. The automated sequence of treatment plans with moving junctions in the comfortable supine position negating the need for manual junction matching or junction shifts avoiding potential treatment errors and also facilitating delivery of anesthesia where necessary.
Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna
2018-01-01
The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893
Farnsworth, Nikki L.; Walter, Rachelle L.; Hemmati, Alireza; Westacott, Matthew J.; Benninger, Richard K. P.
2016-01-01
Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet. Loss of gap junction coupling disrupts these dynamics, similar to that observed during the development of diabetes. This study investigates the mechanisms by which pro-inflammatory cytokines mediate gap junction coupling. Specifically, as cytokine-induced NO can activate PKCδ, we aimed to understand the role of PKCδ in modulating cytokine-induced changes in gap junction coupling. Isolated mouse and human islets were treated with varying levels of a cytokine mixture containing TNF-α, IL-1β, and IFN-γ. Islet dysfunction was measured by insulin secretion, calcium dynamics, and gap junction coupling. Modulators of PKCδ and NO were applied to determine their respective roles in modulating gap junction coupling. High levels of cytokines caused cell death and decreased insulin secretion. Low levels of cytokine treatment disrupted calcium dynamics and decreased gap junction coupling, in the absence of disruptions to insulin secretion. Decreases in gap junction coupling were dependent on NO-regulated PKCδ, and altered membrane organization of connexin36. This study defines several mechanisms underlying the disruption to gap junction coupling under conditions associated with the development of diabetes. These mechanisms will allow for greater understanding of islet dysfunction and suggest ways to ameliorate this dysfunction during the development of diabetes. PMID:26668311
Mustoe, Anthony M.; Brooks, Charles L.; Al-Hashimi, Hashim M.
2014-01-01
Recent studies have shown that basic steric and connectivity constraints encoded at the secondary structure level are key determinants of 3D structure and dynamics in simple two-way RNA junctions. However, the role of these topological constraints in higher order RNA junctions remains poorly understood. Here, we use a specialized coarse-grained molecular dynamics model to directly probe the thermodynamic contributions of topological constraints in defining the 3D architecture and dynamics of transfer RNA (tRNA). Topological constraints alone restrict tRNA's allowed conformational space by over an order of magnitude and strongly discriminate against formation of non-native tertiary contacts, providing a sequence independent source of folding specificity. Topological constraints also give rise to long-range correlations between the relative orientation of tRNA's helices, which in turn provides a mechanism for encoding thermodynamic cooperativity between distinct tertiary interactions. These aspects of topological constraints make it such that only several tertiary interactions are needed to confine tRNA to its native global structure and specify functionally important 3D dynamics. We further show that topological constraints are conserved across tRNA's different naturally occurring secondary structures. Taken together, our results emphasize the central role of secondary-structure-encoded topological constraints in defining RNA 3D structure, dynamics and folding. PMID:25217593
Low frequency critical current noise and two level system defects in Josephson junctions
NASA Astrophysics Data System (ADS)
Nugroho, Christopher Daniel
The critical current in a Josephson junction is known to exhibit a 1/falpha low frequency noise. Implemented as a superconducting qubit, this low frequency noise can lead to decoherence. While the 1/f noise has been known to arise from an ensemble of two level systems connected to the tunnel barrier, the precise microscopic nature of these TLSs remain a mystery. In this thesis we will present measurements of the 1/f alpha low frequency noise in the critical current and tunneling resistance of Al-AlOx-Al Josephson junctions. Measurements in a wide range of resistively shunted and unshunted junctions confirm the equality of critical current and tunneling resistance noise. That is the critical current fluctuation corresponds to fluctuations of the tunneling resistance. In not too small Al-AlOx-Al junctions we have found that the fractional power spectral density scales linearly with temperature. We confirmed that the 1/falpha power spectrum is the result of a large number of two level systems modulating the tunneling resistance. At small junction areas and low temperatures, the number of thermally active TLSs is insufficient to integrate out a featureless 1/ f spectral shape. By analyzing the spectral variance in small junction areas, we have been able to deduce the TLS defect density, n ≈ 2.53 per micrometer squared per Kelvin spread in the TLS energy per factor e in the TLS lifetimes. This density is consistent with the density of tunneling TLSs found in glassy insulators, as well as the density deduced from coherent TLSs interacting at qubit frequencies. The deduced TLS density combined with the magnitude of the 1/f power spectral density in large area junctions, gives an average TLS effective area, A ˜ 0.3 nanometer squared. In ultra small tunnel junctions, we have studied the time-domain dynamics of isolated TLSs. We have found a TLS whose dynamics is described by the quantum tunneling between the two localized wells, and a one-phonon absorption/emission switching rate. From the quantum limiting rate and the WKB approximation, we estimated that the TLS has a mass and tunneling distance product consistent with an atomic mass tunneling through crystal lattice distances. At higher temperatures TLSs have been found that obey a simple thermal activation dynamics. By analyzing the TLS response to an external electric field, we have deduced that the TLS electric dipole is in the order of, P ˜ 1 electron-Angstrom, consistent with the TLS having the charge of one electron tunneling through a disorder potential of distances, d ˜ 1 Angstrom.
Farnsworth, Nikki L; Walter, Rachelle L; Hemmati, Alireza; Westacott, Matthew J; Benninger, Richard K P
2016-02-12
Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet. Loss of gap junction coupling disrupts these dynamics, similar to that observed during the development of diabetes. This study investigates the mechanisms by which pro-inflammatory cytokines mediate gap junction coupling. Specifically, as cytokine-induced NO can activate PKCδ, we aimed to understand the role of PKCδ in modulating cytokine-induced changes in gap junction coupling. Isolated mouse and human islets were treated with varying levels of a cytokine mixture containing TNF-α, IL-1β, and IFN-γ. Islet dysfunction was measured by insulin secretion, calcium dynamics, and gap junction coupling. Modulators of PKCδ and NO were applied to determine their respective roles in modulating gap junction coupling. High levels of cytokines caused cell death and decreased insulin secretion. Low levels of cytokine treatment disrupted calcium dynamics and decreased gap junction coupling, in the absence of disruptions to insulin secretion. Decreases in gap junction coupling were dependent on NO-regulated PKCδ, and altered membrane organization of connexin36. This study defines several mechanisms underlying the disruption to gap junction coupling under conditions associated with the development of diabetes. These mechanisms will allow for greater understanding of islet dysfunction and suggest ways to ameliorate this dysfunction during the development of diabetes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Myosin II Controls Junction Fluctuations to Guide Epithelial Tissue Ordering.
Curran, Scott; Strandkvist, Charlotte; Bathmann, Jasper; de Gennes, Marc; Kabla, Alexandre; Salbreux, Guillaume; Baum, Buzz
2017-11-20
Under conditions of homeostasis, dynamic changes in the length of individual adherens junctions (AJs) provide epithelia with the fluidity required to maintain tissue integrity in the face of intrinsic and extrinsic forces. While the contribution of AJ remodeling to developmental morphogenesis has been intensively studied, less is known about AJ dynamics in other circumstances. Here, we study AJ dynamics in an epithelium that undergoes a gradual increase in packing order, without concomitant large-scale changes in tissue size or shape. We find that neighbor exchange events are driven by stochastic fluctuations in junction length, regulated in part by junctional actomyosin. In this context, the developmental increase of isotropic junctional actomyosin reduces the rate of neighbor exchange, contributing to tissue order. We propose a model in which the local variance in tension between junctions determines whether actomyosin-based forces will inhibit or drive the topological transitions that either refine or deform a tissue. Copyright © 2017. Published by Elsevier Inc.
NASA Astrophysics Data System (ADS)
Trif, Mircea; Dmytruk, Olesia; Bouchiat, Hélène; Aguado, Ramón; Simon, Pascal
2018-02-01
We theoretically study a Josephson junction based on a semiconducting nanowire subject to a time-dependent flux bias. We establish a general density-matrix approach for the dynamical response of the Majorana junction and calculate the resulting flux-dependent susceptibility using both microscopic and effective low-energy descriptions for the nanowire. We find that the diagonal component of the susceptibility, associated with the dynamics of the Majorana state populations, dominates over the standard Kubo contribution for a wide range of experimentally relevant parameters. The diagonal term, explored, in this Rapid Communication, in the context of Majorana physics, allows probing accurately the presence of Majorana bound states in the junction.
NASA Astrophysics Data System (ADS)
Martinez, Isidoro; Cascales, Juan Pedro; Hong, Jhen-Yong; Lin, Minn-Tsong; Prezioso, Mirko; Riminucci, Alberto; Dediu, Valentin A.; Aliev, Farkhad G.
2016-10-01
The possible influence of internal barrier dynamics on spin, charge transport and their fluctuations in organic spintronics remains poorly understood. Here we present investigation of the electron transport and low frequency noise at temperatures down to 0.3K in magnetic tunnel junctions with an organic PTCDA barriers with thickness up to 5 nm in the tunneling regime and with 200 nm thick Alq3 barrier in the hopping regime. We observed high tunneling magneto-resistance at low temperatures (15-40%) and spin dependent super-poissonian shot noise in organic magnetic tunnel junctions (OMTJs) with PTCDA. The Fano factor exceeds 1.5-2 values which could be caused by interfacial states controlled by spin dependent bunching in the tunneling events through the molecules.1 The bias dependence of the low frequency noise in OMTJs with PTCDA barriers which includes both 1/f and random telegraph noise activated at specific biases will also be discussed. On the other hand, the organic junctions with ferromagnetic electrodes and thick Alq3 barriers present sub-poissonian shot noise which depends on the temperature, indicative of variable range hopping.
Observing Holliday junction branch migration one step at a time
NASA Astrophysics Data System (ADS)
Ha, Taekjip
2004-03-01
During genetic recombination, two homologous DNA molecules undergo strand exchange to form a four-way DNA (Holliday) junction and the recognition and processing of this species by branch migration and junction resolving enzymes determine the outcome. We have used single molecule fluorescence techniques to study two intrinsic structural dynamics of the Holliday junction, stacking conformer transitions and spontaneous branch migration. Our studies show that the dynamics of branch migration, resolved with one base pair resolution, is determined by the stability of conformers which in turn depends on the local DNA sequences. Therefore, the energy landscape of Holliday junction branch migation is not uniform, but is rugged.
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.
Gap and tight junctions in the formation of feather branches: A descriptive ultrastructural study.
Alibardi, Lorenzo
2010-08-20
The present study has focused on the distribution and ultrastructure of gap and tight junctions responsible for the formation of the barb/barbule branching in developing feathers using immunocytochemical detection. Apart from desmosomes, both tight and gap junctions are present between differentiating barb/barbule cells and during keratinization. While gap junctions are rare along the perimeter of these cells, tight junctions tend to remain localized in nodes joining barbule cells and between barb cells of the ramus. Occludin and connexin-26 but not connexin-43 have been detected between barb medullary, barb cortical and barbule cells during formation of barbs. Gap junctions are present in supportive cells located in the vicinity of barbule cells and destined to degenerate, but no close junctions are present between supportive and barb/barbule cells. Close junctions mature into penta-laminar junctions that are present between mature barb/barbule cells. Immunolabeling for occludin and Cx26 is rare along these cornified junctions. The junctions allow barb/barbule cells to remain connected until feather-keratin form the mature corneous syncytium that constitutes the barbs. A discussion of the role of gap and tight junctions during feather morphogenesis is presented. 2010 Elsevier GmbH. All rights reserved.
Lee, Natalie K.; Fok, Ka Wai; White, Amanda; Wilson, Nicole H.; O'Leary, Conor J.; Cox, Hayley L.; Michael, Magdalene; Yap, Alpha S.; Cooper, Helen M.
2016-01-01
To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Loss of Neogenin perturbs AJs and attenuates junctional tension. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain and the WRC is crucial for the spatially restricted recruitment of the WRC to the junction. Thus, we provide the first example of a functional WIRS–WRC interaction in epithelia. We further show that Neogenin regulates cadherin recycling at the AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it influences both cadherin dynamics and junctional tension. PMID:27029596
Comparative 1D and 3D numerical investigation of open-channel junction flows and energy losses
NASA Astrophysics Data System (ADS)
Luo, Hao; Fytanidis, Dimitrios K.; Schmidt, Arthur R.; García, Marcelo H.
2018-07-01
The complexity of open channel confluences stems from flow mixing, secondary circulation, post-confluence flow separation, contraction and backwater effects. These effects in turn result in a large number of parameters required to adequately quantify the junction induced hydraulic resistance and describe mean flow pattern and turbulent flow structures due to flow merging. The recent development in computing power advances the application of 3D Computational Fluid Dynamics (CFD) codes to visualize and understand the Confluence Hydrodynamic Zone (CHZ). Nevertheless, 1D approaches remain the mainstay in large drainage network or waterway system modeling considering computational efficiency and data availability. This paper presents (i) a modified 1D nonlinear dynamic model; (ii) a fully 3D non-hydrostatic, Reynolds-averaged Navier-Stokes Equations (RANS)-based, Computational Fluid Dynamics (CFD) model; (iii) an analysis of changing confluence hydrodynamics and 3D turbulent flow structure under various controls; (iv) a comparison of flow features (i.e. upstream water depths, energy losses and post-confluence contraction) predicted by 1D and 3D models; and (v) parameterization of 3D flow characteristics in 1D modeling through the computation of correction coefficients associated with contraction, energy and momentum. The present comprehensive 3D numerical investigation highlights the driving mechanisms for junction induced energy losses. Moreover, the comparative 1D and 3D study quantifies the deviation of 1D approximations and associated underlying assumptions from the 'true' resultant flow field. The study may also shed light on improving the accuracy of the 1D large network modeling through the parameterization of the complex 3D feature of the flow field and correction of interior boundary conditions at junctions of larger angles and/or with substantial lateral inflows. Moreover, the enclosed numerical investigations may enhance the understanding of the primary mechanisms contributing to hydraulic structure induced turbulent flow behavior and increased hydraulic resistance.
Unique determination of "subatomic" contrast by imaging covalent backbonding.
Sweetman, Adam; Rahe, Philipp; Moriarty, Philip
2014-05-14
The origin of so-called "subatomic" resolution in dynamic force microscopy has remained controversial since its first observation in 2000. A number of detailed experimental and theoretical studies have identified different possible physicochemical mechanisms potentially giving rise to subatomic contrast. In this study, for the first time we are able to assign the origin of a specific instance of subatomic contrast as being due to the back bonding of a surface atom in the tip-sample junction.
Hatte, Guillaume; Prigent, Claude; Tassan, Jean-Pierre
2018-02-05
Epithelia are layers of polarised cells tightly bound to each other by adhesive contacts. Epithelia act as barriers between an organism and its external environment. Understanding how epithelia maintain their essential integrity while remaining sufficiently plastic to allow events such as cytokinesis to take place is a key biological problem. In vertebrates, the remodelling and reinforcement of adherens junctions maintains epithelial integrity during cytokinesis. The involvement of tight junctions in cell division, however, has remained unexplored. Here, we examine the role of tight junctions during cytokinesis in the epithelium of the Xenopus laevis embryo. Depletion of the tight junction-associated proteins ZO-1 and GEF-H1 leads to altered cytokinesis duration and contractile ring geometry. Using a tension biosensor, we show that cytokinesis defects originate from misregulation of tensile forces applied to adherens junctions. Our results reveal that tight junctions regulate mechanical tension applied to adherens junctions, which in turn impacts cytokinesis.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.
Signaling from the Podocyte Intercellular Junction to the Actin Cytoskeleton
George, Britta; Holzman, Lawrence B.
2012-01-01
Observations of hereditary glomerular disease support the contention that podocyte intercellular junction proteins are essential for junction formation and maintenance. Genetic deletion of most of these podocyte intercellular junction proteins results in foot process effacement and proteinuria. This review focuses on the current understanding of molecular mechanisms by which podocyte intercellular junction proteins such as the Nephrin-Neph1-Podocin receptor complex coordinate cytoskeletal dynamics and thus intercellular junction formation, maintenance and injury-dependent remodeling. PMID:22958485
Flotillins control zebrafish epiboly through their role in cadherin-mediated cell-cell adhesion.
Morris, Eduardo A Rios; Bodin, Stéphane; Delaval, Bénédicte; Comunale, Franck; Georget, Virginie; Costa, Manoel L; Lutfalla, Georges; Gauthier-Rouvière, Cécile
2017-05-01
Zebrafish gastrulation and particularly epiboly that involves coordinated movements of several cell layers is a dynamic process for which regulators remain to be identified. We show here that Flotillin 1 and 2, ubiquitous and highly conserved proteins, are required for epiboly. Flotillins knockdown compromised embryo survival, strongly delayed epiboly and impaired deep cell radial intercalation and directed collective migration without affecting enveloping layer cell movement. At the molecular level, we identified that Flotillins are required for the formation of E-cadherin-mediated cell-cell junctions. These results provide the first in vivo evidence that Flotillins regulate E-cadherin-mediated cell-cell junctions to allow epiboly progression. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.
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
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.
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.
NASA Astrophysics Data System (ADS)
Jia, Xingtao; Tang, Huimin; Wang, Shizhuo; Qin, Minghui
2017-02-01
We predict large magnetoresistance (MR) and spin transfer torque (STT) in antiferromagnetic Fe |MgO |FeMn |Cu tunnel junctions based on first-principles scattering theory. MR as large as ˜100 % is found in one junction. Magnetic dynamic simulations show that STT acting on the antiferromagnetic order parameter dominates the spin dynamics, and an electronic bias of order 10-1mV and current density of order 105Acm-2 can switches a junction of three-layer MgO, they are about one order smaller than that in Fe |MgO |Fe junction with the same barrier thickness, respectively. The multiple scattering in the antiferromagnetic region is considered to be responsible for the enhanced spin torque and smaller switching current density.
Alternative splicing regulated by butyrate in bovine epithelial cells.
Wu, Sitao; Li, Congjun; Huang, Wen; Li, Weizhong; Li, Robert W
2012-01-01
As a signaling molecule and an inhibitor of histone deacetylases (HDACs), butyrate exerts its impact on a broad range of biological processes, such as apoptosis and cell proliferation, in addition to its critical role in energy metabolism in ruminants. This study examined the effect of butyrate on alternative splicing in bovine epithelial cells using RNA-seq technology. Junction reads account for 11.28 and 12.32% of total mapped reads between the butyrate-treated (BT) and control (CT) groups. 201,326 potential splicing junctions detected were supported by ≥ 3 junction reads. Approximately 94% of these junctions conformed to the consensus sequence (GT/AG) while ~3% were GC/AG junctions. No AT/AC junctions were observed. A total of 2,834 exon skipping events, supported by a minimum of 3 junction reads, were detected. At least 7 genes, their mRNA expression significantly affected by butyrate, also had exon skipping events differentially regulated by butyrate. Furthermore, COL5A3, which was induced 310-fold by butyrate (FDR <0.001) at the gene level, had a significantly higher number of junction reads mapped to Exon#8 (Donor) and Exon#11 (Acceptor) in BT. This event had the potential to result in the formation of a COL5A3 mRNA isoform with 2 of the 69 exons missing. In addition, 216 differentially expressed transcript isoforms regulated by butyrate were detected. For example, Isoform 1 of ORC1 was strongly repressed by butyrate while Isoform 2 remained unchanged. Butyrate physically binds to and inhibits all zinc-dependent HDACs except HDAC6 and HDAC10. Our results provided evidence that butyrate also regulated deacetylase activities of classical HDACs via its transcriptional control. Moreover, thirteen gene fusion events differentially affected by butyrate were identified. Our results provided a snapshot into complex transcriptome dynamics regulated by butyrate, which will facilitate our understanding of the biological effects of butyrate and other HDAC inhibitors.
Konishi, Tatsuya; Kiguchi, Manabu; Takase, Mai; Nagasawa, Fumika; Nabika, Hideki; Ikeda, Katsuyoshi; Uosaki, Kohei; Ueno, Kosei; Misawa, Hiroaki; Murakoshi, Kei
2013-01-23
The in situ observation of geometrical and electronic structural dynamics of a single molecule junction is critically important in order to further progress in molecular electronics. Observations of single molecular junctions are difficult, however, because of sensitivity limits. Here, we report surface-enhanced Raman scattering (SERS) of a single 4,4'-bipyridine molecule under conditions of in situ current flow in a nanogap, by using nano-fabricated, mechanically controllable break junction (MCBJ) electrodes. When adsorbed at room temperature on metal nanoelectrodes in solution to form a single molecule junction, statistical analysis showed that nontotally symmetric b(1) and b(2) modes of 4,4'-bipyridine were strongly enhanced relative to observations of the same modes in solid or aqueous solutions. Significant changes in SERS intensity, energy (wavenumber), and selectivity of Raman vibrational bands that are coincident with current fluctuations provide information on distinct states of electronic and geometrical structure of the single molecule junction, even under large thermal fluctuations occurring at room temperature. We observed the dynamics of 4,4'-bipyridine motion between vertical and tilting configurations in the Au nanogap via b(1) and b(2) mode switching. A slight increase in the tilting angle of the molecule was also observed by noting the increase in the energies of Raman modes and the decrease in conductance of the molecular junction.
Martin, Bryn A.; Kalata, Wojciech; Shaffer, Nicholas; Fischer, Paul; Luciano, Mark; Loth, Francis
2013-01-01
Elevated or reduced velocity of cerebrospinal fluid (CSF) at the craniovertebral junction (CVJ) has been associated with type I Chiari malformation (CMI). Thus, quantification of hydrodynamic parameters that describe the CSF dynamics could help assess disease severity and surgical outcome. In this study, we describe the methodology to quantify CSF hydrodynamic parameters near the CVJ and upper cervical spine utilizing subject-specific computational fluid dynamics (CFD) simulations based on in vivo MRI measurements of flow and geometry. Hydrodynamic parameters were computed for a healthy subject and two CMI patients both pre- and post-decompression surgery to determine the differences between cases. For the first time, we present the methods to quantify longitudinal impedance (LI) to CSF motion, a subject-specific hydrodynamic parameter that may have value to help quantify the CSF flow blockage severity in CMI. In addition, the following hydrodynamic parameters were quantified for each case: maximum velocity in systole and diastole, Reynolds and Womersley number, and peak pressure drop during the CSF cardiac flow cycle. The following geometric parameters were quantified: cross-sectional area and hydraulic diameter of the spinal subarachnoid space (SAS). The mean values of the geometric parameters increased post-surgically for the CMI models, but remained smaller than the healthy volunteer. All hydrodynamic parameters, except pressure drop, decreased post-surgically for the CMI patients, but remained greater than in the healthy case. Peak pressure drop alterations were mixed. To our knowledge this study represents the first subject-specific CFD simulation of CMI decompression surgery and quantification of LI in the CSF space. Further study in a larger patient and control group is needed to determine if the presented geometric and/or hydrodynamic parameters are helpful for surgical planning. PMID:24130704
Poteser, Michael; Leitinger, Gerd; Pritz, Elisabeth; Platzer, Dieter; Frischauf, Irene; Romanin, Christoph; Groschner, Klaus
2016-10-19
Nanometer-spaced appositions between endoplasmic reticulum and plasma membrane (ER-PM junctions) stabilized by membrane-joining protein complexes are critically involved in cellular Ca 2+ -handling and lipid trafficking. ER-PM junctional architecture and plasticity associated with inter-membrane communication are as yet barely understood. Here, we introduce a method to precisely characterize ER-PM junction morphology and dynamics with high temporal resolution and minimal disturbance of junctional intermembrane communication. We show that expression of soluble cytosolic fluorophores in combination with TIRFM enables to delineate ER and PM distance in the range of 10-150 nm. Live-cell imaging of sub-plasmalemmal structures in RBL-2H3 mast cells by this method, designated as fluorescence density mapping (FDM), revealed profound dynamics of ER-PM contact sites in response to store-depletion. We report the existence of a Ca 2+ -dependent process that expands the junctional ER to enlarge its contact surface with the PM, thereby promoting and stabilizing STIM1-Orai1 competent ER-PM junctions.
Supramolecular motifs in dynamic covalent PEG-hemiaminal organogels
Fox, Courtney H.; ter Hurrne, Gijs M.; Wojtecki, Rudy J.; Jones, Gavin O.; Horn, Hans W.; Meijer, E. W.; Frank, Curtis W.; Hedrick, James L.; García, Jeannette M.
2015-01-01
Dynamic covalent materials are stable materials that possess reversible behaviour triggered by stimuli such as light, redox conditions or temperature; whereas supramolecular crosslinks depend on the equilibrium constant and relative concentrations of crosslinks as a function of temperature. The combination of these two reversible chemistries can allow access to materials with unique properties. Here, we show that this combination of dynamic covalent and supramolecular chemistry can be used to prepare organogels comprising distinct networks. Two materials containing hemiaminal crosslink junctions were synthesized; one material is comprised of dynamic covalent junctions and the other contains hydrogen-bonding bis-hemiaminal moieties. Under specific network synthesis conditions, these materials exhibited self-healing behaviour. This work reports on both the molecular-level detail of hemiaminal crosslink junction formation as well as the macroscopic behaviour of hemiaminal dynamic covalent network (HDCN) elastomeric organogels. These materials have potential applications as elastomeric components in printable materials, cargo carriers and adhesives. PMID:26174864
Britz-McKibbin, Philip; Otsuka, Koji; Terabe, Shigeru
2002-08-01
Simple yet effective methods to enhance concentration sensitivity is needed for capillary electrophoresis (CE) to become a practical method to analyze trace levels of analytes in real samples. In this report, the development of a novel on-line preconcentration technique combining dynamic pH junction and sweeping modes of focusing is applied to the sensitive and selective analysis of three flavin derivatives: riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Picomolar (pM) detectability of flavins by CE with laser-induced fluorescence (LIF) detection is demonstrated through effective focusing of large sample volumes (up to 22% capillary length) using a dual pH junction-sweeping focusing mode. This results in greater than a 1,200-fold improvement in sensitivity relative to conventional injection methods, giving a limit of detection (S/N = 3) of approximately 4.0 pM for FAD and FMN. Flavin focusing is examined in terms of analyte mobility dependence on buffer pH, borate complexation and SDS interaction. Dynamic pH junction-sweeping extends on-line focusing to both neutral (hydrophobic) and weakly acidic (hydrophilic) species and is considered useful in cases when either conventional sweeping or dynamic pH junction techniques used alone are less effective for certain classes of analytes. Enhanced focusing performance by this hyphenated method was demonstrated by greater than a 4-fold reduction in flavin bandwidth, as compared to either sweeping or dynamic pH junction, reflected by analyte detector bandwidths <0.20 cm. Novel on-line focusing strategies are required to improve sensitivity in CE, which may be applied toward more effective biochemical analysis methods for diverse types of analytes.
Experimental Testing and Modeling Analysis of Solute Mixing at Water Distribution Pipe Junctions
Flow dynamics at a pipe junction controls particle trajectories, solute mixing and concentrations in downstream pipes. Here we have categorized pipe junctions into five hydraulic types, for which flow distribution factors and analytical equations for describing the solute mixing ...
Calcium dynamics in cardiac excitatory and non-excitatory cells and the role of gap junction.
Das, Phonindra Nath; Mehrotra, Parul; Mishra, Aseem; Bairagi, Nandadulal; Chatterjee, Samrat
2017-07-01
Calcium ions aid in the generation of action potential in myocytes and are responsible for the excitation-contraction coupling of heart. The heart muscle has specialized patches of cells, called excitatory cells (EC) such as the Sino-atrial node cells capable of auto-generation of action potential and cells which receive signals from the excitatory cells, called non-excitatory cells (NEC) such as cells of the ventricular and auricular walls. In order to understand cardiac calcium homeostasis, it is, therefore, important to study the calcium dynamics taking into account both types of cardiac cells. Here we have developed a model to capture the calcium dynamics in excitatory and non-excitatory cells taking into consideration the gap junction mediated calcium ion transfer from excitatory cell to non-excitatory cell. Our study revealed that the gap junctional coupling between excitatory and non-excitatory cells plays important role in the calcium dynamics. It is observed that any reduction in the functioning of gap junction may result in abnormal calcium oscillations in NEC, even when the calcium dynamics is normal in EC cell. Sensitivity of gap junction is observed to be independent of the pacing rate and hence a careful monitoring is required to maintain normal cardiomyocyte condition. It also highlights that sarcoplasmic reticulum may not be always able to control the amount of cytoplasmic calcium under the condition of calcium overload. Copyright © 2017 Elsevier Inc. All rights reserved.
Josephson junction in the quantum mesoscopic electric circuits with charge discreteness
NASA Astrophysics Data System (ADS)
Pahlavani, H.
2018-04-01
A quantum mesoscopic electrical LC-circuit with charge discreteness including a Josephson junction is considered and a nonlinear Hamiltonian that describing the dynamic of such circuit is introduced. The quantum dynamical behavior (persistent current probability) is studied in the charge and phase regimes by numerical solution approaches. The time evolution of charge and current, number-difference and the bosonic phase and also the energy spectrum of a quantum mesoscopic electric LC-circuit with charge discreteness that coupled with a Josephson junction device are investigated. We show the role of the coupling energy and the electrostatic Coulomb energy of the Josephson junction in description of the quantum behavior and the spectral properties of a quantum mesoscopic electrical LC-circuits with charge discreteness.
Conditions for synchronization in Josephson-junction arrays
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chernikov, A.A.; Schmidt, G.
An effective perturbation theoretical method has been developed to study the dynamics of Josephson Junction series arrays. It is shown that the inclusion of Junction capacitances, often ignored, has a significant impact on synchronization. Comparison of analytic with computational results over a wide range of parameters shows excellent agreement.
Dynamics between actin and the VE-cadherin/catenin complex
Abu Taha, Abdallah; Schnittler, Hans-J
2014-01-01
Endothelial adherens junctions are critical for physiological and pathological processes such as differentiation, maintenance of entire monolayer integrity, and the remodeling. The endothelial-specific VE-cadherin/catenin complex provides the backbone of adherens junctions and acts in close interaction with actin filaments and actin/myosin-mediated contractility to fulfill the junction demands. The functional connection between the cadherin/catenin complex and actin filaments might be either directly through α-catenins, or indirectly e.g., via linker proteins such as vinculin, p120ctn, α-actinin, or EPLIN. However, both junction integrity and dynamic remodeling have to be contemporarily coordinated. The actin-related protein complex ARP2/3 and its activating molecules, such as N-WASP and WAVE, have been shown to regulate the lammellipodia-mediated formation of cell junctions in both epithelium and endothelium. Recent reports now demonstrate a novel aspect of the ARP2/3 complex and the nucleating-promoting factors in the maintenance of endothelial barrier function and junction remodeling of established endothelial cell junctions. Those mechanisms open novel possibilities; not only in fulfilling physiological demands but obtained information may be of critical importance in pathologies such as wound healing, angiogenesis, inflammation, and cell diapedesis. PMID:24621569
Theoretical study of the Hoogsteen-Watson-Crick junctions in DNA.
Cubero, Elena; Luque, F Javier; Orozco, Modesto
2006-02-01
A series of d (AT)(n) oligonucleotides containing mixtures of normal B-type Watson-Crick and antiparallel Hoogsteen helices have been studied using molecular dynamics simulation techniques to analyze the structural and thermodynamic impact of the junction between Watson-Crick and antiparallel Hoogsteen structures. Analysis of molecular dynamics simulations strongly suggests that for all oligonucleotides studied the antiparallel Hoogsteen appears as a reasonable conformation, only slightly less stable than the canonical B-type Watson-Crick one. The junctions between the Watson-Crick and Hoogsteen structures introduces a priori a sharp discontinuity in the helix, because the properties of each type of conformation are very well preserved in the corresponding fragments. However, and quite counterintuitively, junctions do not largely distort the duplex in structural, dynamics or energetic terms. Our results strongly support the possibility that small fragments of antiparallel Hoogsteen duplex might be embedded into large fragments of B-type Watson-Crick helices, making possible protein-DNA interactions that are specific of the antiparallel Hoogsteen conformation.
Theoretical Study of the Hoogsteen–Watson-Crick Junctions in DNA
Cubero, Elena; Luque, F. Javier; Orozco, Modesto
2006-01-01
A series of d (AT)n oligonucleotides containing mixtures of normal B-type Watson-Crick and antiparallel Hoogsteen helices have been studied using molecular dynamics simulation techniques to analyze the structural and thermodynamic impact of the junction between Watson-Crick and antiparallel Hoogsteen structures. Analysis of molecular dynamics simulations strongly suggests that for all oligonucleotides studied the antiparallel Hoogsteen appears as a reasonable conformation, only slightly less stable than the canonical B-type Watson-Crick one. The junctions between the Watson-Crick and Hoogsteen structures introduces a priori a sharp discontinuity in the helix, because the properties of each type of conformation are very well preserved in the corresponding fragments. However, and quite counterintuitively, junctions do not largely distort the duplex in structural, dynamics or energetic terms. Our results strongly support the possibility that small fragments of antiparallel Hoogsteen duplex might be embedded into large fragments of B-type Watson-Crick helices, making possible protein-DNA interactions that are specific of the antiparallel Hoogsteen conformation. PMID:16287814
NASA Astrophysics Data System (ADS)
Ellis, Matthew O. A.; Stamenova, Maria; Sanvito, Stefano
2017-12-01
There exists a significant challenge in developing efficient magnetic tunnel junctions with low write currents for nonvolatile memory devices. With the aim of analyzing potential materials for efficient current-operated magnetic junctions, we have developed a multi-scale methodology combining ab initio calculations of spin-transfer torque with large-scale time-dependent simulations using atomistic spin dynamics. In this work we introduce our multiscale approach, including a discussion on a number of possible schemes for mapping the ab initio spin torques into the spin dynamics. We demonstrate this methodology on a prototype Co/MgO/Co/Cu tunnel junction showing that the spin torques are primarily acting at the interface between the Co free layer and MgO. Using spin dynamics we then calculate the reversal switching times for the free layer and the critical voltages and currents required for such switching. Our work provides an efficient, accurate, and versatile framework for designing novel current-operated magnetic devices, where all the materials details are taken into account.
Low temperature properties of spin filter NbN/GdN/NbN Josephson junctions
NASA Astrophysics Data System (ADS)
Massarotti, D.; Caruso, R.; Pal, A.; Rotoli, G.; Longobardi, L.; Pepe, G. P.; Blamire, M. G.; Tafuri, F.
2017-02-01
A ferromagnetic Josephson junction (JJ) represents a special class of hybrid system where different ordered phases meet and generate novel physics. In this work we report on the transport measurements of underdamped ferromagnetic NbN/GdN/NbN JJs at low temperatures. In these junctions the ferromagnetic insulator gadolinium nitride barrier generates spin-filtering properties and a dominant second harmonic component in the current-phase relation. These features make spin filter junctions quite interesting also in terms of fundamental studies on phase dynamics and dissipation. We discuss the fingerprints of spin filter JJs, through complementary transport measurements, and their implications on the phase dynamics, through standard measurements of switching current distributions. NbN/GdN/NbN JJs, where spin filter properties can be controllably tuned along with the critical current density (Jc), turn to be a very relevant term of reference to understand phase dynamics and dissipation in an enlarged class of JJs, not necessarily falling in the standard tunnel limit characterized by low Jc values.
Kuhn, G C S; Teo, C H; Schwarzacher, T; Heslop-Harrison, J S
2009-05-01
Satellite DNA (satDNA) is a major component of genomes but relatively little is known about the fine-scale organization of unrelated satDNAs residing at the same chromosome location, and the sequence structure and dynamics of satDNA junctions. We studied the organization and sequence junctions of two nonhomologous satDNAs, pBuM and DBC-150, in three species from the neotropical Drosophila buzzatii cluster (repleta group). In situ hybridization to microchromosomes, interphase nuclei and extended DNA fibers showed frequent interspersion of the two satellites in D. gouveai, D. antonietae and, to a lesser extent, D. seriema. We isolated by PCR six pBuM x DBC-150 junctions: four are exclusive to D. gouveai and two are exclusive to D. antonietae. The six junction breakpoints occur at different positions within monomers, suggesting independent origin. Four junctions showed abrupt transitions between the two satellites, whereas two junctions showed a distinct 10 bp tandem duplication before the junction. Unlike pBuM, DBC-150 junction repeats are more variable than randomly cloned monomers and showed diagnostic features in common to a 3-monomer higher-order repeat seen in the sister species D. serido. The high levels of interspersion between pBuM and DBC-150 repeats suggest extensive rearrangements between the two satellites, maybe favored by specific features of the microchromosomes. Our interpretation is that the junctions evolved by multiples events of illegitimate recombination between nonhomologous satDNA repeats, with subsequent rounds of unequal crossing-over expanding the copy number of some of the junctions.
Pump-Probe Noise Spectroscopy of Molecular Junctions.
Ochoa, Maicol A; Selzer, Yoram; Peskin, Uri; Galperin, Michael
2015-02-05
The slow response of electronic components in junctions limits the direct applicability of pump-probe type spectroscopy in assessing the intramolecular dynamics. Recently the possibility of getting information on a sub-picosecond time scale from dc current measurements was proposed. We revisit the idea of picosecond resolution by pump-probe spectroscopy from dc measurements and show that any intramolecular dynamics not directly related to charge transfer in the current direction is missed by current measurements. We propose a pump-probe dc shot noise spectroscopy as a suitable alternative. Numerical examples of time-dependent and average responses of junctions are presented for generic models.
The persistent current and energy spectrum on a driven mesoscopic LC-circuit with Josephson junction
NASA Astrophysics Data System (ADS)
Pahlavanias, Hassan
2018-03-01
The quantum theory for a mesoscopic electric circuit including a Josephson junction with charge discreteness is studied. By considering coupling energy of the mesoscopic capacitor in Josephson junction device, a Hamiltonian describing the dynamics of a quantum mesoscopic electric LC-circuit with charge discreteness is introduced. We first calculate the persistent current on a quantum driven ring including Josephson junction. Then we obtain the persistent current and energy spectrum of a quantum mesoscopic electrical circuit which includes capacitor, inductor, time-dependent external source and Josephson junction.
Supramolecular Systems and Chemical Reactions in Single-Molecule Break Junctions.
Li, Xiaohui; Hu, Duan; Tan, Zhibing; Bai, Jie; Xiao, Zongyuan; Yang, Yang; Shi, Jia; Hong, Wenjing
2017-04-01
The major challenges of molecular electronics are the understanding and manipulation of the electron transport through the single-molecule junction. With the single-molecule break junction techniques, including scanning tunneling microscope break junction technique and mechanically controllable break junction technique, the charge transport through various single-molecule and supramolecular junctions has been studied during the dynamic fabrication and continuous characterization of molecular junctions. This review starts from the charge transport characterization of supramolecular junctions through a variety of noncovalent interactions, such as hydrogen bond, π-π interaction, and electrostatic force. We further review the recent progress in constructing highly conductive molecular junctions via chemical reactions, the response of molecular junctions to external stimuli, as well as the application of break junction techniques in controlling and monitoring chemical reactions in situ. We suggest that beyond the measurement of single molecular conductance, the single-molecule break junction techniques provide a promising access to study molecular assembly and chemical reactions at the single-molecule scale.
L10-MnGa based magnetic tunnel junction for high magnetic field sensor
NASA Astrophysics Data System (ADS)
Zhao, X. P.; Lu, J.; Mao, S. W.; Yu, Z. F.; Wang, H. L.; Wang, X. L.; Wei, D. H.; Zhao, J. H.
2017-07-01
We report on the investigation of the magnetic tunnel junction structure designed for high magnetic field sensors with a perpendicularly magnetized L10-MnGa reference layer and an in-plane magnetized Fe sensing layer. A large linear tunneling magnetoresistance ratio up to 27.4% and huge dynamic range up to 5600 Oe have been observed at 300 K, with a low nonlinearity of 0.23% in the optimized magnetic tunnel junction (MTJ). The field response of tunneling magnetoresistance is discussed to explain the field sensing properties in the dynamic range. These results indicate that L10-MnGa based orthogonal MTJ is a promising candidate for a high performance magnetic field sensor with a large dynamic range, high endurance and low power consumption.
Experimental testing and modeling analysis of solute mixing at water distribution pipe junctions.
Shao, Yu; Jeffrey Yang, Y; Jiang, Lijie; Yu, Tingchao; Shen, Cheng
2014-06-01
Flow dynamics at a pipe junction controls particle trajectories, solute mixing and concentrations in downstream pipes. The effect can lead to different outcomes of water quality modeling and, hence, drinking water management in a distribution network. Here we have investigated solute mixing behavior in pipe junctions of five hydraulic types, for which flow distribution factors and analytical equations for network modeling are proposed. First, based on experiments, the degree of mixing at a cross is found to be a function of flow momentum ratio that defines a junction flow distribution pattern and the degree of departure from complete mixing. Corresponding analytical solutions are also validated using computational-fluid-dynamics (CFD) simulations. Second, the analytical mixing model is further extended to double-Tee junctions. Correspondingly the flow distribution factor is modified to account for hydraulic departure from a cross configuration. For a double-Tee(A) junction, CFD simulations show that the solute mixing depends on flow momentum ratio and connection pipe length, whereas the mixing at double-Tee(B) is well represented by two independent single-Tee junctions with a potential water stagnation zone in between. Notably, double-Tee junctions differ significantly from a cross in solute mixing and transport. However, it is noted that these pipe connections are widely, but incorrectly, simplified as cross junctions of assumed complete solute mixing in network skeletonization and water quality modeling. For the studied pipe junction types, analytical solutions are proposed to characterize the incomplete mixing and hence may allow better water quality simulation in a distribution network. Published by Elsevier Ltd.
Dispersion mechanisms of a tidal river junction in the Sacramento–San Joaquin Delta, California
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gleichauf, Karla T.; Wolfram, Philip J.; Monsen, Nancy E.
In branching channel networks, such as in the Sacramento–San Joaquin River Delta, junction flow dynamics contribute to dispersion of ecologically important entities such as fish, pollutants, nutrients, salt, sediment, and phytoplankton. Flow transport through a junction largely arises from velocity phasing in the form of divergent flow between junction channels for a portion of the tidal cycle. Field observations in the Georgiana Slough junction, which is composed of the North and South Mokelumne rivers, Georgiana Slough, and the Mokelumne River, show that flow phasing differences between these rivers arise from operational, riverine, and tidal forcing. A combination of Acoustic Dopplermore » Current Profile (ADCP) boat transecting and moored ADCPs over a spring–neap tidal cycle (May to June 2012) monitored the variability of spatial and temporal velocity, respectively. Two complementary drifter studies enabled assessment of local transport through the junction to identify small-scale intrajunction dynamics. We supplemented field results with numerical simulations using the SUNTANS model to demonstrate the importance of phasing offsets for junction transport and dispersion. Different phasing of inflows to the junction resulted in scalar patchiness that is characteristic of MacVean and Stacey’s (2011) advective tidal trapping. Furthermore, we observed small-scale junction flow features including a recirculation zone and shear layer, which play an important role in intra-junction mixing over time scales shorter than the tidal cycle (i.e., super-tidal time scales). Thus, the study period spanned open- and closed-gate operations at the Delta Cross Channel. Synthesis of field observations and modeling efforts suggest that management operations related to the Delta Cross Channel can strongly affect transport in the Delta by modifying the relative contributions of tidal and riverine flows, thereby changing the junction flow phasing.« less
Dispersion mechanisms of a tidal river junction in the Sacramento–San Joaquin Delta, California
Gleichauf, Karla T.; Wolfram, Philip J.; Monsen, Nancy E.; ...
2014-12-17
In branching channel networks, such as in the Sacramento–San Joaquin River Delta, junction flow dynamics contribute to dispersion of ecologically important entities such as fish, pollutants, nutrients, salt, sediment, and phytoplankton. Flow transport through a junction largely arises from velocity phasing in the form of divergent flow between junction channels for a portion of the tidal cycle. Field observations in the Georgiana Slough junction, which is composed of the North and South Mokelumne rivers, Georgiana Slough, and the Mokelumne River, show that flow phasing differences between these rivers arise from operational, riverine, and tidal forcing. A combination of Acoustic Dopplermore » Current Profile (ADCP) boat transecting and moored ADCPs over a spring–neap tidal cycle (May to June 2012) monitored the variability of spatial and temporal velocity, respectively. Two complementary drifter studies enabled assessment of local transport through the junction to identify small-scale intrajunction dynamics. We supplemented field results with numerical simulations using the SUNTANS model to demonstrate the importance of phasing offsets for junction transport and dispersion. Different phasing of inflows to the junction resulted in scalar patchiness that is characteristic of MacVean and Stacey’s (2011) advective tidal trapping. Furthermore, we observed small-scale junction flow features including a recirculation zone and shear layer, which play an important role in intra-junction mixing over time scales shorter than the tidal cycle (i.e., super-tidal time scales). Thus, the study period spanned open- and closed-gate operations at the Delta Cross Channel. Synthesis of field observations and modeling efforts suggest that management operations related to the Delta Cross Channel can strongly affect transport in the Delta by modifying the relative contributions of tidal and riverine flows, thereby changing the junction flow phasing.« less
An implicit divalent counterion force field for RNA molecular dynamics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Henke, Paul S.; Mak, Chi H., E-mail: cmak@usc.edu; Center of Applied Mathematical Sciences, University of Southern California, Los Angeles, California 90089
How to properly account for polyvalent counterions in a molecular dynamics simulation of polyelectrolytes such as nucleic acids remains an open question. Not only do counterions such as Mg{sup 2+} screen electrostatic interactions, they also produce attractive intrachain interactions that stabilize secondary and tertiary structures. Here, we show how a simple force field derived from a recently reported implicit counterion model can be integrated into a molecular dynamics simulation for RNAs to realistically reproduce key structural details of both single-stranded and base-paired RNA constructs. This divalent counterion model is computationally efficient. It works with existing atomistic force fields, or coarse-grainedmore » models may be tuned to work with it. We provide optimized parameters for a coarse-grained RNA model that takes advantage of this new counterion force field. Using the new model, we illustrate how the structural flexibility of RNA two-way junctions is modified under different salt conditions.« less
Poromechanics of stick-slip frictional sliding and strength recovery on tectonic faults
Scuderi, Marco M.; Carpenter, Brett M.; Johnson, Paul A.; ...
2015-10-22
Pore fluids influence many aspects of tectonic faulting including frictional strength aseismic creep and effective stress during the seismic cycle. But, the role of pore fluid pressure during earthquake nucleation and dynamic rupture remains poorly understood. Here we report on the evolution of pore fluid pressure and porosity during laboratory stick-slip events as an analog for the seismic cycle. We sheared layers of simulated fault gouge consisting of glass beads in a double-direct shear configuration under true triaxial stresses using drained and undrained fluid conditions and effective normal stress of 5–10 MPa. Shear stress was applied via a constant displacementmore » rate, which we varied in velocity step tests from 0.1 to 30 µm/s. Here, we observe net pore pressure increases, or compaction, during dynamic failure and pore pressure decreases, or dilation, during the interseismic period, depending on fluid boundary conditions. In some cases, a brief period of dilation is attendant with the onset of dynamic stick slip. Our data show that time-dependent strengthening and dynamic stress drop increase with effective normal stress and vary with fluid conditions. For undrained conditions, dilation and preseismic slip are directly related to pore fluid depressurization; they increase with effective normal stress and recurrence time. Microstructural observations confirm the role of water-activated contact growth and shear-driven elastoplastic processes at grain junctions. These results indicate that physicochemical processes acting at grain junctions together with fluid pressure changes dictate stick-slip stress drop and interseismic creep rates and thus play a key role in earthquake nucleation and rupture propagation.« less
NASA Astrophysics Data System (ADS)
Zhang, Lei; Niu, Pingjuan; Li, Yuqiang; Song, Minghui; Zhang, Jianxin; Ning, Pingfan; Chen, Peizhuan
2017-12-01
Ga0.51In0.49P/In0.01Ga0.99As/Ge triple-junction solar cells for space applications were grown on 4 inch Ge substrates by metal organic chemical vapor deposition methods. The triple-junction solar cells were obtained by optimizing the subcell structure, showing a high open-circuit voltage of 2.77 V and a high conversion efficiency of 31% with 30.15 cm2 area under the AM0 spectrum at 25 °C. In addition, the In0.01Ga0.99As middle subcell structure was focused by optimizing in order to improve the anti radiation ability of triple-junction solar cells, and the remaining factor of conversion efficiency for middle subcell structure was enhanced from 84% to 92%. Finally, the remaining factor of external quantum efficiency for triple-junction solar cells was increased from 80% to 85.5%.
Epithelial junction formation requires confinement of Cdc42 activity by a novel SH3BP1 complex
Elbediwy, Ahmed; Zihni, Ceniz; Terry, Stephen J.; Clark, Peter
2012-01-01
Epithelial cell–cell adhesion and morphogenesis require dynamic control of actin-driven membrane remodeling. The Rho guanosine triphosphatase (GTPase) Cdc42 regulates sequential molecular processes during cell–cell junction formation; hence, mechanisms must exist that inactivate Cdc42 in a temporally and spatially controlled manner. In this paper, we identify SH3BP1, a GTPase-activating protein for Cdc42 and Rac, as a regulator of junction assembly and epithelial morphogenesis using a functional small interfering ribonucleic acid screen. Depletion of SH3BP1 resulted in loss of spatial control of Cdc42 activity, stalled membrane remodeling, and enhanced growth of filopodia. SH3BP1 formed a complex with JACOP/paracingulin, a junctional adaptor, and CD2AP, a scaffolding protein; both were required for normal Cdc42 signaling and junction formation. The filamentous actin–capping protein CapZ also associated with the SH3BP1 complex and was required for control of actin remodeling. Epithelial junction formation and morphogenesis thus require a dual activity complex, containing SH3BP1 and CapZ, that is recruited to sites of active membrane remodeling to guide Cdc42 signaling and cytoskeletal dynamics. PMID:22891260
Gap junction- and hemichannel-independent actions of connexins.
Jiang, Jean X; Gu, Sumin
2005-06-10
Connexins have been known to be the protein building blocks of gap junctions and mediate cell-cell communication. In contrast to the conventional dogma, recent evidence suggests that in addition to forming gap junction channels, connexins possess gap junction-independent functions. One important gap junction-independent function for connexins is to serve as the major functional component for hemichannels, the un-apposed halves of gap junctions. Hemichannels, as independent functional units, play roles that are different from that of gap junctions in the cell. The other functions of connexins appear to be gap junction- and hemichannel-independent. Published studies implicate the latter functions of connexins in cell growth, differentiation, tumorigenicity, injury, and apoptosis, although the mechanistic aspects of these actions remain largely unknown. In this review, gap junction- and hemichannel-independent functions of connexins are summarized, and the molecular mechanisms underlying these connexin functions are speculated and discussed.
Wnt-dependent epithelial transitions drive pharyngeal pouch formation
Choe, Chong Pyo; Collazo, Andres; Trinh, Le A.; Pan, Luyuan; Moens, Cecilia B.; Crump, J. Gage
2013-01-01
SUMMARY The pharyngeal pouches, which form by budding of the foregut endoderm, are essential for segmentation of the vertebrate face. To date, the cellular mechanism and segmental nature of such budding have remained elusive. Here, we find that Wnt11r and Wnt4a from the head mesoderm and ectoderm, respectively, play distinct roles in the segmental formation of pouches in zebrafish. Time-lapse microscopy, combined with mutant and tissue-specific transgenic experiments, reveal requirements of Wnt signaling in two phases of endodermal epithelial transitions. Initially, Wnt11r and Rac1 destabilize the endodermal epithelium to promote the lateral movement of pouch-forming cells. Next, Wnt4a and Cdc42 signaling induce the rearrangement of maturing pouch cells into bilayers through junctional localization of the Alcama immunoglobulin-domain protein, which functions to restabilize adherens junctions. We propose that this dynamic control of epithelial morphology by Wnt signaling may be a common theme for the budding of organ anlagen from the endoderm. PMID:23375584
Fabrication of high-quality superconductor-insulator-superconductor junctions on thin SiN membranes
NASA Technical Reports Server (NTRS)
Garcia, Edouard; Jacobson, Brian R.; Hu, Qing
1993-01-01
We have successfully fabricated high-quality and high-current density superconductor-insulator-superconductor (SIS) junctions on freestanding thin silicon nitride (SIN) membranes. These devices can be used in a novel millimeter-wave and THz receiver system which is made using micromachining. The SIS junctions with planar antennas were fabricated first on a silicon wafer covered with a SiN membrane, the Si wafer underneath was then etched away using an anisotropic KOH etchant. The current-voltage characteristics of the SIS junctions remained unchanged after the whole process, and the junctions and the membrane survived thermal cycling.
Time-Resolved Chemical Mapping in Light-Emitting Electrochemical Cells.
Jafari, Mohammad Javad; Liu, Jiang; Engquist, Isak; Ederth, Thomas
2017-01-25
An understanding of the doping and ion distributions in light-emitting electrochemical cells (LECs) is required to approach a realistic conduction model which can precisely explain the electrochemical reactions, p-n junction formation, and ion dynamics in the active layer and to provide relevant information about LECs for systematic improvement of function and manufacture. Here, Fourier-transform infrared (FTIR) microscopy is used to monitor anion density profile and polymer structure in situ and for time-resolved mapping of electrochemical doping in an LEC under bias. The results are in very good agreement with the electrochemical doping model with respect to ion redistribution and formation of a dynamic p-n junction in the active layer. We also physically slow ions by decreasing the working temperature and study frozen-junction formation and immobilization of ions in a fixed-junction LEC device by FTIR imaging. The obtained results show irreversibility of the ion redistribution and polymer doping in a fixed-junction device. In addition, we demonstrate that infrared microscopy is a useful tool for in situ characterization of electroactive organic materials.
Cheng, C Yan; Mruk, Dolores D
2002-10-01
Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.
Intrinsic islet heterogeneity and gap junction coupling determine spatiotemporal Ca²⁺ wave dynamics.
Benninger, Richard K P; Hutchens, Troy; Head, W Steven; McCaughey, Michael J; Zhang, Min; Le Marchand, Sylvain J; Satin, Leslie S; Piston, David W
2014-12-02
Insulin is released from the islets of Langerhans in discrete pulses that are linked to synchronized oscillations of intracellular free calcium ([Ca(2+)]i). Associated with each synchronized oscillation is a propagating calcium wave mediated by Connexin36 (Cx36) gap junctions. A computational islet model predicted that waves emerge due to heterogeneity in β-cell function throughout the islet. To test this, we applied defined patterns of glucose stimulation across the islet using a microfluidic device and measured how these perturbations affect calcium wave propagation. We further investigated how gap junction coupling regulates spatiotemporal [Ca(2+)]i dynamics in the face of heterogeneous glucose stimulation. Calcium waves were found to originate in regions of the islet having elevated excitability, and this heterogeneity is an intrinsic property of islet β-cells. The extent of [Ca(2+)]i elevation across the islet in the presence of heterogeneity is gap-junction dependent, which reveals a glucose dependence of gap junction coupling. To better describe these observations, we had to modify the computational islet model to consider the electrochemical gradient between neighboring β-cells. These results reveal how the spatiotemporal [Ca(2+)]i dynamics of the islet depend on β-cell heterogeneity and cell-cell coupling, and are important for understanding the regulation of coordinated insulin release across the islet. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Head, W Steven; Orseth, Meredith L; Nunemaker, Craig S; Satin, Leslie S; Piston, David W; Benninger, Richard K P
2012-07-01
Insulin is secreted from the islets of Langerhans in coordinated pulses. These pulses are thought to lead to plasma insulin oscillations, which are putatively more effective in lowering blood glucose than continuous levels of insulin. Gap-junction coupling of β-cells by connexin-36 coordinates intracellular free calcium oscillations and pulsatile insulin release in isolated islets, however a role in vivo has not been shown. We test whether loss of gap-junction coupling disrupts plasma insulin oscillations and whether this impacts glucose tolerance. We characterized the connexin-36 knockout (Cx36(-/-)) mouse phenotype and performed hyperglycemic clamps with rapid sampling of insulin in Cx36(-/-) and control mice. Our results show that Cx36(-/-) mice are glucose intolerant, despite normal plasma insulin levels and insulin sensitivity. However, Cx36(-/-) mice exhibit reduced insulin pulse amplitudes and a reduction in first-phase insulin secretion. These changes are similarly found in isolated Cx36(-/-) islets. We conclude that Cx36 gap junctions regulate the in vivo dynamics of insulin secretion, which in turn is important for glucose homeostasis. Coordinated pulsatility of individual islets enhances the first-phase elevation and second-phase pulses of insulin. Because these dynamics are disrupted in the early stages of type 2 diabetes, dysregulation of gap-junction coupling could be an important factor in the development of this disease.
Shi, Jingjing; Zhong, Yang; Fisher, Timothy S; Ruan, Xiulin
2018-05-02
Three different mechanisms are identified to contribute to thermal resistances across a carbon nanotube-graphene junction: material mismatch, nonplanar junction, and defects. To isolate the contributions of each mechanism, we have designed five types of junctions and performed nonequilibrium molecular dynamics simulations. The results show that the contributions from the three mechanisms are similar, each at around 2.5 × 10 -11 m 2 K/W. The relations between thermal boundary resistance and both defect number and turning angle at the interface are also studied.
Specific Cx43 phosphorylation events regulate gap junction turnover in vivo
Solan, Joell L.; Lampe, Paul D.
2014-01-01
Gap junctions, composed of proteins from the connexin gene family, are highly dynamic structures that are regulated by kinase-mediated signaling pathways and interactions with other proteins. Phosphorylation of Connexin43 (Cx43) at different sites controls gap junction assembly, gap junction size and gap junction turnover. Here we present a model describing how Akt, mitogen activated protein kinase (MAPK) and src kinase coordinate to regulate rapid turnover of gap junctions. Specifically, Akt phosphorylates Cx43 at S373 eliminating interaction with zona occludens-1 (ZO-1) allowing gap junctions to enlarge. Then MAPK and src phosphorylate Cx43 to initiate turnover. We integrate published data with new data to test and refine this model. Finally, we propose that differential coordination of kinase activation and Cx43 phosphorylation controls the specific routes of disassembly, e.g., annular junction formation or gap junctions can potentially “unzip” and be internalized/endocytosed into the cell that produced each connexin. PMID:24508467
Moreno, Vanessa; Gonzalo, Pilar; Gómez-Escudero, Jesús; Pollán, Ángela; Acín-Pérez, Rebeca; Breckenridge, Mark; Yáñez-Mó, María; Barreiro, Olga; Orsenigo, Fabrizio; Kadomatsu, Kenji; Chen, Christopher S; Enríquez, José A; Dejana, Elisabetta; Sánchez-Madrid, Francisco; Arroyo, Alicia G
2014-09-01
Cell-cell adhesions are important sites through which cells experience and resist forces. In endothelial cells, these forces regulate junction dynamics and determine endothelial barrier strength. We identify the Ig superfamily member EMMPRIN (also known as basigin) as a coordinator of forces at endothelial junctions. EMMPRIN localization at junctions correlates with endothelial junction strength in different mouse vascular beds. Accordingly, EMMPRIN-deficient mice show altered junctions and increased junction permeability. Lack of EMMPRIN alters the localization and function of VE-cadherin (also known as cadherin-5) by decreasing both actomyosin contractility and tugging forces at endothelial cell junctions. EMMPRIN ensures proper actomyosin-driven maturation of competent endothelial junctions by forming a molecular complex with γ-catenin (also known as junction plakoglobin) and Nm23 (also known as NME1), a nucleoside diphosphate kinase, thereby locally providing ATP to fuel the actomyosin machinery. These results provide a novel mechanism for the regulation of actomyosin contractility at endothelial junctions and might have broader implications in biological contexts such as angiogenesis, collective migration and tissue morphogenesis by coupling compartmentalized energy production to junction assembly. © 2014. Published by The Company of Biologists Ltd.
Moreno, Vanessa; Gonzalo, Pilar; Gómez-Escudero, Jesús; Pollán, Ángela; Acín-Pérez, Rebeca; Breckenridge, Mark; Yáñez-Mó, María; Barreiro, Olga; Orsenigo, Fabrizio; Kadomatsu, Kenji; Chen, Christopher S.; Enríquez, José A.; Dejana, Elisabetta; Sánchez-Madrid, Francisco; Arroyo, Alicia G.
2014-01-01
ABSTRACT Cell–cell adhesions are important sites through which cells experience and resist forces. In endothelial cells, these forces regulate junction dynamics and determine endothelial barrier strength. We identify the Ig superfamily member EMMPRIN (also known as basigin) as a coordinator of forces at endothelial junctions. EMMPRIN localization at junctions correlates with endothelial junction strength in different mouse vascular beds. Accordingly, EMMPRIN-deficient mice show altered junctions and increased junction permeability. Lack of EMMPRIN alters the localization and function of VE-cadherin (also known as cadherin-5) by decreasing both actomyosin contractility and tugging forces at endothelial cell junctions. EMMPRIN ensures proper actomyosin-driven maturation of competent endothelial junctions by forming a molecular complex with γ-catenin (also known as junction plakoglobin) and Nm23 (also known as NME1), a nucleoside diphosphate kinase, thereby locally providing ATP to fuel the actomyosin machinery. These results provide a novel mechanism for the regulation of actomyosin contractility at endothelial junctions and might have broader implications in biological contexts such as angiogenesis, collective migration and tissue morphogenesis by coupling compartmentalized energy production to junction assembly. PMID:24994937
Vortex dynamics in two-dimensional Josephson junction arrays
NASA Astrophysics Data System (ADS)
Ashrafuzzaman, Md.; Capezzali, Massimiliano; Beck, Hans
2003-08-01
The dynamic response of two-dimensional Josephson junction arrays close to, but above the Berezinskii-Kosterlitz-Thouless (BKT) transition temperature is described in terms of the vortex dielectric function ɛ(ω) and the flux noise spectrum Sφ(ω). They are calculated by considering both the contributions of free vortices interacting through a screened Coulomb potential and the pair motion of vortices that are closer to each other than the BKT correlation length. This procedure allows us to understand various anomalous features in ɛ(ω) and in Sφ(ω) that have been observed both experimentally and in dynamic simulations.
Dynamic magnetoelectric effect in ferromagnet/superconductor tunnel junctions.
Trif, Mircea; Tserkovnyak, Yaroslav
2013-08-23
We study the magnetization dynamics in a ferromagnet/insulator/superconductor tunnel junction and the associated buildup of the electrical polarization. We show that for an open circuit, the induced voltage varies strongly and nonmonotonically with the precessional frequency, and can be enhanced significantly by the superconducting correlations. For frequencies much smaller or much larger than the superconducting gap, the voltage drops to zero, while when these two energy scales are comparable, the voltage is peaked at a value determined by the driving frequency. We comment on the potential utilization of the effect for the low-temperature spatially resolved spectroscopy of magnetic dynamics.
Junction Propagation in Organometal Halide Perovskite-Polymer Composite Thin Films.
