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Sample records for 10-4 cm2 v-1

  1. A Cofacially Stacked Electron-Deficient Small Molecule with a High Electron Mobility of over 10 cm(2) V(-1) s(-1) in Air.

    PubMed

    Dou, Jin-Hu; Zheng, Yu-Qing; Yao, Ze-Fan; Lei, Ting; Shen, Xingxing; Luo, Xu-Yi; Yu, Zhi-Ao; Zhang, Shi-Ding; Han, Guangchao; Wang, Zhi; Yi, Yuanping; Wang, Jie-Yu; Pei, Jian

    2015-12-22

    A strong, electron-deficient small molecule, F4 -BDOPV, has a lowest unoccupied molecular orbital (LUMO) level down to -4.44 eV and exhibits cofacial packing in single crystals. These features provide F4 -BDOPV with good ambient stability and large charge-transfer integrals for electrons, leading to a high electron mobility of up to 12.6 cm(2) V(-1) s(-1) in air.

  2. Widely bandgap tunable amorphous Cd-Ga-O oxide semiconductors exhibiting electron mobilities ≥10 cm2 V-1 s-1

    NASA Astrophysics Data System (ADS)

    Yanagi, Hiroshi; Sato, Chiyuki; Kimura, Yota; Suzuki, Issei; Omata, Takahisa; Kamiya, Toshio; Hosono, Hideo

    2015-02-01

    Amorphous oxide semiconductors exhibit large electron mobilities; however, their bandgaps are either too large for solar cells or too small for deep ultraviolet applications depending on the materials system. Herein, we demonstrate that amorphous Cd-Ga-O semiconductors display bandgaps covering the entire 2.5-4.3 eV region while maintaining large electron mobilities ≥10 cm2 V-1 s-1. The band alignment diagram obtained by ultraviolet photoemission spectroscopy and the bandgap values reveal that these semiconductors form type-II heterojunctions with p-type Cu2O, which is suitable for solar cells and solar-blind ultraviolet sensors.

  3. Epitaxial growth of large area single-crystalline few-layer MoS2 with high space charge mobility of 192 cm2 V-1 s-1

    NASA Astrophysics Data System (ADS)

    Ma, Lu; Nath, Digbijoy N.; Lee, Edwin W.; Lee, Choong Hee; Yu, Mingzhe; Arehart, Aaron; Rajan, Siddharth; Wu, Yiying

    2014-08-01

    We report on the vapor-solid growth of single crystalline few-layer MoS2 films on (0001)-oriented sapphire with excellent structural and electrical properties over centimeter length scale. High-resolution X-ray diffraction scans indicated that the films had good out-of-plane ordering and epitaxial registry. A carrier density of ˜2 × 1011 cm-2 and a room temperature mobility of 192 cm2/Vs were extracted from space-charge limited transport regime in the films. The electron mobility was found to exhibit in-plane anisotropy with a ratio of ˜1.8. Theoretical estimates of the temperature-dependent electron mobility including optical phonon, acoustic deformation potential, and remote ionized impurity scattering were found to satisfactorily match the measured data. The synthesis approach reported here demonstrates the feasibility of device quality few-layer MoS2 films with excellent uniformity and high quality.

  4. Growth of ˜5 cm2V-1s-1 mobility, p-type Copper(I) oxide (Cu2O) films by fast atmospheric atomic layer deposition (AALD) at 225°C and below

    NASA Astrophysics Data System (ADS)

    Muñoz-Rojas, D.; Jordan, M.; Yeoh, C.; Marin, A. T.; Kursumovic, A.; Dunlop, L. A.; Iza, D. C.; Chen, A.; Wang, H.; MacManus Driscoll, J. L.

    2012-12-01

    Phase pure, dense Cu2O thin films were grown on glass and polymer substrates at 225°C by rapid atmospheric atomic layer deposition (AALD). Carrier mobilities of 5 cm2V-1s-1 and carrier concentrations of ˜1016 cm-3 were achieved in films of thickness 50 - 120 nm, over a >10 cm2 area. Growth rates were ˜1 nm.min-1 which is two orders of magnitude faster than conventional ALD.. The high mobilities achieved using the atmospheric, low temperature method represent a significant advance for flextronics and flexible solar cells which require growth on plastic substrates.

  5. An ambipolar organic field-effect transistor based on an AIE-active single crystal with a high mobility level of 2.0 cm(2) V(-1) s(-1).

    PubMed

    Deng, Jian; Xu, Yuanxiang; Liu, Liqun; Feng, Cunfang; Tang, Jia; Gao, Yu; Wang, Yan; Yang, Bing; Lu, Ping; Yang, Wensheng; Ma, Yuguang

    2016-02-01

    Organic field-effect transistors (OFETs) based on an aggregation-induced emission (AIE) material were fabricated using a calcium-gold asymmetric electrode system. The devices showed very high and balanced mobility, reaching 2.50 and 2.10 cm(2) V(-1) s(-1), respectively, for electron and hole. Strong green electroluminescence from the single-crystal side edge was observed from all the devices. This work demonstrates that AIE active materials could not only achieve high luminescence, but also be used in light emitting transistors and achieve very high mobility. PMID:26730680

  6. Lessons Learned From CM-2 Modal Testing and Analysis

    NASA Technical Reports Server (NTRS)

    McNelis, Mark E.; Goodnight, Thomas W.; Carney, Kelly S.; Otten, Kim D.

    2002-01-01

    The Combustion Module-2 (CM-2) is a space experiment that launches on Shuttle mission STS-107 in the SPACEHAB Double Research Module. The CM-2 flight hardware is installed into SPACEHAB single and double racks. The CM-2 flight hardware was vibration tested in the launch configuration to characterize the structure's modal response. Cross-orthogonality between test and analysis mode shapes were used to assess model correlation. Lessons learned for pre-test planning and model verification are discussed.

  7. CM-2 Environmental / Modal Testing of Spacehab Racks

    NASA Technical Reports Server (NTRS)

    McNelis, Mark E.; Goodnight, Thomas W.; Farkas, Michael A.

    2001-01-01

    Combined environmental/modal vibration testing has been implemented at the NASA Glenn Research Center's Structural Dynamics Laboratory. The benefits of combined vibration testing are that it facilitates test article modal characterization and vibration qualification testing. The Combustion Module-2 (CM-2) is a space experiment that launches on Shuttle mission STS 107 in the SPACEHAB Research Double Module. The CM-2 flight hardware is integrated into a SPACEHAB single and double rack. CM-2 rack level combined vibration testing was recently completed on a shaker table to characterize the structure's modal response and verify the random vibration response. Control accelerometers and limit force gauges, located between the fixture and rack interface, were used to verify the input excitation. Results of the testing were used to verify the loads and environments for flight on the Shuttle.

  8. Benchmarking and performance analysis of the CM-2. [SIMD computer

    NASA Technical Reports Server (NTRS)

    Myers, David W.; Adams, George B., II

    1988-01-01

    A suite of benchmarking routines testing communication, basic arithmetic operations, and selected kernel algorithms written in LISP and PARIS was developed for the CM-2. Experiment runs are automated via a software framework that sequences individual tests, allowing for unattended overnight operation. Multiple measurements are made and treated statistically to generate well-characterized results from the noisy values given by cm:time. The results obtained provide a comparison with similar, but less extensive, testing done on a CM-1. Tests were chosen to aid the algorithmist in constructing fast, efficient, and correct code on the CM-2, as well as gain insight into what performance criteria are needed when evaluating parallel processing machines.

  9. IEP Prov v.1

    ERIC Educational Resources Information Center

    Steel, Lawrence E.

    2005-01-01

    Perhaps the most time consuming task facing today's busy special educator is keeping up with all the paperwork associated with national, state and local regulations. IEP Pro v.1-a PC and Macintosh compatible CD-ROM program-creates IEP's, then tracks and manages many of the administrative and paperwork tasks associated with running a special…

  10. Microbiological study of the Murchison CM2 meteorite

    NASA Astrophysics Data System (ADS)

    Pikuta, Elena V.; Hoover, Richard B.

    2012-10-01

    In 1864, Louis Pasteur attempted to cultivate living microorganisms from pristine samples of the Orgueil CI1 carbonaceous meteorite. His results were negative and never published, but recorded it in his laboratory notebooks. At that time, only aerobic liquid or agar-based organic reach media were used, as his research on anaerobes had just started. In our laboratory the Murchison CM2 carbonaceous meteorite was selected to expand on these studies for microbiological study by cultivation on anaerobic mineral media. Since the surface could have been more easily contaminated, interior fragments of a sample of the Murchison meteorite were extracted and crushed under sterile conditions. The resulting powder was then mixed in anoxic medium and injected into Hungate tubes containing anaerobic media with various growth substrates at different pH and salinity and incubated at different temperatures. The goal of the experiments was to determine if living cells would grow from the material of freshly fractured interior fragments of the stone. If any growth occurred, work could then be carried out to assess the nature of the environmental contamination by observations of the culture growth (rates of speed and biodiversity); live/dead fluorescent staining to determine contamination level and DNA analysis to establish the microbial species present. In this paper we report the results of that study.

  11. Presolar grains in the CM2 chondrite Sutter's Mill

    NASA Astrophysics Data System (ADS)

    Zhao, Xuchao; Lin, Yangting; Yin, Qing-Zhu; Zhang, Jianchao; Hao, Jialong; Zolensky, Michael; Jenniskens, Peter

    2014-11-01

    The Sutter's Mill (SM) carbonaceous chondrite is a regolith breccia, composed predominantly of CM2 clasts with varying degrees of aqueous alteration and thermal metamorphism. An investigation of presolar grains in four Sutter's Mill sections, SM43, SM51, SM2-4, and SM18, was carried out using NanoSIMS ion mapping technique. A total of 37 C-anomalous grains and one O-anomalous grain have been identified, indicating an abundance of 63 ppm for presolar C-anomalous grains and 2 ppm for presolar oxides. Thirty-one silicon carbide (SiC), five carbonaceous grains, and one Al-oxide (Al2O3) were confirmed based on their elemental compositions determined by C-N-Si and O-Si-Mg-Al isotopic measurements. The overall abundance of SiC grains in Sutter's Mill (55 ppm) is consistent with those in other CM chondrites. The absence of presolar silicates in Sutter's Mill suggests that they were destroyed by aqueous alteration on the parent asteroid. Furthermore, SM2-4 shows heterogeneous distributions of presolar SiC grains (12-54 ppm) in different matrix areas, indicating that the fine-grained matrix clasts come from different sources, with various thermal histories, in the solar nebula.

  12. Considerations for applying VARSKIN mod 2 to skin dose calculations averaged over 10 cm2.

    PubMed

    Durham, James S

    2004-02-01

    VARSKIN Mod 2 is a DOS-based computer program that calculates the dose to skin from beta and gamma contamination either directly on skin or on material in contact with skin. The default area for calculating the dose is 1 cm2. Recently, the U.S. Nuclear Regulatory Commission issued new guidelines for calculating shallow dose equivalent from skin contamination that requires the dose be averaged over 10 cm2. VARSKIN Mod 2 was not filly designed to calculate beta or gamma dose estimates averaged over 10 cm2, even though the program allows the user to calculate doses averaged over 10 cm2. This article explains why VARSKIN Mod 2 overestimates the beta dose when applied to 10 cm2 areas, describes a manual method for correcting the overestimate, and explains how to perform reasonable gamma dose calculations averaged over 10 cm2. The article also describes upgrades underway in Varskin 3. PMID:14744063

  13. Role of the CM2 Protein in the Influenza C Virus Replication Cycle ▿

    PubMed Central

    Furukawa, Takatoshi; Muraki, Yasushi; Noda, Takeshi; Takashita, Emi; Sho, Ri; Sugawara, Kanetsu; Matsuzaki, Yoko; Shimotai, Yoshitaka; Hongo, Seiji

    2011-01-01

    CM2 is the second membrane protein of influenza C virus. Although its biochemical characteristics, coding strategy, and properties as an ion channel have been extensively studied, the role(s) of CM2 in the virus replication cycle remains to be clarified. In order to elucidate this role, in the present study we generated CM2-deficient influenza C virus-like particles (VLPs) and examined the VLP-producing 293T cells, VLPs, and VLP-infected HMV-II cells. Quantification of viral RNA (vRNA) in the VLPs by real-time PCR revealed that the CM2-deficient VLPs contain approximately one-third of the vRNA found in wild-type VLPs although no significant differences were detected in the expression levels of viral components in VLP-producing cells or in the number and morphology of the generated VLPs. This finding suggests that CM2 is involved in the genome packaging process into VLPs. Furthermore, HMV-II cells infected with CM2-deficient VLPs exhibited significantly reduced reporter gene expression. Although CM2-deficient VLPs could be internalized into HMV-II cells as efficiently as wild-type VLPs, a smaller amount of vRNA was detected in the nuclear fraction of CM2-deficient VLP-infected cells than in that of wild-type VLP-infected cells, suggesting that the uncoating process of the CM2-deficient VLPs in the infected cells did not proceed in an appropriate manner. Taken together, the data obtained in the present study indicate that CM2 has a potential role in the genome packaging and uncoating processes of the virus replication cycle. PMID:21106743

  14. Multielectron ultrastrong laser field ionization of Arn+, Krm+ and Xel+ (n <= 9, m <= 9, l <= 12) at intensities from 1015 W cm-2 to 1018 W cm-2

    NASA Astrophysics Data System (ADS)

    Palaniyappan, S.; Di Chiara, A.; Ghebregziabher, I.; Huskins, E. L.; Falkowski, A.; Pajerowski, D.; Walker, B. C.

    2006-07-01

    Ionization yields are reported for Ar, Kr and Xe in ultrastrong fields from 1015 W cm-2 to 1018 W cm-2. Non-sequential ionization (NSI) is shown to be a robust and general feature in ultrahigh field ionization. NSI yields measured are consistent with the trends predicted by a rescattering model, but as one proceeds to higher Z atoms more NSI is observed than predicted theoretically. Additional recollision mechanisms that may need to be considered in future theories of ultrastrong field-atom interactions include 'chain' NSI, NSI from excited states of the atom (e.g. Rydberg states or inner-shell holes) and the possibility of ultrastrong field enhanced recollision/impact processes.

  15. 10 CFR 10.4 - Policy.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Policy. 10.4 Section 10.4 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL... Nuclear Regulatory Commission to carry out its responsibility for the security of the nuclear...

  16. 10 CFR 10.4 - Policy.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Policy. 10.4 Section 10.4 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL... Nuclear Regulatory Commission to carry out its responsibility for the security of the nuclear...

  17. 10 CFR 10.4 - Policy.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Policy. 10.4 Section 10.4 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL... Nuclear Regulatory Commission to carry out its responsibility for the security of the nuclear...

  18. 10 CFR 10.4 - Policy.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Policy. 10.4 Section 10.4 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL... Nuclear Regulatory Commission to carry out its responsibility for the security of the nuclear...

  19. 10 CFR 10.4 - Policy.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Policy. 10.4 Section 10.4 Energy NUCLEAR REGULATORY COMMISSION CRITERIA AND PROCEDURES FOR DETERMINING ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL... Nuclear Regulatory Commission to carry out its responsibility for the security of the nuclear...

  20. 36 CFR 10.4 - Shipment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Shipment. 10.4 Section 10.4 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR DISPOSAL OF... removed by truck. Elk and buffaloes, when not transported by truck, must be crated individually for...

  1. 36 CFR 10.4 - Shipment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Shipment. 10.4 Section 10.4 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR DISPOSAL OF... removed by truck. Elk and buffaloes, when not transported by truck, must be crated individually for...

  2. Development and characterization of a 280 cm2 vanadium/oxygen fuel cell

    NASA Astrophysics Data System (ADS)

    Noack, Jens; Cremers, Carsten; Bayer, Domnik; Tübke, Jens; Pinkwart, Karsten

    2014-05-01

    A vanadium/oxygen fuel cell with an active area of 280 cm2 has been developed. The cell consisted of two membranes with two half-cells and an intermediate chamber. The maximum achieved power density was 23 mW cm-2 at 0.56 V with lambda air = 3 and a 1.6 M V2+ solution at room temperature. The average discharge power density was 19.6 mW cm-2 at a constant current density of 40 mA cm-2 with an average voltage efficiency of 33%. The fuel based energy density was 18.2% of the theoretical value with 11.8 Wh L-1. In comparison with a similarly constructed 50 cm2 cell, both achieved similar performance levels. An analysis using the half-cell potential profiles and by means of impedance spectroscopy revealed that, as for the 50 cm2 cell, the low rate of oxygen reduction reaction significantly affected the performance of the cell. Thus gives potential for the optimization of the cathode reaction and a reduction in the ohmic resistances potential for higher power densities.

  3. GFDL's CM2 global coupled climate models. Part I: Formulation and simulation characteristics

    USGS Publications Warehouse

    Delworth, T.L.; Broccoli, A.J.; Rosati, A.; Stouffer, R.J.; Balaji, V.; Beesley, J.A.; Cooke, W.F.; Dixon, K.W.; Dunne, J.; Dunne, K.A.; Durachta, J.W.; Findell, K.L.; Ginoux, P.; Gnanadesikan, A.; Gordon, C.T.; Griffies, S.M.; Gudgel, R.; Harrison, M.J.; Held, I.M.; Hemler, R.S.; Horowitz, L.W.; Klein, S.A.; Knutson, T.R.; Kushner, P.J.; Langenhorst, A.R.; Lee, H.-C.; Lin, S.-J.; Lu, J.; Malyshev, S.L.; Milly, P.C.D.; Ramaswamy, V.; Russell, J.; Schwarzkopf, M.D.; Shevliakova, E.; Sirutis, J.J.; Spelman, M.J.; Stern, W.F.; Winton, M.; Wittenberg, A.T.; Wyman, B.; Zeng, F.; Zhang, R.

    2006-01-01

    The formulation and simulation characteristics of two new global coupled climate models developed at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL) are described. The models were designed to simulate atmospheric and oceanic climate and variability from the diurnal time scale through multicentury climate change, given our computational constraints. In particular, an important goal was to use the same model for both experimental seasonal to interannual forecasting and the study of multicentury global climate change, and this goal has been achieved. Tw o versions of the coupled model are described, called CM2.0 and CM2.1. The versions differ primarily in the dynamical core used in the atmospheric component, along with the cloud tuning and some details of the land and ocean components. For both coupled models, the resolution of the land and atmospheric components is 2?? latitude ?? 2.5?? longitude; the atmospheric model has 24 vertical levels. The ocean resolution is 1?? in latitude and longitude, with meridional resolution equatorward of 30?? becoming progressively finer, such that the meridional resolution is 1/3?? at the equator. There are 50 vertical levels in the ocean, with 22 evenly spaced levels within the top 220 m. The ocean component has poles over North America and Eurasia to avoid polar filtering. Neither coupled model employs flux adjustments. The co ntrol simulations have stable, realistic climates when integrated over multiple centuries. Both models have simulations of ENSO that are substantially improved relative to previous GFDL coupled models. The CM2.0 model has been further evaluated as an ENSO forecast model and has good skill (CM2.1 has not been evaluated as an ENSO forecast model). Generally reduced temperature and salinity biases exist in CM2.1 relative to CM2.0. These reductions are associated with 1) improved simulations of surface wind stress in CM2.1 and associated changes in oceanic gyre circulations; 2) changes in cloud tuning and

  4. 36 CFR 10.4 - Shipment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CERTAIN WILD ANIMALS § 10.4 Shipment. (a) Elk, buffaloes, and bears may be obtained at the Park and be removed by truck. Elk and buffaloes, when not transported by truck, must be crated individually for...

  5. 36 CFR 10.4 - Shipment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... CERTAIN WILD ANIMALS § 10.4 Shipment. (a) Elk, buffaloes, and bears may be obtained at the Park and be removed by truck. Elk and buffaloes, when not transported by truck, must be crated individually for...

  6. 36 CFR 10.4 - Shipment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... CERTAIN WILD ANIMALS § 10.4 Shipment. (a) Elk, buffaloes, and bears may be obtained at the Park and be removed by truck. Elk and buffaloes, when not transported by truck, must be crated individually for...

  7. CM2 antigen, a potential novel molecule participating in glucuronide transport on rat hepatocyte canalicular membrane.

    PubMed

    Wang, L; Wang, J; Zhou, X; Li, J; Shi, Y; Han, Z; Wang, X; Li, S; Yang, Z; Wang, R; Fan, D; Han, Y

    2012-06-29

    The polarized molecules predominately distributing at hepatocyte canalicular surface play a vital role in disclosing the process of bile formation and etiopathogenisis of cholestatic live diseases. Therefore, it is important to find novel polarized molecules on hepatocyte canalicular membrane. In the present study, canalicular membrane vesicles (CMVs) isolated from rat hepatocyte by density gradient centrifugation were used as immunogens to produce hybridoma and 46 strains of monoclonal antibodies (mAb) against CMVs were obtained. With a series of morphological assay methods, including immunohistochemistry, immunofluorescence and immuno-electron microscope, the antigens recognized by canalicular mAb1 (CM1) and canalicular mAb2 (CM2) were confirmed to predominately distribute at hepatocyte canalicular membrane. Transport activity assay revealed that CM2 could inhibit ATP-dependent E217βG uptake of rat hepatocyte CMVs. Meanwhile, Western blotting analysis showed that the molecular mass of CM2 antigen was approximately 110kDa, which was much less than Mr 180kDa of multidrug resistance-associated protein 2 (MRP2) involved in glucuronide transport. These data indicated that CM2 antigen might be a potential novel molecule participating in glucuronide transport on the hepatocyte canalicular membrane.

  8. Aliphatic amines in Antarctic CR2, CM2, and CM1/2 carbonaceous chondrites

    NASA Astrophysics Data System (ADS)

    Aponte, José C.; McLain, Hannah L.; Dworkin, Jason P.; Elsila, Jamie E.

    2016-09-01

    Meteoritic water-soluble organic compounds provide a unique record of the processes that occurred during the formation of the solar system and the chemistry preceding the origins of life on Earth. We have investigated the molecular distribution, compound-specific δ13C isotopic ratios and enantiomeric compositions of aliphatic monoamines present in the hot acid-water extracts of the carbonaceous chondrites LAP 02342 (CR2), GRA 95229 (CR2), LON 94101 (CM2), LEW 90500 (CM2), and ALH 83100 (CM1/2). Analyses of the concentration of monoamines in these meteorites revealed: (a) the CR2 chondrites studied here contain higher concentrations of monoamines relative to the analyzed CM2 chondrites; (b) the concentration of monoamines decreases with increasing carbon number; and (c) isopropylamine is the most abundant monoamine in these CR2 chondrites, while methylamine is the most abundant amine species in these CM2 and CM1/2 chondrites. The δ13C values of monoamines in CR2 chondrite do not correlate with the number of carbon atoms; however, in CM2 and CM1/2 chondrites, the 13C enrichment decreases with increasing monoamine carbon number. The δ13C values of methylamine in CR2 chondrites ranged from -1 to +10‰, while in CM2 and CM1/2 chondrites the δ13C values of methylamine ranged from +41 to +59‰. We also observed racemic compositions of sec-butylamine, 3-methyl-2-butylamine, and sec-pentylamine in the studied carbonaceous chondrites. Additionally, we compared the abundance and δ13C isotopic composition of monoamines to those of their structurally related amino acids. We found that monoamines are less abundant than amino acids in CR2 chondrites, with the opposite being true in CM2 and CM1/2 chondrites. We used these collective data to evaluate different primordial synthetic pathways for monoamines in carbonaceous chondrites and to understand the potential common origins these molecules may share with meteoritic amino acids.

  9. 27 CFR 10.4 - Jurisdictional limits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF THE TREASURY LIQUORS COMMERCIAL BRIBERY Scope of Regulations § 10.4 Jurisdictional limits. (a.... In the case of malt beverages, this part applies to transactions between an employee, officer, or... similar transactions between an employee, officer, or representative of a trade buyer in such State and...

  10. 44 CFR 10.4 - Policy.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... approach that will ensure the integrated use of the natural and social sciences, and environmental... GENERAL ENVIRONMENTAL CONSIDERATIONS General § 10.4 Policy. (a) FEMA shall act with care to assure that... mitigation and flood insurance, it does so in a manner consistent with national environmental policies....

  11. 44 CFR 10.4 - Policy.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... approach that will ensure the integrated use of the natural and social sciences, and environmental... GENERAL ENVIRONMENTAL CONSIDERATIONS General § 10.4 Policy. (a) FEMA shall act with care to assure that... mitigation and flood insurance, it does so in a manner consistent with national environmental policies....

  12. The EET87513 clast N: A CM2 fragment in an HED polymict breccia

    NASA Technical Reports Server (NTRS)

    Buchanan, P. C.; Zolensky, M. E.; Reid, A. M.; Barrett, R. A.

    1993-01-01

    Xenoliths of material resembling carbonaceous chondrites have been found in several HED polymict breccias. Most workers concluded that these clasts are related to CM2 meteorites on the basis of texture, bulk composition, and mineralogy. Data on clast N, a carbonaceous chondrite fragment from the howardite EET87513 large enough (approximately 4x5mm on the surface of the slab from which it was separated) to extract bulk samples for INAA and oxygen isotope analysis and to provide a thin section for electron microprobe, SEM, and TEM analysis is reported. Preliminary data for this clast were previously reported. INAA was performed at Oregon State University and bulk oxygen isotopic composition was determined at the University of Chicago. These data confirm that EET87513 clast N is a fragment of CM2 material.

  13. Investigation of pyridine carboxylic acids in CM2 carbonaceous chondrites: Potential precursor molecules for ancient coenzymes

    NASA Astrophysics Data System (ADS)

    Smith, Karen E.; Callahan, Michael P.; Gerakines, Perry A.; Dworkin, Jason P.; House, Christopher H.

    2014-07-01

    The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We also report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth.

  14. Investigation of Pyridine Carboxylic Acids in CM2 Carbonaceous Chondrites: Potential Precursor Molecules for Ancient Coenzymes

    NASA Technical Reports Server (NTRS)

    Smith, Karen E.; Callahan, Michael P.; Gerakines, Perry A.; Dworkin, Jason P.; House, Christopher H.

    2014-01-01

    The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We lso report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth.

  15. Investigation of Pyridine Carboxylic Acids in CM2 Carbonaceous Chondrites: Potential Precursor Molecules for Ancient Coenzymes

    NASA Technical Reports Server (NTRS)

    Smith, Karen E.; Callahan, Michael P.; Gerakines, Perry A.; Dworkin, Jason P.; House, Christopher H.

    2014-01-01

    The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We also report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth.

  16. Visual crowding in V1.

    PubMed

    Millin, Rachel; Arman, A Cyrus; Chung, Susana T L; Tjan, Bosco S

    2014-12-01

    In peripheral vision, objects in clutter are difficult to identify. The exact cause of this "crowding" effect is unclear. To perceive coherent shapes in clutter, the visual system must integrate certain local features across receptive fields while preventing others from being combined. It is believed that this selective feature integration-segmentation process is impaired in peripheral vision, leading to crowding. We used functional magnetic resonance imaging (fMRI) to investigate the neural origin of crowding. We found that crowding was associated with suppressed fMRI signal as early as V1, regardless of whether attention was directed toward or away from a target stimulus. This suppression in early visual cortex was greatest for stimuli that produced the strongest crowding. In contrast, the pattern of activity was mixed in higher level visual areas, such as the lateral occipital cortex. These results support the view that the deficiency in feature integration and segmentation in peripheral vision is present at the earliest stages of cortical processing.

  17. Experimental investigation of a 1 kA/cm2 sheet beam plasma cathode electron gun

    NASA Astrophysics Data System (ADS)

    Kumar, Niraj; Narayan Pal, Udit; Kumar Pal, Dharmendra; Prajesh, Rahul; Prakash, Ram

    2015-01-01

    In this paper, a cold cathode based sheet-beam plasma cathode electron gun is reported with achieved sheet-beam current density ˜1 kA/cm2 from pseudospark based argon plasma for pulse length of ˜200 ns in a single shot experiment. For the qualitative assessment of the sheet-beam, an arrangement of three isolated metallic-sheets is proposed. The actual shape and size of the sheet-electron-beam are obtained through a non-conventional method by proposing a dielectric charging technique and scanning electron microscope based imaging. As distinct from the earlier developed sheet beam sources, the generated sheet-beam has been propagated more than 190 mm distance in a drift space region maintaining sheet structure without assistance of any external magnetic field.

  18. Actinic defect counting statistics over 1 cm2 area of EUVL mask blank

    SciTech Connect

    Jeong, Seongtae; Lai, Chih-Wei; Rekawa, Seno; Walton, Chris W.; Bokor, Jeffrey

    2000-02-18

    As a continuation of comparison experiments between EUV inspection and visible inspection of defects on EUVL mask blanks, we report on the result of an experiment where the EUV defect inspection tool is used to perform at-wavelength defect counting over 1 cm{sup 2} of EUVL mask blank. Initial EUV inspection found five defects over the scanned area and the subsequent optical scattering inspection was able to detect all of the five defects. Therefore, if there are any defects that are only detectable by EUV inspection, the density is lower than the order of unity per cm2. An upgrade path to substantially increase the overall throughput of the EUV inspection system is also identified in the manuscript.

  19. Vibration Energy Harvesting Characterization of 1 cm2 Poly(vinylidene fluoride) Generators in Vacuum

    NASA Astrophysics Data System (ADS)

    Cao, Ziping; Zhang, Jinya; Kuwano, Hiroki

    2011-09-01

    In this study, poly(vinylidene fluoride) (PVDF) was used as a piezoelectric element to fabricate small size (two-dimensional area <1 cm2) generators with low resonant frequency (about 100 Hz) for matching the frequency of vibration sources. To clarify the effect of the air damping on the vibration energy harvesting, PVDF generators were investigated in three measurement conditions: “unpackaged in air”, “packaged in air”, and “unpackaged in vacuum”. It was found that the output power of generators “unpackaged in vacuum” was almost twice that of generators “packaged in air” at 0.5g acceleration. With the increase in vibration acceleration, the output power of generators “unpackaged in vacuum” rapidly increased in a quadratic relationship with the acceleration at low acceleration level, and then the increasing ratio decreased at high acceleration. At 4.31g acceleration, the output power reached 100.833 µW.

  20. Compositions of Partly Altered Olivine and Replacement Serpentine in the CM2 Chondrite QUE93005

    NASA Technical Reports Server (NTRS)

    Velbel, M. A.; Tonui, E. K.; Zolensky, M. E.

    2005-01-01

    Some phyllosilicates in CM carbonaceous chondrites formed by aqueous alteration of anhydrous precursor phases. Although broad trends in the compositions of hydrous phyllosilicates are recognized and believed to be related to trends in degree of aqueous alteration, details of the reactions that formed specific secondary minerals remain obscure. This paper reports compositional relationships between remnants of partially pseudomorphically (or alteromorphically) replaced silicates and their alteration products (serpentine) in the CM2 chondrite QUE93005 and compares it with previously published results for ALH81002. Reactants and products were characterized by optical petrography, backscattered scanning electron microscopy (BSEM), and electron microprobe. By focusing on serpentine formed from known reactants (olivines), and on only those instances in which some of the reactant silicate remains, direct compositional relationships between reactants and products, and the elemental mobility required by the reactions, can be established. Additional information is included in the original extended abstract.

  1. Organic blend semiconductors and transistors with hole mobility exceeding 10 cm2/Vs (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Paterson, Alexandra F.; Anthopoulos, Thomas D.

    2015-10-01

    Plastic electronics that can be manufactured using solution-based methods are the subject of great research interest due to their potential for low-cost, large-area electronic applications. The interest in this field has led to considerable research and subsequent advances in device performance. To this end solution-processed organic thin-film transistors (OTFTs) have shown impressive improvements in recent years through the increasing values of charge carrier mobility. Here we report the development of next generation organic blend materials for OTFTs with hole mobilities of 10 cm2/Vs. These high performance devices have been achieved using a novel semiconducting blend system comprising of an amorphous-like conjugated polymer and a high mobility small molecule. The combination of a highly crystalline small molecule with the polymer binder aids the formation of uniform films as well as enables an element of control over the nucleation and growth of the small molecule. The polymer binders investigated belongs to the family of indacenodithiophene-based copolymers which are renowned for their high carrier mobilities regardless of their apparent structural disorder. The addition of the polymer with carefully chosen small molecules is found to further increase the hole mobility of the resulting blend OTFT to over 10 cm2/Vs. These organic devices provide an interesting insight into this rather complex blend system, highlighting the correlation between the morphology developed following solution processing and device performance, as well as exploring the role of each of the two components in the blend in terms of their contribution to charge transport.

  2. Spectral content of buried Ag foils at 1016 W/cm2 laser illuminationa)

    NASA Astrophysics Data System (ADS)

    Huntington, C. M.; Maddox, B. R.; Park, H.-S.; Prisbrey, S.; Remington, B. A.

    2014-11-01

    Sources of 5-12 keV thermal Heα x-rays are readily generated by laser irradiation of mid-Z foils at intensities >1014 W/cm2, and are widely used as probes for inertial confinement fusion and high-energy-density experiments. Higher energy 17-50 keV x-ray sources are efficiently produced from "cold" Kα emission using short pulse, petawatt lasers at intensities >1018 W/cm2 [H.-S. Park, B. R. Maddox et al., "High-resolution 17-75 keV backlighters for high energy density experiments," Phys. Plasmas 15(7), 072705 (2008); B. R. Maddox, H. S. Park, B. A. Remington et al., "Absolute measurements of x-ray backlighter sources at energies above 10 keV," Phys. Plasmas 18(5), 056709 (2011)]. However, when long pulse (>1 ns) lasers are used with Z > 30 elements, the spectrum contains contributions from both K shell transitions and from ionized atomic states. Here we show that by sandwiching a silver foil between layers of high-density carbon, the ratio of Kα:Heα in the x-ray spectrum is significant increased over directly illuminated Ag foils, with narrower lines from K-shell transitions. Additionally, the emission volume is more localized for the sandwiched target, producing a more planar x-ray sheet. This technique may be useful for generating probes requiring spectral purity and a limited spatial extent, for example, in incoherent x-ray Thomson scattering experiments.

  3. The amino acid composition of the Sutter's Mill CM2 carbonaceous chondrite

    NASA Astrophysics Data System (ADS)

    Burton, Aaron S.; Glavin, Daniel P.; Elsila, Jamie E.; Dworkin, Jason P.; Jenniskens, Peter; Yin, Qing-Zhu

    2014-11-01

    We determined the abundances and enantiomeric compositions of amino acids in Sutter's Mill fragment #2 (designated SM2) recovered prior to heavy rains that fell April 25-26, 2012, and two other meteorite fragments, SM12 and SM51, that were recovered postrain. We also determined the abundance, enantiomeric, and isotopic compositions of amino acids in soil from the recovery site of fragment SM51. The three meteorite stones experienced terrestrial amino acid contamination, as evidenced by the low D/L ratios of several proteinogenic amino acids. The D/L ratios were higher in SM2 than in SM12 and SM51, consistent with rain introducing additional L-amino acid contaminants to SM12 and SM51. Higher percentages of glycine, β-alanine, and γ-amino-n-butyric acid were observed in free form in SM2 and SM51 compared with the soil, suggesting that these free amino acids may be indigenous. Trace levels of D+L-β-aminoisobutyric acid (β-AIB) observed in all three meteorites are not easily explained as terrestrial contamination, as β-AIB is rare on Earth and was not detected in the soil. Bulk carbon and nitrogen and isotopic ratios of the SM samples and the soil also indicate terrestrial contamination, as does compound-specific isotopic analysis of the amino acids in the soil. The amino acid abundances in SM2, the most pristine SM meteorite analyzed here, are approximately 20-fold lower than in the Murchison CM2 carbonaceous chondrite. This may be due to thermal metamorphism in the Sutter's Mill parent body at temperatures greater than observed for other aqueously altered CM2 meteorites.

  4. Methylmercury degradation by Pseudomonas putida V1.

    PubMed

    Cabral, Lucélia; Yu, Ri-Qing; Crane, Sharron; Giovanella, Patricia; Barkay, Tamar; Camargo, Flávio A O

    2016-08-01

    Environmental contamination of mercury (Hg) has caused public health concerns with focuses on the neurotoxic substance methylmercury, due to its bioaccumulation and biomagnification in food chains. The goals of the present study were to examine: (i) the transformation of methylmercury, thimerosal, phenylmercuric acetate and mercuric chloride by cultures of Pseudomonas putida V1, (ii) the presence of the genes merA and merB in P. putida V1, and (iii) the degradation pathways of methylmercury by P. putida V1. Strain V1 cultures readily degraded methylmercury, thimerosal, phenylmercury acetate, and reduced mercuric chloride into gaseous Hg(0). However, the Hg transformation in LB broth by P. putida V1 was influenced by the type of Hg compounds. The merA gene was detected in P. putida V1, on the other hand, the merB gene was not detected. The sequencing of this gene, showed high similarity (100%) to the mercuric reductase gene of other Pseudomonas spp. Furthermore, tests using radioactive (14)C-methylmercury indicated an uncommon release of (14)CO2 concomitant with the production of Hg(0). The results of the present work suggest that P. putida V1 has the potential to remove methylmercury from contaminated sites. More studies are warranted to determine the mechanism of removal of methylmercury by P. putida V1. PMID:27062344

  5. A minimum column density of 1 g cm(-2) for massive star formation.

    PubMed

    Krumholz, Mark R; McKee, Christopher F

    2008-02-28

    Massive stars are very rare, but their extreme luminosities make them both the only type of young star we can observe in distant galaxies and the dominant energy sources in the Universe today. They form rarely because efficient radiative cooling keeps most star--forming gas clouds close to isothermal as they collapse, and this favours fragmentation into stars of one solar mass or lower. Heating of a cloud by accreting low-mass stars within it can prevent fragmentation and allow formation of massive stars, but the necessary properties for a cloud to form massive stars-and therefore where massive stars form in a galaxy--have not yet been determined. Here we show that only clouds with column densities of at least 1 g cm(-2) can avoid fragmentation and form massive stars. This threshold, and the environmental variation of the stellar initial mass function that it implies, naturally explain the characteristic column densities associated with massive star clusters and the difference between the radial profiles of Halpha and ultraviolet emission in galactic disks. The existence of a threshold also implies that the initial mass function should show detectable variation with environment within the Galaxy, that the characteristic column densities of clusters containing massive stars should vary between galaxies, and that star formation rates in some galactic environments may have been systematically underestimated.

  6. On the Behavior of Phosphorus During the Aqueous Alteration of CM2 Carbonaceous Chondrites

    NASA Technical Reports Server (NTRS)

    Brearley, Adrian J.; Chizmadia, Lysa J.

    2005-01-01

    During the earliest period of solar system formation, water played an important role in the evolution of primitive dust, both after accretion of planetesimals and possible before accretion within the protoplanetary disk. Many chondrites show evidence of variable degrees of aqueous alteration, the CM2 chondrites being among the most studied [1]. This group of chondrites is characterized by mineral assemblages of both primary and secondary alteration phases. Hence, these meteorites retain a particularly important record of the reactions that occurred between primary high temperature nebular phases and water. Studies of these chondrites can provide information on the conditions and environments of aqueous alteration and the mobility of elements during alteration. This latter question is at the core of a debate concerning the location of aqueous alteration, i.e. whether alteration occurred predominantly within a closed system after accretion (parent body alteration) or whether some degree of alteration occurred within the solar nebula or on ephemeral protoplanetary bodies prior to accretion. At the core of the parent body alteration model is the hypothesis that elemental exchange between different components, principally chondrules and matrix, must have occurred. chondrules and matrix, must have occurred. In this study, we focus on the behavior of the minor element, phosphorus. This study was stimulated by observations of the behavior of P during the earliest stages of alteration in glassy mesostasis in type II chondrules in CR chondrites and extends the preliminary observations of on Y791198 to other CM chondrites.

  7. N-15-Rich Organic Globules in a Cluster IDP and the Bells CM2 Chondrite

    NASA Technical Reports Server (NTRS)

    Messenger, S.; Nakamura-Messenger, K.; Keller, Lindsay P.

    2008-01-01

    Organic matter in primitive meteorites and chondritic porous interplanetary dust particles (CP IDPs) is commonly enriched in D/H and 15N/14N relative to terrestrial values [1-3]. These anomalies are ascribed to the partial preservation of presolar cold molecular cloud material [1]. Some meteorites and IDPs contain m-size inclusions with extreme H and N isotopic anomalies [2-4], possibly due to preserved pristine primordial organic grains. We recently showed that the in the Tagish Lake meteorite, the principle carriers of these anomalies are sub- m, hollow organic globules [5]. The globules likely formed by photochemical processing of organic ices in a cold molecular cloud or the outermost regions of the protosolar disk [5]. We proposed that similar materials should be common among primitive meteorites, IDPs, and comets. Similar objects have been observed in organic extracts of carbonaceous chondrites [6-8], however their N and H isotopic compositions are generally unknown. Bulk H and N isotopic compositions may indicate which meteorites best preserve interstellar organic compounds. Thus, we selected the Bells CM2 carbonaceous chondrites for study based on its large bulk 15N (+335 %) and D (+990 %) [9].

  8. Fe and O EELS Studies of Ion Irradiated Murchison CM2 Carbonaceous Chondrite Matrix

    NASA Technical Reports Server (NTRS)

    Keller, L. P.; Christofferson, R.; Dukes, C. A.; Baragiola, R. A.; Rahman, Z.

    2015-01-01

    Introduction: The physical and chemical response of hydrated carbonaceous chondrite materials to space weathering processes is poorly understood. Improving this understanding is a key part of establishing how regoliths on primitive carbonaceous asteroids respond to space weathering processes, knowledge that supports future sample return missions (Hayabusa 2 and OSIRISREx) that are targeting objects of this type. We previously reported on He+ irradiation of Murchison matrix and showed that the irradiation resulted in amorphization of the matrix phyllosilicates, loss of OH, and surface vesiculation. Here, we report electron energy-loss spectroscopy (EELS) measurements of the irradiated material with emphasis on the Fe and O speciation. Sample and Methods: A polished thin section of the Murchison CM2 carbonaceous chondrite was irradiated with 4 kilovolts He(+) (normal incidence) to a total dose of 1 x 10(exp 18) He(+) per square centimeter. We extracted thin sections from both irradiated and unirradiated regions in matrix using focused ion beam (FIB) techniques with electron beam deposition for the protective carbon strap to minimize surface damage artifacts from the FIB milling. The FIB sections were analyzed using a JEOL 2500SE scanning and transmission electron microscope (STEM) equipped with a Gatan Tridiem imaging filter. EELS spectra were collected from 50 nanometer diameter regions with an energy resolution of 0.7 electronvolts FWHM at the zero loss. EELS spectra were collected at low electron doses to minimize possible artifacts from electron-beam irradiation damage. Results and Discussion: Fe L (sub 2,3) EELS spectra from matrix phyllosilicates in CM chondrites show mixed Fe(2+)/Fe(3+) oxidation states with Fe(3+)/Sigma Fe approximately 0.5. Fe L(sub 2,3) spectra from the irradiated/ amorphized matrix phyllosilicates show higher Fe(2+)/Fe(3+) ratios compared to spectra obtained from pristine material at depths beyond the implantation/amorphization layer. We

  9. Formation of spinel-, hibonite-rich inclusions found in CM2 carbonaceous chrondrites

    SciTech Connect

    Simon, S B; Grossman, L; Hutcheon, I D; Phinney, D L; Weber, P K; Fallon, S J

    2005-11-03

    We report petrography, mineral chemistry, bulk chemistry, and bulk isotopic compositions of a suite of 40 spinel-rich inclusions from the Murchison (CM2) carbonaceous chondrite. Seven types of inclusions are identified based on mineralogy: spinel-hibonite-perovskite; spinel-perovskite-pyroxene; spinel-perovskite-melilite; spinel-hibonite-perovskite-melilite; spinel-hibonite; spinel-pyroxene; and spinel-melilite-anorthite. Hibonite-bearing inclusions have Ti-poor spinel compared to the hibonite-free ones, and spinel-hibonite-perovskite inclusions have the highest average bulk TiO{sub 2} contents (7.8 wt%). The bulk CaO/Al{sub 2}O{sub 3} ratios of the inclusions range from 0.005-0.21, well below the solar value of 0.79. Hibonite-, spinel-rich inclusions consist of phases that are not predicted by condensation calculations to coexist; in the equilibrium sequence, hibonite is followed by melilite, which is followed by spinel. Therefore, hibonite-melilite or melilite-spinel inclusions should be dominant instead. One explanation for the 'missing melilite' is that it condensed as expected but was lost due to evaporation of Mg and Ca during heating and melting of spherule precursors. If this theory were correct, melilite-poor spherules would have isotopically heavy Mg and Ca. Except for one inclusion with F{sub Mg} = 4.3 {+-} 2.6{per_thousand}/amu and another with isotopically light Ca (F{sub Ca} = 3.4 {+-} 2.0{per_thousand}/amu), however, all the inclusions we analyzed have normal isotopic compositions within their 2{sigma} uncertainties. Thus, we found no evidence for significant mass-dependent fractionation. Our preferred explanation for the general lack of melilite among hibonite-, spinel-bearing inclusions is kinetic inhibition of melilite condensation relative to spinel. Because of similarities between the crystal structures of hibonite and spinel, it should be easier for spinel to form from hibonite than for melilite to do so.

  10. Impact-Induced Chondrule Deformation and Aqueous Alteration of CM2 Murchison

    NASA Technical Reports Server (NTRS)

    Hanna, R. D.; Zolensky, M.; Ketcham, R. A.; Behr, W. M.; Martinez, J. E.

    2014-01-01

    Deformed chondrules in CM2 Murchison have been found to define a prominent foliation [1,2] and lineation [3] in 3D using X-ray computed tomography (XCT). It has been hypothesized that chondrules in foliated chondrites deform by "squeezing" into surrounding pore space [4,5], a process that also likely removes primary porosity [6]. However, shock stage classification based on olivine extinction in Murchison is consistently low (S1-S2) [4-5,7] implying that significant intracrystalline plastic deformation of olivine has not occurred. One objective of our study is therefore to determine the microstructural mechanisms and phases that are accommodating the impact stress and resulting in relative displacements within the chondrules. Another question regarding impact deformation in Murchison is whether it facilitated aqueous alteration as has been proposed for the CMs which generally show a positive correlation between degree of alteration and petrofabric strength [7,2]. As pointed out by [2], CM Murchison represents a unique counterpoint to this correlation: it has a strong petrofabric but a relatively low degree of aqueous alteration. However, Murchison may not represent an inconsistency to the proposed causal relationship between impact and alteration, if it can be established that the incipient aqueous alteration post-dated chondrule deformation. Methods: Two thin sections from Murchison sample USNM 5487 were cut approximately perpendicular to the foliation and parallel to lineation determined by XCT [1,3] and one section was additionally polished for EBSD. Using a combination of optical petrography, SEM, EDS, and EBSD several chondrules were characterized in detail to: determine phases, find microstructures indicative of strain, document the geometric relationships between grain-scale microstructures and the foliation and lineation direction, and look for textural relationships of alteration minerals (tochilinite and Mg-Fe serpentine) that indicate timing of their

  11. 19 CFR 10.4 - Internal-revenue marks; erasure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Internal-revenue marks; erasure. 10.4 Section 10.4 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... and Returned § 10.4 Internal-revenue marks; erasure. Internal-revenue brands or marks on casks...

  12. 17 CFR 10.4 - Business address; hours.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Business address; hours. 10.4 Section 10.4 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION RULES OF PRACTICE General Provisions § 10.4 Business address; hours. The Office of Proceedings is located at Three...

  13. Nanoimprinted polymer lasers with threshold below 100 W/cm2 using mixed-order distributed feedback resonators.

    PubMed

    Wang, Yue; Tsiminis, Georgios; Kanibolotsky, Alexander L; Skabara, Peter J; Samuel, Ifor D W; Turnbull, Graham A

    2013-06-17

    Organic semiconductor lasers were fabricated by UV-nanoimprint lithography with thresholds as low as 57 W/cm(2) under 4 ns pulsed operation. The nanoimprinted lasers employed mixed-order distributed feedback resonators, with second-order gratings surrounded by first-order gratings, combined with a light-emitting conjugated polymer. They were pumped by InGaN LEDs to produce green-emitting lasers, with thresholds of 208 W/cm(2) (102 nJ/pulse). These hybrid lasers incorporate a scalable UV-nanoimprint lithography process, compatible with high-performance LEDs, therefore we have demonstrated a coherent, compact, low-cost light source.

  14. Comparison of visible and near-infrared reflectance spectra of CM2 carbonaceous chondrites and primitive asteroids

    NASA Technical Reports Server (NTRS)

    Vilas, F.; Hiroi, T.; Zolensky, M. E.

    1993-01-01

    Spectra of primitive asteroids (defined as C, P, and D classes and associated subclasses) were compared to the limited number of spectra of CM2 carbonaceous chondrites. An absorption feature located at 0.7 microns attributed to an Fe(+2) - Fe(+3) charge transfer absorption in iron oxides in phyllosilicates is apparent in some of the CM2 carbonaceous chondrite spectra and many of the asteroid spectra. Sawyer found a correlation between the area of the 0.7 micron feature and the mean semimajor axis of the asteroids. Spectra of a larger sample of carbonaceous chondrites, including 7 CM2 chondrites, covering a spectral interval of 0.30-2.5 microns were recently obtained using the Relab instrument at Brown University. These spectra were compared with spectrophotometric asteroid observations in a separate abstract. Those spectra of CM2 chondrites were isolated into the UV, visible and near-infrared spectral regions in order to compare them with high-quality narrowband reflectance spectra.

  15. Successful Capture, Extraction and Identification of Hypervelocity CM2 Meteorite Fragments Shot by Light-Gas Gun

    NASA Technical Reports Server (NTRS)

    Snead, C.; Westphal, A. J.; Dominguez, G.; Zolensky, M. E.

    2003-01-01

    Here we report the successful capture, extraction and identification of two fragments of a CM2 meteorite (ALH83100) into lowdensity aerogel. The shot was carried out at the AVGR at NASAARC. A mixture of powdered ALH83100 and borosilicate glass microspheres was shot at 4.55.0 km/sec into 50 mg cm silicate aerogel.

  16. 46 CFR 111.10-4 - Power requirements, generating sources.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... services include cooking, heating, air conditioning (where installed), domestic refrigeration, mechanical... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Supply § 111.10-4 Power requirements, generating sources....

  17. V1 mechanisms underlying chromatic contrast detection

    PubMed Central

    Hass, Charles A.

    2013-01-01

    To elucidate the cortical mechanisms of color vision, we recorded from individual primary visual cortex (V1) neurons in macaque monkeys performing a chromatic detection task. Roughly 30% of the neurons that we encountered were unresponsive at the monkeys' psychophysical detection threshold (PT). The other 70% were responsive at threshold but on average, were slightly less sensitive than the monkey. For these neurons, the relationship between neurometric threshold (NT) and PT was consistent across the four isoluminant color directions tested. A corollary of this result is that NTs were roughly four times lower for stimuli that modulated the long- and middle-wavelength sensitive cones out of phase. Nearly one-half of the neurons that responded to chromatic stimuli at the monkeys' detection threshold also responded to high-contrast luminance modulations, suggesting a role for neurons that are jointly tuned to color and luminance in chromatic detection. Analysis of neuronal contrast-response functions and signal-to-noise ratios yielded no evidence for a special set of “cardinal color directions,” for which V1 neurons are particularly sensitive. We conclude that at detection threshold—as shown previously with high-contrast stimuli—V1 neurons are tuned for a diverse set of color directions and do not segregate naturally into red–green and blue–yellow categories. PMID:23446689

  18. Tropical Atlantic climate simulated in the GFDL CM2.5 high-resolution coupled climate model

    NASA Astrophysics Data System (ADS)

    Doi, T.; Vecchi, G. A.; Rosati, A. J.; Delworth, T. L.

    2012-12-01

    Using two fully coupled ocean-atmosphere models of CM2.1 (the Climate Model version 2.1 developed at the Geophysical Fluid Dynamics Laboratory) and CM2.5 (a new high-resolution climate model based on CM2.1), the characteristics and sources of SST and precipitation biases associated with the Atlantic ITCZ have been investigated. CM2.5 has an improved simulation of the annual mean and the annual cycle of the rainfall over the Sahel and the northern South America, while CM2.1 shows excessive Sahel rainfall and lack of northern South America rainfall in boreal summer. This marked improvement in CM2.5 is due to not only high-resolved orography, but also a significant reduction of biases in the seasonal meridional migration of the ITCZ. In particular, the seasonal northward migration of the ITCZ in boreal summer is coupled to the seasonal variation of the SST and a subsurface doming of the thermocline in the northeastern tropical Atlantic, known as the Guinea Dome. Improvements in the ITCZ allow for better representation of the coupled processes that are important for an abrupt seasonally phase-locked decay of the interannual SST anomaly in the northern tropical Atlantic. Nevertheless, the differences between CM2.5 and CM2.1 were not sufficient to reduce the warm SST biases in the eastern equatorial region and Angola-Benguela Area. The weak bias of southerly winds along the southwestern African coast associated with the excessive southward migration bias of the ITCZ may be a key to improve the warm SST biases there. Also, response of climate conditions in the Atlantic Hurricane Main Development Region (MDR) to doubling of atmospheric CO2 with CM2.5 has been explored. In the annual mean, the SST in the MDR warms by about 2°C in the CO2 doubling run relative to the Control run, the trade winds become weaker in the northern tropical Atlantic, and the rainfall increases over the ITCZ and its northern region. The amplitude of the annual cycle of the SST over the MDR is not

  19. 46 CFR 111.10-4 - Power requirements, generating sources.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 111.10-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Supply § 111.10-4 Power requirements, generating sources. (a) The aggregate capacity of the electric ship's service generating sources required in § 111.10-3...

  20. 46 CFR 111.10-4 - Power requirements, generating sources.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 111.10-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Supply § 111.10-4 Power requirements, generating sources. (a) The aggregate capacity of the electric ship's service generating sources required in § 111.10-3...

  1. 40 CFR 10.4 - Evidence to be submitted.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Evidence to be submitted. 10.4 Section... FEDERAL TORT CLAIMS ACT Procedures § 10.4 Evidence to be submitted. (a) Death. In support of a claim based on death, the claimant may be required to submit the following evidence or information: (1)...

  2. 40 CFR 10.4 - Evidence to be submitted.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Evidence to be submitted. 10.4 Section... FEDERAL TORT CLAIMS ACT Procedures § 10.4 Evidence to be submitted. (a) Death. In support of a claim based on death, the claimant may be required to submit the following evidence or information: (1)...

  3. 46 CFR 111.10-4 - Power requirements, generating sources.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 111.10-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Supply § 111.10-4 Power requirements, generating sources. (a) The aggregate capacity of the electric ship's service generating sources required in § 111.10-3...

  4. 46 CFR 111.10-4 - Power requirements, generating sources.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 111.10-4 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Power Supply § 111.10-4 Power requirements, generating sources. (a) The aggregate capacity of the electric ship's service generating sources required in § 111.10-3...

  5. TOUGH+ v1.5 Core Code

    2015-08-27

    TOUGH+ v1.5 is a numerical code for the simulation of multi-phase, multi-component flow and transport of mass and heat through porous and fractured media, and represents the third update of the code since its first release [Moridis et al., 2008]. TOUGH+ is a successor to the TOUGH2 [Pruess et al., 1991; 2012] family of codes for multi-component, multiphase fluid and heat flow developed at the Lawrence Berkeley National Laboratory. It is written in standard FORTRANmore » 95/2003, and can be run on any computational platform (workstations, PC, Macintosh). TOUGH+ v1.5 employs dynamic memory allocation, thus minimizing storage requirements. It has a completely modular structure, follows the tenets of Object-Oriented Programming (OOP), and involves the advanced features of FORTRAN 95/2003, i.e., modules, derived data types, the use of pointers, lists and trees, data encapsulation, defined operators and assignments, operator extension and overloading, use of generic procedures, and maximum use of the powerful intrinsic vector and matrix processing operations. TOUGH+ v1.5 is the core code for its family of applications, i.e., the part of the code that is common to all its applications. It provides a description of the underlying physics and thermodynamics of non-isothermal flow, of the mathematical and numerical approaches, as well as a detailed explanation of the general (common to all applications) input requirements, options, capabilities and output specifications. The core code cannot run by itself: it needs to be coupled with the code for the specific TOUGH+ application option that describes a particular type of problem. The additional input requirements specific to a particular TOUGH+ application options and related illustrative examples can be found in the corresponding User’s Manual.« less

  6. TOUGH+ v1.5 Core Code

    SciTech Connect

    Moridis, George J.

    2015-08-27

    TOUGH+ v1.5 is a numerical code for the simulation of multi-phase, multi-component flow and transport of mass and heat through porous and fractured media, and represents the third update of the code since its first release [Moridis et al., 2008]. TOUGH+ is a successor to the TOUGH2 [Pruess et al., 1991; 2012] family of codes for multi-component, multiphase fluid and heat flow developed at the Lawrence Berkeley National Laboratory. It is written in standard FORTRAN 95/2003, and can be run on any computational platform (workstations, PC, Macintosh). TOUGH+ v1.5 employs dynamic memory allocation, thus minimizing storage requirements. It has a completely modular structure, follows the tenets of Object-Oriented Programming (OOP), and involves the advanced features of FORTRAN 95/2003, i.e., modules, derived data types, the use of pointers, lists and trees, data encapsulation, defined operators and assignments, operator extension and overloading, use of generic procedures, and maximum use of the powerful intrinsic vector and matrix processing operations. TOUGH+ v1.5 is the core code for its family of applications, i.e., the part of the code that is common to all its applications. It provides a description of the underlying physics and thermodynamics of non-isothermal flow, of the mathematical and numerical approaches, as well as a detailed explanation of the general (common to all applications) input requirements, options, capabilities and output specifications. The core code cannot run by itself: it needs to be coupled with the code for the specific TOUGH+ application option that describes a particular type of problem. The additional input requirements specific to a particular TOUGH+ application options and related illustrative examples can be found in the corresponding User’s Manual.

  7. 39 CFR 10.4 - Financial disclosure reports.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... particular calendar year is required to file a public report in accordance with 5 CFR 2634.204(c). (b) Person... CONDUCT FOR POSTAL SERVICE GOVERNORS (ARTICLE X) § 10.4 Financial disclosure reports. (a) Requirement...

  8. RealGasBrine v1.0 option of TOUGH+ v1.5

    SciTech Connect

    Moridis, George

    2015-02-27

    RealGasBrine v1.0 is a numerical code that for the simulation of the behavior of gas-bearing porous and/fractured geologic media. It is an option of TOUGH+ v1.5 [Moridis, 2014], a successor to the TOUGH2 [Pruess et al., 1999; 2012] family of codes for multi-component, multiphase ?uid and heat ?ow developed at the Lawrence Berkeley National Laboratory. RealGasBrine v1.0 needs the TOUGH+ v1.5 core code in order to compile and execute. It is written in standard FORTRAN 95/2003, and can be run on any computational platform (workstation, PC, Macintosh) for which such compilers are available. RealGasBrine v1.0 describes the non-isothermal two- (for pure water) or three-phase (for brine) flow of an aqueous phase and a real gas mixture in a gas-bearing medium, with a particular focus in ultra-tight (such as tight-sand and shale gas) systems. Up to 12 individual real gases can be tracked, and salt can precipitate as solid halite. The capabilities of the code include coupled flow and thermal effects, real gas behavior, Darcy and non-Darcy flow, several isotherm options of gas sorption onto the grains of the porous media, complex fracture descriptions, gas solubility into water, and geomechanical effects on flow properties. RealGasBrine v1.0 allows the study of flow and transport of fluids and heat over a wide range of time frames and spatial scales not only in gas reservoirs, but also in any problem involving the flow of gases in geologic media, including the geologic storage of greenhouse gas mixtures, the behavior of geothermal reservoirs with multi-component condensable (H2O and CO2) and non-condensable gas mixtures, the transport of water and released H2 in nuclear waste storage applications, etc.

  9. A 50 EW/cm;2 Ti:sapphire laser system for studying relativistic light-matter interactions.

    PubMed

    Walker, B; Toth, C; Fittinghoff, D; Guo, T; Kim, D E; Rose-Petruck, C; Squier, J; Yamakawa, K; Wilson, K; Barty, C

    1999-11-01

    A 10-Hz repetition rate, 60-TW peak power, Ti:sapphire laser system was developed for use in experiments where relativistic effects dominate the physics. The temporal, spectral, energy and spatial characteristics of the laser pulses were measured in single shot format. The pulse duration ranged from 22 fs to 25 fs and the pulse energy averaged 1.3 J. Atomic photoionization measurements quantified the peak intensity of the laser pulse in situ. The measurements indicated an intensity of at least 510 19 W/cm 2 was produced.

  10. Coulomb-Boltzmann-Shifted distribution in laser-generated plasmas from 1010 up to 1019 W/cm2 intensities

    NASA Astrophysics Data System (ADS)

    Torrisi, L.

    2016-02-01

    The charge production from laser-generated plasmas generates not isotropically ion acceleration in vacuum and with mean kinetic energy proportional to the ion charge state. The ion velocity depends on many factors of which the most important are the plasma temperature, the adiabatic gas expansion in vacuum and the Coulomb acceleration. The ion energy distributions of the emitted ions from the plasma can be well explained by the Coulomb-Boltzmann-Shifted function, with a cut-off limitation at high energy for a wide range of laser intensities. It can be applied for intensities of 1010 W/cm2, when plasma is produced only in the backward direction from thick targets (backward plasma acceleration regime), as well as at intensities of the order of 1019 W/cm2, when plasma is produced in the forward direction from thin targets in target-normal sheath acceleration regime. It loses of validity in radiation pressure acceleration regime, at which ions are emitted near mono-energetically.

  11. HYDRATE v1.5 OPTION OF TOUGH+ v1.5

    SciTech Connect

    Moridis, George

    2015-08-27

    HYDRATE v1.5 is a numerical code that for the simulation of the behavior of hydrate-bearing geologic systems, and represents the third update of the code since its first release [Moridis et al., 2008]. It is an option of TOUGH+ v1.5 [Moridis and Pruess, 2014], a successor to the TOUGH2 [Pruess et al., 1999, 2012] family of codes for multi-component, multiphase fluid and heat flow developed at the Lawrence Berkeley National Laboratory. HYDRATE v1.5 needs the TOUGH+ v1.5 core code in order to compile and execute. It is written in standard FORTRAN 95/2003, and can be run on any computational platform (workstation, PC, Macintosh) for which such compilers are available. By solving the coupled equations of mass and heat balance, the fully operational TOUGH+HYDRATE code can model the non-isothermal gas release, phase behavior and flow of fluids and heat under conditions typical of common natural CH4-hydrate deposits (i.e., in the permafrost and in deep ocean sediments) in complex geological media at any scale (from laboratory to reservoir) at which Darcy’s law is valid. TOUGH+HYDRATE v1.5 includes both an equilibrium and a kinetic model of hydrate formation and dissociation. The model accounts for heat and up to four mass components, i.e., water, CH4, hydrate, and water-soluble inhibitors such as salts or alcohols. These are partitioned among four possible phases (gas phase, liquid phase, ice phase and hydrate phase). Hydrate dissociation or formation, phase changes and the corresponding thermal effects are fully described, as are the effects of inhibitors. The model can describe all possible hydrate dissociation mechanisms, i.e., depressurization, thermal stimulation, salting-out effects and inhibitor-induced effects.

  12. HYDRATE v1.5 OPTION OF TOUGH+ v1.5

    2015-08-27

    HYDRATE v1.5 is a numerical code that for the simulation of the behavior of hydrate-bearing geologic systems, and represents the third update of the code since its first release [Moridis et al., 2008]. It is an option of TOUGH+ v1.5 [Moridis and Pruess, 2014], a successor to the TOUGH2 [Pruess et al., 1999, 2012] family of codes for multi-component, multiphase fluid and heat flow developed at the Lawrence Berkeley National Laboratory. HYDRATE v1.5 needs themore » TOUGH+ v1.5 core code in order to compile and execute. It is written in standard FORTRAN 95/2003, and can be run on any computational platform (workstation, PC, Macintosh) for which such compilers are available. By solving the coupled equations of mass and heat balance, the fully operational TOUGH+HYDRATE code can model the non-isothermal gas release, phase behavior and flow of fluids and heat under conditions typical of common natural CH4-hydrate deposits (i.e., in the permafrost and in deep ocean sediments) in complex geological media at any scale (from laboratory to reservoir) at which Darcy’s law is valid. TOUGH+HYDRATE v1.5 includes both an equilibrium and a kinetic model of hydrate formation and dissociation. The model accounts for heat and up to four mass components, i.e., water, CH4, hydrate, and water-soluble inhibitors such as salts or alcohols. These are partitioned among four possible phases (gas phase, liquid phase, ice phase and hydrate phase). Hydrate dissociation or formation, phase changes and the corresponding thermal effects are fully described, as are the effects of inhibitors. The model can describe all possible hydrate dissociation mechanisms, i.e., depressurization, thermal stimulation, salting-out effects and inhibitor-induced effects.« less

  13. RealGasBrine v1.0 option of TOUGH+ v1.5

    2015-02-27

    RealGasBrine v1.0 is a numerical code that for the simulation of the behavior of gas-bearing porous and/fractured geologic media. It is an option of TOUGH+ v1.5 [Moridis, 2014], a successor to the TOUGH2 [Pruess et al., 1999; 2012] family of codes for multi-component, multiphase ?uid and heat ?ow developed at the Lawrence Berkeley National Laboratory. RealGasBrine v1.0 needs the TOUGH+ v1.5 core code in order to compile and execute. It is written in standard FORTRANmore » 95/2003, and can be run on any computational platform (workstation, PC, Macintosh) for which such compilers are available. RealGasBrine v1.0 describes the non-isothermal two- (for pure water) or three-phase (for brine) flow of an aqueous phase and a real gas mixture in a gas-bearing medium, with a particular focus in ultra-tight (such as tight-sand and shale gas) systems. Up to 12 individual real gases can be tracked, and salt can precipitate as solid halite. The capabilities of the code include coupled flow and thermal effects, real gas behavior, Darcy and non-Darcy flow, several isotherm options of gas sorption onto the grains of the porous media, complex fracture descriptions, gas solubility into water, and geomechanical effects on flow properties. RealGasBrine v1.0 allows the study of flow and transport of fluids and heat over a wide range of time frames and spatial scales not only in gas reservoirs, but also in any problem involving the flow of gases in geologic media, including the geologic storage of greenhouse gas mixtures, the behavior of geothermal reservoirs with multi-component condensable (H2O and CO2) and non-condensable gas mixtures, the transport of water and released H2 in nuclear waste storage applications, etc.« less

  14. Backward-going MeV electrons and gamma rays from 1018 W/cm2 laser interactions with water

    NASA Astrophysics Data System (ADS)

    Feister, Scott; Morrison, John T.; Frische, Kyle D.; Orban, Chris; Ovchinnikov, Vladimir M.; Nees, John A.; Austin, Drake R.; Chowdhury, Enam A.; Freeman, Richard R.; Roquemore, W. Melvyn

    2015-05-01

    Gamma rays with ~1 MeV energy are measured following the relativistic interaction of a 3 mJ, 1018 W/cm2 short pulse laser with a 30 μm diameter flowing water column. Contrary to expectations, radiation emission is peaked in the direction opposite to the normally-incident laser propagation (specular direction). Experimental measurements and particle-in-cell (PIC) simulations of laser-plasma interaction show a pre-formed-plasma-dependent, backward-going, beam-like primary electron source. The MeV component of the electron and gamma ray spectrum, which is more than five times the ponderomotive energy scale of the laser, is highly sensitive to the presence of a nanosecond-timescale laser pre-pulse. This research was sponsored by the Quantum and Non-Equilibrium Processes Division of the Air Force Office of Scientific Research, under the management of Dr. Enrique Parra, Program Manager.

  15. Spin-Hall-Effect-Assisted Electroresistance in Antiferromagnets via 105 A/cm2 dc Current

    NASA Astrophysics Data System (ADS)

    Han, Jiahao; Wang, Yuyan; Pan, Feng; Song, Cheng

    2016-08-01

    Antiferromagnet (AFM) spintronics with reduced electrical current is greatly expected to process information with high integration and low power consumption. In Pt/FeMn and Ta/FeMn hybrids, we observe significant resistance variation (up to 7% of the total resistance) manipulated by 105 A/cm2 dc current. We have excluded the contribution of isotropic structural effects, and confirmed the critical role of the spin Hall injection from Pt (or Ta) to FeMn. This electrical current-manipulated resistance (i.e. electroresistance) is proposed to be attributed to the spin-Hall-effect-induced spin-orbit torque in FeMn. Similar results have also been detected in plain IrMn films, where the charge current generates spin current via the spin Hall effect with the existence of Ir atoms. All the measurements are free from external magnetic fields and ferromagnets. Our findings present an interesting step towards high-efficiency spintronic devices.

  16. Xenoliths in the CM2 Carbonaceous Chondrite LON 94101: Implications for Complex Mixing on the Asteroidal Parent Body

    NASA Technical Reports Server (NTRS)

    Lindgren, P.; Lee, M. R.; Sofe, M.; Zolensky, M. E.

    2011-01-01

    Xenoliths are foreign clasts that oc-cur in various classes of meteorites, e.g. [1,2,3]. A re-cent study reveals the presence of several distinct classes of xenoliths in regolith-bearing meteorites, in-cluding in over 20 different carbonaceous chondrites [4]. The most common types of xenoliths are fine-grained hydrous clasts, often referred to as C1 or CI clasts in the literature, although their mineralogy is actually more similar to hydrous micrometeorites [5,6]. Xenoliths in meteorites present an opportunity to study material not yet classified or available as separate meteorites, and can provide additional information on processes in the dynamic early history of the Solar Sys-tem. Here we have performed chemical and mineralogi-cal analyses of xenoliths in the CM2 carbonaceous chondrite LON 94101, using scanning electron micro-scopy (SEM) and transmission electron microscopy (TEM).

  17. High e+/e- Ratio Dense Pair Creation with 1021W.cm-2 Laser Irradiating Solid Targets

    NASA Astrophysics Data System (ADS)

    Liang, E.; Clarke, T.; Henderson, A.; Fu, W.; Lo, W.; Taylor, D.; Chaguine, P.; Zhou, S.; Hua, Y.; Cen, X.; Wang, X.; Kao, J.; Hasson, H.; Dyer, G.; Serratto, K.; Riley, N.; Donovan, M.; Ditmire, T.

    2015-09-01

    We report results of new pair creation experiments using ~100 Joule pulses of the Texas Petawatt Laser to irradiate solid gold and platinum targets, with intensities up to ~1.9 × 1021 W.cm-2 and pulse durations as short as ~130 fs. Positron to electron (e+/e-) ratios >15% were observed for many thick disk and rod targets, with the highest e+/e- ratio reaching ~50% for a Pt rod. The inferred pair yield was ~ few ×1010 with emerging pair density reaching ~1015/cm3 so that the pair skin depth becomes < pair jet transverse size. These results represent major milestones towards the goal of creating a significant quantity of dense pair-dominated plasmas with e+/e- approaching 100% and pair skin depth ≪ pair plasma size, which will have wide-ranging applications to astrophysics and fundamental physics.

  18. Analysis of the biases in the downward shortwave surface flux in the GFDL CM2.1 general circulation model

    NASA Astrophysics Data System (ADS)

    Freidenreich, Stuart M.; Ramaswamy, V.

    2011-04-01

    Simulations of downward shortwave surface fluxes by the coupled Geophysical Fluid Dynamics Laboratory (GFDL) CM2.1 general circulation model are compared against climatology derived from the Baseline Surface Radiation Network (BSRN), Global Energy Balance Archive, and International Satellite Cloud Climatology Project ISCCP-FD data sets. The spatial pattern of the model's biases is evaluated. An investigation is made of how these relate to accompanying biases in total cloud amount and aerosol optical depth and how they affect the surface temperature simulation. Comparing CM2.1's clear-sky fluxes against BSRN site values, for European, Asian, and North American locations, there are underestimates in the direct and overestimates in the diffuse, resulting in underestimates in the total flux. These are related to overestimates of sulfate aerosol optical depth, arising owing to the behavior of the parameterization function for hygroscopic growth of these aerosols at very high relative humidity. Contrastingly, flux overestimate biases at lower latitude locations are associated with underestimates in sea-salt and carbonaceous aerosol amounts. All-sky flux biases consist of underestimates for North America, Eurasia, southern Africa, and northern oceanic regions and overestimates for the Amazon region, equatorial Africa, off the west coast of the Americas, and southern oceanic regions. These biases show strong correlations with cloud amount biases. There are modest correlations of the flux biases with cool surface temperature biases over North America and Eurasia, warm biases over the Amazon region, and cool (warm) biases over the northern (southern) oceanic regions. Analyses assuming nonhygroscopicity illustrate that there is a reduction of surface temperature biases accompanying a reduction of sulfate aerosol optical depth biases, whereas a more significant improvement in the temperature simulation requires refining the model's simulation of cloudiness.

  19. Targeting voltage gated sodium channels NaV1.7, Na V1.8, and Na V1.9 for treatment of pathological cough.

    PubMed

    Muroi, Yukiko; Undem, Bradley J

    2014-02-01

    Recent advances in our understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that drugs capable of selective blockade of NaV subtypes may be a safe and effective strategy for the treatment of unwanted cough. Among the nine NaV subtypes (NaV1.1-NaV1.9), the afferent nerves involved in initiating cough, in common with nociceptive neurons in the somatosensory system, express mainly NaV1.7, NaV1.8, and NaV1.9. Although knowledge about the effect of selectively blocking these channels on the cough reflex is limited, their biophysical properties indicate that each may contribute to the hypertussive and allotussive state that typifies subacute and chronic nonproductive cough.

  20. Gas-Phase Oxidation of Cm+ and Cm2+ -- Thermodynamics of neutral and ionized CmO

    SciTech Connect

    Gibson, John K; Haire, Richard G.; Santos, Marta; Pires de Matos, Antonio; Marcalo, Joaquim

    2008-12-08

    Fourier transform ion cyclotron resonance mass spectrometry was employed to study the products and kinetics of gas-phase reactions of Cm+ and Cm2+; parallel studies were carried out with La+/2+, Gd+/2+ and Lu+/2+. Reactions with oxygen-donor molecules provided estimates for the bond dissociation energies, D[M+-O](M = Cm, Gd, Lu). The first ionization energy, IE[CmO], was obtained from the reactivity of CmO+ with dienes, and the second ionization energies, IE[MO+](M = Cm, La, Gd, Lu), from the rates of electron-transfer reactions from neutrals to the MO2+ ions. The following thermodynamic quantities for curium oxide molecules were obtained: IE[CmO]= 6.4+-0.2 eV; IE[CmO+]= 15.8+-0.4 eV; D[Cm-O]= 710+-45 kJ mol-1; D[Cm+-O]= 670+-40 kJ mol-1; and D[Cm2+-O]= 342+-55 kJ mol-1. Estimates for the M2+-O bond energies for M = Cm, La, Gd and Lu are all intermediate between D[N2-O]and D[OC-O]--i.e., 167 kJ mol-1< D[M2+-O]< 532 kJ mol-1 -- such that the four MO2+ ions fulfill the thermodynamic requirement for catalytic O-atom transport from N2O to CO. It was demonstrated that the kinetics are also favorable and that the CmO2+, LaO2+, GdO2+ and LuO2+ dipositive ions each catalyze the gas-phase oxidation of CO to CO2 by N2O. The CmO2+ ion appeared during the reaction of Cm+ with O2 when the intermediate, CmO+, was not collisionally cooled -- although its formation is kinetically and/or thermodynamically unfavorable, CmO2+ is a stable species.

