Science.gov

Sample records for 4-5 atomic percent

  1. Median CBO Salary Rises by 4.5 Percent, Annual Study Finds.

    ERIC Educational Resources Information Center

    Business Officer, 1997

    1997-01-01

    An annual national survey of college and university salaries found chief business officers' salaries rose 4.5 percent in 1996-97, less than the previous year. Salaries of women and minority CBOs continued to gain equity with that of men. Rates of increase varied by institution type. Salary gains for all administrative job types were less than in…

  2. Atomic accuracy models from 4.5 Å cryo-electron microscopy data with density-guided iterative local refinement

    PubMed Central

    Li, Xueming; Brunner, Matthias J.; Xu, Chunfu; Conticello, Vincent; Egelman, Edward; Marlovits, Thomas; Cheng, Yifan; Baker, David

    2015-01-01

    Direct electron detectors have made it possible to generate electron density maps at near atomic resolution using cryo-electron microscopy single particle reconstructions. Critical current questions include how best to build models into these maps, how high quality a map is required to generate an accurate model, and how to cross-validate models in a system independent way. We describe a modeling approach that integrates Monte Carlo optimization with local density guided moves, Rosetta all-atom refinement, and real space B-factor fitting, yielding accurate models from experimental maps for three different systems with resolutions 4.5 Å or higher. We characterize model accuracy as a function of data quality, and present a model validation statistic that correlates with model accuracy over the three test systems. PMID:25707030

  3. The Use of Gas Chromatography and Mass Spectrometry to Introduce General Chemistry Students to Percent Mass and Atomic Mass Calculations

    ERIC Educational Resources Information Center

    Pfennig, Brian W.; Schaefer, Amy K.

    2011-01-01

    A general chemistry laboratory experiment is described that introduces students to instrumental analysis using gas chromatography-mass spectrometry (GC-MS), while simultaneously reinforcing the concepts of mass percent and the calculation of atomic mass. Working in small groups, students use the GC to separate and quantify the percent composition…

  4. Auger electron spectroscopy study of surface segregation in the binary alloys copper-1 atomic percent indium, copper-2 atomic percent tin, and iron-6.55 atomic percent silicon

    NASA Technical Reports Server (NTRS)

    Ferrante, J.

    1973-01-01

    Auger electron spectroscopy was used to examine surface segregation in the binary alloys copper-1 at. % indium, copper-2 at. % tin and iron-6.55 at. % silicon. The copper-tin and copper-indium alloys were single crystals oriented with the /111/ direction normal to the surface. An iron-6.5 at. % silicon alloy was studied (a single crystal oriented in the /100/ direction for study of a (100) surface). It was found that surface segregation occurred following sputtering in all cases. Only the iron-silicon single crystal alloy exhibited equilibrium segregation (i.e., reversibility of surface concentration with temperature) for which at present we have no explanation. McLean's analysis for equilibrium segregation at grain boundaries did not apply to the present results, despite the successful application to dilute copper-aluminum alloys. The relation of solute atomic size and solubility to surface segregation is discussed. Estimates of the depth of segregation in the copper-tin alloy indicate that it is of the order of a monolayer surface film.

  5. Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement.

    PubMed

    DiMaio, Frank; Song, Yifan; Li, Xueming; Brunner, Matthias J; Xu, Chunfu; Conticello, Vincent; Egelman, Edward; Marlovits, Thomas C; Cheng, Yifan; Baker, David

    2015-04-01

    We describe a general approach for refining protein structure models on the basis of cryo-electron microscopy maps with near-atomic resolution. The method integrates Monte Carlo sampling with local density-guided optimization, Rosetta all-atom refinement and real-space B-factor fitting. In tests on experimental maps of three different systems with 4.5-Å resolution or better, the method consistently produced models with atomic-level accuracy largely independently of starting-model quality, and it outperformed the molecular dynamics-based MDFF method. Cross-validated model quality statistics correlated with model accuracy over the three test systems. PMID:25707030

  6. The epitaxial growth of (1 1 1) oriented monocrystalline Si film based on a 4:5 Si-to-SiC atomic lattice matching interface

    SciTech Connect

    Yang, Chen; Chen, Zhiming; Hu, Jichao; Ren, Zhanqiang; Lin, Shenghuang

    2012-06-15

    Highlights: ► A monocrystalline Si film was demonstrated by XRD to epitaxially grow on the 6H-SiC substrate. ► A 4:5 Si-to-SiC lattice matching structure was observed at the Si/SiC interface. ► The calculated value of the actual lattice mismatch is only 0.26%. ► Defects can be effectively reduced at the 4:5 Si-to-SiC lattice matching Si/SiC interface. -- Abstract: Due to a huge lattice mismatch of about 20% theoretically existing between SiC and Si, it is difficult for growing monocrystalline Si/SiC heterojunction to realize the light control of SiC devices. However, based on a 4:5 Si-to-SiC atomic lattice matching interface structure, the monocrystalline Si films were epitaxially prepared on the 6H-SiC (0 0 0 1) substrate by hot-wall chemical vapor deposition in our work. The film was characterized by X-ray diffraction analysis with only (1 1 1) orientation occurring. The X-ray rocking curves illustrated good symmetry with a full width at half maximum of 0.4339° omega. A 4:5 Si-to-SiC atomic matching structure of the Si/6H-SiC interface clearly observed by the transmission electron microscope revealed the essence of growing the monocrystalline Si film on the SiC substrate.

  7. Thermal effects in equilibrium surface segregation in a copper/10-atomic-percent-aluminum alloy using Auger electron spectroscopy

    NASA Technical Reports Server (NTRS)

    Ferrante, J.

    1972-01-01

    Equilibrium surface segregation of aluminum in a copper-10-atomic-percent-aluminum single crystal alloy oriented in the /111/ direction was demonstrated by using Auger electron spectroscopy. This crystal was in the solid solution range of composition. Equilibrium surface segregation was verified by observing that the aluminum surface concentration varied reversibly with temperature in the range 550 to 850 K. These results were curve fitted to an expression for equilibrium grain boundary segregation and gave a retrieval energy of 5780 J/mole (1380 cal/mole) and a maximum frozen-in surface coverage three times the bulk layer concentration. Analyses concerning the relative merits of sputtering calibration and the effects of evaporation are also included.

  8. Solidification analysis of a centrifugal atomizer using the Al-32.7wt.percent Cu alloy

    NASA Astrophysics Data System (ADS)

    Osborne, Matthew Gary

    1997-12-01

    A centrifugal atomizer (spinning disk variety) was designed and constructed for the production of spherical metal powders, 100-1000 microns in diameter in an inert atmosphere. Initial atomization experiments revealed the need for a better understanding of how the liquid metal was atomized and how the liquid droplets solidified. To investigate particle atomization, Ag was atomized in air and the process recorded on high-speed film. To investigate particle solidification, Al-32.7wt.% Cu was atomized under inert atmosphere and the subsequent particles were examined microscopically to determine solidification structure and rate. This dissertation details the experimental procedures used in producing the Al-Cu eutectic alloy particles, examination of the particle microstructures, and determination of the solidification characteristics (e.g., solidification rate) of various phases. Finally, correlations are proposed between the operation of the centrifugal atomizer and the observed solidification spacings. This research was supported in part by the Office of Basic Energy Science, USDOE. The Ames laboratory is operated by Iowa State University for the U.S. Department of Energy under contract number W-7405-Eng-82.

  9. METALLURGICAL PROGRAMS: CALCULATION OF MASS FROM VOLUME, DENSITY OF MIXTURES, AND CONVERSION OF ATOMIC TO WEIGHT PERCENT

    NASA Technical Reports Server (NTRS)

    Degroh, H.

    1994-01-01

    The Metallurgical Programs include three simple programs which calculate solutions to problems common to metallurgical engineers and persons making metal castings. The first program calculates the mass of a binary ideal (alloy) given the weight fractions and densities of the pure components and the total volume. The second program calculates the densities of a binary ideal mixture. The third program converts the atomic percentages of a binary mixture to weight percentages. The programs use simple equations to assist the materials staff with routine calculations. The Metallurgical Programs are written in Microsoft QuickBASIC for interactive execution and have been implemented on an IBM PC-XT/AT operating MS-DOS 2.1 or higher with 256K bytes of memory. All instructions needed by the user appear as prompts as the software is used. Data is input using the keyboard only and output is via the monitor. The Metallurgical programs were written in 1987.

  10. Quantum and all-atom molecular dynamics simulations of protonation and divalent ion binding to phosphatidylinositol 4,5-bisphosphate (PIP2).

    PubMed

    Slochower, David R; Huwe, Peter J; Radhakrishnan, Ravi; Janmey, Paul A

    2013-07-18

    Molecular dynamics calculations have been used to determine the structure of phosphatidylinositol 4,5 bisphosphate (PIP2) at the quantum level and to quantify the propensity for PIP2 to bind two physiologically relevant divalent cations, Mg(2+) and Ca(2+). We performed a geometry optimization at the Hartree-Fock 6-31+G(d) level of theory in vacuum and with a polarized continuum dielectric to determine the conformation of the phospholipid headgroup in the presence of water and its partial charge distribution. The angle between the headgroup and the acyl chains is nearly perpendicular, suggesting that in the absence of other interactions the inositol ring would lie flat along the cytoplasmic surface of the plasma membrane. Next, we employed hybrid quantum mechanics/molecular mechanics (QM/MM) simulations to investigate the protonation state of PIP2 and its interactions with magnesium or calcium. We test the hypothesis suggested by prior experiments that binding of magnesium to PIP2 is mediated by a water molecule that is absent when calcium binds. These results may explain the selective ability of calcium to induce the formation of PIP2 clusters and phase separation from other lipids. PMID:23786273

  11. Quantum and All-Atom Molecular Dynamics Simulations of Protonation and Divalent Ion Binding to Phosphatidylinositol 4,5-Bisphosphate (PIP2)

    PubMed Central

    Slochower, David R.; Huwe, Peter J.; Radhakrishnan, Ravi; Janmey, Paul A.

    2014-01-01

    Molecular dynamics calculations have been used to determine the structure of phosphatidylinositol 4,5 bisphosphate (PIP2) at the quantum level and to quantify the propensity for PIP2 to bind two physiologically relevant divalent cations, Mg2+ and Ca2+. We performed a geometry optimization at the Hartree-Fock 6-31+G(d) level of theory in vacuum and with a polarized continuum dielectric to determine the conformation of the phospholipid headgroup in the presence of water and its partial charge distribution. The angle between the headgroup and the acyl chains is nearly perpendicular, suggesting that in the absence of other interactions, the inositol ring would lie flat along the cytoplasmic surface of the plasma membrane. Next, we employed hybrid quantum mechanics / molecular mechanics (QM/MM) simulations to investigate the protonation state of PIP2 and its interactions with magnesium or calcium. We test the hypothesis suggested by prior experiments that binding of magnesium to PIP2 is mediated by a water molecule that is absent when calcium binds. These results may explain the selective ability of calcium to induce the formation of PIP2 clusters and phase separation from other lipids. PMID:23786273

  12. Study on the effects of nitrilotriproprionic acid and 4,5-dihydroxy-1,3-benzene disulphonate on the fractionation of beryllium in human serum using graphite furnace atomic absorption spectrometry

    PubMed Central

    Stephan, Chadi H; Fournier, Michel; Brousseau, Pauline; Sauvé, Sébastien

    2008-01-01

    Background Occupational exposure to beryllium may cause Chronic Beryllium Disease (CBD), a lung disorder initiated by an electrostatic interaction with the MHC class II human leukocyte antigen (HLA). Molecular studies have found a significant correlation between the electrostatic potential at the HLA-DP surface and disease susceptibility. CBD can therefore be treated by chelation therapy. In this work, we studied the effect of two complexing agents, nitrilotriproprionic acid (NTP) and 4,5-dihydroxy-1,3-benzene disulphonate (Tiron), on the fractionation of beryllium in human serum analysed by graphite furnace atomic absorption spectrometry (GFAAS). Results We found the average serum beryllium concentration of fourteen non-exposed individuals to be 0.53 (± 0.14) μg l-1, with 21 (± 3)% of the beryllium mass bound to the low molecular weight fraction (LMW), and 79 (± 3)% bound to the high molecular weight fraction (HMW). The addition of Tiron increased the beryllium mass in the HMW fraction, while NTP was not seen to have any influence on the fractionation of beryllium between the two fractions. NTP was, however, shown to complex 94.5% of the Be mass in the LMW fraction. The beryllium GFAAS detection limit, calculated as three times the standard deviation of 10 replicates of the lowest standard (0.05 μg L-1), was 6.0 (± 0.2) ng L-1. Conclusion The concentration of beryllium or its fractionation in human serum was not affected by sex or smoking habit. On average, three quarters of the beryllium in serum were found in the HMW fraction. Of the two ligands tested, only Tiron was effective in mobilising beryllium under physiological conditions, thus increasing the Be content in the HMW fraction. PMID:18479524

  13. The effect of 0.1 atomic percent zirconium on the cyclic oxidation behavior of beta-NiAl for 300 hours at 1200 C

    NASA Technical Reports Server (NTRS)

    Barrett, C. A.

    1988-01-01

    The long time effect of 0.1 at percent Zr (0.2 wt percent Zr) on the cyclic oxidation behavior of hipped beta-NiAl was studied. Oxidation testing was performed in static air at 1200 C for up to 3000 one-hour exposure cycles. Specific weight change versus time data was modeled with the COSP computer program to analyze cyclic oxidation behavior. The Zr-free stoichiometric alloy oxidized and spalled randomly to bare metal between cycles at a rate high enough to deplete Al to a low enough level that oxidation breakaway took place as nonprotective NiO replaced the alpha-Al2O3/NiAl2O4 scale as the controlling oxide. The Zr minimized this severe type of spalling maintaining the protective alpha-Al2O3 scale even out to 3000 hours for the stoichiometric alloy with no significant Al depletion. A third beta-NiAl alloy containing 0.1 at percent Zr but with 10 percent less Al than the stoichiometric alloy was also tested and showed some depletion of Al, but the protective Al2O3/NiAl2O4 was still maintained to close to 2700 hours.

  14. The effect of 0.1 atomic percent zirconium on the cyclic oxidation behavior of beta-NiAl for 3000 hours at 1200 C

    NASA Technical Reports Server (NTRS)

    Barrett, C. A.

    1989-01-01

    The long time effect of 0.1 at percent Zr (0.2 wt percent Zr) on the cyclic oxidation behavior of hipped beta-NiAl was studied. Oxidation testing was performed in static air at 1200 C for up to 3000 one-hour exposure cycles. Specific weight change versus time data was modeled with the COSP computer program to analyze cyclic oxidation behavior. The Zr-free stoichiometric alloy oxidized and spalled randomly to bare metal between cycles at a rate high enough to deplete Al to a low enough level that oxidation breakaway took place as nonprotective NiO replaced the alpha-Al203/NiAl204 scale as the controlling oxide. The Zr minimized this severe type of spalling maintaining the protective alpha-Al203 scale even out to 3000 hours for the stoichiometric alloy with no significant Al depletion. A third beta-NiAl alloy containing 0.1 at percent Zr but with 10 percent less Al than the stoichiometric alloy was also tested and showed some depletion of Al, but the protective Al203/NiAl204 was still maintained to close to 2700 hours.

  15. 2,4,5-Trichlorophenol

    Integrated Risk Information System (IRIS)

    2,4,5 - Trichlorophenol ; CASRN 95 - 95 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcino

  16. The Teaching of Percent.

    ERIC Educational Resources Information Center

    Szymanski, T.

    1998-01-01

    Proposes looking at the percent symbol (%) as an operator, which means to divide any number in front of it by 100. Stresses the importance of using correct words to describe the numbers generated in percent calculations. Explains how to (1) calculate percent using equivalent fractions; (2) divide fraction numerators by denominators, retaining the…

  17. Meaning of percent sunshine

    SciTech Connect

    Sands, J.

    1983-05-01

    The meaning of the term percent of possible sunshine is discussed. The Percent of Possible Sunshine (POPS) is published monthly with annual summaries by the National Climatic Data Center (NCDC) for 168 locations, and is a measure of how long the sun shines, not how much sunshine there is. The weakness of the POPS as a serious indicator of solar performance is pointed out.

  18. Percents Can Make Sense

    ERIC Educational Resources Information Center

    Zambo, Ron

    2008-01-01

    This article describes instructional activities designed to help students develop an understanding of the multiple relationships between fractions and percents and unit price as they develop their mental-math abilities. (Contains 4 figures.)

  19. Singlet-triplet energy splitting between 1D and 3D (1s2 2s nd), n = 3, 4, 5, and 6, Rydberg states of the beryllium atom (9Be) calculated with all-electron explicitly correlated Gaussian functions

    NASA Astrophysics Data System (ADS)

    Sharkey, Keeper L.; Bubin, Sergiy; Adamowicz, Ludwik

    2014-11-01

    Accurate variational nonrelativistic quantum-mechanical calculations are performed for the five lowest 1D and four lowest 3D states of the 9Be isotope of the beryllium atom. All-electron explicitly correlated Gaussian (ECG) functions are used in the calculations and their nonlinear parameters are optimized with the aid of the analytical energy gradient determined with respect to these parameters. The effect of the finite nuclear mass is directly included in the Hamiltonian used in the calculations. The singlet-triplet energy gaps between the corresponding 1D and 3D states, are reported.

  20. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  1. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  2. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  3. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  4. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  5. 1,2,4,5-Tetrachlorobenzene

    Integrated Risk Information System (IRIS)

    1,2,4,5 - Tetrachlorobenzene ; CASRN 95 - 94 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonca

  6. Inspiration: One Percent and Rising

    ERIC Educational Resources Information Center

    Walling, Donovan R.

    2009-01-01

    Inventor Thomas Edison once famously declared, "Genius is one percent inspiration and ninety-nine percent perspiration." If that's the case, then the students the author witnessed at the International Student Media Festival (ISMF) last November in Orlando, Florida, are geniuses and more. The students in the ISMF pre-conference workshop had much to…

  7. Percents Are Not Natural Numbers

    ERIC Educational Resources Information Center

    Jacobs, Jennifer A.

    2013-01-01

    Adults are prone to treating percents, one representational format of rational numbers, as novel cases of natural number. This suggests that percent values are not differentiated from natural numbers; a conceptual shift from the natural numbers to the rational numbers has not yet occurred. This is most surprising, considering people are inundated…

  8. 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)

    Integrated Risk Information System (IRIS)

    2,4,5 - Trichlorophenoxyacetic acid ( 2,4,5 - T ) ; CASRN 93 - 76 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard

  9. 2(2,4,5-Trichlorophenoxy) propionic acid (2,4,5-TP)

    Integrated Risk Information System (IRIS)

    2 ( 2,4,5 - Trichlorophenoxy ) propionic acid ( 2,4,5 - TP ) ; CASRN 93 - 72 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Hea

  10. Pump-probe photoelectron velocity-map imaging of autoionizing singly excited 4s{sup 1}4p{sup 6}np{sup 1}(n=7,8) and doubly excited 4s{sup 2}4p{sup 4}5s{sup 1}6p{sup 1} resonances in atomic krypton

    SciTech Connect

    Doughty, Benjamin; Haber, Louis H.; Leone, Stephen R.

    2011-10-15

    Pump-probe photoelectron velocity-map imaging, using 27-eV high-harmonic excitation and 786-nm ionization, is used to resolve overlapping autoionizing resonances in atomic krypton, obtaining two-photon photoelectron angular distributions (PADs) for singly and doubly excited states. Two features in the photoelectron spectrum are assigned to singly excited 4s{sup 1}4p{sup 6}np{sup 1} (n = 7,8) configurations and four features provide information about double excitation configurations. The anisotropy parameters for the singly excited 7p configuration are measured to be {beta}{sub 2} = 1.61 {+-} 0.06 and {beta}{sub 4} = 1.54 {+-} 0.16 while the 8p configuration gives {beta}{sub 2} = 1.23 {+-} 0.19 and {beta}{sub 4} = 0.60 {+-} 0.15. These anisotropies most likely represent the sum of overlapping PADs from states of singlet and triplet spin multiplicities. Of the four bands corresponding to ionization of doubly excited states, two are assigned to 4s{sup 2}4p{sup 4}5s{sup 1}6p{sup 1} configurations that are probed to different J-split ion states. The two remaining doubly excited states are attributed to a previously observed, but unassigned, resonance in the vacuum-ultraviolet photoabsorption spectrum. The PADs from each of the double excitation states are also influenced by overlap from neighboring states that are not completely spectrally resolved. The anisotropies of the observed double excitation states are reported, anticipating future theoretical and experimental work to separate the overlapping PADs into the state resolved PADs. The results can be used to test theories of excited state ionization.

  11. Microstructural examination of irradiated V-(4-5%)Cr-(4-5%)Ti.

    SciTech Connect

    Gelles, D. S.

    1998-05-04

    Microstructural examination results are reported for two heats of V-(4-5%) Cr-(4-5%)Ti irradiated in the EBR-II X530 experiment to 4.5 dpa at {approximately}400 C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to be affected by preirradiation heat treatment at 950-1125 C. There was no evidence for a significant density of large (diameter >10 nm) dislocation loops or network dislocations. Analytical investigations successfully demonstrated that the precipitates were enriched in titanium, depleted in vanadium and contained no nitrogen. These results are discussed in terms of future alloy development options.

  12. Thermophysical and mechanical properties of V-(4-5)%Cr-(4-5)%Ti alloys

    SciTech Connect

    Zinkle, S.J.

    1998-03-01

    Solid solution V-Cr-Ti alloys exhibit a good combination of high thermal conductivity, adequate tensile strength, and low thermal expansion. The key thermophysical and mechanical properties for V-(4-5)%Cr-(4-5)%Ti alloys are summarized in this report. Some of these data are available in the ITER Materials Properties Handbook (IMPH), whereas other data have been collected from recent studies. The IMPH is updated regularly, and should be used as the reference point for design calculations whenever possible.

  13. Microstructural examination of V-(4-5%) Cr-(4-5%)Ti irradiated in X530

    SciTech Connect

    Gelles, D.S.; Chung, H.M.

    1997-08-01

    Microstructural examination results are reported for two heats of V-(4-5%)Cr-(4-5%)Ti irradiated in the X530 experiment to {approximately}400{degrees}C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to be affected by preirradiation heat treatment at 950-1125{degrees}C. There was no evidence for a significant density of large (diameter >10 nm) dislocation loops or network dislocations.

  14. Tensile properties of V-(4-5)Cr-(4-5)Ti alloys

    SciTech Connect

    Chung, H.M.; Nowicki, L.; Busch, D.; Smith, D.L.

    1996-04-01

    The current focus of the U.S program of research on V-base alloys is on V-(4-5)Cr(4-5)Ti that contains 500-1000 wppm Si. in this paper, we present experimental results on baseline tensile properties of two laboratory-scale heats of this alloy and of a 500-kg production heat of V-4Cr-4Ti (heat 832665) that were measured at 23-700 C. Both the production- and laboratory scale heats of the reference alloy V-4Cr-4Ti exhibited excellent tensile properties at temperatures up to {approx}650{degrees}C.

  15. Microstructural examination of irradiated V-(4-5%)Cr-(4-5%)Ti

    SciTech Connect

    Gelles, D.S.; Rice, P.M.; Zinkle, S.J.; Chung, H.M.