Shan, Xin; Li, Junqiang; Chen, Mingming; Geske, Thomas; Bade, Sri Ganesh R; Yu, Zhibin
2017-06-01
With the emergence of organometal halide perovskite semiconductors, it has been discovered that a p-i-n junction can be formed in situ due to the migration of ionic species in the perovskite when a bias is applied. In this work, we investigated the junction formation dynamics in methylammonium lead tribromide (MAPbBr 3 )/polymer composite thin films. It was concluded that the p- and n- doped regions propagated into the intrinsic region with an increasing bias, leading to a reduced intrinsic perovskite layer thickness and the formation of an effective light-emitting junction regardless of perovskite layer thicknesses (300 nm to 30 μm). The junction propagation also played a major role in deteriorating the LED operation lifetime. Stable perovskite LEDs can be achieved by restricting the junction propagation after its formation.
Dynamical photo-induced electronic properties of molecular junctions
NASA Astrophysics Data System (ADS)
Beltako, K.; Michelini, F.; Cavassilas, N.; Raymond, L.
2018-03-01
Nanoscale molecular-electronic devices and machines are emerging as promising functional elements, naturally flexible and efficient, for next-generation technologies. A deeper understanding of carrier dynamics in molecular junctions is expected to benefit many fields of nanoelectronics and power devices. We determine time-resolved charge current flowing at the donor-acceptor interface in molecular junctions connected to metallic electrodes by means of quantum transport simulations. The current is induced by the interaction of the donor with a Gaussian-shape femtosecond laser pulse. Effects of the molecular internal coupling, metal-molecule tunneling, and light-donor coupling on photocurrent are discussed. We then define the time-resolved local density of states which is proposed as an efficient tool to describe the absorbing molecule in contact with metallic electrodes. Non-equilibrium reorganization of hybridized molecular orbitals through the light-donor interaction gives rise to two phenomena: the dynamical Rabi shift and the appearance of Floquet-like states. Such insights into the dynamical photoelectronic structure of molecules are of strong interest for ultrafast spectroscopy and open avenues toward the possibility of analyzing and controlling the internal properties of quantum nanodevices with pump-push photocurrent spectroscopy.
A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells.
Higaki, Takumi; Kutsuna, Natsumaro; Akita, Kae; Takigawa-Imamura, Hisako; Yoshimura, Kenji; Miura, Takashi
2016-04-01
Plant leaf epidermal cells exhibit a jigsaw puzzle-like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo.
Advance of Mechanically Controllable Break Junction for Molecular Electronics.
Wang, Lu; Wang, Ling; Zhang, Lei; Xiang, Dong
2017-06-01
Molecular electronics stands for the ultimate size of functional elements, keeping up with an unstoppable trend over the past few decades. As a vital component of molecular electronics, single molecular junctions have attracted significant attention from research groups all over the world. Due to its pronounced superiority, the mechanically controllable break junctions (MCBJ) technique has been widely applied to characterize the dynamic performance of single molecular junctions. This review presents a system analysis for single-molecule junctions and offers an overview of four test-beds for single-molecule junctions, thus offering more insight into the mechanisms of electron transport. We mainly focus on the development of state-of-the-art mechanically controlled break junctions. The three-terminal gated MCBJ approaches are introduced to manipulate the electron transport of molecules, and MCBJs are combined with characterization techniques. Additionally, applications of MCBJs and remarkable properties of single molecules are addressed. Finally, the challenges and perspective for the mechanically controllable break junctions technique are provided.
A multilayered approach to superconducting tunnel junction x ray detectors
NASA Technical Reports Server (NTRS)
Rippert, E. D.; Song, S. N.; Ketterson, J. B.; Maglic, S. R.; Lomatch, S.; Thomas, C.; Cheida, M. A.; Ulmer, M. P.
1992-01-01
'First generation' superconducting tunnel junction X-ray detectors (characterized by a single tunnel junction in direct contact with its substrate, with totally external amplification) remain more than an order of magnitude away from their theoretical energy resolutions which are in the order of eV's. The difficulties that first generation devices are encountering are being attacked by a 'second generation' of superconducting X-ray detector designs including quasiparticle trapping configurations and Josephson junction arrays. A second generation design concept, the multilayered superconducting tunnel junction X-ray detector, consisting of tens to hundreds of tunnel junctions stacked on top of one another (a superlattice), is presented. Some of the possibilities of this engineered materials approach include the tuning of phonon transmission characteristics of the material, suppression of parasitic quasiparticle trapping and intrinsic amplification.
NASA Astrophysics Data System (ADS)
Stefanatos, Dionisis; Paspalakis, Emmanuel
2018-05-01
In this article we consider a bosonic Josephson junction, a model system composed by two coupled nonlinear quantum oscillators which can be implemented in various physical contexts, initially prepared in a product of weakly populated coherent states. We quantify the maximum achievable entanglement between the modes of the junction and then use shortcuts to adiabaticity, a method developed to speed up adiabatic quantum dynamics, as well as numerical optimization, to find time-dependent controls (the nonlinearity and the coupling of the junction) which bring the system to a maximally entangled state.
Classical analogs for Rabi-oscillations, Ramsey-fringes, and spin-echo in Josephson junctions
NASA Astrophysics Data System (ADS)
Marchese, J. E.; Cirillo, M.; Grønbech-Jensen, N.
2007-08-01
We investigate the results of recently published experiments on the quantum behavior of Josephson circuits in terms of the classical modeling based on the resistively and capacitively-shunted (RCSJ) junction model. Our analysis shows evidence for a close analogy between the nonlinear behavior of a pulsed microwave-driven Josephson junction at low temperature and low dissipation and the experimental observations reported for the Josephson circuits. Specifically, we demonstrate that Rabi-oscillations, Ramsey-fringes, and spin-echo observations are not phenomena with a unique quantum interpretation. In fact, they are natural consequences of transients to phase-locking in classical nonlinear dynamics and can be observed in a purely classical model of a Josephson junction when the experimental recipe for the application of microwaves is followed and the experimental detection scheme followed. We therefore conclude that classical nonlinear dynamics can contribute to the understanding of relevant experimental observations of Josephson response to various microwave perturbations at very low temperature and low dissipation.
Transition between B-DNA and Z-DNA: free energy landscape for the B-Z junction propagation.
Lee, Juyong; Kim, Yang-Gyun; Kim, Kyeong Kyu; Seok, Chaok
2010-08-05
Canonical, right-handed B-DNA can be transformed into noncanonical, left-handed Z-DNA in vitro at high salt concentrations or in vivo under physiological conditions. The molecular mechanism of this drastic conformational transition is still unknown despite numerous studies. Inspired by the crystal structure of a B-Z junction and the previous zipper model, we show here, with the aid of molecular dynamics simulations, that a stepwise propagation of a B-Z junction is a highly probable pathway for the B-Z transition. In this paper, the movement of a B-Z junction by a two-base-pair step in a double-strand nonamer, [d(GpCpGpCpGpCpGpCpG)](2), is considered. Targeted molecular dynamics simulations and umbrella sampling for this transition resulted in a transition pathway with a free energy barrier of 13 kcal/mol. This barrier is much more favorable than those obtained from previous atomistic simulations that lead to concerted transitions of the whole strands. The free energy difference between B-DNA and Z-DNA evaluated from our simulation is 0.9 kcal/mol per dinucleotide unit, which is consistent with previous experiments. The current computation thus strongly supports the proposal that the B-Z transition involves a relatively fast extension of B-DNA or Z-DNA by sequential propagation of B-Z junctions once nucleation of junctions is established.
CLASP2 interacts with p120-catenin and governs microtubule dynamics at adherens junctions
Shahbazi, Marta N.; Megias, Diego; Epifano, Carolina; Akhmanova, Anna; Gundersen, Gregg G.; Fuchs, Elaine
2013-01-01
Classical cadherins and their connections with microtubules (MTs) are emerging as important determinants of cell adhesion. However, the functional relevance of such interactions and the molecular players that contribute to tissue architecture are still emerging. In this paper, we report that the MT plus end–binding protein CLASP2 localizes to adherens junctions (AJs) via direct interaction with p120-catenin (p120) in primary basal mouse keratinocytes. Reductions in the levels of p120 or CLASP2 decreased the localization of the other protein to cell–cell contacts and altered AJ dynamics and stability. These features were accompanied by decreased MT density and altered MT dynamics at intercellular junction sites. Interestingly, CLASP2 was enriched at the cortex of basal progenitor keratinocytes, in close localization to p120. Our findings suggest the existence of a new mechanism of MT targeting to AJs with potential functional implications in the maintenance of proper cell–cell adhesion in epidermal stem cells. PMID:24368809
Hou, Baoke; Fu, Yan; Weng, Chuanhuang; Liu, Weiping; Zhao, Congjian; Yin, Zheng Qin
2017-01-01
Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods. PMID:28473754
Dynamics of Defects and Dopants in Complex Systems: Si and Oxide Surfaces and Interfaces
NASA Astrophysics Data System (ADS)
Kirichenko, Taras; Yu, Decai; Banarjee, Sanjay; Hwang, Gyeong
2004-10-01
Fabrication of forthcoming nanometer scale electronic devices faces many difficulties including formation of extremely shallow and highly doped junctions. At present, ultra-low-energy ion implantation followed by high-temperature thermal annealing is most widely used to fabricate such ultra-shallow junctions. In the process, a great challenge lies in achieving precise control of redistribution and electrical activation of dopant impurities. Native defects (such as vacancies and interstitials) generated during implantation are known to be mainly responsible for the TED and also influence significantly the electrical activation/deactivation. Defect-dopant dynamics is rather well understood in crystalline Si and SiO2. However, little is known about their diffusion and annihilation (or precipitation) at the surfaces and interfaces, despite its growing importance in determining junction profiles as device dimensions get smaller. In this talk, we will present our density functional theory calculation results on the atomic and electronic structure and dynamical behavior of native defects and dopant-defect complexes in disordered/strained Si and oxide systems, such as i) clean and absorbent-modified Si(100) surface and subsurface layers, ii) amorphous-crystalline Si interfaces and iii) amorphous SiO2/Si interfaces. The fundamental understanding and data is essential in developing a comprehensive kinetic model for junction formation, which would contribute greatly in improving current process technologies.
Lee, Wonbae; Gillies, John P.; Jose, Davis; Israels, Brett A.; von Hippel, Peter H.; Marcus, Andrew H.
2016-01-01
Gene 32 protein (gp32) is the single-stranded (ss) DNA binding protein of the bacteriophage T4. It binds transiently and cooperatively to ssDNA sequences exposed during the DNA replication process and regulates the interactions of the other sub-assemblies of the replication complex during the replication cycle. We here use single-molecule FRET techniques to build on previous thermodynamic studies of gp32 binding to initiate studies of the dynamics of the isolated and cooperative binding of gp32 molecules within the replication complex. DNA primer/template (p/t) constructs are used as models to determine the effects of ssDNA lattice length, gp32 concentration, salt concentration, binding cooperativity and binding polarity at p/t junctions. Hidden Markov models (HMMs) and transition density plots (TDPs) are used to characterize the dynamics of the multi-step assembly pathway of gp32 at p/t junctions of differing polarity, and show that isolated gp32 molecules bind to their ssDNA targets weakly and dissociate quickly, while cooperatively bound dimeric or trimeric clusters of gp32 bind much more tightly, can ‘slide’ on ssDNA sequences, and exhibit binding dynamics that depend on p/t junction polarities. The potential relationships of these binding dynamics to interactions with other components of the T4 DNA replication complex are discussed. PMID:27694621
CZE determination of submicromolar level of phenol in seawater using improved dynamic pH junction.
Yasuno, Koki; Fukushi, Keiichi
2016-10-01
Using an improved dynamic pH junction as an on-line concentration procedure, we developed CZE for determining submicromolar phenol in seawater for chloride to phenol concentration ratios of 1 000 000. To enhance the effect of conventional dynamic pH junction, a saturated fatty acid solution was injected into the capillary after sample injection. We named the procedure an improved dynamic pH junction. The method requires no sample pretreatment. The following optimum conditions were established: BGE, 40 mM sodium tetraborate decahydrate adjusted to pH 9.8 containing 0.001% m/v hexadimethrine bromide; 190 nm detection wavelength; 18 s (370 nL) vacuum injection period of sample; a saturated fatty acid solution, 30 mM sodium n-hexanoate; 20 s (420 nL) vacuum injection period of the sodium n-hexanoate; and 15 kV applied voltage with the sample inlet side as the cathode. The LOD for phenol was 5.9 μg/L at S/N of 3. The respective values of the RSD (intraday) of the peak area, peak height, and migration time for phenol were 1.9, 2.9, and 0.46%. The recoveries of phenol (25-100 μg/L) spiked into the natural seawater sample obtained using the peak areas were 92-110%. The proposed method was applied to simple biodegradation experiments using natural seawater samples containing phenol. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Non-invasive microfluidic gap junction assay.
Chen, Sisi; Lee, Luke P
2010-03-01
Gap junctions are protein channels between cells that allow direct electrical and metabolic coupling via the exchange of biomolecules and ions. Their expression, though ubiquitous in most mammalian cell types, is especially important for the proper functioning of cardiac and neuronal systems. Many existing methods for studying gap junction communication suffer from either unquantifiable data or difficulty of use. Here, we measure the extent of dye spread and effective diffusivities through gap junction connected cells using a quantitative microfluidic cell biology platform. After loading dye by hydrodynamic focusing of calcein/AM, dye transfer dynamics into neighboring, unexposed cells can be monitored via timelapse fluorescent microscopy. By using a selective microfluidic dye loading over a confluent layer of cells, we found that high expression of gap junctions in C6 cells transmits calcein across the monolayer with an effective diffusivity of 3.4 x 10(-13) m(2)/s, which are highly coupled by Cx43. We also found that the gap junction blocker 18alpha-GA works poorly in the presence of serum even at high concentrations (50 microM); however, it is highly effective down to 2.5 microM in the absence of serum. Furthermore, when the drug is washed out, dye spread resumes rapidly within 1 min for all doses, indicating the drug does not affect transcriptional regulation of connexins in these Cx43+ cells, in contrast to previous studies. This integrated microfluidic platform enables the in situ monitoring of gap junction communication, yielding dynamic information about intercellular molecular transfer and pharmacological inhibition and recovery.
Synchronization of a Josephson junction array in terms of global variables
NASA Astrophysics Data System (ADS)
Vlasov, Vladimir; Pikovsky, Arkady
2013-08-01
We consider an array of Josephson junctions with a common LCR load. Application of the Watanabe-Strogatz approach [Physica DPDNPDT0167-278910.1016/0167-2789(94)90196-1 74, 197 (1994)] allows us to formulate the dynamics of the array via the global variables only. For identical junctions this is a finite set of equations, analysis of which reveals the regions of bistability of the synchronous and asynchronous states. For disordered arrays with distributed parameters of the junctions, the problem is formulated as an integro-differential equation for the global variables; here stability of the asynchronous states and the properties of the transition synchrony-asynchrony are established numerically.
An, Seongpil; Jo, Hong Seok; Kim, Do-Yeon; Lee, Hyun Jun; Ju, Byeong-Kwon; Al-Deyab, Salem S; Ahn, Jong-Hyun; Qin, Yueling; Swihart, Mark T; Yarin, Alexander L; Yoon, Sam S
2016-09-01
Self-junctioned copper nanofiber transparent flexible films are produced using electrospinning and electroplating processes that provide high performances of T = 97% and Rs = 0.42 Ω sq(-1) by eliminating junction resistance at wire intersections. The film remains conductive after being stretched by up to 770% (films with T = 76%) and after 1000 cycles of bending to a 5 mm radius. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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.
Complexity in neuronal noise depends on network interconnectivity.
Serletis, Demitre; Zalay, Osbert C; Valiante, Taufik A; Bardakjian, Berj L; Carlen, Peter L
2011-06-01
"Noise," or noise-like activity (NLA), defines background electrical membrane potential fluctuations at the cellular level of the nervous system, comprising an important aspect of brain dynamics. Using whole-cell voltage recordings from fast-spiking stratum oriens interneurons and stratum pyramidale neurons located in the CA3 region of the intact mouse hippocampus, we applied complexity measures from dynamical systems theory (i.e., 1/f(γ) noise and correlation dimension) and found evidence for complexity in neuronal NLA, ranging from high- to low-complexity dynamics. Importantly, these high- and low-complexity signal features were largely dependent on gap junction and chemical synaptic transmission. Progressive neuronal isolation from the surrounding local network via gap junction blockade (abolishing gap junction-dependent spikelets) and then chemical synaptic blockade (abolishing excitatory and inhibitory post-synaptic potentials), or the reverse order of these treatments, resulted in emergence of high-complexity NLA dynamics. Restoring local network interconnectivity via blockade washout resulted in resolution to low-complexity behavior. These results suggest that the observed increase in background NLA complexity is the result of reduced network interconnectivity, thereby highlighting the potential importance of the NLA signal to the study of network state transitions arising in normal and abnormal brain dynamics (such as in epilepsy, for example).
Burns, Joseph C.
2014-01-01
Sensory hair cell (HC) loss is a major cause of permanent hearing and balance impairments for humans and other mammals. Yet, fish, amphibians, reptiles, and birds readily replace HCs and recover from such sensory deficits. It is unknown what prevents replacement in mammals, but cell replacement capacity declines contemporaneously with massive postnatal thickening of F-actin bands at the junctions between vestibular supporting cells (SCs). In non-mammals, SCs can give rise to regenerated HCs, and the bands remain thin even in adults. Here we investigated the stability of the F-actin bands between SCs in ears from chickens and mice and Madin-Darby canine kidney cells. Pharmacological experiments and fluorescence recovery after photobleaching (FRAP) of SC junctions in utricles from mice that express a γ-actin–GFP fusion protein showed that the thickening F-actin bands develop increased resistance to depolymerization and exceptional stability that parallels a sharp decline in the cell replacement capacity of the maturing mammalian ear. The FRAP recovery rate and the mobile fraction of γ-actin–GFP both decreased as the bands thickened with age and became highly stabilized. In utricles from neonatal mice, time-lapse recordings in the vicinity of dying HCs showed that numerous SCs change shape and organize multicellular actin purse strings that reseal the epithelium. In contrast, adult SCs appeared resistant to deformation, with resealing responses limited to just a few neighboring SCs that did not form purse strings. The exceptional stability of the uniquely thick F-actin bands at the junctions of mature SCs may play an important role in restricting dynamic repair responses in mammalian vestibular epithelia. PMID:24478379
Burns, Joseph C; Corwin, Jeffrey T
2014-01-29
Sensory hair cell (HC) loss is a major cause of permanent hearing and balance impairments for humans and other mammals. Yet, fish, amphibians, reptiles, and birds readily replace HCs and recover from such sensory deficits. It is unknown what prevents replacement in mammals, but cell replacement capacity declines contemporaneously with massive postnatal thickening of F-actin bands at the junctions between vestibular supporting cells (SCs). In non-mammals, SCs can give rise to regenerated HCs, and the bands remain thin even in adults. Here we investigated the stability of the F-actin bands between SCs in ears from chickens and mice and Madin-Darby canine kidney cells. Pharmacological experiments and fluorescence recovery after photobleaching (FRAP) of SC junctions in utricles from mice that express a γ-actin-GFP fusion protein showed that the thickening F-actin bands develop increased resistance to depolymerization and exceptional stability that parallels a sharp decline in the cell replacement capacity of the maturing mammalian ear. The FRAP recovery rate and the mobile fraction of γ-actin-GFP both decreased as the bands thickened with age and became highly stabilized. In utricles from neonatal mice, time-lapse recordings in the vicinity of dying HCs showed that numerous SCs change shape and organize multicellular actin purse strings that reseal the epithelium. In contrast, adult SCs appeared resistant to deformation, with resealing responses limited to just a few neighboring SCs that did not form purse strings. The exceptional stability of the uniquely thick F-actin bands at the junctions of mature SCs may play an important role in restricting dynamic repair responses in mammalian vestibular epithelia.
Baden, Craig; Whitley, Alexander; López-Araujo, Javier; Popple, Richard; Duan, Jun; Kim, Robert
2016-01-01
Aim To report outcomes for patients with para-aortic lymph node positive cervical cancer treated with a dynamic field-matching technique. Background PET staging of cervical cancer has increased identification of patients with para-aortic lymph node metastasis. IMRT enables dose escalation in this area, but matching IMRT fields with traditional whole pelvis fields presents a challenge. Materials and methods From 2003 to 2012, 20 patients with cervical cancer and para-aortic lymph node metastasis were treated utilizing the dynamic field-matching technique. As opposed to single-isocenter half-beam junction techniques, this technique employs wedge-shaped dose junctions for the abutment of fields. We reviewed the records of all patients who completed treatment with the technique and abstracted treatment, toxicity, and disease-related outcome data for analysis. Results Median prescribed dose to the whole pelvis field was 45 Gy and para-aortic IMRT field 50.4 Gy. All but 3 patients underwent HDR (13 pts) or LDR (4 pts) brachytherapy. All patients developed lower GI toxicity; 10 grade 1, 9 grade 2, and 1 grade 4 (enterovaginal fistula). Median DFS was 12.4 months with 1 and 2-year DFS 60.0% and 38.1%. One-year OS was 83.7% and 2-year OS, 64.4%. A total of 10 patients developed recurrence; none occurred at the matched junction. Conclusions The dynamic field-matching technique provides a means for joining conventional whole pelvis fields and para-aortic IMRT fields that substantially reduces dose deviations at the junction due to field mismatch. Treatment with the dynamic matching technique is simple, effective, and tolerated with no apparent increase in toxicity. PMID:26900356
A Theoretical Model of Jigsaw-Puzzle Pattern Formation by Plant Leaf Epidermal Cells
Higaki, Takumi; Kutsuna, Natsumaro; Akita, Kae; Takigawa-Imamura, Hisako; Yoshimura, Kenji; Miura, Takashi
2016-01-01
Plant leaf epidermal cells exhibit a jigsaw puzzle–like pattern that is generated by interdigitation of the cell wall during leaf development. The contribution of two ROP GTPases, ROP2 and ROP6, to the cytoskeletal dynamics that regulate epidermal cell wall interdigitation has already been examined; however, how interactions between these molecules result in pattern formation remains to be elucidated. Here, we propose a simple interface equation model that incorporates both the cell wall remodeling activity of ROP GTPases and the diffusible signaling molecules by which they are regulated. This model successfully reproduces pattern formation observed in vivo, and explains the counterintuitive experimental results of decreased cellulose production and increased thickness. Our model also reproduces the dynamics of three-way cell wall junctions. Therefore, this model provides a possible mechanism for cell wall interdigitation formation in vivo. PMID:27054467
Liu, Bing; Wang, Qin; Yuan, Dong-dong; Hong, Xiao-ting; Tao, Liang
2011-04-01
Clinical combination of some traditional Chinese medical herbs, including berberine, with irradiation is demonstrated to improve efficacy of tumor radiotherapy, yet the mechanisms for such effect remain largely unknown. The present study investigated the effect of berberine on apoptosis induced by X-rays irradiation and the relation between this effect and gap junction intercellular communication (GJIC). The role of gap junctions in the modulation of X-rays irradiation-induced apoptosis was explored by manipulation of connexin (Cx) expression, and gap junction function, using oleamide, a GJIC inhibitor, and berberine. In transfected HeLa cells, Cx32 expression increased apoptosis induced by X-rays irradiation, while inhibition of gap junction by oleamide reduced the irradiation responses, indicating the dependence of X-rays irradiation-induced apoptosis on GJIC. Berberine, at the concentrations without cytotoxicity, enhanced apoptosis induced by irradiation only in the presence of functional gap junctions. These results suggest that berberine potentizes cell apoptosis induced by X-rays irradiation, probably through enhancement of gap junction activity.
A micropatterning approach for imaging Cx43 dynamic trafficking to cell-cell borders
Zhang, Shan-Shan; Hong, SoonGweon; Kléber, André G.; Lee, Luke P.; Shaw, Robin M.
2014-01-01
The precise expression and timely delivery of connexin 43 (Cx43) proteins to form gap junctions are essential for electrical coupling of cardiomyocytes. Growing evidence supports a cytoskeletal-based trafficking paradigm for Cx43 delivery directly to adherens junctions at the intercalated disc. A limitation of Cx43 localization assays in cultured cells, in which cell-cell contacts are essential, is the inability to control for cell geometry or reproducibly generate contact points. Here we present a micropatterned cell pairing system well suited for live microscopy to examine how the microtubule and actin cytoskeleton confer specificity to Cx43 trafficking to precisely defined cell-cell junctions. This system can also be adapted for other cell types and used to study dynamic intracellular movements of other proteins important for cell-cell communication‥ PMID:24444605
Conformational trapping of mismatch recognition complex MSH2/MSH3 on repair-resistant DNA loops.
Lang, Walter H; Coats, Julie E; Majka, Jerzy; Hura, Greg L; Lin, Yuyen; Rasnik, Ivan; McMurray, Cynthia T
2011-10-18
Insertion and deletion of small heteroduplex loops are common mutations in DNA, but why some loops are prone to mutation and others are efficiently repaired is unknown. Here we report that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics of their junctions. MSH2/MSH3 binds, bends, and dissociates from repair-competent loops to signal downstream repair. Repair-resistant Cytosine-Adenine-Guanine (CAG) loops adopt a unique DNA junction that traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA. We envision that junction dynamics is an active participant and a conformational regulator of repair signaling, and governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation.
Charge creation and nucleation of the longitudinal plasma wave in coupled Josephson junctions
NASA Astrophysics Data System (ADS)
Shukrinov, Yu. M.; Hamdipour, M.
2010-11-01
We study the phase dynamics in coupled Josephson junctions described by a system of nonlinear differential equations. Results of detailed numerical simulations of charge creation in the superconducting layers and the longitudinal plasma wave (LPW) nucleation are presented. We demonstrate the different time stages in the development of the LPW and present the results of FFT analysis at different values of bias current. The correspondence between the breakpoint position on the outermost branch of current voltage characteristics (CVC) and the growing region in time dependence of the electric charge in the superconducting layer is established. The effects of noise in the bias current and the external microwave radiation on the charge dynamics of the coupled Josephson junctions are found. These effects introduce a way to regulate the process of LPW nucleation in the stack of IJJ.
Invariant submanifold for series arrays of Josephson junctions.
Marvel, Seth A; Strogatz, Steven H
2009-03-01
We study the nonlinear dynamics of series arrays of Josephson junctions in the large-N limit, where N is the number of junctions in the array. The junctions are assumed to be identical, overdamped, driven by a constant bias current, and globally coupled through a common load. Previous simulations of such arrays revealed that their dynamics are remarkably simple, hinting at the presence of some hidden symmetry or other structure. These observations were later explained by the discovery of N-3 constants of motion, the choice of which confines the resulting flow in phase space to a low-dimensional invariant manifold. Here we show that the dimensionality can be reduced further by restricting attention to a special family of states recently identified by Ott and Antonsen. In geometric terms, the Ott-Antonsen ansatz corresponds to an invariant submanifold of dimension one less than that found earlier. We derive and analyze the flow on this submanifold for two special cases: an array with purely resistive loading and another with resistive-inductive-capacitive loading. Our results recover (and in some instances improve) earlier findings based on linearization arguments.
Kasioulis, Ioannis
2017-01-01
Detachment of newborn neurons from the neuroepithelium is required for correct neuronal architecture and functional circuitry. This process, also known as delamination, involves adherens-junction disassembly and acto-myosin-mediated abscission, during which the centrosome is retained while apical/ciliary membranes are shed. Cell-biological mechanisms mediating delamination are, however, poorly understood. Using live-tissue and super-resolution imaging, we uncover a centrosome-nucleated wheel-like microtubule configuration, aligned with the apical actin cable and adherens-junctions within chick and mouse neuroepithelial cells. These microtubules maintain adherens-junctions while actin maintains microtubules, adherens-junctions and apical end-foot dimensions. During neuronal delamination, acto-myosin constriction generates a tunnel-like actin-microtubule configuration through which the centrosome translocates. This movement requires inter-dependent actin and microtubule activity, and we identify drebrin as a potential coordinator of these cytoskeletal dynamics. Furthermore, centrosome compromise revealed that this organelle is required for delamination. These findings identify new cytoskeletal configurations and regulatory relationships that orchestrate neuronal delamination and may inform mechanisms underlying pathological epithelial cell detachment. PMID:29058679
AmeriFlux US-Bn2 Bonanza Creek, 1987 Burn site near Delta Junction
Randerson, James [University of California, Irvine
2016-01-01
This is the AmeriFlux version of the carbon flux data for the site US-Bn2 Bonanza Creek, 1987 Burn site near Delta Junction. Site Description - The Delta Junction 1987 Burn site is located near Delta Junction, just to the north of the Alaska Range in interior Alaska. All three Delta Junction sites are within a 15-km radius of one another. Composed of a combination of alluvial outwashes, floodplains, and low terraces dissected by glacial streams originating in the nearby Alaska Range. The Granite Creek fire burned ~20,000 ha of black spruce (Picea mariana) during 1987. Approximately half of the dead boles remained upright in 2004, while the other half had fallen over or had become entangled with other boles.
AmeriFlux US-Bn3 Bonanza Creek, 1999 Burn site near Delta Junction
Randerson, James [University of California, Irvine
2016-01-01
This is the AmeriFlux version of the carbon flux data for the site US-Bn3 Bonanza Creek, 1999 Burn site near Delta Junction. Site Description - The Delta Junction 1999 Burn site is located near Delta Junction, just to the north of the Alaska Range in interior Alaska. All three Delta Junction sites are within a 15-km radius of one another. Composed of a combination of alluvial outwashes, floodplains, and low terraces dissected by glacial streams originating in the nearby Alaska Range. The Donnelly Flats fire burned ~7,600 ha of black spruce (Picea mariana) during June 1999. The boles of the black spruce remained standing 3 years after the fire. 70% of the surface was not covered by vascular plants.
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
MLC-based penumbra softener of EDW borders to reduce junction inhomogeneities.
Szpala, Stanislaw; Kohli, Kirpal
2017-05-01
Junctions of fields are known to be susceptible to developing cold or hot spots in the presence of even small geometrical misalignments. Reduction of these dose inhomogeneities can be accomplished through decreasing the dose gradients in the penumbra, but currently it cannot be done for enhanced dynamic wedges (EDW). An MLC-based penumbra softener was developed in the developer mode of TrueBeam linacs to reduce dose gradients across the side border of EDWs. The movement of each leaf was individually synchronized with the movement of the dynamic Y jaw to soften the penumbra in the same manner along the entire field border, in spite of the presence of the dose gradient of the EDW. Junction homogeneity upon field misalignment for side-matched EDWs was examined with the MV imager. The fluence inhomogeneities were reduced from about 30% per mm of shift of the field borders for the conventional EDW to about 2% per mm for the softened-penumbra plan. The junction in a four-field monoisocentric breast plan delivered to the Rando phantom was assessed with film. The dose inhomogeneities across the junction in the superior-inferior direction were reduced from about 20% to 25% per mm for the conventional fields to about 5% per mm. The dose near the softened junction of the breast plan with no shifts did not deviate from the conventional plan by more than about 4%. The newly-developed softened-penumbra junction of EDW (and/or open) fields was shown to reduce sensitivity to misalignments without increasing complexity of the planning or delivery. This methodology needs to be adopted by the manufacturers for clinical use. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.
Fast and High Dynamic Range Imaging with Superconducting Tunnel Junction Detectors
NASA Astrophysics Data System (ADS)
Matsuo, Hiroshi
2014-08-01
We have demonstrated a combined test of the submillimeter-wave SIS photon detectors and GaAs-JFET cryogenic integrated circuits. A relatively large background photo-current can be read out by fast-reset integrating amplifiers. An integration time of 1 ms enables fast frame rate readout and large dynamic range imaging, with an expected dynamic range of 8,000 in 1 ms. Ultimate fast and high dynamic range performance of superconducting tunnel junction detectors (STJ) will be obtained when photon counting capabilities are employed. In the terahertz frequencies, when input photon rate of 100 MHz is measured, the photon bunching gives us enough timing resolution to be used as phase information of intensity fluctuation. Application of photon statistics will be a new tool in the terahertz frequency region. The design parameters of STJ terahertz photon counting detectors are discussed.
Sushko, Gennady B; Verkhovtsev, Alexey V; Yakubovich, Alexander V; Schramm, Stefan; Solov'yov, Andrey V
2014-08-21
The process of self-diffusion of titanium atoms in a bulk material, on grain junctions and on surface is explored numerically in a broad temperature range by means of classical molecular dynamics simulation. The analysis is carried out for a nanoscale cylindrical sample consisting of three adjacent sectors and various junctions between nanocrystals. The calculated diffusion coefficient varies by several orders of magnitude for different regions of the sample. The calculated values of the bulk diffusion coefficient correspond reasonably well to the experimental data obtained for solid and molten states of titanium. Investigation of diffusion in the nanocrystalline titanium is of a significant importance because of its numerous technological applications. This paper aims to reduce the lack of data on diffusion in titanium and describe the processes occurring in bulk, at different interfaces and on surface of the crystalline titanium.
Broadband spectrally dynamic solid state illumination source
NASA Astrophysics Data System (ADS)
Nicol, David B.; Asghar, Ali; Gupta, Shalini; Kang, Hun; Pan, Ming; Strassburg, Martin; Summers, Chris; Ferguson, Ian T.
2006-06-01
Solid state lighting has done well recently in niche markets such as signage and displays, however, no available SSL technologies incorporate all the necessary attributes for general illumination. Development of a novel solid state general illumination source is discussed here. Two LEDs emitting at two distinct wavelengths can be monolithically grown and used to excite two or more phosphors with varied excitation spectra. The combined phosphorescence spectrum can then be controlled by adjusting the relative intensities of the two LED emissions. Preliminary phosphor analysis shows such a scheme to be viable for use in a spectrally dynamic broadband general illumination source. A tunnel junction is envisioned as a means of current spreading in a buried layer for three terminal operation. However, tunnel junction properties in GaN based materials are not well understood, and require further optimization to be practical devices. Preliminary results on GaN tunnel junctions are presented here as well.
Landauer’s formula with finite-time relaxation: Kramers’ crossover in electronic transport
Gruss, Daniel; Velizhanin, Kirill A.; Zwolak, Michael
2016-04-20
Landauer’s formula is the standard theoretical tool to examine ballistic transport in nano- and meso-scale junctions, but it necessitates that any variation of the junction with time must be slow compared to characteristic times of the system, e.g., the relaxation time of local excitations. Transport through structurally dynamic junctions is, however, increasingly of interest for sensing, harnessing fluctuations, and real-time control. Here, we calculate the steady-state current when relaxation of electrons in the reservoirs is present and demonstrate that it gives rise to three regimes of behavior: weak relaxation gives a contact-limited current; strong relaxation localizes electrons, distorting their naturalmore » dynamics and reducing the current; and in an intermediate regime the Landauer view of the system only is recovered. Lastly, we also demonstrate that a simple equation of motion emerges, which is suitable for efficiently simulating time-dependent transport.« less
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
Stout, Randy F; Snapp, Erik Lee; Spray, David C
2015-09-25
Gap junctions (GJs) are made up of plaques of laterally clustered intercellular channels and the membranes in which the channels are embedded. Arrangement of channels within a plaque determines subcellular distribution of connexin binding partners and sites of intercellular signaling. Here, we report the discovery that some connexin types form plaque structures with strikingly different degrees of fluidity in the arrangement of the GJ channel subcomponents of the GJ plaque. We uncovered this property of GJs by applying fluorescence recovery after photobleaching to GJs formed from connexins fused with fluorescent protein tags. We found that connexin 26 (Cx26) and Cx30 GJs readily diffuse within the plaque structures, whereas Cx43 GJs remain persistently immobile for more than 2 min after bleaching. The cytoplasmic C terminus of Cx43 was required for stability of Cx43 plaque arrangement. We provide evidence that these qualitative differences in GJ arrangement stability reflect endogenous characteristics, with the caveat that the sizes of the GJs examined were necessarily large for these measurements. We also uncovered an unrecognized effect of non-monomerized fluorescent protein on the dynamically arranged GJs and the organization of plaques composed of multiple connexin types. Together, these findings redefine our understanding of the GJ plaque structure and should be considered in future studies using fluorescent protein tags to probe dynamics of highly ordered protein complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Ahir, Bhavesh K; Pratten, Margaret K
2014-01-01
Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.
MarvelD3 couples tight junctions to the MEKK1–JNK pathway to regulate cell behavior and survival
Steed, Emily; Elbediwy, Ahmed; Vacca, Barbara; Dupasquier, Sébastien; Hemkemeyer, Sandra A.; Suddason, Tesha; Costa, Ana C.; Beaudry, Jean-Bernard; Zihni, Ceniz; Gallagher, Ewen; Pierreux, Christophe E.
2014-01-01
MarvelD3 is a transmembrane component of tight junctions, but there is little evidence for a direct involvement in the junctional permeability barrier. Tight junctions also regulate signaling mechanisms that guide cell proliferation; however, the transmembrane components that link the junction to such signaling pathways are not well understood. In this paper, we show that MarvelD3 is a dynamic junctional regulator of the MEKK1–c-Jun NH2-terminal kinase (JNK) pathway. Loss of MarvelD3 expression in differentiating Caco-2 cells resulted in increased cell migration and proliferation, whereas reexpression in a metastatic tumor cell line inhibited migration, proliferation, and in vivo tumor formation. Expression levels of MarvelD3 inversely correlated with JNK activity, as MarvelD3 recruited MEKK1 to junctions, leading to down-regulation of JNK phosphorylation and inhibition of JNK-regulated transcriptional mechanisms. Interplay between MarvelD3 internalization and JNK activation tuned activation of MEKK1 during osmotic stress, leading to junction dissociation and cell death in MarvelD3-depleted cells. MarvelD3 thus couples tight junctions to the MEKK1–JNK pathway to regulate cell behavior and survival. PMID:24567356
Phase retrapping in a pointlike φ Josephson junction: the butterfly effect.
Goldobin, E; Kleiner, R; Koelle, D; Mints, R G
2013-08-02
We consider a φ Josephson junction, which has a bistable zero-voltage state with the stationary phases ψ = ±φ. In the nonzero voltage state the phase "moves" viscously along a tilted periodic double-well potential. When the tilting is reduced quasistatically, the phase is retrapped in one of the potential wells. We study the viscous phase dynamics to determine in which well (-φ or +φ) the phase is retrapped for a given damping, when the junction returns from the finite-voltage state back to the zero-voltage state. In the limit of low damping, the φ Josephson junction exhibits a butterfly effect-extreme sensitivity of the destination well on damping. This leads to an impossibility to predict the destination well.
Ito, Satoko; Hyodo, Toshinori; Hasegawa, Hitoki; Yuan, Hong; Hamaguchi, Michinari; Senga, Takeshi
2010-09-17
Gap junctional communication, which is mediated by the connexin protein family, is essential for the maintenance of normal tissue function and homeostasis. Loss of intercellular communication results in a failure to coordinately regulate cellular functions, and it can facilitate tumorigenesis. Expression of oncogenes and stimulation with cytokines has been shown to suppress intercellular communication; however, the exact mechanism by which intercellular communication is disrupted by these factors remains uncertain. In this report, we show that Akt is essential for the disruption of gap junctional communication in v-Src-transformed cells. In addition, inhibition of Akt restores gap junctional communication after it is suppressed by TNF-α signaling. Furthermore, we demonstrate that the expression of a constitutively active form of Akt1, but not of Akt2 or Akt3, is sufficient to suppress gap junctional communication. Our results clearly define Akt1 as one of the critical regulators of gap junctional communication. Copyright © 2010 Elsevier Inc. All rights reserved.
An investigation of the SNS Josephson junction as a three-terminal device. Ph.D. Thesis
NASA Technical Reports Server (NTRS)
Meissner, H.; Prans, G. P.
1973-01-01
A particular phenomenon of the SNS Josephson junction was investigated; i.e., control by a current entering the normal region and leaving through one of the superconducting regions. The effect of the control current on the junction was found to be dependent upon the ration of the resistances of the two halves of the N layer. A low frequency, lumped, nonlinear model was proposed to describe the electrical characteristics of the device, and a method was developed to plot the dynamic junction resistance as a function of junction current. The effective thermal noise temperature of the sample was determined. Small signal linearized analysis of the device suggests its use as an impedance transformer, although geometric limitations must be overcome. Linear approximation indicates that it is reciprocal and no power gain is possible. It is felt that, with suitable metallurgical and geometrical improvements, the device has promise to become a superconducting transistor.
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
DOE Office of Scientific and Technical Information (OSTI.GOV)
Torregrosa, Frank; Etienne, Hasnaa; Sempere, Guillaume
In order to achieve the requirements for P+/N junctions for <45 nm ITRS nodes, ultra low energy and high dose implantations are needed. Classical beamline implantation is now limited in low energies, compared to Plasma Immersion Ion Implantation (PIII) which efficiency is no more to prove for the realization of Ultra-Shallow Junctions (USJ) in semiconductor applications : this technique allows to get ultimate shallow profiles (as implanted) due to no lower limitation of energy and high dose rate. Electrical activation is also a big issue since it has to afford high electrical activation rate with very low diffusion. Laser annealingmore » is one of the candidates for the 45 nm node. This paper presents electrical and physico-chemical characterizations of junctions realized with BF3 PIII followed by laser thermal processing with aim to obtain ultra-shallow junctions. Different implantation conditions (acceleration voltage/dose) and laser conditions (laser types, fluence/number of shots) are used for this study. Pre-amorphization is also used to confine the junction depth, and is shown to have a positive effect on junction depth but leads in higher junction leakage due to the remaining of EOR defects. The characterization is done using Optical characterization tool (SEMILAB) for sheet resistance and junction leakage measurements. SIMS is used for Boron profile and junction depth.« less
Exploring Instructive Physiological Signaling with the Bioelectric Tissue Simulation Engine
Pietak, Alexis; Levin, Michael
2016-01-01
Bioelectric cell properties have been revealed as powerful targets for modulating stem cell function, regenerative response, developmental patterning, and tumor reprograming. Spatio-temporal distributions of endogenous resting potential, ion flows, and electric fields are influenced not only by the genome and external signals but also by their own intrinsic dynamics. Ion channels and electrical synapses (gap junctions) both determine, and are themselves gated by, cellular resting potential. Thus, the origin and progression of bioelectric patterns in multicellular tissues is complex, which hampers the rational control of voltage distributions for biomedical interventions. To improve understanding of these dynamics and facilitate the development of bioelectric pattern control strategies, we developed the BioElectric Tissue Simulation Engine (BETSE), a finite volume method multiphysics simulator, which predicts bioelectric patterns and their spatio-temporal dynamics by modeling ion channel and gap junction activity and tracking changes to the fundamental property of ion concentration. We validate performance of the simulator by matching experimentally obtained data on membrane permeability, ion concentration and resting potential to simulated values, and by demonstrating the expected outcomes for a range of well-known cases, such as predicting the correct transmembrane voltage changes for perturbation of single cell membrane states and environmental ion concentrations, in addition to the development of realistic transepithelial potentials and bioelectric wounding signals. In silico experiments reveal factors influencing transmembrane potential are significantly different in gap junction-networked cell clusters with tight junctions, and identify non-linear feedback mechanisms capable of generating strong, emergent, cluster-wide resting potential gradients. The BETSE platform will enable a deep understanding of local and long-range bioelectrical dynamics in tissues, and assist the development of specific interventions to achieve greater control of pattern during morphogenesis and remodeling. PMID:27458581
Wasteneys, Geoffrey
2013-01-01
During cellular morphogenesis, changes in cell shape and cell junction topology are fundamental to normal tissue and organ development. Here we show that apoplastic Glycophosphatidylinositol (GPI)-anchored Lipid Transfer Protein (LTPG) is excluded from cell junctions and flat wall regions, and passively accumulates around their borders in the epidermal cells of Arabidopsis thaliana. Beginning with intense accumulation beneath highly curved cell junction borders, this enrichment is gradually lost as cells become more bulbous during their differentiation. In fully mature epidermal cells, YFP-LTPG often shows a fibrous cellulose microfibril-like pattern within the bulging outer faces. Physical contact between a flat glass surface and bulbous cell surface induces rapid and reversible evacuation from contact sites and accumulation to the curved wall regions surrounding the contact borders. Thus, LTPG distribution is dynamic, responding to changes in cell shape and wall curvature during cell growth and differentiation. We hypothesize that this geometry-based mechanism guides wax-carrying LTPG to functional sites, where it may act to “seal” the vulnerable border surrounding cell-cell junctions and assist in cell wall fortification and cuticular wax deposition. PMID:24260561
NASA Astrophysics Data System (ADS)
Boshier, Malcolm; Ryu, Changhyun; Blackburn, Paul; Blinova, Alina; Henderson, Kevin
2014-05-01
The painted potential is a time-averaged optical dipole potential which is able to create arbitrary and dynamic two dimensional potentials for Bose Einstein condensates (BECs). This poster reports three recent experiments using this technique. First, we have realized the dc atom SQUID geometry of a BEC in a toroidal trap with two Josephson junctions. We observe Josephson effects, measure the critical current of the junctions, and find dynamic behavior that is in good agreement with the simple Josephson equations for a tunnel junction with the ideal sinusoidal current-phase relation expected for the parameters of the experiment. Second, we have used free expansion of a rotating toroidal BEC to create matter wave Bessel beams, which are of interest because perfect Bessel beams (plane waves with amplitude profiles described by Bessel functions) propagate without diffraction. Third, we have realized the basic circuit elements necessary to create complex matter wave circuits. We launch BECs at arbitrary velocity along straight waveguides, propagate them around curved waveguides and stadium-shaped waveguide traps, and split them coherently at y-junctions that can also act as switches. Supported by LANL/LDRD.
Kamasawa, N; Furman, C S; Davidson, K G V; Sampson, J A; Magnie, A R; Gebhardt, B R; Kamasawa, M; Yasumura, T; Zumbrunnen, J R; Pickard, G E; Nagy, J I; Rash, J E
2006-11-03
Neuronal gap junctions are abundant in both outer and inner plexiform layers of the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally-identified gap junctions were reported primarily in the functionally-defined and anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We used freeze-fracture replica immunogold labeling and confocal microscopy to quantitatively analyze the morphologies and distributions of neuronal gap junctions in the IPL of adult rat and mouse retina. Under "baseline" conditions (photopic illumination/general anesthesia), 649 neuronal gap junctions immunogold-labeled for connexin36 were identified in rat IPL, of which 375 were photomapped to OFF vs. ON sublaminae. In contrast to previous reports, the volume-density of gap junctions was equally abundant in both sublaminae. Five distinctive morphologies of gap junctions were identified: conventional crystalline and non-crystalline "plaques" (71% and 3%), plus unusual "string" (14%), "ribbon" (7%) and "reticular" (2%) forms. Plaque and reticular gap junctions were distributed throughout the IPL. However, string and ribbon gap junctions were restricted to the OFF sublamina, where they represented 48% of gap junctions in that layer. In string and ribbon junctions, curvilinear strands of connexons were dispersed over 5 to 20 times the area of conventional plaques having equal numbers of connexons. To define morphologies of gap junctions under different light-adaptation conditions, we examined an additional 1150 gap junctions from rats and mice prepared after 30 min of photopic, mesopic and scotopic illumination, with and without general anesthesia. Under these conditions, string and ribbon gap junctions remained abundant in the OFF sublamina and absent in the ON sublamina. Abundant gap junctions in the OFF sublamina of these two rodents with rod-dominant retinas revealed previously-undescribed but extensive pathways for inter-neuronal communication; and the wide dispersion of connexons in string and ribbon gap junctions suggests unique structural features of gap junctional coupling in the OFF vs. ON sublamina.
Endoplasmic reticulum-plasma membrane junctions: structure, function and dynamics.
Okeke, Emmanuel; Dingsdale, Hayley; Parker, Tony; Voronina, Svetlana; Tepikin, Alexei V
2016-06-01
Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are contact sites between the ER and the PM; the distance between the two organelles in the junctions is below 40 nm and the membranes are connected by protein tethers. A number of molecular tools and technical approaches have been recently developed to visualise, modify and characterise properties of ER-PM junctions. The junctions serve as the platforms for lipid exchange between the organelles and for cell signalling, notably Ca(2+) and cAMP signalling. Vice versa, signalling events regulate the development and properties of the junctions. Two Ca(2+) -dependent mechanisms of de novo formation of ER-PM junctions have been recently described and characterised. The junction-forming proteins and lipids are currently the focus of vigorous investigation. Junctions can be relatively short-lived and simple structures, forming and dissolving on the time scale of a few minutes. However, complex, sophisticated and multifunctional ER-PM junctions, capable of attracting numerous protein residents and other cellular organelles, have been described in some cell types. The road from simplicity to complexity, i.e. the transformation from simple 'nascent' ER-PM junctions to advanced stable multiorganellar complexes, is likely to become an attractive research avenue for current and future junctologists. Another area of considerable research interest is the downstream cellular processes that can be activated by specific local signalling events in the ER-PM junctions. Studies of the cell physiology and indeed pathophysiology of ER-PM junctions have already produced some surprising discoveries, likely to expand with advances in our understanding of these remarkable organellar contact sites. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tarlinton, D.; Strasser, A.; McLean, M.
1995-04-01
Mouse B cell precursors containing Ig D{sub H}J{sub H} junctions in one particular reading frame are selectively lost during B cell development. In this register, arbitrarily referred to as reading frame 2, D{sub H}J{sub H} junctions give rise to an open reading frame starting upstream of the D{sub H} element and including the D{sub H}J{sub H}-peptide fused to the constant region of IgM. Expression of this protein, called D{mu}, has been strongly implicated in the loss of B cell precursors containing reading frame 2 D{sub H}J{sub H} junctions. In an attempt to elucidate the means of D{mu} counterselection, we havemore » examined the reading frame distribution of D{sub H}J{sub H} junctions in peripheral B cells from mice transgenic for either the human bcl-2 oncogene or for a functionally rearranged Ig {mu} heavy chain. In bcl-2 transgenic mice, reading frame 2 accounted for < 5% of the D{sub H}J{sub H} junctions in peripheral B cells, a value not significantly different from controls. Reading frames 1 and 3 were equally represented among the remaining junctions. By contrast, the reading frame distribution of endogenous D{sub H}J{sub H} junctions in splenic B cells from Ig {mu} heavy chain transgenic mice showed no evidence of bias against D{mu} encoding D{sub H}J{sub H} junctions. Reading frames 2 and 3 accounted for 27% and 30% of the sequenced D{sub H}J{sub H} junctions, respectively, and the remaining 43% were reading frame 1. Thus although the presence of BCL-2 cannot prevent the selective loss of reading frame 2 D{sub H}J{sub H} B cells, a functional {mu} heavy chain can. These results suggest that D{mu}-expressing B cell precursors may be selectively lost because of the premature and inappropriate cessation of heavy chain gene rearrangement rather than because of the induction of an apoptotic process which can be blocked by BCL-2. 42 refs., 4 figs., 4 tabs.« less
NASA Astrophysics Data System (ADS)
Yuan, Li; Wang, Lejia; Garrigues, Alvar R.; Jiang, Li; Annadata, Harshini Venkata; Anguera Antonana, Marta; Barco, Enrique; Nijhuis, Christian A.
2018-04-01
Solid-state molecular tunnel junctions are often assumed to operate in the Landauer regime, which describes essentially activationless coherent tunnelling processes. In solution, on the other hand, charge transfer is described by Marcus theory, which accounts for thermally activated processes. In practice, however, thermally activated transport phenomena are frequently observed also in solid-state molecular junctions but remain poorly understood. Here, we show experimentally the transition from the Marcus to the inverted Marcus region in a solid-state molecular tunnel junction by means of intra-molecular orbital gating that can be tuned via the chemical structure of the molecule and applied bias. In the inverted Marcus region, charge transport is incoherent, yet virtually independent of temperature. Our experimental results fit well to a theoretical model that combines Landauer and Marcus theories and may have implications for the interpretation of temperature-dependent charge transport measurements in molecular junctions.
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.
Spatio-temporal regulation of connexin43 phosphorylation and gap junction dynamics.
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.
Thompson, Damien; Nijhuis, Christian A
2016-10-18
This Account describes a body of research in atomic level design, synthesis, physicochemical characterization, and macroscopic electrical testing of molecular devices made from ferrocene-functionalized alkanethiol molecules, which are molecular diodes, with the aim to identify, and resolve, the failure modes that cause leakage currents. The mismatch in size between the ferrocene headgroup and alkane rod makes waxlike highly dynamic self-assembled monolayers (SAMs) on coinage metals that show remarkable atomic-scale sensitivity in their electrical properties. Our results make clear that molecular tunnel junction devices provide an excellent testbed to probe the electronic and supramolecular structures of SAMs on inorganic substrates. Contacting these SAMs to a eutectic "EGaIn" alloy top-electrode, we designed highly stable long-lived molecular switches of the form electrode-SAM-electrode with robust rectification ratios of up to 3 orders of magnitude. The graphic that accompanies this conspectus displays a computed SAM packing structure, illustrating the lollipop shape of the molecules that gives dynamic SAM supramolecular structures and also the molecule-electrode van der Waals (vdW) contacts that must be controlled to form good SAM-based devices. In this Account, we first trace the evolution of SAM-based electronic devices and rationalize their operation using energy level diagrams. We describe the measurement of device properties using near edge X-ray absorption fine structure spectroscopy, cyclic voltammetry, and X-ray photoelectron spectroscopy complemented by molecular dynamics and electronic structure calculations together with large numbers of electrical measurements. We discuss how data obtained from these combined experimental/simulation codesign studies demonstrate control over the supramolecular and electronic structure of the devices, tuning odd-even effects to optimize inherent packing tendencies of the molecules in order to minimize leakage currents in the junctions. It is now possible, but still very costly to create atomically smooth electrodes and we discuss progress toward masking electrode imperfections using cooperative molecule-electrode contacts that are only accessible by dynamic SAM structures. Finally, the unique ability of SAM devices to achieve simultaneously high and atom-sensitive electrical switching is summarized and discussed. While putting these structures to work as real world electronic devices remains very challenging, we speculate on the scientific and technological advances that are required to further improve electronic and supramolecular structure, toward the creation of high yields of long-lived molecular devices with (very) large, reproducible rectification ratios.
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.
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.
Quantum Dynamics of a d-wave Josephson Junction
NASA Astrophysics Data System (ADS)
Bauch, Thilo
2007-03-01
Thilo Bauch ^1, Floriana Lombardi ^1, Tobias Lindstr"om ^2, Francesco Tafuri ^3, Giacomo Rotoli ^4, Per Delsing ^1, Tord Claeson ^1 1 Quantum Device Physics Laboratory, Department of Microtechnology and Nanoscience, MC2, Chalmers University of Technology, S-412 96 G"oteborg, Sweden. 2 National Physical Laboratory, Queens Road, Teddington, Middlesex TW11 0LW, UK. 3 Istituto Nazionale per la Fisica della Materia-Dipartimento Ingegneria dell'Informazione, Seconda Universita di Napoli, Aversa (CE), Italy. 4 Dipartimento di Ingegneria Meccanica, Energetica e Gestionale, Universita of L'Aquila, Localita Monteluco, L'Aquila, Italy. We present direct observation of macroscopic quantum properties in an all high critical temperature superconductor d-wave Josephson junction. Although dissipation caused by low energy excitations is expected to strongly suppress quantum effects we demonstrate macroscopic quantum tunneling [1] and energy level quantization [2] in our d-wave Josephson junction. The results clearly indicate that the role of dissipation mechanisms in high temperature superconductors has to be revised, and may also have consequences for a new class of solid state ``quiet'' quantum bit with superior coherence time. We show that the dynamics of the YBCO grain boundary Josephson junctions fabricated on a STO substrate are strongly affected by their environment. As a first approximation we model the environment by the stray capacitance and stray inductance of the junction electrodes. The total system consisting of the junction and stray elements has two degrees of freedom resulting in two characteristic resonance frequencies. Both frequencies have to be considered to describe the quantum mechanical behavior of the Josephson circuit. [1] T. Bauch et al, Phys. Rev. Lett. 94, 087003 (2005). [2] T. Bauch et al, Science 311, 57 (2006).
NASA Astrophysics Data System (ADS)
Hamdipour, Mohammad
2018-04-01
We study an array of coupled Josephson junction of superconductor/insulator/superconductor type (SIS junction) as a model for high temperature superconductors with layered structure. In the current-voltage characteristics of this system there is a breakpoint region in which a net electric charge appear on superconducting layers, S-layers, of junctions which motivate us to study the charge dynamics in this region. In this paper first of all we show a current voltage characteristics (CVC) of Intrinsic Josephson Junctions (IJJs) with N=3 Junctions, then we show the breakpoint region in that CVC, then we try to investigate the chaos in this region. We will see that at the end of the breakpoint region, behavior of the system is chaotic and Lyapunov exponent become positive. We also study the route by which the system become chaotic and will see this route is bifurcation. Next goal of this paper is to show the self similarity in the bifurcation diagram of the system and detailed analysis of bifurcation diagram.
Myosin II promotes the anisotropic loss of the apical domain during Drosophila neuroblast ingression
Simões, Sérgio; Oh, Youjin; Wang, Michael F.Z.; Fernandez-Gonzalez, Rodrigo
2017-01-01
Epithelial–mesenchymal transitions play key roles in development and cancer and entail the loss of epithelial polarity and cell adhesion. In this study, we use quantitative live imaging of ingressing neuroblasts (NBs) in Drosophila melanogaster embryos to assess apical domain loss and junctional disassembly. Ingression is independent of the Snail family of transcriptional repressors and down-regulation of Drosophila E-cadherin (DEcad) transcription. Instead, the posttranscriptionally regulated decrease in DEcad coincides with the reduction of cell contact length and depends on tension anisotropy between NBs and their neighbors. A major driver of apical constriction and junctional disassembly are periodic pulses of junctional and medial myosin II that result in progressively stronger cortical contractions during ingression. Effective contractions require the molecular coupling between myosin and junctions and apical relaxation of neighboring cells. Moreover, planar polarization of myosin leads to the loss of anterior–posterior junctions before the loss of dorsal–ventral junctions. We conclude that planar-polarized dynamic actomyosin networks drive apical constriction and the anisotropic loss of cell contacts during NB ingression. PMID:28363972
Cdc42 regulates junctional actin but not cell polarization in the Caenorhabditis elegans epidermis
Zilberman, Yuliya; Abrams, Joshua; Anderson, Dorian C.
2017-01-01
During morphogenesis, adherens junctions (AJs) remodel to allow changes in cell shape and position while preserving adhesion. Here, we examine the function of Rho guanosine triphosphatase CDC-42 in AJ formation and regulation during Caenorhabditis elegans embryo elongation, a process driven by asymmetric epidermal cell shape changes. cdc-42 mutant embryos arrest during elongation with epidermal ruptures. Unexpectedly, we find using time-lapse fluorescence imaging that cdc-42 is not required for epidermal cell polarization or junction assembly, but rather is needed for proper junctional actin regulation during elongation. We show that the RhoGAP PAC-1/ARHGAP21 inhibits CDC-42 activity at AJs, and loss of PAC-1 or the interacting linker protein PICC-1/CCDC85A-C blocks elongation in embryos with compromised AJ function. pac-1 embryos exhibit dynamic accumulations of junctional F-actin and an increase in AJ protein levels. Our findings identify a previously unrecognized molecular mechanism for inhibiting junctional CDC-42 to control actin organization and AJ protein levels during epithelial morphogenesis. PMID:28903999
FSGS3/CD2AP is a barbed-end capping protein that stabilizes actin and strengthens adherens junctions
Brieher, William M.
2013-01-01
By combining in vitro reconstitution biochemistry with a cross-linking approach, we have identified focal segmental glomerulosclerosis 3/CD2-associated protein (FSGS3/CD2AP) as a novel actin barbed-end capping protein responsible for actin stability at the adherens junction. FSGS3/CD2AP colocalizes with E-cadherin and α-actinin-4 at the apical junction in polarized Madin-Darby canine kidney (MDCK) cells. Knockdown of FSGS3/CD2AP compromised actin stability and decreased actin accumulation at the adherens junction. Using a novel apparatus to apply mechanical stress to cell–cell junctions, we showed that knockdown of FSGS3/CD2AP compromised adhesive strength, resulting in tearing between cells and disruption of barrier function. Our results reveal a novel function of FSGS3/CD2AP and a previously unrecognized role of barbed-end capping in junctional actin dynamics. Our study underscores the complexity of actin regulation at cell–cell contacts that involves actin activators, inhibitors, and stabilizers to control adhesive strength, epithelial behavior, and permeability barrier integrity. PMID:24322428
Peltier cooling in molecular junctions
NASA Astrophysics Data System (ADS)
Cui, Longji; Miao, Ruijiao; Wang, Kun; Thompson, Dakotah; Zotti, Linda Angela; Cuevas, Juan Carlos; Meyhofer, Edgar; Reddy, Pramod
2018-02-01
The study of thermoelectricity in molecular junctions is of fundamental interest for the development of various technologies including cooling (refrigeration) and heat-to-electricity conversion1-4. Recent experimental progress in probing the thermopower (Seebeck effect) of molecular junctions5-9 has enabled studies of the relationship between thermoelectricity and molecular structure10,11. However, observations of Peltier cooling in molecular junctions—a critical step for establishing molecular-based refrigeration—have remained inaccessible. Here, we report direct experimental observations of Peltier cooling in molecular junctions. By integrating conducting-probe atomic force microscopy12,13 with custom-fabricated picowatt-resolution calorimetric microdevices, we created an experimental platform that enables the unified characterization of electrical, thermoelectric and energy dissipation characteristics of molecular junctions. Using this platform, we studied gold junctions with prototypical molecules (Au-biphenyl-4,4'-dithiol-Au, Au-terphenyl-4,4''-dithiol-Au and Au-4,4'-bipyridine-Au) and revealed the relationship between heating or cooling and charge transmission characteristics. Our experimental conclusions are supported by self-energy-corrected density functional theory calculations. We expect these advances to stimulate studies of both thermal and thermoelectric transport in molecular junctions where the possibility of extraordinarily efficient energy conversion has been theoretically predicted2-4,14.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Xiang; Zhao, Fang
Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit themore » expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.« less
NASA Astrophysics Data System (ADS)
Neri, Elettra; Scazza, Francesco; Roati, Giacomo
2018-04-01
Quantum systems out of equilibrium offer the possibility of understanding intriguing and challenging problems in modern physics. Studying transport properties is not only valuable to unveil fundamental properties of quantum matter but it is also an excellent tool for developing new quantum devices which inherently employ quantum-mechanical effects. In this contribution, we present our experimental studies on quantum transport using ultracold Fermi gases of 6Li atoms. We realize the analogous of a Josephson junction by bisecting fermionic superfluids by a thin optical barrier. We observe coherent dynamics in both the population and in the relative phase between the two reservoirs. For critical parameters, the superfluid dynamics exhibits both coherent and resistive flow due to phase-slippage events manifesting as vortices propagating into the bulk. We uncover also a regime of strong dissipation where the junction operation is irreversibly affected by vortex proliferation. Our studies open new directions for investigating dissipation and superfluid transport in strongly correlated fermionic systems.