  1. Spin-Hall-Effect-Assisted Electroresistance in Antiferromagnets via 10(5) A/cm(2) dc Current.

    PubMed

    Han, Jiahao; Wang, Yuyan; Pan, Feng; Song, Cheng

    2016-01-01

    Antiferromagnet (AFM) spintronics with reduced electrical current is greatly expected to process information with high integration and low power consumption. In Pt/FeMn and Ta/FeMn hybrids, we observe significant resistance variation (up to 7% of the total resistance) manipulated by 10(5) A/cm(2) dc current. We have excluded the contribution of isotropic structural effects, and confirmed the critical role of the spin Hall injection from Pt (or Ta) to FeMn. This electrical current-manipulated resistance (i.e. electroresistance) is proposed to be attributed to the spin-Hall-effect-induced spin-orbit torque in FeMn. Similar results have also been detected in plain IrMn films, where the charge current generates spin current via the spin Hall effect with the existence of Ir atoms. All the measurements are free from external magnetic fields and ferromagnets. Our findings present an interesting step towards high-efficiency spintronic devices. PMID:27546199

  2. Clasts in the CM2 carbonaceous chondrite Lonewolf Nunataks 94101: Evidence for aqueous alteration prior to complex mixing

    NASA Astrophysics Data System (ADS)

    Lindgren, Paula; Lee, Martin R.; Sofe, Mahmood R.; Zolensky, Michael E.

    2013-06-01

    Clasts in the CM2 carbonaceous chondrite Lonewolf Nunataks (LON) 94101 have been characterized using scanning and transmission electron microscopy and electron microprobe analysis to determine their degrees of aqueous alteration, and the timing of alteration relative to incorporation of clasts into the host. The provenance of the clasts, and the mechanism by which they were incorporated and mixed with their host material are also considered. Results show that at least five distinct types of clasts occur in LON 94101, of which four have been aqueously altered to various degrees and one is largely anhydrous. The fact that they have had different alteration histories implies that the main part of aqueous activity occurred prior to the mixing and assimilation of the clasts with their host. Further, the presence of such a variety of clasts suggests complex mixing in a dynamic environment involving material from various sources. Two of the clasts, one containing approximately 46 vol% carbonate and the other featuring crystals of pyrrhotite up to approximately 1 mm in size, are examples of unusual lithologies and indicate concentration of chemical elements in discrete areas of the parent body(ies), possibly by flow of aqueous solutions.

  3. Spin-Hall-Effect-Assisted Electroresistance in Antiferromagnets via 105 A/cm2 dc Current

    PubMed Central

    Han, Jiahao; Wang, Yuyan; Pan, Feng; Song, Cheng

    2016-01-01

    Antiferromagnet (AFM) spintronics with reduced electrical current is greatly expected to process information with high integration and low power consumption. In Pt/FeMn and Ta/FeMn hybrids, we observe significant resistance variation (up to 7% of the total resistance) manipulated by 105 A/cm2 dc current. We have excluded the contribution of isotropic structural effects, and confirmed the critical role of the spin Hall injection from Pt (or Ta) to FeMn. This electrical current-manipulated resistance (i.e. electroresistance) is proposed to be attributed to the spin-Hall-effect-induced spin-orbit torque in FeMn. Similar results have also been detected in plain IrMn films, where the charge current generates spin current via the spin Hall effect with the existence of Ir atoms. All the measurements are free from external magnetic fields and ferromagnets. Our findings present an interesting step towards high-efficiency spintronic devices. PMID:27546199

  4. Extreme variability among mammalian V1R gene families

    PubMed Central

    Young, Janet M.; Massa, Hillary F.; Hsu, Li; Trask, Barbara J.

    2010-01-01

    We report an evolutionary analysis of the V1R gene family across 37 mammalian genomes. V1Rs comprise one of three chemosensory receptor families expressed in the vomeronasal organ, and contribute to pheromone detection. We first demonstrate that Trace Archive data can be used effectively to determine V1R family sizes and to obtain sequences of most V1R family members. Analyses of V1R sequences from trace data and genome assemblies show that species-specific expansions previously observed in only eight species were prevalent throughout mammalian evolution, resulting in “semi-private” V1R repertoires for most mammals. The largest families are found in mouse and platypus, whose V1R repertoires have been published previously, followed by mouse lemur and rabbit (∼215 and ∼160 intact V1Rs, respectively). In contrast, two bat species and dolphin possess no functional V1Rs, only pseudogenes, and suffered inactivating mutations in the vomeronasal signal transduction gene Trpc2. We show that primate V1R decline happened prior to acquisition of trichromatic vision, earlier during evolution than was previously thought. We also show that it is extremely unlikely that decline of the dog V1R repertoire occurred in response to selective pressures imposed by humans during domestication. Functional repertoire sizes in each species correlate roughly with anatomical observations of vomeronasal organ size and quality; however, no single ecological correlate explains the very diverse fates of this gene family in different mammalian genomes. V1Rs provide one of the most extreme examples observed to date of massive gene duplication in some genomes, with loss of all functional genes in other species. PMID:19952141

  5. Extreme variability among mammalian V1R gene families.

    PubMed

    Young, Janet M; Massa, Hillary F; Hsu, Li; Trask, Barbara J

    2010-01-01

    We report an evolutionary analysis of the V1R gene family across 37 mammalian genomes. V1Rs comprise one of three chemosensory receptor families expressed in the vomeronasal organ, and contribute to pheromone detection. We first demonstrate that Trace Archive data can be used effectively to determine V1R family sizes and to obtain sequences of most V1R family members. Analyses of V1R sequences from trace data and genome assemblies show that species-specific expansions previously observed in only eight species were prevalent throughout mammalian evolution, resulting in "semi-private" V1R repertoires for most mammals. The largest families are found in mouse and platypus, whose V1R repertoires have been published previously, followed by mouse lemur and rabbit (approximately 215 and approximately 160 intact V1Rs, respectively). In contrast, two bat species and dolphin possess no functional V1Rs, only pseudogenes, and suffered inactivating mutations in the vomeronasal signal transduction gene Trpc2. We show that primate V1R decline happened prior to acquisition of trichromatic vision, earlier during evolution than was previously thought. We also show that it is extremely unlikely that decline of the dog V1R repertoire occurred in response to selective pressures imposed by humans during domestication. Functional repertoire sizes in each species correlate roughly with anatomical observations of vomeronasal organ size and quality; however, no single ecological correlate explains the very diverse fates of this gene family in different mammalian genomes. V1Rs provide one of the most extreme examples observed to date of massive gene duplication in some genomes, with loss of all functional genes in other species. PMID:19952141

  6. Network interactions: non-geniculate input to V1.

    PubMed

    Muckli, Lars; Petro, Lucy S

    2013-04-01

    The strongest connections to V1 are fed back from neighbouring area V2 and from a network of higher cortical areas (e.g. V3, V5, LOC, IPS and A1), transmitting the results of cognitive operations such as prediction, attention and imagination. V1 is therefore at the receiving end of a complex cortical processing cascade and not only at the entrance stage of cortical processing of retinal input. One elegant strategy to investigate this information-rich feedback to V1 is to eliminate feedforward input, that is, exploit V1's retinotopic organisation to isolate subregions receiving no direct bottom-up stimulation. We highlight the diverse mechanisms of cortical feedback, ranging from gain control to predictive coding, and conclude that V1 is involved in rich internal communication processes. PMID:23402951

  7. CO/H2 Abundance Ratio ≈ 10-4 in a Protoplanetary Disk

    NASA Astrophysics Data System (ADS)

    France, Kevin; Herczeg, Gregory J.; McJunkin, Matthew; Penton, Steven V.

    2014-10-01

    The relative abundances of atomic and molecular species in planet-forming disks around young stars provide important constraints on photochemical disk models and provide a baseline for calculating disk masses from measurements of trace species. A knowledge of absolute abundances, those relative to molecular hydrogen (H2), are challenging because of the weak rovibrational transition ladder of H2 and the inability to spatially resolve different emission components within the circumstellar environment. To address both of these issues, we present new contemporaneous measurements of CO and H2 absorption through the "warm molecular layer" of the protoplanetary disk around the Classical T Tauri Star RW Aurigae A. We use a newly commissioned observing mode of the Hubble Space Telescope Cosmic Origins Spectrograph to detect warm H2 absorption in this region for the first time. An analysis of the emission and absorption spectrum of RW Aur shows components from the accretion region near the stellar photosphere, the molecular disk, and several outflow components. The warm H2 and CO absorption lines are consistent with a disk origin. We model the 1092-1117 Å spectrum of RW Aur to derive log10 N(H2) = 19.90+0.33-0.22 cm-2 at T rot(H2) = 440 ± 39 K. The CO A - X bands observed from 1410 to 1520 Å are best fit by log10 N(CO) = 16.1 +0.3-0.5 cm-2 at T rot(CO) = 200+650-125 K. Combining direct measurements of the H I, H2, and CO column densities, we find a molecular fraction in the warm disk surface of f H2 >= 0.47 and derive a molecular abundance ratio of CO/H2 = 1.6+4.7-1.3 × 10-4, both consistent with canonical interstellar dense cloud values. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute. STScI is operated by the Association of Universities for Research in Astronomy, Inc. under NASA contract NAS 5-26555.

  8. Comet P/2010 V1 as a Natural Disintegration Laboratory

    NASA Astrophysics Data System (ADS)

    Jewitt, David; Weaver, Harold A.; Mutchler, Maximilian J.; Agarwal, Jessica; Meech, Karen Jean; Li, Jing; Kleyna, Jan; Ishiguro, Masateru; Wainscoat, Richard J.; Hui, Man-To

    2016-10-01

    Discovered in outburst in 2010, Jupiter-family comet P/2010 V1 (Ikeya-Murukami) was found to be split in observations at the end of 2015. We used the Hubble Space Telescope to obtain deep images of P/2010 V1 at high angular resolution in the 2016 January to March period. The resulting data, by far the best yet obtained for any split or disrupting comet, show the astrometric, photometric and morphological evolution of about 30 fragments. We will present the first results for the velocity dispersion, photometric distribution and variability and discuss the measurements in terms of models for the breakup.

  9. Efficient Receptive Field Tiling in Primate V1.

    PubMed

    Nauhaus, Ian; Nielsen, Kristina J; Callaway, Edward M

    2016-08-17

    The primary visual cortex (V1) encodes a diverse set of visual features, including orientation, ocular dominance (OD), and spatial frequency (SF), whose joint organization must be precisely structured to optimize coverage within the retinotopic map. Prior experiments have only identified efficient coverage based on orthogonal maps. Here we used two-photon calcium imaging to reveal an alternative arrangement for OD and SF maps in macaque V1; their gradients run parallel but with unique spatial periods, whereby low-SF regions coincide with monocular regions. Next we mapped receptive fields and found surprisingly precise micro-retinotopy that yields a smaller point-image and requires more efficient inter-map geometry, thus underscoring the significance of map relationships. While smooth retinotopy is constraining, studies suggest that it improves both wiring economy and the V1 population code read downstream. Altogether, these data indicate that connectivity within V1 is finely tuned and precise at the level of individual neurons. PMID:27499086

  10. Is H2O present on Io? The detection of a new strong band near 3590/cm (2.79 microns)

    NASA Astrophysics Data System (ADS)

    Salama, F.; Allamandola, L. J.; Sandford, S. A.; Bregman, J. D.; Witteborn, F. C.; Cruikshank, D. P.

    1994-02-01

    A strong absorption band at 3590 +/- 20/cm (2.790 +/- 0.015 microns) has been discovered in the spectrum of Io using the Kuiper Airborne Observatory (KAO). The 2nu1 + nu3 combination mode of solid SO2 falls at this position. Since SO2 is abundant on Io it must contribute to the new band. However, a band due to H2O was predicted near this frequency in Io's spectrum based on laboratory experiments of H2O:SO2 mixed Io ice analogs which were used to assign the two weak, variable features at 3370 and 3170/cm (2.97 and 3.15 microns) to trace amounts of H2O frozen in solid SO2 on Io. The new band probably originates from both SO2 and H2O. Unfortunately, the spectral resolution of the data is insufficient to settle the issue of whether there are two resolvable components.

  11. Schottky barrier diodes of corundum-structured gallium oxide showing on-resistance of 0.1 mΩ·cm2 grown by MIST EPITAXY®

    NASA Astrophysics Data System (ADS)

    Oda, Masaya; Tokuda, Rie; Kambara, Hitoshi; Tanikawa, Tomochika; Sasaki, Takahiro; Hitora, Toshimi

    2016-02-01

    Thin-film corundum-structured gallium oxide (α-Ga2O3) Schottky barrier diodes (SBDs) were fabricated by growing α-Ga2O3 layers on sapphire substrates by the safe, low-cost, and energy-saving MIST EPITAXY® technique, followed by lifting off the α-Ga2O3 layers from the substrates. The SBDs exhibited on-resistance and breakdown voltage of 0.1 mΩ·cm2 and 531 V (SBD1) or 0.4 mΩ·cm2 and 855 V (SBD2), respectively. These results will encourage the future evolution of low-cost and high-performance SBDs with α-Ga2O3.

  12. 26 CFR 36.3121(l)(10)-4 - Payment of amounts equivalent to tax.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Payment of amounts equivalent to tax. 36.3121(l)(10)-4 Section 36.3121(l)(10)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... SUBSIDIARIES § 36.3121(l)(10)-4 Payment of amounts equivalent to tax. A domestic corporation which has...

  13. 26 CFR 36.3121(l)(10)-4 - Payment of amounts equivalent to tax.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 15 2012-04-01 2012-04-01 false Payment of amounts equivalent to tax. 36.3121(l)(10)-4 Section 36.3121(l)(10)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... SUBSIDIARIES § 36.3121(l)(10)-4 Payment of amounts equivalent to tax. A domestic corporation which has...

  14. Exploring V1 by modeling the perceptual quality of images.

    PubMed

    Zhang, Fan; Jiang, Wenfei; Autrusseau, Florent; Lin, Weisi

    2014-01-24

    We propose an image quality model based on phase and amplitude differences between a reference and a distorted image. The proposed model is motivated by the fact that polar representations can separate visual information in a more independent and efficient manner than Cartesian representations in the primary visual cortex (V1). We subsequently estimate the model parameters from a large subjective data set using maximum likelihood methods. By comparing the various model hypotheses on the functional form about the phase and amplitude, we find that: (a) discrimination of visual orientation is important for quality assessment and yet a coarse level of such discrimination seems sufficient; and (b) a product-based amplitude-phase combination before pooling is effective, suggesting an interesting viewpoint about the functional structure of the simple cells and complex cells in V1.

  15. Ongoing Slow Fluctuations in V1 Impact on Visual Perception.

    PubMed

    Wohlschläger, Afra M; Glim, Sarah; Shao, Junming; Draheim, Johanna; Köhler, Lina; Lourenço, Susana; Riedl, Valentin; Sorg, Christian

    2016-01-01

    The human brain's ongoing activity is characterized by intrinsic networks of coherent fluctuations, measured for example with correlated functional magnetic resonance imaging signals. So far, however, the brain processes underlying this ongoing blood oxygenation level dependent (BOLD) signal orchestration and their direct relevance for human behavior are not sufficiently understood. In this study, we address the question of whether and how ongoing BOLD activity within intrinsic occipital networks impacts on conscious visual perception. To this end, backwardly masked targets were presented in participants' left visual field only, leaving the ipsi-lateral occipital areas entirely free from direct effects of task throughout the experiment. Signal time courses of ipsi-lateral BOLD fluctuations in visual areas V1 and V2 were then used as proxies for the ongoing contra-lateral BOLD activity within the bilateral networks. Magnitude and phase of these fluctuations were compared in trials with and without conscious visual perception, operationalized by means of subjective confidence ratings. Our results show that ipsi-lateral BOLD magnitudes in V1 were significantly higher at times of peak response when the target was perceived consciously. A significant difference between conscious and non-conscious perception with regard to the pre-target phase of an intrinsic-frequency regime suggests that ongoing V1 fluctuations exert a decisive impact on the access to consciousness already before stimulation. Both effects were absent in V2. These results thus support the notion that ongoing slow BOLD activity within intrinsic networks covering V1 represents localized processes that modulate the degree of readiness for the emergence of visual consciousness. PMID:27601986

  16. Ongoing Slow Fluctuations in V1 Impact on Visual Perception

    PubMed Central

    Wohlschläger, Afra M.; Glim, Sarah; Shao, Junming; Draheim, Johanna; Köhler, Lina; Lourenço, Susana; Riedl, Valentin; Sorg, Christian

    2016-01-01

    The human brain’s ongoing activity is characterized by intrinsic networks of coherent fluctuations, measured for example with correlated functional magnetic resonance imaging signals. So far, however, the brain processes underlying this ongoing blood oxygenation level dependent (BOLD) signal orchestration and their direct relevance for human behavior are not sufficiently understood. In this study, we address the question of whether and how ongoing BOLD activity within intrinsic occipital networks impacts on conscious visual perception. To this end, backwardly masked targets were presented in participants’ left visual field only, leaving the ipsi-lateral occipital areas entirely free from direct effects of task throughout the experiment. Signal time courses of ipsi-lateral BOLD fluctuations in visual areas V1 and V2 were then used as proxies for the ongoing contra-lateral BOLD activity within the bilateral networks. Magnitude and phase of these fluctuations were compared in trials with and without conscious visual perception, operationalized by means of subjective confidence ratings. Our results show that ipsi-lateral BOLD magnitudes in V1 were significantly higher at times of peak response when the target was perceived consciously. A significant difference between conscious and non-conscious perception with regard to the pre-target phase of an intrinsic-frequency regime suggests that ongoing V1 fluctuations exert a decisive impact on the access to consciousness already before stimulation. Both effects were absent in V2. These results thus support the notion that ongoing slow BOLD activity within intrinsic networks covering V1 represents localized processes that modulate the degree of readiness for the emergence of visual consciousness.

  17. Ongoing Slow Fluctuations in V1 Impact on Visual Perception

    PubMed Central

    Wohlschläger, Afra M.; Glim, Sarah; Shao, Junming; Draheim, Johanna; Köhler, Lina; Lourenço, Susana; Riedl, Valentin; Sorg, Christian

    2016-01-01

    The human brain’s ongoing activity is characterized by intrinsic networks of coherent fluctuations, measured for example with correlated functional magnetic resonance imaging signals. So far, however, the brain processes underlying this ongoing blood oxygenation level dependent (BOLD) signal orchestration and their direct relevance for human behavior are not sufficiently understood. In this study, we address the question of whether and how ongoing BOLD activity within intrinsic occipital networks impacts on conscious visual perception. To this end, backwardly masked targets were presented in participants’ left visual field only, leaving the ipsi-lateral occipital areas entirely free from direct effects of task throughout the experiment. Signal time courses of ipsi-lateral BOLD fluctuations in visual areas V1 and V2 were then used as proxies for the ongoing contra-lateral BOLD activity within the bilateral networks. Magnitude and phase of these fluctuations were compared in trials with and without conscious visual perception, operationalized by means of subjective confidence ratings. Our results show that ipsi-lateral BOLD magnitudes in V1 were significantly higher at times of peak response when the target was perceived consciously. A significant difference between conscious and non-conscious perception with regard to the pre-target phase of an intrinsic-frequency regime suggests that ongoing V1 fluctuations exert a decisive impact on the access to consciousness already before stimulation. Both effects were absent in V2. These results thus support the notion that ongoing slow BOLD activity within intrinsic networks covering V1 represents localized processes that modulate the degree of readiness for the emergence of visual consciousness. PMID:27601986

  18. An uncertainty principle underlying the functional architecture of V1.

    PubMed

    Barbieri, Davide; Citti, Giovanna; Sanguinetti, Gonzalo; Sarti, Alessandro

    2012-01-01

    We present a model of the morphology of orientation maps in V1 based on the uncertainty principle of the SE(2) group. Starting from the symmetries of the cortex, suitable harmonic analysis instruments are used to obtain coherent states in the Fourier domain as minimizers of the uncertainty. Cortical activities related to orientation maps are then obtained by projection on a suitable cortical Fourier basis.

  19. A study on surface slant encoding in V1

    PubMed Central

    Siddiqui, Mohammed Sultan Mohiuddin; Bhaumik, Basabi

    2013-01-01

    Inter-ocular differences in spatial frequency occur during binocular viewing of a surface slanted in depth. Cortical cells with inter-ocular differences in preferred spatial frequency (dif-frequency cells) are expected to detect surfaces slanted in depth or vertical surface slant. Using our reaction-diffusion model, we obtain receptive fields and responses of simple cells in layer IV in cat V1. The dif-frequency cells in the model cortex have tilt in binocular receptive field but we show that tilt by itself does not indicate slant selectivity. We studied cell responses to binocular combination of spatial frequencies (SFs) by varying the SF ratio of the input gratings to the left and right eye in the range of 0.35–3. This range of SF ratio corresponds to surface slant variation of −85° to 85°. The mean binocular tuning hwhh (half width at half height) is 41°. Except for a small number (2.5%) of cells, most dif-frequency cells respond almost equally well for fronto-parallel surfaces. In the literature cells with inter-ocular difference in preferred orientation (IDPO) were expected to encode horizontal surface slant. In the model cat V1 mean hwhh in binocular orientation tuning curve for cells with IDPO is 39°. The wide binocular tuning width in dif-frequency cells and cells with IDPO imply that in cat V1 neither dif-frequency cells nor cells with IDPO detect surface slant. PMID:24298241

  20. A Neurodynamical Model of Brightness Induction in V1

    PubMed Central

    Penacchio, Olivier; Otazu, Xavier; Dempere-Marco, Laura

    2013-01-01

    Brightness induction is the modulation of the perceived intensity of an area by the luminance of surrounding areas. Recent neurophysiological evidence suggests that brightness information might be explicitly represented in V1, in contrast to the more common assumption that the striate cortex is an area mostly responsive to sensory information. Here we investigate possible neural mechanisms that offer a plausible explanation for such phenomenon. To this end, a neurodynamical model which is based on neurophysiological evidence and focuses on the part of V1 responsible for contextual influences is presented. The proposed computational model successfully accounts for well known psychophysical effects for static contexts and also for brightness induction in dynamic contexts defined by modulating the luminance of surrounding areas. This work suggests that intra-cortical interactions in V1 could, at least partially, explain brightness induction effects and reveals how a common general architecture may account for several different fundamental processes, such as visual saliency and brightness induction, which emerge early in the visual processing pathway. PMID:23717536

  1. Dynamics of cell and tissue growth acquired by means of 25 mm2 to 10 cm2 lens-free imaging

    NASA Astrophysics Data System (ADS)

    Momey, F.; Coutard, J.-G.; Bordy, T.; Navarro, F.; Menneteau, M.; Dinten, J.-M.; Allier, C.

    2015-03-01

    In this paper, we discuss a new methodology based on lens-free imaging to perform wound healing assay with unprecedented statistics. Our video lens-free microscopy setup is a simple optical system featuring only a CMOS sensor and a semi coherent illumination system. Yet it is a powerful means for the real-time monitoring of cultivated cells. It presents several key advantages, e.g., integration into standard incubator, compatibility with standard cell culture protocol, simplicity and ease of use. It can perform the follow-up in a large field of view (25 mm2) of several crucial parameters during the culture of cells i.e. their motility, their proliferation rate or their death. Consequently the setup can gather large statistics both in space and time. But in the case of tissue growth experiments, the field of view of 25 mm2 remains not sufficient and results can be biased depending on the position of the device with respect to the recipient of the cell culture. Hence, to conduct exhaustive wound healing assay, here we propose to enlarge the field of view up to 10 cm2 through two different approaches. The first method consists in performing a scan of the cell culture by moving the source/sensor couple and then stitch the stack of images. The second is to make an acquisition by scanning with a line scan camera. The two approaches are compared in term of resolution, complexity and acquisition time. Next we have performed acquisitions of wound healing assay (keratinocytes HaCaT) both in real-time (25 mm2) and in final point (10 cm2) to assess the combination of these two complementary modalities. In the future, we aim at combining directly super wide field of view acquisitions (>10 cm2) with real time ability inside the incubator.

  2. MgZnO/ZnO heterostructures with electron mobility exceeding 1 × 10(6) cm(2)/Vs.

    PubMed

    Falson, Joseph; Kozuka, Yusuke; Uchida, Masaki; Smet, Jurgen H; Arima, Taka-Hisa; Tsukazaki, Atsushi; Kawasaki, Masashi

    2016-01-01

    The inherently complex chemical and crystallographic nature of oxide materials has suppressed the purities achievable in laboratory environments, obscuring the rich physical degrees of freedom these systems host. In this manuscript we provide a systematic approach to defect identification and management in oxide molecular beam epitaxy grown MgZnO/ZnO heterostructures which host two-dimensional electron systems. We achieve samples displaying electron mobilities in excess of 1 × 10(6) cm(2)/Vs. This data set for the MgZnO/ZnO system firmly establishes that the crystalline quality has become comparable to traditional semiconductor materials. PMID:27229479

  3. MgZnO/ZnO heterostructures with electron mobility exceeding 1 × 106 cm2/Vs

    PubMed Central

    Falson, Joseph; Kozuka, Yusuke; Uchida, Masaki; Smet, Jurgen H.; Arima, Taka-hisa; Tsukazaki, Atsushi; Kawasaki, Masashi

    2016-01-01

    The inherently complex chemical and crystallographic nature of oxide materials has suppressed the purities achievable in laboratory environments, obscuring the rich physical degrees of freedom these systems host. In this manuscript we provide a systematic approach to defect identification and management in oxide molecular beam epitaxy grown MgZnO/ZnO heterostructures which host two-dimensional electron systems. We achieve samples displaying electron mobilities in excess of 1 × 106 cm2/Vs. This data set for the MgZnO/ZnO system firmly establishes that the crystalline quality has become comparable to traditional semiconductor materials. PMID:27229479

  4. MgZnO/ZnO heterostructures with electron mobility exceeding 1 × 106 cm2/Vs

    NASA Astrophysics Data System (ADS)

    Falson, Joseph; Kozuka, Yusuke; Uchida, Masaki; Smet, Jurgen H.; Arima, Taka-Hisa; Tsukazaki, Atsushi; Kawasaki, Masashi

    2016-05-01

    The inherently complex chemical and crystallographic nature of oxide materials has suppressed the purities achievable in laboratory environments, obscuring the rich physical degrees of freedom these systems host. In this manuscript we provide a systematic approach to defect identification and management in oxide molecular beam epitaxy grown MgZnO/ZnO heterostructures which host two-dimensional electron systems. We achieve samples displaying electron mobilities in excess of 1 × 106 cm2/Vs. This data set for the MgZnO/ZnO system firmly establishes that the crystalline quality has become comparable to traditional semiconductor materials.

  5. High-voltage thin-film GaN LEDs fabricated on ceramic substrates: the alleviated droop effect at 670 W/cm(2).

    PubMed

    Tsai, M L; Liao, J H; Yeh, J H; Hsu, T C; Hon, S J; Chung, T Y; Lai, K Y

    2013-11-01

    High-voltage thin-film GaN LEDs with the emission wavelength of 455 nm were fabricated on ceramic substrates (230 W/m · K). The high-voltage operation was achieved by three cascaded sub-LEDs with dielectric passivation and metal bridges conformally deposited on the side walls. Under the driving power of 670 W/cm(2), the high-voltage LEDs exhibit much alleviated efficiency droop and the operative temperature below 80 °C. The excellent performances were attributed to the improved current spreading within each sub-LED and the superior heat sinking of the ceramic substrate.

  6. Reflectance Spectra of CM2 Chondrite Mighei Irradiated with Pulsed Laser and Implications for Low-Albedo Asteroids and Martian Moons

    NASA Technical Reports Server (NTRS)

    Moroz, L. V.; Hiroi, T.; Shingareva, T. V.; Basilevsky, A. T.; Fisenko, A. V.; Semjonova, L. F.; Pieters, C. M.

    2004-01-01

    Micrometeoritic bombardment is an important space weathering process modifying surface optical properties of airless solar system bodies. We have used irradiation with a microsecond pulsed laser as an experimental method to simulate such a process on various targets. The experiment discussed here was performed on a powdered sample of CM2 carbonaceous chondrite Mighei. Shingareva et al. report the details of experimental procedure as well as the results of mineralogical and chemical studies of the irradiated material. Here we present reflectance spectra of irradiated Mighei samples and discuss their spectral properties compared to those of non-irradiated meteorite and low-albedo small solar system bodies.

  7. AMINO ACID ANALYSES OF THE ANTARCTIC CM2 METEORITES ALH 83100 AND LEW 90500 USING LIQUID CHROMATOGRAPHY-TIME OF FLIGHT-MASS SPECTROMETRY

    NASA Technical Reports Server (NTRS)

    Glavin, D. P.; Dworkin, J. P.; Aubrey, A.; Botta, O.; Doty, J. H., III; Bada, J. L.

    2001-01-01

    The investigation of organic compounds in primitive carbonaceous meteorites provides a record of the chemical processes that occurred in the early solar system. In particular, amino acids have been shown to be potential indicators in tracing the nature of carbonaceous chondrite parent bodies [ 13. The delivery of amino acids by carbonaceous chondrites to the early Earth could have been any important source of the Earth's prebiotic organic inventory [2]. Over 80 different amino acids have been detected in the Murchison CM2 meteorite, most of them completely non-existent in the terrestrial biosphere [3]. We have optimized a new liquid chromatography-time-of-flight-mass spectrometry (LC-ToF-MS) technique coupled with OPAMAC derivatization in order to detect amino acids in meteorite extracts by UV fluorescence and exact mass simultaneously. The detection limit of the LC-ToF-MS instrument for amino acids is at least 3 orders of magnitude lower than traditional GC-MS techniques. Here we report on the first analyses of amino acids and their enantiomeric abundances in the CM2 carbonaceous meteorites ALH 83100, LEW 90500, and Murchison using this new LC-ToF-MS instrument configuration. Amino acid analyses of any kind for the CM meteorite ALH 83100 have not previously been reported.

  8. Tailoring gadolinium-doped ceria-based solid oxide fuel cells to achieve 2 W cm(-2) at 550 °C.

    PubMed

    Lee, Jin Goo; Park, Jeong Ho; Shul, Yong Gun

    2014-06-04

    Low-temperature operation is necessary for next-generation solid oxide fuel cells due to the wide variety of their applications. However, significant increases in the fuel cell losses appear in the low-temperature solid oxide fuel cells, which reduce the cell performance. To overcome this problem, here we report Gd0.1Ce0.9O1.95-based low-temperature solid oxide fuel cells with nanocomposite anode functional layers, thin electrolytes and core/shell fibre-structured Ba0.5Sr0.5Co0.8Fe0.2O3-δ-Gd0.1Ce0.9O1.95 cathodes. In particular, the report describes the use of the advanced electrospinning and Pechini process in the preparation of the core/shell-fibre-structured cathodes. The fuel cells show a very high performance of 2 W cm(-2) at 550 °C in hydrogen, and are stable for 300 h even under the high current density of 1 A cm(-2). Hence, the results suggest that stable and high-performance solid oxide fuel cells at low temperatures can be achieved by modifying the microstructures of solid oxide fuel cell components.

  9. Current density and catalyst-coated membrane resistance distribution of hydro-formed metallic bipolar plate fuel cell short stack with 250 cm2 active area

    NASA Astrophysics Data System (ADS)

    Haase, S.; Moser, M.; Hirschfeld, J. A.; Jozwiak, K.

    2016-01-01

    An automotive fuel cell with an active area of 250 cm2 is investigated in a 4-cell short stack with a current and temperature distribution device next to the bipolar plate with 560 current and 140 temperature segments. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this current scan shunt module. The applied fuel cell consists of bipolar plates constructed of 75-μm-thick, welded stainless-steel foils and a graphitic coating. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this module with a 6% deviation in in-plane conductivity. The current density distribution is evaluated up to 2.4 A cm-2. The entire cell's investigated volumetric power density is 4.7 kW l-1, and its gravimetric power density is 4.3 kW kg-1 at an average cell voltage of 0.5 V. The current density distribution is determined without influencing the operating cell. In addition, the current density distribution in the catalyst-coated membrane and its effective resistivity distribution with a finite volume discretisation of Ohm's law are evaluated. The deviation between the current density distributions in the catalyst-coated membrane and the bipolar plate is determined.

  10. MEG studies of human vision: Retinotopic organization of V1

    SciTech Connect

    Aine, C.; George, J.; Ranken, D.; Best, E.; Tiee, W.; Vigil, V.; Flynn, E.; Wood, C.; Supek, S.

    1993-12-31

    A primary goal of noninvasive studies of human vision is to identify and characterize multiple visual areas in the human brain analogous to those identified in studies of nonhuman primates. By combining functional MEG measurements with images of individual anatomy derived from MRI, the authors hope to determine the location and arrangement of multiple visual areas in human cortex and to probe their functional significance. The authors have identified several different visual areas thus far which appear to be topographically organized. This paper focuses on the retinotopic characterization of the primary visual area (V1) in humans.

  11. Hydrogen File Capture v1.0.DLL

    2006-03-28

    Postprocessor for the use with GoldSim commercial software. The program is intended as a DLL for use with a GoldSim model simulation to copy input/output files created during the simulation to a central location on a local LAN. The software is used as part of a modeling package that consists of GoldSim.exe and other external codes linked and executed during a GoldSim model simulation. The FileCapture_v1.0.DLL is used to run Monte Carlo analyses with amore » GoldSim simulation that is executed using the distributed processing module. When distributed processing (i.e., multi-processor run) is used for a GoldSim Model simulation that is comprised of one or more codes linked with the GoldSim.exe, it is sometimes necessary to capture the default input and/or output files generated by the external codes linked with the GoldSim.exe program. Using the input file "FileCapture.In' to list the filenames and path, FileCapture_v1.0.DLL copies the files listed in 'FileCapture.in' from each node on the LAN to a folder called 'FCAP Files' created in the location gie as the path. The DLL will execute for each realization and append 00xxx a number indication which realization the file was generated from.« less

  12. Columnar organization of orientation domains in V1

    NASA Astrophysics Data System (ADS)

    Liedtke, Joscha; Wolf, Fred

    In the primary visual cortex (V1) of primates and carnivores, the functional architecture of basic stimulus selectivities appears similar across cortical layers (Hubel & Wiesel, 1962) justifying the use of two-dimensional cortical models and disregarding organization in the third dimension. Here we show theoretically that already small deviations from an exact columnar organization lead to non-trivial three-dimensional functional structures. We extend two-dimensional random field models (Schnabel et al., 2007) to a three-dimensional cortex by keeping a typical scale in each layer and introducing a correlation length in the third, columnar dimension. We examine in detail the three-dimensional functional architecture for different cortical geometries with different columnar correlation lengths. We find that (i) topological defect lines are generally curved and (ii) for large cortical curvatures closed loops and reconnecting topological defect lines appear. This theory extends the class of random field models by introducing a columnar dimension and provides a systematic statistical assessment of the three-dimensional functional architecture of V1 (see also (Tanaka et al., 2011)).

  13. AREST-CT V1.0 software verification

    SciTech Connect

    Chen, Y.; Engel, D.W.; McGrail, B.P.; Lessor, K.S.

    1995-07-01

    The Analyzer for Radionuclide Source-Term with Chemical Transport (AREST-CT) is a scientific computer code designed for performance assessments of engineered barrier system (EBS) concepts for the underground storage of nuclear waste, including high-level, intermediate, and low-level wastes. The AREST-CT code has features for analyzing the degradation of and release of radionuclides from the waste form, chemical reactions that depend on time and space, and transport of the waste and other products through the EBS. This document provides a description of the verification testing that has been performed on the initial version of ARESTCT (V1.0). Software verification is the process of confirming that the models and algorithms have been correctly implemented into a computer code. Software verification for V1.0 consisted of testing the individual modules (unit tests) and a test of the fully-coupled model (integration testing). The integration test was done by comparing the results from AREST-CT with the results from the reactive transport code CIRF.A. The test problem consisted of a 1-D analysis of the release, transport, and precipitation of {sup 99}{Tc} in an idealized LLW disposal system. All verification tests showed that AREST-CT works properly and in accordance with design specifications.

  14. Contextual Feedback to Superficial Layers of V1

    PubMed Central

    Muckli, Lars; De Martino, Federico; Vizioli, Luca; Petro, Lucy S.; Smith, Fraser W.; Ugurbil, Kamil; Goebel, Rainer; Yacoub, Essa

    2015-01-01

    Summary Neuronal cortical circuitry comprises feedforward, lateral, and feedback projections, each of which terminates in distinct cortical layers [1–3]. In sensory systems, feedforward processing transmits signals from the external world into the cortex, whereas feedback pathways signal the brain’s inference of the world [4–11]. However, the integration of feedforward, lateral, and feedback inputs within each cortical area impedes the investigation of feedback, and to date, no technique has isolated the feedback of visual scene information in distinct layers of healthy human cortex. We masked feedforward input to a region of V1 cortex and studied the remaining internal processing. Using high-resolution functional brain imaging (0.8 mm3) and multivoxel pattern information techniques, we demonstrate that during normal visual stimulation scene information peaks in mid-layers. Conversely, we found that contextual feedback information peaks in outer, superficial layers. Further, we found that shifting the position of the visual scene surrounding the mask parametrically modulates feedback in superficial layers of V1. Our results reveal the layered cortical organization of external versus internal visual processing streams during perception in healthy human subjects. We provide empirical support for theoretical feedback models such as predictive coding [10, 12] and coherent infomax [13] and reveal the potential of high-resolution fMRI to access internal processing in sub-millimeter human cortex. PMID:26441356

  15. Speculations on a relativistic strong focusing self-collider with very high luminosity (≥10 40 cm -2s -1): Macroproduction of antinuclei and other micro cross section events and formation of ambiplasma

    NASA Astrophysics Data System (ADS)

    Maglich, Bogdan C.

    1988-08-01

    The luminosity of the weak focusing self-collider (ESCOL) is intrinsically 10 8-10 10 times greater than that of conventional colliding beams, due to the product of the solid angle factor, ˜10 6, and the neutralization factor, ˜10 2 -10 4. We extrapolate to 10-GeV protons the parameters of a recent low energy experiment demonstrating that a 1-MeV deuteron beam, stored in ESCOL as migma, can be neutralized bo oscillating electrons and operate an order of magnitude above the space charge limit without instabilities. With the number density achieved in ESCOL, n = 3.2 × 10 9 ions cm -3, such a relativistic strong focusing self-collider (XYDER) would have a luminosity L ˜ 10 38 cm -2 s -1 for 10-GeV-on-10-GeV protons (equivalent to 250 GeV beam-on-target). At the diamagnetic "limit" density, which for 10 tesla is n = 10 12 ions cm -3, l ˜ 10 43 cm -2 s -1; this would produce 4 × 10 16 antiprotons/s (2 gram of overlinep/year). Other particles, rare nuclei, and rare effects produced with micro- (10 -16), nano- (10 -9 b), and picoscopic (10 -12 b) cross sections will be macro-produced in XYDER. A newly proposed annular magnet would provide a large volume of stored, V = 10 9 cm 3, as well as automatic ejection along the +z and -z axes of the overlinep's and other particles whose momentum is lower than that of the primary proton migma. Antiprotons, being produced with low rapidity, will have energies below 1 GeV in COM, and thus are suitable for beaming, extraction, cooling, abd slowing down to be either stored for space propulsion or used as a source for acceleration. If the magnetic field strength is adjusted for the antiprotons to be confined, an unusual plasma will be formed, consisting of the protons, antiprotons, electrons, and positrons (from pion-muon-electron decays), and similar to Alfvèns "ambiplasman". Its plasmic beta will be unity already at low densities (˜10 11 cm -3 where ωpi/ ωci ≤ 1); the ion-to-electron "temperature" ratio will never achieve

  16. The oxygen isotope evolution of parent body aqueous solutions as recorded by multiple carbonate generations in the Lonewolf Nunataks 94101 CM2 carbonaceous chondrite

    NASA Astrophysics Data System (ADS)

    Lee, M. R.; Sofe, M. R.; Lindgren, P.; Starkey, N. A.; Franchi, I. A.

    2013-11-01

    The CM2 carbonaceous chondrite LON 94101 contains aragonite and two generations of calcite that provide snapshots of the chemical and isotopic evolution of aqueous solutions during parent body alteration. Aragonite was the first carbonate to crystallize. It is rare, heterogeneously distributed within the meteorite matrix, and its mean oxygen isotope values are δ18O 39.9 ± 0.6‰, Δ17O -0.3 ± 1.0‰ (1σ). Calcite precipitated soon afterwards, and following a fall in solution Mg/Ca ratios, to produce small equant grains with a mean oxygen isotope value of δ18O 37.5 ± 0.7‰, Δ17O 1.4 ± 1.1‰ (1σ). These grains were partially or completely replaced by serpentine and tochilinite prior to precipitation of the second generation of calcite, which occluded an open fracture to form a millimetre-sized vein, and replaced anhydrous silicates within chondrules and the matrix. The vein calcite has a mean composition of δ18O 18.4 ± 0.3‰, Δ17O -0.5 ± 0.5‰ (1σ). Petrographic and isotopic results therefore reveal two discrete episodes of mineralisation that produced calcite generations with contrasting δ18O, and mean Δ17O values. The aragonite and equant calcite crystallized over a relatively brief period early in the aqueous alteration history of the parent body, and from static fluids that were evolving chemically in response to mineral dissolution and precipitation. The second calcite generation crystallized from solutions of a lower Δ17O, and a lower δ18O and/or higher temperature. As two generations of calcite whose petrographic characteristics and oxygen isotopic compositions are similar to those in LON 94101 occur in at least one other CM2, multiphase carbonate mineralisation could be the typical outcome of the sequence of chemical reactions during parent body aqueous alteration. It is equally possible however that the second generation of calcite formed in response to an event such as impact fracturing and concomitant fluid mobilisation that affected

  17. Physiological interactions between Na(v)1.7 and Na(v)1.8 sodium channels: a computer simulation study.

    PubMed

    Choi, Jin-Sung; Waxman, Stephen G

    2011-12-01

    We have examined the question of how the level of expression of sodium channel Na(v)1.8 affects the function of dorsal root ganglion (DRG) neurons that also express Na(v)1.7 channels and, conversely, how the level of expression of sodium channel Na(v)1.7 affects the function of DRG neurons that also express Na(v)1.8, using computer simulations. Our results demonstrate several previously undescribed effects of expression of Na(v)1.7: 1) at potentials more negative than -50 mV, increasing Na(v)1.7 expression reduces current threshold. 2) Na(v)1.7 reduces, but does not eliminate, the dependence of action potential (AP) threshold on membrane potential. 3) In cells that express Na(v)1.8, the presence of Na(v)1.7 results in larger amplitude subthreshold oscillations and increases the frequency of repetitive firing. Our results also demonstrate multiple effects of expression of Na(v)1.8: 1) dependence of current threshold on membrane potential is eliminated or reversed by expression of Na(v)1.8 at ≥50% of normal values. 2) Expression of Na(v)1.8 alone, in the absence of Na(v)1.7, can support subthreshold oscillation. 3) Na(v)1.8 is required for generation of overshooting APs, and its expression results in a prolonged AP with an inflection of the falling phase. 4) Increasing levels of expression of Na(v)1.8 result in a reduction in the voltage threshold for AP generation. 5) Increasing levels of expression of Na(v)1.8 result in an attenuation of Na(v)1.7 current during activity evoked by sustained depolarization due, at least in part, to accumulation of fast inactivation by Na(v)1.7 following the first AP. These results indicate that changes in the level of expression of Na(v)1.7 and Na(v)1.8 may provide a regulatory mechanism that tunes the excitability of small DRG neurons. PMID:21940606

  18. Three-dimensional nanostructured bilayer solid oxide fuel cell with 1.3 W/cm(2) at 450 °C.

    PubMed

    An, Jihwan; Kim, Young-Beom; Park, Joonsuk; Gür, Turgut M; Prinz, Fritz B

    2013-09-11

    Obtaining high power density at low operating temperatures has been an ongoing challenge in solid oxide fuel cells (SOFC), which are efficient engines to generate electrical energy from fuels. Here we report successful demonstration of a thin-film three-dimensional (3-D) SOFC architecture achieving a peak power density of 1.3 W/cm(2) obtained at 450 °C. This is made possible by nanostructuring of the ultrathin (60 nm) electrolyte interposed with a nanogranular catalytic interlayer at the cathode/electrolyte interface. We attribute the superior cell performance to significant reduction in both the ohmic and the polarization losses due to the combined effects of employing an ultrathin film electrolyte, enhancement of effective area by 3-D architecture, and superior catalytic activity by the ceria-based interlayer at the cathode. These insights will help design high-efficiency SOFCs that operate at low temperatures with power densities that are of practical significance.

  19. X-Ray Radiation Measurements With Photodiodes In Plasmas Generated By 1017 W/Cm2 Intensity Krf Excimer Laser Pulses

    NASA Astrophysics Data System (ADS)

    Rácz, E.; Földes, I. B.; Ryć, L.

    2006-01-01

    Experiments were carried out using a prepulse-free hybrid KrF excimer-dye laser system (700fs pulse duration, 248nm wavelength, 15mJ pulse energy). The intensity of the p-polarized, focused laser beam was 1.5ṡ1017 W/cm2. Vacuum ultraviolet (VUV) and x-rays from solid state laser plasmas were generated in the laser-plasma interaction of subpicosecond laser pulses of nonrelativistic laser intensities. An x-ray sensitive FLM photodiode (ITE, Warsaw) was used to detect x-rays between 1-19 keV in front of the targets. The diode was filtered by a 4μm Al foil. The dependence of the x-ray flux on laser intensity and the angular distribution of x-rays for aluminum and copper targets in the half space of the front side of the targets were investigated.

  20. Compositions of Partly Altered Olivine and Replacement Serpentine in the CM2 Chondrites QUE93005 and Nogoya: Implications for Scales of Elemental Redistribution During Aqueous Alteration

    NASA Technical Reports Server (NTRS)

    Velbel, M. A.; Tonui, E. K.; Zolensky, M. E.

    2003-01-01

    Some phyllosilicates in CM carbonaceous chondrites formed by aqueous alteration of anhydrous precursor phases. Although broad trends in the compositions of hydrous phyllosilicates are recognized and believed to be related to trends in degree of aqueous alteration, details of the reactions that formed specific secondary minerals remain obscure. This paper reports compositional relationships between remnants of partially pseudomorphically replaced silicates and their alteration products (serpentine) in the CM2 chondrites QUE93005 and Nogoya and compares both with previously published results for Allan Hills 81002. By focusing on serpentine formed from known reactants (olivines), and on only those instances in which some of the reactant silicate remains, direct compositional relationships between reactants and products, and the elemental mobility required by the reactions, can be established.

  1. NIMS Radiance Point Spectra of Gaspra V1.0

    NASA Astrophysics Data System (ADS)

    Granahan, J. C.

    2014-10-01

    This data volume contains radiometrically corrected point spectra of asteroid 951 as acquired by the Galileo spacecraft Near Infrared Mapping Spectrometer (NIMS) on October 29, 1991. They record the spectra collected as the Galileo spacecraft approached the target asteroid. These data are products of the calibration of the raw data number files gap015tn.qub, gap035tn.qub, gap036tn.qub, gap037tn.qub, and gap038tn.qub (DATA SET ID ='GO-A-NIMS-3 TUBE-V1.0') with calibration factors acquired during the first Earth/Moon encounter of the Galileo mission. These raw data .qub files are archived in the Imaging Node of the NASA Planetary Data System (PDS). The calibrated spectra consist of radiance measurements for wavelengths between 0.7 - 5.2 micrometers.

  2. Modified MBE hardware and techniques and role of gallium purity for attainment of two dimensional electron gas mobility >35×106 cm2/V s in AlGaAs/GaAs quantum wells grown by MBE

    NASA Astrophysics Data System (ADS)

    Gardner, Geoffrey C.; Fallahi, Saeed; Watson, John D.; Manfra, Michael J.

    2016-05-01

    We provide evidence that gallium purity is the primary impediment to attainment of ultra-high mobility in a two-dimensional electron gas (2DEG) in AlGaAs/GaAs heterostructures grown by molecular beam epitaxy (MBE). The purity of gallium can be enhanced dramatically by in-situ high temperature outgassing within an operating MBE. Based on analysis of data from an initial growth campaign in a new MBE system and modifications employed for a 2nd growth campaign, we have produced 2DEGs with low temperature mobility μ in excess of 35×106 cm2/V s at density n=3.0×1011/cm2 and μ=18×106 cm2/V s at n=1.1×1011/cm2. Our 2nd campaign data indicate that gallium purity remains the factor currently limiting μ<40×106 cm2/V s. We describe strategies to overcome this limitation.

  3. Targeting Voltage Gated Sodium Channels NaV1.7, NaV1.8, and NaV1.9 for Treatment of Pathological Cough

    PubMed Central

    Muroi, Yukiko

    2015-01-01

    Recent advances in our understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that drugs capable of selective blockade of NaV subtypes may be a safe and effective strategy for the treatment of unwanted cough. Among the nine NaV subtypes (NaV1.1–NaV1.9), the afferent nerves involved in initiating cough, in common with nociceptive neurons in the somatosensory system, express mainly NaV1.7, NaV1.8, and NaV1.9. Although knowledge about the effect of selectively blocking these channels on the cough reflex is limited, their biophysical properties indicate that each may contribute to the hypertussive and allotussive state that typifies subacute and chronic nonproductive cough. PMID:24272479

  4. Scalable high-power (>1kW/cm^2) diode laser stacks based on silicon monolithic micro-channel coolers

    NASA Astrophysics Data System (ADS)

    Reichert, Patrick; Fouksman, Michael; Zhou, Hailong; Nabors, David; Alcala, Jiro; Tolman, Sherry; Toivonen, Mika; Lehkonen, Sami; Haapamaa, Jouko

    2007-02-01

    We describe the performance and reliability of high power vertical diode stacks based on silicon monolithic microchannel coolers (SiMMs) operating at >1000W/cm2 CW at 808 and 940nm. The monolithic nature of these stacks makes them inherently robust and compact. Typical emitting dimensions for a 10-bar stack are ~8.8mm × 10mm with CW output power up to 1.5kW. Originally developed at Lawrence Livermore National Laboratory and now actively being developed for commercial applications at Coherent, this technology offers several advantages over current copper-based micro-channel coolers. These devices do not require use of DI water, strict monitoring and control of the pH level, careful control of the water velocity, or sealed cooling systems. The need for hydrostatic seals is also drastically reduced. A typical ten bar stack requires only 2 o-ring seals, compared to 20 such seals for a similar stack using copper microchannel cooling. Mature and readily available wet etching technology allows for cost effective batch fabrication of the sub-mount structure while achieving repeatable high precision components based on photolithographic fabrication processes.

  5. Performance of a 64-channel, 3.2×3.2 cm2 SiPM tile for TOF-PET application

    NASA Astrophysics Data System (ADS)

    Ferri, Alessandro; Acerbi, Fabio; Gola, Alberto; Piemonte, Claudio; Paternoster, Giovanni; Zorzi, Nicola

    2016-07-01

    In this work, we present a new 3.2×3.2 cm2 detector tile, composed of 8×8 single SiPMs, having a regular 4 mm pitch in both the X and Y directions. The tile fill factor is 85%. We produced two versions of the tile with different SiPM technologies: RGB-HD and NUV. The first one features square micro-cells with 25 μm pitch, a PDE peaked at 550 nm and a DCR of 300 kHz/mm2, at 20 °C and at maximum detection efficiency. The second one features micro-cells with 40 μm pitch and a PDE peaked in the blue part of the spectrum. The dark count rate at 20 °C and at maximum PDE is 100 kHz/mm2. In this work, we show the energy and timing resolution measurements at 511 keV obtained coupling the two tiles to an 8×8 LYSO array with a pixel size of 4×4×22 mm3, perfectly matching the photo-detector array.

  6. Nanostructured multielement (TiHfZrNbVTa)N coatings before and after implantation of N+ ions (1018 cm-2): Their structure and mechanical properties

    NASA Astrophysics Data System (ADS)

    Pogrebnjak, A. D.; Bondar, O. V.; Borba, S. O.; Abadias, G.; Konarski, P.; Plotnikov, S. V.; Beresnev, V. M.; Kassenova, L. G.; Drodziel, P.

    2016-10-01

    Multielement high entropy alloy (HEA) nitride (TiHfZrNbVTa)N coatings were deposited by vacuum arc and their structural and mechanical stability after implantation of high doses of N+ ions, 1018 cm-2, were investigated. The crystal structure and phase composition were characterized by X-ray diffraction (XRD) and Transmission Electron Microscopy, while depth-resolved nanoindentation tests were used to determine the evolution of hardness and elastic modulus along the implantation depth. XRD patterns show that coatings exhibit a main phase with fcc structure, which preferred orientation varies from (1 1 1) to (2 0 0), depending on the deposition conditions. First-principles calculations reveal that the presence of Nb atoms could favor the formation of solid solution with fcc structure in multielement HEA nitride. TEM results showed that amorphous and nanostructured phases were formed in the implanted coating sub-surface layer (∼100 nm depth). Concentration of nitrogen reached 90 at% in the near-surface layer after implantation, and decreased at higher depth. Nanohardness of the as-deposited coatings varied from 27 to 38 GPa depending on the deposition conditions. Ion implantation led to a significant decrease of the nanohardness to 12 GPa in the implanted region, while it reaches 24 GPa at larger depths. However, the H/E ratio is ⩾0.1 in the sub-surface layer due to N+ implantation, which is expected to have beneficial effect on the wear properties.

  7. Characterization of thin pixel sensor modules interconnected with SLID technology irradiated to a fluence of 2ṡ1015 neq/cm2.

    NASA Astrophysics Data System (ADS)

    Weigell, P.; Andricek, L.; Beimforde, M.; Macchiolo, A.; Moser, H.-G.; Nisius, R.; Richter, R.-H.

    2011-12-01

    A new module concept for future ATLAS pixel detector upgrades is presented, where thin n-in-p silicon sensors are connected to the front-end chip exploiting the novel Solid Liquid Interdiffusion technique (SLID) and the signals are read out via Inter Chip Vias (ICV) etched through the front-end. This should serve as a proof of principle for future four-side buttable pixel assemblies for the ATLAS upgrades, without the cantilever presently needed in the chip for the wire bonding. The SLID interconnection, developed by the Fraunhofer EMFT, is a possible alternative to the standard bump-bonding. It is characterized by a very thin eutectic Cu-Sn alloy and allows for stacking of different layers of chips on top of the first one, without destroying the pre-existing bonds. This paves the way for vertical integration technologies. Results of the characterization of the first pixel modules interconnected through SLID as well as of one sample irradiated to 2ṡ1015 neq/cm2 are discussed. Additionally, the etching of ICV into the front-end wafers was started. ICVs will be used to route the signals vertically through the front-end chip, to newly created pads on the backside. In the EMFT approach the chip wafer is thinned to (50-60) μm.

  8. Membraneless, room-temperature, direct borohydride/cerium fuel cell with power density of over 0.25 W/cm2.

    PubMed

    Da Mota, Nicolas; Finkelstein, David A; Kirtland, Joseph D; Rodriguez, Claudia A; Stroock, Abraham D; Abruña, Héctor D

    2012-04-11

    The widespread adoption and deployment of fuel cells as an alternative energy technology have been hampered by a number of formidable technical challenges, including the cost and long-term stability of electrocatalyst and membrane materials. We present a microfluidic fuel cell that overcomes many of these obstacles while achieving power densities in excess of 250 mW/cm(2). The poisoning and sluggish reaction rate associated with CO-contaminated H(2) and methanol, respectively, are averted by employing the promising, high-energy density fuel borohydride. The high-overpotential reaction of oxygen gas at the cathode is supplanted by the high-voltage reduction of cerium ammonium nitrate. Expensive, ineffective membrane materials are replaced with laminar flow and a nonselective, porous convection barrier to separate the fuel and oxidant streams. The result is a Nafion-free, room-temperature fuel cell that has the highest power density per unit mass of Pt catalyst employed for a non-H(2) fuel cell, and exceeds the power density of a typical H(2) fuel cell by 50%.

  9. Aging characteristics of blue InGaN micro-light emitting diodes at an extremely high current density of 3.5 kA cm-2

    NASA Astrophysics Data System (ADS)

    Tian, Pengfei; Althumali, Ahmad; Gu, Erdan; Watson, Ian M.; Dawson, Martin D.; Liu, Ran

    2016-04-01

    The aging characteristics of blue InGaN micro-light emitting diodes (micro-LEDs) with different sizes have been studied at an extremely high current density 3.5 kA cm-2 for emerging micro-LED applications including visible light communication (VLC), micro-LED pumped organic lasers and optogenetics. The light output power of micro-LEDs first increases and then decreases due to the competition of Mg activation in p-GaN layer and defect generation in the active region. The smaller micro-LEDs show less light output power degradation compared with larger micro-LEDs, which is attributed to the lower junction temperature of smaller micro-LEDs. It is found that the high current density without additional junction temperature cannot induce significant micro-LED degradation at room temperature but the combination of the high current density and high junction temperature leads to strong degradation. Furthermore, the cluster LEDs, composed of a micro-LED array, have been developed with both high light output power and less light output degradation for micro-LED applications in solid state lighting and VLC.

  10. Collinear integration affects visual search at V1.

    PubMed

    Chow, Hiu Mei; Jingling, Li; Tseng, Chia-huei

    2013-08-29

    Perceptual grouping plays an indispensable role in figure-ground segregation and attention distribution. For example, a column pops out if it contains element bars orthogonal to uniformly oriented element bars. Jingling and Tseng (2013) have reported that contextual grouping in a column matters to visual search behavior: When a column is grouped into a collinear (snakelike) structure, a target positioned on it became harder to detect than on other noncollinear (ladderlike) columns. How and where perceptual grouping interferes with selective attention is still largely unknown. This article contributes to this little-studied area by asking whether collinear contour integration interacts with visual search before or after binocular fusion. We first identified that the previously mentioned search impairment occurs with a distractor of five or nine elements but not one element in a 9 × 9 search display. To pinpoint the site of this effect, we presented the search display with a short collinear bar (one element) to one eye and the extending collinear bars to the other eye, such that when properly fused, the combined binocular collinear length (nine elements) exceeded the critical length. No collinear search impairment was observed, implying that collinear information before binocular fusion shaped participants' search behavior, although contour extension from the other eye after binocular fusion enhanced the effect of collinearity on attention. Our results suggest that attention interacts with perceptual grouping as early as V1.

  11. Investigation of rat bone fracture healing using pulsed 1.5 MHz, 30 mW/cm(2) burst ultrasound--axial distance dependency.

    PubMed

    Fung, Chak-Hei; Cheung, Wing-Hoi; Pounder, Neill M; de Ana, F Javier; Harrison, Andrew; Leung, Kwok-Sui

    2014-03-01

    This study investigated the effect of LIPUS on fracture healing when fractures were exposed to ultrasound at three axial distances: z=0 mm, 60 mm, and 130 mm. We applied LIPUS to rat fracture at these three axial distances mimicking the exposure condition of human fractures at different depths under the soft tissue. Measurement of LIPUS shows pressure variations in near field (nearby transducer); uniform profile was found beyond it (far field). We asked whether different positions of the fracture within the ultrasound field cause inconsistent biological effect during the healing process. Closed femoral fractured Sprague-Dawley rats were randomized into control, near-field (0mm), mid-near field (60 mm) or far-field (130 mm) groups. Daily LIPUS treatment (plane, but apodized source, see details in the text; 2.2 cm in diameter; 1.5 MHz sine waves repeating at 1 kHz PRF; spatial average temporal average intensity, ISATA=30 mW/cm(2)) was given to fracture site at the three axial distances. Weekly radiographs and endpoint microCT, histomorphometry, and mechanical tests were performed. The results showed that the 130 mm group had the highest tissue mineral density; and significantly higher mechanical properties than control at week 4. The 60 mm and 0 mm groups had significantly higher (i.e. p<0.05) woven bone percentage than control group in radiological, microCT and histomorphometry measurements. In general, LIPUS at far field augmented callus mineralization and mechanical properties; while near field and mid-near field enhanced woven bone formation. Our results indicated the therapeutic effect of LIPUS is dependent on the axial distance of the ultrasound beam. Therefore, the depth of fracture under the soft tissue affects the biological effect of LIPUS. Clinicians have to be aware of the fracture depth when LIPUS is applied transcutaneously.

  12. Blisters on the Anterior Shin in 3 Research Subjects After a 1-MHz, 1.5-W/cm 2, Continuous Ultrasound Treatment: A Case Series

    PubMed Central

    Frye, Jamie L; Johns, Lennart D; Tom, James A; Ingersoll, Christopher D

    2007-01-01

    Context: Clinicians should consider multiple factors when estimating tissue-heating rates. Objective: To report 3 separate occurrences of blisters during an ultrasound treatment experiment. Background: While we were conducting a research experiment comparing the measurement capabilities of 2 different intramuscular temperature devices, 3 female participants (age = 26.33 ± 3.79 years, height = 169.34 ± 3.89 cm, mass = 63.39 ± 3.81 kg) out of 16 healthy volunteers (7 men: age = 22.83 ± 1.17 years, height = 170.61 ± 7.77 cm, mass = 74.62 ± 19.24 kg; 9 women: age = 24.22 ± 2.73 years, height = 171.88 ± 6.35 cm, mass = 73.99 ± 18.55 kg) developed blisters on the anterior shin after a 1-MHz, 1.5-W/cm 2 continuous ultrasound treatment delivered to the triceps surae muscle. Differential Diagnosis: Allergies; chemical reaction with cleaning agents; sunburn; negative interaction between the temperature measurement instruments and the ultrasound field; the ultrasound transducer not being calibrated properly, producing a nonuniform field and creating a hot spot or heating differently when compared with other ultrasound devices; the smaller anatomy of our female subjects; or a confounding interaction among these factors. Treatment: Participants were given standard minor burn care by a physician. Uniqueness: (1) The development of blisters on the anterior aspect of the shin as a result of an ultrasound treatment to the posterior aspect of the triceps surae muscle and (2) muscle tissue heating rates ranging from 0.19°C to 1.1°C/min, when ultrasound researchers have suggested tissue heating in the range of 0.3°C/min with these settings. Conclusions: These adverse events raise important questions regarding treatment application and potential differences in heating and quality control among different ultrasound devices from different manufacturers. PMID:18060000

  13. One-year Outcomes of Pachymetry and Epithelium Thicknesses after Accelerated (45 mW/cm(2)) Transepithelial Corneal Collagen Cross-linking for Keratoconus Patients.

    PubMed

    Zhang, Xiaoyu; Sun, Ling; Chen, Yingjun; Li, Meiyan; Tian, Mi; Zhou, Xingtao

    2016-01-01

    The thickness of corneal pachymetry and the epithelium after accelerated (45 mW/cm(2)) transepithelial corneal collagen cross-linking (CXL) for keratoconus were assessed in this prospective case series study. Twenty-eight patients were treated for keratoconus. The mean Kmax was 56.18 ± 7.90. The thinnest point, as assessed by optical coherence tomography (OCT), was 443.18 ± 39.75 μm. Accelerated transepithelial CXL was performed, and corrected distance visual acuity (CDVA), corneal topography, and OCT were recorded at 1 week postoperatively as well as at 1, 3, 6, and 12 months. The surgery was uneventful in all eyes. Postoperative epithelial edema was observed and faded in 3 days. The postoperative Kmax was 54.56 ± 8.81, 55.78 ± 8.11, 56.37 ± 8.71, 55.80 ± 7.92, and 55.47 ± 8.24 at 1 week, 1 month, 3 months, 6 months, and 12 months, respectively (all, P > 0.05). The thinnest postoperative corneal point, 439.04 ± 44.99 μm, was observed at 12 months (P = 0.109). The epithelial thickness decreased during the first postoperative week then showed a gradual recovery. Postoperative pachymetry thickness showed no significant changes for up to 12 months. Postoperative epithelial thickness decreased temporarily, then stabilized at month 12. Accelerated transepithelial CXL was shown to be effective and safe for the treatment of keratoconus. PMID:27597655

  14. Hydrogen and carbon isotopic ratios of polycyclic aromatic compounds in two CM2 carbonaceous chondrites and implications for prebiotic organic synthesis

    NASA Astrophysics Data System (ADS)

    Huang, Yongsong; Aponte, José C.; Zhao, Jiaju; Tarozo, Rafael; Hallmann, Christian

    2015-09-01

    Study of meteoritic organic compounds offers a unique opportunity to understand the origins of the organic matter in the early Solar System. Meteoritic polycyclic aromatic hydrocarbons (PAHs) and heteropolycyclic aromatic compounds (HACs) have been studied for over fifty years, however; their hydrogen stable isotopic ratios (δD) have never been reported. Compound-specific δD measurements of PAHs and HACs are important, in part because the carbon isotopic ratios (δ13C) of various meteoritic PAHs cannot be readily distinguished from their terrestrial counterparts and it is difficult to rule out terrestrial contamination based on carbon isotopic ratios alone. In this study, we have extracted and identified more than sixty PAHs and HACs present in two CM2 carbonaceous chondrites Murchison and LON 94101. Their carbon and hydrogen stable isotopic ratios (δ13C and δD) were measured and used to discuss about their synthetic environments and formation mechanisms. The concentration of aromatic compounds is ∼30% higher in Murchison than in the Antarctic meteorite LON 94101, but both samples contained similar suites of PAHs and HACs. All PAHs and HACs found exhibited positive δD values (up to 1100‰) consistent with an extraterrestrial origin, indicating the relatively low δ13C values are indeed an inherent feature of the meteoritic aromatic compounds. The hydrogen isotopic data suggest aromatic compounds in carbonaceous chondrites were mainly formed in the cold interstellar environments. Molecular level variations in hydrogen and carbon isotopic values offer new insights to the formation pathways for the aromatic compounds in carbonaceous chondrites.

  15. Aqueous Alteration of Carbonaceous Chondrites: New Insights from Comparative Studies of Two Unbrecciated CM2 Chondrites, Y 791198 and ALH 81002

    NASA Technical Reports Server (NTRS)

    Chizmadia, L. J.; Brearley, A. J.

    2004-01-01

    Carbonaceous chondrites are an important resource for understanding the physical and chemical conditions in the early solar system. In particular, a long-standing question concerns the role of water in the cosmochemical evolution of carbonaceous chondrites. It is well established that extensive hydration of primary nebular phases occurred in the CM and CI chondrites, but the location where this alteration occurred remains controversial. In the CM2 chondrites, hydration formed secondary phases such as serpentine, tochilinite, pentlandite, carbonate and PCP. There are several textural observations which suggest that alteration occurred before the accretion of the final CM parent asteroid, i.e. preaccretionary alteration. Conversely, there is a significant body of evidence that supports parent-body alteration. In order to test these two competing hypotheses further, we studied two CM chondrites, Y-791198 and ALH81002, two meteorites that exhibit widely differing degrees of aqueous alteration. In addition, both meteorites have primary accretionary textures, i.e. experienced minimal asteroidal brecciation. Brecciation significantly complicates the task of unraveling alteration histories, mixing components that have been altered to different degrees from different locations on the same asteroidal parent body. Alteration in Y-791198 is mostly confined to chondrule mesostases, FeNi metal and fine-grained matrix and rims. In comparison, the primary chondrule silicates in ALH81002 have undergone extensive replacement by secondary hydrous phases. This study focuses on compositional and textural relationships between chondrule mesostasis and the associated rim materials. Our hypothesis is: both these components are highly susceptible to aqueous alteration and should be sensitive recorders of the alteration process. For parent body alteration, we expect systematic coupled mineralogical and compositional changes in rims and altered mesostasis, as elemental exchange between these

  16. Investigation of rat bone fracture healing using pulsed 1.5 MHz, 30 mW/cm(2) burst ultrasound--axial distance dependency.

    PubMed

    Fung, Chak-Hei; Cheung, Wing-Hoi; Pounder, Neill M; de Ana, F Javier; Harrison, Andrew; Leung, Kwok-Sui

    2014-03-01

    This study investigated the effect of LIPUS on fracture healing when fractures were exposed to ultrasound at three axial distances: z=0 mm, 60 mm, and 130 mm. We applied LIPUS to rat fracture at these three axial distances mimicking the exposure condition of human fractures at different depths under the soft tissue. Measurement of LIPUS shows pressure variations in near field (nearby transducer); uniform profile was found beyond it (far field). We asked whether different positions of the fracture within the ultrasound field cause inconsistent biological effect during the healing process. Closed femoral fractured Sprague-Dawley rats were randomized into control, near-field (0mm), mid-near field (60 mm) or far-field (130 mm) groups. Daily LIPUS treatment (plane, but apodized source, see details in the text; 2.2 cm in diameter; 1.5 MHz sine waves repeating at 1 kHz PRF; spatial average temporal average intensity, ISATA=30 mW/cm(2)) was given to fracture site at the three axial distances. Weekly radiographs and endpoint microCT, histomorphometry, and mechanical tests were performed. The results showed that the 130 mm group had the highest tissue mineral density; and significantly higher mechanical properties than control at week 4. The 60 mm and 0 mm groups had significantly higher (i.e. p<0.05) woven bone percentage than control group in radiological, microCT and histomorphometry measurements. In general, LIPUS at far field augmented callus mineralization and mechanical properties; while near field and mid-near field enhanced woven bone formation. Our results indicated the therapeutic effect of LIPUS is dependent on the axial distance of the ultrasound beam. Therefore, the depth of fracture under the soft tissue affects the biological effect of LIPUS. Clinicians have to be aware of the fracture depth when LIPUS is applied transcutaneously. PMID:24239510

  17. One-year Outcomes of Pachymetry and Epithelium Thicknesses after Accelerated (45 mW/cm2) Transepithelial Corneal Collagen Cross-linking for Keratoconus Patients

    PubMed Central

    Zhang, Xiaoyu; Sun, Ling; Chen, Yingjun; Li, Meiyan; Tian, Mi; Zhou, Xingtao

    2016-01-01

    The thickness of corneal pachymetry and the epithelium after accelerated (45 mW/cm2) transepithelial corneal collagen cross-linking (CXL) for keratoconus were assessed in this prospective case series study. Twenty-eight patients were treated for keratoconus. The mean Kmax was 56.18 ± 7.90. The thinnest point, as assessed by optical coherence tomography (OCT), was 443.18 ± 39.75 μm. Accelerated transepithelial CXL was performed, and corrected distance visual acuity (CDVA), corneal topography, and OCT were recorded at 1 week postoperatively as well as at 1, 3, 6, and 12 months. The surgery was uneventful in all eyes. Postoperative epithelial edema was observed and faded in 3 days. The postoperative Kmax was 54.56 ± 8.81, 55.78 ± 8.11, 56.37 ± 8.71, 55.80 ± 7.92, and 55.47 ± 8.24 at 1 week, 1 month, 3 months, 6 months, and 12 months, respectively (all, P > 0.05). The thinnest postoperative corneal point, 439.04 ± 44.99 μm, was observed at 12 months (P = 0.109). The epithelial thickness decreased during the first postoperative week then showed a gradual recovery. Postoperative pachymetry thickness showed no significant changes for up to 12 months. Postoperative epithelial thickness decreased temporarily, then stabilized at month 12. Accelerated transepithelial CXL was shown to be effective and safe for the treatment of keratoconus. PMID:27597655

  18. Attention selects informative neural populations in human V1.

    PubMed

    Verghese, Preeti; Kim, Yee-Joon; Wade, Alex R

    2012-11-14

    In a neural population driven by a simple grating stimulus, different subpopulations are maximally informative about changes to the grating's orientation and contrast. In theory, observers should attend to the optimal subpopulation when switching between orientation and contrast discrimination tasks. Here we used source-imaged, steady-state visual evoked potentials and visual psychophysics to determine whether this is the case. Observers fixated centrally while static targets were presented bilaterally along with a cue indicating task type (contrast or orientation modulation detection) and task location (left or right). Changes in neuronal activity were measured by quantifying frequency-tagged responses from flickering "reporter" gratings surrounding the targets. To determine the orientation tuning of attentionally modulated neurons, we measured responses for three different probe-reporter angles: 0, 20, and 45°. We estimated frequency-tagged cortical activity using a minimum norm inverse procedure combined with realistic MR-derived head models and retinotopically mapped visual areas. Estimates of neural activity from regions of interest centered on V1 showed that attention to a spatial location clearly increased the amplitude of the neural response in that location. More importantly, the pattern of modulation depended on the task. For orientation discrimination, attentional modulation showed a sharp peak in the population tuned 20° from the target orientation, whereas for contrast discrimination the enhancement was more broadly tuned. Similar tuning functions for orientation and contrast discrimination were obtained from psychophysical adaptation studies. These findings indicate that humans attend selectively to the most informative neural population and that these populations change depending on the nature of the task. PMID:23152620

  19. 26 CFR 1.414(v)-1 - Catch-up contributions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Catch-up contributions. 1.414(v)-1 Section 1.414(v)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(v)-1...

  20. 26 CFR 1.414(v)-1 - Catch-up contributions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Catch-up contributions. 1.414(v)-1 Section 1.414(v)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(v)-1...

  1. 26 CFR 1.414(v)-1 - Catch-up contributions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Catch-up contributions. 1.414(v)-1 Section 1.414(v)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(v)-1...

  2. Determinants in CaV1 Channels That Regulate the Ca2+ Sensitivity of Bound Calmodulin*

    PubMed Central

    Halling, D. Brent; Georgiou, Dimitra K.; Black, D. J.; Yang, Guojun; Fallon, Jennifer L.; Quiocho, Florante A.; Pedersen, Steen E.; Hamilton, Susan L.

