Sample records for channel structure final

  1. Manipulation of cells' position across a microfluidic channel using a series of continuously varying herringbone structures

    NASA Astrophysics Data System (ADS)

    Jung, Yugyung; Hyun, Ji-chul; Choi, Jongchan; Atajanov, Arslan; Yang, Sung

    2017-12-01

    Controlling cells' movement is an important technique in biological analysis that is performed within a microfluidic system. Many external forces are utilized for manipulation of cells, including their position in the channel. These forces can effectively control cells in a desired manner. Most of techniques used to manipulate cells require sophisticated set-ups and equipment to generate desired effect. The exception to this is the use of hydrodynamic force. In this study, a series of continuously varying herringbone structures is proposed for positioning cells in a microfluidic channel using hydrodynamic force. This structure was experimentally developed by changing parameters, such as the length of the herringbone's apex, the length of the herringbone's base and the ratio of the height of the flat channel to the height of the herringbone structure. Results of this study, have demonstrated that the length of the herringbone's apex and the ratio of the heights of the flat channel and the herringbone structure were crucial parameters influencing positioning of cells at 100 μl/h flow rate. The final design was fixed at 170 and 80 μm for the length of herringbone's apex and the length of herringbone's base, respectively. The average position of cells in this device was 34 μm away from the side wall in a 200 μm wide channel. Finally, to substantiate a practical application of the herringbone structure for positioning, cells were randomly introduced into a microfluidic device, containing an array of trapping structures together with a series of herringbone structures along the channel. The cells were moved toward the trapping structure by the herringbone structure and the trapping efficiency was increased. Therefore, it is anticipated that this device will be utilized to continuously control cells' position without application of external forces.

  2. Channelization in porous media driven by erosion and deposition.

    PubMed

    Jäger, R; Mendoza, M; Herrmann, H J

    2017-01-01

    We develop and validate a new model to study simultaneous erosion and deposition in three-dimensional porous media. We study the changes of the porous structure induced by the deposition and erosion of matter on the solid surface and find that when both processes are active, channelization in the porous structure always occurs. The channels can be stable or only temporary depending mainly on the driving mechanism. Whereas a fluid driven by a constant pressure drop in general does not form steady channels, imposing a constant flux always produces stable channels within the porous structure. Furthermore we investigate how changes of the local deposition and erosion properties affect the final state of the porous structure, finding that the larger the range of wall shear stress for which there is neither erosion nor deposition, the more steady channels are formed in the structure.

  3. Assessment of the effects of regional channel stability and sediment transport on roadway hydraulic structures : final report.

    DOT National Transportation Integrated Search

    2014-06-01

    Rivers and streams evolve all the time. As a result, no stream channel is absolutely stable. Channels evolve at various speeds both vertically (degradation/aggradation) and horizontally (meander : migration). They also respond to man-made changes ran...

  4. Structure of the CLC-1 chloride channel from Homo sapiens.

    PubMed

    Park, Eunyong; MacKinnon, Roderick

    2018-05-29

    CLC channels mediate passive Cl - conduction, while CLC transporters mediate active Cl - transport coupled to H + transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl - conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl - at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl - affinity distinguish CLC channels and transporters. © 2018, Park & MacKinnon.

  5. Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin

    PubMed Central

    Bae, Chanhyung; Anselmi, Claudio; Kalia, Jeet; Jara-Oseguera, Andres; Schwieters, Charles D; Krepkiy, Dmitriy; Won Lee, Chul; Kim, Eun-Hee; Kim, Jae Il; Faraldo-Gómez, José D; Swartz, Kenton J

    2016-01-01

    Venom toxins are invaluable tools for exploring the structure and mechanisms of ion channels. Here, we solve the structure of double-knot toxin (DkTx), a tarantula toxin that activates the heat-activated TRPV1 channel. We also provide improved structures of TRPV1 with and without the toxin bound, and investigate the interactions of DkTx with the channel and membranes. We find that DkTx binds to the outer edge of the external pore of TRPV1 in a counterclockwise configuration, using a limited protein-protein interface and inserting hydrophobic residues into the bilayer. We also show that DkTx partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning and channel activation. Finally, we find that the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation. Collectively, our findings reveal a novel mode of toxin-channel recognition that has important implications for the mechanism of thermosensation. DOI: http://dx.doi.org/10.7554/eLife.11273.001 PMID:26880553

  6. Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

    PubMed Central

    Sepúlveda, Francisco V.; Pablo Cid, L.; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142

  7. Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy.

    PubMed

    Michalakis, Stylianos; Becirovic, Elvir; Biel, Martin

    2018-03-07

    The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca 2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application.

  8. Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

    PubMed Central

    Biel, Martin

    2018-01-01

    The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application. PMID:29518895

  9. Organization of the channel-switching process in parallel computer systems based on a matrix optical switch

    NASA Technical Reports Server (NTRS)

    Golomidov, Y. V.; Li, S. K.; Popov, S. A.; Smolov, V. B.

    1986-01-01

    After a classification and analysis of electronic and optoelectronic switching devices, the design principles and structure of a matrix optical switch is described. The switching and pair-exclusion operations in this type of switch are examined, and a method for the optical switching of communication channels is elaborated. Finally, attention is given to the structural organization of a parallel computer system with a matrix optical switch.

  10. High-performance low-cost back-channel-etch amorphous gallium-indium-zinc oxide thin-film transistors by curing and passivation of the damaged back channel.

    PubMed

    Park, Jae Chul; Ahn, Seung-Eon; Lee, Ho-Nyeon

    2013-12-11

    High-performance, low-cost amorphous gallium-indium-zinc oxide (a-GIZO) thin-film-transistor (TFT) technology is required for the next generation of active-matrix organic light-emitting diodes. A back-channel-etch structure is the most appropriate device structure for high-performance, low-cost a-GIZO TFT technology. However, channel damage due to source/drain etching and passivation-layer deposition has been a critical issue. To solve this problem, the present work focuses on overall back-channel processes, such as back-channel N2O plasma treatment, SiOx passivation deposition, and final thermal annealing. This work has revealed the dependence of a-GIZO TFT characteristics on the N2O plasma radio-frequency (RF) power and frequency, the SiH4 flow rate in the SiOx deposition process, and the final annealing temperature. On the basis of these results, a high-performance a-GIZO TFT with a field-effect mobility of 35.7 cm(2) V(-1) s(-1), a subthreshold swing of 185 mV dec(-1), a switching ratio exceeding 10(7), and a satisfactory reliability was successfully fabricated. The technology developed in this work can be realized using the existing facilities of active-matrix liquid-crystal display industries.

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

    Ahn, Cheol Hyoun; Hee Kim, So; Gu Yun, Myeong

    In this study, we proposed the artificially designed channel structure in oxide thin-film transistors (TFTs) called a “step-composition gradient channel.” We demonstrated Al step-composition gradient Al-Zn-O (AZO) channel structures consisting of three AZO layers with different Al contents. The effects of stacking sequence in the step-composition gradient channel on performance and electrical stability of bottom-gate TFT devices were investigated with two channels of inverse stacking order (ascending/descending step-composition). The TFT with ascending step-composition channel structure (5 → 10 → 14 at. % Al composition) showed relatively negative threshold voltage (−3.7 V) and good instability characteristics with a reduced threshold voltage shift (Δmore » 1.4 V), which was related to the alignment of the conduction band off-set within the channel layer depending on the Al contents. Finally, the reduced Al composition in the initial layer of ascending step-composition channel resulted in the best field effect mobility of 4.5 cm{sup 2}/V s. We presented a unique active layer of the “step-composition gradient channel” in the oxide TFTs and explained the mechanism of adequate channel design.« less

  12. IBRD sonar scour monitoring project : real-time river channel-bed monitoring at the Chariton and Mississippi Rivers in Missouri, 2007-09, final report, January 2010.

    DOT National Transportation Integrated Search

    2010-01-01

    Scour and depositional responses to hydrologic events have been important to the scientific community studying sediment transport as well as potential effects on bridges and other hydraulic structures within riverine systems. A river channel-bed moni...

  13. Dimensional metrology of lab-on-a-chip internal structures: a comparison of optical coherence tomography with confocal fluorescence microscopy.

    PubMed

    Reyes, D R; Halter, M; Hwang, J

    2015-07-01

    The characterization of internal structures in a polymeric microfluidic device, especially of a final product, will require a different set of optical metrology tools than those traditionally used for microelectronic devices. We demonstrate that optical coherence tomography (OCT) imaging is a promising technique to characterize the internal structures of poly(methyl methacrylate) devices where the subsurface structures often cannot be imaged by conventional wide field optical microscopy. The structural details of channels in the devices were imaged with OCT and analyzed with an in-house written ImageJ macro in an effort to identify the structural details of the channel. The dimensional values obtained with OCT were compared with laser-scanning confocal microscopy images of channels filled with a fluorophore solution. Attempts were also made using confocal reflectance and interferometry microscopy to measure the channel dimensions, but artefacts present in the images precluded quantitative analysis. OCT provided the most accurate estimates for the channel height based on an analysis of optical micrographs obtained after destructively slicing the channel with a microtome. OCT may be a promising technique for the future of three-dimensional metrology of critical internal structures in lab-on-a-chip devices because scans can be performed rapidly and noninvasively prior to their use. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  14. Emitter signal separation method based on multi-level digital channelization

    NASA Astrophysics Data System (ADS)

    Han, Xun; Ping, Yifan; Wang, Sujun; Feng, Ying; Kuang, Yin; Yang, Xinquan

    2018-02-01

    To solve the problem of emitter separation under complex electromagnetic environment, a signal separation method based on multi-level digital channelization is proposed in this paper. A two-level structure which can divide signal into different channel is designed first, after that, the peaks of different channels are tracked using the track filter and the coincident signals in time domain are separated in time-frequency domain. Finally, the time domain waveforms of different signals are acquired by reverse transformation. The validness of the proposed method is proved by experiment.

  15. Thermally activated TRP channels: molecular sensors for temperature detection.

    PubMed

    Castillo, Karen; Diaz-Franulic, Ignacio; Canan, Jonathan; Gonzalez-Nilo, Fernando; Latorre, Ramon

    2018-01-24

    Temperature sensing is one of the oldest capabilities of living organisms, and is essential for sustaining life, because failure to avoid extreme noxious temperatures can result in tissue damage or death. A subset of members of the transient receptor potential (TRP) ion channel family is finely tuned to detect temperatures ranging from extreme cold to noxious heat, giving rise to thermoTRP channels. Structural and functional experiments have shown that thermoTRP channels are allosteric proteins, containing different domains that sense changes in temperature, among other stimuli, triggering pore opening. Although temperature-dependence is well characterized in thermoTRP channels, the molecular nature of temperature-sensing elements remains unknown. Importantly, thermoTRP channels are involved in pain sensation, related to pathological conditions. Here, we provide an overview of thermoTRP channel activation. We also discuss the structural and functional evidence supporting the existence of an intrinsic temperature sensor in this class of channels, and we explore the basic thermodynamic principles for channel activation. Finally, we give a view of their role in painful pathophysiological conditions.

  16. Isolation and Characterization of a High Affinity Peptide Inhibitor of ClC-2 Chloride Channels*

    PubMed Central

    Thompson, Christopher H.; Olivetti, Pedro R.; Fuller, Matthew D.; Freeman, Cody S.; McMaster, Denis; French, Robert J.; Pohl, Jan; Kubanek, Julia; McCarty, Nael A.

    2009-01-01

    The ClC protein family includes voltage-gated chloride channels and chloride/proton exchangers. In eukaryotes, ClC proteins regulate membrane potential of excitable cells, contribute to epithelial transport, and aid in lysosomal acidification. Although structure/function studies of ClC proteins have been aided greatly by the available crystal structures of a bacterial ClC chloride/proton exchanger, the availability of useful pharmacological tools, such as peptide toxin inhibitors, has lagged far behind that of their cation channel counterparts. Here we report the isolation, from Leiurus quinquestriatus hebraeus venom, of a peptide toxin inhibitor of the ClC-2 chloride channel. This toxin, GaTx2, inhibits ClC-2 channels with a voltage-dependent apparent KD of ∼20 pm, making it the highest affinity inhibitor of any chloride channel. GaTx2 slows ClC-2 activation by increasing the latency to first opening by nearly 8-fold but is unable to inhibit open channels, suggesting that this toxin inhibits channel activation gating. Finally, GaTx2 specifically inhibits ClC-2 channels, showing no inhibitory effect on a battery of other major classes of chloride channels and voltage-gated potassium channels. GaTx2 is the first peptide toxin inhibitor of any ClC protein. The high affinity and specificity displayed by this toxin will make it a very powerful pharmacological tool to probe ClC-2 structure/function. PMID:19574231

  17. Thermal Analysis of AlGaN/GaN High-Electron-Mobility Transistor and Its RF Power Efficiency Optimization with Source-Bridged Field-Plate Structure.

    PubMed

    Kwak, Hyeon-Tak; Chang, Seung-Bo; Jung, Hyun-Gu; Kim, Hyun-Seok

    2018-09-01

    In this study, we consider the relationship between the temperature in a two-dimensional electron gas (2-DEG) channel layer and the RF characteristics of an AlGaN/GaN high-electron-mobility transistor by changing the geometrical structure of the field-plate. The final goal is to achieve a high power efficiency by decreasing the channel layer temperature. First, simulations were performed to compare and contrast the experimental data of a conventional T-gate head structure. Then, a source-bridged field-plate (SBFP) structure was used to obtain the lower junction temperature in the 2-DEG channel layer. The peak electric field intensity was reduced, and a decrease in channel temperature resulted in an increase in electron mobility. Furthermore, the gate-to-source capacitance was increased by the SBFP structure. However, under the large current flow condition, the SBFP structure had a lower maximum temperature than the basic T-gate head structure, which improved the device electron mobility. Eventually, an optimum position of the SBFP was used, which led to higher frequency responses and improved the breakdown voltages. Hence, the optimized SBFP structure can be a promising candidate for high-power RF devices.

  18. Dynamics of internal pore opening in KV channels probed by a fluorescent unnatural amino acid

    PubMed Central

    Kalstrup, Tanja; Blunck, Rikard

    2013-01-01

    Atomic-scale models on the gating mechanism of voltage-gated potassium channels (Kv) are based on linear interpolations between static structures of their initial and final state derived from crystallography and molecular dynamics simulations, and, thus, lack dynamic structural information. The lack of information on dynamics and intermediate states makes it difficult to associate the structural with the dynamic functional data obtained with electrophysiology. Although voltage-clamp fluorometry fills this gap, it is limited to sites extracellularly accessible, when the key region for gating is located at the cytosolic side of the channels. Here, we solved this problem by performing voltage-clamp fluorometry with a fluorescent unnatural amino acid. By using an orthogonal tRNA-synthetase pair, the fluorescent unnatural amino acid was incorporated in the Shaker voltage-gated potassium channel at key regions that were previously inaccessible. Thus, we defined which parts act independently and which parts act cooperatively and found pore opening to occur in two sequential transitions. PMID:23630265

  19. Strain localization in a fossilized subduction channel: Insights from the Cycladic Blueschist Unit (Syros, Greece)

    NASA Astrophysics Data System (ADS)

    Laurent, Valentin; Jolivet, Laurent; Roche, Vincent; Augier, Romain; Scaillet, Stéphane; Cardello, Giovanni Luca

    2016-03-01

    Syros Island is worldwide known for its preservation of HP-LT parageneses in the Cycladic Blueschist Unit (CBU) providing one of the best case-studies to understand the tectonometamorphic evolution of a subduction channel. Conflicting structural interpretations have been proposed to explain the geological architecture of Syros, in part reflecting a lack of consensus about the tectonic structure of the CBU. In this study, the geological and tectonometamorphic maps of Syros have been entirely redrawn in order to decipher the structure of a fossilized subduction channel. Based on structural and petrological observations, the CBU has been subdivided into three subunits separated by major ductile shear zones. New observations of the Vari Unit confirm that it rests on top of the CBU through a detachment or exhumation fault. While retrograde top-to-the E/NE shearing overprinting prograde deformation is widespread across the island, the prograde deformation has been only locally preserved within the less retrograded units. We show that after the prograde top-to-the S/SW shearing deformation, the CBU was exhumed by an overall top-to-the E/NE shearing from the depth of the eclogite-facies all the way to the depth of the greenschist-facies and finally, to the brittle crust. The exhumation process encompassed the syn-orogenic stage (contemporaneous of subduction, within the subduction channel - Eocene) to the post-orogenic stage (contemporaneous with the formation of the Aegean Sea - Oligocene to Miocene). From syn-orogenic to post-orogenic exhumation, deformation progressively localized toward the base of the CBU, along large-scale ductile shear zones, allowing the preservation of earlier HP-LT structures and HP-LT metamorphic parageneses. Finally, this study brings new insights on the tectonometamorphic evolution of a subduction channel showing how strain localizes during the history of an accretionary complex, both during the prograde and retrograde history.

  20. Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations.

    PubMed

    Subbotina, Julia; Yarov-Yarovoy, Vladimir; Lees-Miller, James; Durdagi, Serdar; Guo, Jiqing; Duff, Henry J; Noskov, Sergei Yu

    2010-11-01

    The hERG1 gene (Kv11.1) encodes a voltage-gated potassium channel. Mutations in this gene lead to one form of the Long QT Syndrome (LQTS) in humans. Promiscuous binding of drugs to hERG1 is known to alter the structure/function of the channel leading to an acquired form of the LQTS. Expectably, creation and validation of reliable 3D model of the channel have been a key target in molecular cardiology and pharmacology for the last decade. Although many models were built, they all were limited to pore domain. In this work, a full model of the hERG1 channel is developed which includes all transmembrane segments. We tested a template-driven de-novo design with ROSETTA-membrane modeling using side-chain placements optimized by subsequent molecular dynamics (MD) simulations. Although backbone templates for the homology modeled parts of the pore and voltage sensors were based on the available structures of KvAP, Kv1.2 and Kv1.2-Kv2.1 chimera channels, the missing parts are modeled de-novo. The impact of several alignments on the structure of the S4 helix in the voltage-sensing domain was also tested. Herein, final models are evaluated for consistency to the reported structural elements discovered mainly on the basis of mutagenesis and electrophysiology. These structural elements include salt bridges and close contacts in the voltage-sensor domain; and the topology of the extracellular S5-pore linker compared with that established by toxin foot-printing and nuclear magnetic resonance studies. Implications of the refined hERG1 model to binding of blockers and channels activators (potent new ligands for channel activations) are discussed. © 2010 Wiley-Liss, Inc.

  1. MO-DE-207A-05: Dictionary Learning Based Reconstruction with Low-Rank Constraint for Low-Dose Spectral CT

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

    Xu, Q; Stanford University School of Medicine, Stanford, CA; Liu, H

    Purpose: Spectral CT enabled by an energy-resolved photon-counting detector outperforms conventional CT in terms of material discrimination, contrast resolution, etc. One reconstruction method for spectral CT is to generate a color image from a reconstructed component in each energy channel. However, given the radiation dose, the number of photons in each channel is limited, which will result in strong noise in each channel and affect the final color reconstruction. Here we propose a novel dictionary learning method for spectral CT that combines dictionary-based sparse representation method and the patch based low-rank constraint to simultaneously improve the reconstruction in each channelmore » and to address the inter-channel correlations to further improve the reconstruction. Methods: The proposed method has two important features: (1) guarantee of the patch based sparsity in each energy channel, which is the result of the dictionary based sparse representation constraint; (2) the explicit consideration of the correlations among different energy channels, which is realized by patch-by-patch nuclear norm-based low-rank constraint. For each channel, the dictionary consists of two sub-dictionaries. One is learned from the average of the images in all energy channels, and the other is learned from the average of the images in all energy channels except the current channel. With average operation to reduce noise, these two dictionaries can effectively preserve the structural details and get rid of artifacts caused by noise. Combining them together can express all structural information in current channel. Results: Dictionary learning based methods can obtain better results than FBP and the TV-based method. With low-rank constraint, the image quality can be further improved in the channel with more noise. The final color result by the proposed method has the best visual quality. Conclusion: The proposed method can effectively improve the image quality of low-dose spectral CT. This work is partially supported by the National Natural Science Foundation of China (No. 61302136), and the Natural Science Basic Research Plan in Shaanxi Province of China (No. 2014JQ8317).« less

  2. Structure and Environment Influence in DNA Conduction

    NASA Technical Reports Server (NTRS)

    Adessi, C.; Walch, S.; Anantram, M. P.; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    Results for transmission through a poly(G) DNA molecule are presented. We show that a modification of the rise of a B-DNA form can induce a shift of the conduction channel toward the valence one. We clearly prove that deformation of the backbone of the molecule has a significant influence on hole transport. Finally, we observe that the presence of ionic species, such Na, near the molecule can create new conduction channels.

  3. Channel branching ratios in CH2CN- photodetachment: Rotational structure and vibrational energy redistribution in autodetachment

    NASA Astrophysics Data System (ADS)

    Lyle, Justin; Wedig, Olivia; Gulania, Sahil; Krylov, Anna I.; Mabbs, Richard

    2017-12-01

    We report photoelectron spectra of CH2CN-, recorded at photon energies between 13 460 and 15 384 cm-1, which show rapid intensity variations in particular detachment channels. The branching ratios for various spectral features reveal rotational structure associated with autodetachment from an intermediate anion state. Calculations using equation-of-motion coupled-cluster method with single and double excitations reveal the presence of two dipole-bound excited anion states (a singlet and a triplet). The computed oscillator strength for the transition to the singlet dipole-bound state provides an estimate of the autodetachment channel contribution to the total photoelectron yield. Analysis of the different spectral features allows identification of the dipole-bound and neutral vibrational levels involved in the autodetachment processes. For the most part, the autodetachment channels are consistent with the vibrational propensity rule and normal mode expectation. However, examination of the rotational structure shows that autodetachment from the ν3 (v = 1 and v = 2) levels of the dipole-bound state displays behavior counter to the normal mode expectation with the final state vibrational level belonging to a different mode.

  4. Laser-guided, intersecting discharge channels for the final beam transport in heavy-ion fusion

    NASA Astrophysics Data System (ADS)

    Niemann, C.; Neff, S.; Tauschwitz, A.; Penache, D.; Birkner, R.; Constantin, C.; Knobloch, R.; Presura, R.; Rosmej, F. B.; Hoffmann, D. H. H.; Yu, S. S.

    2003-06-01

    Ion-beam transport in space charge neutralizing discharge channels has been proposed for the final focus and chamber transport in a heavy-ion fusion reactor. A driver scenario with two-sided target illumination requires a system of two intersecting discharges to transport beams of the same charge from opposite sides towards the fusion target. In this article we report on experiments on the creation of free-standing, intersecting high-current discharge channels. The discharges are initiated in ammonia gas (NH3) in a metallic chamber by two perpendicular CO2-laser beams, which resonantly heat and subsequently rarefy the gas along the laser paths before the breakdown. These low density channels guide the discharges along the predefined paths and also around the 90° angles without any mechanical guiding structures. In this way stable X-, T-, and L-shaped discharges with currents in excess of 40 kA, at pressures of a few mbar were created with a total length of 110 cm. An 11.4 A MeV 58Ni+12 beam from the UNILAC (Universal Linear Accelerator) linear accelerator was used to probe the line-integrated ion-optical properties of the central channel in a T-shaped discharge.

  5. Multiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel

    PubMed Central

    Goldschen-Ohm, Marcel P.; Capes, Deborah L.; Oelstrom, Kevin M.; Chanda, Baron

    2013-01-01

    Voltage-dependent Na+ channels are crucial for electrical signalling in excitable cells. Membrane depolarization initiates asynchronous movements in four non-identical voltage-sensing domains of the Na+ channel. It remains unclear to what extent this structural asymmetry influences pore gating as compared with outwardly rectifying K+ channels, where channel opening results from a final concerted transition of symmetric pore gates. Here we combine single channel recordings, cysteine accessibility and voltage clamp fluorimetry to probe the relationships between voltage sensors and pore conformations in an inactivation deficient Nav1.4 channel. We observe three distinct conductance levels such that DI-III voltage sensor activation is kinetically correlated with formation of a fully open pore, whereas DIV voltage sensor movement underlies formation of a distinct subconducting pore conformation preceding inactivation in wild-type channels. Our experiments reveal that pore gating in sodium channels involves multiple transitions driven by asynchronous movements of voltage sensors. These findings shed new light on the mechanism of coupling between activation and fast inactivation in voltage-gated sodium channels. PMID:23322038

  6. Fluid mixing in droplet-based microfluidics with T junction and convergent-divergent sinusoidal microchannels.

    PubMed

    Yang, Li; Li, Shanshan; Liu, Jixiao; Cheng, Jingmeng

    2018-02-01

    To explore and utilize the advantages of droplet-based microfluidics, hydrodynamics, and mixing process within droplets traveling though the T junction channel and convergent-divergent sinusoidal microchannels are studied by numerical simulations and experiments, respectively. In the T junction channel, the mixing efficiency is significantly influenced by the twirling effect, which controls the initial distributions of the mixture during the droplet formation stage. Therefore, the internal recirculating flow can create a convection mechanism, thus improving mixing. The twirling effect is noticeably influenced by the velocity of the continuous phase; in the sinusoidal channel, the Dean vortices and droplet deformation are induced by centrifugal force and alternative velocity gradient, thus enhancing the mixing efficiency. The best mixing occurred when the droplet size is comparable with the channel width. Finally, we propose a unique optimized structure, which includes a T junction inlet joined to a sinusoidal channel. In this structure, the mixing of fluids in the droplets follows two routes: One is the twirling effect and symmetric recirculation flow in the straight channel. The other is the asymmetric recirculation and droplet deformation in the winding and variable cross-section. Among the three structures, the optimized structure has the best mixing efficiency at the shortest mixing time (0.25 ms). The combination of the twirling effect, variable cross-section effect, and Dean vortices greatly intensifies the chaotic flow. This study provides the insight of the mixing process and may benefit the design and operations of droplet-based microfluidics. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Stratification and salt-wedge in the Seomjin river estuary under the idealized tidal influence

    NASA Astrophysics Data System (ADS)

    Hwang, Jin Hwan; Jang, Dongmin; Kim, Yong Hoon

    2017-12-01

    Advection, straining, and vertical mixing play primary roles in the process of estuarine stratification. Estuaries can be classified as salt-wedge, partially-mixed or well-mixed depending on the vertical density structure determined by the balancing of advection, mixing and straining. In particular, straining plays a major role in the stratification of the estuarine water body along the estuarine channel. Also, the behavior of a salt wedge with a halocline shape in a stratified channel can be controlled by the competition between straining and mixing induced by buoyancy from the riverine source and tidal forcing. The present study uses Finite Volume Coastal Ocean Model (FVCOM) to show that straining and vertical mixing play major roles in controlling along-channel flow and stratification structures in the Seomjin river estuary (SRE) under idealized conditions. The Potential Energy Anomaly (PEA) dynamic equation quantifies the governing processes thereby enabling the determination of the stratification type. By comparing terms in the equation, we examined how the relative strengths of straining and mixing alter the stratification types in the SRE due to changes in river discharge and the depth resulting from dredging activities. SRE under idealized tidal forcing tends to be partially-mixed based on an analysis of the balance between terms and the vertical structure of salinity, and the morphological and hydrological change in SRE results in the shift of stratification type. While the depth affects the mixing, the freshwater discharge mainly controls the straining, and the balance between mixing and straining determines the final state of the stratification in an estuarine channel. As a result, the development and location of a salt wedge along the channel in a partially mixed and highly stratified condition is also determined by the ratio of straining to mixing. Finally, our findings confirm that the contributions of mixing and straining can be assessed by using the conventional non-dimensional parameters with respect to salt-wedge behavior.

  8. Function and dysfunction of CNG channels: insights from channelopathies and mouse models.

    PubMed

    Biel, Martin; Michalakis, Stylianos

    2007-06-01

    Channels directly gated by cyclic nucleotides (CNG channels) are important cellular switches that mediate influx of Na+ and Ca2+ in response to increases in the intracellular concentration of cAMP and cGMP. In photoreceptors and olfactory receptor neurons, these channels serve as final targets for cGMP and cAMP signaling pathways that are initiated by the absorption of photons and the binding of odorants, respectively. CNG channels have been also found in other types of neurons and in non-excitable cells. However, in most of these cells, the physiological role of CNG channels has yet to be determined. CNG channels have a complex heteromeric structure. The properties of individual subunits that assemble in specific stoichiometries to the native channels have been extensively investigated in heterologous expression systems. Recently, mutations in human CNG channel genes leading to inherited diseases (so-called channelopathies) have been functionally characterized. Moreover, mouse knockout models were generated to define the role of CNG channel proteins in vivo. In this review, we will summarize recent insights into the physiological and pathophysiological role of CNG channel proteins that have emerged from genetic studies in mice and humans.

  9. Marine Toxins Targeting Ion Channels

    PubMed Central

    Arias, Hugo R.

    2006-01-01

    This introductory minireview points out the importance of ion channels for cell communication. The basic concepts on the structure and function of ion channels triggered by membrane voltage changes, the so-called voltage-gated ion channels (VGICs), as well as those activated by neurotransmitters, the so-called ligand-gated ion channel (LGICs), are introduced. Among the most important VGIC superfamiles, we can name the voltage-gated Na+ (NaV), Ca2+ (CaV), and K+ (KV) channels. Among the most important LGIC super families, we can include the Cys-loop or nicotinicoid, the glutamate-activated (GluR), and the ATP-activated (P2XnR) receptor superfamilies. Ion channels are transmembrane proteins that allow the passage of different ions in a specific or unspecific manner. For instance, the activation of NaV, CaV, or KV channels opens a pore that is specific for Na+, Ca2+, or K+, respectively. On the other hand, the activation of certain LGICs such as nicotinic acetylcholine receptors, GluRs, and P2XnRs allows the passage of cations (e.g., Na+, K+, and/or Ca2+), whereas the activation of other LGICs such as type A γ-butyric acid and glycine receptors allows the passage of anions (e.g., Cl− and/or HCO3−). In this regard, the activation of NaV and CaV as well as ligand-gated cation channels produce membrane depolarization, which finally leads to stimulatory effects in the cell, whereas the activation of KV as well as ligand-gated anion channels induce membrane hyperpolarization that finally leads to inhibitory effects in the cell. The importance of these ion channel superfamilies is emphasized by considering their physiological functions throughout the body as well as their pathophysiological implicance in several neuronal diseases. In this regard, natural molecules, and especially marine toxins, can be potentially used as modulators (e.g., inhibitors or prolongers) of ion channel functions to treat or to alleviate a specific ion channel-linked disease (e.g., channelopaties).

  10. The Influence of channel length to the characteristics of CuPc based OFET thin films

    NASA Astrophysics Data System (ADS)

    Sujarwata; Handayani, L.; Mosik; Fianti

    2018-03-01

    The main focus of this research is to characterize organic field effect transistor (OFET) thin films based on CuPc with a bottom-contact structure and varied channel length. OFET was prepared by Si substrate cleaning in the ultrasonic cleaner first, then deposition of the source and drain electrodes on the substrate with vacuum evaporation at room temperature, and finally CuPc thin film deposition among the source, drain, and gate electrodes. The distance between source anddrain electrodes is the channel length of the CuPc thin film. In this research, the channel length was varied; 100 μm, 200 μm and 300 μm, with the same active areas of 2.9-3.42 V and different current, IDS. The result showed that the shorter channel length causes, the bigger IDS flowing on the OFET

  11. Computational Methods of Studying the Binding of Toxins From Venomous Animals to Biological Ion Channels: Theory and Applications

    PubMed Central

    Chen, Rong; Chung, Shin-Ho

    2013-01-01

    The discovery of new drugs that selectively block or modulate ion channels has great potential to provide new treatments for a host of conditions. One promising avenue revolves around modifying or mimicking certain naturally occurring ion channel modulator toxins. This strategy appears to offer the prospect of designing drugs that are both potent and specific. The use of computational modeling is crucial to this endeavor, as it has the potential to provide lower cost alternatives for exploring the effects of new compounds on ion channels. In addition, computational modeling can provide structural information and theoretical understanding that is not easily derivable from experimental results. In this review, we look at the theory and computational methods that are applicable to the study of ion channel modulators. The first section provides an introduction to various theoretical concepts, including force-fields and the statistical mechanics of binding. We then look at various computational techniques available to the researcher, including molecular dynamics, Brownian dynamics, and molecular docking systems. The latter section of the review explores applications of these techniques, concentrating on pore blocker and gating modifier toxins of potassium and sodium channels. After first discussing the structural features of these channels, and their modes of block, we provide an in-depth review of past computational work that has been carried out. Finally, we discuss prospects for future developments in the field. PMID:23589832

  12. A Fast, Open EEG Classification Framework Based on Feature Compression and Channel Ranking

    PubMed Central

    Han, Jiuqi; Zhao, Yuwei; Sun, Hongji; Chen, Jiayun; Ke, Ang; Xu, Gesen; Zhang, Hualiang; Zhou, Jin; Wang, Changyong

    2018-01-01

    Superior feature extraction, channel selection and classification methods are essential for designing electroencephalography (EEG) classification frameworks. However, the performance of most frameworks is limited by their improper channel selection methods and too specifical design, leading to high computational complexity, non-convergent procedure and narrow expansibility. In this paper, to remedy these drawbacks, we propose a fast, open EEG classification framework centralized by EEG feature compression, low-dimensional representation, and convergent iterative channel ranking. First, to reduce the complexity, we use data clustering to compress the EEG features channel-wise, packing the high-dimensional EEG signal, and endowing them with numerical signatures. Second, to provide easy access to alternative superior methods, we structurally represent each EEG trial in a feature vector with its corresponding numerical signature. Thus, the recorded signals of many trials shrink to a low-dimensional structural matrix compatible with most pattern recognition methods. Third, a series of effective iterative feature selection approaches with theoretical convergence is introduced to rank the EEG channels and remove redundant ones, further accelerating the EEG classification process and ensuring its stability. Finally, a classical linear discriminant analysis (LDA) model is employed to classify a single EEG trial with selected channels. Experimental results on two real world brain-computer interface (BCI) competition datasets demonstrate the promising performance of the proposed framework over state-of-the-art methods. PMID:29713262

  13. Molecular Dynamics Simulation Reveals Specific Interaction Sites between Scorpion Toxins and Kv1.2 Channel: Implications for Design of Highly Selective Drugs

    PubMed Central

    Yuan, Shouli; Gao, Bin

    2017-01-01

    The Kv1.2 channel plays an important role in the maintenance of resting membrane potential and the regulation of the cellular excitability of neurons, whose silencing or mutations can elicit neuropathic pain or neurological diseases (e.g., epilepsy and ataxia). Scorpion venom contains a variety of peptide toxins targeting the pore region of this channel. Despite a large amount of structural and functional data currently available, their detailed interaction modes are poorly understood. In this work, we choose four Kv1.2-targeted scorpion toxins (Margatoxin, Agitoxin-2, OsK-1, and Mesomartoxin) to construct their complexes with Kv1.2 based on the experimental structure of ChTx-Kv1.2. Molecular dynamics simulation of these complexes lead to the identification of hydrophobic patches, hydrogen-bonds, and salt bridges as three essential forces mediating the interactions between this channel and the toxins, in which four Kv1.2-specific interacting amino acids (D353, Q358, V381, and T383) are identified for the first time. This discovery might help design highly selective Kv1.2-channel inhibitors by altering amino acids of these toxins binding to the four channel residues. Finally, our results provide new evidence in favor of an induced fit model between scorpion toxins and K+ channel interactions. PMID:29104247

  14. In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K+ Channels; Interaction and New Targets

    PubMed Central

    Moreno, Cristina; de la Cruz, Alicia; Valenzuela, Carmen

    2016-01-01

    Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the KV channel modulation by PUFAs: (i) the exact residues involved in PUFAs-KV channels interaction; (ii) the structural PUFAs determinants important for their effects on KV channels; (iii) the mechanism of the gating modulation of KV channels and, finally, (iv) the PUFAs modulation of a few new targets present in smooth muscle cells (SMC), KCa1.1, K2P, and KATP channels, involved in vascular relaxation. PMID:27933000

  15. 76 FR 59121 - Notice of Availability of the Record of Decision for the Final Environmental Impact Statement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... lined open channels; grade control structures; bridges and drainage crossings; building pads; and water quality control facilities (sedimentation control, flood control, debris, and water quality basins). The... facilities (sedimentation control, flood debris, and water quality basins); regular and ongoing maintenance...

  16. Localization and Molecular Determinants of the Hanatoxin Receptors on the Voltage-Sensing Domains of a K+ Channel

    PubMed Central

    Li-Smerin, Yingying; Swartz, Kenton J.

    2000-01-01

    Hanatoxin inhibits voltage-gated K+ channels by modifying the energetics of activation. We studied the molecular determinants and physical location of the Hanatoxin receptors on the drk1 voltage-gated K+ channel. First, we made multiple substitutions at three previously identified positions in the COOH terminus of S3 to examine whether these residues interact intimately with the toxin. We also examined a region encompassing S1–S3 using alanine-scanning mutagenesis to identify additional determinants of the toxin receptors. Finally, guided by the structure of the KcsA K+ channel, we explored whether the toxin interacts with the peripheral extracellular surface of the pore domain in the drk1 K+ channel. Our results argue for an intimate interaction between the toxin and the COOH terminus of S3 and suggest that the Hanatoxin receptors are confined within the voltage-sensing domains of the channel, at least 20–25 Å away from the central pore axis. PMID:10828242

  17. Multi-Dielectric Brownian Dynamics and Design-Space-Exploration Studies of Permeation in Ion Channels.

    PubMed

    Siksik, May; Krishnamurthy, Vikram

    2017-09-01

    This paper proposes a multi-dielectric Brownian dynamics simulation framework for design-space-exploration (DSE) studies of ion-channel permeation. The goal of such DSE studies is to estimate the channel modeling-parameters that minimize the mean-squared error between the simulated and expected "permeation characteristics." To address this computational challenge, we use a methodology based on statistical inference that utilizes the knowledge of channel structure to prune the design space. We demonstrate the proposed framework and DSE methodology using a case study based on the KcsA ion channel, in which the design space is successfully reduced from a 6-D space to a 2-D space. Our results show that the channel dielectric map computed using the framework matches with that computed directly using molecular dynamics with an error of 7%. Finally, the scalability and resolution of the model used are explored, and it is shown that the memory requirements needed for DSE remain constant as the number of parameters (degree of heterogeneity) increases.

  18. Protein patterning in polycarbonate microfluidic channels

    NASA Astrophysics Data System (ADS)

    Thomson, David A.; Hayes, Jason P.; Thissen, Helmut

    2004-03-01

    In this work protein patterning has been achieved within a polycarbonate microfluidic device. Channel structures were first coated with plasma polymerized allylamine (ALAPP) followed by the "cloud point" deposition of polyethylene oxide (PEO), a protein repellent molecule. Excimer laser micromachining was used to pattern the PEO to control protein localization. Subsequent removal of a sacrificial layer of polycarbonate resulted in the patterned polymer coating only in the channels of a simple fluidic device. Following a final diffusion bonding fabrication step the devices were filled with a buffer containing Streptavidin conjugated with fluorescein, and visualized under a confocal fluorescent microscope. This confirmed that protein adhesion occurred only in laser patterned areas. The ability to control protein adhesion in microfludic channels leads to the possibility of generating arrays of proteins or cells within polymer microfludics for cheap automated biosensors and synthesis systems.

  19. Analysis on the cost structure of product recall for reverse supply chain

    NASA Astrophysics Data System (ADS)

    Yanhua, Feng; Xuhui, Xia; Zheng, Yang

    2017-12-01

    The research on the reverse supply chain of product recall mainly focused on the recall network structure, logistics mode and so on. In this paper, when product recall and supply channel are fixed, the specific structure and function expression of cost are analyzed according to the peak season and off-season of recall activities, and whether the assembly manufacturer, supplier and recyclers are cooperated situation, respectively, to build the total cost structure of the function model. Finally, the model is validated correctly through the automotive industry and the electromechanical industry.

  20. CLAS N* Excitation Results from Pion and Kaon Electroproduction

    DOE PAGES

    Carman, Daniel S.

    2018-05-24

    The study of the structure of excited nucleonmore » $N^*$ states employing the electroproduction of exclusive reactions is an important avenue for exploring the nature of the non-perturbative strong interaction. The electrocouplings of $N^*$ states in the mass range below $W$=1.8~GeV have been determined from analyses of CLAS $$\\pi N$$, $$\\eta N$$, and $$\\pi \\pi N$$ data at four-momentum transfers $Q^2$ up to 5~GeV$^2$. The work has made it clear that consistent results from independent analyses of several exclusive channels with different couplings and non-resonant backgrounds but the same $N^*$ electroexcitation amplitudes, is essential to have confidence in the extracted results. In terms of hadronic couplings, many high-lying $N^*$ states preferentially decay through the $$\\pi \\pi N$$ channel, while couplings to $$\\pi N$$ final states become rather small. The resonance parameters determined from $$\\pi N$$ and $$\\pi \\pi N$$ electroproduction can be checked in independent studies of the $KY$ ($$Y = \\Lambda, \\Sigma^0$$) channels. Therefore, data from the $KY$ channels already measured with CLAS will play an important role in $N^*$ structure studies. These comparisons await the development of suitable reaction models. Starting in 2018, a program to study the structure of $N^*$ states in various exclusive electroproduction channels using the new CLAS12 spectrometer will get underway. These studies will probe the structure of $N^*$ states in the mass range up to $W$=3~GeV and $Q^2$ up to 12~GeV$^2$, thus providing a means to access $N^*$ structure information spanning a broad regime encompassing both low- and high-energy degrees of freedom.« less

  1. CLAS N* Excitation Results from Pion and Kaon Electroproduction

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

    Carman, Daniel S.

    The study of the structure of excited nucleonmore » $N^*$ states employing the electroproduction of exclusive reactions is an important avenue for exploring the nature of the non-perturbative strong interaction. The electrocouplings of $N^*$ states in the mass range below $W$=1.8~GeV have been determined from analyses of CLAS $$\\pi N$$, $$\\eta N$$, and $$\\pi \\pi N$$ data at four-momentum transfers $Q^2$ up to 5~GeV$^2$. The work has made it clear that consistent results from independent analyses of several exclusive channels with different couplings and non-resonant backgrounds but the same $N^*$ electroexcitation amplitudes, is essential to have confidence in the extracted results. In terms of hadronic couplings, many high-lying $N^*$ states preferentially decay through the $$\\pi \\pi N$$ channel, while couplings to $$\\pi N$$ final states become rather small. The resonance parameters determined from $$\\pi N$$ and $$\\pi \\pi N$$ electroproduction can be checked in independent studies of the $KY$ ($$Y = \\Lambda, \\Sigma^0$$) channels. Therefore, data from the $KY$ channels already measured with CLAS will play an important role in $N^*$ structure studies. These comparisons await the development of suitable reaction models. Starting in 2018, a program to study the structure of $N^*$ states in various exclusive electroproduction channels using the new CLAS12 spectrometer will get underway. These studies will probe the structure of $N^*$ states in the mass range up to $W$=3~GeV and $Q^2$ up to 12~GeV$^2$, thus providing a means to access $N^*$ structure information spanning a broad regime encompassing both low- and high-energy degrees of freedom.« less

  2. Use of Pressure Sensitive Paint for Diagnostics in Turbomachinery Flows With Shocks

    NASA Technical Reports Server (NTRS)

    Lepicovsky, Jan; Bencic, Timothy J.

    2001-01-01

    The technology of pressure sensitive paint (PSP) is well established in external aerodynamics. In internal flows in narrow channels and in turbomachinery cascades, however, there are still unresolved problems. In particular, the internal flows with complex shock structures inside highly curved channels present a challenge. It is not always easy and straightforward to distinguish between true signals and "ghost" images due to multiple internal reflections in narrow channels. To address some of the problems, investigations were first carried out in a narrow supersonic channel of Mach number 2.5. A single wedge or a combination of two wedges were used to generate a complex shock wave structure in the flow. The experience gained in a small supersonic channel was used for surface pressure measurements on the stator vane of a supersonic throughflow fan. The experimental results for several fan operating conditions are shown in a concise form, including performance map points, midspan static tap pressure distributions, and vane suction side pressure fields. Finally, the PSP technique was used in the NASA transonic flutter cascade to compliment flow visualization data and to acquire backwall pressure fields to assess the cascade flow periodicity. A summary of shortcomings of the pressure sensitive paint technology for internal flow application and lessons learned are presented in the conclusion of the paper.

  3. Use of pressure-sensitive paint for diagnostics in turbomachinery flows with shocks

    NASA Astrophysics Data System (ADS)

    Lepicovsky, J.; Bencic, T. J.

    2002-07-01

    The technology of pressure-sensitive paint (PSP) is well established in external aerodynamics. In internal flows in narrow channels and in turbomachinery cascades, however, there are still unresolved problems. In particular, the internal flows with complex shock structures inside highly curved channels present a challenge. It is not always easy and straightforward to distinguish between true signals and 'ghost' images due to multiple internal reflections in narrow channels. To address some of the problems, investigations were first carried out in a narrow supersonic channel of Mach number 2.5. A single wedge or a combination of two wedges was used to generate a complex shock wave structure in the flow. The experience gained in a small supersonic channel was used for surface pressure measurements on the stator vane of a supersonic throughflow fan. The experimental results for several fan operating conditions are shown in a concise form, including performance map test points, midspan static tap pressure distributions, and vane suction side pressure fields. Finally, the PSP technique was used in the NASA transonic flutter cascade to compliment flow visualization data and to acquire backwall pressure fields to assess the cascade flow periodicity. Lessons learned from this investigation and shortcomings of the PSP technology for internal flow application are presented in the conclusion of the paper.

  4. Two structural components in CNGA3 support regulation of cone CNG channels by phosphoinositides.

    PubMed

    Dai, Gucan; Peng, Changhong; Liu, Chunming; Varnum, Michael D

    2013-04-01

    Cyclic nucleotide-gated (CNG) channels in retinal photoreceptors play a crucial role in vertebrate phototransduction. The ligand sensitivity of photoreceptor CNG channels is adjusted during adaptation and in response to paracrine signals, but the mechanisms involved in channel regulation are only partly understood. Heteromeric cone CNGA3 (A3) + CNGB3 (B3) channels are inhibited by membrane phosphoinositides (PIP(n)), including phosphatidylinositol 3,4,5-triphosphate (PIP(3)) and phosphatidylinositol 4,5-bisphosphate (PIP(2)), demonstrating a decrease in apparent affinity for cyclic guanosine monophosphate (cGMP). Unlike homomeric A1 or A2 channels, A3-only channels paradoxically did not show a decrease in apparent affinity for cGMP after PIP(n) application. However, PIP(n) induced an ∼2.5-fold increase in cAMP efficacy for A3 channels. The PIP(n)-dependent change in cAMP efficacy was abolished by mutations in the C-terminal region (R643Q/R646Q) or by truncation distal to the cyclic nucleotide-binding domain (613X). In addition, A3-613X unmasked a threefold decrease in apparent cGMP affinity with PIP(n) application to homomeric channels, and this effect was dependent on conserved arginines within the N-terminal region of A3. Together, these results indicate that regulation of A3 subunits by phosphoinositides exhibits two separable components, which depend on structural elements within the N- and C-terminal regions, respectively. Furthermore, both N and C regulatory modules in A3 supported PIP(n) regulation of heteromeric A3+B3 channels. B3 subunits were not sufficient to confer PIP(n) sensitivity to heteromeric channels formed with PIP(n)-insensitive A subunits. Finally, channels formed by mixtures of PIP(n)-insensitive A3 subunits, having complementary mutations in N- and/or C-terminal regions, restored PIP(n) regulation, implying that intersubunit N-C interactions help control the phosphoinositide sensitivity of cone CNG channels.

  5. Two structural components in CNGA3 support regulation of cone CNG channels by phosphoinositides

    PubMed Central

    Dai, Gucan; Peng, Changhong; Liu, Chunming

    2013-01-01

    Cyclic nucleotide-gated (CNG) channels in retinal photoreceptors play a crucial role in vertebrate phototransduction. The ligand sensitivity of photoreceptor CNG channels is adjusted during adaptation and in response to paracrine signals, but the mechanisms involved in channel regulation are only partly understood. Heteromeric cone CNGA3 (A3) + CNGB3 (B3) channels are inhibited by membrane phosphoinositides (PIPn), including phosphatidylinositol 3,4,5-triphosphate (PIP3) and phosphatidylinositol 4,5-bisphosphate (PIP2), demonstrating a decrease in apparent affinity for cyclic guanosine monophosphate (cGMP). Unlike homomeric A1 or A2 channels, A3-only channels paradoxically did not show a decrease in apparent affinity for cGMP after PIPn application. However, PIPn induced an ∼2.5-fold increase in cAMP efficacy for A3 channels. The PIPn-dependent change in cAMP efficacy was abolished by mutations in the C-terminal region (R643Q/R646Q) or by truncation distal to the cyclic nucleotide-binding domain (613X). In addition, A3-613X unmasked a threefold decrease in apparent cGMP affinity with PIPn application to homomeric channels, and this effect was dependent on conserved arginines within the N-terminal region of A3. Together, these results indicate that regulation of A3 subunits by phosphoinositides exhibits two separable components, which depend on structural elements within the N- and C-terminal regions, respectively. Furthermore, both N and C regulatory modules in A3 supported PIPn regulation of heteromeric A3+B3 channels. B3 subunits were not sufficient to confer PIPn sensitivity to heteromeric channels formed with PIPn-insensitive A subunits. Finally, channels formed by mixtures of PIPn-insensitive A3 subunits, having complementary mutations in N- and/or C-terminal regions, restored PIPn regulation, implying that intersubunit N–C interactions help control the phosphoinositide sensitivity of cone CNG channels. PMID:23530136

  6. The best of both worlds: automated CMP polishing of channel-cut monochromators

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

    Kasman, Elina; Erdmann, Mark; Stoupin, Stanislav

    2015-09-03

    The use of a channel-cut monochromator is the most straightforward method to ensure that the two reflection surfaces maintain alignment between crystallographic planes without the need for complicated alignment mechanisms. Three basic characteristics that affect monochromator performance are: subsurface damage which contaminates spectral purity; surface roughness which reduces efficiency due to scattering; and surface figure error which imparts intensity structure and coherence distortion in the beam. Standard chemical-mechanical polishing processes and equipment are used when the diffracting surface is easily accessible, such as for single-bounce monochromators. Due to the inaccessibly of the surfaces inside a channel-cut monochromator for polishing, thesemore » optics are generally wet-etched for their final processing. This results in minimal subsurface damage, but very poor roughness and figure error. A new CMP channel polishing instrument design is presented which allows the internal diffracting surface quality of channel-cut crystals to approach that of conventional single-bounce monochromators« less

  7. Scheduling science on television: A comparative analysis of the representations of science in 11 European countries.

    PubMed

    Lehmkuhl, Markus; Karamanidou, Christina; Mörä, Tuomo; Petkova, Kristina; Trench, Brian

    2012-11-01

    This article explores the factors that influence the volume and structure of science programming by European television broadcasters, focussing on differences among channel patterns. It proposes three factors as relevant to understanding differences in science programming: A) the segmentation/fragmentation of television markets; B) the presence of middle sized commercial channels; C) the dependency of public service TV channels on commercial income (trading/advertising). We identified countries whose channel patterns encourage a varied picture of science - namely Sweden, Finland and Germany. They are distinguished from those which show a less differentiated picture and present a smaller volume of science content on television - such as Great Britain and Ireland. Finally, we identified countries whose channel patterns don't encourage a varied picture of science - namely Spain, Greece, Bulgaria and Estonia - and these countries present their small volume of science content at off-peak hours, in contrast to patterns in Great Britain and Ireland.

  8. Calcium-Activated Cl- Channel: Insights on the Molecular Identity in Epithelial Tissues.

    PubMed

    Rottgen, Trey S; Nickerson, Andrew J; Rajendran, Vazhaikkurichi M

    2018-05-10

    Calcium-activated chloride secretion in epithelial tissues has been described for many years. However, the molecular identity of the channel responsible for the Ca 2+ -activated Cl − secretion in epithelial tissues has remained a mystery. More recently, TMEM16A has been identified as a new putative Ca 2+ -activated Cl − channel (CaCC). The primary goal of this article will be to review the characterization of TMEM16A, as it relates to the physical structure of the channel, as well as important residues that confer voltage and Ca 2+ -sensitivity of the channel. This review will also discuss the role of TMEM16A in epithelial physiology and potential associated-pathophysiology. This will include discussion of developed knockout models that have provided much needed insight on the functional localization of TMEM16A in several epithelial tissues. Finally, this review will examine the implications of the identification of TMEM16A as it pertains to potential novel therapies in several pathologies.

  9. Code-Time Diversity for Direct Sequence Spread Spectrum Systems

    PubMed Central

    Hassan, A. Y.

    2014-01-01

    Time diversity is achieved in direct sequence spread spectrum by receiving different faded delayed copies of the transmitted symbols from different uncorrelated channel paths when the transmission signal bandwidth is greater than the coherence bandwidth of the channel. In this paper, a new time diversity scheme is proposed for spread spectrum systems. It is called code-time diversity. In this new scheme, N spreading codes are used to transmit one data symbol over N successive symbols interval. The diversity order in the proposed scheme equals to the number of the used spreading codes N multiplied by the number of the uncorrelated paths of the channel L. The paper represents the transmitted signal model. Two demodulators structures will be proposed based on the received signal models from Rayleigh flat and frequency selective fading channels. Probability of error in the proposed diversity scheme is also calculated for the same two fading channels. Finally, simulation results are represented and compared with that of maximal ration combiner (MRC) and multiple-input and multiple-output (MIMO) systems. PMID:24982925

  10. High-definition polymeric membranes: construction of 3D lithographed channel arrays through control of natural building blocks dynamics.

    PubMed

    Speranza, Valentina; Trotta, Francesco; Drioli, Enrico; Gugliuzza, Annarosa

    2010-02-01

    The fabrication of well-defined interfaces is in high demand in many fields of biotechnologies. Here, high-definition membrane-like arrays are developed through the self-assembly of water droplets, which work as natural building blocks for the construction of ordered channels. Solution viscosity together with the dynamics of the water droplets can decide the final formation of three-dimensional well-ordered patterns resembling anodic structures, especially because solvents denser than water are used. Particularly, the polymer solution viscosity is demonstrated to be a powerful tool for control of the mobility of submerged droplets during the microfabrication process. The polymeric patterns are structured at very high levels of organization and exhibit well-established transport-surface property relationships, considered basics for any types of advanced biotechnologies.

  11. Identification of Potent Chloride Intracellular Channel Protein 1 Inhibitors from Traditional Chinese Medicine through Structure-Based Virtual Screening and Molecular Dynamics Analysis

    PubMed Central

    Wan, Minghui; Liao, Dongjiang; Peng, Guilin; Xu, Xin; Yin, Weiqiang; Guo, Guixin; Jiang, Funeng; Zhong, Weide

    2017-01-01

    Chloride intracellular channel 1 (CLIC1) is involved in the development of most aggressive human tumors, including gastric, colon, lung, liver, and glioblastoma cancers. It has become an attractive new therapeutic target for several types of cancer. In this work, we aim to identify natural products as potent CLIC1 inhibitors from Traditional Chinese Medicine (TCM) database using structure-based virtual screening and molecular dynamics (MD) simulation. First, structure-based docking was employed to screen the refined TCM database and the top 500 TCM compounds were obtained and reranked by X-Score. Then, 30 potent hits were achieved from the top 500 TCM compounds using cluster and ligand-protein interaction analysis. Finally, MD simulation was employed to validate the stability of interactions between each hit and CLIC1 protein from docking simulation, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis was used to refine the virtual hits. Six TCM compounds with top MM-GBSA scores and ideal-binding models were confirmed as the final hits. Our study provides information about the interaction between TCM compounds and CLIC1 protein, which may be helpful for further experimental investigations. In addition, the top 6 natural products structural scaffolds could serve as building blocks in designing drug-like molecules for CLIC1 inhibition. PMID:29147652

  12. Dynamics of the EAG1 K+ channel selectivity filter assessed by molecular dynamics simulations.

    PubMed

    Bernsteiner, Harald; Bründl, Michael; Stary-Weinzinger, Anna

    2017-02-26

    EAG1 channels belong to the KCNH family of voltage gated potassium channels. They are expressed in several brain regions and increased expression is linked to certain cancer types. Recent cryo-EM structure determination finally revealed the structure of these channels in atomic detail, allowing computational investigations. In this study, we performed molecular dynamics simulations to investigate the ion binding sites and the dynamical behavior of the selectivity filter. Our simulations suggest that sites S2 and S4 form stable ion binding sites, while ions placed at sites S1 and S3 rapidly switched to sites S2 and S4. Further, ions tended to dissociate away from S0 within less than 20 ns, due to increased filter flexibility. This was followed by water influx from the extracellular side, leading to a widening of the filter in this region, and likely non-conductive filter configurations. Simulations with the inactivation-enhancing mutant Y464A or Na + ions lead to trapped water molecules behind the SF, suggesting that these simulations captured early conformational changes linked to C-type inactivation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. A complicated complex: Ion channels, voltage sensing, cell membranes and peptide inhibitors.

    PubMed

    Zhang, Alan H; Sharma, Gagan; Undheim, Eivind A B; Jia, Xinying; Mobli, Mehdi

    2018-04-21

    Voltage-gated ion channels (VGICs) are specialised ion channels that have a voltage dependent mode of action, where ion conduction, or gating, is controlled by a voltage-sensing mechanism. VGICs are critical for electrical signalling and are therefore important pharmacological targets. Among these, voltage-gated sodium channels (Na V s) have attracted particular attention as potential analgesic targets. Na V s, however, comprise several structurally similar subtypes with unique localisations and distinct functions, ranging from amplification of action potentials in nociception (e.g. Na V 1.7) to controlling electrical signalling in cardiac function (Na V 1.5). Understanding the structural basis of Na V function is therefore of great significance, both to our knowledge of electrical signalling and in development of subtype and state selective drugs. An important tool in this pursuit has been the use of peptides from animal venoms as selective Na V modulators. In this review, we look at peptides, particularly from spider venoms, that inhibit Na V s by binding to the voltage sensing domain (VSD) of this channel, known as gating modifier toxins (GMT). In the first part of the review, we look at the structural determinants of voltage sensing in VGICs, the gating cycle and the conformational changes that accompany VSD movement. Next, the modulation of the analgesic target Na V 1.7 by GMTs is reviewed to develop bioinformatic tools that, based on sequence information alone, can identify toxins that are likely to inhibit this channel. The same approach is also used to define VSD sequences, other than that from Na V 1.7, which are likely to be sensitive to this class of toxins. The final section of the review focuses on the important role of the cellular membrane in channel modulation and also how the lipid composition affects measurements of peptide-channel interactions both in binding kinetics measurements in solution and in cell-based functional assays. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Method for producing components with internal architectures, such as micro-channel reactors, via diffusion bonding sheets

    DOEpatents

    Alman, David E [Corvallis, OR; Wilson, Rick D [Corvallis, OR; Davis, Daniel L [Albany, OR

    2011-03-08

    This invention relates to a method for producing components with internal architectures, and more particularly, this invention relates to a method for producing structures with microchannels via the use of diffusion bonding of stacked laminates. Specifically, the method involves weakly bonding a stack of laminates forming internal voids and channels with a first generally low uniaxial pressure and first temperature such that bonding at least between the asperites of opposing laminates occurs and pores are isolated in interfacial contact areas, followed by a second generally higher isostatic pressure and second temperature for final bonding. The method thereby allows fabrication of micro-channel devices such as heat exchangers, recuperators, heat-pumps, chemical separators, chemical reactors, fuel processing units, and combustors without limitation on the fin aspect ratio.

  15. FDD Massive MIMO Channel Estimation With Arbitrary 2D-Array Geometry

    NASA Astrophysics Data System (ADS)

    Dai, Jisheng; Liu, An; Lau, Vincent K. N.

    2018-05-01

    This paper addresses the problem of downlink channel estimation in frequency-division duplexing (FDD) massive multiple-input multiple-output (MIMO) systems. The existing methods usually exploit hidden sparsity under a discrete Fourier transform (DFT) basis to estimate the cdownlink channel. However, there are at least two shortcomings of these DFT-based methods: 1) they are applicable to uniform linear arrays (ULAs) only, since the DFT basis requires a special structure of ULAs, and 2) they always suffer from a performance loss due to the leakage of energy over some DFT bins. To deal with the above shortcomings, we introduce an off-grid model for downlink channel sparse representation with arbitrary 2D-array antenna geometry, and propose an efficient sparse Bayesian learning (SBL) approach for the sparse channel recovery and off-grid refinement. The main idea of the proposed off-grid method is to consider the sampled grid points as adjustable parameters. Utilizing an in-exact block majorization-minimization (MM) algorithm, the grid points are refined iteratively to minimize the off-grid gap. Finally, we further extend the solution to uplink-aided channel estimation by exploiting the angular reciprocity between downlink and uplink channels, which brings enhanced recovery performance.

  16. Spitting cobras: fluid jets in nature as models for technical applications

    NASA Astrophysics Data System (ADS)

    Balmert, Alexander; Hess, David; Brücker, Christoph; Bleckmann, Horst; Westhoff, Guido

    2011-04-01

    Spitting cobras defend themselves by ejecting rapid jets of venom through their fangs towards the face of an offender. To generate these jets, the venom delivery system of spitting cobras has some unique adaptations, such as prominent ridges on the surface of the venom channel. We examined the fluid acceleration mechanisms in three spitting cobra species of the genus Naja. To investigate the liquid-flow through the venom channel we built a three-dimensional 60:1 scale model. First we determined the three-dimensional structure of the channel by using microcomputer tomography. With help of the micro computer tomographical data we then created a negative form out of wax. Finally, silicon was casted around the wax form and the wax removed, resulting in a completely transparent model of the cobrás venom channel. The physical-chemical properties of the cobra venom were measured by micro rheometry and tensiometry. Thereafter, an artificial fluid with similar properties was generated. Particle image velocimetry (PIV) was performed to visualize the flow of the artificial liquid in the three-dimensional model. Our experiments show how the surface structure of the venom channel determines the liquid flow through the channel and ultimately the form of the liquid jet. Understanding the biological mechanisms of venom ejection helps to enhance industrial processes such as water jet cutting and cleaning as well as injection methods in technical and medical sectors, e.g. liquid microjet dissection in microsurgery.

  17. Inter-subunit interactions across the upper voltage sensing-pore domain interface contribute to the concerted pore opening transition of Kv channels.

    PubMed

    Shem-Ad, Tzilhav; Irit, Orr; Yifrach, Ofer

    2013-01-01

    The tight electro-mechanical coupling between the voltage-sensing and pore domains of Kv channels lies at the heart of their fundamental roles in electrical signaling. Structural data have identified two voltage sensor pore inter-domain interaction surfaces, thus providing a framework to explain the molecular basis for the tight coupling of these domains. While the contribution of the intra-subunit lower domain interface to the electro-mechanical coupling that underlies channel opening is relatively well understood, the contribution of the inter-subunit upper interface to channel gating is not yet clear. Relying on energy perturbation and thermodynamic coupling analyses of tandem-dimeric Shaker Kv channels, we show that mutation of upper interface residues from both sides of the voltage sensor-pore domain interface stabilizes the closed channel state. These mutations, however, do not affect slow inactivation gating. We, moreover, find that upper interface residues form a network of state-dependent interactions that stabilize the open channel state. Finally, we note that the observed residue interaction network does not change during slow inactivation gating. The upper voltage sensing-pore interaction surface thus only undergoes conformational rearrangements during channel activation gating. We suggest that inter-subunit interactions across the upper domain interface mediate allosteric communication between channel subunits that contributes to the concerted nature of the late pore opening transition of Kv channels.

  18. Vibrationally resolved photoelectron angular distributions for H/sub 2/ in the range 17 eVless than or equal toh. nu. less than or equal to39 eV

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

    Parr, A.C.; Hardis, J.E.; Southworth, S.H.

    1988-01-15

    Vibrationally resolved photoelectron angular distributions have been measured for photoionization of H/sub 2/ over the range 17 eVless than or equal toh..nu..less than or equal to39 eV using independent instrumentation at two synchro- tron radiation facilities. The present data greatly extend and add vibrational resolution to earlier variable-wavelength measurements. The average magnitude of the asymmetry parameter continues to lie lower than the best independent-electron calculations. Broad structure is observed for the first time, possibly indicating the effects of channel interaction with dissociative, doubly excited states of H/sub 2/. Neither the average magnitude nor the gross wavelength-dependent structure vary strongly withmore » the final vibrational channel.« less

  19. Using a micro-molding process to fabricate polymeric wavelength filters

    NASA Astrophysics Data System (ADS)

    Chuang, Wei-Ching; Lee, An-Chen; Ho, Chi-Ting

    2008-08-01

    A procedure for fabricating a high aspect ratio periodic structure on a UV polymer at submicron order using holographic interferometry and molding processes is described. First, holographic interferometry using a He-Cd (325 nm) laser was used to create the master of the periodic line structure on an i-line sub-micron positive photoresist film. A 20 nm nickel thin film was then sputtered on the photoresist. The final line pattern on a UV polymer was obtained from casting against the master mold. Finally, a SU8 polymer was spun on the polymer grating to form a planar waveguide or a channel waveguide. The measurement results show that the waveguide length could be reduced for the waveguide having gratings with a high aspect ratio.

  20. Recirculating, passive micromixer with a novel sawtooth structure.

    PubMed

    Nichols, Kevin P; Ferullo, Julia R; Baeumner, Antje J

    2006-02-01

    A microfluidic device capable of recirculating nano to microlitre volumes in order to efficiently mix solutions is described. The device consists of molded polydimethyl siloxane (PDMS) channels with pressure inlet and outlet holes sealed by a glass lid. Recirculation is accomplished by a repeatedly reciprocated flow over an iterated sawtooth structure. The sawtooth structure serves to change the fluid velocity of individual streamlines differently depending on whether the fluid is flowing backwards or forward over the structure. Thus, individual streamlines can be accelerated or decelerated relative to the other streamlines to allow sections of the fluid to interact that would normally be linearly separated. Low Reynolds numbers imply that the process is reversible, neglecting diffusion. Computer simulations were carried out using FLUENT. Subsequently, fluorescent indicators were employed to experimentally verify these numerical simulations of the recirculation principal. Finally, mixing of a carboxyfluorescein labeled DMSO plug with an unlabeled DMSO plug across an immiscible hydrocarbon plug was investigated. At cycling rates of 1 Hz across five sawtooth units, the time was recorded to reach steady state in the channels, i.e. until both DMSO plugs had the same fluorescence intensity. In the case of the sawtooth structures, steady state was reached five times faster than in channels without sawtooth structures, which verified what would be expected based on numerical simulations. The microfluidic mixer is unique due to its versatility with respect to scaling, its potential to also mix solutions containing small particles such as beads and cells, and its ease of fabrication and use.

  1. A comparison of EBSD based strain indicators for the study of Fe-3Si steel subjected to cyclic loading

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

    Schayes, Claire; Valeo Engine Electrical Systems, 2 Rue André Boulle, 94046 Créteil; Bouquerel, Jérémie, E-mail: jeremie.bouquerel@univ-lille1.fr

    The current work aims at proposing an EBSD-based indicator for fatigue damage of a Fe-3Si steel. At the same time direct observation of dislocation structures is provided by electron channelling contrast imaging (ECCI). The investigation consisted in processing the EBSD data from patterns collected on specimen subjected to low cycle fatigue. It revealed two different regimes depending on the applied total strain variation which is explained by the identification of the dislocations structures and their evolution. At low strain variation, strain accommodation occurs by planar glide of dislocations uniformly distributed throughout the grains. No misorientation evolution is observed. At highermore » strain variation, the vein-channel structure is observed within the grain and the wall-channel structure in the vicinity of grain boundaries. The misorientation between these two dislocation structures is evaluated at about 0.7° which is detected by the EBSD analyses and explains the increase of the different misorientation based criteria. The EBSD study enables also the prediction of crack initiation mode. Finally, this study points out the limits of the EBSD technique as no misorientation evolution is detected at small strain variation. Indeed, the lattice distortion is too weak to be detected by conventional EBSD. - Highlights: • Microstructure investigation of the fatigue behaviour of an iron-silicon steel • Use of cECCI to investigate the fatigue dislocations structures • Characterisation of local plastic accommodation through EBSD misorientation criteria.« less

  2. Conformational Changes and Slow Dynamics through Microsecond Polarized Atomistic Molecular Simulation of an Integral Kv1.2 Ion Channel

    PubMed Central

    Bjelkmar, Pär; Niemelä, Perttu S.; Vattulainen, Ilpo; Lindahl, Erik

    2009-01-01

    Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins—not to mention numerous applications in drug design. Here, we present a full 1 µs atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120° rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation (∼35°) of the extracellular end of all S4 segments is present also in a reference 0.5 µs simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 310 helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4–lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5–1 µs). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations. PMID:19229308

  3. Divalent ions are potential permeating blockers of the non-selective NaK ion channel: combined QM and MD based investigations.

    PubMed

    Sadhu, Biswajit; Sundararajan, Mahesh; Bandyopadhyay, Tusar

    2017-10-18

    The bacterial NaK ion channel is distinctly different from other known ion channels due to its inherent non-selective feature. One of the unexplored and rather interesting features is its ability to permeate divalent metal ions (such as Ca 2+ and Ba 2+ ) and not monovalent alkali metal ions. Several intriguing questions about the energetics and structural aspects still remain unanswered. For instance, what causes Ca 2+ to permeate as well as block the selectivity filter (SF) of the NaK ion channel and act as a "permeating blocker"? How and at what energetic cost does another chemical congener, Sr 2+ , as well as Ba 2+ , a potent blocker of the K + ion channel, permeate through the SF of the NaK ion channel? Finally, how do their translocation energetics differ from those of monovalent ions such as K + ? Here, in an attempt to address these outstanding issues, we elucidate the structure, binding and selectivity of divalent ions (Ca 2+ , Sr 2+ and Ba 2+ ) as they permeate through the SF of the NaK ion channel using all-atom molecular dynamics simulations and density functional theory based calculations. We unveil mechanistic insight into this translocation event using well-tempered metadynamics simulations in a polarizable environment using the mean-field model of water and incorporating electronic continuum corrections for ions via charge rescaling. The results show that, akin to K + coordination, Sr 2+ and Ba 2+ bind at the SF in a very similar fashion and remain octa-coordinated at all sites. Interestingly, differing from its local hydration structure, Ca 2+ interacts with eight carbonyls to remain at the middle of the S3 site. Furthermore, the binding of divalent metals at SF binding sites is more favorable than the binding of K + . However, their permeation through the extracellular entrance faces a considerably higher energetic barrier compared to that for K + , which eventually manifests their inherent blocking feature.

  4. Magmatic structures in the Krkonoše Jizera Plutonic Complex, Bohemian Massif: evidence for localized multiphase flow and small-scale thermal mechanical instabilities in a granitic magma chamber

    NASA Astrophysics Data System (ADS)

    Žák, Jiří; Klomínský, Josef

    2007-08-01

    The present paper examines magmatic structures in the Jizera and Liberec granites of the Krkonoše-Jizera Plutonic Complex, Bohemian Massif. The magmatic structures are here interpreted to preserve direct field evidence for highly localized magma flow and other processes in crystal-rich mushes, and to capture the evolution of physical processes in an ancient granitic magma chamber. We propose that after chamber-wide mixing and hybridization, as suggested by recent petrological studies, laminar magma flow became highly localized to weaker channel-like domains within the higher-strength crystal framework. Mafic schlieren formed at flow rims, and their formation presumably involved gravitational settling and velocity gradient flow sorting coupled with interstitial melt escape. Local thermal or compositional convection may have resulted in the formation of vertical schlieren tubes and ladder dikes whereas subhorizontal tubes or channels formed during flow driven by lateral gradients in magma pressure. After the cessation or deceleration of channel flow, gravity-driven processes (settling of crystals and enclaves, gravitational differentiation, development of downward dripping instabilities), accompanied by compaction, filter pressing and melt segregation, dominated in the crystal mush within the flow channels. Subsequently, magmatic folds developed in schlieren layers and the magma chamber recorded complex, late magmatic strains at high magma crystallinities. Late-stage magma pulsing into localized submagmatic cracks represents the latest events of magmatic history of the chamber prior to its final crystallization. We emphasize that the most favorable environments for the formation and preservation of magmatic structures, such as those hosted in the Jizera and Liberec granites, are slowly cooling crystal-rich mushes. Therefore, where preserved in plutons, these structures may lend strong support for a "mush model" of magmatic systems.