Quantized thermal transport in single-atom junctions
NASA Astrophysics Data System (ADS)
Cui, Longji; Jeong, Wonho; Hur, Sunghoon; Matt, Manuel; Klöckner, Jan C.; Pauly, Fabian; Nielaba, Peter; Cuevas, Juan Carlos; Meyhofer, Edgar; Reddy, Pramod
2017-03-01
Thermal transport in individual atomic junctions and chains is of great fundamental interest because of the distinctive quantum effects expected to arise in them. By using novel, custom-fabricated, picowatt-resolution calorimetric scanning probes, we measured the thermal conductance of gold and platinum metallic wires down to single-atom junctions. Our work reveals that the thermal conductance of gold single-atom junctions is quantized at room temperature and shows that the Wiedemann-Franz law relating thermal and electrical conductance is satisfied even in single-atom contacts. Furthermore, we quantitatively explain our experimental results within the Landauer framework for quantum thermal transport. The experimental techniques reported here will enable thermal transport studies in atomic and molecular chains, which will be key to investigating numerous fundamental issues that thus far have remained experimentally inaccessible.
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
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.
NASA Astrophysics Data System (ADS)
Bai, Ke-Ke; Zhou, Jiao-Jiao; Wei, Yi-Cong; Qiao, Jia-Bin; Liu, Yi-Wen; Liu, Hai-Wen; Jiang, Hua; He, Lin
2018-01-01
Creation of high-quality p -n junctions in graphene monolayer is vital in studying many exotic phenomena of massless Dirac fermions. However, even with the fast progress of graphene technology for more than ten years, it remains conspicuously difficult to generate nanoscale and atomically sharp p -n junctions in graphene. Here, we realized nanoscale p -n junctions with atomically sharp boundaries in graphene monolayer by using monolayer vacancy island of Cu surface. The generated sharp p -n junctions with the height as high as 660 meV isolate the graphene above the Cu monolayer vacancy island as nanoscale graphene quantum dots (GQDs) in a continuous graphene sheet. Massless Dirac fermions are confined by the p -n junctions for a finite time to form quasibound states in the GQDs. By using scanning tunneling microscopy, we observe resonances of quasibound states in the GQDs with various sizes and directly visualize effects of geometries of the GQDs on the quantum interference patterns of the quasibound states, which allow us to test the quantum electron optics based on graphene in atomic scale.
Discontinuous solutions of Hamilton-Jacobi equations on networks
NASA Astrophysics Data System (ADS)
Graber, P. J.; Hermosilla, C.; Zidani, H.
2017-12-01
This paper studies optimal control problems on networks without controllability assumptions at the junctions. The Value Function associated with the control problem is characterized as the solution to a system of Hamilton-Jacobi equations with appropriate junction conditions. The novel feature of the result lies in that the controllability conditions are not needed and the characterization remains valid even when the Value Function is not continuous.
Connexin-deficiency affects expression levels of glial glutamate transporters within the cerebrum.
Unger, Tina; Bette, Stefanie; Zhang, Jiong; Theis, Martin; Engele, Jürgen
2012-01-06
The glial glutamate transporter subtypes, GLT-1/EAAT-2 and GLAST/EAAT-1 clear the bulk of extracellular glutamate and are severely dysregulated in various acute and chronic brain diseases. Despite the previous identification of several extracellular factors modulating glial glutamate transporter expression, our knowledge of the regulatory network controlling glial glutamate transport in health and disease still remains incomplete. In studies with cultured cortical astrocytes, we previously obtained evidence that glial glutamate transporter expression is also affected by gap junctions/connexins. To assess whether gap junctions would likewise control the in vivo expression of glial glutamate transporters, we have now assessed their expression levels in brains of conditional Cx43 knockout mice, total Cx30 knockouts, as well as Cx43/Cx30 double knockouts. We found that either knocking out Cx30, Cx43, or both increases GLT-1/EAAT-2 protein levels in the cerebral cortex to a similar extent. By contrast, GLAST/EAAT-1 protein levels maximally increased in cerebral cortices of Cx30/Cx43 double knockouts, implying that gap junctions differentially affect the expression of GLT-1/EAAT-2 and GLAST/EAAT-1. Quantitative PCR analysis further revealed that increases in glial glutamate transporter expression are brought about by transcriptional and translational/posttranslational processes. Moreover, GLT-1/EAAT-2- and GLAST/EAAT-1 protein levels remained unchanged in the hippocampi of Cx43/Cx30 double knockouts when compared to Cx43fl/fl controls, indicating brain region-specific effects of gap junctions on glial glutamate transport. Since astrocytic gap junction coupling is affected in various forms of brain injuries, our findings point to gap junctions/connexins as important regulators of glial glutamate turnover in the diseased cerebral cortex. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Wary, Mélanie; Eynaud, Frédérique; Kissel, Catherine; Londeix, Laurent; Rossignol, Linda; Lapuyade, Joanna; Castéra, Marie-Hélène; Billy, Isabelle
2018-01-01
Dansgaard-Oeschger and Heinrich events constitute ones of the most enigmatic features of the last glacial period. Many studies have focused on their characteristic millennial climatic variability, testing atmospheric/cryospheric/oceanic couplings, but major uncertainties and discrepancies still remain. A new scenario, robustly supported by an approach coupling paleoreconstructions and freshwater hosing experiments simulating Heinrich-type perturbations, has recently emerged. Reconciling most of the up to now hypothesized theories, it suggests the occurrence of a regional seesaw between a cooled-down North Atlantic Ocean and warmed-up Nordic Seas during cold atmospheric phases, in relation to enhanced subsurface advection of warm Atlantic waters re-emerging in the Norwegian Sea. The associated ocean warming, thus reaching Nordic basins at a critical location beyond the Faeroe-Shetland sill, is proposed to be involved in the concomitant release of European icebergs. Here we further investigate this promising scenario over the 35-41 ka BP interval by (i) outlining its precise spatial pattern in a crucial area, i.e. the junction between the North Atlantic and the Norwegian Sea close to European ice-sheets, (ii) resolving its very fine temporal and regional evolution during critical transitions associated with the onset of warm advection, i.e. Greenland Interstadial to Greenland Stadial and Greenland Interstadial to Heinrich Stadial, and (iii) assessing its impact on the spatio-temporal dynamic of iceberg discharges from the European and Laurentide ice-sheets during cold stadial episodes especially including Heinrich event 4.
Carbon Nanotubes: Molecular Electronic Components
NASA Technical Reports Server (NTRS)
Srivastava, Deepak; Saini, Subhash; Menon, Madhu
1997-01-01
The carbon Nanotube junctions have recently emerged as excellent candidates for use as the building blocks in the formation of nanoscale molecular electronic networks. While the simple joint of two dissimilar tubes can be generated by the introduction of a pair of heptagon-pentagon defects in an otherwise perfect hexagonal graphene sheet, more complex joints require other mechanisms. In this work we explore structural characteristics of complex 3-point junctions of carbon nanotubes using a generalized tight-binding molecular-dynamics scheme. The study of pi-electron local densities of states (LDOS) of these junctions reveal many interesting features, most prominent among them being the defect-induced states in the gap.
KAMASAWA, N.; FURMAN, C. S.; DAVIDSON, K. G. V.; SAMPSON, J. A.; MAGNIE, A. R.; GEBHARDT, B. R.; KAMASAWA, M.; YASUMURA, T.; ZUMBRUNNEN, J. R.; PICKARD, G. E.; NAGY, J. I.; RASH, J. E.
2007-01-01
Neuronal gap junctions are abundant in both outer and inner plexiform layers of the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally-identified gap junctions were reported primarily in the functionally-defined and anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We used freeze-fracture replica immunogold labeling and confocal microscopy to quantitatively analyze the morphologies and distributions of neuronal gap junctions in the IPL of adult rat and mouse retina. Under “baseline” conditions (photopic illumination/general anesthesia), 649 neuronal gap junctions immunogold-labeled for connexin36 were identified in rat IPL, of which 375 were photomapped to OFF vs. ON sublaminae. In contrast to previous reports, the volume-density of gap junctions was equally abundant in both sublaminae. Five distinctive morphologies of gap junctions were identified: conventional crystalline and non-crystalline “plaques” (71% and 3%), plus unusual “string” (14%), “ribbon” (7%) and “reticular” (2%) forms. Plaque and reticular gap junctions were distributed throughout the IPL. However, string and ribbon gap junctions were restricted to the OFF sublamina, where they represented 48% of gap junctions in that layer. In string and ribbon junctions, curvilinear strands of connexons were dispersed over 5 to 20 times the area of conventional plaques having equal numbers of connexons. To define morphologies of gap junctions under different light-adaptation conditions, we examined an additional 1150 gap junctions from rats and mice prepared after 30 min of photopic, mesopic and scotopic illumination, with and without general anesthesia. Under these conditions, string and ribbon gap junctions remained abundant in the OFF sublamina and absent in the ON sublamina. Abundant gap junctions in the OFF sublamina of these two rodents with rod-dominant retinas revealed previously-undescribed but extensive pathways for inter-neuronal communication; and the wide dispersion of connexons in string and ribbon gap junctions suggests unique structural features of gap junctional coupling in the OFF vs. ON sublamina. PMID:17010526
Measure Guideline: Optimizing the Configuration of Flexible Duct Junction Boxes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Beach, R.; Burdick, A.
2014-03-01
This measure guideline offers additional recommendations to heating, ventilation, and air conditioning (HVAC) system designers for optimizing flexible duct, constant-volume HVAC systems using junction boxes within Air Conditioning Contractors of America (ACCA) Manual D guidance. IBACOS used computational fluid dynamics software to explore and develop guidance to better control the airflow effects of factors that may impact pressure losses within junction boxes among various design configurations. These recommendations can help to ensure that a system aligns more closely with the design and the occupants' comfort expectations. Specifically, the recommendations described herein show how to configure a rectangular box with fourmore » outlets, a triangular box with three outlets, metal wyes with two outlets, and multiple configurations for more than four outlets. Designers of HVAC systems, contractors who are fabricating junction boxes on site, and anyone using the ACCA Manual D process for sizing duct runs will find this measure guideline invaluable for more accurately minimizing pressure losses when using junction boxes with flexible ducts.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gardner, Jasmine M.; Abrams, Cameron F.; Deserno, Markus
We use a combination of coarse-grained molecular dynamics simulations and theoretical modeling to examine three-junctions in mixed lipid bilayer membranes. These junctions are localized defect lines in which three bilayers merge in such a way that each bilayer shares one monolayer with one of the other two bilayers. The resulting local morphology is non-lamellar, resembling the threefold symmetric defect lines in inverse hexagonal phases, but it regularly occurs during membrane fission and fusion events. We realize a system of junctions by setting up a honeycomb lattice, which in its primitive cell contains two hexagons and four three-line junctions, permitting usmore » to study their stability as well as their line tension. We specifically consider the effects of lipid composition and intrinsic curvature in binary mixtures, which contain a fraction of negatively curved lipids in a curvature-neutral background phase. Three-junction stability results from a competition between the junction and an open edge, which arises if one of the three bilayers detaches from the other two. We show that the stable phase is the one with the lower defect line tension. The strong and opposite monolayer curvatures present in junctions and edges enhance the mole fraction of negatively curved lipids in junctions and deplete it in edges. This lipid sorting affects the two line tensions and in turn the relative stability of the two phases. It also leads to a subtle entropic barrier for the transition between junction and edge that is absent in uniform membranes.« less
Phase-dependent noise in Josephson junctions
NASA Astrophysics Data System (ADS)
Sheldon, Forrest; Peotta, Sebastiano; Di Ventra, Massimiliano
2018-03-01
In addition to the usual superconducting current, Josephson junctions (JJs) support a phase-dependent conductance related to the retardation effect of tunneling quasi-particles. This introduces a dissipative current with a memory-resistive (memristive) character that should also affect the current noise. By means of the microscopic theory of tunnel junctions we compute the complete current autocorrelation function of a Josephson tunnel junction and show that this memristive component gives rise to both a previously noted phase-dependent thermal noise, and an undescribed non-stationary, phase-dependent dynamic noise. As experiments are approaching ranges in which these effects may be observed, we examine the form and magnitude of these processes. Their phase dependence can be realized experimentally as a hysteresis effect and may be used to probe defects present in JJ based qubits and in other superconducting electronics applications.
Voltage noise of current-driven vortices in disordered Josephson junction arrays.
He, G L; Zhao, Z G; Liu, S; Yang, Y H; Liu, M; Xing, D Y
2006-08-16
Dynamical phenomena of moving vortices and voltage noise spectra are studied in disordered Josephson junction arrays (JJAs). The plastic motion of vortices, smectic flow, and moving Bragg glass phases are separated by two dynamic melting transitions driven by current. From the voltage noise spectra of moving vortices, it is found that the driving current plays an important role in the melting of pinning vortices glass and ordering of moving vortices. The features of noise spectra obtained in the disordered JJA model have been observed recently in the high-temperature superconductor Bi(2)Sr(2)CaCu(2)O(y) near the first-order melting transition, indicating that both of them are related to each other.
Correlation of doping, structure, and carrier dynamics in a single GaN nanorod
NASA Astrophysics Data System (ADS)
Zhou, Xiang; Lu, Ming-Yen; Lu, Yu-Jung; Gwo, Shangjr; Gradečak, Silvija
2013-06-01
We report the nanoscale optical investigation of a single GaN p-n junction nanorod by cathodoluminescence (CL) in a scanning transmission electron microscope. CL emission characteristic of dopant-related transitions was correlated to doping and structural defect in the nanorod, and used to determine p-n junction position and minority carrier diffusion lengths of 650 nm and 165 nm for electrons and holes, respectively. Temperature-dependent CL study reveals an activation energy of 19 meV for non-radiative recombination in Mg-doped GaN nanorods. These results directly correlate doping, structure, carrier dynamics, and optical properties of GaN nanostructure, and provide insights for device design and fabrication.
Highly doped layer for tunnel junctions in solar cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fetzer, Christopher M.
A highly doped layer for interconnecting tunnel junctions in multijunction solar cells is presented. The highly doped layer is a delta doped layer in one or both layers of a tunnel diode junction used to connect two or more p-on-n or n-on-p solar cells in a multijunction solar cell. A delta doped layer is made by interrupting the epitaxial growth of one of the layers of the tunnel diode, depositing a delta dopant at a concentration substantially greater than the concentration used in growing the layer of the tunnel diode, and then continuing to epitaxially grow the remaining tunnel diode.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hu, Zixuan; Ratner, Mark A.; Seideman, Tamar, E-mail: t-seideman@northwestern.edu
2014-12-14
We develop a numerical approach for simulating light-induced charge transport dynamics across a metal-molecule-metal conductance junction. The finite-difference time-domain method is used to simulate the plasmonic response of the metal structures. The Huygens subgridding technique, as adapted to Lorentz media, is used to bridge the vastly disparate length scales of the plasmonic metal electrodes and the molecular system, maintaining accuracy. The charge and current densities calculated with classical electrodynamics are transformed to an electronic wavefunction, which is then propagated through the molecular linker via the Heisenberg equations of motion. We focus mainly on development of the theory and exemplify ourmore » approach by a numerical illustration of a simple system consisting of two silver cylinders bridged by a three-site molecular linker. The electronic subsystem exhibits fascinating light driven dynamics, wherein the charge density oscillates at the driving optical frequency, exhibiting also the natural system timescales, and a resonance phenomenon leads to strong conductance enhancement.« less
Modulation of Intestinal Paracellular Transport by Bacterial Pathogens.
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.
Sarin, Yogesh Kumar
2017-07-01
The postnatal treatment of asymptomatic unilateral hydronephrosis due to ureteropelvic junction obstruction remains controversial, and the timing of and indications for surgical intervention are continuously debated. There is no consensus on the best follow-up during expectant management. The various modalities and parameters have been discussed along with their pros and cons and an attempt has been made to clear up the controversies.
Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina
2016-02-01
A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Gap Junctional Coupling is Essential for Epithelial Repair in the Avian Cochlea
Nickel, Regina; Forge, Andrew
2014-01-01
The loss of auditory hair cells triggers repair responses within the population of nonsensory supporting cells. When hair cells are irreversibly lost from the mammalian cochlea, supporting cells expand to fill the resulting lesions in the sensory epithelium, an initial repair process that is dependent on gap junctional intercellular communication (GJIC). In the chicken cochlea (the basilar papilla or BP), dying hair cells are extruded from the epithelium and supporting cells expand to fill the lesions and then replace hair cells via mitotic and/or conversion mechanisms. Here, we investigated the involvement of GJIC in the initial epithelial repair process in the aminoglycoside-damaged BP. Gentamicin-induced hair cell loss was associated with a decrease of chicken connexin43 (cCx43) immunofluorescence, yet cCx30-labeled gap junction plaques remained. Fluorescence recovery after photobleaching experiments confirmed that the GJIC remained robust in gentamicin-damaged explants, but regionally asymmetric coupling was no longer evident. Dye injections in slice preparations from undamaged BP explants identified cell types with characteristic morphologies along the neural-abneural axis, but these were electrophysiologically indistinct. In gentamicin-damaged BP, supporting cells expanded to fill space formerly occupied by hair cells and displayed more variable electrophysiological phenotypes. When GJIC was inhibited during the aminoglycoside damage paradigm, the epithelial repair response halted. Dying hair cells were retained within the sensory epithelium and supporting cells remained unexpanded. These observations suggest that repair of the auditory epithelium shares common mechanisms across vertebrate species and emphasize the importance of functional gap junctions in maintaining a homeostatic environment permissive for subsequent hair cell regeneration. PMID:25429127
A Sarsa(λ)-based control model for real-time traffic light coordination.
Zhou, Xiaoke; Zhu, Fei; Liu, Quan; Fu, Yuchen; Huang, Wei
2014-01-01
Traffic problems often occur due to the traffic demands by the outnumbered vehicles on road. Maximizing traffic flow and minimizing the average waiting time are the goals of intelligent traffic control. Each junction wants to get larger traffic flow. During the course, junctions form a policy of coordination as well as constraints for adjacent junctions to maximize their own interests. A good traffic signal timing policy is helpful to solve the problem. However, as there are so many factors that can affect the traffic control model, it is difficult to find the optimal solution. The disability of traffic light controllers to learn from past experiences caused them to be unable to adaptively fit dynamic changes of traffic flow. Considering dynamic characteristics of the actual traffic environment, reinforcement learning algorithm based traffic control approach can be applied to get optimal scheduling policy. The proposed Sarsa(λ)-based real-time traffic control optimization model can maintain the traffic signal timing policy more effectively. The Sarsa(λ)-based model gains traffic cost of the vehicle, which considers delay time, the number of waiting vehicles, and the integrated saturation from its experiences to learn and determine the optimal actions. The experiment results show an inspiring improvement in traffic control, indicating the proposed model is capable of facilitating real-time dynamic traffic control.
Two dimensional thermal and charge mapping of power thyristors
NASA Technical Reports Server (NTRS)
Hu, S. P.; Rabinovici, B. M.
1975-01-01
The two dimensional static and dynamic current density distributions within the junction of semiconductor power switching devices and in particular the thyristors were obtained. A method for mapping the thermal profile of the device junctions with fine resolution using an infrared beam and measuring the attenuation through the device as a function of temperature were developed. The results obtained are useful in the design and quality control of high power semiconductor switching devices.
Binary dislocation junction formation and strength in hexagonal close-packed crystals
Wu, Chi -Chin; Aubry, Sylvie; Arsenlis, Athanasios; ...
2015-12-17
This work examines binary dislocation interactions, junction formation and junction strengths in hexagonal close-packed ( hcp ) crystals. Through a line-tension model and dislocation dynamics (DD) simulations, the interaction and dissociation of different sets of binary junctions are investigated involving one dislocation on the (011¯0) prismatic plane and a second dislocation on one of the following planes: (0001) basal, (11¯00) prismatic, (11¯01) primary pyramidal, or (2¯112) secondary pyramidal. Varying pairs of Burgers vectors are chosen from among the common types the basal type < a > 1/3 < 112¯0 >, prismatic type < c > <0001>, and pyramidal type
Raleigh, David R; Marchiando, Amanda M; Zhang, Yong; Shen, Le; Sasaki, Hiroyuki; Wang, Yingmin; Long, Manyuan; Turner, Jerrold R
2010-04-01
In vitro studies have demonstrated that occludin and tricellulin are important for tight junction barrier function, but in vivo data suggest that loss of these proteins can be overcome. The presence of a heretofore unknown, yet related, protein could explain these observations. Here, we report marvelD3, a novel tight junction protein that, like occludin and tricellulin, contains a conserved four-transmembrane MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain. Phylogenetic tree reconstruction; analysis of RNA and protein tissue distribution; immunofluorescent and electron microscopic examination of subcellular localization; characterization of intracellular trafficking, protein interactions, dynamic behavior, and siRNA knockdown effects; and description of remodeling after in vivo immune activation show that marvelD3, occludin, and tricellulin have distinct but overlapping functions at the tight junction. Although marvelD3 is able to partially compensate for occludin or tricellulin loss, it cannot fully restore function. We conclude that marvelD3, occludin, and tricellulin define the tight junction-associated MARVEL protein family. The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation.
Abnous, Khalil; Danesh, Noor Mohammad; Ramezani, Mohammad; Taghdisi, Seyed Mohammad; Emrani, Ahmad Sarreshtehdar
2018-08-22
Herein, a novel colorimetric aptasensor was introduced for detection of cocaine based on the formation of three-way junction pockets on the surfaces of gold nanoparticles (AuNPs) and the catalytic activity of the surfaces of AuNPs. Simplicity and detection of cocaine in a short time (only 35 min) are some of the unique features of the proposed sensing strategy. In the presence of cocaine, triple-fragment aptamer (TFA) forms on the surfaces of AuNPs, leading to a significant decrease of the catalytic activity of AuNPs and the color of samples remains yellow. In the absence of target, TFA does not form on the surfaces of AuNPs and 4-Nitrophenol, as a colorimetric agent, has more access to the surfaces of AuNPs, resulting in the reduction of 4-Nitrophenol and the color of sample changes from yellow to colorless. The sensing strategy showed good specificity, a limit of detection (LOD) of 440 pM and a dynamic range over 2-100 nM. The sensing method was also successfully applied to detect cocaine in spiked human serum samples with recovery of 94.71-98.63%. Copyright © 2018 Elsevier B.V. All rights reserved.
Actin filament curvature biases branching direction
NASA Astrophysics Data System (ADS)
Wang, Evan; Risca, Viviana; Chaudhuri, Ovijit; Chia, Jia-Jun; Geissler, Phillip; Fletcher, Daniel
2012-02-01
Actin filaments are key components of the cellular machinery, vital for a wide range of processes ranging from cell motility to endocytosis. Actin filaments can branch, and essential in this process is a protein complex known as the Arp2/3 complex, which nucleate new ``daughter'' filaments from pre-existing ``mother'' filaments by attaching itself to the mother filament. Though much progress has been made in understanding the Arp2/3-actin junction, some very interesting questions remain. In particular, F-actin is a dynamic polymer that undergoes a wide range of fluctuations. Prior studies of the Arp2/3-actin junction provides a very static notion of Arp2/3 binding. The question we ask is how differently does the Arp2/3 complex interact with a straight filament compared to a bent filament? In this study, we used Monte Carlo simulations of a surface-tethered worm-like chain to explore possible mechanisms underlying the experimental observation that there exists preferential branch formation by the Arp2/3 complex on the convex face of a curved filament. We show that a fluctuation gating model in which Arp2/3 binding to the actin filament is dependent upon a rare high-local-curvature shape fluctuation of the filament is consistent with the experimental data.
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
Nanes, Benjamin A.; Kowalczyk, Andrew P.
2014-01-01
Adherens junctions are important mediators of intercellular adhesion, but they are not static structures. They are regularly formed, broken, and rearranged in a variety of situations, requiring changes in the amount of cadherins, the main adhesion molecule in adherens junctions, present at the cell surface. Thus, endocytosis, degradation, and recycling of cadherins are crucial for dynamic regulation of adherens junctions and control of intercellular adhesion. In this chapter, we review the involvement of cadherin endocytosis in development and disease. We discuss the various endocytic pathways available to cadherins, the adaptors involved, and the sorting of internalized cadherin for recycling or lysosomal degradation. In addition, we review the regulatory pathways controlling cadherin endocytosis and degradation, including regulation of cadherin endocytosis by catenins, cadherin ubiquitination, and growth factor receptor signaling pathways. Lastly, we discuss the proteolytic cleavage of cadherins at the plasma membrane. PMID:22674073
Jmy regulates oligodendrocyte differentiation via modulation of actin cytoskeleton dynamics.
Azevedo, Maria M; Domingues, Helena S; Cordelières, Fabrice P; Sampaio, Paula; Seixas, Ana I; Relvas, João B
2018-05-06
During central nervous system development, oligodendrocytes form structurally and functionally distinct actin-rich protrusions that contact and wrap around axons to assemble myelin sheaths. Establishment of axonal contact is a limiting step in myelination that relies on the oligodendrocyte's ability to locally coordinate cytoskeletal rearrangements with myelin production, under the control of a transcriptional differentiation program. The molecules that provide fine-tuning of actin dynamics during oligodendrocyte differentiation and axon ensheathment remain largely unidentified. We performed transcriptomics analysis of soma and protrusion fractions from rat brain oligodendrocyte progenitors and found a subcellular enrichment of mRNAs in newly-formed protrusions. Approximately 30% of protrusion-enriched transcripts encode proteins related to cytoskeleton dynamics, including the junction mediating and regulatory protein Jmy, a multifunctional regulator of actin polymerization. Here, we show that expression of Jmy is upregulated during myelination and is required for the assembly of actin filaments and protrusion formation during oligodendrocyte differentiation. Quantitative morphodynamics analysis of live oligodendrocytes showed that differentiation is driven by a stereotypical actin network-dependent "cellular shaping" program. Disruption of actin dynamics via knockdown of Jmy leads to a program fail resulting in oligodendrocytes that do not acquire an arborized morphology and are less efficient in contacting neurites and forming myelin wraps in co-cultures with neurons. Our findings provide new mechanistic insight into the relationship between cell shape dynamics and differentiation in development. © 2018 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Fourmaux-Demange, V.; Brûlet, A.; Boué, F.; Davidson, P.; Keller, P.; Cotton, J. P.
2000-04-01
We have studied the rheology and the conformation of stretched comb-like liquid-crystalline polymers. Both the influence of the comb-like structure and the specific effect of the nematic interaction on the dynamics are investigated. For this purpose, two isomers of a comb-like polymetacrylate polymer, of well-defined molecular weights, were synthesized: one displays a nematic phase over a wide range of temperature, the other one has only an isotropic phase. Even with high degrees of polymerization N, between 40 and 1000, the polymer chains studied were not entangled. The stress-strain curves during the stretching and relaxation processes show differences between the isotropic and nematic comb-like polymers. They suggest that, in the nematic phase, the chain dynamics is more cooperative than for a usual linear polymer. Small-angle neutron scattering has been used in order to determine the evolution of the chain conformation after stretching, as a function of the duration of relaxation t_r. The conformation can be described with two parameters only: λ_p, the global deformation of the polymer chain, and p, the number of statistical units of locally relaxed sub-chains. For the comb-like polymer, the chain deformation is pseudo-affine: λ_p is always smaller than λ (the deformation ratio of the whole sample). In the isotropic phase, λ_p has a constant value, while p increases as t_r. This latter behavior is not that expected for non-entangled chains, in which p varies as {t_r}^{1/2} (Rouse model). In the nematic phase, λ_p decreases as a stretched exponential function of t_r, while p remains constant. The dynamics of the comb-like polymers is discussed in terms of living clusters from which junctions are produced by interactions between side chains. The nematic interaction increases the lifetime of these junctions and, strikingly, the relaxation is the same at all scales of the whole polymer chain.
Yuan, Zhiquan; Xiao, Xiaohua; Li, Gongke
2013-11-22
A simple and efficient dynamic pH junction high-speed counter-current chromatography method was developed and further applied to the online extraction, separation and purification of alkaloids from Stephania cepharantha by coupling with microwave-assisted extraction. Mineral acid and organic base were added into the mobile phase and the sample solution, respectively, leading to the formation of a dynamic pH junction in the column and causing focus of alkaloids. Selective focus of analytes can be achieved on the basis of velocity changes of the pH junction through appropriate selection of solvent systems and optimization of additive concentrations. The extract can be directly introduced into the HSCCC for the online extraction, separation and purification of alkaloids from S. cepharantha. Continuous separation can be easily achieved with the same solvent system. Under the optimum conditions, 6.0 g original sample was extracted with 60 mL of the upper phase of hexane-ethyl acetate-methanol-water (1:1:1:1, v/v/v/v) containing 10% triethylamine under 50 °C and 400 W irradiation power for 10 min, the extracts were directly separated and purified by high-speed counter-current chromatography. A total of 5.7 mg sinomenine, 8.3mg 6,7-di-O-acetylsinococuline, 17.9 mg berbamine, 12.7 mg isotetrandrine and 14.6 mg cepharanthine were obtained with purities of 96.7%, 93.7%, 98.7%, 97.3% and 99.3%, respectively. The online method provides good selectivity to ionizable compounds and improves the separation and purification efficiency of the high-speed counter-current chromatography technique. It has good potential for separation and purification of effective compounds from natural products. Copyright © 2013 Elsevier B.V. All rights reserved.
Denker, Elsa; Sehring, Ivonne M; Dong, Bo; Audisso, Julien; Mathiesen, Birthe; Jiang, Di
2015-05-01
Regulation of lumen growth is crucial to ensure the correct morphology, dimensions and function of a tubular structure. How this is controlled is still poorly understood. During Ciona intestinalis notochord tubulogenesis, single extracellular lumen pockets grow between pairs of cells and eventually fuse into a continuous tube. Here, we show that lumen growth exhibits a lag phase, during which the luminal membranes continue to grow but the expansion of the apical/lateral junction pauses for ∼30 min. Inhibition of non-muscle myosin II activity abolishes this lag phase and accelerates expansion of the junction, resulting in the formation of narrower lumen pockets partially fusing into a tube of reduced size. Disruption of actin dynamics, conversely, causes a reversal of apical/lateral junction expansion, leading to a dramatic conversion of extracellular lumen pockets to intracellular vacuoles and a tubulogenesis arrest. The onset of the lag phase is correlated with a de novo accumulation of actin that forms a contractile ring at the apical/lateral junctions. This actin ring actively restricts the opening of the lumen in the transverse plane, allowing sufficient time for lumen growth via an osmotic process along the longitudinal dimension. The dynamics of lumen formation is controlled by the TGFβ pathway and ROCK activity. Our findings reveal a TGFβ-ROCK-actomyosin contractility axis that coordinates lumen growth, which is powered by the dynamics of luminal osmolarity. The regulatory system may function like a sensor/checkpoint that responds to the change of luminal pressure and fine-tunes actomyosin contractility to effect proper tubulogenesis. © 2015. Published by The Company of Biologists Ltd.
High temperature current mirror amplifier
Patterson, III, Raymond B.
1984-05-22
A high temperature current mirror amplifier having biasing means in the transdiode connection of the input transistor for producing a voltage to maintain the base-collector junction reversed-biased and a current means for maintaining a current through the biasing means at high temperatures so that the base-collector junction of the input transistor remained reversed-biased. For accuracy, a second current mirror is provided with a biasing means and current means on the input leg.
Jeon, Pyo Jin; Lee, Young Tack; Lim, June Yeong; Kim, Jin Sung; Hwang, Do Kyung; Im, Seongil
2016-02-10
Black phosphorus (BP) nanosheet is two-dimensional (2D) semiconductor with distinct band gap and attracting recent attention from researches because it has some similarity to gapless 2D semiconductor graphene in the following two aspects: single element (P) for its composition and quite high mobilities depending on its fabrication conditions. Apart from several electronic applications reported with BP nanosheet, here we report for the first time BP nanosheet-ZnO nanowire 2D-1D heterojunction applications for p-n diodes and BP-gated junction field effect transistors (JFETs) with n-ZnO channel on glass. For these nanodevices, we take advantages of the mechanical flexibility of p-type conducting of BP and van der Waals junction interface between BP and ZnO. As a result, our BP-ZnO nanodimension p-n diode displays a high ON/OFF ratio of ∼10(4) in static rectification and shows kilohertz dynamic rectification as well while ZnO nanowire channel JFET operations are nicely demonstrated by BP gate switching in both electrostatics and kilohertz dynamics.
Anomalous Photovoltaic Response of Graphene-on-GaN Schottky Photodiodes.
Lee, Jae Hyung; Lee, Won Woo; Yang, Dong Won; Chang, Won Jun; Kwon, Sun Sang; Park, Won Il
2018-04-25
Graphene has attracted great attention as an alternative to conventional metallic or transparent conducting electrodes. Despite its similarities with conventional electrodes, recent studies have shown that a single-atom layer of graphene possesses unique characteristics, such as a tunable work function and transparencies for electric potential, reactivity, and wetting. Nevertheless, a systematic analysis of graphene and semiconductor junction characteristics has not yet been carried out. Here, we report the photoresponse characteristics of graphene-on-GaN Schottky junction photodiodes (Gr-GaN SJPDs), showing a typical rectifying behavior and distinct photovoltaic and photoelectric responses. Following the initial abrupt response to UV illumination, the Gr-GaN SJPDs exhibited a distinct difference in photocarrier dynamics depending on the applied bias voltage, which is characterized by either a negative or positive change in photocurrent with time. We propose underlying mechanisms for the anomalous photocarrier dynamics based on the interplay between electrostatic molecular interactions over the one-atom-thick graphene and GaN junction and trapped photocarriers at the defect states in the GaN thin film.
Fontes, Joseph D.; Ramsey, Jon; Polk, Jeremy M; Koop, Andre; Denisova, Janna V.; Belousov, Andrei B.
2015-01-01
Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed. PMID:26017008
Fullerene Derived Molecular Electronic Devices
NASA Technical Reports Server (NTRS)
Menon, Madhu; Srivastava, Deepak; Saini, Subbash
1998-01-01
The carbon Nanotube junctions have recently emerged as excellent candidates for use as the building blocks in the formation of nanoscale electronic devices. While the simple joint of two dissimilar tubes can be generated by the introduction of a pair of heptagon-pentagon defects in an otherwise perfect hexagonal grapheme sheet, more complex joints require other mechanisms. In this work we explore structural and electronic properties of complex 3-point junctions of carbon nanotubes using a generalized tight-binding molecular-dynamics scheme.
NASA Astrophysics Data System (ADS)
Zhang, Henggui; Garratt, Clifford J.; Kharche, Sanjay; Holden, Arun V.
2009-06-01
Human atrial tissue is an excitable system, in which myocytes are excitable elements, and cell-to-cell electrotonic interactions are via diffusive interactions of cell membrane potentials. We developed a family of excitable system models for human atrium at cellular, tissue and anatomical levels for both normal and chronic atrial fibrillation (AF) conditions. The effects of AF-induced remodelling of cell membrane ionic channels (reaction kinetics) and intercellular gap junctional coupling (diffusion) on atrial excitability, conduction of excitation waves and dynamics of re-entrant excitation waves are quantified. Both ionic channel and gap junctional coupling remodelling have rate dependent effects on atrial propagation. Membrane channel conductance remodelling allows the propagation of activity at higher rates than those sustained in normal tissue or in tissue with gap junctional remodelling alone. Membrane channel conductance remodelling is essential for the propagation of activity at rates higher than 300/min as seen in AF. Spatially heterogeneous gap junction coupling remodelling increased the risk of conduction block, an essential factor for the genesis of re-entry. In 2D and 3D anatomical models, the dynamical behaviours of re-entrant excitation waves are also altered by membrane channel modelling. This study provides insights to understand the pro-arrhythmic effects of AF-induced reaction and diffusion remodelling in atrial tissue.
Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission
NASA Astrophysics Data System (ADS)
Rouach, Nathalie; Koulakoff, Annette; Abudara, Veronica; Willecke, Klaus; Giaume, Christian
2008-12-01
Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.
Astroglial metabolic networks sustain hippocampal synaptic transmission.
Rouach, Nathalie; Koulakoff, Annette; Abudara, Veronica; Willecke, Klaus; Giaume, Christian
2008-12-05
Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.
Superpoissonian shot noise in organic magnetic tunnel junctions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cascales, Juan Pedro; Martinez, Isidoro; Aliev, Farkhad G., E-mail: farkhad.aliev@uam.es
Organic molecules have recently revolutionized ways to create new spintronic devices. Despite intense studies, the statistics of tunneling electrons through organic barriers remains unclear. Here, we investigate conductance and shot noise in magnetic tunnel junctions with 3,4,9,10-perylene-teracarboxylic dianhydride (PTCDA) barriers a few nm thick. For junctions in the electron tunneling regime, with magnetoresistance ratios between 10% and 40%, we observe superpoissonian shot noise. The Fano factor exceeds in 1.5–2 times the maximum values reported for magnetic tunnel junctions with inorganic barriers, indicating spin dependent bunching in tunneling. We explain our main findings in terms of a model which includes tunnelingmore » through a two level (or multilevel) system, originated from interfacial bonds of the PTCDA molecules. Our results suggest that interfaces play an important role in the control of shot noise when electrons tunnel through organic barriers.« less
Atomistic simulations of highly conductive molecular transport junctions under realistic conditions
NASA Astrophysics Data System (ADS)
French, William R.; Iacovella, Christopher R.; Rungger, Ivan; Souza, Amaury Melo; Sanvito, Stefano; Cummings, Peter T.
2013-04-01
We report state-of-the-art atomistic simulations combined with high-fidelity conductance calculations to probe structure-conductance relationships in Au-benzenedithiolate (BDT)-Au junctions under elongation. Our results demonstrate that large increases in conductance are associated with the formation of monatomic chains (MACs) of Au atoms directly connected to BDT. An analysis of the electronic structure of the simulated junctions reveals that enhancement in the s-like states in Au MACs causes the increases in conductance. Other structures also result in increased conductance but are too short-lived to be detected in experiment, while MACs remain stable for long simulation times. Examinations of thermally evolved junctions with and without MACs show negligible overlap between conductance histograms, indicating that the increase in conductance is related to this unique structural change and not thermal fluctuation. These results, which provide an excellent explanation for a recently observed anomalous experimental result [Bruot et al., Nat. Nanotechnol., 2012, 7, 35-40], should aid in the development of mechanically responsive molecular electronic devices.We report state-of-the-art atomistic simulations combined with high-fidelity conductance calculations to probe structure-conductance relationships in Au-benzenedithiolate (BDT)-Au junctions under elongation. Our results demonstrate that large increases in conductance are associated with the formation of monatomic chains (MACs) of Au atoms directly connected to BDT. An analysis of the electronic structure of the simulated junctions reveals that enhancement in the s-like states in Au MACs causes the increases in conductance. Other structures also result in increased conductance but are too short-lived to be detected in experiment, while MACs remain stable for long simulation times. Examinations of thermally evolved junctions with and without MACs show negligible overlap between conductance histograms, indicating that the increase in conductance is related to this unique structural change and not thermal fluctuation. These results, which provide an excellent explanation for a recently observed anomalous experimental result [Bruot et al., Nat. Nanotechnol., 2012, 7, 35-40], should aid in the development of mechanically responsive molecular electronic devices. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr00459g
Totland, Max Z; Bergsland, Christian H; Fykerud, Tone A; Knudsen, Lars M; Rasmussen, Nikoline L; Eide, Peter W; Yohannes, Zeremariam; Sørensen, Vigdis; Brech, Andreas; Lothe, Ragnhild A; Leithe, Edward
2017-09-01
Intercellular communication via gap junctions has an important role in controlling cell growth and in maintaining tissue homeostasis. Connexin 43 (Cx43; also known as GJA1) is the most abundantly expressed gap junction channel protein in humans and acts as a tumor suppressor in multiple tissue types. Cx43 is often dysregulated at the post-translational level during cancer development, resulting in loss of gap junctions. However, the molecular basis underlying the aberrant regulation of Cx43 in cancer cells has remained elusive. Here, we demonstrate that the oncogenic E3 ubiquitin ligase NEDD4 regulates the Cx43 protein level in HeLa cells, both under basal conditions and in response to protein kinase C activation. Furthermore, overexpression of NEDD4, but not a catalytically inactive form of NEDD4, was found to result in nearly complete loss of gap junctions and increased lysosomal degradation of Cx43 in both HeLa and C33A cervical carcinoma cells. Collectively, the data provide new insights into the molecular basis underlying the regulation of gap junction size and represent the first evidence that an oncogenic E3 ubiquitin ligase promotes loss of gap junctions and Cx43 degradation in human carcinoma cells. © 2017. Published by The Company of Biologists Ltd.
High temperature current mirror amplifier
Patterson, R.B. III.
1984-05-22
Disclosed is a high temperature current mirror amplifier having biasing means in the transdiode connection of the input transistor for producing a voltage to maintain the base-collector junction reversed-biased and a current means for maintaining a current through the biasing means at high temperatures so that the base-collector junction of the input transistor remained reversed-biased. For accuracy, a second current mirror is provided with a biasing means and current means on the input leg. 2 figs.
DETAIL VIEW OF FILTER PRESS REMAINS, BOILER, SECONDARY ORE BIN, ...
DETAIL VIEW OF FILTER PRESS REMAINS, BOILER, SECONDARY ORE BIN, TRAM TRESTLE AND WATER TANK, LOOKING NORTHWEST. HIS VIEW IS TAKEN FROM THE THIRD LEVEL OF THE MILL, NEARBY THE BLACKSMITH'S FORGE. - Keane Wonder Mine, Park Route 4 (Daylight Pass Cutoff), Death Valley Junction, Inyo County, CA
Measure Guideline: Optimizing the Configuration of Flexible Duct Junction Boxes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Beach, R.; Burdick, A.
2014-03-01
This measure guideline offers additional recommendations to heating, ventilation, and air conditioning (HVAC) system designers for optimizing flexible duct, constant-volume HVAC systems using junction boxes within Air Conditioning Contractors of America (ACCA) Manual D guidance (Rutkowski, H. Manual D -- Residential Duct Systems, 3rd edition, Version 1.00. Arlington, VA: Air Conditioning Contractors of America, 2009.). IBACOS used computational fluid dynamics software to explore and develop guidance to better control the airflow effects of factors that may impact pressure losses within junction boxes among various design configurations (Beach, R., Prahl, D., and Lange, R. CFD Analysis of Flexible Duct Junction Boxmore » Design. Golden, CO: National Renewable Energy Laboratory, submitted for publication 2013). These recommendations can help to ensure that a system aligns more closely with the design and the occupants' comfort expectations. Specifically, the recommendations described herein show how to configure a rectangular box with four outlets, a triangular box with three outlets, metal wyes with two outlets, and multiple configurations for more than four outlets. Designers of HVAC systems, contractors who are fabricating junction boxes on site, and anyone using the ACCA Manual D process for sizing duct runs will find this measure guideline invaluable for more accurately minimizing pressure losses when using junction boxes with flexible ducts.« less
A Sarsa(λ)-Based Control Model for Real-Time Traffic Light Coordination
Zhu, Fei; Liu, Quan; Fu, Yuchen; Huang, Wei
2014-01-01
Traffic problems often occur due to the traffic demands by the outnumbered vehicles on road. Maximizing traffic flow and minimizing the average waiting time are the goals of intelligent traffic control. Each junction wants to get larger traffic flow. During the course, junctions form a policy of coordination as well as constraints for adjacent junctions to maximize their own interests. A good traffic signal timing policy is helpful to solve the problem. However, as there are so many factors that can affect the traffic control model, it is difficult to find the optimal solution. The disability of traffic light controllers to learn from past experiences caused them to be unable to adaptively fit dynamic changes of traffic flow. Considering dynamic characteristics of the actual traffic environment, reinforcement learning algorithm based traffic control approach can be applied to get optimal scheduling policy. The proposed Sarsa(λ)-based real-time traffic control optimization model can maintain the traffic signal timing policy more effectively. The Sarsa(λ)-based model gains traffic cost of the vehicle, which considers delay time, the number of waiting vehicles, and the integrated saturation from its experiences to learn and determine the optimal actions. The experiment results show an inspiring improvement in traffic control, indicating the proposed model is capable of facilitating real-time dynamic traffic control. PMID:24592183
Structural and functional diversity of cadherin at the adherens junction
2011-01-01
Adhesion between cells is essential to the evolution of multicellularity. Indeed, morphogenesis in animals requires firm but flexible intercellular adhesions that are mediated by subcellular structures like the adherens junction (AJ). A key component of AJs is classical cadherins, a group of transmembrane proteins that maintain dynamic cell–cell associations in many animal species. An evolutionary reconstruction of cadherin structure and function provides a comprehensive framework with which to appreciate the diversity of morphogenetic mechanisms in animals. PMID:21708975
Study of charge-phase diagrams for coupled system of Josephson junctions
NASA Astrophysics Data System (ADS)
Hamdipour, M.; Shukrinov, Y. U. M.
2010-11-01
Dynamics of stacked intrinsic Josephson junctions (IJJ) in the high-Tc superconductors is theoretically investigated. We calculate the current-voltage characteristics (CVC) of IJJ and study the breakpoint region on the outermost branch of the CVC for the stacks with 9 IJJ. A method for investigation of the fine structure in CVC of IJJ based on the recording the "phase-charge" diagrams is suggested. It is demonstrated that this method reflects the main features of the breakpoint region.
Diao, Honglu; Xiao, Shuo; Howerth, Elizabeth W; Zhao, Fei; Li, Rong; Ard, Mary B; Ye, Xiaoqin
2013-08-01
Gap junctions have an important role in cell-to-cell communication, a process obviously required for embryo implantation. Uterine luminal epithelium (LE) is the first contact for an implanting embryo and is critical for the establishment of uterine receptivity. Microarray analysis of the LE from peri-implantation mouse uterus showed low-level expression of 19 gap junction proteins in preimplantation LE and upregulation of gap junction protein, beta 2 (GJB2, connexin 26, Cx26) in postimplantation LE. Time course study using in situ hybridization and immunofluorescence revealed upregulation of GJB2 in the LE surrounding the implantation site before decidualization. Similar dynamic expression of GJB2 was observed in the LE of artificially decidualized mice but not pseudopregnant mice. To determine the potential function of uterine gap junctions in embryo implantation, carbenoxolone (CBX), a broad gap junction blocker, was injected i.p. (100 mg/kg) or via local uterine fat pad (10 mg/kg) into pregnant mice on Gestation Day 3 at 1800 h, a few hours before embryo attachment to the LE. These CBX treatments disrupted embryo implantation, suggesting local effects of CBX in the uterus. However, i.p. injection of glycyrrhizic acid (100 mg/kg), which shares similar structure and multiple properties with CBX but is ineffective in blocking gap junctions, did not affect embryo implantation. Carbenoxolone also inhibited oil-induced artificial decidualization, concomitant with suppressed molecular changes and ultrastructural transformations associated with uterine preparation for embryo implantation, underscoring the adverse effect of CBX on uterine preparation for embryo implantation. These data demonstrate that uterine gap junctions are important for embryo implantation.
Naz, Anam; Obaid, Ayesha; Awan, Faryal M.; Ikram, Aqsa; Ahmad, Jamil; Ali, Amjad
2017-01-01
Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells. PMID:28932213
NASA Astrophysics Data System (ADS)
Esposito, Daniel V.
2015-08-01
Solid-state junctions based on a metal-insulator-semiconductor (MIS) architecture are of great interest for a number of optoelectronic applications such as photovoltaics, photoelectrochemical cells, and photodetection. One major advantage of the MIS junction compared to the closely related metal-semiconductor junction, or Schottky junction, is that the thin insulating layer (1-3 nm thick) that separates the metal and semiconductor can significantly reduce the density of undesirable interfacial mid-gap states. The reduction in mid-gap states helps "un-pin" the junction, allowing for significantly higher built-in-voltages to be achieved. A second major advantage of the MIS junction is that the thin insulating layer can also protect the underlying semiconductor from corrosion in an electrochemical environment, making the MIS architecture well-suited for application in (photo)electrochemical applications. In this presentation, discontinuous Si-based MIS junctions immersed in electrolyte are explored for use as i.) photoelectrodes for solar-water splitting in photoelectrochemical cells (PECs) and ii.) position-sensitive photodetectors. The development and optimization of MIS photoelectrodes for both of these applications relies heavily on understanding how processing of the thin SiO2 layer impacts the properties of nano- and micro-scale MIS junctions, as well as the interactions of the insulating layer with the electrolyte. In this work, we systematically explore the effects of insulator thickness, synthesis method, and chemical treatment on the photoelectrochemical and electrochemical properties of these MIS devices. It is shown that electrolyte-induced inversion plays a critical role in determining the charge carrier dynamics within the MIS photoelectrodes for both applications.
Naz, Anam; Obaid, Ayesha; Awan, Faryal M; Ikram, Aqsa; Ahmad, Jamil; Ali, Amjad
2017-01-01
Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells.
Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks
Xu, Jianfeng; Lan, Yueheng
2015-01-01
Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347
Watt, Janet Tilden; Ponce, David A.; Graymer, Russell W.; Jachens, Robert C.; Simpson, Robert W.
2014-01-01
While an enormous amount of research has been focused on trying to understand the geologic history and neotectonics of the San Andreas-Calaveras fault (SAF-CF) junction, fundamental questions concerning fault geometry and mechanisms for slip transfer through the junction remain. We use potential-field, geologic, geodetic, and seismicity data to investigate the 3-D geologic framework of the SAF-CF junction and identify potential slip-transferring structures within the junction. Geophysical evidence suggests that the San Andreas and Calaveras fault zones dip away from each other within the northern portion of the junction, bounding a triangular-shaped wedge of crust in cross section. This wedge changes shape to the south as fault geometries change and fault activity shifts between fault strands, particularly along the Calaveras fault zone (CFZ). Potential-field modeling and relocated seismicity suggest that the Paicines and San Benito strands of the CFZ dip 65° to 70° NE and form the southwest boundary of a folded 1 to 3 km thick tabular body of Coast Range Ophiolite (CRO) within the Vallecitos syncline. We identify and characterize two steeply dipping, seismically active cross structures within the junction that are associated with serpentinite in the subsurface. The architecture of the SAF-CF junction presented in this study may help explain fault-normal motions currently observed in geodetic data and help constrain the seismic hazard. The abundance of serpentinite and related CRO in the subsurface is a significant discovery that not only helps constrain the geometry of structures but may also help explain fault behavior and the tectonic evolution of the SAF-CF junction.
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.
Resolving metal-molecule interfaces at single-molecule junctions
NASA Astrophysics Data System (ADS)
Komoto, Yuki; Fujii, Shintaro; Nakamura, Hisao; Tada, Tomofumi; Nishino, Tomoaki; Kiguchi, Manabu
2016-05-01
Electronic and structural detail at the electrode-molecule interface have a significant influence on charge transport across molecular junctions. Despite the decisive role of the metal-molecule interface, a complete electronic and structural characterization of the interface remains a challenge. This is in no small part due to current experimental limitations. Here, we present a comprehensive approach to obtain a detailed description of the metal-molecule interface in single-molecule junctions, based on current-voltage (I-V) measurements. Contrary to conventional conductance studies, this I-V approach provides a correlated statistical description of both, the degree of electronic coupling across the metal-molecule interface, and the energy alignment between the conduction orbital and the Fermi level of the electrode. This exhaustive statistical approach was employed to study single-molecule junctions of 1,4-benzenediamine (BDA), 1,4-butanediamine (C4DA), and 1,4-benzenedithiol (BDT). A single interfacial configuration was observed for both BDA and C4DA junctions, while three different interfacial arrangements were resolved for BDT. This multiplicity is due to different molecular adsorption sites on the Au surface namely on-top, hollow, and bridge. Furthermore, C4DA junctions present a fluctuating I-V curve arising from the greater conformational freedom of the saturated alkyl chain, in sharp contrast with the rigid aromatic backbone of both BDA and BDT.
Progress toward the development of dual junction GaAs/Ge solar cells
NASA Technical Reports Server (NTRS)
Lillington, D. R.; Krut, D. D.; Cavicchi, B. T.; Ralph, E.; Chung, M.
1991-01-01
Large area GaAs/Ge cells offer substantial promise for increasing the power output from existing silicon solar array designs and for providing an enabled technology for missions hitherto impossible using silicon. Single junction GaAs/Ge cells offer substantial advantages in both size, weight, and cost compared to GaAs cells but the efficiency is limited to approximately 19.2 to 20 percent AMO. The thermal absorptance of GaAs/Ge cells is also worse than GaAs/GaAs cells (0.88 vs 0.81 typ.) due to the absorption in the Ge substrate. On the other hand dual junction GaAs/Ge cells offer efficiencies up to ultimately 24 percent AMO in sizes up to 8 x 8 cm but there are still technological issues remaining to achieve current matching in the GaAs and Ge cells. This can be achieved through tuned antireflection (AR) coatings, improved quality of the GaAs growth, improved quality Ge wafers and the use of a Back Surface Field (BSF)/Back Surface Reflector (BSR) in the Ge cell. Although the temperature coefficients of efficiency and voltage are higher for dual junction GaAs/Ge cells, it has been shown elsewhere that for typical 28 C cell efficiencies of 22 percent (dual junction) vs 18.5 percent (single junction) there is a positive power tradeoff up to temperatures as high as 120 C. Due to the potential ease of fabrication of GaAs/Ge dual junction cells there is likely to be only a small cost differential compared to single junction cells.
PASTA: splice junction identification from RNA-Sequencing data
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
Ileocecocolic strictures in two captive cheetahs (Acinonyx jubatus jubatus).
Travis, Erika K; Duncan, Mary; Weber, Martha; Adkesson, Michael J; Junge, Randall E
2007-12-01
Intestinal strictures were diagnosed in two captive cheetahs (Acinonyx jubatus jubatus). The cheetahs presented with lethargy, anorexia, diarrhea, and weight loss. The first cheetah had a stricture of the ileocecocolic junction diagnosed at necropsy. The second had an ileocecocolic stricture causing obstruction that was diagnosed at surgery. After resection and anastomosis, the cheetah recovered well. The etiology of the strictures remains undetermined. Intestinal stricture, particularly of the ileocecocolic junction, should be considered as a differential diagnosis for cheetahs with nonspecific gastrointestinal signs.
Leakage current evaluation for pn junctions formed in DC and RF MeV ion implanted wells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yanagisawa, Yasunobu; Honda, Mitsuharu; Ogasawara, Makota
1996-12-31
The leakage current of pn junctions formed in DC and RF MeV implanted wells have been evaluated. There is no substantial difference in the leakage current levels between the continuous and pulsive beam implantations. However, the leakage current, so called diffusion current, for RF implanted wells is slightly higher than that for DC implanted wells on some condition. This suggests a possibility that relatively higher density of residual defects remains in the case of RIF implant.
Baranwal, Somesh
2015-01-01
Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. PMID:25792565
Lechuga, Susana; Baranwal, Somesh; Ivanov, Andrei I
2015-05-01
Adherens junctions (AJs) and tight junctions (TJs) are crucial regulators of the integrity and restitution of the intestinal epithelial barrier. The structure and function of epithelial junctions depend on their association with the cortical actin cytoskeleton that, in polarized epithelial cells, is represented by a prominent perijunctional actomyosin belt. The assembly and stability of the perijunctional cytoskeleton is controlled by constant turnover (disassembly and reassembly) of actin filaments. Actin-interacting protein (Aip) 1 is an emerging regulator of the actin cytoskeleton, playing a critical role in filament disassembly. In this study, we examined the roles of Aip1 in regulating the structure and remodeling of AJs and TJs in human intestinal epithelium. Aip1 was enriched at apical junctions in polarized human intestinal epithelial cells and normal mouse colonic mucosa. Knockdown of Aip1 by RNA interference increased the paracellular permeability of epithelial cell monolayers, decreased recruitment of AJ/TJ proteins to steady-state intercellular contacts, and attenuated junctional reassembly in a calcium-switch model. The observed defects of AJ/TJ structure and functions were accompanied by abnormal organization and dynamics of the perijunctional F-actin cytoskeleton. Moreover, loss of Aip1 impaired the apico-basal polarity of intestinal epithelial cell monolayers and inhibited formation of polarized epithelial cysts in 3-D Matrigel. Our findings demonstrate a previously unanticipated role of Aip1 in regulating the structure and remodeling of intestinal epithelial junctions and early steps of epithelial morphogenesis. Copyright © 2015 the American Physiological Society.
Mapping the dynamics of force transduction at cell–cell junctions of epithelial clusters
Ng, Mei Rosa; Besser, Achim; Brugge, Joan S; Danuser, Gaudenz
2014-01-01
Force transduction at cell-cell adhesions regulates tissue development, maintenance and adaptation. We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters. Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell-cell junctions. At the multi-cellular scale, cell-cell force exchange depended on the cell position within a cluster, and was adaptive to reconfigurations due to cell divisions or positional rearrangements. Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors. These data provide insights into mechanisms that could control mechanical stress homeostasis in dynamic epithelial tissues, and highlight our methods as a resource for the study of mechanotransduction in cell-cell adhesions. DOI: http://dx.doi.org/10.7554/eLife.03282.001 PMID:25479385
NASA Astrophysics Data System (ADS)
Barangi, Mahmood; Mazumder, Pinaki
2015-11-01
A theoretical model quantifying the effect of temperature variations on the magnetic properties and static and dynamic behavior of the straintronics magnetic tunneling junction is presented. Four common magnetostrictive materials (Nickel, Cobalt, Terfenol-D, and Galfenol) are analyzed to determine their temperature sensitivity and to provide a comprehensive database for different applications. The variations of magnetic anisotropies are studied in detail for temperature levels up to the Curie temperature. The energy barrier of the free layer and the critical voltage required for flipping the magnetization vector are inspected as important metrics that dominate the energy requirements and noise immunity when the device is incorporated into large systems. To study the dynamic thermal noise, the effect of the Langevin thermal field on the free layer's magnetization vector is incorporated into the Landau-Lifshitz-Gilbert equation. The switching energy, flipping delay, write, and hold error probabilities are studied, which are important metrics for nonvolatile memories, an important application of the straintronics magnetic tunneling junctions.
Atomically Thin Al2O3 Films for Tunnel Junctions
NASA Astrophysics Data System (ADS)
Wilt, Jamie; Gong, Youpin; Gong, Ming; Su, Feifan; Xu, Huikai; Sakidja, Ridwan; Elliot, Alan; Lu, Rongtao; Zhao, Shiping; Han, Siyuan; Wu, Judy Z.
2017-06-01
Metal-insulator-metal tunnel junctions are common throughout the microelectronics industry. The industry standard AlOx tunnel barrier, formed through oxygen diffusion into an Al wetting layer, is plagued by internal defects and pinholes which prevent the realization of atomically thin barriers demanded for enhanced quantum coherence. In this work, we employ in situ scanning tunneling spectroscopy along with molecular-dynamics simulations to understand and control the growth of atomically thin Al2O3 tunnel barriers using atomic-layer deposition. We find that a carefully tuned initial H2O pulse hydroxylated the Al surface and enabled the creation of an atomically thin Al2O3 tunnel barrier with a high-quality M -I interface and a significantly enhanced barrier height compared to thermal AlOx . These properties, corroborated by fabricated Josephson junctions, show that atomic-layer deposition Al2O3 is a dense, leak-free tunnel barrier with a low defect density which can be a key component for the next generation of metal-insulator-metal tunnel junctions.
Nonadiabatic effect on the quantum heat flux control.
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.
Neto, Filipa; Klaus-Bergmann, Alexandra; Ong, Yu Ting; Alt, Silvanus; Vion, Anne-Clémence; Szymborska, Anna; Carvalho, Joana R; Hollfinger, Irene; Bartels-Klein, Eireen; Franco, Claudio A
2018-01-01
Formation of blood vessel networks by sprouting angiogenesis is critical for tissue growth, homeostasis and regeneration. How endothelial cells arise in adequate numbers and arrange suitably to shape functional vascular networks is poorly understood. Here we show that YAP/TAZ promote stretch-induced proliferation and rearrangements of endothelial cells whilst preventing bleeding in developing vessels. Mechanistically, YAP/TAZ increase the turnover of VE-Cadherin and the formation of junction associated intermediate lamellipodia, promoting both cell migration and barrier function maintenance. This is achieved in part by lowering BMP signalling. Consequently, the loss of YAP/TAZ in the mouse leads to stunted sprouting with local aggregation as well as scarcity of endothelial cells, branching irregularities and junction defects. Forced nuclear activity of TAZ instead drives hypersprouting and vascular hyperplasia. We propose a new model in which YAP/TAZ integrate mechanical signals with BMP signaling to maintain junctional compliance and integrity whilst balancing endothelial cell rearrangements in angiogenic vessels. PMID:29400648
Revenu, Céline; Streichan, Sebastian; Donà, Erika; Lecaudey, Virginie; Hufnagel, Lars; Gilmour, Darren
2014-03-01
The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process.