    2009-01-01

    Calmodulin binds to IQ motifs in the α1 subunit of CaV1.1 and CaV1.2, but the affinities of calmodulin for the motif and for Ca2+ are higher when bound to CaV1.2 IQ. The CaV1.1 IQ and CaV1.2 IQ sequences differ by four amino acids. We determined the structure of calmodulin bound to CaV1.1 IQ and compared it with that of calmodulin bound to CaV1.2 IQ. Four methionines in Ca2+-calmodulin form a hydrophobic binding pocket for the peptide, but only one of the four nonconserved amino acids (His-1532 of CaV1.1 and Tyr-1675 of CaV1.2) contacts this calmodulin pocket. However, Tyr-1675 in CaV1.2 contributes only modestly to the higher affinity of this peptide for calmodulin; the other three amino acids in CaV1.2 contribute significantly to the difference in the Ca2+ affinity of the bound calmodulin despite having no direct contact with calmodulin. Those residues appear to allow an interaction with calmodulin with one lobe Ca2+-bound and one lobe Ca2+-free. Our data also provide evidence for lobe-lobe interactions in calmodulin bound to CaV1.2. PMID:19473981

  3. Determining temperature distribution in tissue in the focal plane of the high (>100 W/cm(2)) intensity focused ultrasound beam using phase shift of ultrasound echoes.

    PubMed

    Karwat, Piotr; Kujawska, Tamara; Lewin, Peter A; Secomski, Wojciech; Gambin, Barbara; Litniewski, Jerzy

    2016-02-01

    In therapeutic applications of High Intensity Focused Ultrasound (HIFU) the guidance of the HIFU beam and especially its focal plane is of crucial importance. This guidance is needed to appropriately target the focal plane and hence the whole focal volume inside the tumor tissue prior to thermo-ablative treatment and beginning of tissue necrosis. This is currently done using Magnetic Resonance Imaging that is relatively expensive. In this study an ultrasound method, which calculates the variations of speed of sound in the locally heated tissue volume by analyzing the phase shifts of echo-signals received by an ultrasound scanner from this very volume is presented. To improve spatial resolution of B-mode imaging and minimize the uncertainty of temperature estimation the acoustic signals were transmitted and received by 8 MHz linear phased array employing Synthetic Transmit Aperture (STA) technique. Initially, the validity of the algorithm developed was verified experimentally in a tissue-mimicking phantom heated from 20.6 to 48.6 °C. Subsequently, the method was tested using a pork loin sample heated locally by a 2 MHz pulsed HIFU beam with focal intensity ISATA of 129 W/cm(2). The temperature calibration of 2D maps of changes in the sound velocity induced by heating was performed by comparison of the algorithm-determined changes in the sound velocity with the temperatures measured by thermocouples located in the heated tissue volume. The method developed enabled ultrasound temperature imaging of the heated tissue volume from the very inception of heating with the contrast-to-noise ratio of 3.5-12 dB in the temperature range 21-56 °C. Concurrently performed, conventional B-mode imaging revealed CNR close to zero dB until the temperature reached 50 °C causing necrosis. The data presented suggest that the proposed method could offer an alternative to MRI-guided temperature imaging for prediction of the location and extent of the thermal lesion prior to applying the

  4. Determining temperature distribution in tissue in the focal plane of the high (>100 W/cm(2)) intensity focused ultrasound beam using phase shift of ultrasound echoes.

    PubMed

    Karwat, Piotr; Kujawska, Tamara; Lewin, Peter A; Secomski, Wojciech; Gambin, Barbara; Litniewski, Jerzy

    2016-02-01

    In therapeutic applications of High Intensity Focused Ultrasound (HIFU) the guidance of the HIFU beam and especially its focal plane is of crucial importance. This guidance is needed to appropriately target the focal plane and hence the whole focal volume inside the tumor tissue prior to thermo-ablative treatment and beginning of tissue necrosis. This is currently done using Magnetic Resonance Imaging that is relatively expensive. In this study an ultrasound method, which calculates the variations of speed of sound in the locally heated tissue volume by analyzing the phase shifts of echo-signals received by an ultrasound scanner from this very volume is presented. To improve spatial resolution of B-mode imaging and minimize the uncertainty of temperature estimation the acoustic signals were transmitted and received by 8 MHz linear phased array employing Synthetic Transmit Aperture (STA) technique. Initially, the validity of the algorithm developed was verified experimentally in a tissue-mimicking phantom heated from 20.6 to 48.6 °C. Subsequently, the method was tested using a pork loin sample heated locally by a 2 MHz pulsed HIFU beam with focal intensity ISATA of 129 W/cm(2). The temperature calibration of 2D maps of changes in the sound velocity induced by heating was performed by comparison of the algorithm-determined changes in the sound velocity with the temperatures measured by thermocouples located in the heated tissue volume. The method developed enabled ultrasound temperature imaging of the heated tissue volume from the very inception of heating with the contrast-to-noise ratio of 3.5-12 dB in the temperature range 21-56 °C. Concurrently performed, conventional B-mode imaging revealed CNR close to zero dB until the temperature reached 50 °C causing necrosis. The data presented suggest that the proposed method could offer an alternative to MRI-guided temperature imaging for prediction of the location and extent of the thermal lesion prior to applying the

  5. 26 CFR 36.3121(l)(10)-4 - Payment of amounts equivalent to tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Payment of amounts equivalent to tax. 36.3121(l... (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE CONTRACT COVERAGE OF EMPLOYEES OF FOREIGN SUBSIDIARIES § 36.3121(l)(10)-4 Payment of amounts equivalent to tax. A domestic corporation which has...

  6. 26 CFR 36.3121(l)(10)-4 - Payment of amounts equivalent to tax.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Payment of amounts equivalent to tax. 36.3121(l... (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE CONTRACT COVERAGE OF EMPLOYEES OF FOREIGN SUBSIDIARIES § 36.3121(l)(10)-4 Payment of amounts equivalent to tax. A domestic corporation which has...

  7. 26 CFR 36.3121(l)(10)-4 - Payment of amounts equivalent to tax.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 15 2011-04-01 2011-04-01 false Payment of amounts equivalent to tax. 36.3121(l... (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE CONTRACT COVERAGE OF EMPLOYEES OF FOREIGN SUBSIDIARIES § 36.3121(l)(10)-4 Payment of amounts equivalent to tax. A domestic corporation which has...

  8. 15 CFR 10.4 - Establishment of the Standard Review Committee.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... THE DEVELOPMENT OF VOLUNTARY PRODUCT STANDARDS § 10.4 Establishment of the Standard Review Committee... of producers, distributors, and users or consumers of product for which a standard is sought or any... shall be required to approve any actions taken by the committee except for the action of recommending...

  9. POSTNATAL PHENOTYPE AND LOCALIZATION OF SPINAL CORD V1 DERIVED INTERNEURONS

    PubMed Central

    Alvarez, Francisco J.; Jonas, Philip C.; Sapir, Tamar; Hartley, Robert; Berrocal, Maria C.; Geiman, Eric J.; Todd, Andrew J.; Goulding, Martyn

    2010-01-01

    Developmental studies identified four classes (V0, V1, V2, V3) of embryonic interneurons in the ventral spinal cord. Very little however is known about their adult phenotypes. In order to further characterize interneuron cell types in the adult, the location, neurotransmitter phenotype, calcium-buffering protein expression and axon distributions of V1-derived neurons in the mouse spinal cord was determined. In the mature (P20 and older) spinal cord, most V1-derived neurons are located in lateral LVII and in LIX, few in medial LVII and none in LVIII. Approximately 40% express calbindin and/or parvalbumin, while few express calretinin. Of seven groups of ventral interneurons identified according to calcium-buffering protein expression, two groups (1 and 4) correspond with V1-derived neurons. Group 1 are Renshaw cells and intensely express calbindin and coexpress parvalbumin and calretinin. They represent 9% of the V1 population. Group 4 express only parvalbumin and represent 27% of V1-derived neurons. V1-derived group 4 neurons receive contacts from primary sensory afferents and are therefore proprioceptive interneurons and the most ventral neurons in this group receive convergent calbindin-IR Renshaw cell inputs. This subgroup resembles Ia inhibitory interneurons (IaINs) and represents 13% of V1-derived neurons. Adult V1-interneuron axons target LIX and LVII and some enter the deep dorsal horn. V1-axons do not cross the midline. V1 derived axonal varicosities were mostly (>80%) glycinergic and a third were GABAergic. None were glutamatergic or cholinergic. In summary, V1 interneurons develop into ipsilaterally projecting, inhibitory interneurons that include Renshaw cells, Ia inhibitory interneurons and other unidentified proprioceptive interneurons. PMID:16255029

  10. 10. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO SOUTHWEST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO SOUTHWEST, WITH AUTOMATIC CUTTER (LEFT), PRESS (CENTER), AND WRAPPER (RIGHT); LARGE CHUTE AT CENTER FROM 5TH FLOOR BINS TO 3RD FLOOR SOAP MILLS; OVERHEAD AND FLOOR (LOWER RIGHT) FINISHED GOODS CONVEYORS TO G BLOCK (HAER NO. NJ-71-NN) - Colgate & Company Jersey City Plant, Building No. B-14, 54-58 Grand Street, Jersey City, Hudson County, NJ

  11. Long-range cortical connections give rise to a robust velocity map of V1.

    PubMed

    Sheridan, Phillip

    2015-11-01

    This paper proposes a two-dimensional velocity model (2DVM) of the primary visual cortex (V1). The model's novel aspect is that it specifies a particular pattern of long-range cortical temporal connections, via the Connection Algorithm, and shows how the addition of these connections to well-known spatial properties of V1 transforms V1 into a velocity map. The map implies a number of organizational properties of V1: (1) the singularity of each orientation pinwheel contributes to the detection of slow-moving spots across the visual field; (2) the speed component of neuronal velocity selectivity decreases monotonically across each joint orientation contour line for parallel motion and increases monotonically for orthogonal motion; (3) the cells that are direction selective to slow-moving objects are situated in the periphery of V1; and (4) neurons in distinct pinwheels tend to be connected to neurons with similar tuning preferences in other pinwheels. The model accounts for various types of known illusionary perceptions of human vision: perceptual filling-in, illusionary orientation and visual crowding. The three distinguishing features of 2DVM are: (1) it unifies the functional properties of the conventional energy model of V1; (2) it directly relates the functional properties to the known structure of the upper layers of V1; and (3) it implies that the spatial selectivity features of V1 are side effects of its more important role as a velocity map of the visual field. PMID:26343820

  12. A V1-vascular vasopressin antagonist suitable for radioiodination and photoaffinity labeling

    SciTech Connect

    Thibonnier, M.; Chehade, N.; Hinko, A. )

    1990-06-01

    We have previously characterized the V1-vascular arginine vasopressin (AVP) receptors of human platelets. We now report on a radiomonoiodinated and photoreactive V1-vascular AVP antagonist (V1-ag) to be used for the purification of human V1-vascular AVP receptors. The V1-ag, d(CH2)5Tyr(Me)Tyr(NH2)AVP was modified by radiomonoiodination of d(CH2)5-Tyr(Me)Tyr(NH2)AVP with the Iodogen technique, and derivatization of d(CH2)5Tyr(Me)Tyr(125I)(NH2)-AVP with the photoreactive crosslinker, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB) (each step included HPLC purification). In competition experiments, the affinity of these V1-ag for the human platelet AVP receptors remained excellent. Irreversible photoaffinity labeling of the platelet V1-vascular AVP receptor was successfully achieved by UV lamp exposure (365 nm, 20 min). Thus, AzBz-d(CH2)5Tyr(Me)Tyr(125I)(NH2)AVP is a promising tool to use for the purification of human V1-vascular AVP receptors.

  13. Properties of V1 neurons tuned to conjunctions of visual features: application of the V1 saliency hypothesis to visual search behavior.

    PubMed

    Zhaoping, Li; Zhe, Li

    2012-01-01

    From a computational theory of V1, we formulate an optimization problem to investigate neural properties in the primary visual cortex (V1) from human reaction times (RTs) in visual search. The theory is the V1 saliency hypothesis that the bottom-up saliency of any visual location is represented by the highest V1 response to it relative to the background responses. The neural properties probed are those associated with the less known V1 neurons tuned simultaneously or conjunctively in two feature dimensions. The visual search is to find a target bar unique in color (C), orientation (O), motion direction (M), or redundantly in combinations of these features (e.g., CO, MO, or CM) among uniform background bars. A feature singleton target is salient because its evoked V1 response largely escapes the iso-feature suppression on responses to the background bars. The responses of the conjunctively tuned cells are manifested in the shortening of the RT for a redundant feature target (e.g., a CO target) from that predicted by a race between the RTs for the two corresponding single feature targets (e.g., C and O targets). Our investigation enables the following testable predictions. Contextual suppression on the response of a CO-tuned or MO-tuned conjunctive cell is weaker when the contextual inputs differ from the direct inputs in both feature dimensions, rather than just one. Additionally, CO-tuned cells and MO-tuned cells are often more active than the single feature tuned cells in response to the redundant feature targets, and this occurs more frequently for the MO-tuned cells such that the MO-tuned cells are no less likely than either the M-tuned or O-tuned neurons to be the most responsive neuron to dictate saliency for an MO target. PMID:22719829

  14. Vasopressin receptors V1a and V2 are not osmosensors.

    PubMed

    Lykke, Kasper; Assentoft, Mette; Fenton, Robert A; Rosenkilde, Mette M; MacAulay, Nanna

    2015-08-01

    Herein, we investigated whether G protein-coupled signaling via the vasopressin receptors of the V1a and V2 subtypes (V1aR and V2R) could be obtained as a direct response to hyperosmolar challenges and/or whether hyperosmolar challenges could augment classical vasopressin-dependent V1aR signaling. The V1aR-dependent response was monitored indirectly via its effects on aquaporin 4 (AQP4) when heterologously expressed in Xenopus oocytes and V1aR and V2R function was directly monitored following heterologous expression in COS-7 cells. A tendency toward an osmotically induced, V1aR-mediated reduction in AQP4-dependent water permeability was observed, although osmotic challenges failed to mimic vasopressin-dependent V1aR-mediated internalization of AQP4. Direct monitoring of inositol phosphate (IP) production of V1aR-expressing COS-7 cells demonstrated an efficient vasopressin-dependent response that was, however, independent of hyperosmotic challenges. Similarly, the cAMP production by the V2R was unaffected by hyperosmotic challenges although, in contrast to the V1aR, the V2R displayed an ability to support alternative signaling (IP production) at higher concentration of vasopressin. V1aR and V2R respond directly to vasopressin exposure, but they do not have an ability to act as osmo- or volume sensors when exposed to an osmotic gradient in the absence or presence of vasopressin. PMID:26311834

  15. Mechanical modulation of ATP-binding affinity of V1-ATPase.

    PubMed

    Tirtom, Naciye Esma; Okuno, Daichi; Nakano, Masahiro; Yokoyama, Ken; Noji, Hiroyuki

    2013-01-01

    V(1)-ATPase is a rotary motor protein that rotates the central shaft in a counterclockwise direction hydrolyzing ATP. Although the ATP-binding process is suggested to be the most critical reaction step for torque generation in F(1)-ATPase (the closest relative of V(1)-ATPase evolutionarily), the role of ATP binding for V(1)-ATPase in torque generation has remained unclear. In the present study, we performed single-molecule manipulation experiments on V(1)-ATPase from Thermus thermophilus to investigate how the ATP-binding process is modulated upon rotation of the rotary shaft. When V(1)-ATPase showed an ATP-waiting pause, it was stalled at a target angle and then released. Based on the response of the V(1)-ATPase released, the ATP-binding probability was determined at individual stall angles. It was observed that the rate constant of ATP binding (k(on)) was exponentially accelerated with forward rotation, whereas the rate constant of ATP release (k(off)) was exponentially reduced. The angle dependence of the k(off) of V(1)-ATPase was significantly smaller than that of F(1)-ATPase, suggesting that the ATP-binding process is not the major torque-generating step in V(1)-ATPase. When V(1)-ATPase was stalled at the mean binding angle to restrict rotary Brownian motion, k(on) was evidently slower than that determined from free rotation, showing the reaction rate enhancement by conformational fluctuation. It was also suggested that shaft of V(1)-ATPase should be rotated at least 277° in a clockwise direction for efficient release of ATP under ATP-synthesis conditions.

  16. Diverse Anhydrous Silicates in a Fine-Grained Rim in the Weakly Altered CM2 Chondrite Queen Elizabeth Range 97990: Evidence for the Localized Preservation of Pristine Nebular Dust in CM Chondrites.

    NASA Astrophysics Data System (ADS)

    Brearley, A. J.

    2016-08-01

    A fine-grained rim the QUE 97990 CM2 chondrite contains diverse submicron crystalline anhydrous silicates, including olivines, low-Ca and high Ca pyroxenes and represents a more pristine sample of nebular dust than is present in most CM chondrites.

  17. Low-level laser therapy, at 60 J/cm2 associated with a Biosilicate® increase in bone deposition and indentation biomechanical properties of callus in osteopenic rats

    NASA Astrophysics Data System (ADS)

    Fangel, Renan; Sérgio Bossini, Paulo; Cláudia Renno, Ana; Araki Ribeiro, Daniel; Chenwei Wang, Charles; Luri Toma, Renata; Okino Nonaka, Keico; Driusso, Patrícia; Antonio Parizotto, Nivaldo; Oishi, Jorge

    2011-07-01

    We investigate the effects of a novel bioactive material (Biosilicate®) and low-level laser therapy (LLLT), at 60 J/cm2, on bone-fracture consolidation in osteoporotic rats. Forty female Wistar rats are submitted to the ovariectomy, to induce osteopenia. Eight weeks after the ovariectomy, the animals are randomly divided into four groups, with 10 animals each: bone defect control group; bone defect filled with Biosilicate group; bone defect irradiated with laser at 60 J/cm2 group; bone defect filled with Biosilicate and irradiated with LLLT, at 60 J/cm2 group. Laser irradiation is initiated immediately after surgery and performed every 48 h for 14 days. Histopathological analysis points out that bone defects are predominantly filled with the biomaterial in specimens treated with Biosilicate. In the 60-J/cm2 laser plus Biosilicate group, the biomaterial fills all bone defects, which also contained woven bone and granulation tissue. Also, the biomechanical properties are increased in the animals treated with Biosilicate associated to lasertherapy. Our results indicate that laser therapy improves bone repair process in contact with Biosilicate as a result of increasing bone formation as well as indentation biomechanical properties.

  18. Membrane permeable local anesthetics modulate Na(V)1.5 mechanosensitivity.

    PubMed

    Beyder, Arthur; Strege, Peter R; Bernard, Cheryl; Farrugia, Gianrico

    2012-01-01

    Voltage-gated sodium selective ion channel Na(V)1.5 is expressed in the heart and the gastrointestinal tract, which are mechanically active organs. Na(V)1.5 is mechanosensitive at stimuli that gate other mechanosensitive ion channels. Local anesthetic and antiarrhythmic drugs act upon Na(V)1.5 to modulate activity by multiple mechanisms. This study examined whether Na(V)1.5 mechanosensitivity is modulated by local anesthetics. Na(V)1.5 channels were expressed in HEK-293 cells, and mechanosensitivity was tested in cell-attached and excised inside-out configurations. Using a novel protocol with paired voltage ladders and short pressure pulses, negative patch pressure (-30 mmHg) in both configurations produced a hyperpolarizing shift in the half-point of the voltage-dependence of activation (V(1/2a)) and inactivation (V(1/2i)) by about -10 mV. Lidocaine (50 µM) inhibited the pressure-induced shift of V(1/2a) but not V(1/2i). Lidocaine inhibited the tonic increase in pressure-induced peak current in a use-dependence protocol, but it did not otherwise affect use-dependent block. The local anesthetic benzocaine, which does not show use-dependent block, also effectively blocked a pressure-induced shift in V(1/2a). Lidocaine inhibited mechanosensitivity in Na(V)1.5 at the local anesthetic binding site mutated (F1760A). However, a membrane impermeable lidocaine analog QX-314 did not affect mechanosensitivity of F1760A Na(V)1.5 when applied from either side of the membrane. These data suggest that the mechanism of lidocaine inhibition of the pressure-induced shift in the half-point of voltage-dependence of activation is separate from the mechanisms of use-dependent block. Modulation of Na(V)1.5 mechanosensitivity by the membrane permeable local anesthetics may require hydrophobic access and may involve membrane-protein interactions.

  19. V1R promoters are well conserved and exhibit common putative regulatory motifs

    PubMed Central

    Stewart, Robert; Lane, Robert P

    2007-01-01

    Background The mouse vomeronasal organ (VNO) processes chemosensory information, including pheromone signals that influence reproductive behaviors. The sensory neurons of the VNO express two types of chemosensory receptors, V1R and V2R. There are ~165 V1R genes in the mouse genome that have been classified into ~12 divergent subfamilies. Each sensory neuron of the apical compartment of the VNO transcribes only one of the repertoire of V1R genes. A model for mutually exclusive V1R transcription in these cells has been proposed in which each V1R gene might compete stochastically for a single transcriptional complex. This model predicts that the large repertoire of divergent V1R genes in the mouse genome contains common regulatory elements. In this study, we have characterized V1R promoter regions by comparative genomics and by mapping transcription start sites. Results We find that transcription is initiated from ~1 kb promoter regions that are well conserved within V1R subfamilies. While cross-subfamily homology is not evident by traditional methods, we developed a heuristic motif-searching tool, LogoAlign, and applied this tool to identify motifs shared within the promoters of all V1R genes. Our motif-searching tool exhibits rapid convergence to a relatively small number of non-redundant solutions (97% convergence). We also find that the best motifs contain significantly more information than those identified in controls, and that these motifs are more likely to be found in the immediate vicinity of transcription start sites than elsewhere in gene blocks. The best motifs occur near transcription start sites of ~90% of all V1R genes and across all of the divergent subfamilies. Therefore, these motifs are candidate binding sites for transcription factors involved in V1R co-regulation. Conclusion Our analyses show that V1R subfamilies have broad and well conserved promoter regions from which transcription is initiated. Results from a new motif-finding algorithm, Logo

  20. Multi-Object Spectroscopy with OSIRIS at the 10.4 m GTC

    NASA Astrophysics Data System (ADS)

    Cabrera-Lavers, A.

    2016-10-01

    OSIRIS is the first light instrument of the 10.4 m GTC. Apart from standard imaging and spectroscopic observing modes, multi-object spectroscopic observations with OSIRIS instrument were initiated in March 2014, with extraordinary success both in the users' demand as well as in the data quality obtained. In this contribution we give a brief description of the process for requesting and defining MOS observations with OSIRIS. We present some numbers on the accuracy obtained in the mask design and on-sky positioning, based on real data obtained at the telescope during the first year of operation of this observing mode.

  1. Financial services FY 1995 site support program plan WBS 6.10.4

    SciTech Connect

    Vodney, E.P.

    1994-09-01

    This is the signed Financial Service fiscal year 1995 Site Support Program Plan, Work Breakdown Structure 6.10.4, for the Hanford site. This plan is intended to enable the contractor to accomplish the following: ensure financial integrity in all Westinghouse Hanford Company (WHC) operation while supporting the programmatic activities of WHC, the US Department of Energy, Richland Operations Office, and other Hanford contractors; provide efficient and effective financial services, and value added audits and review that enable management to enhance future operational results.

  2. Molecular Evolutionary Characterization of a V1R Subfamily Unique to Strepsirrhine Primates

    PubMed Central

    Yoder, Anne D.; Chan, Lauren M.; dos Reis, Mario; Larsen, Peter A.; Campbell, C. Ryan; Rasoloarison, Rodin; Barrett, Meredith; Roos, Christian; Kappeler, Peter; Bielawski, Joseph; Yang, Ziheng

    2014-01-01

    Vomeronasal receptor genes have frequently been invoked as integral to the establishment and maintenance of species boundaries among mammals due to the elaborate one-to-one correspondence between semiochemical signals and neuronal sensory inputs. Here, we report the most extensive sample of vomeronasal receptor class 1 (V1R) sequences ever generated for a diverse yet phylogenetically coherent group of mammals, the tooth-combed primates (suborder Strepsirrhini). Phylogenetic analysis confirms our intensive sampling from a single V1R subfamily, apparently unique to the strepsirrhine primates. We designate this subfamily as V1Rstrep. The subfamily retains extensive repertoires of gene copies that descend from an ancestral gene duplication that appears to have occurred prior to the diversification of all lemuriform primates excluding the basal genus Daubentonia (the aye-aye). We refer to the descendent clades as V1Rstrep-α and V1Rstrep-β. Comparison of the two clades reveals different amino acid compositions corresponding to the predicted ligand-binding site and thus potentially to altered functional profiles between the two. In agreement with previous studies of the mouse lemur (genus, Microcebus), the majority of V1Rstrep gene copies appear to be intact and under strong positive selection, particularly within transmembrane regions. Finally, despite the surprisingly high number of gene copies identified in this study, it is nonetheless probable that V1R diversity remains underestimated in these nonmodel primates and that complete characterization will be limited until high-coverage assembled genomes are available. PMID:24398377

  3. Molecular evolutionary characterization of a V1R subfamily unique to strepsirrhine primates.

    PubMed

    Yoder, Anne D; Chan, Lauren M; dos Reis, Mario; Larsen, Peter A; Campbell, C Ryan; Rasoloarison, Rodin; Barrett, Meredith; Roos, Christian; Kappeler, Peter; Bielawski, Joseph; Yang, Ziheng

    2014-01-01

    Vomeronasal receptor genes have frequently been invoked as integral to the establishment and maintenance of species boundaries among mammals due to the elaborate one-to-one correspondence between semiochemical signals and neuronal sensory inputs. Here, we report the most extensive sample of vomeronasal receptor class 1 (V1R) sequences ever generated for a diverse yet phylogenetically coherent group of mammals, the tooth-combed primates (suborder Strepsirrhini). Phylogenetic analysis confirms our intensive sampling from a single V1R subfamily, apparently unique to the strepsirrhine primates. We designate this subfamily as V1Rstrep. The subfamily retains extensive repertoires of gene copies that descend from an ancestral gene duplication that appears to have occurred prior to the diversification of all lemuriform primates excluding the basal genus Daubentonia (the aye-aye). We refer to the descendent clades as V1Rstrep-α and V1Rstrep-β. Comparison of the two clades reveals different amino acid compositions corresponding to the predicted ligand-binding site and thus potentially to altered functional profiles between the two. In agreement with previous studies of the mouse lemur (genus, Microcebus), the majority of V1Rstrep gene copies appear to be intact and under strong positive selection, particularly within transmembrane regions. Finally, despite the surprisingly high number of gene copies identified in this study, it is nonetheless probable that V1R diversity remains underestimated in these nonmodel primates and that complete characterization will be limited until high-coverage assembled genomes are available. PMID:24398377

  4. rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant

    PubMed Central

    Petrarca, Claudia; Clemente, Emanuela; Toto, Valentina; Iezzi, Manuela; Rossi, Cosmo; Zanotta, Stefania; Mistrello, Gianni; Zanoni, Ivan; Granucci, Francesca; Arioli, Stefania; Mora, Diego; Guglielmetti, Simone; Paganelli, Roberto; Di Gioacchino, Mario

    2014-01-01

    Lactobacilli are able to induce upregulation of co-stimulatory molecules in DCs with Th1 cytokines production and increase in Treg activity. This could explain the observed effectiveness of the prolonged administration of lactobacilli in the prevention of allergic disorders in infants and envisage the possible use of bacteria expressing the allergen for the specific immunotherapy of allergic diseases. Hence, we evaluated Streptococcus thermophilus (ST) expressing rBet v 1 as allergen delivery tool and adjuvant factor for immunotherapy in Betv1-sensitized mice. rBet v 1 gene was introduced and expressed in ST (ST[rBet v 1]). BALB/c mice were sensitized with rBet v 1 and then treated with either ST alone, ST[rBet v 1], or the combination of ST and rBet v 1, for 20 days. After 2 aerosol challenges, Treg frequency, in vitro allergen-induced cytokines, rBet v 1-specific IgE and IgG2a, and bronchial histology were made in harvested spleen, sera, and lung. Results were compared with those obtained from not-treated/sensitized mice. ST[rBet v 1] induced immunological and histological changes typical of successful SIT: increased frequency of Tregs and expression of Foxp3; decreased allergen-specific IgE/IgG2a ratio; decrease of in vitro rBet v 1-induced IL-4 from spleen cells; increased allergen-induced IL-10 and IFN-γ; drop of bronchial eosinophilia. ST and ST+rBet v 1 combination, even though induced a slight increase in the frequency of Tregs and moderate allergen-induced IL-10, were ineffective in reducing bronchial eosinophilia, allergen induced IL-4 and rBet v 1-specific IgE/IgG2a ratio. ST[rBet v 1] has tolerogenic and Th-1 skewing properties and efficiently delivers the allergen to the gut immune-system restraining and readdressing the established specific Th2 response toward the allergen in mice. PMID:24603094

  5. Accurate prediction of V1 location from cortical folds in a surface coordinate system

    PubMed Central

    Hinds, Oliver P.; Rajendran, Niranjini; Polimeni, Jonathan R.; Augustinack, Jean C.; Wiggins, Graham; Wald, Lawrence L.; Rosas, H. Diana; Potthast, Andreas; Schwartz, Eric L.; Fischl, Bruce

    2008-01-01

    Previous studies demonstrated substantial variability of the location of primary visual cortex (V1) in stereotaxic coordinates when linear volume-based registration is used to match volumetric image intensities (Amunts et al., 2000). However, other qualitative reports of V1 location (Smith, 1904; Stensaas et al., 1974; Rademacher et al., 1993) suggested a consistent relationship between V1 and the surrounding cortical folds. Here, the relationship between folds and the location of V1 is quantified using surface-based analysis to generate a probabilistic atlas of human V1. High-resolution (about 200 μm) magnetic resonance imaging (MRI) at 7 T of ex vivo human cerebral hemispheres allowed identification of the full area via the stria of Gennari: a myeloarchitectonic feature specific to V1. Separate, whole-brain scans were acquired using MRI at 1.5 T to allow segmentation and mesh reconstruction of the cortical gray matter. For each individual, V1 was manually identified in the high-resolution volume and projected onto the cortical surface. Surface-based intersubject registration (Fischl et al., 1999b) was performed to align the primary cortical folds of individual hemispheres to those of a reference template representing the average folding pattern. An atlas of V1 location was constructed by computing the probability of V1 inclusion for each cortical location in the template space. This probabilistic atlas of V1 exhibits low prediction error compared to previous V1 probabilistic atlases built in volumetric coordinates. The increased predictability observed under surface-based registration suggests that the location of V1 is more accurately predicted by the cortical folds than by the shape of the brain embedded in the volume of the skull. In addition, the high quality of this atlas provides direct evidence that surface-based intersubject registration methods are superior to volume-based methods at superimposing functional areas of cortex, and therefore are better

  6. rBet v 1 immunotherapy of sensitized mice with Streptococcus thermophilus as vehicle and adjuvant.

    PubMed

    Petrarca, Claudia; Clemente, Emanuela; Toto, Valentina; Iezzi, Manuela; Rossi, Cosmo; Zanotta, Stefania; Mistrello, Gianni; Zanoni, Ivan; Granucci, Francesca; Arioli, Stefania; Mora, Diego; Guglielmetti, Simone; Paganelli, Roberto; Di Gioacchino, Mario

    2014-01-01

    Lactobacilli are able to induce upregulation of co-stimulatory molecules in DCs with Th1 cytokines production and increase in Treg activity. This could explain the observed effectiveness of the prolonged administration of lactobacilli in the prevention of allergic disorders in infants and envisage the possible use of bacteria expressing the allergen for the specific immunotherapy of allergic diseases. Hence, we evaluated Streptococcus thermophilus (ST) expressing rBet v 1 as allergen delivery tool and adjuvant factor for immunotherapy in Betv1-sensitized mice. rBet v 1 gene was introduced and expressed in ST (ST[rBet v 1]). BALB/c mice were sensitized with rBet v 1 and then treated with either ST alone, ST[rBet v 1], or the combination of ST and rBet v 1, for 20 days. After 2 aerosol challenges, Treg frequency, in vitro allergen-induced cytokines, rBet v 1-specific IgE and IgG2a, and bronchial histology were made in harvested spleen, sera, and lung. Results were compared with those obtained from not-treated/sensitized mice. ST[rBet v 1] induced immunological and histological changes typical of successful SIT: increased frequency of Tregs and expression of Foxp3; decreased allergen-specific IgE/IgG2a ratio; decrease of in vitro rBet v 1-induced IL-4 from spleen cells; increased allergen-induced IL-10 and IFN-γ; drop of bronchial eosinophilia. ST and ST+rBet v 1 combination, even though induced a slight increase in the frequency of Tregs and moderate allergen-induced IL-10, were ineffective in reducing bronchial eosinophilia, allergen induced IL-4 and rBet v 1-specific IgE/IgG2a ratio. ST[rBet v 1] has tolerogenic and Th-1 skewing properties and efficiently delivers the allergen to the gut immune-system restraining and readdressing the established specific Th2 response toward the allergen in mice. PMID:24603094

  7. The Bet v 1 fold: an ancient, versatile scaffold for binding of large, hydrophobic ligands

    PubMed Central

    2008-01-01

    Background The major birch pollen allergen, Bet v 1, is a member of the ubiquitous PR-10 family of plant pathogenesis-related proteins. In recent years, a number of diverse plant proteins with low sequence similarity to Bet v 1 was identified. In addition, determination of the Bet v 1 structure revealed the existence of a large superfamily of structurally related proteins. In this study, we aimed to identify and classify all Bet v 1-related structures from the Protein Data Bank and all Bet v 1-related sequences from the Uniprot database. Results Structural comparisons of representative members of already known protein families structurally related to Bet v 1 with all entries of the Protein Data Bank yielded 47 structures with non-identical sequences. They were classified into eleven families, five of which were newly identified and not included in the Structural Classification of Proteins database release 1.71. The taxonomic distribution of these families extracted from the Pfam protein family database showed that members of the polyketide cyclase family and the activator of Hsp90 ATPase homologue 1 family were distributed among all three superkingdoms, while members of some bacterial families were confined to a small number of species. Comparison of ligand binding activities of Bet v 1-like superfamily members revealed that their functions were related to binding and metabolism of large, hydrophobic compounds such as lipids, hormones, and antibiotics. Phylogenetic relationships within the Bet v 1 family, defined as the group of proteins with significant sequence similarity to Bet v 1, were determined by aligning 264 Bet v 1-related sequences. A distance-based phylogenetic tree yielded a classification into 11 subfamilies, nine exclusively containing plant sequences and two subfamilies of bacterial proteins. Plant sequences included the pathogenesis-related proteins 10, the major latex proteins/ripening-related proteins subfamily, and polyketide cyclase

  8. Co-evolutionary dynamics of the bacteria Vibrio sp. CV1 and phages V1G, V1P1, and V1P2: implications for phage therapy.

    PubMed

    Barbosa, Camilo; Venail, Patrick; Holguin, Angela V; Vives, Martha J

    2013-11-01

    Bacterial infections are the second largest cause of mortality in shrimp hatcheries. Among them, bacteria from the genus Vibrio constitute a major threat. As the use of antibiotics may be ineffective and banned from the food sector, alternatives are required. Historically, phage therapy, which is the use of bacteriophages, is thought to be a promising option to fight against bacterial infections. However, as for antibiotics, resistance can be rapidly developed. Since the emergence of resistance is highly undesirable, a formal characterization of the dynamics of its acquisition is mandatory. Here, we explored the co-evolutionary dynamics of resistance between the bacteria Vibrio sp. CV1 and the phages V1G, V1P1, and V1P2. Single-phage treatments as well as a cocktail composed of the three phages were considered. We found that in the presence of a single phage, bacteria rapidly evolved resistance, and the phages decreased their infectivity, suggesting that monotherapy may be an inefficient treatment to fight against Vibrio infections in shrimp hatcheries. On the contrary, the use of a phage cocktail considerably delayed the evolution of resistance and sustained phage infectivity for periods in which shrimp larvae are most susceptible to bacterial infections, suggesting the simultaneous use of multiple phages as a serious strategy for the control of vibriosis. These findings are very promising in terms of their consequences to different industrial and medical scenarios where bacterial infections are present. PMID:24013213

  9. Sodium channel diversity in the vestibular ganglion: NaV1.5, NaV1.8, and tetrodotoxin-sensitive currents.

    PubMed

    Liu, Xiao-Ping; Wooltorton, Julian R A; Gaboyard-Niay, Sophie; Yang, Fu-Chia; Lysakowski, Anna; Eatock, Ruth Anne

    2016-05-01

    Firing patterns differ between subpopulations of vestibular primary afferent neurons. The role of sodium (NaV) channels in this diversity has not been investigated because NaV currents in rodent vestibular ganglion neurons (VGNs) were reported to be homogeneous, with the voltage dependence and tetrodotoxin (TTX) sensitivity of most neuronal NaV channels. RT-PCR experiments, however, indicated expression of diverse NaV channel subunits in the vestibular ganglion, motivating a closer look. Whole cell recordings from acutely dissociated postnatal VGNs confirmed that nearly all neurons expressed NaV currents that are TTX-sensitive and have activation midpoints between -30 and -40 mV. In addition, however, many VGNs expressed one of two other NaV currents. Some VGNs had a small current with properties consistent with NaV1.5 channels: low TTX sensitivity, sensitivity to divalent cation block, and a relatively negative voltage range, and some VGNs showed NaV1.5-like immunoreactivity. Other VGNs had a current with the properties of NaV1.8 channels: high TTX resistance, slow time course, and a relatively depolarized voltage range. In two NaV1.8 reporter lines, subsets of VGNs were labeled. VGNs with NaV1.8-like TTX-resistant current also differed from other VGNs in the voltage dependence of their TTX-sensitive currents and in the voltage threshold for spiking and action potential shape. Regulated expression of NaV channels in primary afferent neurons is likely to selectively affect firing properties that contribute to the encoding of vestibular stimuli. PMID:26936982

  10. Nociceptor-specific gene deletion using heterozygous NaV1.8-Cre recombinase mice.

    PubMed

    Stirling, L Caroline; Forlani, Greta; Baker, Mark D; Wood, John N; Matthews, Elizabeth A; Dickenson, Anthony H; Nassar, Mohammed A

    2005-01-01

    NaV1.8 is a voltage-gated sodium channel expressed only in a subset of sensory neurons of which more than 85% are nociceptors. In order to delete genes in nociceptive neurons, we generated heterozygous transgenic mice expressing Cre recombinase under the control of the NaV1.8 promoter. Functional Cre recombinase expression replicated precisely the expression pattern of NaV1.8. Cre expression began at embryonic day 14 in small diameter neurons in dorsal root, trigeminal and nodose ganglia, but was absent in non-neuronal or CNS tissues into adulthood. Sodium channel subtypes were normal in isolated DRG neurons. Pain behaviour in response to mechanical or thermal stimuli, and in acute, inflammatory and neuropathic pain was also normal. These data demonstrate that the heterozygous NaV1.8-Cre mouse line is a useful tool to analyse the effects of deleting floxed genes on pain behaviour. PMID:15621361

  11. Stabilization of the Dimeric Birch Pollen Allergen Bet v 1 Impacts Its Immunological Properties*

    PubMed Central

    Kofler, Stefan; Ackaert, Chloé; Samonig, Martin; Asam, Claudia; Briza, Peter; Horejs-Hoeck, Jutta; Cabrele, Chiara; Ferreira, Fatima; Duschl, Albert; Huber, Christian; Brandstetter, Hans

    2014-01-01

    Many allergens share several biophysical characteristics, including the capability to undergo oligomerization. The dimerization mechanism in Bet v 1 and its allergenic properties are so far poorly understood. Here, we report crystal structures of dimeric Bet v 1, revealing a noncanonical incorporation of cysteine at position 5 instead of genetically encoded tyrosine. Cysteine polysulfide bridging stabilized different dimeric assemblies, depending on the polysulfide linker length. These dimers represent quaternary arrangements that are frequently observed in related proteins, reflecting their prevalence in unmodified Bet v 1. These conclusions were corroborated by characteristic immunologic properties of monomeric and dimeric allergen variants. Hereby, residue 5 could be identified as an allergenic hot spot in Bet v 1. The presented results refine fundamental principles in protein chemistry and emphasize the importance of protein modifications in understanding the molecular basis of allergenicity. PMID:24253036

  12. 10.4% Efficient triple organic solar cells containing near infrared absorbers

    NASA Astrophysics Data System (ADS)

    Meerheim, Rico; Körner, Christian; Oesen, Benjamin; Leo, Karl

    2016-03-01

    The efficiency of organic solar cells can be increased by serially stacked subcells with spectrally different absorber materials. For the triple junction devices presented here, we use the small molecule donor materials DCV5T-Me for the green region and Tol2-benz-bodipy or Ph2-benz-bodipy as near infrared absorbers. The broader spectral response allows an efficiency increase from a pure DCV5T-Me triple cell to a triple junction containing a Ph2-benz-bodipy subcell, reaching 10.4%. As often observed for organic photovoltaics, the efficiency is further increased at low light intensities to 11%, which allows improved energy harvesting under real outdoor conditions and better performance indoor.

  13. Protein kinase A modulation of CaV1.4 calcium channels

    PubMed Central

    Sang, Lingjie; Dick, Ivy E.; Yue, David T.

    2016-01-01

    The regulation of L-type Ca2+ channels by protein kinase A (PKA) represents a crucial element within cardiac, skeletal muscle and neurological systems. Although much work has been done to understand this regulation in cardiac CaV1.2 Ca2+ channels, relatively little is known about the closely related CaV1.4 L-type Ca2+ channels, which feature prominently in the visual system. Here we find that CaV1.4 channels are indeed modulated by PKA phosphorylation within the inhibitor of Ca2+-dependent inactivation (ICDI) motif. Phosphorylation of this region promotes the occupancy of calmodulin on the channel, thus increasing channel open probability (PO) and Ca2+-dependent inactivation. Although this interaction seems specific to CaV1.4 channels, introduction of ICDI1.4 to CaV1.3 or CaV1.2 channels endows these channels with a form of PKA modulation, previously unobserved in heterologous systems. Thus, this mechanism may not only play an important role in the visual system but may be generalizable across the L-type channel family. PMID:27456671

  14. Protein kinase A modulation of CaV1.4 calcium channels

    NASA Astrophysics Data System (ADS)

    Sang, Lingjie; Dick, Ivy E.; Yue, David T.

    2016-07-01

    The regulation of L-type Ca2+ channels by protein kinase A (PKA) represents a crucial element within cardiac, skeletal muscle and neurological systems. Although much work has been done to understand this regulation in cardiac CaV1.2 Ca2+ channels, relatively little is known about the closely related CaV1.4 L-type Ca2+ channels, which feature prominently in the visual system. Here we find that CaV1.4 channels are indeed modulated by PKA phosphorylation within the inhibitor of Ca2+-dependent inactivation (ICDI) motif. Phosphorylation of this region promotes the occupancy of calmodulin on the channel, thus increasing channel open probability (PO) and Ca2+-dependent inactivation. Although this interaction seems specific to CaV1.4 channels, introduction of ICDI1.4 to CaV1.3 or CaV1.2 channels endows these channels with a form of PKA modulation, previously unobserved in heterologous systems. Thus, this mechanism may not only play an important role in the visual system but may be generalizable across the L-type channel family.

  15. Topographic organization of V1 projections through the corpus callosum in humans.

    PubMed

    Saenz, M; Fine, I

    2010-10-01

    The visual cortex in each hemisphere is linked to the opposite hemisphere by axonal projections that pass through the splenium of the corpus callosum. Visual-callosal connections in humans and macaques are found along the V1/V2 border where the vertical meridian is represented. Here we identify the topography of V1 vertical midline projections through the splenium within six human subjects with normal vision using diffusion-weighted MR imaging and probabilistic diffusion tractography. Tractography seed points within the splenium were classified according to their estimated connectivity profiles to topographic subregions of V1, as defined by functional retinotopic mapping. First, we report a ventral-dorsal mapping within the splenium with fibers from ventral V1 (representing the upper visual field) projecting to the inferior-anterior corner of the splenium and fibers from dorsal V1 (representing the lower visual field) projecting to the superior-posterior end. Second, we also report an eccentricity gradient of projections from foveal-to-peripheral V1 subregions running in the anterior-superior to posterior-inferior direction, orthogonal to the dorsal-ventral mapping. These results confirm and add to a previous diffusion MRI study (Dougherty et al., 2005) which identified a dorsal/ventral mapping of human splenial fibers. These findings yield a more detailed view of the structural organization of the splenium than previously reported and offer new opportunities to study structural plasticity in the visual system.

  16. Single-molecule Analysis of Inhibitory Pausing States of V1-ATPase*

    PubMed Central

    Uner, Naciye Esma; Nishikawa, Yoshihiro; Okuno, Daichi; Nakano, Masahiro; Yokoyama, Ken; Noji, Hiroyuki

    2012-01-01

    V1-ATPase, the hydrophilic V-ATPase domain, is a rotary motor fueled by ATP hydrolysis. Here, we found that Thermus thermophilus V1-ATPase shows two types of inhibitory pauses interrupting continuous rotation: a short pause (SP, 4.2 s) that occurred frequently during rotation, and a long inhibitory pause (LP, >30 min) that terminated all active rotations. Both pauses occurred at the same angle for ATP binding and hydrolysis. Kinetic analysis revealed that the time constants of inactivation into and activation from the SP were too short to represent biochemically predicted ADP inhibition, suggesting that SP is a newly identified inhibitory state of V1-ATPase. The time constant of inactivation into LP was 17 min, consistent with one of the two time constants governing the inactivation process observed in bulk ATPase assay. When forcibly rotated in the forward direction, V1 in LP resumed active rotation. Solution ADP suppressed the probability of mechanical activation, suggesting that mechanical rotation enhanced inhibitory ADP release. These features were highly consistent with mechanical activation of ADP-inhibited F1, suggesting that LP represents the ADP-inhibited state of V1-ATPase. Mechanical activation largely depended on the direction and angular displacement of forced rotation, implying that V1-ATPase rotation modulates the off rate of ADP. PMID:22736762

  17. Modulation of V1 Spike Response by Temporal Interval of Spatiotemporal Stimulus Sequence

    PubMed Central

    Kim, Taekjun; Kim, HyungGoo R.; Kim, Kayeon; Lee, Choongkil

    2012-01-01

    The spike activity of single neurons of the primary visual cortex (V1) becomes more selective and reliable in response to wide-field natural scenes compared to smaller stimuli confined to the classical receptive field (RF). However, it is largely unknown what aspects of natural scenes increase the selectivity of V1 neurons. One hypothesis is that modulation by surround interaction is highly sensitive to small changes in spatiotemporal aspects of RF surround. Such a fine-tuned modulation would enable single neurons to hold information about spatiotemporal sequences of oriented stimuli, which extends the role of V1 neurons as a simple spatiotemporal filter confined to the RF. In the current study, we examined the hypothesis in the V1 of awake behaving monkeys, by testing whether the spike response of single V1 neurons is modulated by temporal interval of spatiotemporal stimulus sequence encompassing inside and outside the RF. We used two identical Gabor stimuli that were sequentially presented with a variable stimulus onset asynchrony (SOA): the preceding one (S1) outside the RF and the following one (S2) in the RF. This stimulus configuration enabled us to examine the spatiotemporal selectivity of response modulation from a focal surround region. Although S1 alone did not evoke spike responses, visual response to S2 was modulated for SOA in the range of tens of milliseconds. These results suggest that V1 neurons participate in processing spatiotemporal sequences of oriented stimuli extending outside the RF. PMID:23091631

  18. Statistical Comparison of Spike Responses to Natural Stimuli in Monkey Area V1 With Simulated Responses of a Detailed Laminar Network Model for a Patch of V1

    PubMed Central

    Schuch, Klaus; Logothetis, Nikos K.; Maass, Wolfgang

    2011-01-01

    A major goal of computational neuroscience is the creation of computer models for cortical areas whose response to sensory stimuli resembles that of cortical areas in vivo in important aspects. It is seldom considered whether the simulated spiking activity is realistic (in a statistical sense) in response to natural stimuli. Because certain statistical properties of spike responses were suggested to facilitate computations in the cortex, acquiring a realistic firing regimen in cortical network models might be a prerequisite for analyzing their computational functions. We present a characterization and comparison of the statistical response properties of the primary visual cortex (V1) in vivo and in silico in response to natural stimuli. We recorded from multiple electrodes in area V1 of 4 macaque monkeys and developed a large state-of-the-art network model for a 5 × 5-mm patch of V1 composed of 35,000 neurons and 3.9 million synapses that integrates previously published anatomical and physiological details. By quantitative comparison of the model response to the “statistical fingerprint” of responses in vivo, we find that our model for a patch of V1 responds to the same movie in a way which matches the statistical structure of the recorded data surprisingly well. The deviation between the firing regimen of the model and the in vivo data are on the same level as deviations among monkeys and sessions. This suggests that, despite strong simplifications and abstractions of cortical network models, they are nevertheless capable of generating realistic spiking activity. To reach a realistic firing state, it was not only necessary to include both N-methyl-d-aspartate and GABAB synaptic conductances in our model, but also to markedly increase the strength of excitatory synapses onto inhibitory neurons (>2-fold) in comparison to literature values, hinting at the importance to carefully adjust the effect of inhibition for achieving realistic dynamics in current network

  19. Rationally Targeted Mutations at the V1V2 Domain of the HIV-1 Envelope to Augment Virus Neutralization by Anti-V1V2 Monoclonal Antibodies.

    PubMed

    Shen, Guomiao; Upadhyay, Chitra; Zhang, Jing; Pan, Ruimin; Zolla-Pazner, Susan; Kong, Xiang-Peng; Hioe, Catarina E

    2015-01-01

    HIV-1 envelope glycoproteins (Env) are the only viral antigens present on the virus surface and serve as the key targets for virus-neutralizing antibodies. However, HIV-1 deploys multiple strategies to shield the vulnerable sites on its Env from neutralizing antibodies. The V1V2 domain located at the apex of the HIV-1 Env spike is known to encompass highly variable loops, but V1V2 also contains immunogenic conserved elements recognized by cross-reactive antibodies. This study evaluates human monoclonal antibodies (mAbs) against V2 epitopes which overlap with the conserved integrin α4β7-binding LDV/I motif, designated as the V2i (integrin) epitopes. We postulate that the V2i Abs have weak or no neutralizing activities because the V2i epitopes are often occluded from antibody recognition. To gain insights into the mechanisms of the V2i occlusion, we evaluated three elements at the distal end of the V1V2 domain shown in the structure of V2i epitope complexed with mAb 830A to be important for antibody recognition of the V2i epitope. Amino-acid substitutions at position 179 that restore the LDV/I motif had minimal effects on virus sensitivity to neutralization by most V2i mAbs. However, a charge change at position 153 in the V1 region significantly increased sensitivity of subtype C virus ZM109 to most V2i mAbs. Separately, a disulfide bond introduced to stabilize the hypervariable region of V2 loop also enhanced virus neutralization by some V2i mAbs, but the effects varied depending on the virus. These data demonstrate that multiple elements within the V1V2 domain act independently and in a virus-dependent fashion to govern the antibody recognition and accessibility of V2i epitopes, suggesting the need for multi-pronged strategies to counter the escape and the shielding mechanisms obstructing the V2i Abs from neutralizing HIV-1. PMID:26491873

  20. Antisense-mediated knockdown of Na(V)1.8, but not Na(V)1.9, generates inhibitory effects on complete Freund's adjuvant-induced inflammatory pain in rat.

    PubMed

    Yu, Yao-Qing; Zhao, Feng; Guan, Su-Min; Chen, Jun

    2011-01-01

    Tetrodotoxin-resistant (TTX-R) sodium channels Na(V)1.8 and Na(V)1.9 in sensory neurons were known as key pain modulators. Comparing with the widely reported Na(V)1.8, roles of Na(V)1.9 on inflammatory pain are poorly studied by antisense-induced specific gene knockdown. Here, we used molecular, electrophysiological and behavioral methods to examine the effects of antisense oligodeoxynucleotide (AS ODN) targeting Na(V)1.8 and Na(V)1.9 on inflammatory pain. Following complete Freund's adjuvant (CFA) inflammation treatment, Na(V)1.8 and Na(V)1.9 in rat dorsal root ganglion (DRG) up-regulated mRNA and protein expressions and increased sodium current densities. Immunohistochemical data demonstrated that Na(V)1.8 mainly localized in medium and small-sized DRG neurons, whereas Na(V)1.9 only expressed in small-sized DRG neurons. Intrathecal (i.t.) delivery of AS ODN was used to down-regulate Na(V)1.8 or Na(V)1.9 expressions confirmed by immunohistochemistry and western blot. Unexpectedly, behavioral tests showed that only Na(V)1.8 AS ODN, but not Na(V)1.9 AS ODN could reverse CFA-induced heat and mechanical hypersensitivity. Our data indicated that TTX-R sodium channels Na(V)1.8 and Na(V)1.9 in primary sensory neurons played distinct roles in CFA-induced inflammatory pain and suggested that antisense oligodeoxynucleotide-mediated blocking of key pain modulator might point toward a potential treatment strategy against certain types of inflammatory pain. PMID:21572961

  1. CRMP2 protein SUMOylation modulates NaV1.7 channel trafficking.

    PubMed

    Dustrude, Erik T; Wilson, Sarah M; Ju, Weina; Xiao, Yucheng; Khanna, Rajesh

    2013-08-23

    Voltage-gated sodium channel (NaV) trafficking is incompletely understood. Post-translational modifications of NaVs and/or auxiliary subunits and protein-protein interactions have been posited as NaV-trafficking mechanisms. Here, we tested if modification of the axonal collapsin response mediator protein 2 (CRMP2) by a small ubiquitin-like modifier (SUMO) could affect NaV trafficking; CRMP2 alters the extent of NaV slow inactivation conferred by the anti-epileptic (R)-lacosamide, implying NaV-CRMP2 functional coupling. Expression of a CRMP2 SUMOylation-incompetent mutant (CRMP2-K374A) in neuronal model catecholamine A differentiated (CAD) cells did not alter lacosamide-induced NaV slow inactivation compared with CAD cells expressing wild type CRMP2. Like wild type CRMP2, CRMP2-K374A expressed robustly in CAD cells. Neurite outgrowth, a canonical CRMP2 function, was moderately reduced by the mutation but was still significantly higher than enhanced GFP-transfected cortical neurons. Notably, huwentoxin-IV-sensitive NaV1.7 currents, which predominate in CAD cells, were significantly reduced in CAD cells expressing CRMP2-K374A. Increasing deSUMOylation with sentrin/SUMO-specific protease SENP1 or SENP2 in wild type CRMP2-expressing CAD cells decreased NaV1.7 currents. Consistent with a reduction in current density, biotinylation revealed a significant reduction in surface NaV1.7 levels in CAD cells expressing CRMP2-K374A; surface NaV1.7 expression was also decreased by SENP1 + SENP2 overexpression. Currents in HEK293 cells stably expressing NaV1.7 were reduced by CRMP2-K374A in a manner dependent on the E2-conjugating enzyme Ubc9. No decrement in current density was observed in HEK293 cells co-expressing CRMP2-K374A and NaV1.1 or NaV1.3. Diminution of sodium currents, largely NaV1.7, was recapitulated in sensory neurons expressing CRMP2-K374A. Our study elucidates a novel regulatory mechanism that utilizes CRMP2 SUMOylation to choreograph NaV1.7 trafficking.

  2. Molecular cloning and expression of a bush related CmV1 gene in tropical pumpkin.

    PubMed

    Wu, Tao; Cao, Jiashu

    2010-02-01

    A bush-type plant was selected from tropical pumpkin 'cga' (Cucurbita moschata Duchesne) in order to study the vine development in C. moschata. In this study, a novel gene encoding NADH dehydrogenase was isolated from the vine line (cgaV) of C. moschata, that was not expressed in the near isogenic bush line (cgaBu). This gene, designated as CmV1 (C. moschata vine 1), was 545 bp in length and was composed of a 477 bp open reading frame, which had 99% nucleotide similarity to the chloroplast ndhJ gene for NADH dehydrogenase subunit J from Brassica oleracea. The deduced amino acid sequence of CmV1 had 99% similarity to NADH dehydrogenase subunit J from Arabidopsis and had 98% similarity to NADH dehydrogenase subunit from Barbarea verna. Analysis of the basic characteristics of the CmV1 protein revealed that it has one Respiratory chain NADH dehydrogenase 30 kD subunit signature, three N-myristoylation sites, one Casein kinase II phosphorylation site, and one Protein kinase C phosphorylation site. Reverse transcriptase-PCR analysis showed that CmV1 was expressed at a high level in the internodes and hypocotyls and was expressed stronger in elongating internodes than in fully expanded internodes. In conclusion, results obtained in the present study suggest that CmV1 gene might play important roles in vine elongation of tropical pumpkin.

  3. Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior.

    PubMed

    Ferris, Craig F; Lu, Shi-Fang; Messenger, Tara; Guillon, Christophe D; Heindel, Ned; Miller, Marvin; Koppel, Gary; Robert Bruns, F; Simon, Neal G

    2006-02-01

    Arginine vasopressin functions as a neurochemical signal in the brain to affect social behavior. There is an expanding literature from animal and human studies showing that vasopressin, through the vasopressin 1A receptor (V1A), can stimulate aggressive behavior. Using a novel monocylic beta lactam platform, a series of orally active vasopressin V1a antagonists was developed with high affinity for the human receptor. SRX251 was chosen from this series of V1a antagonists to screen for effects on serenic activity in a resident-intruder model of offensive aggression. Resident, male Syrian golden hamsters were given oral doses of SRX251 or intraperitoneal Manning compound, a selective V1a receptor antagonist with reduced brain penetrance, at doses of 0.2 microg, 20 microg, 2 mg/kg or vehicle. When tested 90-120 min later, SRX251, but not Manning compound, caused a significant dose-dependent reduction in offensive aggression toward intruders as measured by latency to bite and number of bites. The reduction in aggression persisted for over 6 h and was no longer present 12 h post treatment. SRX251 did not alter the amount of time the resident investigated the intruder, olfactory communication, general motor activity, or sexual motivation. These data corroborate previous studies showing a role for vasopressin neurotransmission in aggression and suggest that V1a receptor antagonists may be used to treat interpersonal violence co-occurring with such illness as ADHD, autism, bipolar disorder, and substance abuse. PMID:16504276

  4. [Structure of Response and Dynamics of Preferred Orientation in Cat's V1 Neurons].

    PubMed

    Kozhukhov, S A; Saltykov, K A; Lazareva, N A

    2016-01-01

    Preferred orientation of V1 neurons was changed during the respons time course. In order to reveal mechanisms of such changes, spike trains of single neurons to flashed bars of different orientations were studied by means of principal component and frequency-domain analysis of the spike density functions. There was found out that: 1. contribution of each of the components was dependent on the stimulus orientation. 2. the principal components of V1 neurons responses contain different kinds of transient and sustained parts and rhythmic oscillations in the theta/alpha and beta-bands. 3. There was no correlation between transient parts as well as between rhythmic oscillations within the same frequency band in different components. Taken together, the data obtained allow us to suggest that during generation of response there is a shift of dominance of the components with different orientations which determines the dynamics of the preferred orientations of V1 neurons. PMID:27263274

  5. V1 neurons respond to luminance changes faster than contrast changes.

    PubMed

    Wang, Wen-Liang; Li, Ran; Ding, Jian; Tao, Louis; Li, Da-Peng; Wang, Yi

    2015-12-04

    Luminance and contrast are two major attributes of objects in the visual scene. Luminance and contrast information received by visual neurons are often updated simultaneously. We examined the temporal response properties of neurons in the primary visual cortex (V1) to stimuli whose luminance and contrast were simultaneously changed by 50 Hz. We found that response tuning to luminance changes precedes tuning to contrast changes in V1. For most V1 neurons, the onset time of response tuning to luminance changes was shorter than that to contrast changes. Most neurons carried luminance information in the early response stage, while all neurons carried both contrast and luminance information in the late response stage. The early luminance response suggests that cortical processing for luminance is not as slow as previously thought.

  6. V1 neurons respond to luminance changes faster than contrast changes

    PubMed Central

    Wang, Wen-Liang; Li, Ran; Ding, Jian; Tao, Louis; Li, Da-Peng; Wang, Yi

    2015-01-01

    Luminance and contrast are two major attributes of objects in the visual scene. Luminance and contrast information received by visual neurons are often updated simultaneously. We examined the temporal response properties of neurons in the primary visual cortex (V1) to stimuli whose luminance and contrast were simultaneously changed by 50 Hz. We found that response tuning to luminance changes precedes tuning to contrast changes in V1. For most V1 neurons, the onset time of response tuning to luminance changes was shorter than that to contrast changes. Most neurons carried luminance information in the early response stage, while all neurons carried both contrast and luminance information in the late response stage. The early luminance response suggests that cortical processing for luminance is not as slow as previously thought. PMID:26634691

  7. Synthesis, Structure, and Characterization of Cu4S10(4-methylpyridine)4

    NASA Technical Reports Server (NTRS)

    Hepp, Aloysius F.; Richman, Robert M.; Duraj, Stan A.; Andras, Maria T.; Moore, Hall L.; Sabat, Michal; Eckles, William E.; Martuch, Robert A.

    1996-01-01

    The title compound, Cu4S10(4-methylpyridine)(sub 4) (dot) 4-methylpyridine was prepared by three different reactions: the oxidation of copper powder by sulfur and the reaction of copper (I) sulfide (or CuBr (dot) SMe2) with excess sulfur, both in the coordinating solvent, 4-methylpyridine. Red crystals of the compound obtained by layering with hexanes were subjected to single crystal X-ray diffraction. The structure was refined to R = 0.026 and R(sub w) = 0.036 in a space group P1bar (No. 2), with Z = 2, a = 13.983 (2) A, b = 15.384 (2) A, c = 9.660 (1) A, alpha = 93.87 (1)deg., beta = 93.38 (1)deg., gamma = 99.78 (1)deg., V = 2037.9 (9) A(exp 3). The compound has approximate S(sub 4) symmetry and consists of two pentasulfide chains linking four Cu(I) ions, each with a corrdinating 2-methylpyridine. The infrared spectrum was dominated by absorption due to coordinated 4-methylpyridine with several low-energy peaks attributable to S-S stretches, which were also observed by Raman spectroscopy. A featureless electronic absorption spectrum yielded a single peak in the near ultraviolet upon computer enhancement (lambda = 334 nm, epsilon = 10,000), most likely an intraligand transition. Cyclic voltammetry indicates that the polysulfide complex undergoes irrversible oxidation and reduction at +0.04 and -0.34 V vs. SCE, respectively, at 298 K in 4-methylpyridine when swept at 20 mV/sec. The electrochemical behavior was unvaried even at sweep rates as high as 100 V/sec.

  8. Empowering Reentrant Projections from V5 to V1 Boosts Sensitivity to Motion.

    PubMed

    Romei, Vincenzo; Chiappini, Emilio; Hibbard, Paul B; Avenanti, Alessio

    2016-08-22

    Evidence from macaques [1] and humans [2, 3] has shown that back projections from extrastriate areas to the primary visual area (V1) determine whether visual awareness will arise. For example, reentrant projections from the visual motion area (V5) to V1 are considered to be critical for awareness of motion [2, 3]. If these projections are also instrumental to functional processing of moving stimuli [4-8], then increasing synaptic efficacy in V5-V1 connections should induce functionally relevant short-term plastic changes, resulting in enhanced perception of visual motion. Using transcranial magnetic stimulation (TMS), we applied a novel cortico-cortical paired associative stimulation (ccPAS) protocol to transiently enhance visual motion sensitivity and demonstrate both the functional relevance of V5-V1 reentrant projections to motion perception and their plasticity. Specifically, we found that ccPAS aimed at strengthening reentrant connectivity from V5 to V1 (but not in the opposite direction) enhanced the human ability to perceive coherent visual motion. This perceptual enhancement followed the temporal profile of Hebbian plasticity [9-18] and was observed only when an optimal timing of 20 ms between TMS pulses [2, 3, 5, 6] was used, not when TMS pulses were delivered synchronously. Thus, plastic change is critically dependent on both the direction and timing of connectivity; if either of these requirements was not met, perceptual enhancement did not take place. We therefore provide novel causal evidence that V5-V1 back projections, instrumental to motion perception, are functionally malleable. These findings have implications for theoretical models of visual awareness and for the rehabilitation of visual deficits. PMID:27524488

  9. Correlation of Vision Loss with Tactile-Evoked V1 Responses in Retinitis Pigmentosa

    PubMed Central

    Cunningham, Samantha I.; Weiland, James D.; Bao, Pinglei; Lopez-Jaime, Gilberto Raul; Tjan, Bosco S.

    2014-01-01

    Neuroimaging studies have shown that the visual cortex of visually impaired humans is active during tactile tasks. We sought to determine if this cross-modal activation in the primary visual cortex is correlated with vision loss in individuals with retinitis pigmentosa (RP), an inherited degenerative photoreceptor disease that progressively diminishes vision later in life. RP and sighted subjects completed three tactile tasks: a symmetry discrimination task, a Braille-dot counting task, and a sandpaper roughness discrimination task. We measured tactile-evoked blood oxygenation level dependent (BOLD) responses using functional magnetic resonance imaging (fMRI). For each subject, we quantified the cortical extent of the tactile-evoked response by the proportion of modulated voxels within the primary visual cortex (V1) and its strength by the mean absolute modulation amplitude of the modulated voxels. We characterized vision loss in terms of visual acuity and the areal proportion of V1 that corresponds to the preserved visual field. Visual acuity and proportion of the preserved visual field both had a highly significant effect on the cortical extent of the V1 BOLD response to tactile stimulation, while visual acuity also had a significant effect on the strength of the V1 response. These effects of vision loss on cross-modal responses were reliable despite high inter-subject variability. Controlling for task-evoked responses in the primary somatosensory cortex (S1) across subjects further strengthened the effects of vision loss on cross-model responses in V1. We propose that such cross-modal responses in V1 and other visual areas may be used as a cortically localized biomarker to account for individual differences in visual performance following sight recovery treatments. PMID:25449160

  10. Population Response Propagation to Extrastriate Areas Evoked by Intracortical Electrical Stimulation in V1

    PubMed Central

    Fehérvári, Tamás D.; Yagi, Tetsuya

    2016-01-01

    The mouse visual system has multiple extrastriate areas surrounding V1 each with a distinct representation of the visual field and unique functional and connectivity profiles, which are believed to form two parallel processing streams, similar to the ventral and dorsal streams in primates. At the same time, mouse visual areas have a high degree of interconnectivity, in particular V1 sends input to all higher visual areas. The study of these direct connections can further our understanding of the cortical processing of visual signals in the early mammalian cortex. Several studies have been published about the anatomy of these connections, but an in vivo electrophysiological characterization and comparison of the transmission to multiple extrastriate areas has not yet been reported. We used intracortical electrical stimulation combined with RH1691 VSD imaging in adult C57BL/6 mice in urethane anesthesia to analyze interareal transmission from V1 to extrastriate areas in superficial cortical layers. We found seven extrastriate response sites (five lateral, two medial) in a spatial pattern similar to area maps of the mouse visual cortex and, by shifting the location of V1 stimulation, demonstrated that the evoked responses in LM and AL were in accordance with the visuotopic mappings of these areas known from anatomy and in vivo studies. These two sites, considered to be gateways to their processing streams, had shorter latencies and faster transmission speeds than other extrastriate response sites. Short latency differences between response sites, and that TTX injection into LM reduced but did not eliminate other extrastriate responses indicated that the evoked cortical activity was, at least partially, transmitted directly from V1 to extrastriate areas. This study reports on analysis of interareal transmission from V1 to multiple extrastriate areas in mouse using intracortical electrical stimulation in vivo. PMID:26903816

  11. Integrated Assessment of Hadley Centre (HadCM2) Climate-Change Impacts on Agricultural Productivity and Irrigation Water Supply in the Conterminous United States. Part II. Regional Agricultural Production in 2030 and 2095.

    SciTech Connect

    Izaurralde, R Cesar C.; Rosenberg, Norman J.; Brown, Robert A.; Thomson, Allison M.

    2003-06-30

    This study used scenarios of the HadCM2 GCM and the EPIC agroecosystem model to evaluate climate change impacts on crop yields and ecosystem processes. Baseline climate data were obtained from records for 1961-1990. The scenario runs for 2025-2034 and 2090-2099 were extracted from a HadCM2 run. EPIC was run on 204 representative farms under current climate and two 10-y periods centered on 2030 and 2095, each at CO2 concentrations of 365 and 560 ppm. Texas, New Mexico, Colorado, Utah, Arizona, and California are projected to experience significant temperature increases by 2030. Slight cooling is expected by 2030 in Alabama, Florida, Maine, Montana, Idaho, and Utah. Larger areas are projected to experience increased warming by 2095. Uniform precipitation increases are expected by 2030 in the NE. These increases are predicted to expand to the eastern half of the country by 2095. EPIC simulated yield increases for the Great Lakes, Corn Belt and Northeast regions. Simulated yields of irrigated corn yields were predicted to increase in almost all regions. Soybean yields could decrease in the Northern and Southern Plains, the Corn Belt, Delta, Appalachian, and Southeast regions and increase in the Lakes and Northeast regions. Simulated wheat yields exhibited upward yield trends under scenarios of climate change. National corn production in 2030 and 2095 could be affected by changes in three major producing regions. In 2030, corn production could increase in the Corn Belt and Lakes regions but decrease in the Northern Plains leading to an overall decrease in national production. National wheat production is expected to increase during both future periods. A proxy indicator was developed to provide a sense of where in the country, and when water would be available to satisfy change in irrigation demand for corn and alfalfa production as these are influenced by the HadCM2 scenarios and CO2-fertilization.

  12. Fully Enzymatic Membraneless Glucose|Oxygen Fuel Cell That Provides 0.275 mA cm(-2) in 5 mM Glucose, Operates in Human Physiological Solutions, and Powers Transmission of Sensing Data.

    PubMed

    Ó Conghaile, Peter; Falk, Magnus; MacAodha, Domhnall; Yakovleva, Maria E; Gonaus, Christoph; Peterbauer, Clemens K; Gorton, Lo; Shleev, Sergey; Leech, Dónal

    2016-02-16

    Coimmobilization of pyranose dehydrogenase as an enzyme catalyst, osmium redox polymers [Os(4,4'-dimethoxy-2,2'-bipyridine)2(poly(vinylimidazole))10Cl](+) or [Os(4,4'-dimethyl-2,2'-bipyridine)2(poly(vinylimidazole))10Cl](+) as mediators, and carbon nanotube conductive scaffolds in films on graphite electrodes provides enzyme electrodes for glucose oxidation. The recombinant enzyme and a deglycosylated form, both expressed in Pichia pastoris, are investigated and compared as biocatalysts for glucose oxidation using flow injection amperometry and voltammetry. In the presence of 5 mM glucose in phosphate-buffered saline (PBS) (50 mM phosphate buffer solution, pH 7.4, with 150 mM NaCl), higher glucose oxidation current densities, 0.41 mA cm(-2), are obtained from enzyme electrodes containing the deglycosylated form of the enzyme. The optimized glucose-oxidizing anode, prepared using deglycosylated enzyme coimmobilized with [Os(4,4'-dimethyl-2,2'-bipyridine)2(poly(vinylimidazole))10Cl](+) and carbon nanotubes, was coupled with an oxygen-reducing bilirubin oxidase on gold nanoparticle dispersed on gold electrode as a biocathode to provide a membraneless fully enzymatic fuel cell. A maximum power density of 275 μW cm(-2) is obtained in 5 mM glucose in PBS, the highest to date under these conditions, providing sufficient power to enable wireless transmission of a signal to a data logger. When tested in whole human blood and unstimulated human saliva maximum power densities of 73 and 6 μW cm(-2) are obtained for the same fuel cell configuration, respectively. PMID:26750758

  13. Direct total cross section measurement of the {sup 16}O({alpha}, {gamma}){sup 20}Ne reaction at E{sub c.m.}=2.26 MeV

    SciTech Connect

    Hager, U.; Greife, U.; Brown, J. R.; Buchmann, L.; Fallis, J.; Hutcheon, D.; Ottewell, D.; Ruiz, C.; Sjue, S.; Carmona-Gallardo, M.; Erikson, L.; Vockenhuber, C.

    2011-08-15

    In stellar helium burning, {sup 16}O represents the endpoint of the helium-burning sequence due to the low rate of {sup 16}O({alpha},{gamma}){sup 20}Ne. We present a new direct measurement of the total capture reaction rate of {sup 16}O({alpha},{gamma}){sup 20}Ne at E{sub c.m.}=2.26 MeV employing the DRAGON recoil separator. For the first time, the total S factor and its contributing direct capture transitions could be determined in one experiment.

  14. Low level laser therapy (AlGaInP) applied at 5J/cm2 reduces the proliferation of Staphylococcus aureus MRSA in infected wounds and intact skin of rats*

    PubMed Central

    Silva, Daniela Conceição Gomes Gonçalves e; Plapler, Helio; da Costa, Mateus Matiuzzi; Silva, Silvio Romero Gonçalves e; de Sá, Maria da Conceição Aquino; Silva, Benedito Sávio Lima e

    2013-01-01

    BACKGROUND Laser therapy is a low cost, non-invasive procedure with good healing results. Doubts exist as to whether laser therapy action on microorganisms can justify research aimed at investigating its possible effects on bacteria-infected wounds. OBJECTIVE To assess the effect of low intensity laser on the rate of bacterial contamination in infected wounds in the skin of rats. METHODS An experimental study using 56 male Wistar rats. The animals were randomly divided into eight groups of seven each. Those in the "infected" groups were infected by Staphylococcus aureus MRSA in the dorsal region. Red laser diode (AlGaInP) 658nm, 5J/cm2 was used to treat the animals in the "treated" groups in scan for 3 consecutive days. Samples were drawn before inoculating bacteria and following laser treatment. For statistical analysis we used the nonparametric Wilcoxon (paired data) method with a significance level of p <0.05. RESULTS The statistical analysis of median values showed that the groups submitted to laser treatment had low bacterial proliferation. CONCLUSION The laser (AlGaInP), with a dose of 5J/cm2 in both intact skin and in wounds of rats infected with Staphylococcus aureus MRSA, is shown to reduce bacterial proliferation. PMID:23539003

  15. A visual motion sensor based on the properties of V1 and MT neurons.

    PubMed

    Perrone, John A

    2004-01-01

    The motion response properties of neurons increase in complexity as one moves from primary visual cortex (V1), up to higher cortical areas such as the middle temporal (MT) and the medial superior temporal area (MST). Many of the features of V1 neurons can now be replicated using computational models based on spatiotemporal filters. However until recently, relatively little was known about how the motion analysing properties of MT neurons could originate from the V1 neurons that provide their inputs. This has constrained the development of models of the MT-MST stages which have been linked to higher level motion processing tasks such as self-motion perception and depth estimation. I describe the construction of a motion sensor built up in stages from two spatiotemporal filters with properties based on V1 neurons. The resulting composite sensor is shown to have spatiotemporal frequency response profiles, speed and direction tuning responses that are comparable to MT neurons. The sensor is designed to work with digital images and can therefore be used as a realistic front-end to models of MT and MST neuron processing; it can be probed with the same two-dimensional motion stimuli used to test the neurons and has the potential to act as a building block for more complex models of motion processing. PMID:15135991

  16. Tracing path-guided apparent motion in human primary visual cortex V1.

    PubMed

    Akselrod, Michel; Herzog, Michael H; Öğmen, Haluk

    2014-08-14

    Vision is a constructive process. For example, a square, flashed at two distinct locations one after the other, appears to move smoothly between the two locations rather than as two separate flashes (apparent motion). Apparent motion is usually perceived along the shortest path between locations. Previous studies have shown that retinotopic activity in V1 correlates well with the subjective filling-in in apparent motion. If V1 activity truly reflects illusory motion, it should flexibly reflect filling-in of any path, subjectively perceived. Here, we used a path-guided apparent motion paradigm in which a faint cue, presented in addition to the squares, leads to a curved illusory motion path. We found retinotopic activity in V1 to reflect the illusory filling-in of the curved path, similarly to filling-in with linear, shortest paths. Moreover, our results show that activity along the linear path was less selective to stimulus conditions than the activity along the curved path. This finding may be interpreted as V1 activity representing a small subset of infinitely many possible solutions to ambiguous stimuli, whilst giving more weight to the shortest path/energy solution.