  5. Extracting Effective Higgs Couplings in the Golden Channel

    DOE PAGES

    Chen, Yi; Vega-Morales, Roberto

    2014-04-08

    Kinematic distributions in Higgs decays to four charged leptons, the so called ‘golden channel, are a powerful probe of the tensor structure of its couplings to neutral electroweak gauge bosons. In this study we construct the first part of a comprehensive analysis framework designed to maximize the information contained in this channel in order to perform direct extraction of the various possible Higgs couplings. We first complete an earlier analytic calculation of the leading order fully differential cross sections for the golden channel signal and background to include the 4e and 4μ final states with interference between identical final states.more » We also examine the relative fractions of the different possible combinations of scalar-tensor couplings by integrating the fully differential cross section over all kinematic variables as well as show various doubly differential spectra for both the signal and background. From these analytic expressions we then construct a ‘generator level’ analysis framework based on the maximum likelihood method. Then, we demonstrate the ability of our framework to perform multi-parameter extractions of all the possible effective couplings of a spin-0 scalar to pairs of neutral electroweak gauge bosons including any correlations. Furthermore, this framework provides a powerful method for study of these couplings and can be readily adapted to include the relevant detector and systematic effects which we demonstrate in an accompanying study to follow.« less

  6. Rough energy landscapes in protein folding: dimeric E. coli Trp repressor folds through three parallel channels.

    PubMed

    Gloss, L M; Simler, B R; Matthews, C R

    2001-10-05

    The folding mechanism of the dimeric Escherichia coli Trp repressor (TR) is a kinetically complex process that involves three distinguishable stages of development. Following the formation of a partially folded, monomeric ensemble of species, within 5 ms, folding to the native dimer is controlled by three kinetic phases. The rate-limiting step in each phase is either a non-proline isomerization reaction or a dimerization reaction, depending on the final denaturant concentration. Two approaches have been employed to test the previously proposed folding mechanism of TR through three parallel channels: (1) unfolding double-jump experiments demonstrate that all three folding channels lead directly to native dimer; and (2) the differential stabilization of the transition state for the final step in folding and the native dimer, by the addition of salt, shows that all three channels involve isomerization of a dimeric species. A refined model for the folding of Trp repressor is presented, in which all three channels involve a rapid dimerization reaction between partially folded monomers followed by the isomerization of the dimeric intermediates to yield native dimer. The ensemble of partially folded monomers can be captured at equilibrium by low pH; one-dimensional proton NMR spectra at pH 2.5 demonstrate that monomers exist in two distinct, slowly interconverting conformations. These data provide a potential structural explanation for the three-channel folding mechanism of TR: random association of two different monomeric forms, which are distinguished by alternative packing modes of the core dimerization domain and the DNA-binding, helix-turn-helix, domain. One, perhaps both, of these packing modes contains non-native contacts. Copyright 2001 Academic Press.

  7. GABA receptors and T-type Ca2+ channels crosstalk in thalamic networks.

    PubMed

    Leresche, Nathalie; Lambert, Régis C

    2017-06-07

    Although the thalamus presents a rather limited repertoire of GABAergic cell types compare to other CNS area, this structure is a privileged system to study how GABA impacts neuronal network excitability. Indeed both glutamatergic thalamocortical (TC) and GABAergic nucleus reticularis thalami (NRT) neurons present a high expression of T-type voltage-dependent Ca 2+ channels whose activation that shapes the output of the thalamus critically depends upon a preceding hyperpolarisation. Because of this strict dependence, a tight functional link between GABA mediated hyperpolarization and T-currents characterizes the thalamic network excitability. In this review we summarize a number of studies showing that the relationships between the various thalamic GABA A/B receptors and T-channels are complex and bidirectional. We discuss how this dynamic interaction sets the global intrathalamic network activity and its long-term plasticity and highlight how the functional relationship between GABA release and T-channel-dependent excitability is finely tuned by the T-channel activation itself. Finally, we illustrate how an impaired balance between T-channels and GABA receptors can lead to pathologically abnormal cellular and network behaviours. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

    PubMed Central

    Conti, Luca; Renhorn, Jakob; Gabrielsson, Anders; Turesson, Fredrik; Liin, Sara I; Lindahl, Erik; Elinder, Fredrik

    2016-01-01

    Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions – a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel. PMID:27278891

  9. Laser beam coupling with capillary discharge plasma for laser wakefield acceleration applications

    NASA Astrophysics Data System (ADS)

    Bagdasarov, G. A.; Sasorov, P. V.; Gasilov, V. A.; Boldarev, A. S.; Olkhovskaya, O. G.; Benedetti, C.; Bulanov, S. S.; Gonsalves, A.; Mao, H.-S.; Schroeder, C. B.; van Tilborg, J.; Esarey, E.; Leemans, W. P.; Levato, T.; Margarone, D.; Korn, G.

    2017-08-01

    One of the most robust methods, demonstrated to date, of accelerating electron beams by laser-plasma sources is the utilization of plasma channels generated by the capillary discharges. Although the spatial structure of the installation is simple in principle, there may be some important effects caused by the open ends of the capillary, by the supplying channels etc., which require a detailed 3D modeling of the processes. In the present work, such simulations are performed using the code MARPLE. First, the process of capillary filling with cold hydrogen before the discharge is fired, through the side supply channels is simulated. Second, the simulation of the capillary discharge is performed with the goal to obtain a time-dependent spatial distribution of the electron density near the open ends of the capillary as well as inside the capillary. Finally, to evaluate the effectiveness of the beam coupling with the channeling plasma wave guide and of the electron acceleration, modeling of the laser-plasma interaction was performed with the code INF&RNO.

  10. Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

    NASA Astrophysics Data System (ADS)

    Conti, Luca; Renhorn, Jakob; Gabrielsson, Anders; Turesson, Fredrik; Liin, Sara I.; Lindahl, Erik; Elinder, Fredrik

    2016-06-01

    Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel.

  11. Joint channel/frequency offset estimation and correction for coherent optical FBMC/OQAM system

    NASA Astrophysics Data System (ADS)

    Wang, Daobin; Yuan, Lihua; Lei, Jingli; wu, Gang; Li, Suoping; Ding, Runqi; Wang, Dongye

    2017-12-01

    In this paper, we focus on analysis of the preamble-based joint estimation for channel and laser-frequency offset (LFO) in coherent optical filter bank multicarrier systems with offset quadrature amplitude modulation (CO-FBMC/OQAM). In order to reduce the noise impact on the estimation accuracy, we proposed an estimation method based on inter-frame averaging. This method averages the cross-correlation function of real-valued pilots within multiple FBMC frames. The laser-frequency offset is estimated according to the phase of this average. After correcting LFO, the final channel response is also acquired by averaging channel estimation results within multiple frames. The principle of the proposed method is analyzed theoretically, and the preamble structure is thoroughly designed and optimized to suppress the impact of inherent imaginary interference (IMI). The effectiveness of our method is demonstrated numerically using different fiber and LFO values. The obtained results show that the proposed method can improve transmission performance significantly.

  12. Lattice Boltzmann simulation of immiscible displacement in the cavity with different channel configurations

    NASA Astrophysics Data System (ADS)

    Lou, Qin; Zang, Chenqiang; Yang, Mo; Xu, Hongtao

    In this work, the immiscible displacement in a cavity with different channel configurations is studied using an improved pseudo-potential lattice Boltzmann equation (LBE) model. This model overcomes the drawback of the dependence of the fluid properties on the grid size, which exists in the original pseudo-potential LBE model. The approach is first validated by the Laplace law. Then, it is employed to study the immiscible displacement process. The influences of different factors, such as the surface wettability, the distance between the gas cavity and liquid cavity and the surface roughness of the channel are investigated. Numerical results show that the displacement efficiency increases and the displacement time decreases with the increase of the surface contact angle. On the other hand, the displacement efficiency increases with increasing distance between the gas cavity and the liquid cavity at first and finally reaches a constant value. As for the surface roughness, two structures (a semicircular cavity and a semicircular bulge) are studied. The comprehensive results show that although the displacement processes for both the structures depend on the surface wettability, they present quite different behaviors. Specially, for the roughness structure constituted by the semicircular cavity, the displacement efficiency decreases and displacement time increases evidently with the size of the semicircular cavity for the small contact angle. The trend slows down as the increase of the contact angle. Once the contact angle exceeds a certain value, the size of the semicircular cavity almost has no influence on the displacement process. While for the roughness structure of a semicircular bulge, the displacement efficiency increases with the size of bulge first and then it decreases for the small contact angle. The displacement efficiency increases first and finally reaches a constant for the large contact angle. The results also show that the displacement time has an extreme value in these cases for the small contact angles.

  13. Fabrication of monolithic microfluidic channels in diamond with ion beam lithography

    NASA Astrophysics Data System (ADS)

    Picollo, F.; Battiato, A.; Boarino, L.; Ditalia Tchernij, S.; Enrico, E.; Forneris, J.; Gilardino, A.; Jakšić, M.; Sardi, F.; Skukan, N.; Tengattini, A.; Olivero, P.; Re, A.; Vittone, E.

    2017-08-01

    In the present work, we report on the monolithic fabrication by means of ion beam lithography of hollow micro-channels within a diamond substrate, to be employed for microfluidic applications. The fabrication strategy takes advantage of ion beam induced damage to convert diamond into graphite, which is characterized by a higher reactivity to oxidative etching with respect to the chemically inert pristine structure. This phase transition occurs in sub-superficial layers thanks to the peculiar damage profile of MeV ions, which mostly damage the target material at their end of range. The structures were obtained by irradiating commercial CVD diamond samples with a micrometric collimated C+ ion beam at three different energies (4 MeV, 3.5 MeV and 3 MeV) at a total fluence of 2 × 1016 cm-2. The chosen multiple-energy implantation strategy allows to obtain a thick box-like highly damaged region ranging from 1.6 μm to 2.1 μm below the sample surface. High-temperature annealing was performed to both promote the graphitization of the ion-induced amorphous layer and to recover the pristine crystalline structure in the cap layer. Finally, the graphite was removed by ozone etching, obtaining monolithic microfluidic structures. These prototypal microfluidic devices were tested injecting aqueous solutions and the evidence of the passage of fluids through the channels was confirmed by confocal fluorescent microscopy.

  14. Toward Understanding the Outer Membrane Uptake of Small Molecules by Pseudomonas aeruginosa*

    PubMed Central

    Eren, Elif; Parkin, Jamie; Adelanwa, Ayodele; Cheneke, Belete; Movileanu, Liviu; Khalid, Syma; van den Berg, Bert

    2013-01-01

    Because small molecules enter Gram-negative bacteria via outer membrane (OM) channels, understanding OM transport is essential for the rational design of improved and new antibiotics. In the human pathogen Pseudomonas aeruginosa, most small molecules are taken up by outer membrane carboxylate channel (Occ) proteins, which can be divided into two distinct subfamilies, OccD and OccK. Here we characterize substrate transport mediated by Occ proteins belonging to both subfamilies. Based on the determination of the OccK2-glucuronate co-crystal structure, we identify the channel residues that are essential for substrate transport. We further show that the pore regions of the channels are rigid in the OccK subfamily and highly dynamic in the OccD subfamily. We also demonstrate that the substrate carboxylate group interacts with central residues of the basic ladder, a row of arginine and lysine residues that leads to and away from the binding site at the channel constriction. Moreover, the importance of the basic ladder residues corresponds to their degree of conservation. Finally, we apply the generated insights by converting the archetype of the entire family, OccD1, from a basic amino acid-specific channel into a channel with a preference for negatively charged amino acids. PMID:23467408

  15. Inertial microfluidic physics.

    PubMed

    Amini, Hamed; Lee, Wonhee; Di Carlo, Dino

    2014-08-07

    Microfluidics has experienced massive growth in the past two decades, and especially with advances in rapid prototyping researchers have explored a multitude of channel structures, fluid and particle mixtures, and integration with electrical and optical systems towards solving problems in healthcare, biological and chemical analysis, materials synthesis, and other emerging areas that can benefit from the scale, automation, or the unique physics of these systems. Inertial microfluidics, which relies on the unconventional use of fluid inertia in microfluidic platforms, is one of the emerging fields that make use of unique physical phenomena that are accessible in microscale patterned channels. Channel shapes that focus, concentrate, order, separate, transfer, and mix particles and fluids have been demonstrated, however physical underpinnings guiding these channel designs have been limited and much of the development has been based on experimentally-derived intuition. Here we aim to provide a deeper understanding of mechanisms and underlying physics in these systems which can lead to more effective and reliable designs with less iteration. To place the inertial effects into context we also discuss related fluid-induced forces present in particulate flows including forces due to non-Newtonian fluids, particle asymmetry, and particle deformability. We then highlight the inverse situation and describe the effect of the suspended particles acting on the fluid in a channel flow. Finally, we discuss the importance of structured channels, i.e. channels with boundary conditions that vary in the streamwise direction, and their potential as a means to achieve unprecedented three-dimensional control over fluid and particles in microchannels. Ultimately, we hope that an improved fundamental and quantitative understanding of inertial fluid dynamic effects can lead to unprecedented capabilities to program fluid and particle flow towards automation of biomedicine, materials synthesis, and chemical process control.

  16. A new mechanism of voltage-dependent gating exposed by KV10.1 channels interrupted between voltage sensor and pore.

    PubMed

    Tomczak, Adam P; Fernández-Trillo, Jorge; Bharill, Shashank; Papp, Ferenc; Panyi, Gyorgy; Stühmer, Walter; Isacoff, Ehud Y; Pardo, Luis A

    2017-05-01

    Voltage-gated ion channels couple transmembrane potential changes to ion flow. Conformational changes in the voltage-sensing domain (VSD) of the channel are thought to be transmitted to the pore domain (PD) through an α-helical linker between them (S4-S5 linker). However, our recent work on channels disrupted in the S4-S5 linker has challenged this interpretation for the KCNH family. Furthermore, a recent single-particle cryo-electron microscopy structure of K V 10.1 revealed that the S4-S5 linker is a short loop in this KCNH family member, confirming the need for an alternative gating model. Here we use "split" channels made by expression of VSD and PD as separate fragments to investigate the mechanism of gating in K V 10.1. We find that disruption of the covalent connection within the S4 helix compromises the ability of channels to close at negative voltage, whereas disconnecting the S4-S5 linker from S5 slows down activation and deactivation kinetics. Surprisingly, voltage-clamp fluorometry and MTS accessibility assays show that the motion of the S4 voltage sensor is virtually unaffected when VSD and PD are not covalently bound. Finally, experiments using constitutively open PD mutants suggest that the presence of the VSD is structurally important for the conducting conformation of the pore. Collectively, our observations offer partial support to the gating model that assumes that an inward motion of the C-terminal S4 helix, rather than the S4-S5 linker, closes the channel gate, while also suggesting that control of the pore by the voltage sensor involves more than one mechanism. © 2017 Tomczak et al.

  17. A new mechanism of voltage-dependent gating exposed by KV10.1 channels interrupted between voltage sensor and pore

    PubMed Central

    Fernández-Trillo, Jorge; Bharill, Shashank; Panyi, Gyorgy; Stühmer, Walter; Isacoff, Ehud Y.

    2017-01-01

    Voltage-gated ion channels couple transmembrane potential changes to ion flow. Conformational changes in the voltage-sensing domain (VSD) of the channel are thought to be transmitted to the pore domain (PD) through an α-helical linker between them (S4–S5 linker). However, our recent work on channels disrupted in the S4–S5 linker has challenged this interpretation for the KCNH family. Furthermore, a recent single-particle cryo-electron microscopy structure of KV10.1 revealed that the S4–S5 linker is a short loop in this KCNH family member, confirming the need for an alternative gating model. Here we use “split” channels made by expression of VSD and PD as separate fragments to investigate the mechanism of gating in KV10.1. We find that disruption of the covalent connection within the S4 helix compromises the ability of channels to close at negative voltage, whereas disconnecting the S4–S5 linker from S5 slows down activation and deactivation kinetics. Surprisingly, voltage-clamp fluorometry and MTS accessibility assays show that the motion of the S4 voltage sensor is virtually unaffected when VSD and PD are not covalently bound. Finally, experiments using constitutively open PD mutants suggest that the presence of the VSD is structurally important for the conducting conformation of the pore. Collectively, our observations offer partial support to the gating model that assumes that an inward motion of the C-terminal S4 helix, rather than the S4–S5 linker, closes the channel gate, while also suggesting that control of the pore by the voltage sensor involves more than one mechanism. PMID:28360219

  18. Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry.

    PubMed

    González-López, Antonio; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

    2016-05-01

    This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dose ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.

  19. Technical Note: Statistical dependences between channels in radiochromic film readings. Implications in multichannel dosimetry

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

    González-López, Antonio, E-mail: antonio.gonzalez7@carm.es; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

    Purpose: This note studies the statistical relationships between color channels in radiochromic film readings with flatbed scanners. The same relationships are studied for noise. Finally, their implications for multichannel film dosimetry are discussed. Methods: Radiochromic films exposed to wedged fields of 6 MV energy were read in a flatbed scanner. The joint histograms of pairs of color channels were used to obtain the joint and conditional probability density functions between channels. Then, the conditional expectations and variances of one channel given another channel were obtained. Noise was extracted from film readings by means of a multiresolution analysis. Two different dosemore » ranges were analyzed, the first one ranging from 112 to 473 cGy and the second one from 52 to 1290 cGy. Results: For the smallest dose range, the conditional expectations of one channel given another channel can be approximated by linear functions, while the conditional variances are fairly constant. The slopes of the linear relationships between channels can be used to simplify the expression that estimates the dose by means of the multichannel method. The slopes of the linear relationships between each channel and the red one can also be interpreted as weights in the final contribution to dose estimation. However, for the largest dose range, the conditional expectations of one channel given another channel are no longer linear functions. Finally, noises in different channels were found to correlate weakly. Conclusions: Signals present in different channels of radiochromic film readings show a strong statistical dependence. By contrast, noise correlates weakly between channels. For the smallest dose range analyzed, the linear behavior between the conditional expectation of one channel given another channel can be used to simplify calculations in multichannel film dosimetry.« less

  20. The Open Gate of the KV1.2 Channel: Quantum Calculations Show the Key Role of Hydration

    PubMed Central

    Kariev, Alisher M.; Njau, Philipa; Green, Michael E.

    2014-01-01

    The open gate of the Kv1.2 voltage-gated potassium channel can just hold a hydrated K+ ion. Quantum calculations starting from the x-ray coordinates of the channel confirm this, showing little change from the x-ray coordinates for the protein. Water molecules not in the x-ray coordinates, and the ion itself, are placed by the calculation. The water molecules, including their orientation and hydrogen bonding, with and without an ion, are critical for the path of the ion, from the solution to the gate. A sequence of steps is postulated in which the potential experienced by the ion in the pore is influenced by the position of the ion. The gate structure, with and without the ion, has been optimized. The charges on the atoms and bond lengths have been calculated using natural bond orbital calculations, giving K+ ∼0.77 charges, rather than 1.0. The PVPV hinge sequence has been mutated in silico to PVVV (P407V in the 2A79 numbering). The water structure around the ion becomes discontinuous, separated into two sections, above and below the ion. PVPV conservation closely relates to maintaining the water structure. Finally, these results have implications concerning gating. PMID:24507595

  1. Lipid bilayers suspended on microfabricated supports

    NASA Astrophysics Data System (ADS)

    Ogier, Simon D.; Bushby, Richard J.; Cheng, Yaling; Cox, Tim I.; Evans, Stephen D.; Knowles, Peter F.; Miles, Robert E.; Pattison, Ian

    2001-03-01

    The plasma membrane, that exists as part of many animal and plant cells, is a regulator for the transport of ions and small molecules across cell boundaries. Two main components involved are the phospholipid bilayer and the transport proteins. This paper details the construction of a micromachined support for bilayers (MSB) as a first step towards the development of highly selective and highly sensitive ion-channel based biosensors. The device consists of a ~100 micrometer hole in a polymeric support above a cavity that can hold ~25 nL of electrolyte. Electrodes attached to the structure allow the resistance of the membranes to be measured using d.c. conductivity. The MSB is made in two halves, using SU8 ultra-thick resist, which are subsequently bonded together to make the final structure. A layer of gold, surrounding the aperture, enables self-assembled monolayers of alkanethiols to be used to make the polymeric structure biocompatible. Lipid membranes have been formed over these holes with resistances comparable with those of natural membranes >10 MOhmcm^2. The ion-channel gramicidin has successfully been incorporated into the bilayer and its activity monitored. It is proposed that this type of device could be used not only for studying membrane transport phenomena but also as part of an ion-channel based biosensor.

  2. Modeling the human Nav1.5 sodium channel: structural and mechanistic insights of ion permeation and drug blockade

    PubMed Central

    Ahmed, Marawan; Jalily Hasani, Horia; Ganesan, Aravindhan; Houghton, Michael; Barakat, Khaled

    2017-01-01

    Abnormalities in the human Nav1.5 (hNav1.5) voltage-gated sodium ion channel (VGSC) are associated with a wide range of cardiac problems and diseases in humans. Current structural models of hNav1.5 are still far from complete and, consequently, their ability to study atomistic interactions of this channel is very limited. Here, we report a comprehensive atomistic model of the hNav1.5 ion channel, constructed using homology modeling technique and refined through long molecular dynamics simulations (680 ns) in the lipid membrane bilayer. Our model was comprehensively validated by using reported mutagenesis data, comparisons with previous models, and binding to a panel of known hNav1.5 blockers. The relatively long classical MD simulation was sufficient to observe a natural sodium permeation event across the channel’s selectivity filters to reach the channel’s central cavity, together with the identification of a unique role of the lysine residue. Electrostatic potential calculations revealed the existence of two potential binding sites for the sodium ion at the outer selectivity filters. To obtain further mechanistic insight into the permeation event from the central cavity to the intracellular region of the channel, we further employed “state-of-the-art” steered molecular dynamics (SMD) simulations. Our SMD simulations revealed two different pathways through which a sodium ion can be expelled from the channel. Further, the SMD simulations identified the key residues that are likely to control these processes. Finally, we discuss the potential binding modes of a panel of known hNav1.5 blockers to our structural model of hNav1.5. We believe that the data presented here will enhance our understanding of the structure–property relationships of the hNav1.5 ion channel and the underlying molecular mechanisms in sodium ion permeation and drug interactions. The results presented here could be useful for designing safer drugs that do not block the hNav1.5 channel. PMID:28831242

  3. Numerical investigation of the thermal and electrical performances for combined solar photovoltaic/thermal (PV/T) modules based on internally extruded fin flow channel

    NASA Astrophysics Data System (ADS)

    Deng, Y. C.; Li, Q. P.; Wang, G. J.

    2017-11-01

    A solar photovoltaic/thermal (PV/T) module based on internally extruded fin flow channel was investigated numerically in this paper. First of all, the structures of the thin plate heat exchanger and the PV/T module were presented. Then, a numerical model of the PV/T module considering solar irradiation, fluid flow and heat transfer was developed to analyze the performance of the module. Finally, the steady electrical and thermal efficiencies of the PV/T module at different inlet water temperatures and mass flow rates were achieved. These numerical results supply theory basis for practical application of the PV/T module.

  4. Real time coarse orientation detection in MR scans using multi-planar deep convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Bhatia, Parmeet S.; Reda, Fitsum; Harder, Martin; Zhan, Yiqiang; Zhou, Xiang Sean

    2017-02-01

    Automatically detecting anatomy orientation is an important task in medical image analysis. Specifically, the ability to automatically detect coarse orientation of structures is useful to minimize the effort of fine/accurate orientation detection algorithms, to initialize non-rigid deformable registration algorithms or to align models to target structures in model-based segmentation algorithms. In this work, we present a deep convolution neural network (DCNN)-based method for fast and robust detection of the coarse structure orientation, i.e., the hemi-sphere where the principal axis of a structure lies. That is, our algorithm predicts whether the principal orientation of a structure is in the northern hemisphere or southern hemisphere, which we will refer to as UP and DOWN, respectively, in the remainder of this manuscript. The only assumption of our method is that the entire structure is located within the scan's field-of-view (FOV). To efficiently solve the problem in 3D space, we formulated it as a multi-planar 2D deep learning problem. In the training stage, a large number coronal-sagittal slice pairs are constructed as 2-channel images to train a DCNN to classify whether a scan is UP or DOWN. During testing, we randomly sample a small number of coronal-sagittal 2-channel images and pass them through our trained network. Finally, coarse structure orientation is determined using majority voting. We tested our method on 114 Elbow MR Scans. Experimental results suggest that only five 2-channel images are sufficient to achieve a high success rate of 97.39%. Our method is also extremely fast and takes approximately 50 milliseconds per 3D MR scan. Our method is insensitive to the location of the structure in the FOV.

  5. The recent development and applications of fluidic channels by 3D printing.

    PubMed

    Zhou, Yufeng

    2017-10-18

    The technology of "Lab-on-a-Chip" allows the synthesis and analysis of chemicals and biological substance within a portable or handheld device. The 3D printed structures enable precise control of various geometries. The combination of these two technologies in recent years makes a significant progress. The current approaches of 3D printing, such as stereolithography, polyjet, and fused deposition modeling, are introduced. Their manufacture specifications, such as surface roughness, resolution, replication fidelity, cost, and fabrication time, are compared with each other. Finally, novel application of 3D printed channel in biology are reviewed, including pathogenic bacteria detection using magnetic nanoparticle clusters in a helical microchannel, cell stimulation by 3D chemical gradients, perfused functional vascular channels, 3D tissue construct, organ-on-a-chip, and miniaturized fluidic "reactionware" devices for chemical syntheses. Overall, the 3D printed fluidic chip is becoming a powerful tool in the both medical and chemical industries.

  6. Unique Structural Features and Sequence Motifs of Proline Utilization A (PutA)

    PubMed Central

    Singh, Ranjan K.; Tanner, John J.

    2013-01-01

    Proline utilization A proteins (PutAs) are bifunctional enzymes that catalyze the oxidation of proline to glutamate using spatially separated proline dehydrogenase and pyrroline-5-carboxylate dehydrogenase active sites. Here we use the crystal structure of the minimalist PutA from Bradyrhizobium japonicum (BjPutA) along with sequence analysis to identify unique structural features of PutAs. This analysis shows that PutAs have secondary structural elements and domains not found in the related monofunctional enzymes. Some of these extra features are predicted to be important for substrate channeling in BjPutA. Multiple sequence alignment analysis shows that some PutAs have a 17-residue conserved motif in the C-terminal 20–30 residues of the polypeptide chain. The BjPutA structure shows that this motif helps seal the internal substrate-channeling cavity from the bulk medium. Finally, it is shown that some PutAs have a 100–200 residue domain of unknown function in the C-terminus that is not found in minimalist PutAs. Remote homology detection suggests that this domain is homologous to the oligomerization beta-hairpin and Rossmann fold domain of BjPutA. PMID:22201760

  7. Application of Plasma Waveguides to High Energy Accelerators

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

    Milchberg, Howard M

    2013-03-30

    The eventual success of laser-plasma based acceleration schemes for high-energy particle physics will require the focusing and stable guiding of short intense laser pulses in reproducible plasma channels. For this goal to be realized, many scientific issues need to be addressed. These issues include an understanding of the basic physics of, and an exploration of various schemes for, plasma channel formation. In addition, the coupling of intense laser pulses to these channels and the stable propagation of pulses in the channels require study. Finally, new theoretical and computational tools need to be developed to aid in the design and analysismore » of experiments and future accelerators. Here we propose a 3-year renewal of our combined theoretical and experimental program on the applications of plasma waveguides to high-energy accelerators. During the past grant period we have made a number of significant advances in the science of laser-plasma based acceleration. We pioneered the development of clustered gases as a new highly efficient medium for plasma channel formation. Our contributions here include theoretical and experimental studies of the physics of cluster ionization, heating, explosion, and channel formation. We have demonstrated for the first time the generation of and guiding in a corrugated plasma waveguide. The fine structure demonstrated in these guides is only possible with cluster jet heating by lasers. The corrugated guide is a slow wave structure operable at arbitrarily high laser intensities, allowing direct laser acceleration, a process we have explored in detail with simulations. The development of these guides opens the possibility of direct laser acceleration, a true miniature analogue of the SLAC RF-based accelerator. Our theoretical studies during this period have also contributed to the further development of the simulation codes, Wake and QuickPIC, which can be used for both laser driven and beam driven plasma based acceleration schemes. We will continue our development of advanced simulation tools by modifying the QuickPIC algorithm to allow for the simulation of plasma particle pick-up by the wake fields. We have also performed extensive simulations of plasma slow wave structures for efficient THz generation by guided laser beams or accelerated electron beams. We will pursue experimental studies of direct laser acceleration, and THz generation by two methods, ponderomotive-induced THz polarization, and THz radiation by laser accelerated electron beams. We also plan to study both conventional and corrugated plasma channels using our new 30 TW in our new lab facilities. We will investigate production of very long hydrogen plasma waveguides (5 cm). We will study guiding at increasing power levels through the onset of laser-induced cavitation (bubble regime) to assess the role played by the preformed channel. Experiments in direct acceleration will be performed, using laser plasma wakefields as the electron injector. Finally, we will use 2-colour ionization of gases as a high frequency THz source (<60 THz) in order for femtosecond measurements of low plasma densities in waveguides and beams.« less

  8. An electrostatic potassium channel opener targeting the final voltage sensor transition

    PubMed Central

    Börjesson, Sara I.

    2011-01-01

    Free polyunsaturated fatty acids (PUFAs) modulate the voltage dependence of voltage-gated ion channels. As an important consequence thereof, PUFAs can suppress epileptic seizures and cardiac arrhythmia. However, molecular details for the interaction between PUFA and ion channels are not well understood. In this study, we have localized the site of action for PUFAs on the voltage-gated Shaker K channel by introducing positive charges on the channel surface, which potentiated the PUFA effect. Furthermore, we found that PUFA mainly affects the final voltage sensor movement, which is closely linked to channel opening, and that specific charges at the extracellular end of the voltage sensor are critical for the PUFA effect. Because different voltage-gated K channels have different charge profiles, this implies channel-specific PUFA effects. The identified site and the pharmacological mechanism will potentially be very useful in future drug design of small-molecule compounds specifically targeting neuronal and cardiac excitability. PMID:21624947

  9. Identification of a Cholesterol-Binding Pocket in Inward Rectifier K+ (Kir) Channels

    PubMed Central

    Fürst, Oliver; Nichols, Colin G.; Lamoureux, Guillaume; D’Avanzo, Nazzareno

    2014-01-01

    Cholesterol is the major sterol component of all mammalian plasma membranes. Recent studies have shown that cholesterol inhibits both bacterial (KirBac1.1 and KirBac3.1) and eukaryotic (Kir2.1) inward rectifier K+ (Kir) channels. Lipid-sterol interactions are not enantioselective, and the enantiomer of cholesterol (ent-cholesterol) does not inhibit Kir channel activity, suggesting that inhibition results from direct enantiospecific binding to the channel, and not indirect effects of changes to the bilayer. Furthermore, conservation of the effect of cholesterol among prokaryotic and eukaryotic Kir channels suggests an evolutionary conserved cholesterol-binding pocket, which we aimed to identify. Computational experiments were performed by docking cholesterol to the atomic structures of Kir2.2 (PDB: 3SPI) and KirBac1.1 (PDB: 2WLL) using Autodock 4.2. Poses were assessed to ensure biologically relevant orientation and then clustered according to location and orientation. The stability of cholesterol in each of these poses was then confirmed by molecular dynamics simulations. Finally, mutation of key residues (S95H and I171L) in this putative binding pocket found within the transmembrane domain of Kir2.1 channels were shown to lead to a loss of inhibition by cholesterol. Together, these data provide support for this location as a biologically relevant pocket. PMID:25517146

  10. Optimization of a new flow design for solid oxide cells using computational fluid dynamics modelling

    NASA Astrophysics Data System (ADS)

    Duhn, Jakob Dragsbæk; Jensen, Anker Degn; Wedel, Stig; Wix, Christian

    2016-12-01

    Design of a gas distributor to distribute gas flow into parallel channels for Solid Oxide Cells (SOC) is optimized, with respect to flow distribution, using Computational Fluid Dynamics (CFD) modelling. The CFD model is based on a 3d geometric model and the optimized structural parameters include the width of the channels in the gas distributor and the area in front of the parallel channels. The flow of the optimized design is found to have a flow uniformity index value of 0.978. The effects of deviations from the assumptions used in the modelling (isothermal and non-reacting flow) are evaluated and it is found that a temperature gradient along the parallel channels does not affect the flow uniformity, whereas a temperature difference between the channels does. The impact of the flow distribution on the maximum obtainable conversion during operation is also investigated and the obtainable overall conversion is found to be directly proportional to the flow uniformity. Finally the effect of manufacturing errors is investigated. The design is shown to be robust towards deviations from design dimensions of at least ±0.1 mm which is well within obtainable tolerances.

  11. Self-regenerating and hybrid irreversible/reversible PDMS microfluidic devices.

    PubMed

    Shiroma, Letícia S; Piazzetta, Maria H O; Duarte-Junior, Gerson F; Coltro, Wendell K T; Carrilho, Emanuel; Gobbi, Angelo L; Lima, Renato S

    2016-05-16

    This paper outlines a straightforward, fast, and low-cost method to fabricate polydimethylsiloxane (PDMS) chips. Termed sandwich bonding (SWB), this method requires only a laboratory oven. Initially, SWB relies on the reversible bonding of a coverslip over PDMS channels. The coverslip is smaller than the substrate, leaving a border around the substrate exposed. Subsequently, a liquid composed of PDMS monomers and a curing agent is poured onto the structure. Finally, the cover is cured. We focused on PDMS/glass chips because of their key advantages in microfluidics. Despite its simplicity, this method created high-performance microfluidic channels. Such structures featured self-regeneration after leakages and hybrid irreversible/reversible behavior. The reversible nature was achieved by removing the cover of PDMS with acetone. Thus, the PDMS substrate and glass coverslip could be detached for reuse. These abilities are essential in the stages of research and development. Additionally, SWB avoids the use of surface oxidation, half-cured PDMS as an adhesive, and surface chemical modification. As a consequence, SWB allows surface modifications before the bonding, a long time for alignment, the enclosure of sub-micron channels, and the prototyping of hybrid devices. Here, the technique was successfully applied to bond PDMS to Au and Al.

  12. Self-regenerating and hybrid irreversible/reversible PDMS microfluidic devices

    PubMed Central

    Shiroma, Letícia S.; Piazzetta, Maria H. O.; Duarte-Junior, Gerson F.; Coltro, Wendell K. T.; Carrilho, Emanuel; Gobbi, Angelo L.; Lima, Renato S.

    2016-01-01

    This paper outlines a straightforward, fast, and low-cost method to fabricate polydimethylsiloxane (PDMS) chips. Termed sandwich bonding (SWB), this method requires only a laboratory oven. Initially, SWB relies on the reversible bonding of a coverslip over PDMS channels. The coverslip is smaller than the substrate, leaving a border around the substrate exposed. Subsequently, a liquid composed of PDMS monomers and a curing agent is poured onto the structure. Finally, the cover is cured. We focused on PDMS/glass chips because of their key advantages in microfluidics. Despite its simplicity, this method created high-performance microfluidic channels. Such structures featured self-regeneration after leakages and hybrid irreversible/reversible behavior. The reversible nature was achieved by removing the cover of PDMS with acetone. Thus, the PDMS substrate and glass coverslip could be detached for reuse. These abilities are essential in the stages of research and development. Additionally, SWB avoids the use of surface oxidation, half-cured PDMS as an adhesive, and surface chemical modification. As a consequence, SWB allows surface modifications before the bonding, a long time for alignment, the enclosure of sub-micron channels, and the prototyping of hybrid devices. Here, the technique was successfully applied to bond PDMS to Au and Al. PMID:27181918

  13. A combined coarse-grained and all-atom simulation of TRPV1 channel gating and heat activation

    PubMed Central

    Qin, Feng

    2015-01-01

    The transient receptor potential (TRP) channels act as key sensors of various chemical and physical stimuli in eukaryotic cells. Despite years of study, the molecular mechanisms of TRP channel activation remain unclear. To elucidate the structural, dynamic, and energetic basis of gating in TRPV1 (a founding member of the TRPV subfamily), we performed coarse-grained modeling and all-atom molecular dynamics (MD) simulation based on the recently solved high resolution structures of the open and closed form of TRPV1. Our coarse-grained normal mode analysis captures two key modes of collective motions involved in the TRPV1 gating transition, featuring a quaternary twist motion of the transmembrane domains (TMDs) relative to the intracellular domains (ICDs). Our transition pathway modeling predicts a sequence of structural movements that propagate from the ICDs to the TMDs via key interface domains (including the membrane proximal domain and the C-terminal domain), leading to sequential opening of the selectivity filter followed by the lower gate in the channel pore (confirmed by modeling conformational changes induced by the activation of ICDs). The above findings of coarse-grained modeling are robust to perturbation by lipids. Finally, our MD simulation of the ICD identifies key residues that contribute differently to the nonpolar energy of the open and closed state, and these residues are predicted to control the temperature sensitivity of TRPV1 gating. These computational predictions offer new insights to the mechanism for heat activation of TRPV1 gating, and will guide our future electrophysiology and mutagenesis studies. PMID:25918362

  14. Merging Structural Motifs of Functionalized Amino Acids and α-Aminoamides Results in Novel Anticonvulsant Compounds with Significant Effects on Slow and Fast Inactivation of Voltage-Gated Sodium Channels and in the Treatment of Neuropathic Pain

    PubMed Central

    2011-01-01

    We recently reported that merging key structural pharmacophores of the anticonvulsant drugs lacosamide (a functionalized amino acid) with safinamide (an α-aminoamide) resulted in novel compounds with anticonvulsant activities superior to that of either drug alone. Here, we examined the effects of six such chimeric compounds on Na+-channel function in central nervous system catecholaminergic (CAD) cells. Using whole-cell patch clamp electrophysiology, we demonstrated that these compounds affected Na+ channel fast and slow inactivation processes. Detailed electrophysiological characterization of two of these chimeric compounds that contained either an oxymethylene ((R)-7) or a chemical bond ((R)-11) between the two aromatic rings showed comparable effects on slow inactivation, use-dependence of block, development of slow inactivation, and recovery of Na+ channels from inactivation. Both compounds were equally effective at inducing slow inactivation; (R)-7 shifted the fast inactivation curve in the hyperpolarizing direction greater than (R)-11, suggesting that in the presence of (R)-7 a larger fraction of the channels are in an inactivated state. None of the chimeric compounds affected veratridine- or KCl-induced glutamate release in neonatal cortical neurons. There was modest inhibition of KCl-induced calcium influx in cortical neurons. Finally, a single intraperitoneal administration of (R)-7, but not (R)-11, completely reversed mechanical hypersensitivity in a tibial-nerve injury model of neuropathic pain. The strong effects of (R)-7 on slow and fast inactivation of Na+ channels may contribute to its efficacy and provide a promising novel therapy for neuropathic pain, in addition to its antiepileptic potential. PMID:21765969

  15. The electrostatics of VDAC: implications for selectivity and gating.

    PubMed

    Choudhary, Om P; Ujwal, Rachna; Kowallis, William; Coalson, Rob; Abramson, Jeff; Grabe, Michael

    2010-02-26

    The voltage-dependent anion channel (VDAC) is the major pathway mediating the transfer of metabolites and ions across the mitochondrial outer membrane. Two hallmarks of the channel in the open state are high metabolite flux and anion selectivity, while the partially closed state blocks metabolites and is cation selective. Here we report the results from electrostatics calculations carried out on the recently determined high-resolution structure of murine VDAC1 (mVDAC1). Poisson-Boltzmann calculations show that the ion transfer free energy through the channel is favorable for anions, suggesting that mVDAC1 represents the open state. This claim is buttressed by Poisson-Nernst-Planck calculations that predict a high single-channel conductance indicative of the open state and an anion selectivity of 1.75--nearly a twofold selectivity for anions over cations. These calculations were repeated on mutant channels and gave selectivity changes in accord with experimental observations. We were then able to engineer an in silico mutant channel with three point mutations that converted mVDAC1 into a channel with a preference for cations. Finally, we investigated two proposals for how the channel gates between the open and the closed state. Both models involve the movement of the N-terminal helix, but neither motion produced the observed voltage sensitivity, nor did either model result in a cation-selective channel, which is observed experimentally. Thus, we were able to rule out certain models for channel gating, but the true motion has yet to be determined. Copyright (c) 2009. Elsevier Ltd. All rights reserved.

  16. ASIC3 Channels Integrate Agmatine and Multiple Inflammatory Signals through the Nonproton Ligand Sensing Domain

    PubMed Central

    2010-01-01

    Background Acid-sensing ion channels (ASICs) have long been known to sense extracellular protons and contribute to sensory perception. Peripheral ASIC3 channels represent natural sensors of acidic and inflammatory pain. We recently reported the use of a synthetic compound, 2-guanidine-4-methylquinazoline (GMQ), to identify a novel nonproton sensing domain in the ASIC3 channel, and proposed that, based on its structural similarity with GMQ, the arginine metabolite agmatine (AGM) may be an endogenous nonproton ligand for ASIC3 channels. Results Here, we present further evidence for the physiological correlation between AGM and ASIC3. Among arginine metabolites, only AGM and its analog arcaine (ARC) activated ASIC3 channels at neutral pH in a sustained manner similar to GMQ. In addition to the homomeric ASIC3 channels, AGM also activated heteromeric ASIC3 plus ASIC1b channels, extending its potential physiological relevance. Importantly, the process of activation by AGM was highly sensitive to mild acidosis, hyperosmolarity, arachidonic acid (AA), lactic acid and reduced extracellular Ca2+. AGM-induced ASIC3 channel activation was not through the chelation of extracellular Ca2+ as occurs with increased lactate, but rather through a direct interaction with the newly identified nonproton ligand sensing domain. Finally, AGM cooperated with the multiple inflammatory signals to cause pain-related behaviors in an ASIC3-dependent manner. Conclusions Nonproton ligand sensing domain might represent a novel mechanism for activation or sensitization of ASIC3 channels underlying inflammatory pain-sensing under in vivo conditions. PMID:21143836

  17. Dopamine negatively modulates the NCA ion channels in C. elegans

    PubMed Central

    Topalidou, Irini; Pereira, Laura

    2017-01-01

    The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels. PMID:28968387

  18. Dopamine negatively modulates the NCA ion channels in C. elegans.

    PubMed

    Topalidou, Irini; Cooper, Kirsten; Pereira, Laura; Ailion, Michael

    2017-10-01

    The NALCN/NCA ion channel is a cation channel related to voltage-gated sodium and calcium channels. NALCN has been reported to be a sodium leak channel with a conserved role in establishing neuronal resting membrane potential, but its precise cellular role and regulation are unclear. The Caenorhabditis elegans orthologs of NALCN, NCA-1 and NCA-2, act in premotor interneurons to regulate motor circuit activity that sustains locomotion. Recently we found that NCA-1 and NCA-2 are activated by a signal transduction pathway acting downstream of the heterotrimeric G protein Gq and the small GTPase Rho. Through a forward genetic screen, here we identify the GPCR kinase GRK-2 as a new player affecting signaling through the Gq-Rho-NCA pathway. Using structure-function analysis, we find that the GPCR phosphorylation and membrane association domains of GRK-2 are required for its function. Genetic epistasis experiments suggest that GRK-2 acts on the D2-like dopamine receptor DOP-3 to inhibit Go signaling and positively modulate NCA-1 and NCA-2 activity. Through cell-specific rescuing experiments, we find that GRK-2 and DOP-3 act in premotor interneurons to modulate NCA channel function. Finally, we demonstrate that dopamine, through DOP-3, negatively regulates NCA activity. Thus, this study identifies a pathway by which dopamine modulates the activity of the NCA channels.

  19. Molecular Properties of neurotoxin receptors sites associated with sodium channels from mammalian brain.

    PubMed

    Catterall, W A; Hartshorne, R P; Beneski, D A

    1982-01-01

    Neurotoxins that act at specific receptor sites on voltage-sensitive sodium channels have been used as molecular probes to identify and purify protein components of sodium channels from mammalian brain. Photoreactive derivatives of scorpion toxin have been prepared and used to covalently label sodium channels in intact synaptosomes. Two polypeptides, alpha with Mr approximately 270,000 and beta with Mr approximately 38,000, are specifically labeled indicating that they are components of the scorpion toxin receptor site on the sodium channel. The sodium channel can be solubilized with retention of specific binding of [3H] saxitoxin using nonionic detergents such as Triton X-100. The solubilized saxitoxin receptor has molecular weight of 316,000 +/- 63,000 and binds 0.9 g of Triton X-100 and phospholipid per g of protein. The solubilized receptor can be purified 750-fold by ion exchange chromatography, wheat germ lectin/Sepharose chromatography and sucrose gradient sedimentation to a final specific activity of 1488 pmol/mg. Analysis of the polypeptide chain composition of the most highly purified fractions indicates that alpha and beta comprise 65% of the protein of these fractions and are only the polypeptides whose presence correlates with saxitoxin binding activity. These studies lead to a working hypothesis of sodium channel structure in which the intact channel is comprised of a complex with Mr of approximately 316,000 containing one mole of alpha (Mr approximately 270,000) and one to three moles of beta (Mr approximately 38,000).

  20. Activation of TRPM7 channels by small molecules under physiological conditions.

    PubMed

    Hofmann, T; Schäfer, S; Linseisen, M; Sytik, L; Gudermann, T; Chubanov, V

    2014-12-01

    Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a cation channel covalently linked to a protein kinase domain. TRPM7 is ubiquitously expressed and regulates key cellular processes such as Mg(2+) homeostasis, motility, and proliferation. TRPM7 is involved in anoxic neuronal death, cardiac fibrosis, and tumor growth. The goal of this work was to identify small molecule activators of the TRPM7 channel and investigate their mechanism of action. We used an aequorin bioluminescence-based assay to screen for activators of the TRPM7 channel. Valid candidates were further characterized using patch clamp electrophysiology. We identified 20 drug-like compounds with various structural backbones that can activate the TRPM7 channel. Among them, the δ opioid antagonist naltriben was studied in greater detail. Naltriben's action was selective among the TRP channels tested. Naltriben activates TRPM7 currents without prior depletion of intracellular Mg(2+) even under conditions of low PIP2. Moreover, naltriben interfered with the effect of the TRPM7 inhibitor NS8593. Finally, our experiments with TRPM7 variants carrying mutations in the pore, TRP, and kinase domains indicate that the site of TRPM7 activation by this small-molecule ligand is most likely located in or near the TRP domain. In conclusion, we identified the first organic small-molecule activators of TRPM7 channels, thus providing new experimental tools to study TRPM7 function in native cellular environments.

  1. Enhance performance of micro direct methanol fuel cell by in situ CO2 removal using novel anode flow field with superhydrophobic degassing channels

    NASA Astrophysics Data System (ADS)

    Liang, Junsheng; Luo, Ying; Zheng, Sheng; Wang, Dazhi

    2017-05-01

    Capillary blocking caused by CO2 bubbles in anode flow field (AFF) is one of the bottlenecks for performance improvement of a micro direct methanol fuel cell (μDMFC). In this work, we present a novel AFF structure with nested layout of hydrophilic fuel channels and superhydrophobic degassing channels which can remove most of CO2 from AFF before it is released to the fuel channels. The new AFFs are fabricated on Ti substrates by using micro photochemical etching combined with anodization and fluorination treatments. Performance of the μDMFCs with and without superhydrophobic degassing channels in their AFF is comparatively studied. Results show that the superhydrophobic degassing channels can significantly speed up the exhaust of CO2 from the AFF. CO2 clogging is not observed in the new AFFs even when their comparison AFFs have been seriously blocked by CO2 slugs under the same operating conditions. 55% and 60% of total CO2 produced in μDMFCs with N-serpentine and N-spiral AFF can be respectively removed by the superhydrophobic degassing channels. The power densities of the μDMFCs equipped with new serpentine and spiral AFFs are respectively improved by 30% and 90% compared with those using conventional AFFs. This means that the new AFFs developed in this work can effectively prevent CO2-induced capillary blocking in the fuel channels, and finally significantly improve the performance of the μDMFCs.

  2. Pharmacological Modulation of Diacylglycerol-Sensitive TRPC3/6/7 Channels

    PubMed Central

    Harteneck, Christian; Gollasch, Maik

    2011-01-01

    Members of the classic type of transient receptor potential channels (TRPC) represent important molecules involved in hormonal signal transduction. TRPC3/6/7 channels are of particular interest as they are components of phospholipase C driven signalling pathways. Upon receptor-activation, G-protein-mediated stimulation of phospholipase C results in breakdown of phosphatidylinositides leading to increased intracellular diacylglycerol and inositol-trisphosphate levels. Diacylglycerol activates protein kinase C, but more interestingly diacylglycerol directly activates TRPC2/3/6/7 channels. Molecular cloning, expression and characterization of TRP channels enabled reassignment of traditional inhibitors of receptor-dependent calcium entry such as SKF-96365 and 2-APB as blockers of TRPC3/6/7 and several members of non-classic TRP channels. Furthermore, several enzyme inhibitors have also been identified as TRP channel blockers, such as ACA, a phospholipase A2 inhibitor, and W-7, a calmodulin antagonist. Finally, the naturally occurring secondary plant compound hyperforin has been identified as TRPC6-selective drug, providing an exciting proof of concept that it is possible to generate TRPC-selective channel modulators. The description of Pyr3 as the first TRPC3-selective inhibitor shows that not only nature but also man is able to generate TRP-selective modulators. The review sheds lights on the current knowledge and historical development of pharmacological modulators of TRPC3/6/7. Our analysis indicates that Pyr3 and hyperforin provide promising core structures for the development of new, selective and more potent modulators of TRPC3/6/7 activity. PMID:20932261

  3. The open gate of the K(V)1.2 channel: quantum calculations show the key role of hydration.

    PubMed

    Kariev, Alisher M; Njau, Philipa; Green, Michael E

    2014-02-04

    The open gate of the Kv1.2 voltage-gated potassium channel can just hold a hydrated K(+) ion. Quantum calculations starting from the x-ray coordinates of the channel confirm this, showing little change from the x-ray coordinates for the protein. Water molecules not in the x-ray coordinates, and the ion itself, are placed by the calculation. The water molecules, including their orientation and hydrogen bonding, with and without an ion, are critical for the path of the ion, from the solution to the gate. A sequence of steps is postulated in which the potential experienced by the ion in the pore is influenced by the position of the ion. The gate structure, with and without the ion, has been optimized. The charges on the atoms and bond lengths have been calculated using natural bond orbital calculations, giving K(+) ~0.77 charges, rather than 1.0. The PVPV hinge sequence has been mutated in silico to PVVV (P407V in the 2A79 numbering). The water structure around the ion becomes discontinuous, separated into two sections, above and below the ion. PVPV conservation closely relates to maintaining the water structure. Finally, these results have implications concerning gating. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. A Unitary Anesthetic Binding Site at High Resolution

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

    Vedula, L. Sangeetha; Brannigan, Grace; Economou, Nicoleta J.

    2009-10-21

    Propofol is the most widely used injectable general anesthetic. Its targets include ligand-gated ion channels such as the GABA{sub A} receptor, but such receptor-channel complexes remain challenging to study at atomic resolution. Until structural biology methods advance to the point of being able to deal with systems such as the GABA{sub A} receptor, it will be necessary to use more tractable surrogates to probe the molecular details of anesthetic recognition. We have previously shown that recognition of inhalational general anesthetics by the model protein apoferritin closely mirrors recognition by more complex and clinically relevant protein targets; here we show thatmore » apoferritin also binds propofol and related GABAergic anesthetics, and that the same binding site mediates recognition of both inhalational and injectable anesthetics. Apoferritin binding affinities for a series of propofol analogs were found to be strongly correlated with the ability to potentiate GABA responses at GABA{sub A} receptors, validating this model system for injectable anesthetics. High resolution x-ray crystal structures reveal that, despite the presence of hydrogen bond donors and acceptors, anesthetic recognition is mediated largely by van der Waals forces and the hydrophobic effect. Molecular dynamics simulations indicate that the ligands undergo considerable fluctuations about their equilibrium positions. Finally, apoferritin displays both structural and dynamic responses to anesthetic binding, which may mimic changes elicited by anesthetics in physiologic targets like ion channels.« less

  5. A Unitary Anesthetic Binding Site at High Resolution

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

    L Vedula; G Brannigan; N Economou

    2011-12-31

    Propofol is the most widely used injectable general anesthetic. Its targets include ligand-gated ion channels such as the GABA{sub A} receptor, but such receptor-channel complexes remain challenging to study at atomic resolution. Until structural biology methods advance to the point of being able to deal with systems such as the GABA{sub A} receptor, it will be necessary to use more tractable surrogates to probe the molecular details of anesthetic recognition. We have previously shown that recognition of inhalational general anesthetics by the model protein apoferritin closely mirrors recognition by more complex and clinically relevant protein targets; here we show thatmore » apoferritin also binds propofol and related GABAergic anesthetics, and that the same binding site mediates recognition of both inhalational and injectable anesthetics. Apoferritin binding affinities for a series of propofol analogs were found to be strongly correlated with the ability to potentiate GABA responses at GABA{sub A} receptors, validating this model system for injectable anesthetics. High resolution x-ray crystal structures reveal that, despite the presence of hydrogen bond donors and acceptors, anesthetic recognition is mediated largely by van der Waals forces and the hydrophobic effect. Molecular dynamics simulations indicate that the ligands undergo considerable fluctuations about their equilibrium positions. Finally, apoferritin displays both structural and dynamic responses to anesthetic binding, which may mimic changes elicited by anesthetics in physiologic targets like ion channels.« less

  6. A Unitary Anesthetic-Binding Site at High Resolution

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

    Vedula, L.; Brannigan, G; Economou, N

    2009-01-01

    Propofol is the most widely used injectable general anesthetic. Its targets include ligand-gated ion channels such as the GABAA receptor, but such receptor-channel complexes remain challenging to study at atomic resolution. Until structural biology methods advance to the point of being able to deal with systems such as the GABA{sub A} receptor, it will be necessary to use more tractable surrogates to probe the molecular details of anesthetic recognition. We have previously shown that recognition of inhalational general anesthetics by the model protein apoferritin closely mirrors recognition by more complex and clinically relevant protein targets; here we show that apoferritinmore » also binds propofol and related GABAergic anesthetics, and that the same binding site mediates recognition of both inhalational and injectable anesthetics. Apoferritin binding affinities for a series of propofol analogs were found to be strongly correlated with the ability to potentiate GABA responses at GABA{sub A} receptors, validating this model system for injectable anesthetics. High resolution x-ray crystal structures reveal that, despite the presence of hydrogen bond donors and acceptors, anesthetic recognition is mediated largely by van der Waals forces and the hydrophobic effect. Molecular dynamics simulations indicate that the ligands undergo considerable fluctuations about their equilibrium positions. Finally, apoferritin displays both structural and dynamic responses to anesthetic binding, which may mimic changes elicited by anesthetics in physiologic targets like ion channels.« less

  7. Sol-gel layers for ceramic microsystems application

    NASA Astrophysics Data System (ADS)

    Czok, Mateusz; Golonka, Leszek

    2016-11-01

    This paper describes research on sol-gel solutions preparation process. Utilize of a sol-gel layers in the LTCC technology for reduction of surface roughness and influence on the ceramics properties is examined and described. The influence of sol-gel layer on possible sedimentation of dyes or biological substances in channels, mixers or chambers of ceramic microfluidic structures was investigated. Moreover, properties of sol-gel coated surfaces have been precisely examined and described. Finally, positive results of conducted experiments made it possible to design and manufacture a simple microfluidic ceramic structure, with embedded protective layer of sol-gel, for fluorescence measurements.

  8. The effect of nozzle-exit-channel shape on resultant fiber diameter in melt-electrospinning

    NASA Astrophysics Data System (ADS)

    Esmaeilirad, Ahmad; Ko, Junghyuk; Rukosuyev, Maxym V.; Lee, Jason K.; Lee, Patrick C.; Jun, Martin B. G.

    2017-01-01

    In recent decades, electrospinning using a molten poly (ε-caprolactone) resin has gained attention for creating fibrous tissue scaffolds. The topography and diameter control of such electrospun microfibers is an important issue for their different applications in tissue engineering. Charge density, initial nozzle-exit-channel cross-sectional area, nozzle to collector distance, viscosity, and processing temperature are the most important input parameters that affect the final electrospun fiber diameters. In this paper we will show that the effect of nozzle-exit-channel shape is as important as the other effective parameters in a resultant fiber diameter. However, to the best of our knowledge, the effect of nozzle-exit-channel shapes on a resultant fiber diameter have not been studied before. Comparing rectangular and circular nozzles with almost the same exit-channel cross-sectional areas in a similar processing condition showed that using a rectangular nozzle resulted in decreasing final fiber diameter up to 50%. Furthermore, the effect of processing temperature on the final fiber topography was investigated.

  9. The bankfull hydraulic geometry of evolving meander bends

    NASA Astrophysics Data System (ADS)

    Monegaglia, F.; Tubino, M.; Zolezzi, G.

    2017-12-01

    Changes in the bankfull hydraulic geometry of meandering rivers associated with meander growth from incipient meandering to cutoffs have seldom been analysed in detail. Such information is also needed by meander morphodynamic models, most of which simulate the evolution of bankfull channel geometry by simply accounting for channel slope reduction inversely proportional to elongation, while changes in bankfull channel width are often neglected or, when they are considered, they are not consistent with the few available observations. To address these gaps we first perform an extensive, systematic, bend-scale evolutionary analysis of bankfull channel widths in several large meandering rivers in the Amazon basin, over a three decades time period, from remotely sensed field data. The analysis consistently show a slight decreasing trend of the bankfull channel width during the planform evolution towards cutoff. Furthermore, we develop a physically based model for the evolution of bankfull channel geometry during the planform development of meandering rivers. The model is based on the conservation of sediment discharge. An integrated one-dimensional Exner equation that accounts for meander elongation, sediment supply conservation and sediment income from the channel banks, allows us to predict the evolution of the channel slope. The evolution of the channel width is modeled through a threshold equation. The model correctly predicts the slight variability of channel width during meander development and a gentler reduction of the channel slope, which is mitigated by the conservation of sediment supply. The bankfull geometry of highly dynamic meandering rivers is predicted to be elongation-dominated, while the one related to slowly evolving meandering rivers is sediment supply-dominated. Finally, we discuss the implications of the proposed modeling framework in terms of planform structure, meander shape and morphodynamic influence.

  10. AN INVESTIGATION OF TIME LAG MAPS USING THREE-DIMENSIONAL SIMULATIONS OF HIGHLY STRATIFIED HEATING

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

    Winebarger, Amy R.; Lionello, Roberto; Downs, Cooper

    2016-11-10

    The location and frequency of coronal energy release provide a significant constraint on the coronal heating mechanism. The evolution of the intensity observed in coronal structures found from time lag analysis of Atmospheric Imaging Assembly (AIA) data has been used to argue that heating must occur sporadically. Recently, we have demonstrated that quasi-steady, highly stratified (footpoint) heating can produce results qualitatively consistent with the evolution of observed coronal structures. The goals of this paper are to demonstrate that time lag analysis of 3D simulations of footpoint heating are qualitatively consistent with time lag analysis of observations and to use themore » 3D simulations to further understand whether time lag analysis is a useful tool in defining the evolution of coronal structures. We find the time lag maps generated from simulated data are consistent with the observed time lag maps. We next investigate several example points. In some cases, the calculated time lag reflects the evolution of a unique loop along the line of sight, though there may be additional evolving structures along the line of sight. We confirm that using the multi-peak AIA channels can produce time lags that are difficult to interpret. We suggest using a different high temperature channel, such as an X-ray channel. Finally, we find that multiple evolving structures along the line of sight can produce time lags that do not represent the physical properties of any structure along the line of sight, although the cross-correlation coefficient of the lightcurves is high. Considering the projected geometry of the loops may reduce some of the line-of-sight confusion.« less

  11. Channel characteristics and coordination in three-echelon dual-channel supply chain

    NASA Astrophysics Data System (ADS)

    Saha, Subrata

    2016-02-01

    We explore the impact of channel structure on the manufacturer, the distributer, the retailer and the entire supply chain by considering three different channel structures in radiance of with and without coordination. These structures include a traditional retail channel and two manufacturer direct channels with and without consistent pricing. By comparing the performance of the manufacturer, the distributer and the retailer, and the entire supply chain in three different supply chain structures, it is established analytically that, under some conditions, a dual channel can outperform a single retail channel; as a consequence, a coordination mechanism is developed that not only coordinates the dual channel but also outperforms the non-cooperative single retail channel. All the analytical results are further analysed through numerical examples.

  12. Microfabrication of channel arrays promotes vessel-like network formation in cardiac cell construct and vascularization in vivo.

    PubMed

    Zieber, Liran; Or, Shira; Ruvinov, Emil; Cohen, Smadar

    2014-06-01

    Pre-vascularization is important for the reconstruction of dense and metabolically active myocardial tissue and its integration with the host myocardium after implantation. Herein, we demonstrate that the fabrication of micro-channels in alginate scaffold combined with the presentation of adhesion peptides and an angiogenic growth factor promote vessel-like networks in the construct, both in vitro and in vivo. Using a CO2 laser engraving system, 200 µm diameter channels were formed from top to bottom of the 2 mm thick alginate scaffold, with a channel-to-channel distance of 400 µm. Cells were seeded in a sequential manner onto the scaffolds: first, human umbilical vascular endothelial cells (HUVECs) were seeded and cultured for three days, then neonatal rat cardiomyocytes (CMs) and cardiofibroblasts were added at a final cell ratio of 50:35:15, respectively, and the constructs were cultivated for an additional seven days. A vessel-like network was formed within the cell constructs, wherein HUVECs were organized around the channels in a multilayer manner, while the CMs were located in-between the channels and exhibited the characteristic morphological features of a mature cardiac fiber. Acellular scaffolds with the affinity-bound basic fibroblast growth factor were implanted subcutaneously in mice. Increased cell penetration into the channeled scaffold and greater vessel density were found in comparison with the nonchanneled scaffolds. Our results thus point to the importance of micro-channels as a major structural promoter of vascularization in scaffolds, in conjunction with the sequential preculture of ECs and angiogenic factor presentation.

  13. Nonsequential double ionization channels control of Ar with few-cycle elliptically polarized laser pulse by carrier-envelope-phase.

    PubMed

    Ben, Shuai; Wang, Tian; Xu, Tongtong; Guo, Jing; Liu, Xueshen

    2016-04-04

    The carrier-envelop-phase (CEP) dependence of nonsequential double ionization (NSDI) of atomic Ar with few-cycle elliptically polarized laser pulse is investigated using 2D classical ensemble method. We distinguish two particular recollision channels in NSDI, which are recollision-impact ionization (RII) and recollision-induced excitation with subsequent ionization (RESI). We separate the RII and RESI channels according to the delay time between recollision and final double ionization. By tracing the history of the trajectories, we find the electron correlation spectra as well as the competition between the two channels are sensitively dependent on the laser field CEP. Finally, control can be achieved between the two channels by varying the CEP.

  14. Lightning energetics: Estimates of energy dissipation in channels, channel radii, and channel-heating risetimes

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

    Borovsky, J.E.

    1998-05-01

    In this report, several lightning-channel parameters are calculated with the aid of an electrodynamic model of lightning. The electrodynamic model describes dart leaders and return strokes as electromagnetic waves that are guided along conducting lightning channels. According to the model, electrostatic energy is delivered to the channel by a leader, where it is stored around the outside of the channel; subsequently, the return stroke dissipates this locally stored energy. In this report this lightning-energy-flow scenario is developed further. Then the energy dissipated per unit length in lightning channels is calculated, where this quantity is now related to the linear chargemore » density on the channel, not to the cloud-to-ground electrostatic potential difference. Energy conservation is then used to calculate the radii of lightning channels: their initial radii at the onset of return strokes and their final radii after the channels have pressure expanded. Finally, the risetimes for channel heating during return strokes are calculated by defining an energy-storage radius around the channel and by estimating the radial velocity of energy flow toward the channel during a return stroke. In three appendices, values for the linear charge densities on lightning channels are calculated, estimates of the total length of branch channels are obtained, and values for the cloud-to-ground electrostatic potential difference are estimated. {copyright} 1998 American Geophysical Union« less

  15. Design of boron carbide-shielded irradiation channel of the outer irradiation channel of the Ghana Research Reactor-1 using MCNP.

    PubMed

    Abrefah, R G; Sogbadji, R B M; Ampomah-Amoako, E; Birikorang, S A; Odoi, H C; Nyarko, B J B

    2011-01-01

    The MCNP model for the Ghana Research Reactor-1 was redesigned to incorporate a boron carbide-shielded irradiation channel in one of the outer irradiation channels. Extensive investigations were made before arriving at the final design of only one boron carbide covered outer irradiation channel; as all the other designs that were considered did not give desirable results of neutronic performance. The concept of redesigning a new MCNP model, which has a boron carbide-shielded channel is to equip the Ghana Research Reactor-1 with the means of performing efficient epithermal neutron activation analysis. After the simulation, a comparison of the results from the original MCNP model for the Ghana Research Reactor-1 and the new redesigned model of the boron carbide shielded channel was made. The final effective criticality of the original MCNP model for the GHARR-1 was recorded as 1.00402 while that of the new boron carbide designed model was recorded as 1.00282. Also, a final prompt neutron lifetime of 1.5245 × 10(-4)s was recorded for the new boron carbide designed model while a value of 1.5571 × 10(-7)s was recorded for the original MCNP design of the GHARR-1. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. New insights on the voltage dependence of the KCa3.1 channel block by internal TBA.

    PubMed

    Banderali, Umberto; Klein, Hélène; Garneau, Line; Simoes, Manuel; Parent, Lucie; Sauvé, Rémy

    2004-10-01

    We present in this work a structural model of the open IKCa (KCa3.1) channel derived by homology modeling from the MthK channel structure, and used this model to compute the transmembrane potential profile along the channel pore. This analysis showed that the selectivity filter and the region extending from the channel inner cavity to the internal medium should respectively account for 81% and 16% of the transmembrane potential difference. We found however that the voltage dependence of the IKCa block by the quaternary ammonium ion TBA applied internally is compatible with an apparent electrical distance delta of 0.49 +/- 0.02 (n = 6) for negative potentials. To reconcile this observation with the electrostatic potential profile predicted for the channel pore, we modeled the IKCa block by TBA assuming that the voltage dependence of the block is governed by both the difference in potential between the channel cavity and the internal medium, and the potential profile along the selectivity filter region through an effect on the filter ion occupancy states. The resulting model predicts that delta should be voltage dependent, being larger at negative than positive potentials. The model also indicates that raising the internal K+ concentration should decrease the value of delta measured at negative potentials independently of the external K+ concentration, whereas raising the external K+ concentration should minimally affect delta for concentrations >50 mM. All these predictions are born out by our current experimental results. Finally, we found that the substitutions V275C and V275A increased the voltage sensitivity of the TBA block, suggesting that TBA could move further into the pore, thus leading to stronger interactions between TBA and the ions in the selectivity filter. Globally, these results support a model whereby the voltage dependence of the TBA block in IKCa is mainly governed by the voltage dependence of the ion occupancy states of the selectivity filter.

  17. Bead lightning formation

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

    Ludwig, G.O.; Saba, M.M.F.; Division of Space Geophysics, National Space Research Institute, 12227-010, Sao Jose dos Campos, SP

    2005-09-15

    Formation of beaded structures in triggered lightning discharges is considered in the framework of both magnetohydrodynamic (MHD) and hydrodynamic instabilities. It is shown that the space periodicity of the structures can be explained in terms of the kink and sausage type instabilities in a cylindrical discharge with anomalous viscosity. In particular, the fast growth rate of the hydrodynamic Rayleigh-Taylor instability, which is driven by the backflow of air into the channel of the decaying return stroke, dominates the initial evolution of perturbations during the decay of the return current. This instability is responsible for a significant enhancement of the anomalousmore » viscosity above the classical level. Eventually, the damping introduced at the current channel edge by the high level of anomalous viscous stresses defines the final length scale of bead lightning. Later, during the continuing current stage of the lightning flash, the MHD pinch instability persists, although with a much smaller growth rate that can be enhanced in a M-component event. The combined effect of these instabilities may explain various aspects of bead lightning.« less

  18. Wind-induced structural response of a large telescope

    NASA Astrophysics Data System (ADS)

    Smith, David R.; Avitabile, Peter; Gwaltney, Geoff; Cho, Myung; Sheehan, Michael

    2004-09-01

    In May of 2000, the construction progress of the Gemini South 8m telescope at Cerro Pachon in Chile was such that the telescope and dome were installed and able to move, but the primary mirror had not been installed. This provided a unique opportunity to make extensive tests of the structure in its nearly-completed state, including a modal impact test and simultaneous measurements of wind pressure and structural response. The testing was even more comprehensive because the Gemini dome design allows for a wide range of wind flow configurations, from nearly enclosed to almost fully exposed. In these tests, the operating response of 24 surface pressures on the primary mirror cell, 5 wind velocity channels (each with direction vector information), and more than 70 channels of accelerometers on the telescope structure were measured. The data were taken in a variety of wind loading configurations. While previous analysis efforts have focused on the wind velocity and pressure measurement, this paper investigates the dynamic behavior of the telescope structure itself. Specifically, the discussion includes the participation of the modes measured in the modal impact test as a function of wind loading configuration. Data that indicate the most important frequency ranges in the operating response of the telescope are also presented. Finally, the importance of the response of the enclosure on the structural vibration of the telescope structure is discussed.

  19. Architecture and Channel-Belt Clustering in the Fluvial lower Wasatch Formation, Uinta Basin, Utah

    NASA Astrophysics Data System (ADS)

    Pisel, J. R.; Pyles, D. R.; Bracken, B.; Rosenbaum, C. D.

    2013-12-01

    The Eocene lower Wasatch Formation of the Uinta Basin contains exceptional outcrops of low net-sand content (27% sand) fluvial strata. This study quantitatively documents the stratigraphy of a 7 km wide by 300 meter thick strike-oriented outcrop in order to develop a quantitative data base that can be used to improve our knowledge of how some fluvial systems evolve over geologic time scales. Data used to document the outcrop are: (1) 550 meters of decimeter to half meter scale resolution stratigraphic columns that document grain size and physical sedimentary structures; (2) detailed photopanels used to document architectural style and lithofacies types in the outcrop; (3) thickness, width, and spatial position for all channel belts in the outcrop, and (4) directional measurements of paleocurrent indicators. Two channel-belt styles are recognized: lateral and downstream accreting channel belts; both of which occur as either single or multi-story. Floodplain strata are well exposed and consist of overbank fines and sand-rich crevasse splay deposits. Key upward and lateral characteristics of the outcrop documented herein are the following. First, the shapes of 243 channels are documented. The average width, thickness and aspect ratios of the channel belts are 110 m, 7 m, and 16:1, respectively. Importantly, the size and shape of channel belts does not change upward through the 300 meter transect. Second, channels are documented to spatially cluster. 9 clusters are documented using a spatial statistic. Key upward patterns in channel belt clustering are a marked change from non-amalgamated isolated channel-belt clusters to amalgamated channel-belt clusters. Critically, stratal surfaces can be correlated from mudstone units within the clusters to time-equivalent floodplain strata adjacent to the cluster demonstrating that clusters are not confined within fluvial valleys. Finally, proportions of floodplain and channel belt elements underlying clusters and channel belts vary with the style of clusters and channel belts laterally and vertically within the outcrop.

  20. Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.