    1998-03-01

    Microstructural examination results are reported for two heats of V-(4-5%)Cr-(4-5%)Ti irradiated in the EBR-II X530 experiment to {approximately}4 dpa at {approximately}400 C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to b affected by preirradiation heat treatment at 950--1125 C. There was no evidence for a significant density of large (diameter >10 nm) dislocation loops or network dislocations. Analytical investigators successfully demonstrated that the precipitates were enriched in titanium, depleted in vanadium and contained no nitrogen.

  16. Degradation of 4,5-dichloroguaiacol by soil microorganisms.

    PubMed

    González, B; Brezny, R; Herrera, M; Joyce, T W

    1995-09-01

    No microorganisms could be isolated from chemostats or from a soil column fed with 4,5-dichloroguaiacol as the only carbon source. If guaiacol was added to chemostats with 4,5-dichloroguaiacol, either soil microbial consortia or guaiacol-degrading bacteria could dechlorinate the 4,5-dichloroguaiacol provided it was <0.2MM. A microbial consortium from farm soil removed 4,5-dichloroguaiacol under aerobic or anoxic conditions, with or without chlorolignin. Dichlorocatechol was the only 4,5-dichloroguaiacol-derived metabolite detected. In aerobic incubations, 4,5-dichlorocatechol was further degraded whereas under anoxic conditions it accumulated. PMID:24414909

  17. 45 CFR 4.5 - Effect of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Effect of regulations. 4.5 Section 4.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION SERVICE OF PROCESS § 4.5 Effect of regulations. The regulations in this part are intended solely to identify Department officials who...

  18. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Notice by publication. 4.5 Section 4.5 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the complaint that is mailed to the...

  19. 45 CFR 4.5 - Effect of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Effect of regulations. 4.5 Section 4.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION SERVICE OF PROCESS § 4.5 Effect of regulations. The regulations in this part are intended solely to identify Department officials who...

  20. 45 CFR 4.5 - Effect of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Effect of regulations. 4.5 Section 4.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION SERVICE OF PROCESS § 4.5 Effect of regulations. The regulations in this part are intended solely to identify Department officials who...

  1. Calcium Promotes the Formation of Syntaxin 1 Mesoscale Domains through Phosphatidylinositol 4,5-Bisphosphate*

    PubMed Central

    Platen, Mitja; Junius, Meike; Diederichsen, Ulf; Schaap, Iwan A. T.; Honigmann, Alf; Jahn, Reinhard; van den Bogaart, Geert

    2016-01-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a minor component of total plasma membrane lipids, but it has a substantial role in the regulation of many cellular functions, including exo- and endocytosis. Recently, it was shown that PI(4,5)P2 and syntaxin 1, a SNARE protein that catalyzes regulated exocytosis, form domains in the plasma membrane that constitute recognition sites for vesicle docking. Also, calcium was shown to promote syntaxin 1 clustering in the plasma membrane, but the molecular mechanism was unknown. Here, using a combination of superresolution stimulated emission depletion microscopy, FRET, and atomic force microscopy, we show that Ca2+ acts as a charge bridge that specifically and reversibly connects multiple syntaxin 1/PI(4,5)P2 complexes into larger mesoscale domains. This transient reorganization of the plasma membrane by physiological Ca2+ concentrations is likely to be important for Ca2+-regulated secretion. PMID:26884341

  2. Metal complexes of 4,5-dimethylpyrazole-3-carboxaldehyde phenylthiosemicarbazone

    NASA Astrophysics Data System (ADS)

    El-Dissouky, Ali

    Several new transition metal complexes derived from 4,5-dimethyl-3-carboxaldehyde phenyl- thiosemicarbazone, LH, have been synthesized. The complexes are of stoichiometry, [CoL 2]X, X = Cl -, Br -, ClO -4 or NO -3, [MnL 2] and [CuX nL m], X = Cl -, Br -, NCS - or N -3; n = 1 or 0; m = 1 or 2 and L = the anion of LH. All complexes have been characterized by elemental analysis, spectral (i.r., electronic, NMR, ESR) and magnetic measurements. The ligand acts as tridentate monobasic co-ordinated to the metal ion via azomethine, pyrazole (N 2) nitrogen atoms and the thiolo-sulphur. The ligand field and ESR parameters are used to interpret the nature of bonding of LH with the metal ion, ground state and the ligand field strength of LH and the various co-ordinated simple ions. The coupling constants of various co-ordinated nuclei with copper (II) are estimated from ESR spectra of copper (II) complexes.

  3. Processable, high temperature polymers from 1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene and bis-dienes

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B.

    1988-01-01

    1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene reacts with various anthracene end-capped polyimide oligomers to form Diels-Alder cycloaddition copolymers. The polymers are soluble in common organic solvents, and have molecular weights of approximately 21,000 to 32,000. These resins exhibit lower weight loss in air than in nitrogen. This is suggested to be due to dehydration (loss of water ranges from 2 to 5 percent) at temperatures of 390 to 400 C to give thermooxidatively stable pentiptycene units along the polymer backbone. Because of their high softening points and good thermooxidative stability, the polymers have potential as processable, matrix resins for high temperature composite applications.

  4. Addition polymers from 1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene and Bis-dienes: Processable resins for high temperature application

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B.

    1987-01-01

    1,4,5,8-Tetrahydro-1,4;5,8-diepoxyanthracene reacts with various anthracene endcapped polyimide oligomers to form Diels-Alder cycloaddition copolymers. The polymers are soluble in common organic solvents, and have molecular weights of approximately 21,000 to 32,000. Interestingly, these resins appear to be more stable in air then in nitrogen. This is shown to be due to a unique dehydration (loss of water ranges from 2 to 5 percent) at temperatures of 390 to 400 C to give thermo-oxidatively stable pentiptycene units along the polymer backbone. Because of their high softening points and good thermo-oxidative stability, the polymers have potential as processible, matrix resins for high temperature composite applications.

  5. Beyond Marbles: Percent Change and Social Justice

    ERIC Educational Resources Information Center

    Denny, Flannery

    2013-01-01

    In the author's eighth year of teaching, she hit a wall teaching percent change. Percent change is one of the few calculations taught in math classes that shows up regularly in the media, and one that she often does in her head to make sense of the world around her. Despite this, she had been teaching percent change using textbook problems about…

  6. Elimination of 2,4,5,2',4',5'-hexachlorobiphenyl by the purple sea urchin, Strongylocentrotus purpuratus, following single exposure

    SciTech Connect

    Tjeerdema, R.S.; Jacobs, R.S.

    1987-06-01

    Understanding the fate of a single PCB isomer in a resident species may aid in assessing the risk to the marine community. Therefore, the elimination of 2,4,5,2',4',5'-hexachlorobiphenyl (HCBP) by the purple sea urchin, Strongylocentrotus purpuratus, following a single exposure, was investigated. The purple sea urchin was chosen because of its economic importance and ability to proliferate in certain polluted conditions. Single exposure may best mimic the effects of intermittent oceanic incineration or disposal, and 2,4,5,2',4',5'-HCBP was chosen due to its presence in common PCB mixtures and high chlorine content, thus strong lipophilicity.

  7. 43 CFR 1610.4-5 - Formulation of alternatives.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Formulation of alternatives. 1610.4-5 Section 1610.4-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING...

  8. 43 CFR 1610.4-5 - Formulation of alternatives.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Formulation of alternatives. 1610.4-5... Management Planning § 1610.4-5 Formulation of alternatives. At the direction of the Field Manager, in collaboration with any cooperating agencies, BLM will consider all reasonable resource management...

  9. 43 CFR 1610.4-5 - Formulation of alternatives.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Formulation of alternatives. 1610.4-5... Management Planning § 1610.4-5 Formulation of alternatives. At the direction of the Field Manager, in collaboration with any cooperating agencies, BLM will consider all reasonable resource management...

  10. 43 CFR 1610.4-5 - Formulation of alternatives.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Formulation of alternatives. 1610.4-5... Management Planning § 1610.4-5 Formulation of alternatives. At the direction of the Field Manager, in collaboration with any cooperating agencies, BLM will consider all reasonable resource management...

  11. 43 CFR 2650.4-5 - National forest lands.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false National forest lands. 2650.4-5 Section... Selections: Generally § 2650.4-5 National forest lands. Every conveyance which includes lands within the boundaries of a national forest shall, as to such lands, contain reservations that: (a) Until December...

  12. 43 CFR 2650.4-5 - National forest lands.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false National forest lands. 2650.4-5 Section... Selections: Generally § 2650.4-5 National forest lands. Every conveyance which includes lands within the boundaries of a national forest shall, as to such lands, contain reservations that: (a) Until December...

  13. 43 CFR 2650.4-5 - National forest lands.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false National forest lands. 2650.4-5 Section... Selections: Generally § 2650.4-5 National forest lands. Every conveyance which includes lands within the boundaries of a national forest shall, as to such lands, contain reservations that: (a) Until December...

  14. 43 CFR 2650.4-5 - National forest lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false National forest lands. 2650.4-5 Section... Selections: Generally § 2650.4-5 National forest lands. Every conveyance which includes lands within the boundaries of a national forest shall, as to such lands, contain reservations that: (a) Until December...

  15. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7... Federal Elections FEDERAL ELECTION COMMISSION PUBLIC RECORDS AND THE FREEDOM OF INFORMATION ACT § 4.5..., provided that such statute (A) requires that the matters be withheld from the public in such a manner as...

  16. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7... Federal Elections FEDERAL ELECTION COMMISSION PUBLIC RECORDS AND THE FREEDOM OF INFORMATION ACT § 4.5..., provided that such statute (A) requires that the matters be withheld from the public in such a manner as...

  17. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7... Federal Elections FEDERAL ELECTION COMMISSION PUBLIC RECORDS AND THE FREEDOM OF INFORMATION ACT § 4.5..., provided that such statute (A) requires that the matters be withheld from the public in such a manner as...

  18. 41 CFR 51-4.5 - Violations by nonprofit agencies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Violations by nonprofit agencies. 51-4.5 Section 51-4.5 Public Contracts and Property Management Other Provisions Relating to Public Contracts COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED...

  19. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Notice by publication. 4.5... COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the... where the USPTO's Web site is unavailable for publication will the USPTO publish the Notice of...

  20. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Notice by publication. 4.5... COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the... where the USPTO's Web site is unavailable for publication will the USPTO publish the Notice of...

  1. Aromatic fluorine compounds. II. 1,2,4,5-Tetrafluorobenzene and related compounds

    USGS Publications Warehouse

    Finger, G.C.; Reed, F.H.; Burness, D.M.; Fort, D.M.; Blough, R.R.

    1951-01-01

    The synthesis and properties of 1,2,4,5-tetrafluorobenzene and a group of bromofluoro and chlorofluorobenzenes with a predominating 1,2,4,5-structure are described. Flash point and surface tension data for the fluorinated benzenes and the influence of chlorine substitution upon these values were studied. Under nitration conditions, 1,2,4,5-tetrafluorobenzene will not form a nitro derivative, but will undergo a preferential 1,4-fluorine displacement-oxidation mechanism to give 2,5-difluoro-1,4-benzoquinone. Diazotization reactions on 2-nitro-3,4,6-trifluoroaniline reveal that the nitro group or a fluorine atom in the 4- or 6-position may become labilized, under certain conditions, and undergo replacement.

  2. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7..., or foreign agency or authority or any private institution which furnished information on...

  3. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7..., or foreign agency or authority or any private institution which furnished information on...

  4. 4,5-Diphenyl-1-methylimidazole: An Undergraduate Laboratory Experiment.

    ERIC Educational Resources Information Center

    Anastas, Paul T.; And Others

    1985-01-01

    Background information and procedures used are provided for the synthesis of 4,5-diphenyl-methylimidazole. This experiment on the chemistry of heterocycles is ideally suited for beginning undergraduate organic chemistry students. (JN)

  5. ANCHOR SETTING PLAN FOR PIERS 1, 2, 3, 4, 5 ...

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

    ANCHOR SETTING PLAN FOR PIERS 1, 2, 3, 4, 5 AND 6, APALACHICOLA RIVER BRIDGE, SHEET 5505 TO 8-M1 - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  6. SeizAlert could give patients 4.5 hour warning of seizure

    ScienceCinema

    Dr. Lee Hively and Kara Kruse

    2010-01-08

    One percent of Americans, 3 million people, suffer from epilepsy. And their lives are about to be dramatically changed by scientists at Oak Ridge National Laboratory. For 15 years, Dr. Lee Hively has been working on "SeizAlert", a seizure-detecting device that resembles a common PDA. "It allows us to analyze scalp brain waves and give us up to 4.5 hours' forewarning of that event," he said. With the help of partner Kara Kruse, he's now able to help patients predict the previously unpredictable.

  7. SeizAlert could give patients 4.5 hour warning of seizure

    SciTech Connect

    Dr. Lee Hively and Kara Kruse

    2009-01-16

    One percent of Americans, 3 million people, suffer from epilepsy. And their lives are about to be dramatically changed by scientists at Oak Ridge National Laboratory. For 15 years, Dr. Lee Hively has been working on "SeizAlert", a seizure-detecting device that resembles a common PDA. "It allows us to analyze scalp brain waves and give us up to 4.5 hours' forewarning of that event," he said. With the help of partner Kara Kruse, he's now able to help patients predict the previously unpredictable.

  8. Breathing 100 percent oxygen compared with 50 percent oxygen:50 percent nitrogen reduces altitude-induced venous gas emboli

    NASA Technical Reports Server (NTRS)

    Webb, James T.; Pilmanis, Andrew A.

    1993-01-01

    The study investigates effects of 40 zero-prebreathe decompressions of male subjects to 8.3-6.8 psia for 6 h while they were breathing 100 percent oxygen and performing moderate exercise. No decompression sickness (DCS) symptoms were observed. Severe venous gas emboli (VGE) were not detected at 8.3 psia, but were present during 10, 20, and 40 percent of the exposures at 7.8, 7.3, and 6.8 psia, respectively. Zero-prebreathe decompression while breathing 100 percent oxygen results in significantly lower VGE and DCS risk levels than while breathing a 50:50 mix. It is shown that 7.3 psia EVA pressure suits with 100 percent oxygen should be safer than 8.3 psia suits with a 50:50 mix.

  9. 3,4,5-Trinitropyrazole-based energetic salts.

    PubMed

    Zhang, Yanqiang; Guo, Yong; Joo, Young-Hyuk; Parrish, Damon A; Shreeve, Jean'ne M

    2010-09-17

    High-density energetic salts that are comprised of nitrogen-rich cations and the 3,4,5-trinitropyrazolate anion were synthesized in high yield by neutralization or metathesis reactions. The resulting salts were fully characterized by (1)H, (13)C NMR, and IR spectroscopy; differential scanning calorimetry; and elemental analysis. Additionally, the structures of the 3,5-diaminotriazolium and triaminoguanidinium 3,4,5-trinitropyrazolates were confirmed by single-crystal X-ray diffraction. Based on the measured densities and calculated heats of formation, the detonation performances (pressure: 23.74-31.89 GPa; velocity: 7586-8543 ms(-1); Cheetah 5.0) of the 3,4,5-trinitropyrazolate salts are comparable with 1,3,5-triamino-2,4,6-trinitrobenzene (TATB; 31.15 GPa and 8114 ms(-1)). Impact sensitivities were determined to be no less than 35 J by hammer tests, which places these salts in the insensitive class. PMID:20661962

  10. Crystal structures of three 3,4,5-tri-meth-oxy-benzamide-based derivatives.

    PubMed

    Gomes, Ligia R; Low, John Nicolson; Oliveira, Catarina; Cagide, Fernando; Borges, Fernanda

    2016-05-01

    The crystal structures of three benzamide derivatives, viz. N-(6-hy-droxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C16H25NO5, (1), N-(6-anilinohex-yl)-3,4,5-tri-meth-oxy-benzamide, C22H30N2O4, (2), and N-(6,6-di-eth-oxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C20H33NO6, (3), are described. These compounds differ only in the substituent at the end of the hexyl chain and the nature of these substituents determines the differences in hydrogen bonding between the mol-ecules. In each mol-ecule, the m-meth-oxy substituents are virtually coplanar with the benzyl ring, while the p-meth-oxy substituent is almost perpendicular. The carbonyl O atom of the amide rotamer is trans related with the amidic H atom. In each structure, the benzamide N-H donor group and O acceptor atoms link the mol-ecules into C(4) chains. In 1, a terminal -OH group links the mol-ecules into a C(3) chain and the combined effect of the C(4) and C(3) chains is a ribbon made up of screw related R 2 (2)(17) rings in which the ⋯O-H⋯ chain lies in the centre of the ribbon and the tri-meth-oxy-benzyl groups forms the edges. In 2, the combination of the benzamide C(4) chain and the hydrogen bond formed by the terminal N-H group to an O atom of the 4-meth-oxy group link the mol-ecules into a chain of R 2 (2)(17) rings. In 3, the mol-ecules are linked only by C(4) chains. PMID:27308017

  11. Percent solids measurement using Coriolis technology

    SciTech Connect

    Smith, S.; Schietinger, M.

    1995-12-31

    In many industrial processes, measurement of percent solids is vital to product quality. Percent solids values are most often derived form measurement of density, specific gravity and refractive index. In the lab and in the process, measurement methods range from nuclear and refractometer to vibrating tube. For on-line measurement, Coriolis technology, a vibrating tube approach, is playing a more significant role. Coriolis technology is best known for the performance and benefits it provides for direct mass flow measurement. This discussion focuses on Coriolis technology as an option for percent solids measurement and its ability to provide real-time data for controlling the process, maintaining consistency, improving quality, and controlling costs. The combined abilities of a Coriolis mass flowmeter to provide direct mass flow and percent solids information simultaneously provides real-time control that is unattainable with any other single technology.

  12. An evaluation of 10 percent and 20 percent benzocaine gels in patients with acute toothaches

    PubMed Central

    Hersh, Elliot V.; Ciancio, Sebastian G.; Kuperstein, Arthur S.; Stoopler, Eric T.; Moore, Paul A.; Boynes, Sean G.; Levine, Steven C.; Casamassimo, Paul; Leyva, Rina; Mathew, Tanya; Shibly, Othman; Creighton, Paul; Jeffers, Gary E.; Corby, Patricia M.A.; Turetzky, Stanley N.; Papas, Athena; Wallen, Jillian; Idzik-Starr, Cynthia; Gordon, Sharon M.

    2013-01-01

    Background The authors evaluated the efficacy and tolerability of 10 percent and 20 percent benzocaine gels compared with those of a vehicle (placebo) gel for the temporary relief of toothache pain. They also assessed the compliance with the label dose administration directions on the part of participants with toothache pain. Methods Under double-masked conditions, 576 participants self-applied study gel to an open tooth cavity and surrounding oral tissues. Participants evaluated their pain intensity and pain relief for 120 minutes. The authors determined the amount of gel the participants applied. Results The responders’ rates (the primary efficacy parameter), defined as the percentage of participants who had an improvement in pain intensity as exhibited by a pain score reduction of at least one unit on the dental pain scale from baseline for two consecutive assessments any time between the five- and 20-minute points, were 87.3 percent, 80.7 percent and 70.4 percent, respectively, for 20 percent benzocaine gel, 10 percent benzocaine gel and vehicle gel. Both benzocaine gels were significantly (P ≤ .05) better than vehicle gel; the 20 percent benzocaine gel also was significantly (P ≤ .05) better than the 10 percent benzocaine gel. The mean amount of gel applied was 235.6 milligrams, with 88.2 percent of participants applying 400 mg or less. Conclusions Both 10 percent and 20 percent benzocaine gels were more efficacious than the vehicle gel, and the 20 percent benzocaine gel was more efficacious than the 10 percent benzocaine gel. All treatments were well tolerated by participants. Practical Implications Patients can use 10 percent and 20 percent benzocaine gels to temporarily treat toothache pain safely. PMID:23633700

  13. 2,2\\',4,4\\',5-Pentabromodiphenyl ether (BDE-99)

    Integrated Risk Information System (IRIS)

    EPA / 635 / R - 07 / 006F www.epa.gov / iris TOXICOLOGICAL REVIEW OF 2,2 ' , 4,4 ' , 5 - PENTABROMODIPHENYL ETHER ( BDE - 99 ) ( CAS No . 60348 - 60 - 9 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) June 2008 U.S . Environmental Protection Agency Washington ,

  14. CURRICULUM GUIDE FOR SCIENCE, GRADES 4-5-6.

    ERIC Educational Resources Information Center

    GRAHAM, KATHRYN A.; AND OTHERS

    COURSE CONTENT, ACTIVITIES, AND REFERENCE INFORMATION FOR TEACHING SCIENCE IN GRADES 4, 5, AND 6 ARE INCLUDED IN THIS VOLUME. INTRODUCTORY REMARKS RELATE TO AN APPROACH TO TEACHING SCIENCE AND THE GENERAL OBJECTIVES OF THE SCIENCE PROGRAM. THE FIVE UNITS INCLUDED FOR GRADE 4 ARE (1) INSECTS AND SPIDERS, (2) LIVING THINGS OF SIMILAR AREAS, (3) THE…

  15. Multicultural Education Guide for Grades 4, 5, and 8.

    ERIC Educational Resources Information Center

    Millbrae School District, CA.

    This resource guide, prepared by teachers, is designed to incorporate minority group studies into the district's social studies curriculum at levels 4, 5, and 8 as a start toward goals specified in the state law. Introductory material discusses the California Education Code requirements, local district policy, and the work of the curriculum…

  16. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the complaint that is mailed to the invention promoter is returned undelivered, then the USPTO will primarily... in the Official Gazette and/or the Federal Register. The invention promoter will be given 30...

  17. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the complaint that is mailed to the invention promoter is returned undelivered, then the USPTO will primarily... in the Official Gazette and/or the Federal Register. The invention promoter will be given 30...

  18. 13. PRATT STREET BULKHEAD: SECTIONS 2, 3, 4, 5, AND ...

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

    13. PRATT STREET BULKHEAD: SECTIONS 2, 3, 4, 5, AND 6, DRAWER 10, PLAN NO. 1, 1 IN. = 15 FT. AND 1/2 IN. = 1 FT., APRIL 25, 1906, DRAWING SHOWS DESIGN FOR PRATT STREET BULKHEAD BETWEEN PIERS - Baltimore Inner Harbor, Pier 5, South of Pratt Street between Market Place & Concord Street, Baltimore, Independent City, MD

  19. 4.5 Doses to Patients in Diagnostics

    NASA Astrophysics Data System (ADS)

    Noßke, D.; Mattsson, S.; Johansson, L.

    This document is part of Subvolume A 'Fundamentals and Data in Radiobiology, Radiation Biophysics, Dosimetry and Medical Radiological Protection' of Volume 7 'Medical Radiological Physics' of Landolt-Börnstein - Group VIII 'Advanced Materials and Technologies'. It contains the Section '4.5 Doses to Patients in Diagnostics' of the Chapter '4 Dosimetry in Nuclear Medicine Diagnosis and Therapy' with the contents:

  20. Understanding the O4,5 edge structure of actinide metals

    SciTech Connect

    Butterfield, M; Moore, K; der Laan, G v; Wall, M; Haire, D

    2007-12-12

    Using electron energy-loss spectroscopy (EELS) and many-electron atomic spectral calculations, we examine the O{sub 4,5} (5d {yields} 5f) edge structure of the ground-state {alpha} phase of Th, U, Np, Pu, Am, and Cm metal. Results show that the dipole-allowed transitions are contained within the giant resonance and that the small pre-peak in the actinide 5d {yields} 5f transition should not be labeled the O{sub 5} peak, but rather the {Delta}S=1 peak. Lastly, we present for the first time the O{sub 4,5} EELS spectra for Np, Am, and Cm metal.