  17. Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors

    PubMed Central

    Koshimizu, Taka-aki; Kashiwazaki, Aki; Taniguchi, Junichi

    2016-01-01

    Reducing Na+ in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na+-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na+ sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly, and a small fraction is in the plasma membrane. Decreases in external Na+ increased cell surface [3H]AVP binding and decreased receptor internalization. Substitution of Na+ by Cs+ or NH4+ inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na+ over Cs+. Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations. PMID:27138239

  18. Ligand Recognition of the Major Birch Pollen Allergen Bet v 1 is Isoform Dependent

    PubMed Central

    Seutter von Loetzen, Christian; Jacob, Thessa; Hartl-Spiegelhauer, Olivia; Vogel, Lothar; Schiller, Dirk; Spörlein-Güttler, Cornelia; Schobert, Rainer; Vieths, Stefan; Hartl, Maximilian Johannes; Rösch, Paul

    2015-01-01

    Each spring millions of patients suffer from allergies when birch pollen is released into the air. In most cases, the major pollen allergen Bet v 1 is the elicitor of the allergy symptoms. Bet v 1 comes in a variety of isoforms that share virtually identical conformations, but their relative concentrations are plant-specific. Glycosylated flavonoids, such as quercetin-3-O-sophoroside, are the physiological ligands of Bet v 1, and here we found that three isoforms differing in their allergenic potential also show an individual, highly specific binding behaviour for the different ligands. This specificity is driven by the sugar moieties of the ligands rather than the flavonols. While the influence of the ligands on the allergenicity of the Bet v 1 isoforms may be limited, the isoform and ligand mixtures add up to a complex and thus individual fingerprint of the pollen. We suggest that this mixture is not only acting as an effective chemical sunscreen for pollen DNA, but may also play an important role in recognition processes during pollination. PMID:26042900

  19. Robust Supersolidity in the V1- V2 Extended Bose-Hubbard Model

    NASA Astrophysics Data System (ADS)

    Greene, Nicole; Pixley, Jedediah

    2016-05-01

    Motivated by ultra-cold atomic gases with long-range interactions in an optical lattice we study the effects of the next-nearest neighbor interaction on the extended Bose-Hubbard model on a square lattice. Using the variational Gutzwiller approach with a four-site unit cell we determine the ground state phase diagrams as a function of the model parameters. We focus on the interplay of each interaction between the nearest neighbor (V1) , the next-nearest neighbor (V2) , and the onsite repulsion (U). We find various super-solid phases that can be described by one of the ordering wave-vectors (π, 0), (0, π) , and (π, π) . In the limits V1, V2 V1, V2 >U we find phases reminiscent of the limit V2 = 0 but with a richer super solid structure. For V1

  20. Visual recognition memory, manifest as long-term habituation, requires synaptic plasticity in V1

    PubMed Central

    Cooke, Sam F.; Komorowski, Robert W.; Kaplan, Eitan S.; Gavornik, Jeffrey P.; Bear, Mark F.

    2015-01-01

    Familiarity with stimuli that bring neither reward nor punishment, manifested through behavioural habituation, enables organisms to detect novelty and devote cognition to important elements of the environment. Here we describe in mice a form of long-term behavioural habituation to visual grating stimuli that is selective for stimulus orientation. Orientation-selective habituation (OSH) can be observed both in exploratory behaviour in an open arena, and in a stereotyped motor response to visual stimuli in head-restrained mice. We show that the latter behavioural response, termed a vidget, requires V1. Parallel electrophysiological recordings in V1 reveal that plasticity, in the form of stimulus-selective response potentiation (SRP), occurs in layer 4 of V1 as OSH develops. Local manipulations of V1 that prevent and reverse electrophysiological modifications likewise prevent and reverse memory demonstrated behaviourally. These findings suggest that a form of long-term visual recognition memory is stored via synaptic plasticity in primary sensory cortex. PMID:25599221

  1. Different glutamate receptors convey feedforward and recurrent processing in macaque V1.

    PubMed

    Self, Matthew W; Kooijmans, Roxana N; Supèr, Hans; Lamme, Victor A; Roelfsema, Pieter R

    2012-07-01

    Neurons in the primary visual cortex (V1) receive feedforward input from the thalamus, which shapes receptive-field properties. They additionally receive recurrent inputs via horizontal connections within V1 and feedback from higher visual areas that are thought to be important for conscious visual perception. Here, we investigated what roles different glutamate receptors play in conveying feedforward and recurrent inputs in macaque V1. As a measure of recurrent processing, we used figure-ground modulation (FGM), the increased activity of neurons representing figures compared with background, which depends on feedback from higher areas. We found that feedforward-driven activity was strongly reduced by the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas this drug had no effect on FGM. In contrast, blockers of the NMDA receptor reduced FGM, whereas their effect on visually driven activity varied with the subunit specificity of the drug. The NMDA receptor blocker 2-amino-5-phosphonovalerate (APV) caused a slight reduction of the visual response, whereas ifenprodil, which targets NMDA receptors containing the NMDA receptor NR2B subunit, increased the visual response. These findings demonstrate that glutamate receptors contribute differently to feedforward and recurrent processing in V1 and suggest ways to selectively disrupt recurrent processing so that its role in visual perception can be elucidated. PMID:22615394

  2. SSE-GIS v1.03 Web Mapping Application Now Available

    Atmospheric Science Data Center

    2016-07-07

    SSE-GIS v1.03 Web Mapping Application Now Available Wednesday, July 6, 2016 ... you haven’t already noticed the link to the new SSE-GIS web application on the SSE homepage entitled “GIS Web Mapping Applications and Services”, we invite you to visit the site. ...

  3. Decavanadate Toxicology and Pharmacological Activities: V10 or V1, Both or None?

    PubMed Central

    Aureliano, M.

    2016-01-01

    This review covers recent advances in the understanding of decavanadate toxicology and pharmacological applications. Toxicological in vivo studies point out that V10 induces several changes in several oxidative stress parameters, different from the ones observed for vanadate (V1). In in vitro studies with mitochondria, a particularly potent V10 effect, in comparison with V1, was observed in the mitochondrial depolarization (IC50 = 40 nM) and oxygen consumption (99 nM). It is suggested that mitochondrial membrane depolarization is a key event in decavanadate induction of necrotic cardiomyocytes death. Furthermore, only decavanadate species and not V1 potently inhibited myosin ATPase activity stimulated by actin (IC50 = 0.75 μM) whereas exhibiting lower inhibition activities for Ca2+-ATPase activity (15 μM) and actin polymerization (17 μM). Because both calcium pump and actin decavanadate interactions lead to its stabilization, it is likely that V10 interacts at specific locations with these proteins that protect against hydrolysis but, on the other hand, it may induce V10 reduction to oxidovanadium(IV). Putting it all together, it is suggested that the pharmacological applications of V10 species and compounds whose mechanism of action is still to be clarified might involve besides V10 and V1 also vanadium(IV) species. PMID:26904166

  4. Differences in V1 and V2 ski skating techniques described by accelerometers.

    PubMed

    Myklebust, H; Losnegard, T; Hallén, J

    2014-12-01

    The aims of the study were to describe the differences between the ski skating techniques V1 and V2 and evaluate reproducibility in complex cyclic hip movements measured by accelerometers. Fourteen elite senior male cross-country skiers rollerskied twice for 1 min (V1 and V2) at 4° inclination and 3 m/s. Tests were repeated after 20 min and again 4 months later. Five triaxial accelerometers were attached to the subject's hip (os sacrum), poles, and ski boots. Post-processing included transforming to an approximately global coordinate system, normalization for cycle time, double integration for displacement, and revealing temporal patterns. Different acceleration patterns between techniques and large correlation coefficients (Pearson's r = 0.6-0.9) between repeated trials were seen for most parameters. In V2, the hip was lowered [-10.9 (1.2) cm], whereas in V1, the hip was elevated [4.8 (1.5) cm] during the pole thrust. In conclusion, V2 but not V1 showed similarities to double poling in the way that potential energy is gained between poling strokes and transferred to propulsion during the poling action. Elite skiers reproduce their own individual patterns. One triaxial accelerometer on the lower back can distinguish techniques and might be useful in field research as well as in providing individual feedback on daily technique training.

  5. Kinomer v. 1.0: a database of systematically classified eukaryotic protein kinases.

    PubMed

    Martin, David M A; Miranda-Saavedra, Diego; Barton, Geoffrey J

    2009-01-01

    The regulation of protein function through reversible phosphorylation by protein kinases and phosphatases is a general mechanism controlling virtually every cellular activity. Eukaryotic protein kinases can be classified into distinct, well-characterized groups based on amino acid sequence similarity and function. We recently reported a highly sensitive and accurate hidden Markov model-based method for the automatic detection and classification of protein kinases into these specific groups. The Kinomer v. 1.0 database presented here contains annotated classifications for the protein kinase complements of 43 eukaryotic genomes. These span the taxonomic range and include fungi (16 species), plants (6), diatoms (1), amoebas (2), protists (1) and animals (17). The kinomes are stored in a relational database and are accessible through a web interface on the basis of species, kinase group or a combination of both. In addition, the Kinomer v. 1.0 HMM library is made available for users to perform classification on arbitrary sequences. The Kinomer v. 1.0 database is a continually updated resource where direct comparison of kinase sequences across kinase groups and across species can give insights into kinase function and evolution. Kinomer v. 1.0 is available at http://www.compbio.dundee.ac.uk/kinomer/.

  6. AVP-induced pulmonary vasodilation during specific V1 receptor block in conscious dogs.

    PubMed

    Nyhan, D P; Clougherty, P W; Murray, P A

    1987-09-01

    Our objectives were 1) to determine whether exogenously administered arginine vasopressin (AVP) can exert a vasoactive influence on the pulmonary circulation of conscious dogs during specific vasopressinergic-1 (V1) receptor block, and 2) to assess the extent to which the pulmonary vascular response to AVP during V1 receptor block is mediated by either sympathetic beta-adrenergic or cholinergic receptor activation or by cyclooxygenase pathway activation. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. In dogs pretreated with a specific V1 receptor antagonist [d(CH2)5 AVP, 10 micrograms/kg iv], AVP infusion (7.6 ng.kg-1 X min-1 iv) increased (P less than 0.01) Q from 139 +/- 6 to 175 +/- 8 ml.min-1 X kg-1, and decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure: PAP-PCWP) over the entire range of Q studied (140 to 80 ml.min-1 X kg-1). This pulmonary vasodilator response to AVP during V1 block was also observed following sympathetic beta-adrenergic block alone, following combined sympathetic beta-adrenergic and cholinergic block, and following cyclooxygenase pathway inhibition. Thus exogenous administration of AVP during specific V1 receptor block results in active, nonflow-dependent pulmonary vasodilation. This pulmonary vasodilator response is not mediated by reflex activation of sympathetic beta-adrenergic or cholinergic receptors or by metabolites of the cyclooxygenase pathway over a broad range of Q. PMID:2888317

  7. Chromatic detection from cone photoreceptors to V1 neurons to behavior in rhesus monkeys.

    PubMed

    Hass, Charles A; Angueyra, Juan M; Lindbloom-Brown, Zachary; Rieke, Fred; Horwitz, Gregory D

    2015-01-01

    Chromatic sensitivity cannot exceed limits set by noise in the cone photoreceptors. To determine how close neurophysiological and psychophysical chromatic sensitivity come to these limits, we developed a parameter-free model of stimulus encoding in the cone outer segments, and we compared the sensitivity of the model to the psychophysical sensitivity of monkeys performing a detection task and to the sensitivity of individual V1 neurons. Modeled cones had a temporal impulse response and a noise power spectrum that were derived from in vitro recordings of macaque cones, and V1 recordings were made during performance of the detection task. The sensitivity of the simulated cone mosaic, the V1 neurons, and the monkeys were tightly yoked for low-spatiotemporal-frequency isoluminant modulations, indicating high-fidelity signal transmission for this class of stimuli. Under the conditions of our experiments and the assumptions for our model, the signal-to-noise ratio for these stimuli dropped by a factor of ∼3 between the cones and perception. Populations of weakly correlated V1 neurons narrowly exceeded the monkeys' chromatic sensitivity but fell well short of the cones' chromatic sensitivity, suggesting that most of the behavior-limiting noise lies between the cone outer segments and the output of V1. The sensitivity gap between the cones and behavior for achromatic stimuli was larger than for chromatic stimuli, indicating greater postreceptoral noise. The cone mosaic model provides a means to compare visual sensitivity across disparate stimuli and to identify sources of noise that limit visual sensitivity. PMID:26523737

  8. Fine Mapping of Virescent Leaf Gene v-1 in Cucumber (Cucumis sativus L.).

    PubMed

    Miao, Han; Zhang, Shengping; Wang, Min; Wang, Ye; Weng, Yiqun; Gu, Xingfang

    2016-09-22

    Leaf color mutants are common in higher plants that can be used as markers in crop breeding or as an important tool in understanding regulatory mechanisms in chlorophyll biosynthesis and chloroplast development. In virescent leaf mutants, young leaves are yellow in color, which gradually return to normal green when the seedlings grow large. In the present study, we conducted phenotypic characterization and genetic mapping of the cucumber virescent leaf mutant 9110Gt conferred by the v-1 locus. Total chlorophyll and carotenoid content in 9110Gt was reduced by 44% and 21%, respectively, as compared with its wild type parental line 9110G. Electron microscopic investigation revealed fewer chloroplasts per cell and thylakoids per chloroplast in 9110Gt than in 9110G. Fine genetic mapping allowed for the assignment of the v-1 locus to a 50.4 kb genomic DNA region in chromosome 6 with two flanking markers that were 0.14 and 0.16 cM away from v-1, respectively. Multiple lines of evidence supported CsaCNGCs as the only candidate gene for the v-1 locus, which encoded a cyclic-nucleotide-gated ion channel protein. A single nucleotide change in the promoter region of v-1 seemed to be associated with the virescent color change in 9110Gt. Real-time PCR revealed significantly lower expression of CsaCNGCs in the true leaves of 9110Gt than in 9110G. This was the first report that connected the CsaCNGCs gene to virescent leaf color change, which provided a useful tool to establish linkages among virescent leaf color change, chloroplast development, chlorophyll biosynthesis, and the functions of the CsaCNGCs gene.

  9. Fine Mapping of Virescent Leaf Gene v-1 in Cucumber (Cucumis sativus L.)

    PubMed Central

    Miao, Han; Zhang, Shengping; Wang, Min; Wang, Ye; Weng, Yiqun; Gu, Xingfang

    2016-01-01

    Leaf color mutants are common in higher plants that can be used as markers in crop breeding or as an important tool in understanding regulatory mechanisms in chlorophyll biosynthesis and chloroplast development. In virescent leaf mutants, young leaves are yellow in color, which gradually return to normal green when the seedlings grow large. In the present study, we conducted phenotypic characterization and genetic mapping of the cucumber virescent leaf mutant 9110Gt conferred by the v-1 locus. Total chlorophyll and carotenoid content in 9110Gt was reduced by 44% and 21%, respectively, as compared with its wild type parental line 9110G. Electron microscopic investigation revealed fewer chloroplasts per cell and thylakoids per chloroplast in 9110Gt than in 9110G. Fine genetic mapping allowed for the assignment of the v-1 locus to a 50.4 kb genomic DNA region in chromosome 6 with two flanking markers that were 0.14 and 0.16 cM away from v-1, respectively. Multiple lines of evidence supported CsaCNGCs as the only candidate gene for the v-1 locus, which encoded a cyclic-nucleotide-gated ion channel protein. A single nucleotide change in the promoter region of v-1 seemed to be associated with the virescent color change in 9110Gt. Real-time PCR revealed significantly lower expression of CsaCNGCs in the true leaves of 9110Gt than in 9110G. This was the first report that connected the CsaCNGCs gene to virescent leaf color change, which provided a useful tool to establish linkages among virescent leaf color change, chloroplast development, chlorophyll biosynthesis, and the functions of the CsaCNGCs gene. PMID:27669214

  10. Chromatic detection from cone photoreceptors to V1 neurons to behavior in rhesus monkeys

    PubMed Central

    Hass, Charles A.; Angueyra, Juan M.; Lindbloom-Brown, Zachary; Rieke, Fred; Horwitz, Gregory D.

    2015-01-01

    Chromatic sensitivity cannot exceed limits set by noise in the cone photoreceptors. To determine how close neurophysiological and psychophysical chromatic sensitivity come to these limits, we developed a parameter-free model of stimulus encoding in the cone outer segments, and we compared the sensitivity of the model to the psychophysical sensitivity of monkeys performing a detection task and to the sensitivity of individual V1 neurons. Modeled cones had a temporal impulse response and a noise power spectrum that were derived from in vitro recordings of macaque cones, and V1 recordings were made during performance of the detection task. The sensitivity of the simulated cone mosaic, the V1 neurons, and the monkeys were tightly yoked for low-spatiotemporal-frequency isoluminant modulations, indicating high-fidelity signal transmission for this class of stimuli. Under the conditions of our experiments and the assumptions for our model, the signal-to-noise ratio for these stimuli dropped by a factor of ∼3 between the cones and perception. Populations of weakly correlated V1 neurons narrowly exceeded the monkeys' chromatic sensitivity but fell well short of the cones' chromatic sensitivity, suggesting that most of the behavior-limiting noise lies between the cone outer segments and the output of V1. The sensitivity gap between the cones and behavior for achromatic stimuli was larger than for chromatic stimuli, indicating greater postreceptoral noise. The cone mosaic model provides a means to compare visual sensitivity across disparate stimuli and to identify sources of noise that limit visual sensitivity. PMID:26523737

  11. Fine Mapping of Virescent Leaf Gene v-1 in Cucumber (Cucumis sativus L.).

    PubMed

    Miao, Han; Zhang, Shengping; Wang, Min; Wang, Ye; Weng, Yiqun; Gu, Xingfang

    2016-01-01

    Leaf color mutants are common in higher plants that can be used as markers in crop breeding or as an important tool in understanding regulatory mechanisms in chlorophyll biosynthesis and chloroplast development. In virescent leaf mutants, young leaves are yellow in color, which gradually return to normal green when the seedlings grow large. In the present study, we conducted phenotypic characterization and genetic mapping of the cucumber virescent leaf mutant 9110Gt conferred by the v-1 locus. Total chlorophyll and carotenoid content in 9110Gt was reduced by 44% and 21%, respectively, as compared with its wild type parental line 9110G. Electron microscopic investigation revealed fewer chloroplasts per cell and thylakoids per chloroplast in 9110Gt than in 9110G. Fine genetic mapping allowed for the assignment of the v-1 locus to a 50.4 kb genomic DNA region in chromosome 6 with two flanking markers that were 0.14 and 0.16 cM away from v-1, respectively. Multiple lines of evidence supported CsaCNGCs as the only candidate gene for the v-1 locus, which encoded a cyclic-nucleotide-gated ion channel protein. A single nucleotide change in the promoter region of v-1 seemed to be associated with the virescent color change in 9110Gt. Real-time PCR revealed significantly lower expression of CsaCNGCs in the true leaves of 9110Gt than in 9110G. This was the first report that connected the CsaCNGCs gene to virescent leaf color change, which provided a useful tool to establish linkages among virescent leaf color change, chloroplast development, chlorophyll biosynthesis, and the functions of the CsaCNGCs gene. PMID:27669214

  12. Single-Trial Analysis of V1 Responses Suggests Two Transmission States

    NASA Technical Reports Server (NTRS)

    Shah, A. S.; Knuth, K. H.; Truccolo, W. A.; Mehta, A. D.; McGinnis, T.; OConnell, N.; Ding, M.; Bressler, S. L.; Schroeder, C. E.

    2002-01-01

    Sensory processing in the visual, auditory, and somatosensory systems is often studied by recording electrical activity in response to a stimulus of interest. Typically, multiple trial responses to the stimulus are averaged to isolate the stereotypic response from noise. However, averaging ignores dynamic variability in the neuronal response, which is potentially critical to understanding stimulus-processing schemes. Thus, we developed the multiple component, Event-Related Potential (mcERP) model. This model asserts that multiple components, defined as stereotypic waveforms, comprise the stimulus-evoked response and that these components may vary in amplitude and latency from trial to trial. Application of this model to data recorded simultaneously from all six laminae of V1 in an awake, behaving monkey performing a visual discrimination yielded three components. The first component localized to granular V1, the second was located in supragranular V1, and the final component displayed a multi-laminar distribution. These modeling results, which take into account single-trial response dynamics, illustrated that the initial activation of VI occurs in the granular layer followed by activation in the supragranular layers. This finding is expected because the average response in those layers demonstrates the same progression and because anatomical evidence suggests that the feedforward input in V1 enters the granular layer and progresses to supragranular layers. In addition to these findings, the granular component of the model displayed several interesting trial-to-trial characteristics including (1) a bimodal latency distribution, (2) a latency-related variation in response amplitude, (3) a latency correlation with the supragranular component, and (4) an amplitude and latency association with the multi-laminar component. Direct analyses of the single-trial data were consistent with these model predictions. These findings suggest that V1 has at least 2 transmission

  13. Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy

    PubMed Central

    Linhart, B; Narayanan, M; Focke-Tejkl, M; Wrba, F; Vrtala, S; Valenta, R

    2014-01-01

    Background Vaccines consisting of allergen-derived peptides lacking IgE reactivity and allergen-specific T cell epitopes bound to allergen-unrelated carrier molecules have been suggested as candidates for allergen-specific immunotherapy. Objective To study whether prophylactic and therapeutic vaccination with carrier-bound peptides from the major birch pollen allergen Bet v 1 lacking allergen-specific T cell epitopes has influence on Bet v 1-specific T cell responses. Methods Three Bet v 1-derived peptides, devoid of Bet v 1-specific T cell epitopes, were coupled to KLH and adsorbed to aluminium hydroxide to obtain a Bet v 1-specific allergy vaccine. Groups of BALB/c mice were immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet v 1- and peptide-specific antibody responses were analysed by ELISA. T cell and cytokine responses to Bet v 1, KLH, and the peptides were studied in proliferation assays. The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies. Results Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides induced a Bet v 1-specific IgG antibody response without priming/boosting of Bet v 1-specific T cells. Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation. Conclusion and Clinical Relevance Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation. PMID:24447086

  14. Structural transformation of Bi1-x/3V1-xMoxO4 solid solutions for light-driven water oxidation.

    PubMed

    Terebilenko, Kateryna V; Bychkov, Konstantin L; Baumer, Vyacheslav N; Slobodyanik, Nikolay S; Pavliuk, Mariia V; Thapper, Anders; Tokmenko, Inna I; Nasieka, Iurii M; Strelchuk, Viktor V

    2016-03-01

    The influence of molybdenum content in the solid solutions of Bi1-x/3V1-xMoxO4 (x = 0.05-0.20) on the morphology, band gap, structure and light-driven water oxidation properties has been studied by scanning electron microscopy, X-ray powder diffraction and vibrational spectroscopy (Raman and infrared). To find out the peculiarities of structural changes for bismuth scheelite-related oxides containing both vanadium and molybdenum crystals of Bi0.98V0.93Mo0.07O4 have been grown from a K-Bi-V-Mo-O high-temperature melt and characterized by single crystal X-ray diffraction. For the scheelite-related framework both V and Mo were found to occupy the same positions lowering the point group symmetry of tetrahedra from 4/m to 2/m giving monoclinic distortion for solid solutions with x = 0.05-0.10. The most promising photocatalytic performance was obtained for Bi0.96Mo0.10V0.90O4, in which the oxygen evolution could reach 21 μM in 50 s under visible light of LEDs, λ = 470 ± 10 nm, and 820 μE cm(-2) s(-1). The changes in catalytic properties are shown to be governed by a crystal structure strain with a maximum obtained for the boundary sample between the monoclinic and tetragonal phase.

  15. Collisional Removal of O2(b1Σ ^+g, v = 1) by Atomic Oxygen

    NASA Astrophysics Data System (ADS)

    Kalogerakis, K. S.; Pejaković, D. A.; Copeland, R. A.; Slanger, T. G.

    2004-12-01

    In the thermosphere, energy transfer between excited O atoms and ground-state molecular oxygen produces O2 in the first two vibrational levels of the b1Σ ^+g state: O(1D) + O2 -> O(3P) + O2(b1Σ ^+g, v = 0, 1). Subsequent radiative decay of O2(b1Σ ^+g, v = 0, 1) to the ground state O2(X3Σ ^-g) results in the Atmospheric Band emissions. Atmospheric observations suggest that above ˜120 km O(3P) plays an important role in removing O2(b1Σ ^+g, v = 1). Therefore, knowledge of the rate coefficient for collisional removal of O2(b1Σ ^+g<, v = 1) by O(3P) is important for detailed understanding of the Atmospheric Band emissions. Measurements are reported of the room-temperature rate coefficient for removal of O2(b1Σ ^+g, v = 1) by O(3P). A commercial F2 laser with pulsed energy output of up to 50 mJ at 157 nm is used to photodissociate a large fraction of molecular oxygen in a O2/N2 mixture. Photodissociation of an O2 molecule produces a ground-state oxygen atom O(3P) and an excited oxygen atom O(1D), and O(1D) rapidly transfers energy to the remaining O2 to produce O2(b1Σ ^+g, v = 0, 1). The O2(b1Σ ^+g, v = 1) population is monitored by observing emission in the O2 (b-X) 1--1 band at 771 nm. To extract the O2(b1Σ ^+g, v = 1) + O(3P) rate coefficient, knowledge of the O(3P) partial pressure or, equivalently, the fraction of dissociated O2, is necessary. Based on the F2 laser fluence, the signal dependence on the fraction of dissociation, and computer modeling, the signals measured in our experiments correspond to about 50% dissociation. Our measurements yield a preliminary value of the rate coefficient for O2(b1Σ ^+g, v = 1) removal by O(3P) of 6 × 10-12 cm3s-1. The results will be compared to the rate coefficients for corresponding processes in the ground and a1Δ g states of O2, and implications of the results for modeling of the upper atmosphere will be discussed. This work is supported by the NSF Aeronomy Program under grant ATM-0209229. The F2 laser was

  16. Determination of the type of stacking faults in single-crystal high-purity diamond with a low dislocation density of <50 cm-2 by synchrotron X-ray topography

    NASA Astrophysics Data System (ADS)

    Masuya, Satoshi; Hanada, Kenji; Uematsu, Takumi; Moribayashi, Tomoya; Sumiya, Hitoshi; Kasu, Makoto

    2016-04-01

    The properties of stacking faults in a single-crystal high-purity diamond with a very low dislocation density of <50 cm-2 and a very low impurity concentration of <0.1 ppm were investigated by synchrotron X-ray topography. We found stacking faults on the {111} plane and determined the fault vector f of the stacking faults to be \\textbf{f} = a/3< 111> on the basis of the f · g extinction criteria. Furthermore, we have found that the partial dislocations are of the Shockley type on the basis of the b · g extinction criteria. Consequently, we concluded that the stacking faults are of the Shockley type and formed because of the decomposition of dislocations with \\textbf{b} = a/2< 1\\bar{1}0> into dislocations with \\textbf{b} = a/6< 2\\bar{1}1> and a/6< 1\\bar{2}\\bar{1}> .

  17. MREG V1.1 : a multi-scale image registration algorithm for SAR applications.

    SciTech Connect

    Eichel, Paul H.

    2013-08-01

    MREG V1.1 is the sixth generation SAR image registration algorithm developed by the Signal Processing&Technology Department for Synthetic Aperture Radar applications. Like its predecessor algorithm REGI, it employs a powerful iterative multi-scale paradigm to achieve the competing goals of sub-pixel registration accuracy and the ability to handle large initial offsets. Since it is not model based, it allows for high fidelity tracking of spatially varying terrain-induced misregistration. Since it does not rely on image domain phase, it is equally adept at coherent and noncoherent image registration. This document provides a brief history of the registration processors developed by Dept. 5962 leading up to MREG V1.1, a full description of the signal processing steps involved in the algorithm, and a user's manual with application specific recommendations for CCD, TwoColor MultiView, and SAR stereoscopy.

  18. Explosive Model Tarantula V1/JWL++ Calibration of LX-17: #2

    SciTech Connect

    Souers, P C; Vitello, P

    2009-05-01

    Tarantula V1 is a kinetic package for reactive flow codes that seeks to describe initiation, failure, dead zones and detonation simultaneously. The most important parameter is P1, the pressure between the initiation and failure regions. Both dead zone formation and failure can be largely controlled with this knob. However, V1 does failure with low settings and dead zones with higher settings, so that it cannot fulfill its purpose in the current format. To this end, V2 is under test. The derivation of the initiation threshold P0 is discussed. The derivation of the initiation pressure-tau curve as an output of Tarantula shows that the initiation package is sound. A desensitization package is also considered.

  19. Second species solutions with an 0(μ v ), 0<v<1, near-Moon passage

    NASA Astrophysics Data System (ADS)

    Perko, L. M.

    1981-06-01

    This paper illustrates the application of the theory for second species solutions with an 0(μ v ), 0<v<1, near-Moon passage to first species-second species bifurcations and to second species-second species bifurcations. It also corrects and improves the asymptotic approximations obtained in the author's previous work on this subject and it establishes a local form of Broucke's Principle for the types of bifurcations studied in this paper.

  20. Poblano v1.0 : a Matlab toolbox for gradient-based optimization.

    SciTech Connect

    Dunlavy, Daniel M.; Acar, Evrim; Kolda, Tamara Gibson

    2010-03-01

    We present Poblano v1.0, a Matlab toolbox for solving gradient-based unconstrained optimization problems. Poblano implements three optimization methods (nonlinear conjugate gradients, limited-memory BFGS, and truncated Newton) that require only first order derivative information. In this paper, we describe the Poblano methods, provide numerous examples on how to use Poblano, and present results of Poblano used in solving problems from a standard test collection of unconstrained optimization problems.

  1. Evaluation of the Early Access STR Kit v1 on the Ion Torrent PGM™ platform.

    PubMed

    Guo, Fei; Zhou, Yishu; Liu, Feng; Yu, Jiao; Song, He; Shen, Hongying; Zhao, Bin; Jia, Fei; Hou, Guangwei; Jiang, Xianhua

    2016-07-01

    The Early Access STR Kit v1 is designed to detect 25-plex loci with next generation sequencing (NGS) technology on the Ion Torrent PGM™ platform, including 16 of 20 expanded Combined DNA Index System (CODIS) core loci (CSF1PO, D1S1656, D2S1338, D2S441, D3S1358, D5S818, D7S820, D8S1179, D10S1248, D13S317, D16S539, D19S433, D21S11, TH01, TPOX and vWA), 8 non-CODIS core loci (D1S1677, D2S1776, D4S2408, D5S2500.AC008791, D6S1043, D6S474, D9S2157 and D14S1434) and Amelogenin. In this study, we compared the Early Access STR Kit v1 with the Ion Torrent™ HID STR 10-plex to find out its improvements and explored an appropriate analytical threshold to enhance the performance. In addition, seven experiments were conducted to evaluate the Early Access STR Kit v1 such as studies of repeatability, concordance, sensitivity, mixtures, degraded samples, case-type samples and pedigrees. Other than a little discordance (0.95%) with CE-STR results observed at D21S11, NGS-STR results correctly reflected the sample being tested. Repeatable results were obtained from both initial PCRs and emPCRs aside from a few variations of allele coverage. Full profiles could be obtained from 100pg input DNA and >48.84% profiles from 10pg input DNA. Mixtures were easily detected at 9:1 and 1:9 ratios. This system could be adapted to case-type samples and degraded samples. As a whole, the Early Access STR Kit v1 is a robust, reliable and reproducible assay for NGS-STR typing and a potential tool for human identification.

  2. Selective V(1a) agonism attenuates vascular dysfunction and fluid accumulation in ovine severe sepsis.

    PubMed

    Rehberg, Sebastian; Yamamoto, Yusuke; Sousse, Linda; Bartha, Eva; Jonkam, Collette; Hasselbach, Anthony K; Traber, Lillian D; Cox, Robert A; Westphal, Martin; Enkhbaatar, Perenlei; Traber, Daniel L

    2012-11-15

    Vasopressin analogs are used as a supplement to norepinephrine in septic shock. The isolated effects of vasopressin agonists on sepsis-induced vascular dysfunction, however, remain controversial. Because V(2)-receptor stimulation induces vasodilation and procoagulant effects, a higher V(1a)- versus V(2)-receptor selectivity might be advantageous. We therefore hypothesized that a sole, titrated infusion of the selective V(1a)-agonist Phe(2)-Orn(8)-Vasotocin (POV) is more effective than the mixed V(1a)-/V(2)-agonist AVP for the treatment of vascular and cardiopulmonary dysfunction in methicillin resistant staphylococcus aureus pneumonia-induced, ovine sepsis. After the onset of hemodynamic instability, awake, chronically instrumented, mechanically ventilated, and fluid resuscitated sheep were randomly assigned to receive continuous infusions of either POV, AVP, or saline solution (control; each n = 6). AVP and POV were titrated to maintain mean arterial pressure above baseline - 10 mmHg. When compared with that of control animals, AVP and POV reduced neutrophil migration (myeloperoxidase activity, alveolar neutrophils) and plasma levels of nitric oxide, resulting in higher mean arterial pressures and a reduced vascular leakage (net fluid balance, chest and abdominal fluid, pulmonary bloodless wet-to-dry-weight ratio, alveolar and septal edema). Notably, POV stabilized hemodynamics at lower doses than AVP. In addition, POV, but not AVP, reduced myocardial and pulmonary tissue concentrations of 3-nitrotyrosine, VEGF, and angiopoietin-2, thereby leading to an abolishment of cumulative fluid accumulation (POV, 9 ± 15 ml/kg vs. AVP, 110 ± 13 ml/kg vs. control, 213 ± 16 ml/kg; P < 0.001 each) and an attenuated cardiopulmonary dysfunction (left ventricular stroke work index, PaO(2)-to-FiO(2) ratio) versus control animals. Highly selective V(1a)-agonism appears to be superior to unselective vasopressin analogs for the treatment of sepsis-induced vascular dysfunction.

  3. Precise visuotopic organization of the blind spot representation in primate V1.

    PubMed

    Azzi, João C B; Gattass, Ricardo; Lima, Bruss; Soares, Juliana G M; Fiorani, Mario

    2015-06-01

    The optic disk is a region of the retina consisting mainly of ganglion cell axons and blood vessels, which generates a visual scotoma known as the blind spot (BS). Information present in the surroundings of the BS can be used to complete the missing information. However, the neuronal mechanisms underlying these perceptual phenomena are poorly understood. We investigate the topography of the BS representation (BSR) in cortical area V1 of the capuchin monkey, using single and multiple electrodes. Receptive fields (RFs) of neurons inside the BSR were investigated using two distinct automatic bias-free mapping methods. The first method (local mapping) consisted of randomly flashing small white squares. For the second mapping method (global mapping), we used a single long bar that moved in one of eight directions. The latter stimulus was capable of eliciting neuronal activity inside the BSR, possibly attributable to long-range surround activity taking place outside the borders of the BSR. Importantly, we found that the neuronal activity inside the BSR is organized topographically in a manner similar to that found in other portions of V1. On average, the RFs inside the BS were larger than those outside. However, no differences in orientation or direction tuning were found between the two regions. We propose that area V1 exhibits a continuous functional topographic map, which is not interrupted in the BSR, as expected by the distribution of photoreceptors in the retina. Thus V1 topography is better described as "visuotopic" rather than as a discontinuous "retinotopic" map. PMID:25761953

  4. V1 spinal neurons regulate the speed of vertebrate locomotor outputs.

    PubMed

    Gosgnach, Simon; Lanuza, Guillermo M; Butt, Simon J B; Saueressig, Harald; Zhang, Ying; Velasquez, Tomoko; Riethmacher, Dieter; Callaway, Edward M; Kiehn, Ole; Goulding, Martyn

    2006-03-01

    The neuronal networks that generate vertebrate movements such as walking and swimming are embedded in the spinal cord. These networks, which are referred to as central pattern generators (CPGs), are ideal systems for determining how ensembles of neurons generate simple behavioural outputs. In spite of efforts to address the organization of the locomotor CPG in walking animals, little is known about the identity and function of the spinal interneuron cell types that contribute to these locomotor networks. Here we use four complementary genetic approaches to directly address the function of mouse V1 neurons, a class of local circuit inhibitory interneurons that selectively express the transcription factor Engrailed1. Our results show that V1 neurons shape motor outputs during locomotion and are required for generating 'fast' motor bursting. These findings outline an important role for inhibition in regulating the frequency of the locomotor CPG rhythm, and also suggest that V1 neurons may have an evolutionarily conserved role in controlling the speed of vertebrate locomotor movements.

  5. Spatial Attention and Temporal Expectation Under Timed Uncertainty Predictably Modulate Neuronal Responses in Monkey V1.

    PubMed

    Sharma, Jitendra; Sugihara, Hiroki; Katz, Yarden; Schummers, James; Tenenbaum, Joshua; Sur, Mriganka

    2015-09-01

    The brain uses attention and expectation as flexible devices for optimizing behavioral responses associated with expected but unpredictably timed events. The neural bases of attention and expectation are thought to engage higher cognitive loci; however, their influence at the level of primary visual cortex (V1) remains unknown. Here, we asked whether single-neuron responses in monkey V1 were influenced by an attention task of unpredictable duration. Monkeys covertly attended to a spot that remained unchanged for a fixed period and then abruptly disappeared at variable times, prompting a lever release for reward. We show that monkeys responded progressively faster and performed better as the trial duration increased. Neural responses also followed monkey's task engagement-there was an early, but short duration, response facilitation, followed by a late but sustained increase during the time monkeys expected the attention spot to disappear. This late attentional modulation was significantly and negatively correlated with the reaction time and was well explained by a modified hazard function. Such bimodal, time-dependent changes were, however, absent in a task that did not require explicit attentional engagement. Thus, V1 neurons carry reliable signals of attention and temporal expectation that correlate with predictable influences on monkeys' behavioral responses. PMID:24836689

  6. Purification and characterization of the V1 vasopressin receptor from rat liver

    SciTech Connect

    Fishman, J.B.; Dickey, B.F.; Attisano, C.; Fine, R.E.

    1987-05-01

    The rat liver V1 vasopressin receptor was purified approximately 21,000-fold from rat liver microsomes. The receptor was solubilized from membranes using the zwitterionic detergent CHAPS (3-((3-cholamidopropyl) dimethylammonio)-1-propanesulfonate). Since the V1 receptor loses its ability to bind ligand when solubilized, the authors devised a liposome reconstitution system to assay vasopressin binding activity during purification. The purified receptor exhibits a K/sub d/ of 6 nm, when, prior to solubilization, the membranes were exposed to 1 m vasopressin. This resulted in the association of a pertussis-toxin insensitive guanine-nucleotide binding protein with the receptor during most of the purification procedure. The authors are further characterizing the V1-associated G-proteins. In the absence of this association, the receptor has a K/sub d/ of 30 nM. Crosslinking of SVI-vasopressin to a partially purified preparation of receptor demonstrated that the receptor had a molecular weight of approximately 68,000 under reducing conditions, and 58,000 under non-reducing conditions. The purification procedure may prove useful in purifying a number of small peptide hormone receptors (e.g., bradykinin, angiotensin II) and perhaps their associated G-proteins as well.

  7. Phosphate solubilizing ability of Emericella nidulans strain V1 isolated from vermicompost.

    PubMed

    Bhattacharya, Satya Sunder; Barman, Soma; Ghosh, Ranjan; Duary, Raj Kumar; Goswami, Linee; Mandal, Narayan C

    2013-10-01

    Phosphorus is one of the key factors that regulate soil fertility. Its deficiencies in soil are largely replenished by chemical fertilizers. The present study was aimed to isolate efficient phosphate solubilizing fungal strains from Eisenia fetida vermicompost. Out of total 30 fungal strains the most efficient phosphate solubilizing one was Emericella (Aspergillus) nidulans V1 (MTCC 11044), identified by custom sequencing of beta-tubulin gene and BLAST analysis. This strain solubilized 13 to 36% phosphate from four different rock phosphates. After three days of incubation of isolated culture with black Mussorie phosphate rock, the highest percentage of phosphate solubilization was 35.5 +/- 1.01 with a pH drop of 4.2 +/- 0.09. Kinetics of solubilization and acid production showed a linear relationship until day five of incubation. Interestingly, from zero to tenth day of incubation, solubility of soil phosphate increased gradually from 4.31 +/- 1.57 to 13.65 +/- 1.82 (mg kg(-1)) recording a maximum of 21.23 +/- 0.54 on day 45 in respect of the V1 isolate. Further, enhanced phosphorus uptake by Phaseolus plants with significant pod yield due to soil inoculation of Emericella nidulans V1 (MTCC 11044), demonstrated its prospect as an effective biofertilizer for plant growth.

  8. V1 spinal neurons regulate the speed of vertebrate locomotor outputs.

    PubMed

    Gosgnach, Simon; Lanuza, Guillermo M; Butt, Simon J B; Saueressig, Harald; Zhang, Ying; Velasquez, Tomoko; Riethmacher, Dieter; Callaway, Edward M; Kiehn, Ole; Goulding, Martyn

    2006-03-01

    The neuronal networks that generate vertebrate movements such as walking and swimming are embedded in the spinal cord. These networks, which are referred to as central pattern generators (CPGs), are ideal systems for determining how ensembles of neurons generate simple behavioural outputs. In spite of efforts to address the organization of the locomotor CPG in walking animals, little is known about the identity and function of the spinal interneuron cell types that contribute to these locomotor networks. Here we use four complementary genetic approaches to directly address the function of mouse V1 neurons, a class of local circuit inhibitory interneurons that selectively express the transcription factor Engrailed1. Our results show that V1 neurons shape motor outputs during locomotion and are required for generating 'fast' motor bursting. These findings outline an important role for inhibition in regulating the frequency of the locomotor CPG rhythm, and also suggest that V1 neurons may have an evolutionarily conserved role in controlling the speed of vertebrate locomotor movements. PMID:16525473

  9. Development and matching of binocular orientation preference in mouse V1

    PubMed Central

    Bhaumik, Basabi; Shah, Nishal P.

    2014-01-01

    Eye-specific thalamic inputs converge in the primary visual cortex (V1) and form the basis of binocular vision. For normal binocular perceptions, such as depth and stereopsis, binocularly matched orientation preference between the two eyes is required. A critical period of binocular matching of orientation preference in mice during normal development is reported in literature. Using a reaction diffusion model we present the development of RF and orientation selectivity in mouse V1 and investigate the binocular orientation preference matching during the critical period. At the onset of the critical period the preferred orientations of the modeled cells are mostly mismatched in the two eyes and the mismatch decreases and reaches levels reported in juvenile mouse by the end of the critical period. At the end of critical period 39% of cells in binocular zone in our model cortex is orientation selective. In literature around 40% cortical cells are reported as orientation selective in mouse V1. The starting and the closing time for critical period determine the orientation preference alignment between the two eyes and orientation tuning in cortical cells. The absence of near neighbor interaction among cortical cells during the development of thalamo-cortical wiring causes a salt and pepper organization in the orientation preference map in mice. It also results in much lower % of orientation selective cells in mice as compared to ferrets and cats having organized orientation maps with pinwheels. PMID:25104927

  10. V1 projection zone signals in human macular degeneration depend on task, not stimulus.

    PubMed

    Masuda, Yoichiro; Dumoulin, Serge O; Nakadomari, Satoshi; Wandell, Brian A

    2008-11-01

    We used functional magnetic resonance imaging to assess abnormal cortical signals in humans with juvenile macular degeneration (JMD). These signals have been interpreted as indicating large-scale cortical reorganization. Subjects viewed a stimulus passively or performed a task; the task was either related or unrelated to the stimulus. During passive viewing, or while performing tasks unrelated to the stimulus, there were large unresponsive V1 regions. These regions included the foveal projection zone, and we refer to them as the lesion projection zone (LPZ). In 3 JMD subjects, we observed highly significant responses in the LPZ while they performed stimulus-related judgments. In control subjects, where we presented the stimulus only within the peripheral visual field, there was no V1 response in the foveal projection zone in any condition. The difference between JMD and control responses can be explained by hypotheses that have very different implications for V1 reorganization. In controls retinal afferents carry signals indicating the presence of a uniform (zero-contrast) region of the visual field. Deletion of retinal input may 1) spur the formation of new cortical pathways that carry task-dependent signals (reorganization), or 2) unmask preexisting task-dependent cortical signals that ordinarily are suppressed by the deleted signals (no reorganization).

  11. Septal oxytocin administration impairs peer affiliation via V1a receptors in female meadow voles.

    PubMed

    Anacker, Allison M J; Christensen, Jennifer D; LaFlamme, Elyssa M; Grunberg, Diana M; Beery, Annaliese K

    2016-06-01

    The peptide hormone oxytocin (OT) plays an important role in social behaviors, including social bond formation. In different contexts, however, OT is also associated with aggression, social selectivity, and reduced affiliation. Female meadow voles form social preferences for familiar same-sex peers under short, winter-like day lengths in the laboratory, and provide a means of studying affiliation outside the context of reproductive pair bonds. Multiple lines of evidence suggest that the actions of OT in the lateral septum (LS) may decrease affiliative behavior, including greater density of OT receptors in the LS of meadow voles that huddle less. We infused OT into the LS of female meadow voles immediately prior to cohabitation with a social partner to determine its effects on partner preference formation. OT prevented the formation of preferences for the partner female. Co-administration of OT with a specific OT receptor antagonist did not reverse the effect, but co-administration of OT with a specific vasopressin 1a receptor (V1aR) antagonist did, indicating that OT in the LS likely acted through V1aRs to decrease partner preference. Receptor autoradiography revealed dense V1aR binding in the LS of female meadow voles. These results suggest that the LS is a brain region that may be responsible for inhibitory effects of OT administration on affiliation, which will be important to consider in therapeutic administrations of OT. PMID:26974500

  12. Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons.

    PubMed

    Renganathan, M; Cummins, T R; Waxman, S G

    2001-08-01

    C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Na(v)1.8 (+/+) and (-/-) small DRG neurons maintained for 2-8 h in vitro to examine the role of sodium channel Na(v)1.8 (alpha-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Na(v)1.8 (+/+) and (-/-) DRG neurons, there were significant differences in action potential electrogenesis. Most Na(v)1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Na(v)1.8 (-/-) neurons produce smaller graded responses. The peak of the response was significantly reduced in Na(v)1.8 (-/-) neurons [31.5 +/- 2.2 (SE) mV] compared with Na(v)1.8 (+/+) neurons (55.0 +/- 4.3 mV). The maximum rise slope was 84.7 +/- 11.2 mV/ms in Na(v)1.8 (+/+) neurons, significantly faster than in Na(v)1.8 (-/-) neurons where it was 47.2 +/- 1.3 mV/ms. Calculations based on the action potential overshoot in Na(v)1.8 (+/+) and (-/-) neurons, following blockade of Ca(2+) currents, indicate that Na(v)1.8 contributes a substantial fraction (80-90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na(+) channels can produce all-or-none action potentials in some Na(v)1.8 (-/-) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Na(v)1.8 (-/-) neurons is more sensitive to membrane depolarization than in Na(v)1.8 (+/+) neurons, and, in the absence of Na(v)1.8, is attenuated with even modest depolarization. These observations

  13. Changes in the expression of NaV1.7, NaV1.8 and NaV1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain.

    PubMed

    Strickland, Iain T; Martindale, Jo C; Woodhams, Peter L; Reeve, Alison J; Chessell, Iain P; McQueen, Daniel S

    2008-07-01

    Voltage-gated sodium channels play an essential role in regulating the excitability of nociceptive primary afferent neurones. In particular the tetrodotoxin-sensitive (TTX-S) Na(V)1.7 and the tetrodotoxin-resistant (TTX-R) Na(V)1.8 and Na(V)1.9 channels have been suggested to play a role in inflammatory pain. Previous work has revealed acute administration of inflammatory mediators, such as Freund's complete adjuvant (FCA) or carrageenan caused an upregulation in the levels of Na(V)1.7 and Na(V)1.8 protein in DRG (dorsal root ganglia) tissue up to 4 days post-insult. In the present study, the expression of Na(V)1.7, Na(V)1.8 and Na(V)1.9 was examined over a 28 day timecourse during a rat model of FCA-induced chronic inflammatory joint pain. Using the retrograde tracer Fast Blue (FB) and specific Na(V)1.7, Na(V)1.8 and Na(V)1.9 sodium channel antibodies, immunohistochemical staining techniques were used to study sodium channel expression in a distinct population of L3-L5 knee joint afferent DRGs. In the ganglia, counts were made of positively labelled cells in the FB population. The results demonstrate that, following FCA injection, Na(V)1.9 expression is upregulated at days 14, 21 and 28 post-FCA, with Na(V)1.7 and Na(V)1.8 showing increased channel expression at days 14 and 28. These observations are accompanied by a unilateral joint hypersensitivity in the FCA-injected knee indicated by a behavioural shift in weight distribution measured using an incapacitance tester. The increased presence of these channels suggests that Na(V)1.7, Na(V)1.8 and Na(V)1.9 play a role, at least in part, in the maintenance of chronic inflammatory pain several weeks after the initial insult. PMID:17950013

  14. Observing Campaign on Hubble's First Variable in M31: M31_V1

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2010-07-01

    An observing campaign is being carried out on M31_V1, the first variable star discovered in M31 by Edwin Hubble. The Hubble Heritage Team, with Dr. Keith Noll (STScI) as P.I., plans to observe M31_V1 with HST, and needs to know the phase of this Cepheid variable. Although basic parameters are known for this star, no recent photometry exists, so observations are required to generate current phase information. In 1925 Edwin Hubble published a note in The Observatory (vol. 48, 139) on "Cepheids in Spiral Nebulae." In 1929, he published a seminal paper in the Astrophysical Journal (vol. 69, 103), "A Spiral Nebula as a Stellar System, Messier 31." This paper discussed in detail the galaxy and the 50 variable stars he found in its outer regions. Hubble remarked that the 40 Cepheids found showed the period-luminosity relationship in a conspicuous manner, enabling distance to the galaxy to be calculated. Furthermore, he said that the results of his calculations supported the value determined by Harlow Shapley of the zero point of the period-luminosity relation. This confirmation of the zero point had significant implications for future extragalactic distance determinations. As the first of the variables on Hubble's list, V1, a Cepheid, is a historical curiosity. M31_V1 is magnitude 19.4V. B-V = +1.28, period is 30.41 days, and amplitude ~ 1.2 magnitudes in B, likely smaller in V. Five nights of data obtained by Arne Henden, AAVSO, show that the variable appears to have peaked on 2010 June 19 at about R=18 and as of July 2 was on its way down. It is recommended that observers use either an Rc filter or observe unfiltered. About an hour or more of exposure per integration will be required to reach S/N = 20, depending on your equipment and sky brightness; multiple exposures and stacking might be necessary to avoid saturating the background. The field is not crowded, and the variable itself is not blended. Contamination from the M31 background should n! ot be prohibitive

  15. Replacement of olivine by serpentine in the Queen Alexandra Range 93005 carbonaceous chondrite (CM2): Reactant-product compositional relations, and isovolumetric constraints on reaction stoichiometry and elemental mobility during aqueous alteration

    NASA Astrophysics Data System (ADS)

    Velbel, Michael A.; Tonui, Eric K.; Zolensky, Michael E.

    2015-01-01

    Isovolumetric replacement of euhedral and anhedral olivine by serpentine produced both centripetal and meshwork textures in the CM2 chondrites ALH 81002 and Nogoya. The compositions of these textural varieties of serpentine are uniform within narrow limits within each previously studied meteorite, independent of the composition of olivine being replaced, and different between the two meteorites. In QUE 93005 (CM2), coarse olivines of widely varying compositions (Fo<76-99) are replaced in a texturally similar manner by compositionally uniform serpentine (Mg0.73±0.05Fe0.27±0.05)3Si2O5(OH)4. The narrow compositional range of serpentine replacing coarse olivine indicates that the aqueous solution from which the serpentine formed was compositionally uniform on scales at least as large as the meteorite (∼2.5 cm in longest dimension). Isovolumetric textures and compositional observations constrain elemental redistribution from coarse olivine to serpentine and to surrounding phases during serpentinization. Regardless of olivine's composition, isovolumetric replacement of coarse olivines by serpentine of the observed composition released more Mg and Si from olivine than was required to form the serpentine. Excess Mg and Si released by olivine destruction and not retained in serpentine were exported from the replaced volume. Olivines with different Fa/Fo proportions contributed different amounts of Fe and Mg to the serpentine. Ferroan olivines released more Fe than required to form the serpentines replacing them, so some of the Fe released from ferroan olivine was exported from the replaced volumes. Forsteritic olivines released less Fe than required to form the serpentines replacing them, so some Fe was imported into the replaced volumes augmenting the small amount of Fe released from forsteritic olivine. In QUE 93005 Fo83.8 is the threshold composition between Fe-exporting and Fe-importing behavior in individual olivine-serpentine pairs, which released exactly the

  16. Dissociation between neural signatures of stimulus and choice in population activity of human V1 during perceptual decision-making.

    PubMed

    Choe, Kyoung Whan; Blake, Randolph; Lee, Sang-Hun

    2014-02-12

    Primary visual cortex (V1) forms the initial cortical representation of objects and events in our visual environment, and it distributes information about that representation to higher cortical areas within the visual hierarchy. Decades of work have established tight linkages between neural activity occurring in V1 and features comprising the retinal image, but it remains debatable how that activity relates to perceptual decisions. An actively debated question is the extent to which V1 responses determine, on a trial-by-trial basis, perceptual choices made by observers. By inspecting the population activity of V1 from human observers engaged in a difficult visual discrimination task, we tested one essential prediction of the deterministic view: choice-related activity, if it exists in V1, and stimulus-related activity should occur in the same neural ensemble of neurons at the same time. Our findings do not support this prediction: while cortical activity signifying the variability in choice behavior was indeed found in V1, that activity was dissociated from activity representing stimulus differences relevant to the task, being advanced in time and carried by a different neural ensemble. The spatiotemporal dynamics of population responses suggest that short-term priors, perhaps formed in higher cortical areas involved in perceptual inference, act to modulate V1 activity prior to stimulus onset without modifying subsequent activity that actually represents stimulus features within V1.

  17. Complete nucleotide sequence of little cherry virus 1 (LChV-1) infecting sweet cherry in China

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little cherry virus 1 (LChV-1), associated with little cherry disease (LCD), has a significant impact on fruit quality of infected sweet cherry trees. We report the full genome sequence of an isolate of LChV-1 from China, detected by small RNA deep sequencing and amplified by overlapping RT-PCR. The...

  18. Outbursting comet P/2010 V1 (Ikeya-Murakami): A miniature comet Holmes

    SciTech Connect

    Ishiguro, Masateru; Jewitt, David; Hanayama, Hidekazu; Miyaji, Takeshi; Fukushima, Hideo; Watanabe, Jun-ichi; Usui, Fumihiko; Sekiguchi, Tomohiko; Yanagisawa, Kenshi; Kuroda, Daisuke; Yoshida, Michitoshi; Ohta, Kouji; Kawai, Nobuyuki

    2014-05-20

    The short-period comet P/2010 V1 (Ikeya-Murakami, hereafter {sup V}1{sup )} was discovered visually by two amateur astronomers. The appearance of the comet was peculiar, consisting of an envelope, a spherical coma near the nucleus and a tail extending in the anti-solar direction. We investigated the brightness and the morphological development of the comet by taking optical images with ground-based telescopes. Our observations show that V1 experienced a large-scale explosion between UT 2010 October 31 and November 3. The color of the comet was consistent with the Sun (g' – R {sub C} = 0.61 ± 0.20, R {sub C} – I {sub C} = 0.20 ± 0.20, and B – R {sub C} = 0.93 ± 0.25), suggesting that dust particles were responsible for the brightening. We used a dynamical model to understand the peculiar morphology, and found that the envelope consisted of small grains (0.3-1 μm) expanding at a maximum speed of 500 ± 40 m s{sup –1}, while the tail and coma were composed of a wider range of dust particle sizes (0.4-570 μm) and expansion speeds 7-390 m s{sup –1}. The total mass of ejecta is ∼5 × 10{sup 8} kg and kinetic energy ∼5 × 10{sup 12} J. These values are much smaller than in the historic outburst of 17P/Holmes in 2007, but the energy per unit mass (1 × 10{sup 4} J kg{sup –1}) is comparable. The energy per unit mass is about 10% of the energy released during the crystallization of amorphous water ice suggesting that crystallization of buried amorphous ice can supply the mass and energy of the outburst ejecta.

  19. Identification of a novel V1-type AVP receptor based on the molecular recognition theory.

    PubMed Central

    Herrera, V. L.; Ruiz-Opazo, N.

    2001-01-01

    BACKGROUND: The molecular recognition theory predicts that binding domains of peptide hormones and their corresponding receptor binding domains evolved from complementary strands of genomic DNA, and that a process of selective evolutionary mutational events within these primordial domains gave rise to the high affinity and high specificity of peptide hormone-receptor interactions observed today in different peptide hormone-receptor systems. Moreover, this theory has been broadened as a general hypothesis that could explain the evolution of intermolecular protein-protein and intramolecular peptide interactions. MATERIALS AND METHODS: Applying a molecular cloning strategy based on the molecular recognition theory, we screened a rat kidney cDNA library with a vasopressin (AVP) antisense oligonucleotide probe, expecting to isolate potential AVP receptors. RESULTS: We isolated a rat kidney cDNA encoding a functional V1-type vasopressin receptor. Structural analysis identified a 135 amino acid-long polypeptide with a single transmembrane domain, quite distinct from the rhodopsin-based G protein-coupled receptor superfamily. Functional analysis of the expressed V1-type receptor in Cos-1 cells revealed AVP-specific binding, AVP-specific coupling to Ca2+ mobilizing transduction system, and characteristic V1-type antagonist inhibition. CONCLUSIONS: This is the second AVP receptor cDNA isolated using AVP antipeptide-based oligonucleotide screening, thus providing compelling evidence in support of the molecular recognition theory as the basis of the evolution of this peptide hormone-receptor system, as well as adds molecular complexity and diversity to AVP receptor systems. PMID:11683375

  20. Outbursting Comet P/2010 V1 (Ikeya-Murakami): A Miniature Comet Holmes

    NASA Astrophysics Data System (ADS)

    Ishiguro, Masateru; Jewitt, David; Hanayama, Hidekazu; Usui, Fumihiko; Sekiguchi, Tomohiko; Yanagisawa, Kenshi; Kuroda, Daisuke; Yoshida, Michitoshi; Ohta, Kouji; Kawai, Nobuyuki; Miyaji, Takeshi; Fukushima, Hideo; Watanabe, Jun-ichi

    2014-05-01

    The short-period comet P/2010 V1 (Ikeya-Murakami, hereafter "V1") was discovered visually by two amateur astronomers. The appearance of the comet was peculiar, consisting of an envelope, a spherical coma near the nucleus and a tail extending in the anti-solar direction. We investigated the brightness and the morphological development of the comet by taking optical images with ground-based telescopes. Our observations show that V1 experienced a large-scale explosion between UT 2010 October 31 and November 3. The color of the comet was consistent with the Sun (g' - R C = 0.61 ± 0.20, R C - I C = 0.20 ± 0.20, and B - R C = 0.93 ± 0.25), suggesting that dust particles were responsible for the brightening. We used a dynamical model to understand the peculiar morphology, and found that the envelope consisted of small grains (0.3-1 μm) expanding at a maximum speed of 500 ± 40 m s-1, while the tail and coma were composed of a wider range of dust particle sizes (0.4-570 μm) and expansion speeds 7-390 m s-1. The total mass of ejecta is ~5 × 108 kg and kinetic energy ~5 × 1012 J. These values are much smaller than in the historic outburst of 17P/Holmes in 2007, but the energy per unit mass (1 × 104 J kg-1) is comparable. The energy per unit mass is about 10% of the energy released during the crystallization of amorphous water ice suggesting that crystallization of buried amorphous ice can supply the mass and energy of the outburst ejecta.

  1. Temperature-Dependent Vibrational Relaxation of NO(v=1) by O Atoms

    NASA Astrophysics Data System (ADS)

    Hwang, E. S.; Castle, K. J.; Dodd, J. A.

    2001-12-01

    For altitudes above about 80 km, oxygen molecules are increasingly dissociated by solar VUV absorption, and O atoms, together with O2 and N2, become a principal constituent of the atmosphere. Collisions of O with ground vibrational state NO efficiently excite NO(v=1), cooling the upper atmosphere by converting a portion of the ambient kinetic energy into 5.3-μ m IR emission which escapes into space. In recent years our group has worked to better characterize the vibrational energy transfer (VET) efficiencies for the NO(v)-O system. In our experiments vibrational relaxation rates are measured; they can be related to the corresponding uppumping rates through detailed balance. The experiment employs a cw microwave source to form O atoms, combined with photolysis of a trace amount of added NO2 to produce vibrationally excited NO. A double-jacketed quartz injector allows the introduction of O and NO2 into the reaction volume while minimizing wall-induced recombination and thermal decomposition, respectively. Oxygen atoms are detected through two-photon laser-induced fluorescence, cross-calibrated against a normalized O-atom signal resulting from photolysis of a known concentration of NO2. The experiment has been used to perform updated 295 K measurements for NO(v=1,2)-O relaxation, and 295-825 K measurements for NO(v=1)-O relaxation. A modest temperature dependence is observed. The variable temperature measurements provide key information for the accurate modeling of the lower thermospheric energy budget and IR radiant intensities. We also present associated quasiclassical trajectory calculations and TIME-GCM predictions of atmospheric temperature and density.

  2. A Convolutional Subunit Model for Neuronal Responses in Macaque V1

    PubMed Central

    Vintch, Brett; Movshon, J. Anthony

    2015-01-01

    The response properties of neurons in the early stages of the visual system can be described using the rectified responses of a set of self-similar, spatially shifted linear filters. In macaque primary visual cortex (V1), simple cell responses can be captured with a single filter, whereas complex cells combine a set of filters, creating position invariance. These filters cannot be estimated using standard methods, such as spike-triggered averaging. Subspace methods like spike-triggered covariance can recover multiple filters but require substantial amounts of data, and recover an orthogonal basis for the subspace in which the filters reside, rather than the filters themselves. Here, we assume a linear-nonlinear-linear-nonlinear (LN-LN) cascade model in which the first LN stage consists of shifted (“convolutional”) copies of a single filter, followed by a common instantaneous nonlinearity. We refer to these initial LN elements as the “subunits” of the receptive field, and we allow two independent sets of subunits, each with its own filter and nonlinearity. The second linear stage computes a weighted sum of the subunit responses and passes the result through a final instantaneous nonlinearity. We develop a procedure to directly fit this model to electrophysiological data. When fit to data from macaque V1, the subunit model significantly outperforms three alternatives in terms of cross-validated accuracy and efficiency, and provides a robust, biologically plausible account of receptive field structure for all cell types encountered in V1. SIGNIFICANCE STATEMENT We present a new subunit model for neurons in primary visual cortex that significantly outperforms three alternative models in terms of cross-validated accuracy and efficiency, and provides a robust and biologically plausible account of the receptive field structure in these neurons across the full spectrum of response properties. PMID:26538653

  3. 6. 6 kV/1. 5 kA-class superconducting fault current limiter development

    SciTech Connect

    Ito, D.; Yoneda, E.S.; Tsurunaga, K.; Tada, T. ); Hara, T.; Ohkuma, T.; Yamamoto, T. )

    1992-01-01

    This paper reports that the authors have developed and tested a 6.6 kV/1.5 kA-class fault current limiter wound with a 42-strand AC superconducting wire having ultra-fine MbTi filaments in a high resistivity matrix. In experiments, voltages up to 7.2 kV were applied to the limiter with phase angles of 0, 45, and 90 degrees. The limiter was able to limit the fault current to 1.8 kA successfully from the 55 kA short-circuit current that would flow in a circuit without limiter.

  4. Interpretation of the predissociation of the CO Rydberg W 1Π (v = 1) level

    NASA Astrophysics Data System (ADS)

    Lefebvre-Brion, H.; Kalemos, A.

    2016-04-01

    With the goal to interpret the experimental results obtained quite recently by Heays et al. [J. Chem. Phys. 141, 144311 (2014)] on the predissociation of the Rydberg W 1Π (v = 1) vibrational level of the CO molecule, we report herein ab initio potential energy curves of some of its valence and Rydberg states of both 1Π and 3Π symmetry. Our results confirm that the above vibrational level is perturbed by a new electronic 1Π state not observed until now. They correctly reproduce the linewidths of predissociation of the two interacting levels.

  5. Key comparison BIPM.RI(I)-K6 of the standards for absorbed dose to water at 10 g cm-2 of the NMIJ, Japan and the BIPM in accelerator photon beams

    NASA Astrophysics Data System (ADS)

    Picard, S.; Burns, D. T.; Roger, P.; Shimizu, M.; Morishita, Y.; Kato, M.; Tanaka, T.; Kurosawa, T.; Saito, N.

    2016-01-01

    A comparison of the dosimetry for accelerator photon beams was carried out between the National Metrology Institute of Japan (NMIJ) and the Bureau International des Poids et Mesures (BIPM) from 9 to 23 April 2015. The comparison was based on the determination of absorbed dose to water at 10 g cm-2 for three radiation qualities at the NMIJ. The results, reported as ratios of the NMIJ and the BIPM evaluations (and with the combined standard uncertainties given in parentheses), are 0.9966 (47) at 6 MV, 0.9965 (60) at 10 MV and 0.9953 (50) at 15 MV. This result is the eighth in the on-going BIPM.RI(I)-K6 series of comparisons. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  6. Enhanced therapeutic anti-inflammatory effect of betamethasone upon topical administration with low frequency, low intensity (20 kHz, 100 mW/cm2) ultrasound exposure on carrageenan-induced arthritis in mice model

    PubMed Central

    Cohen, Gadi; Natsheh, Hiba; Sunny, Youhan; Bawiec, Christopher R.; Touitou, Elka; Lerman, Melissa A.; Lazarovici, Philip; Lewin, Peter A.

    2015-01-01

    The purpose of this work was to investigate whether low frequency, low intensity (LFLI, 20 kHz, <100 mW/cm2, spatial-peak, temporal-peak) ultrasound (US), delivered by a light-weight (<100g), tether-free, fully wearable, battery powered applicator is capable of reducing inflammation in a mouse model of Rheumatoid Arthritis (RA). The therapeutic, acute, anti-inflammatory effect was estimated by the relative swelling induced in mice hind limb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near infrared labeled 2-deoxy-glucose (2DG). The outcome of the experiments indicated that the combination of US exposure with topical application of 0.1% w/w betamethasone gel, exhibited statistically significant (p<0.05) enhanced anti-inflammatory properties in comparison with the drug or US treatment alone. The present study underscores the potential benefits of LFLI US assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, safe, LFLI ultrasound promoted non-invasive drug delivery. PMID:26003010

  7. Lidocaine promotes the trafficking and functional expression of Na(v)1.8 sodium channels in mammalian cells.

    PubMed

    Zhao, Juan; Ziane, Rahima; Chatelier, Aurélien; O'leary, Michael E; Chahine, Mohamed

    2007-07-01

    Nociceptive neurons of the dorsal root ganglion (DRG) express a combination of rapidly gating TTX-sensitive and slowly gating TTX-resistant Na currents, and the channels that produce these currents have been cloned. The Na(v)1.7 and Na(v)1.8 channels encode for the rapidly inactivating TTX-sensitive and slowly inactivating TTX-resistant Na currents, respectively. Although the Na(v)1.7 channel expresses well in cultured mammalian cell lines, attempts to express the Na(v)1.8 channel using similar approaches has been met with limited success. The inability to heterologously express Na(v)1.8 has hampered detailed characterization of the biophysical properties and pharmacology of these channels. In this study, we investigated the determinants of Na(v)1.8 expression in tsA201 cells, a transformed variant of HEK293 cells, using a combination of biochemistry, immunochemistry, and electrophysiology. Our data indicate that the unusually low expression levels of Na(v)1.8 in tsA201 cells results from a trafficking defect that traps the channel protein in the endoplasmic reticulum. Incubating the cultured cells with the local anesthetic lidocaine dramatically enhanced the cell surface expression of functional Na(v)1.8 channels. The biophysical properties of the heterologously expressed Na(v)1.8 channel are similar but not identical to those of the TTX-resistant Na current of native DRG neurons, recorded under similar conditions. Our data indicate that the lidocaine acts as a molecular chaperone that promotes efficient trafficking and increased cell surface expression of Na(v)1.8 channels. PMID:17507497

  8. Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology

    PubMed Central

    Stanika, Ruslan; Campiglio, Marta; Pinggera, Alexandra; Lee, Amy; Striessnig, Jörg; Flucher, Bernhard E.; Obermair, Gerald J.

    2016-01-01

    Dendritic spines are the postsynaptic compartments of glutamatergic synapses in the brain. Their number and shape are subject to change in synaptic plasticity and neurological disorders including autism spectrum disorders and Parkinson’s disease. The L-type calcium channel CaV1.3 constitutes an important calcium entry pathway implicated in the regulation of spine morphology. Here we investigated the importance of full-length CaV1.3L and two C-terminally truncated splice variants (CaV1.342A and CaV1.343S) and their modulation by densin-180 and shank1b for the morphology of dendritic spines of cultured hippocampal neurons. Live-cell immunofluorescence and super-resolution microscopy of epitope-tagged CaV1.3L revealed its localization at the base-, neck-, and head-region of dendritic spines. Expression of the short splice variants or deletion of the C-terminal PDZ-binding motif in CaV1.3L induced aberrant dendritic spine elongation. Similar morphological alterations were induced by co-expression of densin-180 or shank1b with CaV1.3L and correlated with increased CaV1.3 currents and dendritic calcium signals in transfected neurons. Together, our findings suggest a key role of CaV1.3 in regulating dendritic spine structure. Under physiological conditions it may contribute to the structural plasticity of glutamatergic synapses. Conversely, altered regulation of CaV1.3 channels may provide an important mechanism in the development of postsynaptic aberrations associated with neurodegenerative disorders. PMID:27708393

  9. Genetic engineering of trimers of hypoallergenic fragments of the major birch pollen allergen, Bet v 1, for allergy vaccination.

    PubMed

    Vrtala, Susanne; Fohr, Monika; Campana, Raffaela; Baumgartner, Christian; Valent, Peter; Valenta, Rudolf

    2011-03-01

    An immunotherapy trial performed in allergic patients with hypoallergenic recombinant fragments, comprising aa 1-74 and 75-160 of the major birch pollen allergen, Bet v 1, has indicated that the induction of allergen-specific IgG responses may be an important mechanism of this treatment. To investigate whether the immunogenicity of the rBet v 1 fragments can be increased, recombinant trimers of the fragments were produced. For this purpose, DNA trimers of rBet v 1 aa 1-74 as well as of rBet v 1 aa 75-160 were subcloned into expression plasmid pET 17b, expressed in Escherichia coli and purified. The fragments as well as the fragment trimers showed a reduced IgE-binding capacity and allergenic activity compared to rBet v 1 wildtype when tested in allergic patients. Both rBet v 1 aa 75-160 monomer and trimer induced high titers of allergen-specific IgG1 Abs in mice. Interestingly, rBet v 1 aa 1-74 trimer induced a much higher IgG(1) response to rBet v 1 than rBet v 1 aa 1-74 monomer. Consequently, IgG Abs induced with the rBet v 1 aa 1-74 trimer inhibited birch pollen allergic patients' IgE-binding 10-fold more efficiently than IgG Abs induced with the monomer. Our data show that the immunogenicity of allergy vaccines can be increased by oligomerization.

  10. Lidocaine promotes the trafficking and functional expression of Na(v)1.8 sodium channels in mammalian cells.

    PubMed

    Zhao, Juan; Ziane, Rahima; Chatelier, Aurélien; O'leary, Michael E; Chahine, Mohamed

    2007-07-01

    Nociceptive neurons of the dorsal root ganglion (DRG) express a combination of rapidly gating TTX-sensitive and slowly gating TTX-resistant Na currents, and the channels that produce these currents have been cloned. The Na(v)1.7 and Na(v)1.8 channels encode for the rapidly inactivating TTX-sensitive and slowly inactivating TTX-resistant Na currents, respectively. Although the Na(v)1.7 channel expresses well in cultured mammalian cell lines, attempts to express the Na(v)1.8 channel using similar approaches has been met with limited success. The inability to heterologously express Na(v)1.8 has hampered detailed characterization of the biophysical properties and pharmacology of these channels. In this study, we investigated the determinants of Na(v)1.8 expression in tsA201 cells, a transformed variant of HEK293 cells, using a combination of biochemistry, immunochemistry, and electrophysiology. Our data indicate that the unusually low expression levels of Na(v)1.8 in tsA201 cells results from a trafficking defect that traps the channel protein in the endoplasmic reticulum. Incubating the cultured cells with the local anesthetic lidocaine dramatically enhanced the cell surface expression of functional Na(v)1.8 channels. The biophysical properties of the heterologously expressed Na(v)1.8 channel are similar but not identical to those of the TTX-resistant Na current of native DRG neurons, recorded under similar conditions. Our data indicate that the lidocaine acts as a molecular chaperone that promotes efficient trafficking and increased cell surface expression of Na(v)1.8 channels.