    PubMed

    Huang, Weiyun; Liu, Minhao; Yan, S Frank; Yan, Nieng

    2017-06-01

    Voltage-gated sodium (Na v ) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na v channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na v channels, with Na v 1.1 and Na v 1.5 each harboring more than 400 mutations. Na v channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na v channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca v ) channel Ca v 1.1 provides a template for homology-based structural modeling of the evolutionarily related Na v channels. In this Resource article, we summarized all the reported disease-related mutations in human Na v channels, generated a homologous model of human Na v 1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na v channels, the analysis presented here serves as the base framework for mechanistic investigation of Na v channelopathies and for potential structure-based drug discovery.

  1. A membrane-embedded pathway delivers general anesthetics to two interacting binding sites in the Gloeobacter violaceus ion channel.

    PubMed

    Arcario, Mark J; Mayne, Christopher G; Tajkhorshid, Emad

    2017-06-09

    General anesthetics exert their effects on the central nervous system by acting on ion channels, most notably pentameric ligand-gated ion channels. Although numerous studies have focused on pentameric ligand-gated ion channels, the details of anesthetic binding and channel modulation are still debated. A better understanding of the anesthetic mechanism of action is necessary for the development of safer and more efficacious drugs. Herein, we present a computational study identifying two anesthetic binding sites in the transmembrane domain of the Gloeobacter violaceus ligand-gated ion channel (GLIC) channel, characterize the putative binding pathway, and observe structural changes associated with channel function. Molecular simulations of desflurane reveal a binding pathway to GLIC via a membrane-embedded tunnel using an intrasubunit protein lumen as the conduit, an observation that explains the Meyer-Overton hypothesis, or why the lipophilicity of an anesthetic and its potency are generally proportional. Moreover, employing high concentrations of ligand led to the identification of a second transmembrane site (TM2) that inhibits dissociation of anesthetic from the TM1 site and is consistent with the high concentrations of anesthetics required to achieve clinical effects. Finally, asymmetric binding patterns of anesthetic to the channel were found to promote an iris-like conformational change that constricts and dehydrates the ion pore, creating a 13.5 kcal/mol barrier to ion translocation. Together with previous studies, the simulations presented herein demonstrate a novel anesthetic binding site in GLIC that is accessed through a membrane-embedded tunnel and interacts with a previously known site, resulting in conformational changes that produce a non-conductive state of the channel. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Back-channel-etch amorphous indium-gallium-zinc oxide thin-film transistors: The impact of source/drain metal etch and final passivation

    NASA Astrophysics Data System (ADS)

    Nag, Manoj; Bhoolokam, Ajay; Steudel, Soeren; Chasin, Adrian; Myny, Kris; Maas, Joris; Groeseneken, Guido; Heremans, Paul

    2014-11-01

    We report on the impact of source/drain (S/D) metal (molybdenum) etch and the final passivation (SiO2) layer on the bias-stress stability of back-channel-etch (BCE) configuration based amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). It is observed that the BCE configurations TFTs suffer poor bias-stability in comparison to etch-stop-layer (ESL) TFTs. By analysis with transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS), as well as by a comparative analysis of contacts formed by other metals, we infer that this poor bias-stability for BCE transistors having Mo S/D contacts is associated with contamination of the back channel interface, which occurs by Mo-containing deposits on the back channel during the final plasma process of the physical vapor deposited SiO2 passivation.

  3. 76 FR 68117 - Television Broadcasting Services; Panama City, FL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-03

    ...] Television Broadcasting Services; Panama City, FL AGENCY: Federal Communications Commission. ACTION: Final... (``Gray''), the licensee of WJHG-TV, channel 7, Panama City, Florida, requesting the substitution of channel 18 for channel 7 at Panama City. Gray believes it is best to move to a UHF channel after two power...

  4. Emplacement of the Rocche Rosse rhyolite lava flow (Lipari, Aeolian Islands)

    NASA Astrophysics Data System (ADS)

    Bullock, Liam A.; Gertisser, Ralf; O'Driscoll, Brian

    2018-05-01

    The Rocche Rosse lava flow marks the most recent rhyolitic extrusion on Lipari island (Italy), and preserves evidence for a multi-stage emplacement history. Due to the viscous nature of the advancing lava (108 to 1010 Pa s), indicators of complex emplacement processes are preserved in the final flow. This study focuses on structural mapping of the flow to highlight the interplay of cooling, crust formation and underlying slope in the development of rhyolitic lavas. The flow is made up of two prominent lobes, small (< 0.2 m) to large (> 0.2 m) scale folding and a channelled geometry. Foliations dip at 2-4° over the flatter topography close to the vent, and up to 30-50° over steeper mid-flow topography. Brittle faults, tension gashes and conjugate fractures are also evident across flow. Heterogeneous deformation is evident through increasing fold asymmetry from the vent due to downflow cooling and stagnation. A steeper underlying topography mid-flow led to development of a channelled morphology, and compression at topographic breaks resulted in fold superimposition in the channel. We propose an emplacement history that involved the evolution through five stages, each associated with the following flow regimes: (1) initial extrusion, crustal development and small scale folding; (2) extensional strain, stretching lineations and channel development over steeper topography; (3) compression at topographic break, autobrecciation, lobe development and medium scale folding; (4) progressive deformation with stagnation, large-scale folding and re-folding; and (5) brittle deformation following flow termination. The complex array of structural elements observed within the Rocche Rosse lava flow facilitates comparisons to be made with actively deforming rhyolitic lava flows at the Chilean volcanoes of Chaitén and Cordón Caulle, offering a fluid dynamic and structural framework within which to evaluate our data.

  5. Analog and digital transport of RF channels over converged 5G wireless-optical networks

    NASA Astrophysics Data System (ADS)

    Binh, Le Nguyen

    2016-02-01

    Under the exponential increase demand by the emerging 5G wireless access networking and thus data-center based Internet, novel and economical transport of RF channels to and from wireless access systems. This paper presents the transport technologies of RF channels over the analog and digital domain so as to meet the demands of the transport capacity reaching multi-Tbps, in the followings: (i) The convergence of 5G broadband wireless and optical networks and its demands on capacity delivery and network structures; (ii) Analog optical technologies for delivery of both the information and RF carriers to and from multiple-input multiple-output (MIMO) antenna sites so as to control the beam steering of MIMO antenna in the mmW at either 28.6 GHz and 56.8 GHz RF carrier and delivery of channels of aggregate capacity reaching several Tbps; (ii) Transceiver employing advanced digital modulation formats and digital signal processing (DSP) so as to provide 100G and beyond transmission rate to meet the ultra-high capacity demands with flexible spectral grids, hence pay-on-demand services. The interplay between DSP-based and analog transport techniques is examined; (iii) Transport technologies for 5G cloud access networks and associate modulation and digital processing techniques for capacity efficiency; and (iv) Finally the integrated optic technologies with novel lasers, comb generators and simultaneous dual function photonic devices for both demultiplexing/multiplexing and modulation are proposed, hence a system on chip structure can be structured. Quantum dot lasers and matrixes of micro ring resonators are integrated on the same Si-on-Silica substrate are proposed and described.

  6. 512-Channel and 13-Region Simultaneous Recordings Coupled with Optogenetic Manipulation in Freely Behaving Mice

    PubMed Central

    Xie, Kun; Fox, Grace E.; Liu, Jun; Tsien, Joe Z.

    2016-01-01

    The development of technologies capable of recording both single-unit activity and local field potentials (LFPs) over a wide range of brain circuits in freely behaving animals is the key to constructing brain activity maps. Although mice are the most popular mammalian genetic model, in vivo neural recording has been traditionally limited to smaller channel count and fewer brain structures because of the mouse’s small size and thin skull. Here, we describe a 512-channel tetrode system that allows us to record simultaneously over a dozen cortical and subcortical structures in behaving mice. This new technique offers two major advantages – namely, the ultra-low cost and the do-it-yourself flexibility for targeting any combination of many brain areas. We show the successful recordings of both single units and LFPs from 13 distinct neural circuits of the mouse brain, including subregions of the anterior cingulate cortices, retrosplenial cortices, somatosensory cortices, secondary auditory cortex, hippocampal CA1, dentate gyrus, subiculum, lateral entorhinal cortex, perirhinal cortex, and prelimbic cortex. This 512-channel system can also be combined with Cre-lox neurogenetics and optogenetics to further examine interactions between genes, cell types, and circuit dynamics across a wide range of brain structures. Finally, we demonstrate that complex stimuli – such as an earthquake and fear-inducing foot-shock – trigger firing changes in all of the 13 brain regions recorded, supporting the notion that neural code is highly distributed. In addition, we show that localized optogenetic manipulation in any given brain region could disrupt network oscillations and caused changes in single-unit firing patterns in a brain-wide manner, thereby raising the cautionary note of the interpretation of optogenetically manipulated behaviors. PMID:27378865

  7. Entangled state teleportation through a couple of quantum channels composed of XXZ dimers in an Ising- XXZ diamond chain

    NASA Astrophysics Data System (ADS)

    Rojas, M.; de Souza, S. M.; Rojas, Onofre

    2017-02-01

    The quantum teleportation plays an important role in quantum information process, in this sense, the quantum entanglement properties involving an infinite chain structure is quite remarkable because real materials could be well represented by an infinite chain. We study the teleportation of an entangled state through a couple of quantum channels, composed by Heisenberg dimers in an infinite Ising-Heisenberg diamond chain, the couple of chains are considered sufficiently far away from each other to be ignored the any interaction between them. To teleporting a couple of qubits through the quantum channel, we need to find the average density operator for Heisenberg spin dimers, which will be used as quantum channels. Assuming the input state as a pure state, we can apply the concept of fidelity as a useful measurement of teleportation performance of a quantum channel. Using the standard teleportation protocol, we have derived an analytical expression for the output concurrence, fidelity, and average fidelity. We study in detail the effects of coupling parameters, external magnetic field and temperature dependence of quantum teleportation. Finally, we explore the relations between entanglement of the quantum channel, the output entanglement and the average fidelity of the system. Through a kind of phase diagram as a function of Ising-Heisenberg diamond chain model parameters, we illustrate where the quantum teleportation will succeed and a region where the quantum teleportation could fail.

  8. Development of the field of structural physiology

    PubMed Central

    FUJIYOSHI, Yoshinori

    2015-01-01

    Electron crystallography is especially useful for studying the structure and function of membrane proteins — key molecules with important functions in neural and other cells. Electron crystallography is now an established technique for analyzing the structures of membrane proteins in lipid bilayers that closely simulate their natural biological environment. Utilizing cryo-electron microscopes with helium-cooled specimen stages that were developed through a personal motivation to understand the functions of neural systems from a structural point of view, the structures of membrane proteins can be analyzed at a higher than 3 Å resolution. This review covers four objectives. First, I introduce the new research field of structural physiology. Second, I recount some of the struggles involved in developing cryo-electron microscopes. Third, I review the structural and functional analyses of membrane proteins mainly by electron crystallography using cryo-electron microscopes. Finally, I discuss multifunctional channels named “adhennels” based on structures analyzed using electron and X-ray crystallography. PMID:26560835

  9. Design of Channel Type Indirect Blank Holder for Prevention of Wrinkling and Fracture in Hot Stamping Process

    NASA Astrophysics Data System (ADS)

    Choi, Hong-seok; Ha, Se-yoon; Cha, Seung-hoon; kang, Chung-gil; Kim, Byung-min

    2011-08-01

    The hot stamping process has been used in the automotive industry to reduce the weight of the body-in-white and to increase passenger safety via improved crashworthiness. In this study, a new form die with a simple structure that can prevent defects such as wrinkle and fracture is proposed for the manufacture of hot stamped components. The wrinkling at the flange cannot be eliminated when using a conventional form die. It is known that the initiation of wrinkling is influenced by many factors such as the mechanical properties of the sheet material, geometry of the sheet and tool, and other process parameters, including the blank holding force (BHF) and the contact conditions. In this research, channel type indirect blank holder (CIBH) is introduced to replace general blank holder for manufacturing the hot stamped center pillar. First, we investigate the tension force acting on the blank according to the channel shapes. We determine the appropriate range by comparing the tension force with the upper and lower BHFs in a conventional stamping process. We then use FE-analysis to study the influence of the slope angle and corner radius of the channel on the formability. Finally, the center pillar is manufactured using the form die with the selected channel.

  10. Thermo-Elastic Analysis of Internally Cooled Structures Using a Higher Order Theory

    NASA Technical Reports Server (NTRS)

    Arnold, Steven M.; Bednarcyk, Brett A.; Aboudi, Jacob

    2001-01-01

    This paper presents the results of a study on the thermomechanical behavior of internally cooled silicon nitride structures. Silicon nitride is under consideration for elevated temperature aerospace engine applications. and techniques for lowering the operating temperature of structures composed of this material are under development. Lowering the operating temperature provides a large payoff in terms of fatigue life and may be accomplished through the use of thermal barrier coatings (TBC's) and the novel concept of included cooling channels. Herein, an in-depth study is performed on the behavior of a flame-impinged silicon nitride plate with a TBC and internal channels cooled by forced air. The analysis is performed using the higher order theory for functionally graded materials (HOTFGM), which has been developed through NASA Glenn Research Center funding over the past several years. HOTFGM was chosen over the traditional finite element approach as a prelude to an examination of functionally graded silicon nitride structures for which HOTFGM is ideally suited. To accommodate the analysis requirement% of the internally cooled plate problem, two crucial enhancements were made to the two-dimensional Cartesian-based version of HOTFGM. namely, incorporation of internal boundary capabilities and incorporation of convective boundary conditions. Results indicate the viability and large benefits of cooling the plate via forced air through cooling channels. Furthermore, cooling can positively impact the stress and displacement fields present in the plate, yielding an additional payoff in terms of fatigue life. Finally, a spin-off capability resulted from inclusion of internal boundaries within HOTFGM; the ability to simulate the thermo-elastic response of structures with curved surfaces. This new capability is demonstrated, and through comparison with an analytical solution, shown to be viable and accurate.

  11. n-Channel semiconductor materials design for organic complementary circuits.

    PubMed

    Usta, Hakan; Facchetti, Antonio; Marks, Tobin J

    2011-07-19

    Organic semiconductors have unique properties compared to traditional inorganic materials such as amorphous or crystalline silicon. Some important advantages include their adaptability to low-temperature processing on flexible substrates, low cost, amenability to high-speed fabrication, and tunable electronic properties. These features are essential for a variety of next-generation electronic products, including low-power flexible displays, inexpensive radio frequency identification (RFID) tags, and printable sensors, among many other applications. Accordingly, the preparation of new materials based on π-conjugated organic molecules or polymers has been a central scientific and technological research focus over the past decade. Currently, p-channel (hole-transporting) materials are the leading class of organic semiconductors. In contrast, high-performance n-channel (electron-transporting) semiconductors are relatively rare, but they are of great significance for the development of plastic electronic devices such as organic field-effect transistors (OFETs). In this Account, we highlight the advances our team has made toward realizing moderately and highly electron-deficient n-channel oligomers and polymers based on oligothiophene, arylenediimide, and (bis)indenofluorene skeletons. We have synthesized and characterized a "library" of structurally related semiconductors, and we have investigated detailed structure-property relationships through optical, electrochemical, thermal, microstructural (both single-crystal and thin-film), and electrical measurements. Our results reveal highly informative correlations between structural parameters at various length scales and charge transport properties. We first discuss oligothiophenes functionalized with perfluoroalkyl and perfluoroarene substituents, which represent the initial examples of high-performance n-channel semiconductors developed in this project. The OFET characteristics of these compounds are presented with an emphasis on structure-property relationships. We then examine the synthesis and properties of carbonyl-functionalized oligomers, which constitute second-generation n-channel oligothiophenes, in both vacuum- and solution-processed FETs. These materials have high carrier mobilities and good air stability. In parallel, exceptionally electron-deficient cyano-functionalized arylenediimide derivatives are discussed as early examples of thermodynamically air-stable, high-performance n-channel semiconductors; they exhibit record electron mobilities of up to 0.64 cm(2)/V·s. Furthermore, we provide an overview of highly soluble ladder-type macromolecular semiconductors as OFET components, which combine ambient stability with solution processibility. A high electron mobility of 0.16 cm(2)/V·s is obtained under ambient conditions for solution-processed films. Finally, examples of polymeric n-channel semiconductors with electron mobilities as high as 0.85 cm(2)/V·s are discussed; these constitute an important advance toward fully printed polymeric electronic circuitry. Density functional theory (DFT) computations reveal important trends in molecular physicochemical and semiconducting properties, which, when combined with experimental data, shed new light on molecular charge transport characteristics. Our data provide the basis for a fundamental understanding of charge transport in high-performance n-channel organic semiconductors. Moreover, our results provide a road map for developing functional, complementary organic circuitry, which requires combining p- and n-channel transistors.

  12. The Evolution of Transition Region Loops Using IRIS and AIA

    NASA Technical Reports Server (NTRS)

    Winebarger, Amy R.; DePontieu, Bart

    2014-01-01

    Over the past 50 years, the model for the structure of the solar transition region has evolved from a simple transition layer between the cooler chromosphere to the hotter corona to a complex and diverse region that is dominated by complete loops that never reach coronal temperatures. The IRIS slitjaw images show many complete transition region loops. Several of the "coronal" channels in the SDO AIA instrument include contributions from weak transition region lines. In this work, we combine slitjaw images from IRIS with these channels to determine the evolution of the loops. We develop a simple model for the temperature and density evolution of the loops that can explain the simultaneous observations. Finally, we estimate the percentage of AIA emission that originates in the transition region.

  13. Biochemical and Structural Basis for Controlling Chemical Modularity in Fungal Polyketide Biosynthesis

    DOE PAGES

    Winter, Jaclyn M.; Cascio, Duilio; Dietrich, David; ...

    2015-07-14

    Modular collaboration between iterative fungal polyketide synthases (IPKSs) is an important mechanism for generating structural diversity of polyketide natural products. Inter-PKS communication and substrate channeling are controlled in large by the starter unit acyl carrier protein transacylase (SAT) domain found in the accepting IPKS module. Here in this study, we reconstituted the modular biosynthesis of the benzaldehyde core of the chaetoviridin and chaetomugilin azaphilone natural products using the IPKSs CazF and CazM. Our studies revealed a critical role of CazM’s SAT domain in selectively transferring a highly reduced triketide product from CazF. In contrast, a more oxidized triketide that ismore » also produced by CazF and required in later stages of biosynthesis of the final product is not recognized by the SAT domain. The structural basis for the acyl unit selectivity was uncovered by the first X-ray structure of a fungal SAT domain, highlighted by a covalent hexanoyl thioester intermediate in the SAT active site. Finally, the crystal structure of SAT domain will enable protein engineering efforts aimed at mixing and matching different IPKS modules for the biosynthesis of new compounds.« less

  14. Conduction quantization in monolayer MoS2

    NASA Astrophysics Data System (ADS)

    Li, T. S.

    2016-10-01

    We study the ballistic conduction of a monolayer MoS2 subject to a spatially modulated magnetic field by using the Landauer-Buttiker formalism. The band structure depends sensitively on the field strength, and its change has profound influence on the electron conduction. The conductance is found to demonstrate multi-step behavior due to the discrete number of conduction channels. The sharp peak and rectangular structures of the conductance are stretched out as temperature increases, due to the thermal broadening of the derivative of the Fermi-Dirac distribution function. Finally, quantum behavior in the conductance of MoS2 can be observed at temperatures below 10 K.

  15. Sediment Transport into the Swinomish Navigation Channel, Puget Sound—Habitat Restoration versus Navigation Maintenance Needs

    DOE PAGES

    Khangaonkar, Tarang; Nugraha, Adi; Hinton, Steve; ...

    2017-04-21

    The 11 mile (1.6 km) Swinomish Federal Navigation Channel provides a safe and short passage to fishing and recreational craft in and out of Northern Puget Sound by connecting Skagit and Padilla Bays, US State abbrev., USA. A network of dikes and jetties were constructed through the Swinomish corridor between 1893 and 1936 to improve navigation functionality. Over the years, these river training dikes and jetties designed to minimize sedimentation in the channel have deteriorated, resulting in reduced protection of the channel. The need to repair or modify dikes/jetties for channel maintenance, however, may conflict with salmon habitat restoration goalsmore » aimed at improving access, connectivity and brackish water habitat. Several restoration projects have been proposed in the Skagit delta involving breaching, lowering, or removal of dikes. To assess relative merits of the available alternatives, a hydrodynamic model of the Skagit River estuary was developed using the Finite Volume Community Ocean Model (FVCOM). Here, in this paper, we present the refinement and calibration of the model using oceanographic data collected from the years 2006 and 2009 with a focus on the sediment and brackish water transport from the river and Skagit Bay tide flats to the Swinomish Channel. The model was applied to assess the feasibility of achieving the desired dual outcome of (a) reducing sedimentation and shoaling in the Swinomish Channel and (b) providing a direct migration pathway and improved conveyance of freshwater into the Swinomish Channel. Finally, the potential reduction in shoaling through site-specific structure repairs is evaluated. Similarly, the potential to significantly improve of brackish water habitat through dike breach restoration actions using the McGlinn Causeway project example, along with its impacts on sediment deposition in the Swinomish Navigation Channel, is examined« less

  16. Characterizing Social Networks and Communication Channels in a Web-Based Peer Support Intervention.

    PubMed

    Owen, Jason E; Curran, Michaela; Bantum, Erin O'Carroll; Hanneman, Robert

    2016-06-01

    Web and mobile (mHealth) interventions have promise for improving health outcomes, but engagement and attrition may be reducing effect sizes. Because social networks can improve engagement, which is a key mechanism of action, understanding the structure and potential impact of social networks could be key to improving mHealth effects. This study (a) evaluates social network characteristics of four distinct communication channels (discussion board, chat, e-mail, and blog) in a large social networking intervention, (b) predicts membership in online communities, and (c) evaluates whether community membership impacts engagement. Participants were 299 cancer survivors with significant distress using the 12-week health-space.net intervention. Social networking attributes (e.g., density and clustering) were identified separately for each type of network communication (i.e., discussion board, blog, web mail, and chat). Each channel demonstrated high levels of clustering, and being a community member in one communication channel was associated with being in the same community in each of the other channels (φ = 0.56-0.89, ps < 0.05). Predictors of community membership differed across communication channels, suggesting that each channel reached distinct types of users. Finally, membership in a discussion board, chat, or blog community was strongly associated with time spent engaging with coping skills exercises (Ds = 1.08-1.84, ps < 0.001) and total time of intervention (Ds = 1.13-1.80, ps < 0.001). mHealth interventions that offer multiple channels for communication allow participants to expand the number of individuals with whom they are communicating, create opportunities for communicating with different individuals in distinct channels, and likely enhance overall engagement.

  17. Characterizing Social Networks and Communication Channels in a Web-Based Peer Support Intervention

    PubMed Central

    Curran, Michaela; Bantum, Erin O'Carroll; Hanneman, Robert

    2016-01-01

    Abstract Web and mobile (mHealth) interventions have promise for improving health outcomes, but engagement and attrition may be reducing effect sizes. Because social networks can improve engagement, which is a key mechanism of action, understanding the structure and potential impact of social networks could be key to improving mHealth effects. This study (a) evaluates social network characteristics of four distinct communication channels (discussion board, chat, e-mail, and blog) in a large social networking intervention, (b) predicts membership in online communities, and (c) evaluates whether community membership impacts engagement. Participants were 299 cancer survivors with significant distress using the 12-week health-space.net intervention. Social networking attributes (e.g., density and clustering) were identified separately for each type of network communication (i.e., discussion board, blog, web mail, and chat). Each channel demonstrated high levels of clustering, and being a community member in one communication channel was associated with being in the same community in each of the other channels (φ = 0.56–0.89, ps < 0.05). Predictors of community membership differed across communication channels, suggesting that each channel reached distinct types of users. Finally, membership in a discussion board, chat, or blog community was strongly associated with time spent engaging with coping skills exercises (Ds = 1.08–1.84, ps < 0.001) and total time of intervention (Ds = 1.13–1.80, ps < 0.001). mHealth interventions that offer multiple channels for communication allow participants to expand the number of individuals with whom they are communicating, create opportunities for communicating with different individuals in distinct channels, and likely enhance overall engagement. PMID:27327066

  18. Sediment Transport into the Swinomish Navigation Channel, Puget Sound—Habitat Restoration versus Navigation Maintenance Needs

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

    Khangaonkar, Tarang; Nugraha, Adi; Hinton, Steve

    The 11 mile (1.6 km) Swinomish Federal Navigation Channel provides a safe and short passage to fishing and recreational craft in and out of Northern Puget Sound by connecting Skagit and Padilla Bays, US State abbrev., USA. A network of dikes and jetties were constructed through the Swinomish corridor between 1893 and 1936 to improve navigation functionality. Over the years, these river training dikes and jetties designed to minimize sedimentation in the channel have deteriorated, resulting in reduced protection of the channel. The need to repair or modify dikes/jetties for channel maintenance, however, may conflict with salmon habitat restoration goalsmore » aimed at improving access, connectivity and brackish water habitat. Several restoration projects have been proposed in the Skagit delta involving breaching, lowering, or removal of dikes. To assess relative merits of the available alternatives, a hydrodynamic model of the Skagit River estuary was developed using the Finite Volume Community Ocean Model (FVCOM). Here, in this paper, we present the refinement and calibration of the model using oceanographic data collected from the years 2006 and 2009 with a focus on the sediment and brackish water transport from the river and Skagit Bay tide flats to the Swinomish Channel. The model was applied to assess the feasibility of achieving the desired dual outcome of (a) reducing sedimentation and shoaling in the Swinomish Channel and (b) providing a direct migration pathway and improved conveyance of freshwater into the Swinomish Channel. Finally, the potential reduction in shoaling through site-specific structure repairs is evaluated. Similarly, the potential to significantly improve of brackish water habitat through dike breach restoration actions using the McGlinn Causeway project example, along with its impacts on sediment deposition in the Swinomish Navigation Channel, is examined« less

  19. Fusion of multichannel local and global structural cues for photo aesthetics evaluation.

    PubMed

    Luming Zhang; Yue Gao; Zimmermann, Roger; Qi Tian; Xuelong Li

    2014-03-01

    Photo aesthetic quality evaluation is a fundamental yet under addressed task in computer vision and image processing fields. Conventional approaches are frustrated by the following two drawbacks. First, both the local and global spatial arrangements of image regions play an important role in photo aesthetics. However, existing rules, e.g., visual balance, heuristically define which spatial distribution among the salient regions of a photo is aesthetically pleasing. Second, it is difficult to adjust visual cues from multiple channels automatically in photo aesthetics assessment. To solve these problems, we propose a new photo aesthetics evaluation framework, focusing on learning the image descriptors that characterize local and global structural aesthetics from multiple visual channels. In particular, to describe the spatial structure of the image local regions, we construct graphlets small-sized connected graphs by connecting spatially adjacent atomic regions. Since spatially adjacent graphlets distribute closely in their feature space, we project them onto a manifold and subsequently propose an embedding algorithm. The embedding algorithm encodes the photo global spatial layout into graphlets. Simultaneously, the importance of graphlets from multiple visual channels are dynamically adjusted. Finally, these post-embedding graphlets are integrated for photo aesthetics evaluation using a probabilistic model. Experimental results show that: 1) the visualized graphlets explicitly capture the aesthetically arranged atomic regions; 2) the proposed approach generalizes and improves four prominent aesthetic rules; and 3) our approach significantly outperforms state-of-the-art algorithms in photo aesthetics prediction.

  20. Investigation on micromachining technologies for the realization of LTCC devices and systems

    NASA Astrophysics Data System (ADS)

    Haas, T.; Zeilmann, C.; Bittner, A.; Schmid, U.

    2011-06-01

    Low temperature co-fired ceramics (LTCC) has established as a widespread platform for advanced functional ceramic devices in different applications, such as in the space and aviation sector, for micro machined sensors as well as in micro fluidics. This is due to high reliability, excellent physical properties, especially in the high frequency range, and the possibility to integrate passive components in the monolithic LTCC body, offering the potential for a high degree of miniaturisation. However, for further improvement of this technology and for an ongoing increase of the integration level, the realization of miniaturized structures is of utmost importance. Therefore, novel techniques for micro-machining are required providing channel structures and cavities inside the glass-ceramic body, enabling for further application scenarios. Those techniques are punching, laser cutting and embossing. One of the most limitations of LTCC is the poor thermal conductivity. Hence, the possibility to integrate channels enables innovative active cooling approaches using fluidic media for heat critical devices. Doing so, a by far better cooling effect can be achieved than by passive devices as heat spreaders or heat sinks. Furthermore, the realization of mechanic devices as integrated pressure sensors for operation under harsh environmental conditions can be realized by integrating the membrane directly into the ceramic body. Finally, for high power devices substantial improvement can be provided by filling those channel structures with electrical conductive material, so that the resistivity can be decreased drastically without affecting the topography of the ceramics.

  1. Hybrid Structure Multichannel All-Fiber Current Sensor.

    PubMed

    Jiang, Junzhen; Zhang, Hao; He, Youwu; Qiu, Yishen

    2017-08-02

    We have experimentally developed a hybrid-structure multi-channel all-fiber current sensor with ordinary silica fiber using fiber loop architecture. According to the rationale of time division multiplexing, the sensor combines parallel and serial structures. The purpose of the hybrid-structure multi-channel all-fiber current sensor is to get more information from the different measured points simultaneously. In addition, the hybrid-structure fiber current sensor exhibited a good linear response for each channel. A three-channel experiment was performed in the study and showed that the system could detect different current positions. Each channel could individually detect the current and needed a separate calibration system. Furthermore, the three channels will not affect each other.

  2. Spectrum and Structure of Excited Baryons with CLAS

    NASA Astrophysics Data System (ADS)

    Burkert, Volker D.

    2017-01-01

    In this contribution I discuss recent results in light quark baryon spectroscopy involving CLAS data and higher level analysis results from the partial wave analysis by the Bonn-Gatchina group. New baryon states were discovered largely based on the open strangeness production channels γp → K+Λ and γp → K+Σ0. The data illustrate the great potential of the kaon-hyperon channel in the discovery of higher mass baryon resonances in s-channel production. Other channels with discovery potential, such as γp → pω and γp → ϕp are also discussed. In the second part I will demonstrate on data the sensitivity of meson electroproduction to expose the active degrees of freedom underlying resonance transitions as a function of the probed distance scale. For several of the prominent excited states in the lower mass range the short distance behavior is described by a core of three dressed-quarks with running quark mass, and meson-baryon contributions make up significant parts of the excitation strength at large distances. Finally, I give an outlook of baryon resonance physics at the 12 GeV CEBAF electron accelerator. Talk presented at the CRC-16 Symposium, Bonn University, June 6-9, 2016.

  3. Comparison of long-term evolutionary trajectories of two ephemeral channels after channel-forming extraordinary floods

    NASA Astrophysics Data System (ADS)

    Lotsari, Eliisa; House, Kyle; Alho, Petteri; Baker, Victor

    2017-04-01

    Analyses of the evolutionary trajectories of braided ephemeral channels enable identification of trends, magnitudes and periodicity of the processes that affect the channels. In addition to infrequent great floods, relatively frequent, small discharge events have been shown to be important for the evolution of ephemeral channels. However, evolutionary trajectories have rarely been studied in small ephemeral rivers, that predominantly transport gravel, cobles and boulders. Ephemeral tributary channels typify the Colorado River basin (USA), and two examples are Bronco Creek and Eldorado Canyon. These streams experienced extraordinary great floods in 1971 and 1974 respectively, and they are comparable to each other in both basin size, and climatic conditions. Annual precipitation is less than 50 cm, and the average temperature of each month is above 7°C. More importantly, earlier studies have shown similarities in the hydraulics and geomorphic characteristics of the extraordinary floods, which removed the pre-flood bar and braiding structure from the channels. Thus, these two channels are ideal for comparisons of their evolutionary trajecties. Moreover, the availability of high-resolutions aerial photographs for both channels since 1954 allowed for decadal analyses. Our research has analyzed and compared the long-term evolutionary trajectories of the two ephemeral channels within Colorado River Basin based on series of aerial photos and digital elevation models. (1) We detected the development and adjustment of braiding since the extraordinary floods. The detected parameters include the braiding index, bar area and number, channel area and width, confluence number and density, and the proportion of inactive and active areas. (2) We also analyzed the time required for the ephemeral river system to evolve back to its prior state before the high magnitude floods. Finally, (3) we analyzed whether these temporal changes in channel evolution can reveal new insights as to climatic and environmental conditions for these un-gauged basins.

  4. Multichannel reconfigurable measurement system for hot plasma diagnostics based on GEM-2D detector

    NASA Astrophysics Data System (ADS)

    Wojenski, A. J.; Kasprowicz, G.; Pozniak, K. T.; Byszuk, A.; Chernyshova, M.; Czarski, T.; Jablonski, S.; Juszczyk, B.; Zienkiewicz, P.

    2015-12-01

    In the future magnetically confined fusion research reactors (e.g. ITER tokamak), precise determination of the level of the soft X-ray radiation of plasma with temperature above 30 keV (around 350 mln K) will be very important in plasma parameters optimization. This paper presents the first version of a designed spectrography measurement system. The system is already installed at JET tokamak. Based on the experience gained from the project, the new generation of hardware for spectrography measurements, was designed and also described in the paper. The GEM detector readout structure was changed to 2D in order to perform measurements of i.e. laser generated plasma. The hardware structure of the system was redesigned in order to provide large number of high speed input channels. Finally, this paper also covers the issue of new control software, necessary to set-up a complete system of certain complexity and perform data acquisition. The main goal of the project was to develop a new version of the system, which includes upgraded structure and data transmission infrastructure (i.e. handling large number of measurement channels, high sampling rate).

  5. Application of amphipols for structure-functional analysis of TRP channels.

    PubMed

    Huynh, Kevin W; Cohen, Matthew R; Moiseenkova-Bell, Vera Y

    2014-10-01

    Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for stabilizing integral membrane proteins in detergent-free conditions for structural and functional studies. Transient receptor potential (TRP) ion channels function as tetrameric protein complexes in a diverse range of cellular processes including sensory transduction. Mammalian TRP channels share ~20 % sequence similarity and are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane proteins, structural studies of TRP channels have been limited. Recently, A8-35 was essential in resolving the molecular architecture of the nociceptor TRPA1 and led to the determination of a high-resolution structure of the thermosensitive TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG) detergents have also proven to be useful in stabilizing TRP channels for structural analysis. In this review, we will discuss the impacts of amphipols and MNG detergents on structural studies of TRP channels by cryo-EM. We will compare how A8-35 and MNG detergents interact with the hydrophobic transmembrane domains of TRP channels. In addition, we will discuss what these cryo-EM studies reveal on the importance of screening different types of surfactants toward determining high-resolution structures of TRP channels.

  6. Application of amphipols for structure-functional analysis of TRP channels

    PubMed Central

    Huynh, Kevin W.; Cohen, Matthew R.; Moiseenkova-Bell, Vera Y.

    2014-01-01

    Amphipathic polymers (amphipols), such as A8-35 and SApol, are a new tool for stabilizing integral membrane proteins in detergent-free conditions for structural and functional studies. Transient receptor potential (TRP) ion channels function as tetrameric protein complexes in a diverse range of cellular processes including sensory transduction. Mammalian TRP channels share ~20% sequence similarity and are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPA (ankyrin), TRPM (melastatin), TRPP (polycystin), and TRPML (mucolipin). Due to the inherent difficulties in purifying eukaryotic membrane proteins, structural studies of TRP channels have been limited. Recently, A8-35 was essential in resolving the molecular architecture of the nociceptor TRPA1 and led to the determination of a high resolution structure of the thermosensitive TRPV1 channel by cryo-EM. Newly developed maltose-neopentyl glycol (MNG) detergents have also proven useful in stabilizing TRP channels for structural analysis. In this review, we will discuss the impact of amphipols and MNG detergents on structural studies of TRP channels by cryo-EM. We will compare how A8-35 and MNG detergents interact with the hydrophobic transmembrane (TM) domains of TRP channels. In addition, we will discuss what these cryo-EM studies reveal on the importance of screening different types of surfactants towards determining high resolution structures of TRP channels. PMID:24894720

  7. Microfluidic channel fabrication method

    DOEpatents

    Arnold, Don W.; Schoeniger, Joseph S.; Cardinale, Gregory F.

    2001-01-01

    A new channel structure for microfluidic systems and process for fabricating this structure. In contrast to the conventional practice of fabricating fluid channels as trenches or grooves in a substrate, fluid channels are fabricated as thin walled raised structures on a substrate. Microfluidic devices produced in accordance with the invention are a hybrid assembly generally consisting of three layers: 1) a substrate that can or cannot be an electrical insulator; 2) a middle layer, that is an electrically conducting material and preferably silicon, forms the channel walls whose height defines the channel height, joined to and extending from the substrate; and 3) a top layer, joined to the top of the channels, that forms a cover for the channels. The channels can be defined by photolithographic techniques and are produced by etching away the material around the channel walls.

  8. CNG and HCN channels: two peas, one pod.

    PubMed

    Craven, Kimberley B; Zagotta, William N

    2006-01-01

    Cyclic nucleotide-activated ion channels play a fundamental role in a variety of physiological processes. By opening in response to intracellular cyclic nucleotides, they translate changes in concentrations of signaling molecules to changes in membrane potential. These channels belong to two families: the cyclic nucleotide-gated (CNG) channels and the hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels. The two families exhibit high sequence similarity and belong to the superfamily of voltage-gated potassium channels. Whereas HCN channels are activated by voltage and CNG channels are virtually voltage independent, both channels are activated by cyclic nucleotide binding. Furthermore, the channels are thought to have similar channel structures, leading to similar mechanisms of activation by cyclic nucleotides. However, although these channels are structurally and behaviorally similar, they have evolved to perform distinct physiological functions. This review describes the physiological roles and biophysical behavior of CNG and HCN channels. We focus on how similarities in structure and activation mechanisms result in common biophysical models, allowing CNG and HCN channels to be viewed as a single genre.

  9. Hexadecameric structure of an invertebrate gap junction channel.

    PubMed

    Oshima, Atsunori; Matsuzawa, Tomohiro; Murata, Kazuyoshi; Tani, Kazutoshi; Fujiyoshi, Yoshinori

    2016-03-27

    Innexins are invertebrate-specific gap junction proteins with four transmembrane helices. These proteins oligomerize to constitute intercellular channels that allow for the passage of small signaling molecules associated with neural and muscular electrical activity. In contrast to the large number of structural and functional studies of connexin gap junction channels, few structural studies of recombinant innexin channels are reported. Here we show the three-dimensional structure of two-dimensionally crystallized Caenorhabditis elegans innexin-6 (INX-6) gap junction channels. The N-terminal deleted INX-6 proteins are crystallized in lipid bilayers. The three-dimensional reconstruction determined by cryo-electron crystallography reveals that a single INX-6 gap junction channel comprises 16 subunits, a hexadecamer, in contrast to chordate connexin channels, which comprise 12 subunits. The channel pore diameters at the cytoplasmic entrance and extracellular gap region are larger than those of connexin26. Two bulb densities are observed in each hemichannel, one in the pore and the other at the cytoplasmic side of the hemichannel in the channel pore pathway. These findings imply a structural diversity of gap junction channels among multicellular organisms. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Gas-Liquid Processing in Microchannels

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

    TeGrotenhuis, Ward E.; Stenkamp, Victoria S.; Twitchell, Alvin

    Processing gases and liquids together in microchannels having at least one dimension <1 mm has unique advantages for rapid heat and mass transfer. One approach for managing the two phases is to use porous structures as wicks within microchannels to segregate the liquid phase from the gas phase. Gas-liquid processing is accomplished by providing a gas flow path and inducing flow of the liquid phase through or along the wick under an induced pressure gradient. A variety of unit operations are enabled, including phase separation, partial condensation, absorption, desorption, and distillation. Results are reported of an investigation of microchannel phasemore » separation in a transparent, single-channel device. Next, heat exchange is integrated with the microchannel wick approach to create a partial condenser that also separates the condensate. Finally, the scale-up to a multi-channel phase separator is described.« less

  11. Real-time supervisor system based on trinary logic to control experiments with behaving animals and humans.

    PubMed

    Kutz, D F; Marzocchi, N; Fattori, P; Cavalcanti, S; Galletti, C

    2005-06-01

    A new method is presented based on trinary logic able to check the state of different control variables and synchronously record the physiological and behavioral data of behaving animals and humans. The basic information structure of the method is a time interval of defined maximum duration, called time slice, during which the supervisor system periodically checks the status of a specific subset of input channels. An experimental condition is a sequence of time slices subsequently executed according to the final status of the previous time slice. The proposed method implements in its data structure the possibility to branch like an if-else cascade and the possibility to repeat parts of it recursively like the while-loop. Therefore its data structure contains the most basic control structures of programming languages. The method was implemented using a real-time version of LabVIEW programming environment to program and control our experimental setup. Using this supervision system, we synchronously record four analog data channels at 500 Hz (including eye movements) and the time stamps of up to six neurons at 100 kHz. The system reacts with a resolution within 1 ms to changes of state of digital input channels. The system is set to react to changes in eye position with a resolution within 4 ms. The time slices, experimental conditions, and data are handled by relational databases. This facilitates the construction of new experimental conditions and data analysis. The proposed implementation allows continuous recording without an inter-trial gap for data storage or task management. The implementation can be used to drive electrophysiological experiments of behaving animals and psychophysical studies with human subjects.

  12. 75 FR 13236 - Television Broadcasting Services; Oklahoma City, OK

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-19

    ...] Television Broadcasting Services; Oklahoma City, OK AGENCY: Federal Communications Commission. ACTION: Final... licensee of KWTV-DT, channel 9, Oklahoma City, requesting the substitution of channel 39 for channel 9 at Oklahoma City. DATES: This rule is effective March 19, 2010. FOR FURTHER INFORMATION CONTACT: Adrienne Y...

  13. Redesigning Channel-Forming Peptides: Amino Acid Substitutions that Enhance Rates of Supramolecular Self-Assembly and Raise Ion Transport Activity

    PubMed Central

    Shank, Lalida P.; Broughman, James R.; Takeguchi, Wade; Cook, Gabriel; Robbins, Ashley S.; Hahn, Lindsey; Radke, Gary; Iwamoto, Takeo; Schultz, Bruce D.; Tomich, John M.

    2006-01-01

    Three series of 22-residue peptides derived from the transmembrane M2 segment of the glycine receptor α1-subunit (M2GlyR) have been designed, synthesized, and tested to determine the plasticity of a channel-forming sequence and to define whether channel pores with enhanced conductive properties could be created. Sixteen sequences were examined for aqueous solubility, solution-association tendency, secondary structure, and half-maximal concentration for supramolecular assembly, channel activity, and ion transport properties across epithelial monolayers. All peptides interact strongly with membranes: associating with, inserting across, and assembling to form homooligomeric bundles when in micromolar concentrations. Single and double amino acid replacements involving arginine and/or aromatic amino acids within the final five C-terminal residues of the peptide cause dramatic effects on the concentration dependence, yielding a range of K1/2 values from 36 ± 5 to 390 ± 220 μM for transport activity. New water/lipid interfacial boundaries were established for the transmembrane segment using charged or aromatic amino acids, thus limiting the peptides' ability to move perpendicularly to the plane of the bilayer. Formation of discrete water/lipid interfacial boundaries appears to be necessary for efficient supramolecular assembly and high anion transport activity. A peptide sequence is identified that may show efficacy in channel replacement therapy for channelopathies such as cystic fibrosis. PMID:16387776

  14. Li0.5Al0.5Mg2(MoO4)3

    PubMed Central

    Ennajeh, Ines; Zid, Mohamed Faouzi; Driss, Ahmed

    2013-01-01

    The title compound, lithium/aluminium dimagnesium tetra­kis­[orthomolybdate(VI)], was prepared by a solid-state reaction route. The crystal structure is built up from MgO6 octa­hedra and MoO4 tetra­hedra sharing corners and edges, forming two types of chains running along [100]. These chains are linked into layers parallel to (010) and finally linked by MoO4 tetra­hedra into a three-dimensional framework structure with channels parallel to [001] in which lithium and aluminium cations equally occupy the same position within a distorted trigonal–bipyramidal coordination environment. The title structure is isotypic with LiMgIn(MoO4)3, with the In site becoming an Mg site and the fully occupied Li site a statistically occupied Li/Al site in the title structure. PMID:24426975

  15. Slow wave structures using twisted waveguides for charged particle applications

    DOEpatents

    Kang, Yoon W.; Fathy, Aly E.; Wilson, Joshua L.

    2012-12-11

    A rapidly twisted electromagnetic accelerating structure includes a waveguide body having a central axis, one or more helical channels defined by the body and disposed around a substantially linear central axial channel, with central portions of the helical channels merging with the linear central axial channel. The structure propagates electromagnetic waves in the helical channels which support particle beam acceleration in the central axial channel at a phase velocity equal to or slower than the speed of light in free space. Since there is no variation in the shape of the transversal cross-section along the axis of the structure, inexpensive mechanical fabrication processes can be used to form the structure, such as extrusion, casting or injection molding. Also, because the field and frequency of the resonant mode depend on the whole structure rather than on dimensional tolerances of individual cells, no tuning of individual cells is needed. Accordingly, the overall operating frequency may be varied with a tuning/phase shifting device located outside the resonant waveguide structure.

  16. Sunn Hemp Cover Cropping and Organic Fertilizer Effects on the Nematode Community Under Temperate Growing Conditions

    PubMed Central

    Hinds, Jermaine; Wang, Koon-Hui; Marahatta, Sharadchandra P.; Meyer, Susan L. F.; Hooks, Cerruti R. R.

    2013-01-01

    Field experiments were conducted in Maryland to investigate the influence of sunn hemp cover cropping in conjunction with organic and synthetic fertilizers on the nematode community in a zucchini cropping system. Two field treatments, zucchini planted into a sunn hemp living and surface mulch (SH) and zucchini planted into bare-ground (BG) were established during three field seasons from 2009 to 2011. In 2009, although SH slightly increased nematode richness compared with BG by the first harvest (P < 0.10), it reduced nematode diversity and enrichment indices (P < 0.01 and P < 0.10, respectively) and increased the channel index (P < 0.01) compared to BG at the final harvest. This suggests a negative impact of SH on nematode community structure. The experiment was modified in 2010 and 2011 where the SH and BG main plots were further split into two subplots to investigate the added influence of an organic vs. synthetic fertilizer. In 2010, when used as a living and surface mulch in a no-till system, SH increased bacterivorous, fungivorous, and total nematodes (P < 0.05) by the final zucchini harvest, but fertilizer type did not influence nematode community structure. In 2011, when incorporated into the soil before zucchini planting, SH increased the abundance of bacterivorous and fungivorous nematodes early in the cropping season. SH increased species richness also at the end of the season (P < 0.05). Fertilizer application did not appear to influence nematodes early in the season. However, in late season, organic fertilizers increased enrichment and structure indices and decreased channel index by the end of the zucchini cropping cycle. PMID:24379485

  17. [Mechanisms of action of voltage-gated sodium channel ligands].

    PubMed

    Tikhonov, D B

    2007-05-01

    The voltage-gated sodium channels play a key role in the generation of action potential in excitable cells. Sodium channels are targeted by a number of modulating ligands. Despite numerous studies, the mechanisms of action of many ligands are still unknown. The main cause of the problem is the absence of the channel structure. Sodium channels belong to the superfamily of P-loop channels that also the data abowt includes potassium and calcium channels and the channels of ionotropic glutamate receptors. Crystallization of several potassium channels has opened a possibility to analyze the structure of other members of the superfamily using the homology modeling approach. The present study summarizes the results of several recent modelling studies of such sodium channel ligands as tetrodotoxin, batrachotoxin and local anesthetics. Comparison of available experimental data with X-ray structures of potassium channels has provided a new level of understanding of the mechanisms of action of sodium channel ligands and has allowed proposing several testable hypotheses.

  18. 75 FR 28757 - Security Zone; Potomac River, Washington Channel, Washington, DC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-24

    ...-AA87 Security Zone; Potomac River, Washington Channel, Washington, DC AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary security zone in certain waters of Washington Channel on the Potomac River. The security zone is necessary to provide for the...

  19. Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating

    PubMed Central

    Kim, Dorothy M.; Nimigean, Crina M.

    2016-01-01

    Voltage-gated potassium channels play a fundamental role in the generation and propagation of the action potential. The discovery of these channels began with predictions made by early pioneers, and has culminated in their extensive functional and structural characterization by electrophysiological, spectroscopic, and crystallographic studies. With the aid of a variety of crystal structures of these channels, a highly detailed picture emerges of how the voltage-sensing domain reports changes in the membrane electric field and couples this to conformational changes in the activation gate. In addition, high-resolution structural and functional studies of K+ channel pores, such as KcsA and MthK, offer a comprehensive picture on how selectivity is achieved in K+ channels. Here, we illustrate the remarkable features of voltage-gated potassium channels and explain the mechanisms used by these machines with experimental data. PMID:27141052

  20. Synchrotron X-ray footprinting as a method to visualize water in proteins

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

    Gupta, Sayan; Feng, Jun; Chan, Leanne Jade G.

    The vast majority of biomolecular processes are controlled or facilitated by water interactions. In enzymes, regulatory proteins, membrane-bound receptors and ion-channels, water bound to functionally important residues creates hydrogen-bonding networks that underlie the mechanism of action of the macromolecule. High-resolution X-ray structures are often difficult to obtain with many of these classes of proteins because sample conditions, such as the necessity of detergents, often impede crystallization. Other biophysical techniques such as neutron scattering, nuclear magnetic resonance and Fourier transform infrared spectroscopy are useful for studying internal water, though each has its own advantages and drawbacks, and often a hybrid approachmore » is required to address important biological problems associated with protein–water interactions. One major area requiring more investigation is the study of bound water molecules which reside in cavities and channels and which are often involved in both the structural and functional aspects of receptor, transporter and ion channel proteins. Recently, significant progress has been made in synchrotron-based radiolytic labeling and mass spectroscopy techniques for both the identification of bound waters and for characterizing the role of water in protein conformational changes at a high degree of spatial and temporal resolution. Finally, here the latest developments and future capabilities of this method for investigating water–protein interactions and its synergy with other synchrotron-based methods are discussed.« less

  1. Synchrotron X-ray footprinting as a method to visualize water in proteins

    DOE PAGES

    Gupta, Sayan; Feng, Jun; Chan, Leanne Jade G.; ...

    2016-07-27

    The vast majority of biomolecular processes are controlled or facilitated by water interactions. In enzymes, regulatory proteins, membrane-bound receptors and ion-channels, water bound to functionally important residues creates hydrogen-bonding networks that underlie the mechanism of action of the macromolecule. High-resolution X-ray structures are often difficult to obtain with many of these classes of proteins because sample conditions, such as the necessity of detergents, often impede crystallization. Other biophysical techniques such as neutron scattering, nuclear magnetic resonance and Fourier transform infrared spectroscopy are useful for studying internal water, though each has its own advantages and drawbacks, and often a hybrid approachmore » is required to address important biological problems associated with protein–water interactions. One major area requiring more investigation is the study of bound water molecules which reside in cavities and channels and which are often involved in both the structural and functional aspects of receptor, transporter and ion channel proteins. Recently, significant progress has been made in synchrotron-based radiolytic labeling and mass spectroscopy techniques for both the identification of bound waters and for characterizing the role of water in protein conformational changes at a high degree of spatial and temporal resolution. Finally, here the latest developments and future capabilities of this method for investigating water–protein interactions and its synergy with other synchrotron-based methods are discussed.« less

  2. Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.

    PubMed

    Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika

    2018-02-01

    Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Mechanism of the Pseudoirreversible Binding of Amantadine to the M2 Proton Channel.

    PubMed

    Llabrés, Salomé; Juárez-Jiménez, Jordi; Masetti, Matteo; Leiva, Rosana; Vázquez, Santiago; Gazzarrini, Sabrina; Moroni, Anna; Cavalli, Andrea; Luque, F Javier

    2016-11-30

    The M2 proton channel of influenza A virus is an integral membrane protein involved in the acidification of the viral interior, a step necessary for the release of the viral genetic material and replication of new virions. The aim of this study is to explore the mechanism of drug (un)binding to the M2 channel in order to gain insight into the structural and energetic features relevant for the development of novel inhibitors. To this end, we have investigated the binding of amantadine (Amt) to the wild type (wt) M2 channel and its V27A variant using multiple independent molecular dynamics simulations, exploratory conventional metadynamics, and multiple-walkers well-tempered metadynamics calculations. The results allow us to propose a sequential mechanism for the (un)binding of Amt to the wt M2 channel, which involves the adoption of a transiently populated intermediate (up state) leading to the thermodynamically favored down binding mode in the channel pore. Furthermore, they suggest that chloride anions play a relevant role in stabilizing the down binding mode of Amt to the wt channel, giving rise to a kinetic trapping that explains the experimentally observed pseudoirreversible inhibition of the wt channel by Amt. We propose that this trapping mechanism underlies the inhibitory activity of potent M2 channel blockers, as supported by the experimental confirmation of the irreversible binding of a pyrrolidine analogue from electrophysiological current assays. Finally, the results reveal that the thermodynamics and kinetics of Amt (un)binding is very sensitive to the V27A mutation, providing a quantitative rationale to the drastic decrease in inhibitory potency against the V27A variant. Overall, these findings pave the way to explore the inhibitory activity of Amt-related analogues in mutated M2 channel variants, providing guidelines for the design of novel inhibitors against resistant virus strains.

  4. Functional assembly of Kv7.1/Kv7.5 channels with emerging properties on vascular muscle physiology.

    PubMed

    Oliveras, Anna; Roura-Ferrer, Meritxell; Solé, Laura; de la Cruz, Alicia; Prieto, Angela; Etxebarria, Ainhoa; Manils, Joan; Morales-Cano, Daniel; Condom, Enric; Soler, Concepció; Cogolludo, Angel; Valenzuela, Carmen; Villarroel, Alvaro; Comes, Núria; Felipe, Antonio

    2014-07-01

    Voltage-dependent K(+) (Kv) channels from the Kv7 family are expressed in blood vessels and contribute to cardiovascular physiology. Although Kv7 channel blockers trigger muscle contractions, Kv7 activators act as vasorelaxants. Kv7.1 and Kv7.5 are expressed in many vessels. Kv7.1 is under intense investigation because Kv7.1 blockers fail to modulate smooth muscle reactivity. In this study, we analyzed whether Kv7.1 and Kv7.5 may form functional heterotetrameric channels increasing the channel diversity in vascular smooth muscles. Kv7.1 and Kv7.5 currents elicited in arterial myocytes, oocyte, and mammalian expression systems suggest the formation of heterotetrameric complexes. Kv7.1/Kv7.5 heteromers, exhibiting different pharmacological characteristics, participate in the arterial tone. Kv7.1/Kv7.5 associations were confirmed by coimmunoprecipitation, fluorescence resonance energy transfer, and fluorescence recovery after photobleaching experiments. Kv7.1/Kv7.5 heterotetramers were highly retained at the endoplasmic reticulum. Studies in HEK-293 cells, heart, brain, and smooth and skeletal muscles demonstrated that the predominant presence of Kv7.5 stimulates release of Kv7.1/Kv7.5 oligomers out of lipid raft microdomains. Electrophysiological studies supported that KCNE1 and KCNE3 regulatory subunits further increased the channel diversity. Finally, the analysis of rat isolated myocytes and human blood vessels demonstrated that Kv7.1 and Kv7.5 exhibited a differential expression, which may lead to channel diversity. Kv7.1 and Kv7.5 form heterotetrameric channels increasing the diversity of structures which fine-tune blood vessel reactivity. Because the lipid raft localization of ion channels is crucial for cardiovascular physiology, Kv7.1/Kv7.5 heteromers provide efficient spatial and temporal regulation of smooth muscle function. Our results shed light on the debate about the contribution of Kv7 channels to vasoconstriction and hypertension. © 2014 American Heart Association, Inc.

  5. Channel-resolved photo- and Auger-electron spectroscopy of halogenated hydrocarbons

    NASA Astrophysics Data System (ADS)

    Ablikim, Utuq; Kaderiya, B.; Kumarapan, V.; Kushawaha, R.; Rudenko, A.; Rolles, D.; Xiong, H.; Berrah, N.; Bomme, C.; Savelyev, E.; Kilcoyne, D.

    2016-05-01

    Inner-shell photoelectron and Auger electron spectra of polyatomic molecules such as halogenated hydrocarbons are typically hard to interpret and assign due to many overlapping states that form broad bands even in high-resolution measurements. With the help of electron-ion-ion coincidence measurements performed using the velocity map imaging technique, we are able to detect high-energy (<= 150 eV) photo- and Auger electrons in coincidence with two- or many-body ionic fragmentation channels. Such channel-resolved measurements allow disentangling the overlapping electronic structures and help assigning individual components of the electron spectra to specific potential surfaces and final states. In this work, we present measurements on CH3 I, CH2 IBr, and CH2 ICl molecules in the gas-phase using soft x-ray light provided by the Advanced Light Source at LBNL. This project is supported by the DOE, Office of Science, BES, Division of Chemical, Geological and Biological Sciences under Award Number DE-FG02-86ER13491 (U.A., B.K., V.K., A.R., D.R.) and Award Number DE-SC0012376 (H.X., N.B.).

  6. Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

    PubMed Central

    Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

    2016-01-01

    The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca2+-activated K+ channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity. PMID:26725737

  7. Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels.

    PubMed

    Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

    2016-01-01

    The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca(2+)-activated K(+) channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity.

  8. Molecular-Dynamics Simulations of ELIC a Prokaryotic Homologue of the Nicotinic Acetylcholine Receptor

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

    Cheng, Xiaolin; Ivanov, Ivaylo N; Wang, Hailong

    2009-01-01

    The ligand-gated ion channel from Erwinia chrysanthemi (ELIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor (nAChR) that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. ELIC is similar to the nAChR in its primary sequence and overall subunit organization, but despite their structural similarity, it is not clear whether these two ligand-gated ion channels operate in a similar manner. Further, it is not known to what extent mechanistic insights gleaned from the ELIC structure translate to eukaryotic counterparts such as the nAChR. Here we use molecular-dynamics simulations to probe the conformational dynamics andmore » hydration of the transmembrane pore of ELIC. The results are compared with those from our previous simulation of the human ?7 nAChR. Overall, ELIC displays increased stability compared to the nAChR, whereas the two proteins exhibit remarkable similarity in their global motion and flexibility patterns. The majority of the increased stability of ELIC does not stem from the deficiency of the models used in the simulations, and but rather seems to have a structural basis. Slightly altered dynamical correlation features are also observed among several loops within the membrane region. In sharp contrast to the nAChR, ELIC is completely dehydrated from the pore center to the extracellular end throughout the simulation. Finally, the simulation of an ELIC mutant substantiates the important role of F246 on the stability, hydration and possibly function of the ELIC channel.« less

  9. Facile fabrication of a rigid and chemically resistant micromixer system from photocurable inorganic polymer by static liquid photolithography (SLP).

    PubMed

    Fang, Qingling; Kim, Dong-Pyo; Li, Xiaodong; Yoon, Tae-Ho; Li, Yihe

    2011-08-21

    Highly effective mixing in microchannels is important for most chemical reactions conducted in microfluidic chips. To obtain a rigid and chemically resistant micromixer system at low cost, we fabricated a Y-shaped microchannel with built-in mixer structures by static liquid photolithography (SLP) from methacrylated polyvinylsilazane (MPVSZ) as an inorganic polymer photoresist which was then converted to a silicate phase by hydrolysis in vaporized ammonia atmosphere at 80 °C. The microchannel incorporating herringbone mixer structures was bonded with a matching polydimethylsiloxane (PDMS) open channel which was pre-coated by perhydropolysilazane (PHPS)-based mixture, and finally treated by additional hydrolysis at room temperature to convert the PHPS layer to a silica phase. Finally, the chemical resistance of the microfluidic system with embedded micromixer was confirmed with various solvents, and the excellent mixing performance in a short mixing length of 2.3 cm was demonstrated by injecting two different colored fluids into the microchannel. This journal is © The Royal Society of Chemistry 2011

  10. A Crash Course in Calcium Channels.

    PubMed

    Zamponi, Gerald W

    2017-12-20

    Much progress has been made in understanding the molecular physiology and pharmacology of calcium channels. Recently, there have been tremendous advances in learning about calcium channel structure and function through crystallography and cryo-electron microscopy studies. Here, I will give an overview of our knowledge about calcium channels, and highlight two recent studies that give important insights into calcium channel structure.

  11. Large wood recruitment and transport during large floods: A review

    NASA Astrophysics Data System (ADS)

    Comiti, F.; Lucía, A.; Rickenmann, D.

    2016-09-01

    Large wood (LW) elements transported during large floods are long known to have the capacity to induce dangerous obstructions along the channel network, mostly at bridges and at hydraulic structures such as weirs. However, our current knowledge of wood transport dynamics during high-magnitude flood events is still very scarce, mostly because these are (locally) rare and thus unlikely to be directly monitored. Therefore, post-event surveys are invaluable ways to get insights (although indirectly) on LW recruitment processes, transport distance, and factors inducing LW deposition - all aspects that are crucial for the proper management of river basins related to flood hazard mitigation. This paper presents a review of the (quite limited) literature available on LW transport during large floods, drawing extensively on the authors' own experience in mountain and piedmont rivers, published and unpublished. The overall picture emerging from these studies points to a high, catchment-specific variability in all the different processes affecting LW dynamics during floods. Specifically, in the LW recruitment phase, the relative floodplain (bank erosion) vs. hillslope (landslide and debris flows) contribution in mountain rivers varies substantially, as it relates to the extent of channel widening (which depends on many variables itself) but also to the hillslope-channel connectivity of LW mobilized on the slopes. As to the LW transport phase within the channel network, it appears to be widely characterized by supply-limited conditions; whereby LW transport rates (and thus volumes) are ultimately constrained by the amount of LW that is made available to the flow. Indeed, LW deposition during floods was mostly (in terms of volume) observed at artificial structures (bridges) in all the documented events. This implies that the estimation of LW recruitment and the assessment of clogging probabilities for each structure (for a flood event of given magnitude) are the most important aspects for the prediction of LW transport magnitude at any cross section along the river network. Finally, the review discusses the optimal strategies to manage LW-related hazard, which should consider riparian vegetation and in-channel dead wood as key components of river ecosystems and thus should interfere with LW (as well as with sediment) transport dynamics only for limited spatial and temporal scales.

  12. The dipole moment of membrane proteins: potassium channel protein and beta-subunit.

    PubMed

    Takashima, S

    2001-12-25

    The mechanism of ion channel opening is one of the most fascinating problems in membrane biology. Based on phenomenological studies, early researchers suggested that the elementary process of ion channel opening may be the intramembrane charge movement or the orientation of dipolar proteins in the channel. In spite of the far reaching significance of these hypotheses, it has not been possible to formulate a comprehensive molecular theory for the mechanism of channel opening. This is because of the lack of the detailed knowledge on the structure of channel proteins. In recent years, however, the research on the structure of channel proteins made marked advances and, at present, we are beginning to have sufficient information on the structure of some of the channel proteins, e.g. potassium-channel protein and beta-subunits. With these new information, we are now ready to have another look at the old hypothesis, in particular, the dipole moment of channel proteins being the voltage sensor for the opening and closing of ion channels. In this paper, the dipole moments of potassium channel protein and beta-subunit, are calculated using X-ray diffraction data. A large dipole moment was found for beta-subunits while the dipole moment of K-channel protein was found to be considerably smaller than that of beta-subunits. These calculations were conducted as a preliminary study of the comprehensive research on the dipolar structure of channel proteins in excitable membranes, above all, sodium channel proteins.

  13. Structure of the full-length TRPV2 channel by cryo-EM

    NASA Astrophysics Data System (ADS)

    Huynh, Kevin W.; Cohen, Matthew R.; Jiang, Jiansen; Samanta, Amrita; Lodowski, David T.; Zhou, Z. Hong; Moiseenkova-Bell, Vera Y.

    2016-03-01

    Transient receptor potential (TRP) proteins form a superfamily Ca2+-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a `minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ~5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels.

  14. Structure of the full-length TRPV2 channel by cryo-EM

    PubMed Central

    Huynh, Kevin W.; Cohen, Matthew R.; Jiang, Jiansen; Samanta, Amrita; Lodowski, David T.; Zhou, Z. Hong; Moiseenkova-Bell, Vera Y.

    2016-01-01

    Transient receptor potential (TRP) proteins form a superfamily Ca2+-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a ‘minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2–6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels. PMID:27021073

  15. Structure of the full-length TRPV2 channel by cryo-EM.

    PubMed

    Huynh, Kevin W; Cohen, Matthew R; Jiang, Jiansen; Samanta, Amrita; Lodowski, David T; Zhou, Z Hong; Moiseenkova-Bell, Vera Y

    2016-03-29

    Transient receptor potential (TRP) proteins form a superfamily Ca(2+)-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a 'minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels.

  16. The hitchhiker’s guide to the voltage-gated sodium channel galaxy

    PubMed Central

    2016-01-01

    Eukaryotic voltage-gated sodium (Nav) channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling. Given their central role in electrical excitability, it is not surprising that (a) inherited mutations in genes encoding for Nav channels and their accessory subunits have been linked to excitability disorders in brain, muscle, and heart; and (b) Nav channels are targeted by various drugs and naturally occurring toxins. Although the overall architecture and behavior of these channels are likely to be similar to the more well-studied voltage-gated potassium channels, eukaryotic Nav channels lack structural and functional symmetry, a notable difference that has implications for gating and selectivity. Activation of voltage-sensing modules of the first three domains in Nav channels is sufficient to open the channel pore, whereas movement of the domain IV voltage sensor is correlated with inactivation. Also, structure–function studies of eukaryotic Nav channels show that a set of amino acids in the selectivity filter, referred to as DEKA locus, is essential for Na+ selectivity. Structures of prokaryotic Nav channels have also shed new light on mechanisms of drug block. These structures exhibit lateral fenestrations that are large enough to allow drugs or lipophilic molecules to gain access into the inner vestibule, suggesting that this might be the passage for drug entry into a closed channel. In this Review, we will synthesize our current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts. PMID:26712848

  17. Fault Diagnostics for Turbo-Shaft Engine Sensors Based on a Simplified On-Board Model

    PubMed Central

    Lu, Feng; Huang, Jinquan; Xing, Yaodong

    2012-01-01

    Combining a simplified on-board turbo-shaft model with sensor fault diagnostic logic, a model-based sensor fault diagnosis method is proposed. The existing fault diagnosis method for turbo-shaft engine key sensors is mainly based on a double redundancies technique, and this can't be satisfied in some occasions as lack of judgment. The simplified on-board model provides the analytical third channel against which the dual channel measurements are compared, while the hardware redundancy will increase the structure complexity and weight. The simplified turbo-shaft model contains the gas generator model and the power turbine model with loads, this is built up via dynamic parameters method. Sensor fault detection, diagnosis (FDD) logic is designed, and two types of sensor failures, such as the step faults and the drift faults, are simulated. When the discrepancy among the triplex channels exceeds a tolerance level, the fault diagnosis logic determines the cause of the difference. Through this approach, the sensor fault diagnosis system achieves the objectives of anomaly detection, sensor fault diagnosis and redundancy recovery. Finally, experiments on this method are carried out on a turbo-shaft engine, and two types of faults under different channel combinations are presented. The experimental results show that the proposed method for sensor fault diagnostics is efficient. PMID:23112645

  18. Fault diagnostics for turbo-shaft engine sensors based on a simplified on-board model.

    PubMed

    Lu, Feng; Huang, Jinquan; Xing, Yaodong

    2012-01-01

    Combining a simplified on-board turbo-shaft model with sensor fault diagnostic logic, a model-based sensor fault diagnosis method is proposed. The existing fault diagnosis method for turbo-shaft engine key sensors is mainly based on a double redundancies technique, and this can't be satisfied in some occasions as lack of judgment. The simplified on-board model provides the analytical third channel against which the dual channel measurements are compared, while the hardware redundancy will increase the structure complexity and weight. The simplified turbo-shaft model contains the gas generator model and the power turbine model with loads, this is built up via dynamic parameters method. Sensor fault detection, diagnosis (FDD) logic is designed, and two types of sensor failures, such as the step faults and the drift faults, are simulated. When the discrepancy among the triplex channels exceeds a tolerance level, the fault diagnosis logic determines the cause of the difference. Through this approach, the sensor fault diagnosis system achieves the objectives of anomaly detection, sensor fault diagnosis and redundancy recovery. Finally, experiments on this method are carried out on a turbo-shaft engine, and two types of faults under different channel combinations are presented. The experimental results show that the proposed method for sensor fault diagnostics is efficient.

  19. Hemoglobin crystals immersed in liquid oxygen reveal diffusion channels.

    PubMed

    Terrell, James Ross; Gumpper, Ryan H; Luo, Ming

    2018-01-08

    Human hemoglobin (HbA) transports molecular oxygen (O 2 ) from the lung to tissues where the partial pressure of O 2 is lower. O 2 binds to HbA at the heme cofactor and is stabilized by a distal histidine (HisE7). HisE7 has been observed to occupy opened and closed conformations, and is postulated to act as a gate controlling the binding/release of O 2 . However, it has been suggested that HbA also contains intraprotein oxygen channels for entrances/exits far from the heme. In this study, we developed a novel method of crystal immersion in liquid oxygen prior to X-ray data collection. In the crystals immersed in liquid oxygen, the heme center was oxidized to generate aquomethemoglobin. Increases of structural flexibility were also observed in regions that are synonymous with previously postulated oxygen channels. These regions also correspond to medically relevant mutations which affect O 2 affinity. The way HbA utilizes these O 2 channels could have a profound impact on understanding the relationship of HbA O 2 transport within these disease conditions. Finally, the liquid oxygen immersion technique can be utilized as a new tool to crystallographically examine proteins and protein complexes which utilize O 2 for enzyme catalysis or transport. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. High-Performance Anti-Retransmission Deception Jamming Utilizing Range Direction Multiple Input and Multiple Output (MIMO) Synthetic Aperture Radar (SAR).

    PubMed

    Wang, Ruijia; Chen, Jie; Wang, Xing; Sun, Bing

    2017-01-09

    Retransmission deception jamming seriously degrades the Synthetic Aperture Radar (SAR) detection efficiency and can mislead SAR image interpretation by forming false targets. In order to suppress retransmission deception jamming, this paper proposes a novel multiple input and multiple output (MIMO) SAR structure range direction MIMO SAR, whose multiple channel antennas are vertical to the azimuth. First, based on the multiple channels of range direction MIMO SAR, the orthogonal frequency division multiplexing (OFDM) linear frequency modulation (LFM) signal was adopted as the transmission signal of each channel, which is defined as a sub-band signal. This sub-band signal corresponds to the transmission channel. Then, all of the sub-band signals are modulated with random initial phases and concurrently transmitted. The signal form is more complex and difficult to intercept. Next, the echoes of the sub-band signal are utilized to synthesize a wide band signal after preprocessing. The proposed method will increase the signal to interference ratio and peak amplitude ratio of the signal to resist retransmission deception jamming. Finally, well-focused SAR imagery is obtained using a conventional imaging method where the retransmission deception jamming strength is degraded and defocused. Simulations demonstrated the effectiveness of the proposed method.