  1. Heat treatment effects on tensile properties of V-(4-5) wt.% Cr-(4-5) wt.% Ti alloys

    SciTech Connect

    Natesan, K.; Soppet, W.K.

    1997-08-01

    Effects of thermomechanical treatments on microstructures and mechanical properties are of interest for long term application of V-Cr-Ti alloys in fusion reactor systems. Influence of thermal annealing at 1050{degrees}C on stress/strain behavior, maximum engineering strength, and uniform and total elongation were evaluated. The results show that multiple annealing has minimal effect on the tensile properties of V-(4-5)Cr-(4-5)Ti alloys tested at room temperature and at 500{degrees}C.

  2. Degradation of 2,4,5-trichlorophenol by the lignin-degrading basidiomycete Phanerochaete chrysosporium.

    PubMed Central

    Joshi, D K; Gold, M H

    1993-01-01

    Under secondary metabolic conditions the white rot basidiomycete Phanerochaete chrysosporium rapidly mineralizes 2,4,5-trichlorophenol. The pathway for degradation of 2,4,5-trichlorophenol was elucidated by the characterization of fungal metabolites and oxidation products generated by purified lignin peroxidase (LiP) and manganese peroxidase (MnP). The multistep pathway involves cycles of peroxidase-catalyzed oxidative dechlorination reactions followed by quinone reduction reactions to yield the key intermediate 1,2,4,5-tetrahydroxybenzene, which is presumably ring cleaved. In the first step of the pathway, 2,4,5-trichlorophenol is oxidized to 2,5-dichloro-1,4-benzoquinone by either MnP or Lip. 2,5-Dichloro-1,4-benzoquinone is then reduced to 2,5-dichloro-1,4-hydroquinone. The 2,5-dichloro-1,4-hydroquinone is oxidized by MnP to generate 5-chloro-4-hydroxy-1,2-benzoquinone. The orthoquinone is in turn reduced to 5-chloro-1,2,4-trihydroxybenzene. Finally, the 5-chlorotrihydroxybenzene undergoes another cycle of oxidative dechlorination and reduction reactions to generate 1,2,4,5-tetrahydroxybenzene. The latter is presumably ring cleaved, with subsequent degradation to CO2. In this pathway, the substrate is oxidatively dechlorinated by LiP or MnP in a reaction which produces a quinone. The quinone intermediate is recycled by a reduction reaction to regenerate an intermediate which is again a substrate for peroxidase-catalyzed oxidative dechlorination. This pathway apparently results in the removal of all three chlorine atoms before ring cleavage occurs. PMID:8328802

  3. 4.5 Meter high level waste canister study

    SciTech Connect

    Calmus, R. B.

    1997-10-01

    The Tank Waste Remediation System (TWRS) Storage and Disposal Project has established the Immobilized High-Level Waste (IBLW) Storage Sub-Project to provide the capability to store Phase I and II BLW products generated by private vendors. A design/construction project, Project W-464, was established under the Sub-Project to provide the Phase I capability. Project W-464 will retrofit the Hanford Site Canister Storage Building (CSB) to accommodate the Phase I I-ILW products. Project W-464 conceptual design is currently being performed to interim store 3.0 m-long BLW stainless steel canisters with a 0.61 in diameter, DOE is considering using a 4.5 in canister of the same diameter to reduce permanent disposal costs. This study was performed to assess the impact of replacing the 3.0 in canister with the 4.5 in canister. The summary cost and schedule impacts are described.

  4. The NIF 4.5-m nTOF Detectors

    SciTech Connect

    Moran, M J; Bond, E J; Clancy, T J; Eckart, M J; Khater, H Y; Glebov, V Y

    2012-05-07

    The first several campaigns of laser fusion experiments at the National Ignition Facility (NIF) included a family of high-sensitivity scintillator/photodetector neutron-time-of-flight (nTOF) detectors for measuring DD and DT neutron yields. The detectors provided consistent neutron yield benchmarks from below 1E9 (DD) to nearly 1E15 (DT). The detectors demonstrated DT yield measurement precisions better than 5%, but the absolute accuracy relies on cross calibration with independent measurements of absolute neutron yield. The 4.5-m nTOF data have provided a useful testbed for testing improvements in nTOF data processing, especially with respect to improving the accuracies of the detector impulse response functions. The resulting improvements in data analysis methods have produced more accurate results. In summary, results from the NIF 4.5-m nTOF detectors have provided consistent measurements of DD and DT neutron yields from laser-fusion implosions.

  5. New 4,5-dichlorophthalhydrazidate-bridged chained coordination polymers

    NASA Astrophysics Data System (ADS)

    Jin, Juan; Wu, Di; Jia, Ming-Jun; Peng, Yu; Yu, Jie-Hui; Wang, Yu-Chang; Xu, Ji-Qing

    2011-03-01

    The hydrothermal self-assemblies of Pb 2+/Cd 2+ salt, 4,5-dichlorophthalic acid (dcpha), N 2H 4·H 2O together with 1,10-phenanthroline·H 2O (phen) or 2,2'-bipyridine (bpy) generated two new monoacylhydrazidate-bridged 1-D chained coordination polymers [Pb 2(DCPTH) 4(phen) 2] 1 and [Cd 3(DCPTH) 2(dcph) 2(bpy) 2] 2 (DCPTH=4,5-dichlorophthalhydrazidate, dcph=4,5-dichlorophthalate). The monoacylhydrazidate ligand DCPTH originated from the hydrothermal in situ acylation reaction between dcpha and N 2H 4·H 2O. In compound 1, two types of coordination modes for DCPTH are found, which link alternately the Pb(II) centers into a 1-D chain structure of compound 1 with ancillary phen molecules. In compound 2, DCPTH and dcph as the mixed bridges extend the Cd(II) centers into a 1-D chain structure of compound 2 with auxiliary bpy molecules. DCPTH in compound 2 shows a different coordination mode from those observed in compound 1.

  6. Analysis of the Rotational Spectra of 2,3,4,5,6-PENTAFLUOROTOLUENE and 1-CHLORO-2,3,4,5,6-PENTAFLUOROBENZENE

    NASA Astrophysics Data System (ADS)

    Osthoff, Ashley A.; Peebles, Rebecca A.; Peebles, Sean A.; Grubbs, Garry S. Grubbs, II; Cooke, Stephen A.; Pate, Brooks H.; Neill, Justin L.; Muckle, Matt T.

    2009-06-01

    The microwave spectra of two substituted pentafluorobenzenes have been obtained. 2,3,4,5,6-Pentafluorotoluene was measured using the FTMW spectrometer at Eastern Illinois University and the chirped-pulse FTMW spectrometer at University of North Texas. The heavy atom structure has been obtained from the assigned ^{13}C transitions and is in reasonable agreement with ab initio calculations at the MP2/6-311++G(2d, 2p) level. The ground state rotational constants are A = 1036.61253(10) MHz, B = 1030.94126(10) MHz, and C = 516.92062(9) MHz, and the single dipole moment component is μ_b = 1.98(17) D. Very small splittings for many of the assigned transitions and multiple, as yet unassigned, lines were presumably due to excited torsional states of the methyl group. In a related study, the microwave spectrum of 1-chloro-2,3,4,5,6-pentafluorobenzene was obtained for both the ^{35}Cl and the ^{37}Cl isotopologues using the chirped-pulse microwave spectrometer at University of Virginia. The preliminary ground state rotational constants for this compound are A = 1028.5403(14) MHz, B = 751.8198(3) MHz and C = 434.3533(4) MHz for ^{35}Cl and A = 1028.5435(7) MHz, B = 734.4786(2) MHz and C = 428.5082(2) MHz for ^{37}Cl. Initial fits of the nuclear quadrupole coupling constants give χ_{aa} = -79.512(15) MHz, χ_{bb} = 43.593(8) MHz, χ_{cc} = 35.92(2) MHz for the ^{35}Cl species and χ_{aa} = -62.68(2) MHz, χ_{bb} = 34.38(4) MHz, χ_{cc} = 28.29(17) MHz for the ^{37}Cl species. These results will be compared with pentafluorotoluene to observe the effects on the structure of the benzene ring when substituting a chlorine atom for a methyl group.

  7. Estimating a percent reduction in load

    NASA Astrophysics Data System (ADS)

    Millard, Steven P.

    This article extends the work of Cohn et al. [1989] on estimating constituent loads to the problem of estimating a percent reduction in load. Three estimators are considered: the maximum likelihood (MLE), a ``bias-corrected'' maximum likelihood (BCMLE), and the minimum variance unbiased (MVUE). In terms of root-mean-square error, both the MVUE and BCMLE are superior to the MLE, and for the cases considered here there is no appreciable difference between the MVUE and the BCMLE. The BCMLE is constructed from quantities computed by most regression packages and is therefore simpler to compute than the MVUE (which involves approximating an infinite series). All three estimators are applied to a case study in which an agricultural tax in the Everglades agricultural area is tied to an observed percent reduction in phosphorus load. For typical hydrological data, very large sample sizes (of the order of 100 observations each in the baseline period and after) are required to estimate a percent reduction in load with reasonable precision.

  8. Software for the Canadian Advanced Nanospace eXperiment-4/5 (CanX-4/-5) Mission

    NASA Astrophysics Data System (ADS)

    Leonard, Matthew Leigh

    The CanX-4 and CanX-5 mission currently under development at The University of Toronto Institute for Aerospace Studies Space Flight Laboratory UTIAS/SFL is a challenging formation flying technology demonstration. Its requirements of sub-metre control accuracy have yet to be realized with nanosatellites. Many large technical challenges must be addressed in order to ensure the success of the CanX-4/5 mission. This includes the development of software for an intersatellite communication system, integration and optimization of key formation flying algorithms onto the Payload On-Board Computer as well as the development of a Hardware-In-The-Loop simulator for full on-orbit mission simulations. This thesis will provide background knowledge of the Space Flight Laboratory and its activities, the CanX-4/5 mission, and finally highlight the authors contributions to overcoming each of these technical challenges and ensuring the success of the CanX-4 and CanX-5 mission.

  9. Influence of lipolysis on the mobilization of 2,4,5,2'4',5'-hexachlorobiphenyl from adipocytes in vitro

    SciTech Connect

    Gallenberg, L.A.; Ring, B.J.; Vodicnik, M.J.

    1987-01-01

    Epididymal adipocytes, isolated from rats pretreated with (/sup 14/C)-2,4,5,2',4',5'-hexachlorobiphenyl (6-CB), were utilized to examine the relationship between the mobilization of lipid and 6-CB and to determine whether 6-CB was differentially associated with subcellular organelles over time as has been demonstrated for newly synthesized lipid. Lipolysis, depleted approximately 1% of total cellular triacylglycerols (TG) regardless of time from treatment with 6-CB. The percentage of cellular 6-CB released from adipocytes to incubation buffer infranatants was not correlated with the magnitude of lipolysis produced over the 50-min incubation period; nor was the percentage of 6-CB released to the buffers correlated with the length of the incubation period, regardless of the presence of ISO. Although adipocytes responded similarly to lipolytic stimuli independent of time (days) since 6-CB treatment, significant decreases were found in the percentage of 6-CB released from adipocytes over time. The in vitro labeling of this newly synthesized TG in fat cells with (U-/sup 14/C)glucose or (1-/sup 14/C)palmitate demonstrated that TG was differentially distributed among adipocyte organelles. Newly synthesized TG was also the first to be mobilized under lipolytic stimulus. 6-CB was not released in a similar fashion, since radioactivity associated with the chemical levels of (/sup 14/C)-6-CB and glucose-derived /sup 14/C in buffers were not correlated over time.

  10. ED case managers save $4.5 million.

    PubMed

    2011-08-01

    Emergency department case managers at Lee Memorial Health System in Fort Myers, FL saved more than $4.5 million by ensuring that patients were in the right status and transferring patients who did not meet admission criteria to a more appropriate level of care. Case managers and social workers cover the emergency department at peak hours, seven days a week. Case managers screen patients for admission criteria and make sure admission orders are complete and correct. Case managers and social workers coordinate community services and placement for patients who don't meet admission criteria. Social workers intervene when there are concerns about abuse and neglect, and they facilitate placement to other acute care facilities. PMID:21789904

  11. Inositol 1,4,5-trisphosphate induced calcium waves

    NASA Astrophysics Data System (ADS)

    Falcke, M.

    Traveling waves of high concentration of Ca2+ are observed in many different cells and have attracted great interest in experimental and theoretical biological research in recent years. They are created by the nonlinear dynamics of the release and uptake of Ca2+ by intracellular Ca2+ stores like the endoplasmatic or sarcoplasmatic reticulum. Their characteristics depend on other cellular organelles and components like mitochondria and Ca2+ buffers too. Here, we present some mathematical models and results of recent research on intracellular Ca2+ waves generated by the inositol 1,4,5-trisphosphate receptor channel including the modeling of Calcium induced Calcium release, buffer dynamics, impact of mitochondria on wave formation and the effect of the spatial discreteness of the channels releasing Ca2+. Modeling of the communication of Ca2+ waves to adjacent cells through gap junctions concludes this report.

  12. A mechanistic study of the photodegradation of herbicide 2,4,5-trichlorophenoxyacetic acid in aqueous solution.

    PubMed

    Yurkova, Maria P; Pozdnyakov, Ivan P; Plyusnin, Victor F; Grivin, Vycheslav P; Bazhin, Nikolay M; Kruppa, Alexandr I; Maksimova, Tatiana A

    2013-04-01

    Photodegradation of herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in aqueous solution was investigated by stationary (254 nm) and nanosecond laser (266 nm) flash photolysis techniques. It was shown that in the primary photochemical step both photoionization (which generates a hydrated electron-radical cation pair) and heterolytic cleavage of a C-Cl bond takes place. The major products of substitution of one of the chlorine atoms in the 2-, 4- or 5-position by a hydroxyl group as well as the products of hydroxylation of the benzene ring in 3- and 6-positions were identified by HPLC and LC-MS methods. The complexation of 2,4,5-T with β- and γ-cyclodextrins (β(γ)CD) was investigated. The influence of such complexation on the quantum yield of herbicide photolysis and on the ratio of photodegradation products was determined. PMID:23085749

  13. Intracellular calcium channels: inositol-1,4,5-trisphosphate receptors

    PubMed Central

    Fedorenko, Olena A.; Popugaeva, Elena; Enomoto, Masahiro; Stathopulos, Peter B.; Ikura, Mitsuhiko; Bezprozvanny, Ilya

    2014-01-01

    The inositol-1,4,5-trisphosphate receptors (InsP3Rs) are the major intracellular Ca2+-release channels in cells. Activity of InsP3Rs is essential for elementary and global Ca2+ events in the cell. There are three InsP3Rs isoforms that are present in mammalian cells. In this review review we will focus primarily on InsP3R type 1. The InsP3R1 is a predominant isoform in neurons and it is most extensively studied isoform. Combination of biophysical and structural methods revealed key mechanisms of InsP3R function and modulation. Cell biological and biochemical studies lead to identification of a large number of InsP3R-binding proteins. InsP3Rs are involved in the regulation of numerous physiological processes, including learning and memory, proliferation, differentiation, development and cell death. Malfunction of InsP3R1 play a role in a number of neurodegenerative disorders and other disease states. InsP3Rs represent a potentially valuable drug target for treatment of these disorders and for modulating activity of neurons and other cells. Future studies will provide better understanding of physiological functions of InsP3Rs in health and disease. PMID:24300389

  14. 4.5-kW Hall Effect Thruster Evaluated

    NASA Technical Reports Server (NTRS)

    Mason, Lee S.

    2000-01-01

    As part of an Interagency Agreement with the Air Force Research Lab (AFRL), a space simulation test of a Russian SPT 140 Hall Effect Thruster was completed in September 1999 at Vacuum Facility 6 at the NASA Glenn Research Center at Lewis Field. The thruster was subjected to a three-part test sequence that included thrust and performance characterization, electromagnetic interference, and plume contamination. SPT 140 is a 4.5-kW thruster developed under a joint agreement between AFRL, Atlantic Research Corp, and Space Systems/Loral, and was manufactured by the Fakal Experimental Design Bureau of Russia. All objectives were satisfied, and the thruster performed exceptionally well during the 120-hr test program, which comprised 33 engine firings. The Glenn testing provided a critical contribution to the thruster development effort, and the large volume and high pumping speed of this vacuum facility was key to the test s success. The low background pressure (1 10 6 torr) provided a more accurate representation of space vacuum than is possible in most vacuum chambers. The facility had been upgraded recently with new cryogenic pumps and sputter shielding to support the active electric propulsion program at Glenn. The Glenn test team was responsible for all test support equipment, including the thrust stand, power supplies, data acquisition, electromagnetic interference measurement equipment, and the contamination measurement system.

  15. How I Love My 80 Percenters

    NASA Technical Reports Server (NTRS)

    Maturo, Anthony J.

    2002-01-01

    Don't ever take your support staff for granted. By support staff, I mean the people in personnel, logistics, and finance; the ones who can make things happen with a phone call or a signature, or by the same token frustrate you to no end by their inaction; these are people you must depend on. I've spent a lot of time thinking about how to cultivate relationships with my support staff that work to the advantage of both of us. The most important thing that have learned working with people, any people--and I will tell you how I learned this in a minute--is there are some folks you just can't motivate, so forget it, don't try; others you certainly can with a little psychology and some effort; and the best of the bunch, what I call the 80 percenters, you don't need to motivate because they're already on the team and performing beautifully. The ones you can't change are rocks. Face up to it, and just kick them out of your way. I have a reputation with the people who don't want to perform or be part of the team. They don't come near me. If someone's a rock, I pick up on it right away, and I will walk around him or her to find someone better. The ones who can be motivated I take time to nurture. I consider them my projects. A lot of times these wannabes are people who want to help but don't know how. Listen, you can work with them. Lots of people in organizations have the mindset that all that matters are the regulations. God forbid if you ever work outside those regulations. They've got one foot on that regulation and they're holding it tight like a baby holds a blanket. What you're looking for is that first sign that their minds are opening. Usually you hear it in their vocabulary. What used to sound like "We can't do that ... the regulations won't allow it ... we have never done this before," well, suddenly that changes to "We have options ... let's take a look at the options ... let me research this and get back to you." The 80 percenters you want to nurture too, but

  16. Dendrite growth morphologies in rapidly solidified Al-4.5wt.%Cu droplets

    NASA Astrophysics Data System (ADS)

    Bedel, M.; Reinhart, G.; Bogno, A.-A.; Nguyen-Thi, H.; Boller, E.; Gandin, Ch-A.; Henein, H.

    2016-03-01

    The impulse atomization process developed at the University of Alberta (Canada) enables metallic powders to be solidified with controlled process parameters and improved properties. In order to investigate the microstructure morphologies in droplets of Al- 4.5wt.%Cu alloys, three-dimensional reconstructions of several droplets are obtained by using synchrotron X-ray micro-tomography, allowing a visualization of the inner microstructure in three dimensions. The analysis of the reconstructed volumes reveals that a wide range of morphology, from highly branched to “finger-bundle”, can be obtained for different droplets of similar diameter and produced in the same batch. Unexpectedly for this alloy, microstructural features also indicate that the development of the dendrite arms (primary and of higher orders) occurs in most droplets along <111> crystallographic axes, instead of the usual <100> directions observed in conventional casting technologies.

  17. VLF study of low magnitude Earthquakes (4.5

    NASA Astrophysics Data System (ADS)

    Wolbang, Daniel; Biernat, Helfried; Schwingenschuh, Konrad; Eichelberger, Hans; Prattes, Gustav; Besser, Bruno; Boudjada, Mohammed; Rozhnoi, Alexander; Solovieva, Maria; Biagi, Pier Francesco; Friedrich, Martin

    2014-05-01

    In the course of the European VLF/LF radio receiver network (International Network for Frontier Research on Earthquake Precursors, INFREP), radio signals in the frequency range from 10-50 kilohertz are received, continuously recorded (temporal resolution 20 seconds) and analyzed in the Graz/Austria knot. The radio signals are generated by dedicated distributed transmitters and detected by INFREP receivers in Europe. In case the signal is crossing an earthquake preparation zone, we are in principle able to detect seismic activity if the signal to noise ratio is high enough. The requirements to detect a seismic event with the radio link methods are given by the magnitude M of the Earthquake (EQ), the EQ preparation zone and the Fresnel zone. As pointed out by Rozhnoi et al. (2009), the VLF methods are suitable for earthquakes M>5.0. Furthermore, the VLF/LF radio link gets only disturbed if it is crossing the EQ preparation zone which is described by Molchanov et al. (2008). In the frame of this project I analyze low seismicity EQs (M≤5.6) in south/eastern Europe in the time period 2011-2013. My emphasis is on two seismic events with magnitudes 5.6 and 4.8 which we are not able to adequately characterize using our single parameter VLF method. I perform a fine structure analysis of the residua of various radio links crossing the area around the particular 2 EQs. Depending on the individual paths not all radio links are crossing the EQ preparation zone directly, so a comparative study is possible. As a comparison I analyze with the same method the already good described EQ of L'Aquila/Italy in 2009 with M=6.3 and radio links which are crossing directly the EQ preparation zone. In the course of this project we try to understand in more detail why it is so difficult to detect EQs with 4.5

  18. Molecular Determinants of Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2) Binding to Transient Receptor Potential V1 (TRPV1) Channels*

    PubMed Central

    Poblete, Horacio; Oyarzún, Ingrid; Olivero, Pablo; Comer, Jeffrey; Zuñiga, Matías; Sepulveda, Romina V.; Báez-Nieto, David; González Leon, Carlos; González-Nilo, Fernando; Latorre, Ramón

    2015-01-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been recognized as an important activator of certain transient receptor potential (TRP) channels. More specifically, TRPV1 is a pain receptor activated by a wide range of stimuli. However, whether or not PI(4,5)P2 is a TRPV1 agonist remains open to debate. Utilizing a combined approach of mutagenesis and molecular modeling, we identified a PI(4,5)P2 binding site located between the TRP box and the S4-S5 linker. At this site, PI(4,5)P2 interacts with the amino acid residues Arg-575 and Arg-579 in the S4-S5 linker and with Lys-694 in the TRP box. We confirmed that PI(4,5)P2 behaves as a channel agonist and found that Arg-575, Arg-579, and Lys-694 mutations to alanine reduce PI(4,5)P2 binding affinity. Additionally, in silico mutations R575A, R579A, and K694A showed that the reduction in binding affinity results from the delocalization of PI(4,5)P2 in the binding pocket. Molecular dynamics simulations indicate that PI(4,5)P2 binding induces conformational rearrangements of the structure formed by S6 and the TRP domain, which cause an opening of the lower TRPV1 channel gate. PMID:25425643

  19. Ion channel regulation by phosphoinositides analyzed with VSPs—PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility

    PubMed Central

    Rjasanow, Alexandra; Leitner, Michael G.; Thallmair, Veronika; Halaszovich, Christian R.; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs. PMID

  20. DRINKING WATER CRITERIA DOCUMENT FOR 2(2,4,5-TRICHLOROPHENOXY)PROPIONIC ACID (2,4,5-TP) (FINAL DRAFT)

    EPA Science Inventory

    The Office of Drinking Water (ODW), U.S. Environmental Protection Agency has prepared a Drinking Water Criteria Document on 2,4,5-TP. This Criteria Document is an extensive review of the following topics: Physical and chemical properties of 2,4,5-TP; Toxicokinetics and human expo...