  11. Ultra-broad gain quantum cascade lasers tunable from 6.5 to 10.4 μm.

    PubMed

    Xie, Feng; Caneau, C; Leblanc, H; Ho, M-T; Zah, C

    2015-09-01

    We present a quantum cascade laser structure with an ultra-broad gain profile that covers the wavelength range from 6.5 to 10.4 μm. In a grating-tuned external cavity, we demonstrated continuous tuning from 1027  cm(-1) to 1492  cm(-1) with this broad gain laser chip. We also fabricated distributed feedback quantum cascade laser arrays with this active region design and varied grating periods. We demonstrated single wavelength lasing from 962 (10.4) to 1542  cm(-1) (6.5 μm). The frequency coverage (580  cm(-1)) is about 46% of center frequency.

  12. Swift J1822.3-1606: Optical spectroscopy of the counterpart candidates from the 10.4m GTC

    NASA Astrophysics Data System (ADS)

    de Ugarte Postigo, A.; Munoz-Darias, T.

    2011-07-01

    We have performed optical spectroscopy of the two objects (S1 and S2; ATEL #3496, #3502) present within the Swift/XRT error circle of the Soft Gamma-ray Repeater (SGR) candidate, Swift J1822.3-1606 (ATEL #3488, #3489, #3490, #3491, #3493, #3501, #3503). Observations were performed on July 20, 2011 using the OSIRIS spectrograph at the 10.4m Gran Telescopio de Canarias (GTC) telescope in La Palma, Spain.

  13. Serological Profile of Torque Teno Sus Virus Species 1 (TTSuV1) in Pigs and Antigenic Relationships between Two TTSuV1 Genotypes (1a and 1b), between Two Species (TTSuV1 and -2), and between Porcine and Human Anelloviruses

    PubMed Central

    Huang, Yao-Wei; Harrall, Kylie K.; Dryman, Barbara A.; Opriessnig, Tanja; Vaughn, Eric M.; Roof, Michael B.

    2012-01-01

    The family Anelloviridae includes human and animal torque teno viruses (TTVs) with extensive genetic diversity. The antigenic diversity among anelloviruses has never been assessed. Using torque teno sus virus (TTSuV) as a model, we describe here the first investigation of the antigenic relationships among different anelloviruses. Using a TTSuV genotype 1a (TTSuV1a) or TTSuV1b enzyme-linked immunosorbent assay (ELISA) based on the respective putative ORF1 capsid antigen and TTSuV1-specific real-time PCR, the combined serological and virological profile of TTSuV1 infection in pigs was determined and compared with that of TTSuV2. TTSuV1 is likely not associated with porcine circovirus-associated disease (PCVAD), because both the viral loads and antibody levels were not different between affected and unaffected pigs and because there was no synergistic effect of concurrent PCV2/TTSuV1 infections. We did observe a higher correlation of IgG antibody levels between anti-TTSuV1a and -TTSuV1b than between anti-TTSuV1a or -1b and anti-TTSuV2 antibodies in these sera, implying potential antigenic cross-reactivity. To confirm this, rabbit antisera against the putative capsid proteins of TTSuV1a, TTSuV1b, or TTSuV2 were generated, and the antigenic relationships among these TTSuVs were analyzed by an ELISA and by an immunofluorescence assay (IFA) using PK-15 cells transfected with one of the three TTSuV ORF1 constructs. The results demonstrate antigenic cross-reactivity between the two genotypes TTSuV1a and TTSuV1b but not between the two species TTSuV1a or -1b and TTSuV2. Furthermore, an anti-genogroup 1 human TTV antiserum did not react with any of the three TTSuV antigens. These results have important implications for an understanding of the diversity of anelloviruses as well as for the classification and vaccine development of TTSuVs. PMID:22811540

  14. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies

    PubMed Central

    Doria-Rose, Nicole A.; Schramm, Chaim A.; Gorman, Jason; Moore, Penny L.; Bhiman, Jinal N.; DeKosky, Brandon J.; Ernandes, Michael J.; Georgiev, Ivelin S.; Kim, Helen J.; Pancera, Marie; Staupe, Ryan P.; Altae-Tran, Han R.; Bailer, Robert T.; Crooks, Ema T.; Cupo, Albert; Druz, Aliaksandr; Garrett, Nigel J.; Hoi, Kam H.; Kong, Rui; Louder, Mark K.; Longo, Nancy S.; McKee, Krisha; Nonyane, Molati; O’Dell, Sijy; Roark, Ryan S.; Rudicell, Rebecca S.; Schmidt, Stephen D.; Sheward, Daniel J.; Soto, Cinque; Wibmer, Constantinos Kurt; Yang, Yongping; Zhang, Zhenhai; Mullikin, James C.; Binley, James M.; Sanders, Rogier W.; Wilson, Ian A.; Moore, John P.; Ward, Andrew B.; Georgiou, George; Williamson, Carolyn; Abdool Karim, Salim S.; Morris, Lynn; Kwong, Peter D.; Shapiro, Lawrence; Mascola, John R.

    2015-01-01

    Summary Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from CAPRISA-donor CAP256; each antibody contained the protruding tyrosine-sulfated, anionic antigen-binding loop (CDR H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30–38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation, an important vaccine insight. PMID:24590074

  15. Looming sensitive cortical regions without V1 input: evidence from a patient with bilateral cortical blindness

    PubMed Central

    Hervais-Adelman, Alexis; Legrand, Lore B.; Zhan, Minye; Tamietto, Marco; de Gelder, Beatrice; Pegna, Alan J.

    2015-01-01

    Fast and automatic behavioral responses are required to avoid collision with an approaching stimulus. Accordingly, looming stimuli have been found to be highly salient and efficient attractors of attention due to the implication of potential collision and potential threat. Here, we address the question of whether looming motion is processed in the absence of any functional primary visual cortex and consequently without awareness. For this, we investigated a patient (TN) suffering from complete, bilateral damage to his primary visual cortex. Using an fMRI paradigm, we measured TN's brain activation during the presentation of looming, receding, rotating, and static point lights, of which he was unaware. When contrasted with other conditions, looming was found to produce bilateral activation of the middle temporal areas, as well as the superior temporal sulcus and inferior parietal lobe (IPL). The latter are generally thought to be involved in multisensory processing of motion in extrapersonal space, as well as attentional capture and saliency. No activity was found close to the lesioned V1 area. This demonstrates that looming motion is processed in the absence of awareness through direct subcortical projections to areas involved in multisensory processing of motion and saliency that bypass V1. PMID:26557059

  16. Population responses in V1 encode different figures by response amplitude.

    PubMed

    Gilad, Ariel; Slovin, Hamutal

    2015-04-22

    The visual system simultaneously segregates between several objects presented in a visual scene. The neural code for encoding different objects or figures is not well understood. To study this question, we trained two monkeys to discriminate whether two elongated bars are either separate, thus generating two different figures, or connected, thus generating a single figure. Using voltage-sensitive dyes, we imaged at high spatial and temporal resolution V1 population responses evoked by the two bars, while keeping their local attributes similar among the two conditions. In the separate condition, unlike the connected condition, the population response to one bar is enhanced, whereas the response to the other is simultaneously suppressed. The response to the background remained unchanged between the two conditions. This divergent pattern developed ∼200 ms poststimulus onset and could discriminate well between the separate and connected single trials. The stimulus separation saliency and behavioral report were highly correlated with the differential response to the bars. In addition, the proximity and/or the specific location of the connectors seemed to have only a weak effect on this late activity pattern, further supporting the involvement of top-down influences. Additional neural codes were less informative about the separate and connected conditions, with much less consistency and discriminability compared with a response amplitude code. We suggest that V1 is involved in the encoding of each figure by different neuronal response amplitude, which can mediate their segregation and perception. PMID:25904787

  17. Adaptation to visual stimulation modifies the burst firing property of V1 neurons.

    PubMed

    Liu, Rui-Long; Wang, Ke; Meng, Jian-Jun; Hua, Tian-Miao; Liang, Zhen; Xi, Min-Min

    2013-06-01

    The mean firing rate of visual cortical neurons is reduced after prolonged visual stimulation, but the underlying process by which this occurs as well as the biological significance of this phenomenon remains unknown. Computational neuroscience studies indicate that high-frequency bursts in stimulus-driven responses can be transmitted across synapses more reliably than isolated spikes, and thus may carry accurate stimulus-related information. Our research examined whether or not adaptation affects the burst firing property of visual cortical neurons by examining changes in the burst firing changes of V1 neurons during adaptation to the preferred visual stimulus. The results show that adaptation to prolonged visual stimulation significantly decreased burst frequency (bursts/s) and burst length (spikes/burst), but increased burst duration and the interspike interval within bursts. These results suggest that the adaptation of V1 neurons to visual stimulation may result in a decrease of feedforward response gain but an increase of functional activities from lateral and/or feedback connections, which could lead to a reduction in the effectiveness of adapted neurons in transmitting information to its driven neurons.

  18. Vasopressin eliminates the expression of familiar odor bias in neonatal female mice through V1aR

    PubMed Central

    Hammock, Elizabeth A.D.; Law, Caitlin S.; Levitt, Pat

    2014-01-01

    Summary V1aR has a well established role in the neural regulation of adult mammalian social behavior. The role of V1aR in developmentally emerging social behavior is less well understood. We mapped V1aR at post-natal day 8 (P8) and demonstrate developmentally-specific expression in the neocortex and hippocampus. We tested the ability of male and female C57BL/6J mice to show orienting bias to a familiar odor at this age. We demonstrate that females, but not males, show an orienting bias for odors previously paired with the mother, which is eliminated by V1aR signaling. Arginine-vasopressin (AVP) and the vasopressin V1a receptor (V1aR) acting within the forebrain are involved in social behavior in adult animals. Much less is known about the function of V1aR in neurobehavioral development. In the present study, at post-natal day 8 (P8) in neonatal C57BL/6J mice, we map V1aR and use an olfactory exposure paradigm to assess a role for V1aR on olfactory preferences. In addition to V1aR in the lateral septum and ventral tegmental area, we observe V1aR in the neocortex and hippocampus, not typically observed in adult mice, implicating a developmental sensitive period for V1aR to modulate these brain areas in an experience-dependent manner. Males and females were tested on P8 for orienting preferences after exposure to a non-social odor, presented either when the mother was in the home cage (contingent) or when the mother had been removed from the home cage (not contingent). Wild-type female mice show a selective orienting bias toward the exposed odor, but only in the contingent condition. Males did not show orienting bias after either training condition. Female Avpr1a-/- mice showed strong familiar odor bias, regardless of the training condition. This finding led us to test the ability of AVP to diminish odor bias in females. Central application of AVP eliminated odor bias in Avpr1a+/+, but not Avpr1a-/- female mice. Together, these data indicate that AVP acting at V1a

  19. U.S. Regional Agricultural Production in 2030 and 2095: Response to CO2 Fertilization and Hadley Climate Model (HadCM2) Projections of Greenhouse-Forced Climatic Change

    SciTech Connect

    NJ Rosenberg; RC Izaurralde: RA Brown

    1999-11-19

    Research activities underway to evaluate potential consequences of climate change and variability on the agriculture, water resources, and other U.S. sectors were mandated by the Global Change Research Act of 1990. These activities are being carried out in a public-private partnership under the guidance of the U.S. Global Change Research Program. Researchers at Pacific Northwest National Laboratory (PNNL) have been using integrated assessment methodologies to appraise the possible impacts of global warming and climatic variability on the behavior of managed and natural systems. This interim PNNL report contributes to the U.S. National Assessment process with an analysis of the modeled impacts of climatic changes projected by the Hadley/UKMO (HadCM2) general circulation model on agricultural productivity and selected environmental variables. The construction of climatic data for the simulation runs followed general guidelines established by the U.S. National Assessment Synthesis Team. The baseline climate data were obtained from national records for the period 1961 - 1990. The scenario runs for two future periods (2025 - 2030 and 2090 - 2099) were extracted from results of a HadCM2 run distributed at a half-degree spatial resolution. The Erosion Productivity Impact Calculator (EPIC) was used to simulate the behavior of 204 "representative farms" (i.e., soil-climate-management combinations) under baseline climate, the two future periods and their combinations with two levels of atmospheric C02 concentrations (365 and 560 ppm). Analysis of simulation results identified areas in Texas, New Mexico, Colorado, Utah, Arizona, and California that would experience large temperature increases by 2030. Slight cooling is expected by 2030 in parts of Alabama, Florida, Maine, Montana, Idaho, and Utah. Larger areas will experience increased warming by 2095. Uniform precipitation increases are expected by 2030 in the north eastern quarter of the country. These uniform precipitation

  20. NaV1.8 channels are expressed in large, as well as small, diameter sensory afferent neurons.

    PubMed

    Ramachandra, Renuka; McGrew, Stephanie Y; Baxter, James C; Howard, Jason R; Elmslie, Keith S

    2013-01-01

    Sensory neurons in the dorsal root ganglia (DRG) express a subset of voltage dependent sodium channels (NaV) including NaV1.1, 1.6, 1.7, 1.8 and 1.9. Previous work supported preferential localization of NaV1.8 channels to small-medium diameter, nociceptive afferent neurons. However, we recently published evidence that NaV1.8 was the dominant NaV channel expressed in the somas of small, medium and large diameter muscle afferent neurons, which is consistent with other reports. Here, we extend those results to show that NaV1.8 expression is not correlated with afferent neuron diameter. Using immunocytochemistry, we found NaV1.8 expression in ~50% of sensory afferent neurons with diameters ranging from 20 to 70 µm. In addition, electrophysiological analysis shows that the kinetic and inactivation properties of NaV1.8 current are invariant with neuron size. These data add further support to the idea that NaV1.8 contributes to the electrical excitability of both nociceptive and non-nociceptive sensory neurons. PMID:23064159

  1. Axotomy does not up-regulate expression of sodium channel Na(v)1.8 in Purkinje cells.

    PubMed

    Black, J A; Dusart, I; Sotelo, C; Waxman, S G

    2002-05-30

    Aberrant expression of the sensory neuron specific (SNS) sodium channel Na(v)1.8 has been demonstrated in cerebellar Purkinje cells in experimental models of multiple sclerosis (MS) and in human MS. The aberrant expression of Na(v)1.8, which is normally present in primary sensory neurons but not in the CNS, may perturb cerebellar function, but the mechanisms that trigger it are not understood. Because axotomy can provoke changes in Na(v)1.8 expression in dorsal root ganglion (DRG) neurons, we tested the hypothesis that axotomy can provoke an up-regulation of Na(v)1.8 expression in Purkinje cells, using a surgical model that transects axons of Purkinje cells in lobules IIIb-VII in the rat. In situ hybridization and immunocytochemistry did not reveal an up-regulation of Na(v)1.8 mRNA or protein in axotomized Purkinje cells. Hybridization and immunostaining signals for the sodium channel Na(v)1.6 were clearly present, demonstrating that sodium channel transcripts and protein were present in experimental cerebella. These results demonstrate that axotomy does not trigger the expression of Na(v)1.8 in Purkinje cells. PMID:12007840

  2. Integrate-and-fire vs Poisson models of LGN input to V1 cortex: noisier inputs reduce orientation selectivity.

    PubMed

    Lin, I-Chun; Xing, Dajun; Shapley, Robert

    2012-12-01

    One of the reasons the visual cortex has attracted the interest of computational neuroscience is that it has well-defined inputs. The lateral geniculate nucleus (LGN) of the thalamus is the source of visual signals to the primary visual cortex (V1). Most large-scale cortical network models approximate the spike trains of LGN neurons as simple Poisson point processes. However, many studies have shown that neurons in the early visual pathway are capable of spiking with high temporal precision and their discharges are not Poisson-like. To gain an understanding of how response variability in the LGN influences the behavior of V1, we study response properties of model V1 neurons that receive purely feedforward inputs from LGN cells modeled either as noisy leaky integrate-and-fire (NLIF) neurons or as inhomogeneous Poisson processes. We first demonstrate that the NLIF model is capable of reproducing many experimentally observed statistical properties of LGN neurons. Then we show that a V1 model in which the LGN input to a V1 neuron is modeled as a group of NLIF neurons produces higher orientation selectivity than the one with Poisson LGN input. The second result implies that statistical characteristics of LGN spike trains are important for V1's function. We conclude that physiologically motivated models of V1 need to include more realistic LGN spike trains that are less noisy than inhomogeneous Poisson processes.

  3. Low-voltage back-gated atmospheric pressure chemical vapor deposition based graphene-striped channel transistor with high-κ dielectric showing room-temperature mobility > 11,000 cm(2)/V·s.

    PubMed

    Smith, Casey; Qaisi, Ramy; Liu, Zhihong; Yu, Qingkai; Hussain, Muhammad Mustafa

    2013-07-23

    Utilization of graphene may help realize innovative low-power replacements for III-V materials based high electron mobility transistors while extending operational frequencies closer to the THz regime for superior wireless communications, imaging, and other novel applications. Device architectures explored to date suffer a fundamental performance roadblock due to lack of compatible deposition techniques for nanometer-scale dielectrics required to efficiently modulate graphene transconductance (gm) while maintaining low gate capacitance-voltage product (CgsVgs). Here we show integration of a scaled (10 nm) high-κ gate dielectric aluminum oxide (Al2O3) with an atmospheric pressure chemical vapor deposition (APCVD)-derived graphene channel composed of multiple 0.25 μm stripes to repeatedly realize room-temperature mobility of 11,000 cm(2)/V·s or higher. This high performance is attributed to the APCVD graphene growth quality, excellent interfacial properties of the gate dielectric, conductivity enhancement in the graphene stripes due to low tox/Wgraphene ratio, and scaled high-κ dielectric gate modulation of carrier density allowing full actuation of the device with only ±1 V applied bias. The superior drive current and conductance at Vdd = 1 V compared to other top-gated devices requiring undesirable seed (such as aluminum and poly vinyl alcohol)-assisted dielectric deposition, bottom gate devices requiring excessive gate voltage for actuation, or monolithic (nonstriped) channels suggest that this facile transistor structure provides critical insight toward future device design and process integration to maximize CVD-based graphene transistor performance.

  4. A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway

    SciTech Connect

    Zhang, Xuenong; Wei, Han; Liu, Ziwei; Yuan, Qianying; Wei, Anhua; Shi, Du; Yang, Xian; Ruan, Jinlan

    2013-07-15

    Protoapigenone is a unique flavonoid and enriched in many ferns, showing potent antitumor activity against a broad spectrum of human cancer cell lines. RY10-4, a modified version of protoapigenone, manifested better anti-proliferation activity in human breast cancer cell line MCF-7. The cytotoxicity of RY10-4 against MCF-7 cells is exhibited in both time- and concentration-dependent manners. Here we investigated a novel effect of RY10-4 mediated autophagy in autophagy defect MCF-7 cells. Employing immunofluorescence assay for microtubule-associated protein light-chain 3 (LC3), monodansylcadaverine staining, Western blotting analyses for LC3 and p62 as well as ultrastructural analysis by transmission electron microscopy, we showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Meanwhile, inhibition of autophagy by pharmacological and genetic approaches significantly increased the viability of RY10-4 treated cells, suggesting that the autophagy induced by RY10-4 played as a promotion mechanism for cell death. Further studies revealed that RY10-4 suppressed the activation of mTOR and p70S6K via the Akt/mTOR pathway. Our results provided new insights for the mechanism of RY10-4 induced cell death and the cause of RY10-4 showing better antitumor activity than protoapigenone, and supported further evidences for RY10-4 as a lead to design a promising antitumor agent. - Highlights: • We showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. • Autophagy induced by RY10-4 played as a promotion mechanism for cell death. • RY10-4 induced autophagy in MCF-7 cell through the Akt/mTOR pathway. • We provided new insights for the mechanism of RY10-4 induced cell death.

  5. Ca(V)1.3-driven SK channel activation regulates pacemaking and spike frequency adaptation in mouse chromaffin cells.

    PubMed

    Vandael, David H F; Zuccotti, Annalisa; Striessnig, Joerg; Carbone, Emilio

    2012-11-14

    Mouse chromaffin cells (MCCs) fire spontaneous action potentials (APs) at rest. Ca(v)1.3 L-type calcium channels sustain the pacemaker current, and their loss results in depolarized resting potentials (V(rest)), spike broadening, and remarkable switches into depolarization block after BayK 8644 application. A functional coupling between Ca(v)1.3 and BK channels has been reported but cannot fully account for the aforementioned observations. Here, using Ca(v)1.3(-/-) mice, we investigated the role of Ca(v)1.3 on SK channel activation and how this functional coupling affects the firing patterns induced by sustained current injections. MCCs express SK1-3 channels whose tonic currents are responsible for the slow irregular firing observed at rest. Percentage of frequency increase induced by apamin was found inversely correlated to basal firing frequency. Upon stimulation, MCCs build-up Ca(v)1.3-dependent SK currents during the interspike intervals that lead to a notable degree of spike frequency adaptation (SFA). The major contribution of Ca(v)1.3 to the subthreshold Ca(2+) charge during an AP-train rather than a specific molecular coupling to SK channels accounts for the reduced SFA of Ca(v)1.3(-/-) MCCs. Low adaptation ratios due to reduced SK activation associated with Ca(v)1.3 deficiency prevent the efficient recovery of Na(V) channels from inactivation. This promotes a rapid decline of AP amplitudes and facilitates early onset of depolarization block following prolonged stimulation. Thus, besides serving as pacemaker, Ca(v)1.3 slows down MCC firing by activating SK channels that maintain Na(V) channel availability high enough to preserve stable AP waveforms, even upon high-frequency stimulation of chromaffin cells during stress responses. PMID:23152617

  6. Characterization of PR-10 genes from eight Betula species and detection of Bet v 1 isoforms in birch pollen

    PubMed Central

    Schenk, Martijn F; Cordewener, Jan HG; America, Antoine HP; van't Westende, Wendy PC; Smulders, Marinus JM; Gilissen, Luud JWJ

    2009-01-01

    Background Bet v 1 is an important cause of hay fever in northern Europe. Bet v 1 isoforms from the European white birch (Betula pendula) have been investigated extensively, but the allergenic potency of other birch species is unknown. The presence of Bet v 1 and closely related PR-10 genes in the genome was established by amplification and sequencing of alleles from eight birch species that represent the four subgenera within the genus Betula. Q-TOF LC-MSE was applied to identify which PR-10/Bet v 1 genes are actually expressed in pollen and to determine the relative abundances of individual isoforms in the pollen proteome. Results All examined birch species contained several PR-10 genes. In total, 134 unique sequences were recovered. Sequences were attributed to different genes or pseudogenes that were, in turn, ordered into seven subfamilies. Five subfamilies were common to all birch species. Genes of two subfamilies were expressed in pollen, while each birch species expressed a mixture of isoforms with at least four different isoforms. Isoforms that were similar to isoforms with a high IgE-reactivity (Bet v 1a = PR-10.01A01) were abundant in all species except B. lenta, while the hypoallergenic isoform Bet v 1d (= PR-10.01B01) was only found in B. pendula and its closest relatives. Conclusion Q-TOF LC-MSE allows efficient screening of Bet v 1 isoforms by determining the presence and relative abundance of these isoforms in pollen. B. pendula contains a Bet v 1-mixture in which isoforms with a high and low IgE-reactivity are both abundant. With the possible exception of B. lenta, isoforms identical or very similar to those with a high IgE-reactivity were found in the pollen proteome of all examined birch species. Consequently, these species are also predicted to be allergenic with regard to Bet v 1 related allergies. PMID:19257882

  7. VSTM-v1, a potential myeloid differentiation antigen that is downregulated in bone marrow cells from myeloid leukemia patients.

    PubMed

    Xie, Min; Li, Ting; Li, Ning; Li, Jinlan; Yao, Qiumei; Han, Wenling; Ruan, Guorui

    2015-01-01

    Leukocyte differentiation antigens often represent important markers for the diagnosis, classification, prognosis, and therapeutic targeting of myeloid leukemia. Herein, we report a potential leukocyte differentiation antigen gene VSTM1 (V-set and transmembrane domain-containing 1) that was downregulated in bone marrow cells from leukemia patients and exhibited a higher degree of promoter methylation. The expression level of its predominant encoded product, VSTM1-v1, was positively correlated with myeloid cell maturation state. Restoration of VSTM1-v1 expression inhibited myeloid leukemia cells' growth. Therefore, VSTM1-v1 might represent an important myeloid leukocyte differentiation antigen and provide a potential target for the diagnosis and treatment of leukemia.

  8. Insulator to Correlated Metal Transition in V1−xMoxO2

    SciTech Connect

    Holman, K.; McQueen, T; Williams, A; Klimczuk, T; Stephens, P; Zandbergen, H; Xu, Q; Ronning, F; Cava, R

    2009-01-01

    Although many materials display the transition from insulating to metallic behavior on doping, only a few, such as VO2, have the right combination of crystal structure and physical properties to serve as model systems. Here we report the electronic and structural characteristics of the insulator to metal transition in V1-xMoxO2, which we have studied over the range 0.0=x=0.50 through characterization of the electrical resistivity, magnetic susceptibility, specific heat, and average- and short-range crystal structures. We find that metal-metal pairing exists in small domains in the doped metallic phases and an unexpected phenomenology for the crossover between a Curie-Weiss insulating regime and an intermediate mass metallic regime. An electronic phase diagram is presented.

  9. Collisional vibrational energy transfer of OH (A 2Sigma + , v'=1)

    NASA Astrophysics Data System (ADS)

    Williams, Leah R.; Crosley, David R.

    1996-05-01

    Vibrational energy transfer (VET) and quenching of the v'=1 level of A 2Σ+ OH have been studied using laser-induced fluorescence in a discharge flow cell at room temperature. VET cross sections (Å2) are N2, 30.1±2.8; O2, 2.8±0.3; Ar, 0.56±0.05; H2O, 8.6±0.6. The rotational energy distribution in v'=0 following the VET event was determined for nine colliders. It is nonthermal, generally populating high rotational levels. There are three broad categories of colliders that cause varying degrees of vibrational to rotational energy transfer; H2, D2, and CH4 show the least; N2, CO2, CF4, and N2O more; and O2 and Ar the most, with about one-third of the vibrational energy appearing as OH rotation.

  10. Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy

    PubMed Central

    Yang, Linlin; Li, Quanmin; Liu, Xinming; Liu, Shiguang

    2016-01-01

    Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause–effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy. PMID:27608006

  11. Roles of Voltage-Gated Tetrodotoxin-Sensitive Sodium Channels NaV1.3 and NaV1.7 in Diabetes and Painful Diabetic Neuropathy.

    PubMed

    Yang, Linlin; Li, Quanmin; Liu, Xinming; Liu, Shiguang

    2016-01-01

    Diabetes mellitus (DM) is a common chronic medical problem worldwide; one of its complications is painful peripheral neuropathy, which can substantially erode quality of life and increase the cost of management. Despite its clinical importance, the pathogenesis of painful diabetic neuropathy (PDN) is complex and incompletely understood. Voltage-gated sodium channels (VGSCs) link many physiological processes to electrical activity by controlling action potentials in all types of excitable cells. Two isoforms of VGSCs, NaV1.3 and NaV1.7, which are encoded by the sodium voltage-gated channel alpha subunit 3 and 9 (Scn3A and Scn9A) genes, respectively, have been identified in both peripheral nociceptive neurons of dorsal root ganglion (DRG) and pancreatic islet cells. Recent advances in our understanding of tetrodotoxin-sensitive (TTX-S) sodium channels NaV1.3 and NaV1.7 lead to the rational doubt about the cause-effect relation between diabetes and painful neuropathy. In this review, we summarize the roles of NaV1.3 and NaV1.7 in islet cells and DRG neurons, discuss the link between DM and painful neuropathy, and present a model, which may provide a starting point for further studies aimed at identifying the mechanisms underlying diabetes and painful neuropathy. PMID:27608006

  12. Adaptive behavior of neighboring neurons during adaptation-induced plasticity of orientation tuning in V1

    PubMed Central

    2009-01-01

    Background Sensory neurons display transient changes of their response properties following prolonged exposure to an appropriate stimulus (adaptation). In adult cat primary visual cortex, orientation-selective neurons shift their preferred orientation after being adapted to a non-preferred orientation. The direction of those shifts, towards (attractive) or away (repulsive) from the adapter depends mostly on adaptation duration. How the adaptive behavior of a neuron is related to that of its neighbors remains unclear. Results Here we show that in most cases (75%), cells shift their preferred orientation in the same direction as their neighbors. We also found that cells shifting preferred orientation differently from their neighbors (25%) display three interesting properties: (i) larger variance of absolute shift amplitude, (ii) wider tuning bandwidth and (iii) larger range of preferred orientations among the cluster of cells. Several response properties of V1 neurons depend on their location within the cortical orientation map. Our results suggest that recording sites with both attractive and repulsive shifts following adaptation may be located in close proximity to iso-orientation domain boundaries or pinwheel centers. Indeed, those regions have a more diverse orientation distribution of local inputs that could account for the three properties above. On the other hand, sites with all cells shifting their preferred orientation in the same direction could be located within iso-orientation domains. Conclusions Our results suggest that the direction and amplitude of orientation preference shifts in V1 depend on location within the orientation map. This anisotropy of adaptation-induced plasticity, comparable to that of the visual cortex itself, could have important implications for our understanding of visual adaptation at the psychophysical level. PMID:20003453

  13. A User's Manual for MASH V1.5 - A Monte Carlo Adjoint Shielding Code System

    SciTech Connect

    C. O. Slater; J. M. Barnes; J. O. Johnson; J.D. Drischler

    1998-10-01

    The Monte Carlo ~djoint ~ielding Code System, MASH, calculates neutron and gamma- ray environments and radiation protection factors for armored military vehicles, structures, trenches, and other shielding configurations by coupling a forward discrete ordinates air- over-ground transport calculation with an adjoint Monte Carlo treatment of the shielding geometry. Efficiency and optimum use of computer time are emphasized. The code system includes the GRTUNCL and DORT codes for air-over-ground transport calculations, the MORSE code with the GIFT5 combinatorial geometry package for adjoint shielding calculations, and several peripheral codes that perform the required data preparations, transformations, and coupling functions. The current version, MASH v 1.5, is the successor to the original MASH v 1.0 code system initially developed at Oak Ridge National Laboratory (ORNL). The discrete ordinates calculation determines the fluence on a coupling surface surrounding the shielding geometry due to an external neutron/gamma-ray source. The Monte Carlo calculation determines the effectiveness of the fluence at that surface in causing a response in a detector within the shielding geometry, i.e., the "dose importance" of the coupling surface fluence. A coupling code folds the fluence together with the dose importance, giving the desired dose response. The coupling code can determine the dose response as a function of the shielding geometry orientation relative to the source, distance from the source, and energy response of the detector. This user's manual includes a short description of each code, the input required to execute the code along with some helpful input data notes, and a representative sample problem.

  14. Defect structure of epitaxial CrxV1-x thin films on MgO(001)

    SciTech Connect

    Kaspar, Tiffany C.; Bowden, Mark E.; Wang, Chongmin; Shutthanandan, V.; Manandhar, Sandeep; van Ginhoven, Renee M.; Wirth, Brian D.; Kurtz, Richard J.

    2014-01-01

    Epitaxial thin films of CrxV1-x over the entire composition range were deposited on MgO(001) by molecular beam epitaxy. The films exhibited the expected 45° in-plane rotation with no evidence of phase segregation or spinodal decomposition. Pure Cr, with the largest lattice mismatch to MgO, exhibited full relaxation and cubic lattice parameters. As the lattice mismatch decreased with alloy composition, residual epitaxial strain was observed. For 0.2 ≤ x ≤ 0.4 the films were coherently strained to the substrate with associated tetragonal distortion; near the lattice-matched composition of x = 0.33, the films exhibited strain-free pseudomorphic matching to MgO. Unusually, films on the Cr-rich side of the lattice-matched composition exhibited more in-plane compression than expected from the bulk lattice parameters; this result was confirmed with both x-ray diffraction and Rutherford backscattering spectrometry channeling measurements. Although thermal expansion mismatch in the heterostructure may play a role, the dominant mechanism for this phenomenon is still unknown. High resolution transmission electron microscopy was utilized to characterize the misfit dislocation network present at the film/MgO interface. Dislocations were found to be present with a non-uniform distribution, which is attributed to the Volmer-Weber growth mode of the films. The CrxV1-x / MgO(001) system can serve as a model system to study both the fundamentals of defect formation in bcc films and the interplay between nanoscale defects such as dislocations and radiation damage.

  15. Stratospheric temperature profile from balloon-borne measurements of the 10.4-micron band of CO2

    NASA Technical Reports Server (NTRS)

    Rinsland, C. P.; Goldman, A.; Murcray, F.J.; Murcray, D. G.; Smith, M. A. H.; Seals, R. K., Jr.; Larsen, J. C.; Rinsland, P. L.

    1983-01-01

    The technique of nonlinear least squares spectral curve fitting has been used to derive the stratospheric vertical temperature profile from balloon-borne measurements of the 10.4 micron band of CO2. The spectral data were obtained at sunset with the approximately 0.02 per cm resolution University of Denver interferometer system from a float altitude of 33.5 km near Alamogordo, New Mexico, on 23 March 1981. The r.m.s. deviation between the retrieved temperature profile and correlative radiosonde measurements is 2.2 K.

  16. Stratospheric temperature profile from balloon-borne measurements of the 10.4-micron band of CO2

    NASA Astrophysics Data System (ADS)

    Rinsland, C. P.; Goldman, A.; Murcray, F. J.; Murcray, D. G.; Smith, M. A. H.; Seals, R. K., Jr.; Larsen, J. C.; Rinsland, P. L.

    1983-10-01

    The technique of nonlinear least squares spectral curve fitting has been used to derive the stratospheric vertical temperature profile from balloon-borne measurements of the 10.4 micron band of CO2. The spectral data were obtained at sunset with the approximately 0.02 per cm resolution University of Denver interferometer system from a float altitude of 33.5 km near Alamogordo, New Mexico, on 23 March 1981. The r.m.s. deviation between the retrieved temperature profile and correlative radiosonde measurements is 2.2 K.

  17. Molecular epidemiological analyses of Cryptosporidium parvum virus 1 (CSpV1), a symbiotic virus of Cryptosporidium parvum, in Japan.

    PubMed

    Murakoshi, Fumi; Ichikawa-Seki, Madoka; Aita, Junya; Yaita, Seiko; Kinami, Aiko; Fujimoto, Katsuhisa; Nishikawa, Yoshifumi; Murakami, Shin; Horimoto, Taisuke; Kato, Kentaro

    2016-01-01

    We show that Cryptosporidium parvum virus 1 (CSpV1), a member of the family Partitiviridae, genus Cryspovirus that can infect Cryptosporidium parvum, is a new candidate for high-resolution tool for tracing C. parvum. CSpV1 was detected in all C. parvum-positive samples tested. Phylogenetic analysis of dsRNA1 sequence from CSpV1 can distinguish infected areas of C. parvum on the national level. Sequences detected in samples from Iwate prefecture and other islands (Tanegashima, and Okinawa) belonged to a single clade. This system can differentiate the samples from Hokkaido and south part of Japan as well as from other countries. Samples from Iwate, Tanegashima, and Okinawa belonged to a single subclade, respectively. Therefore, the CSpV1 dsRNA sequences reflect the regional distribution of their host and have potential as a high-resolution tool to trace C. parvum IIaA15G2R1 subtype.

  18. Questioning the Specificity of ASRS-v1.1 to Accurately Detect ADHD in Substance Abusing Populations

    ERIC Educational Resources Information Center

    Chiasson, Jean-Pierre; Stavro, Katherine; Rizkallah, Elie; Lapierre, Luc; Dussault, Maxime; Legault, Louis; Potvin, Stephane

    2012-01-01

    Objective: To assess the specificity of the Adult ADHD Self-Report Scale (ASRS-v1.1) in detecting ADHD among individuals with substance use disorders (SUDs). Method: A chart review of 183 SUD patients was conducted. Patients were screened for ADHD with the ASRS-v1.1 and were later assessed by a psychiatrist specialized in ADHD. Results: Among SUD…

  19. The role of Na(V)1.8 sodium channel in the maintenance of chronic inflammatory hypernociception.

    PubMed

    Villarreal, Cristiane Flora; Sachs, Daniela; Cunha, Fernando de Queiroz; Parada, Carlos Amílcar; Ferreira, Sérgio Henrique

    2005-09-30

    We previously described an animal model of persistent inflammatory sensitization of nociceptors. In this model the hypernociception persists for more than 30 days after the cessation of 2 weeks of daily intraplantar treatment with prostaglandin E(2) (PGE(2)). The tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel Na(V)1.8 is considered a characteristic of primary afferent nociceptive C fibers and plays an important role in acute hypernociception. In the present study, the relevance of the Na(V)1.8 channel was investigated in this model of persistent mechanical hypernociception in rats. In the PGE(2)-induced persistent hypernociception, but not in the single injection-induced acute hypernociception, the mRNA expression (RT-PCR) of Na(V)1.8 in dorsal root ganglia (DRG) was up-regulated. A similar increase of Na(V)1.8 mRNA was observed when DbcAMP was used to induce persistent hypernociception. Four daily intrathecal administrations of oligodeoxynucleotides (ODN) antisense against Na(V)1.8 decreased the mRNA encoding Na(V)1.8 in DRG. The intrathecal administration of ODN antisense prevented the PGE(2)-induced acute hypernociception and significantly reduced ongoing PGE(2)-induced persistent hypernociception. A parallel restoration of the persistent hypernociception and up-regulation of Na(V)1.8 mRNA was observed after the cessation of ODN antisense treatment. These results suggest the participation of Na(V)1.8 channels in the development and maintenance of chronic inflammatory hyperalgesia, and confirm their involvement in the acute inflammatory hypernociception. PMID:16043287

  20. Sodium channel Na(v)1.7 is essential for lowering heat pain threshold after burn injury.

    PubMed

    Shields, Shannon D; Cheng, Xiaoyang; Uçeyler, Nurcan; Sommer, Claudia; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2012-08-01

    Marked hypersensitivity to heat and mechanical (pressure) stimuli develop after a burn injury, but the neural mechanisms underlying these effects are poorly understood. In this study, we establish a new mouse model of focal second-degree burn injury to investigate the molecular and cellular basis for burn injury-induced pain. This model features robust injury-induced behavioral effects and tissue-specific altered cytokine profile, but absence of glial activation in spinal dorsal horn. Three voltage-gated sodium channels, Na(v)1.7, Na(v)1.8, and Na(v)1.9, are preferentially expressed in peripheral somatosensory neurons of the dorsal root ganglia (DRGs) and have been implicated in injury-induced neuronal hyperexcitability. Using knock-out mice, we provide evidence that Na(v)1.7 selectively contributes to burn-induced hypersensitivity to heat, but not mechanical, stimuli. After burn model injury, wild-type mice display increased sensitivity to heat stimuli, and a normally non-noxious warm stimulus induces activity-dependent Fos expression in spinal dorsal horn neurons. Strikingly, both effects are absent in Na(v)1.7 conditional knock-out (cKO) mice. Furthermore, burn injury increases density and shifts activation of tetrodotoxin-sensitive currents in a hyperpolarized direction, both pro-excitatory properties, in DRG neurons from wild-type but not Na(v)1.7 cKO mice. We propose that, in sensory neurons damaged by burn injury to the hindpaw, Na(v)1.7 currents contribute to the hyperexcitability of sensory neurons, their communication with postsynaptic spinal pain pathways, and behavioral thresholds to heat stimuli. Our results offer insights into the molecular and cellular mechanisms of modality-specific pain signaling, and suggest Na(v)1.7-blocking drugs may be effective in burn patients. PMID:22875917

  1. Target Selection of Proprioceptive and Motor Axon Synapses on Neonatal V1-Derived Ia Inhibitory Interneurons and Renshaw Cells

    PubMed Central

    Siembab, Valerie C.; Smith, Courtney A.; Zagoraiou, Laskaro; Berrocal, Maria C.; Mentis, George Z.; Alvarez, Francisco J.

    2011-01-01

    The diversity of premotor interneurons in the mammalian spinal cord is generated from a few phylogenetically conserved embryonic classes of interneurons (V0, V1, V2, V3). Their mechanisms of diversification remain unresolved, although these are clearly important to understand motor circuit assembly in the spinal cord. Some Ia inhibitory interneurons (IaINs) and all Renshaw cells (RCs) derive from embryonic V1 interneurons; however, in adult they display distinct functional properties and synaptic inputs, for example proprioceptive inputs preferentially target IaINs, while motor axons target RCs. Previously, we found that both inputs converge on RCs in neonates, raising the possibility that proprioceptive (VGLUT1-positive) and motor axon synapses (VAChT-positive) initially target several different V1 interneurons populations and then become selected or deselected postnatally. Alternatively, specific inputs might precisely connect only with predefined groups of V1 interneurons. To test these hypotheses we analyzed synaptic development on V1-derived IaINs and compared them to RCs of the same age and spinal cord levels. V1-interneurons were labeled using genetically encoded lineage markers in mice. The results show that although neonatal V1-derived IaINs and RCs are competent to receive proprioceptive synapses, these synapses preferentially target the proximal somato-dendritic regions of IaINs and postnatally proliferate on IaINs, but not on RCs. In contrast, cholinergic synapses on RCs are specifically derived from motor axons, while on IaINs they originate from Pitx2 V0c interneurons. Thus, motor, proprioceptive, and even some interneuron inputs are biased toward specific subtypes of V1-interneurons. Postnatal strengthening of these inputs is later superimposed on this initial preferential targeting. PMID:20963823

  2. Investigation of quasielastic muon-neutrino scattering on nuclei at E{sub v} < 1 GeV

    SciTech Connect

    Agababyan, N. M.; Ammosov, V. V.; Atayan, M.; Grigoryan, N.; Gulkanyan, H.; Ivanilov, A. A. Karamyan, Zh.; Korotkov, B. A.

    2007-10-15

    Quasielastic muon-neutrino scattering on nuclei of propane-Freon mixture at energies in the range E{sub v} < 1 GeV is studied. The multiplicity, momentum, and emission-angle distributions of final protons are measured along with the dependence of the mean values for these distributions on the neutrino energy in the range 0.2 < E{sub v} < 1 GeV.

  3. Pharmacological characterization of FE 201874, the first selective high affinity rat V1A vasopressin receptor agonist

    PubMed Central

    Marir, Rafik; Virsolvy, Anne; Wisniewski, Kazimierz; Mion, Julie; Haddou, Dominique; Galibert, Evelyne; Meraihi, Zahia; Desarménien, Michel G; Guillon, Gilles

    2013-01-01

    BACKGROUND AND PURPOSE Distinct vasopressin receptors are involved in different physiological and behavioural functions. Presently, no selective agonist is available to specifically elucidate the functional roles of the V1A receptor in the rat, one of the most widely used animal models. FE 201874 is a new derivative of the human selective V1A receptor agonist F180. In this study, we performed a multi-approach pharmacological and functional characterization of FE 201874 to determine whether it is selective for V1A receptors. EXPERIMENTAL APPROACH We modified an available human selective V1A receptor agonist (F180) and determined its pharmacological properties in cell lines expressing vasopressin/oxytocin receptors (affinity and coupling to second messenger cascades), in an ex vivo model (aorta ring contraction) and in vivo in rats (proliferation of adrenal cortex glomerulosa cells and lactation). KEY RESULTS FE 201874 exhibited nanomolar affinity for the rat V1A receptor; it was highly selective towards the rat V1B and V2 vasopressin receptors and behaved as a full V1A agonist in all the pharmacological tests performed. FE 201874 bound to the oxytocin receptor, but with moderate affinity, and behaved as an oxytocin antagonist in vitro, but not in vivo. CONCLUSIONS AND IMPLICATIONS On functional grounds, all the data demonstrate that FE 201874 is the first selective agonist of the rat V1A receptor isoform available. Hence, FE 201874 may have potential as a treatment for the vasodilator-induced hypotension occurring in conditions such as septic shock and could be the most suitable compound for discriminating between the behavioural effects of arginine vasopressin and oxytocin. PMID:23725319

  4. Low resistivity WxV1-xO2-based multilayer structure with high temperature coefficient of resistance for microbolometer applications

    NASA Astrophysics Data System (ADS)

    Émond, Nicolas; Hendaoui, Ali; Chaker, Mohamed

    2015-10-01

    Materials that exhibit semiconductor-to-metal phase transition (SMT) are commonly used as sensing layers for the fabrication of uncooled microbolometers. The development of highly responsive microbolometers would benefit from using a sensing material that possesses a large thermal coefficient of resistance (TCR) close to room temperature and a resistivity low enough to compromise between noise reduction and high TCR, while it should also satisfies the requirements of current CMOS technology. Moreover, a TCR that remains constant when the IR camera surrounding temperature varies would contribute to achieve reliable temperature measurements without additional corrections steps for TCR temperature dependence. In this paper, the characteristics of the SMT occurring in undoped and tungsten-doped vanadium dioxide thin films deposited on LaAlO3 (100) substrates are investigated. They are further exploited to fabricate a WxV1-xO2 (0 ≤ x ≤ 2.5) multilayer structure exhibiting a bottom-up gradient of tungsten content. This MLS displays a combination of properties that is promising for application to uncooled microbolometer, such as a large TCR of -10.4%/ °C and low resistivity values ranging from 0.012 to 0.10 Ω-cm over the temperature range 22 °C-42 °C.

  5. Deletion of the L-type Calcium Channel CaV1.3 but not CaV1.2 Results in a Diminished sAHP in Mouse CA1 Pyramidal Neurons

    PubMed Central

    Gamelli, Amy E.; McKinney, Brandon C.; White, Jessica A.; Murphy, Geoffrey G.

    2009-01-01

    Trains of action potentials in CA1 pyramidal neurons are followed by a prolonged calcium-dependent post-burst afterhyperpolarization (AHP) that serves to limit further firing to a sustained depolarizing input. A reduction in the AHP accompanies acquisition of several types of learning and increases in the AHP are correlated with age-related cognitive impairment. The AHP develops primarily as the result of activation of outward calcium-activated potassium currents; however the precise source of calcium for activation of the AHP remains unclear. There is substantial experimental evidence suggesting that calcium influx via voltage-gated L-type calcium channels (L-VGCCs) contributes to the generation of the AHP. Two L-VGCC subtypes are predominately expressed in the hippocampus, CaV1.2 and CaV1.3, however it is not known which L-VGCC subtype is involved in generation of the AHP. This ambiguity is due in large part to the fact that at present there are no subunit-specific agonists or antagonists. Therefore, using mice in which the gene encoding CaV1.2 or CaV1.3 was deleted, we sought to determine the impact of alterations in levels of these two L-VCGG subtypes on neuronal excitability. No differences in any AHP measure were seen between neurons from CaV1.2 knockout mice and controls. However, the total area of the AHP was significantly smaller in neurons from CaV1.3 knockout mice as compared to neurons from wildtype controls. A significant reduction in the amplitude of the AHP was also seen at the 1 sec time point in neurons from CaV1.3 knockout mice as compared to those from controls. Reductions in both the area and 1 sec amplitude suggest the involvement of calcium influx via CaV1.3 in the slow AHP (sAHP). Thus, the results of our study demonstrate that deletion of CaV1.3, but not CaV1.2, significantly impacts the generation of the sAHP. PMID:20014384

  6. Mesostructured Metal Germanium Sulfide and Selenide Materials Based on the Tetrahedral [Ge 4S 10] 4- and [Ge 4Se 10] 4- Units: Surfactant Templated Three-Dimensional Disordered Frameworks Perforated with Worm Holes

    NASA Astrophysics Data System (ADS)

    Wachhold, Michael; Kasthuri Rangan, K.; Lei, Ming; Thorpe, M. F.; Billinge, Simon J. L.; Petkov, Valeri; Heising, Joy; Kanatzidis, Mercouri G.

    2000-06-01

    The polymerization of [Ge4S10]4- and [Ge4Se10]4- unit clusters with the divalent metal ions Zn2+, Cd2+, Hg2+, Ni2+, and Co2+ in the presence of various surfactant cations leads to novel mesostructured phases. The surfactants are the quaternary ammonium salts C12H25NMe3Br, C14H29NMe3Br, C16H33NMe3Br, and C18H37NMe3Br, which play the role of templates, helping to assemble a three-dimensional mesostructured metal-germanium chalcogenide framework. These materials are stoichiometric in nature and have the formula of (R-NMe3)2[MGe4Q10] (Q=S, Se). The local atomic structure was probed by X-ray diffuse scattering and pair distribution function analysis methods and indicates that the adamantane clusters stay intact while the linking metal atoms possess a tetrahedral coordination environment. A model can be derived, from the comparison of measured and simulated X-ray powder diffraction patterns, describing the structure as an amorphous three-dimensional framework consisting of adamantane [Ge4Q10]4- units that are bridged by tetrahedral coordinated M2+ cations. The network structures used in the simulations were derived from corresponding disordered structures developed for amorphous silicon. The frameworks in (R-NMe3)2[MGe4Q10] are perforated with worm hole-like tunnels, occupied by the surfactant cations, which show no long-range order. This motif is supported by transmission electron microscopy images of these materials. The pore sizes of these channels were estimated to lie in the range of 20-30 Å, depending on the appointed surfactant cation length. The framework wall thickness of ca. 10 Å is thereby independent from the surfactant molecules used. Up to 80% of the surfactant molecules can be removed by thermal degradation under vacuum without loss of mesostructural integrity. Physical, chemical, and spectroscopic properties of these materials are discussed.

  7. Three-dimensional hydration layer mapping on the (10.4) surface of calcite using amplitude modulation atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Marutschke, Christoph; Walters, Deron; Cleveland, Jason; Hermes, Ilka; Bechstein, Ralf; Kühnle, Angelika

    2014-08-01

    Calcite, the most stable modification of calcium carbonate, is a major mineral in nature. It is, therefore, highly relevant in a broad range of fields such as biomineralization, sea water desalination and oil production. Knowledge of the surface structure and reactivity of the most stable cleavage plane, calcite (10.4), is pivotal for understanding the role of calcite in these diverse areas. Given the fact that most biological processes and technical applications take place in an aqueous environment, perhaps the most basic—yet decisive—question addresses the interaction of water molecules with the calcite (10.4) surface. In this work, amplitude modulation atomic force microscopy is used for three-dimensional (3D) mapping of the surface structure and the hydration layers above the surface. An easy-to-use scanning protocol is implemented for collecting reliable 3D data. We carefully discuss a comprehensible criterion for identifying the solid-liquid interface within our data. In our data three hydration layers form a characteristic pattern that is commensurate with the underlying calcite surface.

  8. Three-dimensional hydration layer mapping on the (10.4) surface of calcite using amplitude modulation atomic force microscopy.

    PubMed

    Marutschke, Christoph; Walters, Deron; Walters, Deron; Hermes, Ilka; Bechstein, Ralf; Kühnle, Angelika

    2014-08-22

    Calcite, the most stable modification of calcium carbonate, is a major mineral in nature. It is, therefore, highly relevant in a broad range of fields such as biomineralization, sea water desalination and oil production. Knowledge of the surface structure and reactivity of the most stable cleavage plane, calcite (10.4), is pivotal for understanding the role of calcite in these diverse areas. Given the fact that most biological processes and technical applications take place in an aqueous environment, perhaps the most basic - yet decisive - question addresses the interaction of water molecules with the calcite (10.4) surface. In this work, amplitude modulation atomic force microscopy is used for three-dimensional (3D) mapping of the surface structure and the hydration layers above the surface. An easy-to-use scanning protocol is implemented for collecting reliable 3D data. We carefully discuss a comprehensible criterion for identifying the solid-liquid interface within our data. In our data three hydration layers form a characteristic pattern that is commensurate with the underlying calcite surface. PMID:25074402

  9. Three-dimensional hydration layer mapping on the (10.4) surface of calcite using amplitude modulation atomic force microscopy.

    PubMed

    Marutschke, Christoph; Walters, Deron; Walters, Deron; Hermes, Ilka; Bechstein, Ralf; Kühnle, Angelika

    2014-08-22

    Calcite, the most stable modification of calcium carbonate, is a major mineral in nature. It is, therefore, highly relevant in a broad range of fields such as biomineralization, sea water desalination and oil production. Knowledge of the surface structure and reactivity of the most stable cleavage plane, calcite (10.4), is pivotal for understanding the role of calcite in these diverse areas. Given the fact that most biological processes and technical applications take place in an aqueous environment, perhaps the most basic - yet decisive - question addresses the interaction of water molecules with the calcite (10.4) surface. In this work, amplitude modulation atomic force microscopy is used for three-dimensional (3D) mapping of the surface structure and the hydration layers above the surface. An easy-to-use scanning protocol is implemented for collecting reliable 3D data. We carefully discuss a comprehensible criterion for identifying the solid-liquid interface within our data. In our data three hydration layers form a characteristic pattern that is commensurate with the underlying calcite surface.

  10. Gating and modulation of presumptive NaV1.9 channels in enteric and spinal sensory neurons.

    PubMed

    Coste, Bertrand; Osorio, Nancy; Padilla, Françoise; Crest, Marcel; Delmas, Patrick

    2004-05-01

    The NaV1.9 subunit is expressed in nociceptive dorsal root ganglion (DRG) neurons and sensory myenteric neurons in which it generates 'persistent' tetrodotoxin-resistant (TTX-R) Na+ currents of yet unknown physiological functions. Here, we have analyzed these currents in details by combining single-channel and whole-cell recordings from cultured rat DRG and myenteric neurons. Comparison of single-channel with whole-cell data indicates that recording using internal CsCl best reflects the basic electrical features of NaV1.9 currents. Inclusion of fluoride in the pipette solution caused a negative shift in the activation and inactivation gates of NaV1.9 but not NaV1.8. Fluoride acts by promoting entry of NaV1.9 channels into a preopen closed state, which causes a strong bias towards opening and enhances the ability of sensory neurons to sustain spiking. Thus, the modulation of the resting-closed states of NaV1.9 channels strongly influences nociceptor excitability and may provide a mechanism by which inflammatory mediators alter pain threshold. PMID:15121184

  11. Predator odor-evoked BOLD activation in the awake rat: Modulation by oxytocin and V1a vasopressin receptor antagonists

    PubMed Central

    Reed, Michael D.; Price, Katherine E.; Archbold, Jonathan; Moffa, Anthony; Febo, Marcelo

    2013-01-01

    Modulators of unconditioned fear are potential targets for developing treatments for anxiety disorders. We used blood oxygen level dependent (BOLD) MRI to investigate the pattern of brain activity during the presentation of a predator odor (cat fur) and a repulsive novel odor, butyric acid (BA), to awake rats. We further tested whether odor-evoked BOLD activation involved oxytocin (OT) and vasopressin V1a receptors. Animals were subdivided into groups either administered an intracerebroventricular injection of artificial cerebrospinal fluid (CSF), an OT receptor antagonist or a V1a antagonist (125 ng/10 μL each) 90 min before studies. BA odor evoked robust brain activation across olfactory, sensory, memory and limbic regions. The magnitude of BOLD activation across these regions was greater for BA than with cat fur. However, blockade of OT and V1a receptors differentially modulated odor evoked neural activity, particularly in the amygdala. OT and V1a antagonism preferentially modulated BOLD responding to BA in the cortical amygdala. While, OT and V1a antagonisms preferentially modulated BOLD responding to cat fur in the central amygdala. The data suggest that although OT receptors modulate BOLD activation in response to a novel and repulsive odor such as BA, vasopressin V1a receptors exert a modulatory influence on the neural response to a predator odor. PMID:23219972

  12. A Possible Role for End-Stopped V1 Neurons in the Perception of Motion: A Computational Model

    PubMed Central

    Zarei Eskikand, Parvin; Kameneva, Tatiana; Ibbotson, Michael R.; Burkitt, Anthony N.; Grayden, David B.

    2016-01-01

    We present a model of the early stages of processing in the visual cortex, in particular V1 and MT, to investigate the potential role of end-stopped V1 neurons in solving the aperture problem. A hierarchical network is used in which the incoming motion signals provided by complex V1 neurons and end-stopped V1 neurons proceed to MT neurons at the next stage. MT neurons are categorized into two types based on their function: integration and segmentation. The role of integration neurons is to propagate unambiguous motion signals arriving from those V1 neurons that emphasize object terminators (e.g. corners). Segmentation neurons detect the discontinuities in the input stimulus to control the activity of integration neurons. Although the activity of the complex V1 neurons at the terminators of the object accurately represents the direction of the motion, their level of activity is less than the activity of the neurons along the edges. Therefore, a model incorporating end-stopped neurons is essential to suppress ambiguous motion signals along the edges of the stimulus. It is shown that the unambiguous motion signals at terminators propagate over the rest of the object to achieve an accurate representation of motion. PMID:27741307

  13. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

    SciTech Connect

    McLellan, Jason S.; Pancera, Marie; Carrico, Chris; Gorman, Jason; Julien, Jean-Philippe; Khayat, Reza; Louder, Robert; Pejchal, Robert; Sastry, Mallika; Dai, Kaifan; O’Dell, Sijy; Patel, Nikita; Shahzad-ul-Hussan, Syed; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Zhu, Jiang; Boyington, Jeffrey C.; Chuang, Gwo-Yu; Diwanji, Devan; Georgiev, Ivelin; Kwon, Young Do; Lee, Doyung; Louder, Mark K.; Moquin, Stephanie; Schmidt, Stephen D.; Yang, Zhi-Yong; Bonsignori, Mattia; Crump, John A.; Kapiga, Saidi H.; Sam, Noel E.; Haynes, Barton F.; Burton, Dennis R.; Koff, Wayne C.; Walker, Laura M.; Phogat, Sanjay; Wyatt, Richard; Orwenyo, Jared; Wang, Lai-Xi; Arthos, James; Bewley, Carole A.; Mascola, John R.; Nabel, Gary J.; Schief, William R.; Ward, Andrew B.; Wilson, Ian A.; Kwong, Peter D.

    2012-12-13

    Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded {beta}-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which - with PG9 - involves a site of vulnerability comprising just two glycans and a strand.

  14. What does Neural Plasticity Tell us about Role of Primary Visual Cortex (V1) in Visual Awareness?

    PubMed

    Silvanto, Juha; Rees, Geraint

    2011-01-01

    The complete loss of visual awareness resulting from a lesion to the primary visual cortex (V1) suggests that this region is indispensable for conscious visual perception. There are however a number cases of conscious perception in the absence of V1 which appear to challenge this conclusion. These include reports of patients with bilateral V1 lesions sustained at an early age whose conscious vision has spontaneously recovered, as well as stroke patients who have recovered some conscious vision with the help of rehabilitation programs. In addition, the phenomenon of hemianopic completion and percepts induced by brain stimulation suggest that V1 may not be necessary for conscious perception in all circumstances. Furthermore, that the visual abilities in the cat are associated with the recovery of normal extrastriate tuning properties rather than emulation of V1 functions suggests that there is nothing unique about the functional properties of this region in visual awareness. Rather, the dramatic effect of a V1 lesion on visual awareness may be due to its role in providing the majority of extrastriate visual input, the loss of which abolishes normal neural responsiveness throughout the visual cortex. PMID:21713187

  15. Turkey Astrovirus Type 1 (TAstV-1) and Chicken Astrovirus (CAstV) Detection in Brazilian Chicken Flocks.

    PubMed

    Espinoza, Luis Luna; Beserra, Laila A R; Soares, Rodrigo M; Gregori, Fabio

    2016-09-01

    Astrovirus is a common cause of enteritis in humans and domestic animals. Here we report the detection of turkey astrovirus type 1 (TAstV-1) and chicken astrovirus (CAstV) in avian farms. Sixty fecal sample pools (five or six birds of the same flock), from chickens without apparent clinical symptoms of enteric disease from farms located in six Brazilian states, were screened by an ORF1b PCR, followed by nucleotide sequencing of amplified products and phylogenetic analysis. Six samples tested positive for TAstV-1 and two for CAstV. One positive sample of each detected virus (TAstV-1 and CAstV) had the complete ORF2 sequenced. Data for the ORF2 sequence indicate that Brazilian TAstV-1 was divergent from TAstV-1 (United States), previously described infecting turkeys, and Brazilian CAstV clustered together with the U.K. group, subgroup B-II, associated with enteritis and growth retardation in chicks. This study provides updated information about CAstV and the first report of detection of TAstV-1 in Brazilian chickens, supporting the diagnostic of enteritis and epidemiologic surveillance in poultry health. PMID:27610731

  16. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9

    PubMed Central

    McLellan, Jason S.; Pancera, Marie; Carrico, Chris; Gorman, Jason; Julien, Jean-Philippe; Khayat, Reza; Louder, Robert; Pejchal, Robert; Sastry, Mallika; Dai, Kaifan; O’Dell, Sijy; Patel, Nikita; Shahzad-ul-Hussan, Syed; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Zhu, Jiang; Boyington, Jeffrey C.; Chuang, Gwo-Yu; Diwanji, Devan; Georgiev, Ivelin; Kwon, Young Do; Lee, Doyung; Louder, Mark K.; Moquin, Stephanie; Schmidt, Stephen D.; Yang, Zhi-Yong; Bonsignori, Mattia; Crump, John A.; Kapiga, Saidi H.; Sam, Noel E.; Haynes, Barton F.; Burton, Dennis R.; Koff, Wayne C.; Walker, Laura M.; Phogat, Sanjay; Wyatt, Richard; Orwenyo, Jared; Wang, Lai-Xi; Arthos, James; Bewley, Carole A.; Mascola, John R.; Nabel, Gary J.; Schief, William R.; Ward, Andrew B.; Wilson, Ian A.; Kwong, Peter D.

    2012-01-01

    Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which—with PG9—involves a site of vulnerability comprising just two glycans and a strand. PMID:22113616

  17. Structures of HIV-1-Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design

    PubMed Central

    Gorman, Jason; Soto, Cinque; Yang, Max M.; Davenport, Thaddeus M.; Guttman, Miklos; Bailer, Robert T.; Chambers, Michael; Chuang, Gwo-Yu; DeKosky, Brandon J.; Doria-Rose, Nicole A.; Druz, Aliaksandr; Ernandes, Michael J.; Georgiev, Ivelin S.; Jarosinski, Marissa C.; Joyce, M. Gordon; Lemmin, Thomas M.; Leung, Sherman; Louder, Mark K.; McDaniel, Jonathan R.; Narpala, Sandeep; Pancera, Marie; Stuckey, Jonathan; Wu, Xueling; Yang, Yongping; Zhang, Baoshan; Zhou, Tongqing; Mullikin, James C.; Baxa, Ulrich; Georgiou, George; McDermott, Adrian B.; Bonsignori, Mattia; Haynes, Barton F.; Moore, Penny L.; Morris, Lynn; Lee, Kelly K.; Shapiro, Lawrence; Mascola, John R.; Kwong, Peter D.

    2016-01-01

    Broadly neutralizing antibodies (bNAbs) against HIV-1-Env V1V2 arise in multiple donors. However, atomic-level interactions had only been determined with antibodies from a single donor, making commonalities in recognition uncertain. Here we report the co-crystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third. These V1V2-directed bNAbs utilized strand-strand interactions between a protruding antibody loop and a V1V2 strand, but differed in their N-glycan recognition. Ontogeny analysis indicated protruding loops to develop early, with glycan interactions maturing over time. Altogether, the multidonor information suggested V1V2-directed bNAbs to form an ‘extended class’, for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class. PMID:26689967

  18. Ca2+ entry into neurons is facilitated by cooperative gating of clustered CaV1.3 channels

    PubMed Central

    Moreno, Claudia M; Dixon, Rose E; Tajada, Sendoa; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Santana, Luis F

    2016-01-01

    CaV1.3 channels regulate excitability in many neurons. As is the case for all voltage-gated channels, it is widely assumed that individual CaV1.3 channels behave independently with respect to voltage-activation, open probability, and facilitation. Here, we report the results of super-resolution imaging, optogenetic, and electrophysiological measurements that refute this long-held view. We found that the short channel isoform (CaV1.3S), but not the long (CaV1.3L), associates in functional clusters of two or more channels that open cooperatively, facilitating Ca2+ influx. CaV1.3S channels are coupled via a C-terminus-to-C-terminus interaction that requires binding of the incoming Ca2+ to calmodulin (CaM) and subsequent binding of CaM to the pre-IQ domain of the channels. Physically-coupled channels facilitate Ca2+ currents as a consequence of their higher open probabilities, leading to increased firing rates in rat hippocampal neurons. We propose that cooperative gating of CaV1.3S channels represents a mechanism for the regulation of Ca2+ signaling and electrical activity. DOI: http://dx.doi.org/10.7554/eLife.15744.001 PMID:27187148

  19. Tetrodotoxin-resistant sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN in afferent neurons innervating urinary bladder in control and spinal cord injured rats.

    PubMed

    Black, Joel A; Cummins, Theodore R; Yoshimura, Naoki; de Groat, William C; Waxman, Stephen G

    2003-02-14

    Tetrodotoxin-resistant (TTX-R) sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) neurons. The urinary bladder is innervated by small afferent neurons from L6/S1 DRG, of which approximately 75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder afferent neurons. In the present study, we demonstrate that Na(v)1.8 is expressed in both bladder and non-bladder afferent neurons, while Na(v)1.9 is expressed in non-bladder afferent neurons but is rarely observed in bladder afferent neurons. In spinal cord transected rats 28-32 days following transection, there is a decreased expression of Na(v)1.8 sodium channels in bladder afferents, but no change in the expression of Na(v)1.8 in non-bladder afferent neurons. Both bladder and non-bladder afferent neurons exhibit limited increases in Na(v)1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder afferent neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these neurons following spinal cord injury. PMID:12560118

  20. Down-regulation of CaV1.2 channels during hypertension: how fewer CaV1.2 channels allow more Ca2+ into hypertensive arterial smooth muscle

    PubMed Central

    Tajada, Sendoa; Cidad, Pilar; Colinas, Olaia; Santana, L Fernando; López-López, José R; Pérez-García, M Teresa

    2013-01-01

    Hypertension is a clinical syndrome characterized by increased arterial tone. Although the mechanisms are varied, the generally accepted view is that increased CaV1.2 channel function is a common feature of this pathological condition. Here, we investigated the mechanisms underlying vascular dysfunction in a mouse model of genetic hypertension. Contrary to expectation, we found that whole-cell CaV1.2 currents (ICa) were lower in hypertensive (BPH line) than normotensive (BPN line) myocytes. However, local CaV1.2 sparklet activity was higher in BPH cells, suggesting that the relatively low ICa in these cells was produced by a few hyperactive CaV1.2 channels. Furthermore, our data suggest that while the lower expression of the pore-forming α1c subunit of CaV1.2 currents underlies the lower ICa in BPH myocytes, the increased sparklet activity was due to a different composition in the auxiliary subunits of the CaV1.2 complexes. ICa currents in BPN cells were produced by channels composed of α1c/α2δ/β3 subunits, while in BPH myocytes currents were probably generated by the opening of channels formed by α1c/α2δ/β2 subunits. In addition, Ca2+ sparks evoked large conductance, Ca2+-activated K+ (BK) currents of lower magnitude in BPH than in BPN myocytes, because BK channels were less sensitive to Ca2+. Our data are consistent with a model in which a decrease in the global number of CaV1.2 currents coexist with the existence of a subpopulation of highly active channels that dominate the resting Ca2+ influx. The decrease in BK channel activity makes the hyperpolarizing brake ineffective and leads BPH myocytes to a more contracted resting state. PMID:24167226

  1. BADGER v1.0: A Fortran equation of state library

    NASA Astrophysics Data System (ADS)

    Heltemes, T. A.; Moses, G. A.

    2012-12-01

    The BADGER equation of state library was developed to enable inertial confinement fusion plasma codes to more accurately model plasmas in the high-density, low-temperature regime. The code had the capability to calculate 1- and 2-T plasmas using the Thomas-Fermi model and an individual electron accounting model. Ion equation of state data can be calculated using an ideal gas model or via a quotidian equation of state with scaled binding energies. Electron equation of state data can be calculated via the ideal gas model or with an adaptation of the screened hydrogenic model with ℓ-splitting. The ionization and equation of state calculations can be done in local thermodynamic equilibrium or in a non-LTE mode using a variant of the Busquet equivalent temperature method. The code was written as a stand-alone Fortran library for ease of implementation by external codes. EOS results for aluminum are presented that show good agreement with the SESAME library and ionization calculations show good agreement with the FLYCHK code. Program summaryProgram title: BADGERLIB v1.0 Catalogue identifier: AEND_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEND_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 41 480 No. of bytes in distributed program, including test data, etc.: 2 904 451 Distribution format: tar.gz Programming language: Fortran 90. Computer: 32- or 64-bit PC, or Mac. Operating system: Windows, Linux, MacOS X. RAM: 249.496 kB plus 195.630 kB per isotope record in memory Classification: 19.1, 19.7. Nature of problem: Equation of State (EOS) calculations are necessary for the accurate simulation of high energy density plasmas. Historically, most EOS codes used in these simulations have relied on an ideal gas model. This model is inadequate for low

  2. Optical observations of Swift J1822.3-1606 with the 10.4m Gran Telescopio Canarias

    NASA Astrophysics Data System (ADS)

    Rea, N.; Mignani, R. P.; Israel, G. L.; Esposi, P.

    2011-07-01

    We observed the field of the new Soft Gamma-ray Repeater (SGR), Swift J1822.3-1606 (Cummings et al., Atel #3488) with the 10.4m Gran Telescopio Canarias (GranTeCan). Images have been taken with the OSIRIS camera, a two-chip CCD with a nominal 7.8'x7.8' arcmin field of view and a pixel size of 0.125". Observations have been taken in the z-Sloan-band on 2011 July 21st (unfortunately in bright lunar time, with a large sky background and a seeing ranging from 1-2.5") with exposure times of 54-108s.

  3. MIRADAS: The Multi-Object R=22K Near-IR Spectropolarimeter for the 10.4-meter GTC

    NASA Astrophysics Data System (ADS)

    Eikenberry, Stephen S.; MIRADAS Consortium

    2016-01-01

    The Mid-resolution InfRAreD Astronomical Spectrograph (MIRADAS), a near-infrared multi-object echelle spectrograph operating at spectral resolution R=22,000 over the 1-2.5µm bandpass, is being developed by an international consosrtium for the 10.4-meter Gran Telescopio Canarias (GTC). The MIRADAS consortium includes the University of Florida, Universidad de Barcelona, Universidad Complutense de Madrid, Instituto de Astrofísica de Canarias, as well as industrial partners in the US and Europe. MIRADAS completed its Final Design Review in mid-2015, and is currently undergoing fabrication, with planned first light in 2018/2019. In this paper, we review the overall science drivers and system design for MIRADAS, including key technologies such as cryogenic robotic probe arms, macroslicer mini-IFUs, full Stokes polarimetry, and a highly flexible observing configuration.

  4. Combination therapy of RY10-4 with the γ-secretase inhibitor DAPT shows promise in treating HER2-amplified breast cancer

    PubMed Central

    Su, Feng; Zhu, Shilin; Ruan, Jinlan; Muftuoglu, Yagmur; Zhang, Longbo; Yuan, Qianying

    2016-01-01

    RY10-4, a novel protoapigenone analog, shows potent cytotoxicity against human breast cancer cells. However, breast cancer cell lines overexpressing human epidermal growth factor receptor 2 (HER2), SKBR3 and BT474, showed less sensitivity to RY10-4 when compared to breast cancer cells lines expressing lower levels of HER2, such as MDA-MB-231 and MCF-7 cells. This was associated with aberrant hyperactivity in Notch signaling in cells treated with RY10-4, since treatment with RY10-4 causes an increase in Notch activity by 2-to3.5-fold in SKBR3 and BT474 cell lines. The increase in activity was abrogated with a γ-secretase inhibitor, DAPT, or with Notch1 small-interfering RNA (si-Notch1). Cell proliferation was inhibited more effectively by RY10-4 plus DAPT or si-Notch1 than either agent alone. RY10-4 plus DAPT increases apoptosis in both HER2-overexpressing cell lines by two-fold compared to RY10-4 alone, while DAPT alone has no significant effects on apoptosis. In addition, we previously found RY10-4 could inhibit tumor growth through the PI3K/AKT pathway. Here we report that the combination of RY10-4 and DAPT exhibit additive suppression on AKT phosphorylation, contributing to the anti-cancer effects. In an animal model, this combination therapy inhibits the growth of SKBR3 tumor xenografts in nude mice to a greater extent than treatment with either reagent alone. These results indicate that the aberrant activation of Notch signaling impedes the inhibitory effect of RY10-4 on HER2-amplified cell proliferation. Furthermore, these adverse effects can be prevented by treatment combining RY10-4 with a Notch pathway inhibitor. PMID:26716652

  5. NIMS Radiance Point Spectra of Ida and Dactyl V1.0

    NASA Astrophysics Data System (ADS)

    Granahan, J. C.

    2013-08-01

    This data volume contains radiometrically corrected point spectra of asteroid 243 Ida and a spectrum of the asteroid satellite Dactyl (Ida I) as acquired by the Galileo spacecraft Near Infrared Mapping Spectrometer (NIMS) on August 28, 1993. They record the spectra collected as the Galileo spacecraft approached the 243 Ida system. These data are products of the calibration of the raw data number files idu002tn.qub, idu005tn.qub, idu006tn.qub, idu007tn.qub, idu019tn.qub, idu020tn.qub, idu022tn.qub, idu028tn.qub, idu032tn.qub, idu033tn.qub, and idu035tn.qub (DATA SET ID ='GO-A-NIMS-3-TUBE-V1.0') with calibration factors acquired during the Jovian tour of the Galileo mission. These raw data .qub files are archived in the Imaging Node of the NASA Planetary Data System (PDS). The calibrated spectra consist of radiance and incidence/flux measurements for wavelengths between 0.7 - 5.2 micrometers.

  6. Understanding layer 4 of the cortical circuit: a model based on cat V1.

    PubMed

    Miller, Kenneth D

    2003-01-01

    This paper reviews theoretical and experimental results on the processing of layer 4, the input-recipient layer, of cat primary visual cortex (V1). A wide range of experimental data can be understood from a model in which response tuning of layer 4 cells is largely determined by a local interplay of feedforward excitation (from thalamus) and feedforward inhibition (from layer 4 inhibitory interneurons driven by thalamus). Feedforward inhibition dominates excitation, inherits its tuning from the thalamic input and sharpens the tuning of excitatory cells. At least a strong component of the feedforward inhibition received by a cell is spatially opponent to the excitation it receives, meaning that inhibition is driven by dark in regions of the visual field in which excitation is driven by light, and vice versa. The idea of opponent inhibition can be generalized to mean inhibition driven by input patterns that are strongly anti-correlated with the patterns that excite a cell. This paper argues that dominant feedforward opponent inhibition may be a general principle of cortical layer 4. This leads to the suggestion that the properties that show columnar organization--invariance across the vertical depth of cortex--may be properties that are shared by 'opposite' (anticorrelated) stimulus pairs. This contrasts with the more common idea that a column represents a set of cells that all share similar stimulus preferences. PMID:12466218

  7. Unusual Galactic Cosmic Ray Intensity and Spectral Changes Observed by V1 Near The Heliopause

    NASA Astrophysics Data System (ADS)

    Webber, W. R.; Quenby, J. J.