Characterization of a Novel Water Pocket Inside the Human Cx26 Hemichannel Structure
Araya-Secchi, Raul; Perez-Acle, Tomas; Kang, Seung-gu; Huynh, Tien; Bernardin, Alejandro; Escalona, Yerko; Garate, Jose-Antonio; Martínez, Agustin D.; García, Isaac E.; Sáez, Juan C.; Zhou, Ruhong
2014-01-01
Connexins (Cxs) are a family of vertebrate proteins constituents of gap junction channels (GJCs) that connect the cytoplasm of adjacent cells by the end-to-end docking of two Cx hemichannels. The intercellular transfer through GJCs occurs by passive diffusion allowing the exchange of water, ions, and small molecules. Despite the broad interest to understand, at the molecular level, the functional state of Cx-based channels, there are still many unanswered questions regarding structure-function relationships, perm-selectivity, and gating mechanisms. In particular, the ordering, structure, and dynamics of water inside Cx GJCs and hemichannels remains largely unexplored. In this work, we describe the identification and characterization of a believed novel water pocket—termed the IC pocket—located in-between the four transmembrane helices of each human Cx26 (hCx26) monomer at the intracellular (IC) side. Using molecular dynamics (MD) simulations to characterize hCx26 internal water structure and dynamics, six IC pockets were identified per hemichannel. A detailed characterization of the dynamics and ordering of water including conformational variability of residues forming the IC pockets, together with multiple sequence alignments, allowed us to propose a functional role for this cavity. An in vitro assessment of tracer uptake suggests that the IC pocket residue Arg-143 plays an essential role on the modulation of the hCx26 hemichannel permeability. PMID:25099799
Measurement of Quantum Phase-Slips in Josephson Junction Chains
NASA Astrophysics Data System (ADS)
Guichard, Wiebke
2011-03-01
Quantum phase-slip dynamics in Josephson junction chains could provide the basis for the realization of a new type of topologically protected qubit or for the implementation of a new current standard. I will present measurements of the effect of quantum phase-slips on the ground state of a Josephson junction chain. We can tune in situ the strength of the phase-slips. These phase-slips are the result of fluctuations induced by the finite charging energy of each junction in the chain. Our measurements demonstrate that a Josephson junction chain under phase bias constraint behaves in a collective way. I will also show evidence of coherent phase-slip interference, the so called Aharonov-Casher effect. This phenomenon is the dual of the well known Aharonov-Bohm interference. In collaboration with I.M. Pop, Institut Neel, C.N.R.S. and Universite Joseph Fourier, BP 166, 38042 Grenoble, France; I. Protopopov, L. D. Landau Institute for Theoretical Physics, Kosygin str. 2, Moscow 119334, Russia and Institut fuer Nanotechnologie, Karlsruher Institut fuer Technologie, 76021 Karlsruhe, Germany; and F. Lecocq, Z. Peng, B. Pannetier, O. Buisson, Institut Neel, C.N.R.S. and Universite Joseph Fourier. European STREP MIDAS, ANR QUANTJO.
Quench dynamics of the Josephson current in a topological Josephson junction
NASA Astrophysics Data System (ADS)
Sun, Dihao; Liu, Jie
2018-01-01
The 4 π -periodic Josephson effect is a distinguishing feature of a topological Josephson junction. However, stringent conditions make it hard to observe in experiments. In this work, we study the transient transport properties in a topological Josephson junction numerically. We show that the 4 π Josephson current can be sustained under nonequilibrium conditions. The properties of the Josephson current are analyzed for different conditions and three main regimes are identified. First, when both the superconducting wires of the Josephson junction lie in the topologically nontrivial region, a 4 π Josephson current can appear upon suddenly applying a dc voltage. Second, when one superconducting wire lies in the trivial region, while the other wire lies in the nontrivial region, the Josephson current is 2 π periodic but the component of the higher-order Josephson current increases. Third, when both wires lie in the trivial region, a stable 2 π Josephson current is observed. Most importantly, the fractional Josephson effect is fragile in the presence of disorder. Hence experiments should be designed carefully to eliminate the effect of disorder. These results could be helpful to optimize fine-tuning of the experimental parameters to observe the 4 π -periodic Josephson current in a topological Josephson junction.
Dynamic formation of ER–PM junctions presents a lipid phosphatase to regulate phosphoinositides
Jensen, Jill B.; Vivas, Oscar; Kruse, Martin; Traynor-Kaplan, Alexis E.; Hille, Bertil
2016-01-01
Endoplasmic reticulum–plasma membrane (ER–PM) contact sites play an integral role in cellular processes such as excitation–contraction coupling and store-operated calcium entry (SOCE). Another ER–PM assembly is one tethered by the extended synaptotagmins (E-Syt). We have discovered that at steady state, E-Syt2 positions the ER and Sac1, an integral ER membrane lipid phosphatase, in discrete ER–PM junctions. Here, Sac1 participates in phosphoinositide homeostasis by limiting PM phosphatidylinositol 4-phosphate (PI(4)P), the precursor of PI(4,5)P2. Activation of G protein–coupled receptors that deplete PM PI(4,5)P2 disrupts E-Syt2–mediated ER–PM junctions, reducing Sac1’s access to the PM and permitting PM PI(4)P and PI(4,5)P2 to recover. Conversely, depletion of ER luminal calcium and subsequent activation of SOCE increases the amount of Sac1 in contact with the PM, depleting PM PI(4)P. Thus, the dynamic presence of Sac1 at ER–PM contact sites allows it to act as a cellular sensor and controller of PM phosphoinositides, thereby influencing many PM processes. PMID:27044890
Desrochers, Jane; Duncan, Neil A
2014-01-01
Cells in the intervertebral disc, as in other connective tissues including tendon, ligament and bone, form interconnected cellular networks that are linked via functional gap junctions. These cellular networks may be necessary to affect a coordinated response to mechanical and environmental stimuli. Using confocal microscopy with fluorescence recovery after photobleaching methods, we explored the in situ strain environment of the outer annulus of an intact bovine disc and the effect of high-level flexion on gap junction signalling. The in situ strain environment in the extracellular matrix of the outer annulus under high flexion load was observed to be non-uniform with the extensive cellular processes remaining crimped sometimes at flexion angles greater than 25°. A significant transient disruption of intercellular communication via functional gap junctions was measured after 10 and 20 min under high flexion load. This study illustrates that in healthy annulus fibrosus tissue, high mechanical loads can impede the functioning of the gap junctions. Future studies will explore more complex loading conditions to determine whether losses in intercellular communication can be permanent and whether gap junctions in aged and degenerated tissues become more susceptible to load. The current research suggests that cellular structures such as gap junctions and intercellular networks, as well as other cell-cell and cell-matrix interconnections, need to be considered in computational models in order to fully understand how macroscale mechanical signals are transmitted across scales to the microscale and ultimately into a cellular biosynthetic response in collagenous tissues.
Yi, Chenju; Teillon, Jérémy; Koulakoff, Annette; Berry, Hugues; Giaume, Christian
2018-06-01
Intercellular communication through gap junction channels plays a key role in cellular homeostasis and in synchronizing physiological functions, a feature that is modified in number of pathological situations. In the brain, astrocytes are the cell population that expresses the highest amount of gap junction proteins, named connexins. Several techniques have been used to assess the level of gap junctional communication in astrocytes, but so far they remain very difficult to apply in adult brain tissue. Here, using specific loading of astrocytes with sulforhodamine 101, we adapted the gap-FRAP (Fluorescence Recovery After Photobleaching) to acute hippocampal slices from 9 month-old adult mice. We show that gap junctional communication monitored in astrocytes with this technique was inhibited either by pharmacological treatment with a gap junctional blocker or in mice lacking the two main astroglial connexins, while a partial inhibition was measured when only one connexin was knocked-out. We validate this approach using a mathematical model of sulforhodamine 101 diffusion in an elementary astroglial network and a quantitative analysis of the exponential fits to the fluorescence recovery curves. Consequently, we consider that the adaptation of the gap-FRAP technique to acute brain slices from adult mice provides an easy going and valuable approach that allows overpassing this age-dependent obstacle and will facilitate the investigation of gap junctional communication in adult healthy or pathological brain. Copyright © 2018 Elsevier B.V. All rights reserved.
In situ structure and dynamics of DNA origami determined through molecular dynamics simulations
Yoo, Jejoong; Aksimentiev, Aleksei
2013-01-01
The DNA origami method permits folding of long single-stranded DNA into complex 3D structures with subnanometer precision. Transmission electron microscopy, atomic force microscopy, and recently cryo-EM tomography have been used to characterize the properties of such DNA origami objects, however their microscopic structures and dynamics have remained unknown. Here, we report the results of all-atom molecular dynamics simulations that characterized the structural and mechanical properties of DNA origami objects in unprecedented microscopic detail. When simulated in an aqueous environment, the structures of DNA origami objects depart from their idealized targets as a result of steric, electrostatic, and solvent-mediated forces. Whereas the global structural features of such relaxed conformations conform to the target designs, local deformations are abundant and vary in magnitude along the structures. In contrast to their free-solution conformation, the Holliday junctions in the DNA origami structures adopt a left-handed antiparallel conformation. We find the DNA origami structures undergo considerable temporal fluctuations on both local and global scales. Analysis of such structural fluctuations reveals the local mechanical properties of the DNA origami objects. The lattice type of the structures considerably affects global mechanical properties such as bending rigidity. Our study demonstrates the potential of all-atom molecular dynamics simulations to play a considerable role in future development of the DNA origami field by providing accurate, quantitative assessment of local and global structural and mechanical properties of DNA origami objects. PMID:24277840
In situ structure and dynamics of DNA origami determined through molecular dynamics simulations.
Yoo, Jejoong; Aksimentiev, Aleksei
2013-12-10
The DNA origami method permits folding of long single-stranded DNA into complex 3D structures with subnanometer precision. Transmission electron microscopy, atomic force microscopy, and recently cryo-EM tomography have been used to characterize the properties of such DNA origami objects, however their microscopic structures and dynamics have remained unknown. Here, we report the results of all-atom molecular dynamics simulations that characterized the structural and mechanical properties of DNA origami objects in unprecedented microscopic detail. When simulated in an aqueous environment, the structures of DNA origami objects depart from their idealized targets as a result of steric, electrostatic, and solvent-mediated forces. Whereas the global structural features of such relaxed conformations conform to the target designs, local deformations are abundant and vary in magnitude along the structures. In contrast to their free-solution conformation, the Holliday junctions in the DNA origami structures adopt a left-handed antiparallel conformation. We find the DNA origami structures undergo considerable temporal fluctuations on both local and global scales. Analysis of such structural fluctuations reveals the local mechanical properties of the DNA origami objects. The lattice type of the structures considerably affects global mechanical properties such as bending rigidity. Our study demonstrates the potential of all-atom molecular dynamics simulations to play a considerable role in future development of the DNA origami field by providing accurate, quantitative assessment of local and global structural and mechanical properties of DNA origami objects.
Nomura, Kazuaki; Obata, Kazufumi; Keira, Takashi; Miyata, Ryo; Hirakawa, Satoshi; Takano, Ken-ichi; Kohno, Takayuki; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi
2014-02-18
Pseudomonas aeruginosa causes chronic respiratory disease, and the elastase enzyme that it produces increases the permeability of airway epithelial cells owing to the disruption of tight junctions. P. aeruginosa is also implicated in prolonged chronic rhinosinusitis. However, the effects of P. aeruginosa elastase (PE) against the barrier formed by human nasal epithelial cells (HNECs) remain unknown. To investigate the mechanisms involved in the disruption of tight junctions by PE in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were used. The hTERT-HNECs were pretreated with inhibitors of various signal transduction pathways, PKC, MAPK, p38MAPK, PI3K, JNK, NF-κB, EGF receptor, proteasome, COX1 and COX2 before treatment with PE. Some cells were pretreated with siRNA and agonist of protease activated receptor-2 (PAR-2) before treatment with PE. Expression and structures of tight junctions were determined by Western blotting, real-time PCR, immunostaining and freeze-fracture. Transepithelial electrical resistance (TER) was examined as the epithelial barrier function. PE treatment transiently disrupted the epithelial barrier and downregulated the transmembrane proteins claudin-1 and -4, occludin, and tricellulin, but not the scaffold PDZ-expression proteins ZO-1 and -2 and adherens junction proteins E-cadherin and β-catenin. The transient downregulation of tight junction proteins was controlled via distinct signal transduction pathways such as the PKC, MAPK, PI3K, p38 MAPK, JNK, COX-1 and -2, and NF-κB pathways. Furthermore, treatment with PE transiently decreased PAR-2 expression, which also regulated the expression of the tight junction proteins. Treatment with a PAR-2 agonist prevented the downregulation of the tight junction proteins after PE treatment in HNECs. PE transiently disrupts tight junctions in HNECs and downregulates PAR-2. The transient disruption of tight junctions by PE might occur repeatedly during chronic rhinosinusitis.
2014-01-01
Background Pseudomonas aeruginosa causes chronic respiratory disease, and the elastase enzyme that it produces increases the permeability of airway epithelial cells owing to the disruption of tight junctions. P. aeruginosa is also implicated in prolonged chronic rhinosinusitis. However, the effects of P. aeruginosa elastase (PE) against the barrier formed by human nasal epithelial cells (HNECs) remain unknown. Methods To investigate the mechanisms involved in the disruption of tight junctions by PE in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were used. The hTERT-HNECs were pretreated with inhibitors of various signal transduction pathways, PKC, MAPK, p38MAPK, PI3K, JNK, NF-κB, EGF receptor, proteasome, COX1 and COX2 before treatment with PE. Some cells were pretreated with siRNA and agonist of protease activated receptor-2 (PAR-2) before treatment with PE. Expression and structures of tight junctions were determined by Western blotting, real-time PCR, immunostaining and freeze-fracture. Transepithelial electrical resistance (TER) was examined as the epithelial barrier function. Results PE treatment transiently disrupted the epithelial barrier and downregulated the transmembrane proteins claudin-1 and -4, occludin, and tricellulin, but not the scaffold PDZ-expression proteins ZO-1 and -2 and adherens junction proteins E-cadherin and β-catenin. The transient downregulation of tight junction proteins was controlled via distinct signal transduction pathways such as the PKC, MAPK, PI3K, p38 MAPK, JNK, COX-1 and -2, and NF-κB pathways. Furthermore, treatment with PE transiently decreased PAR-2 expression, which also regulated the expression of the tight junction proteins. Treatment with a PAR-2 agonist prevented the downregulation of the tight junction proteins after PE treatment in HNECs. Conclusions PE transiently disrupts tight junctions in HNECs and downregulates PAR-2. The transient disruption of tight junctions by PE might occur repeatedly during chronic rhinosinusitis. PMID:24548792
Ballistic One-Dimensional InAs Nanowire Cross-Junction Interconnects.
Gooth, Johannes; Borg, Mattias; Schmid, Heinz; Schaller, Vanessa; Wirths, Stephan; Moselund, Kirsten; Luisier, Mathieu; Karg, Siegfried; Riel, Heike
2017-04-12
Coherent interconnection of quantum bits remains an ongoing challenge in quantum information technology. Envisioned hardware to achieve this goal is based on semiconductor nanowire (NW) circuits, comprising individual NW devices that are linked through ballistic interconnects. However, maintaining the sensitive ballistic conduction and confinement conditions across NW intersections is a nontrivial problem. Here, we go beyond the characterization of a single NW device and demonstrate ballistic one-dimensional (1D) quantum transport in InAs NW cross-junctions, monolithically integrated on Si. Characteristic 1D conductance plateaus are resolved in field-effect measurements across up to four NW-junctions in series. The 1D ballistic transport and sub-band splitting is preserved for both crossing-directions. We show that the 1D modes of a single injection terminal can be distributed into multiple NW branches. We believe that NW cross-junctions are well-suited as cross-directional communication links for the reliable transfer of quantum information as required for quantum computational systems.
Van Campenhout, Claude A.; Eitelhuber, Andrea; Gloeckner, Christian J.; Giallonardo, Patrizia; Gegg, Moritz; Oller, Heide; Grant, Seth G.N.; Krappmann, Daniel; Ueffing, Marius; Lickert, Heiko
2011-01-01
Summary The Drosophila Discs large (Dlg) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dlg homologs have been identified; however, their functions in cell polarity remain poorly understood. Here, we demonstrate that the X-linked mental retardation gene product Dlg3 contributes to apical-basal polarity and epithelial junction formation in mouse organizer tissues, as well as to planar cell polarity in the inner ear. We purified complexes associated with Dlg3 in polarized epithelial cells, including proteins regulating directed trafficking and tight junction formation. Remarkably, of the four Dlg family members, Dlg3 exerts a distinct function by recruiting the ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs. We found that these interactions are required for Dlg3 monoubiquitination, apical membrane recruitment, and tight junction consolidation. Our findings reveal an unexpected evolutionary diversification of the vertebrate Dlg family in basolateral epithelium formation. PMID:21920314
Binding configurations and intramolecular strain in single-molecule devices.
Rascón-Ramos, Habid; Artés, Juan Manuel; Li, Yuanhui; Hihath, Joshua
2015-05-01
The development of molecular-scale electronic devices has made considerable progress over the past decade, and single-molecule transistors, diodes and wires have all been demonstrated. Despite this remarkable progress, the agreement between theoretically predicted conductance values and those measured experimentally remains limited. One of the primary reasons for these discrepancies lies in the difficulty to experimentally determine the contact geometry and binding configuration of a single-molecule junction. In this Article, we apply a small-amplitude, high-frequency, sinusoidal mechanical signal to a series of single-molecule devices during junction formation and breakdown. By measuring the current response at this frequency, it is possible to determine the most probable binding and contact configurations for the molecular junction at room temperature in solution, and to obtain information about how an applied strain is distributed within the molecular junction. These results provide insight into the complex configuration of single-molecule devices, and are in excellent agreement with previous predictions from theoretical models.
Tak, Hye-Jin; Park, Tae-Jin; Piao, Zhenngu; Lee, Sang-Hwy
2017-01-01
Syngnathia is a congenital craniofacial disorder characterized by bony or soft tissue fusion of upper and lower jaws. Previous studies suggested some causative signals, such as Foxc1 or Bmp4, cause the disruption of maxillomandibular identity, but their location and the interactive signals involved remain unexplored. We wanted to examine the embryonic origin of syngnathia based on the assumption that it may be located at the separation between the maxillary and mandibular processes. This region, known as the maxillomandibular junction (MMJ), is involved in segregation of cranial neural crest-derived mesenchyme into the presumptive upper and lower jaws. Here we investigated the role of Fgf, Bmp, and retinoid signaling during development of MMJ in chicken embryos. By changing the levels of these signals with bead implants, we induced syngnathia with microstomia on the treated side, which showed increased Barx1 and neural cell adhesion molecule (NCAM) expression. Redistribution of proliferating cells was also observed at the proximal region to maxillary and mandibular arch around MMJ. We propose that interactive molecular signaling by Fgfs, Bmps, and retinoids around MMJ is required for normal separation of the maxilla and mandible, as well as the proper positioning of beak commissure during early facial morphogenesis. Developmental Dynamics 246:28-40, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Examination of a Junction-Box Adhesion Test for Use in Photovoltaic Module Qualification: Preprint
DOE Office of Scientific and Technical Information (OSTI.GOV)
Miller, D. C.; Wohlgemuth, J. H.
2012-08-01
Engineering robust adhesion of the junction-box (j-box) is a hurdle typically encountered by photovoltaic (PV) module manufacturers during product development. 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' IEC qualification test is proposed to verify the basic robustness of its adhesion system. The details of the proposed test will be described, in addition to the preliminary results obtained using representative materials and components. The described discovery experiments examine moisture-cured silicone, foam tape, and hot-melt adhesives used inmore » conjunction with PET or glass module 'substrates.' To be able to interpret the results, a set of material-level characterizations was performed, including thermogravimetric analysis, differential scanning calorimetry, and dynamic mechanical analysis. PV j-boxes were adhered to a substrate, loaded with a prescribed weight, and then placed inside an environmental chamber (at 85C, 85% relative humidity). Some systems did not remain attached through the discovery experiments. Observed failure modes include delamination (at the j-box/adhesive or adhesive/substrate interface) and phase change/creep. The results are discussed in the context of the application requirements, in addition to the plan for the formal experiment supporting the proposed modification to the qualification test.« less
Falk, Matthias M; Baker, Susan M; Gumpert, Anna M; Segretain, Dominique; Buckheit, Robert W
2009-07-01
Double-membrane-spanning gap junction (GJ) channels cluster into two-dimensional arrays, termed plaques, to provide direct cell-to-cell communication. GJ plaques often contain circular, channel-free domains ( approximately 0.05-0.5 mum in diameter) identified >30 y ago and termed nonjunctional membrane (NM) domains. We show, by expressing the GJ protein connexin43 (Cx43) tagged with green fluorescent protein, or the novel photoconvertible fluorescent protein Dendra2, that NM domains appear to be remnants generated by the internalization of small GJ channel clusters that bud over time from central plaque areas. Channel clusters internalized within seconds forming endocytic double-membrane GJ vesicles ( approximately 0.18-0.27 mum in diameter) that were degraded by lysosomal pathways. Surprisingly, NM domains were not repopulated by surrounding channels and instead remained mobile, fused with each other, and were expelled at plaque edges. Quantification of internalized, photoconverted Cx43-Dendra2 vesicles indicated a GJ half-life of 2.6 h that falls within the estimated half-life of 1-5 h reported for GJs. Together with previous publications that revealed continuous accrual of newly synthesized channels along plaque edges and simultaneous removal of channels from plaque centers, our data suggest how the known dynamic channel replenishment of functional GJ plaques can be achieved. Our observations may have implications for the process of endocytic vesicle budding in general.
Bar dynamics and channel junctions in scale-experiments of estuaries
NASA Astrophysics Data System (ADS)
Leuven, J.; Braat, L.; van Dijk, W. M.; Haas, T. D.; Kleinhans, M. G.
2017-12-01
The evolution of channels and bars in estuaries has high socio-economic relevance, with strong implications for navigation, dredging and ecology. However, the spatial and temporal evolution of channels and bars in estuaries is poorly understood. Here, we study feedbacks of bar morphodynamics on widening and narrowing of estuaries. Therefore, we conducted an experiment in a 20 m long and 3 m wide tilting flume (the 'Metronome'), in which we monitored the evolution of a self-formed estuary that developed from an intial straight channel into an irregular planform with multiple channels, braided bars and a meandering ebb channel. At locations where the estuary width is confined, major channel junctions occur, while the zones between the junctions are characterised by high braiding indices, periodically migrating channels and a relatively large estuary width. The junction locations were forced by the in- and outflow locations on the sides of the ebb-tidal delta and at the location where the channel pattern transitions from multiple channels into a single channel. In the middle of the estuary, self-confinement occurred by sedimentation on the sides of the estuary, which caused another major junction. The channel orientation at the junctions steers the morphodynamics of channels and bars immediately landward and seaward, because the orientation of inflow from the ebb-tidal delta and landward river perpetually varies. In natural systems major junction locations are mostly forced by inherited geology or human engineering. However, this study concludes that even without external forcing, the estuary planform will not converge to an ideal shape but will self-confine at major junctions and widens in the adjacent zones, resulting in an irregular planform shape.
Mechanics of flow and sediment transport in delta distributary channels
Nelson, Jonathan M.; Kinzel, Paul J.; Duc Toan, Duong; Shimizu, Yasuyuki; McDonald, Richard R.
2011-01-01
boundary conditions. Over time, the pattern of erosion and deposition in the distributary channels gives rise to variations in the amount of water and sediment routed into them. In the simplest case, this results in channel switching on deltas, but in a more general sense these dynamics produce a rich suite of interesting morphologic change contributing both to the evolution of the channel distributary network and the overall evolution of the delta. As part of a study to develop a better understanding of these processes, we conducted a field study measuring the detailed morphology of the Hong-Luoc junction on the Red River downstream of Hanoi, Vietnam. This junction was selected for such a study because it has a 1,000-year history, modern observations suggest that it is currently switching (changing the proportion of sediment and streamflow provided to each of the distributary channels), and hydrologic configuration of the junction allows for the study of two bifurcations and one confluence in a single junction complex. In this paper, our morphologic observations are used in computational flow models to show how flow and sediment transport changes as a function of total discharge upstream of the junction. This is a key component of understanding how the junction attains stability over a range of flows or how imbalances in the distribution of flow and sediment transport lead to destabilization of the channel bifurcation.
Voltage-induced ferromagnetic resonance in magnetic tunnel junctions.
Zhu, Jian; Katine, J A; Rowlands, Graham E; Chen, Yu-Jin; Duan, Zheng; Alzate, Juan G; Upadhyaya, Pramey; Langer, Juergen; Amiri, Pedram Khalili; Wang, Kang L; Krivorotov, Ilya N
2012-05-11
We demonstrate excitation of ferromagnetic resonance in CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJs) by the combined action of voltage-controlled magnetic anisotropy (VCMA) and spin transfer torque (ST). Our measurements reveal that GHz-frequency VCMA torque and ST in low-resistance MTJs have similar magnitudes, and thus that both torques are equally important for understanding high-frequency voltage-driven magnetization dynamics in MTJs. As an example, we show that VCMA can increase the sensitivity of an MTJ-based microwave signal detector to the sensitivity level of semiconductor Schottky diodes.
Electron transfer dynamics of bistable single-molecule junctions.
Danilov, Andrey V; Kubatkin, Sergey E; Kafanov, Sergey G; Flensberg, Karsten; Bjørnholm, Thomas
2006-10-01
We present transport measurements of single-molecule junctions bridged by a molecule with three benzene rings connected by two double bonds and with thiol end-groups that allow chemical binding to gold electrodes. The I-V curves show switching behavior between two distinct states. By statistical analysis of the switching events, we show that a 300 meV mode mediates the transition between the two states. We propose that breaking and reformation of a S-H bond in the contact zone between molecule and electrode explains the observed bistability.
Suppression of the "Quasiclassical" proximity gap in correlated-metal--superconductor structures.
Nikolić, Branislav K; Freericks, J K; Miller, P
2002-02-18
We study the energy and spatial dependence of the local density of states in a superconductor--correlated-metal--superconductor Josephson junction, where the correlated metal is a non-Fermi liquid (described by the Falicov-Kimball model). Many-body correlations are treated with dynamical mean-field theory, extended to inhomogeneous systems. While quasiclassical theories predict a minigap in the spectrum of a disordered Fermi liquid which is proximity-coupled within a mesoscopic junction, we find that increasing electron correlations destroy any minigap that might be opened in the absence of many-body correlations.
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.
Yamada, Masayoshi; Kushima, Ryoji; Oda, Ichiro; Mojtahed, Kaveh; Nonaka, Satoru; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Matsubara, Akiko; Taniguchi, Hirokazu; Sekine, Shigeki; Saito, Yutaka; Shimoda, Tadakazu
2014-01-01
Although many gastric cancers arise in chronic gastritis, the association between adenocarcinoma of the esophagogastric junction and the status of background gastritis remains unclear. We aim to investigate the histological status of gastritis in the background fundic gland mucosa of adenocarcinoma of the esophagogastric junction. The present study included 121 consecutive patients with superficial adenocarcinoma of the esophagogastric junction obtained by surgical and/or endoscopic resection. We re-evaluated the histogenesis of adenocarcinoma of the esophagogastric junction, including the background fundic gland mucosa using the Updated Sydney System. The prevalence of histologic atrophic gastric mucosa with gastritis (positive gastritis), non-atrophic gastric mucosa without gastritis (negative gastritis) and Barrett's adenocarcinoma was examined. Histologic-positive gastritis was found in 67 (55%) of all patients, in 24 (38%) of 63 Barrett's adenocarcinoma patients and in 43 (74%) of 58 non-Barrett's adenocarcinoma patients (P < 0.01). A higher female ratio in non-Barrett's adenocarcinoma with gastritis patients `and younger age in non-Barrett's adenocarcinoma without gastritis patients were shown. There were no differences in clinicopathological features related to the gastritis status in Barrett's adenocarcinoma patients. Reflux esophagitis was observed in most (81%) of all patients, and 32 (74%) of the non-Barrett's adenocarcinoma with gastritis patients. In the 67 positive gastritis patients, the mean Updated Sydney System scores of glandular atrophy and intestinal metaplasia were 1.45 and 1.10, respectively, and these scores were higher in the non-Barrett's adenocarcinoma patients than in the Barrett's adenocarcinoma patients. This study suggests that about half of the patients with adenocarcinoma of the esophagogastric junction harbor histological gastritis. Adenocarcinoma of the esophagogastric junction is considered to be a heterogeneous entity, including Barrett's esophagus-related, positive gastritis-related, and Barrett's esophagus and gastritis-unrelated adenocarcinoma of the esophagogastric junction.
Chen, Florence; Ohashi, Norifumi; Li, Wensheng; Eckman, Christopher; Nguyen, Justin H.
2010-01-01
Brain edema in acute liver failure (ALF) remains lethal. The role of vasogenic mechanisms of brain edema has not been explored. We previously demonstrated that matrix metalloproteinase-9 (MMP-9) contributes to the pathogenesis of brain edema. Here, we show that MMP-9 mediates disruptions in tight junction proteins in vitro and in brains of mice with ALF. We transfected murine brain endothelial cells with MMP-9 cDNA using pc DNA3.1 (+)/Myc-His A expression vector. Tissue inhibitor of matrix metalloproteinases (TIMP-1) cDNA transfection or GM6001 was used to inhibit MMP-9. ALF was induced in mice with azoxymethane. Endogenous overexpression of MMP-9 in brain endothelial cells resulted in significant degradation of tight junction proteins occludin and claudin-5. The alterations in tight junction proteins correlated with increased permeability to FITC-dextran molecules. The degradation of tight junction proteins and the increased permeability were reversed by TIMP-1 and GM6001. Similar results were found when MMP-9 was exogenously added to brain EC. We also found that tight junction proteins degradation was reversed with GM6001 in brains of mice with ALF. Conclusions Tight junction proteins are significantly perturbed in brains of mice with ALF. These data corroborate the important role of MMP-9 in the vasogenic mechanism of brain edema in ALF. PMID:19821483
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
Entropy Production Within a Pulsed Bose-Einstein Condensate
NASA Astrophysics Data System (ADS)
Heinisch, Christoph; Holthaus, Martin
2016-10-01
We suggest to subject anharmonically trapped Bose-Einstein condensates to sinusoidal forcing with a smooth, slowly changing envelope, and to measure the coherence of the system after such pulses. In a series of measurements with successively increased maximum forcing strength, one then expects an adiabatic return of the condensate to its initial state as long as the pulses remain sufficiently weak. In contrast, once the maximum driving amplitude exceeds a certain critical value there should be a drastic loss of coherence, reflecting significant heating induced by the pulse. This predicted experimental signature is traced to the loss of an effective adiabatic invariant, and to the ensuing breakdown of adiabatic motion of the system's Floquet state when the many-body dynamics become chaotic. Our scenario is illustrated with the help of a two-site model of a forced bosonic Josephson junction, but should also hold for other, experimentally accessible configurations.
Identical phase oscillators with global sinusoidal coupling evolve by Mobius group action.
Marvel, Seth A; Mirollo, Renato E; Strogatz, Steven H
2009-12-01
Systems of N identical phase oscillators with global sinusoidal coupling are known to display low-dimensional dynamics. Although this phenomenon was first observed about 20 years ago, its underlying cause has remained a puzzle. Here we expose the structure working behind the scenes of these systems by proving that the governing equations are generated by the action of the Mobius group, a three-parameter subgroup of fractional linear transformations that map the unit disk to itself. When there are no auxiliary state variables, the group action partitions the N-dimensional state space into three-dimensional invariant manifolds (the group orbits). The N-3 constants of motion associated with this foliation are the N-3 functionally independent cross ratios of the oscillator phases. No further reduction is possible, in general; numerical experiments on models of Josephson junction arrays suggest that the invariant manifolds often contain three-dimensional regions of neutrally stable chaos.
Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas
2015-04-21
Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.
Low-noise current amplifier based on mesoscopic Josephson junction.
Delahaye, J; Hassel, J; Lindell, R; Sillanpää, M; Paalanen, M; Seppä, H; Hakonen, P
2003-02-14
We used the band structure of a mesoscopic Josephson junction to construct low-noise amplifiers. By taking advantage of the quantum dynamics of a Josephson junction, i.e., the interplay of interlevel transitions and the Coulomb blockade of Cooper pairs, we created transistor-like devices, Bloch oscillating transistors, with considerable current gain and high-input impedance. In these transistors, the correlated supercurrent of Cooper pairs is controlled by a small base current made up of single electrons. Our devices reached current and power gains on the order of 30 and 5, respectively. The noise temperature was estimated to be around 1 kelvin, but noise temperatures of less than 0.1 kelvin can be realistically achieved. These devices provide quantum-electronic building blocks that will be useful at low temperatures in low-noise circuit applications with an intermediate impedance level.
Phase dynamics of single long Josephson junction in MgB2 superconductor
NASA Astrophysics Data System (ADS)
Chimouriya, Shanker Pd.; Ghimire, Bal Ram; Kim, Ju H.
2018-05-01
A system of perturbed sine Gordon equations is derived to a superconductor-insulator-superconductor (SIS) long Joseph-son junction as an extension of the Ambegaokar-Baratoff relation, following the long route of path integral formalism. A computer simulation is performed by discretizing the equations using finite difference approximation and applied to the MgB2 superconductor with SiO2 as the junction material. The solution of unperturbed sG equation is taken as the initial profile for the simulation and observed how the perturbation terms play the role to modify it. It is found initial profile deformed as time goes on. The variation of total Josephson current has also been observed. It is found that, the perturbation terms play the role for phase frustration. The phase frustration achieves quicker for high tunneling current.
Pinet-Charvet, Caroline; Geller, Sarah; Desroziers, Elodie; Ottogalli, Monique; Lomet, Didier; Georgelin, Christine; Tillet, Yves; Franceschini, Isabelle; Vaudin, Pascal; Duittoz, Anne
2016-01-01
Episodic release of GnRH is essential for reproductive function. In vitro studies have established that this episodic release is an endogenous property of GnRH neurons and that GnRH secretory pulses are associated with synchronization of GnRH neuron activity. The cellular mechanisms by which GnRH neurons synchronize remain largely unknown. There is no clear evidence of physical coupling of GnRH neurons through gap junctions to explain episodic synchronization. However, coupling of glial cells through gap junctions has been shown to regulate neuron activity in their microenvironment. The present study investigated whether glial cell communication through gap junctions plays a role in GnRH neuron activity and secretion in the mouse. Our findings show that Glial Fibrillary Acidic Protein-expressing glial cells located in the median eminence in close vicinity to GnRH fibers expressed Gja1 encoding connexin-43. To study the impact of glial-gap junction coupling on GnRH neuron activity, an in vitro model of primary cultures from mouse embryo nasal placodes was used. In this model, GnRH neurons possess a glial microenvironment and were able to release GnRH in an episodic manner. Our findings show that in vitro glial cells forming the microenvironment of GnRH neurons expressed connexin-43 and displayed functional gap junctions. Pharmacological blockade of the gap junctions with 50 μM 18-α-glycyrrhetinic acid decreased GnRH secretion by reducing pulse frequency and amplitude, suppressed neuronal synchronization and drastically reduced spontaneous electrical activity, all these effects were reversed upon 18-α-glycyrrhetinic acid washout.
NASA Astrophysics Data System (ADS)
Cronin, V. S.
2012-12-01
First generation ideas of the kinematic stability of triple junctions lead to the common belief that the geometry of ridge-ridge-ridge (RRR) triple junctions remains constant over time under conditions of symmetric spreading. Given constant relative motion between each plate pair -- that is, the pole of plate relative motion is fixed to both plates in each pair during finite motion, as assumed in many accounts of plate kinematics -- there would be no boundary mismatch at the triple junction and no apparent kinematic reason why a microplate might develop there. But if, in a given RRR triple junction, the finite motion of one plate as observed from the other plate is not circular (as is generally the case, given the three-plate problem of plate kinematics), the geometry of the ridges and the triple junction will vary with time (Cronin, 1992, Tectonophys 207, 287-301). To explore the possible consequences of non-circular finite motion between plates at an RRR triple junction, a simple model was coded based on the cycloid finite-motion model (e.g., Cronin, 1987, Geology 15, 1006-1009) using NNR-MORVEL56 velocities for individual plates (Argus et al., 2011, G3 12, doi: 10.1029/2011GC003751). Initial assumptions include a spherical Earth, symmetric spreading, and constant angular velocities during the modeled finite time interval. The assumed-constant angular velocity vectors constitute a reference frame for observing finite plate motion. Typical results are [1] that the triple junction migrates relative to a coordinate system fixed to the angular-velocity vectors, [2] ridge axes rotates relative to each other, and [3] a boundary mismatch develops at the synthetic triple junction that might result in microplate nucleation. In a model simulating the Galapagos triple junction between the Cocos, Nazca and Pacific plates whose initial state did not include the Galapagos microplate, the mismatch gap was as much as ~3.4 km during 3 Myr of model displacement (see figure). The centroid of the synthetic triple junction translates ~81 km toward azimuth ~352° in 3 Myr. Of course, the details will vary as different angular velocity vectors are used; however, modeling indicates that non-circular finite relative motion between adjacent plates generally results in boundary mismatches and rotation of ridge segments relative to each other at RRR triple junctions. Left: synthetic Galapagos triple junction at initial model time, without a microplate. Right: synthetic triple junction after 3 Myr displacement, illustrating the resulting boundary mismatch (gap) and rotated ridge axes.
Rash, J E; Olson, C O; Pouliot, W A; Davidson, K G V; Yasumura, T; Furman, C S; Royer, S; Kamasawa, N; Nagy, J I; Dudek, F E
2007-10-26
Suprachiasmatic nucleus (SCN) neurons generate circadian rhythms, and these neurons normally exhibit loosely-synchronized action potentials. Although electrotonic coupling has long been proposed to mediate this neuronal synchrony, ultrastructural studies have failed to detect gap junctions between SCN neurons. Nevertheless, it has been proposed that neuronal gap junctions exist in the SCN; that they consist of connexin32 or, alternatively, connexin36; and that connexin36 knockout eliminates neuronal coupling between SCN neurons and disrupts circadian rhythms. We used confocal immunofluorescence microscopy and freeze-fracture replica immunogold labeling to examine the distributions of connexin30, connexin32, connexin36, and connexin43 in rat and mouse SCN and used whole-cell recordings to re-assess electrotonic and tracer coupling. Connexin32-immunofluorescent puncta were essentially absent in SCN but connexin36 was relatively abundant. Fifteen neuronal gap junctions were identified ultrastructurally, all of which contained connexin36 but not connexin32, whereas nearby oligodendrocyte gap junctions contained connexin32. In adult SCN, one neuronal gap junction was >600 connexons, whereas 75% were smaller than 50 connexons, which may be below the limit of detectability by fluorescence microscopy and thin-section electron microscopy. Whole-cell recordings in hypothalamic slices revealed tracer coupling with neurobiotin in <5% of SCN neurons, and paired recordings (>40 pairs) did not reveal obvious electrotonic coupling or synchronized action potentials, consistent with few neurons possessing large gap junctions. However, most neurons had partial spikes or spikelets (often <1 mV), which remained after QX-314 [N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide] had blocked sodium-mediated action potentials within the recorded neuron, consistent with spikelet transmission via small gap junctions. Thus, a few "miniature" gap junctions on most SCN neurons appear to mediate weak electrotonic coupling between limited numbers of neuron pairs, thus accounting for frequent detection of partial spikes and hypothetically providing the basis for "loose" electrical or metabolic synchronization of electrical activity commonly observed in SCN neuronal populations during circadian rhythms.
Bruggeman, Leslie A; Martinka, Scott; Simske, Jeffrey S
2007-02-01
Cell junctions in the nephron are highly specialized to perform specific and distinct filtration and reabsorption functions. The mature kidney forms complex cell junctions including slit diaphragms that prevent the passage of serum proteins into the filtrate, and tubule cell junctions that regulate specific paracellular ion reuptake. We have investigated the expression of TM4SF10 (Trans-Membrane tetra(4)-Span Family 10) in mouse kidneys. TM4SF10 is the vertebrate orthologue of Caenorhabditis elegans VAB-9, a tetraspan adherens junction protein in the PMP22/EMP/Claudin family of proteins. We found that TM4SF10 localizes at the basal-most region of podocyte precursors before the capillary loop stage, at some tubule precursors, and at the ureteric bud junction with S-shaped bodies. Overall expression of TM4SF10 peaked at postnatal day 4 and was virtually absent in adult kidneys. The very limited expression of TM4SF10 protein that persisted into adulthood was restricted to a few tubule segments but remained localized to the basal region of lateral membranes. In undifferentiated cultured podocytes, TM4SF10 localized to the perinuclear region and translocated to the cell membrane after Cadherin appearance at cell-cell contacts. TM4SF10 colocalized with ZO1 and p120ctn in undifferentiated confluent podocytes and also colocalized with the tips of actin filaments at cell contacts. Upon differentiation of cultured podocytes, TM4SF10 protein disappeared from cell contacts and expression ceased. These results suggest that TM4SF10 functions during differentiation of podocytes and may participate in the maturation of cell junctions from simple adherens junctions to elaborate slit diaphragms. TM4SF10 may define a new class of Claudin-like proteins that function during junctional development.
NASA Astrophysics Data System (ADS)
Loppini, A.; Pedersen, M. G.; Braun, M.; Filippi, S.
2017-09-01
The importance of gap-junction coupling between β cells in pancreatic islets is well established in mouse. Such ultrastructural connections synchronize cellular activity, confine biological heterogeneity, and enhance insulin pulsatility. Dysfunction of coupling has been associated with diabetes and altered β -cell function. However, the role of gap junctions between human β cells is still largely unexplored. By using patch-clamp recordings of β cells from human donors, we previously estimated electrical properties of these channels by mathematical modeling of pairs of human β cells. In this work we revise our estimate by modeling triplet configurations and larger heterogeneous clusters. We find that a coupling conductance in the range 0.005 -0.020 nS/pF can reproduce experiments in almost all the simulated arrangements. We finally explore the consequence of gap-junction coupling of this magnitude between β cells with mutant variants of the ATP-sensitive potassium channels involved in some metabolic disorders and diabetic conditions, translating studies performed on rodents to the human case. Our results are finally discussed from the perspective of therapeutic strategies. In summary, modeling of more realistic clusters with more than two β cells slightly lowers our previous estimate of gap-junction conductance and gives rise to patterns that more closely resemble experimental traces.
Cervera, Javier; Meseguer, Salvador; Mafe, Salvador
2017-08-17
We have studied theoretically the microRNA (miRNA) intercellular transfer through voltage-gated gap junctions in terms of a biophysically grounded system of coupled differential equations. Instead of modeling a specific system, we use a general approach describing the interplay between the genetic mechanisms and the single-cell electric potentials. The dynamics of the multicellular ensemble are simulated under different conditions including spatially inhomogeneous transcription rates and local intercellular transfer of miRNAs. These processes result in spatiotemporal changes of miRNA, mRNA, and ion channel protein concentrations that eventually modify the bioelectrical states of small multicellular domains because of the ensemble average nature of the electrical potential. The simulations allow a qualitative understanding of the context-dependent nature of the effects observed when specific signaling molecules are transferred through gap junctions. The results suggest that an efficient miRNA intercellular transfer could permit the spatiotemporal control of small cellular domains by the conversion of single-cell genetic and bioelectric states into multicellular states regulated by the gap junction interconnectivity.
SQUID magnetometers for low-frequency applications
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ryhaenen, T.; Seppae, H.; Ilmoniemi, R.
1989-09-01
The authors present a novel formulation for SQUID operation, which enables them to evaluate and compare the sensitivity and applicability of different devices. SQUID magnetometers for low-frequency applications are analyzed, taking into account the coupling circuits and electronics. They discuss nonhysteretic and hysteretic single-junction rf SQUIDs, but the main emphasis is on the dynamics, sensitivity, and coupling considerations of dc-SQUID magnetometers. A short review of current ideas on thin-film, dc-SQUID design presents the problems in coupling and the basic limits of sensitivity. The fabrication technology of tunnel-junction devices is discussed with emphasis on how it limits critical current densities, specificmore » capacitances of junctions, minimum linewidths, conductor separations, etc. Properties of high-temperature superconductors are evaluated on the basis of recently published results on increased flux creep, low density of current carriers, and problems in fabricating reliable junctions. The optimization of electronics for different types of SQUIDs is presented. Finally, the most important low-frequency applications of SQUIDs in biomagnetism, metrology, geomagnetism, and some physics experiments demonstrate the various possibilities that state-of-the-art SQUIDs can provide.« less
Direct determination of minority carrier diffusion lengths at axial GaAs nanowire p-n junctions.
Gutsche, Christoph; Niepelt, Raphael; Gnauck, Martin; Lysov, Andrey; Prost, Werner; Ronning, Carsten; Tegude, Franz-Josef
2012-03-14
Axial GaAs nanowire p-n diodes, possibly one of the core elements of future nanowire solar cells and light emitters, were grown via the Au-assisted vapor-liquid-solid mode, contacted by electron beam lithography, and investigated using electron beam induced current measurements. The minority carrier diffusion lengths and dynamics of both, electrons and holes, were determined directly at the vicinity of the p-n junction. The generated photocurrent shows an exponential decay on both sides of the junction and the extracted diffusion lengths are about 1 order of magnitude lower compared to bulk material due to surface recombination. Moreover, the observed strong diameter-dependence is well in line with the surface-to-volume ratio of semiconductor nanowires. Estimating the surface recombination velocities clearly indicates a nonabrupt p-n junction, which is in essential agreement with the model of delayed dopant incorporation in the Au-assisted vapor-liquid-solid mechanism. Surface passivation using ammonium sulfide effectively reduces the surface recombination and thus leads to higher minority carrier diffusion lengths. © 2012 American Chemical Society
NASA Astrophysics Data System (ADS)
Dassonneville, B.; Murani, A.; Ferrier, M.; Guéron, S.; Bouchiat, H.
2018-05-01
One of the best known causes of dissipation in ac-driven quantum systems stems from photon absorption causing transitions between levels. Dissipation can also be caused by the retarded response to the time-dependent excitation, and in general gives insight into the system's relaxation times and mechanisms. Here we address the dissipation in a mesoscopic normal wire with superconducting contacts, that sustains a dissipationless supercurrent at zero frequency and that may therefore naively be expected to remain dissipationless at a frequency lower than the superconducting gap. We probe the high-frequency linear response of such a normal metal/superconductor (NS) ring to a time-dependent flux by coupling it to a highly sensitive multimode microwave resonator. Far from being the simple, dissipationless derivative of the supercurrent-versus-phase relation, the ring's ac susceptibility also displays a dissipative component whose phase dependence is a signature of the dynamical processes occurring within the Andreev spectrum. We show how dissipation is driven by the competition between two mechanisms. The first is the relaxation of the Andreev level distribution function, while the second corresponds to microwave-induced transitions within the spectrum. Depending on the relative strength of those contributions, dissipation can be maximal at π , a phase at which the proximity-induced minigap closes, or can be maximal near π /2 , a phase at which the dc supercurrent is maximal. We also find that the dissipative response paradoxically increases at low temperature and can even exceed the normal-state conductance. The results are successfully confronted with theoretical predictions of the Kubo linear response and time-dependent Usadel equations, derived from the Bogoliubov-de Gennes Hamiltonian describing the SNS junction. These experiments thus demonstrate the power of the ac susceptibility measurement of individual hybrid mesoscopic systems in probing in a controlled way the quantum dynamics of Andreev bound states. By spanning different physical regimes, our experiments provide unique access to inelastic scattering and spectroscopy of an isolated quantum coherent system, and reveal the associated relaxation times. This technique should be a tool of choice to investigate topological superconductivity and detect the topological protection of edge states.
Vaezi, Alec; Bauer, Christoph; Vasioukhin, Valeri; Fuchs, Elaine
2002-09-01
To enable stratification and barrier function, the epidermis must permit self-renewal while maintaining adhesive connections. By generating K14-GFP-actin mice to monitor actin dynamics in cultured primary keratinocytes, we uncovered a role for the actin cytoskeleton in establishing cellular organization. During epidermal sheet formation, a polarized network of nascent intercellular junctions and radial actin cables assemble in the apical plane of the monolayer. These actin fibers anchor to a central actin-myosin network, creating a tension-based plane of cytoskeleton across the apical surface of the sheet. Movement of the sheet surface relative to its base expands the zone of intercellular overlap, catalyzing new sites for nascent intercellular junctions. This polarized cytoskeleton is dependent upon alpha-catenin, Rho, and Rock, and its regulation may be important for wound healing and/or stratification, where coordinated tissue movements are involved.
Regulation of tight junction permeability with switch-like speed.
Beyenbach, Klaus W
2003-09-01
The case is made that tight junctions can undergo large reversible conductance changes in a matter of seconds and yet preserve their permselectivity. The diuretic peptide leucokinin transforms (renal) Malpighian tubules of the yellow fever mosquito from a moderately tight epithelium to a leaky epithelium by increasing the chloride-conductance of the paracellular shunt pathway. The nine-fold increase in the paracellular chloride-conductance brings about a non-selective stimulation of transepithelial sodium chloride and potassium chloride secretion, as expected from a conductance increase in the pathway taken by the counterion of sodium and potassium. The leucokinin signaling pathway consists in part of a receptor coupled G-protein, phospholipase C, inositol-1,4,5-trisphosphate, and increased intracellular calcium concentration that bring about the increase in the paracellular, tight junction chloride-conductance. As the conductance of the tight junction pathway increases it becomes more selective for the transepithelial passage of chloride. Epithelial cells in Malpighian tubules taper to tight junctions at their lateral edges exposing them directly to apical and serosal solutions. Furthermore, evolutionary pressures to excrete salt and water at high rates without the aid of glomerular filtration have led to powerful mechanisms of tubular secretion, capable of diuresis when the mosquito is challenged with the volume expansion of a blood meal. The tubular diuresis is mediated in part by increasing the paracellular chloride conductance. Thus, anatomical and physiological specializations in Malpighian tubules combine to yield the evidence for the dynamic hormonal regulation of the tight junction pathway.
Heat transport through atomic contacts.
Mosso, Nico; Drechsler, Ute; Menges, Fabian; Nirmalraj, Peter; Karg, Siegfried; Riel, Heike; Gotsmann, Bernd
2017-05-01
Heat transport and dissipation at the nanoscale severely limit the scaling of high-performance electronic devices and circuits. Metallic atomic junctions serve as model systems to probe electrical and thermal transport down to the atomic level as well as quantum effects that occur in one-dimensional (1D) systems. Whereas charge transport in atomic junctions has been studied intensively in the past two decades, heat transport remains poorly characterized because it requires the combination of a high sensitivity to small heat fluxes and the formation of stable atomic contacts. Here we report heat-transfer measurements through atomic junctions and analyse the thermal conductance of single-atom gold contacts at room temperature. Simultaneous measurements of charge and heat transport reveal the proportionality of electrical and thermal conductance, quantized with the respective conductance quanta. This constitutes a verification of the Wiedemann-Franz law at the atomic scale.
Transitional neonatal hydronephrosis: fact or fantasy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Homsy, Y.L.; Williot, P.; Danais, S.
1986-07-01
Hydronephrosis secondary to an anomalous ureteropelvic junction was detected antenatally in more than 60 neonatal renal units Those 21 units that exhibited partial obstruction or dilatation without obstruction were selected for this study. They were assessed and followed by serial diuretic isotope renography (99mtechnetium-diethylenetriaminepentaacetic acid augmented with furosemide) and ultrasonography. Excretory urography was used selectively. Of the 17 renal units that could be assessed 88 per cent demonstrated labile ureteropelvic junctions. Indeed, in 3 to 6 months, when the definitive status seemed to be attained, 41 per cent (7 units) had deteriorated, 12 per cent (2 units) remained stable andmore » 47 per cent (8 units) underwent spontaneous improvement. We recommend a 3 to 6-month observation period for patients with hydronephrosis secondary to ureteropelvic junction anomalies when definite obstruction cannot be confirmed by isotope renography.« less
GSK3- and PRMT-1–dependent modifications of desmoplakin control desmoplakin–cytoskeleton dynamics
Albrecht, Lauren V.; Zhang, Lichao; Shabanowitz, Jeffrey; Purevjav, Enkhsaikhan; Towbin, Jeffrey A.; Hunt, Donald F.
2015-01-01
Intermediate filament (IF) attachment to intercellular junctions is required for skin and heart integrity, but how the strength and dynamics of this attachment are modulated during normal and pathological remodeling is poorly understood. We show that glycogen synthase kinase 3 (GSK3) and protein arginine methyltransferase 1 (PRMT-1) cooperate to orchestrate a series of posttranslational modifications on the IF-anchoring protein desmoplakin (DP) that play an essential role in coordinating cytoskeletal dynamics and cellular adhesion. Front-end electron transfer dissociation mass spectrometry analyses of DP revealed six novel serine phosphorylation sites dependent on GSK3 signaling and four novel arginine methylation sites including R2834, the mutation of which has been associated with arrhythmogenic cardiomyopathy (AC). Inhibition of GSK3 or PRMT-1 or overexpression of the AC-associated mutant R2834H enhanced DP–IF associations and delayed junction assembly. R2834H blocked the GSK3 phosphorylation cascade and reduced DP–GSK3 interactions in cultured keratinocytes and in the hearts of transgenic R2834H DP mice. Interference with this regulatory machinery may contribute to skin and heart diseases. PMID:25733715
Short-time dynamics of molecular junctions after projective measurement
NASA Astrophysics Data System (ADS)
Tang, Gaomin; Xing, Yanxia; Wang, Jian
2017-08-01
In this work, we study the short-time dynamics of a molecular junction described by Anderson-Holstein model using full-counting statistics after projective measurement. The coupling between the central quantum dot (QD) and two leads was turned on at remote past and the system is evolved to steady state at time t =0 , when we perform the projective measurement in one of the lead. Generating function for the charge transfer is expressed as a Fredholm determinant in terms of Keldysh nonequilibrium Green's function in the time domain. It is found that the current is not constant at short times indicating that the measurement does perturb the system. We numerically compare the current behaviors after the projective measurement with those in the transient regime where the subsystems are connected at t =0 . The universal scaling for high-order cumulants is observed for the case with zero QD occupation due to the unidirectional transport at short times. The influences of electron-phonon interaction on short-time dynamics of electric current, shot noise, and differential conductance are analyzed.
Terahertz Josephson spectral analysis and its applications
NASA Astrophysics Data System (ADS)
Snezhko, A. V.; Gundareva, I. I.; Lyatti, M. V.; Volkov, O. Y.; Pavlovskiy, V. V.; Poppe, U.; Divin, Y. Y.
2017-04-01
Principles of Hilbert-transform spectral analysis (HTSA) are presented and advantages of the technique in the terahertz (THz) frequency range are discussed. THz HTSA requires Josephson junctions with high values of characteristic voltages I c R n and dynamics described by a simple resistively shunted junction (RSJ) model. To meet these requirements, [001]- and [100]-tilt YBa2Cu3O7-x bicrystal junctions with deviations from the RSJ model less than 1% have been developed. Demonstrators of Hilbert-transform spectrum analyzers with various cryogenic environments, including integration into Stirling coolers, are described. Spectrum analyzers have been characterized in the spectral range from 50 GHz to 3 THz. Inside a power dynamic range of five orders, an instrumental function of the analyzers has been found to have a Lorentz form around a single frequency of 1.48 THz with a spectral resolution as low as 0.9 GHz. Spectra of THz radiation from optically pumped gas lasers and semiconductor frequency multipliers have been studied with these spectrum analyzers and the regimes of these radiation sources were optimized for a single-frequency operation. Future applications of HTSA will be related with quick and precise spectral characterization of new radiation sources and identification of substances in the THz frequency range.
Modelling wound closure in an epithelial cell sheet using the cellular Potts model.
Noppe, Adrian R; Roberts, Anthony P; Yap, Alpha S; Gomez, Guillermo A; Neufeld, Zoltan
2015-10-01
We use a two-dimensional cellular Potts model to represent the behavior of an epithelial cell layer and describe its dynamics in response to a microscopic wound. Using an energy function to describe properties of the cells, we found that the interaction between contractile tension along cell-cell junctions and cell-cell adhesion plays an important role not only in determining the dynamics and morphology of cells in the monolayer, but also in influencing whether or not a wound in the monolayer will close. Our results suggest that, depending on the balance between cell-cell adhesion and junctional tension, mechanics of the monolayer can either correspond to a hard or a soft regime that determines cell morphology and polygonal organization in the monolayer. Moreover, the presence of a wound in a hard regime, where junctional tension is significant, can lead to two results: (1) wound closure or (2) an initial increase and expansion of the wound area towards an equilibrium value. Theoretical approximations and simulations allowed us to determine the thresholds in the values of cell-cell adhesion and initial wound size that allow the system to lead to wound closure. Overall, our results suggest that around the site of injury, changes in the balance between contraction and adhesion determine whether or not non-monotonous wound closure occurs.
Ultralow power artificial synapses using nanotextured magnetic Josephson junctions.
Schneider, Michael L; Donnelly, Christine A; Russek, Stephen E; Baek, Burm; Pufall, Matthew R; Hopkins, Peter F; Dresselhaus, Paul D; Benz, Samuel P; Rippard, William H
2018-01-01
Neuromorphic computing promises to markedly improve the efficiency of certain computational tasks, such as perception and decision-making. Although software and specialized hardware implementations of neural networks have made tremendous accomplishments, both implementations are still many orders of magnitude less energy efficient than the human brain. We demonstrate a new form of artificial synapse based on dynamically reconfigurable superconducting Josephson junctions with magnetic nanoclusters in the barrier. The spiking energy per pulse varies with the magnetic configuration, but in our demonstration devices, the spiking energy is always less than 1 aJ. This compares very favorably with the roughly 10 fJ per synaptic event in the human brain. Each artificial synapse is composed of a Si barrier containing Mn nanoclusters with superconducting Nb electrodes. The critical current of each synapse junction, which is analogous to the synaptic weight, can be tuned using input voltage spikes that change the spin alignment of Mn nanoclusters. We demonstrate synaptic weight training with electrical pulses as small as 3 aJ. Further, the Josephson plasma frequencies of the devices, which determine the dynamical time scales, all exceed 100 GHz. These new artificial synapses provide a significant step toward a neuromorphic platform that is faster, more energy-efficient, and thus can attain far greater complexity than has been demonstrated with other technologies.
Ultralow power artificial synapses using nanotextured magnetic Josephson junctions
Schneider, Michael L.; Donnelly, Christine A.; Russek, Stephen E.; Baek, Burm; Pufall, Matthew R.; Hopkins, Peter F.; Dresselhaus, Paul D.; Benz, Samuel P.; Rippard, William H.
2018-01-01
Neuromorphic computing promises to markedly improve the efficiency of certain computational tasks, such as perception and decision-making. Although software and specialized hardware implementations of neural networks have made tremendous accomplishments, both implementations are still many orders of magnitude less energy efficient than the human brain. We demonstrate a new form of artificial synapse based on dynamically reconfigurable superconducting Josephson junctions with magnetic nanoclusters in the barrier. The spiking energy per pulse varies with the magnetic configuration, but in our demonstration devices, the spiking energy is always less than 1 aJ. This compares very favorably with the roughly 10 fJ per synaptic event in the human brain. Each artificial synapse is composed of a Si barrier containing Mn nanoclusters with superconducting Nb electrodes. The critical current of each synapse junction, which is analogous to the synaptic weight, can be tuned using input voltage spikes that change the spin alignment of Mn nanoclusters. We demonstrate synaptic weight training with electrical pulses as small as 3 aJ. Further, the Josephson plasma frequencies of the devices, which determine the dynamical time scales, all exceed 100 GHz. These new artificial synapses provide a significant step toward a neuromorphic platform that is faster, more energy-efficient, and thus can attain far greater complexity than has been demonstrated with other technologies. PMID:29387787
Junctional complexes in the inner cyst tissue of the cysticercoid of Hymenolepis diminuta (Cestoda).
Richards, K S; Arme, C
1983-10-01
The inner cyst tissue development is anteriad and centripetal. The cells produce lamellar extensions which assume parallel alignment. The first contact points (approximately 4 days post-infection) establish heptalaminar (gap) junctions. Lamellar attenuation results in a decreased intercellular space, and at 5-6 days pentalaminar junctions (with fused outer plasmalemma leaflets to give an electron-dense, approximately 3 nm wide O-O line) occur. This is the first maturation (M1) stage. The O-O lines are permeable to lanthanum, and evidence of their possible transformation from heptalaminar junctions is presented. Continued lamellar attenuation, associated with scolex retraction and subsequent growth, results in cytoplasmic occlusion and contact between the inner leaflets of the same lamella. The resultant electron-dense I-I line is approximately 3 nm wide; the O-O line is now less electron-dense and thinner (approximately 2 nm). This final maturation (M2) stage, resembling vertebrate myelin, occurs over limited areas; closely adjacent regions either remaining at the M1 stage, or not displaying junctional complexes. Since in vivo and in vitro excystment can occur before the M2 stage, the inner cyst tissue is not considered to be protective against the definitive host. That the tissue may function in limiting nutrient flow, thus regulating the size of the presumptive adult, is discussed.
Mechanical Control of Myotendinous Junction Formation and Tendon Differentiation during Development.
Valdivia, Mauricio; Vega-Macaya, Franco; Olguín, Patricio
2017-01-01
The development of the musculoskeletal system is a great model to study the interplay between chemical and mechanical inter-tissue signaling in cell adhesion, tissue morphogenesis and differentiation. In both vertebrates and invertebrates (e.g., Drosophila melanogaster ) the formation of muscle-tendon interaction generates mechanical forces which are required for myotendinous junction maturation and tissue differentiation. In addition, these forces must be withstood by muscles and tendons in order to prevent detachment from each other, deformation or even losing their integrity. Extracellular matrix remodeling at the myotendinous junction is key to resist mechanical load generated by muscle contraction. Recent evidences in vertebrates indicate that mechanical forces generated during junction formation regulate chemical signaling leading to extracellular matrix remodeling, however, the mechanotransduction mechanisms associated to this response remains elusive. In addition to extracellular matrix remodeling, the ability of Drosophila tendon-cells to bear mechanical load depends on rearrangement of tendon cell cytoskeleton, thus studying the molecular mechanisms involved in this process is critical to understand the contribution of mechanical forces to the development of the musculoskeletal system. Here, we review recent findings regarding the role of chemical and mechanical signaling in myotendinous junction formation and tendon differentiation, and discuss molecular mechanisms of mechanotransduction that may allow tendon cells to withstand mechanical load during development of the musculoskeletal system.
Generation of constant-amplitude radio-frequency sweeps at a tunnel junction for spin resonance STM
DOE Office of Scientific and Technical Information (OSTI.GOV)
Paul, William; Lutz, Christopher P.; Heinrich, Andreas J.
2016-07-15
We describe the measurement and successful compensation of the radio-frequency transfer function of a scanning tunneling microscope over a wide frequency range (15.5–35.5 GHz) and with high dynamic range (>50 dB). The precise compensation of cabling resonances and attenuations is critical for the production of constant-voltage frequency sweeps for electric-field driven electron spin resonance (ESR) experiments. We also demonstrate that a well-calibrated tunnel junction voltage is necessary to avoid spurious ESR peaks that can arise due to a non-flat transfer function.
A p-i-n junction diode based on locally doped carbon nanotube network
Liu, Xiaodong; Chen, Changxin; Wei, Liangming; Hu, Nantao; Song, Chuanjuan; Liao, Chenghao; He, Rong; Dong, Xusheng; Wang, Ying; Liu, Qinran; Zhang, Yafei
2016-01-01
A p-i-n junction diode constructed by the locally doped network of single-walled carbon nanotubes (SWNTs) was investigated. In this diode, the two opposite ends of the SWNT-network channel were selectively doped by triethyloxonium hexachloroantimonate (OA) and polyethylenimine (PEI) to obtain the air-stable p- and n-type SWNTs respectively while the central area of the SWNT-network remained intrinsic state, resulting in the formation of a p-i-n junction with a strong built-in electronic field in the SWNTs. The results showed that the forward current and the rectification ratio of the diode increased as the doping degree increased. The forward current of the device could also be increased by decreasing the channel length. A high-performance p-i-n junction diode with a high rectification ratio (~104), large forward current (~12.2 μA) and low reverse saturated current (~1.8 nA) was achieved with the OA and PEI doping time of 5 h and 18 h for a channel length of ~6 μm. PMID:26996610
A p-i-n junction diode based on locally doped carbon nanotube network.