  1. Synthesis of pyrimido[4,5-c]azepine- and pyrimido[4,5-c]oxepine-based γ-secretase modulators.

    PubMed

    Wu, Yong-Jin; Zhang, Yunhui; Toyn, Jeremy H; Macor, John E; Thompson, Lorin A

    2016-03-15

    This Letter describes an efficient ring-closing metathesis approach to 2-chloro-4-amino-pyrimido[4,5-c]azepines and 2-chloro-4-amino-pyrimido[4,5-c]oxepines. These chlorides were applied to the synthesis of several potent γ-secretase modulators (GSMs). PMID:26898338

  2. DISTRIBUTION OF 2,4,5-TRICHLOROPHENOXYACETIC ACID IN THE MOUSE FETUS

    EPA Science Inventory

    The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) readily crosses the placenta in the mouse on gestational day 13. Concentrations of 2,4,5-T in maternal tissues and fetuses were obvious at 30 min., highest at 8 h, diminished by 24 h and almost entirely eliminated by 48 h....

  3. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  4. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  5. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  6. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  7. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  8. 42 CFR 4.5 - Use of materials from the collections.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Use of materials from the collections. 4.5 Section 4.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.5 Use of materials from the collections. (a) Unrestricted...

  9. 42 CFR 4.5 - Use of materials from the collections.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Use of materials from the collections. 4.5 Section 4.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.5 Use of materials from the collections. (a) Unrestricted...

  10. 42 CFR 4.5 - Use of materials from the collections.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Use of materials from the collections. 4.5 Section 4.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.5 Use of materials from the collections. (a) Unrestricted...

  11. One-Pot Synthesis of Benzo[4,5]imidazo[2,1-a]isoquinolines and Isoquinolino[3,4-b]quinoxalines via Tandem Cyclization Strategies.

    PubMed

    Bagdasarian, Alex L; Nguyen, Huy H; Palazzo, Teresa A; Fettinger, James C; Haddadin, Makhluf J; Kurth, Mark J

    2016-05-01

    Two operationally simple one-pot protocols have been developed for the synthesis of amino-functionalized benzo[4,5]imidazo[2,1-a]isoquinolines and isoquinolino[3,4-b]quinoxalines. Optimization data and substrate scope for these atom-economical transformations, which engage commercially available o-phenylenediamines and o-cyanobenzaldehydes, are discussed. PMID:27030441

  12. Structure and Catalytic Mechanism of 3-Ketosteroid-Δ4-(5α)-dehydrogenase from Rhodococcus jostii RHA1 Genome*

    PubMed Central

    van Oosterwijk, Niels; Knol, Jan; Dijkhuizen, Lubbert; van der Geize, Robert; Dijkstra, Bauke W.

    2012-01-01

    3-Ketosteroid Δ4-(5α)-dehydrogenases (Δ4-(5α)-KSTDs) are enzymes that introduce a double bond between the C4 and C5 atoms of 3-keto-(5α)-steroids. Here we show that the ro05698 gene from Rhodococcus jostii RHA1 codes for a flavoprotein with Δ4-(5α)-KSTD activity. The 1.6 Å resolution crystal structure of the enzyme revealed three conserved residues (Tyr-319, Tyr-466, and Ser-468) in a pocket near the isoalloxazine ring system of the FAD co-factor. Site-directed mutagenesis of these residues confirmed that they are absolutely essential for catalytic activity. A crystal structure with bound product 4-androstene-3,17-dione showed that Ser-468 is in a position in which it can serve as the base abstracting the 4β-proton from the C4 atom of the substrate. Ser-468 is assisted by Tyr-319, which possibly is involved in shuttling the proton to the solvent. Tyr-466 is at hydrogen bonding distance to the C3 oxygen atom of the substrate and can stabilize the keto-enol intermediate occurring during the reaction. Finally, the FAD N5 atom is in a position to be able to abstract the 5α-hydrogen of the substrate as a hydride ion. These features fully explain the reaction catalyzed by Δ4-(5α)-KSTDs. PMID:22833669

  13. Control of diverse subcellular processes by a single multi-functional lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2].

    PubMed

    Kolay, Sourav; Basu, Urbashi; Raghu, Padinjat

    2016-06-15

    Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a multi-functional lipid that regulates several essential subcellular processes in eukaryotic cells. In addition to its well-established function as a substrate for receptor-activated signalling at the plasma membrane (PM), it is now recognized that distinct PI(4,5)P2 pools are present at other organelle membranes. However, a long-standing question that remains unresolved is the mechanism by which a single lipid species, with an invariant functional head group, delivers numerous functions without loss of fidelity. In the present review, we summarize studies that have examined the molecular processes that shape the repertoire of PI(4,5)P2 pools in diverse eukaryotes. Collectively, these studies indicate a conserved role for lipid kinase isoforms in generating functionally distinct pools of PI(4,5)P2 in diverse metazoan species. The sophistication underlying the regulation of multiple functions by PI(4,5)P2 is also shaped by mechanisms that regulate its availability to enzymes involved in its metabolism as well as molecular processes that control its diffusion at nanoscales in the PM. Collectively, these mechanisms ensure the specificity of PI(4,5)P2 mediated signalling at eukaryotic membranes. PMID:27288030

  14. All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane

    NASA Astrophysics Data System (ADS)

    Keddie, Neil S.; Slawin, Alexandra M. Z.; Lebl, Tomas; Philp, Douglas; O'Hagan, David

    2015-06-01

    The highest-energy stereoisomer of 1,2,3,4,5,6-hexafluorocyclohexane, in which all of the fluorines are ‘up’, is prepared in a 12-step protocol. The molecule adopts a classic chair conformation with alternate C-F bonds aligned triaxially, clustering three highly electronegative fluorine atoms in close proximity. This generates a cyclohexane with a high molecular dipole (μ = 6.2 D), unusual in an otherwise aliphatic compound. X-ray analysis indicates that the intramolecular Fax···Fax distances (˜2.77 Å) are longer than the vicinal Fax···Feq­ distances (˜2.73 Å) suggesting a tension stabilizing the chair conformation. In the solid state the molecules pack in an orientation consistent with electrostatic ordering. Our synthesis of this highest-energy isomer demonstrates the properties that accompany the placement of axial fluorines on a cyclohexane and the unusual property of a facially polarized ring in organic chemistry. Derivatives have potential as new motifs for the design of functional organic molecules or for applications in supramolecular chemistry design.

  15. Molecular structure, spectroscopic and DFT computational studies on 4,5-bis(tert-butylsulfanyl)phthalonitrile

    NASA Astrophysics Data System (ADS)

    Tanak, H.

    2015-06-01

    The molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO) 1H and 13C NMR chemical shift values of 4,5-bis(tert-butylsulfanyl)phthalonitrile in the ground state were calculated using the density functional method (B3LYP) with 6-311++G(d,p) basis set. The calculated results show that the optimized geometry can well reproduce the crystal structure, and the theoretical vibrational frequencies and chemical shift values show good agreement with experimental values. To investigate the NLO properties of the title compound, the electric dipole moment (μ), the polarizability (α) and the first hyperpolarizability (β) were calculated using the density functional B3LYP method with the 6-311++G(d,p) basis set. For the results, the title compound shows nonzero (β) value revealing second order NLO behavior. The molecular electrostatic potential (MEP) at the B3LYP/6-311++G(d,p) basis optimized geometry has also been calculated to predict reactive sites for electrophilic or nucleophilic attack for the title compound.

  16. Fe L-shell lines from n (n=4, 5, 6) to 2 transitions

    NASA Astrophysics Data System (ADS)

    Chen, H.; Beiersdorfer, P.; Brown, G.; Behar, E.

    2003-03-01

    Fe L-shell emission lines at wavelengths less than 10 angstroms come from n (n great than 3) to 2 transitions. These lines embed information such as electron density and temperature that is of fundamental importance to understanding the physics of astrophysical objects. Unresolved by previous x-ray observatories, these low wavelength Fe lines are clearly observable by Chandra and XMM x-ray satellites. To meet the needs of using these lines as diagnostics, we have studied the n to 2 transitions (n = 4, 5, 6) Fe L-shell lines using the atomic codes HULLAC and FAC. Using the LLNL electron beam ion trap, we also made laboratory measurements for this wavelength region, following the success of our Fe L-shell emission lines for the 3-2 transitions (Brown et al, APJ supp. 2002). Our measurements and their comparison with code simulations will be reported, together with a discussion of the possible use of these low wavelength lines as diagnostics for astrophysics. This work was performed under the auspices of the U.S. DOE by LLNL under contract No. W-7405-Eng-48 and supported by NASA SARA grants to LLNL, GSFC, and Columbia University.

  17. n-3 polyunsaturated fatty acids suppress CD4(+) T cell proliferation by altering phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] organization.

    PubMed

    Hou, Tim Y; Barhoumi, Rola; Fan, Yang-Yi; Rivera, Gonzalo M; Hannoush, Rami N; McMurray, David N; Chapkin, Robert S

    2016-01-01

    The mechanisms by which n-3 polyunsaturated fatty acids (n-3 PUFA), abundant in fish oil, exert their anti-inflammatory effects have not been rigorously defined. We have previously demonstrated that n-3 PUFA decrease the amount of phosphatidylinositol-(4,5)-bisphosphate, [PI(4,5)P2], in CD4(+) T cells, leading to suppressed actin remodeling upon activation. Since discrete pools of PI(4,5)P2 exist in the plasma membrane, we determined whether n-3 PUFA modulate spatial organization of PI(4,5)P2 relative to raft and non-raft domains. We used Förster resonance energy transfer (FRET) to demonstrate that lipid raft mesodomains in the plasma membrane of CD4(+) T cells enriched in n-3 PUFA display increased co-clustering of Lck(N10) and LAT(ΔCP), markers of lipid rafts. CD4(+) T cells enriched in n-3 PUFA also exhibited a depleted plasma membrane non-raft PI(4,5)P2 pool as detected by decreased co-clustering of Src(N15), a non-raft marker, and PH(PLC-δ), a PI(4,5)P2 reporter. Incubation with exogenous PI(4,5)P2 rescued the effects on the non-raft PI(4,5)P2 pool, and reversed the suppression of T cell proliferation in CD4(+) T cells enriched with n-3 PUFA. Furthermore, CD4(+) T cells isolated from mice fed a 4% docosahexaenoic acid (DHA)-enriched diet exhibited a decrease in the non-raft pool of PI(4,5)P2, and exogenous PI(4,5)P2 reversed the suppression of T cell proliferation. Finally, these effects were not due to changes to post-translational lipidation, since n-3 PUFA did not alter the palmitoylation status of signaling proteins. These data demonstrate that n-3 PUFA suppress T cell proliferation by altering plasma membrane topography and the spatial organization of PI(4,5)P2. PMID:26476105

  18. 2-(4-Meth-oxy-phen-yl)-1-pentyl-4,5-di-phenyl-1H-imidazole.

    PubMed

    Simpson, Jim; Mohamed, Shaaban K; Marzouk, Adel A; Talybov, Avtandil H; Abdelhamid, Antar A

    2013-01-01

    The title compound, C27H28N2O, is a lophine (2,4,5-triphenyl-1H-imidazole) derivative with an n-pentyl chain on the amine N atom and a 4-meth-oxy substituent on the benzene ring. The two phenyl and meth-oxy-benzene rings are inclined to the imidazole ring at angles of 25.32 (7), 76.79 (5) and 35.42 (7)°, respectively, while the meth-oxy substituent lies close to the plane of its benzene ring, with a maximum deviation of 0.126 (3) Å for the meth-oxy C atom. In the crystal, inversion dimers linked by pairs of C-H⋯O hydrogen bonds generate R2(2)(22) loops. These dimers are stacked along the a-axis direction. PMID:23476433

  19. 1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

    PubMed Central

    Mielgo, Antonia

    2016-01-01

    Summary Asymmetric catalysis represents a very powerful tool for the synthesis of enantiopure compounds. In this context the main focus has been directed not only to the search for new efficient chiral catalysts, but also to the development of efficient pronucleophiles. This review highlights the utility and first examples of 1H-imidazol-4(5H)-ones and thiazol-4(5H)-ones as pronucleophiles in catalytic asymmetric reactions. PMID:27340482

  20. Isopropyl­aminium 2-carb­oxy-4,5-di­chloro­benzoate

    PubMed Central

    Smith, Graham; Wermuth, Urs D.

    2010-01-01

    In the structure of the 1:1 proton-transfer compound of isopropyl­amine with 4,5-dichloro­phthalic acid, C3H10N+·C8H3Cl2O4 −, the three cation H-atom donors associate with three separate carboxyl O-atom anion acceptors, giving conjoint cyclic R 4 4(12), R 4 4(16) hydrogen-bonding cation–anion inter­actions in a one-dimensional ribbon structure. In the anions, the carboxyl groups lie slightly out of the plane of the benzene ring [maximum deviations = 0.439 (1) for a carboxylic acid O atom and 0.433 (1) Å for a carboxyl­ate O atom]. However, the syn-related proton of the carboxylic acid group forms the common short intra­molecular O—H⋯Ocarbox­yl hydrogen bond. PMID:21580024

  1. Specific receptor for inositol-1,4,5-trisphosphate in permeabilized rabbit neutrophils

    SciTech Connect

    Bradford, P.G.; Spat, A.; Rubin, R.P.

    1986-03-05

    Neutrophil chemotaxis and degranulation are resultant, in part, from the mobilization of intracellular calcium by inositol-1,4,5-trisphosphate ((1,4,5)IP/sub 3/), one of the products of chemoattractant-stimulated phospholipase C activity. High specific activity (ca. 40 Ci/mmol) (/sup 32/P)(1,4,5)IP/sub 3/ was prepared from (..gamma..-/sup 32/P)ATP-labeled human erythrocyte ghosts and was used in binding assays with saponin-permeabilized rabbit peritoneal neutrophils. At 4/sup 0/C and in the presence of inhibitors of the IP/sub 3/ 5-phosphomonoesterase, (/sup 32/P)(1,4,5)IP/sub 3/ rapidly associated with a specific binding component which saturated within 60s. Nonspecific binding, taken as the residual binding in the presence of 10 ..mu..M (1,4,5)IP/sub 3/, was 15% of the total. No specific binding was detected using intact cells. The specific binding to permeable cells was reversible (t/sup 1/2/ approx. 60s) and could be inhibited in a dose-dependent manner by (1,4,5)IP/sub 3/ (EC/sub 50/ = 30 nM) and by other calcium mobilizing inositol phosphates ((2,4,5)IP/sub 3/) but not by inactive analogs ((1,4)IP/sub 2/, (4,5)IP/sub 2/, (1)IP). The dose-responses of (1,4,5)IP/sub 3/ and (2,4,5)IP/sub 3/ in inhibiting (/sup 32/P)(1,4,5)IP/sub 3/ specific binding correlated well with their abilities to release Ca/sup 2 +/ from nonmitochondrial vesicular stores in the same preparation of cells, suggesting that the authors have identified the physiological receptor for (1,4,5)IP/sub 3/.

  2. Crystal structures of three 3,4,5-tri­meth­oxy­benzamide-based derivatives

    PubMed Central

    Gomes, Ligia R.; Low, John Nicolson; Oliveira, Catarina; Cagide, Fernando; Borges, Fernanda

    2016-01-01

    The crystal structures of three benzamide derivatives, viz. N-(6-hy­droxy­hex­yl)-3,4,5-tri­meth­oxy­benzamide, C16H25NO5, (1), N-(6-anilinohex­yl)-3,4,5-tri­meth­oxy­benzamide, C22H30N2O4, (2), and N-(6,6-di­eth­oxy­hex­yl)-3,4,5-tri­meth­oxy­benzamide, C20H33NO6, (3), are described. These compounds differ only in the substituent at the end of the hexyl chain and the nature of these substituents determines the differences in hydrogen bonding between the mol­ecules. In each mol­ecule, the m-meth­oxy substituents are virtually coplanar with the benzyl ring, while the p-meth­oxy substituent is almost perpendicular. The carbonyl O atom of the amide rotamer is trans related with the amidic H atom. In each structure, the benzamide N—H donor group and O acceptor atoms link the mol­ecules into C(4) chains. In 1, a terminal –OH group links the mol­ecules into a C(3) chain and the combined effect of the C(4) and C(3) chains is a ribbon made up of screw related R 2 2(17) rings in which the ⋯O—H⋯ chain lies in the centre of the ribbon and the tri­meth­oxy­benzyl groups forms the edges. In 2, the combination of the benzamide C(4) chain and the hydrogen bond formed by the terminal N—H group to an O atom of the 4-meth­oxy group link the mol­ecules into a chain of R 2 2(17) rings. In 3, the mol­ecules are linked only by C(4) chains. PMID:27308017

  3. Role of calcium in membrane interactions by PI(4,5)P₂-binding proteins.

    PubMed

    Monteiro, Marina E; Sarmento, Maria J; Fernandes, Fábio

    2014-10-01

    Ca²⁺ and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] are key agents in membrane-associated signalling events. Their temporal and spatial regulation is crucial for activation or recruitment of proteins in the plasma membrane. In fact, the interaction of several signalling proteins with PI(4,5)P₂ has been shown to be tightly regulated and dependent on the presence of Ca²⁺, with co-operative binding in some cases. In these proteins, PI(4,5)P₂ and Ca²⁺ binding typically occurs at different binding sites. In addition, several PI(4,5)P₂-binding proteins are known targets of calmodulin (CaM), which, depending on the presence of calcium, can compete with PI(4,5)P₂ for protein interaction, translating Ca²⁺ transient microdomains into variations of PI(4,5)P₂ lateral organization in time and space. The present review highlights different examples of calcium-dependent PI(4,5)P₂-binding proteins and discusses the possible impact of this dual regulation on fine-tuning of protein activity by triggering target membrane binding in the presence of subtle changes in the levels of calcium or PI(4,5)P₂. PMID:25233429

  4. QSAR studies on 3-(4-biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] Pyridine derivatives as angiotensin II (AT1) receptor antagonist.

    PubMed

    Sharma, Mukesh C

    2015-06-01

    QSAR studies were performed for correlating the chemical composition of 3-(4-biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridines bearing aryl acetic acid esters and acetamides as angiotensin II AT(1) receptor antagonist. Four different quantitative structure-property relationship (QSAR) methods namely two-dimensional (2D-QSAR), group-based QSAR, k-nearest neighbor and Pharmacophore Modeling were employed to obtain statistically significant models. The statistically significant best 2D-QSAR model having correlation coefficient r(2) = 0:8940 and cross-validated squared correlation coefficient q(2) = 0:7648 with external predictive ability of pred_r(2) = 0:8177,pred_r(2)se = 0.4119 and best group-based QSAR model having r(2) = 0:7392 and q(2) = 0:6710with pred_r(2) = 0:7503was developed by SA-principal component regression. The most predictive k-nearest neighbor model derived from the superposition of conformations has good cross-validated q(2) = 0:7637 and satisfied predictive ability r(2)_pred = 0.7143. Continuing with compounds of substituted 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridine derivatives chemical feature-based pharmacophore models with lowest RMSD value (0.3292 Å) consists of two Hac (Hydrogen bond acceptor), negative ionizable, and two AroC (Aromatic) features are important for the activity. The study suggested that substitution of group at R, R 1, R 2 and Ar, and position on 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridine ring with more electronegative nature and low bulkiness are favorable for the antihypertensive activity. These theoretical results may provide a useful reference for understanding the action mechanism and designing potential angiotensin II (AT1) receptor antagonist. PMID:26215494

  5. Inositol 1,4,5-trisphosphate receptor subtypes differentially recognize regioisomers of D-myo-inositol 1,4,5-trisphosphate.

    PubMed Central

    Hirata, M; Takeuchi, H; Riley, A M; Mills, S J; Watanabe, Y; Potter, B V

    1997-01-01

    The Ins(1,4,5)P3 regioisomers, Ins(1,4,6)P3 and Ins(1,3,6)P3, which can mimic the 1,4,5-arrangement on the inositol ring of Ins(1,4,5)P3, were examined for Ca2+ release by using four types of saponin-permeabilized cell possessing various abundances of receptor subtypes, with special reference to the relation of potency to receptor subtype. Ins(1,4,6)P3 and Ins(1,3,6)P3 were weak agonists in rat basophilic leukaemic cells (RBL cells), which possess predominantly subtype II receptors, with respective potencies of 1/200 and less than 1/500 that of Ins(1,4,5)P3 [the EC50 values were 0.2, 45 and more than 100 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively]. Similar rank order potencies were also evaluated for the displacement of [3H]Ins(1,4,5)P3 bound to RBL cell membranes by these regioisomers. However, they caused Ca2+ release from GH3 rat pituitary cells possessing predominantly subtype I receptors more potently; Ins(1,4,6)P3 and Ins(1,3,6)P3 evoked release at respective concentrations of only one-third and one-twentieth that of Ins(1,4,5)P3 (the EC50 values were 0.4, 1.2 and 8 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In COS-1 African green-monkey kidney cells, with the relative abundances of 37% of the subtype II and of 62% of the subtype III receptor, potencies of 1/40 and approx. 1/200 for Ins(1, 4,6)P3 and Ins(1,3,6)P3 respectively were exhibited relative to Ins(1,4,5)P3 (the EC50 values were 0.4, 15 and approx. 80 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In HL-60 human leukaemic cells, in spite of the dominant presence of subtype I receptors (71%), similar respective potencies to those seen with COS-1 cells were exhibited (the EC50 values were 0.3, 15 and approx. 100 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). These results indicate that these regioisomers are the first ligands that distinguish between receptor subtypes; the present observations are of

  6. Selected fretting-wear-resistant coatings for titanium - 6-percent-aluminum - 4-percent-vanadium alloy

    NASA Technical Reports Server (NTRS)

    Bill, R. C.

    1976-01-01

    A titanium - 6-percent-aluminum - 4-percent-vanadium alloy (Ti-6Al-4V) was subjected to fretting-wear exposures against uncoated Ti-6Al-4V as a baseline and against various coatings and surface treatments applied to Ti-6Al-4V. The coatings evaluated included plasma-sprayed tungsten carbide with 12 percent cobalt, aluminum oxide with 13 percent titanium oxide, chromium oxide, and aluminum bronze with 10 percent aromatic polyester; polymer-bonded polyimide, polyimide with graphite fluoride, polyimide with molybdenum disulfide (MoS2), and methyl phenyl silicone bonded MoS2, preoxidation surface treatment, a nitride surface treatment, and a sputtered MoS2 coating. Results of wear measurements on both the coated and uncoated surfaces after 300,000 fretting cycles indicated that the polyimide coating was the most wear resistant and caused the least wear to the uncoated mating surface.

  7. 24 CFR 4.5 - Notice and documentation of assistance subject to section 102(a).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Notice and documentation of assistance subject to section 102(a). 4.5 Section 4.5 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HUD REFORM ACT Accountability in the Provision of HUD...

  8. 47 CFR 4.5 - Definitions of outage, special offices and facilities, and 911 special facilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Definitions of outage, special offices and facilities, and 911 special facilities. 4.5 Section 4.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL DISRUPTIONS TO COMMUNICATIONS Reporting Requirements for Disruptions to Communications §...