    2015-06-01

    We discuss here two unusual increases of cosmic ray intensity that were observed by V1 in the last 1.1 AU before it crossed the heliopause in 2012 August, at 121.5 AU. These two increases are roughly similar in amplitude and result in a total increase in ˜1 GV cosmic ray nuclei of over 50% and 0.01 GV electrons of a factor ˜2. During the first increase the changes in the B field are small. After the first increase the B field changes become large and during the second increase the B field variations and cosmic ray changes are correlated to within ± one day. During these time intervals, the rigidity dependence of the increases of GCR H and He nuclei from 100-600 MeV/nuc resemble those used to describe the solar modulation near the Earth during a large transient decrease but the ratio between the intensity changes of H, He, and electrons are different. The magnitude of these increases at Voyager is ˜1/3 of the modulation that is required to produce the total modulation of protons, helium nuclei, and electrons between the local interstellar intensities and those observed at the Earth at the 2009 sunspot minima. This may imply that a significant part of the residual solar modulation at times of sunspot minima occurs near the heliopause itself.

  8. Population representation of visual information in areas V1 and V2 of amblyopic macaques.

    PubMed

    Shooner, Christopher; Hallum, Luke E; Kumbhani, Romesh D; Ziemba, Corey M; Garcia-Marin, Virginia; Kelly, Jenna G; Majaj, Najib J; Movshon, J Anthony; Kiorpes, Lynne

    2015-09-01

    Amblyopia is a developmental disorder resulting in poor vision in one eye. The mechanism by which input to the affected eye is prevented from reaching the level of awareness remains poorly understood. We recorded simultaneously from large populations of neurons in the supragranular layers of areas V1 and V2 in 6 macaques that were made amblyopic by rearing with artificial strabismus or anisometropia, and 1 normally reared control. In agreement with previous reports, we found that cortical neuronal signals driven through the amblyopic eyes were reduced, and that cortical neurons were on average more strongly driven by the non-amblyopic than by the amblyopic eyes. We analyzed multiunit recordings using standard population decoding methods, and found that visual signals from the amblyopic eye, while weakened, were not degraded enough to explain the behavioral deficits. Thus additional losses must arise in downstream processing. We tested the idea that under monocular viewing conditions, only signals from neurons dominated by - rather than driven by - the open eye might be used. This reduces the proportion of neuronal signals available from the amblyopic eye, and amplifies the interocular difference observed at the level of single neurons. We conclude that amblyopia might arise in part from degradation in the neuronal signals from the amblyopic eye, and in part from a reduction in the number of signals processed by downstream areas.

  9. Membrane Potential Dynamics of Spontaneous and Visually Evoked Gamma Activity in V1 of Awake Mice

    PubMed Central

    Perrenoud, Quentin; Pennartz, Cyriel M. A.; Gentet, Luc J.

    2016-01-01

    Cortical gamma activity (30–80 Hz) is believed to play important functions in neural computation and arises from the interplay of parvalbumin-expressing interneurons (PV) and pyramidal cells (PYRs). However, the subthreshold dynamics underlying its emergence in the cortex of awake animals remain unclear. Here, we characterized the intracellular dynamics of PVs and PYRs during spontaneous and visually evoked gamma activity in layers 2/3 of V1 of awake mice using targeted patch-clamp recordings and synchronous local field potentials (LFPs). Strong gamma activity patterned in short bouts (one to three cycles), occurred when PVs and PYRs were depolarizing and entrained their membrane potential dynamics regardless of the presence of visual stimulation. PV firing phase locked unconditionally to gamma activity. However, PYRs only phase locked to visually evoked gamma bouts. Taken together, our results indicate that gamma activity corresponds to short pulses of correlated background synaptic activity synchronizing the output of cortical neurons depending on external sensory drive. PMID:26890123

  10. NMR Structure of Francisella tularensis Virulence Determinant Reveals Structural Homology to Bet v1 Allergen Proteins.

    PubMed

    Zook, James; Mo, Gina; Sisco, Nicholas J; Craciunescu, Felicia M; Hansen, Debra T; Baravati, Bobby; Cherry, Brian R; Sykes, Kathryn; Wachter, Rebekka; Van Horn, Wade D; Fromme, Petra

    2015-06-01

    Tularemia is a potentially fatal bacterial infection caused by Francisella tularensis, and is endemic to North America and many parts of northern Europe and Asia. The outer membrane lipoprotein, Flpp3, has been identified as a virulence determinant as well as a potential subunit template for vaccine development. Here we present the first structure for the soluble domain of Flpp3 from the highly infectious Type A SCHU S4 strain, derived through high-resolution solution nuclear magnetic resonance (NMR) spectroscopy; the first structure of a lipoprotein from the genus Francisella. The Flpp3 structure demonstrates a globular protein with an electrostatically polarized surface containing an internal cavity-a putative binding site based on the structurally homologous Bet v1 protein family of allergens. NMR-based relaxation studies suggest loop regions that potentially modulate access to the internal cavity. The Flpp3 structure may add to the understanding of F. tularensis virulence and contribute to the development of effective vaccines.

  11. Oxidation characteristics of Ti-25Al-10Nb-3V-1Mo intermetallic alloy

    NASA Technical Reports Server (NTRS)

    Wallace, Terryl A.; Clark, Ronald K.; Sankaran, Sankara N.; Wiedemann, Karl E.

    1990-01-01

    Static oxidation kinetics of the super-alpha 2 titanium-aluminide alloy Ti-25Al-10Nb-3V-1Mo (at. percent) were investigated in air over the temperature range of 650 to 1000 C using thermogravimetric analysis. The oxidation kinetics were complex at all exposure temperatures and displayed up to three distinct oxidation rates. Breakaway oxidation occurred after long exposure times at high temperatures. Oxidation products were determined using x ray diffraction techniques, electron microprobe analysis, and energy dispersive x ray analysis. Oxide scale morphology was examined by scanning electron microscopy of the surfaces and cross sections of oxidized specimens. The oxides during the parabolic stages were compact and multilayered, consisting primarily of TiO2 doped with Nb, a top layer of Al2O3, and a thin bottom layer of TiN. The transition between the second and third parabolic stage was found to be linked to the formation of a TiAl layer at the oxide-metal interface. Porosity was formed during the third stage, causing degradation of the oxide and the beginning of breakaway oxidation.

  12. Correlations in V1 are reduced by stimulation outside the receptive field.

    PubMed

    Snyder, Adam C; Morais, Michael J; Kohn, Adam; Smith, Matthew A

    2014-08-20

    The trial-to-trial response variability of nearby cortical neurons is correlated. These correlations may strongly influence population coding performance. Numerous studies have shown that correlations can be dynamically modified by attention, adaptation, learning, and potent stimulus drive. However, the mechanisms that influence correlation strength remain poorly understood. Here we test whether correlations are influenced by presenting stimuli outside the classical receptive field (RF) of visual neurons, where they recruit a normalization signal termed surround suppression. We recorded simultaneously the activity of dozens of cells using microelectrode arrays implanted in the superficial layers of V1 in anesthetized, paralyzed macaque monkeys. We presented annular stimuli that encircled--but did not impinge upon--the RFs of the recorded cells. We found that these "extra-classical" stimuli reduced correlations in the absence of stimulation of the RF, closely resembling the decorrelating effects of stimulating the RFs directly. Our results suggest that normalization signals may be an important mechanism for modulating correlations. PMID:25143603

  13. Identification of novel NaV1.7 antagonists using high throughput screening platforms.

    PubMed

    Klement, Goran; Babich, Olga; Larsson, Olof; Lund, Per-Eric; Malmberg, Asa; Sandberg, Lars; Sands, Zara A; Dabrowski, Michael

    2012-11-01

    Congenital Insensitivity to Pain (CIP) is a loss of function mutation resulting in a truncated NaV1.7 protein, suggesting a pivotal role in pain signaling and rendering it an important pharmaceutical target for multiple pain conditions. The structural homology in the NaV-channel family makes it challenging to design effective analgesic compounds without inducing for example cardiotoxicity or seizure liabilities. An additional approach to structural isoform selectivity is to identify compounds with use- or state-dependent profiles, i.e. inhibition efficacy based on the gating of the ion channel. In general nerve cells in damaged or inflamed tissue are more depolarized and electrically active compared to healthy nerve cells in for instance the heart. This observation has led to the design of two types of screening protocols emulating the voltage condition of peripheral neurons or cardiac tissue. The two voltage protocols have been developed to identify both use- and state-dependent antagonists. In this paper we describe an attempt to merge the two different protocols into one to increase screening efficacy, while retaining relevant state- and use-dependent pharmacology. The new protocol is constructed of two stimulation pulses and a slow voltage ramp for simultaneous assessment of resting and state-dependent block. By comparing all protocols we show that the new protocol indeed filter compounds for state-dependence and increase the prediction power of selecting use-dependent compounds. PMID:22934951

  14. The arginine vasopressin V1b receptor gene and prosociality: Mediation role of emotional empathy.

    PubMed

    Wu, Nan; Shang, Siyuan; Su, Yanjie

    2015-09-01

    The vasopressin V1b receptor (AVPR1B) gene has been shown to be closely associated with bipolar disorder and depression. However, whether it relates to positive social outcomes, such as empathy and prosocial behavior, remains unknown. This study explored the possible role of the AVPR1B gene rs28373064 in empathy and prosociality. A total of 256 men, who were genetically unrelated, non-clinical ethnic Han Chinese college students, participated in the study. Prosociality was tested by measuring the prosocial tendencies of cognitive and emotional empathy using the Interpersonal Reactivity Index (IRI). The single nucleotide polymorphism (SNP), rs28373064, was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The results suggest that the AVPR1B gene rs28373064 is linked to emotional empathy and prosociality. The mediation analysis indicated that the effect of the AVPR1B gene on prosociality might be mediated by emotional empathy. This study demonstrated the link between the AVPR1B gene and prosociality and provided evidence that emotional empathy might mediate the relation between the AVPR1B gene and prosociality.

  15. Versican V1 Overexpression Induces a Myofibroblast-Like Phenotype in Cultured Fibroblasts

    PubMed Central

    Carthy, Jon M.; Meredith, Anna J.; Boroomand, Seti; Abraham, Thomas; Luo, Zongshu; Knight, Darryl; McManus, Bruce M.

    2015-01-01

    Background Versican, a chondroitin sulphate proteoglycan, is one of the key components of the provisional extracellular matrix expressed after injury. The current study evaluated the hypothesis that a versican-rich matrix alters the phenotype of cultured fibroblasts. Methods and Results The full-length cDNA for the V1 isoform of human versican was cloned and the recombinant proteoglycan was expressed in murine fibroblasts. Versican expression induced a marked change in fibroblast phenotype. Functionally, the versican-expressing fibroblasts proliferated faster and displayed enhanced cell adhesion, but migrated slower than control cells. These changes in cell function were associated with greater N-cadherin and integrin β1 expression, along with increased FAK phosphorylation. The versican-expressing fibroblasts also displayed expression of smooth muscle α-actin, a marker of myofibroblast differentiation. Consistent with this observation, the versican fibroblasts displayed increased synthetic activity, as measured by collagen III mRNA expression, as well as a greater capacity to contract a collagen lattice. These changes appear to be mediated, at least in part, by an increase in active TGF-β signaling in the versican expressing fibroblasts, and this was measured by phosphorylation and nuclear accumulation of SMAD2. Conclusions Collectively, these data indicate versican expression induces a myofibroblast-like phenotype in cultured fibroblasts. PMID:26176948

  16. Sensory neuron proteins interact with the intracellular domains of sodium channel NaV1.8.

    PubMed

    Malik-Hall, Misbah; Poon, W-Y Louisa; Baker, Mark D; Wood, John N; Okuse, Kenji

    2003-02-20

    Voltage-gated sodium channels initiate and propagate action potentials in excitable cells. The tetrodotoxin-resistant Na(+) channel (Na(V)1.8/SNS) is expressed in damage-sensing neurons (nociceptors) and plays an important role in pain pathways. Expression of high levels of functional Na(V)1.8 in heterologous cells has proved problematic, even in the presence of known sodium channel accessory beta-subunits. This suggests that other regulatory proteins are required for normal levels of Na(V)1.8 expression. Here we report the use of a yeast two-hybrid system and a rat dorsal root ganglion cDNA library to identify 28 different clones encoding proteins which interact with intracellular domains of Na(V)1.8. Many clones are expressed at high levels in small diameter DRG neurons as judged by in situ hybridization. Interacting proteins include cytoplasmic elements and linker proteins (e.g. beta-actin and moesin), enzymes (e.g. inositol polyphosphate 5-phosphatase and TAO2 thousand and one protein kinase), channels and membrane-associated proteins (voltage-dependent anion channel VDAC3V and tetraspanin), as well as motor proteins (dynein intermediate and light chain) and transcripts encoding previously undescribed proteins. Immunoprecipitation (pull-down) assays confirm that some of the proteins interact with, and may hence regulate, Na(V)1.8 in vivo. PMID:12591166

  17. Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel mutant.

    PubMed

    Leipold, Enrico; Hanson-Kahn, Andrea; Frick, Miya; Gong, Ping; Bernstein, Jonathan A; Voigt, Martin; Katona, Istvan; Oliver Goral, R; Altmüller, Janine; Nürnberg, Peter; Weis, Joachim; Hübner, Christian A; Heinemann, Stefan H; Kurth, Ingo

    2015-01-01

    Gain-of-function mutations in the human SCN11A-encoded voltage-gated Na(+) channel NaV1.9 cause severe pain disorders ranging from neuropathic pain to congenital pain insensitivity. However, the entire spectrum of the NaV1.9 diseases has yet to be defined. Applying whole-exome sequencing we here identify a missense change (p.V1184A) in NaV1.9, which leads to cold-aggravated peripheral pain in humans. Electrophysiological analysis reveals that p.V1184A shifts the voltage dependence of channel opening to hyperpolarized potentials thereby conferring gain-of-function characteristics to NaV1.9. Mutated channels diminish the resting membrane potential of mouse primary sensory neurons and cause cold-resistant hyperexcitability of nociceptors, suggesting a mechanistic basis for the temperature dependence of the pain phenotype. On the basis of direct comparison of the mutations linked to either cold-aggravated pain or pain insensitivity, we propose a model in which the physiological consequence of a mutation, that is, augmented versus absent pain, is critically dependent on the type of NaV1.9 hyperactivity. PMID:26645915

  18. V1 is not uniquely identified by polarity reversals of responses to upper and lower visual field stimuli

    PubMed Central

    Ales, Justin M.; Yates, Jacob L.; Norcia, Anthony M.

    2010-01-01

    The cruciform hypothesis states that if a visual evoked potential component originates in V1, then stimuli placed in the upper versus lower visual fields will generate responses with opposite polarity at the scalp. This diagnostic has been used by many studies as a definitive marker of V1 sources. To provide an empirical test of the validity of the cruciform hypothesis, we generated forward models of cortical areas V1, V2 and V3 that were based on realistic estimates of the 3-D shape of these areas and the shape and conductivity of the brain, skull and scalp. Functional MRI was used to identify the location of early visual areas and anatomical MRI data was used construct detailed cortical surface reconstructions and to generate boundary element method forward models of the electrical conductivity of each participant’s head. These two data sets for each subject were used to generate simulated scalp activity from the dorsal and ventral subdivisions of each visual area that correspond to the lower and upper visual field representations, respectively. The predicted topographies show that sources in V1 do not fully conform to the cruciform sign-reversal. Moreover, contrary to the model, retinotopic visual areas V2 and V3 show polarity reversals for upper and lower field stimuli. The presence of a response polarity inversion for upper versus lower field stimuli is therefore an insufficient criterion for identifying responses as having originated in V1. PMID:20488247

  19. Resistance to pathologic cardiac hypertrophy and reduced expression of CaV1.2 in Trpc3-depleted mice.

    PubMed

    Han, Jung Woo; Lee, Young Ho; Yoen, Su-In; Abramowitz, Joel; Birnbaumer, Lutz; Lee, Min Goo; Kim, Joo Young

    2016-10-01

    Sustained elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) reprograms cardiovascular cell fate, leading to cellular hypertrophy via Ca(2+)-calmodulin/calcineurin (Cn)/NFAT activation. Accumulating evidence suggests that transient receptor potential canonical (Trpc) channels play important roles in the development of pathologic cardiac hypertrophy. Here, we demonstrated that Trpc3 mediates pathologic cardiac hypertrophy in neurohumoral elevation via direct regulation of CaV1.2 expressions. Elevated PE (phenylephrine) was maintained in mice by continuous infusion using an osmotic pump. Wild-type (WT) mice, but not Trpc3 (-/-) showed a sudden decrease in blood pressure (BP) or death following elevation of BP under conditions of elevated PE. Trpc3 (-/-) mesenteric artery showed decreased PE-stimulated vasoconstriction. Analysis of morphology, function, and pathologic marker expression revealed that PE elevation caused pathologic cardiac hypertrophy in WT mice, which was prevented by deletion of Trpc3. Interestingly, protection by Trpc3 deletion seemed to be a result of reduced cardiac CaV1.2 expressions. Basal and PE induced increased expression of protein and mRNA of CaV1.2 was decreased in Trpc3 (-/-) heart. Accordingly, altered expression of CaV1.2 was observed by knockdown or stimulation of Trpc3 in cardiomyocytes. These findings suggest that Trpc3 is a mediator of pathologic cardiac hypertrophy not only through mediating part of the Ca(2+) influx, but also through control of CaV1.2 expressions.

  20. Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel mutant

    PubMed Central

    Leipold, Enrico; Hanson-Kahn, Andrea; Frick, Miya; Gong, Ping; Bernstein, Jonathan A.; Voigt, Martin; Katona, Istvan; Oliver Goral, R.; Altmüller, Janine; Nürnberg, Peter; Weis, Joachim; Hübner, Christian A.; Heinemann, Stefan H.; Kurth, Ingo

    2015-01-01

    Gain-of-function mutations in the human SCN11A-encoded voltage-gated Na+ channel NaV1.9 cause severe pain disorders ranging from neuropathic pain to congenital pain insensitivity. However, the entire spectrum of the NaV1.9 diseases has yet to be defined. Applying whole-exome sequencing we here identify a missense change (p.V1184A) in NaV1.9, which leads to cold-aggravated peripheral pain in humans. Electrophysiological analysis reveals that p.V1184A shifts the voltage dependence of channel opening to hyperpolarized potentials thereby conferring gain-of-function characteristics to NaV1.9. Mutated channels diminish the resting membrane potential of mouse primary sensory neurons and cause cold-resistant hyperexcitability of nociceptors, suggesting a mechanistic basis for the temperature dependence of the pain phenotype. On the basis of direct comparison of the mutations linked to either cold-aggravated pain or pain insensitivity, we propose a model in which the physiological consequence of a mutation, that is, augmented versus absent pain, is critically dependent on the type of NaV1.9 hyperactivity. PMID:26645915

  1. Distribution, prevalence, and genetic analysis of Panulirus argus virus 1 (PaV1) from the Caribbean Sea.

    PubMed

    Moss, Jessica; Behringer, Donald; Shields, Jeffrey D; Baeza, Antonio; Aguilar-Perera, Alfonso; Bush, Phillippe G; Dromer, Clement; Herrera-Moreno, Alejandro; Gittens, Lester; Matthews, Thomas R; McCord, Michael R; Schärer, Michelle T; Reynal, Lionel; Truelove, Nathanial; Butler, Mark J

    2013-05-27

    The pathogenic virus Panulirus argus virus 1 (PaV1) was first discovered in Caribbean spiny lobsters Panulirus argus from the Florida Keys (USA) in 1999 and has since been reported in Belize, Mexico, and Cuba; its distribution in the wider Caribbean is unknown. We collected tissue samples from adult spiny lobsters from 30 locations in 14 countries bordering the Caribbean Sea and used molecular diagnostics to assay for the presence of PaV1. PaV1 occurred primarily in the northern areas of the Caribbean, where its prevalence was highest. The virus was not found in lobsters from the southeastern Caribbean, and its prevalence was lowest in the southwestern Caribbean. DNA sequence analysis was performed on a fragment of the viral DNA to examine the genetic diversity of PaV1 on a Caribbean-wide scale. Sequence variation in the viral DNA fragment was high, with 61 unique alleles identified from 9 areas. The sharing of viral alleles in lobsters from distant locations supports the hypothesis of a strong genetic connectivity among lobsters within the Caribbean, and further supports the hypothesis that postlarvae infected with PaV1 may serve to disperse the virus over long distances.

  2. The Functional Property Changes of Muscular Na(v)1.4 and Cardiac Na(v)1.5 Induced by Scorpion Toxin BmK AGP-SYPU1 Mutants Y42F and Y5F.

    PubMed

    Meng, Xiangxue; Xu, Yijia; Zhao, Mingyi; Wang, Fangyang; Ma, Yuanyuan; Jin, Yao; Liu, Yanfeng; Song, Yongbo; Zhang, Jinghai

    2015-05-19

    Scorpion toxins are invaluable therapeutic leads and pharmacological tools which influence the voltage-gated sodium channels. However, the details were still unclear about the structure-function relationship of scorpion toxins on VGSC subtypes. In the previous study, we reported one α-type scorpion toxin Bmk AGP-SYPU1 and its two mutants (Y5F and Y42F) which had been demonstrated to ease pain in mice acetic acid writhing test. However, the function of Bmk AGP-SYPU1 on VGSCs is still unknown. In this study, we examined the effects of BmK AGP-SYPU1 and its two mutants (Y5F and Y42F) on hNa(v)1.4 and hNa(v)1.5 heterologously expressed CHO cell lines by using Na⁺-specialized fluorescent dye and whole-cell patch clamp. The data showed that BmK AGP-SYPU1 displayed as an activator of hNa(v)1.4 and hNa(v)1.5, which might indeed contribute to its biotoxicity to muscular and cardiac system and exhibited the functional properties of both the α-type and β-type scorpion toxin. Notably, Y5F mutant exhibited lower activatory effects on hNa(v)1.4 and hNa(v)1.5 compared with BmK AGP-SYPU1. Y42F was an enhanced activator and confirmed that the conserved Tyr42 was the key amino acid involved in bioactivity or biotoxicity. These data provided a deep insight into the structure-function relationship of BmK AGP-SYPU1, which may be the guidance for engineering α-toxin with high selectivity on VGSC subtypes. PMID:25919575

  3. VizieR Online Data Catalog: Hubble Source Catalog (V1 and V2) (Whitmore+, 2016)

    NASA Astrophysics Data System (ADS)

    Whitmore, B. C.; Allam, S. S.; Budavari, T.; Casertano, S.; Downes, R. A.; Donaldson, T.; Fall, S. M.; Lubow, S. H.; Quick, L.; Strolger, L.-G.; Wallace, G.; White, R. L.

    2016-10-01

    The HSC v1 contains members of the WFPC2, ACS/WFC, WFC3/UVIS and WFC3/IR Source Extractor source lists from HLA version DR8 (data release 8). The crossmatching process involves adjusting the relative astrometry of overlapping images so as to minimize positional offsets between closely aligned sources in different images. After correction, the astrometric residuals of crossmatched sources are significantly reduced, to typically less than 10mas. The relative astrometry is supported by using Pan-STARRS, SDSS, and 2MASS as the astrometric backbone for initial corrections. In addition, the catalog includes source nondetections. The crossmatching algorithms and the properties of the initial (Beta 0.1) catalog are described in Budavari & Lubow (2012ApJ...761..188B). The HSC v2 contains members of the WFPC2, ACS/WFC, WFC3/UVIS and WFC3/IR Source Extractor source lists from HLA version DR9.1 (data release 9.1). The crossmatching process involves adjusting the relative astrometry of overlapping images so as to minimize positional offsets between closely aligned sources in different images. After correction, the astrometric residuals of crossmatched sources are significantly reduced, to typically less than 10mas. The relative astrometry is supported by using Pan-STARRS, SDSS, and 2MASS as the astrometric backbone for initial corrections. In addition, the catalog includes source nondetections. The crossmatching algorithms and the properties of the initial (Beta 0.1) catalog are described in Budavari & Lubow (2012ApJ...761..188B). Hubble Source Catalog Acknowledgement: Based on observations made with the NASA/ESA Hubble Space Telescope, and obtained from the Hubble Legacy Archive, which is a collaboration between the Space Telescope Science Institute (STScI/NASA), the Space Telescope European Coordinating Facility (ST-ECF/ESAC/ESA) and the Canadian Astronomy Data Centre (CADC/NRC/CSA). (2 data files).

  4. Application of the MASH v1.0 Code System to radiological warfare radiation threats

    SciTech Connect

    Johnson, J.O.; Santoro, R.T.; Smith, M.S.

    1994-03-01

    Nuclear hardening capabilities of US and foreign ground force systems is a primary concern of the Department of Defense (DoD) and US Army. The Monte Carlo Adjoint Shielding Code System -- MASH v1.0 was developed at Oak Ridge National Laboratory (ORNL) to analyze these capabilities, i.e. the shielding effectiveness, for prompt radiation from a nuclear weapon detonation. Rapidly changing world events and the proliferation of nuclear weapons related technology have increased the kinds of nuclear threats to include intentionally dispersed radiation sources and fallout from tactical nuclear weapons used in the modern AirLand battlefield scenario. Consequently, a DoD area of increasing interest focuses on determining the shielding effectiveness of foreign and US armored vehicles to radiological warfare and fallout radiation threats. To demonstrate the applicability of MASH for analyzing dispersed radiation source problems, calculations have been completed for two distributed sources; a dispersed radiation environment simulated by a uniformly distributed {sup 60}Co source, and a {sup 235}U fission weapon fallout source. Fluence and dose assessments were performed for the free-field, the inside of a steel-walled two-meter box, in a phantom standing in the free-field, and in a phantom standing in the two-meter box. The results indicate substantial radiation protection factors for the {sup 60}Co dispersed radiation source and the fallout source compared to the prompt radiation protection factors. The dose protection factors ranged from 40 to 95 for the two-meter box and from 55 to 123 for the mid-gut position of the phantom standing in the box. The results further indicate that a {sup 60}Co source might be a good first order approximation for a tactical fission weapon fallout protection factor analysis.

  5. Transgenic rice seeds accumulating recombinant hypoallergenic birch pollen allergen Bet v 1 generate giant protein bodies.

    PubMed

    Wang, Shuyi; Takahashi, Hideyuki; Kajiura, Hiroyuki; Kawakatsu, Taiji; Fujiyama, Kazuhito; Takaiwa, Fumio

    2013-06-01

    A versatile hypoallergenic allergen derivative against multiple allergens is an ideal tolerogen for allergen-specific immunotherapy. Such a tolerogen should exhibit high efficacy, without side effects, when administered at high doses and should be applicable to several allergens. Tree pollen chimera 7 (TPC7), a hypoallergenic Bet v 1 tolerogen against birch pollen allergy, was previously selected by DNA shuffling of 14 types of Fagales tree pollen allergens. In this study, transgenic rice seed accumulating TPC7 was generated as an oral vaccine against birch pollen allergy by expressing this protein as a secretory protein using the N-terminal signal peptide and the C-terminal KDEL tag under the control of an endosperm-specific glutelin promoter. The highest level of TPC7 accumulation was approximately 207 µg grain(-1). Recombinant TPC7 is a glycoprotein with high mannose-type N-glycan, but without β1,2-xylose or α1,3-fucose, suggesting that TPC7 is retained in the endoplasmic reticulum (ER). TPC7 is deposited as a novel, giant spherical ER-derived protein body, >20 µm in diameter, which is referred to as the TPC7 body. Removal of the KDEL retention signal or mutation of a cysteine residue resulted in an alteration of TPC7 body morphology, and deletion of the signal peptide prevented the accumulation of TPC7 in rice seeds. Therefore, the novel TPC7 bodies may have formed aggregates within the ER lumen, primarily due to the intrinsic physicochemical properties of the protein.

  6. Quality Assessment and Collection V1.1 Reprocessing of the Suomi NPP VIIRS LAND Records

    NASA Astrophysics Data System (ADS)

    Devadiga, S.; Davidson, C. C.; Sarkar, S.; Ye, G.; Hattori, M.; Praderas, C.; Kalb, V.; Nguyen, A.; Hamilton, C.; Kuyper, J.; Roman, M. O.; Mauoka, E.

    2014-12-01

    The Land Product Evaluation and Algorithm Testing Element (PEATE) is an important element of the Suomi National Polar-orbiting Partnership (SNPP) at NASA's Goddard Space Flight Center. The primary goals of NASA's Land PEATE are to assess the quality of the Visible Infrared Imaging Radiometer Suite (VIIRS) Land operational products made by the Interface Data Processing System (IDPS), and to recommend improvements to the operational algorithms to meet NASA's Land science needs. The Land PEATE uses a version of the MODIS Adaptive Processing System (MODAPS), NPPDAPS, which has been modified to run the IDPS operational algorithms, as well as software provided by the NASA SNPP Land Science Team. Since the early pre-launch period (c. 2009) the Land PEATE has used the MODIS Land Data Operational Product Evaluation (LDOPE) team for evaluation of the data records generated by NPPDAPS.In June 2014, Land PEATE completed Collection V1.1 reprocessing of the SNPP VIIRS Land products from the beginning (Jan 19, 2012) of the SNPP mission to current day using the best of the IDPS operational and NASA Land science team provided algorithms. The processing used the refined LUTs provided by the NASA VIIRS Calibration Support Team (VCST) for the L1B Sensor Data Records (SDR), including LUTs for calibration and stray light correction of the VIIRS Day/Night Band. In addition to generating the operational SDRs, Intermediate Products (IPs), and Environmental Data Records (EDRs) this reprocessing also produced Diagnostics Data Records, MODIS heritage L3 gridded products using the VIIRS observations. This paper describes approaches used to assess the quality of the products from operational processing and reprocessing of VIIRS records at Land PEATE. The paper also presents results from inter-comparison of records from this reprocessing with the MODIS heritage products. Our analysis verified that MODIS quality data records can be produced using the VIIRS observations, however with additional

  7. Phase Locking of Multiple Single Neurons to the Local Field Potential in Cat V1.

    PubMed

    Martin, Kevan A C; Schröder, Sylvia

    2016-02-24

    The local field potential (LFP) is thought to reflect a temporal reference for neuronal spiking, which may facilitate information coding and orchestrate the communication between neural populations. To explore this proposed role, we recorded the LFP and simultaneously the spike activity of one to three nearby neurons in V1 of anesthetized cats during the presentation of drifting sinusoidal gratings, binary dense noise stimuli, and natural movies. In all stimulus conditions and during spontaneous activity, the average LFP power at frequencies >20 Hz was higher when neurons were spiking versus not spiking. The spikes were weakly but significantly phase locked to all frequencies of the LFP. The average spike phase of the LFP was stable across high and low levels of LFP power, but the strength of phase locking at low frequencies (≤10 Hz) increased with increasing LFP power. In a next step, we studied how strong stimulus responses of single neurons are reflected in the LFP and the LFP-spike relationship. We found that LFP power was slightly increased and phase locking was slightly stronger during strong compared with weak stimulus-locked responses. In summary, the coupling strength between high frequencies of the LFP and spikes was not strongly modulated by LFP power, which is thought to reflect spiking synchrony, nor was it strongly influenced by how strongly the neuron was driven by the stimulus. Furthermore, a comparison between neighboring neurons showed no clustering of preferred LFP phase. We argue that hypotheses on the relevance of phase locking in their current form are inconsistent with our findings.

  8. Stark, Zeeman, and hyperfine properties of v=0, v=1, and the equilibrium configuration of hydrogen fluoride

    NASA Astrophysics Data System (ADS)

    Bass, Steven M.; DeLeon, Robert L.; Muenter, J. S.

    1987-04-01

    Molecular beam electric resonance spectroscopy has been done on the v=0 and v=1 states of hydrogen fluoride in external electric and magnetic fields. The v=1 state was populated using a color center laser. v=0, v=1, and equilibrium configuration results have been obtained for the HF dipole moment, fluorine and proton spin rotation interactions, fluorine and proton magnetic shielding anisotropies, both direct and indirect spin-spin interactions, rotational magnetic moment, and magnetic susceptibility. All of these properties can be extrapolated to v=2 with high accuracy and to higher states with reasonable confidence. First and second derivatives with respect to internuclear distance have also been obtained for several of these properties. Comparisons of HF and DF dipole moments indicate significant differences arising from Born-Oppenheimer breakdown.

  9. A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis

    PubMed Central

    Wu, Fenfen; Mi, Wentao; Burns, Dennis K.; Fu, Yu; Gray, Hillery F.; Struyk, Arie F.; Cannon, Stephen C.

    2011-01-01

    Hypokalemic periodic paralysis (HypoPP) is an ion channelopathy of skeletal muscle characterized by attacks of muscle weakness associated with low serum K+. HypoPP results from a transient failure of muscle fiber excitability. Mutations in the genes encoding a calcium channel (CaV1.1) and a sodium channel (NaV1.4) have been identified in HypoPP families. Mutations of NaV1.4 give rise to a heterogeneous group of muscle disorders, with gain-of-function defects causing myotonia or hyperkalemic periodic paralysis. To address the question of specificity for the allele encoding the NaV1.4-R669H variant as a cause of HypoPP and to produce a model system in which to characterize functional defects of the mutant channel and susceptibility to paralysis, we generated knockin mice carrying the ortholog of the gene encoding the NaV1.4-R669H variant (referred to herein as R669H mice). Homozygous R669H mice had a robust HypoPP phenotype, with transient loss of muscle excitability and weakness in low-K+ challenge, insensitivity to high-K+ challenge, dominant inheritance, and absence of myotonia. Recovery was sensitive to the Na+/K+-ATPase pump inhibitor ouabain. Affected fibers had an anomalous inward current at hyperpolarized potentials, consistent with the proposal that a leaky gating pore in R669H channels triggers attacks, whereas a reduction in the amplitude of action potentials implies additional loss-of-function changes for the mutant NaV1.4 channels. PMID:21881211

  10. Persistent modification of Na{sub v}1.9 following chronic exposure to insecticides and pyridostigmine bromide

    SciTech Connect

    Nutter, Thomas J. Cooper, Brian Y.

    2014-06-15

    Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na{sub v}1.8, but increased K{sub v}7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na{sub v}1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na{sub v}1.9, but significant increases in the amplitude of Na{sub v}1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na{sub v}1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na{sub v}1.9 expressed in muscle and vascular nociceptors. The reported increases in K{sub v}7 amplitude may have been an adaptive response to increased Na{sub v}1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na{sub v}1.9 and K{sub v}7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were

  11. Similar molecular determinants on Rem mediate two distinct modes of inhibition of CaV1.2 channels

    PubMed Central

    Puckerin, Akil A.; Chang, Donald D.; Subramanyam, Prakash; Colecraft, Henry M.

    2016-01-01

    ABSTRACT Rad/Rem/Rem2/Gem (RGK) proteins are Ras-like GTPases that potently inhibit all high-voltage-gated calcium (CaV1/CaV2) channels and are, thus, well-positioned to tune diverse physiological processes. Understanding how RGK proteins inhibit CaV channels is important for perspectives on their (patho)physiological roles and could advance their development and use as genetically-encoded CaV channel blockers. We previously reported that Rem can block surface CaV1.2 channels in 2 independent ways that engage distinct components of the channel complex: (1) by binding auxiliary β subunits (β-binding-dependent inhibition, or BBD); and (2) by binding the pore-forming α1C subunit N-terminus (α1C-binding-dependent inhibition, or ABD). By contrast, Gem uses only the BBD mechanism to block CaV1.2. Rem molecular determinants required for BBD CaV1.2 inhibition are the distal C-terminus and the guanine nucleotide binding G-domain which interact with the plasma membrane and CaVβ, respectively. However, Rem determinants for ABD CaV1.2 inhibition are unknown. Here, combining fluorescence resonance energy transfer, electrophysiology, systematic truncations, and Rem/Gem chimeras we found that the same Rem distal C-terminus and G-domain also mediate ABD CaV1.2 inhibition, but with different interaction partners. Rem distal C-terminus interacts with α1C N-terminus to anchor the G-domain which likely interacts with an as-yet-unidentified site. In contrast to some previous studies, neither the C-terminus of Rem nor Gem was sufficient to inhibit CaV1/CaV2 channels. The results reveal that similar molecular determinants on Rem are repurposed to initiate 2 independent mechanisms of CaV1.2 inhibition. PMID:27115600

  12. Astronomical component estimation (ACE v.1) by time-variant sinusoidal modeling

    NASA Astrophysics Data System (ADS)

    Sinnesael, Matthias; Zivanovic, Miroslav; De Vleeschouwer, David; Claeys, Philippe; Schoukens, Johan

    2016-09-01

    Accurately deciphering periodic variations in paleoclimate proxy signals is essential for cyclostratigraphy. Classical spectral analysis often relies on methods based on (fast) Fourier transformation. This technique has no unique solution separating variations in amplitude and frequency. This characteristic can make it difficult to correctly interpret a proxy's power spectrum or to accurately evaluate simultaneous changes in amplitude and frequency in evolutionary analyses. This drawback is circumvented by using a polynomial approach to estimate instantaneous amplitude and frequency in orbital components. This approach was proven useful to characterize audio signals (music and speech), which are non-stationary in nature. Paleoclimate proxy signals and audio signals share similar dynamics; the only difference is the frequency relationship between the different components. A harmonic-frequency relationship exists in audio signals, whereas this relation is non-harmonic in paleoclimate signals. However, this difference is irrelevant for the problem of separating simultaneous changes in amplitude and frequency. Using an approach with overlapping analysis frames, the model (Astronomical Component Estimation, version 1: ACE v.1) captures time variations of an orbital component by modulating a stationary sinusoid centered at its mean frequency, with a single polynomial. Hence, the parameters that determine the model are the mean frequency of the orbital component and the polynomial coefficients. The first parameter depends on geologic interpretations, whereas the latter are estimated by means of linear least-squares. As output, the model provides the orbital component waveform, either in the depth or time domain. Uncertainty analyses of the model estimates are performed using Monte Carlo simulations. Furthermore, it allows for a unique decomposition of the signal into its instantaneous amplitude and frequency. Frequency modulation patterns reconstruct changes in

  13. Hybrid superconducting a.c. current limiter extrapolation 63 kV-1 250 A

    NASA Astrophysics Data System (ADS)

    Tixador, P.; Levêque, J.; Brunet, Y.; Pham, V. D.

    1994-04-01

    (150 V/50 A) a permis de valider expérimentalement cette conception. Nous aborderons l'extrapolation d'un limiteur de taille industrielle (63 kV/1 250 A). Les résultats seront comparés à des limiteurs supraconducteurs résistifs et de type DASC.

  14. Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8.

    PubMed

    Lai, Josephine; Gold, Michael S; Kim, Chang Sook; Bian, Di; Ossipov, Michael H; Hunter, John C; Porreca, Frank

    2002-01-01

    Neuropathic pain is a debilitating chronic syndrome that often arises from injuries to peripheral nerves. Such pain has been hypothesized to be the result of an aberrant expression and function of sodium channels at the site of injury. Here, we show that intrathecal administration of specific antisense oligodeoxynucleotides (ODN) to the peripheral tetrodotoxin (TTX)-resistant sodium channel, NaV1.8, resulted in a time-dependent uptake of the ODN by dorsal root ganglion (DRG) neurons, a selective "knock-down" of the expression of NaV1.8, and a reduction in the slow-inactivating, TTX-resistant sodium current in the DRG cells. The ODN treatment also reversed neuropathic pain induced by spinal nerve injury, without affecting non-noxious sensation or response to acute pain. These data provide direct evidence linking NaV1.8 to neuropathic pain. As NaV1.8 expression is restricted to sensory neurons, this channel offers a highly specific and effective molecular target for the treatment of neuropathic pain. PMID:11790477

  15. CATS-ISS_L2O_N-M7.2-V1-05_05kmLay

    Atmospheric Science Data Center

    2016-10-24

    CATS-ISS_L2O_N-M7.2-V1-05_05kmLay Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  16. V1 and V2b interneurons secure the alternating flexor-extensor motor activity mice require for limbed locomotion

    PubMed Central

    Zhang, Jingming; Lanuza, Guillermo M.; Britz, Olivier; Wang, Zhi; Siembab, Valerie C.; Zhang, Ying; Velasquez, Tomoko; Alvarez, Francisco J.; Frank, Eric; Goulding, Martyn

    2014-01-01

    SUMMARY The reciprocal activation of flexor and extensor muscles constitutes the fundamental mechanism that tetrapod vertebrates use for locomotion and limb-driven reflex behaviors. This aspect of motor coordination is controlled by inhibitory neurons in the spinal cord; however, the identity of the spinal interneurons that serve this function is not known. Here we show that the production of an alternating flexor-extensor motor rhythm depends on the composite activities of two classes of ventrally-located inhibitory neurons, V1 and V2b interneurons (INs). Abrogating V1 and V2b IN-derived neurotransmission in the isolated spinal cord results in a synchronous pattern of L2 flexor-related and L5 extensor-related locomotor activity. Mice lacking V1 and V2b inhibition are unable to articulate their limb joints and display marked deficits in limb-driven reflex movements. Taken together, these findings identify V1- and V2b-derived neurons as the core interneuronal components of the limb central pattern generator (CPG) that coordinate flexor-extensor motor activity. PMID:24698273

  17. CATS-ISS_L2O_D-M7.1-V1-05_05kmPro

    Atmospheric Science Data Center

    2016-10-25

    CATS-ISS_L2O_D-M7.1-V1-05_05kmPro Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  18. CATS-ISS_L2O_N-M7.2-V1-05_05kmPro

    Atmospheric Science Data Center

    2016-10-24

    CATS-ISS_L2O_N-M7.2-V1-05_05kmPro Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  19. Graded Ca2+/calmodulin-dependent coupling of voltage-gated CaV1.2 channels

    PubMed Central

    Dixon, Rose E; Moreno, Claudia M; Yuan, Can; Opitz-Araya, Ximena; Binder, Marc D; Navedo, Manuel F; Santana, Luis F

    2015-01-01

    In the heart, reliable activation of Ca2+ release from the sarcoplasmic reticulum during the plateau of the ventricular action potential requires synchronous opening of multiple CaV1.2 channels. Yet the mechanisms that coordinate this simultaneous opening during every heartbeat are unclear. Here, we demonstrate that CaV1.2 channels form clusters that undergo dynamic, reciprocal, allosteric interactions. This ‘functional coupling’ facilitates Ca2+ influx by increasing activation of adjoined channels and occurs through C-terminal-to-C-terminal interactions. These interactions are initiated by binding of incoming Ca2+ to calmodulin (CaM) and proceed through Ca2+/CaM binding to the CaV1.2 pre-IQ domain. Coupling fades as [Ca2+]i decreases, but persists longer than the current that evoked it, providing evidence for ‘molecular memory’. Our findings suggest a model for CaV1.2 channel gating and Ca2+-influx amplification that unifies diverse observations about Ca2+ signaling in the heart, and challenges the long-held view that voltage-gated channels open and close independently. DOI: http://dx.doi.org/10.7554/eLife.05608.001 PMID:25714924

  20. V1 and v2b interneurons secure the alternating flexor-extensor motor activity mice require for limbed locomotion.

    PubMed

    Zhang, Jingming; Lanuza, Guillermo M; Britz, Olivier; Wang, Zhi; Siembab, Valerie C; Zhang, Ying; Velasquez, Tomoko; Alvarez, Francisco J; Frank, Eric; Goulding, Martyn

    2014-04-01

    Reciprocal activation of flexor and extensor muscles constitutes the fundamental mechanism that tetrapod vertebrates use for locomotion and limb-driven reflex behaviors. This aspect of motor coordination is controlled by inhibitory neurons in the spinal cord; however, the identity of the spinal interneurons that serve this function is not known. Here, we show that the production of an alternating flexor-extensor motor rhythm depends on the composite activities of two classes of ventrally located inhibitory neurons, V1 and V2b interneurons (INs). Abrogating V1 and V2b IN-derived neurotransmission in the isolated spinal cord results in a synchronous pattern of L2 flexor-related and L5 extensor-related locomotor activity. Mice lacking V1 and V2b inhibition are unable to articulate their limb joints and display marked deficits in limb-driven reflex movements. Taken together, these findings identify V1- and V2b-derived neurons as the core interneuronal components of the limb central pattern generator (CPG) that coordinate flexor-extensor motor activity.

  1. CATS-ISS_L2O_N-M7.2-V1-03_05kmPro

    Atmospheric Science Data Center

    2016-04-27

    CATS-ISS_L2O_N-M7.2-V1-03_05kmPro Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  2. CATS-ISS_L2O_N-M7.2-V1-04_05kmPro

    Atmospheric Science Data Center

    2016-06-30

    CATS-ISS_L2O_N-M7.2-V1-04_05kmPro Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  3. CATS-ISS_L2O_D-M7.2-V1-04_05kmLay

    Atmospheric Science Data Center

    2016-06-30

    CATS-ISS_L2O_D-M7.2-V1-04_05kmLay Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  4. CATS-ISS_L2O_N-M7.2-V1-03_05kmLay

    Atmospheric Science Data Center

    2016-04-27

    CATS-ISS_L2O_N-M7.2-V1-03_05kmLay Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  5. CATS-ISS_L2O_D-M7.2-V1-03_05kmLay

    Atmospheric Science Data Center

    2016-04-27

    CATS-ISS_L2O_D-M7.2-V1-03_05kmLay The Cloud-Aerosol Transport System (CATS) is a three wavelength, polarization-sensitive lidar that provides ... in the Earth's atmosphere. Project Title:  CATS Discipline:  Clouds Aerosols Version:  ...

  6. CATS-ISS_L2O_N-M7.2-V1-04_05kmLay

    Atmospheric Science Data Center

    2016-06-30

    CATS-ISS_L2O_N-M7.2-V1-04_05kmLay Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  7. CATS-ISS_L2O_D-M7.2-V1-04_05kmPro

    Atmospheric Science Data Center

    2016-06-30

    CATS-ISS_L2O_D-M7.2-V1-04_05kmPro Project Title:  CATS Discipline:  Clouds Aerosols Version:  ... and Order:  ASDC Order Tool Product Browse Tool:  CATS Order Tool OPeNDAP Access:  OPeNDAP Parameters:  ...

  8. Release of Bet v 1 from birch pollen from 5 European countries. Results from the HIALINE study

    NASA Astrophysics Data System (ADS)

    The HIALINE working Group; Buters, Jeroen T. M.; Thibaudon, Michel; Smith, Matt; Kennedy, Roy; Rantio-Lehtimäki, Auli; Albertini, Roberto; Reese, Gerald; Weber, Bernhard; Galan, Carmen; Brandao, Rui; Antunes, Celia M.; Jäger, Siegfried; Berger, Uwe; Celenk, Sevcan; Grewling, Łukasz; Jackowiak, Bogdan; Sauliene, Ingrida; Weichenmeier, Ingrid; Pusch, Gudrun; Sarioglu, Hakan; Ueffing, Marius; Behrendt, Heidrun; Prank, Marje; Sofiev, Mikhail; Cecchi, Lorenzo

    2012-08-01

    Exposure to allergens is pivotal in determining sensitization and allergic symptoms in individuals. Pollen grain counts in ambient air have traditionally been assessed to estimate airborne allergen exposure. However, the exact allergen content of ambient air is unknown. We therefore monitored atmospheric concentrations of birch pollen grains and the matched major birch pollen allergen Bet v 1 simultaneously across Europe within the EU-funded project HIALINE (Health Impacts of Airborne Allergen Information Network).Pollen count was assessed with Hirst type pollen traps at 10 l min-1 at sites in France, United Kingdom, Germany, Italy and Finland. Allergen concentrations in ambient air were sampled at 800 l min-1 with a Chemvol® high-volume cascade impactor equipped with stages PM > 10 μm, 10 μm > PM > 2.5 μm, and in Germany also 2.5 μm > PM > 0.12 μm. The major birch pollen allergen Bet v 1 was determined with an allergen specific ELISA. Bet v 1 isoform patterns were analyzed by 2D-SDS-PAGE blots and mass spectrometric identification. Basophil activation was tested in an FcɛR1-humanized rat basophil cell line passively sensitized with serum of a birch pollen symptomatic patient.Compared to 10 previous years, 2009 was a representative birch pollen season for all stations. About 90% of the allergen was found in the PM > 10 μm fraction at all stations. Bet v 1 isoforms pattern did not vary substantially neither during ripening of pollen nor between different geographical locations. The average European allergen release from birch pollen was 3.2 pg Bet v 1/pollen and did not vary much between the European countries. However, in all countries a >10-fold difference in daily allergen release per pollen was measured which could be explained by long-range transport of pollen with a deviating allergen release. Basophil activation by ambient air extracts correlated better with airborne allergen than with pollen concentration.Although Bet v 1 is a mixture of different

  9. Release of Bet v 1 from birch pollen from 5 European countries. Results from the HIALINE study

    NASA Astrophysics Data System (ADS)

    Buters, Jeroen T. M.; Thibaudon, Michel; Smith, Matt; Kennedy, Roy; Rantio-Lehtimäki, Auli; Albertini, Roberto; Reese, Gerald; Weber, Bernhard; Galan, Carmen; Brandao, Rui; Antunes, Celia M.; Jäger, Siegfried; Berger, Uwe; Celenk, Sevcan; Grewling, Łukasz; Jackowiak, Bogdan; Sauliene, Ingrida; Weichenmeier, Ingrid; Pusch, Gudrun; Sarioglu, Hakan; Ueffing, Marius; Behrendt, Heidrun; Prank, Marje; Sofiev, Mikhail; Cecchi, Lorenzo; Hialine Working Group

    2012-08-01

    Exposure to allergens is pivotal in determining sensitization and allergic symptoms in individuals. Pollen grain counts in ambient air have traditionally been assessed to estimate airborne allergen exposure. However, the exact allergen content of ambient air is unknown. We therefore monitored atmospheric concentrations of birch pollen grains and the matched major birch pollen allergen Bet v 1 simultaneously across Europe within the EU-funded project HIALINE (Health Impacts of Airborne Allergen Information Network). Pollen count was assessed with Hirst type pollen traps at 10 l min-1 at sites in France, United Kingdom, Germany, Italy and Finland. Allergen concentrations in ambient air were sampled at 800 l min-1 with a Chemvol® high-volume cascade impactor equipped with stages PM > 10 μm, 10 μm > PM > 2.5 μm, and in Germany also 2.5 μm > PM > 0.12 μm. The major birch pollen allergen Bet v 1 was determined with an allergen specific ELISA. Bet v 1 isoform patterns were analyzed by 2D-SDS-PAGE blots and mass spectrometric identification. Basophil activation was tested in an FcɛR1-humanized rat basophil cell line passively sensitized with serum of a birch pollen symptomatic patient. Compared to 10 previous years, 2009 was a representative birch pollen season for all stations. About 90% of the allergen was found in the PM > 10 μm fraction at all stations. Bet v 1 isoforms pattern did not vary substantially neither during ripening of pollen nor between different geographical locations. The average European allergen release from birch pollen was 3.2 pg Bet v 1/pollen and did not vary much between the European countries. However, in all countries a >10-fold difference in daily allergen release per pollen was measured which could be explained by long-range transport of pollen with a deviating allergen release. Basophil activation by ambient air extracts correlated better with airborne allergen than with pollen concentration. Although Bet v 1 is a mixture of different

  10. Engraftment of retrovirally transduced Bet v 1-GFP expressing bone marrow cells leads to allergen-specific tolerance.

    PubMed

    Gattringer, Martina; Baranyi, Ulrike; Pilat, Nina; Hock, Karin; Klaus, Christoph; Buchberger, Elisabeth; Ramsey, Haley; Iacomini, John; Valenta, Rudolf; Wekerle, Thomas

    2013-09-01

    Molecular chimerism is a promising strategy to induce tolerance to disease-causing antigens expressed on genetically modified haematopoietic stem cells. The approach was employed successfully in models of autoimmunity and organ transplantation. Recently, we demonstrated that molecular chimerism induces robust and lasting tolerance towards the major grass pollen allergen Phl p 5. Since allergens are a group of antigens differing widely in their function, origin and structure we further examined the effectiveness of molecular chimerism using the Phl p 5-unrelated major birch pollen allergen Bet v 1, co-expressed with the reporter GFP. Besides, inhibition of CD26 was used to promote engraftment of modified stem cells. Retrovirus VSV-Betv1-GFP was generated to transduce 5-FU-mobilized BALB/c hematopoietic cells to express membrane-bound Bet v 1 (VSV-GFP virus was used as control). Myeloablated BALB/c mice received Betv1-GFP or GFP expressing bone marrow cells, pre-treated with a CD26 inhibitor. Chimerism was followed by flow cytometry. Tolerance was assessed by measuring allergen-specific isotype levels in sera, RBL assays and T-cell proliferation assays. Mice transplanted with transduced BMC developed multi-lineage molecular chimerism which remained stable long-term (>8 months). After repeated immunizations with Bet v 1 and Phl p 5 serum levels of Bet v 1-specific antibodies (IgE, IgG1, IgG2a, IgG3 and IgA) remained undetectable in Betv1-GFP chimeras while high levels of Phl p 5-specific antibodies developed. Likewise, basophil degranulation was induced in response to Phl p 5 but not to Bet v 1 and specific non-responsiveness to Bet v 1 was observed in proliferation assays. These data demonstrate successful tolerization towards Bet v 1 by molecular chimerism. Stable long-term chimerism was achieved under inhibition of CD26. These results provide evidence for the broad applicability of molecular chimerism as tolerance strategy in allergy.

  11. Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer.

    PubMed

    Hernandez-Plata, Everardo; Ortiz, Cindy S; Marquina-Castillo, Brenda; Medina-Martinez, Ingrid; Alfaro, Ana; Berumen, Jaime; Rivera, Manuel; Gomora, Juan C

    2012-05-01

    Functional activity of voltage-gated sodium channels (VGSC) has been associated to the invasion and metastasis behaviors of prostate, breast and some other types of cancer. We previously reported the functional expression of VGSC in primary cultures and biopsies derived from cervical cancer (CaC). Here, we investigate the relative expression levels of VGSC subunits and its possible role in CaC. Quantitative real-time PCR revealed that mRNA levels of Na(V) 1.6 α-subunit in CaC samples were ∼40-fold higher than in noncancerous cervical (NCC) biopsies. A Na(V) 1.7 α-subunit variant also showed increased mRNA levels in CaC (∼20-fold). All four Na(V) β subunits were also detected in CaC samples, being Na(V) β1 the most abundant. Proteins of Na(V) 1.6 and Na(V) 1.7 α-subunits were immunolocalized in both NCC and CaC biopsies and in CaC primary cultures as well; however, although in NCC sections proteins were mainly relegated to the plasma membrane, in CaC biopsies and primary cultures the respective signal was stronger and widely distributed in both cytoplasm and plasma membrane. Functional activity of Na(V) 1.6 channels in the plasma membrane of CaC cells was confirmed by whole-cell patch-clamp experiments using Cn2, a Na(V) 1.6-specific toxin, which blocked ∼30% of the total sodium current. Blocking of sodium channels VGSC with tetrodotoxin and Cn2 did not affect proliferation neither migration, but reduced by ∼20% the invasiveness of CaC primary culture cells in vitro assays. We conclude that Na(V) 1.6 is upregulated in CaC and could serve as a novel molecular marker for the metastatic behavior of this carcinoma.

  12. Activation of tetrodotoxin-resistant sodium channel NaV1.9 in rat primary sensory neurons contributes to melittin-induced pain behavior.

    PubMed

    Yu, Yao-Qing; Zhao, Zhen-Yu; Chen, Xue-Feng; Xie, Fang; Yang, Yan; Chen, Jun

    2013-03-01

    Tetrodotoxin-resistant (TTX-R) sodium channels NaV1.8 and NaV1.9 in dorsal root ganglion (DRG) neurons play important roles in pathological pain. We recently reported that melittin, the major toxin of whole bee venom, induced action potential firings in DRG neurons even in the presence of a high concentration (500 nM) of TTX, indicating the contribution of TTX-R sodium channels. This hypothesis is fully investigated in the present study. After subcutaneous injection of melittin, NaV1.8 and NaV1.9 significantly upregulate mRNA and protein expressions, and related sodium currents also increase. Double immunohistochemical results show that NaV1.8-positive neurons are mainly medium- and small-sized, whereas NaV1.9-positive ones are only small-sized. Antisense oligodeoxynucleotides (AS ODNs) targeting NaV1.8 and NaV1.9 are used to evaluate functional significance of the increased expressions of TTX-R sodium channels. Behavioral tests demonstrate that AS ODN targeting NaV1.9, but not NaV1.8, reverses melittin-induced heat hypersensitivity. Neither NaV1.8 AS ODN nor NaV1.9 AS ODN affects melittin-induced mechanical hypersensitivity. These results provide previously unknown evidence that upregulation of NaV1.9, but not NaV1.8, in small-sized DRG neurons contributes to melittin-induced heat hypersensitivity. Furthermore, melittin-induced biological effect indicates a potential strategy to study properties of TTX-R sodium channels. PMID:23264124

  13. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

    PubMed

    Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

    2016-01-01

    Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure. PMID:26383867

  14. Reactive species modify NaV1.8 channels and affect action potentials in murine dorsal root ganglion neurons.

    PubMed

    Schink, Martin; Leipold, Enrico; Schirmeyer, Jana; Schönherr, Roland; Hoshi, Toshinori; Heinemann, Stefan H

    2016-01-01

    Dorsal root ganglion (DRG) neurons are important relay stations between the periphery and the central nervous system and are essential for somatosensory signaling. Reactive species are produced in a variety of physiological and pathophysiological conditions and are known to alter electric signaling. Here we studied the influence of reactive species on the electrical properties of DRG neurons from mice with the whole-cell patch-clamp method. Even mild stress induced by either low concentrations of chloramine-T (10 μM) or low-intensity blue light irradiation profoundly diminished action potential frequency but prolonged single action potentials in wild-type neurons. The impact on evoked action potentials was much smaller in neurons deficient of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel NaV1.8 (NaV1.8(-/-)), the channel most important for the action potential upstroke in DRG neurons. Low concentrations of chloramine-T caused a significant reduction of NaV1.8 peak current and, at higher concentrations, progressively slowed down inactivation. Blue light had a smaller effect on amplitude but slowed down NaV1.8 channel inactivation. The observed effects were less apparent for TTX-sensitive NaV channels. NaV1.8 is an important reactive-species-sensitive component in the electrical signaling of DRG neurons, potentially giving rise to loss-of-function and gain-of-function phenomena depending on the type of reactive species and their effective concentration and time of exposure.

  15. Capping protein regulatory cycle driven by CARMIL and V-1 may promote actin network assembly at protruding edges

    PubMed Central

    Fujiwara, Ikuko; Remmert, Kirsten; Piszczek, Grzegorz; Hammer, John A.

    2014-01-01

    Although capping protein (CP) terminates actin filament elongation, it promotes Arp2/3-dependent actin network assembly and accelerates actin-based motility both in vitro and in vivo. In vitro, capping protein Arp2/3 myosin I linker (CARMIL) antagonizes CP by reducing its affinity for the barbed end and by uncapping CP-capped filaments, whereas the protein V-1/myotrophin sequesters CP in an inactive complex. Previous work showed that CARMIL can readily retrieve CP from the CP:V-1 complex, thereby converting inactive CP into a version with moderate affinity for the barbed end. Here we further clarify the mechanism of this exchange reaction, and we demonstrate that the CP:CARMIL complex created by complex exchange slows the rate of barbed-end elongation by rapidly associating with, and dissociating from, the barbed end. Importantly, the cellular concentrations of V-1 and CP determined here argue that most CP is sequestered by V-1 at steady state in vivo. Finally, we show that CARMIL is recruited to the plasma membrane and only at cell edges undergoing active protrusion. Assuming that CARMIL is active only at this location, our data argue that a large pool of freely diffusing, inactive CP (CP:V-1) feeds, via CARMIL-driven complex exchange, the formation of weak-capping complexes (CP:CARMIL) at the plasma membrane of protruding edges. In vivo, therefore, CARMIL should promote Arp2/3-dependent actin network assembly at the leading edge by promoting barbed-end capping there. PMID:24778263

  16. /sup 125/I)-(d(CH2)5, Sar7)AVP: a selective radioligand for V1 vasopressin receptors

    SciTech Connect

    Kelly, J.M.; Abrahams, J.M.; Phillips, P.A.; Mendelsohn, F.A.; Grzonka, Z.; Johnston, C.I.

    1989-01-01

    Arginine8-vasopressin (AVP) acts on vascular and hepatic V1 receptors to influence blood pressure and glycogenolysis respectively. We have radioiodinated the AVP V1 receptor antagonist, (1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic-acid), 7-sarcosine, 8-arginine) vasopressin ((d(CH2)5, Sar7)AVP) and determined its receptor-binding properties in rat liver and kidney plasma membranes. The binding was of high affinity to single classes of receptors (liver: Kd = 3.0 nM and Bmax = 530 +/- 10 fmol/mg protein, kidney: Kd = 0.5 +/- 0.9 nM and Bmax = 11 +/- 8 fmol/mg protein). Competition of (125I)-(d(CH2)5, Sar7)AVP binding by unlabelled AVP analogues gave the following order of potency in both tissues, consistent with that expected for binding to a V1 receptor: (d(CH2)5, Tyr(Me)2)AVP greater than AVP greater than (d(CH2)5, D-Ile2, Ile4) AVP greater than DDAVP. No degradation of (125I)-(d(CH2)5, Sar7)AVP during incubation or storage was detected by HPLC analysis. We have used (125I)-(d(CH2)5, Sar7)AVP and in vitro autoradiography to demonstrate its use in localizing brain AVP receptors. These studies suggest that (125I)-(d(CH2)5, Sar7)AVP is a suitable selective radioligand for labelling V1 receptors and will provide a valuable tool for the study of the localization and regulation of AVP V1 receptors in tissues and in receptor isolation.

  17. A FORTRAN-90 Low-Energy Electron Diffraction program (LEED90 v1.1)

    NASA Astrophysics Data System (ADS)

    Blanco-Rey, Maria; de Andres, Pedro; Held, Georg; King, David A.

    2004-08-01

    We describe a FORTRAN-90 program to compute low-energy electron diffraction I(V) curves. Plane-waves and layer doubling are used to compute the inter-layer multiple-scattering, while the intra-layer multiple-scattering is computed in the standard way expanding the wavefield on a basis of spherical waves. The program is kept as general as possible, in order to allow testing different parts of multiple-scattering calculations. In particular, it can handle non-diagonal t-matrices describing the scattering of non-spherical potentials, anisotropic vibrations, anharmonicity, etc. The program does not use old FORTRAN flavours, and has been written keeping in mind the advantage for parallelism brought forward by FORTRAN-90. Program summaryTitle of program: LEED90 Catalogue number: ADUE Program summary URL:http://cpc.sc.qub.ac.uk/summaries/ADUE Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland. Computers: Alpha ev6-21264 (700 MHz) and Pentium-IV. Operating system: Digital UNIX V5.0 and Linux (Red Hat 8.0). Programming language: FORTRAN-90/95 (Compaq True64 compiler, and Intel Fortran Compiler 7.0 for Linux). High-speed storage required for the test run: minimum 64 Mbytes, it can grow to more depending on the system considered. Disk storage required: None No. of bits in a word: 64 and 32 No. of lines in distributed program, including test data, etc.: 17 953 No. of bytes in distributed program, including test data, etc.: 100 051 Distribution format: tar.gz Nature of problem: We describe the FORTRAN-90 program LEED90 (v1.1) to compute dynamical I(V) curves using layer-doubling. The program has been designed to be able to take, as an option, input from non-diagonal t-matrix, e.g., representing a molecule, temperature corrections for anisotropic/anharmonic vibrations, or non-spherical muffin-tin potentials. Method of solution: The intra-layer multiple-scattering problem is solved by adding self-consistently spherical wave amplitudes

  18. Compositional study of asteroids in the Erigone collisional family using visible spectroscopy at the 10.4m GTC

    NASA Astrophysics Data System (ADS)

    Morate, David; de León, Julia; De Prá, Mário; Licandro, Javier; Cabrera-Lavers, Antonio; Campins, Humberto; Pinilla-Alonso, Noemí; Alí-Lagoa, Víctor

    2015-11-01

    Asteroid families are formed by the fragments produced by the disruption of a common parent body (Bendjoya & Zappalà 2002). Primitive asteroids in the solar system are believed to have undergone less thermal processing than the S-complex asteroids. Thus, study of primitive asteroid families provides information about the solar system formation period. The Erigone collisional family, together with other three families (Polana, Clarissa and Sulamitis), are believed to be the origin of the two primitive Near-Earth asteroids that are the main targets of the NASA’s OSIRIS-REx ((101955) Bennu) and JAXA’s Hayabusa 2 ((162173) 1999 JU3) missions (Campins et al. 2010; Campins et al. 2013; Lauretta et al. 2010; Tsuda et al. 2013). These spacecrafts will visit the asteroids, and a sample of their surface material will be returned to Earth. Understanding of the families that are considered potential sources will enhance the scientific return of the missions. The main goal of the work presented here is to characterize the Erigone collisional family. Asteroid (163) Erigone has been classified as a primitive object (Bus 1999; Bus & Binzel 2002), and we expect the members of this family to be consistent with the spectral type of the parent body. We have obtained visible spectra (0.5-0.9 μm) for 101 members of the Erigone family, using the OSIRIS instrument at the 10.4m Gran Telescopio Canarias. We performed a taxonomical classification of these asteroids, finding that the number of primitive objects in our sample is in agreement with the hypothesis of a common parent body. In addition, we have found a significant fraction of asteroids in our sample that present evidences of aqueous alteration. Study of aqueous alterations is important, as it can give information on the heating processes of the early Solar System, and for the associated astrobiological implications (it has been suggested that the Earth’s present water supply was brought here by asteroids, instead of comets

  19. Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects.

    PubMed

    Duque-Wilckens, Natalia; Steinman, Michael Q; Laredo, Sarah A; Hao, Rebecca; Perkeybile, Allison M; Bales, Karen L; Trainor, Brian C

    2016-11-01

    Vasopressin V1a receptors (V1aR) are thought to contribute to the pathophysiology of psychiatric disorders such as anxiety and depression, sparking interest in V1aR as a therapeutic target. Although the global effects of V1aR have been documented, less is known about the specific neural circuits mediating these effects. Moreover, few studies have examined context-specific V1aR function in both males and females. By using the California mouse, we first studied the effects of sex and social defeat stress on V1aR binding in the forebrain. In females but not males, V1aR binding in the bed nucleus of the stria terminalis (BNST) was negatively correlated to social interaction behavior. In females stress also increased V1aR binding in the nucleus accumbens (NAc). Infusions of V1aR antagonist in to the medioventral BNST (BNSTmv) had anxiogenic effects only in animals naïve to defeat. For males, inhibition of V1aR in BNSTmv had anxiogenic effects in social and nonsocial contexts, but for females, anxiogenic effects were limited to social contexts. In stressed females, inhibition of V1aR in the NAc shell had no effect on social interaction behavior, but had an anxiogenic effect in an open field test. These data suggest that V1aR in BNSTmv have anxiolytic and prosocial effects in males, and that in females, prosocial and anxiolytic effects of V1aR appear to be mediated independently by receptors in the BNSTmv and NAc shell, respectively. These findings suggest that males have more overlap in neural circuits modulating anxiety in social and nonsocial contexts than females. PMID:27452721

  20. DCPT v1.0 - New particle tracker for modeling transport in dual-continuum - User's Manual

    SciTech Connect

    Pan, Lehua; Liu, Hui Hai; Cushey, Mark; Bodvarsson, Gudmundur

    2001-04-01

    DCPT (Dual-Continuum Particle Tracker) V1.0 is a new software for simulating solute transport in the subsurface. It is based on the random-walk method for modeling transport processes such as advection, dispersion/diffusion, linear sorption, radioactive decay, and fracture-matrix mass exchange (in fractured porous media). The user shall provide flow-field and other parameters in the form of input files. In Comparison to several analytical and numerical solutions for a number of test cases, DCPT shows excellent performance in both accuracy and efficiency. This report serves as a user's manual of DCPT V1.0. It includes theoretical basis, numerical methods, software structure, input/output description, and examples.

  1. Automated Patch Clamp Analysis of nAChα7 and Na(V)1.7 Channels.

    PubMed

    Obergrussberger, Alison; Haarmann, Claudia; Rinke, Ilka; Becker, Nadine; Guinot, David; Brueggemann, Andrea; Stoelzle-Feix, Sonja; George, Michael; Fertig, Niels

    2014-01-01

    Automated patch clamp devices are now commonly used for studying ion channels. A useful modification of this approach is the replacement of the glass pipet with a thin planar glass layer with a small hole in the middle. Planar patch clamp devices, such as the three described in this unit, are overtaking glass pipets in popularity because they increase throughput, are easier to use, provide for the acquisition of high-quality and information-rich data, and allow for rapid perfusion and temperature control. Covered in this unit are two challenging targets in drug discovery: voltage-gated sodium subtype 1.7 (Na(V)1.7) and nicotinic acetylcholine α7 receptors (nAChα7R). Provided herein are protocols for recording activation and inactivation kinetics of Na(V)1.7, and activation and allosteric modulation of nAChα7R. PMID:24934604

  2. Response evaluation criteria for solid tumours in dogs (v1.0): a Veterinary Cooperative Oncology Group (VCOG) consensus document.

    PubMed

    Nguyen, S M; Thamm, D H; Vail, D M; London, C A

    2015-09-01

    In veterinary medical oncology, there is currently no standardized protocol for assessing response to therapy in solid tumours. The lack of such a formalized guideline makes it challenging to critically compare outcome measures across various treatment protocols. The Veterinary Cooperative Oncology Group (VCOG) membership consensus document presented here is based on the recommendations of a subcommittee of American College of Veterinary Internal Medicine (ACVIM) board-certified veterinary oncologists. This consensus paper has used the human response evaluation criteria in solid tumours (RECIST v1.1) as a framework to establish standard procedures for response assessment in canine solid tumours that is meant to be easy to use, repeatable and applicable across a variety of clinical trial structures in veterinary oncology. It is hoped that this new canine RECIST (cRECIST v1.0) will be adopted within the veterinary oncology community and thereby facilitate the comparison of current and future treatment protocols used for companion animals with cancer.

  3. SiO masers from AGB stars in the vibrationally excited v = 1, v = 2, and v = 3 states

    NASA Astrophysics Data System (ADS)

    Desmurs, J.-F.; Bujarrabal, V.; Lindqvist, M.; Alcolea, J.; Soria-Ruiz, R.; Bergman, P.

    2014-05-01

    Context. The v = 1 and v = 2 J = 1-0 (43 GHz), and v = 1 J = 2-1 (86 GHz) SiO masers are intense in asymptotic giant branch (AGB) stars and have been mapped using very long baseline interferometry (VLBI) showing ring-like distributions. Those of the v = 1, v = 2 J = 1-0 masers are similar, but the spots are rarely coincident, while the v = 1 J = 2-1 maser arises from a well-separated region farther out. These relative locations can be explained by models tools that include the overlap of two IR lines of SiO and H2O. The v = 3 J = 1-0 line is not directly affected by any line overlap and its spot structure and position, relative to the other lines, is a good test to the standard pumping models. Aims: The aim of this project are to gain insight into the properties and the general theoretical considerations of the different SiO masers that can help to understand them. Methods: We present single-dish and simultaneous VLBI observations of the v = 1, v = 2, and v = 3 J = 1-0 maser transitions of 28SiO in several AGB stars. The results are compared to the predictions of radiative models of SiO masers that both include and not include the effect of IR line overlap. Results: The spatial distribution of the SiO maser emission in the v = 3 J = 1-0 transition from AGB stars is systematically composed of a series of spots that occupy a ring-like structure (as often found in SiO masers). The overall ring structure is extremely similar to that found in the other 43 GHz transitions and is very different from the structure of the v = 1 J = 2-1 maser. The positions of the individual spots of the different 43 GHz lines are, however, very rarely coincident, which in general is separated by about 0.3 AU (between 1 and 5 mas). These results are very difficult to reconcile with standard pumping models, which predict that the masers of rotational transitions within a given vibrational state require very similar excitation conditions (since the levels are placed practically at the same

  4. Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain

    PubMed Central

    Deuis, Jennifer R.; Wingerd, Joshua S.; Winter, Zoltan; Durek, Thomas; Dekan, Zoltan; Sousa, Silmara R.; Zimmermann, Katharina; Hoffmann, Tali; Weidner, Christian; Nassar, Mohammed A.; Alewood, Paul F.; Lewis, Richard J.; Vetter, Irina

    2016-01-01

    Loss-of-function mutations of NaV1.7 lead to congenital insensitivity to pain, a rare condition resulting in individuals who are otherwise normal except for the inability to sense pain, making pharmacological inhibition of NaV1.7 a promising therapeutic strategy for the treatment of pain. We characterized a novel mouse model of NaV1.7-mediated pain based on intraplantar injection of the scorpion toxin OD1, which is suitable for rapid in vivo profiling of NaV1.7 inhibitors. Intraplantar injection of OD1 caused spontaneous pain behaviors, which were reversed by co-injection with NaV1.7 inhibitors and significantly reduced in NaV1.7−/− mice. To validate the use of the model for profiling NaV1.7 inhibitors, we determined the NaV selectivity and tested the efficacy of the reported NaV1.7 inhibitors GpTx-1, PF-04856264 and CNV1014802 (raxatrigine). GpTx-1 selectively inhibited NaV1.7 and was effective when co-administered with OD1, but lacked efficacy when delivered systemically. PF-04856264 state-dependently and selectively inhibited NaV1.7 and significantly reduced OD1-induced spontaneous pain when delivered locally and systemically. CNV1014802 state-dependently, but non-selectively, inhibited NaV channels and was only effective in the OD1 model when delivered systemically. Our novel model of NaV1.7-mediated pain based on intraplantar injection of OD1 is thus suitable for the rapid in vivo characterization of the analgesic efficacy of NaV1.7 inhibitors. PMID:26999206

  5. Relaxation of NH(a(1)Delta, v = 1) in collisions with H((2)S): an experimental and theoretical study.

    PubMed

    Defazio, P; Petrongolo, C; McBane, G C; Adam, L; Hack, W; Akpinar, S; Schinke, R

    2009-12-31

    Collisions of electronically and vibrationally excited NH(a(1)Delta, v = 1) with H atoms were investigated by experimental, quantum mechanical (QM) wavepacket, and quasiclassical trajectory (QCT) methods. The NH(a(1)Delta, v = 1) total loss rate constant, corresponding to the sum of the NH vibrational relaxation, N((2)D)+H(2) formation, and electronic quenching to NH(X(3)Sigma(-)), was measured at room temperature. Most of the calculations were performed within the Born-Oppenheimer approximation, neglecting electronic quenching due to Renner-Teller coupling because QCT calculations showed that for the loss of NH(a(1)Delta, v = 1) the contribution of quenching is negligible. The QM study included Coriolis couplings, and the QCT study counted only trajectories ending close to a vibrational quantum level of the product diatom. The collisions are dominated by long-lived intermediate complexes, and QM probabilities and cross sections thus exhibit pronounced resonances. QM and QCT cross sections and rate coefficients of the various processes are in very good agreement. The measured rate constant is (9.1 +/- 3.3) x 10(-11) cm(3) s(-1), compared with (14.4 +/- 0.5) x 10(-11) and (15.6 +/- 1.6) x 10(-11) cm(3) s(-1), as obtained from QM and QCT calculations, respectively. The reason for the theoretical overestimation is unknown.