Liu, Xiaodong; Chen, Changxin; Wei, Liangming; Hu, Nantao; Song, Chuanjuan; Liao, Chenghao; He, Rong; Dong, Xusheng; Wang, Ying; Liu, Qinran; Zhang, Yafei
2016-03-21
A p-i-n junction diode constructed by the locally doped network of single-walled carbon nanotubes (SWNTs) was investigated. In this diode, the two opposite ends of the SWNT-network channel were selectively doped by triethyloxonium hexachloroantimonate (OA) and polyethylenimine (PEI) to obtain the air-stable p- and n-type SWNTs respectively while the central area of the SWNT-network remained intrinsic state, resulting in the formation of a p-i-n junction with a strong built-in electronic field in the SWNTs. The results showed that the forward current and the rectification ratio of the diode increased as the doping degree increased. The forward current of the device could also be increased by decreasing the channel length. A high-performance p-i-n junction diode with a high rectification ratio (~10(4)), large forward current (~12.2 μA) and low reverse saturated current (~1.8 nA) was achieved with the OA and PEI doping time of 5 h and 18 h for a channel length of ~6 μm.
Yang, Tiefeng; Zheng, Biyuan; Wang, Zhen; Xu, Tao; Pan, Chen; Zou, Juan; Zhang, Xuehong; Qi, Zhaoyang; Liu, Hongjun; Feng, Yexin; Hu, Weida; Miao, Feng; Sun, Litao; Duan, Xiangfeng; Pan, Anlian
2017-12-04
High-quality two-dimensional atomic layered p-n heterostructures are essential for high-performance integrated optoelectronics. The studies to date have been largely limited to exfoliated and restacked flakes, and the controlled growth of such heterostructures remains a significant challenge. Here we report the direct van der Waals epitaxial growth of large-scale WSe 2 /SnS 2 vertical bilayer p-n junctions on SiO 2 /Si substrates, with the lateral sizes reaching up to millimeter scale. Multi-electrode field-effect transistors have been integrated on a single heterostructure bilayer. Electrical transport measurements indicate that the field-effect transistors of the junction show an ultra-low off-state leakage current of 10 -14 A and a highest on-off ratio of up to 10 7 . Optoelectronic characterizations show prominent photoresponse, with a fast response time of 500 μs, faster than all the directly grown vertical 2D heterostructures. The direct growth of high-quality van der Waals junctions marks an important step toward high-performance integrated optoelectronic devices and systems.
Ibebunjo, Chikwendu; Chick, Joel M.; Kendall, Tracee; Eash, John K.; Li, Christine; Zhang, Yunyu; Vickers, Chad; Wu, Zhidan; Clarke, Brian A.; Shi, Jun; Cruz, Joseph; Fournier, Brigitte; Brachat, Sophie; Gutzwiller, Sabine; Ma, QiCheng; Markovits, Judit; Broome, Michelle; Steinkrauss, Michelle; Skuba, Elizabeth; Galarneau, Jean-Rene; Gygi, Steven P.
2013-01-01
Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia and might contribute to its pathogenesis, we determined global gene expression profiles in muscles of rats aged 6, 12, 18, 21, 24, and 27 months. These rats exhibit sarcopenia beginning at 21 months. Correlation of the gene expression versus muscle mass or age changes, and functional annotation analysis identified gene signatures of sarcopenia distinct from gene signatures of aging. Specifically, mitochondrial energy metabolism (e.g., tricarboxylic acid cycle and oxidative phosphorylation) pathway genes were the most downregulated and most significantly correlated with sarcopenia. Also, perturbed were genes/pathways associated with neuromuscular junction patency (providing molecular evidence of sarcopenia-related functional denervation and neuromuscular junction remodeling), protein degradation, and inflammation. Proteomic analysis of samples at 6, 18, and 27 months confirmed the depletion of mitochondrial energy metabolism proteins and neuromuscular junction proteins. Together, these findings suggest that therapeutic approaches that simultaneously stimulate mitochondrogenesis and reduce muscle proteolysis and inflammation have potential for treating sarcopenia. PMID:23109432
Site-Selection in Single-Molecule Junction for Highly Reproducible Molecular Electronics.
Kaneko, Satoshi; Murai, Daigo; Marqués-González, Santiago; Nakamura, Hisao; Komoto, Yuki; Fujii, Shintaro; Nishino, Tomoaki; Ikeda, Katsuyoshi; Tsukagoshi, Kazuhito; Kiguchi, Manabu
2016-02-03
Adsorption sites of molecules critically determine the electric/photonic properties and the stability of heterogeneous molecule-metal interfaces. Then, selectivity of adsorption site is essential for development of the fields including organic electronics, catalysis, and biology. However, due to current technical limitations, site-selectivity, i.e., precise determination of the molecular adsorption site, remains a major challenge because of difficulty in precise selection of meaningful one among the sites. We have succeeded the single site-selection at a single-molecule junction by performing newly developed hybrid technique: simultaneous characterization of surface enhanced Raman scattering (SERS) and current-voltage (I-V) measurements. The I-V response of 1,4-benzenedithiol junctions reveals the existence of three metastable states arising from different adsorption sites. Notably, correlated SERS measurements show selectivity toward one of the adsorption sites: "bridge sites". This site-selectivity represents an essential step toward the reliable integration of individual molecules on metallic surfaces. Furthermore, the hybrid spectro-electric technique reveals the dependence of the SERS intensity on the strength of the molecule-metal interaction, showing the interdependence between the optical and electronic properties in single-molecule junctions.
Zhang, Yanxi; Ye, Gang; Soni, Saurabh; Qiu, Xinkai; Krijger, Theodorus L.; Jonkman, Harry T.; Carlotti, Marco; Sauter, Eric; Zharnikov, Michael
2018-01-01
Quantum interference effects (QI) are of interest in nano-scale devices based on molecular tunneling junctions because they can affect conductance exponentially through minor structural changes. However, their utilization requires the prediction and deterministic control over the position and magnitude of QI features, which remains a significant challenge. In this context, we designed and synthesized three benzodithiophenes based molecular wires; one linearly-conjugated, one cross-conjugated and one cross-conjugated quinone. Using eutectic Ga–In (EGaIn) and CP-AFM, we compared them to a well-known anthraquinone in molecular junctions comprising self-assembled monolayers (SAMs). By combining density functional theory and transition voltage spectroscopy, we show that the presence of an interference feature and its position can be controlled independently by manipulating bond topology and electronegativity. This is the first study to separate these two parameters experimentally, demonstrating that the conductance of a tunneling junction depends on the position and depth of a QI feature, both of which can be controlled synthetically. PMID:29896382
A p-i-n junction diode based on locally doped carbon nanotube network
NASA Astrophysics Data System (ADS)
Liu, Xiaodong; Chen, Changxin; Wei, Liangming; Hu, Nantao; Song, Chuanjuan; Liao, Chenghao; He, Rong; Dong, Xusheng; Wang, Ying; Liu, Qinran; Zhang, Yafei
2016-03-01
A p-i-n junction diode constructed by the locally doped network of single-walled carbon nanotubes (SWNTs) was investigated. In this diode, the two opposite ends of the SWNT-network channel were selectively doped by triethyloxonium hexachloroantimonate (OA) and polyethylenimine (PEI) to obtain the air-stable p- and n-type SWNTs respectively while the central area of the SWNT-network remained intrinsic state, resulting in the formation of a p-i-n junction with a strong built-in electronic field in the SWNTs. The results showed that the forward current and the rectification ratio of the diode increased as the doping degree increased. The forward current of the device could also be increased by decreasing the channel length. A high-performance p-i-n junction diode with a high rectification ratio (~104), large forward current (~12.2 μA) and low reverse saturated current (~1.8 nA) was achieved with the OA and PEI doping time of 5 h and 18 h for a channel length of ~6 μm.
Smucker, Joseph D; Sasso, Rick C
2006-05-15
Independent computer-based literature review of articles pertaining to instrumentation and fusion of junctional injuries of the cervical spine. To review and discuss the evolution of instrumentation techniques and systems used in the treatment of cervical spine junctional injuries. Instrumentation of junctional injuries of the cervical spine has been limited historically by failure to achieve rigid internal fixation in multiple planes. The evolution of these techniques has required increased insight into the morphology and unique biomechanics of the structures to be instrumented. Computer-based literature search of Ovid and PubMed databases. Extensive literature search yielded insights into the evolution of systems initially based on onlay bone graft combined with wiring techniques. Such techniques have come to include systems incorporating rigid, longitudinal struts that accommodate multiplanar screws placed in the lateral masses, pedicles, transarticular regions, and occipital bone. Despite a rapid evolution of techniques and instrumentation technologies, it remains incumbent on the physician to provide the patient with a surgical procedure that balances the likelihood of a favorable outcome with the risk inherent in the implementation of the procedure.
Path selection rules for droplet trains in single-lane microfluidic networks
NASA Astrophysics Data System (ADS)
Amon, A.; Schmit, A.; Salkin, L.; Courbin, L.; Panizza, P.
2013-07-01
We investigate the transport of periodic trains of droplets through microfluidic networks having one inlet, one outlet, and nodes consisting of T junctions. Variations of the dilution of the trains, i.e., the distance between drops, reveal the existence of various hydrodynamic regimes characterized by the number of preferential paths taken by the drops. As the dilution increases, this number continuously decreases until only one path remains explored. Building on a continuous approach used to treat droplet traffic through a single asymmetric loop, we determine selection rules for the paths taken by the drops and we predict the variations of the fraction of droplets taking these paths with the parameters at play including the dilution. Our results show that as dilution decreases, the paths are selected according to the ascending order of their hydrodynamic resistance in the absence of droplets. The dynamics of these systems controlled by time-delayed feedback is complex: We observe a succession of periodic regimes separated by a wealth of bifurcations as the dilution is varied. In contrast to droplet traffic in single asymmetric loops, the dynamical behavior in networks of loops is sensitive to initial conditions because of extra degrees of freedom.
Taylor, Dane; Skardal, Per Sebastian; Sun, Jie
2016-01-01
Synchronization is central to many complex systems in engineering physics (e.g., the power-grid, Josephson junction circuits, and electro-chemical oscillators) and biology (e.g., neuronal, circadian, and cardiac rhythms). Despite these widespread applications—for which proper functionality depends sensitively on the extent of synchronization—there remains a lack of understanding for how systems can best evolve and adapt to enhance or inhibit synchronization. We study how network modifications affect the synchronization properties of network-coupled dynamical systems that have heterogeneous node dynamics (e.g., phase oscillators with non-identical frequencies), which is often the case for real-world systems. Our approach relies on a synchrony alignment function (SAF) that quantifies the interplay between heterogeneity of the network and of the oscillators and provides an objective measure for a system’s ability to synchronize. We conduct a spectral perturbation analysis of the SAF for structural network modifications including the addition and removal of edges, which subsequently ranks the edges according to their importance to synchronization. Based on this analysis, we develop gradient-descent algorithms to efficiently solve optimization problems that aim to maximize phase synchronization via network modifications. We support these and other results with numerical experiments. PMID:27872501
Markovian Dynamics of Josephson Parametric Amplification
NASA Astrophysics Data System (ADS)
Kaiser, Waldemar; Haider, Michael; Russer, Johannes A.; Russer, Peter; Jirauschek, Christian
2017-09-01
In this work, we derive the dynamics of the lossy DC pumped non-degenerate Josephson parametric amplifier (DCPJPA). The main element in a DCPJPA is the superconducting Josephson junction. The DC bias generates the AC Josephson current varying the nonlinear inductance of the junction. By this way the Josephson junction acts as the pump oscillator as well as the time varying reactance of the parametric amplifier. In quantum-limited amplification, losses and noise have an increased impact on the characteristics of an amplifier. We outline the classical model of the lossy DCPJPA and derive the available noise power spectral densities. A classical treatment is not capable of including properties like spontaneous emission which is mandatory in case of amplification at the quantum limit. Thus, we derive a quantum mechanical model of the lossy DCPJPA. Thermal losses are modeled by the quantum Langevin approach, by coupling the quantized system to a photon heat bath in thermodynamic equilibrium. The mode occupation in the bath follows the Bose-Einstein statistics. Based on the second quantization formalism, we derive the Heisenberg equations of motion of both resonator modes. We assume the dynamics of the system to follow the Markovian approximation, i.e. the system only depends on its actual state and is memory-free. We explicitly compute the time evolution of the contributions to the signal mode energy and give numeric examples based on different damping and coupling constants. Our analytic results show, that this model is capable of including thermal noise into the description of the DC pumped non-degenerate Josephson parametric amplifier.
Method for producing a thin sample band in a microchannel device
Griffiths, Stewart K [Livermore, CA; Nilson, Robert H [Cardiff, CA
2004-08-03
The present invention improves the performance of microchannel systems for chemical and biological synthesis and analysis by providing a method and apparatus for producing a thin band of a species sample. Thin sample bands improve the resolution of microchannel separation processes, as well as many other processes requiring precise control of sample size and volume. The new method comprises a series of steps in which a species sample is manipulated by controlled transport through a junction formed at the intersection of four or more channels. A sample is first inserted into the end of one of these channels in the vicinity of the junction. Next, this sample is thinned by transport across the junction one or more times. During these thinning steps, flow enters the junction through one of the channels and exists through those remaining, providing a divergent flow field that progressively stretches and thins the band with each traverse of the junction. The thickness of the resulting sample band may be smaller than the channel width. Moreover, the thickness of the band may be varied and controlled by altering the method alone, without modification to the channel or junction geometries. The invention is applicable to both electroosmotic and electrophoretic transport, to combined electrokinetic transport, and to some special cases in which bulk fluid transport is driven by pressure gradients. It is further applicable to channels that are open, filled with a gel or filled with a porous or granular material.
Apparatus for producing a thin sample band in a microchannel system
Griffiths, Stewart K [Livermore, CA; Nilson, Robert H [Cardiff, CA
2008-05-13
The present invention improves the performance of microchannel systems for chemical and biological synthesis and analysis by providing a method and apparatus for producing a thin band of a species sample. Thin sample bands improve the resolution of microchannel separation processes, as well as many other processes requiring precise control of sample size and volume. The new method comprises a series of steps in which a species sample is manipulated by controlled transport through a junction formed at the intersection of four or more channels. A sample is first inserted into the end of one of these channels in the vicinity of the junction. Next, this sample is thinned by transport across the junction one or more times. During these thinning steps, flow enters the junction through one of the channels and exists through those remaining, providing a divergent flow field that progressively stretches and thins the band with each traverse of the junction. The thickness of the resulting sample band may be smaller than the channel width. Moreover, the thickness of the band may be varied and controlled by altering the method alone, without modification to the channel or junction geometries. The invention is applicable to both electroosmotic and electrophoretic transport, to combined electrokinetic transport, and to some special cases in which bulk fluid transport is driven by pressure gradients. It is further applicable to channels that are open, filled with a gel or filled with a porous or granular material.
The inverse hall-petch relation in nanocrystalline metals: A discrete dislocation dynamics analysis
NASA Astrophysics Data System (ADS)
Quek, Siu Sin; Chooi, Zheng Hoe; Wu, Zhaoxuan; Zhang, Yong Wei; Srolovitz, David J.
2016-03-01
When the grain size in polycrystalline materials is reduced to the nanometer length scale (nanocrystallinity), observations from experiments and atomistic simulations suggest that the yield strength decreases (softening) as the grain size is decreased. This is in contrast to the Hall-Petch relation observed in larger sized grains. We incorporated grain boundary (GB) sliding and dislocation emission from GB junctions into the classical DDD framework, and recovered the smaller is weaker relationship observed in nanocrystalline materials. This current model shows that the inverse Hall-Petch behavior can be obtained through a relief of stress buildup at GB junctions from GB sliding by emitting dislocations from the junctions. The yield stress is shown to vary with grain size, d, by a d 1 / 2 relationship when grain sizes are very small. However, pure GB sliding alone without further plastic accomodation by dislocation emission is grain size independent.
Modeling Bloch oscillations in nanoscale Josephson junctions.
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
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
DOE Office of Scientific and Technical Information (OSTI.GOV)
Guo, P.; Yu, G. Q.; Wei, H. X.
Electron-beam evaporated MgO-based magnetic tunnel junctions have been fabricated with the CoFeB free layer deposited at Ar pressure from 1 to 4 mTorr, and their tunneling process has been studied as a function of temperature and bias voltage. By changing the growth pressure, the junction dynamic conductance dI/dV, inelastic electron tunneling spectrum d²I/dV², and tunneling magnetoresistance vary with temperature. Moreover, the low-energy magnon cutoff energy E {sub C} derived from the conductance versus temperature curve agrees with interface magnon energy obtained directly from the inelastic electron tunneling spectrum, which demonstrates that interface magnons are involved in the electron tunneling process,more » opening an additional conductance channel and thus enhancing the total conductance.« less
Non-linear wave phenomena in Josephson elements for superconducting electronics
NASA Astrophysics Data System (ADS)
Christiansen, P. L.; Parmentier, R. D.; Skovgaard, O.
1985-07-01
The long and intermediate length Josephson tunnel junction oscillator with overlap geometry of linear and circular configuration, is investigated by computational solution of the perturbed sine-Gordon equation model and by experimental measurements. The model predicts the experimental results very well. Line oscillators as well as ring oscillators are treated. For long junctions soliton perturbation methods are developed and turn out to be efficient prediction tools, also providing physical understanding of the dynamics of the oscillator. For intermediate length junctions expansions in terms of linear cavity modes reduce computational costs. The narrow linewidth of the electromagnetic radiation (typically 1 kHz of a line at 10 GHz) is demonstrated experimentally. Corresponding computer simulations requiring a relative accuracy of less than 10 to the -7th power are performed on supercomputer CRAY-1-S. The broadening of linewidth due to external microradiation and internal thermal noise is determined.
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.
Suhovskih, Anastasia V; Kashuba, Vladimir I; Klein, George; Grigorieva, Elvira V
2017-01-02
Microenvironment and stromal fibroblasts are able to inhibit tumor cell proliferation both through secreted signaling molecules and direct cell-cell interactions but molecular mechanisms of these effects remain unclear. In this study, we investigated a role of cell-cell contact-related molecules (protein ECM components, proteoglycans (PGs) and junction-related molecules) in intercellular communications between the human TERT immortalized fibroblasts (BjTERT fibroblasts) and normal (PNT2) or cancer (LNCaP, PC3, DU145) prostate epithelial cells. It was shown that BjTERT-PNT2 cell coculture resulted in significant decrease of both BjTERT and PNT2 proliferation rates and reorganization of transcriptional activity of cell-cell contact-related genes in both cell types. Immunocytochemical staining revealed redistribution of DCN and LUM in PNT2 cells and significant increase of SDC1 at the intercellular contact zones between BjTERT and PNT2 cells, suggesting active involvement of the PGs in cell-cell contacts and contact inhibition of cell proliferation. Unlike to PNT2 cells, PC3 cells did not respond to BjTERT in terms of PGs expression, moderately increased transcriptional activity of junctions-related genes (especially tight junction) and failed to establish PC3-BjTERT contacts. At the same time, PC3 cells significantly down-regulated junctions-related genes (especially focal adhesions and adherens junctions) in BjTERT fibroblasts resulting in visible preference for homotypic PC3-PC3 over heterotypic PC3-BjTERT contacts and autonomous growth of PC3 clones. Taken together, the results demonstrate that an instructing role of fibroblasts to normal prostate epithelial cells is revoked by cancer cells through deregulation of proteoglycans and junction molecules expression and overall disorganization of fibroblast-cancer cell communication.
Demonstration of the Potential of Magnetic Tunnel Junctions for a Universal RAM Technology
NASA Astrophysics Data System (ADS)
Gallagher, William J.
2000-03-01
Over the past four years, tunnel junctions with magnetic electrodes have emerged as promising devices for future magnetoresistive sensing and for information storage. This talk will review advances in these devices, focusing particularly on the use of magnetic tunnel junctions for magnetic random access memory (MRAM). Exchange-biased versions of magnetic tunnel junctions (MTJs) in particular will be shown to have useful properties for forming magnetic memory storage elements in a novel cross-point architecture. Exchange-biased MTJ elements have been made with areas as small as 0.1 square microns and have shown magnetoresistance values exceeding 40 The potential of exchange-biased MTJs for MRAM has been most seriously explored in a demonstration experiment involving the integration of 0.25 micron CMOS technology with a special magnetic tunnel junction "back end." The magnetic back end is based upon multi-layer magnetic tunnel junction growth technology which was developed using research-scale equipment and one-inch size substrates. For the demonstration, the CMOS wafers processed through two metal layers were cut into one-inch squares for depositions of bottom-pinned exchange-biased magnetic tunnel junctions. The samples were then processed through four additional lithographic levels to complete the circuits. The demonstration focused attention on a number of processing and device issues that were addressed successfully enough that key performance aspects of MTJ MRAM were demonstrated in 1 K bit arrays, including reads and writes in less than 10 ns and nonvolatility. While other key issues remain to be addressed, these results suggest that MTJ MRAM might simultaneously provide much of the functionality now provided separately by SRAM, DRAM, and NVRAM.
Magnetic tunnel junction thermocouple for thermoelectric power harvesting
NASA Astrophysics Data System (ADS)
Böhnert, T.; Paz, E.; Ferreira, R.; Freitas, P. P.
2018-05-01
The thermoelectric power generated in magnetic tunnel junctions (MTJs) is determined as a function of the tunnel barrier thickness for a matched electric circuit. This study suggests that lower resistance area product and higher tunnel magnetoresistance will maximize the thermoelectric power output of the MTJ structures. Further, the thermoelectric behavior of a series of two MTJs, a MTJ thermocouple, is investigated as a function of its magnetic configurations. In an alternating magnetic configurations the thermovoltages cancel each other, while the magnetic contribution remains. A large array of MTJ thermocouples could amplify the magnetic thermovoltage signal significantly.
Krasner, Danielle S.; Daley, James M.; Sung, Patrick; Niu, Hengyao
2015-01-01
DNA double-strand breaks can be eliminated via non-homologous end joining or homologous recombination. Non-homologous end joining is initiated by the association of Ku with DNA ends. In contrast, homologous recombination entails nucleolytic resection of the 5′-strands, forming 3′-ssDNA tails that become coated with replication protein A (RPA). Ku restricts end access by the resection nuclease Exo1. It is unclear how partial resection might affect Ku engagement and Exo1 restriction. Here, we addressed these questions in a reconstituted system with yeast proteins. With blunt-ended DNA, Ku protected against Exo1 in a manner that required its DNA end-binding activity. Despite binding poorly to ssDNA, Ku could nonetheless engage a 5′-recessed DNA end with a 40-nucleotide (nt) ssDNA overhang, where it localized to the ssDNA-dsDNA junction and efficiently blocked resection by Exo1. Interestingly, RPA could exclude Ku from a partially resected structure with a 22-nt ssDNA tail and thus restored processing by Exo1. However, at a 40-nt tail, Ku remained stably associated at the ssDNA-dsDNA junction, and RPA simultaneously engaged the ssDNA region. We discuss a model in which the dynamic equilibrium between Ku and RPA binding to a partially resected DNA end influences the timing and efficiency of the resection process. PMID:26067273
Dynamic electrical response of solar cells
NASA Technical Reports Server (NTRS)
Catani, J. P.
1981-01-01
The dynamic response of a solar generator is of primary importance as much for the design and development of electrical power conditioning hardware as for the analysis of electromagnetic compatibility. A mathematical model of photo-batteries was developed on the basis of impedance measurements performed under differing conditions of temperature, light intensity, before and after irradiation. This model was compared with that derived from PN junction theory and to static measurements. These dynamic measurements enabled the refinement of an integration method capable of determining, under normal laboratory conditions, the dynamic response of a generator to operational lighting conditions.
Alberini, Giulio; Benfenati, Fabio
2017-01-01
Tight-junctions between epithelial cells of biological barriers are specialized molecular structures that regulate the flux of solutes across the barrier, parallel to cell walls. The tight-junction backbone is made of strands of transmembrane proteins from the claudin family, but the molecular mechanism of its function is still not completely understood. Recently, the crystal structure of a mammalian claudin-15 was reported, displaying for the first time the detailed features of transmembrane and extracellular domains. Successively, a structural model of claudin-15-based paracellular channels has been proposed, suggesting a putative assembly that illustrates how claudins associate in the same cell (via cis interactions) and across adjacent cells (via trans interactions). Although very promising, the model offers only a static conformation, with residues missing in the most important extracellular regions and potential steric clashes. Here we present detailed atomic models of paracellular single and double pore architectures, obtained from the putative assembly and refined via structural modeling and all-atom molecular dynamics simulations in double membrane bilayer and water environment. Our results show an overall stable configuration of the complex with a fluctuating pore size. Extracellular residue loops in trans interaction are able to form stable contacts and regulate the size of the pore, which displays a stationary radius of 2.5–3.0 Å at the narrowest region. The side-by-side interactions of the cis configuration are preserved via stable hydrogen bonds, already predicted by cysteine crosslinking experiments. Overall, this work introduces an improved version of the claudin-15-based paracellular channel model that strengthens its validity and that can be used in further computational studies to understand the structural features of tight-junctions regulation. PMID:28863193
van Oostendorp, S E; Tan, E C T H; Geeraedts, L M G
2016-09-13
Exsanguination following trauma is potentially preventable. Extremity tourniquets have been successfully implemented in military and civilian prehospital care. Prehospital control of bleeding from the torso and junctional area's remains challenging but offers a great potential to improve survival rates. This review aims to provide an overview of potential treatment options in both clinical as preclinical state of research on truncal and junctional bleeding. Since many options have been developed for application in the military primarily, translation to the civilian situation is discussed. Medline (via Pubmed) and Embase were searched to identify known and potential prehospital treatment options. Search terms were|: haemorrhage/hemorrhage, exsanguination, junctional, truncal, intra-abdominal, intrathoracic, intervention, haemostasis/hemostasis, prehospital, en route, junctional tourniquet, REBOA, resuscitative thoracotomy, emergency thoracotomy, pelvic binder, pelvic sheet, circumferential. Treatment options were listed per anatomical site: axilla, groin, thorax, abdomen and pelvis Also, the available evidence was graded in (pre) clinical stadia of research. Identified treatment options were wound clamps, injectable haemostatic sponges, pelvic circumferential stabilizers, resuscitative thoracotomy, resuscitative endovascular balloon occlusion of the aorta (REBOA), intra-abdominal gas insufflation, intra-abdominal self-expanding foam, junctional and truncal tourniquets. A total of 70 papers on these aforementioned options was retrieved. No clinical reports on injectable haemostatic sponges, intra-abdominal insufflation or self-expanding foam injections and one type of junctional tourniquets were available. Options to stop truncal and junctional traumatic haemorrhage in the prehospital arena are evolving and may offer a potentially great survival advantage. Because of differences in injury pattern, time to definitive care, different prehospital scenario's and level of proficiency of care providers; successful translation of various military applications to the civilian situation has to be awaited. Overall, the level of evidence on the retrieved adjuncts is extremely low.
Carbon Nanotube Based Molecular Electronics
NASA Technical Reports Server (NTRS)
Srivastava, Deepak; Saini, Subhash; Menon, Madhu
1998-01-01
Carbon nanotubes and the nanotube heterojunctions have recently emerged as excellent candidates for nanoscale molecular electronic device components. Experimental measurements on the conductivity, rectifying behavior and conductivity-chirality correlation have also been made. While quasi-one dimensional simple heterojunctions between nanotubes with different electronic behavior can be generated by introduction of a pair of heptagon-pentagon defects in an otherwise all hexagon graphene sheet. Other complex 3- and 4-point junctions may require other mechanisms. Structural stability as well as local electronic density of states of various nanotube junctions are investigated using a generalized tight-binding molecular dynamics (GDBMD) scheme that incorporates non-orthogonality of the orbitals. The junctions investigated include straight and small angle heterojunctions of various chiralities and diameters; as well as more complex 'T' and 'Y' junctions which do not always obey the usual pentagon-heptagon pair rule. The study of local density of states (LDOS) reveal many interesting features, most prominent among them being the defect-induced states in the gap. The proposed three and four pointjunctions are one of the smallest possible tunnel junctions made entirely of carbon atoms. Furthermore the electronic behavior of the nanotube based device components can be taylored by doping with group III-V elements such as B and N, and BN nanotubes as a wide band gap semiconductor has also been realized in experiments. Structural properties of heteroatomic nanotubes comprising C, B and N will be discussed.
Wu, Minnie M.; Covington, Elizabeth D.; Lewis, Richard S.
2014-01-01
Following endoplasmic reticulum (ER) Ca2+ depletion, STIM1 and Orai1 complexes assemble autonomously at ER–plasma membrane (PM) junctions to trigger store-operated Ca2+ influx. One hypothesis to explain this process is a diffusion trap in which activated STIM1 diffusing in the ER becomes trapped at junctions through interactions with the PM, and STIM1 then traps Orai1 in the PM through binding of its calcium release-activated calcium activation domain. We tested this model by analyzing STIM1 and Orai1 diffusion using single-particle tracking, photoactivation of protein ensembles, and Monte Carlo simulations. In resting cells, STIM1 diffusion is Brownian, while Orai1 is slightly subdiffusive. After store depletion, both proteins slow to the same speeds, consistent with complex formation, and are confined to a corral similar in size to ER–PM junctions. While the escape probability at high STIM:Orai expression ratios is <1%, it is significantly increased by reducing the affinity of STIM1 for Orai1 or by expressing the two proteins at comparable levels. Our results provide direct evidence that STIM-Orai complexes are trapped by their physical connections across the junctional gap, but also reveal that the complexes are surprisingly dynamic, suggesting that readily reversible binding reactions generate free STIM1 and Orai1, which engage in constant diffusional exchange with extrajunctional pools. PMID:25057023
Marston, Daniel J.; Higgins, Christopher D.; Peters, Kimberly A.; Cupp, Timothy D.; Dickinson, Daniel J.; Pani, Ariel M.; Moore, Regan P.; Cox, Amanda H.; Kiehart, Daniel P.; Goldstein, Bob
2016-01-01
Summary Apical constriction is a change in cell shape that drives key morphogenetic events including gastrulation and neural tube formation. Apical force-producing actomyosin networks drive apical constriction by contracting while connected to cell-cell junctions. The mechanisms by which developmental patterning regulates these actomyosin networks and associated junctions with spatial precision are not fully understood. Here, we identify a myosin light chain kinase MRCK-1 as a key regulator of C. elegans gastrulation that integrates spatial and developmental patterning information. We show that MRCK-1 is required for activation of contractile actomyosin dynamics and elevated cortical tension in the apical cell cortex of endodermal precursor cells. MRCK-1 is apically localized by active Cdc42 at the external, cell-cell contact-free surfaces of apically constricting cells, downstream of cell fate determination mechanisms. We establish that the junctional components α-catenin, β-catenin, and cadherin become highly enriched at the apical junctions of apically-constricting cells, and that MRCK-1 and myosin activity are required in vivo for this enrichment. Taken together, our results define mechanisms that position a myosin activator to a specific cell surface where it both locally increases cortical tension and locally enriches junctional components to facilitate apical constriction. These results reveal crucial links that can tie spatial information to local force generation to drive morphogenesis. PMID:27451898
Internal Electric Field Modulation in Molecular Electronic Devices by Atmosphere and Mobile Ions.
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.
Multicomponent order parameter superconductivity of Sr2RuO4 revealed by topological junctions
NASA Astrophysics Data System (ADS)
Anwar, M. S.; Ishiguro, R.; Nakamura, T.; Yakabe, M.; Yonezawa, S.; Takayanagi, H.; Maeno, Y.
2017-06-01
Single crystals of the Sr2RuO4 -Ru eutectic system are known to exhibit enhanced superconductivity at 3 K in addition to the bulk superconductivity of Sr2RuO4 at 1.5 K. The 1.5 K phase is believed to be a spin-triplet, chiral p -wave state with a multicomponent order parameter, giving rise to chiral domain structure. In contrast, the 3 K phase is attributable to enhanced superconductivity of Sr2RuO4 in the strained interface region between Ru inclusion of a few to tens of micrometers in size and the surrounding Sr2RuO4 . We investigate the dynamic behavior of a topological junction, where a superconductor is surrounded by another superconductor. Specifically, we fabricated Nb/Ru/Sr2RuO4 topological superconducting junctions, in which the difference in phase winding between the s -wave superconductivity in Ru microislands induced from Nb and the superconductivity of Sr2RuO4 mainly governs the junction behavior. Comparative results of the asymmetry, hysteresis, and noise in junctions with different sizes, shapes, and configurations of Ru inclusions are explained by the chiral domain-wall motion in these topological junctions. Furthermore, a striking difference between the 1.5 and 3 K phases is clearly revealed: the large noise in the 1.5 K phase sharply disappears in the 3 K phase. These results confirm the multicomponent order-parameter superconductivity of the bulk Sr2RuO4 , consistent with the chiral p -wave state, and the proposed nonchiral single-component superconductivity of the 3 K phase.
There are four dynamically and functionally distinct populations of E-cadherin in cell junctions
Erami, Zahra; Timpson, Paul; Yao, Wu; Zaidel-Bar, Ronen; Anderson, Kurt I.
2015-01-01
ABSTRACT E-cadherin is a trans-membrane tumor suppressor responsible for epithelial cell adhesion. E-cadherin forms adhesive clusters through combined extra-cellular cis- and trans-interactions and intracellular interaction with the actin cytoskeleton. Here we identify four populations of E-cadherin within cell junctions based on the molecular interactions which determine their mobility and adhesive properties. Adhesive and non-adhesive populations of E-cadherin each consist of mobile and immobile fractions. Up to half of the E-cadherin immobilized in cell junctions is non-adhesive. Incorporation of E-cadherin into functional adhesions require all three adhesive interactions, with deletion of any one resulting in loss of effective cell-cell adhesion. Interestingly, the only interaction which could independently slow the diffusion of E-cadherin was the tail-mediated intra-cellular interaction. The adhesive and non-adhesive mobile fractions of E-cadherin can be distinguished by their sensitivity to chemical cross-linking with adhesive clusters. Our data define the size, mobility, and adhesive properties of four distinct populations of E-cadherin within cell junctions, and support association with the actin cytoskeleton as the first step in adhesion formation. PMID:26471767
Hissar-Alai and the Pamirs: Junction and Position in the System of Mobile Belts of Central Asia
NASA Astrophysics Data System (ADS)
Leonov, M. G.; Rybin, A. K.; Batalev, V. Yu.; Matyukov, V. E.; Shchelochkov, G. G.
2018-01-01
The position of the Pamirs and the Hissar-Alai mountainous system in the structure of Central Asia and features of their junction are considered. It is shown that their outer contours and tectonic infrastructure are significantly distinct in the planar pattern: latitudinally linear and arched for the Hissar-Alai and the Pamirs, respectively. These structures logically match those of the Central Asian and Alpine-Himalayan belts, respectively. The Pamir orogen is a relatively autonomous structural element of the crust, which is located discordantly relative to the country lithospheric blocks. Most of the Pamirs (at least, the Northern and Central) probably form a giant allochthon on the ancient basement of the Tarim and Afghan-Tajik blocks. The junction zone of these two "hard" crustal segments is reflected in the transverse Transpamir threshold, which is expressed in the relief, deep structure, and seismicity. The specific geological structure of the junction zone of the Pamirs and Hissar-Alai (systems of the Tarim, Alai, and Afghan-Tajik troughs) is shown. It suggested that this zone is a damper, which significantly neutralizes the dynamic influence of the Pamir and the southernmost elements of the Pamir-Punjab syntax on Hissar-Alai structures.
Ivanova, Elena; Yee, Christopher W; Baldoni, Robert; Sagdullaev, Botir T
2016-09-01
In retinal degenerative disease (RD), the diminished light signal from dying photoreceptors has been considered the sole cause of visual impairment. Recent studies show a 10-fold increase in spontaneous activity in the RD network, challenging this paradigm. This aberrant activity forms a new barrier for the light signal, and not only exacerbates the loss of vision, but also may stand in the way of visual restoration. This activity originates in AII amacrine cells and relies on excessive activation of gap junctions. However, it remains unclear whether aberrant activity affects central visual processing and what mechanisms lead to this excessive activation of gap junctions. By combining genetic manipulation with electrophysiological recordings of light-induced activity in both living mice and isolated wholemount retina, we demonstrate that aberrant activity extends along retinotectal projections to alter activity in higher brain centers. Next, to selectively eliminate Cx36-containing gap junctions, which are the primary type expressed by AII amacrine cells, we crossed rd10 mice, a slow-degenerating model of RD, with Cx36 knockout mice. We found that retinal aberrant activity was reduced in the rd10/Cx36KO mice compared to rd10 controls, a direct evidence for involvement of Cx36-containing gap junctions in generating aberrant activity in RD. These data provide an essential support for future experiments to determine if selectively targeting these gap junctions could be a valid strategy for reducing aberrant activity and restoring light responses in RD. Copyright © 2015 Elsevier Ltd. All rights reserved.
Connexin40 and connexin43 determine gating properties of atrial gap junction channels.
Lin, Xianming; Gemel, Joanna; Glass, Aaron; Zemlin, Christian W; Beyer, Eric C; Veenstra, Richard D
2010-01-01
While ventricular gap junctions contain only Cx43, atrial gap junctions contain both Cx40 and Cx43; yet the functional consequences of this co-expression remain poorly understood. We quantitated the expression of Cx40 and Cx43 and their contributions to atrial gap junctional conductance (g(j)). Neonatal murine atrial myocytes showed similar abundances of Cx40 and Cx43 proteins, while ventricular myocytes contained at least 20 times more Cx43 than Cx40. Since Cx40 gap junction channels are blocked by 2 mM spermine while Cx43 channels are unaffected, we used spermine block as a functional dual whole cell patch clamp assay to determine Cx40 contributions to cardiac g(j). Slightly more than half of atrial g(j) and
NASA Astrophysics Data System (ADS)
Sharma, Basant Lal
2018-05-01
Based on the well known nearest-neighbor tight-binding approximation for graphene, an exact expression for the electronic conductance across a zigzag nanoribbon/armchair nanotube junction is presented for non-interacting electrons. The junction results from the removal of a half-row of zigzag dimers in armchair nanotube, or equivalently by partial rolling of zigzag nanoribbon and insertion of a half-row of zigzag dimers in between. From the former point of view, a discrete form of Dirichlet condition is imposed on a zigzag half-line of dimers assuming the vanishing of wave function outside the physical structure. A closed form expression is provided for the reflection and transmission moduli for the outgoing wave modes for each given electronic wave mode incident from either side of the junction. It is demonstrated that such a contact junction between the nanotube and nanoribbon exhibits negligible backscattering, and the transmission has been found to be nearly ballistic. In contrast to the previously reported studies for partially unzipped carbon nanotubes (CNTs), using the same tight binding model, it is found that due to the "defect" there is certain amount of mixing between the electronic wave modes with even and odd reflection symmetries. But the junction remains a perfect valley filter for CNTs at certain energy ranges. Applications aside from the electronic case, include wave propagation in quasi-one-dimensional honeycomb structures of graphene-like constitution. The paper includes several numerical calculations, analytical derivations, and graphical results, which complement the provision of succinct closed form expressions.
Gap junction coupling is required for tumor cell migration through lymphatic endothelium.
Karpinich, Natalie O; Caron, Kathleen M
2015-05-01
The lymphatic vasculature is a well-established conduit for metastasis, but the mechanisms by which tumor cells interact with lymphatic endothelial cells (LECs) to facilitate escape remain poorly understood. Elevated levels of the lymphangiogenic peptide adrenomedullin are found in many tumors, and we previously characterized that its expression is necessary for lymphatic vessel growth within both tumors and sentinel lymph nodes and for distant metastasis. This study used a tumor cell-LEC coculture system to identify a series of adrenomedullin-induced events that facilitated transendothelial migration of the tumor cells through a lymphatic monolayer. High levels of adrenomedullin expression enhanced adhesion of tumor cells to LECs, and further analysis revealed that adrenomedullin promoted gap junction coupling between LECs as evidenced by spread of Lucifer yellow dye. Adrenomedullin also enhanced heterocellular gap junction coupling as demonstrated by Calcein dye transfer from tumor cells into LECs. This connexin-mediated gap junction intercellular communication was necessary for tumor cells to undergo transendothelial migration because pharmacological blockade of this heterocellular communication prevented the ability of tumor cells to transmigrate through the lymphatic monolayer. In addition, treatment of LECs with adrenomedullin caused nuclear translocation of β-catenin, a component of endothelial cell junctions, causing an increase in transcription of the downstream target gene C-MYC. Importantly, blockade of gap junction intercellular communication prevented β-catenin nuclear translocation. Our findings indicate that maintenance of cell-cell communication is necessary to facilitate a cascade of events that lead to tumor cell migration through the lymphatic endothelium. © 2015 American Heart Association, Inc.
Wang, De-Guo; Zhang, Feng-Xiang; Chen, Ming-Long; Zhu, Hong-Jun; Yang, Bing; Cao, Ke-Jiang
2014-04-01
Mesenchymal stem cells (MSCs) with elevated levels of connexin 43 (Cx43) have been shown to exhibit improved protection for ischemic hearts. However, it remains unclear whether Cx43 is involved in the paracrine actions of angiogenesis, the major mechanism of cell therapy. In the present study, an in vitro model with deprivation of oxygen and a murine myocardial infarction model with permanent ligation of the left anterior‑descending (LAD) coronary artery were used to determine whether gap junctions in MSCs promote angiogenesis. It was observed that MSCs that overexpressed Cx43 (MSCs‑Cx43), improve the cardiac function of infarcted myocardium as compared with control MSCs (MSCs‑vector) and MSCs with Cx43 knocked down by small interfering RNA (MSCs‑siCx43), accompanied with a reduction of infarct size and an increase in the vascular density and maturity. Increased levels of representative angiogenic factors [vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)] were produced by MSCs‑Cx43 compared with MSCs‑siCx43 in vivo and in vitro. However, neither Cx43 formed gap junction specific inhibitor (Cx43 mimetic peptide) or gap junction opener (antiarrhythmic peptide) affected the production of VEGF and bFGF in MSCs under hypoxic stress. These data support the hypothesis that Cx43 in MSCs promotes angiogenesis in the infarcted heart, independent of gap junction formation.
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
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.
Shao, Ximing; Liu, Ke; Fan, Yi; Ding, Zhihao; Chen, Min; Zhu, Minyan; Weinstein, Lee S; Li, Hongchang; Li, Huashun
2015-11-20
Sphingosine-1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor (GPCR), controls vascular stability by stabilizing vascular endothelial (VE)-cadherin junctional localization and inhibiting vascular endothelial growth factor receptor 2 (VEGFR2) signaling. However, the molecular mechanisms that link S1PR1 signaling to intracellular effectors remain unknown. In this study, we demonstrate that the heterotrimeric G protein subfamily member Gαs, encoded by GNAS, acts as a relay mediator of S1PR1 signaling to control vascular integrity by stabilizing VE-cadherin at endothelial junctions. The endothelial cell-specific deletion of Gαs in mice causes early embryonic lethality with massive hemorrhage and a disorganized vasculature. The immunostaining results revealed that Gαs deletion remarkably reduces the junctional localization of VE-cadherin, whereas the mural cell coverage of the vessels is not impaired. In addition, we found that Gαs depletion blocks the S1PR1-activation induced VE-cadherin stabilization at junctions, supporting that Gαs acts downstream of S1PR1 signaling. Thus, our results demonstrate that Gαs is an essential mediator to relay S1PR1 signaling and maintain vascular integrity. Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.
Role of the gut endoderm in relaying left-right patterning in mice.
Viotti, Manuel; Niu, Lei; Shi, Song-Hai; Hadjantonakis, Anna-Katerina
2012-01-01
Establishment of left-right (LR) asymmetry occurs after gastrulation commences and utilizes a conserved cascade of events. In the mouse, LR symmetry is broken at a midline structure, the node, and involves signal relay to the lateral plate, where it results in asymmetric organ morphogenesis. How information transmits from the node to the distantly situated lateral plate remains unclear. Noting that embryos lacking Sox17 exhibit defects in both gut endoderm formation and LR patterning, we investigated a potential connection between these two processes. We observed an endoderm-specific absence of the critical gap junction component, Connexin43 (Cx43), in Sox17 mutants. Iontophoretic dye injection experiments revealed planar gap junction coupling across the gut endoderm in wild-type but not Sox17 mutant embryos. They also revealed uncoupling of left and right sides of the gut endoderm in an isolated domain of gap junction intercellular communication at the midline, which in principle could function as a barrier to communication between the left and right sides of the embryo. The role for gap junction communication in LR patterning was confirmed by pharmacological inhibition, which molecularly recapitulated the mutant phenotype. Collectively, our data demonstrate that Cx43-mediated communication across gap junctions within the gut endoderm serves as a mechanism for information relay between node and lateral plate in a process that is critical for the establishment of LR asymmetry in mice.
Ion Separation using a Y-Junction Carbon Nanotube
NASA Astrophysics Data System (ADS)
Park, Jae Hyun; Sinnott, Susan; Aluru, Narayana
2005-11-01
Using molecular dynamics simulations, we show that a Y-junction carbon nanotube can be used to separate potassium and chloride ions from a KCl solution. The system consists of a KCl solution chamber connected to an (8,8) carbon nanotube, which acts as the stem. Two carbon nanotube branches of sizes (5,5) and (6,6) are connected to the (8,8) nanotube forming the Y-junction. Uncharged (5,5) and (6,6) carbon nanotubes show close to zero occupancy for transport of potassium and chloride ions. By functionalizing a (5,5) carbon nanotube with a negative charge, we show that we can selectively transport potassium ions. Similarly, by functionalizing a (6,6) carbon nanotube with a positive charge, we can selectively transport chloride ions. By performing molecular dynamics simulations on the entire system comprising the two branches, stem and the KCl solution chamber, we show that perfect ion separation is observed when (5,5) and (6,6) nanotubes are charged with σw,(5,5)=-0.181 C/m^2 and σw,(6,6)=+0.143 C/m^2, respectively, whereas for the system with σw,(5,5)=-0.168 C/m^2 and σw,(6,6)=+0.131 C/m^2 the separation is not perfect because of the formation of ion pairs. We discuss the formation and control of ion pairing, which is a common phenomenon in confined nanochannels.
Ankyrin-G Inhibits Endocytosis of Cadherin Dimers.
Cadwell, Chantel M; Jenkins, Paul M; Bennett, Vann; Kowalczyk, Andrew P
2016-01-08
Dynamic regulation of endothelial cell adhesion is central to vascular development and maintenance. Furthermore, altered endothelial adhesion is implicated in numerous diseases. Therefore, normal vascular patterning and maintenance require tight regulation of endothelial cell adhesion dynamics. However, the mechanisms that control junctional plasticity are not fully understood. Vascular endothelial cadherin (VE-cadherin) is an adhesive protein found in adherens junctions of endothelial cells. VE-cadherin mediates adhesion through trans interactions formed by its extracellular domain. Trans binding is followed by cis interactions that laterally cluster the cadherin in junctions. VE-cadherin is linked to the actin cytoskeleton through cytoplasmic interactions with β- and α-catenin, which serve to increase adhesive strength. Furthermore, p120-catenin binds to the cytoplasmic tail of cadherin and stabilizes it at the plasma membrane. Here we report that induced cis dimerization of VE-cadherin inhibits endocytosis independent of both p120 binding and trans interactions. However, we find that ankyrin-G, a protein that links membrane proteins to the spectrin-actin cytoskeleton, associates with VE-cadherin and inhibits its endocytosis. Ankyrin-G inhibits VE-cadherin endocytosis independent of p120 binding. We propose a model in which ankyrin-G associates with and inhibits the endocytosis of VE-cadherin cis dimers. Our findings support a novel mechanism for regulation of VE-cadherin endocytosis through ankyrin association with cadherin engaged in lateral interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Co-percolation to tune conductive behaviour in dynamical metallic nanowire networks.
Fairfield, J A; Rocha, C G; O'Callaghan, C; Ferreira, M S; Boland, J J
2016-11-03
Nanowire networks act as self-healing smart materials, whose sheet resistance can be tuned via an externally applied voltage stimulus. This memristive response occurs due to modification of junction resistances to form a connectivity path across the lowest barrier junctions in the network. While most network studies have been performed on expensive noble metal nanowires like silver, networks of inexpensive nickel nanowires with a nickel oxide coating can also demonstrate resistive switching, a common feature of metal oxides with filamentary conduction. However, networks made from solely nickel nanowires have high operation voltages which prohibit large-scale material applications. Here we show, using both experiment and simulation, that a heterogeneous network of nickel and silver nanowires allows optimization of the activation voltage, as well as tuning of the conduction behavior to be either resistive switching, memristive, or a combination of both. Small percentages of silver nanowires, below the percolation threshold, induce these changes in electrical behaviour, even for low area coverage and hence very transparent films. Silver nanowires act as current concentrators, amplifying conductivity locally as shown in our computational dynamical activation framework for networks of junctions. These results demonstrate that a heterogeneous nanowire network can act as a cost-effective adaptive material with minimal use of noble metal nanowires, without losing memristive behaviour that is essential for smart sensing and neuromorphic applications.
Fast, clash-free RNA conformational morphing using molecular junctions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heliou, Amelie; Budday, Dominik; Fonseca, Rasmus
Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groupsmore » of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.« less
Fast, clash-free RNA conformational morphing using molecular junctions
Heliou, Amelie; Budday, Dominik; Fonseca, Rasmus; ...
2017-03-13
Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groupsmore » of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.« less
NASA Technical Reports Server (NTRS)
McNelis, Mark E.; Staab, Lucas D.; Akers, James C.; Hughes, William O.; Chang, Li C.; Hozman, Aron D.; Henry, Michael W.
2012-01-01
The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) has led the design and build of the new world-class vibroacoustic test capabilities at the NASA GRC's Plum Brook Station in Sandusky, Ohio, USA from 2007 to 2011. SAIC-Benham has completed construction of a new reverberant acoustic test facility to support the future testing needs of NASA's space exploration program and commercial customers. The large Reverberant Acoustic Test Facility (RATF) is approximately 101,000 cubic feet in volume and was designed to operate at a maximum empty chamber acoustic overall sound pressure level (OASPL) of 163 dB. This combination of size and acoustic power is unprecedented amongst the world s known active reverberant acoustic test facilities. Initial checkout acoustic testing was performed on March 2011 by SAIC-Benham at test levels up to 161 dB OASPL. During testing, several branches of the gaseous nitrogen (GN2) piping system, which supply the fluid to the noise generating acoustic modulators, failed at their T-junctions connecting the 12 in. supply line to their respective 4 in. branch lines. The problem was initially detected when the oxygen sensors in the horn room indicated a lower than expected oxygen level from which was inferred GN2 leaks in the piping system. In subsequent follow up inspections, cracks were identified in the failed T-junction connections through non-destructive evaluation testing. Through structural dynamic modeling of the piping system, the root cause of the T-junction connection failures was determined. The structural dynamic assessment identified several possible corrective design improvements to the horn room piping system. The effectiveness of the chosen design repairs were subsequently evaluated in September 2011 during acoustic verification testing to 161 dB OASPL.
NASA Technical Reports Server (NTRS)
McNelis, Mark E.; Staab, Lucas D.; Akers, James C.; Hughes, WIlliam O.; Chang, Li, C.; Hozman, Aron D.; Henry, Michael W.
2012-01-01
The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) has led the design and build of the new world-class vibroacoustic test capabilities at the NASA GRC's Plum Brook Station in Sandusky, Ohio, USA from 2007-2011. SAIC-Benham has completed construction of a new reverberant acoustic test facility to support the future testing needs of NASA's space exploration program and commercial customers. The large Reverberant Acoustic Test Facility (RATF) is approximately 101,000 cu ft in volume and was designed to operate at a maximum empty chamber acoustic overall sound pressure level (OASPL) of 163 dB. This combination of size and acoustic power is unprecedented amongst the world's known active reverberant acoustic test facilities. Initial checkout acoustic testing was performed on March 2011 by SAIC-Benham at test levels up to 161 dB OASPL. During testing, several branches of the gaseous nitrogen (GN2) piping system, which supply the fluid to the noise generating acoustic modulators, failed at their "t-junctions" connecting the 12 inch supply line to their respective 4 inch branch lines. The problem was initially detected when the oxygen sensors in the horn room indicated a lower than expected oxygen level from which was inferred GN2 leaks in the piping system. In subsequent follow up inspections, cracks were identified in the failed "t-junction" connections through non-destructive evaluation testing . Through structural dynamic modeling of the piping system, the root cause of the "t-junction" connection failures was determined. The structural dynamic assessment identified several possible corrective design improvements to the horn room piping system. The effectiveness of the chosen design repairs were subsequently evaluated in September 2011 during acoustic verification testing to 161 dB OASPL.
The stress polarity pathway: AMPK ‘GIV’-es protection against metabolic insults
Ghosh, Pradipta
2017-01-01
Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis. How AMPK protects the epithelium remained unknown until recently Aznar et al. identified GIV/Girdin as a novel effector of AMPK at the cell-cell junctions; phosphorylation of GIV at a single site by AMPK appears to be both necessary and sufficient for strengthening tight junctions and preserving cell polarity and epithelial barrier function in the face of energetic stress. Here we review the fundamentals of this specialized signaling pathway that buttresses cell-cell junctions against stress-induced collapse and discuss its pathophysiologic relevance in the context of a variety of diseases, including cancers, diabetes, aging, and the growing list of beneficial effects of the AMPK-activator, Metformin. PMID:28209925
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
Microfabrication of microsystem-enabled photovoltaic (MEPV) cells
NASA Astrophysics Data System (ADS)
Nielson, Gregory N.; Okandan, Murat; Cruz-Campa, Jose L.; Resnick, Paul J.; Wanlass, Mark W.; Clews, Peggy J.; Pluym, Tammy C.; Sanchez, Carlos A.; Gupta, Vipin P.
2011-02-01
Microsystem-Enabled Photovoltaic (MEPV) cells allow solar PV systems to take advantage of scaling benefits that occur as solar cells are reduced in size. We have developed MEPV cells that are 5 to 20 microns thick and down to 250 microns across. We have developed and demonstrated crystalline silicon (c-Si) cells with solar conversion efficiencies of 14.9%, and gallium arsenide (GaAs) cells with a conversion efficiency of 11.36%. In pursuing this work, we have identified over twenty scaling benefits that reduce PV system cost, improve performance, or allow new functionality. To create these cells, we have combined microfabrication techniques from various microsystem technologies. We have focused our development efforts on creating a process flow that uses standard equipment and standard wafer thicknesses, allows all high-temperature processing to be performed prior to release, and allows the remaining post-release wafer to be reprocessed and reused. The c-Si cell junctions are created using a backside point-contact PV cell process. The GaAs cells have an epitaxially grown junction. Despite the horizontal junction, these cells also are backside contacted. We provide recent developments and details for all steps of the process including junction creation, surface passivation, metallization, and release.
Tanaka, Yoshihiro; Kosuga, Toshiyuki; Komatsu, Shuhei; Okamoto, Kazuma; Shoda, Katsutoshi; Arita, Tomohiro; Konishi, Hirotaka; Morimura, Ryo; Murayama, Yasutoshi; Shiozaki, Atsushi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Fujiwara, Hitoshi; Otsuji, Eigo
2017-11-01
A 39-year-old woman visited our hospital because of epigastric pain. Gastrointestinal endoscopy revealed a gastric submucosal tumor, 30mm in size, with ulcer locating near to the esophagogastric junction, and it was diagnosed with GIST by the endoscopic ultrasonography-guided fine needle aspiration. Then, she underwent laparoscopic surgery for the removal of gastric GIST. After peeling around the upper stomach, the local resection of the stomach was performed with linear staplers in the minor axis direction under the vision of the endoscope and laparoscope. Histopathological examinations confirmed that the tumor was GIST with an intermediate risk, and all surgical margins were free of GIST cells. Local resection with the laparoscopy endoscopy cooperative surgery(LECS)technique is a very useful way of the removal of gastric GISTs locating near to the esophagogastric junction in terms of the remnant gastric functions. Meanwhile, because the standard LECS requires the opening of the gastric lumen, there remains concerns about the intraperitoneal tumor dissemination for the gastric GIST with ulcer. We herein reported a case of laparoscopic local resection for a gastric GIST with ulcer locating near to the esophagogastric junction without gastric opening.
NASA Astrophysics Data System (ADS)
Fulmek, P. L.; Haumer, P.; Wenzl, F. P.; Nemitz, W.; Nicolics, J.
2017-03-01
Estimating the junction temperature and its dynamic behavior in dependence of various operating conditions is an important issue, since these properties influence the optical characteristics as well as the aging processes of a light-emitting diode (LED). Particularly for high-power LEDs and pulsed operation, the dynamic behavior and the resulting thermal cycles are of interest. The forward voltage method relies on the existence of a time-independent unique triple of forward-voltage, forward-current, and junction temperature. These three figures should as well uniquely define the optical output power and spectrum, as well as the loss power of the LED, which is responsible for an increase of the junction temperature. From transient FEM-simulations one may expect an increase of the temperature of the active semiconductor layer of some 1/10 K within the first 10 μs. Most of the well-established techniques for junction temperature measurement via forward voltage method evaluate the measurement data several dozens of microseconds after switching on or switching off and estimate the junction temperature by extrapolation towards the time of switching. In contrast, the authors developed a measurement procedure with the focus on the first microseconds after switching. Besides a fast data acquisition system, a precise control of the switching process is required, i.e. a precisely defined current pulse amplitude with fast rise-time and negligible transient by-effects. We start with a short description of the measurement setup and the newly developed control algorithm for the generation of short current pulses. The thermal characterization of the LED chip during the measurement procedures is accomplished by an IR thermography system and transient finite element simulations. The same experimental setup is used to investigate the optical properties of the LED in an Ulbricht-sphere. Our experiments are performed on InGaN LED chips mounted on an Al based insulated metal substrate (IMS), giving a comprehensive picture of the transient behavior of the forward voltage of this type of high power LED.
Unpaired Majorana modes in Josephson-Junction Arrays with gapless bulk excitations
Pino, M.; Tsvelik, A.; Ioffe, L. B.
2015-11-06
In this study, the search for Majorana bound states in solid-state physics has been limited to materials that display a gap in their bulk spectrum. We show that such unpaired states appear in certain quasi-one-dimensional Josephson-junction arrays with gapless bulk excitations. The bulk modes mediate a coupling between Majorana bound states via the Ruderman-Kittel-Yosida-Kasuya mechanism. As a consequence, the lowest energy doublet acquires a finite energy difference. For a realistic set of parameters this energy splitting remains much smaller than the energy of the bulk eigenstates even for short chains of length L~10.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sellers, D. G.; Chen, E. Y.; Doty, M. F.
2016-05-21
We investigate the effect of doping on the mechanisms of carrier escape from intermediate states in delta-doped InAs/GaAs intermediate band solar cells. The intermediate states arise from InAs quantum dots embedded in a GaAs p-i-n junction cell. We find that doping the sample increases the number of excited-state carriers participating in a cycle of trapping and carrier escape via thermal, optical, and tunneling mechanisms. However, we find that the efficiency of the optically-driven carrier escape mechanism is independent of doping and remains small.
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.
Chaotic electrical activity of living β-cells in the mouse pancreatic islet
NASA Astrophysics Data System (ADS)
Kanno, Takahiro; Miyano, Takaya; Tokuda, Isao; Galvanovskis, Juris; Wakui, Makoto
2007-02-01
To test for chaotic dynamics of the insulin producing β-cell and explore its biological role, we observed the action potentials with the perforated patch clamp technique, for isolated cells as well as for intact cells of the mouse pancreatic islet. The time series obtained were analyzed using nonlinear diagnostic algorithms associated with the surrogate method. The isolated cells exhibited short-term predictability and visible determinism, in the steady state response to 10 mM glucose, while the intact cells did not. In the latter case, determinism became visible after the application of a gap junction inhibitor. This tendency was enhanced by the stimulation with tolbutamide. Our observations suggest that, thanks to the integration of individual chaotic dynamics via gap junction coupling, the β-cells will lose memory of fluctuations occurring at any instant in their electrical activity more rapidly with time. This is likely to contribute to the functional stability of the islet against uncertain perturbations.
Crossing Over from Attractive to Repulsive Interactions in a Tunneling Bosonic Josephson Junction.
Spagnolli, G; Semeghini, G; Masi, L; Ferioli, G; Trenkwalder, A; Coop, S; Landini, M; Pezzè, L; Modugno, G; Inguscio, M; Smerzi, A; Fattori, M
2017-06-09
We explore the interplay between tunneling and interatomic interactions in the dynamics of a bosonic Josephson junction. We tune the scattering length of an atomic ^{39}K Bose-Einstein condensate confined in a double-well trap to investigate regimes inaccessible to other superconducting or superfluid systems. In the limit of small-amplitude oscillations, we study the transition from Rabi to plasma oscillations by crossing over from attractive to repulsive interatomic interactions. We observe a critical slowing down in the oscillation frequency by increasing the strength of an attractive interaction up to the point of a quantum phase transition. With sufficiently large initial oscillation amplitude and repulsive interactions, the system enters the macroscopic quantum self-trapping regime, where we observe coherent undamped oscillations with a self-sustained average imbalance of the relative well population. The exquisite agreement between theory and experiments enables the observation of a broad range of many body coherent dynamical regimes driven by tunable tunneling energy, interactions and external forces, with applications spanning from atomtronics to quantum metrology.
NASA Astrophysics Data System (ADS)
Wang, Hui; Blencowe, M. P.; Armour, A. D.; Rimberg, A. J.
2017-09-01
We give a semiclassical analysis of the average photon number as well as photon number variance (Fano factor F ) for a Josephson junction (JJ) embedded microwave cavity system, where the JJ is subject to a fluctuating (i.e., noisy) bias voltage with finite dc average. Through the ac Josephson effect, the dc voltage bias drives the effectively nonlinear microwave cavity mode into an amplitude squeezed state (F <1 ), as has been established previously [Armour et al., Phys. Rev. Lett. 111, 247001 (2013), 10.1103/PhysRevLett.111.247001], but bias noise acts to degrade this squeezing. We find that the sensitivity of the Fano factor to bias voltage noise depends qualitatively on which stable fixed point regime the system is in for the corresponding classical nonlinear steady-state dynamics. Furthermore, we show that the impact of voltage bias noise is most significant when the cavity is excited to states with large average photon number.