  9. 47 CFR 4.5 - Definitions of outage, special offices and facilities, and 911 special facilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Definitions of outage, special offices and facilities, and 911 special facilities. 4.5 Section 4.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL DISRUPTIONS TO COMMUNICATIONS Reporting Requirements for Disruptions to Communications §...

  10. Phenanthro[4,5-fgh]quinoxaline-Fused Subphthalocyanines: Synthesis, Structure, and Spectroscopic Characterization.

    PubMed

    Pan, Houhe; Liu, Wenbo; Wang, Chiming; Wang, Kang; Jiang, Jianzhuang

    2016-07-01

    A series of four phenanthro[4,5-fgh]quinoxaline-fused subphthalocyanine derivatives 0-3 containing zero, one, two, and three phenanthro[4,5-fgh]quinoxaline moieties, respectively, were isolated from the mixed cyclotrimerization reaction of 2,9-di-tert-butylphenanthro[4,5-fgh]quinoxaline-5,6-dicarbonitrile with 4,5-bis(2,6-diisopropylphenoxy)phthalonitrile and characterized by a series of spectroscopic methods including MALDI-TOF mass, (1) H NMR, electronic absorption, magnetic circular dichroism (MCD), and fluorescence spectroscopy. The molecular structures for the compounds 0 and 2 were clearly revealed on the basis of single-crystal X-ray diffraction analysis. Their electrochemical properties were also studied by cyclic voltammetry. In particular, theoretical calculations in combination with the electronic absorption and electrochemical analyses revealed the significant influence of the fused-phenanthro[4,5-fgh]quinoxaline units on the electronic structures. PMID:27123546

  11. Synthesis and biological activity of substituted-4,5,6,7-tetrahydrothieno pyridines: a review.

    PubMed

    Sangshetti, Jaiprakash N; Zambare, Abhay S; Khan, Firoz A Kalam; Gonjari, Indrajeet; Zaheer, Zahid

    2014-01-01

    4,5,6,7-Tetrahydrothieno pyridine is an important class of heterocyclic nucleus. Various 4,5,6,7-tetrahydrothieno pyridine derivatives have been synthesized and evaluated for various biological activities in different models with desired findings. Some analogs have shown potent biological activities and may be considered as lead molecule for the development of future drugs. Number of drug molecules are available in the market and many molecules are in clinical development containing 4,5,6,7-tetrahydrothieno pyridine nucleus as an important core. This review is an attempt to organize the chemical and biological aspects of 4,5,6,7-tetrahydrothieno pyridine analogs reported in last 20 year to till date. Review mainly focuses on the important role of the core in synthesis of drug or drug intermediates giving emphasis on synthetic schemes and biological activities of the different 4,5,6,7-tetrahydrothieno pyridine analogs. PMID:25373848

  12. Intercalative pyrimido[4',5':4,5]thieno(2,3-b)quinolines induce apoptosis in leukemic cells: a comparative study of methoxy and morpholino substitution.

    PubMed

    Shahabuddin, M S; Nambiar, Mridula; Advirao, Gopal M; Raghavan, Sathees C

    2011-10-01

    DNA intercalating molecules are promising anticancer agents. Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and affect major physiological functions. In the present study, we have characterized two molecules with the same chemical backbone but different side chains, namely 8-methoxy pyrimido[4',5':4,5]thieno (2,3-b)quinoline-4(3H)-one (MPTQ) and 4-morpholino pyrimido[4',5':4,5]thieno(2,3-b)quinoline (morpho-PTQ) at the 8th and 4th position, respectively. Although both MPTQ and morpho-PTQ show similar biophysical properties with high DNA affinity, here we show that they differ in their biological activities. We find that MPTQ is many fold more potent than morpho-PTQ and is cytotoxic against different leukemic cell lines. IC(50) value of methoxy PTQ was estimated between 2-15 µM among the leukemic cells studied, while it was more than 200 µM when morpho-PTQ was used. Cell cycle analysis shows an increase in sub-G1 phase, without any particular cell cycle arrest. Annexin V staining in conjunction with comet assay and DNA fragmentation suggest that MPTQ induces cytotoxicity by activating apoptosis. Thus the observed low IC(50) value of MPTQ makes it a promising cancer chemotherapeutic agent. PMID:20424886

  13. Formation and metabolism of inositol 1,4,5-trisphosphate in human platelets.

    PubMed Central

    Daniel, J L; Dangelmaier, C A; Smith, J B

    1987-01-01

    1. myo-[3H]Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], when added to lysed platelets, was rapidly converted into [3H]inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4], which was in turn converted into [3H]inositol 1,3,4-trisphosphate [Ins(1,3,4)P3]. This result demonstrates that platelets have the same metabolic pathways for interconversion of inositol polyphosphates that are found in other cells. 2. Labelling of platelets with [32P]Pi, followed by h.p.l.c., was used to measure thrombin-induced changes in the three inositol polyphosphates. Interfering compounds were removed by a combination of enzymic and non-enzymic techniques. 3. Ins(1,4,5)P3 was formed rapidly, and reached a maximum at about 4 s. It was also rapidly degraded, and was no longer detectable after 30-60 s. 4. Formation of Ins(1,3,4,5)P4 was almost as rapid as that of Ins(1,4,5)P3, and it remained detectable for a longer time. 5. Ins(1,3,4)P3 was formed after an initial lag, and this isomer reached its maximum, which was 10-fold higher than that of Ins(1,4,5)P3, at 30 s. 6. Comparison of the intracellular Ca2+ concentration as measured with fura-2 indicates that agents other than Ins(1,4,5)P3 are responsible for the sustained maintenance of a high concentration of intracellular Ca2+. It is proposed that either Ins(1,3,4)P3 or Ins(1,3,4,5)P4 may also be Ca2+-mobilizing agents. PMID:3499898

  14. Natural selection for 2,4,5-trichlorophenoxyacetic acid mineralizing bacteria in agent orange contaminated soil.

    PubMed

    Rice, J F; Menn, F M; Hay, A G; Sanseverino, J; Sayler, G S

    2005-12-01

    Agent Orange contaminated soils were utilized in direct enrichment culture studies to isolate 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D) mineralizing bacteria. Two bacterial cultures able to grow at the expense of 2,4,5-T and/or 2,4-D were isolated. The 2,4,5-T degrading culture was a mixed culture containing two bacteria, Burkholderia species strain JR7B2 and Burkholderia species strain JR7B3. JR7B3 was able to metabolize 2,4,5-T as the sole source of carbon and energy, and demonstrated the ability to affect metabolism of 2,4-D to a lesser degree. Strain JR7B3 was able to mineralize 2,4,5-T in pure culture and utilized 2,4,5-T in the presence of 0.01% yeast extract. Subsequent characterization of the 2,4-D degrading culture showed that one bacterium, Burkholderia species strain JRB1, was able to utilize 2,4-D as a sole carbon and energy source in pure culture. Polymerase chain reaction (PCR) experiments utilizing known genetic sequences from other 2,4-D and 2,4,5-T degrading bacteria demonstrated that these organisms contain gene sequences similar to tfdA, B, C, E, and R (Strain JRB1) and the tftA, C, and E genes (Strain JR7B3). Expression analysis confirmed that tftA, C, and E and tfdA, B, and C were transcribed during 2,4,5-T and 2,4-D dependent growth, respectively. The results indicate a strong selective pressure for 2,4,5-T utilizing strains under field condition. PMID:15865343

  15. Manpower Considers CETA 5 Percent Set-Aside

    ERIC Educational Resources Information Center

    American Vocational Journal, 1978

    1978-01-01

    Joan Wills, from the National Governor's Association (NGA), explains NGA's recommendation to eliminate CETA's five percent set-aside for vocational education. (This article summarizes her presentation at the annual vocational convention.) (Editor)

  16. 26 CFR 301.6226(b)-1 - 5-percent group.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... beginning prior to October 4, 2001, see § 301.6226(b)-1T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false 5-percent group. 301.6226(b)-1 Section 301.6226... ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6226(b)-1 5-percent group. (a) In...

  17. 26 CFR 301.6226(b)-1 - 5-percent group.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... beginning prior to October 4, 2001, see § 301.6226(b)-1T contained in 26 CFR part 1, revised April 1, 2001. ... 26 Internal Revenue 18 2011-04-01 2011-04-01 false 5-percent group. 301.6226(b)-1 Section 301.6226... ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6226(b)-1 5-percent group. (a) In...

  18. Thorium and uranium M-shell x-ray production cross sections by 4.5-11.3 MeV carbon ion and 4.5-13.5 MeV oxygen ion bombardment

    NASA Astrophysics Data System (ADS)

    Phinney, L. C.; Lapicki, G.; Weathers, D. L.; Naab, F. U.; Duggan, J. L.; McDaniel, F. D.

    2012-02-01

    The M-shell x-ray production cross sections for thorium and uranium have been measured for carbon ions with energies from 4.5 to 11.3 MeV with the charge state q increasing from 2 to 4, and oxygen ions with energies from 4.5 to 13.5 MeV with the charge state q increasing from 2 to 5. These cross sections are compared to the predictions of the first Born (PWBA+OBKN) and ECUSAR ionization theories, which were evaluated in a novel manner for the C+q and O+q energies and charge states of the data and converted to x-ray production cross sections with atomic parameters for a singly ionized M-shell and multiple ionization in the outer shells. Individual groups of M-shell transitions are also compared to the two ionization theories. The ECUSAR theory is shown to describe the measurements better than the first Born approximation. It is found to be in generally good agreement for all the total M-shell x-ray production and M-shell lines except for the Mγ cross sections. Reasons for the overestimation of the Mγ data are discussed.

  19. Synthesis, spectroscopic characterization, X-ray structure and DFT studies on 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium chloride hydrate.

    PubMed

    Türkyılmaz, Murat; Özdemir, Namık; Baran, Yakup

    2011-11-01

    The title molecular salt, 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-5-ium chloride hydrate (C(12)H(14)N(3)O(+)·Cl-·H(2)O), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of the title compound in the ground state have been calculated using the density functional theory (DFT/B3LYP) method with the 6-31++G(d,p) and 6-311++G(d,p) basis sets, and compared with the experimental data. Besides, molecular electrostatic potential (MEP) distribution and non-linear optical properties of the title compound were investigated by theoretical calculations at the B3LYP/6-311++G(d,p) level. PMID:21820352

  20. Synthesis, spectroscopic characterization, X-ray structure and DFT studies on 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1 H-imidazo[4,5- c]pyridin-5-ium chloride hydrate

    NASA Astrophysics Data System (ADS)

    Türkyılmaz, Murat; Özdemir, Namık; Baran, Yakup

    2011-11-01

    The title molecular salt, 4-(2-hydroxyphenyl)-4,5,6,7-tetrahydro-1 H-imidazo[4,5- c]pyridin-5-ium chloride hydrate (C 12H 14N 3O +·Clˉ·H 2O), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. In addition to the molecular geometry from X-ray experiment, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) 1H and 13C NMR chemical shift values of the title compound in the ground state have been calculated using the density functional theory (DFT/B3LYP) method with the 6-31++G(d,p) and 6-311++G(d,p) basis sets, and compared with the experimental data. Besides, molecular electrostatic potential (MEP) distribution and non-linear optical properties of the title compound were investigated by theoretical calculations at the B3LYP/6-311++G(d,p) level.

  1. RCP4.5: A Pathway for Stabilization of Radiative Forcing by 2100

    SciTech Connect

    Thomson, Allison M.; Calvin, Katherine V.; Smith, Steven J.; Kyle, G. Page; Volke, April C.; Patel, Pralit L.; Delgado Arias, Sabrina; Bond-Lamberty, Benjamin; Wise, Marshall A.; Clarke, Leon E.; Edmonds, James A.

    2011-07-29

    Representative Concentration Pathway (RCP) 4.5 is a scenario that stabilizes radiative forcing at 4.5 W m{sup -2} in the year 2100 without ever exceeding that value. Simulated with the Global Change Assessment Model (GCAM), RCP4.5 includes long-term, global emissions of greenhouse gases, short-lived species, and land-use-land-cover in a global economic framework. RCP4.5 was updated from earlier GCAM scenarios to incorporate historical emissions and land cover information common to the RCP process and follows a cost-minimizing pathway to reach the target radiative forcing. The imperative to limit emissions in order to reach this target drives changes in the energy system, including shifts to electricity, to lower emissions energy technologies and to the deployment of carbon capture and geologic storage technology. In addition, the RCP4.5 emissions price also applies to land use emissions; as a result, forest lands expand from their present day extent. The simulated future emissions and land use were downscaled from the regional simulation to a grid to facilitate transfer to climate models. While there are many alternative pathways to achieve a radiative forcing level of 4.5 W m{sup -2}, the application of the RCP4.5 provides a common platform for climate models to explore the climate system response to stabilizing the anthropogenic components of radiative forcing.

  2. Mouse nucleolin binds to 4.5S RNAH, a small noncoding RNA

    SciTech Connect

    Hirose, Yutaka Harada, Fumio

    2008-01-04

    4.5S RNAH is a rodent-specific small noncoding RNA that exhibits extensive homology to the B1 short interspersed element. Although 4.5S RNAH is known to associate with cellular poly(A)-terminated RNAs and retroviral genomic RNAs, its function remains unclear. In this study, we analyzed 4.5S RNAH-binding proteins in mouse nuclear extracts using gel mobility shift and RNA-protein UV cross-linking assays. We found that at least nine distinct polypeptides (p170, p110, p93, p70, p48, p40, p34, p20, and p16.5) specifically interacted with 4.5S RNAHin vitro. Using anti-La antibody, p48 was identified as mouse La protein. To identify the other 4.5S RNAH-binding proteins, we performed expression cloning from a mouse cDNA library and obtained cDNA clones derived from nucleolin mRNA. We identified p110 as nucleolin using nucleolin-specific antibodies. UV cross-linking analysis using various deletion mutants of nucleolin indicated that the third of four tandem RNA recognition motifs is a major determinant for 4.5S RNAH recognition. Immunoprecipitation of nucleolin from the subcellular fractions of mouse cell extracts revealed that a portion of the endogenous 4.5S RNAH was associated with nucleolin and that this complex was located in both the nucleoplasm and nucleolus.

  3. Mouse nucleolin binds to 4.5S RNAh, a small noncoding RNA.

    PubMed

    Hirose, Yutaka; Harada, Fumio

    2008-01-01

    4.5S RNAh is a rodent-specific small noncoding RNA that exhibits extensive homology to the B1 short interspersed element. Although 4.5S RNAh is known to associate with cellular poly(A)-terminated RNAs and retroviral genomic RNAs, its function remains unclear. In this study, we analyzed 4.5S RNAh-binding proteins in mouse nuclear extracts using gel mobility shift and RNA-protein UV cross-linking assays. We found that at least nine distinct polypeptides (p170, p110, p93, p70, p48, p40, p34, p20, and p16.5) specifically interacted with 4.5S RNAhin vitro. Using anti-La antibody, p48 was identified as mouse La protein. To identify the other 4.5S RNAh-binding proteins, we performed expression cloning from a mouse cDNA library and obtained cDNA clones derived from nucleolin mRNA. We identified p110 as nucleolin using nucleolin-specific antibodies. UV cross-linking analysis using various deletion mutants of nucleolin indicated that the third of four tandem RNA recognition motifs is a major determinant for 4.5S RNAh recognition. Immunoprecipitation of nucleolin from the subcellular fractions of mouse cell extracts revealed that a portion of the endogenous 4.5S RNAh was associated with nucleolin and that this complex was located in both the nucleoplasm and nucleolus. PMID:17971306

  4. LPS-induced clustering of CD14 triggers generation of PI(4,5)P2.

    PubMed

    Płóciennikowska, Agnieszka; Zdioruk, Mykola I; Traczyk, Gabriela; Świątkowska, Anna; Kwiatkowska, Katarzyna

    2015-11-15

    Bacterial lipopolysaccharide (LPS) induces strong pro-inflammatory reactions after sequential binding to CD14 protein and TLR4 receptor. Here, we show that CD14 controls generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in response to LPS binding. In J774 cells and HEK293 cells expressing CD14 exposed to 10-100 ng/ml LPS, the level of PI(4,5)P2 rose in a biphasic manner with peaks at 5-10 min and 60 min. After 5-10 min of LPS stimulation, CD14 underwent prominent clustering in the plasma membrane, accompanied by accumulation of PI(4,5)P2 and type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms Iα and Iγ (encoded by Pip5k1a and Pip5k1c, respectively) in the CD14 region. Clustering of CD14 with antibodies, without LPS and TLR4 participation, was sufficient to trigger PI(4,5)P2 elevation. The newly generated PI(4,5)P2 accumulated in rafts, which also accommodated CD14 and a large portion of PIP5K Iα and PIP5K Iγ. Silencing of PIP5K Iα and PIP5K Iγ, or application of drugs interfering with PI(4,5)P2 synthesis and availability, abolished the LPS-induced PI(4,5)P2 elevation and inhibited downstream pro-inflammatory reactions. Taken together, these data indicate that LPS induces clustering of CD14, which triggers PI(4,5)P2 generation in rafts that is required for maximal pro-inflammatory signaling of TLR4. PMID:26446256

  5. Is inositol (1,3,4,5)-tetrakisphosphate a new second messenger

    SciTech Connect

    Hansen, C.A.; Williamson, J.R.

    1986-05-01

    Hormone-stimulated hydrolysis of inositol (Ins) lipids results in the rapid formation of Ins(1,4,5)P/sub 3/, the second messenger for intracellular Ca/sup 2 +/ mobilization. Recently, a more polar inositol phosphate, Ins(1,3,4,5)P/sub 4/ as well as its probable hydrolysis product Ins(1,3,4)P/sub 3/ have been reported to accumulate in carbachol-stimulated brain slices. Vasopressin addition to hepatocytes prelabeled with (/sup 3/H)-Ins also showed a rapid increase of Ins(1,3,4,5)P/sub 4/, which was similar to that of Ins(1,4,5)P/sub 3/, while the accumulation of Ins(1,3,4)P/sub 3/ was slower. In order to examine whether Ins(1,3,4,5)P/sub 4/ has any functional effects on Ca/sup 2 +/ homeostasis, it was synthesized enzymatically from (/sup 3/H)-Ins(1,4,5)P/sub 3/ using a partially purified phosphoinositol kinase activity from rat brain cortex. (/sup 3/H)-labeled inositol phosphates were separated by anion exchange chromatography and analyzed by HPLC using ammonium formate/phosphoric acid gradient elution. Preliminary experiments indicate that Ins(1,3,4,5)P/sub 4/ up to 10 ..mu..M does not release Ca/sup 2 +/ from vesicular pools in saponin-permeabilized hepatocytes. It has a slight inhibitory effect on Ins(1,4,5)P/sub 3/-induced Ca/sup 2 +/ release. The effect of Ins(1,3,4,5)P/sub 4/ on plasma membrane Ca/sup 2 +/ fluxes are presently being investigated.

  6. A series of 2, 4, 5-trisubstituted oxazole: Synthesis, characterization and DFT modelling

    NASA Astrophysics Data System (ADS)

    Kadam, Vinay S.; Shaikh, Saminaparwin G.; Patel, Arun L.

    2016-06-01

    A new series of 2,4,5-trisubstituted oxazole were synthesized with good yields using simple methodology. All the compounds were thoroughly characterized by IR, NMR (1H and 13C) and mass spectrometry and structures of 2-(4-butyloxyphenyl)-4,5-dimethyloxazole (5b) and 4,5-dimethyl-2-(4-(octyloxy)phenyl)oxazole(5e) were unambiguously determined by X-ray crystallography. Evidently, the crystal structures of these compounds showed C-H⋯N and C-H⋯O intermolecular interactions. The electronic structures of these compounds were also studied by DFT at B3LYP/6-311G ++ level of theory.

  7. Enantioselective synthesis and antioxidant activity of 3,4,5-substituted piperidine derivatives.

    PubMed

    Kim, Jin Ho; Shyam, Pranab K; Kim, Mi Jeong; Lee, Hwa-Jung; Lee, Jeong Tae; Jang, Hye-Young

    2016-07-01

    In this study, 3,4,5-trisubstituted piperidines were synthesized enantioselectively, and their antioxidant activity was evaluated. The 3,4,5-trisubstituted piperidines containing TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and a spatially proximal hydroxy group showed good antioxidant activity. Some of these compounds showed IC50 values in a nanomolar range, comparable to that of TEMPO. Probably the TEMPO generated from the homolysis of the CON bond of 3,4,5-trisubstituted piperidines functions as a radical-scavenging entity, and the hydroxy group of piperidines has a synergistic effect to the antioxidant activity. PMID:27177825

  8. Energetic Trinitro- and Fluorodinitroethyl Ethers of 1,2,4,5-Tetrazines.

    PubMed

    Chavez, David E; Parrish, Damon A; Mitchell, Lauren

    2016-07-18

    Several new energetic ethyl ethers of 1,2,4,5-tetrazine have been synthesized. These molecules display good thermal stability, good oxygen balance, and high densities. Included in these studies are a 2,2,2-trinitroethoxy 1,2,4,5-tetrazine and two fluorodinitroethoxy 1,2,4,5-tetrazines. One of these compounds was converted into the di-N-oxide derivative. The sensitivity of these materials towards destructive stimuli was determined, and overall the materials show promising energetic performance properties. PMID:27273564

  9. Heterogeneous nucleation of the primary phase in the rapid solidification of Al-4.5wt%Cu alloy droplet

    NASA Astrophysics Data System (ADS)

    Maitre, A.; Bogno, A.-A.; Bedel, M.; Reinhart, G.; Henein, H.

    2015-06-01

    This paper reports on rapid solidification of Al-Cu alloys. A heterogeneous nucleation/growth model coupled with a thermal model of a falling droplet through a stagnant gas was developed. The primary undercooling as well as the number of nucleation points was compared with Al-Cu alloy droplets produced by Impulse Atomization (IA). Based on experimental results from Neutron Diffraction, secondary (eutectic) phases were obtained. Then, primary and secondary undercoolings were estimated using the metastable extensions of solidus and liquidus lines calculated by Thermo-Calc. Moreover, Synchrotron X-ray microtomography has been performed on Al-4.5wt%Cu droplets. The undercoolings are in good agreement. Results also evidence the presence of one nucleation point and are in agreement with the experimental observations.

  10. 2,4,5,2',4',5'-Hexachlorobiphenyl-lipoprotein (LDL, HDL, VLDL) interaction and induced lipidosis in cultured skin fibroblasts

    SciTech Connect

    Kling, D.; Becker, M.M.; Kruth, H.S.; Gamble, W.

    1984-06-01

    2,4,5,2',4',5'-Hexachlorobiphenyl (HCB) induced cytoplasmic inclusions and lipidosis in normal (AG1437) and hypercholesterolemic (GM488) human skin fibroblasts. Quantitative and qualitative microscopic fluorescence analysis showed that the cytoplasmic inclusions are formed as early as 3 hr after treatment with HCB. The inclusions contain lipids but no detectable nonesterified cholesterol or cholesteryl ester. High density lipoproteins (HDL), low density lipoproteins (LDL), and very low density lipoproteins (VLDL) facilitate the apparent uptake of HCB by skin fibroblasts. HDL and LDL appeared to reverse the induction of cytoplasmic inclusions and lipidosis when cells were pretreated with HCB, the HCB was removed from media, and the cells were incubated with LDL or HDL. The results suggest that lipoproteins participate in the uptake and egress of HCB from skin fibroblasts.