  1. High-Performance Anti-Retransmission Deception Jamming Utilizing Range Direction Multiple Input and Multiple Output (MIMO) Synthetic Aperture Radar (SAR)

    PubMed Central

    Wang, Ruijia; Chen, Jie; Wang, Xing; Sun, Bing

    2017-01-01

    Retransmission deception jamming seriously degrades the Synthetic Aperture Radar (SAR) detection efficiency and can mislead SAR image interpretation by forming false targets. In order to suppress retransmission deception jamming, this paper proposes a novel multiple input and multiple output (MIMO) SAR structure range direction MIMO SAR, whose multiple channel antennas are vertical to the azimuth. First, based on the multiple channels of range direction MIMO SAR, the orthogonal frequency division multiplexing (OFDM) linear frequency modulation (LFM) signal was adopted as the transmission signal of each channel, which is defined as a sub-band signal. This sub-band signal corresponds to the transmission channel. Then, all of the sub-band signals are modulated with random initial phases and concurrently transmitted. The signal form is more complex and difficult to intercept. Next, the echoes of the sub-band signal are utilized to synthesize a wide band signal after preprocessing. The proposed method will increase the signal to interference ratio and peak amplitude ratio of the signal to resist retransmission deception jamming. Finally, well-focused SAR imagery is obtained using a conventional imaging method where the retransmission deception jamming strength is degraded and defocused. Simulations demonstrated the effectiveness of the proposed method. PMID:28075367

  2. Computer Aided Synthesis or Measurement Schemes for Telemetry applications

    DTIC Science & Technology

    1997-09-02

    5.2.5. Frame structure generation The algorithm generating the frame structure should take as inputs the sampling frequency requirements of the channels...these channels into the frame structure. Generally there can be a lot of ways to divide channels among groups. The algorithm implemented in...groups) first. The algorithm uses the function "try_permutation" recursively to distribute channels among the groups, and the function "try_subtable

  3. Probing TeV scale top-philic resonances with boosted top-tagging at the high luminosity LHC

    DOE PAGES

    Kim, Jeong Han; Kong, Kyoungchul; Lee, Seung J.; ...

    2016-08-24

    Here, we investigate the discovery potential of singly produced top-philic resonances at the high luminosity (HL) LHC in the four-top final state. Our analysis spans over the fully-hadronic, semi-leptonic, and same-sign dilepton channels where we present concrete search strategies adequate to a boosted kinematic regime and high jet-multiplicity environments. We utilize the Template Overlap Method (TOM) with newly developed template observables for tagging boosted top quarks, a large-radius jet variablemore » $$M_J$$ and customized b-tagging tactics for background discrimination. Our results show that the same-sign dilepton channel gives the best sensitivity among the considered channels, with an improvement of significance up to 10%-20% when combined with boosted-top tagging. Both the fully-hadronic and semi-leptonic channels yield comparable discovery potential and contribute to further enhancements in the sensitivity by combining all channels. Finally, we show the sensitivity of a top-philic resonance at the LHC and HL-LHC by showing the $$2\\sigma$$ exclusion limit and $$5\\sigma$$ discovery reach, including a combination of all three channels.« less

  4. Birth of a hydraulic jump

    NASA Astrophysics Data System (ADS)

    Duchesne, Alexis; Bohr, Tomas; Andersen, Anders

    2017-11-01

    The hydraulic jump, i.e., the sharp transition between a supercritical and a subcritical free-surface flow, has been extensively studied in the past centuries. However, ever since Leonardo da Vinci asked it for the first time, an important question has been left unanswered: How does a hydraulic jump form? We present an experimental and theoretical study of the formation of stationary hydraulic jumps in centimeter wide channels. Two starting situations are considered: The channel is, respectively, empty or filled with liquid, the liquid level being fixed by the wetting properties and the boundary conditions. We then change the flow-rate abruptly from zero to a constant value. In an empty channel, we observe the formation of a stationary hydraulic jump in a two-stage process: First, the channel fills by the advancing liquid front, which undergoes a transition from supercritical to subcritical at some position in the channel. Later the influence of the downstream boundary conditions makes the jump move slowly upstream to its final position. In the pre-filled channel, the hydraulic jump forms at the injector edge and then moves downstream to its final position.

  5. TRPC Channel Structure and Properties.

    PubMed

    Feng, Shengjie

    2017-01-01

    TRPC channels are the first identified members in the TRP family. They function as either homo- or heterotetramers regulating intracellular Ca 2+ concentration in response to numerous physiological or pathological stimuli. TRPC channels are nonselective cation channels permeable to Ca 2+ . The properties and the functional domains of TRPC channels have been identified by electrophysiological and biochemical methods. However, due to the large size, instability, and flexibility of their complexes, the structures of the members in TRPC family remain unrevealed. More efforts should be made on structure analysis and generating good tools, including specific antibodies, agonist, and antagonist.

  6. Subglacial drainage patterns of Devon Island, Canada: detailed comparison of rivers and subglacial meltwater channels

    NASA Astrophysics Data System (ADS)

    Grau Galofre, Anna; Jellinek, A. Mark; Osinski, Gordon R.; Zanetti, Michael; Kukko, Antero

    2018-04-01

    Subglacial meltwater channels (N-channels) are attributed to erosion by meltwater in subglacial conduits. They exert a major control on meltwater accumulation at the base of ice sheets, serving as drainage pathways and modifying ice flow rates. The study of exposed relict subglacial channels offers a unique opportunity to characterize the geomorphologic fingerprint of subglacial erosion as well as study the structure and characteristics of ice sheet drainage systems. In this study we present detailed field and remote sensing observations of exposed subglacial meltwater channels in excellent preservation state on Devon Island (Canadian Arctic Archipelago). We characterize channel cross section, longitudinal profiles, and network morphologies and establish the spatial extent and distinctive characteristics of subglacial drainage systems. We use field-based GPS measurements of subglacial channel longitudinal profiles, along with stereo imagery-derived digital surface models (DSMs), and novel kinematic portable lidar data to establish a detailed characterization of subglacial channels in our field study area, including their distinction from rivers and other meltwater drainage systems. Subglacial channels typically cluster in groups of ˜ 10 channels and are oriented perpendicular to active or former ice margins. Although their overall direction generally follows topographic gradients, channels can be oblique to topographic gradients and have undulating longitudinal profiles. We also observe that the width of first-order tributaries is 1 to 2 orders of magnitude larger than in Devon Island river systems and approximately constant. Furthermore, our findings are consistent with theoretical expectations drawn from analyses of flow driven by gradients in effective water pressure related to variations in ice thickness. Our field and remote sensing observations represent the first high-resolution study of the subglacial geomorphology of the high Arctic, and provide quantitative and qualitative descriptions of subglacial channels that revisit well-established field identification guidelines. Distinguishing subglacial channels in topographic data is critical for understanding the emergence, geometry, and extent of channelized meltwater systems and their role in ice sheet drainage. The final aim of this study is to facilitate the identification of subglacial channel networks throughout the globe by using remote sensing techniques, which will improve the detection of these systems and help to build understanding of the underlying mechanics of subglacial channelized drainage.

  7. Ion Selectivity Mechanism in a Bacterial Pentameric Ligand-Gated Ion Channel

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

    Fritsch, Sebastian; Ivanov, Ivaylo; Wang, Hailong

    2010-01-01

    The proton-gated ion channel from Gloeobacter violaceus (GLIC) is a prokaryotic homolog of the eukaryotic nicotinic acetylcholine receptor that responds to the binding of neurotransmitter acetylcholine and mediates fast signal transmission. Recent emergence of a high-resolution crystal structure of GLIC captured in a potentially open state allowed detailed, atomic-level insight into ion conduction and selectivity mechanisms in these channels. Herein, we have examined the barriers to ion conduction and origins of ion selectivity in the GLIC channel by the construction of potential-of-mean-force profiles for sodium and chloride ions inside the transmembrane region. Our calculations reveal that the GLIC channel ismore » open for a sodium ion to transport, but presents a 11 kcal/mol free energy barrier for a chloride ion. Our collective findings identify three distinct contributions to the observed preference for the permeant ions. First, there is a substantial contribution due to a ring of negatively charged glutamate residues (E-2 ) at the narrow intracellular end of the channel. The negative electrostatics of this region and the ability of the glutamate side chains to directly bind cations would strongly favor the passage of sodium ions while hindering translocation of chloride ions. Second, our results imply a significant hydrophobic contribution to selectivity linked to differences in the desolvation penalty for the sodium versus chloride ions in the central hydrophobic region of the pore. This hydrophobic contribution is evidenced by the large free energy barriers experienced by Cl in the middle of the pore for both GLIC and the E-2 A mutant. Finally, there is a distinct contribution arising from the overall negative electrostatics of the channel.« less

  8. Mechanisms of action of ligands of potential-dependent sodium channels.

    PubMed

    Tikhonov, D B

    2008-06-01

    Potential-dependent sodium channels play a leading role in generating action potentials in excitable cells. Sodium channels are the site of action of a variety of modulator ligands. Despite numerous studies, the mechanisms of action of many modulators remain incompletely understood. The main reason that many important questions cannot be resolved is that there is a lack of precise data on the structures of the channels themselves. Structurally, potential-dependent sodium channels are members of the P-loop channel superfamily, which also include potassium and calcium channels and glutamate receptor channels. Crystallization of a series of potassium channels showed that it was possible to analyze the structures of different members of the superfamily using the "homologous modeling" method. The present study addresses model investigations of the actions of ligands of sodium channels, including tetrodotoxin and batrachotoxin, as well as local anesthetics. Comparison of experimental data on sodium channel ligands with x-ray analysis data allowed us to reach a new level of understanding of the mechanisms of channel modulation and to propose a series of experimentally verifiable hypotheses.

  9. CryoEM structure of a prokaryotic cyclic nucleotide-gated ion channel

    PubMed Central

    James, Zachary M.; Borst, Andrew J.; Haitin, Yoni; Frenz, Brandon; DiMaio, Frank; Zagotta, William N.; Veesler, David

    2017-01-01

    Cyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-regulated (HCN) ion channels play crucial physiological roles in phototransduction, olfaction, and cardiac pace making. These channels are characterized by the presence of a carboxyl-terminal cyclic nucleotide-binding domain (CNBD) that connects to the channel pore via a C-linker domain. Although cyclic nucleotide binding has been shown to promote CNG and HCN channel opening, the precise mechanism underlying gating remains poorly understood. Here we used cryoEM to determine the structure of the intact LliK CNG channel isolated from Leptospira licerasiae—which shares sequence similarity to eukaryotic CNG and HCN channels—in the presence of a saturating concentration of cAMP. A short S4–S5 linker connects nearby voltage-sensing and pore domains to produce a non–domain-swapped transmembrane architecture, which appears to be a hallmark of this channel family. We also observe major conformational changes of the LliK C-linkers and CNBDs relative to the crystal structures of isolated C-linker/CNBD fragments and the cryoEM structures of related CNG, HCN, and KCNH channels. The conformation of our LliK structure may represent a functional state of this channel family not captured in previous studies. PMID:28396445

  10. NPPB structure-specifically activates TRPA1 channels.

    PubMed

    Liu, Kun; Samuel, Manoj; Ho, Melisa; Harrison, Richard K; Paslay, Jeff W

    2010-07-01

    TRPA1 channels have been found to play an important role in mammalian pain sensation, especially when the pain is caused by chemicals on site of inflammation. A large number of structurally diverse chemicals are found to activate TRPA1 channels, implicating a potential chemosensor in neuronal nociception. Identification of the channel activation by cysteine modification through covalent chemical reaction provides arguments for the diversity of the agonist structures. However, it is largely unknown how nonreactive compounds activate TRPA1 channels. Here, we report that NPPB, a classic Cl(-) channel blocker, potently activated human TRPA1 channels overexpressed in mammalian HEK-293 cells. This effect was confirmed in Ca(2+) imaging assay, patch clamp whole cell and single channel recordings. The NPPB response was quick, fully reversible and replicable, contrary to the effect of covalent modification by AITC. The mutagenesis studies revealed a refreshed look at several mutations known to be critical for the actions of AITC and menthol. The blocking profile of NPPB on these mutants showed that the NPPB activation was similar to that of FTS and different from AITC and menthol. The results indicated a possible close interaction between S5 and N-terminal domains of the channel. We also tested a group of NPPB analogs on TRPA1 channel activities. The results demonstrated that NPPB activation was tightly associated with chemical structure. None of the single chemical group was sufficient to activate the channel, indicating that NPPB activated TRPA1 through a structure-specific mechanism. (c) 2010 Elsevier Inc. All rights reserved.

  11. Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide–gated channels

    PubMed Central

    Lam, Yee Ling; Zeng, Weizhong; Derebe, Mehabaw Getahun

    2015-01-01

    Calcium permeability and the concomitant calcium block of monovalent ion current (“Ca2+ block”) are properties of cyclic nucleotide–gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca2+ block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca2+ block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca2+ block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca2+ block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca2+ block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca2+ block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca2+ block. PMID:26283200

  12. Structural implications of weak Ca2+ block in Drosophila cyclic nucleotide-gated channels.

    PubMed

    Lam, Yee Ling; Zeng, Weizhong; Derebe, Mehabaw Getahun; Jiang, Youxing

    2015-09-01

    Calcium permeability and the concomitant calcium block of monovalent ion current ("Ca(2+) block") are properties of cyclic nucleotide-gated (CNG) channel fundamental to visual and olfactory signal transduction. Although most CNG channels bear a conserved glutamate residue crucial for Ca(2+) block, the degree of block displayed by different CNG channels varies greatly. For instance, the Drosophila melanogaster CNG channel shows only weak Ca(2+) block despite the presence of this glutamate. We previously constructed a series of chimeric channels in which we replaced the selectivity filter of the bacterial nonselective cation channel NaK with a set of CNG channel filter sequences and determined that the resulting NaK2CNG chimeras displayed the ion selectivity and Ca(2+) block properties of the parent CNG channels. Here, we used the same strategy to determine the structural basis of the weak Ca(2+) block observed in the Drosophila CNG channel. The selectivity filter of the Drosophila CNG channel is similar to that of most other CNG channels except that it has a threonine at residue 318 instead of a proline. We constructed a NaK chimera, which we called NaK2CNG-Dm, which contained the Drosophila selectivity filter sequence. The high resolution structure of NaK2CNG-Dm revealed a filter structure different from those of NaK and all other previously investigated NaK2CNG chimeric channels. Consistent with this structural difference, functional studies of the NaK2CNG-Dm chimeric channel demonstrated a loss of Ca(2+) block compared with other NaK2CNG chimeras. Moreover, mutating the corresponding threonine (T318) to proline in Drosophila CNG channels increased Ca(2+) block by 16 times. These results imply that a simple replacement of a threonine for a proline in Drosophila CNG channels has likely given rise to a distinct selectivity filter conformation that results in weak Ca(2+) block. © 2015 Lam et al.

  13. Towards fundamental understanding of ultracold KRb

    NASA Astrophysics Data System (ADS)

    Kotochigova, Svetlana

    2009-05-01

    The recent formation of ultracold KRb molecules in their absolute rovibrational ground state [1] has created great promise for study of collective phenomena that rely on the long-range interactions between polar molecules. Here we discuss the theoretical analysis of various essential properties of the KRb molecules [2] that accompanied these experimental advances. This analysis is based on multi-channel bound-state calculations of both ground and excited electronic states. We have found that the theoretical hyperfine and Zeeman mixed X^1&+circ; and a^3&+circ; vibrational structure shows excellent agreement with the experimentally observed structure. In addition, multi-channel calculations of the rovibrational structure of the excited state potentials have allowed us to find the optimal transitions to the lowest v=0 vibrational levels. Finally, we examine the dynamic polarizability of vibrationally cold KRb molecules as a function of laser frequency. Based on this knowledge, laser frequencies can be selected to minimize decoherence from loss of molecules due to spontaneous or laser-induced transitions. [1] K.-K. Ni, S. Ospelkaus, M. H. G. de Miranda, A. Peer, B. Neyenhuis, J. J. Zirbel, S. Kotochigova, P. S. Julienne, D. S. Jin, and J. Ye, Science 322, 231 (2008). [2] S. Kotochigova, E. Tiesinga, and P. S. Julienne, submitted to New J. Phys. (2009).

  14. Low- and high-index sol-gel films for planar and channel-doped waveguides

    NASA Astrophysics Data System (ADS)

    Canva, Michael; Chaput, Frederic; Lahlil, Khalid; Rachet, Vincent; Goudket, Helene; Boilot, Jean-Pierre; Levy, Yves

    2001-11-01

    In view of realizing integrated optic components based on effects such as electro-optic, chi(2):chi(2) cascading, stimulated emission,... one has to first synthesize materials with the proper functionality; this may be achieved by doping solid state matrices by the appropriate organic chromophores. Second, and as important, these materials have to be properly structured into the final optical guiding structures. We shall report on issues related to the realization of chromophore-doped planar waveguides as well as channel waveguides. These structures were realized by either photo-transformation such as photo- chromism and photo-bleaching or reactive ion etching technique, starting with chromophore doped sol-gel materials at high loading contents for which optical index may be controlled via the local dopant concentration. With these materials and techniques, waveguides and components characterized by propagation losses of the order of a cm-1, measured off the edge of the absorption band of the doping species, were fabricated. In order to be also able to study and use waveguide functionalized with low concentration of chromophore species, we developed new sol-gel materials of high optical index, yet low temperature processed. These new films are under study to evaluate their potential as host for organic doped waveguides devices.

  15. Role of Structural Asymmetry in Controlling Drop Spacing in Microfluidic Ladder Networks

    NASA Astrophysics Data System (ADS)

    Wang, William; Maddala, Jeevan; Vanapalli, Siva; Rengasamy, Raghunathan

    2012-02-01

    Manipulation of drop spacing is crucial to many processes in microfluidic devices including drop coalescence, detection and storage. Microfluidic ladder networks ---where two droplet-carrying parallel channels are connected by narrow bypass channels through which the motion of drops is forbidden---have been proposed as a means to control relative separation between pairs of drops. Prior studies in microfluidic ladder networks with vertical bypasses, which possess fore-aft structural symmetry, have revealed that pairs of drops can only undergo reduction in drop spacing at the ladder exit. We investigate the dynamics of drops in microfluidic ladder networks with both vertical and slanted bypasses. Our analytical results indicate that unlike symmetric ladder networks, structural asymmetry introduced by a single slanted bypass can be used to modulate the relative spacing between drops, enabling them to contract, synchronize, expand or even flip at the ladder exit. Our experiments confirm all the behaviors predicted by theory. Numerical analysis further shows that ladders containing several identical bypasses can only linearly transform the input drop spacing. Finally, we find that ladders with specific combinations of vertical and slanted bypasses can generate non-linear transformation of input drop spacing, despite the absence of drop decision-making events at the bypass junctions.

  16. High voltage MOSFET devices and methods of making the devices

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

    Banerjee, Sujit; Matocha, Kevin; Chatty, Kiran

    A SiC MOSFET device having low specific on resistance is described. The device has N+, P-well and JFET regions extended in one direction (Y-direction) and P+ and source contacts extended in an orthogonal direction (X-direction). The polysilicon gate of the device covers the JFET region and is terminated over the P-well region to minimize electric field at the polysilicon gate edge. In use, current flows vertically from the drain contact at the bottom of the structure into the JFET region and then laterally in the X direction through the accumulation region and through the MOSFET channels into the adjacent N+more » region. The current flowing out of the channel then flows along the N+ region in the Y-direction and is collected by the source contacts and the final metal. Methods of making the device are also described.« less

  17. Three levels of neuroelectronic interfacing: silicon chips with ion channels, nerve cells, and brain tissue.

    PubMed

    Fromherz, Peter

    2006-12-01

    We consider the direct electrical interfacing of semiconductor chips with individual nerve cells and brain tissue. At first, the structure of the cell-chip contact is studied. Then we characterize the electrical coupling of ion channels--the electrical elements of nerve cells--with transistors and capacitors in silicon chips. On that basis it is possible to implement signal transmission between microelectronics and the microionics of nerve cells in both directions. Simple hybrid neuroelectronic systems are assembled with neuron pairs and with small neuronal networks. Finally, the interfacing with capacitors and transistors is extended to brain tissue cultured on silicon chips. The application of highly integrated silicon chips allows an imaging of neuronal activity with high spatiotemporal resolution. The goal of the work is an integration of neuronal network dynamics with digital electronics on a microscopic level with respect to experiments in brain research, medical prosthetics, and information technology.

  18. High voltage MOSFET devices and methods of making the devices

    DOEpatents

    Banerjee, Sujit; Matocha, Kevin; Chatty, Kiran

    2015-12-15

    A SiC MOSFET device having low specific on resistance is described. The device has N+, P-well and JFET regions extended in one direction (Y-direction) and P+ and source contacts extended in an orthogonal direction (X-direction). The polysilicon gate of the device covers the JFET region and is terminated over the P-well region to minimize electric field at the polysilicon gate edge. In use, current flows vertically from the drain contact at the bottom of the structure into the JFET region and then laterally in the X direction through the accumulation region and through the MOSFET channels into the adjacent N+ region. The current flowing out of the channel then flows along the N+ region in the Y-direction and is collected by the source contacts and the final metal. Methods of making the device are also described.

  19. B^+→ K^-π ^+π ^+: Three-Body Final State Interactions and Kπ Isospin States

    NASA Astrophysics Data System (ADS)

    Nogueira, J. H. Alvarenga; Frederico, T.; Lourenço, O.

    2017-03-01

    In this exploratory study, final state interactions are considered to formulate the B meson decay amplitude for the Kπ π channel. The Faddeev decomposition of the Bethe-Salpeter equation is used in order to build a relativistic three-body model within the light-front framework. The S-wave scattering amplitude for the Kπ system is considered in the 1/2 and 3/2 isospin channels with the set of inhomogeneous integral equations solved perturbatively. In comparison with previous results for the D meson decay in the same channel, one has to consider the different partonic processes, which build the source amplitudes, and the larger absorption to other decay channels appears, that are important features to be addressed. As in the D decay case, the convergence of the rescattering perturbative series is also achieved with two-loop contributions.

  20. Search for evidence of supersymmetry in the like-sign dimuon channel at the DO experiment

    NASA Astrophysics Data System (ADS)

    Yurkewicz, Adam

    Supersymmetry (SUSY) is a proposed symmetry between fermions and bosons. If this symmetry does exist, it is clearly broken since only half of the particle spectrum is observed. One model which provides a simple breaking mechanism is called minimal supergravity (mSUGRA) inspired SUSY. One clean final state predicted by this model is a trilepton final state from chargino and neutralino decays. In this analysis, these events are sought in 239 +/- 16 pb -1 of DO Run II data by requiring like-sign dimuon pairs. Requiring only two muons increases the signal acceptance, and adding the like-sign requirement reduces the Standard Model background from Drell-Yan dimuon pairs and the various resonances in the dimuon spectrum. The reach into some parts of mSUGRA parameter space will be greater when searching with the like-sign dilepton final state than the trilepton final state. Combining results from a search in the like-sign dilepton channels with searches in the trilepton channels provides increased sensitivity in the search for supersymmetry. In this dissertation, the best-ever DO limit on the total cross section for associated chargino and neutralino production with leptonic final states is presented.

  1. Detecting the impact of bank and channel modification on invertebrate communities in Mediterranean temporary streams (Sardinia, SW Italy).

    PubMed

    Buffagni, Andrea; Tenchini, Roberta; Cazzola, Marcello; Erba, Stefania; Balestrini, Raffaella; Belfiore, Carlo; Pagnotta, Romano

    2016-09-15

    We hypothesized that reach-scale, bank and channel modification would impact benthic communities in temporary rivers of Sardinia, when pollution and water abstraction are not relevant. A range of variables were considered, which include both artificial structures/alterations and natural features observed in a stream reach. Multivariate regression trees (MRT) were used to assess the effects of the explanatory variables on invertebrate assemblages and five groups, characterized by different habitat modification and/or features, were recognized. Four node variables determined the splits in the MRT analysis: channel reinforcement, tree-related bank and channel habitats, channel modification and bank modification. Continuity of trees in the river corridor diverged among MRT groups and significant differences among groups include presence of alders, extent of channel shading and substrate diversity. Also, the percentage of in-stream organic substrates, in particular CPOM/Xylal, showed highly significant differences among groups. For practical applications, thresholds for the extent of channel reinforcement (40%) and modification (10%) and for bank alteration (≈30%) were provided, that can be used to guide the implementation of restoration measures. In moderately altered river reaches, a significant extent of tree-related habitats (≈5%) can noticeably mitigate the effects of morphological alteration on aquatic invertebrates. The outcomes highlight the importance of riparian zone management as an opportune, achievable prospect in the restoration of Mediterranean temporary streams. The impact of bank and channel modification on ecological status (sensu WFD) was investigated and the tested benthic metrics, especially those based on abundance data, showed legible differences among MRT groups. Finally, bank and channel modification appears to be a potential threat for the conservation of a few Sardo-Corsican endemic species. The introduction of management criteria that openly use information on endemic species seems crucial to reduce the risk of improving overall ecological status while depleting biodiversity. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Insights into channel dysfunction from modelling and molecular dynamics simulations.

    PubMed

    Musgaard, Maria; Paramo, Teresa; Domicevica, Laura; Andersen, Ole Juul; Biggin, Philip C

    2018-04-01

    Developments in structural biology mean that the number of different ion channel structures has increased significantly in recent years. Structures of ion channels enable us to rationalize how mutations may lead to channelopathies. However, determining the structures of ion channels is still not trivial, especially as they necessarily exist in many distinct functional states. Therefore, the use of computational modelling can provide complementary information that can refine working hypotheses of both wild type and mutant ion channels. The simplest but still powerful tool is homology modelling. Many structures are available now that can provide suitable templates for many different types of ion channels, allowing a full three-dimensional interpretation of mutational effects. These structural models, and indeed the structures themselves obtained by X-ray crystallography, and more recently cryo-electron microscopy, can be subjected to molecular dynamics simulations, either as a tool to help explore the conformational dynamics in detail or simply as a means to refine the models further. Here we review how these approaches have been used to improve our understanding of how diseases might be linked to specific mutations in ion channel proteins. This article is part of the Special Issue entitled 'Channelopathies.' Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Proposed structure of putative glucose channel in GLUT1 facilitative glucose transporter.

    PubMed Central

    Zeng, H; Parthasarathy, R; Rampal, A L; Jung, C Y

    1996-01-01

    A family of structurally related intrinsic membrane proteins (facilitative glucose transporters) catalyzes the movement of glucose across the plasma membrane of animal cells. Evidence indicates that these proteins show a common structural motif where approximately 50% of the mass is embedded in lipid bilayer (transmembrane domain) in 12 alpha-helices (transmembrane helices; TMHs) and accommodates a water-filled channel for substrate passage (glucose channel) whose tertiary structure is currently unknown. Using recent advances in protein structure prediction algorithms we proposed here two three-dimensional structural models for the transmembrane glucose channel of GLUT1 glucose transporter. Our models emphasize the physical dimension and water accessibility of the channel, loop lengths between TMHs, the macrodipole orientation in four-helix bundle motif, and helix packing energy. Our models predict that five TMHs, either TMHs 3, 4, 7, 8, 11 (Model 1) or TMHs 2, 5, 11, 8, 7 (Model 2), line the channel, and the remaining TMHs surround these channel-lining TMHs. We discuss how our models are compatible with the experimental data obtained with this protein, and how they can be used in designing new biochemical and molecular biological experiments in elucidation of the structural basis of this important protein function. Images FIGURE 1 FIGURE 2 FIGURE 4 FIGURE 5 PMID:8770183

  4. Analysis of electronic structure of amorphous InGaZnO/SiO{sub 2} interface by angle-resolved X-ray photoelectron spectroscopy

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

    Ueoka, Y.; Ishikawa, Y.; Maejima, N.

    2013-10-28

    The electronic structures of amorphous indium gallium zinc oxide (a-IGZO) on a SiO{sub 2} layers before and after annealing were observed by constant final state X-ray photoelectron spectroscopy (CFS-XPS) and X-ray adsorption near-edge structure spectroscopy (XANES). From the results of angle-resolved CFS-XPS, the change in the electronic state was clearly observed in the a-IGZO bulk rather than in the a-IGZO/SiO{sub 2} interface. This suggests that the electronic structures of the a-IGZO bulk strongly affected the thin-film transistor characteristics. The results of XANES indicated an increase in the number of tail states upon atmospheric annealing (AT). We consider that the increasemore » in the number of tail states decreased the channel mobility of AT samples.« less

  5. Nucleation and growth mechanism for flame synthesis of MoO2 hollow microchannels with nanometer wall thickness.

    PubMed

    Merchan-Merchan, Wilson; Saveliev, Alexei V; Taylor, Aaron M

    2009-12-01

    The growth and morphological evolution of molybdenum-oxide microstructures formed in the high temperature environment of a counter-flow oxy-fuel flame using molybdenum probes is studied. Experiments conducted using various probe retention times show the sequence of the morphological changes. The morphological row begins with micron size objects exhibiting polygonal cubic shape, develops into elongated channels, changes to large structures with leaf-like shape, and ends in dendritic structures. Time of probe-flame interaction is found to be a governing parameter controlling the wide variety of morphological patterns; a molecular level growth mechanism is attributed to their development. This study reveals that the structures are grown in several consecutive stages: material "evaporation and transportation", "transformation", "nucleation", "initial growth", "intermediate growth", and "final growth". XRD analysis shows that the chemical compositions of all structures correspond to MoO(2).

  6. Manipulating riparian vegetation, large wood, and discharge in a gravel-cobble bed stream: channel response

    NASA Astrophysics Data System (ADS)

    McDowell, P. F.

    2016-12-01

    The Middle Fork John Day River at Oxbow Conservation Area, northeastern Oregon, experienced heavy cattle grazing for a number of decades and was dredge mined for gold in the 1930s-50s. As a result of dredging, flow was divided between the original meandering channel on the southern part of the floodplain and a straight dredged channel on the northern part of the floodplain. The Confederated Tribes of the Warm Springs acquired this property and began planning floodplain and instream restoration focused primarily on anadromous and resident salmonids. In 2000, cattle grazing in the riparian zone was eliminated, resulting in expansion of sedges and other plants on banks, bars and the channel bed. In 2003, riparian planting of woody vegetation began. In 2011, log structures were constructed in the south channel. The overarching goals of the log structure project were: 1) to add bank protection and roughness to accommodate the planned increase in discharge, and 2) to provide fish cover, pools, and channel complexity. In 2013, the north channel was closed and all flow was put in the south channel. This paper examines channel morphological response to these multiple actions. Channel adjustment was monitored through repeated channel cross-section surveys, longitudinal profile surveys, and analysis of planform change using high-resolution aerial imagery. I hypothesized that channel adjustment would be greatest where banks were less protected, and where bed materials were more mobile due to smaller size or local hydraulic factors such as bend curvature. The results indicate that there has been significant reorganization of riffle-pool structure in the longitudinal profile, but less change in cross-sections and planform. Cross-sections, both at log structures and not at structures, show limited bar aggradation and bank erosion. Some modest erosion occurred on banks protected by log structures. There is no increase in pool depth. The hypothesized relationship between channel change and hydraulic factors is not supported. With healthy riparian vegetation and log structures, this reach is relatively resistant to change, yet it continues to have an active and mobile gravel-cobble bed, even in years with modest floods.

  7. Construction dynamics of a lava channel

    NASA Astrophysics Data System (ADS)

    Harris, Andrew J. L.; Favalli, Massimiliano; Mazzarini, Francesco; Hamilton, Christopher W.

    2009-05-01

    We use a kinematic GPS and laser range finder survey of a 200 m-long section of the Muliwai a Pele lava channel (Mauna Ulu, Kilauea) to examine the construction processes and flow dynamics responsible for the channel-levee structure. The levees comprise three packages. The basal package comprises an 80-150 m wide 'a'a flow in which a ˜2 m deep and ˜11 m wide channel became centred. This is capped by a second package of thin (<45 cm thick) sheets of pahoehoe extending no more than 50 m from the channel. The upper-most package comprises localised 'a'a overflows. The channel itself contains two blockages located 130 m apart and composed of levee chunks veneered with overflow lava. The channel was emplaced over 50 h, spanning 30 May-2 June, 1974, with the flow front arriving at our section (4.4 km from the vent) 8 h after the eruption began. The basal 'a'a flow thickness yields effusion rates of 35 m3 s-1 for the opening phase, with the initial flow advancing across the mapped section at ˜10 m/min. Short-lived overflows of fluid pahoehoe then built the levee cap, increasing the apparent channel depth to 4.8 m. There were at least six pulses at 90-420 m3 s-1, causing overflow of limited extent lasting no more than 5 min. Brim-full flow conditions were thus extremely short-lived. During a dominant period of below-bank flow, flow depth was ˜2 m with an effusion rate of ˜35 m3 s-1, consistent with the mean output rate (obtained from the total flow bulk volume) of 23-54 m3 s-1. During pulses, levee chunks were plucked and floated down channel to form blockages. In a final low effusion rate phase, lava ponded behind the lower blockage to form a syn-channel pond that fed 'a'a overflow. After the end of the eruption the roofed-over pond continued to drain through the lower blockage, causing the roof to founder. Drainage emplaced inflated flows on the channel floor below the lower blockage for a further ˜10 h. The complex processes involved in levee-channel construction of this short-lived case show that care must be taken when using channel dimensions to infer flow dynamics. In our case, the full channel depth is not exposed. Instead the channel floor morphology reflects late stage pond filling and drainage rather than true channel-contained flow. Components of the compound levee relate to different flow regimes operating at different times during the eruption and associated with different effusion rates, flow dynamics and time scales. For example, although high effusion rate, brim-full flow was maintained for a small fraction of the channel lifetime, it emplaced a pile of pahoehoe overflow units that account for 60% of the total levee height. We show how time-varying volume flux is an important parameter in controlling channel construction dynamics. Because the complex history of lava delivery to a channel system is recorded by the final channel morphology, time-varying flow dynamics can be determined from the channel morphology. Developing methods for quantifying detailed flux histories for effusive events from the evidence in outcrop is therefore highly valuable. We here achieve this by using high-resolution spatial data for a channel system at Kilauea. This study not only indicates those physical and dynamic characteristics that are typical for basaltic lava flows on Hawaiian volcanoes, but also a methodology that can be widely applied to effusive basaltic eruptions.

  8. Oligomeric state of purified transient receptor potential melastatin-1 (TRPM1), a protein essential for dim light vision.

    PubMed

    Agosto, Melina A; Zhang, Zhixian; He, Feng; Anastassov, Ivan A; Wright, Sara J; McGehee, Jennifer; Wensel, Theodore G

    2014-09-26

    Transient receptor potential melastatin-1 (TRPM1) is essential for the light-induced depolarization of retinal ON bipolar cells. TRPM1 likely forms a multimeric channel complex, although almost nothing is known about the structure or subunit composition of channels formed by TRPM1 or any of its close relatives. Recombinant TRPM1 was robustly expressed in insect cells, but only a small fraction was localized to the plasma membrane. Similar intracellular localization was observed when TRPM1 was heterologously expressed in mammalian cells. TRPM1 was affinity-purified from Sf9 cells and complexed with amphipol, followed by detergent removal. In blue native gels and size exclusion chromatography, TRPM1 migrated with a mobility consistent with detergent- or amphipol-bound dimers. Cross-linking experiments were also consistent with a dimeric subunit stoichiometry, and cryoelectron microscopy and single particle analysis without symmetry imposition yielded a model with approximate 2-fold symmetrical features. Finally, electron microscopy of TRPM1-antibody complexes revealed a large particle that can accommodate TRPM1 and two antibody molecules. Taken together, these data indicate that purified TRPM1 is mostly dimeric. The three-dimensional structure of TRPM1 dimers is characterized by a small putative transmembrane domain and a larger domain with a hollow cavity. Blue native gels of solubilized mouse retina indicate that TRPM1 is present in two distinct complexes: one similar in size to the recombinant protein and one much larger. Because dimers are likely not functional ion channels, these results suggest that additional partner subunits participate in forming the transduction channel required for dim light vision and the ON pathway. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. An improved approximate network blocking probability model for all-optical WDM Networks with heterogeneous link capacities

    NASA Astrophysics Data System (ADS)

    Khan, Akhtar Nawaz

    2017-11-01

    Currently, analytical models are used to compute approximate blocking probabilities in opaque and all-optical WDM networks with the homogeneous link capacities. Existing analytical models can also be extended to opaque WDM networking with heterogeneous link capacities due to the wavelength conversion at each switch node. However, existing analytical models cannot be utilized for all-optical WDM networking with heterogeneous structure of link capacities due to the wavelength continuity constraint and unequal numbers of wavelength channels on different links. In this work, a mathematical model is extended for computing approximate network blocking probabilities in heterogeneous all-optical WDM networks in which the path blocking is dominated by the link along the path with fewer number of wavelength channels. A wavelength assignment scheme is also proposed for dynamic traffic, termed as last-fit-first wavelength assignment, in which a wavelength channel with maximum index is assigned first to a lightpath request. Due to heterogeneous structure of link capacities and the wavelength continuity constraint, the wavelength channels with maximum indexes are utilized for minimum hop routes. Similarly, the wavelength channels with minimum indexes are utilized for multi-hop routes between source and destination pairs. The proposed scheme has lower blocking probability values compared to the existing heuristic for wavelength assignments. Finally, numerical results are computed in different network scenarios which are approximately equal to values obtained from simulations. Since January 2016, he is serving as Head of Department and an Assistant Professor in the Department of Electrical Engineering at UET, Peshawar-Jalozai Campus, Pakistan. From May 2013 to June 2015, he served Department of Telecommunication Engineering as an Assistant Professor at UET, Peshawar-Mardan Campus, Pakistan. He also worked as an International Internship scholar in the Fukuda Laboratory, National Institute of Informatics, Tokyo, Japan on the topic large-scale simulation for internet topology analysis. His research interests include design and analysis of optical WDM networks, network algorithms, network routing, and network resource optimization problems.

  10. 75 FR 30714 - Endangered and Threatened Wildlife and Plants: Final Rulemaking To Establish Take Prohibitions...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-02

    ... Channel Islands from the list of areas known to be occupied by Southern DPS green sturgeon, noting that... green sturgeon occur in waters around the California Channel Islands and we specifically noted this in... sturgeon occurred in the waters around the Channel Islands, the take prohibitions under the ESA 4(d) rule...

  11. Redundancy in Simultaneously Presented Audio-Visual Message Elements as a Determinant of Recall. Final Report.

    ERIC Educational Resources Information Center

    Baldwin, Thomas F.

    Man seems unable to retain different information from different senses or channels simultaneously; one channel gains full attention. However, it is hypothesized that if the message elements arriving simultaneously from audio and visual channels are redundant, man will retain the information. An attempt was made to measure redundancy in the audio…

  12. 77 FR 59892 - Carbon and Certain Alloy Steel Wire Rod From Mexico: Affirmative Final Determination of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... merchandise, the expectations of the ultimate users, the use of the merchandise, the channels of marketing... expectations of the ultimate users, the use of the merchandise, and the channels of marketing in any meaningful... Comment 7: Fourth Prong of the Minor Alteration Analysis--Channels of Trade and Advertising Comment 8...

  13. Alternative stream channel maintenance at bridge crossings : final report.

    DOT National Transportation Integrated Search

    2017-02-01

    Ohio Department of Transportation (ODOT) forces undertake routine and sometimes extensive maintenance of stream channels that impact the performance and safety of bridges. Unfortunately, county crews have limited options available to solve maintenanc...

  14. 77 FR 38210 - Channel Spacing and Bandwidth Limitations for Certain Economic Area (EA)-Based 800 MHz...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... Specialized Mobile Radio Licensees AGENCY: Federal Communications Commission. ACTION: Final rule; announcement... Specialized Mobile Radio (SMR) licensees to exceed a legacy channel spacing requirement and bandwidth...

  15. Physical Hydraulic Model of Side-Channel Spillway of Lambuk DAM, Bali

    NASA Astrophysics Data System (ADS)

    Harifa, A. C.; Sholichin, M.; Othman, F. B.

    2013-12-01

    The spillway is among the most important structures of a dam project. A spillway is designed to prevent overtopping of a dam at a place that is not designed for overtopping. Side-channel spillways are commonly used to release water flow from a reservoir in places where the sides are steep and have a considerable height above the dam. Experimental results were collected with a hydraulic model of the side-channel spillway for releasing the peak overflow of Lambuk Dam. This dam is, located on the Lambuk River, which is a tributary of the Yeh Hoo River ~ 34.6 km north of Denpasar on the island of Bali. The bituminous geomembrane faced dam is 24 m in height, with a 35-m wide spillway. The length of the side channel is 35 m long, with 58 m of transition channel, 67.37 m of chuteway channel and 22.71 m of stilling basin. The capacity of the spillway is 231.91 m3/s and the outlet works capacity is 165.28 m3/s. The reservoir is designed for irrigation and water supply. The purpose of this study was to optimize the designed of the structure and to ensure its safe operation. In hydraulic model may help the decision-makers to visualize the flow field before selecting a ';suitable' design. The hydraulic model study was performed to ensure passage of the maximum discharge at maximum reservoir capacity; to study the spillway approach conditions, water surface profiles, and flow patterns in the chuteway; and to reveal potential demerits of the proposed hydraulic design of various structures and explore solutions. The model was constructed at 1 : 40 scale, Reservoir topography was modeled using concrete, the river bed using sand and some gravel, the river berm using concrete, and the spillway and channel using Plexiglas. Water was measured using Rectangular contracted weir. Design floods (with return period in year) were Q2 = 111.40 m3/s, Q5 = 136.84 m3/s, Q10 = 159.32 m3/s, Q25 = 174.61 m3/s, Q50 = 185.13 m3/s, Q100 = 198.08 m3/s, Q200 = 210.55 m3/s, Q1000 = 231.91 m3/s and the probable maximum flood was 476.88 m3/s. Hydraulic analysis of spillway used USBR method for spillway, Hind's equation for the side channel, energy equation with standard step method for the transition and chuteway channel. Local scouring depth was calculated using the Schotlisch and Veronise equation. Total head on crest spillway for Q2 = 0.92 m, Q1000 = 1.68 m and for QPMF = 1.92 m. The highest measurement error is 3.16% according to the total head on crest spillway. Cavitation was observed in chuteway. Flow is subcritical (Froude < 1) in the side channel and supercritical in the transition channel. The final design for the spillway and chuteway were safe from impact of cavitation, pulsating flow, and local scouring.

  16. Photodissociation of the carbon monoxide dication in the (3)Σ(-) manifold: Quantum control simulation towards the C(2+) + O channel.

    PubMed

    Vranckx, S; Loreau, J; Vaeck, N; Meier, C; Desouter-Lecomte, M

    2015-10-28

    The photodissociation and laser assisted dissociation of the carbon monoxide dication X(3)Π CO(2+) into the (3)Σ(-) states are investigated. Ab initio electronic structure calculations of the adiabatic potential energy curves, radial nonadiabatic couplings, and dipole moments for the X (3)Π state are performed for 13 excited (3)Σ(-) states of CO(2+). The photodissociation cross section, calculated by time-dependent methods, shows that the C(+) + O(+) channels dominate the process in the studied energy range. The carbon monoxide dication CO(2+) is an interesting candidate for control because it can be produced in a single, long lived, v = 0 vibrational state due to the instability of all the other excited vibrational states of the ground (3)Π electronic state. In a spectral range of about 25 eV, perpendicular transition dipoles couple this (3)Π state to a manifold of (3)Σ(-) excited states leading to numerous C(+) + O(+) channels and a single C(2+) + O channel. This unique channel is used as target for control calculations using local control theory. We illustrate the efficiency of this method in order to find a tailored electric field driving the photodissociation in a manifold of strongly interacting electronic states. The selected local pulses are then concatenated in a sequence inspired by the "laser distillation" strategy. Finally, the local pulse is compared with optimal control theory.

  17. Superconductivity in three-dimensional spin-orbit coupled semimetals

    NASA Astrophysics Data System (ADS)

    Savary, Lucile; Ruhman, Jonathan; Venderbos, Jörn W. F.; Fu, Liang; Lee, Patrick A.

    2017-12-01

    Motivated by the experimental detection of superconductivity in the low-carrier density half-Heusler compound YPtBi, we study the pairing instabilities of three-dimensional strongly spin-orbit coupled semimetals with a quadratic band touching point. In these semimetals the electronic structure at the Fermi energy is described by spin j =3/2 quasiparticles, which are fundamentally different from those in ordinary metals with spin j =1/2 . For both local and nonlocal pairing channels in j =3/2 materials we develop a general approach to analyzing pairing instabilities, thereby providing the computational tools needed to investigate the physics of these systems beyond phenomenological considerations. Furthermore, applying our method to a generic density-density interaction, we establish that: (i) The pairing strengths in the different symmetry channels uniquely encode the j =3/2 nature of the Fermi surface band structure—a manifestation of the fundamental difference with ordinary metals. (ii) The leading odd-parity pairing instabilities are different for electron doping and hole doping. Finally, we argue that polar phonons, i.e., Coulomb interactions mediated by the long-ranged electric polarization of the optical phonon modes, provide a coupling strength large enough to account for a Kelvin-range transition temperature in the s -wave channel, and are likely to play an important role in the overall attraction in non-s -wave channels. Moreover, the explicit calculation of the coupling strengths allows us to conclude that the two largest non-s -wave contributions occur in nonlocal channels, in contrast with what has been commonly assumed.

  18. Roderick MacKinnon and Ion Channels - Potassium Channels and Sodium

    Science.gov Websites

    very first potassium channel structure, which revealed the way that positively charged potassium ions explain how a fundamental feedback loop worked. Now, with the structure of the voltage-dependent ion channel, based on research carried out at The Rockefeller University, the National Synchrotron Light

  19. Development of III-V p-MOSFETs with high-kappa gate stack for future CMOS applications

    NASA Astrophysics Data System (ADS)

    Nagaiah, Padmaja

    As the semiconductor industry approaches the limits of traditional silicon CMOS scaling, non-silicon materials and new device architectures are gradually being introduced to improve Si integrated circuit performance and continue transistor scaling. Recently, the replacement of SiO2 with a high-k material (HfO2) as gate dielectric has essentially removed one of the biggest advantages of Si as channel material. As a result, alternate high mobility materials are being considered to replace Si in the channel to achieve higher drive currents and switching speeds. III-V materials in particular have become of great interest as channel materials, owing to their superior electron transport properties. However, there are several critical challenges that need to be addressed before III-V based CMOS can replace Si CMOS technology. Some of these challenges include development of a high quality, thermally stable gate dielectric/III-V interface, and improvement in III-V p-channel hole mobility to complement the n-channel mobility, low source/drain resistance and integration onto Si substrate. In this thesis, we would be addressing the first two issues i.e. the development high performance III-V p-channels and obtaining high quality III-V/high-k interface. We start with using the device architecture of the already established InGaAs n-channels as a baseline to understand the effect of remote scattering from the high-k oxide and oxide/semiconductor interface on channel transport properties such as electron mobility and channel electron concentration. Temperature dependent Hall electron mobility measurements were performed to separate various scattering induced mobility limiting factors. Dependence of channel mobility on proximity of the channel to the oxide interface, oxide thickness, annealing conditions are discussed. The results from this work will be used in the design of the p-channel MOSFETs. Following this, InxGa1-xAs (x>0.53) is chosen as channel material for developing p-channel MOSFETs. Band engineering, strain induced valence band splitting and quantum confinement is used to improve channel hole mobility. Experimental results on the Hall hole mobility is presented for InxGa1-xAs channels with varying In content, thickness of the quantum well and temperature. Then, high mobility InxGa 1-xAs heterostructure thus obtained are integrated with in-situ deposited high-k gate oxide required for high performance p-MOSFET and discuss the challenges associated with the gated structure and draw conclusions on this material system. Antimonide based channel materials such as GaSb and InxGa 1-xSb are explored for III-V based p-MOSFETs in last two chapters. Options for Sb based strained QW channels to obtain maximum hole mobility by varying the strain, channel and barrier material, thickness of the layers etc. is discussed followed by the growth of these Sb channels on GaAs and InP substrates using molecular beam epitaxy. The physical properties of the structures such as the heterostructure quality, alloy content and surface roughness are examined via TEM, XRD and AFM. Following this, electrical measurement results on Hall hole mobility is presented. The effect of strain, alloy content, temperature and thickness on channel mobility and concentration is reported. Development of GaSb n- and p-MOS capacitor structures with in-situ deposited HfO2 gate oxide dielectric using in-situ deposited amorphous Si (a-Si) interface passivation layer (IPL) to improve the interface quality of high-k oxide and (In)GaSb surface is presented. In-situ deposited gate oxides such as Al2O3 and combination oxide of Al 2O3 and HfO2 with and without the a-Si IPL are also explored as alternate gate dielectrics. Subsequently, MOS capacitor structures using buried InGaSb QWs are demonstrated. Development of an inversion type bulk GaSb with implanted source-drain contacts and in-situ deposited gate oxide HfO2 gate oxide is discussed. The merits of biaxial compressive strain is demonstrated on strained surface and buried channel In0.36 Ga0.64Sb QW MOSFETs with thin top barrier and in-situ deposited a-Si IPL and high-k HfO2 as well as combination Al 2O3+HfO2 gate stacks and ex-situ atomic layer deposited (ALD) combination gate oxide and with thin 2 nm InAs surface passivation layer is presented. Finally, summary of the salient results from the different chapters is provided with recommendations for future research.

  20. Molecular mechanism of ATP binding and ion channel activation in P2X receptors

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

    Hattori, Motoyuki; Gouaux, Eric

    P2X receptors are trimeric ATP-activated ion channels permeable to Na{sup +}, K{sup +} and Ca{sup 2+}. The seven P2X receptor subtypes are implicated in physiological processes that include modulation of synaptic transmission, contraction of smooth muscle, secretion of chemical transmitters and regulation of immune responses. Despite the importance of P2X receptors in cellular physiology, the three-dimensional composition of the ATP-binding site, the structural mechanism of ATP-dependent ion channel gating and the architecture of the open ion channel pore are unknown. Here we report the crystal structure of the zebrafish P2X4 receptor in complex with ATP and a new structure ofmore » the apo receptor. The agonist-bound structure reveals a previously unseen ATP-binding motif and an open ion channel pore. ATP binding induces cleft closure of the nucleotide-binding pocket, flexing of the lower body {beta}-sheet and a radial expansion of the extracellular vestibule. The structural widening of the extracellular vestibule is directly coupled to the opening of the ion channel pore by way of an iris-like expansion of the transmembrane helices. The structural delineation of the ATP-binding site and the ion channel pore, together with the conformational changes associated with ion channel gating, will stimulate development of new pharmacological agents.« less

  1. Method of producing microchannel and nanochannel articles

    DOEpatents

    D'Urso, Brian R.

    2010-05-04

    A method of making an article having channels therethrough includes the steps of: providing a ductile structure defining at least one macro-channel, the macro-channel containing a salt; drawing the ductile structure in the axial direction of the at least one macro-channel to reduce diameter of the macro-channel; and contacting the salt with a solvent to dissolve the salt to produce an article having at least one microchannel.

  2. Outward Rectification of Voltage-Gated K+ Channels Evolved at Least Twice in Life History

    PubMed Central

    Riedelsberger, Janin; Dreyer, Ingo; Gonzalez, Wendy

    2015-01-01

    Voltage-gated potassium (K+) channels are present in all living systems. Despite high structural similarities in the transmembrane domains (TMD), this K+ channel type segregates into at least two main functional categories—hyperpolarization-activated, inward-rectifying (Kin) and depolarization-activated, outward-rectifying (Kout) channels. Voltage-gated K+ channels sense the membrane voltage via a voltage-sensing domain that is connected to the conduction pathway of the channel. It has been shown that the voltage-sensing mechanism is the same in Kin and Kout channels, but its performance results in opposite pore conformations. It is not known how the different coupling of voltage-sensor and pore is implemented. Here, we studied sequence and structural data of voltage-gated K+ channels from animals and plants with emphasis on the property of opposite rectification. We identified structural hotspots that alone allow already the distinction between Kin and Kout channels. Among them is a loop between TMD S5 and the pore that is very short in animal Kout, longer in plant and animal Kin and the longest in plant Kout channels. In combination with further structural and phylogenetic analyses this finding suggests that outward-rectification evolved twice and independently in the animal and plant kingdom. PMID:26356684

  3. Outward Rectification of Voltage-Gated K+ Channels Evolved at Least Twice in Life History.

    PubMed

    Riedelsberger, Janin; Dreyer, Ingo; Gonzalez, Wendy

    2015-01-01

    Voltage-gated potassium (K+) channels are present in all living systems. Despite high structural similarities in the transmembrane domains (TMD), this K+ channel type segregates into at least two main functional categories-hyperpolarization-activated, inward-rectifying (Kin) and depolarization-activated, outward-rectifying (Kout) channels. Voltage-gated K+ channels sense the membrane voltage via a voltage-sensing domain that is connected to the conduction pathway of the channel. It has been shown that the voltage-sensing mechanism is the same in Kin and Kout channels, but its performance results in opposite pore conformations. It is not known how the different coupling of voltage-sensor and pore is implemented. Here, we studied sequence and structural data of voltage-gated K+ channels from animals and plants with emphasis on the property of opposite rectification. We identified structural hotspots that alone allow already the distinction between Kin and Kout channels. Among them is a loop between TMD S5 and the pore that is very short in animal Kout, longer in plant and animal Kin and the longest in plant Kout channels. In combination with further structural and phylogenetic analyses this finding suggests that outward-rectification evolved twice and independently in the animal and plant kingdom.

  4. Structural model of the open–closed–inactivated cycle of prokaryotic voltage-gated sodium channels

    PubMed Central

    Bagnéris, Claire; Naylor, Claire E.; McCusker, Emily C.

    2015-01-01

    In excitable cells, the initiation of the action potential results from the opening of voltage-gated sodium channels. These channels undergo a series of conformational changes between open, closed, and inactivated states. Many models have been proposed for the structural transitions that result in these different functional states. Here, we compare the crystal structures of prokaryotic sodium channels captured in the different conformational forms and use them as the basis for examining molecular models for the activation, slow inactivation, and recovery processes. We compare structural similarities and differences in the pore domains, specifically in the transmembrane helices, the constrictions within the pore cavity, the activation gate at the cytoplasmic end of the last transmembrane helix, the C-terminal domain, and the selectivity filter. We discuss the observed differences in the context of previous models for opening, closing, and inactivation, and present a new structure-based model for the functional transitions. Our proposed prokaryotic channel activation mechanism is then compared with the activation transition in eukaryotic sodium channels. PMID:25512599

  5. TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6.

    PubMed

    van Goor, Mark K C; Hoenderop, Joost G J; van der Wijst, Jenny

    2017-06-01

    Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture. While this field is still in its infancy, it has increased our understanding of molecular channel regulation and holds great promise for future structure-function studies of these ion channels. This review will summarize the mechanisms that control the systemic calcium balance, as well as extrapolate structural views to the molecular functioning of TRPV5/6 channels in epithelial calcium transport. Copyright © 2016. Published by Elsevier B.V.

  6. Hillslope to fluvial process domain transitions in headwater catchments

    NASA Astrophysics Data System (ADS)

    Williams, Karen Mary

    The landscape is partitioned into hillslopes and unchanneled valleys (hollows), and colluvial (hillslope controlled) and alluvial (self-formed) channels. The key issue for any study of headwater catchments is the rational distinction between these elements. Accurate identification of process domain transitions from hillslopes to hollows, hollows to colluvial channels and colluvial to alluvial channels, are not obvious either in the field or from topographic data derived from remotely sensed data such as laser derived (LIDAR) digital elevation models. The research in this dissertation investigates the spatial arrangement of these landforms and how hillslope and fluvial process domains interact in two pairs of headwater catchments in southwest and central Montana, using LIDAR data. This dissertation uses digital terrain analysis of LIDAR-derived topography and field studies to investigate methods of detection, modeling, and prediction of process transitions from the hillslope to fluvial domains and within the fluvial domain, from colluvial to alluvial channel reaches. Inflections in the scaling relationships between landscape parameters such as flowpath length, unit stream power (a metric of the energy expended by the channel in doing work), and drainage area were used to detect transitions in flow regimes characteristic of hillslope, unchanneled valleys, and channeled landforms. Using the scale-invariant properties of fluvial systems as a threshold condition, magnitude-frequency distributions of curvature and the derivative of aspect were also used to detect hillslope, fluvial, and transitional process domains. Finally, within the classification of channeled landforms, the transition from colluvial to alluvial channels was detected using the presence/absence of repeating patterns in the power spectra of fluvial energy and channel form parameters. LIDAR-derived scaling relations and magnitude-frequency distributions successfully detected and predicted locations of mapped channel heads and hollows and spatial regions of process transitions. Subreaches of arguably alluvial channel conditions were also identified in power spectra. However, extrinsic forcing limits ability to detect a clear transition from colluvial to fully alluvial conditions. Headwater catchments present a mosaic of process domains, in large determined by local structure and lithology. However, process domain transitions appear detectable and statistically, though not deterministically, predictable, irrespective of setting.

  7. Intractable hyperkalemia due to nicorandil induced potassium channel syndrome.

    PubMed

    Chowdhry, Vivek; Mohanty, B B

    2015-01-01

    Nicorandil is a commonly used antianginal agent, which has both nitrate-like and ATP-sensitive potassium (K ATP ) channel activator properties. Activation of potassium channels by nicorandil causes expulsion of potassium ions into the extracellular space leading to membrane hyperpolarization, closure of voltage-gated calcium channels and finally vasodilatation. However, on the other hand, being an activator of K ATP channel, it can expel K + ions out of the cells and can cause hyperkalemia. Here, we report a case of nicorandil induced hyperkalemia unresponsive to medical treatment in a patient with diabetic nephropathy.

  8. A novel method for structure-based prediction of ion channel conductance properties.

    PubMed Central

    Smart, O S; Breed, J; Smith, G R; Sansom, M S

    1997-01-01

    A rapid and easy-to-use method of predicting the conductance of an ion channel from its three-dimensional structure is presented. The method combines the pore dimensions of the channel as measured in the HOLE program with an Ohmic model of conductance. An empirically based correction factor is then applied. The method yielded good results for six experimental channel structures (none of which were included in the training set) with predictions accurate to within an average factor of 1.62 to the true values. The predictive r2 was equal to 0.90, which is indicative of a good predictive ability. The procedure is used to validate model structures of alamethicin and phospholamban. Two genuine predictions for the conductance of channels with known structure but without reported conductances are given. A modification of the procedure that calculates the expected results for the effect of the addition of nonelectrolyte polymers on conductance is set out. Results for a cholera toxin B-subunit crystal structure agree well with the measured values. The difficulty in interpreting such studies is discussed, with the conclusion that measurements on channels of known structure are required. Images FIGURE 1 FIGURE 3 FIGURE 4 FIGURE 6 FIGURE 10 PMID:9138559

  9. Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age

    PubMed Central

    Oiki, Shigetoshi

    2015-01-01

    The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the ‘frozen’ crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. PMID:25833254

  10. Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age.

    PubMed

    Oiki, Shigetoshi

    2015-06-15

    The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the 'frozen' crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  11. Extracellular blockade of K(+) channels by TEA: results from molecular dynamics simulations of the KcsA channel.

    PubMed

    Crouzy, S; Bernèche, S; Roux, B

    2001-08-01

    TEA is a classical blocker of K(+) channels. From mutagenesis studies, it has been shown that external blockade by TEA is strongly dependent upon the presence of aromatic residue at Shaker position 449 which is located near the extracellular entrance to the pore (Heginbotham, L., and R. MacKinnon. 1992. Neuron. 8:483-491). The data suggest that TEA interacts simultaneously with the aromatic residues of the four monomers. The determination of the 3-D structure of the KcsA channel using X-ray crystallography (Doyle, D.A., J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, and R. MacKinnon. 1998. Science. 280:69-77) has raised some issues that remain currently unresolved concerning the interpretation of these observations. In particular, the center of the Tyr82 side chains in KcsA (corresponding to position 449 in Shaker) forms a square of 11.8-A side, a distance which is too large to allow simultaneous interactions of a TEA molecule with the four aromatic side chains. In this paper, the external blockade by TEA is explored by molecular dynamics simulations of an atomic model of KcsA in an explicit phospholipid bilayer with aqueous salt solution. It is observed, in qualitative accord with the experimental results, that TEA is stable when bound to the external side of the wild-type KcsA channel (with Tyr82), but is unstable when bound to a mutant channel in which the tyrosine residue has been substituted by a threonine. The free energy profile of TEA relative to the pore is calculated using umbrella sampling simulations to characterize quantitatively the extracellular blockade. It is found, in remarkable agreement with the experiment, that the TEA is more stably bound by 2.3 kcal/mol to the channel with four tyrosine residues. In the case of the wild-type KcsA channel, TEA (which has the shape of a flattened oblate spheroid) acts as an ideal plug blocking the pore. In contrast, it is considerably more off-centered and tilted in the case of the mutant channel. The enhanced stability conferred by the tyrosine residues does not arise from Pi-cation interactions, but appears to be due to differences in the hydration structure of the TEA. Finally, it is shown that the experimentally observed voltage dependence of TEA block, which is traditionally interpreted in terms of the physical position of the TEA along the axis of the pore, must arise indirectly via coupling with the ions in the pore.

  12. Experimental Assessment of Different Receiver Structures for Underwater Acoustic Communications over Multipath Channels

    PubMed Central

    Zhang, Guosong; Hovem, Jens M.; Dong, Hefeng

    2012-01-01

    Underwater communication channels are often complicated, and in particular multipath propagation may cause intersymbol interference (ISI). This paper addresses how to remove ISI, and evaluates the performance of three different receiver structures and their implementations. Using real data collected in a high-frequency (10–14 kHz) field experiment, the receiver structures are evaluated by off-line data processing. The three structures are multichannel decision feedback equalizer (DFE), passive time reversal receiver (passive-phase conjugation (PPC) with a single channel DFE), and the joint PPC with multichannel DFE. In sparse channels, dominant arrivals represent the channel information, and the matching pursuit (MP) algorithm which exploits the channel sparseness has been investigated for PPC processing. In the assessment, it is found that: (1) it is advantageous to obtain spatial gain using the adaptive multichannel combining scheme; and (2) the MP algorithm improves the performance of communications using PPC processing. PMID:22438755

  13. Electron cryo-microscopy structure of the canonical TRPC4 ion channel

    PubMed Central

    Vinayagam, Deivanayagabarathy; Mager, Thomas; Apelbaum, Amir; Bothe, Arne; Merino, Felipe; Hofnagel, Oliver; Gatsogiannis, Christos

    2018-01-01

    Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3.6 Å. The structure reveals the molecular architecture of the cation conducting pore, including the selectivity filter and lower gate. The cytoplasmic domain contains two key hubs that have been shown to interact with modulating proteins. Structural comparisons with other TRP channels give novel insights into the general architecture and domain organization of this superfamily of channels and help to understand their function and pharmacology. PMID:29717981

  14. Using in-process measurements of open-gate structures to evaluate threshold voltage of normally-off GaN-based high electron mobility transistors

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

    Hou, Bin; Ma, Xiao-Hua, E-mail: xhma@xidian.edu.cn, E-mail: yhao@xidian.edu.cn; Chen, Wei-Wei

    The parameters of open-gate structures treated with different etching time were monitored during the gate recess process, and their impacts on the threshold voltage (V{sub th}) of final fabricated AlGaN/GaN high electron mobility transistors (HEMTs) based on open-gate structures were discussed in this paper. It is found that V{sub th} can exceed 0 V when channel resistance in the recessed region (R{sub on-open}) increases over ∼275 Ω mm, maximum current (I{sub Dmax}) decreases below ∼29 mA/mm, or recessed barrier thickness (t{sub RB}) is below ∼7.5 nm. In addition, t{sub RB} obtained by atomic force microscopy measurements and C-V measurements are also compared. Finally,more » theoretical common criteria based on the experimental results of this work for t{sub RB} and R{sub on-open} were established to evaluate the V{sub th} of a regular normally-off AlGaN/GaN HEMTs. The results indicate that these parameters of open-gate structure can be utilized to achieve normally-off HEMTs with controllable V{sub th}.« less

  15. Coherent communication with continuous quantum variables

    NASA Astrophysics Data System (ADS)

    Wilde, Mark M.; Krovi, Hari; Brun, Todd A.

    2007-06-01

    The coherent bit (cobit) channel is a resource intermediate between classical and quantum communication. It produces coherent versions of teleportation and superdense coding. We extend the cobit channel to continuous variables by providing a definition of the coherent nat (conat) channel. We construct several coherent protocols that use both a position-quadrature and a momentum-quadrature conat channel with finite squeezing. Finally, we show that the quality of squeezing diminishes through successive compositions of coherent teleportation and superdense coding.

  16. Biochemical Characterization of Cone Cyclic Nucleotide-gated (CNG) Channel Using the Infrared Fluorescence Detection System

    PubMed Central

    Ding, Xi-Qin; Matveev, Alexander; Singh, Anil; Komori, Naoka; Matsumoto, Hiroyuki

    2012-01-01

    Cone vision mediated by photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Cone CNG channel is composed of two structurally related subunit types, CNGA3 and CNGB3. Naturally occurring mutations in cone CNG channel are associated with a variety of cone diseases including achromatopsia, progressive cone dystrophy, and some maculopathies. Nevertheless, our understanding of the structure of cone CNG channel is quite limited. This is, in part, due to the challenge of studying cones in a rod-dominant mammalian retina. We have demonstrated a robust expression of cone CNG channel and lack of rod CNG channel in the cone-dominant Nrl−/− retina and shown that the Nrl−/− mouse line is a valuable model to study cone CNG channel. This work examined the complex structure of cone CNG channel using infrared fluorescence Western detection combined with chemical cross-linking and blue native-PAGE. Our results suggest that the native cone CNG channel is a heterotetrameric complex likely at a stoichiometry of three CNGA3 and one CNGB3. PMID:22183405

  17. Structural Determinants of the Transient Receptor Potential 1 (TRPV1) Channel Activation by Phospholipid Analogs*

    PubMed Central

    Morales-Lázaro, Sara L.; Serrano-Flores, Barbara; Llorente, Itzel; Hernández-García, Enrique; González-Ramírez, Ricardo; Banerjee, Souvik; Miller, Duane; Gududuru, Veeresh; Fells, James; Norman, Derek; Tigyi, Gabor; Escalante-Alcalde, Diana; Rosenbaum, Tamara

    2014-01-01

    The transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal protein that responds to various stimuli, including capsaicin (the pungent compound found in chili peppers), extracellular acid, and basic intracellular pH, temperatures close to 42 °C, and several lipids. Lysophosphatidic acid (LPA), an endogenous lipid widely associated with neuropathic pain, is an agonist of the TRPV1 channel found in primary afferent nociceptors and is activated by other noxious stimuli. Agonists or antagonists of lipid and other chemical natures are known to possess specific structural requirements for producing functional effects on their targets. To better understand how LPA and other lipid analogs might interact and affect the function of TRPV1, we set out to determine the structural features of these lipids that result in the activation of TRPV1. By changing the acyl chain length, saturation, and headgroup of these LPA analogs, we established strict requirements for activation of TRPV1. Among the natural LPA analogs, we found that only LPA 18:1, alkylglycerophosphate 18:1, and cyclic phosphatidic acid 18:1, all with a monounsaturated C18 hydrocarbon chain activate TRPV1, whereas polyunsaturated and saturated analogs do not. Thus, TRPV1 shows a more restricted ligand specificity compared with LPA G-protein-coupled receptors. We synthesized fatty alcohol phosphates and thiophosphates and found that many of them with a single double bond in position Δ9, 10, or 11 and Δ9 cyclopropyl group can activate TRPV1 with efficacy similar to capsaicin. Finally, we developed a pharmacophore and proposed a mechanistic model for how these lipids could induce a conformational change that activates TRPV1. PMID:25035428

  18. Influence of the cytoplasmic domains of aquaporin-4 on water conduction and array formation.

    PubMed

    Mitsuma, Tadanori; Tani, Kazutoshi; Hiroaki, Yoko; Kamegawa, Akiko; Suzuki, Hiroshi; Hibino, Hiroshi; Kurachi, Yoshihisa; Fujiyoshi, Yoshinori

    2010-10-01

    Phosphorylation of Ser180 in cytoplasmic loop D has been shown to reduce the water permeability of aquaporin (AQP) 4, the predominant water channel in the brain. However, when the structure of the S180D mutant (AQP4M23S180D), which was generated to mimic phosphorylated Ser180, was determined to 2.8 Å resolution using electron diffraction patterns, it showed no significant differences from the structure of the wild-type channel. High-resolution density maps usually do not resolve protein regions that are only partially ordered, but these can sometimes be seen in lower-resolution density maps calculated from electron micrographs. We therefore used images of two-dimensional crystals and determined the structure of AQP4M23S180D at 10 A resolution. The features of the 10-A density map are consistent with those of the previously determined atomic model; in particular, there were no indications of any obstruction near the cytoplasmic pore entrance. In addition, water conductance measurements, both in vitro and in vivo, show the same water permeability for wild-type and mutant AQP4M23, suggesting that the S180D mutation neither reduces water conduction through a conformational change nor reduces water conduction by interacting with a protein that would obstruct the cytoplasmic channel entrance. Finally, the 10-A map shows a cytoplasmic density in between four adjacent tetramers that most likely represents the association of four N termini. This finding supports the critical role of the N terminus of AQP4 in the stabilization of orthogonal arrays, as well as their interference through lipid modification of cysteine residues in the longer N-terminal isoform. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Structural determinants of the transient receptor potential 1 (TRPV1) channel activation by phospholipid analogs.

    PubMed

    Morales-Lázaro, Sara L; Serrano-Flores, Barbara; Llorente, Itzel; Hernández-García, Enrique; González-Ramírez, Ricardo; Banerjee, Souvik; Miller, Duane; Gududuru, Veeresh; Fells, James; Norman, Derek; Tigyi, Gabor; Escalante-Alcalde, Diana; Rosenbaum, Tamara

    2014-08-29

    The transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal protein that responds to various stimuli, including capsaicin (the pungent compound found in chili peppers), extracellular acid, and basic intracellular pH, temperatures close to 42 °C, and several lipids. Lysophosphatidic acid (LPA), an endogenous lipid widely associated with neuropathic pain, is an agonist of the TRPV1 channel found in primary afferent nociceptors and is activated by other noxious stimuli. Agonists or antagonists of lipid and other chemical natures are known to possess specific structural requirements for producing functional effects on their targets. To better understand how LPA and other lipid analogs might interact and affect the function of TRPV1, we set out to determine the structural features of these lipids that result in the activation of TRPV1. By changing the acyl chain length, saturation, and headgroup of these LPA analogs, we established strict requirements for activation of TRPV1. Among the natural LPA analogs, we found that only LPA 18:1, alkylglycerophosphate 18:1, and cyclic phosphatidic acid 18:1, all with a monounsaturated C18 hydrocarbon chain activate TRPV1, whereas polyunsaturated and saturated analogs do not. Thus, TRPV1 shows a more restricted ligand specificity compared with LPA G-protein-coupled receptors. We synthesized fatty alcohol phosphates and thiophosphates and found that many of them with a single double bond in position Δ9, 10, or 11 and Δ9 cyclopropyl group can activate TRPV1 with efficacy similar to capsaicin. Finally, we developed a pharmacophore and proposed a mechanistic model for how these lipids could induce a conformational change that activates TRPV1. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Dark matter annihilation with s-channel internal Higgsstrahlung

    DOE PAGES

    Kumar, Jason; Liao, Jiajun; Marfatia, Danny

    2016-05-31

    We study the scenario of fermionic dark matter that annihilates to standard model fermions through an s-channel axial vector mediator. We point out that the well-known chirality suppression of the annihilation cross section can be alleviated by s-channel internal Higgsstrahlung. The shapes of the cosmic ray spectra are identical to that of t-channel internal Higgsstrahlung in the limit of a heavy mediating particle. Unlike the general case of t-channel bremsstrahlung, s-channel Higgsstrahlung can be the dominant annihilation process even for Dirac dark matter. Finally, since the s-channel mediator can be a standard model singlet, collider searches for the mediator aremore » easily circumvented.« less

  1. Dark matter annihilation with s-channel internal Higgsstrahlung

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

    Kumar, Jason; Liao, Jiajun; Marfatia, Danny

    We study the scenario of fermionic dark matter that annihilates to standard model fermions through an s-channel axial vector mediator. We point out that the well-known chirality suppression of the annihilation cross section can be alleviated by s-channel internal Higgsstrahlung. The shapes of the cosmic ray spectra are identical to that of t-channel internal Higgsstrahlung in the limit of a heavy mediating particle. Unlike the general case of t-channel bremsstrahlung, s-channel Higgsstrahlung can be the dominant annihilation process even for Dirac dark matter. Finally, since the s-channel mediator can be a standard model singlet, collider searches for the mediator aremore » easily circumvented.« less

  2. Searching for new leads to treat epilepsy. Target-based virtual screening for the discovery of anticonvulsant agents.

    PubMed

    Palestro, Pablo; Enrique, Nicolas; Goicoechea, Sofia; Villalba, María Luisa; Sabatier, Laureano Leonel; Martin, Pedro; Milesi, Veronica; Bruno-Blanch, Luis E; Gavernet, Luciana

    2018-06-05

    The purpose of this investigation is to contribute to the development of new anticonvulsant drugs to treat patients with refractory epilepsy. We applied a virtual screening protocol that involved the search into molecular databases of new compounds and known drugs to find small molecules that interact with the open conformation of the Nav1.2 pore. As the 3D structure of human Nav1.2 is not available, we first assembled 3D models of the target, in closed and open conformations. After the virtual screening, the resulting candidates were submitted to a second virtual filter, to find compounds with better chances of being effective for the treatment of P-glycoprotein (P-gp) mediated resistant epilepsy. Again, we built a model of the 3D structure of human P-gp and we validated the docking methodology selected to propose the best candidates, which were experimentally tested on Nav1.2 channels by patch clamp techniques and in vivo by MES-test. Patch clamp studies allowed us to corroborate that our candidates, drugs used for the treatment of other pathologies like Ciprofloxacin, Losartan and Valsartan, exhibit inhibitory effects on Nav1.2 channel activity. Additionally, a compound synthesized in our lab, N,N´-diphenethylsulfamide, interacts with the target and also triggers significant Na1.2 channel inhibitory action. Finally, in-vivo studies confirmed the anticonvulsant action of Valsartan, Ciprofloxacin and N.N´-diphenethylsulfamide.