Grain Refinement Kinetics in a Low Alloyed Cu–Cr–Zr Alloy Subjected to Large Strain Deformation
Morozova, Anna; Borodin, Elijah; Bratov, Vladimir; Zherebtsov, Sergey; Kaibyshev, Rustam
2017-01-01
This paper investigates the microstructural evolution and grain refinement kinetics of a solution-treated Cu–0.1Cr–0.06Zr alloy during equal channel angular pressing (ECAP) at a temperature of 673 K via route BC. The microstructural change during plastic deformation was accompanied by the formation of the microband and an increase in the misorientations of strain-induced subboundaries. We argue that continuous dynamic recrystallization refined the initially coarse grains, and discuss the dynamic recrystallization kinetics in terms of grain/subgrain boundary triple junction evolution. A modified Johnson–Mehl–Avrami–Kolmogorov relationship with a strain exponent of about 1.49 is used to express the strain dependence of the triple junctions of high-angle boundaries. Severe plastic deformation by ECAP led to substantial strengthening of the Cu–0.1Cr–0.06Zr alloy. The yield strength increased from 60 MPa in the initial state to 445 MPa after a total strain level of 12. PMID:29210990
Hydrodynamically induced oscillations and traffic dynamics in 1D microfludic networks
NASA Astrophysics Data System (ADS)
Bartolo, Denis; Jeanneret, Raphael
2011-03-01
We report on the traffic dynamics of particles driven through a minimal microfluidic network. Even in the minimal network consisting in a single loop, the traffic dynamics has proven to yield complex temporal patterns, including periodic, multi-periodic or chaotic sequences. This complex dynamics arises from the strongly nonlinear hydrodynamic interactions between the particles, that takes place at a junction. To better understand the consequences of this nontrivial coupling, we combined theoretical, numerical and experimental efforts and solved the 3-body problem in a 1D loop network. This apparently simple dynamical system revealed a rich and unexpected dynamics, including coherent spontaneous oscillations along closed orbits. Striking similarities between Hamiltonian systems and this driven dissipative system will be explained.
Llewellyn, Sue; Hobson, J Allan
2015-07-01
This article argues both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep contribute to overnight episodic memory processes but their roles differ. Episodic memory may have evolved from memory for spatial navigation in animals and humans. Equally, mnemonic navigation in world and mental space may rely on fundamentally equivalent processes. Consequently, the basic spatial network characteristics of pathways which meet at omnidirectional nodes or junctions may be conserved in episodic brain networks. A pathway is formally identified with the unidirectional, sequential phases of an episodic memory. In contrast, the function of omnidirectional junctions is not well understood. In evolutionary terms, both animals and early humans undertook tours to a series of landmark junctions, to take advantage of resources (food, water and shelter), whilst trying to avoid predators. Such tours required memory for emotionally significant landmark resource-place-danger associations and the spatial relationships amongst these landmarks. In consequence, these tours may have driven the evolution of both spatial and episodic memory. The environment is dynamic. Resource-place associations are liable to shift and new resource-rich landmarks may be discovered, these changes may require re-wiring in neural networks. To realise these changes, REM may perform an associative, emotional encoding function between memory networks, engendering an omnidirectional landmark junction which is instantiated in the cortex during NREM Stage 2. In sum, REM may preplay associated elements of past episodes (rather than replay individual episodes), to engender an unconscious representation which can be used by the animal on approach to a landmark junction in wake. Copyright © 2015 Elsevier Inc. All rights reserved.
Gap junction blockade induces apoptosis in human endometrial stromal cells.
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.
Imaging Ca2+ nanosparks in heart with a new targeted biosensor.
Shang, Wei; Lu, Fujian; Sun, Tao; Xu, Jiejia; Li, Lin-Lin; Wang, Yanru; Wang, Gang; Chen, Liangyi; Wang, Xianhua; Cannell, Mark B; Wang, Shi-Qiang; Cheng, Heping
2014-01-31
In cardiac dyads, junctional Ca2+ directly controls the gating of the ryanodine receptors (RyRs), and is itself dominated by RyR-mediated Ca2+ release from the sarcoplasmic reticulum. Existing probes do not report such local Ca2+ signals because of probe diffusion, so a junction-targeted Ca2+ sensor should reveal new information on cardiac excitation-contraction coupling and its modification in disease states. To investigate Ca2+ signaling in the nanoscopic space of cardiac dyads by targeting a new sensitive Ca2+ biosensor (GCaMP6f) to the junctional space. By fusing GCaMP6f to the N terminus of triadin 1 or junctin, GCaMP6f-triadin 1/junctin was targeted to dyadic junctions, where it colocalized with t-tubules and RyRs after adenovirus-mediated gene transfer. This membrane protein-tagged biosensor displayed ≈4× faster kinetics than native GCaMP6f. Confocal imaging revealed junctional Ca2+ transients (Ca2+ nanosparks) that were ≈50× smaller in volume than conventional Ca2+ sparks (measured with diffusible indicators). The presence of the biosensor did not disrupt normal Ca2+ signaling. Because no indicator diffusion occurred, the amplitude and timing of release measurements were improved, despite the small recording volume. We could also visualize coactivation of subclusters of RyRs within a single junctional region, as well as quarky Ca2+ release events. This new, targeted biosensor allows selective visualization and measurement of nanodomain Ca2+ dynamics in intact cells and can be used to give mechanistic insights into dyad RyR operation in health and in disease states such as when RyRs become orphaned.
Electronic Properties of Carbon Nanotubes and Junctions
NASA Technical Reports Server (NTRS)
Anantram, M. P.; Han, Jie; Yang, Liu; Govindan, T. R.; Jaffe, R.; Saini, Subhash (Technical Monitor)
1998-01-01
Metallic and semiconducting Single Wall Carbon Nanotubes (CNT) have recently been characterized using scanning tunneling microscopy (STM) and the manipulation of individual CNT has been demonstrated. These developments make the prospect of using CNT as molecular wires and possibly as electronic devices an even more interesting one. We have been modeling various electronic properties such as the density of states and the transmission coefficient of CNT wires and junctions. These studies involve first calculating the stability of junctions using molecular dynamics simulations and then calculating the electronic properties using a pi-electron tight binding Hamiltonian. We have developed the expertise to calculate the electronic properties of both finite-sized CNT and CNT systems with semi-infinite boundary conditions. In this poster, we will present an overview of some of our results. The electronic application of CNT that is most promising at this time is their use as molecular wires. The conductance can however be greatly reduced because of reflection due to defects and contacts. We have modeled the transmission through CNT in the presence of two types of defects: weak uniform disorder and strong isolated scatterers. We find that the conductance is affected in significantly different manners due to these defects Junctions of CNT have also been imaged using STM. This makes it essential to derive rules for the formation of junctions between tubes of different chirality, study their relative energies and electronic properties. We have generalized the rules for connecting two different CNT and have calculated the transmission and density of states through CNT junctions. Metallic and semiconducting CNT can be joined to form a stable junction and their current versus voltage characteristics are asymmetric. CNT are deformed by the application of external forces including interactions with a substrate or other CNT. In many experiments, these deformation are expected to occur naturally. We will present some preliminary results of our calculations of the modification of CNT electronic properties as a result of deformations.
Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D.; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas
2015-01-01
Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender’s and receiver’s temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions. PMID:25848050
Wang, Weixiong; Graziano, Francesca; Russo, Vittorio; Ulm, Arthur J; De Kee, Daniel; Khismatullin, Damir B
2013-01-01
The endovascular treatment of intracranial aneurysms remains a challenge, especially when the aneurysm is large in size and has irregular, non-spherical geometry. In this paper, we use computational fluid dynamics to simulate blood flow in a vertebro-basilar junction giant aneurysm for the following three cases: (1) an empty aneurysm, (2) an aneurysm filled with platinum coils, and (3) an aneurysm filled with a yield stress fluid material. In the computational model, blood and the coil-filled region are treated as a non-Newtonian fluid and an isotropic porous medium, respectively. The results show that yield stress fluids can be used for aneurysm embolization provided the yield stress value is 20 Pa or higher. Specifically, flow recirculation in the aneurysm and the size of the inflow jet impingement zone on the aneurysm wall are substantially reduced by yield stress fluid treatment. Overall, this study opens up the possibility of using yield stress fluids for effective embolization of large-volume intracranial aneurysms.
Zelovich, Tamar; Hansen, Thorsten; Liu, Zhen-Fei; ...
2017-03-02
A parameter-free version of the recently developed driven Liouville-von Neumann equation [T. Zelovich et al., J. Chem. Theory Comput. 10(8), 2927-2941 (2014)] for electronic transport calculations in molecular junctions is presented. The single driving rate, appearing as a fitting parameter in the original methodology, is replaced by a set of state-dependent broadening factors applied to the different single-particle lead levels. These broadening factors are extracted explicitly from the self-energy of the corresponding electronic reservoir and are fully transferable to any junction incorporating the same lead model. Furthermore, the performance of the method is demonstrated via tight-binding and extended Hückel calculationsmore » of simple junction models. Our analytic considerations and numerical results indicate that the developed methodology constitutes a rigorous framework for the design of "black-box" algorithms to simulate electron dynamics in open quantum systems out of equilibrium.« less
Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse.
Tallmadge, Rebecca L; Tseng, Chia T; Felippe, M Julia B
2014-10-01
To further studies of neonatal immune responses to pathogens and vaccination, we investigated the dynamics of B lymphocyte development and immunoglobulin (Ig) gene diversity. Previously we demonstrated that equine fetal Ig VDJ sequences exhibit combinatorial and junctional diversity levels comparable to those of adult Ig VDJ sequences. Herein, RACE clones from fetal, neonatal, foal, and adult lymphoid tissue were assessed for Ig lambda light chain combinatorial, junctional, and sequence diversity. Remarkably, more lambda variable genes (IGLV) were used during fetal life than later stages and IGLV gene usage differed significantly with time, in contrast to the Ig heavy chain. Junctional diversity measured by CDR3L length was constant over time. Comparison of Ig lambda transcripts to germline revealed significant increases in nucleotide diversity over time, even during fetal life. These results suggest that the Ig lambda light chain provides an additional dimension of diversity to the equine Ig repertoire. Copyright © 2014 Elsevier Ltd. All rights reserved.
Modulation of Tight Junction Structure and Function by Kinases and Phosphatases Targeting Occludin
Dörfel, Max Johannes; Huber, Otmar
2012-01-01
Tight junctions (TJs) typically represent the most apical contacts in epithelial and endothelial cell layers where they play an essential role in the separation of extracellular or luminal spaces from underlying tissues in the body. Depending on the protein composition, TJs define the barrier characteristics and in addition maintain cell polarity. Two major families of integral membrane proteins form the typical TJ strand network, the tight junction-associated MARVEL protein (TAMP) family members occludin, tricellulin, and MarvelD3 as well as a specific set of claudins. Occludin was the first identified member of these tetraspanins and is now widely accepted as a regulator of TJ assembly and function. Therefore, occludin itself has to be tightly regulated. Phosphorylation of occludin appears to be of central importance in this context. Here we want to summarize current knowledge on the kinases and phosphatases directly modifying occludin, and their role in the regulation of TJ structure, function, and dynamics. PMID:22315516
Nonadiabatic Josephson current pumping by chiral microwave irradiation
NASA Astrophysics Data System (ADS)
Venitucci, B.; Feinberg, D.; Mélin, R.; Douçot, B.
2018-05-01
Irradiating a Josephson junction with microwaves can operate not only on the amplitude but also on the phase of the Josephson current. This requires breaking time-inversion symmetry, which is achieved by introducing a phase lapse between the microwave components acting on the two sides of the junction. General symmetry arguments and the solution of a specific single-level quantum dot model show that this induces chirality in the Cooper pair dynamics due to the topology of the Andreev bound-state wave function. Another essential condition is to break electron-hole symmetry within the junction. A shift of the current-phase relation is obtained, which is controllable in sign and amplitude with the microwave phase and an electrostatic gate, thus producing a "chiral" Josephson transistor. The dot model is solved in the infinite-gap limit by Floquet theory and in the general case with Keldysh nonequilibrium Green's functions. The chiral current is nonadiabatic: it is extremal and changes sign close to resonant chiral transitions between the Andreev bound states.
Connecting Dissipation and Phase Slips in a Josephson Junction between Fermionic Superfluids.
Burchianti, A; Scazza, F; Amico, A; Valtolina, G; Seman, J A; Fort, C; Zaccanti, M; Inguscio, M; Roati, G
2018-01-12
We study the emergence of dissipation in an atomic Josephson junction between weakly coupled superfluid Fermi gases. We find that vortex-induced phase slippage is the dominant microscopic source of dissipation across the Bose-Einstein condensate-Bardeen-Cooper-Schrieffer crossover. We explore different dynamical regimes by tuning the bias chemical potential between the two superfluid reservoirs. For small excitations, we observe dissipation and phase coherence to coexist, with a resistive current followed by well-defined Josephson oscillations. We link the junction transport properties to the phase-slippage mechanism, finding that vortex nucleation is primarily responsible for the observed trends of conductance and critical current. For large excitations, we observe the irreversible loss of coherence between the two superfluids, and transport cannot be described only within an uncorrelated phase-slip picture. Our findings open new directions for investigating the interplay between dissipative and superfluid transport in strongly correlated Fermi systems, and general concepts in out-of-equilibrium quantum systems.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zelovich, Tamar; Hansen, Thorsten; Liu, Zhen-Fei
A parameter-free version of the recently developed driven Liouville-von Neumann equation [T. Zelovich et al., J. Chem. Theory Comput. 10(8), 2927-2941 (2014)] for electronic transport calculations in molecular junctions is presented. The single driving rate, appearing as a fitting parameter in the original methodology, is replaced by a set of state-dependent broadening factors applied to the different single-particle lead levels. These broadening factors are extracted explicitly from the self-energy of the corresponding electronic reservoir and are fully transferable to any junction incorporating the same lead model. Furthermore, the performance of the method is demonstrated via tight-binding and extended Hückel calculationsmore » of simple junction models. Our analytic considerations and numerical results indicate that the developed methodology constitutes a rigorous framework for the design of "black-box" algorithms to simulate electron dynamics in open quantum systems out of equilibrium.« less
NASA Astrophysics Data System (ADS)
Nguyen, Huu Chuong; Szyja, Bartłomiej M.; Doltsinis, Nikos L.
2014-09-01
Density functional theory (DFT) based molecular dynamics simulations have been performed of a 1,4-benzenedithiol molecule attached to two gold electrodes. To model the mechanical manipulation in typical break junction and atomic force microscopy experiments, the distance between two electrodes was incrementally increased up to the rupture point. For each pulling distance, the electric conductance was calculated using the DFT nonequilibrium Green's-function approach for a statistically relevant sample of configurations extracted from the simulation. With increasing mechanical strain, the formation of monoatomic gold wires is observed. The conductance decreases by three orders of magnitude as the initial twofold coordination of the thiol sulfur to the gold is reduced to a single S-Au bond at each electrode and the order in the electrodes is destroyed. Independent of the pulling distance, the conductance was found to fluctuate by at least two orders of magnitude depending on the instantaneous junction geometry.
Mouse rods signal through gap junctions with cones.
Asteriti, Sabrina; Gargini, Claudia; Cangiano, Lorenzo
2014-01-01
Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod-cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod-cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001.
Desforges, Bénédicte; Curmi, Patrick A.; Bounedjah, Ouissame; Nakib, Samir; Hamon, Loic; De Bandt, Jean-Pascal; Pastré, David
2013-01-01
In the organism, quiescent epithelial cells have the potential to resume cycling as a result of various stimuli, including wound healing or oxidative stress. Because quiescent cells have a low polyamine level, resuming their growth requires an increase of their intracellular polyamine levels via de novo polyamine synthesis or their uptake from plasma. Another alternative, explored here, is an intercellular exchange with polyamine-rich cycling cells via gap junctions. We show that polyamines promote gap junction communication between proliferating cells by promoting dynamical microtubule plus ends at the cell periphery and thus allow polyamine exchange between cells. In this way, cycling cells favor regrowth in adjacent cells deprived of polyamines. In addition, intercellular interactions mediated by polyamines can coordinate the translational response to oxidative stress through the formation of stress granules. Some putative in vivo consequences of polyamine-mediated intercellular interactions are also discussed regarding cancer invasiveness and tissue regeneration. PMID:23515223
Mouse rods signal through gap junctions with cones
Asteriti, Sabrina; Gargini, Claudia; Cangiano, Lorenzo
2014-01-01
Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod–cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod–cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001 PMID:24399457
Connecting Dissipation and Phase Slips in a Josephson Junction between Fermionic Superfluids
NASA Astrophysics Data System (ADS)
Burchianti, A.; Scazza, F.; Amico, A.; Valtolina, G.; Seman, J. A.; Fort, C.; Zaccanti, M.; Inguscio, M.; Roati, G.
2018-01-01
We study the emergence of dissipation in an atomic Josephson junction between weakly coupled superfluid Fermi gases. We find that vortex-induced phase slippage is the dominant microscopic source of dissipation across the Bose-Einstein condensate-Bardeen-Cooper-Schrieffer crossover. We explore different dynamical regimes by tuning the bias chemical potential between the two superfluid reservoirs. For small excitations, we observe dissipation and phase coherence to coexist, with a resistive current followed by well-defined Josephson oscillations. We link the junction transport properties to the phase-slippage mechanism, finding that vortex nucleation is primarily responsible for the observed trends of conductance and critical current. For large excitations, we observe the irreversible loss of coherence between the two superfluids, and transport cannot be described only within an uncorrelated phase-slip picture. Our findings open new directions for investigating the interplay between dissipative and superfluid transport in strongly correlated Fermi systems, and general concepts in out-of-equilibrium quantum systems.
Lee, Han Sol; Choi, Kyunghee; Kim, Jin Sung; Yu, Sanghyuck; Ko, Kyeong Rok; Im, Seongil
2017-05-10
We report the fabrication of hybrid PN junction diode and complementary (CMOS) inverters, where 2D p-type MoTe 2 and n-type thin film InGaZnO (IGZO) are coupled for each device process. IGZO thin film was initially patterned by conventional photolithography either for n-type material in a PN diode or for n-channel of top-gate field-effect transistors (FET) in CMOS inverter. The hybrid PN junction diode shows a good ideality factor of 1.57 and quite a high ON/OFF rectification ratio of ∼3 × 10 4 . Under photons, our hybrid PN diode appeared somewhat stable only responding to high-energy photons of blue and ultraviolet. Our 2D nanosheet-oxide film hybrid CMOS inverter exhibits voltage gains as high as ∼40 at 5 V, low power consumption less than around a few nW at 1 V, and ∼200 μs switching dynamics.
NASA Astrophysics Data System (ADS)
Li, Chunhua; Lv, Dashuai; Zhang, Lei; Yang, Feng; Wang, Cunxin; Su, Jiguo; Zhang, Yang
2016-07-01
Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regions between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.
Regulation and impairments of dynamic desmosome and corneodesmosome remodeling.
Kitajima, Yasuo
2013-04-30
Desmosomes and corneodesmosomes are the most important adhering junctions to provide strength for the epidermal sheet structure made of living keratinocytes and enucleated corneocytes, respectively. These junctions are connected directly with transmembrane desmosomal cadherins, desmogleins (Dsgs) and desmocollins (Dscs), mainly Dsg1/Dsc1 and Dsg3/Dsc3 in desmosomes and Dsg1/Dsc1 with corneodesmosin in corneodesmosomes. Dsgs and Dscs are associated with several proteins at their inner cytoplasmic domains to anchor keratin intermediate filaments. Desmosomes are not static, but dynamic units that undergo regular remodeling to allow for keratinocyte outward-migration in the epidermis. Recently, two mutually-reversible desmosomal adhesion states have been recognized, i.e., "stable hyper-adhesion (Ca 2+ -independent)" and "dynamic weak-adhesion (Ca 2+ -dependent)". A remarkable impairment of this remodeling is observed in pemphigus vulgaris (an autoimmune blistering disease), caused by anti-Dsg3 antibodies, generating a weak-adhesion desmosome state. Immediately after formation, corneodesmosomes normally commit to degradation, which is complicatedly regulated by proteolytic cleavage of their respective extracellular portion(s), via kallikrein-regulated peptidases and cathepsins. This proteolytic activity is in turn controlled by a variety of inhibitory agents, including protease inhibitors, cholesterol sulfate, and an acidic gradient. The impairment of protease control causes keratinization disorders. This review focuses on the dynamic regulation of desmosomes and corneodesmosomes in relation to keratinization disorders.
DOE Office of Scientific and Technical Information (OSTI.GOV)
J. M. Capron
2008-05-30
The 100-F-44:2 waste site is a steel pipeline that was discovered in a junction box during confirmatory sampling of the 100-F-26:4 pipeline from December 2004 through January 2005. The 100-F-44:2 pipeline feeds into the 100-F-26:4 subsite vitrified clay pipe (VCP) process sewer pipeline from the 108-F Biology Laboratory at the junction box. In accordance with this evaluation, the confirmatory sampling results support a reclassification of this site to No Action. The current site conditions achieve the remedial action objectives and the corresponding remedial action goals established in the Remaining Sites ROD. The results of confirmatory sampling show that residual contaminantmore » concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also demonstrate that residual contaminant concentrations are protective of groundwater and the Columbia River.« less
Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus.
Jiang, Ming; Li, Haiyan; Zhang, Yongchun; Yang, Ying; Lu, Rong; Liu, Kuancan; Lin, Sijie; Lan, Xiaopeng; Wang, Haikun; Wu, Han; Zhu, Jian; Zhou, Zhongren; Xu, Jianming; Lee, Dong-Kee; Zhang, Lanjing; Lee, Yuan-Cho; Yuan, Jingsong; Abrams, Julian A; Wang, Timothy C; Sepulveda, Antonia R; Wu, Qi; Chen, Huaiyong; Sun, Xin; She, Junjun; Chen, Xiaoxin; Que, Jianwen
2017-10-26
In several organ systems, the transitional zone between different types of epithelium is a hotspot for pre-neoplastic metaplasia and malignancy, but the cells of origin for these metaplastic epithelia and subsequent malignancies remain unknown. In the case of Barrett's oesophagus, intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells. On the basis of a number of experimental models, several alternative cell types have been proposed as the source of this metaplasia but in all cases the evidence is inconclusive: no model completely mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells. Here we describe a transitional columnar epithelium with distinct basal progenitor cells (p63 + KRT5 + KRT7 + ) at the squamous-columnar junction of the upper gastrointestinal tract in a mouse model. We use multiple models and lineage tracing strategies to show that this squamous-columnar junction basal cell population serves as a source of progenitors for the transitional epithelium. On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues (including the anorectal junction) as well as in the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (believed to be a precursor of Barrett's oesophagus) are both characterized by the expansion of the transitional basal progenitor cells. Our findings reveal a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63 + KRT5 + KRT7 + basal cells in this zone are the cells of origin for multi-layered epithelium and Barrett's oesophagus.
Efficient encoding of motion is mediated by gap junctions in the fly visual system.
Wang, Siwei; Borst, Alexander; Zaslavsky, Noga; Tishby, Naftali; Segev, Idan
2017-12-01
Understanding the computational implications of specific synaptic connectivity patterns is a fundamental goal in neuroscience. In particular, the computational role of ubiquitous electrical synapses operating via gap junctions remains elusive. In the fly visual system, the cells in the vertical-system network, which play a key role in visual processing, primarily connect to each other via axonal gap junctions. This network therefore provides a unique opportunity to explore the functional role of gap junctions in sensory information processing. Our information theoretical analysis of a realistic VS network model shows that within 10 ms following the onset of the visual input, the presence of axonal gap junctions enables the VS system to efficiently encode the axis of rotation, θ, of the fly's ego motion. This encoding efficiency, measured in bits, is near-optimal with respect to the physical limits of performance determined by the statistical structure of the visual input itself. The VS network is known to be connected to downstream pathways via a subset of triplets of the vertical system cells; we found that because of the axonal gap junctions, the efficiency of this subpopulation in encoding θ is superior to that of the whole vertical system network and is robust to a wide range of signal to noise ratios. We further demonstrate that this efficient encoding of motion by this subpopulation is necessary for the fly's visually guided behavior, such as banked turns in evasive maneuvers. Because gap junctions are formed among the axons of the vertical system cells, they only impact the system's readout, while maintaining the dendritic input intact, suggesting that the computational principles implemented by neural circuitries may be much richer than previously appreciated based on point neuron models. Our study provides new insights as to how specific network connectivity leads to efficient encoding of sensory stimuli.
NASA Astrophysics Data System (ADS)
Koren, Gad; Lee, Patrick A.
2016-11-01
Pairs fluctuation supercurrents and inverse lifetimes in the pseudogap regime are reported. These were measured on epitaxial c-axis junctions of the cuprates, with a PrBa2Cu3O7-δ barrier sandwiched in between two YBa2Cu3O7-δ or doped YBa2Cu3Oy electrodes, with or without magnetic fields parallel to the a-b planes. All junctions had a Tc(high) ≈85 -90 K and a Tc(low) ≈50 -55 K electrodes, allowing us to study pairs fluctuation supercurrents and inverse lifetimes in between these two temperatures. In junctions with a pseudogap electrode under zero field, an excess current due to pair fluctuations was observed which persisted at temperatures above Tc(low) , in the pseudogap regime, and up to about Tc(high) . No such excess current was observed in junctions without an electrode with a pseudogap. The measured conductance spectra at temperatures above Tc(low) were fitted using a modified fluctuations model by Scalapino [Phys. Rev. Lett. 24, 1052 (1970), 10.1103/PhysRevLett.24.1052] of a junction with a serial resistance. We found that in the pseudogap regime, the conductance vs voltage consists of a narrow peak sitting on top of a very broad peak. This yielded two distinct pairs fluctuation lifetimes in the pseudogap electrode which differ by an order of magnitude up to about Tc(high) . Under in-plane fields, these two lifetime values remain separated in two distinct groups, which varied with increasing field moderately. We also found that detection of Amperian pairing [Phys. Rev. X 4, 031017 (2014), 10.1103/PhysRevX.4.031017] in our cuprate junctions is not feasible, due to Josephson vortices penetration into the superconducting electrodes which drove the necessary field above the depairing field.
Controlling dynamical entanglement in a Josephson tunneling junction
NASA Astrophysics Data System (ADS)
Ziegler, K.
2017-12-01
We analyze the evolution of an entangled many-body state in a Josephson tunneling junction and its dependence on the number of bosons and interaction strength. A N00N state, which is a superposition of two complementary Fock states, appears in the evolution with sufficient probability only for a moderate many-body interaction on an intermediate time scale. This time scale is inversely proportional to the tunneling rate. Many-body interaction strongly supports entanglement: The probability for creating an entangled state decays exponentially with the number of particles without many-body interaction, whereas it decays only like the inverse square root of the number of particles in the presence of many-body interaction.
Juncture flow improvement for wing/pylon configurations by using CFD methodology
NASA Technical Reports Server (NTRS)
Gea, Lie-Mine; Chyu, Wei J.; Stortz, Michael W.; Chow, Chuen-Yen
1993-01-01
Transonic flow field around a fighter wing/pylon configuration was simulated by using an implicit upwinding Navier-Stokes flow solver (F3D) and overset grid technology (Chimera). Flow separation and local shocks near the wing/pylon junction were observed in flight and predicted by numerical calculations. A new pylon/fairing shape was proposed to improve the flow quality. Based on numerical results, the size of separation area is significantly reduced and the onset of separation is delayed farther downstream. A smoother pressure gradient is also obtained near the junction area. This paper demonstrates that computational fluid dynamics (CFD) methodology can be used as a practical tool for aircraft design.
Theory of the Bloch oscillating transistor
NASA Astrophysics Data System (ADS)
Hassel, J.; Seppä, H.
2005-01-01
The Bloch oscillating transistor (BOT) is a device in which single electron current through a normal tunnel junction enhances Cooper pair current in a mesoscopic Josephson junction, leading to signal amplification. In this article we develop a theory in which the BOT dynamics is described as a two-level system. The theory is used to predict current-voltage characteristics and small-signal response. The transition from stable operation into the hysteretic regime is studied. By identifying the two-level switching noise as the main source of fluctuations, the expressions for equivalent noise sources and the noise temperature are derived. The validity of the model is tested by comparing the results with simulations and experiments.
Miyahara, Satoshi; Saito, Mitsumasa; Kanemaru, Takaaki; Villanueva, Sharon Y A M; Gloriani, Nina G; Yoshida, Shin-ichi
2014-01-01
Weil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by pathogenic Leptospira remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of Weil's disease. In this work, we obtained three-dimensional images of infected hamster livers using scanning electron microscope together with freeze-cracking and cross-cutting methods for sample preparation. The images displayed the corkscrew-shaped bacteria, which infiltrated the Disse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and γ-glutamyl transpeptidase levels increased slightly, but not significantly. We also found in ex vivo experiments that pathogenic, but not non-pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1 h after co-incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection. PMID:24945433
AlInAsSb for GaSb-based multi-junction solar cells
NASA Astrophysics Data System (ADS)
Tournet, J.; Rouillard, Y.; Tournié, E.
2018-02-01
Bandgap engineering, by means of alloying or inserting nanostructures, is the bedrock of high efficiency photovoltaics. III-V quaternary alloys in particular enable bandgap tailoring of a multi-junction subcell while conserving a single lattice parameter. Among the possible candidates, AlInAsSb could in theory reach the widest range of bandgap energies while being lattice-matched to InP or GaSb. Although these material systems are still emerging photovoltaic segments, they do offer advantages for multi-junction design. GaSbbased structures in particular can make use of highly efficient GaSb/InAs tunnel junctions to connect the subcells. There has been only little information concerning GaSb-lattice matched AlInAsSb in the literature. The alloy's miscibility gap can be circumvented by the use of non-equilibrium techniques. Nevertheless, appropriate growth conditions remain to be found in order to produce a stable alloy. Furthermore, the abnormally low bandgap energies reported for the material need to be confirmed and interpreted with a multi-junction perspective. In this work, we propose a tandem structure made of an AlInAsSb top cell and a GaSb bottom cell. An epitaxy study of the AlInAsSb alloy lattice-matched to GaSb was first performed. The subcells were then grown and processed. The GaSb subcell yielded an efficiency of 5.9% under 1 sun and the tandem cell is under optimization. Preliminary results are presented in this document.
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.
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..
Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction.
Cohen, Daniel J; Gloerich, Martijn; Nelson, W James
2016-12-20
Epithelial monolayers undergo self-healing when wounded. During healing, cells collectively migrate into the wound site, and the converging tissue fronts collide and form a stable interface. To heal, migrating tissues must form cell-cell adhesions and reorganize from the front-rear polarity characteristic of cell migration to the apical-basal polarity of an epithelium. However, identifying the "stop signal" that induces colliding tissues to cease migrating and heal remains an open question. Epithelial cells form integrin-based adhesions to the basal extracellular matrix (ECM) and E-cadherin-mediated cell-cell adhesions on the orthogonal, lateral surfaces between cells. Current biological tools have been unable to probe this multicellular 3D interface to determine the stop signal. We addressed this problem by developing a unique biointerface that mimicked the 3D organization of epithelial cell adhesions. This "minimal tissue mimic" (MTM) comprised a basal ECM substrate and a vertical surface coated with purified extracellular domain of E-cadherin, and was designed for collision with the healing edge of an epithelial monolayer. Three-dimensional imaging showed that adhesions formed between cells, and the E-cadherin-coated MTM resembled the morphology and dynamics of native epithelial cell-cell junctions and induced the same polarity transition that occurs during epithelial self-healing. These results indicate that E-cadherin presented in the proper 3D context constitutes a minimum essential stop signal to induce self-healing. That the Ecad:Fc MTM stably integrated into an epithelial tissue and reduced migration at the interface suggests that this biointerface is a complimentary approach to existing tissue-material interfaces.
Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction
Cohen, Daniel J.; Gloerich, Martijn; Nelson, W. James
2016-01-01
Epithelial monolayers undergo self-healing when wounded. During healing, cells collectively migrate into the wound site, and the converging tissue fronts collide and form a stable interface. To heal, migrating tissues must form cell–cell adhesions and reorganize from the front-rear polarity characteristic of cell migration to the apical-basal polarity of an epithelium. However, identifying the "stop signal" that induces colliding tissues to cease migrating and heal remains an open question. Epithelial cells form integrin-based adhesions to the basal extracellular matrix (ECM) and E-cadherin–mediated cell–cell adhesions on the orthogonal, lateral surfaces between cells. Current biological tools have been unable to probe this multicellular 3D interface to determine the stop signal. We addressed this problem by developing a unique biointerface that mimicked the 3D organization of epithelial cell adhesions. This "minimal tissue mimic" (MTM) comprised a basal ECM substrate and a vertical surface coated with purified extracellular domain of E-cadherin, and was designed for collision with the healing edge of an epithelial monolayer. Three-dimensional imaging showed that adhesions formed between cells, and the E-cadherin-coated MTM resembled the morphology and dynamics of native epithelial cell–cell junctions and induced the same polarity transition that occurs during epithelial self-healing. These results indicate that E-cadherin presented in the proper 3D context constitutes a minimum essential stop signal to induce self-healing. That the Ecad:Fc MTM stably integrated into an epithelial tissue and reduced migration at the interface suggests that this biointerface is a complimentary approach to existing tissue–material interfaces. PMID:27930308
Strike-slip tectonics during rift linkage
NASA Astrophysics Data System (ADS)
Pagli, C.; Yun, S. H.; Ebinger, C.; Keir, D.; Wang, H.
2017-12-01
The kinematics of triple junction linkage and the initiation of transforms in magmatic rifts remain debated. Strain patterns from the Afar triple junction provide tests of current models of how rifts grow to link in area of incipient oceanic spreading. Here we present a combined analysis of seismicity, InSAR and GPS derived strain rate maps to reveal that the plate boundary deformation in Afar is accommodated primarily by extensional tectonics in the Red Sea and Gulf of Aden rifts, and does not require large rotations about vertical axes (bookshelf faulting). Additionally, models of stress changes and seismicity induced by recent dykes in one sector of the Afar triple junction provide poor fit to the observed strike-slip earthquakes. Instead we explain these patterns as rift-perpendicular shearing at the tips of spreading rifts where extensional strains terminate against less stretched lithosphere. Our results demonstrate that rift-perpendicular strike-slip faulting between rift segments achieves plate boundary linkage during incipient seafloor spreading.
Electronic transport through Al/InN nanowire/Al junctions
Lu, Tzu -Ming; Wang, George T.; Pan, Wei; ...
2016-02-10
We report non-linear electronic transport measurement of Al/Si-doped n-type InN nanowire/Al junctions performed at T = 0.3 K, below the superconducting transition temperature of the Al electrodes. The proximity effect is observed in these devices through a strong dip in resistance at zero bias. In addition to the resistance dip at zero bias, several resistance peaks can be identified at bias voltages above the superconducting gap of the electrodes, while no resistance dip is observed at the superconducting gap. The resistance peaks disappear as the Al electrodes turn normal beyond the critical magnetic field except one which remains visible atmore » fields several times higher than critical magnetic field. An unexpected non-monotonic magnetic field dependence of the peak position is observed. As a result, we discuss the physical origin of these observations and propose that the resistance peaks could be the McMillan-Rowell oscillations arising from different closed paths localized near different regions of the junctions.« less
NASA Astrophysics Data System (ADS)
Picot, Florent; Gueydan, Antoine; Hug, Éric
2017-10-01
Lap joining configuration for Friction Stir Welding process is a methodology mostly dedicated to heterogeneous bonding. This welding technology was applied to join pure titanium with pure aluminum by varying the rotation speed and the movement speed of the tool. Regardless of the process parameters, it was found that the maximum strength of the junction remains almost constant. Microstructural observations by means of Scanning Electron Microscopy and Energy Dispersive Spectrometry analysis enable to describe the interfacial join and reveal asymmetric Cold Lap Defects on the sides of the junction. Chemical analysis shows the presence of one exclusive intermetallic compound through the interface identified as TiAl3. This compound is responsible of the crack spreading of the junction during the mechanical loading. The original version of this article supplied to AIP Publishing contained an accidental inversion of the authors, names. An updated version of this article, with the authors names formatted correctly was published on 20 October 2017.
Giant electrode effect on tunnelling electroresistance in ferroelectric tunnel junctions.
Soni, Rohit; Petraru, Adrian; Meuffels, Paul; Vavra, Ondrej; Ziegler, Martin; Kim, Seong Keun; Jeong, Doo Seok; Pertsev, Nikolay A; Kohlstedt, Hermann
2014-11-17
Among recently discovered ferroelectricity-related phenomena, the tunnelling electroresistance (TER) effect in ferroelectric tunnel junctions (FTJs) has been attracting rapidly increasing attention owing to the emerging possibilities of non-volatile memory, logic and neuromorphic computing applications of these quantum nanostructures. Despite recent advances in experimental and theoretical studies of FTJs, many questions concerning their electrical behaviour still remain open. In particular, the role of ferroelectric/electrode interfaces and the separation of the ferroelectric-driven TER effect from electrochemical ('redox'-based) resistance-switching effects have to be clarified. Here we report the results of a comprehensive study of epitaxial junctions comprising BaTiO(3) barrier, La(0.7)Sr(0.3)MnO(3) bottom electrode and Au or Cu top electrodes. Our results demonstrate a giant electrode effect on the TER of these asymmetric FTJs. The revealed phenomena are attributed to the microscopic interfacial effect of ferroelectric origin, which is supported by the observation of redox-based resistance switching at much higher voltages.
ERIC Educational Resources Information Center
Clarke, John
1970-01-01
Discusses the theory of the Josephson Effect, the derivation of the Josephson voltage-frequency relation, and methods of measuring the fundamental constatn ratio e/h. Various types of Josephson junctions are described. The impact of the measurement of e/h upin the fundamental constants and quantum electro-dynamics is briefly discussed.…
The Nature of Dynamic Arteriolar Vasoreactivity: A Mini-Review and A classification Scheme
1993-06-08
small veins. In this videomicroscopy study we always examined a junction of a true transverse (TR) and a true terminal (TE) arteriole within the muscle...by LDF), comparisons of vascular wall behavior were made from intravital videomicroscopy records. Vasoreactive behavior of the microvessels was
Epidural varix at the cervicothoracic junction: unusual cause of quadriplegia: a case report.
Bapat, Mihir; Metkar, Umesh
2006-02-01
A case report describing an unusual incident of quadriplegia in a young adult male caused by an epidural varix at the cervicothoracic junction. To report an unusual case of quadriplegia caused by an epidural varix at the cervicothoracic junction. Epidural varices are dilated tortuous elongated veins inside the central canal. In degenerative spinal stenosis, these varices are a result of venous stagnation and contribute to the pathogenesis of radicular pain. In the absence of stenosis, primary varicosities develop as a result of dynamic obstruction to venous outflow during spinal movements. A primary epidural varix can produce neurologic deficit similar to a space occupying lesion within the spinal canal. The myeloradiculopathy is of a slow progressive nature. A young man presented with an acute onset flaccid quadriplegia in the absence of significant trauma. Magnetic resonance imaging revealed an extradural space occupying lesion at the cervicothoracic junction that was diagnosed as an isolated epidural varix during surgery. No neurologic recovery occurred. Postoperative magnetic resonance imaging revealed a syrinx in the cervicothoracic cord. In the absence of other precipitating factors, the cord injury was attributed to the epidural varix. A temporary impedance to the venous outflow with the increase in the venous pressure has been hypothesized as the mechanism of cord injury.
Pang, Zunyu; Li, Ming; Yu, Dongshuai; Yan, Zhang; Liu, Xinyi; Ji, Xinglai; Yang, Yang; Hu, Jiansheng; Luo, Kaijun
2015-09-01
Insect cellular immune responses include encapsulation, nodule formation, and phagocytosis. Hemichannels and gap junctions are involved in these cellular actions. Innexins (Inxs: analogous to the vertebrate connexins) form hemichannels and gap junctions, but the molecular mechanisms underlying their biology is still unclear. In this article, we reported a steady-state level of Inxs (SpliInxs) in hemocytes of Spodoptera litura, which formed nonfunctional hemichannels on the cell surface to maintain normal metabolism. We also reported that two innnexins (SpliInx2 and SpliInx3) were expressed significantly higher in hemocytes compared to other tissues, suggesting that they play important roles in hemocytes. Amino acid analysis found that two cysteine residues in two extracellular loops provided the capability for SpliInx2 and SpliInx3 hemichannels to dock into gap junctions. Western blotting demonstrated that both extracellular and intracellular loops of SpliInx3 and the extracellular loops of SpliInx2 might undergo posttranslational modification during the formation of a steady-state hemichannel. During hemichannel formation, SpliInx2 presented as one isoform, while SpliInx3 presented as three isoforms. These results provide fundamental knowledge for further study of how steady-state levels of SpliInxs are dynamically adjusted to perform cellular immune responses under immune challenge. © 2015 Wiley Periodicals, Inc.
NASA Astrophysics Data System (ADS)
Cansever, H.; Narkowicz, R.; Lenz, K.; Fowley, C.; Ramasubramanian, L.; Yildirim, O.; Niesen, A.; Huebner, T.; Reiss, G.; Lindner, J.; Fassbender, J.; Deac, A. M.
2018-06-01
Similar to electrical currents flowing through magnetic multilayers, thermal gradients applied across the barrier of a magnetic tunnel junction may induce pure spin-currents and generate ‘thermal’ spin-transfer torques large enough to induce magnetization dynamics in the free layer. In this study, we describe a novel experimental approach to observe spin-transfer torques induced by thermal gradients in magnetic multilayers by studying their ferromagnetic resonance response in microwave cavities. Utilizing this approach allows for measuring the magnetization dynamics on micron/nano-sized samples in open-circuit conditions, i.e. without the need of electrical contacts. We performed first experiments on magnetic tunnel junctions patterned into 6 × 9 µm2 ellipses from Co2FeAl/MgO/CoFeB stacks. We conducted microresonator ferromagnetic resonance (FMR) under focused laser illumination to induce thermal gradients in the layer stack and compared them to measurements in which the sample was globally heated from the backside of the substrate. Moreover, we carried out broadband FMR measurements under global heating conditions on the same extended films the microstructures were later on prepared from. The results clearly demonstrate the effect of thermal spin-torque on the FMR response and thus show that the microresonator approach is well suited to investigate thermal spin-transfer-driven processes for small temperatures gradients, far below the gradients required for magnetic switching.
Segmentation and Quantitative Analysis of Epithelial Tissues.
Aigouy, Benoit; Umetsu, Daiki; Eaton, Suzanne
2016-01-01
Epithelia are tissues that regulate exchanges with the environment. They are very dynamic and can acquire virtually any shape; at the cellular level, they are composed of cells tightly connected by junctions. Most often epithelia are amenable to live imaging; however, the large number of cells composing an epithelium and the absence of informatics tools dedicated to epithelial analysis largely prevented tissue scale studies. Here we present Tissue Analyzer, a free tool that can be used to segment and analyze epithelial cells and monitor tissue dynamics.
Conductive atomic force microscopy measurements of nanopillar magnetic tunnel junctions
NASA Astrophysics Data System (ADS)
Evarts, E. R.; Hogg, C.; Bain, J. A.; Majetich, S. A.
2009-03-01
Magnetic tunnel junctions have been studied extensively for their magnetoresistance and potential uses in magnetic logic and data storage devices, but little is known about how their performance will scale with size. Here we examined the electronic behavior of 12 nm diameter magnetic tunnel junctions fabricated by a novel nanomasking process. Scanning electron microscopy images indicated feature diameter of 12 nm, and atomic force microscopy showed a height of 5 nm suggesting that unmasked regions have been milled on average to the oxide barrier layer, and areas should have the remnants of the free layer exposed with no remaining nanoparticle. Electrical contact was made to individual nanopillars using a doped-diamond-coated atomic force microscopy probe with a 40 nm radius of curvature at the tip. Off pillar we observed a resistance of 8.1 x 10^5 φ, while on pillar we found a resistance of 2.85 x 10^6 φ. Based on the RA product for this film, 120 φ-μm^2, a 12 nm diameter cylinder with perfect contact would have a resistance of 1.06 x 10^6 φ. The larger experimental value is consistent with a smaller contact area due to damaging the pillar during the ion milling process. The magnetoresistance characteristics of these magnetic tunnel junctions will be discussed.
Vespa, Alisa; Darmon, Alison J; Turner, Christopher E; D'Souza, Sudhir J A; Dagnino, Lina
2003-03-28
Integrin complexes are necessary for proper proliferation and differentiation of epidermal keratinocytes. Differentiation of these cells is accompanied by down-regulation of integrins and focal adhesions as well as formation of intercellular adherens junctions through E-cadherin homodimerization. A central component of integrin adhesion complexes is integrin-linked kinase (ILK), which can induce loss of E-cadherin expression and epithelial-mesenchymal transformation when ectopically expressed in intestinal and mammary epithelia. In cultured primary mouse keratinocytes, we find that ILK protein levels are independent of integrin expression and signaling, since they remain constant during Ca(2+)-induced differentiation. In contrast, keratinocyte differentiation is accompanied by marked reduction in kinase activity in ILK immunoprecipitates and altered ILK subcellular distribution. Specifically, ILK distributes in close apposition to actin fibers along intercellular junctions in differentiated but not in undifferentiated keratinocytes. ILK localization to cell-cell borders occurs independently of integrin signaling and requires Ca(2+) as well as an intact actin cytoskeleton. Further, and in contrast to what is observed in other epithelial cells, ILK overexpression in differentiated keratinocytes does not promote E-cadherin down-regulation and epithelial-mesenchymal transition. Thus, novel tissue-specific mechanisms control the formation of ILK complexes associated with cell-cell junctions in differentiating murine epidermal keratinocytes.
Schneider, Nils-Lasse; Stengl, Monika
2006-03-01
The temporal organization of physiological and behavioral states is controlled by circadian clocks in apparently all eukaryotic organisms. In the cockroach Leucophaea maderae lesion and transplantation studies located the circadian pacemaker in the accessory medulla (AMe). The AMe is densely innervated by gamma-aminobutyric acid (GABA)-immunoreactive and peptidergic neurons, among them the pigment-dispersing factor immunoreactive circadian pacemaker candidates. The large majority of cells of the cockroach AMe spike regularly and synchronously in the gamma frequency range of 25-70 Hz as a result of synaptic and nonsynaptic coupling. Although GABAergic coupling forms assemblies of phase-locked cells, in the absence of synaptic release the cells remain synchronized but fire now at a stable phase difference. To determine whether these coupling mechanisms of AMe neurons, which are independent of synaptic release, are based on electrical synapses between the circadian pacemaker cells the gap-junction blockers halothane, octanol, and carbenoxolone were used in the presence and absence of synaptic transmission. Here, we show that different populations of AMe neurons appear to be coupled by gap junctions to maintain synchrony at a stable phase difference. This synchronization by gap junctions is a prerequisite to phase-locked assembly formation by synaptic interactions and to synchronous gamma-type action potential oscillations within the circadian clock.
Focal adhesion kinase is a regulator of F-actin dynamics
Li, Stephen YT; Mruk, Dolores D; Cheng, C Yan
2013-01-01
During spermatogenesis, spermatogonia (2n, diploid) undergo a series of mitotic divisions as well as differentiation to become spermatocytes, which enter meiosis I to be followed by meiosis II to form round spermatids (1n, haploid), and then differentiate into spermatozoa (1n, haploid) via spermiogenesis. These events take place in the epithelium of the seminiferous tubule, involving extensive junction restructuring at the Sertoli-Sertoli and Sertoli-germ cell interface to allow the transport of developing germ cells across the epithelium. Although structural aspects of these cell-cell junctions have been studied, the underlying mechanism(s) that governs these events has yet to be explored. Earlier studies have shown that a non-receptor protein tyrosine kinase known as focal adhesion kinase (FAK) is a likely regulator of these events due to the stage-specific and spatiotemporal expression of its various phosphorylated/activated forms at the testis-specific anchoring junctions in the testis, as well as its association with actin regulatory proteins. Recent studies have shown that FAK, in particular its two activated phosphorylated forms p-FAK-Tyr407 and p-FAK-Tyr397, are crucial regulators in modulating junction restructuring at the Sertoli cell-cell interface at the blood-testis barrier (BTB) known as the basal ectoplasmic specialization (basal ES), as well as at the Sertoli-spermatid interface called apical ES during spermiogenesis via its effects on the filamentous (F)-actin organization at the ES. We herein summarize and critically evaluate the current knowledge regarding the physiological significance of FAK in regulating BTB and apical ES dynamics by governing the conversion of actin filaments at the ES from a “bundled” to a “de-bundled/branched” configuration and vice versa. We also provide a molecular model on the role of FAK in regulating these events based on the latest findings in the field. PMID:24381802
Nanoscale patterning controls inorganic-membrane interface structure
NASA Astrophysics Data System (ADS)
Almquist, Benjamin D.; Verma, Piyush; Cai, Wei; Melosh, Nicholas A.
2011-02-01
The ability to non-destructively integrate inorganic structures into or through biological membranes is essential to realizing full bio-inorganic integration, including arrayed on-chip patch-clamps, drug delivery, and biosensors. Here we explore the role of nanoscale patterning on the strength of biomembrane-inorganic interfaces. AFM measurements show that inorganic probes functionalized with hydrophobic bands with thicknesses complimentary to the hydrophobic lipid bilayer core exhibit strong attachment in the bilayer. As hydrophobic band thickness increases to 2-3 times the bilayer core the interfacial strength decreases, comparable to homogeneously hydrophobic probes. Analytical calculations and molecular dynamics simulations predict a transition between a `fused' interface and a `T-junction' that matches the experimental results, showing lipid disorder and defect formation for thicker bands. These results show that matching biological length scales leads to more intimate bio-inorganic junctions, enabling rational design of non-destructive membrane interfaces.The ability to non-destructively integrate inorganic structures into or through biological membranes is essential to realizing full bio-inorganic integration, including arrayed on-chip patch-clamps, drug delivery, and biosensors. Here we explore the role of nanoscale patterning on the strength of biomembrane-inorganic interfaces. AFM measurements show that inorganic probes functionalized with hydrophobic bands with thicknesses complimentary to the hydrophobic lipid bilayer core exhibit strong attachment in the bilayer. As hydrophobic band thickness increases to 2-3 times the bilayer core the interfacial strength decreases, comparable to homogeneously hydrophobic probes. Analytical calculations and molecular dynamics simulations predict a transition between a `fused' interface and a `T-junction' that matches the experimental results, showing lipid disorder and defect formation for thicker bands. These results show that matching biological length scales leads to more intimate bio-inorganic junctions, enabling rational design of non-destructive membrane interfaces. Electronic supplementary information (ESI) available: Breakthrough rate as a function of force plots for 5 nm, 10 nm and ∞-probes.. See DOI: 10.1039/c0nr00486c
Vortex motion and dynamical states in Josephson arrays
NASA Astrophysics Data System (ADS)
Trias, Enrique
Underdamped Josephson junction arrays are used as model systems to study novel nonlinear effects. A combination of experiments, numerical simulations, and analytical analysis is used to probe different nonlinear behavior such as intrinsic localized modes, resonances in fully frustrated arrays, Meissner-like states, and vortex ratchets. Circuit models of Josephson networks are also developed, and applied to the design and measurement of parallel array oscillators. Ladder arrays have been used for an experimental study of intrinsic localized modes, or discrete breathers. Measurements of breather stability indicate that the maximum allowable bias current is proportional to the array depinning current while the minimum current is related to a junction retrapping mechanism. This retrapping instability usually leads to the formation of multi-site breathers. Collisions between the two nonlinear excitations in ladder arrays, discrete breathers and vortices, have also been numerically investigated. Discrete breathers act as pinning centers to vortex motion and the collisions can be modeled by an energy barrier activation process. When vortices are thermally induced over this barrier, a two-site breather is created. Experiments also reveal remarkable similarities among the do current-voltage characteristics of several kinds of square and triangular arrays, where two resonant voltages are observed. Simulations indicate that at full frustration a dynamical checkerboard state underlies these similarities. For such a traveling solution, the governing equations of the arrays are reduced to three coupled pendulum equations that have two characteristic resonant frequencies. Finally, a kink ratchet potential has been designed using a parallel array of Josephson junctions with alternating cell inductances and junctions areas. Experiments show that the depinning current depends on the direction of the applied current. Other properties of the depinning current versus applied field, such as a long period and a lack of reflection symmetry, have been observed and explained analytically. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139- 4307. Ph. 617-253-5668; Fax 617-253-1690.)
Zhu, Jing; Wang, Lei; Xu, Xiaowen; Wei, Haiping; Jiang, Wei
2016-04-05
Here, we explored a modular strategy for rational design of nuclease-responsive three-way junctions (TWJs) and fabricated a dynamic DNA device in a "plug-and-play" fashion. First, inactivated TWJs were designed, which contained three functional domains: the inaccessible toehold and branch migration domains, the specific sites of nucleases, and the auxiliary complementary sequence. The actions of different nucleases on their specific sites in TWJs caused the close proximity of the same toehold and branch migration domains, resulting in the activation of the TWJs and the formation of a universal trigger for the subsequent dynamic assembly. Second, two hairpins (H1 and H2) were introduced, which could coexist in a metastable state, initially to act as the components for the dynamic assembly. Once the trigger initiated the opening of H1 via TWJs-driven strand displacement, the cascade hybridization of hairpins immediately switched on, resulting in the formation of the concatemers of H1/H2 complex appending numerous integrated G-quadruplexes, which were used to obtain label-free signal readout. The inherent modularity of this design allowed us to fabricate a flexible DNA dynamic device and detect multiple nucleases through altering the recognition pattern slightly. Taking uracil-DNA glycosylase and CpG methyltransferase M.SssI as models, we successfully realized the butt joint between the uracil-DNA glycosylase and M.SssI recognition events and the dynamic assembly process. Furthermore, we achieved ultrasensitive assay of nuclease activity and the inhibitor screening. The DNA device proposed here will offer an adaptive and flexible tool for clinical diagnosis and anticancer drug discovery.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Chunhua; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 45108; Lv, Dashuai
Riboswitches are noncoding mRNA segments that can regulate the gene expression via altering their structures in response to specific metabolite binding. We proposed a coarse-grained Gaussian network model (GNM) to examine the unfolding and folding dynamics of adenosine deaminase (add) A-riboswitch upon the adenine dissociation, in which the RNA is modeled by a nucleotide chain with interaction networks formed by connecting adjoining atomic contacts. It was shown that the adenine binding is critical to the folding of the add A-riboswitch while the removal of the ligand can result in drastic increase of the thermodynamic fluctuations especially in the junction regionsmore » between helix domains. Under the assumption that the native contacts with the highest thermodynamic fluctuations break first, the iterative GNM simulations showed that the unfolding process of the adenine-free add A-riboswitch starts with the denature of the terminal helix stem, followed by the loops and junctions involving ligand binding pocket, and then the central helix domains. Despite the simplified coarse-grained modeling, the unfolding dynamics and pathways are shown in close agreement with the results from atomic-level MD simulations and the NMR and single-molecule force spectroscopy experiments. Overall, the study demonstrates a new avenue to investigate the binding and folding dynamics of add A-riboswitch molecule which can be readily extended for other RNA molecules.« less
Lallouette, Jules; De Pittà, Maurizio; Ben-Jacob, Eshel; Berry, Hugues
2014-01-01
Traditionally, astrocytes have been considered to couple via gap-junctions into a syncytium with only rudimentary spatial organization. However, this view is challenged by growing experimental evidence that astrocytes organize as a proper gap-junction mediated network with more complex region-dependent properties. On the other hand, the propagation range of intercellular calcium waves (ICW) within astrocyte populations is as well highly variable, depending on the brain region considered. This suggests that the variability of the topology of gap-junction couplings could play a role in the variability of the ICW propagation range. Since this hypothesis is very difficult to investigate with current experimental approaches, we explore it here using a biophysically realistic model of three-dimensional astrocyte networks in which we varied the topology of the astrocyte network, while keeping intracellular properties and spatial cell distribution and density constant. Computer simulations of the model suggest that changing the topology of the network is indeed sufficient to reproduce the distinct ranges of ICW propagation reported experimentally. Unexpectedly, our simulations also predict that sparse connectivity and restriction of gap-junction couplings to short distances should favor propagation while long–distance or dense connectivity should impair it. Altogether, our results provide support to recent experimental findings that point toward a significant functional role of the organization of gap-junction couplings into proper astroglial networks. Dynamic control of this topology by neurons and signaling molecules could thus constitute a new type of regulation of neuron-glia and glia-glia interactions. PMID:24795613
Dynamics and Manipulation of Nanomagnets
NASA Astrophysics Data System (ADS)
Cai, Liufei
This thesis presents my work on the spin dynamics of nanomagnets and investigates the possibility of manipulating nanomagnets by various means. Most of the work has been published. Some has been submitted for publication. The structure of this thesis is as follows. In Chapter 1, I present the theory of manipulation of a nanomagnet by rotating ac fields whose frequency is time dependent. Theory has been developed that maps the problem onto Landau-Zener problem. For the linear frequency sweep the switching phase diagrams are obtained on the amplitude of the ac field and the frequency sweep rate. Switching conditions have been obtained numerically and analytically. For the nonlinear frequency sweep, the optimal time dependence of the frequency is obtained analytically with account of damping that gives the fastest controllable switching of the magnetization. In Chapter 2, interaction between a nanomagnet and a Josephson junction has been studied. The I-V curve of the Josephson junction in the proximity of a nanomagnet shows Shapiro-like steps due to the ac field generated by the precessing magnetic moment. Possibility of switching of the magnetic moment by a time-linear voltage in the Josephson junction is demonstrated. Realization of the optimal switching is suggested that employs two perpendicular Josephson junctions with time-dependent voltage signals. The result is shown to be robust against voltage noises. Quantum-mechanical coupling between the nanomagnet considered as a two-level system and a Josephson junction has been studied and quantum oscillations of the populations of the spin states have been computed. In Chapter 3, the switching dynamics of a nanomagnet embedded in a torsional oscillator that serves as a conducting wire for a spin current has been investigated. Generalized Slonczewski's equation is derived. The coupling of the nanomagnet, the torsional oscillator and the spin current generates a number of interesting phenomena. The mechanically-assisted magnetization switching is studied, in which the magnetization can be reversed by tilting the torsional oscillator. The effect of the torsional oscillator on the switching of the magnetization in the presence of spin-polarized current is computed. Combined effects of the spin current and a mechanical kick of the torsional oscillator have been studied. In Chapter 4, skyrmion dynamics and interaction of the skyrmion with an electron have been studied. Corrections to the spin texture of the skyrmion due to the crystal lattice have been computed. Due to the lattice effects the skyrmion collapses in clean ferromagnetic and anti-ferromagnetic materials. The lifetime of the skyrmion has been computed numerically and compared with analytical theory. In doped anti-ferromagnetic materials the weak attraction between a skyrmion and an electron may generate a bound state. In Chapter 5, experimental results of the NIST group on magnetic multilayer microcantilevers have been analyzed. Theoretical framework has been suggested that explains the observed strong damping effect of the platinum layer on the mechanical oscillations of Py-Pt bilayer cantilevers. The strong spin-orbit coupling of platinum is shown to impede the motion of the domain wall in permalloy and to dramatically increase the damping of the cantilever motion.
Mukherjee, Debraj; Pressman, Barry D; Krakow, Deborah; Rimoin, David L; Danielpour, Moise
2014-09-01
Achondroplasia may be associated with compression at the cervicomedullary junction. Determining which patients are at greatest risk for neurological complications of cervicomedullary compression can be difficult. In the current study the authors reviewed their records to determine the incidence and clinical significance of dynamic cervicomedullary stenosis and obstruction of CSF flow along with surgical outcomes following posterior fossa decompression. The authors reviewed 34 consecutive cases involving symptomatic children with achondroplasia undergoing cervicomedullary decompression performed by a single surgeon over 11 years. Of these patients, 29 had undergone preoperative dynamic MRI of the cervicomedullary junction with cine (cinema) CSF flow studies; 13 of these patients underwent postoperative dynamic MRI studies. Clinical outcomes included changes in polysomnography, head circumference percentile, and fontanel characteristics. Radiographic outcomes included changes in dynamic spinal cord diameter, improvement in CSF flow at the foramen magnum, and change in the Evans ratio. Patients were predominantly female, with a mean age at presentation of 6.6 years and mean follow-up of 3.7 years (range 1-10 years). All patients had moderate to excellent improvement in postoperative polysomnography, slight decrease in average head circumference percentile (from 46.9th percentile to 45.7th percentile), and no subjective worsening of fontanel characteristics. The Evans ratio decreased by 2%, spinal cord diameter increased an average of 3.1 mm, 5.2 mm, and 0.2 mm in the neutral, flexed, and extended positions, respectively, and CSF flow improved qualitatively in all 3 positions. There were no postoperative infections, CSF leaks, or other major complications. None of the patients undergoing initial foramen magnum decompression performed at our medical center required reoperation. Patients with achondroplasia and symptomatic cervicomedullary compression have increased risk of dynamic stenosis at the foramen magnum evident upon dynamic cine MRI. Operative decompression may be offered with low risk of complications or need for reoperation.
Direct single-molecule dynamic detection of chemical reactions.
Guan, Jianxin; Jia, Chuancheng; Li, Yanwei; Liu, Zitong; Wang, Jinying; Yang, Zhongyue; Gu, Chunhui; Su, Dingkai; Houk, Kendall N; Zhang, Deqing; Guo, Xuefeng
2018-02-01
Single-molecule detection can reveal time trajectories and reaction pathways of individual intermediates/transition states in chemical reactions and biological processes, which is of fundamental importance to elucidate their intrinsic mechanisms. We present a reliable, label-free single-molecule approach that allows us to directly explore the dynamic process of basic chemical reactions at the single-event level by using stable graphene-molecule single-molecule junctions. These junctions are constructed by covalently connecting a single molecule with a 9-fluorenone center to nanogapped graphene electrodes. For the first time, real-time single-molecule electrical measurements unambiguously show reproducible large-amplitude two-level fluctuations that are highly dependent on solvent environments in a nucleophilic addition reaction of hydroxylamine to a carbonyl group. Both theoretical simulations and ensemble experiments prove that this observation originates from the reversible transition between the reactant and a new intermediate state within a time scale of a few microseconds. These investigations open up a new route that is able to be immediately applied to probe fast single-molecule physics or biophysics with high time resolution, making an important contribution to broad fields beyond reaction chemistry.