  11. Milestone Report - Complete New Adsorbent Materials for Marine Testing to Demonstrate 4.5 g-U/kg Adsorbent

    SciTech Connect

    Janke, Christopher James; Das, Sadananda; Oyola, Yatsandra; Mayes, Richard T.; Saito, Tomonori; Brown, Suree; Gill, Gary; Kuo, Li-Jung; Wood, Jordana

    2014-08-01

    This report describes work on the successful completion of Milestone M2FT-14OR03100115 (8/20/2014) entitled, “Complete new adsorbent materials for marine testing to demonstrate 4.5 g-U/kg adsorbent”. This effort is part of the Seawater Uranium Recovery Program, sponsored by the U.S. Department of Energy, Office of Nuclear Energy, and involved the development of new adsorbent materials at the Oak Ridge National Laboratory (ORNL) and marine testing at the Pacific Northwest National Laboratory (PNNL). ORNL has recently developed two new families of fiber adsorbents that have demonstrated uranium adsorption capacities greater than 4.5 g-U/kg adsorbent after marine testing at PNNL. One adsorbent was synthesized by radiation-induced graft polymerization of itaconic acid and acrylonitrile onto high surface area polyethylene fibers followed by amidoximation and base conditioning. This fiber showed a capacity of 4.6 g-U/kg adsorbent in marine testing at PNNL. The second adsorbent was prepared by atom-transfer radical polymerization of t-butyl acrylate and acrylonitrile onto halide-functionalized round fibers followed by amidoximation and base hydrolysis. This fiber demonstrated uranium adsorption capacity of 5.4 g-U/kg adsorbent in marine testing at PNNL.

  12. Application of preprocessing filtering on Decision Tree C4.5 and rough set theory

    NASA Astrophysics Data System (ADS)

    Chan, Joseph C. C.; Lin, Tsau Y.

    2001-03-01

    This paper compares two artificial intelligence methods: the Decision Tree C4.5 and Rough Set Theory on the stock market data. The Decision Tree C4.5 is reviewed with the Rough Set Theory. An enhanced window application is developed to facilitate the pre-processing filtering by introducing the feature (attribute) transformations, which allows users to input formulas and create new attributes. Also, the application produces three varieties of data set with delaying, averaging, and summation. The results prove the improvement of pre-processing by applying feature (attribute) transformations on Decision Tree C4.5. Moreover, the comparison between Decision Tree C4.5 and Rough Set Theory is based on the clarity, automation, accuracy, dimensionality, raw data, and speed, which is supported by the rules sets generated by both algorithms on three different sets of data.

  13. 4,5-Dimethylangelicin effects on lymphocytes with and without UV-radiation.

    PubMed

    Gast, W; Rytter, M; Hofmann, C; Haustein, U F; Barth, J; Walther, T

    1987-03-01

    Compared to the linear derivative 8-methoxypsoralen (8-MOP) the angular structured furocoumarin 4,5'-dimethylangelicin (4,5'-DMA) causes smaller photosensitization effects (loss of viability, inhibition of phytohemagglutinin (PHA)-induced transformation rate and E-rosette formation of T-cells, respectively) on cultured human lymphocytes. When 4,5'-DMA or 8-MOP are added to the cultures without additional UV-irradiation, increased or decreased PHA-stimulation rates are observed, respectively. In addition, 4,5'-DMA is able to reduce the binding of sheep erythrocytes to lymphocytes in a higher degree than 8-MOP. These findings suggest different action mechanisms on cytoplasma membranes and intracellular structures of lymphocytes by different furocoumarins. PMID:3653385

  14. BIOTRANSFORMATION OF TRANS-4,5-DIHYDROXY-4,5-DIHYDROBENZO[A]PYRENE TO BENZO[A]PYRENE-BIS-DIOLS AND DNA ADDUCTS BY INDUCED RAT LIVER MICROSOMES

    EPA Science Inventory

    The biotransformation of (+)-trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene trans-B[a]P-4,5-diol), the K-region dihydrodiol of B[a]P, by B-naphthoflavone (BNF)-induced rat liver microsomes was studied. Trans-B[a]P-4,5-diol was metabolized to six major products as characterized by...

  15. Signal-dependent Hydrolysis of Phosphatidylinositol 4,5-Bisphosphate without Activation of Phospholipase C

    PubMed Central

    Lev, Shaya; Katz, Ben; Tzarfaty, Vered; Minke, Baruch

    2012-01-01

    In Drosophila, a phospholipase C (PLC)-mediated signaling cascade, couples photo-excitation of rhodopsin to the opening of the transient receptor potential (TRP) and TRP-like (TRPL) channels. A lipid product of PLC, diacylglycerol (DAG), and its metabolites, polyunsaturated fatty acids (PUFAs) may function as second messengers of channel activation. However, how can one separate between the increase in putative second messengers, change in pH, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) depletion when exploring the TRPL gating mechanism? To answer this question we co-expressed the TRPL channels together with the muscarinic (M1) receptor, enabling the openings of TRPL channels via G-protein activation of PLC. To dissect PLC activation of TRPL into its molecular components, we used a powerful method that reduced plasma membrane-associated PI(4,5)P2 in HEK cells within seconds without activating PLC. Upon the addition of a dimerizing drug, PI(4,5)P2 was selectively hydrolyzed in the cell membrane without producing DAG, inositol trisphosphate, or calcium signals. We show that PI(4,5)P2 is not an inhibitor of TRPL channel activation. PI(4,5)P2 hydrolysis combined with either acidification or application of DAG analogs failed to activate the channels, whereas PUFA did activate the channels. Moreover, a reduction in PI(4,5)P2 levels or inhibition of DAG lipase during PLC activity suppressed the PLC-activated TRPL current. This suggests that PI(4,5)P2 is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating. PMID:22065576

  16. Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis

    PubMed Central

    Botelho, Roberto J.; Teruel, Mary; Dierckman, Renee; Anderson, Richard; Wells, Alan; York, John D.; Meyer, Tobias; Grinstein, Sergio

    2000-01-01

    Phagocytosis requires localized and transient remodeling of actin filaments. Phosphoinositide signaling is believed to play an important role in cytoskeletal organization, but it is unclear whether lipids, which can diffuse along the membrane, can mediate the focal actin assembly required for phagocytosis. We used imaging of fluorescent chimeras of pleckstrin homology and C1 domains in live macrophages to monitor the distribution of phosphatidylinositol-4,5-bisphosphate (4,5-PIP2) and diacylglycerol, respectively, during phagocytosis. Our results reveal a sequence of exquisitely localized, coordinated steps in phospholipid metabolism: a focal, rapid accumulation of 4,5-PIP2 accompanied by recruitment of type Iα phosphatidylinositol phosphate kinase to the phagosomal cup, followed by disappearance of the phosphoinositide as the phagosome seals. Loss of 4,5-PIP2 correlated with mobilization of phospholipase Cγ (PLCγ) and with the localized formation of diacylglycerol. The presence of 4,5-PIP2 and active PLCγ at the phagosome was shown to be essential for effective particle ingestion. The temporal sequence of phosphoinositide metabolism suggests that accumulation of 4,5-PIP2 is involved in the initial recruitment of actin to the phagocytic cup, while its degradation contributes to the subsequent cytoskeletal remodeling. PMID:11134066

  17. Analysis and risk assessment of 4(5)-methylimidazole in brown colored foods and beverages.

    PubMed

    Lee, Sumin; Lee, Kwang-Geun

    2016-01-01

    In this study, the 4(5)-methylimidazole (4(5)-MI) levels in various 144 brown coloured foods and beverages were determined. The brown coloured foods and beverages were 62 processed sauces, 40 coffee, 9 caramel syrups, 18 red ginseng juice and 15 Japanese apricot fruit juice. The amount of 4(5)-MI in brewed coffee (1821.3 ng/g) was the highest level among the samples. The 4(5)-MI concentration in processed sauce (47.6 ng/g) was the lowest level among the samples. The levels of 4(5)-MI in various samples were found as follows: 47.6-1748.5 ng/g in processed sauces, 64.1-1821.3 ng/g in commercial coffee, 115.5-491.9 ng/g in caramel syrups, 91.0-854.1 ng/g in red ginseng juice and 137.6-587.4 ng/g in Japanese apricot fruit juice. Based on the 4(5)-MI levels, the estimated daily intake (EDI) and chronic daily intake (CDI) were calculated. EDI and CDI of red ginseng juice was the highest among all samples, and they were 1618.6 and 1256.8 ng/kg bw/day, respectively. PMID:26653824

  18. Comparing proton conductivity of polymer electrolytes by percent conducting volume

    SciTech Connect

    Kim, Yu Seung; Pivovar, Bryan

    2009-01-01

    Proton conductivity of sulfonated polymers plays a key role in polymer electrolyte membrane fuel cells. Mass based water uptake and ion exchange capacity of sulfonated polymers have been failed to correlating their proton conductivity. In this paper, we report a length scale parameter, percent conductivity volume, which is rather simply obtained from the chemical structure of polymer to compare proton conductivity of wholly aromatic sulfonated polymer perflurosulfonic acid. Morphology effect on proton conductivity at lower RH conditions is discussed using the percent conductivity volume parameter.

  19. Development of high efficiency (14 percent) solar cell array module

    NASA Technical Reports Server (NTRS)

    Iles, P. A.; Khemthong, S.; Olah, S.; Sampson, W. J.; Ling, K. S.

    1980-01-01

    Most effort was concentrated on development of procedures to provide large area (3 in. diameter) high efficiency (16.5 percent AM1, 28 C) P+NN+ solar cells. Intensive tests with 3 in. slices gave consistently lower efficiency (13.5 percent). The problems were identified as incomplete formation of and optimum back surface field (BSF), and interaction of the BSF process and the shallow P+ junction. The problem was shown not to be caused by reduced quality of silicon near the edges of the larger slices.

  20. Spectroscopic (FT-IR, FT-Raman, UV and NMR) investigation and NLO, HOMO-LUMO, NBO analysis of organic 2,4,5-trichloroaniline

    NASA Astrophysics Data System (ADS)

    Govindarajan, M.; Karabacak, M.; Periandy, S.; Tanuja, D.

    2012-11-01

    In this work, the experimental and theoretical study on the molecular structure and vibrational spectra of 2,4,5-trichloroaniline (C6H4NCl3, abbreviated as 2,4,5-TClA) were studied. The FT-IR and FT-Raman spectra were recorded. The molecular geometry and vibrational frequencies in the ground state were calculated by using the Hartree-Fock (HF) and density functional theory (DFT) methods (B3LYP) with 6-311++G(d,p) basis set. Comparison of the observed fundamental vibrational frequencies of 2,4,5-TClA with calculated results by HF and DFT indicates that B3LYP is superior to HF method for molecular vibrational problems. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. The theoretically predicted FT-IR and FT-Raman spectra of the title molecule have been constructed. A study on the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. Besides, molecular electrostatic potential (MEP) and thermodynamic properties were performed. The electric dipole moment (μ) and the first hyperpolarizability (β) values of the investigated molecule were computed using ab initio quantum mechanical calculations. The calculated results also show that the 2,4,5-TClA molecule may have microscopic nonlinear optical (NLO) behavior with non-zero values. Mulliken atomic charges of 2,4,5-TClA was calculated and compared with aniline and chlorobenzene molecules. The 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results.

  1. Spectroscopic (FT-IR, FT-Raman, UV and NMR) investigation and NLO, HOMO-LUMO, NBO analysis of organic 2,4,5-trichloroaniline.

    PubMed

    Govindarajan, M; Karabacak, M; Periandy, S; Tanuja, D

    2012-11-01

    In this work, the experimental and theoretical study on the molecular structure and vibrational spectra of 2,4,5-trichloroaniline (C(6)H(4)NCl(3), abbreviated as 2,4,5-TClA) were studied. The FT-IR and FT-Raman spectra were recorded. The molecular geometry and vibrational frequencies in the ground state were calculated by using the Hartree-Fock (HF) and density functional theory (DFT) methods (B3LYP) with 6-311++G(d,p) basis set. Comparison of the observed fundamental vibrational frequencies of 2,4,5-TClA with calculated results by HF and DFT indicates that B3LYP is superior to HF method for molecular vibrational problems. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. The theoretically predicted FT-IR and FT-Raman spectra of the title molecule have been constructed. A study on the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. Besides, molecular electrostatic potential (MEP) and thermodynamic properties were performed. The electric dipole moment (μ) and the first hyperpolarizability (β) values of the investigated molecule were computed using ab initio quantum mechanical calculations. The calculated results also show that the 2,4,5-TClA molecule may have microscopic nonlinear optical (NLO) behavior with non-zero values. Mulliken atomic charges of 2,4,5-TClA was calculated and compared with aniline and chlorobenzene molecules. The (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results. PMID:22765942

  2. Strain rate dependence of the tensile properties of V-(4--5%)Cr-(4--5%)Ti irradiated in EBR-II and HFBR

    SciTech Connect

    Zinkle, S.J.; Snead, L.L.; Robertson, J.P.; Rowcliffe, A.F.

    1998-03-01

    Elevated temperature tensile tests performed on V-(405)Cr-(4-5)Ti indicate that the yield stress increases with increasing strain rate for irradiation and test temperatures near 200 C, and decreases with increasing strain rate for irradiation and test temperatures near 400 C. This observation is in qualitative agreement with the temperature-dependent strain rate effects observed on unirradiated specimens, and implies that some interstitial solute remains free to migrate in irradiated specimens. Additional strain rate data at different temperatures are needed.

  3. Magnetic properties of YMn{sub x}Al{sub 12{minus}x}(x = 4,5,6)

    SciTech Connect

    Coldea, M.; Coldea, R.; Borodi, G.

    1994-03-01

    Magnetic susceptibility of YMn{sub x}Al{sub 12{minus}x} (x=4,5,6) with ThMn{sub 12} structure was measured at temperatures 90K to 900K. These compounds show varied magnetic behaviors depending upon the relative abundance of Mn atoms in the 8f, 8j and 8i crystallographic sites. In the high temperature range, the temperature dependence of the susceptibility is of the Curie-Weiss type. The occurrence of a Mn moment in YMn{sub 4}Al{sub 8} and YMn{sub 8}Al{sub 6} is strongly correlated with the critical value d{approx}2.6{angstrom} of MD-Mn distance below which the Mn moment collapses. In YMn{sub 8}Al{sub 6} both the magnetic and the nonmagnetic Mn atoms were observed to coexist. It has been revealed that the magnetic character of Mn moment in the 8f sites of these two compounds changes from an itinerant electron type to a local moment type with increasing temperature. A transition to a spin glass state at low temperatures for YMn{sub 5}Al{sub 7}, was suggested.

  4. 48 CFR 1852.219-76 - NASA 8 percent goal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... means an institution determined by the Secretary of Education to meet the requirements of 34 CFR Section... requirements of 13 CFR 124. Women-owned small business concern, as used in this clause, means a small business... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true NASA 8 percent goal....

  5. 48 CFR 1852.219-76 - NASA 8 percent goal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... means an institution determined by the Secretary of Education to meet the requirements of 34 CFR Section... requirements of 13 CFR 124. Women-owned small business concern, as used in this clause, means a small business... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false NASA 8 percent goal....

  6. 48 CFR 1852.219-76 - NASA 8 percent goal.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... means an institution determined by the Secretary of Education to meet the requirements of 34 CFR Section... requirements of 13 CFR 124. Women-owned small business concern, as used in this clause, means a small business... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false NASA 8 percent goal....

  7. 48 CFR 1852.219-76 - NASA 8 percent goal.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... means an institution determined by the Secretary of Education to meet the requirements of 34 CFR Section... requirements of 13 CFR 124. Women-owned small business concern, as used in this clause, means a small business... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false NASA 8 percent goal....

  8. 48 CFR 1852.219-76 - NASA 8 percent goal.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... means an institution determined by the Secretary of Education to meet the requirements of 34 CFR Section... requirements of 13 CFR 124. Women-owned small business concern, as used in this clause, means a small business... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false NASA 8 percent goal....

  9. 35 GHz integrated circuit rectifying antenna with 33 percent efficiency

    NASA Astrophysics Data System (ADS)

    Yoo, T.-W.; Chang, K.

    1991-11-01

    A 35 GHz integrated circuit rectifying antenna (rectenna) has been developed using a microstrip dipole antenna and beam-lead mixer diode. Greater than 33 percent conversion efficiency has been achieved. The circuit should have applications in microwave/millimeter-wave power transmission and detection.

  10. Tricky Times for the Top 10 Percent Program

    ERIC Educational Resources Information Center

    Roach, Ronald

    2007-01-01

    Both supporters and critics of Texas' Top 10 Percent law have been surprised at its popularity, but some UT officials and legislators would like to see the program scaled back. As a Texas state legislator, Jim McReynolds, D-Lufkin, knows a thing or two about influencing the voting positions of his colleagues. This past spring, when Texas House…

  11. School Designed To Use 80 Percent Less Energy

    ERIC Educational Resources Information Center

    American School and University, 1975

    1975-01-01

    The new Terraset Elementary School in Reston, Virginia, uses earth as a cover for the roof area and for about 80 percent of the wall area. A heat recovery system will be used with solar collectors playing a primary role in heating and cooling. (Author/MLF)

  12. 35 GHz integrated circuit rectifying antenna with 33 percent efficiency

    NASA Technical Reports Server (NTRS)

    Yoo, T.-W.; Chang, K.

    1991-01-01

    A 35 GHz integrated circuit rectifying antenna (rectenna) has been developed using a microstrip dipole antenna and beam-lead mixer diode. Greater than 33 percent conversion efficiency has been achieved. The circuit should have applications in microwave/millimeter-wave power transmission and detection.

  13. 24 CFR 100.305 - 80 percent occupancy.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false 80 percent occupancy. 100.305 Section 100.305 Housing and Urban Development Regulations Relating to Housing and Urban Development OFFICE OF ASSISTANT SECRETARY FOR EQUAL OPPORTUNITY, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT...

  14. 32 CFR 48.508 - Certain 100 percent disability retirement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Certain 100 percent disability retirement. 48... disability retirement. An election filed on or after August 13, 1968 is not effective if the member dies within 30 days following retirement from a disability of 100 per centum (under the standard schedule...

  15. 32 CFR 48.508 - Certain 100 percent disability retirement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Certain 100 percent disability retirement. 48... disability retirement. An election filed on or after August 13, 1968 is not effective if the member dies within 30 days following retirement from a disability of 100 per centum (under the standard schedule...

  16. 32 CFR 48.508 - Certain 100 percent disability retirement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Certain 100 percent disability retirement. 48... disability retirement. An election filed on or after August 13, 1968 is not effective if the member dies within 30 days following retirement from a disability of 100 per centum (under the standard schedule...

  17. 32 CFR 48.508 - Certain 100 percent disability retirement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Certain 100 percent disability retirement. 48... disability retirement. An election filed on or after August 13, 1968 is not effective if the member dies within 30 days following retirement from a disability of 100 per centum (under the standard schedule...

  18. 32 CFR 48.508 - Certain 100 percent disability retirement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Certain 100 percent disability retirement. 48... disability retirement. An election filed on or after August 13, 1968 is not effective if the member dies within 30 days following retirement from a disability of 100 per centum (under the standard schedule...

  19. PTEN interaction with tethered bilayer lipid membranes containing PI(4,5)P2

    NASA Astrophysics Data System (ADS)

    Moldovan, R.; Shenoy, S.; Shekhar, P.; Kalinowski, A.; Gericke, A.; Heinrich, F.; Loesche, M.

    2009-03-01

    Synthetic lipid membrane models are frequently used for the study of biophysical processes at cell membranes. We use a robust membrane model, the tethered bilayer lipid membrane (tBLM), based on a (C14)2-(PEO)6-thiol anchor, WC14 [1]. Such membranes can be prepared to contain single phospholipids or complex lipid mixtures [2], including functional lipids involved in cell signaling, such as the highly charged phosphatidylinositol phosphates (PIPs). To study the interaction between the tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) and model membranes we have incorporated phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) in tBLMs and use fluorescence correlation spectroscopy (FCS), neutron reflectometry (NR) and surface plasmon resonance (SPR) for their characterization. NR shows that tBLMs formed with PI(4,5)P2 are complete. FCS of labeled PI(4,5)P2 shows that diffusion occurs at the time scale characteristic of membrane-incorporated lipid. Finally, SPR shows specific binding of PTEN to the model membrane thus confirming the incorporation of PI(4,5)P2 into the tBLM. [1] McGillivray et al, Biointerphases 2, 21-33 (2007) [2] Heinrich et al, Langmuir, submitted

  20. Phosphatidylinositol-3,4,5-Triphosphate and Cellular Signaling: Implications for Obesity and Diabetes

    PubMed Central

    Manna, Prasenjit; Jain, Sushil K.

    2015-01-01

    Phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) is one of the most important phosphoinositides and is capable of activating a wide range of proteins through its interaction with their specific binding domains. Localization and activation of these effector proteins regulate a number of cellular functions, including cell survival, proliferation, cytoskeletal rearrangement, intracellular vesicle trafficking, and cell metabolism. Phosphoinositides have been investigated as an important agonist-dependent second messenger in the regulation of diverse physiological events depending upon the phosphorylation status of their inositol group. Dysregulation in formation as well as metabolism of phosphoinositides is associated with various pathophysiological disorders such as inflammation, allergy, cardiovascular diseases, cancer, and metabolic diseases. Recent studies have demonstrated that the impaired metabolism of PtdIns(3,4,5)P3 is a prime mediator of insulin resistance associated with various metabolic diseases including obesity and diabetes. This review examines the current status of the role of PtdIns(3,4,5)P3 signaling in the regulation of various cellular functions and the implications of dysregulated PtdIns(3,4,5)P3 signaling in obesity, diabetes, and their associated complications. PMID:25721445

  1. Ab initio and molecular dynamics studies of crystalline TNAD (trans-1,4,5,8-tetranitro-1,4,5,8-tetraazadecalin).

    PubMed

    Qiu, Ling; Xiao, He-Ming; Zhu, Wei-Hua; Xiao, Ji-Jun; Zhu, Wei

    2006-06-01

    The structural and electronic properties of the energetic crystal TNAD (trans-1,4,5,8-tetranitro-1,4,5,8- tetraazadecalin) have been studied using plane-wave ab initio calculations based on the density function theory method with the ultrasoft pseudopotentials. It is found that the predicted crystal structure is in good agreement with experimental data and there are strong inter- and intramolecular interactions in bulk TNAD. Band structure calculations indicate that TNAD is an insulator with the band gap of ca. 3.3 eV. The hydrostatic compression effect on TNAD has been studied in the pressure range of 0-600 GPa. The results show that a pressure less than 10 GPa does not significantly change the geometric parameters, charge distributions, and electronic bands. When the pressure is over 10 GPa, increasing the pressure determines significant changes of the geometrical and electronic structures and large broadening of the electronic bands together with a sharp decrease of the band gap. Isothermal-isobaric molecular dynamics simulations at atmospheric pressure were further performed on the TNAD crystal in the temperature range 5-500 K. Average equilibrium lattice parameters and elastic properties as functions of temperature were determined. The thermal expansion coefficients calculated for the crystal indicate anisotropic behavior with the largest expansion along the b axis. PMID:16771311

  2. Physical chemistry of binary organic eutectic and monotectic alloys; 1,2,4,5-tetrachlorobenzene-β-naphthol and 1,2,4,5-tetramethylbenzene-succinonitrile systems

    NASA Astrophysics Data System (ADS)

    Rai, U. S.; Pandey, Pinky; Rai, R. N.