  3. 76 FR 49364 - Radio Broadcasting Services; Gearhart, Madras, and Manzanita, OR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-10

    ... Commission. ACTION: Final rule. SUMMARY: The Audio Division, at the request of Black Hills Broadcasting, L.C... addition, the Audio Division substitutes Channel 248C3 for vacant Channel 228C3 at Manzanita, Oregon, and... coordinates for Channel *243C1 at Madras Oregon, are 44-50-02 NL and 120-45-55 WL. In addition, the Audio...

  4. Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR

    NASA Astrophysics Data System (ADS)

    Lange, Adam; Giller, Karin; Hornig, Sönke; Martin-Eauclaire, Marie-France; Pongs, Olaf; Becker, Stefan; Baldus, Marc

    2006-04-01

    The active site of potassium (K+) channels catalyses the transport of K+ ions across the plasma membrane-similar to the catalytic function of the active site of an enzyme-and is inhibited by toxins from scorpion venom. On the basis of the conserved structures of K+ pore regions and scorpion toxins, detailed structures for the K+ channel-scorpion toxin binding interface have been proposed. In these models and in previous solution-state nuclear magnetic resonance (NMR) studies using detergent-solubilized membrane proteins, scorpion toxins were docked to the extracellular entrance of the K+ channel pore assuming rigid, preformed binding sites. Using high-resolution solid-state NMR spectroscopy, here we show that high-affinity binding of the scorpion toxin kaliotoxin to a chimaeric K+ channel (KcsA-Kv1.3) is associated with significant structural rearrangements in both molecules. Our approach involves a combined analysis of chemical shifts and proton-proton distances and demonstrates that solid-state NMR is a sensitive method for analysing the structure of a membrane protein-inhibitor complex. We propose that structural flexibility of the K+ channel and the toxin represents an important determinant for the high specificity of toxin-K+ channel interactions.

  5. GABA(C) receptors: a molecular view.

    PubMed

    Enz, R

    2001-08-01

    In the central nervous system inhibitory neurotransmission is primarily achieved through activation of receptors for gamma-aminobutyric acid (GABA). Three types of GABA receptors have been identified on the basis of their pharmacological and electrophysiological properties. The predominant type, termed GABA(A), and a recently identified GABA(C) type, form ligand-gated chloride channels, whereas GABA(B) receptors activate separate cation channels via G proteins. Based on their homology to nicotinic acetylcholine receptors, GABA(C) receptors are believed to be oligomeric protein complexes composed of five subunits in a pentameric arrangement. To date up to five different GABA(C) receptors subunits have been identified in various species. Recent studies have shed new light on the biological characteristics of GABA(C) receptors, including the chromosomal localization of its subunit genes and resulting links to deseases, the cloning of new splice variants, the identification of GABA(C) receptor-associated proteins, the identification of domains involved in subunit assembly, and finally structure/function studies examining functional consequences of introduced mutations. This review summarizes recent data in view of the molecular structure of GABA(C) receptors and presents new insights into the biological function of this protein in the retina.

  6. Performance of DPSK with convolutional encoding on time-varying fading channels

    NASA Technical Reports Server (NTRS)

    Mui, S. Y.; Modestino, J. W.

    1977-01-01

    The bit error probability performance of a differentially-coherent phase-shift keyed (DPSK) modem with convolutional encoding and Viterbi decoding on time-varying fading channels is examined. Both the Rician and the lognormal channels are considered. Bit error probability upper bounds on fully-interleaved (zero-memory) fading channels are derived and substantiated by computer simulation. It is shown that the resulting coded system performance is a relatively insensitive function of the choice of channel model provided that the channel parameters are related according to the correspondence developed as part of this paper. Finally, a comparison of DPSK with a number of other modulation strategies is provided.

  7. Structural and functional characterization of a calcium-activated cation channel from Tsukamurella paurometabola

    NASA Astrophysics Data System (ADS)

    Dhakshnamoorthy, Balasundaresan; Rohaim, Ahmed; Rui, Huan; Blachowicz, Lydia; Roux, Benoît

    2016-09-01

    The selectivity filter is an essential functional element of K+ channels that is highly conserved both in terms of its primary sequence and its three-dimensional structure. Here, we investigate the properties of an ion channel from the Gram-positive bacterium Tsukamurella paurometabola with a selectivity filter formed by an uncommon proline-rich sequence. Electrophysiological recordings show that it is a non-selective cation channel and that its activity depends on Ca2+ concentration. In the crystal structure, the selectivity filter adopts a novel conformation with Ca2+ ions bound within the filter near the pore helix where they are coordinated by backbone oxygen atoms, a recurrent motif found in multiple proteins. The binding of Ca2+ ion in the selectivity filter controls the widening of the pore as shown in crystal structures and in molecular dynamics simulations. The structural, functional and computational data provide a characterization of this calcium-gated cationic channel.

  8. Krebs cycle metabolon: structural evidence of substrate channeling revealed by cross-linking and mass spectrometry.

    PubMed

    Wu, Fei; Minteer, Shelley

    2015-02-02

    It has been hypothesized that the high metabolic flux in the mitochondria is due to the self-assembly of enzyme supercomplexes (called metabolons) that channel substrates from one enzyme to another, but there has been no experimental confirmation of this structure or the channeling. A structural investigation of enzyme organization within the Krebs cycle metabolon was accomplished by in vivo cross-linking and mass spectrometry. Eight Krebs cycle enzyme components were isolated upon chemical fixation, and interfacial residues between mitochondrial malate dehydrogenase, citrate synthase, and aconitase were identified. Using constraint protein docking, a low-resolution structure for the three-enzyme complex was achieved, as well as the two-fold symmetric octamer. Surface analysis showed formation of electrostatic channeling upon protein-protein association, which is the first structural evidence of substrate channeling in the Krebs cycle metabolon. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Effects of Phenylalanine Substitutions in Gramicidin A on the Kinetics of Channel Formation in Vesicles and Channel Structure in SDS Micelles

    PubMed Central

    Jordan, J. B.; Easton, P. L.; Hinton, J. F.

    2005-01-01

    The common occurrence of Trp residues at the aqueous-lipid interface region of transmembrane channels is thought to be indicative of its importance for insertion and stabilization of the channel in membranes. To further investigate the effects of Trp→Phe substitution on the structure and function of the gramicidin channel, four analogs of gramicidin A have been synthesized in which the tryptophan residues at positions 9, 11, 13, and 15 are sequentially replaced with phenylalanine. The three-dimensional structure of each viable analog has been determined using a combination of two-dimensional NMR techniques and distance geometry-simulated annealing structure calculations. These phenylalanine analogs adopt a homodimer motif, consisting of two β6.3 helices joined by six hydrogen bonds at their NH2-termini. The replacement of the tryptophan residues does not have a significant effect on the backbone structure of the channels when compared to native gramicidin A, and only small effects are seen on side-chain conformations. Single-channel conductance measurements have shown that the conductance and lifetime of the channels are significantly affected by the replacement of the tryptophan residues (Wallace, 2000; Becker et al., 1991). The variation in conductance appears to be caused by the sequential removal of a tryptophan dipole, thereby removing the ion-dipole interaction at the channel entrance and at the ion binding site. Channel lifetime variations appear to be related to changing side chain-lipid interactions. This is supported by data relating to transport and incorporation kinetics. PMID:15501932

  10. Effects of phenylalanine substitutions in gramicidin A on the kinetics of channel formation in vesicles and channel structure in SDS micelles.

    PubMed

    Jordan, J B; Easton, P L; Hinton, J F

    2005-01-01

    The common occurrence of Trp residues at the aqueous-lipid interface region of transmembrane channels is thought to be indicative of its importance for insertion and stabilization of the channel in membranes. To further investigate the effects of Trp-->Phe substitution on the structure and function of the gramicidin channel, four analogs of gramicidin A have been synthesized in which the tryptophan residues at positions 9, 11, 13, and 15 are sequentially replaced with phenylalanine. The three-dimensional structure of each viable analog has been determined using a combination of two-dimensional NMR techniques and distance geometry-simulated annealing structure calculations. These phenylalanine analogs adopt a homodimer motif, consisting of two beta6.3 helices joined by six hydrogen bonds at their NH2-termini. The replacement of the tryptophan residues does not have a significant effect on the backbone structure of the channels when compared to native gramicidin A, and only small effects are seen on side-chain conformations. Single-channel conductance measurements have shown that the conductance and lifetime of the channels are significantly affected by the replacement of the tryptophan residues (Wallace, 2000; Becker et al., 1991). The variation in conductance appears to be caused by the sequential removal of a tryptophan dipole, thereby removing the ion-dipole interaction at the channel entrance and at the ion binding site. Channel lifetime variations appear to be related to changing side chain-lipid interactions. This is supported by data relating to transport and incorporation kinetics.

  11. Search for evidence of supersymmetry in the like-sign dimuon channel at the D0 experiment

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

    Yurkewicz, Adam

    2004-01-01

    Supersymmetry (SUSY) is a proposed symmetry between fermions and bosons. If this symmetry does exist, it is clearly broken since only half of the particle spectrum is observed. One model which provides a simple breaking mechanism is called minimal supergravity (mSUGRA) inspired SUSY. One clean final state predicted by this model is a trilepton final state from chargino and neutralino decays. In this analysis, these events are sought in 239±16 pb -1 of D0 Run II data by requiring like-sign dimuon pairs. Requiring only two muons increases the signal acceptance, and adding the like-sign requirement reduces the Standard Model backgroundmore » from Drell-Yan dimuon pairs and the various resonances in the dimuon spectrum. The reach into some parts of mSUGRA parameter space will be greater when searching with the like-sign dilepton final state than the trilepton final state. Combining results from a search in the like-sign dilepton channels with searches in the trilepton channels provides increased sensitivity in the search for supersymmetry. In this dissertation, the best-ever D limit on the total cross section for associated chargino and neutralino production with leptonic final states is presented.« less

  12. Stream channel erosion in a rapidly urbanizing region of the US-Mexico border: documenting importance of channel hardpoints with structure-from-motion

    USDA-ARS?s Scientific Manuscript database

    A combination of field surveys and Structure-from-Motion (SfM) techniques were used to document spatial patterns in stream channel geometry in a rapidly urbanizing watershed, Los Laureles Canyon (LLCW), in Tijuana, Mexico. Ground-based SfM was used to map channel dimensions with 10 cm vertical accur...

  13. Characteristics of camel-gate structures with active doping channel profiles

    NASA Astrophysics Data System (ADS)

    Tsai, Jung-Hui; Lour, Wen-Shiung; Laih, Lih-Wen; Liu, Rong-Chau; Liu, Wen-Chau

    1996-03-01

    In this paper, we demonstrate the influence of channel doping profile on the performances of camel-gate field effect transistors (CAMFETs). For comparison, single and tri-step doping channel structures with identical doping thickness products are employed, while other parameters are kept unchanged. The results of a theoretical analysis show that the single doping channel FET with lightly doping active layer has higher barrier height and drain-source saturation current. However, the transconductance is decreased. For a tri-step doping channel structure, it is found that the output drain-source saturation current and the barrier height are enhanced. Furthermore, the relatively voltage independent performances are improved. Two CAMFETs with single and tri-step doping channel structures have been fabricated and discussed. The devices exhibit nearly voltage independent transconductances of 144 mS mm -1 and 222 mS mm -1 for single and tri-step doping channel CAMFETs, respectively. The operation gate voltage may extend to ± 1.5 V for a tri-step doping channel CAMFET. In addition, the drain current densities of > 750 and 405 mA mm -1 are obtained for the tri-step and single doping CAMFETs. These experimental results are inconsistent with theoretical analysis.

  14. X-ray structure of the mammalian GIRK2-βγ G-protein complex

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

    Whorton, Matthew R.; MacKinnon, Roderick

    2013-07-30

    G-protein-gated inward rectifier K + (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5Å resolution crystal structure of the mammalian GIRK2 channel in complex with βγ G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K + channel activity. Short-range atomic and long-range electrostatic interactions stabilize four βγ G-protein subunits at the interfaces between four K + channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation thatmore » is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with ‘membrane delimited’ activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP 2) and intracellular Na + ions participate in multi-ligand regulation of GIRK channels.« less

  15. Tropical Pacific moisture variability: Its detection, synoptic structure and consequences in the general circulation

    NASA Technical Reports Server (NTRS)

    Mcguirk, James P.

    1990-01-01

    Satellite data analysis tools are developed and implemented for the diagnosis of atmospheric circulation systems over the tropical Pacific Ocean. The tools include statistical multi-variate procedures, a multi-spectral radiative transfer model, and the global spectral forecast model at NMC. Data include in-situ observations; satellite observations from VAS (moisture, infrared and visible) NOAA polar orbiters (including Tiros Operational Satellite System (TOVS) multi-channel sounding data and OLR grids) and scanning multichannel microwave radiometer (SMMR); and European Centre for Medium Weather Forecasts (ECHMWF) analyses. A primary goal is a better understanding of the relation between synoptic structures of the area, particularly tropical plumes, and the general circulation, especially the Hadley circulation. A second goal is the definition of the quantitative structure and behavior of all Pacific tropical synoptic systems. Finally, strategies are examined for extracting new and additional information from existing satellite observations. Although moisture structure is emphasized, thermal patterns are also analyzed. Both horizontal and vertical structures are studied and objective quantitative results are emphasized.

  16. Structural basis for the inhibition of voltage-dependent K+ channel by gating modifier toxin

    PubMed Central

    Ozawa, Shin-ichiro; Kimura, Tomomi; Nozaki, Tomohiro; Harada, Hitomi; Shimada, Ichio; Osawa, Masanori

    2015-01-01

    Voltage-dependent K+ (Kv) channels play crucial roles in nerve and muscle action potentials. Voltage-sensing domains (VSDs) of Kv channels sense changes in the transmembrane potential, regulating the K+-permeability across the membrane. Gating modifier toxins, which have been used for the functional analyses of Kv channels, inhibit Kv channels by binding to VSD. However, the structural basis for the inhibition remains elusive. Here, fluorescence and NMR analyses of the interaction between VSD derived from KvAP channel and its gating modifier toxin, VSTx1, indicate that VSTx1 recognizes VSD under depolarized condition. We identified the VSD-binding residues of VSTx1 and their proximal residues of VSD by the cross-saturation (CS) and amino acid selective CS experiments, which enabled to build a docking model of the complex. These results provide structural basis for the specific binding and inhibition of Kv channels by gating modifier toxins. PMID:26382304

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

    Moczydlowski, Edward G.

    Ion channel proteins regulate complex patterns of cellular electrical activity and ionic signaling. Certain K+ channels play an important role in immunological biodefense mechanisms of adaptive and innate immunity. Most ion channel proteins are oligomeric complexes with the conductive pore located at the central subunit interface. The long-term activity of many K+ channel proteins is dependent on the concentration of extracellular K+; however, the mechanism is unclear. Thus, this project focused on mechanisms underlying structural stability of tetrameric K+ channels. Using KcsA of Streptomyces lividans as a model K+ channel of known structure, the molecular basis of tetramer stability wasmore » investigated by: 1. Bioinformatic analysis of the tetramer interface. 2. Effect of two local anesthetics (lidocaine, tetracaine) on tetramer stability. 3. Molecular simulation of drug docking to the ion conduction pore. The results provide new insights regarding the structural stability of K+ channels and its possible role in cell physiology.« less

  18. Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel

    NASA Astrophysics Data System (ADS)

    Long, Stephen B.; Campbell, Ernest B.; MacKinnon, Roderick

    2005-08-01

    Voltage-dependent potassium ion (K+) channels (Kv channels) conduct K+ ions across the cell membrane in response to changes in the membrane voltage, thereby regulating neuronal excitability by modulating the shape and frequency of action potentials. Here we report the crystal structure, at a resolution of 2.9 angstroms, of a mammalian Kv channel, Kv1.2, which is a member of the Shaker K+ channel family. This structure is in complex with an oxido-reductase β subunit of the kind that can regulate mammalian Kv channels in their native cell environment. The activation gate of the pore is open. Large side portals communicate between the pore and the cytoplasm. Electrostatic properties of the side portals and positions of the T1 domain and β subunit are consistent with electrophysiological studies of inactivation gating and with the possibility of K+ channel regulation by the β subunit.

  19. Characterizing Nanoscale Transient Communication.

    PubMed

    Chen, Yifan; Anwar, Putri Santi; Huang, Limin; Asvial, Muhamad

    2016-04-01

    We consider the novel paradigm of nanoscale transient communication (NTC), where certain components of the small-scale communication link are physically transient. As such, the transmitter and the receiver may change their properties over a prescribed lifespan due to their time-varying structures. The NTC systems may find important applications in the biomedical, environmental, and military fields, where system degradability allows for benign integration into life and environment. In this paper, we analyze the NTC systems from the channel-modeling and capacity-analysis perspectives and focus on the stochastically meaningful slow transience scenario, where the coherence time of degeneration Td is much longer than the coding delay Tc. We first develop novel and parsimonious models to characterize the NTC channels, where three types of physical layers are considered: electromagnetism-based terahertz (THz) communication, diffusion-based molecular communication (DMC), and nanobots-assisted touchable communication (TouchCom). We then revisit the classical performance measure of ϵ-outage channel capacity and take a fresh look at its formulations in the NTC context. Next, we present the notion of capacity degeneration profile (CDP), which describes the reduction of channel capacity with respect to the degeneration time. Finally, we provide numerical examples to demonstrate the features of CDP. To the best of our knowledge, the current work represents a first attempt to systematically evaluate the quality of nanoscale communication systems deteriorating with time.

  20. Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain

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

    Worley, P.F.; Baraban, J.M.

    1987-05-01

    The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using (/sup 3/H)batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of (/sup 3/H)BTX-B to brain sections is dependent on potentiating allosteric interactions with scorpion venom and is displaced by BTX-B (Kd approximately 200 nM), aconitine, veratridine, and phenytoin with the same rank order of potencies as described in brain synaptosomes. The maximum number of (/sup 3/H)BTX-B binding sites in forebrain sections also agrees with biochemical determinations. Autoradiographic localizationsmore » indicate that (/sup 3/H)BTX-B binding sites are not restricted to cell bodies and axons but are present in synaptic zones throughout the brain. For example, a particularly dense concentration of these sites in the substantia nigra is associated with afferent terminals of the striatonigral projection. By contrast, myelinated structures possess much lower densities of binding sites. In addition, we present electrophysiological evidence that synaptic transmission, as opposed to axonal conduction, is preferentially sensitive to the action of aconitine and veratridine. Finally, the synaptic block produced by these sodium channel activators is inhibited by phenytoin and carbamazepine at therapeutic anticonvulsant concentrations.« less

  1. The robustness in dynamics of out of equilibrium bidirectional transport systems with constrained entrances

    NASA Astrophysics Data System (ADS)

    Sharma, Natasha; Verma, Atul Kumar; Gupta, Arvind Kumar

    2018-05-01

    Macroscopic and microscopic long-distance bidirectional transfer depends on connections between entrances and exits of various transport mediums. Persuaded by the associations, we introduce a small system module of Totally Asymmetric Simple Exclusion Process including oppositely directed species of particles moving on two parallel channels with constrained entrances. The dynamical rules which characterize the system obey symmetry between the two species and are identical for both the channels. The model displays a rich steady-state behavior, including symmetry breaking phenomenon. The phase diagram is analyzed theoretically within the mean-field approximation and substantiated with Monte Carlo simulations. Relevant mean-field calculations are also presented. We further compared the phase segregation with those observed in previous works, and it is examined that the structure of phase separation in proposed model is distinguished from earlier ones. Interestingly, for phases with broken symmetry, symmetry with respect to channels has been observed as the distinct particles behave differently while the similar type of particles exhibits the same conduct in the system. For symmetric phases, significant properties including currents and densities in the channels are identical for both types of particles. The effect of symmetry breaking occurrence on the Monte Carlo simulation results has also been examined based on particle density histograms. Finally, phase properties of the system having strong size dependency have been explored based on simulations findings.

  2. Brownian Dynamics Simulations of Ion Transport through the VDAC

    PubMed Central

    Lee, Kyu Il; Rui, Huan; Pastor, Richard W.; Im, Wonpil

    2011-01-01

    It is important to gain a physical understanding of ion transport through the voltage-dependent anion channel (VDAC) because this channel provides primary permeation pathways for metabolites and electrolytes between the cytosol and mitochondria. We performed grand canonical Monte Carlo/Brownian dynamics (GCMC/BD) simulations to explore the ion transport properties of human VDAC isoform 1 (hVDAC1; PDB:2K4T) embedded in an implicit membrane. When the MD-derived, space-dependent diffusion constant was used in the GCMC/BD simulations, the current-voltage characteristics and ion number profiles inside the pore showed excellent agreement with those calculated from all-atom molecular-dynamics (MD) simulations, thereby validating the GCMC/BD approach. Of the 20 NMR models of hVDAC1 currently available, the third one (NMR03) best reproduces both experimental single-channel conductance and ion selectivity (i.e., the reversal potential). In addition, detailed analyses of the ion trajectories, one-dimensional multi-ion potential of mean force, and protein charge distribution reveal that electrostatic interactions play an important role in the channel structure and ion transport relationship. Finally, the GCMC/BD simulations of various mutants based on NMR03 show good agreement with experimental ion selectivity. The difference in ion selectivity between the wild-type and the mutants is the result of altered potential of mean force profiles that are dominated by the electrostatic interactions. PMID:21281575

  3. Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels

    PubMed Central

    Riera, CE; Menozzi-Smarrito, C; Affolter, M; Michlig, S; Munari, C; Robert, F; Vogel, H; Simon, SA; le Coutre, J

    2009-01-01

    Background and purpose: Oily extracts of Sichuan and Melegueta peppers evoke pungent sensations mediated by different alkylamides [mainly hydroxy-α-sanshool (α-SOH)] and hydroxyarylalkanones (6-shogaol and 6-paradol). We assessed how transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (TRPV1), two chemosensory ion channels, participate in these pungent sensations. Experimental approach: The structure–activity relationships of these molecules on TRPA1 and TRPV1 was measured by testing natural and synthetic analogues using calcium and voltage imaging on dissociated dorsal root ganglia neurons and human embryonic kidney 293 cells expressing the wild-type channels or specific cysteine mutants using glutathione trapping as a model to probe TRPA1 activation. In addition, using Trpv1 knockout mice, the compounds' aversive responses were measured in a taste brief-access test. Key results: For TRPA1 activation, the cis C6 double bond in the polyenic chain of α-SOH was critical, whereas no structural specificity was required for activation of TRPV1. Both 6-shogaol and 6-paradol were found to activate TRPV1 and TRPA1 channels, whereas linalool, an abundant terpene in Sichuan pepper, activated TRPA1 but not TRPV1 channels. Alkylamides and 6-shogaol act on TRPA1 by covalent bonding whereas none of these compounds activated TRPV1 through such interactions. Finally, TRPV1 mutant mice retained sensitivity to 6-shogaol but were not responsive to α-SOH. Conclusions and implications: The pungent nature of components of Sichuan and Melegueta peppers was mediated via interactions with TRPA1 and TRPV1 channels and may explain the aversive properties of these compounds. PMID:19594761

  4. Cadmium-cysteine coordination in the BK inner pore region and its structural and functional implications.

    PubMed

    Zhou, Yu; Xia, Xiao-Ming; Lingle, Christopher J

    2015-04-21

    To probe structure and gating-associated conformational changes in BK-type potassium (BK) channels, we examined consequences of Cd(2+) coordination with cysteines introduced at two positions in the BK inner pore. At V319C, the equivalent of valine in the conserved Kv proline-valine-proline (PVP) motif, Cd(2+) forms intrasubunit coordination with a native glutamate E321, which would place the side chains of V319C and E321 much closer together than observed in voltage-dependent K(+) (Kv) channel structures, requiring that the proline between V319C and E321 introduces a kink in the BK S6 inner helix sharper than that observed in Kv channel structures. At inner pore position A316C, Cd(2+) binds with modest state dependence, suggesting the absence of an ion permeation gate at the cytosolic side of BK channel. These results highlight fundamental structural differences between BK and Kv channels in their inner pore region, which likely underlie differences in voltage-dependent gating between these channels.

  5. Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel

    PubMed Central

    2017-01-01

    For those interested in the machinery of ion channel gating, the Ca2+ and voltage-activated BK K+ channel provides a compelling topic for investigation, by virtue of its dual allosteric regulation by both voltage and intracellular Ca2+ and because its large-single channel conductance facilitates detailed kinetic analysis. Over the years, biophysical analyses have illuminated details of the allosteric regulation of BK channels and revealed insights into the mechanism of BK gating, e.g., inner cavity size and accessibility and voltage sensor-pore coupling. Now the publication of two structures of an Aplysia californica BK channel—one liganded and one metal free—promises to reinvigorate functional studies and interpretation of biophysical results. The new structures confirm some of the previous functional inferences but also suggest new perspectives regarding cooperativity between Ca2+-binding sites and the relationship between voltage- and Ca2+-dependent gating. Here we consider the extent to which the two structures explain previous functional data on pore-domain properties, voltage-sensor motions, and divalent cation binding and activation of the channel. PMID:29025867

  6. Coincidence studies of diffraction structures in binary encounter electron spectra

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

    Liao, C.; Hagmann, S.; Richard, P.

    The authors have measured binary encounter electron (BEe) production in collisions of 0.3 MeV/u Cu{sup q+} (q=4,12) projectiles on H{sub 2} targets from 0 to 70 degrees with respect to the beam direction. Prominent features are the appearance of the BEe peak splitting and a very strong forward peaked angular distribution which are attributed to the diffractive scattering of the quasifree target electrons in the short range potential of the projectile. Using electron-projectile final charge state coincidence techniques, different collision reaction channels can be separated. Measurements of this type are being pursued.

  7. Beamforming strategy of ULA and UCA sensor configuration in multistatic passive radar

    NASA Astrophysics Data System (ADS)

    Hossa, Robert

    2009-06-01

    A Beamforming Network (BN) concept of Uniform Linear Array (ULA) and Uniform Circular Array (UCA) dipole configuration designed to multistatic passive radar is considered in details. In the case of UCA configuration, computationally efficient procedure of beamspace transformation from UCA to virtual ULA configuration with omnidirectional coverage is utilized. If effect, the idea of the proposed solution is equivalent to the techniques of antenna array factor shaping dedicated to ULA structure. Finally, exemplary results from the computer software simulations of elaborated spatial filtering solutions to reference and surveillance channels are provided and discussed.

  8. Maximum aposteriori joint source/channel coding

    NASA Technical Reports Server (NTRS)

    Sayood, Khalid; Gibson, Jerry D.

    1991-01-01

    A maximum aposteriori probability (MAP) approach to joint source/channel coder design is presented in this paper. This method attempts to explore a technique for designing joint source/channel codes, rather than ways of distributing bits between source coders and channel coders. For a nonideal source coder, MAP arguments are used to design a decoder which takes advantage of redundancy in the source coder output to perform error correction. Once the decoder is obtained, it is analyzed with the purpose of obtaining 'desirable properties' of the channel input sequence for improving overall system performance. Finally, an encoder design which incorporates these properties is proposed.

  9. ZnO-based multiple channel and multiple gate FinMOSFETs

    NASA Astrophysics Data System (ADS)

    Lee, Ching-Ting; Huang, Hung-Lin; Tseng, Chun-Yen; Lee, Hsin-Ying

    2016-02-01

    In recent years, zinc oxide (ZnO)-based metal-oxide-semiconductor field-effect transistors (MOSFETs) have attracted much attention, because ZnO-based semiconductors possess several advantages, including large exciton binding energy, nontoxicity, biocompatibility, low material cost, and wide direct bandgap. Moreover, the ZnO-based MOSFET is one of most potential devices, due to the applications in microwave power amplifiers, logic circuits, large scale integrated circuits, and logic swing. In this study, to enhance the performances of the ZnO-based MOSFETs, the ZnObased multiple channel and multiple gate structured FinMOSFETs were fabricated using the simple laser interference photolithography method and the self-aligned photolithography method. The multiple channel structure possessed the additional sidewall depletion width control ability to improve the channel controllability, because the multiple channel sidewall portions were surrounded by the gate electrode. Furthermore, the multiple gate structure had a shorter distance between source and gate and a shorter gate length between two gates to enhance the gate operating performances. Besides, the shorter distance between source and gate could enhance the electron velocity in the channel fin structure of the multiple gate structure. In this work, ninety one channels and four gates were used in the FinMOSFETs. Consequently, the drain-source saturation current (IDSS) and maximum transconductance (gm) of the ZnO-based multiple channel and multiple gate structured FinFETs operated at a drain-source voltage (VDS) of 10 V and a gate-source voltage (VGS) of 0 V were respectively improved from 11.5 mA/mm to 13.7 mA/mm and from 4.1 mS/mm to 6.9 mS/mm in comparison with that of the conventional ZnO-based single channel and single gate MOSFETs.

  10. 75 FR 22524 - Ocean Dumping; Designation of Ocean Dredged Material Disposal Sites Offshore of the Siuslaw River...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... location to dispose of material dredged from the Siuslaw River navigation channel, and to provide a... sediments from Site A back into the dredged channel resulted in a selection of disposal Sites B and C by the... conflicts. The final Sites are located close to the approach to the Siuslaw River entrance channel but are...

  11. 77 FR 46024 - Purified Carboxymethylcellulose From the Netherlands: Preliminary Results of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-02

    ... the invoice date as the date of sale for the home market and one of the U.S. market channels of distribution (i.e., U.S. market Channel 2) because the date of invoice reflects the date on which the material terms of sale were finalized. For Akzo Nobel's other U.S. market channel of distribution (i.e., U.S...

  12. Demystifying Mechanosensitive Piezo Ion Channels.

    PubMed

    Xu, X Z Shawn

    2016-06-01

    Mechanosensitive channels mediate touch, hearing, proprioception, and blood pressure regulation. Piezo proteins, including Piezo1 and Piezo2, represent a new class of mechanosensitive channels that have been reported to play key roles in most, if not all, of these modalities. The structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels, however, remain mysterious. Two new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel.

  13. Model microswimmers in channels with varying cross section

    NASA Astrophysics Data System (ADS)

    Malgaretti, Paolo; Stark, Holger

    2017-05-01

    We study different types of microswimmers moving in channels with varying cross section and thereby interacting hydrodynamically with the channel walls. Starting from the Smoluchowski equation for a dilute suspension, for which interactions among swimmers can be neglected, we derive analytic expressions for the lateral probability distribution between plane channel walls. For weakly corrugated channels, we extend the Fick-Jacobs approach to microswimmers and thereby derive an effective equation for the probability distribution along the channel axis. Two regimes arise dominated either by entropic forces due to the geometrical confinement or by the active motion. In particular, our results show that the accumulation of microswimmers at channel walls is sensitive to both the underlying swimming mechanism and the geometry of the channels. Finally, for asymmetric channel corrugation, our model predicts a rectification of microswimmers along the channel, the strength and direction of which strongly depends on the swimmer type.

  14. Spatially dependent responses of a large-river fish assemblage to bank stabilization and side channels

    USGS Publications Warehouse

    Reinhold, Ann Marie; Bramblett, Robert G.; Zale, Alexander V.; Poole, Geoffrey C.; Roberts, David W.

    2017-01-01

    The alteration of rivers by anthropogenic bank stabilization to prevent the erosion of economically valuable lands and structures has become commonplace. However, such alteration has ambiguous consequences for fish assemblages, especially in large rivers. Because most large, temperate rivers have impoundments, it can be difficult to separate the influences of bank stabilization structures from those of main-stem impoundments, especially because both stabilization structures and impoundments can cause side-channel loss. Few large rivers are free flowing and retain extensive side channels, but the Yellowstone River (our study area) is one such river. We hypothesized that in this river (1) bank stabilization has changed fish assemblage structure by altering habitats, (2) side-channel availability has influenced fish assemblage structure by providing habitat heterogeneity, and (3) the influences of bank stabilization and side channels on fish assemblages were spatially scale dependent. We developed a spatially explicit framework to test these hypotheses. Fish assemblage structure varied with the extent of bank stabilization and the availability of side channels; however, not all assemblage subsets were influenced. Nevertheless, bank stabilization and side channels had different and sometimes opposite influences on the fish assemblage. The effects of side channels on fish were more consistent and widespread than those of bank stabilization; the catches of more fishes were positively correlated with side-channel availability than with the extent of bank stabilization. The influences of bank stabilization and side channels on the relative abundances of fish also varied, depending on species and river bend geomorphology. The variation in river morphology probably contributed to the assemblage differences between stabilized and reference river bends; stabilized alluvial pools were deeper than reference alluvial pools, but the depths of stabilized and reference bluff pools did not differ. The strengths of the relationships among fish assemblages, bank stabilization, and side channels were spatially scale dependent; optimum spatial scales ranged from less than 200 m to 3,200 m up- and downstream, suggesting that bank stabilization and side channels influenced fish assemblages across multiple spatial scales.

  15. QUANTIFYING STREAM STRUCTURAL PHYSICAL HABITAT ATTRIBUTES USING LIDAR AND HYPERSPECTRAL IMAGERY

    EPA Science Inventory

    Structural physical habitat attributes include indices of stream size, channel gradient, substrate size, habitat complexity and cover, riparian vegetation cover and structure, anthropogenic disturbances and channel-riparian interaction.

  16. Progress on Discrete Fracture Network models with implications on the predictions of permeability and flow channeling structure

    NASA Astrophysics Data System (ADS)

    Darcel, C.; Davy, P.; Le Goc, R.; Maillot, J.; Selroos, J. O.

    2017-12-01

    We present progress on Discrete Fracture Network (DFN) flow modeling, including realistic advanced DFN spatial structures and local fracture transmissivity properties, through an application to the Forsmark site in Sweden. DFN models are a framework to combine fracture datasets from different sources and scales and to interpolate them in combining statistical distributions and stereological relations. The resulting DFN upscaling function - size density distribution - is a model component key to extrapolating fracture size densities between data gaps, from borehole core up to site scale. Another important feature of DFN models lays in the spatial correlations between fractures, with still unevaluated consequences on flow predictions. Indeed, although common Poisson (i.e. spatially random) models are widely used, they do not reflect these geological evidences for more complex structures. To model them, we define a DFN growth process from kinematic rules for nucleation, growth and stopping conditions. It mimics in a simplified way the geological fracturing processes and produces DFN characteristics -both upscaling function and spatial correlations- fully consistent with field observations. DFN structures are first compared for constant transmissivities. Flow simulations for the kinematic and equivalent Poisson DFN models show striking differences: with the kinematic DFN, connectivity and permeability are significantly smaller, down to a difference of one order of magnitude, and flow is much more channelized. Further flow analyses are performed with more realistic transmissivity distribution conditions (sealed parts, relations to fracture sizes, orientations and in-situ stress field). The relative importance of the overall DFN structure in the final flow predictions is discussed.

  17. New insights on hereditary erythrocyte membrane defects.

    PubMed

    Andolfo, Immacolata; Russo, Roberta; Gambale, Antonella; Iolascon, Achille

    2016-11-01

    After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the intervening years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarizes the main features of erythrocyte membrane disorders, dividing them into structural and altered permeability defects, focusing particularly on the most recent advances. New proteins involved in alterations of the red blood cell membrane permeability were recently described. The mechanoreceptor PIEZO1 is the largest ion channel identified to date, the fundamental regulator of erythrocyte volume homeostasis. Missense, gain-of-function mutations in the PIEZO1 gene have been identified in several families as causative of dehydrated hereditary stomatocytosis or xerocytosis. Similarly, the KCNN4 gene, codifying the so called Gardos channel, has been recently identified as a second causative gene of hereditary xerocytosis. Finally, ABCB6 missense mutations were identified in different pedigrees of familial pseudohyperkalemia. New genomic technologies have improved the quality and reduced the time of diagnosis of these diseases. Moreover, they are essential for the identification of the new causative genes. However, many questions remain to solve, and are currently objects of intensive studies. Copyright© Ferrata Storti Foundation.

  18. New insights on hereditary erythrocyte membrane defects

    PubMed Central

    Andolfo, Immacolata; Russo, Roberta; Gambale, Antonella; Iolascon, Achille

    2016-01-01

    After the first proposed model of the red blood cell membrane skeleton 36 years ago, several additional proteins have been discovered during the intervening years, and their relationship with the pathogenesis of the related disorders have been somewhat defined. The knowledge of erythrocyte membrane structure is important because it represents the model for spectrin-based membrane skeletons in all cells and because defects in its structure underlie multiple hemolytic anemias. This review summarizes the main features of erythrocyte membrane disorders, dividing them into structural and altered permeability defects, focusing particularly on the most recent advances. New proteins involved in alterations of the red blood cell membrane permeability were recently described. The mechanoreceptor PIEZO1 is the largest ion channel identified to date, the fundamental regulator of erythrocyte volume homeostasis. Missense, gain-of-function mutations in the PIEZO1 gene have been identified in several families as causative of dehydrated hereditary stomatocytosis or xerocytosis. Similarly, the KCNN4 gene, codifying the so called Gardos channel, has been recently identified as a second causative gene of hereditary xerocytosis. Finally, ABCB6 missense mutations were identified in different pedigrees of familial pseudohyperkalemia. New genomic technologies have improved the quality and reduced the time of diagnosis of these diseases. Moreover, they are essential for the identification of the new causative genes. However, many questions remain to solve, and are currently objects of intensive studies. PMID:27756835

  19. Synthesis of Novel 1,4- Dihydropyridine Derivatives Bearing Biphenyl-2'-Tetrazole Substitution as Potential Dual Angiotensin II Receptors and Calcium Channel Blockers

    PubMed Central

    Shahbazi Mojarrad, Javid; Zamani, Zahra; Nazemiyeh, Hossein; Ghasemi, Saeed; Asgari, Davoud

    2011-01-01

    Introduction: We report the synthesis of novel 1,4-dihydropyridine derivatives containing biphenyl-2'-tetrazole moieties. We hypothesized that merging the key structural elements present in an AT1 receptor antagonist with key structural elements in 1,4-dihydropyridine calcium channel blockers would yield novel analogs with potential dual activity for both receptors. This strategy led to the design and synthesis of dialkyl 1,4-dihydro-2,6-dimethyl-4-[2-n-alkyl-1-[2΄-(1H-tetrazole-5-yl) biphenyl -4-yl] methyl] imidazole-4(or 5)-yl]- 3, 5-pyridinedicarboxylate analogs. Methods: These compounds were obtained by two methods starting from biphenyltetrazolyl-4-(or 5)-imidazolecarboxaldehyde intermediates employing in classical Hantzsch condensation reaction. In the first method, triphenylmethyl protecting group of 4- or 5-carboxaldehyde intermediate was first removed in acidic media and then classical Hantzsch reaction was employed in order to obtain the final products. In the second method, without further deprotection process, protected 4- or 5-carboxaldehyde intermediate directly was used in Hantzsch reaction. Results: The second method was more efficient than the first method since the deprotection and ring closure reaction occurs simultaneously in one pot. Conclusion: Eight novel dihydropridines analogs were synthesized using classic Hantzsch condensation reaction. Chemical structures of the compounds were characterized by 1H NMR, infrared and mass spectroscopy. PMID:24312750

  20. Probing structural features of Alzheimer's amyloid-β pores in bilayers using site-specific amino acid substitutions.

    PubMed

    Capone, Ricardo; Jang, Hyunbum; Kotler, Samuel A; Kagan, Bruce L; Nussinov, Ruth; Lal, Ratnesh

    2012-01-24

    A current hypothesis for the pathology of Alzheimer's disease (AD) proposes that amyloid-β (Aβ) peptides induce uncontrolled, neurotoxic ion flux across cellular membranes. The mechanism of ion flux is not fully understood because no experiment-based Aβ channel structures at atomic resolution are currently available (only a few polymorphic states have been predicted by computational models). Structural models and experimental evidence lend support to the view that the Aβ channel is an assembly of loosely associated mobile β-sheet subunits. Here, using planar lipid bilayers and molecular dynamics (MD) simulations, we show that amino acid substitutions can be used to infer which residues are essential for channel structure. We created two Aβ(1-42) peptides with point mutations: F19P and F20C. The substitution of Phe19 with Pro inhibited channel conductance. MD simulation suggests a collapsed pore of F19P channels at the lower bilayer leaflet. The kinks at the Pro residues in the pore-lining β-strands induce blockage of the solvated pore by the N-termini of the chains. The cysteine mutant is capable of forming channels, and the conductance behavior of F20C channels is similar to that of the wild type. Overall, the mutational analysis of the channel activity performed in this work tests the proposition that the channels consist of a β-sheet rich organization, with the charged/polar central strand containing the mutation sites lining the pore, and the C-terminal strands facing the hydrophobic lipid tails. A detailed understanding of channel formation and its structure should aid studies of drug design aiming to control unregulated Aβ-dependent ion fluxes.

  1. Probing Structural Features of Alzheimer’s Amyloid-β Pores in Bilayers Using Site-Specific Amino Acid Substitutions

    PubMed Central

    2012-01-01

    A current hypothesis for the pathology of Alzheimer’s disease (AD) proposes that amyloid-β (Aβ) peptides induce uncontrolled, neurotoxic ion flux across cellular membranes. The mechanism of ion flux is not fully understood because no experiment-based Aβ channel structures at atomic resolution are currently available (only a few polymorphic states have been predicted by computational models). Structural models and experimental evidence lend support to the view that the Aβ channel is an assembly of loosely associated mobile β-sheet subunits. Here, using planar lipid bilayers and molecular dynamics (MD) simulations, we show that amino acid substitutions can be used to infer which residues are essential for channel structure. We created two Aβ1–42 peptides with point mutations: F19P and F20C. The substitution of Phe19 with Pro inhibited channel conductance. MD simulation suggests a collapsed pore of F19P channels at the lower bilayer leaflet. The kinks at the Pro residues in the pore-lining β-strands induce blockage of the solvated pore by the N-termini of the chains. The cysteine mutant is capable of forming channels, and the conductance behavior of F20C channels is similar to that of the wild type. Overall, the mutational analysis of the channel activity performed in this work tests the proposition that the channels consist of a β-sheet rich organization, with the charged/polar central strand containing the mutation sites lining the pore, and the C-terminal strands facing the hydrophobic lipid tails. A detailed understanding of channel formation and its structure should aid studies of drug design aiming to control unregulated Aβ-dependent ion fluxes. PMID:22242635

  2. Contribution of S4 segments and S4-S5 linkers to the low-voltage activation properties of T-type CaV3.3 channels.

    PubMed

    Sanchez-Sandoval, Ana Laura; Herrera Carrillo, Zazil; Díaz Velásquez, Clara Estela; Delgadillo, Dulce María; Rivera, Heriberto Manuel; Gomora, Juan Carlos

    2018-01-01

    Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30-40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers.

  3. The dynamics of bedrock channel adjustment: Modeling the influence of sediment supply, weathering, and lithology on channel cross-sectional and longitudinal shape

    NASA Astrophysics Data System (ADS)

    Wobus, C.; Tucker, G.; Anderson, R.; Kean, J.; Small, E.; Hancock, G.

    2007-12-01

    The cross-sectional form of a natural river channel controls the capacity of the system to carry water off a landscape, to convey sediment derived from hillslopes, and to erode its bed and banks. Numerical models that describe the response of a landscape to changes in climate or tectonics therefore require formulations that can accommodate changes in channel cross-sectional geometry through time. We have developed a 2D numerical model that computes the formation of a channel in a cohesive, detachment-limited substrate subject to steady, unidirectional flow. Boundary shear stress is calculated using a simple approximation of the flow field in which log-velocity profiles are assumed to apply along vectors that are perpendicular to the local boundary surface. The resulting model predictions for the velocity structure, peak boundary shear stress, and equilibrium channel shape compare well with the predictions of a more sophisticated but more computationally demanding ray-isovel model. For example, the mean velocities computed by the two models are consistent to within ~3%, and the predicted peak shear stress is consistent to within ~7%. The efficiency of our model makes it suitable for calculations of long-term morphologic change both in single cross-sections and in series of cross-sections arrayed downstream. For a uniform substrate, the model predicts a strong tendency toward a fixed width-to-depth ratio, regardless of gradient or discharge. The model predicts power-law relationships between width and discharge with an exponent near 2/5, and between width and gradient with an exponent near -1/5. Recent enhancements to the model include the addition of sediment, which increases the width-to-depth ratio at steady state by favoring erosion of the channel walls relative to the channel bed (the "cover effect"). Inclusion of a probability density function of discharges with a simple parameterization of weathering along channel banks leads to the formation of model strath terraces. Downstream changes in substrate erodibility or tectonic uplift rate lead to step-function changes in channel width, consistent with empirical observations. Finally, explicit inclusion of bedload transport allows channel width, gradient, and the pattern of sediment flux to evolve dynamically, allowing us to explore the response of bedrock channels to both spatial patterns of rock uplift, and temporal variations in sediment input.

  4. Contribution of S4 segments and S4-S5 linkers to the low-voltage activation properties of T-type CaV3.3 channels

    PubMed Central

    Sanchez-Sandoval, Ana Laura; Herrera Carrillo, Zazil; Díaz Velásquez, Clara Estela; Delgadillo, Dulce María; Rivera, Heriberto Manuel

    2018-01-01

    Voltage-gated calcium channels contain four highly conserved transmembrane helices known as S4 segments that exhibit a positively charged residue every third position, and play the role of voltage sensing. Nonetheless, the activation range between high-voltage (HVA) and low-voltage (LVA) activated calcium channels is around 30–40 mV apart, despite the high level of amino acid similarity within their S4 segments. To investigate the contribution of S4 voltage sensors for the low-voltage activation characteristics of CaV3.3 channels we constructed chimeras by swapping S4 segments between this LVA channel and the HVA CaV1.2 channel. The substitution of S4 segment of Domain II in CaV3.3 by that of CaV1.2 (chimera IIS4C) induced a ~35 mV shift in the voltage-dependence of activation towards positive potentials, showing an I-V curve that almost overlaps with that of CaV1.2 channel. This HVA behavior induced by IIS4C chimera was accompanied by a 2-fold decrease in the voltage-dependence of channel gating. The IVS4 segment had also a strong effect in the voltage sensing of activation, while substitution of segments IS4 and IIIS4 moved the activation curve of CaV3.3 to more negative potentials. Swapping of IIS4 voltage sensor influenced additional properties of this channel such as steady-state inactivation, current decay, and deactivation. Notably, Domain I voltage sensor played a major role in preventing CaV3.3 channels to inactivate from closed states at extreme hyperpolarized potentials. Finally, site-directed mutagenesis in the CaV3.3 channel revealed a partial contribution of the S4-S5 linker of Domain II to LVA behavior, with synergic effects observed in double and triple mutations. These findings indicate that IIS4 and, to a lesser degree IVS4, voltage sensors are crucial in determining the LVA properties of CaV3.3 channels, although the accomplishment of this function involves the participation of other structural elements like S4-S5 linkers. PMID:29474447

  5. Physical Immobilization Liposomes in Uniform Zwitterionic Microgel Particles Fabricated in Microcapillary Device

    NASA Astrophysics Data System (ADS)

    Jeong, Eun Seon; Byun, Aram; Kim, Jin Woong

    2014-03-01

    Lipid molecules have both hydrophilic and hydrophobic properties. Since their packing parameter ranges from 0.5 to 1, they self-assemble to form a vesicle structure, liposome. Thanks to the vesicle structure, liposome is able to encapsulate both hydrophilic and hydrophobic active ingredients, thus widening its applicability to pharmaceutical, cosmetic, and food industry. However, its vesicular structure is readily transferred to micelle in the presence of amphiphilic additives with low packing parameters. Therefore, it is critical to developing a technique to overcome this drawback. This study introduces a microfluidic approach to physically immobilize liposome in microgel particles. For this, we generate a uniform liposome-in-oil-in-water emulsion in a capillary-based microfluidic device. Basically, we observe how the flows in micro-channels affect generation of embryo emulsion drops. Then, the uniform emulsion is solidified by using photo-polymerization. Finally, we characterize the particle morphology, membrane fluidity, and mesh property, encapsulation efficiency and releasing.

  6. The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel.

    PubMed

    Minor, D L; Lin, Y F; Mobley, B C; Avelar, A; Jan, Y N; Jan, L Y; Berger, J M

    2000-09-01

    Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the closed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.

  7. A two-dimensional analytical modeling for channel potential and threshold voltage of short channel triple material symmetrical gate Stack (TMGS) DG-MOSFET

    NASA Astrophysics Data System (ADS)

    Tripathi, Shweta

    2016-10-01

    In the present work, a two-dimensional (2D) analytical framework of triple material symmetrical gate stack (TMGS) DG-MOSFET is presented in order to subdue the short channel effects. A lightly doped channel along with triple material gate having different work functions and symmetrical gate stack structure, showcases substantial betterment in quashing short channel effects to a good extent. The device functioning amends in terms of improved exemption to threshold voltage roll-off, thereby suppressing the short channel effects. The encroachments of respective device arguments on the threshold voltage of the proposed structure are examined in detail. The significant outcomes are compared with the numerical simulation data obtained by using 2D ATLAS™ device simulator to affirm and formalize the proposed device structure.

  8. Landslide oil field, San Joaquin Valley, California

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

    Collins, B.P.; March, K.A.; Caballero, J.S.

    1988-03-01

    The Landslide field, located at the southern margin of the San Joaquin basin, was discovered in 1985 by a partnership headed by Channel Exploration Company, on a farm out from Tenneco Oil Company. Initial production from the Tenneco San Emidio 63X-30 was 2064 BOPD, making landslide one of the largest onshore discoveries in California during the past decade. Current production is 7100 BOPD from a sandstone reservoir at 12,500 ft. Fifteen wells have been drilled in the field, six of which are water injectors. Production from the Landslide field occurs from a series of upper Miocene Stevens turbidite sandstones thatmore » lie obliquely across an east-plunging structural nose. These turbidite sandstones were deposited as channel-fill sequences within a narrowly bounded levied channel complex. Both the Landslide field and the larger Yowlumne field, located 3 mi to the northwest, comprise a single channel-fan depositional system that developed in the restricted deep-water portion of the San Joaquin basin. Information from the open-hole logs, three-dimensional surveys, vertical seismic profiles, repeat formation tester data, cores, and pressure buildup tests allowed continuous drilling from the initial discovery to the final waterflood injector, without a single dry hole. In addition, the successful application of three-dimensional seismic data in the Landslide development program has helped correctly image channel-fan anomalies in the southern Maricopa basin, where data quality and severe velocity problems have hampered previous efforts. New exploration targets are currently being evaluated on the acreage surrounding the Landslide discovery and should lead to an interesting new round of drilling activity in the Maricopa basin.« less

  9. EUV high resolution imager on-board solar orbiter: optical design and detector performances

    NASA Astrophysics Data System (ADS)

    Halain, J. P.; Mazzoli, A.; Rochus, P.; Renotte, E.; Stockman, Y.; Berghmans, D.; BenMoussa, A.; Auchère, F.

    2017-11-01

    The EUV high resolution imager (HRI) channel of the Extreme Ultraviolet Imager (EUI) on-board Solar Orbiter will observe the solar atmospheric layers at 17.4 nm wavelength with a 200 km resolution. The HRI channel is based on a compact two mirrors off-axis design. The spectral selection is obtained by a multilayer coating deposited on the mirrors and by redundant Aluminum filters rejecting the visible and infrared light. The detector is a 2k x 2k array back-thinned silicon CMOS-APS with 10 μm pixel pitch, sensitive in the EUV wavelength range. Due to the instrument compactness and the constraints on the optical design, the channel performance is very sensitive to the manufacturing, alignments and settling errors. A trade-off between two optical layouts was therefore performed to select the final optical design and to improve the mirror mounts. The effect of diffraction by the filter mesh support and by the mirror diffusion has been included in the overall error budget. Manufacturing of mirror and mounts has started and will result in thermo-mechanical validation on the EUI instrument structural and thermal model (STM). Because of the limited channel entrance aperture and consequently the low input flux, the channel performance also relies on the detector EUV sensitivity, readout noise and dynamic range. Based on the characterization of a CMOS-APS back-side detector prototype, showing promising results, the EUI detector has been specified and is under development. These detectors will undergo a qualification program before being tested and integrated on the EUI instrument.

  10. Photodissociation of the carbon monoxide dication in the {sup 3}Σ{sup −} manifold: Quantum control simulation towards the C{sup 2+} + O channel

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

    Vranckx, S.; Laboratoire de Chimie Physique; Loreau, J.

    The photodissociation and laser assisted dissociation of the carbon monoxide dication X{sup 3}Π CO{sup 2+} into the {sup 3}Σ{sup −} states are investigated. Ab initio electronic structure calculations of the adiabatic potential energy curves, radial nonadiabatic couplings, and dipole moments for the X {sup 3}Π state are performed for 13 excited {sup 3}Σ{sup −} states of CO{sup 2+}. The photodissociation cross section, calculated by time-dependent methods, shows that the C{sup +} + O{sup +} channels dominate the process in the studied energy range. The carbon monoxide dication CO{sup 2+} is an interesting candidate for control because it can be producedmore » in a single, long lived, v = 0 vibrational state due to the instability of all the other excited vibrational states of the ground {sup 3}Π electronic state. In a spectral range of about 25 eV, perpendicular transition dipoles couple this {sup 3}Π state to a manifold of {sup 3}Σ{sup −} excited states leading to numerous C{sup +} + O{sup +} channels and a single C{sup 2+} + O channel. This unique channel is used as target for control calculations using local control theory. We illustrate the efficiency of this method in order to find a tailored electric field driving the photodissociation in a manifold of strongly interacting electronic states. The selected local pulses are then concatenated in a sequence inspired by the “laser distillation” strategy. Finally, the local pulse is compared with optimal control theory.« less

  11. Strings on a Violin: Location Dependence of Frequency Tuning in Active Dendrites.

    PubMed

    Das, Anindita; Rathour, Rahul K; Narayanan, Rishikesh

    2017-01-01

    Strings on a violin are tuned to generate distinct sound frequencies in a manner that is firmly dependent on finger location along the fingerboard. Sound frequencies emerging from different violins could be very different based on their architecture, the nature of strings and their tuning. Analogously, active neuronal dendrites, dendrites endowed with active channel conductances, are tuned to distinct input frequencies in a manner that is dependent on the dendritic location of the synaptic inputs. Further, disparate channel expression profiles and differences in morphological characteristics could result in dendrites on different neurons of the same subtype tuned to distinct frequency ranges. Alternately, similar location-dependence along dendritic structures could be achieved through disparate combinations of channel profiles and morphological characteristics, leading to degeneracy in active dendritic spectral tuning. Akin to strings on a violin being tuned to different frequencies than those on a viola or a cello, different neuronal subtypes exhibit distinct channel profiles and disparate morphological characteristics endowing each neuronal subtype with unique location-dependent frequency selectivity. Finally, similar to the tunability of musical instruments to elicit distinct location-dependent sounds, neuronal frequency selectivity and its location-dependence are tunable through activity-dependent plasticity of ion channels and morphology. In this morceau, we explore the origins of neuronal frequency selectivity, and survey the literature on the mechanisms behind the emergence of location-dependence in distinct forms of frequency tuning. As a coda to this composition, we present some future directions for this exciting convergence of biophysical mechanisms that endow a neuron with frequency multiplexing capabilities.

  12. Investigating ion channel conformational changes using voltage clamp fluorometry.

    PubMed

    Talwar, Sahil; Lynch, Joseph W

    2015-11-01

    Ion channels are membrane proteins whose functions are governed by conformational changes. The widespread distribution of ion channels, coupled with their involvement in most physiological and pathological processes and their importance as therapeutic targets, renders the elucidation of these conformational mechanisms highly compelling from a drug discovery perspective. Thanks to recent advances in structural biology techniques, we now have high-resolution static molecular structures for members of the major ion channel families. However, major questions remain to be resolved about the conformational states that ion channels adopt during activation, drug modulation and desensitization. Patch-clamp electrophysiology has long been used to define ion channel conformational states based on functional criteria. It achieves this by monitoring conformational changes at the channel gate and cannot detect conformational changes occurring in regions distant from the gate. Voltage clamp fluorometry involves labelling cysteines introduced into domains of interest with environmentally sensitive fluorophores and inferring structural rearrangements from voltage or ligand-induced fluorescence changes. Ion channel currents are monitored simultaneously to verify the conformational status. By defining real time conformational changes in domains distant from the gate, this technique provides unexpected new insights into ion channel structure and function. This review aims to summarise the methodology and highlight recent innovative applications of this powerful technique. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. User's Manual and Final Report for Hot-SMAC GUI Development

    NASA Technical Reports Server (NTRS)

    Yarrington, Phil

    2001-01-01

    A new software package called Higher Order Theory-Structural/Micro Analysis Code (HOT-SMAC) has been developed as an effective alternative to the finite element approach for Functionally Graded Material (FGM) modeling. HOT-SMAC is a self-contained package including pre- and post-processing through an intuitive graphical user interface, along with the well-established Higher Order Theory for Functionally Graded Materials (HOTFGM) thermomechanical analysis engine. This document represents a Getting Started/User's Manual for HOT-SMAC and a final report for its development. First, the features of the software are presented in a simple step-by-step example where a HOT-SMAC model representing a functionally graded material is created, mechanical and thermal boundary conditions are applied, the model is analyzed and results are reviewed. In a second step-by-step example, a HOT-SMAC model of an actively cooled metallic channel with ceramic thermal barrier coating is built and analyzed. HOT-SMAC results from this model are compared to recently published results (NASA/TM-2001-210702) for two grid densities. Finally, a prototype integration of HOTSMAC with the commercially available HyperSizer(R) structural analysis and sizing software is presented. In this integration, local strain results from HyperSizer's structural analysis are fed to a detailed HOT-SMAC model of the flange-to-facesheet bond region of a stiffened panel. HOT-SMAC is then used to determine the peak shear and peel (normal) stresses between the facesheet and bonded flange of the panel and determine the "free edge" effects.

  14. Plant Ion Channels: Gene Families, Physiology, and Functional Genomics Analyses

    PubMed Central

    Ward, John M.; Mäser, Pascal; Schroeder, Julian I.

    2016-01-01

    Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization-and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide–gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport. PMID:18842100

  15. Plant ion channels: gene families, physiology, and functional genomics analyses.

    PubMed

    Ward, John M; Mäser, Pascal; Schroeder, Julian I

    2009-01-01

    Distinct potassium, anion, and calcium channels in the plasma membrane and vacuolar membrane of plant cells have been identified and characterized by patch clamping. Primarily owing to advances in Arabidopsis genetics and genomics, and yeast functional complementation, many of the corresponding genes have been identified. Recent advances in our understanding of ion channel genes that mediate signal transduction and ion transport are discussed here. Some plant ion channels, for example, ALMT and SLAC anion channel subunits, are unique. The majority of plant ion channel families exhibit homology to animal genes; such families include both hyperpolarization- and depolarization-activated Shaker-type potassium channels, CLC chloride transporters/channels, cyclic nucleotide-gated channels, and ionotropic glutamate receptor homologs. These plant ion channels offer unique opportunities to analyze the structural mechanisms and functions of ion channels. Here we review gene families of selected plant ion channel classes and discuss unique structure-function aspects and their physiological roles in plant cell signaling and transport.

  16. Path selection in the growth of rivers

    DOE PAGES

    Cohen, Yossi; Devauchelle, Olivier; Seybold, Hansjörg F.; ...

    2015-11-02

    River networks exhibit a complex ramified structure that has inspired decades of studies. But, an understanding of the propagation of a single stream remains elusive. In this paper, we invoke a criterion for path selection from fracture mechanics and apply it to the growth of streams in a diffusion field. We show that, as it cuts through the landscape, a stream maintains a symmetric groundwater flow around its tip. The local flow conditions therefore determine the growth of the drainage network. We use this principle to reconstruct the history of a network and to find a growth law associated withmore » it. Finally, our results show that the deterministic growth of a single channel based on its local environment can be used to characterize the structure of river networks.« less

  17. Asymmetric ion transport through ion-channel-mimetic solid-state nanopores.

    PubMed

    Guo, Wei; Tian, Ye; Jiang, Lei

    2013-12-17

    Both scientists and engineers are interested in the design and fabrication of synthetic nanofluidic architectures that mimic the gating functions of biological ion channels. The effort to build such structures requires interdisciplinary efforts at the intersection of chemistry, materials science, and nanotechnology. Biological ion channels and synthetic nanofluidic devices have some structural and chemical similarities, and therefore, they share some common features in regulating the traverse ionic flow. In the past decade, researchers have identified two asymmetric ion transport phenomena in synthetic nanofluidic structures, the rectified ionic current and the net diffusion current. The rectified ionic current is a diode-like current-voltage response that occurs when switching the voltage bias. This phenomenon indicates a preferential direction of transport in the nanofluidic system. The net diffusion current occurs as a direct product of charge selectivity and is generated from the asymmetric diffusion through charged nanofluidic channels. These new ion transport phenomena and the elaborate structures that occur in biology have inspired us to build functional nanofluidic devices for both fundamental research and practical applications. In this Account, we review our recent progress in the design and fabrication of biomimetic solid-state nanofluidic devices with asymmetric ion transport behavior. We demonstrate the origin of the rectified ionic current and the net diffusion current. We also identify several influential factors and discuss how to build these asymmetric features into nanofluidic systems by controlling (1) nanopore geometry, (2) surface charge distribution, (3) chemical composition, (4) channel wall wettability, (5) environmental pH, (6) electrolyte concentration gradient, and (7) ion mobility. In the case of the first four features, we build these asymmetric features directly into the nanofluidic structures. With the final three, we construct different environmental conditions in the electrolyte solutions on either side of the nanochannel. The novel and well-controlled nanofluidic phenomena have become the foundation for many promising applications, and we have highlighted several representative examples. Inspired by the electrogenic cell of the electric eel, we have demonstrated a proof-of-concept nanofluidic reverse electrodialysis system (NREDS) that converts salinity gradient energy into electricity by means of net diffusion current. We have also constructed chirality analysis systems into nanofluidic architectures and monitored these sensing events as the change in the degree of ionic current rectification. Moreover, we have developed a biohybrid nanosystem, in which we reconstituted the F0F1-ATPase on a liposome-coated, solid-state nanoporous membrane. By applying a transmembrane proton concentration gradient, the biohybrid nanodevice can synthesize ATP in vitro. These findings have improved our understanding of the asymmetric ion transport phenomena in synthetic nanofluidic systems and offer innovative insights into the design of functional nanofluidic devices.

  18. Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.

    PubMed

    Minor, Daniel L; Findeisen, Felix

    2010-01-01

    Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction, and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium‑dependent inactivation (CDI), and calcium‑dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts.

  19. The structure of a conserved Piezo channel domain reveals a novel beta sandwich fold

    PubMed Central

    Kamajaya, Aron; Kaiser, Jens; Lee, Jonas; Reid, Michelle; Rees, Douglas C.

    2014-01-01

    Summary Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a novel beta sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in Dehydrated Hereditary Stomatocytosis (DHS) patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. PMID:25242456

  20. The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold.

    PubMed

    Kamajaya, Aron; Kaiser, Jens T; Lee, Jonas; Reid, Michelle; Rees, Douglas C

    2014-10-07

    Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2,000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a topologically distinct β sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in dehydrated hereditary stomatocytosis patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be-identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Structure of the voltage-gated K⁺ channel Eag1 reveals an alternative voltage sensing mechanism.

    PubMed

    Whicher, Jonathan R; MacKinnon, Roderick

    2016-08-12

    Voltage-gated potassium (K(v)) channels are gated by the movement of the transmembrane voltage sensor, which is coupled, through the helical S4-S5 linker, to the potassium pore. We determined the single-particle cryo-electron microscopy structure of mammalian K(v)10.1, or Eag1, bound to the channel inhibitor calmodulin, at 3.78 angstrom resolution. Unlike previous K(v) structures, the S4-S5 linker of Eag1 is a five-residue loop and the transmembrane segments are not domain swapped, which suggest an alternative mechanism of voltage-dependent gating. Additionally, the structure and position of the S4-S5 linker allow calmodulin to bind to the intracellular domains and to close the potassium pore, independent of voltage-sensor position. The structure reveals an alternative gating mechanism for K(v) channels and provides a template to further understand the gating properties of Eag1 and related channels. Copyright © 2016, American Association for the Advancement of Science.

  2. Differential compaction influences on structure in West Cameron Block 225 field

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

    Finley, W.R.

    The concept to be illustrated here is the influence on structural configuration of differential compaction caused by lateral variations in stratigraphy, specifically, changes from sand to shale within the same stratigraphic interval, The example chosen to illustrate this concept is West Cameron Block 225 field. As seen in structural stratigraphic cross sections as well as net sand maps constructed in the example field, several channel sands are seen to strongly influence the structural configuration. The basic structure within the field as defined by well and seismic data consists of a gentle, southerly dipping, north south-oriented ridge, bounded by a down-to-the-eastmore » fault on the west flank and a down-to-the-south fault to the north. Gentle roll into these faults closes the north flank of the structure. The stratigraphic section consists of alternating sands and shales of Miocene and Pliocene age. Several of these sands map out as linear sand bodies interpreted to be channels. These channels, representing thickened sand bodies that grade laterally into predominantly shale facies, are oriented in a general east-west direction. The juxtaposition of the basic structural orientation with the orientation of the channel sand(s) sets up a crossing point(s) on the southern flank of the structure. With the advent of differential compaction between the channel sands and the bounding shale faces, a stratigraphic structure is generated. This resulting compaction structure maps out as a double-lobed or saddled high. This effect is amplified as channels in the shallower section stack out over the southern flank of the structure until the southern crest dominates over the northern one. The overall result is one of migrating structural crests caused by variations in compactibility within the stratigraphic section.« less

  3. Wireless Channel Characterization in the 5 GHz Microwave Landing System Extension Band for Airport Surface Areas

    NASA Technical Reports Server (NTRS)

    Matolak, David W.

    2007-01-01

    In this project final report, entitled "Wireless Channel Characterization in the 5 GHz Microwave Landing System Extension Band for Airport Surface Areas," we provide a detailed description and model representation for the wireless channel in the airport surface environment in this band. In this executive summary, we review report contents, describe the achieved objectives and major findings, and highlight significant conclusions and recommendations.

  4. Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca[superscript 2+]·calmodulins

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

    Fallon, Jennifer L.; Baker, Mariah R.; Xiong, Liangwen

    2009-11-10

    Voltage-dependent calcium channels (Ca(V)) open in response to changes in membrane potential, but their activity is modulated by Ca(2+) binding to calmodulin (CaM). Structural studies of this family of channels have focused on CaM bound to the IQ motif; however, the minimal differences between structures cannot adequately describe CaM's role in the regulation of these channels. We report a unique crystal structure of a 77-residue fragment of the Ca(V)1.2 alpha(1) subunit carboxyl terminus, which includes a tandem of the pre-IQ and IQ domains, in complex with Ca(2+).CaM in 2 distinct binding modes. The structure of the Ca(V)1.2 fragment is anmore » unusual dimer of 2 coiled-coiled pre-IQ regions bridged by 2 Ca(2+).CaMs interacting with the pre-IQ regions and a canonical Ca(V)1-IQ-Ca(2+).CaM complex. Native Ca(V)1.2 channels are shown to be a mixture of monomers/dimers and a point mutation in the pre-IQ region predicted to abolish the coiled-coil structure significantly reduces Ca(2+)-dependent inactivation of heterologously expressed Ca(V)1.2 channels.« less

  5. NUTRIENT UPTAKE LENGTH, CHANNEL STRUCTURE, AND TRANSIENT STORAGE IN STREAMS DRAINING HARVESTED AND OLD GROWTH WATERSHEDS

    EPA Science Inventory

    Channel structure and transient storage were correlated with nutrient uptake length in streams draining old-growth and harvested watersheds in the Cascade Mountains of Oregon, and the redwood forests of northwestern California. Channel width and riparian canopy were measured at 1...

  6. Qualitative evaluation of rock weir field performance and failure mechanisms

    USGS Publications Warehouse

    Mooney, David M.; Holmquist-Johnson, Christopher L.; Holburn, Elaina

    2007-01-01

    River spanning loose-rock structures provide sufficient head for irrigation diversion, permit fish passage over barriers, protect banks, stabilize degrading channels, activate side channels, reconnect floodplains, and create in-channel habitat. These structures are called by a variety of names including rock weirs, alphabet (U-, A-, V-, W-) weirs, Jhooks, and rock ramps. These structures share the common characteristics of:Loose rock construction materials (individually placed or dumped rocks with little or no concrete);Extents spanning the width of the river channel; andAn abrupt change in the water surface elevation at low flows.

  7. Ion-binding properties of a K+ channel selectivity filter in different conformations.

    PubMed

    Liu, Shian; Focke, Paul J; Matulef, Kimberly; Bian, Xuelin; Moënne-Loccoz, Pierre; Valiyaveetil, Francis I; Lockless, Steve W

    2015-12-08

    K(+) channels are membrane proteins that selectively conduct K(+) ions across lipid bilayers. Many voltage-gated K(+) (KV) channels contain two gates, one at the bundle crossing on the intracellular side of the membrane and another in the selectivity filter. The gate at the bundle crossing is responsible for channel opening in response to a voltage stimulus, whereas the gate at the selectivity filter is responsible for C-type inactivation. Together, these regions determine when the channel conducts ions. The K(+) channel from Streptomyces lividians (KcsA) undergoes an inactivation process that is functionally similar to KV channels, which has led to its use as a practical system to study inactivation. Crystal structures of KcsA channels with an open intracellular gate revealed a selectivity filter in a constricted conformation similar to the structure observed in closed KcsA containing only Na(+) or low [K(+)]. However, recent work using a semisynthetic channel that is unable to adopt a constricted filter but inactivates like WT channels challenges this idea. In this study, we measured the equilibrium ion-binding properties of channels with conductive, inactivated, and constricted filters using isothermal titration calorimetry (ITC). EPR spectroscopy was used to determine the state of the intracellular gate of the channel, which we found can depend on the presence or absence of a lipid bilayer. Overall, we discovered that K(+) ion binding to channels with an inactivated or conductive selectivity filter is different from K(+) ion binding to channels with a constricted filter, suggesting that the structures of these channels are different.

  8. Investigation of veritcal graded channel doping in nanoscale fully-depleted SOI-MOSFET

    NASA Astrophysics Data System (ADS)

    Ramezani, Zeinab; Orouji, Ali A.