  6. Quantitative inference of population response properties across eccentricity from motion-induced maps in macaque V1

    PubMed Central

    Chen, Ming; Wu, Si; Lu, Haidong D.; Roe, Anna W.

    2013-01-01

    Interpreting population responses in the primary visual cortex (V1) remains a challenge especially with the advent of techniques measuring activations of large cortical areas simultaneously with high precision. For successful interpretation, a quantitatively precise model prediction is of great importance. In this study, we investigate how accurate a spatiotemporal filter (STF) model predicts average response profiles to coherently drifting random dot motion obtained by optical imaging of intrinsic signals in V1 of anesthetized macaques. We establish that orientation difference maps, obtained by subtracting orthogonal axis-of-motion, invert with increasing drift speeds, consistent with the motion streak effect. Consistent with perception, the speed at which the map inverts (the critical speed) depends on cortical eccentricity and systematically increases from foveal to parafoveal. We report that critical speeds and response maps to drifting motion are excellently reproduced by the STF model. Our study thus suggests that the STF model is quantitatively accurate enough to be used as a first model of choice for interpreting responses obtained with intrinsic imaging methods in V1. We show further that this good quantitative correspondence opens the possibility to infer otherwise not easily accessible population receptive field properties from responses to complex stimuli, such as drifting random dot motions. PMID:23197457

  7. Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus

    PubMed Central

    Thélie, Aurore; Desiderio, Simon; Hanotel, Julie; Quigley, Ian; Van Driessche, Benoit; Rodari, Anthony; Borromeo, Mark D.; Kricha, Sadia; Lahaye, François; Croce, Jenifer; Cerda-Moya, Gustavo; Ordoño Fernandez, Jesús; Bolle, Barbara; Lewis, Katharine E.; Sander, Maike; Pierani, Alessandra; Schubert, Michael; Johnson, Jane E.; Kintner, Christopher R.; Pieler, Tomas; Van Lint, Carine; Henningfeld, Kristine A.; Bellefroid, Eric J.; Van Campenhout, Claude

    2015-01-01

    V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show that the transcription factor Prdm12 is selectively expressed in p1 progenitors of the hindbrain and spinal cord in the frog embryo, and that a similar restricted expression profile is observed in the nerve cord of other vertebrates as well as of the cephalochordate amphioxus. Using frog, chick and mice, we analyzed the regulation of Prdm12 and found that its expression in the caudal neural tube is dependent on retinoic acid and Pax6, and that it is restricted to p1 progenitors, due to the repressive action of Dbx1 and Nkx6-1/2 expressed in the adjacent p0 and p2 domains. Functional studies in the frog, including genome-wide identification of its targets by RNA-seq and ChIP-Seq, reveal that vertebrate Prdm12 proteins act as a general determinant of V1 cell fate, at least in part, by directly repressing Dbx1 and Nkx6 genes. This probably occurs by recruiting the methyltransferase G9a, an activity that is not displayed by the amphioxus Prdm12 protein. Together, these findings indicate that Prdm12 promotes V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes, and suggest that this function might have only been acquired after the split of the vertebrate and cephalochordate lineages. PMID:26443638

  8. Parallel processing of face and house stimuli by V1 and specialized visual areas: a magnetoencephalographic (MEG) study

    PubMed Central

    Shigihara, Yoshihito; Zeki, Semir

    2014-01-01

    We used easily distinguishable stimuli of faces and houses constituted from straight lines, with the aim of learning whether they activate V1 on the one hand, and the specialized areas that are critical for the processing of faces and houses on the other, with similar latencies. Eighteen subjects took part in the experiment, which used magnetoencephalography (MEG) coupled to analytical methods to detect the time course of the earliest responses which these stimuli provoke in these cortical areas. Both categories of stimuli activated V1 and areas of the visual cortex outside it at around 40 ms after stimulus onset, and the amplitude elicited by face stimuli was significantly larger than that elicited by house stimuli. These results suggest that “low-level” and “high-level” features of form stimuli are processed in parallel by V1 and visual areas outside it. Taken together with our previous results on the processing of simple geometric forms (Shgihara and Zeki, 2013; Shigihara and Zeki, 2014), the present ones reinforce the conclusion that parallel processing is an important component in the strategy used by the brain to process and construct forms. PMID:25426050

  9. Biophysical characterization data of the artificial protein Octarellin V.1 and binding test with its X-ray helpers.

    PubMed

    Figueroa, Maximiliano; Vandenameele, Julie; Goormaghtigh, Erik; Valerio-Lepiniec, Marie; Minard, Philippe; Matagne, André; Van de Weerdt, Cécile

    2016-09-01

    The artificial protein Octarellin V.1 (http://dx.doi.org/10.1016/j.jsb.2016.05.004[1]) was obtained through a direct evolution process over the de novo designed Octarellin V (http://dx.doi.org/10.1016/S0022-2836(02)01206-8[2]). The protein has been characterized by circular dichroism and fluorescence techniques, in order to obtain data related to its thermo and chemical stability. Moreover, the data for the secondary structure content studied by circular dichroism and infra red techniques is reported for the Octarellin V and V.1. Two crystallization helpers, nanobodies (http://dx.doi.org/10.1038/nprot.2014.039[3]) and αRep (http://dx.doi.org/10.1016/j.jmb.2010.09.048[4]), have been used to create stable complexes. Here we present the data obtained of the binding characterization of the Octarellin V.1 with the crystallization helpers by isothermal titration calorimetry. PMID:27547801

  10. Characterization of 2 genetic variants of Na(v) 1.5-arginine 689 found in patients with cardiac arrhythmias.

    PubMed

    Sottas, Valentin; Rougier, Jean-Sébastien; Jousset, Florian; Kucera, Jan P; Shestak, Anna; Makarov, Leonid M; Zaklyazminskaya, Elena V; Abriel, Hugues

    2013-09-01

    Hundreds of genetic variants in SCN5A, the gene coding for the pore-forming subunit of the cardiac sodium channel, Na(v) 1.5, have been described in patients with cardiac channelopathies as well as in individuals from control cohorts. The aim of this study was to characterize the biophysical properties of 2 naturally occurring Na(v) 1.5 variants, p.R689H and p.R689C, found in patients with cardiac arrhythmias and in control individuals. In addition, this study was motivated by the finding of the variant p.R689H in a family with sudden cardiac death (SCD) in children. When expressed in HEK293 cells, most of the sodium current (I(Na)) biophysical properties of both variants were indistinguishable from the wild-type (WT) channels. In both cases, however, an ∼2-fold increase of the tetrodotoxin-sensitive late I(Na) was observed. Action potential simulations and reconstruction of pseudo-ECGs demonstrated that such a subtle increase in the late I(Na) may prolong the QT interval in a nonlinear fashion. In conclusion, despite the fact that the causality link between p.R689H and the phenotype of the studied family cannot be demonstrated, this study supports the notion that subtle alterations of Na(v) 1.5 variants may increase the risk for cardiac arrhythmias.

  11. The unexpected structure of the designed protein Octarellin V.1 forms a challenge for protein structure prediction tools.

    PubMed

    Figueroa, Maximiliano; Sleutel, Mike; Vandevenne, Marylene; Parvizi, Gregory; Attout, Sophie; Jacquin, Olivier; Vandenameele, Julie; Fischer, Axel W; Damblon, Christian; Goormaghtigh, Erik; Valerio-Lepiniec, Marie; Urvoas, Agathe; Durand, Dominique; Pardon, Els; Steyaert, Jan; Minard, Philippe; Maes, Dominique; Meiler, Jens; Matagne, André; Martial, Joseph A; Van de Weerdt, Cécile

    2016-07-01

    Despite impressive successes in protein design, designing a well-folded protein of more 100 amino acids de novo remains a formidable challenge. Exploiting the promising biophysical features of the artificial protein Octarellin V, we improved this protein by directed evolution, thus creating a more stable and soluble protein: Octarellin V.1. Next, we obtained crystals of Octarellin V.1 in complex with crystallization chaperons and determined the tertiary structure. The experimental structure of Octarellin V.1 differs from its in silico design: the (αβα) sandwich architecture bears some resemblance to a Rossman-like fold instead of the intended TIM-barrel fold. This surprising result gave us a unique and attractive opportunity to test the state of the art in protein structure prediction, using this artificial protein free of any natural selection. We tested 13 automated webservers for protein structure prediction and found none of them to predict the actual structure. More than 50% of them predicted a TIM-barrel fold, i.e. the structure we set out to design more than 10years ago. In addition, local software runs that are human operated can sample a structure similar to the experimental one but fail in selecting it, suggesting that the scoring and ranking functions should be improved. We propose that artificial proteins could be used as tools to test the accuracy of protein structure prediction algorithms, because their lack of evolutionary pressure and unique sequences features.

  12. Callosally projecting neurons in the macaque monkey V1/V2 border are enriched in nonphosphorylated neurofilament protein

    NASA Technical Reports Server (NTRS)

    Hof, P. R.; Ungerleider, L. G.; Adams, M. M.; Webster, M. J.; Gattass, R.; Blumberg, D. M.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Previous immunohistochemical studies combined with retrograde tracing in macaque monkeys have demonstrated that corticocortical projections can be differentiated by their content of neurofilament protein. The present study analyzed the distribution of nonphosphorylated neurofilament protein in callosally projecting neurons located at the V1/V2 border. All of the retrogradely labeled neurons were located in layer III at the V1/V2 border and at an immediately adjacent zone of area V2. A quantitative analysis showed that the vast majority (almost 95%) of these interhemispheric projection neurons contain neurofilament protein immunoreactivity. This observation differs from data obtained in other sets of callosal connections, including homotypical interhemispheric projections in the prefrontal, temporal, and parietal association cortices, that were found to contain uniformly low proportions of neurofilament protein-immunoreactive neurons. Comparably, highly variable proportions of neurofilament protein-containing neurons have been reported in intrahemispheric corticocortical pathways, including feedforward and feedback visual connections. These results indicate that neurofilament protein is a prominent neurochemical feature that identifies a particular population of interhemispheric projection neurons at the V1/V2 border and suggest that this biochemical attribute may be critical for the function of this subset of callosal neurons.

  13. Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque

    NASA Astrophysics Data System (ADS)

    Davis, T. S.; Parker, R. A.; House, P. A.; Bagley, E.; Wendelken, S.; Normann, R. A.; Greger, B.

    2012-12-01

    Objective. It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. Approach. An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. Main results. The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

  14. Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel.

    PubMed

    Murray, Justin K; Ligutti, Joseph; Liu, Dong; Zou, Anruo; Poppe, Leszek; Li, Hongyan; Andrews, Kristin L; Moyer, Bryan D; McDonough, Stefan I; Favreau, Philippe; Stöcklin, Reto; Miranda, Les P

    2015-03-12

    NaV1.7 is a voltage-gated sodium ion channel implicated by human genetic evidence as a therapeutic target for the treatment of pain. Screening fractionated venom from the tarantula Grammostola porteri led to the identification of a 34-residue peptide, termed GpTx-1, with potent activity on NaV1.7 (IC50 = 10 nM) and promising selectivity against key NaV subtypes (20× and 1000× over NaV1.4 and NaV1.5, respectively). NMR structural analysis of the chemically synthesized three disulfide peptide was consistent with an inhibitory cystine knot motif. Alanine scanning of GpTx-1 revealed that residues Trp(29), Lys(31), and Phe(34) near the C-terminus are critical for potent NaV1.7 antagonist activity. Substitution of Ala for Phe at position 5 conferred 300-fold selectivity against NaV1.4. A structure-guided campaign afforded additive improvements in potency and NaV subtype selectivity, culminating in the design of [Ala5,Phe6,Leu26,Arg28]GpTx-1 with a NaV1.7 IC50 value of 1.6 nM and >1000× selectivity against NaV1.4 and NaV1.5.

  15. Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel.

    PubMed

    Murray, Justin K; Ligutti, Joseph; Liu, Dong; Zou, Anruo; Poppe, Leszek; Li, Hongyan; Andrews, Kristin L; Moyer, Bryan D; McDonough, Stefan I; Favreau, Philippe; Stöcklin, Reto; Miranda, Les P

    2015-03-12

    NaV1.7 is a voltage-gated sodium ion channel implicated by human genetic evidence as a therapeutic target for the treatment of pain. Screening fractionated venom from the tarantula Grammostola porteri led to the identification of a 34-residue peptide, termed GpTx-1, with potent activity on NaV1.7 (IC50 = 10 nM) and promising selectivity against key NaV subtypes (20× and 1000× over NaV1.4 and NaV1.5, respectively). NMR structural analysis of the chemically synthesized three disulfide peptide was consistent with an inhibitory cystine knot motif. Alanine scanning of GpTx-1 revealed that residues Trp(29), Lys(31), and Phe(34) near the C-terminus are critical for potent NaV1.7 antagonist activity. Substitution of Ala for Phe at position 5 conferred 300-fold selectivity against NaV1.4. A structure-guided campaign afforded additive improvements in potency and NaV subtype selectivity, culminating in the design of [Ala5,Phe6,Leu26,Arg28]GpTx-1 with a NaV1.7 IC50 value of 1.6 nM and >1000× selectivity against NaV1.4 and NaV1.5. PMID:25658507

  16. Confirmation of immuno-reactivity of the recombinant major birch pollen allergen Bet v 1a by affinity-CIEF.

    PubMed

    Dullnig, Verena; Weiss, Richard; Amon, Sabine; Rizzi, Andreas; Stutz, Hanno

    2009-07-01

    Affinity-CIEF has been applied to characterize a recombinant product of the major birch pollen allergen Betula verrucosa isoform 1a (Bet v 1a) immuno-chemically. For this purpose mAbs of the IgG-type have been produced in-lab from two murine hybridoma lines, specified as clones 2 and 5.1. Both IgG clones were characterized by SDS-PAGE, MALDI-TOF-MS and CIEF. The purified IgG solutions had to be dialysed against 10 mmol/L phosphate (pH 7.4) to prevent IgG precipitation and to ensure appropriate CIEF separation. Both tested monoclonal IgGs (mIgGs) comprised four constituents covering pI ranges of 6.98-7.09 and 6.78-7.03 for clones 2 and 5.1 with major peaks at pI 7.09 and 7.03, respectively. When increasing amounts of Bet v 1a (pI 4.95) were incubated with 2.0 mumol/L mIgG, novel peaks were progressively induced in a pI range slightly more acidic than the focusing region of mIgGs. These peaks grew on the expense of original mIgG peaks. All pI values were calculated using two pI marker compounds with a repeatability of better than 0.03 units. New peaks represent complexes between Bet v 1a and mIgG either of 1:1 or of 2:1 binding stoichiometry. At a molar ratio of 2:1, saturation of both IgG paratopes with allergen (Ag) molecules was achieved as indicated by unbound Bet v 1a. The current CIEF approach addresses the proof of single epitope integrity in the course of immuno-chemical characterization of Bet v 1a. Contrary to traditional immunoassays, affinity CIEF allows for a distinction and relative quantification of mAbs, Ag-antibody complexes and Ag variants coexisting in one sample. PMID:19621361

  17. Simultaneous VLBA polarimetric observations of the v = {1,2} J = 1-0 and v = 1, J = 2-1 SiO maser emission towards VY CMa II: component-level polarization analysis

    NASA Astrophysics Data System (ADS)

    Richter, L.; Kemball, A.; Jonas, J.

    2016-09-01

    This paper presents a component-level comparison of the polarized v = 1 J = 1-0, v = 2 J = 1-0 and v = 1 J = 2-1 SiO maser emission towards the supergiant star VY CMa at milliarcsecond-scale, as observed using the Very Long Baseline Array at λ = 7 and 3 mm. An earlier paper considered overall maser morphology and constraints on SiO maser excitation and pumping derived from these data. The goal of the current paper is to use the measured polarization properties of individual co-spatial components detected across multiple transitions to provide constraints on several competing theories for the transport of polarized maser emission. This approach minimizes the significant effects of spatial blending. We present several diagnostic tests designed to distinguish key features of competing theoretical models for maser polarization. The number of coincident features is limited by sensitivity however, particularly in the v = 1 J = 2-1 transition at 86 GHz, and deeper observations are needed. Preliminary conclusions based on the current data provide some support for: (i) spin-independent solutions for linear polarization; (ii) the influence of geometry on the distribution of fractional linear polarization with intensity; and, (iii) π/2 rotations in linear polarization position angle arising from transitions across the Van Vleck angle (sin 2θ = 2/3) between the maser line of sight and magnetic field. There is weaker evidence for several enumerated non-Zeeman explanations for circular polarization. The expected 2:1 ratio in circular polarization between J = 1-0 and J = 2-1 predicted by standard Zeeman theory cannot unfortunately be tested conclusively due to insufficient coincident components.

  18. Cell membrane expression of cardiac sodium channel Na(v)1.5 is modulated by alpha-actinin-2 interaction.

    PubMed

    Ziane, Rahima; Huang, Hai; Moghadaszadeh, Behzad; Beggs, Alan H; Levesque, Georges; Chahine, Mohamed

    2010-01-12

    Cardiac sodium channel Na(v)1.5 plays a critical role in heart excitability and conduction. The molecular mechanism that underlies the expression of Na(v)1.5 at the cell membrane is poorly understood. Previous studies demonstrated that cytoskeleton proteins can be involved in the regulation of cell surface expression and localization of several ion channels. We performed a yeast two-hybrid screen to identify Na(v)1.5-associated proteins that may be involved in channel function and expression. We identified alpha-actinin-2 as an interacting partner of the cytoplasmic loop connecting domains III and IV of Na(v)1.5 (Na(v)1.5/LIII-IV). Co-immunoprecipitation and His(6) pull-down assays confirmed the physical association between Na(v)1.5 and alpha-actinin-2 and showed that the spectrin-like repeat domain is essential for binding of alpha-actinin-2 to Na(v)1.5. Patch-clamp studies revealed that the interaction with alpha-actinin-2 increases sodium channel density without changing their gating properties. Consistent with these findings, coexpression of alpha-actinin-2 and Na(v)1.5 in tsA201 cells led to an increase in the level of expression of Na(v)1.5 at the cell membrane as determined by cell surface biotinylation. Lastly, immunostaining experiments showed that alpha-actinin-2 was colocalized with Na(v)1.5 along the Z-lines and in the plasma membrane. Our data suggest that alpha-actinin-2, which is known to regulate the functional expression of the potassium channels, may play a role in anchoring Na(v)1.5 to the membrane by connecting the channel to the actin cytoskeleton network.

  19. Amorphous nanostructuralization in HOPG by 1014 W cm-2 laser

    NASA Astrophysics Data System (ADS)

    NISHIMURA, Yasuhiko; KITAGAWA, Yoneyoshi; MORI, Yoshitaka; ISHII, Katsuhiro; HANAYAMA, Ryohei; AZUMA, Hirozumi; HIOKI, Tatsumi; NISHI, Teppei; MOTOHIRO, Tomoyoshi; KOMEDA, Osamu; SEKINE, Takashi; SATO, Nakahiro; KURITA, Takashi; KAWASHIMA, Toshiyuki; KAN, Hirofumi; SUNAHARA, Atsushi; SENTOKU, Yasuhiko; MIURA, Eisuke

    2016-05-01

    This reports provide an amorphous nanostructuralization technique on the surface modification in Highly Oriented Pyrolytic Graphite (HOPG) by using a femtosecond laser. We showed, for the first time, that the surface of HOPG is changed to the amorphous nanostructuralization graphite by using a femtosecond laser-driven compression technique. Our results also suggest that the HOPG surface is changed until the deeper area from the surface by the laser-driven shock wave. A single shot of a femtosecond laser beam (1.27 ∼ 1.33×1014 Wcm∼2 in intensity, with 2 mm-diameter, and 110 fs in pulse width) is irradiated under the vacuum ambience onto a 2 mm-thick of HOPG. The calculated impact pressures on a sample was 8.3 ∼ 8.7 GPa. Crystal structure in the HOPG were analyzed using a Raman spectroscopy and an X-ray diffraction, those analyzing depth from the surface were 50 nm and 350 μm, respectively.

  20. CAP-1A is a novel linker that binds clathrin and the voltage-gated sodium channel Na(v)1.8.

    PubMed

    Liu, Chuanju; Cummins, Theodore R; Tyrrell, Lynda; Black, Joel A; Waxman, Stephen G; Dib-Hajj, Sulayman D

    2005-04-01

    The voltage-gated sodium channel Na(v)1.8 produces a tetrodotoxin-resistant current and plays a key role in nociception. Annexin II/p11 binds to Na(v)1.8 and facilitates insertion of the channel within the cell membrane. However, the mechanisms responsible for removal of specific channels from the cell membrane have not been studied. We have identified a novel protein, clathrin-associated protein-1A (CAP-1A), which contains distinct domains that bind Na(v)1.8 and clathrin. CAP-1A is abundantly expressed in DRG neurons and colocalizes with Na(v)1.8 and can form a multiprotein complex with Na(v)1.8 and clathrin. Coexpression of CAP-1A and Na(v)1.8 in DRG neurons reduces Na(v)1.8 current density by approximately 50% without affecting the endogenous or recombinant tetrodotoxin-sensitive currents. This effect of CAP-1A is blocked by bafilomycin A1 treatment of transfected DRG neurons. CAP-1A thus is the first example of an adapter protein that links clathrin and a sodium channel and may regulate Na(v)1.8 channel density at the cell surface. PMID:15797711

  1. Phosphorylation of sodium channel Na(v)1.8 by p38 mitogen-activated protein kinase increases current density in dorsal root ganglion neurons.

    PubMed

    Hudmon, Andy; Choi, Jin-Sung; Tyrrell, Lynda; Black, Joel A; Rush, Anthony M; Waxman, Stephen G; Dib-Hajj, Sulayman D

    2008-03-19

    The sensory neuron-specific sodium channel Na(v)1.8 and p38 mitogen-activated protein kinase are potential therapeutic targets within nociceptive dorsal root ganglion (DRG) neurons in inflammatory, and possibly neuropathic, pain. Na(v)1.8 channels within nociceptive DRG neurons contribute most of the inward current underlying the depolarizing phase of action potentials. Nerve injury and inflammation of peripheral tissues cause p38 activation in DRG neurons, a process that may contribute to nociceptive neuron hyperexcitability, which is associated with pain. However, how substrates of activated p38 contribute to DRG neuron hyperexcitability is currently not well understood. We report here, for the first time, that Na(v)1.8 and p38 are colocalized in DRG neurons, that Na(v)1.8 within DRG neurons is a substrate for p38, and that direct phosphorylation of the Na(v)1.8 channel by p38 regulates its function in these neurons. We show that direct phosphorylation of Na(v)1.8 at two p38 phospho-acceptor serine residues on the L1 loop (S551 and S556) causes an increase in Na(v)1.8 current density that is not accompanied by changes in gating properties of the channel. Our study suggests a mechanism by which activated p38 contributes to inflammatory, and possibly neuropathic, pain through a p38-mediated increase of Na(v)1.8 current density. PMID:18354022

  2. Animation of natural scene by virtual eye-movements evokes high precision and low noise in V1 neurons.

    PubMed

    Baudot, Pierre; Levy, Manuel; Marre, Olivier; Monier, Cyril; Pananceau, Marc; Frégnac, Yves

    2013-01-01

    Synaptic noise is thought to be a limiting factor for computational efficiency in the brain. In visual cortex (V1), ongoing activity is present in vivo, and spiking responses to simple stimuli are highly unreliable across trials. Stimulus statistics used to plot receptive fields, however, are quite different from those experienced during natural visuomotor exploration. We recorded V1 neurons intracellularly in the anaesthetized and paralyzed cat and compared their spiking and synaptic responses to full field natural images animated by simulated eye-movements to those evoked by simpler (grating) or higher dimensionality statistics (dense noise). In most cells, natural scene animation was the only condition where high temporal precision (in the 10-20 ms range) was maintained during sparse and reliable activity. At the subthreshold level, irregular but highly reproducible membrane potential dynamics were observed, even during long (several 100 ms) "spike-less" periods. We showed that both the spatial structure of natural scenes and the temporal dynamics of eye-movements increase the signal-to-noise ratio by a non-linear amplification of the signal combined with a reduction of the subthreshold contextual noise. These data support the view that the sparsening and the time precision of the neural code in V1 may depend primarily on three factors: (1) broadband input spectrum: the bandwidth must be rich enough for recruiting optimally the diversity of spatial and time constants during recurrent processing; (2) tight temporal interplay of excitation and inhibition: conductance measurements demonstrate that natural scene statistics narrow selectively the duration of the spiking opportunity window during which the balance between excitation and inhibition changes transiently and reversibly; (3) signal energy in the lower frequency band: a minimal level of power is needed below 10 Hz to reach consistently the spiking threshold, a situation rarely reached with visual dense

  3. Molecular data mining to improve antibody-based detection of Grapevine leafroll-associated virus 1 (GLRaV-1).

    PubMed

    Esteves, Filipa; Teixeira Santos, Margarida; Eiras-Dias, José Eduardo; Fonseca, Filomena

    2013-12-01

    Testing for Grapevine leafroll-associated virus 1 (GLRaV-1) is mandatory in certification schemes of propagation material within the EU. Accurate and reliable diagnostic assays are necessary for implementation of this measure. During routine detection of GLRaV-1, using double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) and reverse transcription (RT) followed by polymerase chain reaction (PCR), evidence was obtained that positive samples could be overlooked by either or both detection methods. With the aim of improving serological detection tools for GLRaV-1, a total of 20 isolates were analyzed and 83 new complete capsid protein (CP) gene sequences were obtained. This set, together with the CP sequences available at GenBank was used for a comprehensive in silico analysis. To obtain a specific antibody able to recognize all known CP variants, conserved regions with suitable antigenicity profile were identified along the deduced CP AA sequences and a 14 AA sequence was chosen for commercial peptide synthesis and immunization. Initially polyclonal antibodies were produced and tested, followed by purification of the respective monospecific antibody and conjugation with alkaline phosphatase or fluorescein isothiocyanate (FITC). These serological tools were tested successfully on all the available positive samples and proved adequate for in situ immunoassay (ISIA). Further testing showed that the monospecific antibody could also be used in tissue print immunoblotting (TPIB), a technique that allows rapid processing of large sample sets, which is highly suitable to implement protocols ensuring that, for each vine analyzed, enough random samples are taken and processed, before certification.

  4. Enhancement of the Two-Dimensional Conduction Electron Zeeman Energy Near v=1 by Optical Dynamic Nuclear Polarization

    SciTech Connect

    Bowers, C.R.; Reno, J.L.; Simmons, J.A.; Vitkalov, S.A.

    1998-11-06

    Enhancement of the Zeeman energy of 2D conduction electrons near v = 1 by optical dynamic nuclear polarization (lINP), as observed by the Overhauser shift of the transport detected electron spin resonance, is measured quantitatively for the first time in GaAs/AIGaAs mukiquantum wells. The NMR signal enhancement is obtained under similar conditions in the same sample, allowing the hyperke coupling constant of 3.7T between between the nuclei and 2D conduction electrons to be measured for the first time. The potential to suppress the Zeeman energy by optical DNP is discussed in the context of its potential influence on Skyrmion formation.

  5. The LBB methodology application results performed on the safety related piping of NPP V-1 in Jaslovske Bohunice

    SciTech Connect

    Kupca, L.; Beno, P.

    1997-04-01

    A broad overview of the leak before break (LBB) application to the Slovakian V-1 nuclear power plant is presented in the paper. LBB was applied to the primary cooling circuit and surge lines of both WWER 440 type units, and also used to assess the integrity of safety related piping in the feed water and main steam systems. Experiments and calculations performed included analyses of stresses, material mechanical properties, corrosion, fatigue damage, stability of heavy component supports, water hammer, and leak rates. A list of analysis results and recommendations are included in the paper.

  6. Experimental and computational evidence for an essential role of NaV1.6 in spike initiation at stretch-sensitive colorectal afferent endings.

    PubMed

    Feng, Bin; Zhu, Yi; La, Jun-Ho; Wills, Zachary P; Gebhart, G F

    2015-04-01

    Stretch-sensitive afferents comprise ∼33% of the pelvic nerve innervation of mouse colorectum, which are activated by colorectal distension and encode visceral nociception. Stretch-sensitive colorectal afferent endings respond tonically to stepped or ramped colorectal stretch, whereas dissociated colorectal dorsal root ganglion neurons generally fail to spike repetitively upon stepped current stimulation. The present study investigated this difference in the neural encoding characteristics between the soma and afferent ending using pharmacological approaches in an in vitro mouse colon-nerve preparation and complementary computational simulations. Immunohistological staining and Western blots revealed the presence of voltage-gated sodium channel (NaV) 1.6 and NaV1.7 at sensory neuronal endings in mouse colorectal tissue. Responses of stretch-sensitive colorectal afferent endings were significantly reduced by targeting NaV1.6 using selective antagonists (μ-conotoxin GIIIa and μ-conotoxin PIIIa) or tetrodotoxin. In contrast, neither selective NaV1.8 (A803467) nor NaV1.7 (ProTX-II) antagonists attenuated afferent responses to stretch. Computational simulation of a colorectal afferent ending that incorporated independent Markov models for NaV1.6 and NaV1.7, respectively, recapitulated the experimental findings, suggesting a necessary role for NaV1.6 in encoding tonic spiking by stretch-sensitive afferents. In addition, computational simulation of a dorsal root ganglion soma showed that, by adding a NaV1.6 conductance, a single-spiking neuron was converted into a tonic spiking one. These results suggest a mechanism/channel to explain the difference in neural encoding characteristics between afferent somata and sensory endings, likely caused by differential expression of ion channels (e.g., NaV1.6) at different parts of the neuron. PMID:25652923

  7. The tetrodotoxin-resistant Na+ channel Na (v)1.8 reduces the potency of local anesthetics in blocking C-fiber nociceptors.

    PubMed

    Kistner, Katrin; Zimmermann, Katharina; Ehnert, Corina; Reeh, Peter W; Leffler, Andreas

    2010-04-01

    The generation of action potentials in nociceptive neurons is accomplished by the tetrodotoxin-resistant (TTXr) Na+ channel Na(v)1.8. Following nerve injury, a redistribution of Na(v)1.8 from dorsal root ganglion (DRG) neurons into peripheral axons contributes to hyperexcitability and possibly to neuropathic pain. Na(v)1.8 has been reported to display a lower sensitivity to block by Na+ channel blockers as compared to TTX-sensitive (TTXs) Na(v) subunits. Furthermore, the antinociceptive efficacy of lidocaine is increased in Na(v)1.8-knockout mice. Here, we asked if Na(v)1.8 expression can reduce the susceptibility of sensory neurons to block by lidocaine. Employing wild-type and Na(v)1.8-knockout mice, we examined C-fibers in the skin-nerve preparation and Na+ currents in DRG neurons by patch-clamp recordings. Deletion of Na(v)1.8 resulted in an enhanced tonic block of Na+ currents in DRG neurons held at -80 mV but not at -140 mV. Accordingly, lower concentrations of lidocaine were required for a conduction block of C-fibers from Na(v)1.8-knockout as compared to wild-type mice. The efficacy of lidocaine on neurons lacking Na(v)1.8 was further increased by cold temperatures, due to a synergistic hyperpolarizing shift of the slow inactivation of TTXs Na+ channels by lidocaine and cooling. Finally, the approximately 90% reduction of TTXr Na+ currents in injured neurons from mice with a peripheral nerve injury was accompanied with an enhanced tonic block by lidocaine. In conclusion, our data demonstrate that the expression of Na(v)1.8 in sensory neurons can confine the antinociceptive efficacy of lidocaine and other Na+ channel blockers employed for pain treatment. PMID:20174994

  8. Aberrant Splicing Promotes Proteasomal Degradation of L-type CaV1.2 Calcium Channels by Competitive Binding for CaVβ Subunits in Cardiac Hypertrophy

    PubMed Central

    Hu, Zhenyu; Wang, Jiong-Wei; Yu, Dejie; Soon, Jia Lin; de Kleijn, Dominique P. V.; Foo, Roger; Liao, Ping; Colecraft, Henry M.; Soong, Tuck Wah

    2016-01-01

    Decreased expression and activity of CaV1.2 calcium channels has been reported in pressure overload-induced cardiac hypertrophy and heart failure. However, the underlying mechanisms remain unknown. Here we identified in rodents a splice variant of CaV1.2 channel, named CaV1.2e21+22, that contained the pair of mutually exclusive exons 21 and 22. This variant was highly expressed in neonatal hearts. The abundance of this variant was gradually increased by 12.5-folds within 14 days of transverse aortic banding that induced cardiac hypertrophy in adult mouse hearts and was also elevated in left ventricles from patients with dilated cardiomyopathy. Although this variant did not conduct Ca2+ ions, it reduced the cell-surface expression of wild-type CaV1.2 channels and consequently decreased the whole-cell Ca2+ influx via the CaV1.2 channels. In addition, the CaV1.2e21+22 variant interacted with CaVβ subunits significantly more than wild-type CaV1.2 channels, and competition of CaVβ subunits by CaV1.2e21+22 consequently enhanced ubiquitination and subsequent proteasomal degradation of the wild-type CaV1.2 channels. Our findings show that the resurgence of a specific neonatal splice variant of CaV1.2 channels in adult heart under stress may contribute to heart failure. PMID:27731386

  9. Experimental and computational evidence for an essential role of NaV1.6 in spike initiation at stretch-sensitive colorectal afferent endings

    PubMed Central

    Zhu, Yi; La, Jun-Ho; Wills, Zachary P.; Gebhart, G. F.

    2015-01-01

    Stretch-sensitive afferents comprise ∼33% of the pelvic nerve innervation of mouse colorectum, which are activated by colorectal distension and encode visceral nociception. Stretch-sensitive colorectal afferent endings respond tonically to stepped or ramped colorectal stretch, whereas dissociated colorectal dorsal root ganglion neurons generally fail to spike repetitively upon stepped current stimulation. The present study investigated this difference in the neural encoding characteristics between the soma and afferent ending using pharmacological approaches in an in vitro mouse colon-nerve preparation and complementary computational simulations. Immunohistological staining and Western blots revealed the presence of voltage-gated sodium channel (NaV) 1.6 and NaV1.7 at sensory neuronal endings in mouse colorectal tissue. Responses of stretch-sensitive colorectal afferent endings were significantly reduced by targeting NaV1.6 using selective antagonists (μ-conotoxin GIIIa and μ-conotoxin PIIIa) or tetrodotoxin. In contrast, neither selective NaV1.8 (A803467) nor NaV1.7 (ProTX-II) antagonists attenuated afferent responses to stretch. Computational simulation of a colorectal afferent ending that incorporated independent Markov models for NaV1.6 and NaV1.7, respectively, recapitulated the experimental findings, suggesting a necessary role for NaV1.6 in encoding tonic spiking by stretch-sensitive afferents. In addition, computational simulation of a dorsal root ganglion soma showed that, by adding a NaV1.6 conductance, a single-spiking neuron was converted into a tonic spiking one. These results suggest a mechanism/channel to explain the difference in neural encoding characteristics between afferent somata and sensory endings, likely caused by differential expression of ion channels (e.g., NaV1.6) at different parts of the neuron. PMID:25652923

  10. CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.

    PubMed

    Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas

    2010-05-01

    Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.

  11. Characterization of the honeybee AmNaV1 channel and tools to assess the toxicity of insecticides

    PubMed Central

    Gosselin-Badaroudine, Pascal; Moreau, Adrien; Delemotte, Lucie; Cens, Thierry; Collet, Claude; Rousset, Matthieu; Charnet, Pierre; Klein, Michael L.; Chahine, Mohamed

    2015-01-01

    Pollination is important for both agriculture and biodiversity. For a significant number of plants, this process is highly, and sometimes exclusively, dependent on the pollination activity of honeybees. The large numbers of honeybee colony losses reported in recent years have been attributed to colony collapse disorder. Various hypotheses, including pesticide overuse, have been suggested to explain the disorder. Using the Xenopus oocytes expression system and two microelectrode voltage-clamp, we report the functional expression and the molecular, biophysical, and pharmacological characterization of the western honeybee’s sodium channel (Apis Mellifera NaV1). The NaV1 channel is the primary target for pyrethroid insecticides in insect pests. We further report that the honeybee’s channel is also sensitive to permethrin and fenvalerate, respectively type I and type II pyrethroid insecticides. Molecular docking of these insecticides revealed a binding site that is similar to sites previously identified in other insects. We describe in vitro and in silico tools that can be used to test chemical compounds. Our findings could be used to assess the risks that current and next generation pesticides pose to honeybee populations. PMID:26202396

  12. Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.

    PubMed

    Pancera, Marie; Shahzad-Ul-Hussan, Syed; Doria-Rose, Nicole A; McLellan, Jason S; Bailer, Robert T; Dai, Kaifan; Loesgen, Sandra; Louder, Mark K; Staupe, Ryan P; Yang, Yongping; Zhang, Baoshan; Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E; Blinn, Julie; Alam, S Munir; Haynes, Barton F; Amin, Mohammed N; Wang, Lai-Xi; Burton, Dennis R; Koff, Wayne C; Nabel, Gary J; Mascola, John R; Bewley, Carole A; Kwong, Peter D

    2013-07-01

    HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1-glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization.

  13. Vasotocin neurons and septal V1a-like receptors potently modulate songbird flocking and responses to novelty.

    PubMed

    Kelly, Aubrey M; Kingsbury, Marcy A; Hoffbuhr, Kristin; Schrock, Sara E; Waxman, Brandon; Kabelik, David; Thompson, Richmond R; Goodson, James L

    2011-06-01

    Previous comparisons of territorial and gregarious finches (family Estrildidae) suggest the hypothesis that arginine vasotocin (VT) neurons in the medial bed nucleus of the stria terminalis (BSTm) and V(1a)-like receptors in the lateral septum (LS) promote flocking behavior. Consistent with this hypothesis, we now show that intraseptal infusions of a V(1a) antagonist in male zebra finches (Taeniopygia guttata) reduce gregariousness (preference for a group of 10 versus 2 conspecific males), but have no effect on the amount of time that subjects spend in close proximity to other birds ("contact time"). The antagonist also produces a profound increase in anxiety-like behavior, as exhibited by an increased latency to feed in a novelty-suppressed feeding test. Bilateral knockdown of VT production in the BSTm using LNA-modified antisense oligonucleotides likewise produces increases in anxiety-like behavior and a potent reduction in gregariousness, relative to subjects receiving scrambled oligonucleotides. The antisense oligonucleotides also produced a modest increase in contact time, irrespective of group size. Together, these combined experiments provide clear evidence that endogenous VT promotes preferences for larger flock sizes, and does so in a manner that is coupled to general anxiolysis. Given that homologous peptide circuitry of the BSTm-LS is found across all tetrapod vertebrate classes, these findings may be predictive for other highly gregarious species. PMID:21295577

  14. Pathology and hematology of the Caribbean spiny lobster experimentally infected with Panulirus argus virus 1 (PaV1).

    PubMed

    Li, Caiwen; Shields, Jeffrey D; Ratzlaff, Robert E; Butler, Mark J

    2008-03-01

    We examined the histopathological and hematological response of the Caribbean spiny lobster to experimentally induced infections with Panulirus argus Virus 1 (PaV1). The fixed phagocytes in the hepatopancreas were the primary sites of PaV1 infection in spiny lobsters. Fixed phagocytes were activated in early infections. However, as the disease progressed, the fixed phagocytes became infected and eventually lysed. Infected cells were subsequently observed in the hepatopancreas, gill, heart, hindgut, glial cells around the ventral nerves, and in the cuticular epidermis and foregut. In advanced infections, spongy connective tissues were heavily infected, as were glial cells around the optic nerves. The structure of the hepatopancreas was significantly altered as the disease progressed. The hemal sinuses among the hepatopancreatic tubules filled with massive amounts of cellular aggregates, including infected circulating hemocytes and spongy connective tissues. Atrophy of the hepatopancreatic tubules occurred in the late stage of viral infection. The virus caused significant decreases in total hemocyte counts and significantly altered several constituents in the hemolymph lysates of diseased lobsters, including: glucose, phosphorus, and triglycerides.

  15. Norcoclaurine Synthase Is a Member of the Pathogenesis-Related 10/Bet v1 Protein Family[W

    PubMed Central

    Lee, Eun-Jeong; Facchini, Peter

    2010-01-01

    Norcoclaurine synthase (NCS) catalyzes the first committed step in the biosynthesis of benzylisoquinoline alkaloids (BIAs). NCS from Thalictrum flavum (Tf NCS), Papaver somniferum (Ps NCS1 and Ps NCS2), and Coptis japonica (Cj PR10A) share substantial identity with pathogen-related 10 (PR10) and Bet v1 proteins, whose functions are not well understood. A distinct enzyme (Cj NCS1) with similarity to 2-oxoglutarate–dependent dioxygenases was suggested as the bona fide NCS in C. japonica. Here, we validate the exclusive role of PR10/Bet v1-type NCS enzymes in BIA metabolism. Immunolocalization of Ps NCS2 revealed its cell type–specific occurrence in phloem sieve elements, which contain all other known BIA biosynthetic enzymes. In opium poppy, NCS transcripts and proteins were abundant in root and stem, but at low levels in leaf and carpel. Silencing of NCS in opium poppy profoundly reduced alkaloid levels compared with controls. Immunoprecipitation of NCS from total protein extracts of T. flavum cells resulted in a nearly complete attenuation of NCS activity. A Ps NCS2–green fluorescent protein fusion introduced by microprojectile bombardment into opium poppy cells initially localized to the endoplasmic reticulum but subsequently sorted to the vacuole. In our hands, Cj NCS1 did not catalyze the formation of (S)-norcoclaurine from dopamine and 4-hydroxyphenylacetaldehyde. PMID:21037103

  16. Characterization of the honeybee AmNaV1 channel and tools to assess the toxicity of insecticides.

    PubMed

    Gosselin-Badaroudine, Pascal; Moreau, Adrien; Delemotte, Lucie; Cens, Thierry; Collet, Claude; Rousset, Matthieu; Charnet, Pierre; Klein, Michael L; Chahine, Mohamed

    2015-07-23

    Pollination is important for both agriculture and biodiversity. For a significant number of plants, this process is highly, and sometimes exclusively, dependent on the pollination activity of honeybees. The large numbers of honeybee colony losses reported in recent years have been attributed to colony collapse disorder. Various hypotheses, including pesticide overuse, have been suggested to explain the disorder. Using the Xenopus oocytes expression system and two microelectrode voltage-clamp, we report the functional expression and the molecular, biophysical, and pharmacological characterization of the western honeybee's sodium channel (Apis Mellifera NaV1). The NaV1 channel is the primary target for pyrethroid insecticides in insect pests. We further report that the honeybee's channel is also sensitive to permethrin and fenvalerate, respectively type I and type II pyrethroid insecticides. Molecular docking of these insecticides revealed a binding site that is similar to sites previously identified in other insects. We describe in vitro and in silico tools that can be used to test chemical compounds. Our findings could be used to assess the risks that current and next generation pesticides pose to honeybee populations.

  17. Areas V1 and V2 show microsaccade-related 3-4-Hz covariation in gamma power and frequency.

    PubMed

    Lowet, E; Roberts, M J; Bosman, C A; Fries, P; De Weerd, P

    2016-05-01

    Neuronal gamma-band synchronization (25-80 Hz) in visual cortex appears sustained and stable during prolonged visual stimulation when investigated with conventional averages across trials. However, recent studies in macaque visual cortex have used single-trial analyses to show that both power and frequency of gamma oscillations exhibit substantial moment-by-moment variation. This has raised the question of whether these apparently random variations might limit the functional role of gamma-band synchronization for neural processing. Here, we studied the moment-by-moment variation in gamma oscillation power and frequency, as well as inter-areal gamma synchronization, by simultaneously recording local field potentials in V1 and V2 of two macaque monkeys. We additionally analyzed electrocorticographic V1 data from a third monkey. Our analyses confirm that gamma-band synchronization is not stationary and sustained but undergoes moment-by-moment variations in power and frequency. However, those variations are neither random and nor a possible obstacle to neural communication. Instead, the gamma power and frequency variations are highly structured, shared between areas and shaped by a microsaccade-related 3-4-Hz theta rhythm. Our findings provide experimental support for the suggestion that cross-frequency coupling might structure and facilitate the information flow between brain regions.

  18. Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex

    PubMed Central

    Poort, Jasper; Self, Matthew W.; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R.

    2016-01-01

    Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure–ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both. We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression. We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current–source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure–ground organization. PMID:27522074

  19. Oestrogen directly inhibits the cardiovascular L-type Ca{sup 2+} channel Ca{sub v}1.2

    SciTech Connect

    Ullrich, Nina D. . E-mail: ullrich@pyl.unibe.ch; Koschak, Alexandra; MacLeod, Kenneth T.

    2007-09-21

    Oestrogen can modify the contractile function of vascular smooth muscle and cardiomyocytes. The negative inotropic actions of oestrogen on the heart and coronary vasculature appear to be mediated by L-type Ca{sup 2+} channel (Ca{sub v}1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits the cardiovascular L-type Ca{sup 2+} current, I {sub CaL}. The effect of oestrogen on I {sub CaL} was measured in Ca{sub v}1.2-transfected HEK-293 cells using the whole-cell patch-clamp technique. The current revealed typical activation and inactivation profiles of nifedipine- and cadmium-sensitive I {sub CaL}. Oestrogen (50 {mu}M) rapidly reduced I {sub CaL} by 50% and shifted voltage-dependent activation and availability to more negative potentials. Furthermore, oestrogen blocked the Ca{sup 2+} channel in a rate-dependent way, exhibiting higher efficiency of block at higher stimulation frequencies. Our data suggest that oestrogen inhibits I {sub CaL} through direct interaction of the steroid with the channel protein.

  20. Whole genomic characterization of a Korean human parechovirus type 1 (HPeV1) identifies recombination events.

    PubMed

    Thoi, Truong Cong; Than, Van Thai; Kim, Wonyong

    2014-12-01

    A human parechovirus (HPeV) strain CAU10-NN was detected from a stool sample of a 2-year-old healthy female infant in South Korea using a metagenomic approach. The CAU10-NN virus was isolated using a cell culture system and its whole genome was analyzed. The RNA genome of the CAU10-NN strain consists of 7,348 nucleotides (nt), excluding a poly(A) tail. A large open reading frame of 6,540 nt that encodes a putative polyprotein precursor of 2,180 amino acids is flanked by a 5'-untranslated region (UTR) of 708 nt and 3'-UTR of 88 nt followed by a poly(A) tail. Phylogenetic analysis shows that the CAU10-NN strain belongs to HPeV1. SimPlot and Bootscan analyses reveal that the virus genome is composed of regions related to corresponding genomic regions of other HPeVs. Recombination analysis indicates that the CAU10-NN strain might be a product of more than one genomic recombination event that occurred among HPeV1, HPeV3, and HPeV4 strains.

  1. A mutation in the V1 end domain of keratin 1 in non-epidermolytic palmar-plantar keratoderma.

    PubMed

    Kimonis, V; DiGiovanna, J J; Yang, J M; Doyle, S Z; Bale, S J; Compton, J G

    1994-12-01

    Mutations in keratin 9 have been found in families with an epidermolytic form of palmar-plantar keratoderma (PPK). In another form of PPK (Unna-Thost type), epidermolysis is not observed histologically. We studied a pedigree with this non-epidermolytic form of PPK. By gene linkage analysis, the type I keratin locus could be excluded but complete linkage with the type II keratin region was found. Sequence analysis identified a single base change in the amino-terminal V1 variable subdomain of keratin 1, which caused a lysine to isoleucine substitution. This non-conservative mutation completely cosegregated with the disease and was not observed in 50 unrelated unaffected individuals. An examination of keratin amino-terminal sequences revealed a previously unreported 22-residue window in the V1 subdomain that is conserved among most type II keratins. The altered lysine is an invariant residue in this conserved sequence. Previously described keratin mutations affect the central regions important for filament assembly and stability, and cause diseases characterized by cellular degeneration or disruption. This is the first disease mutation in a keratin chain variable end region. The observation that it is not associated with epidermolysis supports the concept that the amino-terminal domain of keratins may be involved in supramolecular interactions of keratin filaments rather than stability. Therefore, hyperkeratosis associated with this mutation may be due to perturbations in the interactions of the keratin end domain with other cellular components.

  2. Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16

    SciTech Connect

    Pancera, Marie; Shahzad-ul-Hussan, Syed; Doria-Rose, Nicole A.; McLellan, Jason S.; Bailer, Robert T.; Dai, Kaifan; Loesgen, Sandra; Louder, Mark K.; Staupe, Ryan P.; Yang, Yongping; Zhang, Baoshan; Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E.; Blinn, Julie; Alam, S. Munir; Haynes, Barton F.; Amin, Mohammed N.; Wang, Lai-Xi; Burton, Dennis R.; Koff, Wayne C.; Nabel, Gary J.; Mascola, John R.; Bewley, Carole A; Kwong, Peter D.

    2013-08-05

    HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1–V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1–V2, showing an epitope comprising both high mannose–type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1–glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization.

  3. The role of attention in figure-ground segregation in areas V1 and V4 of the visual cortex.

    PubMed

    Poort, Jasper; Raudies, Florian; Wannig, Aurel; Lamme, Victor A F; Neumann, Heiko; Roelfsema, Pieter R

    2012-07-12

    Our visual system segments images into objects and background. Figure-ground segregation relies on the detection of feature discontinuities that signal boundaries between the figures and the background and on a complementary region-filling process that groups together image regions with similar features. The neuronal mechanisms for these processes are not well understood and it is unknown how they depend on visual attention. We measured neuronal activity in V1 and V4 in a task where monkeys either made an eye movement to texture-defined figures or ignored them. V1 activity predicted the timing and the direction of the saccade if the figures were task relevant. We found that boundary detection is an early process that depends little on attention, whereas region filling occurs later and is facilitated by visual attention, which acts in an object-based manner. Our findings are explained by a model with local, bottom-up computations for boundary detection and feedback processing for region filling. PMID:22794268

  4. Repeated functional convergent effects of NaV1.7 on acid insensitivity in hibernating mammals.

    PubMed

    Liu, Zhen; Wang, Wei; Zhang, Tong-Zuo; Li, Gong-Hua; He, Kai; Huang, Jing-Fei; Jiang, Xue-Long; Murphy, Robert W; Shi, Peng

    2014-02-01

    Hibernating mammals need to be insensitive to acid in order to cope with conditions of high CO2; however, the molecular basis of acid tolerance remains largely unknown. The African naked mole-rat (Heterocephalus glaber) and hibernating mammals share similar environments and physiological features. In the naked mole-rat, acid insensitivity has been shown to be conferred by the functional motif of the sodium ion channel NaV1.7. There is now an opportunity to evaluate acid insensitivity in other taxa. In this study, we tested for functional convergence of NaV1.7 in 71 species of mammals, including 22 species that hibernate. Our analyses revealed a functional convergence of amino acid sequences, which occurred at least six times independently in mammals that hibernate. Evolutionary analyses determined that the convergence results from both parallel and divergent evolution of residues in the functional motif. Our findings not only identify the functional molecules responsible for acid insensitivity in hibernating mammals, but also open new avenues to elucidate the molecular underpinnings of acid insensitivity in mammals.

  5. Targeting Atp6v1c1 Prevents Inflammation and Bone Erosion Caused by Periodontitis and Reveals Its Critical Function in Osteoimmunology

    PubMed Central

    Wang, Lin; Lu, Yun; Li, Qian; Zhu, Zheng; Shao, Jian-Zhong; Chen, Wei

    2015-01-01

    Periodontal disease (Periodontitis) is a serious disease that affects a majority of adult Americans and is associated with other systemic diseases, including diabetes, rheumatoid arthritis, and other inflammatory diseases. While great efforts have been devoted toward understanding the pathogenesis of periodontitis, there remains a pressing need for developing potent therapeutic strategies for targeting this pervasive and destructive disease. In this study, we utilized novel adeno-associated virus (AAV)-mediated Atp6v1c1 knockdown gene therapy to treat bone erosion and inflammatory caused by periodontitis in mouse model. Atp6v1c1 is a subunit of the V-ATPase complex and regulator of the assembly of the V0 and V1 domains of the V-ATPase complex. We demonstrated previously that Atp6v1c1 has an essential function in osteoclast mediated bone resorption. We hypothesized that Atp6v1c1 may be an ideal target to prevent the bone erosion and inflammation caused by periodontitis. To test the hypothesis, we employed AAV RNAi knockdown of Atp6v1c1 gene expression to prevent bone erosion and gingival inflammation simultaneously. We found that lesion-specific injection of AAV-shRNA-Atp6v1c1 into the periodontal disease lesions protected against bone erosion (>85%) and gingival inflammation caused by P. gingivalis W50 infection. AAV-mediated Atp6v1c1 knockdown dramatically reduced osteoclast numbers and inhibited the infiltration of dendritic cells and macrophages in the bacteria-induced inflammatory lesions in periodontitis. Silencing of Atp6v1c1 expression also prevented the expressions of osteoclast-related genes and pro-inflammatory cytokine genes. Our data suggests that AAV-shRNA-Atp6v1c1 treatment can significantly attenuate the bone erosion and inflammation caused by periodontitis, indicating the dual function of AAV-shRNA-Atp6v1c1 as an inhibitor of bone erosion mediated by osteoclasts, and as an inhibitor of inflammation through down-regulation of pro

  6. CaMKII Phosphorylation of Na(V)1.5: Novel in Vitro Sites Identified by Mass Spectrometry and Reduced S516 Phosphorylation in Human Heart Failure.

    PubMed

    Herren, Anthony W; Weber, Darren M; Rigor, Robert R; Margulies, Kenneth B; Phinney, Brett S; Bers, Donald M

    2015-05-01

    The cardiac voltage-gated sodium channel, Na(V)1.5, drives the upstroke of the cardiac action potential and is a critical determinant of myocyte excitability. Recently, calcium (Ca(2+))/calmodulin(CaM)-dependent protein kinase II (CaMKII) has emerged as a critical regulator of Na(V)1.5 function through phosphorylation of multiple residues including S516, T594, and S571, and these phosphorylation events may be important for the genesis of acquired arrhythmias, which occur in heart failure. However, phosphorylation of full-length human Na(V)1.5 has not been systematically analyzed and Na(V)1.5 phosphorylation in human heart failure is incompletely understood. In the present study, we used label-free mass spectrometry to assess phosphorylation of human Na(V)1.5 purified from HEK293 cells with full coverage of phosphorylatable sites and identified 23 sites that were phosphorylated by CaMKII in vitro. We confirmed phosphorylation of S516 and S571 by LC-MS/MS and found a decrease in S516 phosphorylation in human heart failure, using a novel phospho-specific antibody. This work furthers our understanding of the phosphorylation of Na(V)1.5 by CaMKII under normal and disease conditions, provides novel CaMKII target sites for functional validation, and provides the first phospho-proteomic map of full-length human Na(V)1.5.

  7. Mapping the conformational epitope of a neutralizing antibody (AcV1) directed against the AcMNPV GP64 protein

    SciTech Connect

    Zhou Jian; Blissard, Gary W. . E-mail: gwb1@cornell.edu

    2006-09-01

    The envelope glycoprotein GP64 of Autographa californica nucleopolyhedrovirus (AcMNPV) is necessary and sufficient for the acid-induced membrane fusion activity that is required for fusion of the budded virus (BV) envelope and the endosome membrane during virus entry. Infectivity of the budded virus (BV) is neutralized by AcV1, a monoclonal antibody (MAb) directed against GP64. Prior studies indicated that AcV1 recognizes a conformational epitope and does not inhibit virus attachment to the cell, but instead inhibits entry at a step following virus attachment. We found that AcV1 recognition of GP64 was lost upon exposure of GP64 to low pH (pH 4.5) and restored by returning GP64 to pH 6.2. In addition, the AcV1 epitope was lost upon denaturation of GP64 in SDS, but the AcV1 epitope was restored by refolding the protein in the absence of SDS. Using truncated GP64 proteins expressed in insect cells, we mapped the AcV1 epitope to a 24 amino acid region in the central variable domain of GP64. When sequences within the mapped AcV1 epitope were substituted with a c-Myc epitope and the resulting construct was used to replace wt GP64 in recombinant AcMNPV viruses, the modified GP64 protein appeared to function normally. However, an anti-c-Myc monoclonal antibody did not neutralize infectivity of those viruses. Because binding of the c-Myc MAb to the same site in the GP64 sequence did not result in neutralization, these studies suggest that AcV1 neutralization may result from a specific structural constraint caused by AcV1 binding and not simply by steric hindrance caused by antibody binding at this position in GP64.

  8. Frequent occurrence of T cell–mediated late reactions revealed by atopy patch testing with hypoallergenic rBet v 1 fragments

    PubMed Central

    Campana, Raffaela; Moritz, Katharina; Marth, Katharina; Neubauer, Angela; Huber, Hans; Henning, Rainer; Blatt, Katharina; Hoermann, Gregor; Brodie, Tess M.; Kaider, Alexandra; Valent, Peter; Sallusto, Federica; Wöhrl, Stefan; Valenta, Rudolf

    2015-01-01

    Background Late allergic reactions are common in the course of allergen-specific immunotherapy and even occur with allergy vaccines with reduced IgE reactivity. Objective We sought to study atopy patch test (APT) reactions and T-cell responses to the recombinant birch pollen allergen Bet v 1 and recombinant hypoallergenic T-cell epitope–containing Bet v 1 fragments in patients with birch pollen allergy with and without atopic dermatitis (AD). Methods A clinical study was conducted in 15 patients with birch pollen allergy with AD (group 1), 5 patients with birch pollen allergy without AD (group 2), 5 allergic patients without birch pollen allergy (group 3), and 5 nonallergic subjects (group 4) by performing skin prick tests and APTs with rBet v 1 and hypoallergenic rBet v 1 fragments. T-cell, cutaneous lymphocyte antigen (CLA)+ and CCR4+ T-cell and cytokine responses were studied by thymidine uptake, carboxyfluorescein diacetate succinimidyl ester staining, and Luminex technology, respectively. Results rBet v 1 and hypoallergenic rBet v 1 fragments induced APT reactions in not only most of the patients with birch pollen allergy with AD (11/15) but also in most of those without AD (4/5). Patients with birch pollen allergy with AD had higher Bet v 1–specific proliferation of CLA+ and CCR4+ T cells compared with patients with birch pollen allergy without AD. There were no differences in Bet v 1–specific CLA+ and CCR4+ proliferation and cytokine secretion in patients with and without APT reactions. Conclusion Hypoallergenic rBet v 1 fragments induce T cell–dependent late reactions not only in patients with birch pollen allergy with AD but also in those without AD, which can be determined based on APT results but not based on in vitro parameters. PMID:26518092

  9. Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus

    PubMed Central

    Akinfiresoye, Luli R.; Allard, Joanne S.; Lovinger, David M.

    2015-01-01

    Background: We previously reported increased current density through L-type voltage-gated Ca2+ (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown. Methods: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. Results: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. Conclusions: Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis. PMID:25556199

  10. V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1

    PubMed Central

    Morgand, Marion; Bouvin-Pley, Mélanie; Plantier, Jean-Christophe; Moreau, Alain; Alessandri, Elodie; Simon, François; Pace, Craig S.; Pancera, Marie; Ho, David D.; Poignard, Pascal; Bjorkman, Pamela J.; Mouquet, Hugo; Nussenzweig, Michel C.; Kwong, Peter D.; Baty, Daniel; Chames, Patrick; Braibant, Martine

    2016-01-01

    Background: Highly potent broadly neutralizing monoclonal antibodies (bNAbs) have been obtained from individuals infected by HIV-1 group M variants. We analyzed the cross-group neutralization potency of these bNAbs toward non-M primary isolates (PI). Material and Methods: The sensitivity to neutralization was analyzed in a neutralization assay using TZM-bl cells. Twenty-three bNAbs were used, including reagents targeting the CD4-binding site, the N160 glycan-V1/V2 site, the N332 glycan-V3 site, the membrane proximal external region of gp41, and complex epitopes spanning both env subunits. Two bispecific antibodies that combine the inhibitory activity of an anti-CD4 with that of PG9 or PG16 bNAbs were included in the study (PG9-iMab and PG16-iMab). Results: Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O PIs, 1 group N PI, and the group P PI were neutralized by PG9 and/or PG16 or PGT145 at low concentrations (0.04–9.39 μg/mL). None of the non-M PIs was neutralized by the bNAbs targeting other regions at the highest concentration tested, except 10E8 that neutralized weakly 2 group N PIs and 35O22 that neutralized 1 group O PI. The bispecific bNAbs neutralized very efficiently all the non-M PIs with IC50 below 1 μg/mL, except 2 group O strains. Conclusion: The N160 glycan-V1/V2 site is the most conserved neutralizing site within the 4 groups of HIV-1. This makes it an interesting target for the development of HIV vaccine immunogens. The corresponding bNAbs may be useful for immunotherapeutic strategies in patients infected by non-M variants. PMID:26413851

  11. A Selective V1A Receptor Agonist, Selepressin, Is Superior to Arginine Vasopressin and to Norepinephrine in Ovine Septic Shock*

    PubMed Central

    He, Xinrong; Su, Fuhong; Taccone, Fabio Silvio; Laporte, Régent; Kjølbye, Anne Louise; Zhang, Jing; Xie, Keliang; Moussa, Mouhamed Djahoum; Reinheimer, Torsten Michael

    2016-01-01

    Objective: Selective vasopressin V1A receptor agonists may have advantages over arginine vasopressin in the treatment of septic shock. We compared the effects of selepressin, a selective V1A receptor agonist, arginine vasopressin, and norepinephrine on hemodynamics, organ function, and survival in an ovine septic shock model. Design: Randomized animal study. Setting: University hospital animal research laboratory. Subjects: Forty-six adult female sheep. Interventions: Fecal peritonitis was induced in the anesthetized, mechanically ventilated, fluid-resuscitated sheep, and they were randomized in two successive phases. Three late-intervention groups (each n = 6) received IV selepressin (1 pmol/kg/min), arginine vasopressin (0.25 pmol [0.1 mU]/kg/min), or norepinephrine (3 nmol [0.5 μg]/kg/min) when mean arterial pressure remained less than 70 mm Hg despite fluid challenge; study drugs were thereafter titrated to keep mean arterial pressure at 70–80 mm Hg. Three early-intervention groups (each n = 7) received selepressin, arginine vasopressin, or norepinephrine at the same initial infusion rates as for the late intervention, but already when mean arterial pressure had decreased by 10% from baseline; doses were then titrated as for the late intervention. A control group (n = 7) received saline. All animals were observed until death or for a maximum of 30 hours. Measurements and Main Results: In addition to hemodynamic and organ function assessment, plasma interleukin-6 and nitrite/nitrate levels were measured. In the late-intervention groups, selepressin delayed the decrease in mean arterial pressure and was associated with lower lung wet/dry weight ratios than in the other two groups. In the early-intervention groups, selepressin maintained mean arterial pressure and cardiac index better than arginine vasopressin or norepinephrine, slowed the increase in blood lactate levels, and was associated with less lung edema, lower cumulative fluid balance, and lower

  12. Low temperature and magnetic field behaviour of the (Cr{sub 84}Re{sub 16}){sub 89.6}V{sub 10.4} alloy

    SciTech Connect

    Jacobs, B. S. Sheppard, C. J.; Prinsloo, A. R. E.; Lodya, L.

    2014-05-07

    Measurements of the temperature (T) dependence of the magnetic susceptibility (χ) and electrical resistance (R) on an antiferromagnetic (AFM) (Cr{sub 84}Re{sub 16}){sub 89.6}V{sub 10.4} alloy are reported in order to probe the existence of quantum critical behaviour (QCB) utilizing static magnetic fields (H) as a tuning parameter. The results indicate that an increase in H suppresses T{sub N} in such a way that it varies exponentially with increasing H. R(T) measurements show evidence of possible superconducting (SC) behaviour below 1 K at H = 0 T. These results therefore indicate the coexistence of the AFM and SC phases in the (Cr{sub 84}Re{sub 16}){sub 89.6}V{sub 10.4} alloy.

  13. MOSSPATCH V1

    2001-01-31

    This program reduces the data from one-dimensional laser beam arrays from kSA MOS program, k-Space Associates, Ann Arbor, MI. Initial data is recorded without headers in 38 columns, with one row of data per acquisition per laser beam tracked. MOSS Patch can merge several data files together, filters out beam overlaps, and reduces the data. The final data is graphed and saved in a tab-delimited column format with headers that can be plotted in anymore » graphing software.« less

  14. Radio frequency interference survey over the 1.0-10.4 GHz frequency range at the Goldstone-Venus Development Station

    NASA Technical Reports Server (NTRS)

    Gulkis, S.; Olsen, E. T.; Klein, M. J.; Jackson, E. B.

    1989-01-01

    The results of a low sensitivity Radio Frequency Interference (RFI) survey carried out at the Venus Station of the Goldstone Communications Complex are reported. The data cover the spectral range from 1 GHz to 10.4 GHz with a 10-kHz instantaneous bandwidth. Frequency and power levels were observed using a sweep-frequency spectrum analyzer connected to a 1-m diameter antenna pointed at zenith. The survey was conducted from February 16, 1987 through February 24, 1987.

  15. The adenovirus E3-10.4K/14.5K complex mediates loss of cell surface Fas (CD95) and resistance to Fas-induced apoptosis.

    PubMed Central

    Shisler, J; Yang, C; Walter, B; Ware, C F; Gooding, L R

    1997-01-01

    Cytotoxic T cells use Fas (CD95), a member of the tumor necrosis factor (TNF) receptor superfamily, to eliminate virus-infected cells by activation of the apoptotic pathway for cell death. The adenovirus E3 region encodes several proteins that modify immune defenses, including TNF-dependent cell death, which may allow this virus to establish a persistent infection. Here we show that, as an early event during infection, the adenovirus E3-10.4K/14.5K complex selectively induces loss of Fas surface expression and blocks Fas-induced apoptosis of virus-infected cells. Loss of surface Fas occurs within the first 4 h postinfection and is not due to decreased production of Fas protein. The decrease in surface Fas is distinct from the 10.4K/14.5K-mediated loss of the epidermal growth factor receptor on the same cells, because intracellular stores of Fas are not affected. Further, 10.4K/14.5K, which was previously shown to protect against TNF cytolysis, does not induce a loss of TNF receptor, indicating that this complex mediates more than one function to block host defense mechanisms. These results suggest yet another mechanism by which adenovirus modulates host cytotoxic responses that may contribute to persistent infection by human adenoviruses. PMID:9343182

  16. Attention-Induced Variance and Noise Correlation Reduction in Macaque V1 Is Mediated by NMDA Receptors

    PubMed Central

    Herrero, Jose L.; Gieselmann, Marc A.; Sanayei, Mehdi; Thiele, Alexander

    2013-01-01

    Summary Attention improves perception by affecting different aspects of the neuronal code. It enhances firing rates, it reduces firing rate variability and noise correlations of neurons, and it alters the strength of oscillatory activity. Attention-induced rate enhancement in striate cortex requires cholinergic mechanisms. The neuropharmacological mechanisms responsible for attention-induced variance and noise correlation reduction or those supporting changes in oscillatory activity are unknown. We show that ionotropic glutamatergic receptor activation is required for attention-induced rate variance, noise correlation, and LFP gamma power reduction in macaque V1, but not for attention-induced rate modulations. NMDA receptors mediate attention-induced variance reduction and attention-induced noise correlation reduction. Our results demonstrate that attention improves sensory processing by a variety of mechanisms that are dissociable at the receptor level. PMID:23719166

  17. Characteristics of a granular electronic system in Heusler-type Fe2+xV1-xAl.

    PubMed

    Naka, T; Sato, K; Taguchi, M; Shirakawa, N; Nakane, T; Ishikawa, F; Yamada, Yuh; Takaesu, Y; Nakama, T; Matsushita, A

    2013-07-10

    We report comprehensive measurements of the magnetic, transport, and thermal properties of the Heusler-type compound Fe2+xV1-xAl, with x values near the ferromagnetic quantum critical point, xc ∼ 0.05. At T ∼ 60 K, a prominent Schottky-like anomaly appeared in the specific heat; this anomaly was correlated with a smaller pseudo-gap formation in magnetic susceptibility, magnetoresistance, and thermoelectric power. Furthermore, a magnetic anomaly observed in the magnetic susceptibility and resistivity at T ∼ 4 K was suppressed significantly by applying a magnetic field. A magnetically inhomogeneous phase arose below T ∼ 60 K, which appeared to consist of ferromagnetic and paramagnetic clusters.

  18. Ideals generated by traces in the algebra of symplectic reflections {H_{1,{v_{1,}}{v_2}}}( {{I_2}( {2m} )} )

    NASA Astrophysics Data System (ADS)

    Konstein, S. E.; Tyutin, I. V.

    2016-05-01

    The associative algebra of symplectic reflections H: = {H_{1,{v_{1,}}{v_2}}}( {{I_2}( {2m} )} ) based on the group generated by the root system I 2(2m) depends on two parameters, ν 1 and ν 2. For each value of these parameters, the algebra admits an m-dimensional space of traces. A trace tr is said to be degenerate if the corresponding symmetric bilinear form B tr( x, y) = tr( xy) is degenerate. We find all values of the parameters ν 1 and ν 2 for which the space of traces contains degenerate traces and the algebra H consequently has a two-sided ideal. It turns out that a linear combination of degenerate traces is also a degenerate trace. For the ν 1 and ν 2 values corresponding to degenerate traces, we find the dimensions of the space of degenerate traces.

  19. High-throughput measurements of thermochromic behavior in V(1-x)Nb(x)O(2) combinatorial thin film libraries.

    PubMed

    Barron, S C; Gorham, J M; Patel, M P; Green, M L

    2014-10-13

    We describe a high-throughput characterization of near-infrared thermochromism in V1-xNbxO2 combinatorial thin film libraries. The oxide thin film library was prepared with a VO2 crystal structure and a continuous gradient in composition with Nb concentrations in the range of less than 1% to 45%. The thermochromic phase transition from monoclinic to tetragonal was characterized by the accompanying change in near-infrared reflectance. With increasing Nb substitution, the transition temperature was depressed from 65 to 35 °C, as desirable for smart window applications. However, the magnitude of the reflectance change across the thermochromic transition was also reduced with increasing Nb film content. Data collection, handling, and analysis supporting thermochromic characterization were fully automated to achieve high throughput. Using this system, in 14 h, temperature-dependent infrared reflectances were measured at 165 arbitrary locations on a thin film combinatorial library; these measurements were analyzed for thermochromic transitions in minutes.

  20. Nonlinearity of two-photon Ca2+ imaging yields distorted measurements of tuning for V1 neuronal populations.

    PubMed

    Nauhaus, Ian; Nielsen, Kristina J; Callaway, Edward M

    2012-02-01

    We studied the relative accuracy of drifting gratings and noise stimuli for functionally characterizing neural populations using two-photon calcium imaging. Calcium imaging has the potential to distort measurements due to nonlinearity in the conversion from spikes to observed fluorescence. We demonstrate a dramatic impact of fluorescence saturation on functional measurements in ferret V1 by showing that responses to drifting gratings strongly violate contrast invariance of orientation tuning, a fundamental property of the spike rates. The observed relationship is consistent with saturation that clips the high-contrast tuning curve peaks by ∼40%. The nonlinearity was also apparent in mouse V1 responses to drifting gratings, but not as strong as in the ferret. Contrast invariance holds, however, for tuning curves measured with a randomized grating stimulus. This finding is consistent with prior work showing that the linear portion of a linear-nonlinear system can be recovered with reverse correlation. Furthermore, we demonstrate that a noise stimulus is more effective at keeping spike rates in the linear operating regime of a saturating nonlinearity, which both maximizes signal-to-noise ratios and simplifies the recovery of fast spike dynamics from slow calcium transients. Finally, we uncover spatiotemporal receptive fields by removing the nonlinearity and slow calcium transient from a model of fluorescence generation, which allowed us to observe dynamic sharpening of orientation tuning. We conclude that for two-photon recordings it is imperative that one considers the nonlinear distortion when designing stimuli and interpreting results, especially in sensory areas, species, or cell types with high firing rates. PMID:22114159

  1. Dynamic causal modelling of eye movements during pursuit: Confirming precision-encoding in V1 using MEG

    PubMed Central

    Adams, Rick A.; Bauer, Markus; Pinotsis, Dimitris; Friston, Karl J.

    2016-01-01

    This paper shows that it is possible to estimate the subjective precision (inverse variance) of Bayesian beliefs during oculomotor pursuit. Subjects viewed a sinusoidal target, with or without random fluctuations in its motion. Eye trajectories and magnetoencephalographic (MEG) data were recorded concurrently. The target was periodically occluded, such that its reappearance caused a visual evoked response field (ERF). Dynamic causal modelling (DCM) was used to fit models of eye trajectories and the ERFs. The DCM for pursuit was based on predictive coding and active inference, and predicts subjects' eye movements based on their (subjective) Bayesian beliefs about target (and eye) motion. The precisions of these hierarchical beliefs can be inferred from behavioural (pursuit) data. The DCM for MEG data used an established biophysical model of neuronal activity that includes parameters for the gain of superficial pyramidal cells, which is thought to encode precision at the neuronal level. Previous studies (using DCM of pursuit data) suggest that noisy target motion increases subjective precision at the sensory level: i.e., subjects attend more to the target's sensory attributes. We compared (noisy motion-induced) changes in the synaptic gain based on the modelling of MEG data to changes in subjective precision estimated using the pursuit data. We demonstrate that imprecise target motion increases the gain of superficial pyramidal cells in V1 (across subjects). Furthermore, increases in sensory precision – inferred by our behavioural DCM – correlate with the increase in gain in V1, across subjects. This is a step towards a fully integrated model of brain computations, cortical responses and behaviour that may provide a useful clinical tool in conditions like schizophrenia. PMID:26921713

  2. Measurement of vibrational energy transfer of OH (A2S+,v'=1?0) in low-pressure flames

    NASA Astrophysics Data System (ADS)

    Hartlieb, A. T.; Markus, D.; Kreutner, W.; Kohse-Höinghaus, K.