    2000-12-01

    Phase diagrams of 1,2,4,5-tetrachlorobenzene-β-naphthol and 1,2,4,5-tetramethylbenzene-succinonitrile systems which are organic analogues of a nonmetal-nonmetal and a nonmetal-metal system, respectively, show the formation of a simple eutectic (melting point 103.7°C) with 0.71 mole fraction of β-naphthol in the former case and a monotectic (melting point 76.0°C) with 0.07 mole fraction of succinonitrile and a eutectic (melting point 52.5°C) with 0.97 mole fraction of succinonitrile in the latter case. The growth behaviour of the pure components, the eutectics and the monotectic studied by measuring the rate of movement of the solid-liquid interface in a capillary, suggests that the data obey the Hillig-Turnbull equation, v= u(Δ T) n, where v is the growth velocity, Δ T is the undercooling and u and n are constants depending on the nature of the materials involved. From the values of enthalpy of fusion determined by the DSC method using Mettler DSC-4000 system, entropy of fusion, interfacial energy, enthalpy of mixing and excess thermodynamic functions were calculated. The optical microphotographs of pure components and polyphase materials show their characteristic features.

  3. Room-temperature fracture in V-(4-5)Cr-(4-5)Ti tensile specimens irradiated in Fusion-1 BOR-60 experiment

    SciTech Connect

    Gazda, J.; Meshii, M.; Tsai, H.

    1998-09-01

    Specimens of V-(4-5)Cr-(4-5)Ti alloys were irradiated to {approx}18 dpa at 320 C in the Fusion-1 capsule inserted into the BOR-60 reactor. Tensile tests at 23 C indicated dramatic yield strength increase (>300%), lack of work hardening, and minimal (<1%) total elongations. SEM analysis of fracture and side surfaces were conducted to determine reduction in are and the mode of fracture. The reduction of area was negligible. All but one specimen failed by a combination of ductile shear deformation and cleavage crack growth. Transgranular cleavage cracks were initiated by stress concentrations at the tips of the shear bands. In side-view observations, evidence was found of slip bands typically associated with dislocation channeling. No differences due to pre-irradiation heat treatment and heat-to-heat composition variations were detected. The only deviation from this behavior was found in V-4Cr-4Ti-B alloy, which failed in the grip portion by complete cleavage cracking.

  4. A novel DNA intercalator, butylamino-pyrimido[4',5':4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells.

    PubMed

    Shahabuddin, M S; Nambiar, Mridula; Choudhary, Bibha; Advirao, Gopal M; Raghavan, Sathees C

    2010-02-01

    DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics. PMID:19142583

  5. Serum Predictors of Percent Lean Mass in Young Adults.

    PubMed

    Lustgarten, Michael S; Price, Lori L; Phillips, Edward M; Kirn, Dylan R; Mills, John; Fielding, Roger A

    2016-08-01

    Lustgarten, MS, Price, LL, Phillips, EM, Kirn, DR, Mills, J, and Fielding, RA. Serum predictors of percent lean mass in young adults. J Strength Cond Res 30(8): 2194-2201, 2016-Elevated lean (skeletal muscle) mass is associated with increased muscle strength and anaerobic exercise performance, whereas low levels of lean mass are associated with insulin resistance and sarcopenia. Therefore, studies aimed at obtaining an improved understanding of mechanisms related to the quantity of lean mass are of interest. Percent lean mass (total lean mass/body weight × 100) in 77 young subjects (18-35 years) was measured with dual-energy x-ray absorptiometry. Twenty analytes and 296 metabolites were evaluated with the use of the standard chemistry screen and mass spectrometry-based metabolomic profiling, respectively. Sex-adjusted multivariable linear regression was used to determine serum analytes and metabolites significantly (p ≤ 0.05 and q ≤ 0.30) associated with the percent lean mass. Two enzymes (alkaline phosphatase and serum glutamate oxaloacetate aminotransferase) and 29 metabolites were found to be significantly associated with the percent lean mass, including metabolites related to microbial metabolism, uremia, inflammation, oxidative stress, branched-chain amino acid metabolism, insulin sensitivity, glycerolipid metabolism, and xenobiotics. Use of sex-adjusted stepwise regression to obtain a final covariate predictor model identified the combination of 5 analytes and metabolites as overall predictors of the percent lean mass (model R = 82.5%). Collectively, these data suggest that a complex interplay of various metabolic processes underlies the maintenance of lean mass in young healthy adults. PMID:23774283

  6. Matter power spectrum and the challenge of percent accuracy

    NASA Astrophysics Data System (ADS)

    Schneider, Aurel; Teyssier, Romain; Potter, Doug; Stadel, Joachim; Onions, Julian; Reed, Darren S.; Smith, Robert E.; Springel, Volker; Pearce, Frazer R.; Scoccimarro, Roman

    2016-04-01

    Future galaxy surveys require one percent precision in the theoretical knowledge of the power spectrum over a large range including very nonlinear scales. While this level of accuracy is easily obtained in the linear regime with perturbation theory, it represents a serious challenge for small scales where numerical simulations are required. In this paper we quantify the precision of present-day N-body methods, identifying main potential error sources from the set-up of initial conditions to the measurement of the final power spectrum. We directly compare three widely used N-body codes, Ramses, Pkdgrav3, and Gadget3 which represent three main discretisation techniques: the particle-mesh method, the tree method, and a hybrid combination of the two. For standard run parameters, the codes agree to within one percent at k<=1 h Mpc‑1 and to within three percent at k<=10 h Mpc‑1. We also consider the bispectrum and show that the reduced bispectra agree at the sub-percent level for k<= 2 h Mpc‑1. In a second step, we quantify potential errors due to initial conditions, box size, and resolution using an extended suite of simulations performed with our fastest code Pkdgrav3. We demonstrate that the simulation box size should not be smaller than L=0.5 h‑1Gpc to avoid systematic finite-volume effects (while much larger boxes are required to beat down the statistical sample variance). Furthermore, a maximum particle mass of Mp=109 h‑1Msolar is required to conservatively obtain one percent precision of the matter power spectrum. As a consequence, numerical simulations covering large survey volumes of upcoming missions such as DES, LSST, and Euclid will need more than a trillion particles to reproduce clustering properties at the targeted accuracy.

  7. Three-dimensional structure of the complex of actin and DNase I at 4.5 A resolution.

    PubMed Central

    Kabsch, W; Mannherz, H G; Suck, D

    1985-01-01

    The shape of an actin subunit has been derived from an improved 6 A map of the complex of rabbit skeletal muscle actin and bovine pancreatic DNase I obtained by X-ray crystallographic methods. The three-dimensional structure of DNase I determined independently at 2.5 A resolution was compared with the DNase I electron density in the actin:DNase map. The two structures are very similar at 6 A resolution thus leading to an unambiguous identification of actin as well as DNase I electron density. Furthermore the correct hand of the actin structure is determined from the DNase I atomic structure. The resolution of the actin structure was extended to 4.5 A by using a single heavy-atom derivative and the knowledge of the atomic coordinates of DNase I. The dimensions of an actin subunit are 67 A X 40 A X 37 A. It consists of a small and a large domain, the small domain containing the N terminus. Actin is an alpha,beta-protein with a beta-pleated sheet in each domain. These sheets are surrounded by several alpha-helices, comprising at least 40% of the structure. The phosphate peak of the adenine nucleotide is located between the two domains. The complex of actin and DNase I as found in solution (i.e., the actin:DNase I contacts which do not depend on crystal packing) was deduced from a comparison of monoclinic with orthorhombic crystals. Residues 44-46, 51, 52, 60-62 of DNase I are close to a loop region in the small domain of actin. At a distance of approximately 15 A there is a second contact in the large domain in which Glu13 of DNase I is involved. A possible binding region for myosin is discussed. Images Fig. 1. Fig. 2. Fig. 3. PMID:4065103

  8. Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils

    PubMed Central

    Luo, Hongbo R; Mondal, Subhanjan

    2015-01-01

    Neutrophils play critical roles in innate immunity and host defense. However, excessive neutrophil accumulation or hyper-responsiveness of neutrophils can be detrimental to the host system. Thus, the response of neutrophils to inflammatory stimuli needs to be tightly controlled. Many cellular processes in neutrophils are mediated by localized formation of an inositol phospholipid, phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), at the plasma membrane. The PtdIns(3,4,5)P3 signaling pathway is negatively regulated by lipid phosphatases and inositol phosphates, which consequently play a critical role in controlling neutrophil function and would be expected to act as ideal therapeutic targets for enhancing or suppressing innate immune responses. Here, we comprehensively review current understanding about the action of lipid phosphatases and inositol phosphates in the control of neutrophil function in infection and inflammation. PMID:25576302

  9. Syntheses of new imidazole ligand series and evaluation of 1-, 2- and 4,5-imidazole substituent electronic and steric effects on N-donor strengths

    NASA Astrophysics Data System (ADS)

    Eseola, Abiodun O.; Sun, Wen-Hua; Li, Wen; Woods, Joseph A. O.

    2010-12-01

    A series of new imidazole based heterocycles (5-(4,5-diphenyl-1H-imidazol-2-yl)furan-2-yl)methyl acetate ( Him-dp), (5-(1H-phenanthro[9,10-d]imidazol-2-yl)furan-2-yl)methyl acetate ( HIm-pt), (5-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)furan-2-yl)methyl acetate ( HIm-phen), 2-(2-nitrophenyl)-4,5-diphenyl-1H-imidazole ( HIm-n), 1-methyl-2-(2-nitrophenyl)-4,5-diphenyl-1H-imidazole ( MeIm-n), N-(2-(1-ethyl-4,5-diphenyl-1H-imidazol-2-yl)phenyl)benzamide ( EtIm-ba) and 2,4-di-tert-butyl-6-(8-(1-ethyl-4,5-diphenyl-1H-imidazol-2-yl)-1,4-dihydroquinolin-2-yl)phenol ( EtIm-q) were synthesized and studied for the dependence of their azole donor characteristics on substituent factors by means of experimentally determined ionization constant data (derived as p Kas), spectroscopic analyses and calculated properties of their DFT optimized molecular geometries performed at the B3LYP/6-311 + G * level. Results showed that the lowest donor strength recorded for HIm-pt (p Ka = 2.67 ± 0.07) could be traced to the extensive electronic conjugation of the azole π-electrons with 4,5- and 2-substituents. On the other hand, the strongest imidazole donor strength in the series was obtained from EtIm-q (p Ka = 4.61 ± 0.04) for which the substituents possessed negligible π-overlap with the azole ring. The experimental results and theoretical calculations lead to conclusions that effective conjugation between the imidazole ring and substituent aromatic groups is accountable for significant withdrawal of charge densities on the imidazole N-donor atom and vice versa. Furthermore, observed donor strengths in the series suggest that electronic inductive effects of the substituents provided lesser impact on donor strength modification of imidazole base and that alkylation of 1-imidazole position did not yield the anticipated push of electron density in favour of the N-donor atom. It is anticipated that the results should promote the understanding of azole-containing bio-macromolecular species

  10. Immunogenicity of Plasmodium yoelii merozoite surface protein 4/5 produced in transgenic plants.

    PubMed

    Wang, Lina; Webster, Diane E; Campbell, Alison E; Dry, Ian B; Wesselingh, Steve L; Coppel, Ross L

    2008-01-01

    Malaria is a major global health problem for which effective control measures are urgently needed. Considerable effort has been focused on the development of effective vaccines against the causative parasite and protective vaccine trials are now being reported. Due to the relative poverty and lack of infrastructure in malaria-endemic areas, a successful immunisation strategy will depend critically on cheap and scaleable methods of vaccine production, distribution and delivery. One promising technology is transgenic plants, both as a bioreactor for the vaccine-manufacturing process as well as a matrix for oral immunisation. In this study, we investigated the feasibility of using transgenic plants to induce protective immunity against malaria infection using Plasmodium yoelii merozoite surface protein 4/5 (PyMSP4/5) in a mouse model of malaria infection. Our data show that the PyMSP4/5 protein can be produced in plants in a configuration that reacts with protective antibodies. Optimisation of codon usage for the PyMSP4/5 gene resulted in significantly increased antigen expression in plants. PyMSP4/5 protein from the codon-optimised construct accumulated to 0.25% of total soluble protein, a sixfold increase over the native gene sequence. Tobacco-made PyMSP4/5 was able to induce antigen-specific antibodies in mice following parenteral delivery, as well as boost the antibody responses induced by DNA vaccination when delivered parenterally or orally. We believe this is the first report to show that plant-made malaria antigens are immunogenic. However, the antibody levels were not high enough to protect the immunised mice against a lethal challenge with P. yoelii. Further strategies are needed to achieve a protective dose, including improvements to antigen expression levels in plants and strategies to enhance the immunogenicity of the expressed antigen. PMID:17681344

  11. Liquid atomization

    NASA Astrophysics Data System (ADS)

    Bayvel, L.; Orzechowski, Z.

    The present text defines the physical processes of liquid atomization, the primary types of atomizers and their design, and ways of measuring spray characteristics; it also presents experimental investigation results on atomizers and illustrative applications for them. Attention is given to the macrostructural and microstructural parameters of atomized liquids; swirl, pneumatic, and rotary atomizers; and optical drop sizing methods, with emphasis on nonintrusive optical methods.

  12. Phosphatidylinositol(4,5)bisphosphate and phosphatidylinositol(4)phosphate in plant tissues. [Pisum sativum

    SciTech Connect

    Irvine, R.F.; Letcher, A.J.; Lander, D.J. ); Dawson, A.P. ); Musgrave, A. ); Drobak, B.K. )

    1989-03-01

    Pea (Pisum sativum) leaf discs or swimming suspensions of Chlamydomonas eugametos were radiolabeled with ({sup 3}H)myo-inositol or ({sup 32}P)Pi and the lipids were extracted, deacylated, and their glycerol moieties removed. The resulting inositol trisphosphate and bisphosphate fractions were examined by periodate degradation, reduction and dephosphorylation, or by incubation with human red cell membranes. Their likely structures were identified as D-myo-inositol(1,4,5)trisphosphate and D-myo-inositol(1,4,)-bisphosphate. It is concluded that plants contain phosphatidylinositol(4)phosphate and phosphatidylinositol(4,5)bisphosphate; no other polyphosphoinositides were detected.

  13. Synthesis, characterization, and crystal structure of 2-iodo-3,4,5-trimethoxybenzoic acid

    NASA Astrophysics Data System (ADS)

    Kolev, Iliyan N.; Petrova, Svetlana P.; Nikolova, Rositsa P.; Dimowa, Louiza T.; Shivachev, Boris L.

    2013-02-01

    This work describes the synthesis of 2-iodo-3,4,5-trimethoxybenzoic acid. The combination of iodine and silver trifluoroacetate (AgTFA) reagents was used successfully for the iodination of 3,4,5-trimetoxybenzoic acid. To improve the efficiency of the synthetic process a significant modification on the experimental design was also performed. The main structural features of the obtained aryl iodide were investigated by a single crystal X-ray diffraction analysis, FTIR, 1H and 13C NMR spectroscopy.

  14. Synthesis and Biological Activity of New [1,3]Thiazolo[4,5-d]pyridazin-4(5H)-ones

    PubMed Central

    Demchenko, Anatoly; Bobkova, Ludmila; Yadlovskiy, Oleh; Buchtiarova, Tatiana; Demchenko, Sergey

    2016-01-01

    A series of novel 2-(N-pyrrolidino, N-piperidino or N-morpholino)-7-phenyl(α-furoyl or α-thienyl)-[1,3]thiazolo[4,5-d]pyridazinones 10a–c, 14–16a,b was synthesized in 78–87% yields via the reaction of methyl 5-benzoyl(α-furoyl or α-thienyl)-2-aminosubstituted-thiazol-4-carboxylates 9a–c, 13a–e with hydrazine. These new compounds have been tested for their in vivo analgesic and anti-inflammatory activities. All compounds have been characterized by 1H-NMR, 13C-NMR spectroscopy, and liquid chromatography–mass spectrometry. PMID:27222602

  15. Synthesis and Biological Activity of New [1,3]Thiazolo[4,5-d]pyridazin-4(5H)-ones.

    PubMed

    Demchenko, Anatoly; Bobkova, Ludmila; Yadlovskiy, Oleh; Buchtiarova, Tatiana; Demchenko, Sergey

    2016-01-01

    A series of novel 2-(N-pyrrolidino, N-piperidino or N-morpholino)-7-phenyl(α-furoyl or α-thienyl)-[1,3]thiazolo[4,5-d]pyridazinones 10a-c, 14-16a,b was synthesized in 78-87% yields via the reaction of methyl 5-benzoyl(α-furoyl or α-thienyl)-2-aminosubstituted-thiazol-4-carboxylates 9a-c, 13a-e with hydrazine. These new compounds have been tested for their in vivo analgesic and anti-inflammatory activities. All compounds have been characterized by (1)H-NMR, (13)C-NMR spectroscopy, and liquid chromatography-mass spectrometry. PMID:27222602

  16. Characteristics of 2,4,5,2',4',5'-hexachlorobiphenyl distribution among lipoproteins in vitro. [Rats and human whole blood, plasma, and lipoprotein fractions

    SciTech Connect

    Vomachka, M.S.; Vodicnik, M.J.; Lech, J.J.

    1983-09-01

    The uptake, distribution, and transfer of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) were examined in vitro with human and rat whole blood, plasma, and lipoprotein fractions. 6-CB distribution between plasma and erythrocytes as well as among lipoproteins was determined following sedimentation of erythrocytes and ultracentrifugal fractionation of plasma. In both rat and human whole blood, 70 to 75% of 6-CB partitioned into plasma and 25 to 30% into erythrocytes. The uptake of 6-CB into plasma was extremely rapid and the rate of uptake was found to be dependent upon temperature. The distribution of 6-CB among lipoproteins was relatively homogeneous with 20 to 30% being distributed in very low-density lipoproteins (VLDL, d . 0.95-1.006 g/ml), 15 to 20% in low-density lipoproteins (LDL, d . 1.006-1.063 g/ml), and 15 to 25% in high-density lipoproteins (HDL, d . 1.063-1.21 g/ml). Over 25% of 6-CB was found in the remaining bottom fraction. In addition, each isolated fraction when incubated alone with 6-CB was shown capable of uptake. The relative proportion of 6-CB among the lipoproteins was independent of the level taken up by plasma. 6-CB was also found to transfer among lipoproteins. This exchange of 6-CB proved to be dependent upon the concentrations of both protein and triacylglycerol in the incubations. Two proteins in the bottom fraction (Bf), albumin and a steroid binding globulin, were capable of competing with the lipoproteins for 6-CB uptake.

  17. AQUEOUS AMMONIA EQUILIBRIUM - TABULATION OF PERCENT UN-IONIZED AMMONIA

    EPA Science Inventory

    The percent of un-ionized ammonia as a function of pH and temperature in aqueous ammonia solutions of zero salinity is presented in tabular form over the following ranges: temperature 0.0 to 40.0 C in increments of 0.2 degree, and pH 5.00 to 12.00 in increments of 0.01 pH unit.

  18. 60. MISSISSIPPI, NOXUBEE CO. MACON MAHORNER' S BRIDGE, 1884, 4.5 ...

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

    60. MISSISSIPPI, NOXUBEE CO. MACON MAHORNER' S BRIDGE, 1884, 4.5 miles S on McLeod-Shuqualak road. Bottom of swing span and top of center pier. Sarcone Photography, Columbus, Ms. Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  19. Low-molecular-weight (4.5S) ribonucleic acid in higher-plant chloroplast ribosomes.

    PubMed Central

    Whitfeld, P R; Leaver, C J; Bottomley, W; Atchison, B

    1978-01-01

    A species of RNA that migrates on 10% (w/v) polyacrylamide gels between 5S and 4S RNA was detected in spinach chloroplasts. This RNA (referred to as 4.5 S RNA) was present in amounts equimolar to the 5S RNA and its molecular weight was estimated to be approx. 33 000. Fractionation of the chloroplast components showed that the 4.5S RNA was associated with the 50 S ribosomal subunit and that it could be removed by washing the ribosomes with a buffer containing 0.01 M-EDTA and 0.5 M-KCl. It did not appear to be a cleavage product of the labile 23 S RNA of spinach chloroplast ribosomes. When 125I-labelled 4.5 S RNA was hybridized to fragments of spinach chloroplast DNA produced by SmaI restriction endonuclease, a single fragment (mol.wt. 1.15 times 10(6)) became labelled. The same DNA fragment also hybridized to chloroplast 5 S RNA and part of the 23 S RNA. It was concluded that the coding sequence for 4.5 S RNA was part of, or immediately adjacent to, the rRNA-gene region in chloroplast DNA . A comparable RNA species was observed in chloroplasts of tobacco and pea leaves. Images Fig. 8. PMID:743229

  20. 26 CFR 1.401(a)(4)-5 - Plan amendments and plan terminations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Plan amendments and plan terminations. 1.401(a... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(a)(4)-5 Plan amendments and plan terminations. (a) Introduction—(1) Overview. This...

  1. 26 CFR 1.401(a)(4)-5 - Plan amendments and plan terminations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Plan amendments and plan terminations. 1.401(a)(4... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(a)(4)-5 Plan amendments and plan terminations. (a) Introduction—(1) Overview. This...

  2. 26 CFR 1.401(a)(4)-5 - Plan amendments and plan terminations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Plan amendments and plan terminations. 1.401(a... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(a)(4)-5 Plan amendments and plan terminations. (a) Introduction—(1) Overview. This paragraph (a)...

  3. 17 CFR 275.206(4)-5 - Political contributions by certain investment advisers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... investment adviser that has reported on its annual updating amendment to Form ADV (17 CFR 279.1) that it has... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Political contributions by....206(4)-5 Political contributions by certain investment advisers. (a) Prohibitions. As a...

  4. 17 CFR 275.206(4)-5 - Political contributions by certain investment advisers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... investment adviser that has reported on its annual updating amendment to Form ADV (17 CFR 279.1) that it has... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Political contributions by....206(4)-5 Political contributions by certain investment advisers. (a) Prohibitions. As a...

  5. 17 CFR 275.206(4)-5 - Political contributions by certain investment advisers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... investment adviser that has reported on its annual updating amendment to Form ADV (17 CFR 279.1) that it has... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Political contributions by....206(4)-5 Political contributions by certain investment advisers. (a) Prohibitions. As a...

  6. 17 CFR 275.206(4)-5 - Political contributions by certain investment advisers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... investment adviser that has reported on its annual updating amendment to Form ADV (17 CFR 279.1) that it has... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Political contributions by....206(4)-5 Political contributions by certain investment advisers. (a) Prohibitions. As a...

  7. 40 CFR 721.10584 - Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10584 Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  8. 40 CFR 721.10584 - Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10584 Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  9. 40 CFR 721.10433 - Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....80(f) and (j) (dry etching agent and chemical vapor deposition agent for the production of...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10433 Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-. (a) Chemical...

  10. 40 CFR 721.10433 - Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....80(f) and (j) (dry etching agent and chemical vapor deposition agent for the production of...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10433 Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-. (a) Chemical...