    2016-10-01

    For achieving reliable transistor, we investigate an amended channel doping (ACD) engineering which improves the electrical and thermal performances of fully-depleted silicon-on-insulator (SOI) MOSFET. We have called the proposed structure with the amended channel doping engineering as ACD-SOI structure and compared it with a conventional fully-depleted SOI MOSFET (C-SOI) with uniform doping distribution using 2-D ATLAS simulator. The amended channel doping is a vertical graded doping that is distributed from the surface of structure with high doping density to the bottom of channel, near the buried oxide, with low doping density. Short channel effects (SCEs) and leakage current suppress due to high barrier height near the source region and electric field modification in the ACD-SOI in comparison with the C-SOI structure. Furthermore, by lower electric field and electron temperature near the drain region that is the place of hot carrier generation, we except the improvement of reliability and gate induced drain lowering (GIDL) in the proposed structure. Undesirable Self heating effect (SHE) that become a critical challenge for SOI MOSFETs is alleviated in the ACD-SOI structure because of utilizing low doping density near the buried oxide. Thus, refer to accessible results, the ACD-SOI structure with graded distribution in vertical direction is a reliable device especially in low power and high temperature applications.

  9. Structure of a CLC chloride ion channel by cryo-electron microscopy

    PubMed Central

    Park, Eunyong; Campbell, Ernest B.; MacKinnon, Roderick

    2017-01-01

    CLC proteins transport chloride (Cl−) ions across cellular membranes to regulate muscle excitability, electrolyte movement across epithelia, and acidification of intracellular organelles. Some CLC proteins are channels that conduct Cl− ions passively, whereas others are secondary active transporters that exchange two Cl− ions for one H+. The structural basis underlying these distinctive transport mechanisms is puzzling because CLC channels and transporters are expected to share the same architecture based on sequence homology. To solve this puzzle we determined the structure of a mammalian CLC channel (CLC-K) using cryo-electron microscopy. A conserved loop in the Cl− transport pathway shows a structure markedly different from that of CLC transporters. Consequently, the cytosolic constriction for Cl− passage is widened in CLC-K such that the kinetic barrier previously postulated for Cl−/H+ transporter function would be reduced. Thus, reduction of a kinetic barrier in CLC channels enables fast flow of Cl− down its electrochemical gradient. PMID:28002411

  10. Theoretical and experimental studies of turbo product code with time diversity in free space optical communication.

    PubMed

    Han, Yaoqiang; Dang, Anhong; Ren, Yongxiong; Tang, Junxiong; Guo, Hong

    2010-12-20

    In free space optical communication (FSOC) systems, channel fading caused by atmospheric turbulence degrades the system performance seriously. However, channel coding combined with diversity techniques can be exploited to mitigate channel fading. In this paper, based on the experimental study of the channel fading effects, we propose to use turbo product code (TPC) as the channel coding scheme, which features good resistance to burst errors and no error floor. However, only channel coding cannot cope with burst errors caused by channel fading, interleaving is also used. We investigate the efficiency of interleaving for different interleaving depths, and then the optimum interleaving depth for TPC is also determined. Finally, an experimental study of TPC with interleaving is demonstrated, and we show that TPC with interleaving can significantly mitigate channel fading in FSOC systems.

  11. Structure and dynamics of the influenza A M2 channel: a comparison of three structures.

    PubMed

    Leonov, Hadas; Arkin, Isaiah T

    2009-11-01

    The M2 protein is an essential component of the Influenza virus' infectivity cycle. It is a homo-tetrameric bundle forming a pH-gated H(+) channel. The structure of M2 was solved by three different groups, using different techniques, protein sequences and pH environment. For example, solid-state NMR spectroscopy was used on a protein in lipid bilayers, while X-ray crystallography and solution NMR spectroscopy were applied on a protein in detergent micelles. The resulting structures from the above efforts are rather distinct. Herein, we examine the different structures under uniform conditions such as a lipid bilayer and specified protonation state. We employ extensive molecular dynamics simulations, in several protonation states, representing both closed and open forms of the channel. Exploring the properties of each of these structures has shown that the X-ray structure is more stable than the other structures according to various criteria, although its water conductance and water-wire formation do not correlate to the protonation state of the channel.

  12. Analysis of inter-residue contacts reveals folding stabilizers in P-loops of potassium, sodium, and TRPV channels.

    PubMed

    Korkosh, V S; Zhorov, B S; Tikhonov, D B

    2016-05-01

    The family of P-loop channels includes potassium, sodium, calcium, cyclic nucleotide-gated and TRPV channels, as well as ionotropic glutamate receptors. Despite vastly different physiological and pharmacological properties, the channels have structurally conserved folding of the pore domain. Furthermore, crystallographic data demonstrate surprisingly similar mutual disposition of transmembrane and membrane-diving helices. To understand determinants of this conservation, here we have compared available high-resolution structures of sodium, potassium, and TRPV1 channels. We found that some residues, which are in matching positions of the sequence alignment, occur in different positions in the 3D alignment. Surprisingly, we found 3D mismatches in well-packed P-helices. Analysis of energetics of individual residues in Monte Carlo minimized structures revealed cyclic patterns of energetically favorable inter- and intra-subunit contacts of P-helices with S6 helices. The inter-subunit contacts are rather conserved in all the channels, whereas the intra-subunit contacts are specific for particular types of the channels. Our results suggest that these residue-residue contacts contribute to the folding stabilization. Analysis of such contacts is important for structural and phylogenetic studies of homologous proteins.

  13. Connexin channels and phospholipids: association and modulation

    PubMed Central

    Locke, Darren; Harris, Andrew L

    2009-01-01

    Background For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood. Results Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s) of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred. Conclusion This study is the first to identify (endogenous) phospholipids that tightly associate with connexin channels. The finding that specific phospholipids are associated with different connexin isoforms suggests connexin-specific regulatory and/or structural interactions with lipid membranes. The results are interpreted in light of connexin channel function and cell biology, as informed by current knowledge of lipid-protein interactions and membrane biophysics. The intimate involvement of distinct phospholipids with different connexins contributes to channel structure and/or function, as well as plaque integrity, and to modulation of connexin channels by lipophilic agents. PMID:19686581

  14. A Specific Two-pore Domain Potassium Channel Blocker Defines the Structure of the TASK-1 Open Pore*

    PubMed Central

    Streit, Anne K.; Netter, Michael F.; Kempf, Franca; Walecki, Magdalena; Rinné, Susanne; Bollepalli, Murali K.; Preisig-Müller, Regina; Renigunta, Vijay; Daut, Jürgen; Baukrowitz, Thomas; Sansom, Mark S. P.; Stansfeld, Phillip J.; Decher, Niels

    2011-01-01

    Two-pore domain potassium (K2P) channels play a key role in setting the membrane potential of excitable cells. Despite their role as putative targets for drugs and general anesthetics, little is known about the structure and the drug binding site of K2P channels. We describe A1899 as a potent and highly selective blocker of the K2P channel TASK-1. As A1899 acts as an open-channel blocker and binds to residues forming the wall of the central cavity, the drug was used to further our understanding of the channel pore. Using alanine mutagenesis screens, we have identified residues in both pore loops, the M2 and M4 segments, and the halothane response element to form the drug binding site of TASK-1. Our experimental data were used to validate a K2P open-pore homology model of TASK-1, providing structural insights for future rational design of drugs targeting K2P channels. PMID:21362619

  15. Structure of a eukaryotic cyclic nucleotide-gated channel

    PubMed Central

    Li, Minghui; Zhou, Xiaoyuan; Wang, Shu; Michailidis, Ioannis; Gong, Ye; Su, Deyuan; Li, Huan; Li, Xueming; Yang, Jian

    2018-01-01

    Summary Cyclic nucleotide-gated (CNG) channels are essential for vision and olfaction. They belong to the voltage-gated ion channel superfamily but their activities are controlled by intracellular cyclic nucleotides instead of transmembrane voltage. Here we report a 3.5 Å-resolution single-particle electron cryomicroscopy structure of a CNG channel from C. elegans in the cGMP-bound open state. The channel has an unusual voltage-sensor-like domain (VSLD), accounting for its deficient voltage dependence. A C-terminal linker connecting S6 and the cyclic nucleotide-binding domain interacts directly with both the VSLD and pore domain, forming a gating ring that couples conformational changes triggered by cyclic nucleotide binding to the gate. The selectivity filter is lined by the carboxylate side chains of a functionally important glutamate and three rings of backbone carbonyls. This structure provides a new framework for understanding mechanisms of ion permeation, gating and channelopathy of CNG channels and cyclic nucleotide modulation of related channels. PMID:28099415

  16. Masked Ballot Voting for Receipt-Free Online Elections

    NASA Astrophysics Data System (ADS)

    Wen, Roland; Buckland, Richard

    To prevent bribery and coercion attacks on voters, current online election schemes rely on strong physical assumptions during the election. We introduce Masked Ballot, an online voting scheme that mitigates these attacks while using a more practical assumption: untappable channels are available but only before the election. During the election voters cast ballots over completely public channels without relying on untappable channels, anonymous channels or trusted devices. Masked Ballot performs only the voting part of an election and is designed to integrate with counting schemes that compute the final election result.

  17. QUANTIFYING STRUCTURAL PHYSICAL HABITAT ATTRIBUTES USING LIDAR AND HYPERSPECTRAL IMAGERY

    EPA Science Inventory

    Structural physical habitat attributes include indices of stream size, channel gradient, substrate size, habitat complexity and cover, riparian vegetation cover and structure, anthropogenic disturbances and channel-riparian interaction. These habitat attributes will vary dependen...

  18. Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.

    PubMed

    Howard, Rebecca J; Trudell, James R; Harris, R Adron

    2014-01-01

    Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy.

  19. Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

    PubMed Central

    Trudell, James R.; Harris, R. Adron

    2014-01-01

    Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

  20. Screening effects in flow through rough channels.

    PubMed

    Andrade, J S; Araújo, A D; Filoche, M; Sapoval, B

    2007-05-11

    A surprising similarity is found between the distribution of hydrodynamic stress on the wall of an irregular channel and the distribution of flux from a purely Laplacian field on the same geometry. This finding is a direct outcome of numerical simulations of the Navier-Stokes equations for flow at low Reynolds numbers in two-dimensional channels with rough walls presenting either deterministic or random self-similar geometries. For high Reynolds numbers, the distribution of wall stresses on deterministic and random fractal rough channels becomes substantially dependent on the microscopic details of the walls geometry. Finally, the effects on the flow behavior of the channel symmetry and aspect ratio are also investigated.

  1. Use of aerial photograph, channel-type interpretations to predict habitat availability in small streams. Restoration project 95505b. Exxon Valdez oil spill restoration project final report

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

    Olson, R.A.

    1995-05-01

    In-stream habitats were quantified and qualified for nine stream channel-types. The channel types were identified using interpretations from stereo pairs of color and infrared aerial photographs. A total of 70 sites were sampled for streams located on the northwest portion of the Kenai Peninsula, in south-central Alaska. Channel-types were a significant predictor (P < 0.05) of the area (sq m) for 9 of 13 habitat types. Channel-types that had similar habitat composition, differed in size and depth of those habitats. Spawning habitat also appeared to be correlated to channel-type, however the within channel-type variability caused the differences to test non-significantmore » P < 0.05.« less

  2. CO-independent modification of K+ channels by tricarbonyldichlororuthenium(II) dimer (CORM-2).

    PubMed

    Gessner, Guido; Sahoo, Nirakar; Swain, Sandip M; Hirth, Gianna; Schönherr, Roland; Mede, Ralf; Westerhausen, Matthias; Brewitz, Hans Henning; Heimer, Pascal; Imhof, Diana; Hoshi, Toshinori; Heinemann, Stefan H

    2017-11-15

    Although toxic when inhaled in high concentrations, the gas carbon monoxide (CO) is endogenously produced in mammals, and various beneficial effects are reported. For potential medicinal applications and studying the molecular processes underlying the pharmacological action of CO, so-called CO-releasing molecules (CORMs), such as tricabonyldichlororuthenium(II) dimer (CORM-2), have been developed and widely used. Yet, it is not readily discriminated whether an observed effect of a CORM is caused by the released CO gas, the CORM itself, or any of its intermediate or final breakdown products. Focusing on Ca 2+ - and voltage-dependent K + channels (K Ca 1.1) and voltage-gated K + channels (Kv1.5, Kv11.1) relevant for cardiac safety pharmacology, we demonstrate that, in most cases, the functional impacts of CORM-2 on these channels are not mediated by CO. Instead, when dissolved in aqueous solutions, CORM-2 has the propensity of forming Ru(CO) 2 adducts, preferentially to histidine residues, as demonstrated with synthetic peptides using mass-spectrometry analysis. For K Ca 1.1 channels we show that H365 and H394 in the cytosolic gating ring structure are affected by CORM-2. For Kv11.1 channels (hERG1) the extracellularly accessible histidines H578 and H587 are CORM-2 targets. The strong CO-independent action of CORM-2 on Kv11.1 and Kv1.5 channels can be completely abolished when CORM-2 is applied in the presence of an excess of free histidine or human serum albumin; cysteine and methionine are further potential targets. Off-site effects similar to those reported here for CORM-2 are found for CORM-3, another ruthenium-based CORM, but are diminished when using iron-based CORM-S1 and absent for manganese-based CORM-EDE1. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Reaction of atomic hydrogen with formic acid.

    PubMed

    Cao, Qian; Berski, Slawomir; Latajka, Zdzislaw; Räsänen, Markku; Khriachtchev, Leonid

    2014-04-07

    We study the reaction of atomic hydrogen with formic acid and characterize the radical products using IR spectroscopy in a Kr matrix and quantum chemical calculations. The reaction first leads to the formation of an intermediate radical trans-H2COOH, which converts to the more stable radical trans-cis-HC(OH)2via hydrogen atom tunneling on a timescale of hours at 4.3 K. These open-shell species are observed for the first time as well as a reaction between atomic hydrogen and formic acid. The structural assignment is aided by extensive deuteration experiments and ab initio calculations at the UMP2 and UCCSD(T) levels of theory. The simplest geminal diol radical trans-cis-HC(OH)2 identified in the present work as the final product of the reaction should be very reactive, and further reaction channels are of particular interest. These reactions and species may constitute new channels for the initiation and propagation of more complex organic species in the interstellar clouds.

  4. Wide-angle camera with multichannel architecture using microlenses on a curved surface.

    PubMed

    Liang, Wei-Lun; Shen, Hui-Kai; Su, Guo-Dung J

    2014-06-10

    We propose a multichannel imaging system that combines the principles of an insect's compound eye and the human eye. The optical system enables a reduction in track length of the imaging device to achieve miniaturization. The multichannel structure is achieved by a curved microlens array, and a Hypergon lens is used as the main lens to simulate the human eye, achieving large field of view (FOV). With this architecture, each microlens of the array transmits a segment of the overall FOV. The partial images are recorded in separate channels and stitched together to form the final image of the whole FOV by image processing. The design is 2.7 mm thick, with 59 channels; the 100°×80° full FOV is optimized using ZEMAX ray-tracing software on an image plane. The image plane size is 4.53  mm×3.29  mm. Given the recent progress in the fabrication of microlenses, this image system has the potential to be commercialized in the near future.

  5. An a 0 resonance in strongly coupled π η , K K ¯ scattering from lattice QCD

    DOE PAGES

    Dudek, Jozef J.; Edwards, Robert G.; Wilson, David J.

    2016-05-11

    Here, we present the first calculation of coupled-channel meson-meson scattering in the isospinmore » $=1$, $G$-parity negative sector, with channels $$\\pi \\eta$$, $$K\\overline{K}$$ and $$\\pi \\eta'$$, in a first-principles approach to QCD. From the discrete spectrum of eigenstates in three volumes extracted from lattice QCD correlation functions we determine the energy dependence of the $S$-matrix, and find that the $S$-wave features a prominent cusp-like structure in $$\\pi \\eta \\to \\pi \\eta$$ close to $$K\\overline{K}$$ threshold coupled with a rapid turn on of amplitudes leading to the $$K\\overline{K}$$ final-state. This behavior is traced to an $$a_0(980)$$-like resonance, strongly coupled to both $$\\pi \\eta$$ and $$K\\overline{K}$$, which is identified with a pole in the complex energy plane, appearing on only a single unphysical Riemann sheet. Consideration of $D$-wave scattering suggests a narrow tensor resonance at higher energy.« less

  6. An a 0 resonance in strongly coupled π η , K K ¯ scattering from lattice QCD

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

    Dudek, Jozef J.; Edwards, Robert G.; Wilson, David J.

    Here, we present the first calculation of coupled-channel meson-meson scattering in the isospinmore » $=1$, $G$-parity negative sector, with channels $$\\pi \\eta$$, $$K\\overline{K}$$ and $$\\pi \\eta'$$, in a first-principles approach to QCD. From the discrete spectrum of eigenstates in three volumes extracted from lattice QCD correlation functions we determine the energy dependence of the $S$-matrix, and find that the $S$-wave features a prominent cusp-like structure in $$\\pi \\eta \\to \\pi \\eta$$ close to $$K\\overline{K}$$ threshold coupled with a rapid turn on of amplitudes leading to the $$K\\overline{K}$$ final-state. This behavior is traced to an $$a_0(980)$$-like resonance, strongly coupled to both $$\\pi \\eta$$ and $$K\\overline{K}$$, which is identified with a pole in the complex energy plane, appearing on only a single unphysical Riemann sheet. Consideration of $D$-wave scattering suggests a narrow tensor resonance at higher energy.« less

  7. Investigation and process optimization of SONOS cell's drain disturb in 2-transistor structure flash arrays

    NASA Astrophysics Data System (ADS)

    Xu, Zhaozhao; Qian, Wensheng; Chen, Hualun; Xiong, Wei; Hu, Jun; Liu, Donghua; Duan, Wenting; Kong, Weiran; Na, Wei; Zou, Shichang

    2017-03-01

    The mechanism and distribution of drain disturb (DD) are investigated in silicon-oxide-nitride-oxide-silicon (SONOS) flash cells. It is shown that DD is the only concern in this paper. First, the distribution of trapped charge in nitride layer is found to be non-localized (trapped in entire nitride layer along the channel) after programming. Likewise, the erase is also non-localized. Then, the main disturb mechanism: Fowler Nordheim tunneling (FNT) has been confirmed in this paper with negligible disturb effect from hot-hole injection (HHI). And then, distribution of DD is confirmed to be non-localized similarly, which denotes that DD exists in entire tunneling oxide (Oxide for short). Next, four process optimization ways are proposed for minimization of DD, and VTH shift is measured. It reveals that optimized lightly doped drain (LDD), halo, and channel implant are required for the fabrication of a robust SONOS cell. Finally, data retention and endurance of the optimized SONOS are demonstrated.

  8. A numerical study of the complex flow structure in a compound meandering channel

    NASA Astrophysics Data System (ADS)

    Moncho-Esteve, Ignacio J.; García-Villalba, Manuel; Muto, Yasu; Shiono, Koji; Palau-Salvador, Guillermo

    2018-06-01

    In this study, we report large eddy simulations of turbulent flow in a periodic compound meandering channel for three different depth conditions: one in-bank and two overbank conditions. The flow configuration corresponds to the experiments of Shiono and Muto (1998). The predicted mean streamwise velocities, mean secondary motions, velocity fluctuations, turbulent kinetic energy as well as mean flood flow angle to meandering channel are in good agreement with the experimental measurements. We have analyzed the flow structure as a function of the inundation level, with particular emphasis on the development of the secondary motions due to the interaction between the main channel and the floodplain flow. Bed shear stresses have been also estimated in the simulations. Floodplain flow has a significant impact on the flow structure leading to significantly different bed shear stress patterns within the main meandering channel. The implications of these results for natural compound meandering channels are also discussed.

  9. The Origins of Transmembrane Ion Channels

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Wilson, Michael A.

    2012-01-01

    Even though membrane proteins that mediate transport of ions and small molecules across cell walls are among the largest and least understood biopolymers in contemporary cells, it is still possible to shed light on their origins and early evolution. The central observation is that transmembrane portions of most ion channels are simply bundles of -helices. By combining results of experimental and computer simulation studies on synthetic models and natural channels, mostly of non-genomic origin, we show that the emergence of -helical channels was protobiologically plausible, and did not require highly specific amino acid sequences. Despite their simple structure, such channels could possess properties that, at the first sight, appear to require markedly larger complexity. Specifically, we explain how the antiamoebin channels, which are made of identical helices, 16 amino acids in length, achieve efficiency comparable to that of highly evolved channels. We further show that antiamoebin channels are extremely flexible, compared to modern, genetically coded channels. On the basis of our results, we propose that channels evolved further towards high structural complexity because they needed to acquire stable rigid structures and mechanisms for precise regulation rather than improve efficiency. In general, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during evolution.

  10. Structure of the Nucleon and its Excitations

    NASA Astrophysics Data System (ADS)

    Kamleh, Waseem; Leinweber, Derek; Liu, Zhan-wei; Stokes, Finn; Thomas, Anthony; Thomas, Samuel; Wu, Jia-jun

    2018-03-01

    The structure of the ground state nucleon and its finite-volume excitations are examined from three different perspectives. Using new techniques to extract the relativistic components of the nucleon wave function, the node structure of both the upper and lower components of the nucleon wave function are illustrated. A non-trivial role for gluonic components is manifest. In the second approach, the parity-expanded variational analysis (PEVA) technique is utilised to isolate states at finite momenta, enabling a novel examination of the electric and magnetic form factors of nucleon excitations. Here the magnetic form factors of low-lying odd-parity nucleons are particularly interesting. Finally, the structure of the nucleon spectrum is examined in a Hamiltonian effective field theory analysis incorporating recent lattice-QCD determinations of low-lying two-particle scattering-state energies in the finite volume. The Roper resonance of Nature is observed to originate from multi-particle coupled-channel interactions while the first radial excitation of the nucleon sits much higher at approximately 1.9 GeV.

  11. Coherent perfect absorbers: linear control of light with light

    NASA Astrophysics Data System (ADS)

    Baranov, Denis G.; Krasnok, Alex; Shegai, Timur; Alù, Andrea; Chong, Yidong

    2017-12-01

    The absorption of electromagnetic energy by a material is a phenomenon that underlies many applications, including molecular sensing, photocurrent generation and photodetection. Typically, the incident energy is delivered to the system through a single channel, for example, by a plane wave incident on one side of an absorber. However, absorption can be made much more efficient by exploiting wave interference. A coherent perfect absorber is a system in which the complete absorption of electromagnetic radiation is achieved by controlling the interference of multiple incident waves. Here, we review recent advances in the design and applications of such devices. We present the theoretical principles underlying the phenomenon of coherent perfect absorption and give an overview of the photonic structures in which it can be realized, including planar and guided-mode structures, graphene-based systems, parity-symmetric and time-symmetric structures, 3D structures and quantum-mechanical systems. We then discuss possible applications of coherent perfect absorption in nanophotonics, and, finally, we survey the perspectives for the future of this field.

  12. Structures of pseudechetoxin and pseudecin, two snake-venom cysteine-rich secretory proteins that target cyclic nucleotide-gated ion channels: implications for movement of the C-terminal cysteine-rich domain

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

    Suzuki, Nobuhiro; Department of Biochemistry, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602; Yamazaki, Yasuo

    2008-10-01

    The structures of pseudechetoxin and pseudecin suggest that both proteins bind to cyclic nucleotide-gated ion channels in a manner in which the concave surface occludes the pore entrance. Cyclic nucleotide-gated (CNG) ion channels play pivotal roles in sensory transduction by retinal photoreceptors and olfactory neurons. The elapid snake toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein blockers of CNG channels. These toxins belong to a cysteine-rich secretory protein (CRISP) family containing an N-terminal pathogenesis-related proteins of group 1 (PR-1) domain and a C-terminal cysteine-rich domain (CRD). PsTx and Pdc are highly homologous proteins, but their blocking affinitiesmore » on CNG channels are different: PsTx blocks both the olfactory and retinal channels with ∼15–30-fold higher affinity than Pdc. To gain further insights into their structure and function, the crystal structures of PsTx, Pdc and Zn{sup 2+}-bound Pdc were determined. The structures revealed that most of the amino-acid-residue differences between PsTx and Pdc are located around the concave surface formed between the PR-1 domain and the CRD, suggesting that the concave surface is functionally important for CNG-channel binding and inhibition. A structural comparison in the presence and absence of Zn{sup 2+} ion demonstrated that the concave surface can open and close owing to movement of the CRD upon Zn{sup 2+} binding. The data suggest that PsTx and Pdc occlude the pore entrance and that the dynamic motion of the concave surface facilitates interaction with the CNG channels.« less

  13. Relative similarity within purine nucleotide and ligand structures operating on nitric oxide synthetase, guanylyl cyclase and potassium (K ATP, BK Ca) channels.

    PubMed

    Williams, W Robert

    2011-01-01

    Purine nucleotides play a central role in signal transduction events initiated at the cell membrane. The NO-cGMP-cGK pathway, in particular, mediates events involving NOS and some classes of K(+) ion channel. The aim of this study is to investigate relative molecular similarity within the ligands binding to NOS, K(ATP), BK(Ca) channels and regulatory nucleotides. Minimum energy conformers of the ligand structures were superimposed and fitted to L-arginine and the nucleotides of adenine and guanine using a computational program. Distinctive patterns were evident in the fitting of NOS isoform antagonists to L-arginine. K(ATP) channel openers and antagonists superimposed on the glycosidic linkage and imidazole ring of the purine nucleotides, and guanidinium and ribose groups of GTP in the case of glibenclamide. The fits of BK(Ca) channel openers and antagonists to cGMP were characterized by the linear dimensions of their structures; distances between terminal oxy groups in respect of dexamethasone and aldosterone. The findings provide structural evidence for the functional interaction between K(+) channel openers/antagonists and the regulatory nucleotides. Use of the purine nucleotide template systematizes the considerable heterogeneity evident within the structures of ligands operating on K(+) ion channels. © 2010 The Author. JPP © 2010 Royal Pharmaceutical Society.

  14. Ion and Electron Heating Characteristics of Magnetic Re- Connection in Mast Tokamak Merging Experiment

    NASA Astrophysics Data System (ADS)

    Tanabe, Hiroshi; Inomoto, Michiaki; Ono, Yasushi; Yamada, Takuma; Imazawa, Ryota; Cheng, Chio-Zong

    2016-07-01

    We present results of recent studies of high power heating of magnetic reconnection, the fundamental process of several astrophysical events such as solar flare, in the Mega Amp Spherical Tokamak (MAST) - the world largest merging experiment. In addition to the previously reported significant reconnection heating up to ˜1keV [1], detailed local profiles of electron and ion temperature have been measured using a ultra-fine 300 channel Ruby- and a 130 channel YAG-Thomson scattering and a new 32 channel ion Doppler tomography diagnostics [2]. 2D profile measurement of electron temperature revealed highly localized heating structure at the X point with the characteristic scale length of 0.02-0.05m0.3T), a thick layer of closed flux surface surrounding the current sheet sustains the temperature profile for longer time than the electron and ion energy relaxation time ˜4-10ms, finally forming triple peak structures of ion and electron temperatures at the X point and in the downstream. While the peak electron temperature at the X point increases with toroidal field, the bulk electron temperature and the ion temperature in the downstream are unaffected. [1] Y. Ono et.al., Plasma Phys. Control. Fusion 54, 124039 (2012) [2] H. Tanabe et. al., Nucl. Fusion 53, 093027 (2013). [3] H. Tanabe et.al., Phys. Rev. Lett. 115, 215004 (2015)

  15. A New MEMS Gyroscope Used for Single-Channel Damping

    PubMed Central

    Zhang, Zengping; Zhang, Wei; Zhang, Fuxue; Wang, Biao

    2015-01-01

    The silicon micromechanical gyroscope, which will be introduced in this paper, represents a novel MEMS gyroscope concept. It is used for the damping of a single-channel control system of rotating aircraft. It differs from common MEMS gyroscopes in that does not have a drive structure, itself, and only has a sense structure. It is installed on a rotating aircraft, and utilizes the aircraft spin to make its sensing element obtain angular momentum. When the aircraft is subjected to an angular rotation, a periodic Coriolis force is induced in the direction orthogonal to both the angular momentum and the angular velocity input axis. This novel MEMS gyroscope can thus sense angular velocity inputs. The output sensing signal is exactly an amplitude-modulation signal. Its envelope is proportional to the input angular velocity, and the carrier frequency corresponds to the spin frequency of the rotating aircraft, so the MEMS gyroscope can not only sense the transverse angular rotation of an aircraft, but also automatically change the carrier frequency over the change of spin frequency, making it very suitable for the damping of a single-channel control system of a rotating aircraft. In this paper, the motion equation of the MEMS gyroscope has been derived. Then, an analysis has been carried to solve the motion equation and dynamic parameters. Finally, an experimental validation has been done based on a precision three axis rate table. The correlation coefficients between the tested data and the theoretical values are 0.9969, 0.9872 and 0.9842, respectively. These results demonstrate that both the design and sensing mechanism are correct. PMID:25942638

  16. Bayesian sparse channel estimation

    NASA Astrophysics Data System (ADS)

    Chen, Chulong; Zoltowski, Michael D.

    2012-05-01

    In Orthogonal Frequency Division Multiplexing (OFDM) systems, the technique used to estimate and track the time-varying multipath channel is critical to ensure reliable, high data rate communications. It is recognized that wireless channels often exhibit a sparse structure, especially for wideband and ultra-wideband systems. In order to exploit this sparse structure to reduce the number of pilot tones and increase the channel estimation quality, the application of compressed sensing to channel estimation is proposed. In this article, to make the compressed channel estimation more feasible for practical applications, it is investigated from a perspective of Bayesian learning. Under the Bayesian learning framework, the large-scale compressed sensing problem, as well as large time delay for the estimation of the doubly selective channel over multiple consecutive OFDM symbols, can be avoided. Simulation studies show a significant improvement in channel estimation MSE and less computing time compared to the conventional compressed channel estimation techniques.

  17. Enhanced mobility in vertically scaled N-polar high-electron-mobility transistors using GaN/InGaN composite channels

    NASA Astrophysics Data System (ADS)

    Li, Haoran; Wienecke, Steven; Romanczyk, Brian; Ahmadi, Elaheh; Guidry, Matthew; Zheng, Xun; Keller, Stacia; Mishra, Umesh K.

    2018-02-01

    A GaN/InGaN composite channel design for vertically scaled N-polar high-electron-mobility transistor (HEMT) structures is proposed and demonstrated by metal-organic chemical vapor deposition. In a conventional N-polar HEMT structure, as the channel thickness (tch) decreases, the sheet charge density (ns) decreases, the electric field in the channel increases, and the centroid of the two-dimensional electron gas (2DEG) moves towards the back-barrier/channel interface, resulting in stronger scattering and lower electron mobility (μ). In this study, a thin InGaN layer was introduced in-between the channel and the AlGaN cap to increase the 2DEG density and reduce the electric field in the channel and therefore increase the electron mobility. The dependence of μ on the InGaN thickness (tInGaN) and the indium composition (xIn) was investigated for different channel thicknesses. With optimized tInGaN and xIn, significant improvements in electron mobility were observed. For a 6 nm channel HEMT structure, the electron mobility increased from 606 to 1141 cm2/(V.s) when the 6 nm thick pure GaN channel was replaced by the 4 nm GaN/2 nm In0.1Ga0.9N composite channel.

  18. NMR investigation of the isolated second voltage-sensing domain of human Nav1.4 channel.

    PubMed

    Paramonov, A S; Lyukmanova, E N; Myshkin, M Yu; Shulepko, M A; Kulbatskii, D S; Petrosian, N S; Chugunov, A O; Dolgikh, D A; Kirpichnikov, M P; Arseniev, A S; Shenkarev, Z O

    2017-03-01

    Voltage-gated Na + channels are essential for the functioning of cardiovascular, muscular, and nervous systems. The α-subunit of eukaryotic Na + channel consists of ~2000 amino acid residues and encloses 24 transmembrane (TM) helices, which form five membrane domains: four voltage-sensing (VSD) and one pore domain. The structural complexity significantly impedes recombinant production and structural studies of full-sized Na + channels. Modular organization of voltage-gated channels gives an idea for studying of the isolated second VSD of human skeletal muscle Nav1.4 channel (VSD-II). Several variants of VSD-II (~150a.a., four TM helices) with different N- and C-termini were produced by cell-free expression. Screening of membrane mimetics revealed low stability of VSD-II samples in media containing phospholipids (bicelles, nanodiscs) associated with the aggregation of electrically neutral domain molecules. The almost complete resonance assignment of 13 C, 15 N-labeled VSD-II was obtained in LPPG micelles. The secondary structure of VSD-II showed similarity with the structures of bacterial Na + channels. The fragment of S4 TM helix between the first and second conserved Arg residues probably adopts 3 10 -helical conformation. Water accessibility of S3 helix, observed by the Mn 2+ titration, pointed to the formation of water-filled crevices in the micelle embedded VSD-II. 15 N relaxation data revealed characteristic pattern of μs-ms time scale motions in the VSD-II regions sharing expected interhelical contacts. VSD-II demonstrated enhanced mobility at ps-ns time scale as compared to isolated VSDs of K + channels. These results validate structural studies of isolated VSDs of Na + channels and show possible pitfalls in application of this 'divide and conquer' approach. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Structure of the TRPV1 ion channel determined by electron cryo-microscopy.

    PubMed

    Liao, Maofu; Cao, Erhu; Julius, David; Cheng, Yifan

    2013-12-05

    Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5-6 (S5-S6) and the intervening pore loop, which is flanked by S1-S4 voltage-sensor-like domains. TRPV1 has a wide extracellular 'mouth' with a short selectivity filter. The conserved 'TRP domain' interacts with the S4-S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.

  20. Structure of the TRPV1 ion channel determined by electron cryo-microscopy

    PubMed Central

    Liao, Maofu; Cao, Erhu; Julius, David; Cheng, Yifan

    2014-01-01

    Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here, we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4Å resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane helices S5–S6 and the intervening pore loop, which is flanked by S1–S4 voltage sensor-like domains. TRPV1 has a wide extracellular ‘mouth’ with short selectivity filter. The conserved ‘TRP domain’ interacts with the S4–S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including N-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function. PMID:24305160

  1. Crystal Structure of the Ternary Complex of a NaV C-Terminal Domain, a Fibroblast Growth Factor Homologous Factor, and Calmodulin

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

    Wang, Chaojian; Chung, Ben C.; Yan, Haidun

    2012-11-13

    Voltage-gated Na{sup +} (Na{sub V}) channels initiate neuronal action potentials. Na{sub V} channels are composed of a transmembrane domain responsible for voltage-dependent Na{sup +} conduction and a cytosolic C-terminal domain (CTD) that regulates channel function through interactions with many auxiliary proteins, including fibroblast growth factor homologous factors (FHFs) and calmodulin (CaM). Most ion channel structural studies have focused on mechanisms of permeation and voltage-dependent gating but less is known about how intracellular domains modulate channel function. Here we report the crystal structure of the ternary complex of a human NaV CTD, an FHF, and Ca{sup 2+}-free CaM at 2.2 {angstrom}.more » Combined with functional experiments based on structural insights, we present a platform for understanding the roles of these auxiliary proteins in NaV channel regulation and the molecular basis of mutations that lead to neuronal and cardiac diseases. Furthermore, we identify a critical interaction that contributes to the specificity of individual NaV CTD isoforms for distinctive FHFs.« less

  2. Information transmission over an amplitude damping channel with an arbitrary degree of memory

    NASA Astrophysics Data System (ADS)

    D'Arrigo, Antonio; Benenti, Giuliano; Falci, Giuseppe; Macchiavello, Chiara

    2015-12-01

    We study the performance of a partially correlated amplitude damping channel acting on two qubits. We derive lower bounds for the single-shot classical capacity by studying two kinds of quantum ensembles, one which allows us to maximize the Holevo quantity for the memoryless channel and the other allowing the same task but for the full-memory channel. In these two cases we also show the amount of entanglement which is involved in achieving the maximum of the Holevo quantity. For the single-shot quantum capacity we discuss both a lower and an upper bound, achieving a good estimate for high values of the channel transmissivity. We finally compute the entanglement-assisted classical channel capacity.

  3. Photoproduction of π 0 mesons off protons and neutrons in the second and third nucleon resonance regions

    DOE PAGES

    Dieterle, M.; Werthmüller, D.; Abt, S.; ...

    2018-06-21

    Background: Photoproduction of mesons off quasi-free nucleons bound in the deuteron allows to study the elec- tromagnetic excitation spectrum of the neutron and the isospin structure of the excitation of nucleon resonances. The database for such reactions is much more sparse than for free proton targets. Purpose: Study experimentally single π0 photoproduction off quasi-free nucleons from the deuteron. Investigate nuclear effects by a comparison of the results for free protons and quasi-free protons. Use the quasi-free neutron data (corrected for nuclear effects) to test the predictions of reaction models and partial wave analysis (PWA) for γn → nπ 0 derivedmore » from the analysis of the other isospin channels. Methods: High statistics angular distributions and total cross sections for the photoproduction of π 0 mesons off the deuteron with coincident detection of recoil nucleons have been measured for the first time. The experiment was performed at the tagged photon beam of the Mainz Microtron (MAMI) accelerator for photon energies between 0.45 GeV and 1.4 GeV, using an almost 4π electromagnetic calorimeter composed of the Crystal Ball and TAPS detectors. A complete kinematic reconstruction of the final state removed the effects of Fermi motion. Results: Significant effects from final state interactions (FSI) were observed for participant protons in comparison to free proton targets (between 30% and almost 40%). The data in coincidence with recoil neutrons were corrected for such effects under the assumption that they are identical for participant protons and neutrons. Reaction model predictions and PWA for γn → nπ 0, based on fits to data for the other isospin channels, disagreed between themselves and no model provided a good description of the new data. Conclusions: The results demonstrate clearly the importance of a measurement of the fully neutral final state for the isospin decomposition of the cross section. Model refits, for example from the Bonn-Gatchina analysis, show that the new and the previous data for the other three isospin channels can be simultaneously described when the contributions of several partial waves are modified. Finally, the results are also relevant for the suppression of the higher resonance bumps in total photoabsorption on nuclei, which are not well understood.« less

  4. Photoproduction of π 0 mesons off protons and neutrons in the second and third nucleon resonance regions

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

    Dieterle, M.; Werthmüller, D.; Abt, S.

    Background: Photoproduction of mesons off quasi-free nucleons bound in the deuteron allows to study the elec- tromagnetic excitation spectrum of the neutron and the isospin structure of the excitation of nucleon resonances. The database for such reactions is much more sparse than for free proton targets. Purpose: Study experimentally single π0 photoproduction off quasi-free nucleons from the deuteron. Investigate nuclear effects by a comparison of the results for free protons and quasi-free protons. Use the quasi-free neutron data (corrected for nuclear effects) to test the predictions of reaction models and partial wave analysis (PWA) for γn → nπ 0 derivedmore » from the analysis of the other isospin channels. Methods: High statistics angular distributions and total cross sections for the photoproduction of π 0 mesons off the deuteron with coincident detection of recoil nucleons have been measured for the first time. The experiment was performed at the tagged photon beam of the Mainz Microtron (MAMI) accelerator for photon energies between 0.45 GeV and 1.4 GeV, using an almost 4π electromagnetic calorimeter composed of the Crystal Ball and TAPS detectors. A complete kinematic reconstruction of the final state removed the effects of Fermi motion. Results: Significant effects from final state interactions (FSI) were observed for participant protons in comparison to free proton targets (between 30% and almost 40%). The data in coincidence with recoil neutrons were corrected for such effects under the assumption that they are identical for participant protons and neutrons. Reaction model predictions and PWA for γn → nπ 0, based on fits to data for the other isospin channels, disagreed between themselves and no model provided a good description of the new data. Conclusions: The results demonstrate clearly the importance of a measurement of the fully neutral final state for the isospin decomposition of the cross section. Model refits, for example from the Bonn-Gatchina analysis, show that the new and the previous data for the other three isospin channels can be simultaneously described when the contributions of several partial waves are modified. Finally, the results are also relevant for the suppression of the higher resonance bumps in total photoabsorption on nuclei, which are not well understood.« less

  5. Toward automated denoising of single molecular Förster resonance energy transfer data

    NASA Astrophysics Data System (ADS)

    Lee, Hao-Chih; Lin, Bo-Lin; Chang, Wei-Hau; Tu, I.-Ping

    2012-01-01

    A wide-field two-channel fluorescence microscope is a powerful tool as it allows for the study of conformation dynamics of hundreds to thousands of immobilized single molecules by Förster resonance energy transfer (FRET) signals. To date, the data reduction from a movie to a final set containing meaningful single-molecule FRET (smFRET) traces involves human inspection and intervention at several critical steps, greatly hampering the efficiency at the post-imaging stage. To facilitate the data reduction from smFRET movies to smFRET traces and to address the noise-limited issues, we developed a statistical denoising system toward fully automated processing. This data reduction system has embedded several novel approaches. First, as to background subtraction, high-order singular value decomposition (HOSVD) method is employed to extract spatial and temporal features. Second, to register and map the two color channels, the spots representing bleeding through the donor channel to the acceptor channel are used. Finally, correlation analysis and likelihood ratio statistic for the change point detection (CPD) are developed to study the two channels simultaneously, resolve FRET states, and report the dwelling time of each state. The performance of our method has been checked using both simulation and real data.

  6. Search for vector-like charge 2/3 T quarks in proton-proton collisions at $$\\sqrt{s}$$ = 8 TeV

    DOE PAGES

    Khachatryan, Vardan

    2016-01-19

    Our search for fermionic top quark partners T of charge 2/3 is presented. The search is carried out in proton-proton collisions corresponding to an integrated luminosity of 19.7 fb -1 collected at a center-of-mass energy of √s = 8 TeV with the CMS detector at the LHC. The T quarks are assumed to be produced strongly in pairs and can decay into tH, tZ, and bW. The search is performed in five exclusive channels: a singlelepton channel, a multilepton channel, two all-hadronic channels optimized either for the bW or the tH decay, and one channel in which the Higgs bosonmore » decays into two photons. The results are found to be compatible with the standard model expectations in all the investigated final states. Finally, a statistical combination of these results is performed and lower limits on the T quark mass are set. Depending on the branching fractions, lower mass limits between 720 and 920 GeV at 95% confidence level are found. These are among the strongest limits on vector-like T quarks obtained to date.« less

  7. Information processing in network architecture of genome controlled signal transduction circuit. A proposed theoretical explanation.

    PubMed

    Chakraborty, Chiranjib; Sarkar, Bimal Kumar; Patel, Pratiksha; Agoramoorthy, Govindasamy

    2012-01-01

    In this paper, Shannon information theory has been applied to elaborate cell signaling. It is proposed that in the cellular network architecture, four components viz. source (DNA), transmitter (mRNA), receiver (protein) and destination (another protein) are involved. The message transmits from source (DNA) to transmitter (mRNA) and then passes through a noisy channel reaching finally the receiver (protein). The protein synthesis process is here considered as the noisy channel. Ultimately, signal is transmitted from receiver to destination (another protein). The genome network architecture elements were compared with genetic alphabet L = {A, C, G, T} with a biophysical model based on the popular Shannon information theory. This study found the channel capacity as maximum for zero error (sigma = 0) and at this condition, transition matrix becomes a unit matrix with rank 4. The transition matrix will be erroneous and finally at sigma = 1 channel capacity will be localized maxima with a value of 0.415 due to the increased value at sigma. On the other hand, minima exists at sigma = 0.75, where all transition probabilities become 0.25 and uncertainty will be maximum resulting in channel capacity with the minima value of zero.

  8. Design, synthesis and structure-activity relationship of indoxacarb analogs as voltage-gated sodium channel blocker.

    PubMed

    Hao, Wenbo; Fu, Chunling; Yu, Huijuan; Chen, Jian; Xu, Hanhong; Shao, Guang; Jiang, Dingxin

    2015-10-15

    Indoxacarb, the first commercialized pyrazoline-type sodium-channel blocker, is a commonly used insecticide because of high selectivity. To discover sodium-channel blocker with high insecticidal activity, a series of novel indoxacarb analogs were designed and synthesized by judicious structural modifications of the substituent group of C5, C6 in indenone and C'4 in benzene ring. Some analogs exhibited significant insecticidal activities against Spodoptera litura F. and excellent BgNav1-1a channel inhibitory activity. The structure-activity analysis indicated that the presence of strong electron-withdrawing group and decreased steric hindrance of indenone ring (R(1), R(2)) in 5- and 6-position could enhance larvicidal activity and BgNav1-1a channel inhibitory activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Field Investigation of Flow Structure and Channel Morphology at Confluent-Meander Bends

    NASA Astrophysics Data System (ADS)

    Riley, J. D.; Rhoads, B. L.

    2007-12-01

    The movement of water and sediment through drainage networks is inevitably influenced by the convergence of streams and rivers at channel confluences. These focal components of fluvial systems produce a complex hydrodynamic environment, where rapid changes in flow structure and sediment transport occur to accommodate the merging of separate channel flows. The inherent geometric and hydraulic change at confluences also initiates the development of distinct geomorphic features, reflected in the bedform and shape of the channel. An underlying assumption of previous experimental and theoretical models of confluence dynamics has been that converging streams have straight channels with angular configurations. This generalized conceptualization was necessary to establish confluence planform as symmetrical or asymmetrical and to describe subsequent flow structure and geomorphic features at confluences. However, natural channels, particularly those of meandering rivers, curve and bend. This property and observation of channel curvature at natural junctions have led to the hypothesis that natural stream and river confluences tend to occur on the concave outer bank of meander bends. The resulting confluence planform, referred to as a confluent-meander bend, was observed over a century ago but has received little scientific attention. This paper examines preliminary data on three-dimensional flow structure and channel morphology at two natural confluent-meander bends of varying size and with differing tributary entrance locations. The large river confluence of the Vermilion River and Wabash River in west central Indiana and the comparatively small junction of the Little Wabash River and Big Muddy Creek in southeastern Illinois are the location of study sites for field investigation. Measurements of time-averaged three-dimensional velocity components were obtained at these confluences with an acoustic Doppler current profiler for flow events with differing momentum ratios. Bed and channel morphology were also surveyed with a digital fathometer to document geomorphic change. Preliminary analysis of the velocity data reveals the presence of a well-defined shear layer between the converging flows and secondary circulation in the main channel. The tributary channel appears to oppose high velocity flow directed toward the outer bank by centrifugal acceleration through the meander bend of the main channel, thereby diminishing erosion along the cut bank and possibly stabilizing the meander bend channel. The flow structure and channel morphology of the study sites are compared to consider the effect of spatial scale and geometric characteristics on confluent-meander bend dynamics.

  10. Shielded serpentine traveling wave tube deflection structure

    DOEpatents

    Hudson, C.L.; Spector, J.

    1994-12-27

    A shielded serpentine slow wave deflection structure is disclosed having a serpentine signal conductor within a channel groove. The channel groove is formed by a serpentine channel in a trough plate and a ground plane. The serpentine signal conductor is supported at its ends by coaxial feed through connectors. A beam interaction trough intersects the channel groove to form a plurality of beam interaction regions wherein an electron beam may be deflected relative to the serpentine signal conductor. 4 figures.

  11. Self-Optimized Biological Channels in Facilitating the Transmembrane Movement of Charged Molecules

    PubMed Central

    Huyen, V. T. N.; Lap, Vu Cong; Nguyen, V. Lien

    2016-01-01

    We consider an anisotropically two-dimensional diffusion of a charged molecule (particle) through a large biological channel under an external voltage. The channel is modeled as a cylinder of three structure parameters: radius, length, and surface density of negative charges located at the channel interior-lining. These charges induce inside the channel a potential that plays a key role in controlling the particle current through the channel. It was shown that to facilitate the transmembrane particle movement the channel should be reasonably self-optimized so that its potential coincides with the resonant one, resulting in a large particle current across the channel. Observed facilitation appears to be an intrinsic property of biological channels, regardless of the external voltage or the particle concentration gradient. This facilitation is very selective in the sense that a channel of definite structure parameters can facilitate the transmembrane movement of only particles of proper valence at corresponding temperatures. Calculations also show that the modeled channel is nonohmic with the ion conductance which exhibits a resonance at the same channel potential as that identified in the current. PMID:27022394

  12. Resonant interatomic Coulombic decay in HeNe: Electron angular emission distributions

    NASA Astrophysics Data System (ADS)

    Mhamdi, A.; Trinter, F.; Rauch, C.; Weller, M.; Rist, J.; Waitz, M.; Siebert, J.; Metz, D.; Janke, C.; Kastirke, G.; Wiegandt, F.; Bauer, T.; Tia, M.; Cunha de Miranda, B.; Pitzer, M.; Sann, H.; Schiwietz, G.; Schöffler, M.; Simon, M.; Gokhberg, K.; Dörner, R.; Jahnke, T.; Demekhin, Ph. Â. V.

    2018-05-01

    We present a joint experimental and theoretical study of resonant interatomic Coulombic decay (RICD) in HeNe employing high resolution cold target recoil ion momentum spectroscopy and ab initio electronic structure and nuclear dynamics calculations. In particular, laboratory- and molecular-frame angular emission distributions of RICD electrons are examined in detail. The exciting-photon energy-dependent anisotropy parameter β (ω ) , measured for decay events that populate bound HeNe+ ions, is in agreement with the calculations performed for the ground ionic state X2Σ1/2 + . A contribution from the a2Π3 /2 final ionic state is found to be negligible. For the He +Ne+ fragmentation channel, the observed laboratory-frame angular distribution of RICD electrons is explained by a slow homogeneous dissociation of bound vibrational levels of the final ionic state A2Π1 /2 into vibrational continua of the lower lying states X2Σ1/2 + and a2Π3 /2 . Our calculations predict that the angular distributions of RICD electrons in the body-fixed dipole plane provide direct access to the electronic character (i.e., symmetry) of intermediate vibronic resonances. However, because of the very slow dissociation of the A2Π1 /2 state, the molecular-frame angular distributions of RICD electrons in the He +Ne+ fragmentation channel are inaccessible to our coincidence experiment.

  13. Key Technologies and Applications of Gas Drainage in Underground Coal Mine

    NASA Astrophysics Data System (ADS)

    Zhou, Bo; Xue, Sheng; Cheng, Jiansheng; Li, Wenquan; Xiao, Jiaping

    2018-02-01

    It is the basis for the long-drilling directional drilling, precise control of the drilling trajectory and ensuring the effective extension of the drilling trajectory in the target layer. The technology can be used to complete the multi-branch hole construction and increase the effective extraction distance of the coal seam. The gas drainage and the bottom grouting reinforcement in the advanced area are realized, and the geological structure of the coal seam can be proved accurately. It is the main technical scheme for the efficient drainage of gas at home and abroad, and it is applied to the field of geological structure exploration and water exploration and other areas. At present, the data transmission method is relatively mature in the technology and application, including the mud pulse and the electromagnetic wave. Compared with the mud pulse transmission mode, the electromagnetic wave transmission mode has obvious potential in the data transmission rate and drilling fluid, and it is suitable for the coal mine. In this paper, the key technologies of the electromagnetic wave transmission mode are analyzed, including the attenuation characteristics of the electromagnetic transmission channel, the digital modulation scheme, the channel coding method and the weak signal processing technology. A coal mine under the electromagnetic wave drilling prototype is developed, and the ground transmission experiments and down hole transmission test are carried out. The main work includes the following aspects. First, the equivalent transmission line method is used to establish the electromagnetic transmission channel model of coal mine drilling while drilling, and the attenuation of the electromagnetic signal is measured when the electromagnetic channel measured. Second, the coal mine EM-MWD digital modulation method is developed. Third, the optimal linear block code which suitable for EM-MWD communication channel in coal mine is proposed. Fourth, the noise characteristics of well near horizontal directional drilling are analyzed, and the multi-stage filter method is proposed to suppress the natural potential and strong frequency interference signal. And the weak electromagnetic communication signal is extracted from the received signal. Finally, the detailed design of the electromagnetic wave while drilling is given.

  14. Effective pore size and radius of capture for K(+) ions in K-channels.

    PubMed

    Moldenhauer, Hans; Díaz-Franulic, Ignacio; González-Nilo, Fernando; Naranjo, David

    2016-02-02

    Reconciling protein functional data with crystal structure is arduous because rare conformations or crystallization artifacts occur. Here we present a tool to validate the dimensions of open pore structures of potassium-selective ion channels. We used freely available algorithms to calculate the molecular contour of the pore to determine the effective internal pore radius (r(E)) in several K-channel crystal structures. r(E) was operationally defined as the radius of the biggest sphere able to enter the pore from the cytosolic side. We obtained consistent r(E) estimates for MthK and Kv1.2/2.1 structures, with r(E) = 5.3-5.9 Å and r(E) = 4.5-5.2 Å, respectively. We compared these structural estimates with functional assessments of the internal mouth radii of capture (r(C)) for two electrophysiological counterparts, the large conductance calcium activated K-channel (r(C) = 2.2 Å) and the Shaker Kv-channel (r(C) = 0.8 Å), for MthK and Kv1.2/2.1 structures, respectively. Calculating the difference between r(E) and r(C), produced consistent size radii of 3.1-3.7 Å and 3.6-4.4 Å for hydrated K(+) ions. These hydrated K(+) estimates harmonize with others obtained with diverse experimental and theoretical methods. Thus, these findings validate MthK and the Kv1.2/2.1 structures as templates for open BK and Kv-channels, respectively.

  15. 75 FR 71044 - Radio Broadcasting Services; Onekama, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ...-11607] Radio Broadcasting Services; Onekama, MI AGENCY: Federal Communications Commission. ACTION: Final... counterproposal, allots FM Channel 227A at Onekama, Michigan, as a first local aural service. Channel 227A can be..., at coordinates 44-21-48 NL and 86-12-18 WL, without site restriction. The Government of Canada has...

  16. 78 FR 25591 - Radio Broadcasting Services; Crownpoint, New Mexico

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-02

    ... Broadcasting Services; Crownpoint, New Mexico AGENCY: Federal Communications Commission. ACTION: Final rule... Crownpoint, New Mexico. (The symbol ``[dagger]'' will be used to denote a channel reserved as a Tribal... Allotments under New Mexico, is amended by adding Crownpoint, Channel [dagger]297A. [FR Doc. 2013-10310 Filed...

  17. Confinement Aquaculture. Final Report.

    ERIC Educational Resources Information Center

    Delaplaine School District, AR.

    The Delaplaine Agriculture Department Confinement Project, begun in June 1988, conducted a confinement aquaculture program by comparing the growth of channel catfish raised in cages in a pond to channel catfish raised in cages in the Black River, Arkansas. The study developed technology that would decrease costs in the domestication of fish, using…

  18. 78 FR 53054 - Radio Broadcasting Services; Chillicothe, Dublin, Hillsboro, and Marion, Ohio

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [FCC 13-105; MB Docket No. 02-266; RM-10557... Communications Commission. ACTION: Final rule; application for review. SUMMARY: This document denies an... Channel Communications for the reallotment, downgrade in class of channel, and change of community of...

  19. David J. Triggle: Medicinal chemistry, to pharmacology, calcium channels, and beyond.

    PubMed

    Walker, Michael J A

    2015-11-15

    David Triggle's scientific career began as a chemist, went through medicinal chemistry into pharmacology, and finally on to somewhat more philosophical interests in later years. It was a career marked by many contributions to all of those aspects of science. Chief amongst his many contributions, in addition to those in medicinal chemistry, was his work on the drugs known as calcium ion channel blockers or (calcium antagonists). In the calcium ion channel field he was a particularly instrumental figure in sorting out the mechanisms, actions and roles of the class of calcium channel blockers, known chemical and pharmacologically as the dihydropyridines (DHPs) in particular, as well as other calcium blockers of diverse structures. During the course of a long career, and extensive journeys into medicinal chemistry and pharmacology, he published voluminously in terms of papers, reviews, conference proceedings and books. Notably, many of his papers often had limited authorship where, as senior author it reflected his deep involvement in all aspects of the reported work. His work always helped clarify the field while his incisive reviews, together with his role in coordinating and running scientific meetings, were a great help in clarifying and organizing various fields of study. He has had a long and illustrious career, and is wellknown in the world of biomedical science; his contributions are appreciated, and well recognized everywhere. The following article attempts to chart a path through his work and contributions to medicinal chemistry, pharmacology, science, academia and students. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Geologic Mapping of the Olympus Mons Volcano, Mars

    NASA Technical Reports Server (NTRS)

    Bleacher, J. E.; Williams, D. A.; Shean, D.; Greeley, R.

    2012-01-01

    We are in the third year of a three-year Mars Data Analysis Program project to map the morphology of the Olympus Mons volcano, Mars, using ArcGIS by ESRI. The final product of this project is to be a 1:1,000,000-scale geologic map. The scientific questions upon which this mapping project is based include understanding the volcanic development and modification by structural, aeolian, and possibly glacial processes. The project s scientific objectives are based upon preliminary mapping by Bleacher et al. [1] along a approx.80-km-wide north-south swath of the volcano corresponding to High Resolution Stereo Camera (HRSC) image h0037. The preliminary project, which covered approx.20% of the volcano s surface, resulted in several significant findings, including: 1) channel-fed lava flow surfaces are areally more abundant than tube-fed surfaces by a ratio of 5:1, 2) channel-fed flows consistently embay tube-fed flows, 3) lava fans appear to be linked to tube-fed flows, 4) no volcanic vents were identified within the map region, and 5) a Hummocky unit surrounds the summit and is likely a combination of non-channelized flows, dust, ash, and/or frozen volatiles. These results led to the suggestion that the volcano had experienced a transition from long-lived tube-forming eruptions to more sporadic and shorter-lived, channel-forming eruptions, as seen at Hawaiian volcanoes between the tholeiitic shield building phase (Kilauea to Mauna Loa) and alkalic capping phase (Hualalai and Mauna Kea).

  1. Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation

    PubMed Central

    Findeisen, Felix

    2010-01-01

    Voltage-gated calcium channels (CaVs) are large, transmembrane multiprotein complexes that couple membrane depolarization to cellular calcium entry. These channels are central to cardiac action potential propagation, neurotransmitter and hormone release, muscle contraction and calcium-dependent gene transcription. Over the past six years, the advent of high-resolution structural studies of CaV components from different isoforms and CaV modulators has begun to reveal the architecture that underlies the exceptionally rich feedback modulation that controls CaV action. These descriptions of CaV molecular anatomy have provided new, structure-based insights into the mechanisms by which particular channel elements affect voltage-dependent inactivation (VDI), calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). The initial successes have been achieved through structural studies of soluble channel domains and modulator proteins and have proven most powerful when paired with biochemical and functional studies that validate ideas inspired by the structures. Here, we review the progress in this growing area and highlight some key open challenges for future efforts. PMID:21139419

  2. Structural organization of intercellular channels II. Amino terminal domain of the connexins: sequence, functional roles, and structure.

    PubMed

    Beyer, Eric C; Lipkind, Gregory M; Kyle, John W; Berthoud, Viviana M

    2012-08-01

    The amino terminal domain (NT) of the connexins consists of their first 22-23 amino acids. Site-directed mutagenesis studies have demonstrated that NT amino acids are determinants of gap junction channel properties including unitary conductance, permeability/selectivity, and gating in response to transjunctional voltage. The importance of this region has also been emphasized by the identification of multiple disease-associated connexin mutants affecting amino acid residues in the NT region. The first part of the NT is α-helical. The structure of the Cx26 gap junction channel shows that the NT α-helix localizes within the channel, and lines the wall of the pore. Interactions of the amino acid residues in the NT with those in the transmembrane helices may be critical for holding the channel open. The predicted sites of these interactions and the applicability of the Cx26 structure to the NT of other connexins are considered. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. Copyright © 2011. Published by Elsevier B.V.

  3. Dissemination of Continuing Education Materials Via Television Delivery Systems. Final Technical Report and Final Report.

    ERIC Educational Resources Information Center

    Munushian, Jack

    In 1972, the University of Southern California School of Engineering established a 4-channel interactive instructional television network. It was designed to allow employees of participating industries to take regular university science and engineering courses and special continuing education courses at or near their work locations. Final progress…

  4. Small molecule inhibitors of Ca 2+-S100B reveal two protein conformations

    DOE PAGES

    Cavalier, Michael C.; Ansari, Mohd. Imran; Pierce, Adam D.; ...

    2016-01-04

    The drug pentamidine inhibits calcium-dependent complex formation with p53 ( CaS100B·p53) in malignant melanoma (MM) and restores p53 tumor suppressor activity in vivo. However, off-target effects associated with this drug were problematic in MM patients. Structure–activity relationship (SAR) studies were therefore completed in this study with 23 pentamidine analogues, and X-ray structures of CaS100B·inhibitor complexes revealed that the C-terminus of S100B adopts two different conformations, with location of Phe87 and Phe88 being the distinguishing feature and termed the “FF-gate”. For symmetric pentamidine analogues ( CaS100B· 5a, CaS100B· 6b) a channel between sites 1 and 2 on S100B was occluded bymore » residue Phe88, but for an asymmetric pentamidine analogue ( CaS100B· 17), this same channel was open. Finally, the CaS100B· 17 structure illustrates, for the first time, a pentamidine analog capable of binding the “open” form of the “FF-gate” and provides a means to block all three “hot spots” on CaS100B, which will impact next generation CaS100B·p53 inhibitor design.« less

  5. Small molecule inhibitors of Ca 2+-S100B reveal two protein conformations

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

    Cavalier, Michael C.; Ansari, Mohd. Imran; Pierce, Adam D.

    The drug pentamidine inhibits calcium-dependent complex formation with p53 ( CaS100B·p53) in malignant melanoma (MM) and restores p53 tumor suppressor activity in vivo. However, off-target effects associated with this drug were problematic in MM patients. Structure–activity relationship (SAR) studies were therefore completed in this study with 23 pentamidine analogues, and X-ray structures of CaS100B·inhibitor complexes revealed that the C-terminus of S100B adopts two different conformations, with location of Phe87 and Phe88 being the distinguishing feature and termed the “FF-gate”. For symmetric pentamidine analogues ( CaS100B· 5a, CaS100B· 6b) a channel between sites 1 and 2 on S100B was occluded bymore » residue Phe88, but for an asymmetric pentamidine analogue ( CaS100B· 17), this same channel was open. Finally, the CaS100B· 17 structure illustrates, for the first time, a pentamidine analog capable of binding the “open” form of the “FF-gate” and provides a means to block all three “hot spots” on CaS100B, which will impact next generation CaS100B·p53 inhibitor design.« less

  6. Structure, Dynamics, and Allosteric Potential of Ionotropic Glutamate Receptor N-Terminal Domains

    PubMed Central

    Krieger, James; Bahar, Ivet; Greger, Ingo H.

    2015-01-01

    Ionotropic glutamate receptors (iGluRs) are tetrameric cation channels that mediate synaptic transmission and plasticity. They have a unique modular architecture with four domains: the intracellular C-terminal domain (CTD) that is involved in synaptic targeting, the transmembrane domain (TMD) that forms the ion channel, the membrane-proximal ligand-binding domain (LBD) that binds agonists such as L-glutamate, and the distal N-terminal domain (NTD), whose function is the least clear. The extracellular portion, comprised of the LBD and NTD, is loosely arranged, mediating complex allosteric regulation and providing a rich target for drug development. Here, we briefly review recent work on iGluR NTD structure and dynamics, and further explore the allosteric potential for the NTD in AMPA-type iGluRs using coarse-grained simulations. We also investigate mechanisms underlying the established NTD allostery in NMDA-type iGluRs, as well as the fold-related metabotropic glutamate and GABAB receptors. We show that the clamshell motions intrinsically favored by the NTD bilobate fold are coupled to dimeric and higher-order rearrangements that impact the iGluR LBD and ultimately the TMD. Finally, we explore the dynamics of intact iGluRs and describe how it might affect receptor operation in a synaptic environment. PMID:26255587

  7. Simple Ion Channels: From Structure to Electrophysiology and Back

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrzej

    2018-01-01

    A reliable way to establish whether our understanding of a channel is satisfactory is to reproduce its measured ionic conductance over a broad range of applied voltages in computer simulations. In molecular dynamics (MD), this can be done by way of applying an external electric field to the system and counting the number of ions that traverse the channel per unit time. Since this approach is computationally very expensive, we have developed a markedly more efficient alternative in which MD is combined with the electrodiffusion (ED) equation. In this approach, the assumptions of the ED equation can be rigorously tested, and the precision and consistency of the calculated conductance can be determined. We have demonstrated that the full current/voltage dependence and the underlying free energy profile for a simple channel can be reliably calculated from equilibrium or non-equilibrium MD simulations at a single voltage. To carry out MD simulations, a structural model of a channel has to be assumed, which is an important constraint, considering that high-resolution structures are available for only very few simple channels. If the comparison of calculated ionic conductance with electrophysiological data is satisfactory, it greatly increases our confidence that the structure and the function are described sufficiently accurately. We examined the validity of the ED for several channels embedded in phospholipid membranes - four naturally occurring channels: trichotoxin, alamethicin, p7 from hepatitis C virus (HCV) and Vpu from the HIV-1 virus, and a synthetic, hexameric channel, formed by a 21-residue peptide that contains only leucine and serine. All these channels mediate transport of potassium and chloride ions. It was found that the ED equation is satisfactory for these systems. In some of them experimental and calculated electrophysiological properties are in good agreement, whereas in others there are strong indications that the structural models are incorrect.

  8. Ferritin ion channel disorder inhibits Fe(II)/O2 reactivity at distant sites.

    PubMed

    Tosha, Takehiko; Behera, Rabindra K; Theil, Elizabeth C

    2012-11-05

    Ferritins, a complex, mineralized, protein nanocage family essential for life, provide iron concentrates and oxidant protection. Protein-based ion channels and Fe(II)/O(2) catalysis initiate conversion of thousands of Fe atoms to caged, ferritin Fe(2)O(3)·H(2)O minerals. The ion channels consist of six helical segments, contributed by 3 of 12 or 24 polypeptide subunits, around the 3-fold cage axes. The channel structure guides entering Fe(II) ions toward multiple, catalytic, diiron sites buried inside ferritin protein helices, ~20 Å away from channel internal exits. The catalytic product, Fe(III)-O(H)-Fe(III), is a mineral precursor; mineral nucleation begins inside the protein cage with mineral growth in the central protein cavity (5-8 nm diameter). Amino acid substitutions that changed ionic or hydrophobic channel interactions R72D, D122R, and L134P increased ion channel structural disorder (protein crystallographic analyses) and increased Fe(II) exit [chelated Fe(II) after ferric mineral reduction/dissolution]. Since substitutions of some channel carboxylate residues diminished ferritin catalysis with no effect on Fe(II) exit, such as E130A and D127A, we investigated catalysis in ferritins with altered Fe(II) exit, R72D, D122R and L134P. The results indicate that simply changing the ionic properties of the channels, as in the R72D variant, need not change the forward catalytic rate. However, both D122R and L134P, which had dramatic effects on ferritin catalysis, also caused larger effects on channel structure and order, contrasting with R72D. All three amino acid substitutions, however, decreased the stability of the catalytic intermediate, diferric peroxo, even though overall ferritin cage structure is very stable, resisting 80 °C and 6 M urea. The localized structural changes in ferritin subdomains that affect ferritin function over long distances illustrate new properties of the protein cage in natural ferritin function and for applied ferritin uses.

  9. Chasing the open-state structure of pentameric ligand-gated ion channels

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

    Gonzalez-Gutierrez, Giovanni; Wang, Yuhang; Cymes, Gisela D.

    Remarkable advances have been made toward the structural characterization of ion channels in the last two decades. However, the unambiguous assignment of well-defined functional states to the obtained structural models has proved challenging. In the case of the superfamily of nicotinic-receptor channels (also referred to as pentameric ligand-gated ion channels [pLGICs]), for example, two different types of model of the open-channel conformation have been proposed on the basis of structures solved to resolutions better than 4.0 Å. At the level of the transmembrane pore, the open-state models of the proton-gated pLGIC fromGloeobacter violaceus(GLIC) and the invertebrate glutamate-gated Cl –channel (GluCl)more » are very similar to each other, but that of the glycine receptor (GlyR) is considerably wider. Indeed, the mean distances between the axis of ion permeation and the Cα atoms at the narrowest constriction of the pore (position -2') differ by ~2 Å in these two classes of model, a large difference when it comes to understanding the physicochemical bases of ion conduction and charge selectivity. Here, we take advantage of the extreme open-channel stabilizing effect of mutations at pore-facing position 9'. We find that the I9'A mutation slows down entry into desensitization of GLIC to the extent that macroscopic currents decay only slightly by the end of pH 4.5 solution applications to the extracellular side for several minutes. We crystallize (at pH 4.5) two variants of GLIC carrying this mutation and solve their structures to resolutions of 3.12 Å and 3.36 Å. Furthermore, we perform all-atom molecular dynamics simulations of ion permeation and picrotoxinin block, using the different open-channel structural models. On the basis of these results, we favor the notion that the open-channel structure of pLGICs from animals is much closer to that of the narrow models (of GLIC and GluCl) than it is to that of the GlyR.« less

  10. Simulation of cooling efficiency via miniaturised channels in multilayer LTCC for power electronics

    NASA Astrophysics Data System (ADS)

    Pietrikova, Alena; Girasek, Tomas; Lukacs, Peter; Welker, Tilo; Müller, Jens

    2017-03-01

    The aim of this paper is detailed investigation of thermal resistance, flow analysis and distribution of coolant as well as thermal distribution inside multilayer LTCC substrates with embedded channels for power electronic devices by simulation software. For this reason four various structures of internal channels in the multilayer LTCC substrates were designed and simulated. The impact of the volume flow, structures of channels, and power loss of chip was simulated, calculated and analyzed by using the simulation software Mentor Graphics FloEFDTM. The structure, size and location of channels have the significant impact on thermal resistance, pressure of coolant as well as the effectivity of cooling power components (chips) that can be placed on the top of LTCC substrate. The main contribution of this paper is thermal analyze, optimization and impact of 4 various cooling channels embedded in LTCC multilayer structure. Paper investigate, the effect of volume flow in cooling channels for achieving the least thermal resistance of LTCC substrate that is loaded by power thermal chips. Paper shows on the impact of the first chips thermal load on the second chip as well as. This possible new technology could ensure in the case of practical realization effective cooling and increasing reliability of high power modules.

  11. Energy efficiency in cognitive radio network: Study of cooperative sensing using different channel sensing methods

    NASA Astrophysics Data System (ADS)

    Cui, Chenxuan

    When cognitive radio (CR) operates, it starts by sensing spectrum and looking for idle bandwidth. There are several methods for CR to make a decision on either the channel is occupied or idle, for example, energy detection scheme, cyclostationary detection scheme and matching filtering detection scheme [1]. Among them, the most common method is energy detection scheme because of its algorithm and implementation simplicities [2]. There are two major methods for sensing, the first one is to sense single channel slot with varying bandwidth, whereas the second one is to sense multiple channels and each with same bandwidth. After sensing periods, samples are compared with a preset detection threshold and a decision is made on either the primary user (PU) is transmitting or not. Sometimes the sensing and decision results can be erroneous, for example, false alarm error and misdetection error may occur. In order to better control error probabilities and improve CR network performance (i.e. energy efficiency), we introduce cooperative sensing; in which several CR within a certain range detect and make decisions on channel availability together. The decisions are transmitted to and analyzed by a data fusion center (DFC) to make a final decision on channel availability. After the final decision is been made, DFC sends back the decision to the CRs in order to tell them to stay idle or start to transmit data to secondary receiver (SR) within a preset transmission time. After the transmission, a new cycle starts again with sensing. This thesis report is organized as followed: Chapter II review some of the papers on optimizing CR energy efficiency. In Chapter III, we study how to achieve maximal energy efficiency when CR senses single channel with changing bandwidth and with constrain on misdetection threshold in order to protect PU; furthermore, a case study is given and we calculate the energy efficiency. In Chapter IV, we study how to achieve maximal energy efficiency when CR senses multiple channels and each channel with same bandwidth, also, we preset a misdetection threshold and calculate the energy efficiency. A comparison will be shown between two sensing methods at the end of the chapter. Finally, Chapter V concludes this thesis.