Twist1-positive epithelial cells retain adhesive and proliferative capacity throughout dissemination
Shamir, Eliah R.; Coutinho, Kester; Georgess, Dan; Auer, Manfred
2016-01-01
ABSTRACT Dissemination is the process by which cells detach and migrate away from a multicellular tissue. The epithelial-to-mesenchymal transition (EMT) conceptualizes dissemination in a stepwise fashion, with downregulation of E-cadherin leading to loss of intercellular junctions, induction of motility, and then escape from the epithelium. This gain of migratory activity is proposed to be mutually exclusive with proliferation. We previously developed a dissemination assay based on inducible expression of the transcription factor Twist1 and here utilize it to characterize the timing and dynamics of intercellular adhesion, proliferation and migration during dissemination. Surprisingly, Twist1+ epithelium displayed extensive intercellular junctions, and Twist1– luminal epithelial cells could still adhere to disseminating Twist1+ cells. Although proteolysis and proliferation were both observed throughout dissemination, neither was absolutely required. Finally, Twist1+ cells exhibited a hybrid migration mode; their morphology and nuclear deformation were characteristic of amoeboid cells, whereas their dynamic protrusive activity, pericellular proteolysis and migration speeds were more typical of mesenchymal cells. Our data reveal that epithelial cells can disseminate while retaining competence to adhere and proliferate. PMID:27402962
Boattail juncture shaping for spin-stabilized rounds in supersonic flight
NASA Astrophysics Data System (ADS)
Jiajan, W.; Chue, R. S. M.; Nguyen, T.; Yu, S. C. M.
2015-03-01
In this paper, the effects of boattail junction shaping on aerodynamic drag and stability of supersonic spin-stabilized rounds are investigated using computational fluid dynamics. For a generic round body comprising of a secant-ogive nose, a cylindrical body and a conical boattail, the shaping technique was achieved by adding a convex surface of varying degrees of radius of curvature to the junction between the cylindrical body and the boattail. It was shown through numerical simulations that this shaping technique can provide a reduction in aerodynamic drag of up to 5.4 % without destabilizing the round bodies when the radius of curvature is less than 8.8 times the diameter of the cylindrical body. The more gradual change of the flow characteristics, e.g., the pressure over the convex surface, was identified as the main reason for the drag reduction. A unique aspect of the current work is that stability is treated as an integral part of the performance assessment. It was also found that the dynamic instability encountered at large radii of curvature is due to the Magnus effects.
NASA Astrophysics Data System (ADS)
Sarkar, Jayanta; Puska, Antti; Hassel, Juha; Hakonen, Pertti
2014-03-01
Bloch oscillating transistor (BOT) is mesoscopic current amplier based on a combination of a Josephson junction or a squid connected with a large resistor and a NIS junction. We have studied the dynamics of BOT near the bifurcation threshold. This is an important feature for an amplifier as this can be utilized to improve its performance characteristics. We have measured the I - V characteristics of the BOT with different base currents (IB) over a wide range of Josephson coupling energies (EJ) . The current gain (β) is found to be increasing with increasing IB and eventually diverging. We have found a record large β = 50 in our experiment. In order to determine the common mode rejection ratio (CMRR) of a differential pair BOT we have used two BOTs fabricated on the same chip. The common mode port is connected to the bases of the two BOTs and fed with varying voltages; simultaneously emitter currents of the two BOTs are recorded. In our experiment we found a 20dB of CMRR.
NASA Astrophysics Data System (ADS)
Neufeld, Zoltan
Recent studies have demonstrated that mechanical forces can lead to novel mechanisms of pattern formation such as clustering and oscillations in contractile systems. We investigate how contractile forces in mechanically active media can affect bistable front propagation. We found that contraction regulates the front speed or can fully suppress its propagation in space to create a static localized zone. We demonstrate how the interplay between biochemical signaling through positive feedback, combined with diffusion on the cell membrane and mechanical forces generated in the actomyosin cortex, can determine the spatial distribution of RhoA signaling at cell-cell junctions. The dynamical mechanism relies on the balance between a propagating bistable signal that is opposed by an advective flow generated by an actomyosin stress gradient. Experimental observations on the behaviour of the system when contractility is inhibited are in qualitative agreement with the predictions of the model. In collaboration with: Zoltan Neufeld, Guillermo A. Gomez, and Alpha S. Yap, University of Queensland, Brisbane, Australia
Direct single-molecule dynamic detection of chemical reactions
Guan, Jianxin; Jia, Chuancheng; Li, Yanwei; Liu, Zitong; Wang, Jinying; Yang, Zhongyue; Gu, Chunhui; Su, Dingkai; Houk, Kendall N.; Zhang, Deqing; Guo, Xuefeng
2018-01-01
Single-molecule detection can reveal time trajectories and reaction pathways of individual intermediates/transition states in chemical reactions and biological processes, which is of fundamental importance to elucidate their intrinsic mechanisms. We present a reliable, label-free single-molecule approach that allows us to directly explore the dynamic process of basic chemical reactions at the single-event level by using stable graphene-molecule single-molecule junctions. These junctions are constructed by covalently connecting a single molecule with a 9-fluorenone center to nanogapped graphene electrodes. For the first time, real-time single-molecule electrical measurements unambiguously show reproducible large-amplitude two-level fluctuations that are highly dependent on solvent environments in a nucleophilic addition reaction of hydroxylamine to a carbonyl group. Both theoretical simulations and ensemble experiments prove that this observation originates from the reversible transition between the reactant and a new intermediate state within a time scale of a few microseconds. These investigations open up a new route that is able to be immediately applied to probe fast single-molecule physics or biophysics with high time resolution, making an important contribution to broad fields beyond reaction chemistry. PMID:29487914
NASA Astrophysics Data System (ADS)
Shi, Shengjie; Ou, Yongxi; Aradhya, S. V.; Ralph, D. C.; Buhrman, R. A.
2018-01-01
Future applications of spin-orbit torque will require new mechanisms to improve the efficiency of switching nanoscale magnetic tunnel junctions (MTJs), while also controlling the magnetic dynamics to achieve fast nanosecond-scale performance with low-write-error rates. Here, we demonstrate a strategy to simultaneously enhance the interfacial magnetic anisotropy energy and suppress interfacial spin-memory loss by introducing subatomic and monatomic layers of Hf at the top and bottom interfaces of the ferromagnetic free layer of an in-plane magnetized three-terminal MTJ device. When combined with a β -W spin Hall channel that generates spin-orbit torque, the cumulative effect is a switching current density of 5.4 ×106 A /cm2 .
Influence of Contact Angle Boundary Condition on CFD Simulation of T-Junction
NASA Astrophysics Data System (ADS)
Arias, S.; Montlaur, A.
2018-03-01
In this work, we study the influence of the contact angle boundary condition on 3D CFD simulations of the bubble generation process occurring in a capillary T-junction. Numerical simulations have been performed with the commercial Computational Fluid Dynamics solver ANSYS Fluent v15.0.7. Experimental results serve as a reference to validate numerical results for four independent parameters: the bubble generation frequency, volume, velocity and length. CFD simulations accurately reproduce experimental results both from qualitative and quantitative points of view. Numerical results are very sensitive to the gas-liquid-wall contact angle boundary conditions, confirming that this is a fundamental parameter to obtain accurate CFD results for simulations of this kind of problems.
Phase-locking transition in a chirped superconducting Josephson resonator.
Naaman, O; Aumentado, J; Friedland, L; Wurtele, J S; Siddiqi, I
2008-09-12
We observe a sharp threshold for dynamic phase locking in a high-Q transmission line resonator embedded with a Josephson tunnel junction, and driven with a purely ac, chirped microwave signal. When the drive amplitude is below a critical value, which depends on the chirp rate and is sensitive to the junction critical current I0, the resonator is only excited near its linear resonance frequency. For a larger amplitude, the resonator phase locks to the chirped drive and its amplitude grows until a deterministic maximum is reached. Near threshold, the oscillator evolves smoothly in one of two diverging trajectories, providing a way to discriminate small changes in I0 with a nonswitching detector, with potential applications in quantum state measurement.
Mechanism for Si–Si Bond Rupture in Single Molecule Junctions
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Haixing; Kim, Nathaniel T.; Su, Timothy A.
The stability of chemical bonds can be studied experimentally by rupturing single molecule junctions under applied voltage. Here, we compare voltage-induced bond rupture in two Si–Si backbones: one has no alternate conductive pathway whereas the other contains an additional naphthyl pathway in parallel to the Si–Si bond. We show that in contrast to the first system, the second can conduct through the naphthyl group when the Si–Si bond is ruptured using an applied voltage. We investigate this voltage induced Si–Si bond rupture by ab initio density functional theory calculations and molecular dynamics simulations that ultimately demonstrate that the excitation ofmore » molecular vibrational modes by tunneling electrons leads to homolytic Si–Si bond rupture.« less
Mechanism for Si-Si Bond Rupture in Single Molecule Junctions.
Li, Haixing; Kim, Nathaniel T; Su, Timothy A; Steigerwald, Michael L; Nuckolls, Colin; Darancet, Pierre; Leighton, James L; Venkataraman, Latha
2016-12-14
The stability of chemical bonds can be studied experimentally by rupturing single molecule junctions under applied voltage. Here, we compare voltage-induced bond rupture in two Si-Si backbones: one has no alternate conductive pathway whereas the other contains an additional naphthyl pathway in parallel to the Si-Si bond. We show that in contrast to the first system, the second can conduct through the naphthyl group when the Si-Si bond is ruptured using an applied voltage. We investigate this voltage induced Si-Si bond rupture by ab initio density functional theory calculations and molecular dynamics simulations that ultimately demonstrate that the excitation of molecular vibrational modes by tunneling electrons leads to homolytic Si-Si bond rupture.
Network Characteristics of Collective Chemosensing
NASA Astrophysics Data System (ADS)
Sun, Bo; Duclos, Guillaume; Stone, Howard A.
2013-04-01
The collective chemosensing of nonexcitable mammalian cells involves a biochemical network that features gap junction communications and heterogeneous single cell activities. To understand the integrated multicellular chemosensing, we study the calcium dynamics of micropatterned fibroblast cell colonies in response to adenosine triphosphate (ATP) stimulation. We find that the cross-correlation function between the responses of individual cells decays with topological distance as a power law for large colonies and much faster for smaller colonies. Furthermore, the strongly correlated cell pairs tend to form clusters and are more likely to exceed the percolation threshold. At a given topological distance, the cross-correlations exhibit characteristics of Poisson distributions, which allows us to estimate the unitary conductance of a single gap junction which is in good agreement with direct experimental measurements.
Ion bipolar junction transistors
Tybrandt, Klas; Larsson, Karin C.; Richter-Dahlfors, Agneta; Berggren, Magnus
2010-01-01
Dynamic control of chemical microenvironments is essential for continued development in numerous fields of life sciences. Such control could be achieved with active chemical circuits for delivery of ions and biomolecules. As the basis for such circuitry, we report a solid-state ion bipolar junction transistor (IBJT) based on conducting polymers and thin films of anion- and cation-selective membranes. The IBJT is the ionic analogue to the conventional semiconductor BJT and is manufactured using standard microfabrication techniques. Transistor characteristics along with a model describing the principle of operation, in which an anionic base current amplifies a cationic collector current, are presented. By employing the IBJT as a bioelectronic circuit element for delivery of the neurotransmitter acetylcholine, its efficacy in modulating neuronal cell signaling is demonstrated. PMID:20479274
Miyahara, Satoshi; Saito, Mitsumasa; Kanemaru, Takaaki; Villanueva, Sharon Y A M; Gloriani, Nina G; Yoshida, Shin-ichi
2014-08-01
Weil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by pathogenic Leptospira remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of Weil's disease. In this work, we obtained three-dimensional images of infected hamster livers using scanning electron microscope together with freeze-cracking and cross-cutting methods for sample preparation. The images displayed the corkscrew-shaped bacteria, which infiltrated the Disse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and γ-glutamyl transpeptidase levels increased slightly, but not significantly. We also found in ex vivo experiments that pathogenic, but not non-pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1 h after co-incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.
NASA Astrophysics Data System (ADS)
Wen, Yan-Ni; Xia, Ming-Gang; Zhang, Sheng-Li
2016-05-01
By using the VASP, we studied the magnetic and electronic properties of the monolayer lateral hetero-junction WS2-MoS2-nanoribbons (WS2-MoS2-NRs). Our results show that the NRs' edge chirality and width affect significantly its magnetic and electronic properties. The monolayer lateral hetero-junction ZZ-WS2-MoS2-NRs(ZZ: zigzag) exhibitmetallic behavior and have considerable magnetic moment. Their magnetic moments decrease in the order of Nz = 2, 6 and 4 (the width of NRs). While, the magnetic moment decreases with the increased rz (the number of the Mo-S chains, rz ≠ 0 and rz ≠ Nz) at the same width Nz. The NA-AC-WS2-NR (AC: armchair) and NA-AC-WS2-MoS2-NR-1 (the number of the Mo-S chain is 1) show metallic behavior when NA = 3 (the width of NRs). The other monolayer lateral hetero-junction AC-WS2-MoS2-NRs remain the nonmagnetic and semiconductingbehavior as bulk. But they are indirect band-gap except for the NA = 3, rA = 2 (the number of the Mo-S chains) and NA = 7, rA = 0 when NA < 9. However they are direct band-gap when NA ≥ 9. Their lowest and highest band gaps are 0.150 eV and 0.581 eV, respectively. These unique magnetic and electronic properties will provide guidanceon the WS2-MoS2 hetero-junction application in nanodevice.
Yan, Helen H N; Mruk, Dolores D; Cheng, C Yan
2008-01-01
Spermatogenesis that occurs in the seminiferous epithelium of adult mammalian testes is associated with extensive junction restructuring at the Sertoli-Sertoli cell, Sertoli-germ cell, and Sertoli-basement membrane interface. While this morphological phenomenon is known and has been described in great details for decades, the biochemical and molecular changes as well as the mechanisms/signaling pathways that define changes at the cell-cell and cell-matrix interface remain largely unknown until recently. In this chapter, we summarize and discuss findings in the field regarding the coordinated efforts of the anchoring [e.g., adherens junction (AJ), such as basal ectoplasmic specialization (basal ES)] and tight junctions (TJs) that are present in the same microenvironment, such as at the blood-testis barrier (BTB), or at distinctly opposite ends of the Sertoli cell epithelium, such as between apical ectoplasmic specialization (apical ES) in the apical compartment, and the BTB adjacent to the basal compartment of the epithelium. These efforts, in turn, regulate and coordinate different cellular events that occur during the seminiferous epithelial cycle. For instance, the events of spermiation and of preleptotene spermatocyte migration across the BTB both take place concurrently at stage VIII of the epithelial cycle of spermatogenesis. Recent findings suggest that these events are coordinated by protein complexes found at the apical and basal ES and TJ, which are located at different ends of the Sertoli cell epithelium. Besides, we highlight important areas of research that can now be undertaken, and functional studies that can be designed to tackle different issues pertinent to junction restructuring during spermatogenesis.
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.
Nuclear Dynamics at Molecule–Metal Interfaces: A Pseudoparticle Perspective
Galperin, Michael; Nitzan, Abraham
2015-11-20
We discuss nuclear dynamics at molecule-metal interfaces including nonequilibrium molecular junctions. Starting from the many-body states (pseudoparticle) formulation of the molecule-metal system in the molecular vibronic basis, we introduce gradient expansion to reduce the adiabatic nuclear dynamics (that is, nuclear dynamics on a single molecular potential surface) into its semiclassical form while maintaining the effect of the nonadiabatic electronic transitions between different molecular charge states. Finally, this yields a set of equations for the nuclear dynamics in the presence of these nonadiabatic transitions, which reproduce the surface-hopping formulation in the limit of small metal-molecule coupling (where broadening of the molecularmore » energy levels can be disregarded) and Ehrenfest dynamics (motion on the potential of mean force) when information on the different charging states is traced out.« less
Wong, Elissa WP; Lie, Pearl PY; Li, Michelle WM; Mruk, Dolores D; Yan, Helen HN; Mok, Ka-Wai; Mannu, Jayakanthan; Mathur, Premendu P; Lui, Wing-yee; Lee, Will M; Bonanomi, Michele; Silvestrini, Bruno
2011-01-01
The blood-testis barrier (BTB) is a unique ultrastructure in the mammalian testis. Unlike other blood-tissue barriers, such as the blood-brain barrier and the blood-ocular (or blood-retina) barrier which formed by tight junctions (TJ) between endothelial cells of the microvessels, the BTB is constituted by coexisting TJ, basal ectoplasmic specialization (basal ES), desmosomes and gap junctions between adjacent Sertoli cells near the basement membrane of the seminiferous tubule. The BTB also divides the seminiferous epithelium into the apical (or adluminal) and basal compartments so that meiosis I and II and post-meiotic germ cell development can all take place in a specialized microenvironment in the apical compartment behind the BTB. While the unusual anatomical features of the BTB have been known for decades, the physiological function of the coexisting junctions, in particular the desmosome and gap junction, that constitute the BTB was unknown until recently. Based on recently published findings, we critically evaluate the role of the desmosome and gap junction that serve as a signaling platform to coordinate the “opening” and “closing” of the TJ-permeability barrier conferred by TJ and basal ES during the seminiferous epithelial cycle of spermatogenesis. This is made possible by polarity proteins working in concert with nonreceptor protein tyrosine kinases, such as focal adhesion kinase (FAK) and c-Src, at the site to regulate endosome-mediated protein trafficking events (e.g., endocytosis, transcytosis, recycling or protein degradation). These events not only serve to destabilize the existing “old” BTB above preleptotene spermatocytes in transit in “clones” at the BTB, but also contribute to the assembly of “new” BTB below the transiting spermatocytes. Furthermore, hemidesmosomes at the Sertoli cell-basement membrane interface also contribute to the BTB restructuring events at stage VIII of the epithelial cycle. Additionally, the findings that a gap junction at the BTB provides a possible route for the passage of toxicants [e.g., bisphenol A (BPA)] and potential male contraceptives (e.g., adjudin) across the BTB also illustrate that these coexisting junctions, while helpful to maintain the immunological barrier integrity during the transit of spermatocytes, can be the “gateway” to making the BTB so vulnerable to toxicants and/or chemicals, causing male reproductive dysfunction. PMID:22319658
Connexin Communication Compartments and Wound Repair in Epithelial Tissue.
Chanson, Marc; Watanabe, Masakatsu; O'Shaughnessy, Erin M; Zoso, Alice; Martin, Patricia E
2018-05-03
Epithelial tissues line the lumen of tracts and ducts connecting to the external environment. They are critical in forming an interface between the internal and external environment and, following assault from environmental factors and pathogens, they must rapidly repair to maintain cellular homeostasis. These tissue networks, that range from a single cell layer, such as in airway epithelium, to highly stratified and differentiated epithelial surfaces, such as the epidermis, are held together by a junctional nexus of proteins including adherens, tight and gap junctions, often forming unique and localised communication compartments activated for localised tissue repair. This review focuses on the dynamic changes that occur in connexins, the constituent proteins of the intercellular gap junction channel, during wound-healing processes and in localised inflammation, with an emphasis on the lung and skin. Current developments in targeting connexins as corrective therapies to improve wound closure and resolve localised inflammation are also discussed. Finally, we consider the emergence of the zebrafish as a concerted whole-animal model to study, visualise and track the events of wound repair and regeneration in real-time living model systems.
NASA Astrophysics Data System (ADS)
Ji, Xiaochen; Shen, Chao; Wu, Yuanjun; Lu, Jun; Zhao, Jianhua; Zheng, Houzhi
2017-11-01
By biasing a ferromagnetic metal MnGa/10 nm-thick, n-type GaAs quantum well (QW) junction from negative to positive, it is found that its spin dynamics at zero magnetic field is composed of two components with opposite signs. One is excited by a circularly polarized pump beam. The other is induced by ferromagnetic proximity polarization (FPP), which is continuously enhanced as the bias increases towards the positive direction. The time-resolved Kerr rotations have also been measured at a magnetic field of 0.9 Tesla. A phase reversion of Larmor precession is observed as the bias passes through +0.5 V. Following simple quantum mechanics, we become aware of the fact that the transmission and reflection rates of electrons at the interface of MnGa/n-type GaAs QW are enhanced by a factor of ν , which is the attempting frequency of electron onto a ferromagnet/semiconductor interface. That gives a reasonable explanation why the FPP effect in our MnGa/n-type GaAs QW junction is greatly enhanced as biasing it into forward direction.
Proximity coupling in superconductor-graphene heterostructures.
Lee, Gil-Ho; Lee, Hu-Jong
2018-05-01
This review discusses the electronic properties and the prospective research directions of superconductor-graphene heterostructures. The basic electronic properties of graphene are introduced to highlight the unique possibility of combining two seemingly unrelated physics, superconductivity and relativity. We then focus on graphene-based Josephson junctions, one of the most versatile superconducting quantum devices. The various theoretical methods that have been developed to describe graphene Josephson junctions are examined, together with their advantages and limitations, followed by a discussion on the advances in device fabrication and the relevant length scales. The phase-sensitive properties and phase-particle dynamics of graphene Josephson junctions are examined to provide an understanding of the underlying mechanisms of Josephson coupling via graphene. Thereafter, microscopic transport of correlated quasiparticles produced by Andreev reflections at superconducting interfaces and their phase-coherent behaviors are discussed. Quantum phase transitions studied with graphene as an electrostatically tunable 2D platform are reviewed. The interplay between proximity-induced superconductivity and the quantum-Hall phase is discussed as a possible route to study topological superconductivity and non-Abelian physics. Finally, a brief summary on the prospective future research directions is given.
Proximity coupling in superconductor-graphene heterostructures
NASA Astrophysics Data System (ADS)
Lee, Gil-Ho; Lee, Hu-Jong
2018-05-01
This review discusses the electronic properties and the prospective research directions of superconductor-graphene heterostructures. The basic electronic properties of graphene are introduced to highlight the unique possibility of combining two seemingly unrelated physics, superconductivity and relativity. We then focus on graphene-based Josephson junctions, one of the most versatile superconducting quantum devices. The various theoretical methods that have been developed to describe graphene Josephson junctions are examined, together with their advantages and limitations, followed by a discussion on the advances in device fabrication and the relevant length scales. The phase-sensitive properties and phase-particle dynamics of graphene Josephson junctions are examined to provide an understanding of the underlying mechanisms of Josephson coupling via graphene. Thereafter, microscopic transport of correlated quasiparticles produced by Andreev reflections at superconducting interfaces and their phase-coherent behaviors are discussed. Quantum phase transitions studied with graphene as an electrostatically tunable 2D platform are reviewed. The interplay between proximity-induced superconductivity and the quantum-Hall phase is discussed as a possible route to study topological superconductivity and non-Abelian physics. Finally, a brief summary on the prospective future research directions is given.
Remodeling the zonula adherens in response to tension and the role of afadin in this response
Acharya, Bipul R.; Peyret, Grégoire; Fardin, Marc-Antoine; Mège, René-Marc; Ladoux, Benoit; Yap, Alpha S.; Fanning, Alan S.
2016-01-01
Morphogenesis requires dynamic coordination between cell–cell adhesion and the cytoskeleton to allow cells to change shape and move without losing tissue integrity. We used genetic tools and superresolution microscopy in a simple model epithelial cell line to define how the molecular architecture of cell–cell zonula adherens (ZA) is modified in response to elevated contractility, and how these cells maintain tissue integrity. We previously found that depleting zonula occludens 1 (ZO-1) family proteins in MDCK cells induces a highly organized contractile actomyosin array at the ZA. We find that ZO knockdown elevates contractility via a Shroom3/Rho-associated, coiled-coil containing protein kinase (ROCK) pathway. Our data suggest that each bicellular border is an independent contractile unit, with actin cables anchored end-on to cadherin complexes at tricellular junctions. Cells respond to elevated contractility by increasing junctional afadin. Although ZO/afadin knockdown did not prevent contractile array assembly, it dramatically altered cell shape and barrier function in response to elevated contractility. We propose that afadin acts as a robust protein scaffold that maintains ZA architecture at tricellular junctions. PMID:27114502
Kinetic Measurements Reveal Enhanced Protein-Protein Interactions at Intercellular Junctions
Shashikanth, Nitesh; Kisting, Meridith A.; Leckband, Deborah E.
2016-01-01
The binding properties of adhesion proteins are typically quantified from measurements with soluble fragments, under conditions that differ radically from the confined microenvironment of membrane bound proteins in adhesion zones. Using classical cadherin as a model adhesion protein, we tested the postulate that confinement within quasi two-dimensional intercellular gaps exposes weak protein interactions that are not detected in solution binding assays. Micropipette-based measurements of cadherin-mediated, cell-cell binding kinetics identified a unique kinetic signature that reflects both adhesive (trans) bonds between cadherins on opposing cells and lateral (cis) interactions between cadherins on the same cell. In solution, proposed lateral interactions were not detected, even at high cadherin concentrations. Mutations postulated to disrupt lateral cadherin association altered the kinetic signatures, but did not affect the adhesive (trans) binding affinity. Perturbed kinetics further coincided with altered cadherin distributions at junctions, wound healing dynamics, and paracellular permeability. Intercellular binding kinetics thus revealed cadherin interactions that occur within confined, intermembrane gaps but not in solution. Findings further demonstrate the impact of these revealed interactions on the organization and function of intercellular junctions. PMID:27009566
An epidermal plakin that integrates actin and microtubule networks at cellular junctions.
Karakesisoglou, I; Yang, Y; Fuchs, E
2000-04-03
Plakins are cytoskeletal linker proteins initially thought to interact exclusively with intermediate filaments (IFs), but recently were found to associate additionally with actin and microtubule networks. Here, we report on ACF7, a mammalian orthologue of the Drosophila kakapo plakin genetically involved in epidermal-muscle adhesion and neuromuscular junctions. While ACF7/kakapo is divergent from other plakins in its IF-binding domain, it has at least one actin (K(d) = 0.35 microM) and one microtubule (K(d) approximately 6 microM) binding domain. Similar to its fly counterpart, ACF7 is expressed in the epidermis. In well spread epidermal keratinocytes, ACF7 discontinuously decorates the cytoskeleton at the cell periphery, including microtubules (MTs) and actin filaments (AFs) that are aligned in parallel converging at focal contacts. Upon calcium induction of intercellular adhesion, ACF7 and the cytoskeleton reorganize at cell-cell borders but with different kinetics from adherens junctions and desmosomes. Treatments with cytoskeletal depolymerizing drugs reveal that ACF7's cytoskeletal association is dependent upon the microtubule network, but ACF7 also appears to stabilize actin at sites where microtubules and microfilaments meet. We posit that ACF7 may function in microtubule dynamics to facilitate actin-microtubule interactions at the cell periphery and to couple the microtubule network to cellular junctions. These attributes provide a clear explanation for the kakapo mutant phenotype in flies.
NASA Astrophysics Data System (ADS)
Routray, S. R.; Lenka, T. R.
2017-11-01
Now-a-days III-Nitride nanowires with axial (nanodisk) and radial (core/shell/shell-nanowire) junctions are two unique and potential methods for solar energy harvesting adopted by worldwide researchers. In this paper, polarization behavior of GaN/InGaN/GaN junction and its effect on carrier dynamics of nanodisk and CSS-nanowire type solar cells are intensively studied and compared with its planar counterpart by numerical simulations using commercially available Victory TCAD. It is observed that CSS-NW with hexagonal geometrical shapes are robust to detrimental impact of polarization charges and could be good enough to accelerate carrier collection efficiency as compared to nanodisk and planar solar cells. This numerical study provides an innovative aspect of fundamental device physics with respect to polarization charges in CSS-NW and nanodisk type junction towards photovoltaic applications. The internal quantum efficiencies (IQE) are also discussed to evaluate carrier collection mechanisms and recombination losses in each type of junctions of solar cell. Finally, it is interesting to observe a maximum conversion efficiency of 6.46% with 91.6% fill factor from n-GaN/i-In0.1Ga0.9N/p-GaN CSS-nanowire solar cell with an optimized thickness of 180 nm InGaN layer under one Sun AM1.5 illumination.
Tipsmark, C K; Madsen, S S
2012-08-01
Molecular regulation of tight junctions in osmoregulatory epithelia of euryhaline fishes must be extensive during ontogeny and acclimation to salinity changes. In this study, five tight junction proteins were examined in Atlantic salmon (Salmo salar): tight junction associated tricellulin, occludin and claudin-3 isoforms (a, b, c). A survey of tissue distribution in freshwater (FW) salmon showed that tricellulin expression was highest in the intestine. Occludin was detected in tissues with importance for epithelial transport and the order of expression was gill>intestine>kidney. The three claudin-3 isoforms were expressed at highest level in kidney tissue. Transfer of juvenile FW salmon to seawater (SW) elevated intestinal tricellulin and occludin mRNA, and these transcripts were also elevated at the time of best SW-tolerance during the course of smoltification. In the kidney, expression of tricellulin and claudin-3 isoforms was elevated after SW-transfer and tricellulin, occludin, claudin-3a and -3b increased in March before the peak smolt stage. In the gill, none of the examined tight junction proteins were impacted by SW-transfer. The data suggest that expression of tricellulin and occludin is dynamically involved in reorganization of intestinal epithelium and possibly changed paracellular permeability during SW-acclimation. The increased renal tricellulin and claudin-3 expression in SW suggests a role in remodeling of the kidney during SW-acclimation. Copyright © 2012 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Koshelev, Alexei
2013-03-01
Stacks of intrinsic Josephson-junctions are realized in mesas fabricated out of layered superconducting single crystals, such as Bi2Sr2CaCu2O8 (BSCCO). Synchronization of phase oscillations in different junctions can be facilitated by the coupling to the internal cavity mode leading to powerful and coherent electromagnetic radiation in the terahertz frequency range. An important characteristic of this radiation is the shape of the emission line. A finite line width appears due to different noise sources leading to phase diffusion. We investigated the intrinsic line shape caused by the thermal noise for a mesa fabricated on the top of a BSCCO single crystal. In the ideal case of fully synchronized stack the finite line width is coming from two main contributions, the quasiparticle-current noise inside the mesa and the fluctuating radiation in the base crystal. We compute both contributions and conclude that for realistic mesa's parameters the second mechanism typically dominates. The role of the cavity quality factor in the emission line spectrum is clarified. Analytical results were verified by numerical simulations. In real mesa structures part of the stack may not be synchronized and chaotic dynamics of unsynchronized junctions may determine the real line width. Work supported by UChicago Argonne, LLC, under contract No. DE-AC02-06CH11357.
Magnetic field oscillations of the critical current in long ballistic graphene Josephson junctions
NASA Astrophysics Data System (ADS)
Rakyta, Péter; Kormányos, Andor; Cserti, József
2016-06-01
We study the Josephson current in long ballistic superconductor-monolayer graphene-superconductor junctions. As a first step, we have developed an efficient computational approach to calculate the Josephson current in tight-binding systems. This approach can be particularly useful in the long-junction limit, which has hitherto attracted less theoretical interest but has recently become experimentally relevant. We use this computational approach to study the dependence of the critical current on the junction geometry, doping level, and an applied perpendicular magnetic field B . In zero magnetic field we find a good qualitative agreement with the recent experiment of M. Ben Shalom et al. [Nat. Phys. 12, 318 (2016), 10.1038/nphys3592] for the length dependence of the critical current. For highly doped samples our numerical calculations show a broad agreement with the results of the quasiclassical formalism. In this case the critical current exhibits Fraunhofer-like oscillations as a function of B . However, for lower doping levels, where the cyclotron orbit becomes comparable to the characteristic geometrical length scales of the system, deviations from the results of the quasiclassical formalism appear. We argue that due to the exceptional tunability and long mean free path of graphene systems a new regime can be explored where geometrical and dynamical effects are equally important to understand the magnetic field dependence of the critical current.
Silicon Carbide Diodes Characterization at High Temperature and Comparison With Silicon Devices
NASA Technical Reports Server (NTRS)
Lebron-Velilla, Ramon C.; Schwarze, Gene E.; Gardner, Brent G.; Adams, Jerry D., Jr.
2004-01-01
Commercially available silicon carbide (SiC) Schottky diodes from different manufacturers rated at 200, 300, 600, and 1200 V, were electrically tested and characterized as a function of temperature up to 300 C. Electrical tests included both steady state and dynamic tests. Steady state tests produced forward and reverse I-V characteristic curves. Transient tests evaluated the switching performance of the diodes in either a hard-switched DC to DC buck converter or a half-bridge boost converter. For evaluation and comparison purposes, the same tests were performed with current state-of-the-art ultra fast silicon (Si) pn-junction diodes of similar ratings and also a Si Schottky diode. The comparisons made were forward voltage drop at rated current, reverse current at rated voltage, and turn-off peak reverse recovery current and reverse recovery time. In addition, efficiency measurements were taken for the buck DC to DC converter using both the SiC Schottky diodes and the Si pn-junction diodes at different temperatures and frequencies. The test results showed that at high temperature, the forward voltage drop for SiC Schottky diodes is higher than the forward drop of the ultra fast Si pn-junction diodes. As the temperature increased, the forward voltage drop of the SiC Schottky increased while for the ultra fast Si pn-junction diodes, the forward voltage drop decreased as temperature increased. For the elevated temperature steady state reverse voltage tests, the SiC Schottky diodes showed low leakage current at their rated voltage. Likewise, for the transient tests, the SiC Schottky diodes displayed low reverse recovery currents over the range of temperatures tested. Conversely, the Si pn-junction diodes showed increasing peak reverse current values and reverse recovery times with increasing temperature. Efficiency measurements in the DC to DC buck converter showed the advantage of the SiC Schottky diodes over the ultra fast Si pn-junction diodes, especially at the higher temperatures and higher frequencies.
Congenital axis dysmorphism in a medieval skeleton : …secunda a vertendo epistropheus….
Travan, Luciana; Saccheri, Paola; Toso, Francesco; Crivellato, Enrico
2013-05-01
We describe here the axis dysmorphism that we observed in the skeletal remains of a human child dug up from a fifteenth century cemetery located in north-eastern Italy. This bone defect is discussed in the light of pertinent literature. We performed macroscopical examination and CT scan analysis of the axis. Axis structure was remarkably asymmetric. Whilst the left half exhibited normal morphology, the right one was smaller than normal, and its lateral articular surface showed horizontal orientation. In addition, the odontoid process appeared leftward deviated and displayed a supplementary articular-like facet situated on the right side of its surface. These findings suggest a diagnosis of unilateral irregular segmentation of atlas and axis, a rare dysmorphism dependent upon disturbances of notochordal development in early embryonic life. Likewise other malformations of the craniovertebral junction, this axis defect may alter the delicate mechanisms of upper neck movements and cause a complex series of clinical symptoms. This is an emblematic case whereby human skeletal remains may provide valuable information on the anatomical defects of craniovertebral junction.
Could tight junctions regulate the barrier function of the aged skin?
Svoboda, Marek; Bílková, Zuzana; Muthný, Tomáš
2016-03-01
The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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.
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
Autonomous Magnetic Microrobots by Navigating Gates for Multiple Biomolecules Delivery.
Hu, Xinghao; Lim, Byeonghwa; Torati, Sri Ramulu; Ding, Junjia; Novosad, Valentine; Im, Mi-Young; Reddy, Venu; Kim, Kunwoo; Jung, Eunjoo; Shawl, Asif Iqbal; Kim, Eunjoo; Kim, CheolGi
2018-05-08
The precise delivery of biofunctionalized matters is of great interest from the fundamental and applied viewpoints. In spite of significant progress achieved during the last decade, a parallel and automated isolation and manipulation of rare analyte, and their simultaneous on-chip separation and trapping, still remain challenging. Here, a universal micromagnet junction for self-navigating gates of microrobotic particles to deliver the biomolecules to specific sites using a remote magnetic field is described. In the proposed concept, the nonmagnetic gap between the lithographically defined donor and acceptor micromagnets creates a crucial energy barrier to restrict particle gating. It is shown that by carefully designing the geometry of the junctions, it becomes possible to deliver multiple protein-functionalized carriers in high resolution, as well as MCF-7 and THP-1 cells from the mixture, with high fidelity and trap them in individual apartments. Integration of such junctions with magnetophoretic circuitry elements could lead to novel platforms without retrieving for the synchronous digital manipulation of particles/biomolecules in microfluidic multiplex arrays for next-generation biochips. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Rumination syndrome: when the lower oesophageal sphincter rises.
Gourcerol, Guillaume; Dechelotte, Pierre; Ducrotte, Philippe; Leroi, Anne Marie
2011-07-01
Rumination syndrome is an uncommon condition characterised by the self-induced regurgitation from the stomach to the mouth of recently ingested meal that is chewed and reswallowed. Rumination is caused by a voluntary rise in intra-abdominal and intra-gastric pressure leading to the reflux of the gastric content into the oesophagus. However, the precise mechanisms preventing reflux at the gastro-oesophageal junction during the rise in intra-gastric pressure remains unknown. In 5 patients, rumination episodes were monitored using combined multiple intra-luminal impedance monitoring, high resolution manometry, and video-fluoroscopic recording. We showed that the gastro-oesophageal junction moved from the abdominal cavity into the thorax creating a "pseudo-hernia". This occurred at a range of 1.4 ± 0.3 s before the rise in intra-oesophageal pressure and the gastro-oesophageal reflux. This displacement of the gastro-oesophageal junction into thorax, rather than a lower oesophageal sphincter opening, explains the mechanism of voluntary regurgitations occurring during rumination syndrome. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Erosion, transportation and the nature of the Maria
NASA Technical Reports Server (NTRS)
Gold, T.
1971-01-01
Lunar Orbiter and Apollo photographs of the moon and laboratory simulations of a surface transportation mechanism are discussed. Studies of shoulders at junctions of old mountains with flat mare surfaces show that the crater density in the shoulder is lower than that in the neighboring ground. The crisscross pattern is very pronounced on the mountain slope, is on the shoulder in a smaller scale, and is absent on the mare surface. It is concluded that the material forming the shoulders came there as a consequence of a surface transportation mechanism, and that the shoulders reached their present configuration later than the final shaping of the mare surface. Seismic signal transmission and mascon distribution data indicate that the filling of mare basins did not occur in a similar manner. An electrostatic mechanism for surface transportation was studied experimentally by bombarding material with electrons. An electric field resulted which was capable of dislodging and moving grains. It was also found that the junction line between different materials remains sharp, and materials do not mix even when the junction line itself moves.
Current-voltage characteristics of n-AlMgZnO/p-GaN junction diodes
NASA Astrophysics Data System (ADS)
Hsueh, Kuang-Po; Cheng, Po-Wei; Cheng, Yi-Chang; Sheu, Jinn-Kong; Yeh, Yu-Hsiang; Chiu, Hsien-Chin; Wang, Hsiang-Chun
2013-03-01
This study investigates the temperature dependence of the current-voltage (I-V) characteristics of Al-doped MgxZn1-xO/p-GaN junction diodes. Specifically, this study reports the deposition of n-type Al-doped MgxZn1-xO (AMZO) films on p-GaN using a radio-frequency (RF) magnetron sputtering system followed by annealing at 700, 800, 900, and 1000 °C in a nitrogen ambient for 60 seconds, respectively. The AMZO/GaN films were thereafter analyzed using Hall measurement and the x-ray diffraction (XRD) patterns. The XRD results show that the diffraction angles of the annealed AMZO films remain the same as that of GaN without shifting. The n-AMZO/p-GaN diode with 900 °C annealing had the lowest leakage current in forward and reverse bias. However, the leakage current of the diodes did not change significantly with an increase in annealing temperatures. These findings show that the n-AMZO/p-GaN junction diode is feasible for GaN-based heterojunction bipolar transistors (HBTs) and UV light-emitting diodes (LEDs).
Fretting and Corrosion in Modular Shoulder Arthroplasty: A Retrieval Analysis
Panzram, Benjamin
2016-01-01
Tribocorrosion in taper junctions of retrieved anatomic shoulder arthroplasty implants was evaluated. A comparison of the tribocorrosion between cobalt-chromium and titanium alloy stems was conducted and the observations were correlated with the individual's clinical data. Adverse effects caused by metal debris and subsequent elevated serum metal ion levels are frequently reported in total hip arthroplasty. In total shoulder arthroplasty, to date only a small number of retrieval analyses are available and even fewer address the issue of tribocorrosion at the taper junctions. A total of 36 retrieved hemiarthroplasties and total shoulder arthroplasties were assessed using the modified Goldberg score. The prevalence of fretting and corrosion was confirmed in this cohort. Titanium stems seem to be more susceptible to damage caused by tribocorrosion than cobalt-chromium stems. Furthermore, stemless designs offered less tribocorrosion at the taper junction than stemmed designs. A weak correlation between time to revision and increased levels of tribocorrosion was seen. Whether or not tribocorrosion can lead to adverse clinical reactions and causes failure of shoulder arthroplasties remains to be examined. PMID:27433471
Computational Nanotechnology of Materials, Devices, and Machines: Carbon Nanotubes
NASA Technical Reports Server (NTRS)
Srivastava, Deepak; Kwak, Dolhan (Technical Monitor)
2000-01-01
The mechanics and chemistry of carbon nanotubes have relevance for their numerous electronic applications. Mechanical deformations such as bending and twisting affect the nanotube's conductive properties, and at the same time they possess high strength and elasticity. Two principal techniques were utilized including the analysis of large scale classical molecular dynamics on a shared memory architecture machine and a quantum molecular dynamics methodology. In carbon based electronics, nanotubes are used as molecular wires with topological defects which are mediated through various means. Nanotubes can be connected to form junctions.
Computational Nanotechnology of Materials, Electronics and Machines: Carbon Nanotubes
NASA Technical Reports Server (NTRS)
Srivastava, Deepak
2001-01-01
This report presents the goals and research of the Integrated Product Team (IPT) on Devices and Nanotechnology. NASA's needs for this technology are discussed and then related to the research focus of the team. The two areas of focus for technique development are: 1) large scale classical molecular dynamics on a shared memory architecture machine; and 2) quantum molecular dynamics methodology. The areas of focus for research are: 1) nanomechanics/materials; 2) carbon based electronics; 3) BxCyNz composite nanotubes and junctions; 4) nano mechano-electronics; and 5) nano mechano-chemistry.
Li, Jing-Jing; Xing, Shi-Hui; Zhang, Jian; Hong, Hua; Li, Yi-Liang; Dang, Chao; Zhang, Yu-Sheng; Li, Chuo; Fan, Yu-Hua; Yu, Jian; Pei, Zhong; Zeng, Jin-Sheng
2011-11-01
1. Whether damage to the blood-brain barrier (BBB) occurs in remote areas after a focal cortical lesion remains unknown. The present study investigated tight junction-related proteins and tight junction microstructure in the ipsilateral thalamus during the acute stage after middle cerebral artery occlusion (MCAO) and cortical aspiration lesion (CAL) in rats. 2. Thirty-six hypertensive and normotensive rats were subjected to MCAO or CAL; another 18 rats in each group were submitted to sham operation. Zonula Occluden (ZO)-1, occludin and albumin were detected by western blotting 12 and 24 h after surgery. Tight junction microstructure was evaluated using electron microscopy, whereas albumin location in the ipsilateral thalamus was determined using double immunostaining for albumin and occludin or albumin and neuronal nuclei (NeuN) 24 h after surgery. 3. Twenty-four hours after MCAO or CAL, occludin expression was reduced to 78.4% and 81.3%, respectively, compared with control. A reduction in ZO-1 expression in the ipsilateral thalamus (to 79%) was seen only after CAL (P < 0.05). Membrane contact at the tight junction was discontinuous in the ipsilateral thalamus in both MCAO and CAL rats. Albumin levels were 23.2% and 82.5% higher in the ipsilateral thalamus after MCAO and CAL, respectively (P < 0.05). The percentage of the albumin-positive area that coincided with the occludin-positive area in the MCAO and CAL groups was 76.8% and 64.6%, respectively, indicating that albumin was mainly localized around the microvessels. 4. The results of the present study suggest that tight junction integrity decreases during the acute stage in the ipsilateral thalamus after MCAO and CAL in rats. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.
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.
NASA Astrophysics Data System (ADS)
Holmberg, Andreas; Kierkegaard, Axel; Weng, Chenyang
2015-06-01
In this paper, a method for including damping of acoustic energy in regions of strong turbulence is derived for a linearized Navier-Stokes method in the frequency domain. The proposed method is validated and analyzed in 2D only, although the formulation is fully presented in 3D. The result is applied in a study of the linear interaction between the acoustic and the hydrodynamic field in a 2D T-junction, subject to grazing flow at Mach 0.1. Part of the acoustic energy at the upstream edge of the junction is shed as harmonically oscillating disturbances, which are conveyed across the shear layer over the junction, where they interact with the acoustic field. As the acoustic waves travel in regions of strong shear, there is a need to include the interaction between the background turbulence and the acoustic field. For this purpose, the oscillation of the background turbulence Reynold's stress, due to the acoustic field, is modeled using an eddy Newtonian model assumption. The time averaged flow is first solved for using RANS along with a k-ε turbulence model. The spatially varying turbulent eddy viscosity is then added to the spatially invariant kinematic viscosity in the acoustic set of equations. The response of the 2D T-junction to an incident acoustic field is analyzed via a plane wave scattering matrix model, and the result is compared to experimental data for a T-junction of rectangular ducts. A strong improvement in the agreement between calculation and experimental data is found when the modification proposed in this paper is implemented. Discrepancies remaining are likely due to inaccuracies in the selected turbulence model, which is known to produce large errors e.g. for flows with significant rotation, which the grazing flow across the T-junction certainly is. A natural next step is therefore to test the proposed methodology together with more sophisticated turbulence models.
Ultrasensitive mechanical crack-based sensor inspired by the spider sensory system
NASA Astrophysics Data System (ADS)
Kang, Daeshik; Pikhitsa, Peter V.; Choi, Yong Whan; Lee, Chanseok; Shin, Sung Soo; Piao, Linfeng; Park, Byeonghak; Suh, Kahp-Yang; Kim, Tae-Il; Choi, Mansoo
2014-12-01
Recently developed flexible mechanosensors based on inorganic silicon, organic semiconductors, carbon nanotubes, graphene platelets, pressure-sensitive rubber and self-powered devices are highly sensitive and can be applied to human skin. However, the development of a multifunctional sensor satisfying the requirements of ultrahigh mechanosensitivity, flexibility and durability remains a challenge. In nature, spiders sense extremely small variations in mechanical stress using crack-shaped slit organs near their leg joints. Here we demonstrate that sensors based on nanoscale crack junctions and inspired by the geometry of a spider's slit organ can attain ultrahigh sensitivity and serve multiple purposes. The sensors are sensitive to strain (with a gauge factor of over 2,000 in the 0-2 per cent strain range) and vibration (with the ability to detect amplitudes of approximately 10 nanometres). The device is reversible, reproducible, durable and mechanically flexible, and can thus be easily mounted on human skin as an electronic multipixel array. The ultrahigh mechanosensitivity is attributed to the disconnection-reconnection process undergone by the zip-like nanoscale crack junctions under strain or vibration. The proposed theoretical model is consistent with experimental data that we report here. We also demonstrate that sensors based on nanoscale crack junctions are applicable to highly selective speech pattern recognition and the detection of physiological signals. The nanoscale crack junction-based sensory system could be useful in diverse applications requiring ultrahigh displacement sensitivity.
NASA Astrophysics Data System (ADS)
Coburn, Luke; Lopez, Hender; Schouwenaar, Irin-Maya; Yap, Alpha S.; Lobaskin, Vladimir; Gomez, Guillermo A.
2018-03-01
Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood. In this work, we develop a minimal mechanistic model that is able to capture the essential features of epithelial collective responses to injuries. We show that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interfaces as well as contact inhibition of locomotion (CIL) correctly predicts two key properties of epithelial response to injury as: (1) local relaxation of the tissue and (2) collective reorganization involving the extension of cryptic lamellipodia that extend, on average, up to 3 cell diameters from the site of injury and morphometric changes in the basal regions. Our model also suggests that active responses (like the actomyosin purse string and softening of cell-cell junctions) are needed to drive morphometric changes in the apical region. Therefore, our results highlight the importance of the crosstalk between junctional biomechanics, cell substrate adhesion, and CIL, as well as active responses, in guiding the collective rearrangements that are required to preserve the epithelial barrier in response to injury.
McGuire, Jacob D.; Walker, Mary P.; Dusevich, Vladimir; Wang, Yong; Gorski, Jeff P.
2015-01-01
Although mature enamel is predominantly composed of mineral, a previously uncharacterized organic matrix layer remains in the post-eruptive tissue that begins at the dentin enamel junction and extends 200–300 µm towards the outer tooth surface. Identification of the composition of this layer has been hampered by its insolubility; however, we have developed a single step method to isolate the organic enamel matrix relatively intact. After dissociative dissolution of the matrix with SDS and urea, initial characterization by Western blotting and gel zymography indicates the presence of type IV and type VII basement membrane collagens and active matrix metalloproteinase-20. When combined with data from transgenic knockout mice and from human mutations, these data suggest that the enamel organic matrix (EOM) and dentin enamel junction may have a structural and functional relationship with basement membranes, e.g. skin. To clarify this relationship, we hypothesize a “foundation” model which proposes that components of the EOM form a support structure that stabilizes the crystalline enamel layer, and bonds it to the underlying dentin along the dentin enamel junction. Since we have also co-localized an active matrix metalloproteinase to this layer, our hypothesis suggests that, under pathologic conditions, MMP-mediated degradation of the EOM could destabilize the enamel–dentin interface. PMID:25158177
García, Isaac E.; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshimi; Olivero, Pablo; Pérez-Acle, Tomás; González, Carlos; Sáez, Juan C.; Contreras, Jorge E.; Martínez, Agustín D.
2015-01-01
Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like Keratitis Ichthyosis Deafness syndrome (KID). Because in the human skin Cx26 is co-expressed with other connexins, like Cx43 and Cx30, and since KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channels functions remain unknown. In this study we demonstrate that syndromic mutations at the N-terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) show exacerbated hemichannel activity, but nonfunctional gap junction channels; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca2+ overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin. PMID:25625422
Ultrasensitive mechanical crack-based sensor inspired by the spider sensory system.
Kang, Daeshik; Pikhitsa, Peter V; Choi, Yong Whan; Lee, Chanseok; Shin, Sung Soo; Piao, Linfeng; Park, Byeonghak; Suh, Kahp-Yang; Kim, Tae-il; Choi, Mansoo
2014-12-11
Recently developed flexible mechanosensors based on inorganic silicon, organic semiconductors, carbon nanotubes, graphene platelets, pressure-sensitive rubber and self-powered devices are highly sensitive and can be applied to human skin. However, the development of a multifunctional sensor satisfying the requirements of ultrahigh mechanosensitivity, flexibility and durability remains a challenge. In nature, spiders sense extremely small variations in mechanical stress using crack-shaped slit organs near their leg joints. Here we demonstrate that sensors based on nanoscale crack junctions and inspired by the geometry of a spider's slit organ can attain ultrahigh sensitivity and serve multiple purposes. The sensors are sensitive to strain (with a gauge factor of over 2,000 in the 0-2 per cent strain range) and vibration (with the ability to detect amplitudes of approximately 10 nanometres). The device is reversible, reproducible, durable and mechanically flexible, and can thus be easily mounted on human skin as an electronic multipixel array. The ultrahigh mechanosensitivity is attributed to the disconnection-reconnection process undergone by the zip-like nanoscale crack junctions under strain or vibration. The proposed theoretical model is consistent with experimental data that we report here. We also demonstrate that sensors based on nanoscale crack junctions are applicable to highly selective speech pattern recognition and the detection of physiological signals. The nanoscale crack junction-based sensory system could be useful in diverse applications requiring ultrahigh displacement sensitivity.
Yamada, Akio; Irie, Kenji; Fukuhara, Atsunori; Ooshio, Takako; Takai, Yoshimi
2004-09-01
Nectins, Ca(2+)-independent immunoglobulin-like cell adhesion molecules (CAMs), first form cell-cell adhesion where cadherins are recruited, forming adherens junctions (AJs) in epithelial cells and fibroblasts. In addition, nectins recruit claudins, occludin, and junctional adhesion molecules (JAMs) to the apical side of AJs, forming tight junctions (TJs) in epithelial cells. Nectins are associated with these CAMs through peripheral membrane proteins (PMPs), many of which are actin filament-binding proteins. We examined here the roles of the actin cytoskeleton in the association of nectins with other CAMs in MDCK cells stably expressing exogenous nectin-1. The nectin-1-based cell-cell adhesion was formed and maintained irrespective of the presence and absence of the actin filament-disrupting agents, such as cytochalasin D and latrunculin A. In the presence of these agents, only afadin remained at the nectin-1-based cell-cell adhesion sites, whereas E-cadherin and other PMPs at AJs, alpha-catenin, beta-catenin, vinculin, alpha-actinin, ADIP, and LMO7, were not concentrated there. The CAMs at TJs, claudin-1, occludin and JAM-1, or the PMPs at TJs, ZO-1 and MAGI-1, were not concentrated there, either. These results indicate that the actin cytoskeleton is required for the association of the nectin-afadin unit with other CAMs and PMPs at AJs and TJs.
Li, Qisheng; Sodroski, Catherine; Lowey, Brianna; Schweitzer, Cameron J; Cha, Helen; Zhang, Fang; Liang, T Jake
2016-07-05
Hepatitis C virus (HCV) enters the host cell through interactions with a cascade of cellular factors. Although significant progress has been made in understanding HCV entry, the precise mechanisms by which HCV exploits the receptor complex and host machinery to enter the cell remain unclear. This intricate process of viral entry likely depends on additional yet-to-be-defined cellular molecules. Recently, by applying integrative functional genomics approaches, we identified and interrogated distinct sets of host dependencies in the complete HCV life cycle. Viral entry assays using HCV pseudoparticles (HCVpps) of various genotypes uncovered multiple previously unappreciated host factors, including E-cadherin, that mediate HCV entry. E-cadherin silencing significantly inhibited HCV infection in Huh7.5.1 cells, HepG2/miR122/CD81 cells, and primary human hepatocytes at a postbinding entry step. Knockdown of E-cadherin, however, had no effect on HCV RNA replication or internal ribosomal entry site (IRES)-mediated translation. In addition, an E-cadherin monoclonal antibody effectively blocked HCV entry and infection in hepatocytes. Mechanistic studies demonstrated that E-cadherin is closely associated with claudin-1 (CLDN1) and occludin (OCLN) on the cell membrane. Depletion of E-cadherin drastically diminished the cell-surface distribution of these two tight junction proteins in various hepatic cell lines, indicating that E-cadherin plays an important regulatory role in CLDN1/OCLN localization on the cell surface. Furthermore, loss of E-cadherin expression in hepatocytes is associated with HCV-induced epithelial-to-mesenchymal transition (EMT), providing an important link between HCV infection and liver cancer. Our data indicate that a dynamic interplay among E-cadherin, tight junctions, and EMT exists and mediates an important function in HCV entry.
Dynamics of T-Junction Solution Switching Aimed at Patch Clamp Experiments
Auzmendi, Jerónimo A.; Smoler, Mariano; Moffatt, Luciano
2015-01-01
Solutions exchange systems are responsible for the timing of drug application on patch clamp experiments. There are two basic strategies for generating a solution exchange. When slow exchanges are bearable, it is easier to perform the exchange inside the tubing system upstream of the exit port. On the other hand, fast, reproducible, exchanges are usually performed downstream of the exit port. As both strategies are combinable, increasing the performance of upstream exchanges is desirable. We designed a simple method for manufacturing T-junctions (300 μm I.D.) and we measured the time profile of exchange of two saline solutions using a patch pipette with an open tip. Three factors were found to determine the timing of the solution switching: pressure, travelled distance and off-center distance. A linear relationship between the time delay and the travelled distance was found for each tested pressure, showing its dependence to the fluid velocity, which increased with pressure. The exchange time was found to increase quadratically with the delay, although a sizeable variability remains unexplained by this relationship. The delay and exchange times increased as the recording pipette moved away from the center of the stream. Those increases became dramatic as the pipette was moved close to the stream borders. Mass transport along the travelled distance between the slow fluid at the border and the fast fluid at the center seems to contribute to the time course of the solution exchange. This effect would be present in all tubing based devices. Present results might be of fundamental importance for the adequate design of serial compound exchangers which would be instrumental in the discovery of drugs that modulate the action of the physiological agonists of ion channels with the purpose of fine tuning their physiology. PMID:26177538
Sneve, Markus H; Magnussen, Svein; Alnæs, Dag; Endestad, Tor; D'Esposito, Mark
2013-11-01
Visual STM of simple features is achieved through interactions between retinotopic visual cortex and a set of frontal and parietal regions. In the present fMRI study, we investigated effective connectivity between central nodes in this network during the different task epochs of a modified delayed orientation discrimination task. Our univariate analyses demonstrate that the inferior frontal junction (IFJ) is preferentially involved in memory encoding, whereas activity in the putative FEFs and anterior intraparietal sulcus (aIPS) remains elevated throughout periods of memory maintenance. We have earlier reported, using the same task, that areas in visual cortex sustain information about task-relevant stimulus properties during delay intervals [Sneve, M. H., Alnæs, D., Endestad, T., Greenlee, M. W., & Magnussen, S. Visual short-term memory: Activity supporting encoding and maintenance in retinotopic visual cortex. Neuroimage, 63, 166-178, 2012]. To elucidate the temporal dynamics of the IFJ-FEF-aIPS-visual cortex network during memory operations, we estimated Granger causality effects between these regions with fMRI data representing memory encoding/maintenance as well as during memory retrieval. We also investigated a set of control conditions involving active processing of stimuli not associated with a memory task and passive viewing. In line with the developing understanding of IFJ as a region critical for control processes with a possible initiating role in visual STM operations, we observed influence from IFJ to FEF and aIPS during memory encoding. Furthermore, FEF predicted activity in a set of higher-order visual areas during memory retrieval, a finding consistent with its suggested role in top-down biasing of sensory cortex.
Non-Abelian holonomies, charge pumping, and quantum computation with Josephson junctions.
Faoro, Lara; Siewert, Jens; Fazio, Rosario
2003-01-17
Non-Abelian holonomies can be generated and detected in certain superconducting nanocircuits. Here we consider an example where the non-Abelian operations are related to the adiabatic charge dynamics of the Josephson network. We demonstrate that such a device can be applied both for adiabatic charge pumping and as an implementation of a quantum computer.
Huang, X C; Maimaiti, X Y M; Huang, C W; Zhang, L; Li, Z B; Chen, Z G; Gao, X; Chen, T Y
2014-01-01
To further understand the synergistic mechanism of As2O3 and asscorbic acid (AA) in human osteosarcoma MG-63 cells by systems biology analysis. Human osteosarcoma MG-63 cells were treated by As2O3 (1 µmol/L), AA (62.5 µmol/L) and combined drugs (1 µmol/L As2O3 plus 62.5 µmol/L AA). Dynamic morphological characteristics were recorded by Cell-IQ system, and growth rate was calculated. Illumina beadchip assay was used to analyze the differential expression genes in different groups. Synergic effects on differential expression genes (DEGs) were analyzed by mixture linear model and singular value decomposition model. KEGG pathway annotations and GO enrichment analysis were performed to figure out the pathways involved in the synergic effects. We captured 1987 differential expression genes in combined therapy MG-63 cells. FAT1 gene was significantly upregulated in all three groups, which is a promising drug target as an important tumor suppressor analogue; meanwhile, HIST1H2BD gene was markedly downregulated in the As2O3 monotherapy group and the combined therapy group, which was found to be upregulated in prostatic cancer. These two genes might play critical roles in synergetic effects of AA and As2O3, although the exact mechanism needs further investigation. KEGG pathway analysis showed many DEGs were related with tight junction, and GO analysis also indicated that DEGs in the combined therapy cells gathered in occluding junction, apical junction complex, cell junction, and tight junction. AA potentiates the efficacy of As2O3 in MG-63 cells. Systems biology analysis showed the synergic effect on the DEGs.
AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function
Venkatesh, Deepak; Mruk, Dolores; Herter, Jan M.; Cullere, Xavier; Chojnacka, Katarzyna; Cheng, C. Yan; Mayadas, Tanya N.
2017-01-01
The blood-testis barrier (BTB), formed between adjacent Sertoli cells, undergoes extensive remodeling to facilitate the transport of preleptotene spermatocytes across the barrier from the basal to apical compartments of the seminiferous tubules for further development and maturation into spermatozoa. The actin cytoskeleton serves unique structural and supporting roles in this process, but little is known about the role of microtubules and their regulators during BTB restructuring. The large isoform of the cAMP-responsive scaffold protein AKAP9 regulates microtubule dynamics and nucleation at the Golgi. We found that conditional deletion of Akap9 in mice after the initial formation of the BTB at puberty leads to infertility. Akap9 deletion results in marked alterations in the organization of microtubules in Sertoli cells and a loss of barrier integrity despite a relatively intact, albeit more apically localized F-actin and BTB tight junctional proteins. These changes are accompanied by a loss of haploid spermatids due to impeded meiosis. The barrier, however, progressively reseals in older Akap9 null mice, which correlates with a reduction in germ cell apoptosis and a greater incidence of meiosis. However, spermiogenesis remains defective, suggesting additional roles for AKAP9 in this process. Together, our data suggest that AKAP9 and, by inference, the regulation of the microtubule network are critical for BTB function and subsequent germ cell development during spermatogenesis. PMID:26687990
Pak, Alexander J.; Grime, John M. A.; Sengupta, Prabuddha; Chen, Antony K.; Durumeric, Aleksander E. P.; Srivastava, Anand; Yeager, Mark; Briggs, John A. G.; Lippincott-Schwartz, Jennifer; Voth, Gregory A.
2017-01-01
The packaging and budding of Gag polyprotein and viral RNA is a critical step in the HIV-1 life cycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth. We develop a coarse-grained (CG) computational model that is derived from subnanometer resolution structural data. Our simulations recapitulate contiguous and hexameric lattice assembly driven only by weak anisotropic attractions at the helical CA–SP1 junction. Importantly, analysis from CG and single-particle tracking photoactivated localization (spt-PALM) trajectories indicates that viral RNA and the membrane are critical constituents that actively promote Gag multimerization through scaffolding, while overexpression of short competitor RNA can suppress assembly. We also find that the CA amino-terminal domain imparts intrinsic curvature to the Gag lattice. As a consequence, immature lattice growth appears to be coupled to the dynamics of spontaneous membrane deformation. Our findings elucidate a simple network of interactions that regulate the early stages of HIV-1 assembly and budding. PMID:29114055
Yamazaki, Daisuke; Oikawa, Tsukasa; Takenawa, Tadaomi
2007-01-01
During cadherin-dependent cell-cell adhesion, the actin cytoskeleton undergoes dynamic reorganization in epithelial cells. Rho-family small GTPases, which regulate actin dynamics, play pivotal roles in cadherin-dependent cell-cell adhesion; however, the precise molecular mechanisms that underlie cell-cell adhesion formation remain unclear. Here we show that Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE)-mediated reorganization of actin, downstream of Rac plays an important role in normal development of cadherin-dependent cell-cell adhesions in MDCK cells. Rac-induced development of cadherin-dependent adhesions required WAVE2-dependent actin reorganization. The process of cell-cell adhesion is divided into three steps: formation of new cell-cell contacts, stabilization of these new contacts and junction maturation. WAVE1 and WAVE2 were expressed in MDCK cells. The functions of WAVE1 and WAVE2 were redundant in this system but WAVE2 appeared to play a more significant role. During the first step, WAVE2-dependent lamellipodial protrusions facilitated formation of cell-cell contacts. During the second step, WAVE2 recruited actin filaments to new cell-cell contacts and stabilized newly formed cadherin clusters. During the third step, WAVE2-dependent actin reorganization was required for organization and maintenance of mature cell-cell adhesions. Thus, Rac-WAVE-dependent actin reorganization is not only involved in formation of cell-cell adhesions but is also required for their maintenance.