    1997-07-01

    Vibrational energy transfer (VET) and electronic quenching of OH (A2D+) was measured in a low-pressure H2/O2 flame for three rotational levels of OH (v'=1). Rate coefficients for collisions with H2O and N2 were determined. At 1600 K, kVET (N2) is (in 10-11 cm3s-1) 10.1DŽ, 6.1ǃ.8, and 3.8ǃ.3 for N'=0, 5, and 13, respectively. The kVET (H2O) is <1.1ǃ.8. The kQ (N2) is <2.4NJ for both vibrational levels. The kQ (H2O) in v'=1 is 59.1Lj.5, 54.7Lj.4, and 54.9Lj.6 for N'=0, 5, and 13, respectively, and, determined indirectly, 74.6ᆞ.4, 70.6ᆞ.3, and 63.4lj.3 for N'=0, 5, and 13 in v'=0. A multi-level model of OH population dynamics, which is being developed for the quantitative simulation of experimental LIF spectra, was extended to include VET. It was attempted to simulate state-to-state-specific VET coefficients for N2 collisions. From these simulations it appears that angular momentum conservation does not determine the N dependence of the vibrational relaxation step.

  3. Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of NaV1.7 with Efficacy in Rodent Pain Models.

    PubMed

    Focken, Thilo; Liu, Shifeng; Chahal, Navjot; Dauphinais, Maxim; Grimwood, Michael E; Chowdhury, Sultan; Hemeon, Ivan; Bichler, Paul; Bogucki, David; Waldbrook, Matthew; Bankar, Girish; Sojo, Luis E; Young, Clint; Lin, Sophia; Shuart, Noah; Kwan, Rainbow; Pang, Jodie; Chang, Jae H; Safina, Brian S; Sutherlin, Daniel P; Johnson, J P; Dehnhardt, Christoph M; Mansour, Tarek S; Oballa, Renata M; Cohen, Charles J; Robinette, C Lee

    2016-03-10

    We report on a novel series of aryl sulfonamides that act as nanomolar potent, isoform-selective inhibitors of the human sodium channel hNaV1.7. The optimization of these inhibitors is described. We aimed to improve potency against hNaV1.7 while minimizing off-target safety concerns and generated compound 3. This agent displayed significant analgesic effects in rodent models of acute and inflammatory pain and demonstrated that binding to the voltage sensor domain 4 site of NaV1.7 leads to an analgesic effect in vivo. Our findings corroborate the importance of hNaV1.7 as a drug target for the treatment of pain.

  4. Seven novel modulators of the analgesic target NaV 1.7 uncovered using a high-throughput venom-based discovery approach

    PubMed Central

    Klint, Julie K; Smith, Jennifer J; Vetter, Irina; Rupasinghe, Darshani B; Er, Sing Yan; Senff, Sebastian; Herzig, Volker; Mobli, Mehdi; Lewis, Richard J; Bosmans, Frank; King, Glenn F

    2015-01-01

    Background and Purpose Chronic pain is a serious worldwide health issue, with current analgesics having limited efficacy and dose-limiting side effects. Humans with loss-of-function mutations in the voltage-gated sodium channel NaV1.7 (hNaV1.7) are indifferent to pain, making hNaV1.7 a promising target for analgesic development. Since spider venoms are replete with NaV channel modulators, we examined their potential as a source of hNaV1.7 inhibitors. Experimental Approach We developed a high-throughput fluorescent-based assay to screen spider venoms against hNaV1.7 and isolate ‘hit’ peptides. To examine the binding site of these peptides, we constructed a panel of chimeric channels in which the S3b-S4 paddle motif from each voltage sensor domain of hNaV1.7 was transplanted into the homotetrameric KV2.1 channel. Key Results We screened 205 spider venoms and found that 40% contain at least one inhibitor of hNaV1.7. By deconvoluting ‘hit’ venoms, we discovered seven novel members of the NaSpTx family 1. One of these peptides, Hd1a (peptide μ-TRTX-Hd1a from venom of the spider Haplopelma doriae), inhibited hNaV1.7 with a high level of selectivity over all other subtypes, except hNaV1.1. We showed that Hd1a is a gating modifier that inhibits hNaV1.7 by interacting with the S3b-S4 paddle motif in channel domain II. The structure of Hd1a, determined using heteronuclear NMR, contains an inhibitor cystine knot motif that is likely to confer high levels of chemical, thermal and biological stability. Conclusion and Implications Our data indicate that spider venoms are a rich natural source of hNaV1.7 inhibitors that might be useful leads for the development of novel analgesics. PMID:25754331

  5. Mechanisms of a human skeletal myotonia produced by mutation in the C-terminus of NaV1.4: is Ca2+ regulation defective?

    PubMed

    Biswas, Subrata; DiSilvestre, Deborah A; Dong, Peihong; Tomaselli, Gordon F

    2013-01-01

    Mutations in the cytoplasmic tail (CT) of voltage gated sodium channels cause a spectrum of inherited diseases of cellular excitability, yet to date only one mutation in the CT of the human skeletal muscle voltage gated sodium channel (hNaV1.4F1705I) has been linked to cold aggravated myotonia. The functional effects of altered regulation of hNaV1.4F1705I are incompletely understood. The location of the hNaV1.4F1705I in the CT prompted us to examine the role of Ca(2+) and calmodulin (CaM) regulation in the manifestations of myotonia. To study Na channel related mechanisms of myotonia we exploited the differences in rat and human NaV1.4 channel regulation by Ca(2+) and CaM. hNaV1.4F1705I inactivation gating is Ca(2+)-sensitive compared to wild type hNaV1.4 which is Ca(2+) insensitive and the mutant channel exhibits a depolarizing shift of the V1/2 of inactivation with CaM over expression. In contrast the same mutation in the rNaV1.4 channel background (rNaV1.4F1698I) eliminates Ca(2+) sensitivity of gating without affecting the CaM over expression induced hyperpolarizing shift in steady-state inactivation. The differences in the Ca(2+) sensitivity of gating between wild type and mutant human and rat NaV1.4 channels are in part mediated by a divergence in the amino acid sequence in the EF hand like (EFL) region of the CT. Thus the composition of the EFL region contributes to the species differences in Ca(2+)/CaM regulation of the mutant channels that produce myotonia. The myotonia mutation F1705I slows INa decay in a Ca(2+)-sensitive fashion. The combination of the altered voltage dependence and kinetics of INa decay contribute to the myotonic phenotype and may involve the Ca(2+)-sensing apparatus in the CT of NaV1.4. PMID:24324661

  6. Properties of wild-type and fluorescent protein-tagged mouse tetrodotoxin-resistant sodium channel (Na V 1.8) heterologously expressed in rat sympathetic neurons.

    PubMed

    Schofield, Geoffrey G; Puhl, Henry L; Ikeda, Stephen R

    2008-04-01

    The tetrodotoxin (TTX)-resistant Na(+) current arising from Na(V)1.8-containing channels participates in nociceptive pathways but is difficult to functionally express in traditional heterologous systems. Here, we show that injection of cDNA encoding mouse Na(V)1.8 into the nuclei of rat superior cervical ganglion (SCG) neurons results in TTX-resistant Na(+) currents with amplitudes equal to or exceeding the currents arising from natively expressing channels of mouse dorsal root ganglion (DRG) neurons. The activation and inactivation properties of the heterologously expressed Na(V)1.8 Na(+) channels were similar but not identical to native TTX-resistant channels. Most notably, the half-activation potential of the heterologously expressed Na(V)1.8 channels was shifted about 10 mV toward more depolarized potentials. Fusion of fluorescent proteins to the N- or C-termini of Na(V)1.8 did not substantially affect functional expression in SCG neurons. Unexpectedly, fluorescence was not concentrated at the plasma membrane but found throughout the interior of the neuron in a granular pattern. A similar expression pattern was observed in nodose ganglion neurons expressing the tagged channels. In contrast, expression of tagged Na(V)1.8 in HeLa cells revealed a fluorescence pattern consistent with sequestration in the endoplasmic reticulum, thus providing a basis for poor functional expression in clonal cell lines. Our results establish SCG neurons as a favorable surrogate for the expression and study of molecularly defined Na(V)1.8-containing channels. The data also indicate that unidentified factors may be required for the efficient functional expression of Na(V)1.8 with a biophysical phenotype identical to that found in sensory neurons. PMID:18272876

  7. Small interfering RNA-mediated selective knockdown of Na(V)1.8 tetrodotoxin-resistant sodium channel reverses mechanical allodynia in neuropathic rats.

    PubMed

    Dong, X-W; Goregoaker, S; Engler, H; Zhou, X; Mark, L; Crona, J; Terry, R; Hunter, J; Priestley, T

    2007-05-11

    The biophysical properties of a tetrodotoxin resistant (TTXr) sodium channel, Na(V)1.8, and its restricted expression to the peripheral sensory neurons suggest that blocking this channel might have therapeutic potential in various pain states and may offer improved tolerability compared with existing sodium channel blockers. However, the role of Na(V)1.8 in nociception cannot be tested using a traditional pharmacological approach with small molecules because currently available sodium channel blockers do not distinguish between sodium channel subtypes. We sought to determine whether small interfering RNAs (siRNAs) might be capable of achieving the desired selectivity. Using Northern blot analysis and membrane potential measurement, several siRNAs were identified that were capable of a highly-selective attenuation of Na(V)1.8 message as well as functional expression in clonal ND7/23 cells which were stably transfected with the rat Na(V)1.8 gene. Functional knockdown of the channel was confirmed using whole-cell voltage-clamp electrophysiology. One of the siRNA probes showing a robust knockdown of Na(V)1.8 current was evaluated for in vivo efficacy in reversing an established tactile allodynia in the rat chronic constriction nerve-injury (CCI) model. The siRNA, which was delivered to lumbar dorsal root ganglia (DRG) via an indwelling epidural cannula, caused a significant reduction of Na(V)1.8 mRNA expression in lumbar 4 and 5 (L4-L5) DRG neurons and consequently reversed mechanical allodynia in CCI rats. We conclude that silencing of Na(V)1.8 channel using a siRNA approach is capable of producing pain relief in the CCI model and further support a role for Na(V)1.8 in pathological sensory dysfunction. PMID:17367951

  8. The primary circuit materials properties results analysis performed on archive material used in NPP V-1 and Kola NPP Units 1 and 2

    SciTech Connect

    Kupca, L.; Beno, P.

    1997-04-01

    A very brief summary is provided of a primary circuit piping material properties analysis. The analysis was performed for the Bohunice V-1 reactor and the Kola-1 and -2 reactors. Assessment was performed on Bohunice V-1 archive materials and primary piping material cut from the Kola units after 100,000 hours of operation. Main research program tasks included analysis of mechanical properties, corrosion stability, and microstructural properties. Analysis results are not provided.

  9. μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve

    PubMed Central

    Wilson, Michael J.; Yoshikami, Doju; Azam, Layla; Gajewiak, Joanna; Olivera, Baldomero M.; Bulaj, Grzegorz; Zhang, Min-Min

    2011-01-01

    Voltage-gated sodium channels (VGSCs) are important for action potentials. There are seven major isoforms of the pore-forming and gate-bearing α-subunit (NaV1) of VGSCs in mammalian neurons, and a given neuron can express more than one isoform. Five of the neuronal isoforms, NaV1.1, 1.2, 1.3, 1.6, and 1.7, are exquisitely sensitive to tetrodotoxin (TTX), and a functional differentiation of these presents a serious challenge. Here, we examined a panel of 11 μ-conopeptides for their ability to block rodent NaV1.1 through 1.8 expressed in Xenopus oocytes. Although none blocked NaV1.8, a TTX-resistant isoform, the resulting “activity matrix” revealed that the panel could readily discriminate between the members of all pair-wise combinations of the tested isoforms. To examine the identities of endogenous VGSCs, a subset of the panel was tested on A- and C-compound action potentials recorded from isolated preparations of rat sciatic nerve. The results show that the major subtypes in the corresponding A- and C-fibers were NaV1.6 and 1.7, respectively. Ruled out as major players in both fiber types were NaV1.1, 1.2, and 1.3. These results are consistent with immunohistochemical findings of others. To our awareness this is the first report describing a qualitative pharmacological survey of TTX-sensitive NaV1 isoforms responsible for propagating action potentials in peripheral nerve. The panel of μ-conopeptides should be useful in identifying the functional contributions of NaV1 isoforms in other preparations. PMID:21652775

  10. The yptV1 gene encodes a small G-protein in the green alga Volvox carteri: gene structure and properties of the gene product.

    PubMed

    Fabry, S; Nass, N; Huber, H; Palme, K; Jaenicke, L; Schmitt, R

    1992-09-10

    Small G-proteins encoded by ras-like genes are ubiquitous in eukaryotic cells. These G-proteins are believed to play a role in central processes, such as signal transduction, cell differentiation and membrane vesicle transport. By screening genomic and cDNA libraries of the colonial alga, Volvox carteri f. nagariensis, with ypt DNA probes from Zea mays, we have identified the first member of a ypt gene family, yptV1, within a green alga. The 1538-bp yptV1 gene of V. carteri consists of nine exons and eight introns and has three potential polyadenylation sites 210, 420 and 500 bp downstream from the UGA stop codon. The derived 203-amino-acid polypeptide, YptV1, exhibits 81% similarity with Ypt1 from mouse, with the corresponding genes sharing four identical intron positions. Recombinant YptV1 (reYptV1) produced in Escherichia coli retains the ability to bind GTP after SDS-PAGE and immobilization on nitrocellulose. Immunological studies using polyclonal antibodies against reYptV1 indicate that the protein is present in the membrane fraction of a V. carteri extract and is expressed throughout the whole life-cycle of the alga. Similar to other Ras-like proteins, YptV1 contains two conserved C-terminal cysteine residues suggesting post-translational modification(s), such as isoprenylation or palmitoylation, required for membrane anchoring. The presumptive role of YptV1 in cytoplasmic vesicle transport is briefly discussed. PMID:1511889

  11. Arginine vasotocin V1a2 receptor and GnRH-I co-localize in preoptic neurons of the sex changing grouper, Epinephelus adscensionis.

    PubMed

    Kline, Richard J; Holt, G Joan; Khan, Izhar A

    2016-01-01

    The arginine vasotocin/vasopressin (AVT/AVP) and gonadotropin releasing hormone (GnRH) systems are known to control sexual behaviors and reproduction, respectively, in different vertebrate groups. However, a direct functional connection between these two neuroendocrine systems has not been demonstrated for any vertebrate species. Therefore, the objective of this research was to test the hypothesis that AVT acts on the GnRH system via an AVT V1a receptor in a sex changing grouper species, the rock hind, Epinephelus adscensionis. AVT V1a2 receptors were co-localized with GnRH-I on neurons in the preoptic anterior hypothalamus identifying a structural linkage between the AVT system and GnRH-I. Transcripts for avt, gnrh-I, and two AVT receptor subtypes (v1a1 and v1a2) were isolated and characterized for E. adscensionis and their expression was measured in males and females by q-RT-PCR. Translation of V1a-type cDNA sequences revealed two distinct forms of the AVT V1a receptor in E. adscensionis brain similar to those reported for other species. The observation of significantly higher gnrh-I mRNA in the POA+H of rock hind males as compared to females suggests differential regulation of the gnrh-I transcripts in the two sexes of this protogynous species. In male E. adscensionis, but not in females, a negative relationship was seen between plasma 11-ketotestosterone (11-KT) and the v1a1 receptor mRNA levels in the POA+H, while a positive trend was observed between 11-KT and v1a2 receptor mRNA levels, indicating that these receptor forms may be differentially regulated. PMID:26361870

  12. Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models.

    PubMed

    Yang, Shilong; Xiao, Yao; Kang, Di; Liu, Jie; Li, Yuan; Undheim, Eivind A B; Klint, Julie K; Rong, Mingqiang; Lai, Ren; King, Glenn F

    2013-10-22

    Loss-of-function mutations in the human voltage-gated sodium channel NaV1.7 result in a congenital indifference to pain. Selective inhibitors of NaV1.7 are therefore likely to be powerful analgesics for treating a broad range of pain conditions. Herein we describe the identification of µ-SLPTX-Ssm6a, a unique 46-residue peptide from centipede venom that potently inhibits NaV1.7 with an IC50 of ∼25 nM. µ-SLPTX-Ssm6a has more than 150-fold selectivity for NaV1.7 over all other human NaV subtypes, with the exception of NaV1.2, for which the selectivity is 32-fold. µ-SLPTX-Ssm6a contains three disulfide bonds with a unique connectivity pattern, and it has no significant sequence homology with any previously characterized peptide or protein. µ-SLPTX-Ssm6a proved to be a more potent analgesic than morphine in a rodent model of chemical-induced pain, and it was equipotent with morphine in rodent models of thermal and acid-induced pain. This study establishes µ-SPTX-Ssm6a as a promising lead molecule for the development of novel analgesics targeting NaV1.7, which might be suitable for treating a wide range of human pain pathologies.

  13. Toward Precise Interpretation of DEER-Based Distance Distributions: Insights from Structural Characterization of V1 Spin-Labeled Side Chains.

    PubMed

    Balo, Aidin R; Feyrer, Hannes; Ernst, Oliver P

    2016-09-20

    Pulsed electron paramagnetic resonance experiments can measure individual distances between two spin-labeled side chains in proteins in the range of ∼1.5-8 nm. However, the flexibility of traditional spin-labeled side chains leads to diffuse spin density loci and thus distance distributions with relatively broad peaks, thereby complicating the interpretation of protein conformational states. Here we analyzed the spin-labeled V1 side chain, which is internally anchored and hence less flexible. Crystal structures of V1-labeled T4 lysozyme constructs carrying the V1 side chain on α-helical segments suggest that V1 side chains adopt only a few discrete rotamers. In most cases, only one rotamer is observed at a given site, explaining the frequently observed narrow distance distribution for doubly V1-labeled proteins. We used the present data to derive guidelines that may allow distance interpretation of other V1-labeled proteins for higher-precision structural modeling. PMID:27532325

  14. Orientation-Cue Invariant Population Responses to Contrast-Modulated and Phase-Reversed Contour Stimuli in Macaque V1 and V2

    PubMed Central

    An, Xu; Gong, Hongliang; Yin, Jiapeng; Wang, Xiaochun; Pan, Yanxia; Zhang, Xian; Lu, Yiliang; Yang, Yupeng; Toth, Zoltan; Schiessl, Ingo; McLoughlin, Niall; Wang, Wei

    2014-01-01

    Visual scenes can be readily decomposed into a variety of oriented components, the processing of which is vital for object segregation and recognition. In primate V1 and V2, most neurons have small spatio-temporal receptive fields responding selectively to oriented luminance contours (first order), while only a subgroup of neurons signal non-luminance defined contours (second order). So how is the orientation of second-order contours represented at the population level in macaque V1 and V2? Here we compared the population responses in macaque V1 and V2 to two types of second-order contour stimuli generated either by modulation of contrast or phase reversal with those to first-order contour stimuli. Using intrinsic signal optical imaging, we found that the orientation of second-order contour stimuli was represented invariantly in the orientation columns of both macaque V1 and V2. A physiologically constrained spatio-temporal energy model of V1 and V2 neuronal populations could reproduce all the recorded population responses. These findings suggest that, at the population level, the primate early visual system processes the orientation of second-order contours initially through a linear spatio-temporal filter mechanism. Our results of population responses to different second-order contour stimuli support the idea that the orientation maps in primate V1 and V2 can be described as a spatial-temporal energy map. PMID:25188576

  15. Divergent biophysical properties, gating mechanisms, and possible functions of the two skeletal muscle CaV1.1 calcium channel splice variants

    PubMed Central

    Tuluc, Petronel; Flucher, Bernhard E.

    2014-01-01

    Voltage-gated calcium channels are multi-subunit protein complexes that specifically allow calcium ions to enter the cell in response to membrane depolarization. But, for many years it seemed that the skeletal muscle calcium channel CaV1.1 is the exception. The classical splice variant CaV1.1a activates slowly, has a very small current amplitude and poor voltage sensitivity. In fact adult muscle fibers work perfectly well even in the absence of calcium influx. Recently a new splice variant of the skeletal muscle calcium channel CaV1.1e has been characterized. The lack of the 19 amino acid exon 29 in this splice variant results in a rapidly activating calcium channel with high current amplitude and good voltage sensitivity. CaV1.1e is the dominant channel in embryonic muscle, where the expression of this high calcium-conducting CaV1.1 isoform readily explains developmental processes depending on L-type calcium currents. Moreover, the availability of these two structurally similar but functionally distinct channel variants facilitates the analysis of the molecular mechanisms underlying the unique current properties of the classical CaV1.1a channel. PMID:22057633

  16. Sustained inhibition of the NaV1.7 sodium channel by engineered dimers of the domain II binding peptide GpTx-1.

    PubMed

    Murray, Justin K; Biswas, Kaustav; Holder, J Ryan; Zou, Anruo; Ligutti, Joseph; Liu, Dong; Poppe, Leszek; Andrews, Kristin L; Lin, Fen-Fen; Meng, Shi-Yuan; Moyer, Bryan D; McDonough, Stefan I; Miranda, Les P

    2015-11-01

    Many efforts are underway to develop selective inhibitors of the voltage-gated sodium channel NaV1.7 as new analgesics. Thus far, however, in vitro selectivity has proved difficult for small molecules, and peptides generally lack appropriate pharmacokinetic properties. We previously identified the NaV1.7 inhibitory peptide GpTx-1 from tarantula venom and optimized its potency and selectivity via structure-guided analoging. To further understand GpTx-1 binding to NaV1.7, we have mapped the binding site to transmembrane segments 1-4 of the second pseudosubunit internal repeat (commonly referred to as Site 4) using NaV1.5/NaV1.7 chimeric protein constructs. We also report that select GpTx-1 amino acid residues apparently not contacting NaV1.7 can be derivatized with a hydrophilic polymer without adversely affecting peptide potency. Homodimerization of GpTx-1 with a bifunctional polyethylene glycol (PEG) linker resulted in a compound with increased potency and a significantly reduced off-rate, demonstrating the ability to modulate the function and properties of GpTx-1 by linking to additional molecules. PMID:26112439

  17. Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models.

    PubMed

    Yang, Shilong; Xiao, Yao; Kang, Di; Liu, Jie; Li, Yuan; Undheim, Eivind A B; Klint, Julie K; Rong, Mingqiang; Lai, Ren; King, Glenn F

    2013-10-22

    Loss-of-function mutations in the human voltage-gated sodium channel NaV1.7 result in a congenital indifference to pain. Selective inhibitors of NaV1.7 are therefore likely to be powerful analgesics for treating a broad range of pain conditions. Herein we describe the identification of µ-SLPTX-Ssm6a, a unique 46-residue peptide from centipede venom that potently inhibits NaV1.7 with an IC50 of ∼25 nM. µ-SLPTX-Ssm6a has more than 150-fold selectivity for NaV1.7 over all other human NaV subtypes, with the exception of NaV1.2, for which the selectivity is 32-fold. µ-SLPTX-Ssm6a contains three disulfide bonds with a unique connectivity pattern, and it has no significant sequence homology with any previously characterized peptide or protein. µ-SLPTX-Ssm6a proved to be a more potent analgesic than morphine in a rodent model of chemical-induced pain, and it was equipotent with morphine in rodent models of thermal and acid-induced pain. This study establishes µ-SPTX-Ssm6a as a promising lead molecule for the development of novel analgesics targeting NaV1.7, which might be suitable for treating a wide range of human pain pathologies. PMID:24082113

  18. MP-V1 from the Venom of Social Wasp Vespula vulgaris Is a de Novo Type of Mastoparan that Displays Superior Antimicrobial Activities.

    PubMed

    Kim, Yangseon; Son, Minky; Noh, Eun-Young; Kim, Soonok; Kim, Changmu; Yeo, Joo-Hong; Park, Chanin; Lee, Keun Woo; Bang, Woo Young

    2016-01-01

    Mastoparans from the venom of social wasps have attracted considerable attention as effective antibiotic candidates. In this study, mastoparan V1 (MP-V1) from Vespula vulgaris was first disclosed to have a peptide amino acid sequence distinct from typical mastoparans and its biochemical properties and antimicrobial effects were compared with those of typical mastoparans MP-L, -X(V) and -B. Circular dichroism (CD) spectroscopy revealed that MP-V1 and -X(V) form more stable α-helical conformations in lipid membrane-like environments than MP-L and -B. In parallel, these two also showed more effective antimicrobial activities against the pathogens than did MP-L and -B. Although MP-V1 had a less stable α-helical conformation than MP-X(V), it showed stronger antimicrobial effects against Streptococcus mutans and Salmonella enterica than MP-X(V). In the meantime, analysis of hemolytic activity revealed a range of doses (~50 μM) that exhibited little potent cytotoxicity on human erythrocytes. Finally, the atypical MP-V1 peptide amino acid sequence provided important clues to understanding its antimicrobial mechanism from a structural perspective. Therefore, it has been concluded that MP-V1 is a de novo type of mastoparan with superior antimicrobial activities against both pathogenic bacteria and fungi, which may be useful in developing multipurpose antimicrobial drugs against infectious diseases. PMID:27104500

  19. β-Adrenergic–regulated phosphorylation of the skeletal muscle CaV1.1 channel in the fight-or-flight response

    PubMed Central

    Emrick, Michelle A.; Sadilek, Martin; Konoki, Keiichi; Catterall, William A.

    2010-01-01

    CaV1 channels initiate excitation–contraction coupling in skeletal and cardiac muscle. During the fight-or-flight response, epinephrine released by the adrenal medulla and norepinephrine released from sympathetic nerves increase muscle contractility by activation of the β-adrenergic receptor/cAMP-dependent protein kinase pathway and up-regulation of CaV1 channels in skeletal and cardiac muscle. Although the physiological mechanism of this pathway is well defined, the molecular mechanism and the sites of protein phosphorylation required for CaV1 channel regulation are unknown. To identify the regulatory sites of phosphorylation under physiologically relevant conditions, CaV1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac CaV1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that CaV1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas CaV1.1-T1579 is a substrate for casein kinase 2. Treatment of rabbits with isoproterenol to activate β-adrenergic receptors increased phosphorylation of S1575 in skeletal muscle CaV1.1 channels in vivo, and treatment with propranolol to inhibit β-adrenergic receptors reduced phosphorylation. As S1575 and T1579 in CaV1.1 channels and their homologs in CaV1.2 channels are located at a key regulatory interface between the distal and proximal C-terminal domains, it is likely that phosphorylation of these sites in skeletal and cardiac muscle is directly involved in calcium channel regulation in response to the sympathetic nervous system in the fight-or-flight response. PMID:20937870

  20. Beta-adrenergic-regulated phosphorylation of the skeletal muscle Ca(V)1.1 channel in the fight-or-flight response.

    PubMed

    Emrick, Michelle A; Sadilek, Martin; Konoki, Keiichi; Catterall, William A

    2010-10-26

    Ca(V)1 channels initiate excitation-contraction coupling in skeletal and cardiac muscle. During the fight-or-flight response, epinephrine released by the adrenal medulla and norepinephrine released from sympathetic nerves increase muscle contractility by activation of the β-adrenergic receptor/cAMP-dependent protein kinase pathway and up-regulation of Ca(V)1 channels in skeletal and cardiac muscle. Although the physiological mechanism of this pathway is well defined, the molecular mechanism and the sites of protein phosphorylation required for Ca(V)1 channel regulation are unknown. To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2. Treatment of rabbits with isoproterenol to activate β-adrenergic receptors increased phosphorylation of S1575 in skeletal muscle Ca(V)1.1 channels in vivo, and treatment with propranolol to inhibit β-adrenergic receptors reduced phosphorylation. As S1575 and T1579 in Ca(V)1.1 channels and their homologs in Ca(V)1.2 channels are located at a key regulatory interface between the distal and proximal C-terminal domains, it is likely that phosphorylation of these sites in skeletal and cardiac muscle is directly involved in calcium channel regulation in response to the sympathetic nervous system in the fight-or-flight response.

  1. ESAT-6 (EsxA) and TB10.4 (EsxH) based vaccines for pre- and post-exposure tuberculosis vaccination.

    PubMed

    Hoang, Truc; Aagaard, Claus; Dietrich, Jes; Cassidy, Joseph P; Dolganov, Gregory; Schoolnik, Gary K; Lundberg, Carina Vingsbo; Agger, Else Marie; Andersen, Peter

    2013-01-01

    The ESX systems from Mycobacterium tuberculosis are responsible for the secretion of highly immunogenic proteins of key importance for bacterial survival and growth. The two prototypic proteins, ESAT-6 (EsxA from ESX-1) and TB10.4 (EsxH from ESX-3) share a lot of characteristics regarding genome organization, size, antigenic properties, and vaccine potential but the two molecules clearly have very different roles in bacterial physiology. To further investigate the role of ESAT-6 and TB10.4 as preventive and post-exposure tuberculosis vaccines, we evaluated four different fusion-protein vaccines; H1, H4, H56 and H28, that differ only in these two components. We found that all of these vaccines give rise to protection in a conventional prophylactic vaccination model. In contrast, only the ESAT-6-containing vaccines resulted in significant protection against reactivation, when administered post-exposure. This difference in post-exposure activity did not correlate with a difference in gene expression during infection or a differential magnitude or quality of the vaccine-specific CD4 T cells induced by ESAT-6 versus TB10.4-containing vaccines. The post-exposure effect of the ESAT-6 based vaccines was found to be influenced by the infectious load at the time-point of vaccination and was abolished in chronically infected animals with high bacterial loads at the onset of vaccination. Our data demonstrate that there are specific requirements for the immune system to target an already established tuberculosis infection and that ESAT-6 has a unique potential in post-exposure vaccination strategies.

  2. On the Effects on Cortical Spontaneous Activity of the Symmetries of the Network of Pinwheels in Visual Area V1.

    PubMed

    Veltz, Romain; Chossat, Pascal; Faugeras, Olivier

    2015-12-01

    This paper challenges and extends earlier seminal work. We consider the problem of describing mathematically the spontaneous activity of V1 by combining several important experimental observations including (1) the organization of the visual cortex into a spatially periodic network of hypercolumns structured around pinwheels, (2) the difference between short-range and long-range intracortical connections, the first ones being rather isotropic and producing naturally doubly periodic patterns by Turing mechanisms, the second one being patchy, and (3) the fact that the Turing patterns spontaneously produced by the short-range connections and the network of pinwheels have similar periods. By analyzing the PO maps, we are able to classify all possible singular points (the pinwheels) as having symmetries described by a small subset of the wallpaper groups. We then propose a description of the spontaneous activity of V1 using a classical voltage-based neural field model that features isotropic short-range connectivities modulated by non-isotropic long-range connectivities. A key observation is that, with only short-range connections and because the problem has full translational invariance in this case, a spontaneous doubly periodic pattern generates a 2-torus in a suitable functional space which persists as a flow-invariant manifold under small perturbations, for example when turning on the long-range connections. Through a complete analysis of the symmetries of the resulting neural field equation and motivated by a numerical investigation of the bifurcations of their solutions, we conclude that the branches of solutions which are stable over an extended range of parameters are those that correspond to patterns with an hexagonal (or nearly hexagonal) symmetry. The question of which patterns persist when turning on the long-range connections is answered by (1) analyzing the remaining symmetries on the perturbed torus and (2) combining this information with the Poincar

  3. Aircraft routing with minimal climate impact: the REACT4C climate cost function modelling approach (V1.0)

    NASA Astrophysics Data System (ADS)

    Grewe, V.; Frömming, C.; Matthes, S.; Brinkop, S.; Ponater, M.; Dietmüller, S.; Jöckel, P.; Garny, H.; Tsati, E.; Dahlmann, K.; Søvde, O. A.; Fuglestvedt, J.; Berntsen, T. K.; Shine, K. P.; Irvine, E. A.; Champougny, T.; Hullah, P.

    2014-01-01

    In addition to CO2, the climate impact of aviation is strongly influenced by non-CO2 emissions, such as nitrogen oxides, influencing ozone and methane, and water vapour, which can lead to the formation of persistent contrails in ice-supersaturated regions. Because these non-CO2 emission effects are characterised by a short lifetime, their climate impact largely depends on emission location and time; that is to say, emissions in certain locations (or times) can lead to a greater climate impact (even on the global average) than the same emission in other locations (or times). Avoiding these climate-sensitive regions might thus be beneficial to climate. Here, we describe a modelling chain for investigating this climate impact mitigation option. This modelling chain forms a multi-step modelling approach, starting with the simulation of the fate of emissions released at a certain location and time (time-region grid points). This is performed with the chemistry-climate model EMAC, extended via the two submodels AIRTRAC (V1.0) and CONTRAIL (V1.0), which describe the contribution of emissions to the composition of the atmosphere and to contrail formation, respectively. The impact of emissions from the large number of time-region grid points is efficiently calculated by applying a Lagrangian scheme. EMAC also includes the calculation of radiative impacts, which are, in a second step, the input to climate metric formulas describing the global climate impact of the emission at each time-region grid point. The result of the modelling chain comprises a four-dimensional data set in space and time, which we call climate cost functions and which describes the global climate impact of an emission at each grid point and each point in time. In a third step, these climate cost functions are used in an air traffic simulator (SAAM) coupled to an emission tool (AEM) to optimise aircraft trajectories for the North Atlantic region. Here, we describe the details of this new modelling

  4. Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia.

    PubMed

    Xie, Wenrui; Strong, Judith A; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

    2013-08-01

    Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain after local inflammation of the rat lumbar sensory ganglia. In normal dorsal root ganglion (DRG), quantitative polymerase chain reaction showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6 immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8 because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7 because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain and that some pain conditions may be mediated primarily by myelinated A fiber sensory neurons. PMID:23622763

  5. Point mutations at the local anesthetic receptor site modulate the state-dependent block of rat Na v1.4 sodium channels by pyrazoline-type insecticides.

    PubMed

    Silver, Kristopher S; Soderlund, David M

    2007-05-01

    Pyrazoline-type insecticides (PTIs) selectively block sodium channels at membrane potentials that promote slow sodium channel inactivation and are proposed to interact with a site that overlaps the local anesthetic (LA) receptor site. Mutagenesis studies identified two amino acid residues in the S6 segment of homology domain IV (Phe-1579 and Tyr-1586 in the rat Na(v)1.4 sodium channel) as principal elements of the LA receptor. To test the hypothesis that PTIs bind to the LA receptor, we constructed mutated Na(v)1.4/F1579A and Na(v)1.4/Y1586A cDNAs, expressed native and mutated channels in Xenopus oocytes, and examined the effects of these mutations on channel block by three PTIs (indoxacarb, its bioactivation product DCJW, and RH3421) by two-electrode voltage clamp. DCJW and RH3421 had no effect on Na(v)1.4 channels held at -120mV but caused a slowly developing block upon depolarization to -30mV. Estimated IC(50) values following 15min of exposure were 1 and 4muM for DCJW and RH3421, respectively. Indoxacarb failed to block Na(v)1.4 channels under all experimental conditions. Sensitivity to block by DCJW and RH3421 at -30mV was significantly reduced in Na(v)1.4/F1579A channels, a finding that is consistent with the impact of this mutation on drug binding. In contrast to its effect on drug binding, the Y1586A mutation increased the sensitivity of Na(v)1.4 channels held at -30mV to all three compounds, conferring modest sensitivity to indoxacarb and increasing sensitivity to DCJW and RH3421 by 58- and 16-fold, respectively. These results provide direct evidence for the action of PTIs at the LA receptor.

  6. Diencephalic and septal structures containing the avian vasotocin receptor (V1aR) involved in the regulation of food intake in chickens, Gallus gallus.

    PubMed

    Nagarajan, Gurueswar; Jurkevich, Alexander; Kang, Seong W; Kuenzel, Wayne J

    2016-10-01

    Recently, it was found that the avian central vasotocin receptor (V1aR) is associated with the regulation of food intake. To identify V1aR-containing brain structures regulating food intake, a selective V1aR antagonist SR-49059 that induced food intake was administrated intracerebroventricularly in male chickens followed by detection of brain structures using FOS immunoreactivity. Particularly, the hypothalamic core region of the paraventricular nucleus, lateral hypothalamic area, dorsomedial hypothalamic nucleus, a subnucleus of the central extended amygdalar complex [dorsolateral bed nucleus of the stria terminalis], medial septal nucleus and caudal brainstem [nucleus of the solitary tract] showed significantly increased FOS-ir cells. On the other hand, the supraoptic nucleus of the preoptic area and the nucleus of the hippocampal commissure of the septum showed suppressed FOS immunoreactivity in the V1aR antagonist treatment group. Further investigation revealed that neuronal activity of arginine vasotocin (AVT-ir) magnocellular neurons in the supraoptic nucleus, preoptic periventricular nucleus, paraventricular nucleus and ventral periventricular hypothalamic nucleus and most likely corticotropin releasing hormone (CRH-ir) neurons in the nucleus of the hippocampal commissure were reduced following the antagonist treatment. Dual immunofluorescence labeling results showed that perikarya of AVT-ir magnocellular neurons in the preoptic area and hypothalamus were colabeled with V1aR. Within the nucleus of the hippocampal commissure, CRH-ir neurons were shown in close contact with V1aR-ir glial cells. Results of the present study suggest that the V1aR plays a role in the regulation of food intake by modulating neurons that synthesize and release anorectic neuropeptides in the avian brain. PMID:27317836

  7. Subunit positioning and stator filament stiffness in regulation and power transmission in the V1 motor of the Manduca sexta V-ATPase.

    PubMed

    Muench, Stephen P; Scheres, Sjors H W; Huss, Markus; Phillips, Clair; Vitavska, Olga; Wieczorek, Helmut; Trinick, John; Harrison, Michael A

    2014-01-23

    The vacuolar H(+)-ATPase (V-ATPase) is an ATP-driven proton pump essential to the function of eukaryotic cells. Its cytoplasmic V1 domain is an ATPase, normally coupled to membrane-bound proton pump Vo via a rotary mechanism. How these asymmetric motors are coupled remains poorly understood. Low energy status can trigger release of V1 from the membrane and curtail ATP hydrolysis. To investigate the molecular basis for these processes, we have carried out cryo-electron microscopy three-dimensional reconstruction of deactivated V1 from Manduca sexta. In the resulting model, three peripheral stalks that are parts of the mechanical stator of the V-ATPase are clearly resolved as unsupported filaments in the same conformations as in the holoenzyme. They are likely therefore to have inherent stiffness consistent with a role as flexible rods in buffering elastic power transmission between the domains of the V-ATPase. Inactivated V1 adopted a homogeneous resting state with one open active site adjacent to the stator filament normally linked to the H subunit. Although present at 1:1 stoichiometry with V1, both recombinant subunit C reconstituted with V1 and its endogenous subunit H were poorly resolved in three-dimensional reconstructions, suggesting structural heterogeneity in the region at the base of V1 that could indicate positional variability. If the position of H can vary, existing mechanistic models of deactivation in which it binds to and locks the axle of the V-ATPase rotary motor would need to be re-evaluated. PMID:24075871

  8. Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

    PubMed

    Wsol, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L; Cudnoch-Jedrzejewska, A

    2014-01-01

    The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.

  9. Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

    2013-01-01

    Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models, and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain following local inflammation of the rat lumbar sensory ganglia. In normal DRG, quantitative PCR showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6′ immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C-cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8, because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7, because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain, and that some pain conditions may be primarily mediated by myelinated A-fiber sensory neurons. PMID:23622763

  10. Modeling of 10 GeV-1 TeV laser-plasma accelerators using Lorentz boosted simulations

    SciTech Connect

    Vay, J. -L.; Geddes, C. G. R.; Esarey, E.; Schroeder, C. B.; Leemans, W. P.; Cormier-Michel, E.; Grote, D. P.

    2011-12-13

    We study modeling of laser-plasma wakefield accelerators in an optimal frame of reference [J.-L. Vay, Phys. Rev. Lett. 98, 130405 (2007)] that allows direct and efficient full-scale modeling of deeply depleted and beam loaded laser-plasma stages of 10 GeV-1 TeV (parameters not computationally accessible otherwise). This verifies the scaling of plasmaaccelerators to very high energies and accurately models the laser evolution and the accelerated electron beam transverse dynamics and energy spread. Over 4, 5, and 6 orders of magnitude speedup is achieved for the modeling of 10 GeV, 100 GeV, and 1 TeV class stages, respectively. Agreement at the percentage level is demonstrated between simulations using different frames of reference for a 0.1 GeV class stage. In addition, obtaining these speedups and levels of accuracy was permitted by solutions for handling data input (in particular, particle and laser beams injection) and output in a relativistically boosted frame of reference, as well as mitigation of a high-frequency instability that otherwise limits effectiveness.

  11. Kinematics and subpopulations' structure definition of blue fox (Alopex lagopus) sperm motility using the ISAS® V1 CASA system.

    PubMed

    Soler, C; García, A; Contell, J; Segervall, J; Sancho, M

    2014-08-01

    Over recent years, technological advances have brought innovation in assisted reproduction to the agriculture. Fox species are of great economical interest in some countries, but their semen characteristics have not been studied enough. To advance the knowledge of function of fox spermatozoa, five samples were obtained by masturbation, in the breeding season. Kinetic analysis was performed using ISAS® v1 system. Usual kinematic parameters (VCL, VSL, VAP, LIN, STR, WOB, ALH and BCF) were considered. To establish the standardization for the analysis of samples, the minimum number of cells to analyse and the minimum number of fields to capture were defined. In the second step, the presence of subpopulations in blue fox semen was analysed. The minimum number of cells to test was 30, because kinematic parameters remained constant along the groups of analysis. Also, the effectiveness of ISAS® D4C20 counting chamber was studied, showing that the first five squares presented equivalent results, while in the squares six and seven, the kinematic parameters showed a reduction in all of them, but not in the concentration or motility percentage. Kinematic variables were grouped into two principal components (PC). A linear movement characterized PC1, while PC2 showed an oscillatory movement. Three subpopulations were found, varying in structure among different animals.

  12. High-resolution land surface fluxes from satellite and reanalysis data (HOLAPS v1.0): evaluation and uncertainty assessment

    NASA Astrophysics Data System (ADS)

    Loew, Alexander; Peng, Jian; Borsche, Michael

    2016-07-01

    Surface water and energy fluxes are essential components of the Earth system. Surface latent heat fluxes provide major energy input to the atmosphere. Despite the importance of these fluxes, state-of-the-art data sets of surface energy and water fluxes largely differ. The present paper introduces a new framework for the estimation of surface energy and water fluxes at the land surface, which allows for temporally and spatially high-resolved flux estimates at the quasi-global scale (50° S, 50° N) (High resOlution Land Atmosphere Parameters from Space - HOLAPS v1.0). The framework makes use of existing long-term satellite and reanalysis data records and ensures internally consistent estimates of the surface radiation and water fluxes. The manuscript introduces the technical details of the developed framework and provides results of a comprehensive sensitivity and evaluation study. Overall the root mean square difference (RMSD) was found to be 51.2 (30.7) W m-2 for hourly (daily) latent heat flux, and 84 (38) W m-2 for sensible heat flux when compared against 48 FLUXNET stations worldwide. The largest uncertainties of latent heat flux and net radiation were found to result from uncertainties in the solar radiation flux obtained from satellite data products.

  13. Push-Pull Receptive Field Organization and Synaptic Depression: Mechanisms for Reliably Encoding Naturalistic Stimuli in V1

    PubMed Central

    Kremkow, Jens; Perrinet, Laurent U.; Monier, Cyril; Alonso, Jose-Manuel; Aertsen, Ad; Frégnac, Yves; Masson, Guillaume S.

    2016-01-01

    Neurons in the primary visual cortex are known for responding vigorously but with high variability to classical stimuli such as drifting bars or gratings. By contrast, natural scenes are encoded more efficiently by sparse and temporal precise spiking responses. We used a conductance-based model of the visual system in higher mammals to investigate how two specific features of the thalamo-cortical pathway, namely push-pull receptive field organization and fast synaptic depression, can contribute to this contextual reshaping of V1 responses. By comparing cortical dynamics evoked respectively by natural vs. artificial stimuli in a comprehensive parametric space analysis, we demonstrate that the reliability and sparseness of the spiking responses during natural vision is not a mere consequence of the increased bandwidth in the sensory input spectrum. Rather, it results from the combined impacts of fast synaptic depression and push-pull inhibition, the later acting for natural scenes as a form of “effective” feed-forward inhibition as demonstrated in other sensory systems. Thus, the combination of feedforward-like inhibition with fast thalamo-cortical synaptic depression by simple cells receiving a direct structured input from thalamus composes a generic computational mechanism for generating a sparse and reliable encoding of natural sensory events. PMID:27242445

  14. The elevated-temperature mechanical behavior of as-cast and wrought Ti-6Al-4V-1B

    SciTech Connect

    Chen, Wei; Boehlert, C. J.; Howe, Jane Y; Payzant, E Andrew

    2011-01-01

    This work studied the effect of processing on the elevated-temperature [728 K (455 C)] fatigue deformation behavior of Ti-6Al-4V-1B for maximum applied stresses between 300 to 700 MPa (R = 0.1, 5 Hz). The alloy was evaluated in the as-cast form as well as in three wrought forms: cast-and-extruded, powder metallurgy (PM) rolled, and PM extruded. Processing caused significant differences in the microstructure, which in turn impacted the fatigue properties. The PM-extruded material exhibited a fine equiaxed {alpha} + {beta} microstructure and the greatest fatigue resistance among all the studied materials. The {beta}-phase field extrusion followed by cooling resulted in a strong {alpha}-phase texture in which the basal plane was predominately oriented perpendicular to the extrusion axis. The TiB whiskers were also aligned in the extrusion direction. The {alpha}-phase texture in the extrusions resulted in tensile-strength anisotropy. The tensile strength in the transverse orientation was lower than that in the longitudinal orientation, but the strength in the transverse orientation remained greater than that for the as-cast Ti-6Al-4V. The ratcheting behavior during fatigue is also discussed.

  15. PPD v1.0--an integrated, web-accessible database of experimentally determined protein pKa values.

    PubMed

    Toseland, Christopher P; McSparron, Helen; Davies, Matthew N; Flower, Darren R

    2006-01-01

    The Protein pK(a) Database (PPD) v1.0 provides a compendium of protein residue-specific ionization equilibria (pK(a) values), as collated from the primary literature, in the form of a web-accessible postgreSQL relational database. Ionizable residues play key roles in the molecular mechanisms that underlie many biological phenomena, including protein folding and enzyme catalysis. The PPD serves as a general protein pK(a) archive and as a source of data that allows for the development and improvement of pK(a) prediction systems. The database is accessed through an HTML interface, which offers two fast, efficient search methods: an amino acid-based query and a Basic Local Alignment Search Tool search. Entries also give details of experimental techniques and links to other key databases, such as National Center for Biotechnology Information and the Protein Data Bank, providing the user with considerable background information. The database can be found at the following URL: http://www.jenner.ac.uk/PPD. PMID:16381845

  16. The topographical arrangement of cutoff spatial frequencies across lower and upper visual fields in mouse V1.

    PubMed

    Zhang, Xian; An, Xu; Liu, Hanxiao; Peng, Jing; Cai, Shanshan; Wang, Wei; Lin, Da-Ting; Yang, Yupeng

    2015-01-01

    The visual response to spatial frequency (SF), a characteristic of spatial structure across position in space, is of particular importance for animal survival. A natural challenge for rodents is to detect predators as early as possible while foraging. Whether neurons in mouse primary visual cortex (V1) are functionally organized to meet this challenge remains unclear. Combining intrinsic signal optical imaging and single-unit recording, we found that the cutoff SF was much greater for neurons whose receptive fields were located above the mouse. Specifically, we discovered that the cutoff SF increased in a gradient that was positively correlated with the elevation in the visual field. This organization was present at eye opening and persisted through adulthood. Dark rearing delayed the maturation of the cutoff SF globally, but had little impact on the topographical organization of the cutoff SF, suggesting that this regional distribution is innately determined. This form of cortical organization of different SFs may benefit the mouse for detection of airborne threats in the natural environment.

  17. Push-Pull Receptive Field Organization and Synaptic Depression: Mechanisms for Reliably Encoding Naturalistic Stimuli in V1.

    PubMed

    Kremkow, Jens; Perrinet, Laurent U; Monier, Cyril; Alonso, Jose-Manuel; Aertsen, Ad; Frégnac, Yves; Masson, Guillaume S

    2016-01-01

    Neurons in the primary visual cortex are known for responding vigorously but with high variability to classical stimuli such as drifting bars or gratings. By contrast, natural scenes are encoded more efficiently by sparse and temporal precise spiking responses. We used a conductance-based model of the visual system in higher mammals to investigate how two specific features of the thalamo-cortical pathway, namely push-pull receptive field organization and fast synaptic depression, can contribute to this contextual reshaping of V1 responses. By comparing cortical dynamics evoked respectively by natural vs. artificial stimuli in a comprehensive parametric space analysis, we demonstrate that the reliability and sparseness of the spiking responses during natural vision is not a mere consequence of the increased bandwidth in the sensory input spectrum. Rather, it results from the combined impacts of fast synaptic depression and push-pull inhibition, the later acting for natural scenes as a form of "effective" feed-forward inhibition as demonstrated in other sensory systems. Thus, the combination of feedforward-like inhibition with fast thalamo-cortical synaptic depression by simple cells receiving a direct structured input from thalamus composes a generic computational mechanism for generating a sparse and reliable encoding of natural sensory events. PMID:27242445

  18. Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.

    PubMed

    Iwaoka, Emiko; Wang, Shenglan; Matsuyoshi, Nobuyuki; Kogure, Yoko; Aoki, Shunji; Yamamoto, Satoshi; Noguchi, Koichi; Dai, Yi

    2016-01-01

    Evodiae fructus (EF), a fruit of Evodia rutaecarpa Bentham, has long been used as an analgesic drug in traditional Chinese and Japanese medicine. However, the underlying molecular mechanism of its pharmacological action is unclear. Here, using calcium imaging, whole-cell patch-clamp recording, and behavioral analysis, we investigated the pharmacological action of EF and its principal compound, evodiamine, on the transient receptor potential (TRP) V1 channels. Dorsal root ganglion (DRG) neurons and TRPV1- or TRPA1-transfected human embryonic kidney-derived (HEK) 293 cells were used for calcium imaging or whole-cell patch-clamp recording. Twenty male adult Sprague-Dawley rats were used for the capsaicin-induced thermal hyperalgesia behavioral analyses. We found that evodiamine induced significant increases in intracellular calcium and robust inward currents in a subpopulation of isolated rat DRG neurons, most of which were also sensitive to capsaicin. The effect of evodiamine was completely blocked by capsazepine, a competitive antagonist of TRPV1. Evodiamine induced significant inward currents in TRPV1-, but not TRPA1-transfected HEK293 cells. Pretreatment with evodiamine reduced capsaicin-induced currents significantly. Furthermore, the in vivo pre-treatment of evodiamine suppressed thermal hyperalgesia induced by intraplantar injection of capsaicin in rats. These results identify that the analgesic effect of EF and evodiamine may be due to the activation and subsequent desensitization of TRPV1 in sensory neurons.

  19. Local Overexpression of V1a-Vasopressin Receptor Enhances Regeneration in Tumor Necrosis Factor-Induced Muscle Atrophy

    PubMed Central

    Costa, Alessandra; Toschi, Angelica; Murfuni, Ivana; Pelosi, Laura; Sica, Gigliola; Adamo, Sergio; Scicchitano, Bianca Maria

    2014-01-01

    Skeletal muscle atrophy occurs during disuse and aging, or as a consequence of chronic diseases such as cancer and diabetes. It is characterized by progressive loss of muscle tissue due to hypotrophic changes, degeneration, and an inability of the regeneration machinery to replace damaged myofibers. Tumor necrosis factor (TNF) is a proinflammatory cytokine known to mediate muscle atrophy in many chronic diseases and to inhibit skeletal muscle regeneration. In this study, we investigated the role of Arg-vasopressin-(AVP-)dependent pathways in muscles in which atrophy was induced by local overexpression of TNF. AVP is a potent myogenesis-promoting factor and is able to enhance skeletal muscle regeneration by stimulating Ca2+/calmodulin-dependent kinase and calcineurin signaling. We performed morphological and molecular analyses and demonstrated that local over-expression of the AVP receptor V1a enhances regeneration of atrophic muscle. By upregulating the regeneration/differentiation markers, modulating the inflammatory response, and attenuating fibrogenesis, the stimulation of AVP-dependent pathways creates a favourable environment for efficient and sustained muscle regeneration and repair even in the presence of elevated levels of TNF. This study highlights a novel in vivo role for AVP-dependent pathways, which may represent an interesting strategy to counteract muscle decline in aging or in muscular pathologies. PMID:24971321

  20. Action mechanism for 3β-hydroxykaurenoic acid and 4,4-dimethylanthracene-1,9,10(4H)-trione on Botrytis cinerea.

    PubMed

    Mendoza, Leonora; Ribera, Alejandra; Saavedra, Alejandra; Silva, Evelyn; Araya-Maturana, Ramiro; Cotoras, Milena

    2015-01-01

    The mechanism of action of the diterpenoid 3β-hydroxykaurenoic acid and the anthraquinone 4,4-dimethylanthracene-1,9,10(4H)-trione on the phytopathogenic fungus Botrytis cinerea was studied. The effect of both compounds on the respiratory process and on the membrane integrity of B. cinerea was evaluated. The results showed that 3β-hydroxykaurenoic acid inhibited the growth of this fungus by disrupting the plasmatic membrane. This compound also partially affected oxygen consumption of B. cinerea germinating conidia. Conversely, 4,4-dimethylanthracene-1,9,10(4H)-trione did not produce membrane disruption of B. cinerea. The effect of this compound on mycelial growth was notably increased by the presence of an inhibitor of the cyanide-resistant respiration pathway. It also was shown that the anthraquinone inhibited oxygen consumption by about 80%; therefore this compound would act as a potent inhibitor of the cytochrome pathway of the respiratory chain to exert its antifungal effect. PMID:25977212

  1. Cavity-enhanced optical feedback-assisted photo-acoustic spectroscopy with a 10.4 μm external cavity quantum cascade laser

    NASA Astrophysics Data System (ADS)

    Kachanov, A.; Koulikov, S.; Tittel, F. K.

    2013-01-01

    An ultra-sensitive photo-acoustic spectrometer using a 10.4 μm broadly tunable mid-IR external cavity quantum cascade laser (EC-QCL) coupled with optical feedback to an optical power buildup cavity with high reflectivity mirrors was developed and tested. A laser optical power buildup factor of 181 was achieved, which corresponds to an intra-cavity power of 9.6 W at a wavelength of 10.4 μm. With a photo-acoustic resonance cell placed inside the cavity this resulted in the noise-equivalent absorption coefficient of 1.9 × 10-10 cm-1 Hz-1/2, and a normalized noise-equivalent absorption of 1.1 × 10-11 cm-1 W Hz-1/2. A novel photo-acoustic signal normalization technique makes the photo-acoustic spectrometer's response immune to changes and drifts in the EC-QCL excitation power, EC-QCL to cavity coupling efficiency and cavity mirrors aging and contamination. An automatic lock of the EC-QCL to the cavity and optical feedback phase optimization permitted long wavelength scans within the entire EC-QCL spectral tuning range.

  2. Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.

    PubMed

    Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2015-05-01

    Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950

  3. Aquaporin-1 tunes pain perception by interaction with Na(v)1.8 Na+ channels in dorsal root ganglion neurons.

    PubMed

    Zhang, Hua; Verkman, A S

    2010-02-19

    Aquaporin-1 (AQP1) water channels are expressed in the plasma membrane of dorsal root ganglion (DRG) neurons. We found reduced osmotic water permeability in freshly isolated DRG neurons from AQP1(-/-) versus AQP1(+/+) mice. Behavioral studies showed greatly reduced thermal inflammatory pain perception in AQP1(-/-) mice evoked by bradykinin, prostaglandin E(2), and capsaicin as well as reduced cold pain perception. Patch clamp of freshly isolated DRG neurons showed reduced action potential firing in response to current injections. Single action potentials after pulse current injections showed reduced maximum inward current, suggesting impaired Na(v)1.8 Na(+) function. Whole-cell Na(v)1.8 Na(+) currents in Na(v)1.8-expressing ND7-23 cells showed slowed frequency-dependent inactivation after AQP1 transfection. Immunoprecipitation studies showed AQP1- Na(v)1.8 Na(+) interaction, which was verified in live cells by single-particle tracking of quantum dot-labeled AQP1. Our results implicate the involvement of AQP1 in DRG neurons for the perception of inflammatory thermal pain and cold pain, whose molecular basis is accounted for, in part, by reduced Na(v)1.8-dependent membrane Na(+) current. AQP1 is, thus, a novel target for pain management. PMID:20018876

  4. A subtle alternative splicing event of the Na(V)1.8 voltage-gated sodium channel is conserved in human, rat, and mouse.

    PubMed

    Schirmeyer, Jana; Szafranski, Karol; Leipold, Enrico; Mawrin, Christian; Platzer, Matthias; Heinemann, Stefan H

    2010-06-01

    The voltage-gated sodium channel subtype Na(V)1.8 (SCN10A) is exclusively expressed in dorsal root ganglia (DRG) and plays a critical role in pain perception. We isolated mRNA from human, rat, and mouse DRGs and screened for alternatively spliced isoforms of the SCN10A mRNA using 454 sequencing. In all three species, we found an event of subtle alternative splicing at a NAGNAG tandem acceptor that results in isoforms including or lacking glutamine 1030 (Na(V)1.8+Q and Na(V)1.8-Q, respectively) within the cytoplasmic loop between domains II and III. The relative amount of Na(V)1.8-Q mRNA in adult DRG was measured with 14.1 +/- 0.1% in humans and 11.2 +/- 0.2% in rats. This is in contrast to an abundance of 64.3 +/- 0.3% in mouse DRG. Thus, the NAGNAG tandem acceptor in SCN10A is conserved among rodents and humans but its alternative usage apparently occurs with species-specific abundance. Analysis of human Na(V)1.8+Q and -Q isoforms in whole-cell patch-clamp experiments after heterologous expression in the neuroblastoma cell line Neuro-2A revealed no obvious impact of the splicing event on channel function. PMID:19953341

  5. Cloning and overexpression of an important functional gene ATP6V1F encoding a component of vacuolar ATPase from the Giant Panda (Ailuropoda melanoleuca).

    PubMed

    Du, Yu-Jie; Hou, Yi-Ling; Hou, Wan-Ru

    2012-05-01

    ATP6V1F encodes a component of vacuolar ATPase mediating acidification. The cDNA and the genomic sequences of ATP6V1F were cloned successfully for the first time from the Giant Panda (Ailuropoda melanoleuca) using reverse transcription polymerase chain reaction and touchdown-polymerase chain reaction, respectively. The cDNA fragment cloned is 364 bp in size, containing an open reading frame of 360 bp encoding 119 amino acids. Alignment analysis indicated that both ORF and the deduced amino acid sequence are highly conserved. The length of the genomic sequence of the Giant Panda is 2225 bp, including two exons and one intron. Topology prediction showed that there is one protein kinase C phosphorylation site, two Casein kinase II phosphorylation sites, and one N-myristoylation site in the ATP6V1F protein. The ATP6V1F gene was overexpressed in Escherichia coli indicating that ATP6V1F fusion with the N-terminally His-tagged form gave rise to the accumulation of an expected 17 kDa polypeptide, which was according with the predicted protein and also could be used to purify the protein and study its function.

  6. Color tuning in alert macaque V1 assessed with fMRI and single-unit recording shows a bias toward daylight colors.

    PubMed

    Lafer-Sousa, Rosa; Liu, Yang O; Lafer-Sousa, Luis; Wiest, Michael C; Conway, Bevil R

    2012-05-01

    Colors defined by the two intermediate directions in color space, "orange-cyan" and "lime-magenta," elicit the same spatiotemporal average response from the two cardinal chromatic channels in the lateral geniculate nucleus (LGN). While we found LGN functional magnetic resonance imaging (fMRI) responses to these pairs of colors were statistically indistinguishable, primary visual cortex (V1) fMRI responses were stronger to orange-cyan. Moreover, linear combinations of single-cell responses to cone-isolating stimuli of V1 cone-opponent cells also yielded stronger predicted responses to orange-cyan over lime-magenta, suggesting these neurons underlie the fMRI result. These observations are consistent with the hypothesis that V1 recombines LGN signals into "higher-order" mechanisms tuned to noncardinal color directions. In light of work showing that natural images and daylight samples are biased toward orange-cyan, our findings further suggest that V1 is adapted to daylight. V1, especially double-opponent cells, may function to extract spatial information from color boundaries correlated with scene-structure cues, such as shadows lit by ambient blue sky juxtaposed with surfaces reflecting sunshine.

  7. Expression of the major mugwort pollen allergen Art v 1 in tobacco plants and cell cultures: problems and perspectives for allergen production in plants.

    PubMed

    Siegert, Marc; Pertl-Obermeyer, Heidi; Gadermaier, Gabriele; Ferreira, Fatima; Obermeyer, Gerhard

    2012-03-01

    An economic and cheap production of large amounts of recombinant allergenic proteins might become a prerequisite for the common use of microarray-based diagnostic allergy assays which allow a component-specific diagnosis. A molecular pharming strategy was applied to express the major allergen of Artemisia vulgaris pollen, Art v 1, in tobacco plants and tobacco cell cultures. The original Art v 1 with its endogenous signal peptide which directs Art v 1 to the secretory pathway, was expressed in transiently transformed tobacco leaves but was lost in stable transformed tobacco plants during the alternation of generations. Using a light-regulated promoter and "hiding" the recombinant Art v 1 in the ER succeeded in expression of Art v 1 over three generations of tobacco plants and in cell cultures generated from stable transformed plants. However, the amounts of the recombinant allergen were sufficient for analysis but not high enough to allow an economic production. Although molecular pharming has been shown to work well for the production of non-plant therapeutic proteins, it might be less efficient for closely related plant proteins.

  8. Mice with an NaV1.4 sodium channel null allele have latent myasthenia, without susceptibility to periodic paralysis.

    PubMed

    Wu, Fenfen; Mi, Wentao; Fu, Yu; Struyk, Arie; Cannon, Stephen C

    2016-06-01

    Over 60 mutations of SCN4A encoding the NaV1.4 sodium channel of skeletal muscle have been identified in patients with myotonia, periodic paralysis, myasthenia, or congenital myopathy. Most mutations are missense with gain-of-function defects that cause susceptibility to myotonia or periodic paralysis. Loss-of-function from enhanced inactivation or null alleles is rare and has been associated with myasthenia and congenital myopathy, while a mix of loss and gain of function changes has an uncertain relation to hypokalaemic periodic paralysis. To better define the functional consequences for a loss-of-function, we generated NaV1.4 null mice by deletion of exon 12. Heterozygous null mice have latent myasthenia and a right shift of the force-stimulus relation, without evidence of periodic paralysis. Sodium current density was half that of wild-type muscle and no compensation by retained expression of the foetal NaV1.5 isoform was detected. Mice null for NaV1.4 did not survive beyond the second postnatal day. This mouse model shows remarkable preservation of muscle function and viability for haploinsufficiency of NaV1.4, as has been reported in humans, with a propensity for pseudo-myasthenia caused by a marginal Na(+) current density to support sustained high-frequency action potentials in muscle. PMID:27048647

  9. Expression of the major mugwort pollen allergen Art v 1 in tobacco plants and cell cultures: problems and perspectives for allergen production in plants.

    PubMed

    Siegert, Marc; Pertl-Obermeyer, Heidi; Gadermaier, Gabriele; Ferreira, Fatima; Obermeyer, Gerhard

    2012-03-01

    An economic and cheap production of large amounts of recombinant allergenic proteins might become a prerequisite for the common use of microarray-based diagnostic allergy assays which allow a component-specific diagnosis. A molecular pharming strategy was applied to express the major allergen of Artemisia vulgaris pollen, Art v 1, in tobacco plants and tobacco cell cultures. The original Art v 1 with its endogenous signal peptide which directs Art v 1 to the secretory pathway, was expressed in transiently transformed tobacco leaves but was lost in stable transformed tobacco plants during the alternation of generations. Using a light-regulated promoter and "hiding" the recombinant Art v 1 in the ER succeeded in expression of Art v 1 over three generations of tobacco plants and in cell cultures generated from stable transformed plants. However, the amounts of the recombinant allergen were sufficient for analysis but not high enough to allow an economic production. Although molecular pharming has been shown to work well for the production of non-plant therapeutic proteins, it might be less efficient for closely related plant proteins. PMID:22159963

  10. First evidence of Panulirus argus Virus 1 (PaV1) in spiny lobster from Cuba and clinical estimation of its prevalence.

    PubMed

    Cruz Quintana, Yanis; Rodríguez Canul, Rossanna; Vidal Martínez, Victor M

    2011-01-21

    The present study documents the first finding of Panulirus argus Virus 1 (PaV1) in spiny lobster Panulirus argus from Cuba. Samples originated from 2 nursery sites, Matias Keys and Bocas de Alonso Keys, and 2 fishing sites, La Grifa and El Ramajo. Lobsters from the nursery sites (artificial reefs) were collected by SCUBA diving, while those from the fishing sites were collected from artificial shelters known as 'casitas cubanas'. In these shelters it was observed that healthy lobsters tended to avoid infected lobsters. Prevalence of PaV1 in the sampling sites was assessed by using clinical signs such as lethargy, an opaque reddish shell coloration, and milky white hemolymph with loss of clotting activity. The presence of PaV1 was subsequently confirmed by histology and PCR of tissues and hemolymph samples from suspected individuals. Histological sections of the hepatopancreas, gills, gonads, and gut showed infected hemocytes with hypertrophied nuclei and eosinophilic intranuclear Cowdry type A inclusions. A 499 bp band was observed by PCR. The sequence of the amplified fragments was 96% similar to the PaV1 sequence in GenBank. The overall mean prevalence of PaV1 was 4.48% (range: 0 to 9.3%) after pooling the results of the 4 sampling sites.

  11. The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats.

    PubMed

    Shimazaki, Toshiharu; Iijima, Michihiko; Chaki, Shigeyuki

    2006-08-14

    A vasopressin V(1B) receptor antagonist has been shown to exhibit anxiolytic effects in a variety of animal models of anxiety. In the present study, we examined the involvement of the pituitary in the anxiolytic effects of a vasopressin V(1B) receptor antagonist by conducting a social interaction test in rats. In the sham-operated rats, both the vasopressin V(1B) receptor antagonist SSR149415 and the benzodiazepine chlordiazepoxide significantly increased the social behavior of a pair of unfamiliar rats, and the blood adrenocorticotropic hormone levels were markedly increased during the social interaction test. Hypophysectomy also increased the length of time that the animals engaged in social behavior to the same extent as that observed after treatment of the sham-operated rats with anxiolytics. However, while chlordiazepoxide further increased the duration of social interaction in the hypophysectomized rats, the anxiolytic effects of SSR149415 was no longer observed in these animals. These results suggest that the anxiolytic effects of the vasopressin V(1B) receptor antagonist in the social interaction test are mediated through blockade of the vasopressin V(1B) receptor in the pituitary.

  12. Carbamazepine interacts with a slow inactivation state of NaV1.8-like sodium channels.

    PubMed

    Cardenas, Carlos A; Cardenas, Carla G; de Armendi, Alberto J; Scroggs, Reese S

    2006-11-13

    Carbamazepine was tested on high-threshold TTX-resistant Na+ currents (TTX-R-currents), evoked from acutely isolated rat dorsal root ganglion (DRG) cells. Under control conditions, the TTX-R-currents recorded from different DRG cells varied greatly regarding use-dependent inactivation (TTX-R-current UDI), measured as the percent decrease in current amplitude induced by changing the current activation rate from 0.1 Hz to 1.0 Hz. Also, when TTX-R-currents were evoked at 0.1 Hz from a holding potential (hp) of -60 mV, a larger fraction of TTX-R-channels resided tonically in a slow inactivation state in DRG cells with more TTX-R-current UDI versus those with less TTX-R-current UDI. The block of TTX-R-currents evoked from hp -60 mV by 100-microM carbamazepine and the EC50 for carbamazepine block was positively correlated with TTX-R-current UDI. The slope factors estimated for the concentration-response curves averaged 0.68, suggesting the presence of low and high affinity sites. Fitting the data with a two-site binding isotherm gave estimates of 30 microM and 760 microM for the EC50s of the high and low affinity sites, respectively. The fraction of the total fit attributed to the high affinity site was positively correlated with TTX-R-current UDI. Carbamazepine increased the fast and slow time constants for recovery from inactivation and the fraction of the fit attributed to the slow time constant. These data suggest that carbamazepine interacts with a slow inactivation state of TTX-R-channels. This particular mechanism might be exploited in future research aimed at developing pain medications that selectively block Na(V)1.8 channels or Na+ channels in general. PMID:16978779

  13. Tripal v1.1: a standards-based toolkit for construction of online genetic and genomic databases.

    PubMed

    Sanderson, Lacey-Anne; Ficklin, Stephen P; Cheng, Chun-Huai; Jung, Sook; Feltus, Frank A; Bett, Kirstin E; Main, Dorrie

    2013-01-01

    Tripal is an open-source freely available toolkit for construction of online genomic and genetic databases. It aims to facilitate development of community-driven biological websites by integrating the GMOD Chado database schema with Drupal, a popular website creation and content management software. Tripal provides a suite of tools for interaction with a Chado database and display of content therein. The tools are designed to be generic to support the various ways in which data may be stored in Chado. Previous releases of Tripal have supported organisms, genomic libraries, biological stocks, stock collections and genomic features, their alignments and annotations. Also, Tripal and its extension modules provided loaders for commonly used file formats such as FASTA, GFF, OBO, GAF, BLAST XML, KEGG heir files and InterProScan XML. Default generic templates were provided for common views of biological data, which could be customized using an open Application Programming Interface to change the way data are displayed. Here, we report additional tools and functionality that are part of release v1.1 of Tripal. These include (i) a new bulk loader that allows a site curator to import data stored in a custom tab delimited format; (ii) full support of every Chado table for Drupal Views (a powerful tool allowing site developers to construct novel displays and search pages); (iii) new modules including 'Feature Map', 'Genetic', 'Publication', 'Project', 'Contact' and the 'Natural Diversity' modules. Tutorials, mailing lists, download and set-up instructions, extension modules and other documentation can be found at the Tripal website located at http://tripal.info. DATABASE URL: http://tripal.info/. PMID:24163125

  14. Electrophysiological and autoradiographical evidence of V1 vasopressin receptors in the lateral septum of the rat brain

    SciTech Connect

    Raggenbass, M.; Tribollet, E.; Dreifuss, J.J.

    1987-11-01

    Extracellular recordings were obtained from single neurons located in the lateral septum, an area known to receive a vasopressinergic innervation in the rat brain. Approximately half of the neurons tested responded to 8-L-arginine vasopressin (AVP) by a marked increase in firing rate at concentrations greater than 1 nM. The effect of vasopressin was blocked by synthetic structural analogues possessing antagonistic properties on peripheral vasopressin and oxytocin receptors. Oxytocin was much less potent than vasopressin in firing septal neurons, and a selective oxytocic agonist was totally ineffective. The action of vasopressin on neuronal firing was mimicked by the vasopressor agonist (2-phenylalanine,8-ornithine)vasotocin but not by the selective antidiuretic agonist 1-deamino(8-D-arginine)vasopressin. In a parallel study, sites that bind (/sup 3/H)AVP at low concentration (1.5 nM) were found by in vitro autoradiography in the lateral septum. Adjacent sections were also incubated with 1.5 mM (/sup 3/H)AVP and, in addition, with 100 nM (2-phenylalanine,8-ornithine)vasotocin or 1-deamino(8-D-arginine)vasopressin--i.e., the same compounds as those used for the electrophysiological study. Results showed that the vasopressor agonist, but not the antidiuretic agonist, displaced (/sup 3/H)AVP, thus indicating that the vasopressin binding sites detected by autoradiography in the septum were V1 (vasopressor type) rather than V2 (antidiuretic type) receptors. Based on the electrophysiological evidence, we conclude that these receptors, when occupied, lead to increased firing of lateral septal neurons.

  15. Tripal v1.1: a standards-based toolkit for construction of online genetic and genomic databases

    PubMed Central

    Sanderson, Lacey-Anne; Ficklin, Stephen P.; Cheng, Chun-Huai; Jung, Sook; Feltus, Frank A.; Bett, Kirstin E.; Main, Dorrie

    2013-01-01

    Tripal is an open-source freely available toolkit for construction of online genomic and genetic databases. It aims to facilitate development of community-driven biological websites by integrating the GMOD Chado database schema with Drupal, a popular website creation and content management software. Tripal provides a suite of tools for interaction with a Chado database and display of content therein. The tools are designed to be generic to support the various ways in which data may be stored in Chado. Previous releases of Tripal have supported organisms, genomic libraries, biological stocks, stock collections and genomic features, their alignments and annotations. Also, Tripal and its extension modules provided loaders for commonly used file formats such as FASTA, GFF, OBO, GAF, BLAST XML, KEGG heir files and InterProScan XML. Default generic templates were provided for common views of biological data, which could be customized using an open Application Programming Interface to change the way data are displayed. Here, we report additional tools and functionality that are part of release v1.1 of Tripal. These include (i) a new bulk loader that allows a site curator to import data stored in a custom tab delimited format; (ii) full support of every Chado table for Drupal Views (a powerful tool allowing site developers to construct novel displays and search pages); (iii) new modules including ‘Feature Map’, ‘Genetic’, ‘Publication’, ‘Project’, ‘Contact’ and the ‘Natural Diversity’ modules. Tutorials, mailing lists, download and set-up instructions, extension modules and other documentation can be found at the Tripal website located at http://tripal.info. Database URL: http://tripal.info/ PMID:24163125

  16. Comparison of bio-mineralization behavior of Ti-6Al-4V-1Nb and Zr-1Nb nano-tubes formed by anodization

    NASA Astrophysics Data System (ADS)

    Choi, Yong; Hong, Sun I.

    2014-12-01

    Nano-tubes of titanium and zirconium alloys like Ti-6Al-4V-1Nb and Zr-1Nb were prepared by anodization followed by coating with hydroxylapatite (HA) and their bio-mineralization behaviors were compared to develop a bio-compatible material for implants in orthopedics, dentistry and cardiology. Ti-6Al-4V-1Nb weight gain in a simulated body solution increased gradually. The bigger tube diameter was, the heavier HA was deposited. Surface roughness of both alloys increased highly with the increasing diameter of nano-tube. Their surface roughness decreased by HA deposition due to the removal of the empty space of the nano-tubes. Zr-1Nb alloy had faster growth of nano-tubes layers more than Ti-6Al-4V-1Nb alloy.

  17. Development of a μO-Conotoxin Analogue with Improved Lipid Membrane Interactions and Potency for the Analgesic Sodium Channel NaV1.8.

    PubMed

    Deuis, Jennifer R; Dekan, Zoltan; Inserra, Marco C; Lee, Tzong-Hsien; Aguilar,