  12. In-Plane Channel-Structured Catalyst Layer for Polymer Electrolyte Membrane Fuel Cells.

    PubMed

    Lee, Dong-Hyun; Jo, Wonhee; Yuk, Seongmin; Choi, Jaeho; Choi, Sungyu; Doo, Gisu; Lee, Dong Wook; Kim, Hee-Tak

    2018-02-07

    In this study, we present a novel catalyst layer (CL) with in-plane flow channels to enhance the mass transports in polymer electrolyte membrane fuel cells. The CL with in-plane channels on its surface is fabricated by coating a CL slurry onto a surface-treated substrate with the inverse line pattern and transferring the dried CL from the substrate to a membrane. The membrane electrode assembly with the in-plane channel-patterned CL has superior power performances in high current densities compared with an unpatterned, flat CL, demonstrating a significant enhancement of the mass-transport property by the in-plane channels carved in the CL. The performance gain is more pronounced when the channel direction is perpendicular to the flow field direction, indicating that the in-plane channels increase the utilization of the CL under the rib area. An oxygen-transport resistance analysis shows that both molecular and Knudsen diffusion can be facilitated with the introduction of the in-plane channels. The direct CL patterning technique provides a platform for the fabrication of advanced CL structures with a high structural fidelity and design flexibility and a rational guideline for designing high-performance CLs.

  13. Organic toxins as tools to understand ion channel mechanisms and structure.

    PubMed

    Morales-Lázaro, Sara Luz; Hernández-García, Enrique; Serrano-Flores, Barbara; Rosenbaum, Tamara

    2015-01-01

    Ion channels constitute a varied class of membrane proteins with pivotal roles in cellular physiology and that are fundamental for neuronal signaling, hormone secretion and muscle contractility. Hence, it is not unanticipated that toxins from diverse organisms have evolved to modulate the activity of ion channels. For instance, animals such as cone snails, scorpions, spiders and snakes use toxins to immobilize and capture their prey by affecting ion channel function. This is a beautiful example of an evolutionary process that has led to the development of an injection apparatus from predators and to the existence of toxins with high affinity and specificity for a given target. Toxins have been used in the field of ion channel biophysics for several decades to gain insight into the gating mechanisms and the structure of ion channels. Through the use of these peptides, much has been learned about the ion conduction pathways, voltage-sensing mechanisms, pore sizes, kinetics, inactivation processes, etc. This review examines an assortment of toxins that have been used to study different ion channels and describes some key findings about the structure-function relationships in these proteins through the details of the toxin-ion channel interactions.

  14. Diverse Roles for Auxiliary Subunits in Phosphorylation-Dependent Regulation of Mammalian Brain Voltage-Gated Potassium Channels

    PubMed Central

    Vacher, Helene; Trimmer, James S.

    2012-01-01

    Voltage-gated ion channels are a diverse family of signaling proteins that mediate rapid electrical signaling events. Among these, voltage-gated potassium or Kv channels are the most diverse, in part due to the large number of principal (or α) subunits and auxiliary subunits that can assemble in different combinations to generate Kv channel complexes with distinct structures and functions. The diversity of Kv channels underlies much of the variability in the active properties between different mammalian central neurons, and the dynamic changes that lead to experience-dependent plasticity in intrinsic excitability. Recent studies have revealed that Kv channel α subunits and auxiliary subunits are extensively phosphorylated, contributing to additional structural and functional diversity. Here we highlight recent studies that show that auxiliary subunits exert some of their profound effects on dendritic Kv4 and axonal Kv1 channels through phosphorylation-dependent mechanisms, either due to phosphorylation on the auxiliary subunit itself, or by influencing the extent and/or impact of α subunit phosphorylation. The complex effects of auxiliary subunits and phosphorylation provide a potent mechanism to generate additional diversity in the structure and function of Kv4 and Kv1 channels, as well as allowing for dynamic reversible regulation of these important ion channels. PMID:21822597

  15. A fully sealed plastic chip for multiplex PCR and its application in bacteria identification.

    PubMed

    Xu, Youchun; Yan, He; Zhang, Yan; Jiang, Kewei; Lu, Ying; Ren, Yonghong; Wang, Hui; Wang, Shan; Xing, Wanli

    2015-07-07

    Multiplex PCR is an effective tool for simultaneous multiple target detection but is limited by the intrinsic interference and competition among primer pairs when it is performed in one reaction tube. Dividing a multiplex PCR into many single PCRs is a simple strategy to overcome this issue. Here, we constructed a plastic, easy-to-use, fully sealed multiplex PCR chip based on reversible centrifugation for the simultaneous detection of 63 target DNA sequences. The structure of the chip is quite simple, which contains sine-shaped infusing channels and a number of reaction chambers connecting to one side of these channels. Primer pairs for multiplex PCR were sequentially preloaded in the different reaction chambers, and the chip was enclosed with PCR-compatible adhesive tape. For usage, the PCR master mix containing a DNA template is pipetted into the infusing channels and centrifuged into the reaction chambers, leaving the infusing channels filled with air to avoid cross-contamination of the different chambers. Then, the chip is sealed and placed on a flat thermal cycler for PCR. Finally, amplification products can be detected in situ using a fluorescence scanner or recovered by reverse centrifugation for further analyses. Therefore, our chip possesses two functions: 1) it can be used for multi-target detection based on end-point in situ fluorescence detection; and 2) it can work as a sample preparation unit for analyses that need multiplex PCR such as hybridization and target sequencing. The performance of this chip was carefully examined and further illustrated in the identification of 8 pathogenic bacterial genomic DNA samples and 13 drug-resistance genes. Due to simplicity of its structure and operation, accuracy and generality, high-throughput capacity, and versatile functions (i.e., for in situ detection and sample preparation), our multiplex PCR chip has great potential in clinical diagnostics and nucleic acid-based point-of-care testing.

  16. Image defog algorithm based on open close filter and gradient domain recursive bilateral filter

    NASA Astrophysics Data System (ADS)

    Liu, Daqian; Liu, Wanjun; Zhao, Qingguo; Fei, Bowen

    2017-11-01

    To solve the problems of fuzzy details, color distortion, low brightness of the image obtained by the dark channel prior defog algorithm, an image defog algorithm based on open close filter and gradient domain recursive bilateral filter, referred to as OCRBF, was put forward. The algorithm named OCRBF firstly makes use of weighted quad tree to obtain more accurate the global atmospheric value, then exploits multiple-structure element morphological open and close filter towards the minimum channel map to obtain a rough scattering map by dark channel prior, makes use of variogram to correct the transmittance map,and uses gradient domain recursive bilateral filter for the smooth operation, finally gets recovery images by image degradation model, and makes contrast adjustment to get bright, clear and no fog image. A large number of experimental results show that the proposed defog method in this paper can be good to remove the fog , recover color and definition of the fog image containing close range image, image perspective, the image including the bright areas very well, compared with other image defog algorithms,obtain more clear and natural fog free images with details of higher visibility, what's more, the relationship between the time complexity of SIDA algorithm and the number of image pixels is a linear correlation.

  17. An Experimental Study on the Darrieus-Savonius Turbine for the Tidal Current Power Generation

    NASA Astrophysics Data System (ADS)

    Kyozuka, Yusaku

    The Darrieus turbine is popular for tidal current power generation in Japan. It is simple in structure with straight wings rotating around a vertical axis, so that it has no directionality against the motion of tidal flow which changes its direction twice a day. However, there is one defect in the Darrieus turbine; its small starting torque. Once it stops, a Darrieus turbine is hard to re-start until a fairly fast current is exerted on it. To improve the starting torque of the Darrieus turbine used for tidal power generation, a hybrid turbine, composed of a Darrieus turbine and a Savonius rotor is proposed. Hydrodynamic characteristics of a semi-circular section used for the Savonius bucket were measured in a wind tunnel. The torque of a two bucket Savonius rotor was measured in a circulating water channel, where four different configurations of the bucket were compared. A combined Darrieus and Savonius turbine was tested in the circulating water channel, where the effect of the attaching angle between Darrieus wing and Savonius rotor was studied. Finally, power generation experiments using a 48 pole electric generator were conducted in a towing tank and the power coefficients were compared with the results of experiments obtained in the circulating water channel.

  18. Communication: Determining the structure of the N{sub 2}Ar van der Waals complex with laser-based channel-selected Coulomb explosion

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

    Wu, Chengyin, E-mail: cywu@pku.edu.cn; Liu, Yunquan; Gong, Qihuang

    2014-04-14

    We experimentally reconstructed the structure of the N{sub 2}Ar van der Waals complex with the technique of laser-based channel-selected Coulomb explosion imaging. The internuclear distance between the N{sub 2} center of mass and the Ar atom, i.e., the length of the van der Waals bond, was determined to be 3.88 Å from the two-body explosion channels. The angle between the van der Waals bond and the N{sub 2} principal axis was determined to be 90° from the three-body explosion channels. The reconstructed structure was contrasted with our high level ab initio calculations. The agreement demonstrated the potential application of laser-basedmore » Coulomb explosion in imaging transient molecular structure, particularly for floppy van der Waals complexes, whose structures remain difficult to be determined by conventional spectroscopic methods.« less

  19. Optimized expression and purification of NavAb provide the structural insight into the voltage dependence.

    PubMed

    Irie, Katsumasa; Haga, Yukari; Shimomura, Takushi; Fujiyoshi, Yoshinori

    2018-01-01

    Voltage-gated sodium channels are crucial for electro-signalling in living systems. Analysis of the molecular mechanism requires both fine electrophysiological evaluation and high-resolution channel structures. Here, we optimized a dual expression system of NavAb, which is a well-established standard of prokaryotic voltage-gated sodium channels, for E. coli and insect cells using a single plasmid vector to analyse high-resolution protein structures and measure large ionic currents. Using this expression system, we evaluated the voltage dependence and determined the crystal structures of NavAb wild-type and two mutants, E32Q and N49K, whose voltage dependence were positively shifted and essential interactions were lost in voltage sensor domain. The structural and functional comparison elucidated the molecular mechanisms of the voltage dependence of prokaryotic voltage-gated sodium channels. © 2017 Federation of European Biochemical Societies.

  20. Function and structure in glycine receptors and some of their relatives.

    PubMed

    Colquhoun, David; Sivilotti, Lucia G

    2004-06-01

    In the field of ligand-gated ion channels, recent developments, both in the knowledge of structure and in the measurement of function at the single-channel level, have allowed a sensible start to be made on understanding the relationship between structure and function in these proteins. In this review, the cases of glycine, nicotinic ACh and glutamate receptors are compared and contrasted, and problems such as how binding of agonist causes the channel to open, and why partial agonists are partial, are considered. Some observations, both structural and functional, suggest that more attention needs to be paid to conformational changes that occur before the channel opens. Such changes might account for the interaction found between subunits of the glycine receptor while it is still shut and, perhaps, the agonist-dependent structural changes seen in AMPA receptors. They might also complicate our understanding of the binding-gating problem.

  1. Design and simulation of a novel high-efficiency cooling heat-sink structure using fluid-thermodynamics

    NASA Astrophysics Data System (ADS)

    Hongqi, Jing; Li, Zhong; Yuxi, Ni; Junjie, Zhang; Suping, Liu; Xiaoyu, Ma

    2015-10-01

    A novel high-efficiency cooling mini-channel heat-sink structure has been designed to meet the package technology demands of high power density laser diode array stacks. Thermal and water flowing characteristics have been simulated using the Ansys-Fluent software. Owing to the increased effective cooling area, this mini-channel heat-sink structure has a better cooling effect when compared with the traditional macro-channel heat-sinks. Owing to the lower flow velocity in this novel high efficient cooling structure, the chillers' water-pressure requirement is reduced. Meanwhile, the machining process of this high-efficiency cooling mini-channel heat-sink structure is simple and the cost is relatively low, it also has advantages in terms of high durability and long lifetime. This heat-sink is an ideal choice for the package of high power density laser diode array stacks. Project supported by the Defense Industrial Technology Development Program (No. B1320133033).

  2. Numerical Simulation of Induction Channel Furnace to Investigate Efficiency for low Frequencies

    NASA Astrophysics Data System (ADS)

    Hang, N. Tran Thi; Lüdtke, U.

    2018-05-01

    The foundry industry worldwide commonly uses induction channel furnaces to heat and melt alloys. The operating frequency is one of the main issues when constructing an efficient channel furnace. It is possible to choose operating frequencies lower than 50 Hz using a modern IGBT power converter. This work shows the simulation results using ANSYS with the goal of finding the best electrical frequency necessary to operate the induction furnace. First, a two-dimensional model is used to calculate the efficiency depending on frequency. Then, the channel model is extended to a more realistic three-dimensional model. Finally, the influence of frequency, inductor profile, and several components of the induction channel furnace are discussed.

  3. Calculation of the electron wave function in a graded-channel double-heterojunction modulation-doped field-effect transistor

    NASA Technical Reports Server (NTRS)

    Mui, D. S. L.; Patil, M. B.; Morkoc, H.

    1989-01-01

    Three double-heterojunction modulation-doped field-effect transistor structures with different channel composition are investigated theoretically. All of these transistors have an In(x)Ga(1-x)As channel sandwiched between two doped Al(0.3)Ga(0.7)As barriers with undoped spacer layers. In one of the structures, x varies from 0 from either heterojunction to 0.15 at the center of the channel quadratically; in the other two, constant values of x of 0 and 0.15 are used. The Poisson and Schroedinger equations are solved self-consistently for the electron wave function in all three cases. The results showed that the two-dimensional electron gas (2DEG) concentration in the channel of the quadratically graded structure is higher than the x = 0 one and slightly lower than the x = 0.15 one, and the mean distance of the 2DEG is closer to the center of the channel for this transistor than the other two. These two effects have important implications on the electron mobility in the channel.

  4. Structural Insight into Methyl-Coenzyme M Reductase Chemistry using Coenzyme B Analogues†,‡

    PubMed Central

    Cedervall, Peder E.; Dey, Mishtu; Pearson, Arwen R.; Ragsdale, Stephen W.; Wilmot, Carrie M.

    2011-01-01

    Methyl-coenzyme M reductase (MCR) catalyzes the final and rate-limiting step in methane biogenesis; the reduction of methyl-coenzyme M (methyl-SCoM) by coenzyme B (CoBSH) to methane and a heterodisulfide (CoBS-SCoM). Crystallographic studies show that the active site is deeply buried within the enzyme, and contains a highly reduced nickel-tetrapyrrole, coenzyme F430. Methyl-SCoM must enter the active site prior to CoBSH, as species derived from analogues of methyl-SCoM are always observed bound to the F430 nickel in the deepest part of the 30 Å long substrate channel that leads from the protein surface to the active site. The seven-carbon mercaptoalkanoyl chain of CoBSH binds within a 16 Å predominantly hydrophobic part of the channel close to F430, with the CoBSH thiolate lying closest to the nickel at a distance of 8.8 Å. It has previously been suggested that binding of CoBSH initiates catalysis by inducing a conformational change that moves methyl-SCoM closer to the nickel promoting cleavage of the C-S bond of methyl-SCoM. In order to better understand the structural role of CoBSH early in the MCR mechanism, we have determined crystal structures of MCR in complex with four different CoBSH analogues; pentanoyl-, hexanoyl-, octanoyl- and nonanoyl- derivatives of CoBSH (CoB5SH, CoB6SH, CoB8SH and CoB9SH respectively). The data presented here reveal that the shorter CoB5SH mercaptoalkanoyl chain overlays with that of CoBSH, but terminates two units short of the CoBSH thiolate position. In contrast, the mercaptoalkanoyl chain of CoB6SH adopts a different conformation, such that its thiolate is coincident with the position of the CoBSH thiolate. This is consistent with the observation that CoB6SH is a slow substrate. A labile water in the substrate channel was found to be a sensitive indicator for the presence of CoBSH and HSCoM. The longer CoB8SH and CoB9SH analogues can be accommodated in the active site through exclusion of this water. These analogues react with Ni(III)-methyl; a proposed MCR catalytic intermediate of methanogenesis. The CoB8SH thiolate is 2.6 Å closer to the nickel than that of CoBSH, but the additional carbon of CoB9SH only decreases the nickel thiolate distance a further 0.3 Å. Although the analogues did not induce any structural changes in the substrate channel, the thiolates appeared to preferentially bind at two distinct positions in the channel; one being the previously observed CoBSH thiolate position, and the other being at a hydrophobic annulus of residues that lines the channel proximal to the nickel. PMID:20707311

  5. Gating of Connexin Channels by transjunctional-voltage: Conformations and models of open and closed states.

    PubMed

    Bargiello, Thaddeus A; Oh, Seunghoon; Tang, Qingxiu; Bargiello, Nicholas K; Dowd, Terry L; Kwon, Taekyung

    2018-01-01

    Voltage is an important physiologic regulator of channels formed by the connexin gene family. Connexins are unique among ion channels in that both plasma membrane inserted hemichannels (undocked hemichannels) and intercellular channels (aggregates of which form gap junctions) have important physiological roles. The hemichannel is the fundamental unit of gap junction voltage-gating. Each hemichannel displays two distinct voltage-gating mechanisms that are primarily sensitive to a voltage gradient formed along the length of the channel pore (the transjunctional voltage) rather than sensitivity to the absolute membrane potential (V m or V i-o ). These transjunctional voltage dependent processes have been termed V j - or fast-gating and loop- or slow-gating. Understanding the mechanism of voltage-gating, defined as the sequence of voltage-driven transitions that connect open and closed states, first and foremost requires atomic resolution models of the end states. Although ion channels formed by connexins were among the first to be characterized structurally by electron microscopy and x-ray diffraction in the early 1980's, subsequent progress has been slow. Much of the current understanding of the structure-function relations of connexin channels is based on two crystal structures of Cx26 gap junction channels. Refinement of crystal structure by all-atom molecular dynamics and incorporation of charge changing protein modifications has resulted in an atomic model of the open state that arguably corresponds to the physiologic open state. Obtaining validated atomic models of voltage-dependent closed states is more challenging, as there are currently no methods to solve protein structure while a stable voltage gradient is applied across the length of an oriented channel. It is widely believed that the best approach to solve the atomic structure of a voltage-gated closed ion channel is to apply different but complementary experimental and computational methods and to use the resulting information to derive a consensus atomic structure that is then subjected to rigorous validation. In this paper, we summarize our efforts to obtain and validate atomic models of the open and voltage-driven closed states of undocked connexin hemichannels. 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.

  6. Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel

    PubMed Central

    Sauguet, Ludovic; Howard, Rebecca J.; Malherbe, Laurie; Lee, Ui S.; Corringer, Pierre-Jean; Harris, R. Adron; Delarue, Marc

    2014-01-01

    Ethanol alters nerve signalling by interacting with proteins in the central nervous system, particularly pentameric ligand-gated ion channels. A recent series of mutagenesis experiments on Gloeobacter violaceus ligand-gated ion channel, a prokaryotic member of this family, identified a single-site variant that is potentiated by pharmacologically relevant concentrations of ethanol. Here we determine crystal structures of the ethanol-sensitized variant in the absence and presence of ethanol and related modulators, which bind in a transmembrane cavity between channel subunits and may stabilize the open form of the channel. Structural and mutagenesis studies defined overlapping mechanisms of potentiation by alcohols and anaesthetics via the inter-subunit cavity. Furthermore, homology modelling show this cavity to be conserved in human ethanol-sensitive glycine and GABA(A) receptors, and to involve residues previously shown to influence alcohol and anaesthetic action on these proteins. These results suggest a common structural basis for ethanol potentiation of an important class of targets for neurological actions of ethanol. PMID:23591864

  7. Structural analyses of Ca2+/CaM interaction with NaV channel C-termini reveal mechanisms of calcium-dependent regulation

    PubMed Central

    Wang, Chaojian; Chung, Ben C.; Yan, Haidun; Wang, Hong-Gang; Lee, Seok-Yong; Pitt, Geoffrey S.

    2014-01-01

    Ca2+ regulates voltage-gated Na+ (NaV) channels and perturbed Ca2+ regulation of NaV function is associated with epilepsy syndromes, autism, and cardiac arrhythmias. Understanding the disease mechanisms, however, has been hindered by a lack of structural information and competing models for how Ca2+ affects NaV channel function. Here, we report the crystal structures of two ternary complexes of a human NaV cytosolic C-terminal domain (CTD), a fibroblast growth factor homologous factor, and Ca2+/calmodulin (Ca2+/CaM). These structures rule out direct binding of Ca2+ to the NaV CTD, and uncover new contacts between CaM and the NaV CTD. Probing these new contacts with biochemical and functional experiments allows us to propose a mechanism by which Ca2+ could regulate NaV channels. Further, our model provides hints towards understanding the molecular basis of the neurologic disorders and cardiac arrhythmias caused by NaV channel mutations. PMID:25232683

  8. Crystal structure of the epithelial calcium channel TRPV6.

    PubMed

    Saotome, Kei; Singh, Appu K; Yelshanskaya, Maria V; Sobolevsky, Alexander I

    2016-06-23

    Precise regulation of calcium homeostasis is essential for many physiological functions. The Ca(2+)-selective transient receptor potential (TRP) channels TRPV5 and TRPV6 play vital roles in calcium homeostasis as Ca(2+) uptake channels in epithelial tissues. Detailed structural bases for their assembly and Ca(2+) permeation remain obscure. Here we report the crystal structure of rat TRPV6 at 3.25 Å resolution. The overall architecture of TRPV6 reveals shared and unique features compared with other TRP channels. Intracellular domains engage in extensive interactions to form an intracellular 'skirt' involved in allosteric modulation. In the K(+) channel-like transmembrane domain, Ca(2+) selectivity is determined by direct coordination of Ca(2+) by a ring of aspartate side chains in the selectivity filter. On the basis of crystallographically identified cation-binding sites at the pore axis and extracellular vestibule, we propose a Ca(2+) permeation mechanism. Our results provide a structural foundation for understanding the regulation of epithelial Ca(2+) uptake and its role in pathophysiology.

  9. An electrostatic mechanism for Ca2+-mediated regulation of gap junction channels

    PubMed Central

    Bennett, Brad C.; Purdy, Michael D.; Baker, Kent A.; Acharya, Chayan; McIntire, William E.; Stevens, Raymond C.; Zhang, Qinghai; Harris, Andrew L.; Abagyan, Ruben; Yeager, Mark

    2016-01-01

    Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca2+ blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca2+. The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca2+ coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca2+chelation. Computational analysis revealed that Ca2+-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K+ into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore. PMID:26753910

  10. A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.

    PubMed

    Li-Smerin, Y; Hackos, D H; Swartz, K J

    2000-02-01

    Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.

  11. Functional evolution of scorpion venom peptides with an inhibitor cystine knot fold.

    PubMed

    Gao, Bin; Harvey, Peta J; Craik, David J; Ronjat, Michel; De Waard, Michel; Zhu, Shunyi

    2013-06-27

    The ICK (inhibitor cystine knot) defines a large superfamily of polypeptides with high structural stability and functional diversity. Here, we describe a new scorpion venom-derived K+ channel toxin (named λ-MeuKTx-1) with an ICK fold through gene cloning, chemical synthesis, nuclear magnetic resonance spectroscopy, Ca2+ release measurements and electrophysiological recordings. λ-MeuKTx-1 was found to adopt an ICK fold that contains a three-strand anti-parallel β-sheet and a 310-helix. Functionally, this peptide selectively inhibits the Drosophila Shaker K+ channel but is not capable of activating skeletal-type Ca2+ release channels/ryanodine receptors, which is remarkably different from the previously known scorpion venom ICK peptides. The removal of two C-terminal residues of λ-MeuKTx-1 led to the loss of the inhibitory activity on the channel, whereas the C-terminal amidation resulted in the emergence of activity on four mammalian K+ channels accompanied by the loss of activity on the Shaker channel. A combination of structural and pharmacological data allows the recognition of three putative functional sites involved in channel blockade of λ-MeuKTx-1. The presence of a functional dyad in λ-MeuKTx-1 supports functional convergence among scorpion venom peptides with different folds. Furthermore, similarities in precursor organization, exon-intron structure, 3D-fold and function suggest that scorpion venom ICK-type K+ channel inhibitors and Ca2+ release channel activators share a common ancestor and their divergence occurs after speciation between buthidae and non-buthids. The structural and functional characterizations of the first scorpion venom ICK toxin with K+ channel-blocking activity sheds light on functionally divergent and convergent evolution of this conserved scaffold of ancient origin.

  12. Different Ligands of the TRPV3 Cation Channel Cause Distinct Conformational Changes as Revealed by Intrinsic Tryptophan Fluorescence Quenching*

    PubMed Central

    Billen, Bert; Brams, Marijke; Debaveye, Sarah; Remeeva, Alina; Alpizar, Yeranddy A.; Waelkens, Etienne; Kreir, Mohamed; Brüggemann, Andrea; Talavera, Karel; Nilius, Bernd; Voets, Thomas; Ulens, Chris

    2015-01-01

    TRPV3 is a thermosensitive ion channel primarily expressed in epithelial tissues of the skin, nose, and tongue. The channel has been implicated in environmental thermosensation, hyperalgesia in inflamed tissues, skin sensitization, and hair growth. Although transient receptor potential (TRP) channel research has vastly increased our understanding of the physiological mechanisms of nociception and thermosensation, the molecular mechanics of these ion channels are still largely elusive. In order to better comprehend the functional properties and the mechanism of action in TRP channels, high-resolution three-dimensional structures are indispensable, because they will yield the necessary insights into architectural intimacies at the atomic level. However, structural studies of membrane proteins are currently hampered by difficulties in protein purification and in establishing suitable crystallization conditions. In this report, we present a novel protocol for the purification of membrane proteins, which takes advantage of a C-terminal GFP fusion. Using this protocol, we purified human TRPV3. We show that the purified protein is a fully functional ion channel with properties akin to the native channel using planar patch clamp on reconstituted channels and intrinsic tryptophan fluorescence spectroscopy. Using intrinsic tryptophan fluorescence spectroscopy, we reveal clear distinctions in the molecular interaction of different ligands with the channel. Altogether, this study provides powerful tools to broaden our understanding of ligand interaction with TRPV channels, and the availability of purified human TRPV3 opens up perspectives for further structural and functional studies. PMID:25829496

  13. The solution structure of omega-Aga-IVB, a P-type calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.

    PubMed

    Reily, M D; Thanabal, V; Adams, M E

    1995-02-01

    The 48 amino acid peptides omega-Aga-IVA and omega-Aga-IVB are the first agents known to specifically block P-type calcium channels in mammalian brain, thus complementing the existing suite of pharmacological tools used for characterizing calcium channels. These peptides provide a new set of probes for studies aimed at elucidating the structural basis underlying the subtype specificity of calcium channel antagonists. We used 288 NMR-derived constraints in a protocol combining distance geometry and molecular dynamics employing the program DGII, followed by energy minimization with Discover to derive the three-dimensional structure of omega-Aga-IVB. The toxin consists of a well-defined core region, comprising seven solvent-shielded residues and a well-defined triple-stranded beta-sheet. Four loop regions have average backbone rms deviations between 0.38 and 1.31 A, two of which are well-defined type-II beta-turns. Other structural features include disordered C- and N-termini and several conserved basic amino acids that are clustered on one face of the molecule. The reported structure suggests a possible surface for interaction with the channel. This surface contains amino acids that are identical to those of another known P-type calcium channel antagonist, omega-Aga-IVA, and is rich in basic residues that may have a role in binding to the anionic sites in the extracellular regions of the calcium channel.

  14. Channel Control Structures for Souris River, Minot, North Dakota. Hydraulic Model Investigation.

    DTIC Science & Technology

    1981-04-01

    in good agreement with other broad - and sharp - crested weirs . 19. Early testing of the typical type I structure indicated that the size of the riprap...III structure (Figure 4) will consist of a concrete weir with a crest lo- cated 10.0 ft above the channel bottom with a 1-ft-high end sill at the end...to the channel, was effective in preventing significant head differ- ential and damage to the strucLure with overbank flow conditions. The weir crest

  15. Bathymetric and velocimetric surveys at highway bridges crossing the Missouri River near Kansas City, Missouri, June 2–4, 2015

    USGS Publications Warehouse

    Huizinga, Richard J.

    2016-06-22

    A local spatial minimum average channel-bed elevation at structure A7650 (site 10) compared to adjacent sites may indicate this site is at or near a local feature that controls sediment deposition and scour. The average channel-bed elevation values and the distribution of channel-bed elevations imply that sediment unable to deposit near structure A7650 is flushed downstream and deposits at the next downstream site, structure A5817 (site 11).

  16. Conductance of Ion Channels - Theory vs. Experiment

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Wilson, Michael; Mijajlovic, Milan

    2013-01-01

    Transmembrane ion channels mediate a number of essential physiological processes in a cell ranging from regulating osmotic pressure to transmission of neural signals. Kinetics and selectivity of ion transport is of critical importance to a cell and, not surprisingly, it is a subject of numerous experimental and theoretical studies. In this presentation we will analyze in detail computer simulations of two simple channels from fungi - antiamoebin and trichotoxin. Each of these channels is made of an alpha-helical bundle of small, nongenomically synthesized peptides containing a number of rare amino acids and exhibits strong antimicrobial activity. We will focus on calculating ionic conductance defined as the ratio of ionic current through the channel to applied voltage. From molecular dynamics simulations, conductance can be calculated in at least two ways, each involving different approximations. Specifically, the current, given as the number of charges transferred through the channel per unit of time, can be obtained from the number of events in which ions cross the channel during the simulation. This method works well for large currents (high conductance values and/or applied voltages). If the number of crossing events is small, reliable estimates of current are difficult to achieve. Alternatively, conductance can be estimated assuming that ion transport can be well approximated as diffusion in the external potential given by the free energy profile. Then, the current can be calculated by solving the one-dimensional diffusion equation in this external potential and applied voltage (the generalized Nernst-Planck equation). To do so three ingredients are needed: the free energy profile, the position-dependent diffusion coefficient and the diffusive flux of ions into the channel. All these quantities can be obtained from molecular dynamics simulations. An important advantage of this method is that it can be used equally well to estimating large and small currents. In addition, once the free energy profile becomes available the full current-voltage dependence can be readily obtained. For both channels we carried out calculations using both approaches. We also tested the main assumptions underlying the diffusive model, such as uncorrelated nature of individual crossing events and Fickian diffusion. The accuracy and consistency of different methods will be discussed. Finally we will discuss how comparisons between calculated and measured ionic conductance and selectivity of transport can be used for determining structural models of the channels.

  17. Fabrication and Analysis of a Selectively Contacted Dual Channel High Electron Mobility Field-Effect Transistor

    NASA Astrophysics Data System (ADS)

    Khanna, Ravi

    1992-01-01

    A selectively contacted dual-channel high electron mobility transistor (SCD-CHEMT) has been designed, fabricated, and electrically characterized, in order to better understand the properties of two layers of two-dimensional electron gases (2DEGs) confined within a quantum well. The 2DEGs are placed under a Schottky barrier control gate which modulates their sheet charge densities, and by use of auxiliary Schottky barrier gates and two levels of ohmic contacts, electrical contacts to the individual channels in which each 2DEG resides is achieved. The design of the dual channel FET structure, and its practical realization by recourse to process development and fabrication are described, as are the techniques, results, and interpretations of electrical characterizations used to analyze the completed device. Critical fabrication procedures involving photolithography, etching, deposition, shallow and deep ohmic contact formation, and gate formation are developed, and a simple technique to reduce gate leakage by photo-oxidation is demonstrated. Analysis of the completed device is performed using one-dimensional band diagram simulations, magnetotransport and electrical measurements. Magnetotransport studies establish the existence of two 2DEGs within the quantum well at 4K. Drain current vs. drain voltage, and transconductance vs. gate voltage characteristics at room temperature confirm the presence of two 2DEGs and show that current flow between them occurs easily at room temperature. Carrier electron mobility profiles are taken of the 2DEGs and show that the lower 2DEG has a mobility comparable to that of a 2DEG formed at a normal interface, indicating that the "inverted interface problem" has been overcome. Capacitance vs. gate voltage measurements are taken, which are consistent with a simple device model consisting of gate depletion and interelectrode parasitic capacitances. It is concluded from the analysis that the dual channel system resides in three basic states: (1) Both channels are occupied by 2DEGs or (2) The upper channel is depleted, or (3) Both channels depleted. Finally, increase in isolation between the two 2DEGs is dramatically demonstrated at 77K by the drain current vs. drain voltage, and transconductance vs. gate voltage characteristics.

  18. Nanosecond Surface Microdischarges in Multilayer Structures

    NASA Astrophysics Data System (ADS)

    Dubinov, A. E.; Lyubimtseva, V. A.

    2018-05-01

    Multilayer structures in which nanosecond surface microdischarges are generated have been developed, fabricated, and investigated. In these structures, layers are made in the form of thin transparent films, and a plasma discharge channel is formed in thin spacings between the layers. Passage of the discharge channel from one layer into the neighboring layer is implemented via pre-fabricated microholes. Images of microdischarges were obtained which confirmed that their plasma channels are formed according to the route assigned by the holes. The route may follow a fairly complex scheme and have self-intersection points and portions in which the electrons are bound to move in opposition to the electric field. In studying the shape of channels in multilayer strictures, the authors have found a new physical effect which lies in the azimuthal self-orientation of the discharge channel as it passes from one microhole to another.

  19. Carbon dioxide photolysis from 150 to 210 nm: singlet and triplet channel dynamics, UV-spectrum, and isotope effects.

    PubMed

    Schmidt, Johan A; Johnson, Matthew S; Schinke, Reinhard

    2013-10-29

    We present a first principles study of the carbon dioxide (CO2) photodissociation process in the 150- to 210-nm wavelength range, with emphasis on photolysis below the carbon monoxide + singlet channel threshold at ~167 nm. The calculations reproduce experimental absorption cross-sections at a resolution of ~0.5 nm without scaling the intensity. The observed structure in the 150- to 210-nm range is caused by excitation of bending motion supported by the deep wells at bent geometries in the and potential energy surfaces. Predissociation below the singlet channel threshold occurs via spin-orbit coupling to nearby repulsive triplet states. Carbon monoxide vibrational and rotational state distributions in the singlet channel as well as the triplet channel for excitation at 157 nm satisfactorily reproduce experimental data. The cross-sections of individual CO2 isotopologues ((12)C(16)O2, (12)C(17)O(16)O, (12)C(18)O(16)O, (13)C(16)O2, and (13)C(18)O(16)O) are calculated, demonstrating that strong isotopic fractionation will occur as a function of wavelength. The calculations provide accurate, detailed insight into CO2 photoabsorption and dissociation dynamics, and greatly extend knowledge of the temperature dependence of the cross-section to cover the range from 0 to 400 K that is useful for calculations of propagation of stellar light in planetary atmospheres. The model is also relevant for the interpretation of laboratory experiments on mass-independent isotopic fractionation. Finally, the model shows that the mass-independent fractionation observed in a series of Hg lamp experiments is not a result of hyperfine interactions making predissociation of (17)O containing CO2 more efficient.

  20. Second-order Poisson Nernst-Planck solver for ion channel transport

    PubMed Central

    Zheng, Qiong; Chen, Duan; Wei, Guo-Wei

    2010-01-01

    The Poisson Nernst-Planck (PNP) theory is a simplified continuum model for a wide variety of chemical, physical and biological applications. Its ability of providing quantitative explanation and increasingly qualitative predictions of experimental measurements has earned itself much recognition in the research community. Numerous computational algorithms have been constructed for the solution of the PNP equations. However, in the realistic ion-channel context, no second order convergent PNP algorithm has ever been reported in the literature, due to many numerical obstacles, including discontinuous coefficients, singular charges, geometric singularities, and nonlinear couplings. The present work introduces a number of numerical algorithms to overcome the abovementioned numerical challenges and constructs the first second-order convergent PNP solver in the ion-channel context. First, a Dirichlet to Neumann mapping (DNM) algorithm is designed to alleviate the charge singularity due to the protein structure. Additionally, the matched interface and boundary (MIB) method is reformulated for solving the PNP equations. The MIB method systematically enforces the interface jump conditions and achieves the second order accuracy in the presence of complex geometry and geometric singularities of molecular surfaces. Moreover, two iterative schemes are utilized to deal with the coupled nonlinear equations. Furthermore, extensive and rigorous numerical validations are carried out over a number of geometries, including a sphere, two proteins and an ion channel, to examine the numerical accuracy and convergence order of the present numerical algorithms. Finally, application is considered to a real transmembrane protein, the Gramicidin A channel protein. The performance of the proposed numerical techniques is tested against a number of factors, including mesh sizes, diffusion coefficient profiles, iterative schemes, ion concentrations, and applied voltages. Numerical predictions are compared with experimental measurements. PMID:21552336

  1. Carbon dioxide photolysis from 150 to 210 nm: Singlet and triplet channel dynamics, UV-spectrum, and isotope effects

    PubMed Central

    Schmidt, Johan A.; Johnson, Matthew S.; Schinke, Reinhard

    2013-01-01

    We present a first principles study of the carbon dioxide (CO2) photodissociation process in the 150- to 210-nm wavelength range, with emphasis on photolysis below the carbon monoxide + singlet channel threshold at ∼167 nm. The calculations reproduce experimental absorption cross-sections at a resolution of ∼0.5 nm without scaling the intensity. The observed structure in the 150- to 210-nm range is caused by excitation of bending motion supported by the deep wells at bent geometries in the and potential energy surfaces. Predissociation below the singlet channel threshold occurs via spin-orbit coupling to nearby repulsive triplet states. Carbon monoxide vibrational and rotational state distributions in the singlet channel as well as the triplet channel for excitation at 157 nm satisfactorily reproduce experimental data. The cross-sections of individual CO2 isotopologues (12C16O2, 12C17O16O, 12C18O16O, 13C16O2, and 13C18O16O) are calculated, demonstrating that strong isotopic fractionation will occur as a function of wavelength. The calculations provide accurate, detailed insight into CO2 photoabsorption and dissociation dynamics, and greatly extend knowledge of the temperature dependence of the cross-section to cover the range from 0 to 400 K that is useful for calculations of propagation of stellar light in planetary atmospheres. The model is also relevant for the interpretation of laboratory experiments on mass-independent isotopic fractionation. Finally, the model shows that the mass-independent fractionation observed in a series of Hg lamp experiments is not a result of hyperfine interactions making predissociation of 17O containing CO2 more efficient. PMID:23776249

  2. A Folding Zone in the Ribosomal Exit Tunnel for Kv1.3 Helix Formation

    PubMed Central

    Tu, LiWei; Deutsch, Carol

    2010-01-01

    SUMMARY Although it is now clear that protein secondary structure can be acquired early, while the nascent peptide resides within the ribosomal exit tunnel, the principles governing folding of native polytopic proteins have not yet been elucidated. We now report an extensive investigation of native Kv1.3, a voltage-gated K+ channel, including transmembrane and linker segments synthesized in sequence. These native segments form helices vectorially (N- to C-terminus) only in a permissive vestibule located in the last 20Å of the tunnel. Native linker sequences similarly fold in this vestibule. Finally, secondary structure acquired in the ribosome is retained in the translocon. These findings emerge from accessibility studies of a diversity of native transmembrane and linker sequences and may therefore be applicable to protein biogenesis in general. PMID:20060838

  3. Transport of Light Ions in Matter

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Cucinotta, F. A.; Tai, H.; Shinn, J. L.; Chun, S. Y.; Tripathi, R. K.; Sihver, L.

    1998-01-01

    A recent set of light ion experiments are analyzed using the Green's function method of solving the Boltzmann equation for ions of high charge and energy (the GRNTRN transport code) and the NUCFRG2 fragmentation database generator code. Although the NUCFRG2 code reasonably represents the fragmentation of heavy ions, the effects of light ion fragmentation requires a more detailed nuclear model including shell structure and short range correlations appearing as tightly bound clusters in the light ion nucleus. The most recent NTJCFRG2 code is augmented with a quasielastic alpha knockout model and semiempirical adjustments (up to 30 percent in charge removal) in the fragmentation process allowing reasonable agreement with the experiments to be obtained. A final resolution of the appropriate cross sections must await the full development of a coupled channel reaction model in which shell structure and clustering can be accurately evaluated.

  4. Structural Insight into the Assembly of TRPV Channels

    PubMed Central

    Huynh, Kevin W.; Cohen, Matthew R.; Chakrapani, Sudha; Holdaway, Heather A.; Stewart, Phoebe L.; Moiseenkova-Bell, Vera Y.

    2017-01-01

    SUMMARY Transient receptor potential (TRP) proteins are a large family of polymodal nonselective cation channels. The TRP vanilloid (TRPV) subfamily consists of six homologous members with diverse functions. TRPV1–TRPV4 are nonselective cation channels proposed to play a role in nociception, while TRPV5 and TRPV6 are involved in epithelial Ca2+ homeostasis. Here we present the cryo-electron microscopy (cryo-EM) structure of functional, full-length TRPV2 at 13.6 Å resolution. The map reveals that the TRPV2 cytoplasmic domain displays a 4-fold petal-like shape in which high-resolution N-terminal ankyrin repeat domain (ARD) structures can be unambiguously fitted. Fitting of the available ARD structures for other TRPV subfamily members into the TRPV2 EM map suggests that TRPV subfamily members have highly homologous structural topologies. These results allowed us to postulate a structural explanation for the functional diversity among TRPV channels and their differential regulation by proteins and ligands. PMID:24373766

  5. Closing the wedge: Search strategies for extended Higgs sectors with heavy flavor final states

    DOE PAGES

    Gori, Stefania; Kim, Ian-Woo; Shah, Nausheen R.; ...

    2016-04-29

    We consider search strategies for an extended Higgs sector at the high-luminosity LHC14 utilizing multitop final states. In the framework of a two Higgs doublet model, the purely top final states (more » $$t\\bar{t}$$, 4t) are important channels for heavy Higgs bosons with masses in the wedge above 2m t and at low values of tanβ, while a 2b2t final state is most relevant at moderate values of tanβ. We find, in the $$t\\bar{t}$$ H channel, with H→$$t\\bar{t}$$, that both single and three lepton final states can provide statistically significant constraints at low values of tanβ for mA as high as ~750 GeV. When systematics on the $$t\\bar{t}$$ background are taken into account, however, the three lepton final state is more powerful, though the precise constraint depends fairly sensitively on lepton fake rates. We also find that neither 2b2t nor $$t\\bar{t}$$ final states provide constraints on additional heavy Higgs bosons with couplings to tops smaller than the top Yukawa due to expected systematic uncertainties in the tt background.« less

  6. Fabrication of TiO2 Nanosheet Aarrays/Graphene/Cu2O Composite Structure for Enhanced Photocatalytic Activities

    NASA Astrophysics Data System (ADS)

    Huang, Jinzhao; Fu, Ke; Deng, Xiaolong; Yao, Nannan; Wei, Mingzhi

    2017-04-01

    TiO2 NSAs/graphene/Cu2O was fabricated on the carbon fiber to use as photocastalysts by coating Cu2O on the graphene (G) decorated TiO2 nanosheet arrays (NSAs). The research focus on constructing the composite structure and investigating the reason to enhance the photocatalytic ability. The morphological, structural, and photocatalytic properties of the as-synthesized products were characterized. The experimental results indicate that the better photocatalytic performance is ascribed to the following reasons. First, the TiO2 NSAs/graphene/Cu2O composite structure fabricated on the carbon cloth can form a 3D structure which can provide a higher specific surface area and enhance the light absorption. Second, the graphene as an electron sink can accept the photoelectrons from the photoexcited Cu2O which will reduce the recombination. Third, the TiO2 nanosheet can provide more favorable carrier transportation channel which can reduce the recombination of carriers. Finally, the Cu2O can extend the light absorption range.

  7. River channel morphology and hydraulics properties due to introduction of plant basket hydraulic structures for river channel management

    NASA Astrophysics Data System (ADS)

    Kałuża, Tomasz; Radecki-Pawlik, Artur; Plesiński, Karol; Walczak, Natalia; Szoszkiewicz, Krzysztof; Radecki-Pawlik, Bartosz

    2016-04-01

    In the present time integrated water management is directly connected with management and direct works in river channels themselves which are taking into account morphological processes in rivers and improve flow conditions. Our work focused on the hydraulic and hydrodynamic consequences upon the introduction of the concept of the improvement of the hydromorphological conditions of the Flinta River in a given reach following river channel management concept. Based on a comprehensive study of the hydromorphological state of the river, four sections were selected where restoration measures can efficiently improve river habitat conditions in the river. For each section a set of technical and biological measures were proposed and implemented in practice. One of the proposed solutions was to construct plant basket hydraulic structures (PBHS) within the river channel, which are essentially plant barriers working as sediment traps, changing river channel morphology and are in line with concepts of Water Framework Directive. These relatively small structures work as crested weirs and unquestionably change the channel morphology. Along our work we show the results of three-year long (2013-2015) systematic measurements that provided information on the morphological consequences of introducing such structures into a river channel. Our main conclusions are as follows: 1. Plant basket hydraulic structures cause changes in hydrodynamic conditions and result in sediment accumulation and the formation of river backwaters upstream and downstream the obstacle; 2. The introduced plant basket hydraulic structures cause plant debris accumulation which influences the hydrodynamic flow conditions; 3. The installation of plant basket hydraulic structures on the river bed changes flow pattern as well as flow hydrodynamic conditions causing river braiding process; 4. The erosion rate below the plant basket hydraulic structures is due to the hydraulic work conditions of the PBHS and its calculated value was confirmed by direct measurements in the field. In our calculations we used VCmaster software. This Work funded by the National Science Centre allocated based on the number of decision: DEC-2011/01 / B / ST10 / 06959

  8. Suspended liquid subtractive lithography: printing three dimensional channels directly into uncured PDMS

    NASA Astrophysics Data System (ADS)

    Helmer, D.; Voigt, A.; Wagner, S.; Keller, N.; Sachsenheimer, K.; Kotz, F.; Nargang, T. M.; Rapp, B. E.

    2018-02-01

    Polydimethylsiloxane (PDMS) is one of the most widely used polymers for the generation of microfluidic chips. The standard procedures of soft lithography require the formation of a new master structure for every design which is timeconsuming and expensive. All channel generated by soft lithography need to be consecutively sealed by bonding which is a process that can proof to be hard to control. Channel cross-sections are largely restricted to squares or flat-topped designs and the generation of truly three-dimensional designs is not straightforward. Here we present Suspended Liquid Subtractive Lithography (SLSL) a method for generating microfluidic channels of nearly arbitrary three-dimensional structures in PDMS that do not require master formation or bonding and give circular channel cross sections which are especially interesting for mimicking in vivo environments. In SLSL, an immiscible liquid is introduced into the uncured PDMS by a capillary mounted on a 3D printer head. The liquid forms continuous "threads" inside the matrix thus creating void suspended channel structures.

  9. Enhancement-mode two-channel triple quantum dot from an undoped Si/Si 0.8Ge 0.2 quantum well hetero-structure

    DOE PAGES

    Studenikin, S. A.; Gaudreau, L.; Kataoka, K.; ...

    2018-06-04

    Here, we demonstrate coupled triple dot operation and charge sensing capability for the recently introduced quantum dot technology employing undoped Si/Si 0.8Ge 0.2 hetero-structures which also incorporate a single metal-gate layer to simplify fabrication. Si/SiGe hetero-structures with a Ge concentration of 20% rather than the more usual 30% typically encountered offer higher electron mobility. The devices consist of two in-plane parallel electron channels that host a double dot in one channel and a single dot in the other channel. In a device where the channels are sufficiently close a triple dot in a triangular configuration is induced leading to regionsmore » in the charge stability diagram where three charge-addition lines of different slope approach each other and anti-cross. In a device where the channels are further apart, the single dot charge-senses the double dot with relative change of ~2% in the sensor current.« less

  10. Enhancement-mode two-channel triple quantum dot from an undoped Si/Si 0.8Ge 0.2 quantum well hetero-structure

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

    Studenikin, S. A.; Gaudreau, L.; Kataoka, K.

    Here, we demonstrate coupled triple dot operation and charge sensing capability for the recently introduced quantum dot technology employing undoped Si/Si 0.8Ge 0.2 hetero-structures which also incorporate a single metal-gate layer to simplify fabrication. Si/SiGe hetero-structures with a Ge concentration of 20% rather than the more usual 30% typically encountered offer higher electron mobility. The devices consist of two in-plane parallel electron channels that host a double dot in one channel and a single dot in the other channel. In a device where the channels are sufficiently close a triple dot in a triangular configuration is induced leading to regionsmore » in the charge stability diagram where three charge-addition lines of different slope approach each other and anti-cross. In a device where the channels are further apart, the single dot charge-senses the double dot with relative change of ~2% in the sensor current.« less

  11. Towards an understanding of the structural and functional properties of MscL, a mechanosensitive channel in bacteria

    NASA Technical Reports Server (NTRS)

    Blount, P.; Sukharev, S. I.; Moe, P. C.; Nagle, S. K.; Kung, C.

    1996-01-01

    Whether it be to sense a touch, arterial pressure, or an osmotic gradient across a cell membrane, essentially all living organisms require the capability of detecting mechanical force. Electrophysiological evidence has suggested that mechanosensitive ion channels play a major role in many systems where mechanical force is detected. But, despite their biological importance, determination of the most basic structural and functional features of mechanosensitive channels has only recently become possible. A gene called mscL, which was isolated from Escherichia coli, was the first gene shown to encode a mechanosensitive channel activity. This channel directly responds to tension in the membrane; no other proteins are required. MscL appears to be a homohexamer of a 136 amino acid polypeptide that is highly alpha helical, contains two transmembrane domains, and has both the amino and carboxyl termini in the cytoplasm. The study of the MscL protein remains, to date, one of the most viable options for understanding the structural and functional characteristics of a mechanosensitive channel.

  12. Modeling and Reconstruction of Micro-structured 3D Chitosan/Gelatin Porous Scaffolds Using Micro-CT

    NASA Astrophysics Data System (ADS)

    Gong, Haibo; Li, Dichen; He, Jiankang; Liu, Yaxiong; Lian, Qin; Zhao, Jinna

    2008-09-01

    Three dimensional (3D) channel networks are the key to promise the uniform distribution of nutrients inside 3D hepatic tissue engineering scaffolds and prompt elimination of metabolic products out of the scaffolds. 3D chitosan/gelatin porous scaffolds with predefined internal channels were fabricated and a combination of light microscope, laser confocal microscopy and micro-CT were employed to characterize the structure of porous scaffolds. In order to evaluate the flow field distribution inside the micro-structured 3D scaffolds, a computer reconstructing method based on Micro-CT was proposed. According to this evaluating method, a contrast between 3D porous scaffolds with and without predefined internal channels was also performed to assess scaffolds' fluid characters. Results showed that the internal channel of the 3D scaffolds formed the 3D fluid channel network; the uniformity of flow field distribution of the scaffolds fabricated in this paper was better than the simple porous scaffold without micro-fluid channels.

  13. A G-protein-activated inwardly rectifying K+ channel (GIRK4) from human hippocampus associates with other GIRK channels.

    PubMed

    Spauschus, A; Lentes, K U; Wischmeyer, E; Dissmann, E; Karschin, C; Karschin, A

    1996-02-01

    Transcripts of a gene, GIRK4, that encodes for a 419-amino-acid protein and shows high structural similarity to other subfamily members of G-protein-activated inwardly rectifying K+ channels (GIRK) have been identified in the human hippocampus. When expressed in Xenopus oocytes, GIRK4 yielded functional GIRK channels with activity that was enhanced by the stimulation of coexpressed serotonin 1A receptors. GIRK4 potentiated basal and agonist-induced currents mediated by other GIRK channels, possibly because of channel heteromerization. Despite the structural similarity to a putative rat KATP channel, no ATP sensitivity or KATP-typical pharmacology was observed for GIRK4 alone or GIRK4 transfected in conjunction with other GIRK channels in COS-7 cells. In rat brain, GIRK4 is expressed together with three other subfamily members, GIRK1-3, most likely in identical hippocampal neurons. Thus, heteromerization or an unknown molecular interaction may cause the physiological diversity observed within this class of K+ channels.

  14. Search of a solution correction of a lipidic metabolism at acute pancreatitis

    NASA Astrophysics Data System (ADS)

    Anaskin, S. G.; Vlasov, A. P.; Korniletsky, I. D.

    2017-01-01

    Following the results of a pilot study on studying of influence of an emoksipin, verapamil and a reamberin at acute pancreatitis it is possible to say that under the influence of these drugs in fabric structures of the inflamed pancreas there is a decrease in intensity of free radical processes of a lipopereokisleniye, activity of phospholipases, hypoxia phenomena. Level of antioxidant protection of fabric of body increases. In the first three days of supervision the accurate tendency to normalization of the transformed lipidic structure of fabric structures of a pancreas is revealed. At the same time these positive effects are noted in all experienced groups. It demonstrates that though pharmacological drugs are used multidirectional action (antioxidant emoksipin, an antigipoksant reamberin, inhibitor of calcium channels verapamil), they in a varying degree influence on studied pathological (membranodestruktivny, hypoxemic) processes, leading finally to reduction of their expressiveness. So, emoksipin found big ability to increase stability of membranes of pankreatotsit to pathological influence of molecular products the FLOOR, verapamil - to stopping of the activated phospholipases, reamberin - to a hypoxia. The question solution on the key (prevailing) mechanism in trigger processes of sharp pancreatitis of a definite answer has no. Undoubtedly only the fact that efficiency of antioxidant and inhibitor of calcic channels was rather higher. It suggests that free radical processes of a lipopereokisleniye and activity of fosfolipazny systems predetermine the level and nature of defeat of a cellular biomembrane of pankreatotsit already on the earliest terms of inflammatory process.

  15. Tension Behaviour on the Connection of the Cold-Formed Cut-Curved Steel Channel Section

    NASA Astrophysics Data System (ADS)

    Sani, Mohd Syahrul Hisyam Mohd; Muftah, Fadhluhartini; Fakri Muda, Mohd; Siang Tan, Cher

    2017-08-01

    Cold-formed steel (CFS) are utilised as a non-structural and structural element in construction activity especially a residential house and small building roof truss system. CFS with a lot of advantages and some of disadvantages such as buckling that must be prevented for roof truss production are being studied equally. CFS was used as a top chord of the roof truss system which normally a slender section is dramatically influenced to buckling failure and instability of the structure. So, the curved section is produced for a top chord for solving the compression member of the roof truss. Besides, there are lacked of design and production information about the CFS curved channel section. In the study, the CFS is bent by using a cut-curved method because of ease of production, without the use of skilled labour and high cost machine. The tension behaviour of the strengthening method of cut-curved or could be recognised as a connection of the cut-curved section was tested and analysed. There are seven types of connection was selected. From the testing and observation, it is shown the specimen with full weld along the cut section and adds with flange element plate with two self-drilling screws (F7A) was noted to have a higher value of ultimate load. Finally, there are three alternative methods of connection for CFS cut-curved that could be a reference for a contractor and further design.

  16. Mutations that stabilize the open state of the Erwinia chrisanthemi ligand-gated ion channel fail to change the conformation of the pore domain in crystals

    PubMed Central

    Gonzalez-Gutierrez, Giovanni; Lukk, Tiit; Agarwal, Vinayak; Papke, David; Nair, Satish K.; Grosman, Claudio

    2012-01-01

    The determination of structural models of the various stable states of an ion channel is a key step toward the characterization of its conformational dynamics. In the case of nicotinic-type receptors, different structures have been solved but, thus far, these different models have been obtained from different members of the superfamily. In the case of the bacterial member ELIC, a cysteamine-gated channel from Erwinia chrisanthemi, a structural model of the protein in the absence of activating ligand (and thus, conceivably corresponding to the closed state of this channel) has been previously generated. In this article, electrophysiological characterization of ELIC mutants allowed us to identify pore mutations that slow down the time course of desensitization to the extent that the channel seems not to desensitize at all for the duration of the agonist applications (>20 min). Thus, it seems reasonable to conclude that the probability of ELIC occupying the closed state is much lower for the ligand-bound mutants than for the unliganded wild-type channel. To gain insight into the conformation adopted by ELIC under these conditions, we solved the crystal structures of two of these mutants in the presence of a concentration of cysteamine that elicits an intracluster open probability of >0.9. Curiously, the obtained structural models turned out to be nearly indistinguishable from the model of the wild-type channel in the absence of bound agonist. Overall, our findings bring to light the limited power of functional studies in intact membranes when it comes to inferring the functional state of a channel in a crystal, at least in the case of the nicotinic-receptor superfamily. PMID:22474383

  17. [Architecture of receptor-operated ionic channels of biological membranes].

    PubMed

    Bregestovski, P D

    2011-01-01

    Ion channels of biological membranes are the key proteins, which provide bioelectric functioning of living systems. These proteins are homo- or heterooligomers assembled from several identical or different subunits. Understanding the architectural organization and functioning of ion channels has been significantly extended due to resolving the crystal structure of several types of voltage-gated and receptor-operated channels. This review summarizes the information obtained from crystal structures of potassium, nicotinic acetylcholine receptor, P2X, and other ligand-gated ion channels. Despite the differences in the function, topology, ionic selectivity, and the subunit stoichiometry, a high similarity in the principles of organization of these macromolecular complexes has been revealed.

  18. Projection structure of a ClC-type chloride channel at 6.5Å resolution

    NASA Astrophysics Data System (ADS)

    Mindell, Joseph A.; Maduke, Merritt; Miller, Christopher; Grigorieff, Nikolaus

    2001-01-01

    Virtually all cells in all eukaryotic organisms express ion channels of the ClC type, the only known molecular family of chloride-ion-selective channels. The diversity of ClC channels highlights the multitude and range of functions served by gated chloride-ion conduction in biological membranes, such as controlling electrical excitability in skeletal muscle, maintaining systemic blood pressure, acidifying endosomal compartments, and regulating electrical responses of GABA (γ-aminobutyric acid)-containing interneurons in the central nervous system. Previously, we expressed and purified a prokaryotic ClC channel homologue. Here we report the formation of two-dimensional crystals of this ClC channel protein reconstituted into phospholipid bilayer membranes. Cryo-electron microscopic analysis of these crystals yields a projection structure at 6.5Å resolution, which shows off-axis water-filled pores within the dimeric channel complex.

  19. Quantum mechanical calculations of charge effects on gating the KcsA channel.

    PubMed

    Kariev, Alisher M; Znamenskiy, Vasiliy S; Green, Michael E

    2007-05-01

    A series of ab initio (density functional) calculations were carried out on side chains of a set of amino acids, plus water, from the (intracellular) gating region of the KcsA K(+) channel. Their atomic coordinates, except hydrogen, are known from X-ray structures [D.A. Doyle, J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. MacKinnon, The structure of the potassium channel: molecular basis of K(+) conduction and selectivity, Science 280 (1998) 69-77; R. MacKinnon, S.L. Cohen, A. Kuo, A. Lee, B.T. Chait, Structural conservation in prokaryotic and eukaryotic potassium channels, Science 280 (1998) 106-109; Y. Jiang, A. Lee, J. Chen, M. Cadene, B.T. Chait, R. MacKinnon, The open pore conformation of potassium channels. Nature 417 (2001) 523-526], as are the coordinates of some water oxygen atoms. The 1k4c structure is used for the starting coordinates. Quantum mechanical optimization, in spite of the starting configuration, places the atoms in positions much closer to the 1j95, more tightly closed, configuration. This state shows four water molecules forming a "basket" under the Q119 side chains, blocking the channel. When a hydrated K(+) approaches this "basket", the optimized system shows a strong set of hydrogen bonds with the K(+) at defined positions, preventing further approach of the K(+) to the basket. This optimized structure with hydrated K(+) added shows an ice-like 12 molecule nanocrystal of water. If the water molecules exchange, unless they do it as a group, the channel will remain blocked. The "basket" itself appears to be very stable, although it is possible that the K(+) with its hydrating water molecules may be more mobile, capable of withdrawing from the gate. It is also not surprising that water essentially freezes, or forms a kind of glue, in a nanometer space; this agrees with experimental results on a rather different, but similarly sized (nm dimensions) system [K.B. Jinesh, J.W.M. Frenken, Capillary condensation in atomic scale friction: how water acts like a glue, Phys. Rev. Lett. 96 (2006) 166103/1-4]. It also agrees qualitatively with simulations on channels [A. Anishkin, S. Sukharev, Water dynamics and dewetting transitions in the small mechanosensitive channel MscS, Biophys. J. 86 (2004) 2883-2895; O. Beckstein, M.S.P. Sansom, Liquid-vapor oscillations of water in hydrophobic nanopores, Proc. Natl Acad. Sci. U. S. A. 100 (2003) 7063-7068] and on featureless channel-like systems [J. Lu, M.E. Green, Simulation of water in a pore with charges: application to a gating mechanism for ion channels, Prog. Colloid Polym. Sci. 103 (1997) 121-129], in that it forms a boundary on water that is not obvious from the liquid state. The idea that a structure is stable, even if individual molecules exchange, is well known, for example from the hydration shell of ions. We show that when charges are added in the form of protons to the domains (one proton per domain), the optimized structure is open. No stable water hydrogen bonds hold it together; an opening of 11.0 A appears, measured diagonally between non-neighboring domains as glutamine 119 carbonyl O-O distance. This is comparable to the opening in the MthK potassium channel structure that is generally agreed to be open. The appearance of the opening is in rather good agreement with that found by Perozo and coworkers. In contrast, in the uncharged structure this diagonal distance is 6.5 A, and the water "basket" constricts the uncharged opening still further, with the ice-like structure that couples the K(+) ion to the gating region freezing the entrance to the channel. Comparison with our earlier model for voltage gated channels suggests that a similar mechanism may apply in those channels.

  20. 75 FR 18755 - Security Zone; Calcasieu River and Ship Channel, LA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ...-AA87 Security Zone; Calcasieu River and Ship Channel, LA AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: The Coast Guard is disestablishing the permanent safety zone at Trunkline LNG in Lake Charles, LA and replacing it with a security zone with new boundaries. The Coast Guard is also establishing two...

  1. 75 FR 63402 - FM Table of Allotments, Culebra, PR, Charlotte Amalie, and Christiansted, VI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [DA 10-1062; MB Docket No. 08-243; RM-11490] FM Table of Allotments, Culebra, PR, Charlotte Amalie, and Christiansted, VI AGENCY: Federal Communications Commission. ACTION: Final rule. SUMMARY: The Audio Division substitutes Channel 237B for vacant Channel 271B...

  2. 78 FR 28125 - Airworthiness Directives; Twin Commander Aircraft LLC Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-14

    ...), DOT. ACTION: Final rule; request for comments. SUMMARY: We are adopting a new airworthiness directive... channels, left- and right-hand wing main spar frame support channels, and aft pressure bulkhead web. This... Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590. Hand Delivery: U.S. Department of...

  3. L-type Ca2+ channels in the heart: structure and regulation.

    PubMed

    Treinys, Rimantas; Jurevicius, Jonas

    2008-01-01

    This review analyzes the structure and regulation mechanisms of voltage-dependent L-type Ca(2+) channel in the heart. L-type Ca(2+) channels in the heart are composed of four different polypeptide subunits, and the pore-forming subunit alpha(1) is the most important part of the channel. In cardiac myocytes, Ca(2+) enter cell cytoplasm from extracellular space mainly through L-type Ca(2+) channels; these channels are very important system in heart Ca(2+) uptake regulation. L-type Ca(2+) channels are responsible for the activation of sarcoplasmic reticulum channels (RyR2) and force of muscle contraction generation in heart; hence, activity of the heart depends on L-type Ca(2+) channels. Phosphorylation of channel-forming subunits by different kinases is one of the most important ways to change the activity of L-type Ca(2+) channel. Additionally, the activity of L-type Ca(2+) channels depends on Ca(2+) concentration in cytoplasm. Ca(2+) current in cardiac cells can facilitate, and this process is regulated by phosphorylation of L-type Ca(2+) channels and intracellular Ca(2+) concentration. Disturbances in cellular Ca(2+) transport and regulation of L-type Ca(2+) channels are directly related to heart diseases, life quality, and life span.

  4. Effective pore size and radius of capture for K+ ions in K-channels

    PubMed Central

    Moldenhauer, Hans; Díaz-Franulic, Ignacio; González-Nilo, Fernando; Naranjo, David

    2016-01-01

    Reconciling protein functional data with crystal structure is arduous because rare conformations or crystallization artifacts occur. Here we present a tool to validate the dimensions of open pore structures of potassium-selective ion channels. We used freely available algorithms to calculate the molecular contour of the pore to determine the effective internal pore radius (rE) in several K-channel crystal structures. rE was operationally defined as the radius of the biggest sphere able to enter the pore from the cytosolic side. We obtained consistent rE estimates for MthK and Kv1.2/2.1 structures, with rE = 5.3–5.9 Å and rE = 4.5–5.2 Å, respectively. We compared these structural estimates with functional assessments of the internal mouth radii of capture (rC) for two electrophysiological counterparts, the large conductance calcium activated K-channel (rC = 2.2 Å) and the Shaker Kv-channel (rC = 0.8 Å), for MthK and Kv1.2/2.1 structures, respectively. Calculating the difference between rE and rC, produced consistent size radii of 3.1–3.7 Å and 3.6–4.4 Å for hydrated K+ ions. These hydrated K+ estimates harmonize with others obtained with diverse experimental and theoretical methods. Thus, these findings validate MthK and the Kv1.2/2.1 structures as templates for open BK and Kv-channels, respectively. PMID:26831782

  5. Exploring the Structure of the Voltage-gated Na+ Channel by an Engineered Drug Access Pathway to the Receptor Site for Local Anesthetics*

    PubMed Central

    Lukacs, Peter; Gawali, Vaibhavkumar S.; Cervenka, Rene; Ke, Song; Koenig, Xaver; Rubi, Lena; Zarrabi, Touran; Hilber, Karlheinz; Stary-Weinzinger, Anna; Todt, Hannes

    2014-01-01

    Despite the availability of several crystal structures of bacterial voltage-gated Na+ channels, the structure of eukaryotic Na+ channels is still undefined. We used predictions from available homology models and crystal structures to modulate an external access pathway for the membrane-impermeant local anesthetic derivative QX-222 into the internal vestibule of the mammalian rNaV1.4 channel. Potassium channel-based homology models predict amino acid Ile-1575 in domain IV segment 6 to be in close proximity to Lys-1237 of the domain III pore-loop selectivity filter. The mutation K1237E has been shown previously to increase the diameter of the selectivity filter. We found that an access pathway for external QX-222 created by mutations of Ile-1575 was abolished by the additional mutation K1237E, supporting the notion of a close spatial relationship between sites 1237 and 1575. Crystal structures of bacterial voltage-gated Na+ channels predict that the side chain of rNaV1.4 Trp-1531 of the domain IV pore-loop projects into the space between domain IV segment 6 and domain III pore-loop and, therefore, should obstruct the putative external access pathway. Indeed, mutations W1531A and W1531G allowed for exceptionally rapid access of QX-222. In addition, W1531G created a second non-selective ion-conducting pore, bypassing the outer vestibule but probably merging into the internal vestibule, allowing for control by the activation gate. These data suggest a strong structural similarity between bacterial and eukaryotic voltage-gated Na+ channels. PMID:24947510

  6. Structural basis of gating of CNG channels.

    PubMed

    Giorgetti, Alejandro; Nair, Anil V; Codega, Paolo; Torre, Vincent; Carloni, Paolo

    2005-03-28

    Cyclic nucleotide-gated (CNG) ion channels, underlying sensory transduction in vertebrate photoreceptors and olfactory sensory neurons, require cyclic nucleotides to open. Here, we present structural models of the tetrameric CNG channel pore from bovine rod in both open and closed states, as obtained by combining homology modeling-based techniques, experimentally derived spatial constraints and structural patterns present in the PDB database. Gating is initiated by an anticlockwise rotation of the N-terminal region of the C-linker, which is then, transmitted through the S6 transmembrane helices to the P-helix, and in turn from this to the pore lumen, which opens up from 2 to 5A thus allowing for ion permeation. The approach, here presented, is expected to provide a general methodology for model ion channels and their gating when structural templates are available and an extensive electrophysiological analysis has been performed.

  7. A Probabilistic Mass Estimation Algorithm for a Novel 7- Channel Capacitive Sample Verification Sensor

    NASA Technical Reports Server (NTRS)

    Wolf, Michael

    2012-01-01

    A document describes an algorithm created to estimate the mass placed on a sample verification sensor (SVS) designed for lunar or planetary robotic sample return missions. A novel SVS measures the capacitance between a rigid bottom plate and an elastic top membrane in seven locations. As additional sample material (soil and/or small rocks) is placed on the top membrane, the deformation of the membrane increases the capacitance. The mass estimation algorithm addresses both the calibration of each SVS channel, and also addresses how to combine the capacitances read from each of the seven channels into a single mass estimate. The probabilistic approach combines the channels according to the variance observed during the training phase, and provides not only the mass estimate, but also a value for the certainty of the estimate. SVS capacitance data is collected for known masses under a wide variety of possible loading scenarios, though in all cases, the distribution of sample within the canister is expected to be approximately uniform. A capacitance-vs-mass curve is fitted to this data, and is subsequently used to determine the mass estimate for the single channel s capacitance reading during the measurement phase. This results in seven different mass estimates, one for each SVS channel. Moreover, the variance of the calibration data is used to place a Gaussian probability distribution function (pdf) around this mass estimate. To blend these seven estimates, the seven pdfs are combined into a single Gaussian distribution function, providing the final mean and variance of the estimate. This blending technique essentially takes the final estimate as an average of the estimates of the seven channels, weighted by the inverse of the channel s variance.

  8. Methods of fabricating a conductor assembly having a curvilinear arcuate shape

    DOEpatents

    Meinke, Rainer [Melbourne, FL

    2011-08-23

    A method for manufacture of a conductor assembly along a curvilinear axis. The assembly may be of the type which, when conducting current, generates a magnetic field or in which, in the presence of a changing magnetic field, a voltage is induced. In one example, the assembly includes a structure having a curved shape extending along the axis. A surface of the structure is positioned for formation of a channel along the curved shape. The structure is rotated about a second axis. While rotating the structure, a channel is formed in the surface that results in a helical shape in the structure. The channel extends both around and along the first axis.

  9. Modulation of Kv7 channels and excitability in the brain.

    PubMed

    Greene, Derek L; Hoshi, Naoto

    2017-02-01

    Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits.

  10. Modulation of Kv7 channels and excitability in the brain

    PubMed Central

    Greene, Derek L; Hoshi, Naoto

    2016-01-01

    Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits. PMID:27645822

  11. Evaluating Conceptual Site Models with Multicomponent Reactive Transport Modeling

    NASA Astrophysics Data System (ADS)

    Dai, Z.; Heffner, D.; Price, V.; Temples, T. J.; Nicholson, T. J.

    2005-05-01

    Modeling ground-water flow and multicomponent reactive chemical transport is a useful approach for testing conceptual site models and assessing the design of monitoring networks. A graded approach with three conceptual site models is presented here with a field case of tetrachloroethene (PCE) transport and biodegradation near Charleston, SC. The first model assumed a one-layer homogeneous aquifer structure with semi-infinite boundary conditions, in which an analytical solution of the reactive solute transport can be obtained with BIOCHLOR (Aziz et al., 1999). Due to the over-simplification of the aquifer structure, this simulation cannot reproduce the monitoring data. In the second approach we used GMS to develop the conceptual site model, a layer-cake multi-aquifer system, and applied a numerical module (MODFLOW and RT3D within GMS) to solve the flow and reactive transport problem. The results were better than the first approach but still did not fit the plume well because the geological structures were still inadequately defined. In the third approach we developed a complex conceptual site model by interpreting log and seismic survey data with Petra and PetraSeis. We detected a major channel and a younger channel, through the PCE source area. These channels control the local ground-water flow direction and provide a preferential chemical transport pathway. Results using the third conceptual site model agree well with the monitoring concentration data. This study confirms that the bias and uncertainty from inadequate conceptual models are much larger than those introduced from an inadequate choice of model parameter values (Neuman and Wierenga, 2003; Meyer et al., 2004). Numerical modeling in this case provides key insight into the hydrogeology and geochemistry of the field site for predicting contaminant transport in the future. Finally, critical monitoring points and performance indicator parameters are selected for future monitoring to confirm system performance.