The effect of motion and signalling on drivers' ability to predict intentions of other road users.
Lee, Yee Mun; Sheppard, Elizabeth
2016-10-01
Failure in making the correct judgment about the intention of an approaching vehicle at a junction could lead to a collision. This paper investigated the impact of dynamic information on drivers' judgments about the intentions of approaching cars and motorcycles, and whether a valid or invalid signal was provided was also manipulated. Participants were presented with videoclips of vehicles approaching a junction which terminated immediately before the vehicle made any manoeuvre, or images of the final frame of each video. They were asked to judge whether or not the vehicle would turn. Drivers were better in judging the manoeuvre of approaching vehicles in dynamic than static stimuli, for both vehicle types. Drivers were better in judging the manoeuvre of cars than motorcycles for videos, but not for photographs. Drivers were also better in judging the manoeuvre of approaching vehicles when a valid signal was provided than an invalid signal, demonstrating the importance of providing a valid signal while driving. However, drivers were still somewhat successful in their judgments in most of the conditions with an invalid signal, suggesting that drivers were able to focus on other cues to intention. Finally, given that dynamic stimuli more closely reflect the demands of real-life driving there may be a need for drivers to adopt a more cautious approach while inferring a motorcyclist's intentions. Copyright © 2016 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Wan, Danny; Manfrini, Mauricio; Vaysset, Adrien; Souriau, Laurent; Wouters, Lennaert; Thiam, Arame; Raymenants, Eline; Sayan, Safak; Jussot, Julien; Swerts, Johan; Couet, Sebastien; Rassoul, Nouredine; Babaei Gavan, Khashayar; Paredis, Kristof; Huyghebaert, Cedric; Ercken, Monique; Wilson, Christopher J.; Mocuta, Dan; Radu, Iuliana P.
2018-04-01
Magnetic tunnel junctions (MTJs) interconnected via a continuous ferromagnetic free layer were fabricated for spin torque majority gate (STMG) logic. The MTJs are biased independently and show magnetoelectric response under spin transfer torque. The electrical control of these devices paves the way to future spin logic devices based on domain wall (DW) motion. In particular, it is a significant step towards the realization of a majority gate. To our knowledge, this is the first fabrication of a cross-shaped free layer shared by several perpendicular MTJs. The fabrication process can be generalized to any geometry and any number of MTJs. Thus, this framework can be applied to other spin logic concepts based on magnetic interconnect. Moreover, it allows exploration of spin dynamics for logic applications.
NASA Astrophysics Data System (ADS)
Wang, Xiao; Feng, Jiafeng; Guo, Peng; Wei, H. X.; Han, X. F.; Fang, B.; Zeng, Z. M.
2017-12-01
We report the temperature dependence of the spin-torque (ST) driven ferromagnetic resonance in MgO-based magnetic tunnel junction (MTJ) nanopillars with a perpendicularly free layer and an in-plane reference layer. From the evolution of the resonance frequency with magnetic field, we clearly identify the free-layer resonance mode and reference-layer mode. For the reference layer, we demonstrate a monotonic increase in resonance frequency and the effective damping with decreasing temperature, which suggests the saturated magnetization of the reference layer is dominant. However, for the free layer, the frequency and damping exhibit almost no change with temperature, indicating that the perpendicular magnetic anisotropy plays an important role in magnetization dynamics of the free layer.
Solitonic Josephson Thermal Transport
NASA Astrophysics Data System (ADS)
Guarcello, Claudio; Solinas, Paolo; Braggio, Alessandro; Giazotto, Francesco
2018-03-01
We explore the coherent thermal transport sustained by solitons through a long Josephson junction as a thermal gradient across the system is established. We observe that a soliton causes the heat current through the system to increase. Correspondingly, the junction warms up in conjunction with the soliton, with temperature peaks up to, e.g., approximately 56 mK for a realistic Nb-based proposed setup at a bath temperature Tbath=4.2 K . The thermal effects on the dynamics of the soliton are also discussed. Markedly, this system inherits the topological robustness of the solitons. In view of these results, the proposed device can effectively find an application as a superconducting thermal router in which the thermal transport can be locally mastered through solitonic excitations, whose positions can be externally controlled through a magnetic field and a bias current.
Influence of voids distribution on the deformation behavior of nanocrystalline palladium
NASA Astrophysics Data System (ADS)
Bachurin, D. V.
2018-07-01
Uniaxial deformation of three-dimensional nanocrystalline palladium containing porosity in the form of voids was investigated by means of molecular dynamics method. Simulations were performed at temperature of 300 K and at a constant strain rate of 108s-1. Two cases of voids distribution were considered: random and at triple or quadrupole junctions. It has been revealed that both the voids distribution and subsequent annealing at elevated temperature influence the deformation behavior of nanocrystalline palladium. In particular, the presence of voids at grain junctions results in a reduction of the Young's modulus and more pronounced softening effect during plastic deformation. The subsequent annealing evokes shrinkage of voids and strengthening effect. Contribution of grain boundary accommodation processes into both elastic and plastic deformation of nanocrystalline materials is discussed.
Transitional basal cells at the squamous-columnar junction generate Barrett’s oesophagus
Jiang, Ming; Li, Haiyan; Zhang, Yongchun; Yang, Ying; Lu, Rong; Liu, Kuancan; Lin, Sijie; Lan, Xiaopeng; Wang, Haikun; Wu, Han; Zhu, Jian; Zhou, Zhongren; Xu, Jianming; Lee, Dong-Kee; Zhang, Lanjing; Lee, Yuan-Cho; Yuan, Jingsong; Abrams, Julian A.; Wang, Timothy G.; Sepulveda, Antonia R.; Wu, Qi; Chen, Huaiyong; Sun, Xin; She, Junjun; Chen, Xiaoxin; Que, Jianwen
2017-01-01
In several organ systems the transitional zone between different types of epithelia is a hotspot for pre-neoplastic metaplasia and malignancy1–3. However, the cell-of-origin for the metaplastic epithelium and subsequent malignancy, remains obscure1–3. In the case of Barrett’s oesophagus (BE), intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells4. Based on different experimental models, several alternative cell types have been proposed as the source of the metaplasia, but in all cases the evidence is inconclusive and no model completely mimics BE with the presence of intestinal goblet cells5–8. Here, we describe a novel transitional columnar epithelium with distinct basal progenitor cells (p63+ KRT5+ KRT7+) in the squamous-columnar junction (SCJ) in the upper gastrointestinal tract of the mouse. We use multiple models and lineage tracing strategies to show that this unique SCJ basal cell population serves as a source of progenitors for the transitional epithelium. Moreover, upon ectopic expression of CDX2 these transitional basal progenitors differentiate into intestinal-like epithelium including goblet cells, thus reproducing Barrett’s metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues, including the anorectal junction, and, importantly, at the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (MLE) believed to be a precursor of BE are both characterized by the expansion of the transitional basal progenitor cells. Taken together our findings reveal the presence of a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63+ KRT7+ basal cells in this zone are the cell-of-origin for MLE and BE. PMID:29019984
Park, Won Man; Choi, Dae Kyung; Kim, Kyungsoo; Kim, Yongjung J; Kim, Yoon Hyuk
2015-12-01
Spinal fusion surgery is a widely used surgical procedure for sagittal realignment. Clinical studies have reported that spinal fusion may cause proximal junctional kyphosis and failure with disc failure, vertebral fracture, and/or failure at the implant-bone interface. However, the biomechanical injury mechanisms of proximal junctional kyphosis and failure remain unclear. A finite element model of the thoracolumbar spine was used. Nine fusion models with pedicle screw systems implanted at the L2-L3, L3-L4, L4-L5, L5-S1, L2-L4, L3-L5, L4-S1, L2-L5, and L3-S1 levels were developed based on the respective surgical protocols. The developed models simulated flexion-extension using hybrid testing protocol. When spinal fusion was performed at more distal levels, particularly at the L5-S1 level, the following biomechanical properties increased during flexion-extension: range of motion, stress on the annulus fibrosus fibers and vertebra at the adjacent motion segment, and the magnitude of axial forces on the pedicle screw at the uppermost instrumented vertebra. The results of this study demonstrate that more distal fusion levels, particularly in spinal fusion including the L5-S1 level, lead to greater increases in the risk of proximal junctional kyphosis and failure, as evidenced by larger ranges of motion, higher stresses on fibers of the annulus fibrosus and vertebra at the adjacent segment, and higher axial forces on the screw at the uppermost instrumented vertebra in flexion-extension. Therefore, fusion levels should be carefully selected to avoid proximal junctional kyphosis and failure. Copyright © 2015 Elsevier Ltd. All rights reserved.
Assessment of Corrosion, Fretting, and Material Loss of Retrieved Modular Total Knee Arthroplasties.
Martin, Audrey J; Seagers, Kirsten A; Van Citters, Douglas W
2017-07-01
Modular junctions in total hip arthroplasties have been associated with fretting, corrosion, and debris release. The purpose of this study is to analyze damage severity in total knee arthroplasties of a single design by qualitative visual assessment and quantitative material loss measurements to evaluate implant performance and patient impact via material loss. Twenty-two modular knee retrievals of the same manufacturer were identified from an institutional review board-approved database. Junction designs included tapers with an axial screw and tapers with a radial screw. Constructs consisted of 2 metal alloys: CoCr and Ti6Al4V. Components were qualitatively scored and quantitatively measured for corrosion and fretting. Negative values represent adhered material. Statistical differences were analyzed using sign tests. Correlations were tested with a Spearman rank order test (P < .05). The median volumetric material loss and the maximum linear depth for the total population were -0.23 mm 3 and 5.84 μm, respectively. CoCr components in mixed metal junctions had higher maximum linear depth (P = .007) than corresponding Ti components. Fretting scores of Ti6Al4V alloy components in mixed metal junctions were statistically higher than the remaining groups. Taper angle did not correlate with material loss. Results suggest that CoCr components in mixed metal junctions are more vulnerable to corrosion than other components, suggesting preferential corrosion when interfacing with Ti6Al4V. Overall, although corrosion was noted in this series, material loss was low, and none were revised for clinical metal-related reaction. This suggests the clinical impact from corrosion in total knee arthroplasty is low. Copyright © 2017 Elsevier Inc. All rights reserved.
Todman, M G; Baines, R A; Stebbings, L A; Davies, J A; Bacon, J P
1999-01-01
Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.
NASA Astrophysics Data System (ADS)
Jonak-Auer, I.; Synooka, O.; Kraxner, A.; Roger, F.
2017-12-01
With the ongoing miniaturization of CMOS technologies the need for integrated optical sensors on smaller scale CMOS nodes arises. In this paper we report on the development and implementation of different optical sensor concepts in high performance 0.18µm CMOS and high voltage (HV) CMOS technologies on three different substrate materials. The integration process is such that complete modularity of the CMOS processes remains untouched and no additional masks or ion implantation steps are necessary for the sensor integration. The investigated processes support 1.8V and 3V standard CMOS functionality as well as HV transistors capable of operating voltages of 20V and 50V. These processes intrinsically offer a wide variety of junction combinations, which can be exploited for optical sensing purposes. The availability of junction depths from submicron to several microns enables the selection of spectral range from blue to infrared wavelengths. By appropriate layout the contributions of photo-generated carriers outside the target spectral range can be kept to a minimum. Furthermore by making use of other features intrinsically available in 0.18µm CMOS and HV-CMOS processes dark current rates of optoelectronic devices can be minimized. We present TCAD simulations as well as spectral responsivity, dark current and capacitance data measured for various photodiode layouts and the influence of different EPI and Bulk substrate materials thereon. We show examples of spectral responsivity of junction combinations optimized for peak sensitivity in the ranges of 400-500nm, 550-650nm and 700-900nm. Appropriate junction combination enables good spectral resolution for colour sensing applications even without any additional filter implementation. We also show that by appropriate use of shallow trenches dark current values of photodiodes can further be reduced.
N-terminal nesprin-2 variants regulate β-catenin signalling
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Qiuping; Minaisah, Rose-Marie; Ferraro, Elisa
2016-07-15
The spatial compartmentalisation of biochemical signalling pathways is essential for cell function. Nesprins are a multi-isomeric family of proteins that have emerged as signalling scaffolds, herein, we investigate the localisation and function of novel nesprin-2 N-terminal variants. We show that these nesprin-2 variants display cell specific distribution and reside in both the cytoplasm and nucleus. Immunofluorescence microscopy revealed that nesprin-2 N-terminal variants colocalised with β-catenin at cell-cell junctions in U2OS cells. Calcium switch assays demonstrated that nesprin-2 and β-catenin are lost from cell-cell junctions in low calcium conditions whereas emerin localisation at the NE remained unaltered, furthermore, an N-terminal fragmentmore » of nesprin-2 was sufficient for cell-cell junction localisation and interacted with β-catenin. Disruption of these N-terminal nesprin-2 variants, using siRNA depletion resulted in loss of β-catenin from cell-cell junctions, nuclear accumulation of active β-catenin and augmented β-catenin transcriptional activity. Importantly, we show that U2OS cells lack nesprin-2 giant, suggesting that the N-terminal nesprin-2 variants regulate β-catenin signalling independently of the NE. Together, these data identify N-terminal nesprin-2 variants as novel regulators of β-catenin signalling that tether β-catenin to cell-cell contacts to inhibit β-catenin transcriptional activity. - Highlights: • N-terminal nesprin-2 variants display cell specific expression patterns. • N-terminal spectrin repeats of nesprin-2 interact with β-catenin. • N-terminal nesprin-2 variants scaffold β-catenin at cell-cell junctions.. • Nesprin-2 variants play multiple roles in β-catenin signalling.« less
2014-06-02
cal care nurse ( ECCN ) and flight medic arrived at the aid station to prepare the casualty for the MEDEVAC flight. Peripheral intravenous catheter...remained strong. The left leg’s distal pulses, however, were detected by manual palpa- tion by the ECCN . Reassessment of the wound site and bandage
USDA-ARS?s Scientific Manuscript database
Newcastle disease virus (NDV) has been developed as a vector for vaccine and gene therapy purposes. However, the optimal insertion site for foreign gene expression remained to be determined. In the present study, we inserted the green fluorescence protein (GFP) gene into five different intergenic ...
USDA-ARS?s Scientific Manuscript database
Introduction In animal models, maternal obesity (OB) leads to augmented risk of offspring OB. While placental function is influenced by maternal habitus, the effect of maternal obesity on the interacting zones of the placenta [the labyrinth (LZ), junctional (JZ) and metrial gland (MG)] remains unkno...
NASA Astrophysics Data System (ADS)
McGuckin, Terrence
The solid state devices that are pervasive in our society, are based on building blocks composed of interfaces between materials and junctions that manipulate how charge carriers behave in a device. As the dimensions of these devices are reduced to the nanoscale, surfaces and interfaces play a larger role in the behavior of carriers in devices and must be thoroughly investigated to understand not only the material properties but how these materials interact. Separating the effects of these different building blocks is a challenge, as most testing methods measure the performance of the whole device. Semiconductor nanowires represent an excellent test system to explore the limits of size and novel device structures. The behavior of charge carriers in semiconductor nanowire devices under operational conditions is investigated using local probing technique electron beam induced current (EBIC). The behavior of locally excited carriers are driven by the forces of drift, from electric fields within a device at junctions, surfaces, contacts and, applied voltage bias, and diffusion. This thesis presents the results of directly measuring these effects spatially with nanometer resolution, using EBIC in Ge, Si, and complex heterostructure GaAs/AlGaAs nanowire devices. Advancements to the EBIC technique, have pushed the resolution from tens of nanometers down to 1 to 2 nanometers. Depth profiling and tuning of the interaction volume allows for the separating the signal originating from the surface and the interior of the nanowire. Radial junctions and variations in bands can now be analyzed including core/shell hetero-structures. This local carrier probing reveals a number of surprising behaviors; Most notably, directly imaging the evolution of surface traps filling with electrons causing bandbending at the surface of Ge nanowires that leads to an enhancement in the charge separation of electrons and holes, and extracting different characteristic lengths from GaAs and AlGaAs in core/shell nanowires. For new and emerging solid state materials, understanding charge carrier dynamics is crucial to designing functional devices. Presented here are examples of the wide application of EBIC, and its variants, through imaging domains in ferroelectric materials, local electric fields and defects in 2D semiconductor material MoS2, and gradients in doping profiles of solar cells. Measuring the local behavior of carrier dynamics, EBIC has the potential to be a key metrology technique in correlative microscopy, enabling a deeper understanding of materials and how they interact within devices.
Streptococcus pyogenes translocates across an epithelial barrier.
Sumitomo, Tomoko
2017-01-01
Streptococcus pyogenes is a β-hemolytic organism responsible for a wide variety of human diseases that commonly occur as self-limiting purulent diseases of the pharynx and skin. Although the occurrence of invasive infections by S. pyogenes is rare, mortality rates remain high even with progressive medical therapy. As a prerequisite for causing the severe invasive disease, S. pyogenes must invade underlying sterile tissues by translocating across the epithelial barrier. In this study, streptolysin S and SpeB were identified as the novel factors that facilitate bacterial translocation via degradation of intercellular junctions. Furthermore, we found that S. pyogenes exploits host plasminogen for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions. Here, I would like to show our study on bacterial translocation across the epithelial barrier through paracellular route.
Chemoradiotherapy in tumours of the oesophagus and gastro-oesophageal junction.
Hulshof, M C C M; van Laarhoven, H W M
2016-08-01
Oesophageal cancer remains a malignancy with a poor prognosis. However, in the recent 10-15 years relevant progress has been made by the introduction of chemoradiotherapy (CRT) for tumours of the oesophagus or gastro-oesophageal junction. The addition of neo-adjuvant CRT to surgery has significantly improved survival and locoregional control, for both adenocarcinoma and squamous cell carcinoma. For irresectable or medically inoperable patients, definitive CRT has changed the treatment intent from palliative to curative. Definitive CRT is a good alternative for radical surgery in responding patients with squamous cell carcinoma and those running a high risk of surgical morbidity and mortality. For patients with an out-of-field solitary locoregional recurrence after primary curative treatment, definitive CRT can lead to long term survival. Copyright © 2016. Published by Elsevier Ltd.
Surface obstacles in pulsatile flow
NASA Astrophysics Data System (ADS)
Carr, Ian A.; Plesniak, Michael W.
2017-11-01
Flows past obstacles mounted on flat surfaces have been widely studied due to their ubiquity in nature and engineering. For nearly all of these studies, the freestream flow over the obstacle was steady, i.e., constant velocity, unidirectional flow. Unsteady, pulsatile flows occur frequently in biology, geophysics, biomedical engineering, etc. Our study is aimed at extending the comprehensive knowledge base that exists for steady flows to considerably more complex pulsatile flows. Characterizing the vortex and wake dynamics of flows around surface obstacles embedded in pulsatile flows can provide insights into the underlying physics in all wake and junction flows. In this study, we experimentally investigate the wake of two canonical obstacles: a cube and a circular cylinder with an aspect ratio of unity. Our previous studies of a surface-mounted hemisphere in pulsatile flow are used as a baseline for these two new, more complex geometries. Phase-averaged PIV and hot-wire anemometry are used to characterize the dynamics of coherent structures in the wake and at the windward junction of the obstacles. Complex physics occur during the deceleration phase of the pulsatile inflow. We propose a framework for understanding these physics based on self-induced vortex propagation, similar to the phenomena exhibited by vortex rings.
Revealing the distinct folding phases of an RNA three-helix junction.
Plumridge, Alex; Katz, Andrea M; Calvey, George D; Elber, Ron; Kirmizialtin, Serdal; Pollack, Lois
2018-05-14
Remarkable new insight has emerged into the biological role of RNA in cells. RNA folding and dynamics enable many of these newly discovered functions, calling for an understanding of RNA self-assembly and conformational dynamics. Because RNAs pass through multiple structures as they fold, an ensemble perspective is required to visualize the flow through fleetingly populated sets of states. Here, we combine microfluidic mixing technology and small angle X-ray scattering (SAXS) to measure the Mg-induced folding of a small RNA domain, the tP5abc three helix junction. Our measurements are interpreted using ensemble optimization to select atomically detailed structures that recapitulate each experimental curve. Structural ensembles, derived at key stages in both time-resolved studies and equilibrium titrations, reproduce the features of known intermediates, and more importantly, offer a powerful new structural perspective on the time-progression of folding. Distinct collapse phases along the pathway appear to be orchestrated by specific interactions with Mg ions. These key interactions subsequently direct motions of the backbone that position the partners of tertiary contacts for later bonding, and demonstrate a remarkable synergy between Mg and RNA across numerous time-scales.
Macroscopic Quantum Phase-Locking Model for the Quantum Hall = Effect
NASA Astrophysics Data System (ADS)
Wang, Te-Chun; Gou, Yih-Shun
1997-08-01
A macroscopic model of nonlinear dissipative phase-locking between a Josephson-like frequency and a macroscopic electron wave frequency is proposed to explain the Quantum Hall Effect. It is well known that a r.f-biased Josephson junction displays a collective phase-locking behavior which can be described by a non-autonomous second order equation or an equivalent 2+1-dimensional dynamical system. Making a direct analogy between the QHE and the Josephson system, this report proposes a computer-solving nonlinear dynamical model for the quantization of the Hall resistance. In this model, the Hall voltage is assumed to be proportional to a Josephson-like frequency and the Hall current is assumed related to a coherent electron wave frequency. The Hall resistance is shown to be quantized in units of the fine structure constant as the ratio of these two frequencies are locked into a rational winding number. To explain the sample-width dependence of the critical current, the 2DEG under large applied current is further assumed to develop a Josephson-like junction array in which all Josephson-like frequencies are synchronized. Other remarkable features of the QHE such as the resistance fluctuation and the even-denominator states are also discussed within this picture.
NASA Astrophysics Data System (ADS)
Aivazian, Grant; Sun, Dong; Jones, Aaron; Ross, Jason; Yao, Wang; Cobden, David; Xu, Xiaodong
2012-02-01
The remarkable electrical and optical properties of graphene make it a promising material for new optoelectronic applications. However, one important, but so far unexplored, property is the role of hot carriers in charge and energy transport at graphene interfaces. Here we investigate the photocurrent (PC) dynamics at a tunable graphene pn junction using ultrafast scanning PC microscopy. Pump-probe measurements show a temperature dependent relaxation time of photogenerated carriers that increases from 1.5ps at 290K to 4ps at 20K; while the amplitude of the PC is independent of the lattice temperature. These observations imply that it is hot carriers, not phonons, which dominate ultrafast energy transport. Gate dependent measurements show many interesting features such as pump induced saturation, enhancement, and sign reversal of probe generated PC. These observations reveal that the underlying PC mechanism is a combination of the thermoelectric and built-in electric field effects. Our results enhance the understanding of non-equilibrium electron dynamics, electron-electron interactions, and electron-phonon interactions in graphene. They also determine fundamental limits on ultrafast device operation speeds (˜500 GHz) for graphene-based photodetectors.
Snow, Chelsi J.; Henry, Clarissa A.
2009-01-01
Muscle development involves the specification and morphogenesis of muscle fibers that attach to tendons. After attachment, muscles and tendons then function as an integrated unit to transduce force to the skeletal system and stabilize joints. The attachment site is the myotendinous junction, or MTJ, and is the primary site of force transmission. We find that attachment of fast-twitch myofibers to the MTJ correlates with the formation of novel microenvironments within the MTJ. The expression or activation of two proteins involved in anchoring the intracellular cytoskeleton to the extracellular matrix, Focal adhesion kinase (Fak) and β-dystroglycan is up-regulated. Conversely, the extracellular matrix protein Fibronectin (Fn) is down-regulated. This degradation of Fn as fast-twitch fibers attach to the MTJ results in Fn protein defining a novel microenvironment within the MTJ adjacent to slow-twitch, but not fast-twitch, muscle. Interestingly, however, Fak, laminin, Fn and β-dystroglycan concentrate at the MTJ in mutants that do not have slow-twitch fibers. Taken together, these data elucidate novel and dynamic microenvironments within the MTJ and indicate that MTJ morphogenesis is spatially and temporally complex. PMID:18783736
Fan, Tao; Zhao, HaiJun; Zhao, XinGang; Liang, Cong; Wang, YinQian; Gai, QiFei
2017-10-01
Chiari I malformation has been shown to present different cerebrospinal fluid (CSF) flow patterns at the cranial-vertebral junction (CVJ). Posterior fossa decompression is the first-line treatment for symptomatic Chiari I malformation. However, there is still controversy on the indication and selection of decompression procedures. This research aims to investigate the clinical indications, outcomes, and complications of the decompression procedures as alternative treatments for Chiari I malformation, based on the different CSF flow patterns at the cranial-vertebral junction. In this study, 126 Chiari I malformation patients treated with the two decompression procedures were analyzed. According to the preoperative findings obtained by using cine phase-contrast MRI (cine PC-MRI), the abnormal CSF flow dynamics at the CVJ in Chiari I malformation was classified into three patterns. After a preoperative evaluation and an intraoperative ultrasound after craniectomy, the two procedures were alternatively selected to treat the Chiari I malformation. The indication and selection of the two surgical procedures, as well as their outcomes and complications, are reported in detail in this work. Forty-eight patients underwent subdural decompression (SDD), and 78 received subarachnoid manipulation (SAM). Ninety patients were diagnosed as having Chiari I malformation with a syrinx. Two weeks after the operation, the modified Japanese Orthopedic Association (mJOA) scores increased from the preoperative value of 10.67 ± 1.61 to 12.74 ± 2.01 (P < 0.01). The mean duration of follow-up was 24.8 months; the mJOA scores increased from the postoperative value of 12.74 ± 2.01 to 12.79 ± 1.91 at the end of follow-up (P = 0.48). More complications occurred in the patients who underwent SAM than in those who received SDD (SAM 11 of 78 (9.5%) vs SDD 2 of 48 (3.5%)). The abnormal CSF flow dynamics at the CVJ in Chiari I malformation can be classified into three patterns. A SAM procedure is more feasible in Chiari I malformation (CM1) patients with pattern III CSF flow dynamics, whereas a SDD procedure is more suitable for CM1 patients with pattern I CSF flow dynamics. In CM1 patients with pattern II CSF flow dynamics, an intraoperative ultrasound after craniectomy could play an important role in the selection of an effective decompression procedure.
OVERVIEW OF REMAINS OF DEWATERING BUILDING, LOOKING SOUTH TOWARD CYANIDE ...
OVERVIEW OF REMAINS OF DEWATERING BUILDING, LOOKING SOUTH TOWARD CYANIDE PROCESSING AREA. WATER USED IN PROCESSING AT THE STAMP MILL WAS CIRCULATED HERE FOR RECLAMATION. SANDS WERE SETTLED OUT AND DEPOSITED IN ONE OF TWO TAILINGS HOLDING AREAS. CLEARED WATER WAS PUMPED BACK TO THE MILL FOR REUSE. THIS PROCESS WAS ACCOMPLISHED BY THE USE OF SETTLING CONES, EIGHT FEET IN DIAMETER AND SIX FEET HIGH. THE REMAINS OF FOUR CONES ARE AT CENTER, BEHIND THE TANK IN THE FOREGROUND. TO THE LEFT IS THE MAIN ACCESS ROAD BETWEEN THE MILL AND THE PARKING LOT. - Keane Wonder Mine, Park Route 4 (Daylight Pass Cutoff), Death Valley Junction, Inyo County, CA
Broadband photodetector based on carbon nanotube thin film/single layer graphene Schottky junction
NASA Astrophysics Data System (ADS)
Zhang, Teng-Fei; Li, Zhi-Peng; Wang, Jiu-Zhen; Kong, Wei-Yu; Wu, Guo-An; Zheng, Yu-Zhen; Zhao, Yuan-Wei; Yao, En-Xu; Zhuang, Nai-Xi; Luo, Lin-Bao
2016-12-01
In this study, we present a broadband nano-photodetector based on single-layer graphene (SLG)-carbon nanotube thin film (CNTF) Schottky junction. It was found that the as-fabricated device exhibited obvious sensitivity to a wide range of illumination, with peak sensitivity at 600 and 920 nm. In addition, the SLG-CNTF device had a fast response speed (τr = 68 μs, τf = 78 μs) and good reproducibility in a wide range of switching frequencies (50-5400 Hz). The on-off ratio, responsivity, and detectivity of the device were estimated to be 1 × 102, 209 mAW-1 and 4.87 × 1010 cm Hz1/2 W-1, respectively. What is more, other device parameters including linear performance θ and linear dynamic range (LDR) were calculated to be 0.99 and 58.8 dB, respectively, which were relatively better than other carbon nanotube based devices. The totality of the above study signifies that the present SLG-CNTF Schottky junction broadband nano-photodetector may have promising application in future nano-optoelectronic devices and systems.
Investigation of dielectric pocket induced variations in tunnel field effect transistor
NASA Astrophysics Data System (ADS)
Upasana; Narang, Rakhi; Saxena, Manoj; Gupta, Mridula
2016-04-01
The performance of conventional Tunnel FETs struggling from ambipolar issues, insufficient on-current, lower transconductance value, higher delay and lower cut off frequency has been improved by introducing several material and device engineering concepts in past few years. Keeping this in view, another interesting and reliable option i.e. Dielectric Pocket TFET (featuring a dielectric pocket placement near tunneling junction) has been comprehensively and qualitatively demonstrated using ATLAS device simulator. The architecture has been explored in terms of various device electrostatic parameters such as potential, energy band profile, electron and hole concentration, electric field variation and band to band generation rate (GBTB) near the tunneling junction where the Dielectric Pocket (DP) has been introduced. Subsequently, a detailed investigation by changing the position and dielectric constant of pocket at respective junctions has been made where DP induced variations in drain current, transconductance and parasitic capacitance have been examined. The work highlights major improvements over conventional TFET in terms of lower subthreshold swing and threshold voltage, higher drain current and transconductance, improved on-to-off current ratio, suppressed ambipolar conduction and improved dynamic power dissipation issues for low voltage analog and digital applications.
Efimova, Nadia; Svitkina, Tatyana M
2018-05-07
Adherens junctions (AJs) are mechanosensitive cadherin-based intercellular adhesions that interact with the actin cytoskeleton and carry most of the mechanical load at cell-cell junctions. Both Arp2/3 complex-dependent actin polymerization generating pushing force and nonmuscle myosin II (NMII)-dependent contraction producing pulling force are necessary for AJ morphogenesis. Which actin system directly interacts with AJs is unknown. Using platinum replica electron microscopy of endothelial cells, we show that vascular endothelial (VE)-cadherin colocalizes with Arp2/3 complex-positive actin networks at different AJ types and is positioned at the interface between two oppositely oriented branched networks from adjacent cells. In contrast, actin-NMII bundles are located more distally from the VE-cadherin-rich zone. After Arp2/3 complex inhibition, linear AJs split, leaving gaps between cells with detergent-insoluble VE-cadherin transiently associated with the gap edges. After NMII inhibition, VE-cadherin is lost from gap edges. We propose that the actin cytoskeleton at AJs acts as a dynamic push-pull system, wherein pushing forces maintain extracellular VE-cadherin transinteraction and pulling forces stabilize intracellular adhesion complexes. © 2018 Efimova and Svitkina.
Frequency Combs in a Lumped-Element Josephson-Junction Circuit
NASA Astrophysics Data System (ADS)
Khan, Saeed; Türeci, Hakan E.
2018-04-01
We investigate the dynamics of a microwave-driven Josephson junction capacitively coupled to a lumped-element L C oscillator. In the regime of driving where the Josephson junction can be approximated as a Kerr oscillator, this minimal nonlinear system has been previously shown to exhibit a bistability in phase and amplitude. In the present study, we characterize the full phase diagram and show that besides a parameter regime exhibiting bistability, there is also a regime of self-oscillations characterized by a frequency comb in its spectrum. We discuss the mechanism of comb generation which appears to be different from those studied in microcavity frequency combs and mode-locked lasers. We then address the fate of the comblike spectrum in the regime of strong quantum fluctuations, reached when nonlinearity becomes the dominant scale with respect to dissipation. We find that the nonlinearity responsible for the emergence of the frequency combs also leads to its dephasing, leading to broadening and ultimate disappearance of sharp spectral peaks. Our study explores the fundamental question of the impact of quantum fluctuations for quantum systems which do not possess a stable fixed point in the classical limit.
NASA Astrophysics Data System (ADS)
Mailian, Aram; Mailian, Manvel; Shmavonyan, Gagik
2014-03-01
An easy method of obtaining graphene and graphene-based electronic components and circuits by drawing lines or repeatedly rubbing any type of graphite rod along the same path directly on paper and other insulating substrates is suggested. The structure containing rubbed-off layers behaves like a semiconducting material. The surface of the structure demonstrates ordered and oriented character containing few layer graphene. The carrier mobility is anisotropic through the thickness of the structure with the highest value of ~ 104 cm2/V .sec at the surface. Raman spectra of the structures in the near IR at excitation wavelength of 976 nm (1.27 eV) are registered. The observed phenomenon is universal, does not depend on the material of the substrate and could find a widespread application. For example, the junction between two rubbed off layers with different mobilities exhibits a non-Ohmic behavior. I-V characteristic of the junction is symmetrically curved with respect to 0 V. The greater is the difference between the carrier mobility, the higher is the curvature. The dynamic accumulation of the carriers in both sides of the junction creates a barrier responsible for non-Ohmic behavior.
Broadband photodetector based on carbon nanotube thin film/single layer graphene Schottky junction
Zhang, Teng-Fei; Li, Zhi-Peng; Wang, Jiu-Zhen; Kong, Wei-Yu; Wu, Guo-An; Zheng, Yu-Zhen; Zhao, Yuan-Wei; Yao, En-Xu; Zhuang, Nai-Xi; Luo, Lin-Bao
2016-01-01
In this study, we present a broadband nano-photodetector based on single-layer graphene (SLG)-carbon nanotube thin film (CNTF) Schottky junction. It was found that the as-fabricated device exhibited obvious sensitivity to a wide range of illumination, with peak sensitivity at 600 and 920 nm. In addition, the SLG-CNTF device had a fast response speed (τr = 68 μs, τf = 78 μs) and good reproducibility in a wide range of switching frequencies (50–5400 Hz). The on-off ratio, responsivity, and detectivity of the device were estimated to be 1 × 102, 209 mAW−1 and 4.87 × 1010 cm Hz1/2 W−1, respectively. What is more, other device parameters including linear performance θ and linear dynamic range (LDR) were calculated to be 0.99 and 58.8 dB, respectively, which were relatively better than other carbon nanotube based devices. The totality of the above study signifies that the present SLG-CNTF Schottky junction broadband nano-photodetector may have promising application in future nano-optoelectronic devices and systems. PMID:27929053
DOE Office of Scientific and Technical Information (OSTI.GOV)
Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.
2010-07-02
The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors ormore » siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.« less
Felinski, Edward A; Cox, Amy E; Phillips, Brett E; Antonetti, David A
2008-06-01
Tight junctions between vascular endothelial cells help to create the blood-brain and blood-retinal barriers. Breakdown of the retinal tight junction complex is problematic in several disease states including diabetic retinopathy. Glucocorticoids can restore and/or preserve the endothelial barrier to paracellular permeability, although the mechanism remains unclear. We show that glucocorticoid treatment of primary retinal endothelial cells increases content of the tight junction proteins occludin and claudin-5, co-incident with an increase in barrier properties of endothelial monolayers. The glucocorticoid receptor antagonist RU486 reverses both the glucocorticoid-stimulated increase in occludin content and the increase in barrier properties. Transcriptional activity from the human occludin and claudin-5 promoters increases in retinal endothelial cells upon glucocorticoid treatment, and is dependent on the glucocorticoid receptor (GR) as demonstrated by siRNA. Deletion analysis of the occludin promoter reveals a 205bp sequence responsible for the glucocorticoid response. However, this region does not possess a canonical glucocorticoid response element and does not bind to the GR in a chromatin immunoprecipitation (ChIP) assay. Mutational analysis of this region revealed a novel 40bp occludin enhancer element (OEE), containing two highly conserved regions of 10 and 13 base pairs, that is both necessary and sufficient for glucocorticoid-induced gene expression in retinal endothelial cells. These data suggest a novel mechanism for glucocorticoid induction of vascular endothelial barrier properties through increased occludin and claudin-5 gene expression.
Felinski, Edward A.; Cox, Amy E.; Phillips, Brett E.; Antonetti, David A.
2008-01-01
Tight junctions between vascular endothelial cells help to create the blood-brain and blood-retinal barriers. Breakdown of the retinal tight junction complex is problematic in several disease states including diabetic retinopathy. Glucocorticoids can restore and/or preserve the endothelial barrier to paracellular permeability, although the mechanism remains unclear. We show that glucocorticoid treatment of primary retinal endothelial cells increases content of the tight junction proteins occludin and claudin-5, co-incident with an increase in barrier properties of endothelial monolayers. The glucocorticoid receptor antagonist RU486 reverses both the glucocorticoid-stimulated increase in occludin content and the increase in barrier properties. Transcriptional activity from the human occludin and claudin-5 promoters increases in retinal endothelial cells upon glucocorticoid treatment, and is dependent on the glucocorticoid receptor (GR) as demonstrated by siRNA. Deletion analysis of the occludin promoter reveals a 205 bp sequence responsible for the glucocorticoid response. However, this region does not posses a canonical glucocorticoid response element and does not bind to the GR in a chromatin immunoprecipitation (ChIP) assay. Mutational analysis of this region revealed a novel 40 bp occludin enhancer element (OEE), containing two highly-conserved regions of 10 and 13 base pairs, that is both necessary and sufficient for glucocorticoid-induced gene expression in retinal endothelial cells. These data suggest a novel mechanism for glucocorticoid induction of vascular endothelial barrier properties through increased occludin and claudin-5 gene expression. PMID:18501346
Fujimoto, Takaaki; Ohtsuka, Takao; Nakashima, Yohei; Gotoh, Yoshitaka; Date, Kenjiro; Mori, Yasuhisa; Sadakari, Yoshihiko; Takahata, Shunichi; Oda, Yoshinao; Nakamura, Masafumi
2017-02-01
Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC. Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated. Pancreaticobiliary maljunction, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, nine, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and nine of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors. Occult pancreaticobiliary reflux, like PBM and HCPBD, is a risk factor for GBC development. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
Development of the posterior neural tube in human embryos.
Saitsu, Hirotomo; Yamada, Shigehito; Uwabe, Chigako; Ishibashi, Makoto; Shiota, Kohei
2004-12-01
Development of the posterior neural tube (PNT) in human embryos is a complicated process that involves both primary and secondary neurulation. Because normal development of the PNT is not fully understood, pathogenesis of spinal neural tube defects remains elusive. To clarify the mechanism of PNT development, we histologically examined 20 human embryos around the stage of posterior neuropore closure and found that the developing PNT can be divided into three parts: 1) the most rostral region, which corresponds to the posterior part of the primary neural tube, 2) the junctional region of the primary and secondary neural tubes, and 3) the caudal region, which emerges from the neural cord. In the junctional region, the axially-condensed mesenchyme (AM) intervened between the neural plate/tube and the notochord at the stage of posterior neuropore closure, while the notochord was directly attached to the neural plate/tube in the most rostral region. A single cavity was found to be formed in the AM as the presumptive luminal surface cells were radially aligned in the junctional region prior to the formation of the neural cord. The single cavity was continuous with the central cavity of the primary neural tube. In contrast, multiple or isolated cavities were frequently observed in the caudal region of the PNT. Our observation suggests that the junctional region of the PNT is distinct from other regions in terms of the relationship with the notochord and the mode of cavitation during secondary neurulation.
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
Masaki, Tomoyuki; Kojima, Takashi; Okabayashi, Tamaki; Ogasawara, Noriko; Ohkuni, Tsuyoshi; Obata, Kazufumi; Takasawa, Akira; Murata, Masaki; Tanaka, Satoshi; Hirakawa, Satoshi; Fuchimoto, Jun; Ninomiya, Takafumi; Fujii, Nobuhiro; Tsutsumi, Hiroyuki; Himi, Tetsuo; Sawada, Norimasa
2011-01-01
Respiratory syncytial virus (RSV) is the major cause of bronchitis, asthma, and severe lower respiratory tract disease in infants and young children. The airway epithelium, which has a well-developed barrier regulated by tight junctions, is the first line of defense during respiratory virus infection. In upper airway human nasal epithelial cells (HNECs), however, the primary site of RSV infection, the mechanisms of replication and budding of RSV, and the epithelial cell responses, including the tight junctional barrier, remain unknown. To investigate the detailed mechanisms of replication and budding of RSV in HNECs and the epithelial cell responses, we established an RSV-infected model using human telomerase reverse transcriptase–-transfected HNECs. We first found that the expression and barrier function of tight junction molecules claudin-4 and occludin were markedly induced together with production of proinflammatory cytokines interleukin 8 and tumor necrosis factor-α in HNECs after RSV infection, and the induction of tight junction molecules possibly contributed to budding of RSV. Furthermore, the replication and budding of RSV and the epithelial cell responses in HNECs were regulated via a protein kinase C δ/hypoxia-inducible factor-1α/nuclear factor-κB pathway. The control of this pathway in HNECs may be useful not only for prevention of replication and budding of RSV, but also in therapy for RSV-induced respiratory pathogenesis. PMID:21562222
Contraction and elongation: Mechanics underlying cell boundary deformations in epithelial tissue.
Hara, Yusuke
2017-06-01
The cell-cell boundaries of epithelial cells form cellular frameworks at the apical side of tissues. Deformations in these boundaries, for example, boundary contraction and elongation, and the associated forces form the mechanical basis of epithelial tissue morphogenesis. In this review, using data from recent Drosophila studies on cell boundary contraction and elongation, I provide an overview of the mechanism underlying the bi-directional deformations in the epithelial cell boundary, that are sustained by biased accumulations of junctional and apico-medial non-muscle myosin II. Moreover, how the junctional tensions exist on cell boundaries in different boundary dynamics and morphologies are discussed. Finally, some future perspectives on how recent knowledge about single cell boundary-level mechanics will contribute to our understanding of epithelial tissue morphogenesis are discussed. © 2017 Japanese Society of Developmental Biologists.
Analog Approach to Constraint Satisfaction Enabled by Spin Orbit Torque Magnetic Tunnel Junctions.
Wijesinghe, Parami; Liyanagedera, Chamika; Roy, Kaushik
2018-05-02
Boolean satisfiability (k-SAT) is an NP-complete (k ≥ 3) problem that constitute one of the hardest classes of constraint satisfaction problems. In this work, we provide a proof of concept hardware based analog k-SAT solver, that is built using Magnetic Tunnel Junctions (MTJs). The inherent physics of MTJs, enhanced by device level modifications, is harnessed here to emulate the intricate dynamics of an analog satisfiability (SAT) solver. In the presence of thermal noise, the MTJ based system can successfully solve Boolean satisfiability problems. Most importantly, our results exhibit that, the proposed MTJ based hardware SAT solver is capable of finding a solution to a significant fraction (at least 85%) of hard 3-SAT problems, within a time that has a polynomial relationship with the number of variables(<50).
Brane junctions in the Randall-Sundrum scenario
NASA Astrophysics Data System (ADS)
Csáki, Csaba; Shirman, Yuri
2000-01-01
We present static solutions to Einstein's equations corresponding to branes at various angles intersecting in a single 3-brane. Such configurations may be useful for building models with localized gravity via the Randall-Sundrum mechanism. We find that such solutions may exist only if the mechanical forces acting on the junction exactly cancel. In addition to this constraint there are further conditions that the parameters of the theory have to satisfy. We find that at least one of these involves only the brane tensions and cosmological constants, and thus cannot have a dynamical origin. We present these conditions in detail for two simple examples. We discuss the nature of the cosmological constant problem in the framework of these scenarios, and outline the desired features of the brane configurations which may bring us closer towards a resolution of the cosmological constant problem.
Traveling wave parametric amplifier with Josephson junctions using minimal resonator phase matching
DOE Office of Scientific and Technical Information (OSTI.GOV)
White, T. C.; Mutus, J. Y.; Hoi, I.-C.
Josephson parametric amplifiers have become a critical tool in superconducting device physics due to their high gain and quantum-limited noise. Traveling wave parametric amplifiers (TWPAs) promise similar noise performance, while allowing for significant increases in both bandwidth and dynamic range. We present a TWPA device based on an LC-ladder transmission line of Josephson junctions and parallel plate capacitors using low-loss amorphous silicon dielectric. Crucially, we have inserted λ/4 resonators at regular intervals along the transmission line in order to maintain the phase matching condition between pump, signal, and idler and increase gain. We achieve an average gain of 12 dB acrossmore » a 4 GHz span, along with an average saturation power of −92 dBm with noise approaching the quantum limit.« less
Measurements of quasiparticle tunneling dynamics in a band-gap-engineered transmon qubit.
Sun, L; DiCarlo, L; Reed, M D; Catelani, G; Bishop, Lev S; Schuster, D I; Johnson, B R; Yang, Ge A; Frunzio, L; Glazman, L; Devoret, M H; Schoelkopf, R J
2012-06-08
We have engineered the band gap profile of transmon qubits by combining oxygen-doped Al for tunnel junction electrodes and clean Al as quasiparticle traps to investigate energy relaxation due to quasiparticle tunneling. The relaxation time T1 of the qubits is shown to be insensitive to this band gap engineering. Operating at relatively low-E(J)/E(C) makes the transmon transition frequency distinctly dependent on the charge parity, allowing us to detect the quasiparticles tunneling across the qubit junction. Quasiparticle kinetics have been studied by monitoring the frequency switching due to even-odd parity change in real time. It shows the switching time is faster than 10 μs, indicating quasiparticle-induced relaxation has to be reduced to achieve T1 much longer than 100 μs.
Carboni, Fabio; Valle, Mario; Federici, Orietta; Levi Sandri, Giovanni Battista; Camperchioli, Ida; Lapenta, Rocco; Assisi, Daniela; Garofalo, Alfredo
2016-08-01
Esophagojejunal anastomosis leakage after total gastrectomy (TG) for esophagogastric junction (EGJ) adenocarcinoma (ADC) constitutes one of the most serious and sometimes life-threatening complications. Management remains controversial and still challenging. A total of 198 patients operated for type I and II EGJ ADC were reviewed. Diagnosis of leakage was based on a combination of clinical and radiological findings. It was classified including objective endoscopic and clinical parameters requiring different type of treatment. Anastomotic leakage was diagnosed in 14 patients (7%). Two cases recovered with conservative therapy. Six cases underwent endoscopy with clips placement in 2 and partially covered self-expandable metal stent placement in 4. Other two cases underwent reoperation with reconstruction of anastomosis and primary repair respectively. In the last four cases emergency surgery with total esophagectomy and diversion was required. Mortality occurred only in 3 of these patients and overall treatment was successful in 11 patients (78.5%). No consensus has been reached on the best method of esophagojejunal anastomosis leakage management and the rate of failure remains significant. Different options of treatment are available but early detection and multidisciplinary approaches are the keys to obtain successful results irrespective of the employed strategy.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhao, H; Sarkar, V; Paxton, A
Purpose: To explore the feasibility of supraclavicular field treatment by investigating the variation of junction position between tangential and supraclavicular fields during left breast radiation using DIBH technique. Methods: Six patients with left breast cancer treated using DIBH technique were included in this study. AlignRT system was used to track patient’s breast surface. During daily treatment, when the patient’s DIBH reached preset AlignRT tolerance of ±3mm for all principle directions (vertical, longitudinal, and lateral), the remaining longitudinal offset was recorded. The average with standard-deviation and the range of daily longitudinal offset for the entire treatment course were calculated for allmore » six patients (93 fractions totally). The ranges of average ± 1σ and 2σ were calculated, and they represent longitudinal field edge error with the confidence level of 68% and 95%. Based on these longitudinal errors, dose at junction between breast tangential and supraclavicular fields with variable gap/overlap sizes was calculated as a percentage of prescription (on a representative patient treatment plan). Results: The average of longitudinal offset for all patients is 0.16±1.32mm, and the range of longitudinal offset is −2.6 to 2.6mm. The range of longitudinal field edge error at 68% confidence level is −1.48 to 1.16mm, and at 95% confidence level is −2.80 to 2.48mm. With a 5mm and 1mm gap, the junction dose could be as low as 37.5% and 84.9% of prescription dose; with a 5mm and 1mm overlap, the junction dose could be as high as 169.3% and 117.6%. Conclusion: We observed longitudinal field edge error at 95% confidence level is about ±2.5mm, and the junction dose could reach 70% hot/cold between different DIBH. However, over the entire course of treatment, the average junction variation for all patients is within 0.2mm. The results from our study shows it is potentially feasible to treat supraclavicular field with breast tangents.« less
The Association Between P3 Amplitude at Age 11 and Criminal Offending at Age 23
Gao, Yu; Raine, Adrian; Venables, Peter H.; Mednick, Sarnoff A.
2014-01-01
Reduced P3 amplitude to targets is an information-processing deficit associated with adult antisocial behavior and may reflect dysfunction of the temporal-parietal junction. This study aims to examine whether this deficit precedes criminal offending. From a birth cohort of 1,795 children, 73 individuals who become criminal offenders at age 23 and 123 noncriminal individuals were assessed on P3 amplitude. The two groups did not differ on gender, ethnicity, and social adversity. P3 amplitude was measured over the temporal-parietal junction during a visual continuous performance task at age 11, together with antisocial behavior. Criminal convictions were assessed at age 23. Reduced P3 amplitude at age 11 was associated with increased antisocial behavior at age 11. Criminal offenders showed significantly reduced P3 amplitudes to target stimuli compared to controls. Findings remained significant after controlling for antisocial behavior and hyperactivity at age 11 and alcoholism at age 23. P3 deficits at age 11 are associated with adult crime at age 23, suggesting that reduced P3 may be an early neurobiological marker for cognitive and affective processes subserved by the temporal-parietal junction that place a child at risk for adult crime. PMID:22963083
Wang, Nan-Hsuan; Lee, Wan-Li; Her, Guor-Rong
2011-08-15
A strategy based on postcolumn electrophoretic mobility control (EMC) was developed to alleviate the adverse effect of trifluoroacetic acid (TFA) on the liquid chromatography-mass spectrometry (LC-MS) analysis of peptides. The device created to achieve this goal consisted of a poly(dimethylsiloxane) (PDMS)-based junction reservoir, a short connecting capillary, and an electrospray ionization (ESI) sprayer connected to the outlet of the high-performance liquid chromatography (HPLC) column. By apply different voltages to the junction reservoir and the ESI emitter, an electric field was created across the connecting capillary. Due to the electric field, positively charged peptides migrated toward the ESI sprayer, whereas TFA anions remained in the junction reservoir and were removed from the ionization process. Because TFA did not enter the ESI source, ion suppression from TFA was alleviated. Operation of the postcolumn device was optimized using a peptide standard mixture. Under optimized conditions, signals for the peptides were enhanced 9-35-fold without a compromise in separation efficiency. The optimized conditions were also applied to the LC-MS analysis of a tryptic digest of bovine serum albumin.
NASA Technical Reports Server (NTRS)
Messenger, S. R.; Walters, R. J.; Summers, G. P.
1993-01-01
Deep level transient spectroscopy was used to monitor thermal annealing of trapping centers in electron irradiated n(+)p InP junctions grown by metalorganic chemical vapor deposition, at temperatures ranging from 500 up to 650K. Special emphasis is given to the behavior of the minority carrier (electron) traps EA (0.24 eV), EC (0.12 eV), and ED (0.31 eV) which have received considerably less attention than the majority carrier (hole) traps H3, H4, and H5, although this work does extend the annealing behavior of the hole traps to higher temperatures than previously reported. It is found that H5 begins to anneal above 500K and is completely removed by 630K. The electron traps begin to anneal above 540K and are reduced to about half intensity by 630K. Although they each have slightly different annealing temperatures, EA, EC, and ED are all removed by 650K. A new hole trap called H3'(0.33 eV) grows as the other traps anneal and is the only trap remaining at 650K. This annealing behavior is much different than that reported for diffused junctions.
Correlating quantum decoherence and material defects in a Josephson qubit
NASA Astrophysics Data System (ADS)
Hite, D. A.; McDermott, R.; Simmonds, R. W.; Cooper, K. B.; Steffen, M.; Nam, S.; Pappas, D. P.; Martinis, J. M.
2004-03-01
Superconducting tunnel junction devices are promising candidates for constructing quantum bits (qubits) for quantum computation because of their inherently low dissipation and ease of scalability by microfabrication. Recently, the Josephson phase qubit has been characterized spectroscopically as having spurious microwave resonators that couple to the qubit and act as a dominant source of decoherence. While the origin of these spurious resonances remains unknown, experimental evidence points to the material system of the tunnel barrier. Here, we focus on our materials research aimed at elucidating and eliminating these spurious resonators. In particular, we have studied the use of high quality Al films epitaxially grown on Si(111) as the base electrode of the tunnel junction. During each step in the Al/AlOx/Al trilayer growth, we have investigated the structure in situ by AES, AED and LEED. While tunnel junctions fabricated with these epitaxial base electrodes prove to be of non-uniform oxide thickness and too thin, I-V characteristics have shown a lowering of subgap currents by a factor of two. Transport measurements will be correlated with morphological structure for a number of devices fabricated with various degrees of crystalline quality.
Singh, Devesh Kumar; Das, Kuntal Kanti; Mehrotra, Anant; Srivastava, Arun Kumar; Jaiswal, Awadhesh Kumar; Gupta, Pallav; Behari, Sanjay; Kumar, Raj
2013-01-01
Osteoblastoma (OB) is a rare bony neoplasm constituting around 1% of all primary bone tumors. Although the vertebrae and long bones are the most common sites affected by OB, skull remains a relatively uncommon site of occurrence. Aggressive variant of OB is histologically intermediate between an indolent conventional OB and a malignant osteosarcoma. To the best of our knowledge, aggressive osteoblastoma (AO) affecting the craniovertebral junction has not been previously described in the literature. In this report, we present a 34-year-old gentleman who presented with a mass involving the left side of the neck and oral cavity along with ipsilateral lower cranial nerve paresis. Computed tomography and magnetic resonance imaging scans of the craniovertebral junction revealed a heterogeneously enhancing expansile lesion with areas of destruction involving the clivus, left sided jugular foramen and left side of first two cervical vertebras. Angiography showed distortion of the V3 segment of the left vertebral artery and shift of the ipsilateral internal carotid artery. The tumor was maximally excised through far lateral approach. Histopathologic examination revealed a diagnosis of AO. The patient was referred for radiotherapy for the residual tumor and was doing well at 5 months follow-up. PMID:24744565
NASA Astrophysics Data System (ADS)
Jiang, Zhuoling; Wang, Hao; Sanvito, Stefano; Hou, Shimin
2016-03-01
The evolution of the atomic structure and the vibrational and electronic transport properties of gold atomic junctions incorporating molecular and atomic hydrogen upon elongation have been investigated with the nonequilibrium Green's function formalism combined with density functional theory. Our calculations show that for the case of gold junctions doped with a single H2 molecule the low-bias conductance drops rapidly with the electrodes' separation, while it remains almost constant if a single H atom replaces the molecule. In contrast, when one considers two H atoms adsorbed on a gold monatomic chain forming an Au-H-Au-H-Au double-bridge structure, the low-bias conductance increases first and then shows a plateau upon stretching the junction, in perfect agreement with experiments on gold nanocontacts in hydrogen environment. Furthermore, also the distribution of the calculated vibrational energies of the two H atoms is consistent with the experimental result in the low-conductance region, demonstrating clear evidence that hydrogen molecules can dissociate on stretched gold monatomic chains. These findings are helpful to improve our understanding of the structure-property relation of gold nanocontacts and also provide a new prospect for gold nanowires being used as chemical sensors and catalysts.
The association between p3 amplitude at age 11 and criminal offending at age 23.
Gao, Yu; Raine, Adrian; Venables, Peter H; Mednick, Sarnoff A
2013-01-01
Reduced P3 amplitude to targets is an information-processing deficit associated with adult antisocial behavior and may reflect dysfunction of the temporal-parietal junction. This study aims to examine whether this deficit precedes criminal offending. From a birth cohort of 1,795 children, 73 individuals who become criminal offenders at age 23 and 123 noncriminal individuals were assessed on P3 amplitude. The two groups did not differ on gender, ethnicity, and social adversity. P3 amplitude was measured over the temporal-parietal junction during a visual continuous performance task at age 11, together with antisocial behavior. Criminal convictions were assessed at age 23. Reduced P3 amplitude at age 11 was associated with increased antisocial behavior at age 11. Criminal offenders showed significantly reduced P3 amplitudes to target stimuli compared to controls. Findings remained significant after controlling for antisocial behavior and hyperactivity at age 11 and alcoholism at age 23. P3 deficits at age 11 are associated with adult crime at age 23, suggesting that reduced P3 may be an early neurobiological marker for cognitive and affective processes subserved by the temporal-parietal junction that place a child at risk for adult crime.
Jain, Kartik; Ringstad, Geir; Eide, Per-Kristian; Mardal, Kent-André
2017-09-01
Obstruction to the cerebrospinal fluid (CSF) outflow caused by the herniation of cerebellar tonsils as a result of Chiari malformation type I leads to altered CSF hydrodynamics. This contribution explores the minutest characteristics of the CSF hydrodynamics in cervical subarachnoid space (SAS) of a healthy subject and 2 Chiari patients by performing highly resolved direct numerical simulation. The lattice Boltzmann method is used for the simulations because of its scalability on modern supercomputers that allow us to simulate up to approximately 10 9 cells while resolving the Kolmogorov microscales. The results depict that whereas the complex CSF flow remains largely laminar in the SAS of a healthy subject, constriction of the cranio-vertebral junction in Chiari I patients causes manifold fluctuations in the hydrodynamics of the CSF. These fluctuations resemble a flow that is in a transitional regime rather than laminar or fully developed turbulence. The fluctuations confine near the cranio-vertebral junction and are triggered due to the tonsillar herniation, which perturbs the flow as a result of altered anatomy of the SAS. Copyright © 2016 John Wiley & Sons, Ltd.
Saget, Mathieu; Teyssedou, Simon; Prebet, Remi; Vendeuvre, Tanguy; Gayet, Louis-Etienne; Pries, Pierre
2014-08-01
Prospective clinical and radiological study. To evaluate the impact of stand-alone acrylic kyphoplasty in the treatment of recent traumatic fractures of the thoracolumbar spine in young patients. The management of fractures of the thoracolumbar spine without neurological deficit remains controversial. For a long time clinicians could only chose between functional treatment, orthopedic treatment, and traditional surgery. The recent advent of minimally invasive surgical techniques is an interesting alternative. Fifty-four patients with a mean age of 45.8±18.2 years and who had recently sustained a fracture of the thoracolumbar junction were enrolled into the study. Balloon kyphoplasty was performed using acrylic cement. Radiologic assessments (computed tomography scans) and clinical assessments (including Visual Analog Scale and Oswestry Disability Index scores) were used to determine kyphoplasty success and measure patient recovery over 2 years. Kyphoplasty reduced mean vertebral kyphosis from 12.8±5.0 degrees at trauma to 8.2±5.1 degrees at 2-year follow-up. Mean vertebral kyphosis was corrected by -5.7±4.7 degrees (P=0.0001) at the point of first verticalization, with no significant change at the 2-year follow-up visit (+1.1±4.3 degrees, P=0.1058). Kyphoplasty significantly augmented the height of the 6 anterior and intermediate segments. Maximum mean augmentation of intermediate vertebral height after 6 months was (11.6%±15.5%, P<0.0001). Patients tolerated the procedure well and 56% of them returned to work 3 months after kyphoplasty. Kyphoplasty is safe and effective in the correction of nonosteoporotic fractures of the thoracolumbar junction in young patients, and remains stable for at least 2 years postsurgery.
Tang, Juan; Huang, Yapei; Liu, Huiqiong; Zhang, Cengceng; Tang, Dianping
2016-12-01
A new homogeneous electrochemical immunosensing platform was designed for sensitive detection of aflatoxin B 1 (AFB 1 ) in foodstuff. The system consisted of anti-AFB 1 antibody labeled DNA 1 (Ab-DNA 1 ), AFB 1 -bovine serum albumin (BSA)-conjugated DNA 2 (AFB 1 -DNA 2 ), and methylene blue functionalized hairpin DNA. Owing to a specific antigen-antibody reaction between anti-AFB 1 and AFB 1 -BSA, the immunocomplex formed assisted the proximity hybridization of DNA 1 with DNA 2 , thus resulting in the formation of an omega-like DNA junction. Thereafter, the junction opened the hairpin DNA to construct a new double-stranded DNA, which could be readily cleaved by exonuclease III to release the omega-like DNA junction and methylene blue. The dissociated DNA junction could repeatedly hybridize with residual hairpin DNA molecules with exonuclease III-based isothermal cycling amplification, thereby releasing numerous free methylene blue molecules into the detection solution. The as-produced free methylene blue molecules could be captured by a negatively charged indium tin oxide electrode, each of which could produce an electronic signal within the applied potentials. On introduction of target AFB 1 , the analyte competed with AFB 1 -DNA 2 for the conjugated anti-AFB 1 on the Ab-DNA 1 , subsequently decreasing the amount of omega-like DNA junctions formed, hence causing methylene blue labeled hairpin DNA to move far away from the electrode surface. Under optimal conditions the detectable electrochemical signal decreased with increasing amount of target AFB 1 in a dynamic working range of 0.01-30 ng mL -1 with a detection limit of 4.8 pg mL -1 . In addition, the precision and reproducibility of this system were acceptable. Finally, the method was further evaluated for analysis of naturally contaminated or AFB 1 -spiked peanut samples, giving results that matched well with those obtained with a commercial AFB 1 ELISA kit.