  12. Functional validation of Ca2+-binding residues from the crystal structure of the BK ion channel.

    PubMed

    Kshatri, Aravind S; Gonzalez-Hernandez, Alberto J; Giraldez, Teresa

    2018-04-01

    BK channels are dually regulated by voltage and Ca 2+ , providing a cellular mechanism to couple electrical and chemical signalling. Intracellular Ca 2+ concentration is sensed by a large cytoplasmic region in the channel known as "gating ring", which is formed by four tandems of regulator of conductance for K + (RCK1 and RCK2) domains. The recent crystal structure of the full-length BK channel from Aplysia californica has provided new information about the residues involved in Ca 2+ coordination at the high-affinity binding sites located in the RCK1 and RCK2 domains, as well as their cooperativity. Some of these residues have not been previously studied in the human BK channel. In this work we have investigated, through site directed mutagenesis and electrophysiology, the effects of these residues on channel activation by voltage and Ca 2+ . Our results demonstrate that the side chains of two non-conserved residues proposed to coordinate Ca 2+ in the A. californica structure (G523 and E591) have no apparent functional role in the human BK Ca 2+ sensing mechanism. Consistent with the crystal structure, our data indicate that in the human channel the conserved residue R514 participates in Ca 2+ coordination in the RCK1 binding site. Additionally, this study provides functional evidence indicating that R514 also interacts with residues E902 and Y904 connected to the Ca 2+ binding site in RCK2. Interestingly, it has been proposed that this interaction may constitute a structural correlate underlying the cooperative interactions between the two high-affinity Ca 2+ binding sites regulating the Ca 2+ dependent gating of the BK channel. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Premature Mobility of Boulders in Constructed Step-pool River Structures in the Carmel River, CA: The Role of Fish-centric Design Constraints, and Flow on Structural Stability

    NASA Astrophysics Data System (ADS)

    Smith, D. P.; Chow, K.; Luna, L.

    2017-12-01

    The 32 m tall San Clemente Dam (Carmel River, CA) was removed in 2015 to eliminate seismic risk and to improve fish passage for all life stages of steelhead (O. mykiss). Reservoir sediment was sequestered in place, rather than released, and a new 1000 m long channel/floodplain system was constructed to circumvent the stored sediment. The channel comprised a 250 m long, meandering low-gradient reach and a 750 m reach with alternating step-pool sections, plane beds, and resting pools. The floodprone surfaces were compacted, wrapped in geotechnical fabric and vegetated. This study analyzes the geomorphic evolution of the new channel system during its first two years of service based upon detailed field inspection, SfM photogrammetry, orthophoto analysis, and 2d hydraulic modeling. A significant proportion of the step-pool structures experienced premature mobility and several reaches of engineered stream banks were eroded in the first year. Individual, six-tonne boulders were mobilized despite experiencing less than the 3 yr flow. The channel and floodplain were fully repaired following the first year. Strong flows (two 10-yr floods and a 30-yr flood) during the second year catastrophically altered the constructed channel and floodplain. While the low-gradient reach remained intact, each of the original step-pool structures was either completely mobilized and destroyed, buried by gravel, or bypassed by the subsequent channel. Despite the overall structural failure of the constructed channel, the new channel does not block steelhead migration, and can be serendipitously considered an ecological success. Step-pool design was constrained by a fish-centric requirement that steps be 1 ft tall or less. Some constructed "resting pools" filled rather than transport sediment. Using fish-centric constraints in the design, rather than strictly fluvial geomorphic principles may have contributed to early failure of the step-pool structures and other parts of the system.

  14. An approach to emotion recognition in single-channel EEG signals: a mother child interaction

    NASA Astrophysics Data System (ADS)

    Gómez, A.; Quintero, L.; López, N.; Castro, J.

    2016-04-01

    In this work, we perform a first approach to emotion recognition from EEG single channel signals extracted in four (4) mother-child dyads experiment in developmental psychology. Single channel EEG signals are analyzed and processed using several window sizes by performing a statistical analysis over features in the time and frequency domains. Finally, a neural network obtained an average accuracy rate of 99% of classification in two emotional states such as happiness and sadness.

  15. High temperature seal for large structural movements

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M. (Inventor); Dunlap, Jr., Patrick H. (Inventor)

    2004-01-01

    A high temperature sealing system is operative to seal an interface between adjacent hot structures and to minimize parasitic flow between such structures that move relative to one another in-plane or out-of-plane. The sealing system may be used to seal thrust-directing ramp structures of a reusable launch vehicle and includes a channel and a plurality of movable segmented sealing elements. Adjacent ramp structures include edge walls which extend within the channel. The sealing elements are positioned along the sides of the channel and are biased to engage with the inner surfaces of the ramp structures. The segmented sealing elements are movable to correspond to the contour of the thrust-directing ramp structures. The sealing system is operative to prevent high temperature thrust gases that flow along the ramp structures from infiltrating into the interior of the vehicle.

  16. Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites

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

    Derebe, Mehabaw G.; Sauer, David B.; Zeng, Weizhong

    2015-11-30

    Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K{sup +} channel selectivity filters. Combined with single channel electrophysiology, we show that only themore » channel with four ion binding sites is K{sup +} selective, whereas those with two or three are nonselective and permeate Na{sup +} and K{sup +} equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K{sup +} channels is essential for highly selective and efficient permeation of K{sup +} ions.« less

  17. Irrigation channels of the Upper Rhone valley (Switzerland). Geomorphological analysis of a cultural heritage

    NASA Astrophysics Data System (ADS)

    Reynard, Emmanuel

    2016-04-01

    The Upper Rhone valley (Canton of Valais, Switzerland) is characterised by dry climatic conditions that explain the presence of an important network (about 800 km) of irrigation channels - called Bisses in the French-speaking part of the canton or Suonen in the German-speaking area - dating back to the Middle Ages. This network constitutes a cultural heritage and during the last 30 years these agricultural infrastructures have sparked a renewed interest for tourist and cultural reasons. Indeed, the paths along the channels are used as tourist trails and several abandoned channels have been renovated for tourist use. Based on an inventory of the Bisses/Suonen of Valais, the proposed communication has three aims: (1) to analyse the geomorphological context (morphometric analysis, structural geomorphology, main processes) of various types of channels and to show the impact of the geomorphological context on the building techniques; (2) to identify particularly active processes along the channels; (3) to classify the Bisses/Suonen according to their geomorphological value and to their geomorphological sensitivity, and to propose managing measures. Structural and climatic conditions influence the geomorphological context of the channels. In a structural point of view, irrigation channels are developed in three main contexts: (1) in the Aar Massif crystalline basement; (2) in the limestone and marl cover nappes of the Helvetic Alps; (3) in the metamorphic cover nappes of the Penninic domain. The Rhone River valley is boarded by two high mountain ranges: the Penninic Alps in the South and the Bernese Alps in the North. Because of rain shadow effects, the climate is relatively dry and, between Brig and Martigny, annual rainfall is not more than 600 mm at 500 m ASL and 800 mm at 1600 m ASL. Nevertheless, due to important vertical precipitation gradients annual rainfall totals are high at high altitudes. On the southern facing tributary valleys, the dry climatic conditions are accentuated by high insulation and evaporation. Finally, foehn events are quite common. In a climatic point of view, the area can be divided in three main zones: (1) Upstream of Brig, the climate is characterised by cold and wet conditions, and irrigation is not necessary; (2) between Brig and Martigny, the rain shadow effect is responsible of irrigation needs in the lower altitudes, whereas at high altitudes rainfall is sufficient for plant growing without irrigation; (3) downstream of Martigny, the climate is wetter and irrigation is not necessary. In a palaeoclimatic point of view, the Rhone River catchment was characterised by numerous glaciations during the Quaternary. Quaternary glaciers have shaped the valleys (U-shaped valleys, hanged valleys) and the postglacial hydrographical network had to adapt to the glacial valleys (presence of numerous waterfalls, hanged valleys, postglacial gorges, alluvial fans). By crossing climatic and structural contexts, three groups of geomorphological contexts of irrigation channels can be highlighted: (1) In the tributary valleys situated South of the Rhone valley (Penninic Alps) the irrigation channels are simply dug in the valley slopes; several of them are affected by landslides typical of metamorphic rocks of Penninic Alps; (2) In the short tributary valleys of the crystalline Aar Massif - in the valleys North to the city of Visp -, the geomorphological context is characterised by steep slopes both in the tributary valleys and in the south-facing slopes dominating the Rhone River valley. In this area, water channels are cut into the rocks and in some parts they are built in wood pipes hanged along the rock walls; (3) In the tributary valleys of the Helvetic domain - North of the Rhone River between Leuk and Sion - the geological context highly influences the building techniques: due to geological dipping towards Southeast, the tributary valley are dissymmetric: in the dip slopes channels are simply cut in the soil, whereas in the steep opposite sides, they are hanged on the limestone rock walls. In the south-facing slopes of the main valley, differential erosion by the Rhone glacier has formed a complex alternation of hills, depressions and gently dipping slopes very favourable to agriculture; the irrigation network had adapted to this complex geomorphological context.

  18. Design of a micromachined terahertz electromagnetic crystals (EMXT) channel-drop filter on silicon-substrate

    NASA Astrophysics Data System (ADS)

    Zhou, Kai; Liu, Yong; Si, Liming; Lv, Xin

    2013-08-01

    An integrated 0.5 THz electromagnetic crystals(EMXT) channel-drop filter based on PBG structure is presented in this paper. A channel-drop filter is a device in which a narrow bandwidth is redirected to another "drop" waveguide while other frequencies are unaffected. It's capable of extracting a certain frequency from a continuous spectrum in the bus channel and passing it to the test channel. It has potential applications in photonic integrated circuits, radio astronomy, THz spectroscopy, THz communication and remote sensing radar receiver. PBG structures(or photonic crystals) are periodic structures which possess band gaps, where the electromagnetic wave of certain ranges of frequencies cannot pass through and is reflected. The proposed channel-drop filter consists of input waveguide,output waveguide and PBG structure. The proposed filter is simulated using the finite element method and can be fabricated by micro-electromechanical systems (MEMS) technology,due to its low cost, high performance and high processing precision.The filter operation principle and fabrication process are discussed.The simulation results show its ability to filter the frequency of 496GHz with a linewidth of approximately 4GHz and transmission of 27.2 dB above background.The loss at resonant frequency is less than 1dB considering the thickness and roughness of gold layer required by the MEMS process.The channel drop efficiency is 84%.

  19. Economic effects of immigrants on native and foreign-born workers: complementarity, substitutability, and other channels of influence.

    PubMed

    Greenwood, M J; Hunt, G L

    1995-04-01

    The authors use Standard Metropolitan Statistical Area (SMSA) data constructed from 1980 census microdata files and other sources to estimate a structural model of native/foreign-born labor demand and labor supply which distinguishes the effects upon real wages of each type of labor and on the employment of natives. The authors specify, econometrically estimate, and simulate the structural model which incorporates not only a production structure channel through which immigrants influence area real wages and employment, but also demand and native labor supply channels. It is noted that while these are not the only channels through which immigrants may affect native workers, the model nonetheless constitutes a step in the direction of a general equilibrium approach. In the production structure channel, immigrants and natives are found to be substitutes in production. Immigration lowers foreign-born wage rates and leads to lower wages for natives. The negative effects of the production channel usually are ameliorated through the demand channel. Further, immigrants add to local demand through their earnings and potentially through non-labor income, while also lowering unit costs and local prices which enhances real incomes and potentially net exports, and thus the demands for local output and area labor. The author discusses findings of interest from the simulation results based upon an analysis of all areas.

  20. Proton channel models

    PubMed Central

    Pupo, Amaury; Baez-Nieto, David; Martínez, Agustín; Latorre, Ramón; González, Carlos

    2014-01-01

    Voltage-gated proton channels are integral membrane proteins with the capacity to permeate elementary particles in a voltage and pH dependent manner. These proteins have been found in several species and are involved in various physiological processes. Although their primary topology is known, lack of details regarding their structures in the open conformation has limited analyses toward a deeper understanding of the molecular determinants of their function and regulation. Consequently, the function-structure relationships have been inferred based on homology models. In the present work, we review the existing proton channel models, their assumptions, predictions and the experimental facts that support them. Modeling proton channels is not a trivial task due to the lack of a close homolog template. Hence, there are important differences between published models. This work attempts to critically review existing proton channel models toward the aim of contributing to a better understanding of the structural features of these proteins. PMID:24755912

  1. Structure-based membrane dome mechanism for Piezo mechanosensitivity

    PubMed Central

    Guo, Yusong R

    2017-01-01

    Mechanosensitive ion channels convert external mechanical stimuli into electrochemical signals for critical processes including touch sensation, balance, and cardiovascular regulation. The best understood mechanosensitive channel, MscL, opens a wide pore, which accounts for mechanosensitive gating due to in-plane area expansion. Eukaryotic Piezo channels have a narrow pore and therefore must capture mechanical forces to control gating in another way. We present a cryo-EM structure of mouse Piezo1 in a closed conformation at 3.7Å-resolution. The channel is a triskelion with arms consisting of repeated arrays of 4-TM structural units surrounding a pore. Its shape deforms the membrane locally into a dome. We present a hypothesis in which the membrane deformation changes upon channel opening. Quantitatively, membrane tension will alter gating energetics in proportion to the change in projected area under the dome. This mechanism can account for highly sensitive mechanical gating in the setting of a narrow, cation-selective pore. PMID:29231809

  2. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

    PubMed

    Finnerty, Justin John; Peyser, Alexander; Carloni, Paolo

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.

  3. Shielded serpentine traveling wave tube deflection structure

    DOEpatents

    Hudson, Charles L.; Spector, Jerome

    1994-01-01

    A shielded serpentine slow wave deflection structure (10) having a serpene signal conductor (12) within a channel groove (46). The channel groove (46) is formed by a serpentine channel (20) in a trough plate (18) and a ground plane (14). The serpentine signal conductor (12) is supported at its ends by coaxial feed through connectors 28. A beam interaction trough (22) intersects the channel groove (46) to form a plurality of beam interaction regions (56) wherein an electron beam (54) may be deflected relative to the serpentine signal conductor (12).

  4. Structural basis for modulation and agonist specificity of HCN pacemaker channels.

    PubMed

    Zagotta, William N; Olivier, Nelson B; Black, Kevin D; Young, Edgar C; Olson, Rich; Gouaux, Eric

    2003-09-11

    The family of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels are crucial for a range of electrical signalling, including cardiac and neuronal pacemaker activity, setting resting membrane electrical properties and dendritic integration. These nonselective cation channels, underlying the I(f), I(h) and I(q) currents of heart and nerve cells, are activated by membrane hyperpolarization and modulated by the binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated enhancement of channel activity is largely responsible for the increase in heart rate caused by beta-adrenergic agonists. Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore. X-ray crystallographic structures of this C-terminal fragment bound to cAMP or cGMP, together with equilibrium sedimentation analysis, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation. On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism.

  5. 16. DOWNSTREAM VIEW OF OUTLET STRUCTURE AND OUTLET CHANNEL, FROM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. DOWNSTREAM VIEW OF OUTLET STRUCTURE AND OUTLET CHANNEL, FROM WEST END OF EMBANKMENT. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  6. 3D Flow in the Venom Channel of a Spitting Cobra: Do the Ridges in the Fangs Act as Fluid Guide Vanes?

    PubMed Central

    Triep, Michael; Hess, David; Chaves, Humberto; Brücker, Christoph; Balmert, Alexander; Westhoff, Guido; Bleckmann, Horst

    2013-01-01

    The spitting cobra Naja pallida can eject its venom towards an offender from a distance of up to two meters. The aim of this study was to understand the mechanisms responsible for the relatively large distance covered by the venom jet although the venom channel is only of micro-scale. Therefore, we analysed factors that influence secondary flow and pressure drop in the venom channel, which include the physical-chemical properties of venom liquid and the morphology of the venom channel. The cobra venom showed shear-reducing properties and the venom channel had paired ridges that span from the last third of the channel to its distal end, terminating laterally and in close proximity to the discharge orifice. To analyze the functional significance of these ridges we generated a numerical and an experimental model of the venom channel. Computational fluid dynamics (CFD) and Particle-Image Velocimetry (PIV) revealed that the paired interior ridges shape the flow structure upstream of the sharp 90° bend at the distal end. The occurrence of secondary flow structures resembling Dean-type vortical structures in the venom channel can be observed, which induce additional pressure loss. Comparing a venom channel featuring ridges with an identical channel featuring no ridges, one can observe a reduction of pressure loss of about 30%. Therefore it is concluded that the function of the ridges is similar to guide vanes used by engineers to reduce pressure loss in curved flow channels. PMID:23671569

  7. Strangeness Physics at CLAS in the 6 GeV Era

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

    Schumacher, Reinhard A.

    2016-04-01

    A very brief overview is presented of varied strangeness-physics studies that have been conducted with the CLAS system in the era of 6 GeV beam at Jefferson Lab. A full bibliography of articles related to open strangeness production is given, together with some physics context for each work. One natural place where these studies could be continued, using a K L beam and the GlueX detector, is in the further investigation of the Λ(1405) baryon. The line shapes and cross sections of this state were found, using photoproduction at CLAS, to differ markedly in the three possible Σπ final states.more » The analogous strong-interaction reactions using a K L beam could further bring this phenomenon into focus. 1. The CLAS program ran from 1998 to 2012, during the time when the maximum Jefferson Lab beam energy was 6 GeV. An important thrust of this program was to investigate the spectrum of N * and Δ * (non-strange) baryon resonances using photo-and electro-production reactions. To this end, final states containing strange particles (K mesons and low-mass hyperons) played a significant role. The reason for this is partly due to favorable kinemat-ics. When the total invariant energy W (= √ s) of a baryonic system exceeds 1.6 GeV it becomes possible to create the lightest strangeness-containing final state, K + Λ. This is a two-body final state that is straightforward to reconstruct in the CLAS detector system [1], and theoretically it is easier to deal with two-body reaction amplitudes than with three-and higher-body reaction amplitudes. In the mass range W > 1.6 GeV the decay modes of excited nucleons tend to not to favor two-body π-nucleon final states but rather multi-pion states. As input to partial-wave decompositions and resonance-extraction models, therefore, the strangeness-containing final states of high-mass nucleon excitations have had importance. Excited baryons decay through all possible channels simultaneously, constrained by unitarity of course, and channel-coupling is crucial to determining the spectrum of excita-tions. Within this mix of amplitudes, however, the KY decay modes have proven useful. The end result has been, as summarized in the recent edition of the Review of Particle Properties [2], clearer definition of the spectrum of baryonic excitations, with definite contributions from the strangeness sector channels. To this end, strangeness photoproduction cross sections measurements at CLAS for the K + Λ, K + Σ 0 and K 0 Σ + channels on a proton target were published [3–6]. Cross sections are not enough, in general, to define the reaction mechanism, including the underlying N * excitation spectrum. Photoproduction of pseudo-scalar mesons is described by four complex amplitudes, leading to fifteen spin observables in addition to the cross section. Full knowledge of these spin observables would exhaust the information that can be gleaned experimentally about any given reaction channel. Here the hyperonic channels offer another advantage when compared with the non-strange reaction channels: the polarization of most hyperons can be measured directly through their parity-violating weak decay asymmetries. Unlike 163« less

  8. Self-organization of linear nanochannel networks

    NASA Astrophysics Data System (ADS)

    Annabattula, R. K.; Veenstra, J. M.; Mei, Y. F.; Schmidt, O. G.; Onck, P. R.

    2010-06-01

    A theoretical study has been conducted to explore the mechanics of self-organizing channel networks with dimensions in the submicron range and nanorange. The channels form by the partial release and bond back of prestressed thin films. In the release phase, the film spontaneously buckles into wrinkles of a certain wavelength, followed by a bond-back phase in which the final channel geometry is established through cohesive interface attractions. Results are presented in terms of the channel spacing, height, and width as a function of the film stiffness, thickness, eigenstrain, etch width, and interface energy. We have identified two dimensionless parameters that fully quantify the network assembly, showing excellent agreement with experiments. Our results provide valuable insight for the design of submicron and nanoscale channel networks with specific geometries.

  9. Elastic, inelastic, and 1-nucleon transfer channels in the 7Li+120Sn system

    NASA Astrophysics Data System (ADS)

    Kundu, A.; Santra, S.; Pal, A.; Chattopadhyay, D.; Tripathi, R.; Roy, B. J.; Nag, T. N.; Nayak, B. K.; Saxena, A.; Kailas, S.

    2017-03-01

    Background: Simultaneous description of major outgoing channels for a nuclear reaction by coupled-channels calculations using the same set of potential and coupling parameters is one of the difficult tasks to accomplish in nuclear reaction studies. Purpose: To measure the elastic, inelastic, and transfer cross sections for as many channels as possible in 7Li+120Sn system at different beam energies and simultaneously describe them by a single set of model calculations using fresco. Methods: Projectile-like fragments were detected using six sets of Si-detector telescopes to measure the cross sections for elastic, inelastic, and 1-nucleon transfer channels at two beam energies of 28 and 30 MeV. Optical model analysis of elastic data and coupled-reaction-channels (CRC) calculations that include around 30 reaction channels coupled directly to the entrance channel, with respective structural parameters, were performed to understand the measured cross sections. Results: Structure information available in the literature for some of the identified states did not reproduce the present data. Cross sections obtained from CRC calculations using a modified but single set of potential and coupling parameters were able to describe simultaneously the measured data for all the channels at both the measured energies as well as the existing data for elastic and inelastic cross sections at 44 MeV. Conclusions: Non-reproduction of some of the cross sections using the structure information available in the literature which are extracted from reactions involving different projectiles indicates that such measurements are probe dependent. New structural parameters were assigned for such states as well as for several new transfer states whose spectroscopic factors were not known.

  10. Voltage-dependent gating and gating charge measurements in the Kv1.2 potassium channel

    PubMed Central

    Ishida, Itzel G.; Rangel-Yescas, Gisela E.; Carrasco-Zanini, Julia

    2015-01-01

    Much has been learned about the voltage sensors of ion channels since the x-ray structure of the mammalian voltage-gated potassium channel Kv1.2 was published in 2005. High resolution structural data of a Kv channel enabled the structural interpretation of numerous electrophysiological findings collected in various ion channels, most notably Shaker, and permitted the development of meticulous computational simulations of the activation mechanism. The fundamental premise for the structural interpretation of functional measurements from Shaker is that this channel and Kv1.2 have the same characteristics, such that correlation of data from both channels would be a trivial task. We tested these assumptions by measuring Kv1.2 voltage-dependent gating and charge per channel. We found that the Kv1.2 gating charge is near 10 elementary charges (eo), ∼25% less than the well-established 13–14 eo in Shaker. Next, we neutralized positive residues in the Kv1.2 S4 transmembrane segment to investigate the cause of the reduction of the gating charge and found that, whereas replacing R1 with glutamine decreased voltage sensitivity to ∼50% of the wild-type channel value, mutation of the subsequent arginines had a much smaller effect. These data are in marked contrast to the effects of charge neutralization in Shaker, where removal of the first four basic residues reduces the gating charge by roughly the same amount. In light of these differences, we propose that the voltage-sensing domains (VSDs) of Kv1.2 and Shaker might undergo the same physical movement, but the septum that separates the aqueous crevices in the VSD of Kv1.2 might be thicker than Shaker’s, accounting for the smaller Kv1.2 gating charge. PMID:25779871

  11. Determinants of cation transport selectivity: Equilibrium binding and transport kinetics

    PubMed Central

    2015-01-01

    The crystal structures of channels and transporters reveal the chemical nature of ion-binding sites and, thereby, constrain mechanistic models for their transport processes. However, these structures, in and of themselves, do not reveal equilibrium selectivity or transport preferences, which can be discerned only from various functional assays. In this Review, I explore the relationship between cation transport protein structures, equilibrium binding measurements, and ion transport selectivity. The primary focus is on K+-selective channels and nonselective cation channels because they have been extensively studied both functionally and structurally, but the principles discussed are relevant to other transport proteins and molecules. PMID:26078056

  12. Simulation study of short-channel effects of tunnel field-effect transistors

    NASA Astrophysics Data System (ADS)

    Fukuda, Koichi; Asai, Hidehiro; Hattori, Junichi; Mori, Takahiro; Morita, Yukinori; Mizubayashi, Wataru; Masahara, Meishoku; Migita, Shinji; Ota, Hiroyuki; Endo, Kazuhiro; Matsukawa, Takashi

    2018-04-01

    Short-channel effects of tunnel field-effect transistors (FETs) are investigated in detail using simulations of a nonlocal band-to-band tunneling model. Discussion is limited to silicon. Several simulation scenarios were considered to address different effects, such as source overlap and drain offset effects. Adopting the drain offset to suppress the drain leakage current suppressed the short channel effects. The physical mechanism underlying the short-channel behavior of the tunnel FETs (TFETs) was very different from that of metal-oxide-semiconductor FETs (MOSFETs). The minimal gate lengths that do not lose on-state current by one order are shown to be 3 nm for single-gate structures and 2 nm for double gate structures, as determined from the drain offset structure.

  13. Reusable EGaIn-Injected Substrate-Integrated-Waveguide Resonator for Wireless Sensor Applications

    PubMed Central

    Memon, Muhammad Usman; Lim, Sungjoon

    2015-01-01

    The proposed structure in this research is constructed on substrate integrated waveguide (SIW) technology and has a mechanism that produces 16 different and distinct resonant frequencies between 2.45 and 3.05 GHz by perturbing a fundamental TE10 mode. It is a unique method for producing multiple resonances in a radio frequency planar structure without any extra circuitry or passive elements is developed. The proposed SIW structure has four vertical fluidic holes (channels); injecting eutectic gallium indium (EGaIn), also known commonly as liquid metal (LM), into these vertical channels produces different resonant frequencies. Either a channel is empty, or it is filled with LM. In total, the combination of different frequencies produced from four vertical channels is 16. PMID:26569257

  14. The gating mechanism of the large mechanosensitive channel MscL

    NASA Technical Reports Server (NTRS)

    Sukharev, S.; Betanzos, M.; Chiang, C. S.; Guy, H. R.

    2001-01-01

    The mechanosensitive channel of large conductance, MscL, is a ubiquitous membrane-embedded valve involved in turgor regulation in bacteria. The crystal structure of MscL from Mycobacterium tuberculosis provides a starting point for analysing molecular mechanisms of tension-dependent channel gating. Here we develop structural models in which a cytoplasmic gate is formed by a bundle of five amino-terminal helices (S1), previously unresolved in the crystal structure. When membrane tension is applied, the transmembrane barrel expands and pulls the gate apart through the S1-M1 linker. We tested these models by substituting cysteines for residues predicted to be near each other only in either the closed or open conformation. Our results demonstrate that S1 segments form the bundle when the channel is closed, and crosslinking between S1 segments prevents opening. S1 segments interact with M2 when the channel is open, and crosslinking of S1 to M2 impedes channel closing. Gating is affected by the length of the S1-M1 linker in a manner consistent with the model, revealing critical spatial relationships between the domains that transmit force from the lipid bilayer to the channel gate.

  15. Structural determinants of PIP(2) regulation of inward rectifier K(ATP) channels.

    PubMed

    Shyng, S L; Cukras, C A; Harwood, J; Nichols, C G

    2000-11-01

    Phosphatidylinositol 4,5-bisphosphate (PIP(2)) activates K(ATP) and other inward rectifier (Kir) channels. To determine residues important for PIP(2) regulation, we have systematically mutated each positive charge in the COOH terminus of Kir6.2 to alanine. The effects of these mutations on channel function were examined using (86)Rb efflux assays on intact cells and inside-out patch-clamp methods. Both methods identify essentially the same basic residues in two narrow regions (176-222 and 301-314) in the COOH terminus that are important for the maintenance of channel function and interaction with PIP(2). Only one residue (R201A) simultaneously affected ATP and PIP(2) sensitivity, which is consistent with the notion that these ligands, while functionally competitive, are unlikely to bind to identical sites. Strikingly, none of 13 basic residues in the terminal portion (residues 315-390) of the COOH terminus affected channel function when neutralized. The data help to define the structural requirements for PIP(2) sensitivity of K(ATP) channels. Moreover, the regions and residues defined in this study parallel those uncovered in recent studies of PIP(2) sensitivity in other inward rectifier channels, indicating a common structural basis for PIP(2) regulation.

  16. Disturbances of Ligand Potency and Enhanced Degradation of the Human Glycine Receptor at Affected Positions G160 and T162 Originally Identified in Patients Suffering from Hyperekplexia

    PubMed Central

    Atak, Sinem; Langlhofer, Georg; Schaefer, Natascha; Kessler, Denise; Meiselbach, Heike; Delto, Carolyn; Schindelin, Hermann; Villmann, Carmen

    2015-01-01

    Ligand-binding of Cys-loop receptors is determined by N-terminal extracellular loop structures from the plus as well as from the minus side of two adjacent subunits in the pentameric receptor complex. An aromatic residue in loop B of the glycine receptor (GlyR) undergoes direct interaction with the incoming ligand via a cation-π interaction. Recently, we showed that mutated residues in loop B identified from human patients suffering from hyperekplexia disturb ligand-binding. Here, we exchanged the affected human residues by amino acids found in related members of the Cys-loop receptor family to determine the effects of side chain volume for ion channel properties. GlyR variants were characterized in vitro following transfection into cell lines in order to analyze protein expression, trafficking, degradation and ion channel function. GlyR α1 G160 mutations significantly decrease glycine potency arguing for a positional effect on neighboring aromatic residues and consequently glycine-binding within the ligand-binding pocket. Disturbed glycinergic inhibition due to T162 α1 mutations is an additive effect of affected biogenesis and structural changes within the ligand-binding site. Protein trafficking from the ER toward the ER-Golgi intermediate compartment, the secretory Golgi pathways and finally the cell surface is largely diminished, but still sufficient to deliver ion channels that are functional at least at high glycine concentrations. The majority of T162 mutant protein accumulates in the ER and is delivered to ER-associated proteasomal degradation. Hence, G160 is an important determinant during glycine binding. In contrast, T162 affects primarily receptor biogenesis whereas exchanges in functionality are secondary effects thereof. PMID:26733802

  17. Tapered Screened Channel PMD for Cryogenic Liquids

    NASA Astrophysics Data System (ADS)

    Dodge, Franklin T.; Green, Steve T.; Walter, David B.

    2004-02-01

    If a conventional spacecraft propellant management device (PMD) of the screened channel type were employed with a cryogenic liquid, vapor bubbles generated within the channel by heat transfer could ``dry out'' the channel screens and thereby cause the channels to admit large amounts of vapor from the tank into the liquid outflow. This paper describes a new tapered channel design that passively `pumps' bubbles away from the outlet port and vents them into the tank. A predictive mathematical model of the operating principle is presented and discussed. Scale-model laboratory tests were conducted and the mathematical model agreed well with the measured rates of bubble transport velocity. Finally, an example of the use of the predictive model for a realistic spacecraft application is presented. The model predicts that bubble clearing rates are acceptable even in tanks up to 2 m in length.

  18. Nucleon Resonance Structure from Exclusive Meson Electroproduction with CLAS

    DOE PAGES

    Mokeev, Victor I.

    2018-04-06

    Studies of the nucleon resonance electroexcitation amplitudes in a wide range of photon virtualities offer unique information on many facets of strong QCD behind the generation of all prominent excited nucleon states of distinctively different structure. Advances in the evaluation of resonance electroexcitation amplitudes from the data measured with the CLAS detector and the future extension of these studies with the CLAS12 detector at Jefferson Lab are presented in this paper. For the first time, analyses ofmore » $$\\pi^0p$$, $$\\pi^+n$$, $$\\eta p$$, and $$\\pi^+\\pi^-p$$ electroproduction off proton channels have provided electroexcitation amplitudes of most resonances in the mass range up to 1.8 GeV and at photon virtualities $Q^2 < 5$ GeV$^2$. Consistent results on resonance electroexcitation amplitudes determined from different exclusive channels validate a credible extraction of these fundamental quantities. Studies of the resonance electroexcitation amplitudes revealed the $N^*$ structure as a complex interplay between the inner core of three dressed quarks and the external meson-baryon cloud. The successful description of the $$\\Delta(1232)3/2^+$$ and $N(1440)1/2^+$ electrocouplings achieved within the Dyson-Schwinger Equation approach under a traceable connection to the QCD Lagrangian and supported by the novel light front quark model demonstrated the relevance of dressed quarks with dynamically generated masses as an active structural component in baryons. Future experiments with the CLAS12 detector will offer insight into the structure of all prominent resonances at the highest photon virtualities, $Q^2 < 12$ GeV$^2$, ever achieved in exclusive reactions, thus addressing the most challenging problems of the Standard Model on the nature of hadron mass, quark-gluon confinement, and the emergence of nucleon resonance structures from QCD. Finally, a search for new states of hadronic matter, the so-called hybrid-baryons with glue as a structural component, will complete the long term efforts on the resonance spectrum exploration.« less

  19. Nucleon Resonance Structure from Exclusive Meson Electroproduction with CLAS

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

    Mokeev, Victor I.

    Studies of the nucleon resonance electroexcitation amplitudes in a wide range of photon virtualities offer unique information on many facets of strong QCD behind the generation of all prominent excited nucleon states of distinctively different structure. Advances in the evaluation of resonance electroexcitation amplitudes from the data measured with the CLAS detector and the future extension of these studies with the CLAS12 detector at Jefferson Lab are presented in this paper. For the first time, analyses ofmore » $$\\pi^0p$$, $$\\pi^+n$$, $$\\eta p$$, and $$\\pi^+\\pi^-p$$ electroproduction off proton channels have provided electroexcitation amplitudes of most resonances in the mass range up to 1.8 GeV and at photon virtualities $Q^2 < 5$ GeV$^2$. Consistent results on resonance electroexcitation amplitudes determined from different exclusive channels validate a credible extraction of these fundamental quantities. Studies of the resonance electroexcitation amplitudes revealed the $N^*$ structure as a complex interplay between the inner core of three dressed quarks and the external meson-baryon cloud. The successful description of the $$\\Delta(1232)3/2^+$$ and $N(1440)1/2^+$ electrocouplings achieved within the Dyson-Schwinger Equation approach under a traceable connection to the QCD Lagrangian and supported by the novel light front quark model demonstrated the relevance of dressed quarks with dynamically generated masses as an active structural component in baryons. Future experiments with the CLAS12 detector will offer insight into the structure of all prominent resonances at the highest photon virtualities, $Q^2 < 12$ GeV$^2$, ever achieved in exclusive reactions, thus addressing the most challenging problems of the Standard Model on the nature of hadron mass, quark-gluon confinement, and the emergence of nucleon resonance structures from QCD. Finally, a search for new states of hadronic matter, the so-called hybrid-baryons with glue as a structural component, will complete the long term efforts on the resonance spectrum exploration.« less

  20. D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.

    PubMed

    Kisilevsky, Alexandra E; Mulligan, Sean J; Altier, Christophe; Iftinca, Mircea C; Varela, Diego; Tai, Chao; Chen, Lina; Hameed, Shahid; Hamid, Jawed; Macvicar, Brian A; Zamponi, Gerald W

    2008-05-22

    Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.

  1. Multi-photon self-error-correction hyperentanglement distribution over arbitrary collective-noise channels

    NASA Astrophysics Data System (ADS)

    Gao, Cheng-Yan; Wang, Guan-Yu; Zhang, Hao; Deng, Fu-Guo

    2017-01-01

    We present a self-error-correction spatial-polarization hyperentanglement distribution scheme for N-photon systems in a hyperentangled Greenberger-Horne-Zeilinger state over arbitrary collective-noise channels. In our scheme, the errors of spatial entanglement can be first averted by encoding the spatial-polarization hyperentanglement into the time-bin entanglement with identical polarization and defined spatial modes before it is transmitted over the fiber channels. After transmission over the noisy channels, the polarization errors introduced by the depolarizing noise can be corrected resorting to the time-bin entanglement. Finally, the parties in quantum communication can in principle share maximally hyperentangled states with a success probability of 100%.

  2. A MIMO radar quadrature and multi-channel amplitude-phase error combined correction method based on cross-correlation

    NASA Astrophysics Data System (ADS)

    Yun, Lingtong; Zhao, Hongzhong; Du, Mengyuan

    2018-04-01

    Quadrature and multi-channel amplitude-phase error have to be compensated in the I/Q quadrature sampling and signal through multi-channel. A new method that it doesn't need filter and standard signal is presented in this paper. And it can combined estimate quadrature and multi-channel amplitude-phase error. The method uses cross-correlation and amplitude ratio between the signal to estimate the two amplitude-phase errors simply and effectively. And the advantages of this method are verified by computer simulation. Finally, the superiority of the method is also verified by measure data of outfield experiments.

  3. A Channelization-Based DOA Estimation Method for Wideband Signals

    PubMed Central

    Guo, Rui; Zhang, Yue; Lin, Qianqiang; Chen, Zengping

    2016-01-01

    In this paper, we propose a novel direction of arrival (DOA) estimation method for wideband signals with sensor arrays. The proposed method splits the wideband array output into multiple frequency sub-channels and estimates the signal parameters using a digital channelization receiver. Based on the output sub-channels, a channelization-based incoherent signal subspace method (Channelization-ISM) and a channelization-based test of orthogonality of projected subspaces method (Channelization-TOPS) are proposed. Channelization-ISM applies narrowband signal subspace methods on each sub-channel independently. Then the arithmetic mean or geometric mean of the estimated DOAs from each sub-channel gives the final result. Channelization-TOPS measures the orthogonality between the signal and the noise subspaces of the output sub-channels to estimate DOAs. The proposed channelization-based method isolates signals in different bandwidths reasonably and improves the output SNR. It outperforms the conventional ISM and TOPS methods on estimation accuracy and dynamic range, especially in real environments. Besides, the parallel processing architecture makes it easy to implement on hardware. A wideband digital array radar (DAR) using direct wideband radio frequency (RF) digitization is presented. Experiments carried out in a microwave anechoic chamber with the wideband DAR are presented to demonstrate the performance. The results verify the effectiveness of the proposed method. PMID:27384566

  4. In-channel Restoration Structures and the Implications on Hyporheic Exchange: a Laboratory Experiment

    NASA Astrophysics Data System (ADS)

    Han, B.; Chu, H. H.; Endreny, T. A.

    2014-12-01

    In-channel structures, i.e. cross-vanes and J-hooks, are commonly installed in river restoration projects to modify the streambed morphology and stream water surface profile, and are known to change hyporhiec exchange flux and habitats for riverine animals. However, few studies have continuous and accurate pre- and post-treatment data to evaluate the impact of these structures on channel hydraulic gradients and morphology. To quantify the effects of in-channel structures, we developed a scaled physical model of a meandering stream with a cross-vane and 6 J-hooks on a mobile-bed river table. Close-range photogrammetry technique was applied to obtain 3-D water and ground surface profiles with sub-millimeter vertical accuracy and horizontal resolution. The experiment was compared with a control experiment without structures while maintaining the same initial conditions of river bed, floodplain and stream flow. Results indicated that the cross-vane caused an average local head loss that represented 16% of the total stream reach head loss, and a 74% increase in channel load in the entire stream reach. Most J-hooks can create stepwise patterns in stream longitudinal profile, and cross-vane can create even more significant ones. Hydraulic gradients across the intra-meander zone also increased with in-channel structures, i.e. from 2.5% to 3.5% at the meander neck. Scour pools developed downstream of the cross-vane, and mostly around the 4 meander apex J-hooks at their hooked tip. Backwater caused by the cross-vane steepened the local water table profile by an additional 4.2%, and was the primary driver of statistically significant hydraulic gradient increase. Reach scale water and streambed surface profiles from our study provided detailed data to improve the understanding of in-channel structure effects, and may serve as reliable data source in computational modeling of hyporheic exchange.

  5. Development of Scaffolds for Light Harvesting and Photocatalysis from the Coat Protein of Tobacco Mosaic Virus

    NASA Astrophysics Data System (ADS)

    Dedeo, Michel Toussaint

    The utility of a previously developed TMV-based light harvesting system has been dramatically expanded through the introduction of reactive handles for the site-specific modification of the interior and exterior surfaces. Further experiments to reengineer the coat protein have produced structures with unique, unexpected, and useful assembly properties that complement the newly available surface modifications. Energy transfer from chromophores in the RNA channel of self-assembled TMV structures to the exterior was made possible by conjugation of acceptor dyes and porphyrins to the N-terminus. By repositioning the N-terminus to the pore through circular permutation, this process was repeated to create structures that mimic the light harvesting 1 complex of photosynthetic bacteria. To study and improve upon natural photosynthesis, closely packed chromophore arrays and gold nanoparticles were tethered to the pore of stabilized TMV disks through introduction of a uniquely reactive lysine. Finally, a dimeric TMV coat protein was produced to control the distribution and arrangement of synthetic groups with synergistic activity.

  6. Ladder-structured photonic variable delay device

    NASA Technical Reports Server (NTRS)

    Yao, X. Steve (Inventor)

    1998-01-01

    An ladder-structured variable delay device for providing variable true time delay to multiple optical beams simultaneously. The device comprises multiple basic units stacked on top of each other resembling a ladder. Each basic unit comprises a polarization sensitive corner reflector formed by two polarization beamsplitters and a polarization rotator array placed parallel to the hypotenuse of the corner reflector. Controlling an array element of the polarization rotator array causes an optical beam passing through the array element to either go up to a basic unit above it or reflect back towards output. The beams going higher on the ladder experience longer optical path delay. Finally, the ladder-structured variable device can be cascaded with another multi-channel delay device to form a new device which combines the advantages of the two individual devices. This programmable optic device has the properties of high packing density, low loss, easy fabrication, and virtually infinite bandwidth. In addition, the delay is reversible so that the same delay device can be used for both antenna transmitting and receiving.

  7. Functional Annotation of Ion Channel Structures by Molecular Simulation.

    PubMed

    Trick, Jemma L; Chelvaniththilan, Sivapalan; Klesse, Gianni; Aryal, Prafulla; Wallace, E Jayne; Tucker, Stephen J; Sansom, Mark S P

    2016-12-06

    Ion channels play key roles in cell membranes, and recent advances are yielding an increasing number of structures. However, their functional relevance is often unclear and better tools are required for their functional annotation. In sub-nanometer pores such as ion channels, hydrophobic gating has been shown to promote dewetting to produce a functionally closed (i.e., non-conductive) state. Using the serotonin receptor (5-HT 3 R) structure as an example, we demonstrate the use of molecular dynamics to aid the functional annotation of channel structures via simulation of the behavior of water within the pore. Three increasingly complex simulation analyses are described: water equilibrium densities; single-ion free-energy profiles; and computational electrophysiology. All three approaches correctly predict the 5-HT 3 R crystal structure to represent a functionally closed (i.e., non-conductive) state. We also illustrate the application of water equilibrium density simulations to annotate different conformational states of a glycine receptor. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Biophysics of BK Channel Gating.

    PubMed

    Pantazis, A; Olcese, R

    2016-01-01

    BK channels are universal regulators of cell excitability, given their exceptional unitary conductance selective for K(+), joint activation mechanism by membrane depolarization and intracellular [Ca(2+)] elevation, and broad expression pattern. In this chapter, we discuss the structural basis and operational principles of their activation, or gating, by membrane potential and calcium. We also discuss how the two activation mechanisms interact to culminate in channel opening. As members of the voltage-gated potassium channel superfamily, BK channels are discussed in the context of archetypal family members, in terms of similarities that help us understand their function, but also seminal structural and biophysical differences that confer unique functional properties. © 2016 Elsevier Inc. All rights reserved.

  9. Semiblind channel estimation for MIMO-OFDM systems

    NASA Astrophysics Data System (ADS)

    Chen, Yi-Sheng; Song, Jyu-Han

    2012-12-01

    This article proposes a semiblind channel estimation method for multiple-input multiple-output orthogonal frequency-division multiplexing systems based on circular precoding. Relying on the precoding scheme at the transmitters, the autocorrelation matrix of the received data induces a structure relating the outer product of the channel frequency response matrix and precoding coefficients. This structure makes it possible to extract information about channel product matrices, which can be used to form a Hermitian matrix whose positive eigenvalues and corresponding eigenvectors yield the channel impulse response matrix. This article also tests the resistance of the precoding design to finite-sample estimation errors, and explores the effects of the precoding scheme on channel equalization by performing pairwise error probability analysis. The proposed method is immune to channel zero locations, and is reasonably robust to channel order overestimation. The proposed method is applicable to the scenarios in which the number of transmitters exceeds that of the receivers. Simulation results demonstrate the performance of the proposed method and compare it with some existing methods.

  10. Structure of the skeletal muscle calcium release channel activated with Ca2+ and AMP-PCP.

    PubMed Central

    Serysheva, I I; Schatz, M; van Heel, M; Chiu, W; Hamilton, S L

    1999-01-01

    The functional state of the skeletal muscle Ca2+ release channel is modulated by a number of endogenous molecules during excitation-contraction. Using electron cryomicroscopy and angular reconstitution techniques, we determined the three-dimensional (3D) structure of the skeletal muscle Ca2+ release channel activated by a nonhydrolyzable analog of ATP in the presence of Ca2+. These ligands together produce almost maximum activation of the channel and drive the channel population toward a predominately open state. The resulting 30-A 3D reconstruction reveals long-range conformational changes in the cytoplasmic region that might affect the interaction of the Ca2+ release channel with the t-tubule voltage sensor. In addition, a central opening and mass movements, detected in the transmembrane domain of both the Ca(2+)- and the Ca2+/nucleotide-activated channels, suggest a mechanism for channel opening similar to opening-closing of the iris in a camera diaphragm. PMID:10512814

  11. Local electrical properties of n-AlInAs/i-GaInAs electron channel structures characterized by the probe-electron-beam-induced current technique.

    PubMed

    Watanabe, Kentaro; Nokuo, Takeshi; Chen, Jun; Sekiguchi, Takashi

    2014-04-01

    We developed a probe-electron-beam-induced current (probe-EBIC) technique to investigate the electrical properties of n-Al(0.48)In(0.52)As/i-Ga(0.30)In(0.70)As electron channel structures for a high-electron-mobility transistor, grown on a lattice-matched InP substrate and lattice-mismatched GaAs (001) and Si (001) substrates. EBIC imaging of planar surfaces at low magnifications revealed misfit dislocations originating from the AlInAs-graded buffer layer. The cross-sections of GaInAs channel structures on an InP substrate were studied by high-magnification EBIC imaging as well as cathodoluminescence (CL) spectroscopy. EBIC imaging showed that the structure is nearly defect-free and the carrier depletion zone extends from the channel toward the i-AlInAs buffer layer.

  12. A cost-effective protocol for the over-expression and purification of fully-functional and more stable Erwinia chrisanthemi ligand-gated ion channel

    PubMed Central

    Elberson, Benjamin W.; Whisenant, Ty E.; Cortes, D. Marien; Cuello, Luis G.

    2017-01-01

    The Erwinia chrisanthemi ligand-gated ion channel, ELIC, is considered an excellent structural and functional surrogate for the whole pentameric ligand-gated ion channel family. Despite its simplicity, ELIC is structurally capable of undergoing ligand-dependent activation and a concomitant desensitization process. To determine at the molecular level the structural changes underlying ELIC’s function, it is desirable to produce large quantities of protein. This protein should be properly folded, fully-functional and amenable to structural determinations. In the current paper, we report a completely new protocol for the expression and purification of milligram quantities of fully-functional, more stable and crystallizable ELIC. The use of an autoinduction media and inexpensive detergents during ELIC extraction, in addition to the high-quality and large quantity of the purified channel, are the highlights of this improved biochemical protocol. PMID:28279818

  13. Structural Sensitivity of a Prokaryotic Pentameric Ligand-gated Ion Channel to Its Membrane Environment*

    PubMed Central

    Labriola, Jonathan M.; Pandhare, Akash; Jansen, Michaela; Blanton, Michael P.; Corringer, Pierre-Jean; Baenziger, John E.

    2013-01-01

    Although the activity of the nicotinic acetylcholine receptor (nAChR) is exquisitely sensitive to its membrane environment, the underlying mechanisms remain poorly defined. The homologous prokaryotic pentameric ligand-gated ion channel, Gloebacter ligand-gated ion channel (GLIC), represents an excellent model for probing the molecular basis of nAChR sensitivity because of its high structural homology, relative ease of expression, and amenability to crystallographic analysis. We show here that membrane-reconstituted GLIC exhibits structural and biophysical properties similar to those of the membrane-reconstituted nAChR, although GLIC is substantially more thermally stable. GLIC, however, does not possess the same exquisite lipid sensitivity. In particular, GLIC does not exhibit the same propensity to adopt an uncoupled conformation where agonist binding is uncoupled from channel gating. Structural comparisons provide insight into the chemical features that may predispose the nAChR to the formation of an uncoupled state. PMID:23463505

  14. Mechanical Properties of Copper Processed by Equal Channel Angular Pressing

    NASA Astrophysics Data System (ADS)

    Sülleiová, K.; Ballóková, B.; Besterci, M.; Kvačkaj, T.

    2017-12-01

    The development of the nanostructure in commercial pure copper and the strength and ductility after severe plastic deformation (SPD) with the technology of equal channel angular pressing (ECAP) are analysed. Experimental results and analyses showed that both strength and ductility can be increased simultaneously by SPD. The final grain size decreased from the initial 50μm by SPD to 100-300 nm after 10 passes. An increase of the ductility together with an increase of strength caused by SPD are explained by a strong grain refinement and by a dynamic equilibrium of weakening and strengthening, and it is visible on the final static tensile test stress-strain charts.

  15. The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility*

    PubMed Central

    Ding, Xi-Qin; Thapa, Arjun; Ma, Hongwei; Xu, Jianhua; Elliott, Michael H.; Rodgers, Karla K.; Smith, Marci L.; Wang, Jin-Shan; Pittler, Steven J.; Kefalov, Vladimir J.

    2016-01-01

    Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability. As cones comprise only 2–3% of the total photoreceptor population in the wild-type mouse retina, we used Cngb3−/−/Nrl−/− mice with CNGB3 deficiency on a cone-dominant background in our study. We found that, in the absence of CNGB3, CNGA3 was able to travel to the outer segments, co-localize with cone opsin, and form tetrameric complexes. Electroretinogram analyses revealed reduced cone light response amplitude/sensitivity and slower response recovery in Cngb3−/−/Nrl−/− mice compared with Nrl−/− mice. Absence of CNGB3 expression altered the adaptation capacity of cones and severely compromised function in bright light. Biochemical analysis demonstrated that CNGA3 channels lacking CNGB3 were more resilient to proteolysis than CNGA3/CNGB3 channels, suggesting a hindered structural flexibility. Thus, CNGB3 regulates cone light response kinetics and the channel structural flexibility. This work advances our understanding of the biochemical and functional role of CNGB3 in cone photoreceptors. PMID:26893377

  16. 78 FR 33219 - Special Local Regulations; Swim Across the Potomac, Potomac River; National Harbor Access Channel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-04

    ... Channel, MD AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is... provide for the safety of life on navigable waters during the event. This action is intended to temporarily restrict vessel traffic in a portion of the Potomac River during the event. DATES: This rule is...

  17. RNA polymerase pausing and nascent RNA structure formation are linked through clamp domain movement

    PubMed Central

    Hein, Pyae P.; Kolb, Kellie E.; Windgassen, Tricia; Bellecourt, Michael J.; Darst, Seth A.; Mooney, Rachel A.; Landick, Robert

    2014-01-01

    The rates of RNA synthesis and nascent RNA folding into biologically active structures are linked via pausing by RNA polymerase (RNAP). Structures that form within the RNA exit channel can increase pausing by interacting with bacterial RNAP or decrease pausing by preventing backtracking. Conversely, pausing is required for proper folding of some RNAs. Opening of the RNAP clamp domain is proposed to mediate some effects of nascent RNA structures. However, the connections among RNA structure formation, clamp movement, and catalytic activity remain uncertain. We assayed exit-channel structure formation in Escherichia coli RNAP together with disulfide crosslinks that favor closed or open clamp conformations and found that clamp position directly influences RNA structure formation and catalytic activity. We report that exit-channel RNA structures slow pause escape by favoring clamp opening and through interactions with the flap that slow translocation. PMID:25108353

  18. Structural implications of hERG K+ channel block by a high-affinity minimally structured blocker

    PubMed Central

    Helliwell, Matthew V.; Zhang, Yihong; El Harchi, Aziza; Du, Chunyun; Hancox, Jules C.; Dempsey, Christopher E.

    2018-01-01

    Cardiac potassium channels encoded by human ether-à-go-go–related gene (hERG) are major targets for structurally diverse drugs associated with acquired long QT syndrome. This study characterized hERG channel inhibition by a minimally structured high-affinity hERG inhibitor, Cavalli-2, composed of three phenyl groups linked by polymethylene spacers around a central amino group, chosen to probe the spatial arrangement of side chain groups in the high-affinity drug-binding site of the hERG pore. hERG current (IhERG) recorded at physiological temperature from HEK293 cells was inhibited with an IC50 of 35.6 nm with time and voltage dependence characteristic of blockade contingent upon channel gating. Potency of Cavalli-2 action was markedly reduced for attenuated inactivation mutants located near (S620T; 54-fold) and remote from (N588K; 15-fold) the channel pore. The S6 Y652A and F656A mutations decreased inhibitory potency 17- and 75-fold, respectively, whereas T623A and S624A at the base of the selectivity filter also decreased potency (16- and 7-fold, respectively). The S5 helix F557L mutation decreased potency 10-fold, and both F557L and Y652A mutations eliminated voltage dependence of inhibition. Computational docking using the recent cryo-EM structure of an open channel hERG construct could only partially recapitulate experimental data, and the high dependence of Cavalli-2 block on Phe-656 is not readily explainable in that structure. A small clockwise rotation of the inner (S6) helix of the hERG pore from its configuration in the cryo-EM structure may be required to optimize Phe-656 side chain orientations compatible with high-affinity block. PMID:29545312

  19. Crystal Structure of a Fibroblast Growth Factor Homologous Factor (FHF) Defines a Conserved Surface on FHFs for Binding and Modulation of Voltage-gated Sodium Channels

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

    Goetz, R.; Dover, K; Laezza, F

    2009-01-01

    Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel bindingmore » in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs.« less

  20. Crystal structure of the ATP-gated P2X[subscript 4] ion channel in the closed state

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

    Kawate, Toshimitsu; Michel, Jennifer Carlisle; Birdsong, William T.

    2009-08-13

    P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X{sub 4} receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit-subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in {beta}-strands, have largemore » acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the 'gate' is defined by an {approx}8 {angstrom} slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit rearrangement and ion channel opening.« less

  1. Large scale rearrangement of protein domains is associated with voltage gating of the VDAC channel.

    PubMed Central

    Peng, S; Blachly-Dyson, E; Forte, M; Colombini, M

    1992-01-01

    The VDAC channel of the mitochondrial outer membrane is voltage-gated like the larger, more complex voltage-gated channels of the plasma membrane. However, VDAC is a low molecular weight (30 kDa), abundant protein, which is readily purified and reconstituted, making it an ideal system for analyzing the molecular basis for ion selectivity and voltage-gating. We have probed the VDAC channel by subjecting the cloned yeast (S. cerevisiae) VDAC gene to site-directed mutagenesis and introducing the resulting mutant channels into planar bilayers to detect the effects of specific sequence changes on channel properties. This approach has allowed us to formulate and test a model of the open state structure of the VDAC channel. Now we have applied the same approach to analyzing the structure of the channel's low-conducting "closed state" (essentially closed to important metabolites). We have identified protein domains forming the wall of the closed conformation and domains that seem to be removed from the wall of the pore during channel closure. The latter can explain the reduction in pore diameter and volume and the dramatically altered channel selectivity resulting from the channel closure. This process would make a natural coupling between motion of the sensor and channel gating. PMID:1376163

  2. Radioastronomic signal processing cores for the SKA radio telescope

    NASA Astrophysics Data System (ADS)

    Comorett, G.; Chiarucc, S.; Belli, C.

    Modern radio telescopes require the processing of wideband signals, with sample rates from tens of MHz to tens of GHz, and are composed from hundreds up to a million of individual antennas. Digital signal processing of these signals include digital receivers (the digital equivalent of the heterodyne receiver), beamformers, channelizers, spectrometers. FPGAs present the advantage of providing a relatively low power consumption, relative to GPUs or dedicated computers, a wide signal data path, and high interconnectivity. Efficient algorithms have been developed for these applications. Here we will review some of the signal processing cores developed for the SKA telescope. The LFAA beamformer/channelizer architecture is based on an oversampling channelizer, where the channelizer output sampling rate and channel spacing can be set independently. This is useful where an overlap between adjacent channels is required to provide an uniform spectral coverage. The architecture allows for an efficient and distributed channelization scheme, with a final resolution corresponding to a million of spectral channels, minimum leakage and high out-of-band rejection. An optimized filter design procedure is used to provide an equiripple response with a very large number of spectral channels. A wideband digital receiver has been designed in order to select the processed bandwidth of the SKA Mid receiver. The receiver extracts a 2.5 MHz bandwidth form a 14 GHz input bandwidth. The design allows for non-integer ratios between the input and output sampling rates, with a resource usage comparable to that of a conventional decimating digital receiver. Finally, some considerations on quantization of radioastronomic signals are presented. Due to the stochastic nature of the signal, quantization using few data bits is possible. Good accuracies and dynamic range are possible even with 2-3 bits, but the nonlinearity in the correlation process must be corrected in post-processing. With at least 6 bits it is possible to have a very linear response of the instrument, with nonlinear terms below 80 dB, providing the signal amplitude is kept within bounds.

  3. Simulation and Experimental Study of Bipolar Plate on the Performance PEM Fuel cell

    NASA Astrophysics Data System (ADS)

    Chinnasa, Pornchai; Khamsuk, Pattama; Seechalee, Sarunya; Swatsitang, Ekaphan

    2017-09-01

    This research is a simulated and experimental study on effects of bipolar electrodes of a PEM fuel cell on its power conversion efficiency. The PEM fuel cell structure consists of bipolar electrodes, proton exchange membrane with catalysts, flow channels of gases. This research used fuel cell of 49 cm2 in active area as a research sample and the Comsol 4.4 was employed to simulate flow channels which are serpentine pattern for anode and parallel pattern for cathode. The parameters used were calculated effects of such parameters using Comsol 4.4. After the calculation has been completed, the prototype of the PEM fuel cell were fabricated using graphite plate as electrodes which had the channel height of 0.20 cm, proton exchange membrane using carbon-platinum catalyst. Finally, further it was found that the effect of temperature on the power conversion efficiency is not severely. And for anode, the concentration of hydrogen gas was reduced 64 wt% due to the reaction whereas in parallel channel of cathode the oxygen concentration was reduced by only 6 wt% from 23 wt% at the entrance to 17 wt% at the end. The maximum power output of the prototype operated under such condition was 0.28 W/cm2 calculated from maximum power output voltage (Vmp) of 0.70 V and maximum power output current density of 0.42 A/cm2 which was in good agreement with that simulated using Comsol 4.4 which revealed the power output of 0.29 W/cm2.

  4. 17. OUTLET STRUCTURE, LOOKING NORTH. NOTE ALSO THE DRAINAGE CHANNEL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. OUTLET STRUCTURE, LOOKING NORTH. NOTE ALSO THE DRAINAGE CHANNEL AND CONCRETE FLUME ALONG WEST EDGE OF EMBANKMENT. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  5. 21. AERIAL VIEW OF THE OUTLET STRUCTURE AND OUTLET CHANNEL, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. AERIAL VIEW OF THE OUTLET STRUCTURE AND OUTLET CHANNEL, LOOKING UPSTREAM.... Volume XVII, No. 11, December 26, 1939. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA

  6. Simulation of Rutherford backscattering spectrometry from arbitrary atom structures

    DOE PAGES

    Zhang, S.; Univ. of Helsinki; Nordlund, Kai; ...

    2016-10-25

    Rutherford backscattering spectrometry in a channeling direction (RBS/C) is a powerful tool for analysis of the fraction of atoms displaced from their lattice positions. However, it is in many cases not straightforward to analyze what is the actual defect structure underlying the RBS/C signal. To reveal insights of RBS/C signals from arbitrarily complex defective atomic structures, we develop in this paper a method for simulating the RBS/C spectrum from a set of arbitrary read-in atom coordinates (obtained, e.g., from molecular dynamics simulations). We apply the developed method to simulate the RBS/C signals from Ni crystal structures containing randomly displaced atoms,more » Frenkel point defects, and extended defects, respectively. The RBS/C simulations show that, even for the same number of atoms in defects, the RBS/C signal is much stronger for the extended defects. Finally, comparison with experimental results shows that the disorder profile obtained from RBS/C signals in ion-irradiated Ni is due to a small fraction of extended defects rather than a large number of individual random atoms.« less

  7. Structure of the Pseudomonas aeruginosa Type IVa Pilus Secretin at 7.4 Å.

    PubMed

    Koo, Jason; Lamers, Ryan P; Rubinstein, John L; Burrows, Lori L; Howell, P Lynne

    2016-10-04

    Type IVa pili (T4aP) function as bacterial virulence factors. T4aP pass through the outer membranes of Gram-negative bacteria via homo-oligomeric secretins. We present a 7.4 Å cryoelectron microscopy structure of the Pseudomonas aeruginosa PilQ secretin. Peripheral and internal features show that the secretin is composed of 14 subunits with C7 symmetry. The channel is a ribbed cylinder with central peripheral spokes and a central gate closed on the periplasmic side. The structure suggests that during pilus extrusion, the central gate is displaced to the interior walls and that no additional conformational changes are required, as the internal diameter can accommodate the pilus. The N1 domain was resolved, while the N0 and the N-terminal β-domains proposed to bind peptidoglycan were absent in class average images and the final 3D map, indicating a high flexibility. These data provide the highest-resolution structure to date of a T4aP secretin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Angular and polarization trails from effective interactions of Majorana neutrinos at the LHeC

    NASA Astrophysics Data System (ADS)

    Duarte, Lucía; Zapata, Gabriel; Sampayo, Oscar A.

    2018-05-01

    We study the possibility of the LHeC facility to disentangle different new physics contributions to the production of heavy sterile Majorana neutrinos in the lepton number violating channel e-p→ lj+ + 3 jets (l_j≡e ,μ ). This is done investigating the angular and polarization trails of effective operators with distinct Dirac-Lorentz structure contributing to the Majorana neutrino production, which parameterize new physics from a higher energy scale. We study an asymmetry in the angular distribution of the final anti-lepton and the initial electron polarization effect on the number of signal events produced by the vectorial and scalar effective interactions, finding both analyses could well separate their contributions.

  9. Evaluation of selected recurrence measures in discriminating pre-ictal and inter-ictal periods from epileptic EEG data

    NASA Astrophysics Data System (ADS)

    Ngamga, Eulalie Joelle; Bialonski, Stephan; Marwan, Norbert; Kurths, Jürgen; Geier, Christian; Lehnertz, Klaus

    2016-04-01

    We investigate the suitability of selected measures of complexity based on recurrence quantification analysis and recurrence networks for an identification of pre-seizure states in multi-day, multi-channel, invasive electroencephalographic recordings from five epilepsy patients. We employ several statistical techniques to avoid spurious findings due to various influencing factors and due to multiple comparisons and observe precursory structures in three patients. Our findings indicate a high congruence among measures in identifying seizure precursors and emphasize the current notion of seizure generation in large-scale epileptic networks. A final judgment of the suitability for field studies, however, requires evaluation on a larger database.

  10. Fast and Versatile Fabrication of PMMA Microchip Electrophoretic Devices by Laser Engraving

    PubMed Central

    Gabriel, Ellen Flávia Moreira; Coltro, Wendell Karlos Tomazelli; Garcia, Carlos D.

    2014-01-01

    This paper describes the effects of different modes and engraving parameters on the dimensions of microfluidic structures produced in PMMA using laser engraving. The engraving modes included raster and vector while the explored engraving parameters included power, speed, frequency, resolution, line-width and number of passes. Under the optimum conditions, the technique was applied to produce channels suitable for CE separations. Taking advantage of the possibility to cut-through the substrates, the laser was also used to define solution reservoirs (buffer, sample, and waste) and a PDMS-based decoupler. The final device was used to perform the analysis of a model mixture of phenolic compounds within 200 s with baseline resolution. PMID:25113407

  11. Electrical design for origami solar panels and a small spacecraft test mission

    NASA Astrophysics Data System (ADS)

    Drewelow, James; Straub, Jeremy

    2017-05-01

    Efficient power generation is crucial to the design of spacecraft. Mass, volume, and other limitations prevent the use of traditional spacecraft support structures from being suitable for the size of solar array required for some missions. Folding solar panel / panel array systems, however, present a number of design challenges. This paper considers the electrical design of an origami system. Specifically, it considers how to provide low impedance, durable channels for the generated power and the electrical aspects of the deployment system and procedure. The ability to dynamically reconfigure the electrical configuration of the solar cells is also discussed. Finally, a small satellite test mission to demonstrate the technology is proposed, before concluding.

  12. A novel approach for assessments of erythrocyte sedimentation rate.

    PubMed

    Pribush, A; Hatskelzon, L; Meyerstein, N

    2011-06-01

    Previous studies have shown that the dispersed phase of sedimenting blood undergoes dramatic structural changes: Discrete red blood cell (RBC) aggregates formed shortly after a settling tube is filled with blood are combined into a continuous network followed by its collapse via the formation of plasma channels, and finally, the collapsed network is dispersed into individual fragments. Based on this scheme of structural transformation, a novel approach for assessments of erythrocyte sedimentation is suggested. Information about erythrocyte sedimentation is extracted from time records of the blood conductivity measured after a dispersion of RBC network into individual fragments. It was found that the sedimentation velocity of RBC network fragments correlates positively with the intensity of attractive intercellular interactions, whereas no effect of hematocrit (Hct) was observed. Thus, unlike Westergren erythrocyte sedimentation rate, sedimentation data obtained by the proposed method do not require correction for Hct. © 2010 Blackwell Publishing Ltd.

  13. Structure of hadron resonances with a nearby zero of the amplitude

    NASA Astrophysics Data System (ADS)

    Kamiya, Yuki; Hyodo, Tetsuo

    2018-03-01

    We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude. If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the K ¯ N -π Σ amplitude, we discuss the origin of the eigenstates in the Λ (1405 ) region.

  14. Study of the cluster structure of10Be and16C neutron-rich isotopes by means of intermediate energies breakup reactions

    NASA Astrophysics Data System (ADS)

    Dell'Aquila, D.; Acosta, L.; Auditore, L.; Cardella, G.; De Filippo, E.; De Luca, S.; Francalanza, L.; Gnoffo, B.; Lanzalone, G.; Lombardo, I.; Martorana, N. S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Quattrocchi, L.; Rizzo, F.; Rosato, E.; Russotto, P.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.

    2017-06-01

    We describe the results of a new experiment aimed to investigate the possible existence of cluster structures in10Be and16C isotopes. They have been investigated at the FRIBs facility of INFN-LNS by means of an invariant mass analysis on correlated projectile breakup fragments carried out with the CHIMERA 4π detector. From the analysis of the6He+4He channel we found evidence of a new state in10Be at 13.5MeV excitation energy. Concerning16C, we investigated6He+10Be correlated fragments and we found a non-vanishing yield at about 20.5MeV in the corresponding excitation energy spectrum. Finally, we describe few details of a new experiment performed at the FRIBs facility where the CHIMERA detector was coupled to the FARCOS hodoscope, with the aim to improve the presently obtained results.

  15. A New Method to Measure Crack Extension in Nuclear Graphite Based on Digital Image Correlation

    DOE PAGES

    Lai, Shigang; Shi, Li; Fok, Alex; ...

    2017-01-01

    Graphite components, used as moderators, reflectors, and core-support structures in a High-Temperature Gas-Cooled Reactor, play an important role in the safety of the reactor. Specifically, they provide channels for the fuel elements, control rods, and coolant flow. Fracture is the main failure mode for graphite, and breaching of the above channels by crack extension will seriously threaten the safety of a reactor. In this paper, a new method based on digital image correlation (DIC) is introduced for measuring crack extension in brittle materials. Cross-correlation of the displacements measured by DIC with a step function was employed to identify the advancingmore » crack tip in a graphite beam specimen under three-point bending. The load-crack extension curve, which is required for analyzing the R-curve and tension softening behaviors, was obtained for this material. Furthermore, a sensitivity analysis of the threshold value employed for the cross-correlation parameter in the crack identification process was conducted. Finally, the results were verified using the finite element method.« less

  16. A New Method to Measure Crack Extension in Nuclear Graphite Based on Digital Image Correlation

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

    Lai, Shigang; Shi, Li; Fok, Alex

    Graphite components, used as moderators, reflectors, and core-support structures in a High-Temperature Gas-Cooled Reactor, play an important role in the safety of the reactor. Specifically, they provide channels for the fuel elements, control rods, and coolant flow. Fracture is the main failure mode for graphite, and breaching of the above channels by crack extension will seriously threaten the safety of a reactor. In this paper, a new method based on digital image correlation (DIC) is introduced for measuring crack extension in brittle materials. Cross-correlation of the displacements measured by DIC with a step function was employed to identify the advancingmore » crack tip in a graphite beam specimen under three-point bending. The load-crack extension curve, which is required for analyzing the R-curve and tension softening behaviors, was obtained for this material. Furthermore, a sensitivity analysis of the threshold value employed for the cross-correlation parameter in the crack identification process was conducted. Finally, the results were verified using the finite element method.« less

  17. Recent progress of particle migration in viscoelastic fluids.

    PubMed

    Yuan, Dan; Zhao, Qianbin; Yan, Sheng; Tang, Shi-Yang; Alici, Gursel; Zhang, Jun; Li, Weihua

    2018-02-13

    Recently, research on particle migration in non-Newtonian viscoelastic fluids has gained considerable attention. In a viscoelastic fluid, three dimensional (3D) particle focusing can be easily realized in simple channels without the need for any external force fields or complex microchannel structures compared with that in a Newtonian fluid. Due to its promising properties for particle precise focusing and manipulation, this field has been developed rapidly, and research on the field has been shifted from fundamentals to applications. This review will elaborate the recent progress of particle migration in viscoelastic fluids, especially on the aspect of applications. The hydrodynamic forces on the micro/nano particles in viscoelastic fluids are discussed. Next, we elaborate the basic particle migration in viscoelasticity-dominant fluids and elasto-inertial fluids in straight channels. After that, a comprehensive review on the applications of viscoelasticity-induced particle migration (particle separation, cell deformability measurement and alignment, particle solution exchange, rheometry-on-a-chip and others) is presented; finally, we thrash out some perspectives on the future directions of particle migration in viscoelastic fluids.

  18. Preliminary floor, seat, and dummy data

    NASA Technical Reports Server (NTRS)

    Cannon, M. R.; Zimmerman, R. E.

    1986-01-01

    According to preliminary examination of the data, out of 179 data channels that were onboard the aircraft in support of the seat experiments, there is data from 168. There was somewhat more severe environment imposed in the structure of the obstacles than by the ground impact. Therefore, both ground impact and obstacle impact are of interest for crashworthiness experiments. Most of the data channels that were studied are fairly consistent with the physical evidence: they show acceleration levels that are reasonable, and in many cases these integrate out to a reasonable velocity change. Finally, from observation thus far, the ground impact did not fail or significantly damage any seat. Nor did any of the energy absorbers in the modified seats extend. The accelerations do not appear high enough and/or energetic enough to cause this to happen. At this time, the onboard films have not been studied; only some videotape have been viewed. Some of the seats were so badly damaged by the fire that any failures which might have occurred were obscured. A close examination of the onboard films using a stop-action projector will allow a more thorough evaluation.

  19. Comparison of dual-k spacer and single-k spacer for single NWFET and 3-stack NWFET

    NASA Astrophysics Data System (ADS)

    Ko, Hyungwoo; Kim, Jongsu; Kim, Minsoo; Kang, Myounggon; Shin, Hyungcheol

    2018-02-01

    The investigation of the Dual-k spacer through comparative analysis of single nanowire-FET(NWFET)/3-stack NWFET and underlap/overlap channel is conducted. It is known that the dug 3-stack NWFET has better delay characteristics than single NWFET with the use of high permittivity material of Cin in Dual-k spacer structure. In addition, there is no difference of delay between overlap and underlap channel when it used Dual-k spacer structure but underlap channel of Dual-k 3-stack NWFET shows better short channel immunity.

  20. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation

    PubMed Central

    Finnerty, Justin John

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

Top