  11. Fragmentation of silicon nuclei at 4. 5 A GeV/c

    SciTech Connect

    Ahmad, T.; Irfan, M. )

    1991-11-30

    1024 interactions caused by 4.5 A GeV/c {sup 28}Si in emulsion are studied. In this paper result on the mean free path is discussed and compared with the corresponding results obtained for the interactions initiated by other projectiles. Multiplicity distributions for Z = 1, 2 and {ge}3 fragments are also investigated.

  12. Spt4/5 stimulates transcription elongation through the RNA polymerase clamp coiled-coil motif

    PubMed Central

    Hirtreiter, Angela; Damsma, Gerke E.; Cheung, Alan C. M.; Klose, Daniel; Grohmann, Dina; Vojnic, Erika; Martin, Andrew C. R.; Cramer, Patrick; Werner, Finn

    2010-01-01

    Spt5 is the only known RNA polymerase-associated factor that is conserved in all three domains of life. We have solved the structure of the Methanococcus jannaschii Spt4/5 complex by X-ray crystallography, and characterized its function and interaction with the archaeal RNAP in a wholly recombinant in vitro transcription system. Archaeal Spt4 and Spt5 form a stable complex that associates with RNAP independently of the DNA–RNA scaffold of the elongation complex. The association of Spt4/5 with RNAP results in a stimulation of transcription processivity, both in the absence and the presence of the non-template strand. A domain deletion analysis reveals the molecular anatomy of Spt4/5—the Spt5 Nus-G N-terminal (NGN) domain is the effector domain of the complex that both mediates the interaction with RNAP and is essential for its elongation activity. Using a mutagenesis approach, we have identified a hydrophobic pocket on the Spt5 NGN domain as binding site for RNAP, and reciprocally the RNAP clamp coiled-coil motif as binding site for Spt4/5. PMID:20197319

  13. Priming 4.5-Month-Old Infants to Use Height Information by Enhancing Retrieval

    ERIC Educational Resources Information Center

    Wang, Su-hua

    2011-01-01

    How do infants select and use information that is relevant to the task at hand? Infants treat events that involve different spatial relations as distinct, and their selection and use of object information depends on the type of event they encounter. For example, 4.5-month-olds consider information about object height in occlusion events, but…

  14. Bifunctional Ag/C3N4.5 composite nanobelts for photocatalysis and antibacterium.

    PubMed

    Lei, Renbo; Jian, Jikang; Zhang, Zhihua; Song, Bo; Wu, Rong

    2016-09-30

    Multiple functions can be achieved in carbon nitride-based composite nanomaterials by tuning their components and structures. Here, we report on a large-scale synthesis of novel bifunctional Ag/C3N4.5 composite nanobelts (CNBs) with efficient photocatalytic and antibacterial activity. The Ag/C3N4.5 CNBs were synthesized in high yield by a two-step route including a homogeneous precipitation process and a subsequent calcination treatment. The structural, morphological, compositional, and spectroscopic characterizations revealed that the Ag/C3N4.5 CNBs are composed of N-deficient melem ultrathin nanobelts and crystalline Ag nanoparticles attached to the surface of the nanobelts with good contact. The band gap of the Ag/C3N4.5 CNBs is determined to be about 3.04 eV. The efficient photocatalytic and antibacterial activities of the composite nanomaterials are verified by testing the degradation of Rhodamine B (RhB) and the inhibition zone to bacterium E. coli. The work provides a facile route to bifunctional carbon nitride-based composites with potential applications in the fields of the environment and biology. PMID:27560165

  15. The Role of PI(3,4,5)P3 Signaling During Axonal Growth Cone Chemotaxis

    NASA Astrophysics Data System (ADS)

    Henle, Steven J.

    Development of the nervous system is a remarkably complex process that involves the birth of billions of neurons leading to the formation of trillions of synapses. Many biological programs underlie the formation of a functional nervous system. I focused on trying to understand the process by which a newly formed axon navigates a series of signals in the environment that guide it to a synaptic partner. At the tip of the extending neurite is a conical expansion known as the growth cone that primarily is responsible for performing this pathfinding process. In order to do so it senses the environment, and induces a program of intracellular signaling that in turn leads to directed axon extension. My work has focused on understanding this signaling machinery. I have aimed to understand the role the phosphoinositde PI(3,4,5)P3 due to the critical role it plays in amoeboid chemotaxis. I discovered that PI(3,4,5)P3 and its downstream kinase Akt define the leading edge during growth cone chemotaxis and lead to activation of a TRP (Transient Receptor Potential) channel. Furthermore, I found that the PI(3,4,5)P3 phosphatase PTEN appears to be exclusively linked to guiding growth cone migration in response to a gradient of chemorepellent. Taken together my data demonstrate that PI(3,4,5)P3 functions as a key instructive mediator of growth cone chemotaxis.

  16. Effectiveness of Multipurpose Unit Early Classroom Intervention Program for 4-5-Year-Old Children

    ERIC Educational Resources Information Center

    Celebioglu Morkoc, Ozlem; Aktan Acar, Ebru

    2014-01-01

    This research examined the effectiveness of Multipurpose Unit Early Classroom Intervention Program (MUECIP) prepared for 4-5-year-old (48-60 months) children whose development is at risk because of their families' socioeconomic conditions. The research adopted a preliminary test-final test control group trial model. The research participants…

  17. Synthesis and antifungal activity of natural product-based 6-alkyl-2 3 4 5-tetrahydropyridines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a–5g) that mimic the natural products piperideines that were recently identified in the fire ant venom have been synthesized. Compounds 5c–5g with the C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexa...

  18. Ensemble Perception of Size in 4-5-Year-Old Children

    ERIC Educational Resources Information Center

    Sweeny, Timothy D.; Wurnitsch, Nicole; Gopnik, Alison; Whitney, David

    2015-01-01

    Groups of objects are nearly everywhere we look. Adults can perceive and understand the "gist" of multiple objects at once, engaging ensemble-coding mechanisms that summarize a group's overall appearance. Are these group-perception mechanisms in place early in childhood? Here, we provide the first evidence that 4-5-year-old children use…

  19. 4,5-Disubstituted oxazolidinones: High affinity molecular effectors of RNA function.

    PubMed

    Anupam, Rajaneesh; Nayek, Abhijit; Green, Nicholas J; Grundy, Frank J; Henkin, Tina M; Means, John A; Bergmeier, Stephen C; Hines, Jennifer V

    2008-06-15

    The T box transcription antitermination system is a riboswitch found primarily in Gram-positive bacteria which monitors the aminoacylation of the cognate tRNA and regulates a variety of amino acid-related genes. Novel 4,5-disubstituted oxazolidinones were identified as high affinity RNA molecular effectors that modulate the transcription antitermination function of the T box riboswitch. PMID:18502126

  20. 2,2\\',4,4\\',5,5\\'-Hexabromodiphenyl ether (BDE-153)

    Integrated Risk Information System (IRIS)

    2,2 ' , 4,4 ' , 5,5 ' - Hexabromodiphenyl ether ( BDE - 153 ) ; CASRN 68631 - 49 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I (

  1. 2,2\\',3,3\\',4,4\\',5,5\\',6,6\\'-Decabromodiphenyl ether (BDE-209)

    Integrated Risk Information System (IRIS)

    2,2 ' , 3,3 ' , 4,4 ' , 5,5 ' , 6,6 ' - Decabromodiphenyl ether ( BDE - 209 ) ; CASRN 1163 - 19 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process

  2. Strand I: Physical Health. Sensory Perception. Health Curriculum Materials Grades 4, 5, 6.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Elementary Curriculum Development.

    GRADES OR AGES: Grades 4, 5, and 6. SUBJECT MATTER: Sensory perceptions, the organs involved, and eye and hearing care. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into six different sectional steps organized around a gradual, ascending understanding of the sense organs. OBJECTIVES AND ACTIVITIES: The material is divided into…

  3. Physical Education, Junior Division: Grades 4, 5, 6. Curriculum J.5.

    ERIC Educational Resources Information Center

    Ontario Dept. of Education, Toronto.

    This manual was prepared to give teachers assistance in carrying out programs in physical education in grades 4, 5, and 6. Because many schools have space and equipment deficiencies, some emphasis has been placed on improvisation and the fullest possible use of available space and equipment. The manual is divided into two sections: organization…

  4. Synthetic studies towards Zetekitoxin AB: preparation of 4,5-epi-11-hydroxy-saxitoxinol

    PubMed Central

    Pearson, Aaron D.; Williams, Robert M.

    2014-01-01

    A concise synthesis of 4,5-epi-11-hydroxy-saxitoxinol utilizing D-ribose to direct an asymmetric Mannich reaction. This approach allows many modes of reactivity, which can be used to access various analogs of saxitoxin. PMID:25313264

  5. Synthesis of inositol phosphate-based competitive antagonists of inositol 1,4,5-trisphosphate receptors.

    PubMed

    Konieczny, Vera; Stefanakis, John G; Sitsanidis, Efstratios D; Ioannidou, Natalia-Anastasia T; Papadopoulos, Nikolaos V; Fylaktakidou, Konstantina C; Taylor, Colin W; Koumbis, Alexandros E

    2016-02-16

    Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca(2+) channels that are widely expressed in animal cells, where they mediate the release of Ca(2+) from intracellular stores evoked by extracellular stimuli. A diverse array of synthetic agonists of IP3Rs has defined structure-activity relationships, but existing antagonists have severe limitations. We combined analyses of Ca(2+) release with equilibrium competition binding to IP3R to show that (1,3,4,6)IP4 is a full agonist of IP3R1 with lower affinity than (1,4,5)IP3. Systematic manipulation of this meso-compound via a versatile synthetic scheme provided a family of dimeric analogs of 2-O-butyryl-(1,3,4,6)IP4 and (1,3,4,5,6)IP5 that compete with (1,4,5)IP3 for binding to IP3R without evoking Ca(2+) release. These novel analogs are the first inositol phosphate-based competitive antagonists of IP3Rs with affinities comparable to that of the only commonly used competitive antagonist, heparin, the utility of which is limited by off-target effects. PMID:26818818

  6. Preparation of 3,3'-azobis(6-amino-1,2,4,5-tetrazine)

    DOEpatents

    Hiskey, Michael A.; Chavez, David E.; Naud, Darren

    2002-01-01

    The compound of the structure ##STR1## where a, b, c, d and e are 0 or 1 and a+b+c+d+e is from 0 to 5 is disclosed together with the species 3,3'-azobis(6-amino-1,2,4,5-tetrazine) and a process of preparing such compounds.

  7. IMMUNOHISTOCHEMICAL ANALYSIS OF ZNT1, 4, 5, 6, AND 7 IN THE MOUSE GASTROINTESTINAL TRACT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Expression of five zinc transporters (ZnT1, 4, 5, 6, and 7) of the Slc30 family in the mouse gastrointestinal tract was studied by immunohistochemical analysis. The results demonstrated unique expression patterns, levels, and cellular localization among ZnT proteins in the mouse gastrointestinal tra...

  8. Netscape Communicator 4.5. Volume I: The Basic Functions of the Navigator Component.

    ERIC Educational Resources Information Center

    Gallo, Gail; Wichowski, Chester P.

    This first of two guides on Netscape Communicator 4.5 contains six lessons on the basic functions of the Navigator component. Lesson 1 covers terminology and methods to connect to the World Wide Web, hardware needed, and a Netscape Communicator overview. Lesson 2 introduces the Navigator window, toolbars, and menus, and how to change the default…

  9. 28 percent efficient GaAs concentrator solar cells

    NASA Technical Reports Server (NTRS)

    Macmillan, H. F.; Hamaker, H. C.; Kaminar, N. R.; Kuryla, M. S.; Ladle Ristow, M.

    1988-01-01

    AlGaAs/GaAs heteroface solar concentrator cells which exhibit efficiencies in excess of 27 percent at high solar concentrations (over 400 suns, AM1.5D, 100 mW/sq cm) have been fabricated with both n/p and p/n configurations. The best n/p cell achieved an efficiency of 28.1 percent around 400 suns, and the best p/n cell achieved an efficiency of 27.5 percent around 1000 suns. The high performance of these GaAs concentrator cells compared to earlier high-efficiency cells was due to improved control of the metal-organic chemical vapor deposition growth conditions and improved cell fabrication procedures (gridline definition and edge passivation). The design parameters of the solar cell structures and optimized grid pattern were determined with a realistic computer modeling program. An evaluation of the device characteristics and a discussion of future GaAs concentrator cell development are presented.

  10. Relationship between breast sound speed and mammographic percent density

    NASA Astrophysics Data System (ADS)

    Sak, Mark; Duric, Nebojsa; Boyd, Norman; Littrup, Peter; Myc, Lukasz; Faiz, Muhammad; Li, Cuiping; Bey-Knight, Lisa

    2011-03-01

    Despite some shortcomings, mammography is currently the standard of care for breast cancer screening and diagnosis. However, breast ultrasound tomography is a rapidly developing imaging modality that has the potential to overcome the drawbacks of mammography. It is known that women with high breast densities have a greater risk of developing breast cancer. Measuring breast density is accomplished through the use of mammographic percent density, defined as the ratio of fibroglandular to total breast area. Using an ultrasound tomography (UST) prototype, we created sound speed images of the patient's breast, motivated by the fact that sound speed in a tissue is proportional to the density of the tissue. The purpose of this work is to compare the acoustic performance of the UST system with the measurement of mammographic percent density. A cohort of 251 patients was studied using both imaging modalities and the results suggest that the volume averaged breast sound speed is significantly related to mammographic percent density. The Spearman correlation coefficient was found to be 0.73 for the 175 film mammograms and 0.69 for the 76 digital mammograms obtained. Since sound speed measurements do not require ionizing radiation or physical compression, they have the potential to form the basis of a safe, more accurate surrogate marker of breast density.

  11. Electrochemical oxidation of 2,4,5-trichlorophenoxyacetic acid by metal-oxide-coated Ti electrodes.

    PubMed

    Maharana, Dusmant; Xu, Zesheng; Niu, Junfeng; Rao, Neti Nageswara

    2015-10-01

    Electrochemical oxidation of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) over metal-oxide-coated Ti anodes, i.e., Ti/SnO2-Sb/Ce-PbO2, Ti/SnO2-Sb and Ti/RuO2, was examined. The degradation efficiency of over 90% was attained at 20 min at different initial concentrations (0.5-20 mg L(-1)) and initial pH values (3.1-11.2). The degradation efficiencies of 2,4,5-T on Ti/SnO2-Sb/Ce-PbO2, Ti/SnO2-Sb and Ti/RuO2 anodes were higher than 99.9%, 97.2% and 91.5% at 30 min, respectively, and the respective total organic carbon removal ratios were 65.7%, 54.6% and 37.2%. The electrochemical degradation of 2,4,5-T in aqueous solution followed pseudo-first-order kinetics. The compounds, i.e., 2,5-dichlorohydroquinone and 2,5-dihydroxy-p-benzoquinone, have been identified as the main aromatic intermediates by liquid chromatography-mass spectrometry. The results showed that the energy efficiencies of 2,4,5-T (20 mg L(-1)) degradation with Ti/SnO2-Sb/Ce-PbO2 anode at the optimal current densities from 2 to 16 mA cm(-2) ranged from 8.21 to 18.73 kWh m(-3). PMID:25981800

  12. Conformational Changes in Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinase upon Substrate Binding

    PubMed Central

    Baños-Sanz, José Ignacio; Sanz-Aparicio, Julia; Whitfield, Hayley; Hamilton, Chris; Brearley, Charles A.; González, Beatriz

    2012-01-01

    Inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IP5 2-K) catalyzes the synthesis of inositol 1,2,3,4,5,6-hexakisphosphate from ATP and IP5. Inositol 1,2,3,4,5,6-hexakisphosphate is implicated in crucial processes such as mRNA export, DNA editing, and phosphorus storage in plants. We previously solved the first structure of an IP5 2-K, which shed light on aspects of substrate recognition. However, failure of IP5 2-K to crystallize in the absence of inositide prompted us to study putative conformational changes upon substrate binding. We have made mutations to residues on a region of the protein that produces a clasp over the active site. A W129A mutant allowed us to capture IP5 2-K in its different conformations by crystallography. Thus, the IP5 2-K apo-form structure displays an open conformation, whereas the nucleotide-bound form shows a half-closed conformation, in contrast to the inositide-bound form obtained previously in a closed conformation. Both nucleotide and inositide binding produce large conformational changes that can be understood as two rigid domain movements, although local changes were also observed. Changes in intrinsic fluorescence upon nucleotide and inositide binding are in agreement with the crystallographic findings. Our work suggests that the clasp might be involved in enzyme kinetics, with the N-terminal lobe being essential for inositide binding and subsequent conformational changes. We also show how IP5 2-K discriminates between inositol 1,3,4,5-tetrakisphosphate and 3,4,5,6-tetrakisphosphate enantiomers and that substrate preference can be manipulated by Arg130 mutation. Altogether, these results provide a framework for rational design of specific inhibitors with potential applications as biological tools for in vivo studies, which could assist in the identification of novel roles for IP5 2-K in mammals. PMID:22745128

  13. Gliotoxin Suppresses Macrophage Immune Function by Subverting Phosphatidylinositol 3,4,5-Trisphosphate Homeostasis

    PubMed Central

    Schlam, Daniel; Canton, Johnathan; Carreño, Marvin; Kopinski, Hannah; Freeman, Spencer A.; Grinstein, Sergio

    2016-01-01

    ABSTRACT Aspergillus fumigatus, an opportunistic fungal pathogen, spreads in the environment by releasing numerous conidia that are capable of reaching the small alveolar airways of mammalian hosts. In otherwise healthy individuals, macrophages are responsible for rapidly phagocytosing and eliminating these conidia, effectively curbing their germination and consequent invasion of pulmonary tissue. However, under some circumstances, the fungus evades phagocyte-mediated immunity and persists in the respiratory tree. Here, we report that A. fumigatus escapes macrophage recognition by strategically targeting phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] metabolism through gliotoxin, a potent immunosuppressive mycotoxin. Time-lapse microscopy revealed that, in response to the toxin, macrophages cease to ruffle, undergo abrupt membrane retraction, and fail to phagocytose large targets effectively. Gliotoxin was found to prevent integrin activation and interfere with actin dynamics, both of which are instrumental for phagocytosis; similar effects were noted in immortalized and primary phagocytes. Detailed studies of the underlying molecular mechanisms of toxicity revealed that inhibition of phagocytosis is attributable to impaired accumulation of PtdIns(3,4,5)P3 and the associated dysregulation of downstream effectors, including Rac and/or Cdc42. Strikingly, in response to the diacylglycerol mimetic phorbol 12-myristate 13-acetate, gliotoxin-treated macrophages reactivate beta integrins, reestablish actin dynamics, and regain phagocytic capacity, despite the overt absence of plasmalemmal PtdIns(3,4,5)P3. Together, our findings identify phosphoinositide metabolism as a critical upstream target of gliotoxin and also indicate that increased diacylglycerol levels can bypass the requirement for PtdIns(3,4,5)P3 signaling during membrane ruffling and phagocytosis. PMID:27048806

  14. Crystal structures of Schiff base derivatives of 1-(3,4,5-trimethoxybenzylidene)thiosemicarbazide and (E)-N′-(3-nitrobenzylidene)isonicotinohydrazide

    SciTech Connect

    Dileep, C. S. Sridhar, M. A.; Mallesh, L.

    2014-04-24

    The crystal structures of 1-(3,4,5-trimethoxybenzylidene)thiosemicarbazide (1) and N′-(3-nitrobenzylidene) isonicotinohydrazide (2) have been determined by single-crystal X-ray diffraction. In compound 1, the position of C8, O1, O2, O3 atoms are in a distorted trigonal planar geometry. The mean plane of 3,4,5-trimethoxybenzylidene ring forms a dihedral angle of 5.39(14)° with the mean plane of thiosemicarbazide group. In the structure, the molecular packing is stabilized by intermolecular N–H with diaresisN, O–H with diaresisS and intramolecular C–H with diaresisO hydrogen bonds. In compound 2, the position of C8 atom and N1 atom are in a distorted trigonal planar geometry. The mean plane of phenyl ring forms a dihedral angle of 8.09° with that of the pyridine ring. In the structure, the molecular packing is stabilized by intermolecular N–H with diaresisN and intramolecular C–H with diaresisO hydrogen bonds.

  15. Crystal structures of Schiff base derivatives of 1-(3,4,5-trimethoxybenzylidene)thiosemicarbazide and (E)-N'-(3-nitrobenzylidene)isonicotinohydrazide

    NASA Astrophysics Data System (ADS)

    Dileep, C. S.; Mallesh, L.; Sridhar, M. A.

    2014-04-01

    The crystal structures of 1-(3,4,5-trimethoxybenzylidene)thiosemicarbazide (1) and N'-(3-nitrobenzylidene) isonicotinohydrazide (2) have been determined by single-crystal X-ray diffraction. In compound 1, the position of C8, O1, O2, O3 atoms are in a distorted trigonal planar geometry. The mean plane of 3,4,5-trimethoxybenzylidene ring forms a dihedral angle of 5.39(14)° with the mean plane of thiosemicarbazide group. In the structure, the molecular packing is stabilized by intermolecular N-ḦN, O-ḦS and intramolecular C-ḦO hydrogen bonds. In compound 2, the position of C8 atom and N1 atom are in a distorted trigonal planar geometry. The mean plane of phenyl ring forms a dihedral angle of 8.09° with that of the pyridine ring. In the structure, the molecular packing is stabilized by intermolecular N-ḦN and intramolecular C-ḦO hydrogen bonds.

  16. Rotation Sensing with an Atom Interferometer

    SciTech Connect

    Lenef, A.; Hammond, T.D.; Smith, E.T.; Chapman, M.S.; Rubenstein, R.A.; Pritchard, D.E.

    1997-02-01

    We have measured the phase shift induced by rotation of an atom interferometer at rates of -2 to +2 earth rates and obtained 1{percent} agreement with the predicted Sagnac phase shift for atomic matter waves. The rotational rms noise of our interferometer was 42 milliearth rates for 1 sec of integration time, within 9{percent} of shot noise. The high sensitivity and agreement of predicted and measured behavior suggest useful future scientific applications of atom interferometers as inertial sensors. {copyright} {ital 1997} {ital The American Physical Society}

  17. Effects of Solution Heat Treatment on Microstructure and Mechanical Properties of the Mg-4.5Zn-4.5Sn-2Al-0.6Sr Alloy

    NASA Astrophysics Data System (ADS)

    Zhang, Guanghao; Chen, Jihua; Yan, Hongge; Su, Bin

    2014-11-01

    Microstructure and mechanical properties of the Mg-4.5Zn-4.5Sn-2Al-0.6Sr alloy are investigated both in the as-cast condition and after the different three-step solution heat treatments (a solution heat treatment of 310 °C × 4 h + 340 °C × 28 h followed by a high-temperature solution treatment) to explore the optimal solution treatment cycle. The as-cast alloy contains a microstructure consisting of the α-Mg matrix, Mg2Sn, Mg51Zn20, Mg32(Al, Zn)49, and MgSnSr phases. After the solution heat treatment, all the Mg51Zn20, the Mg32(Al, Zn)49 phases, and most of the Mg2Sn phase are dissolved into the matrix, only the MgSnSr phase and a minority of the Mg2Sn phase are remained in the granular form or the fine dot-like. The volume fraction of the residual second phases decreases from 5.61 to 1.84% with the increasing solution time from 0 to 4 h at 420 °C and it decreases from 2.9 to 0.4% with the increasing solution temperature from 420 to 480 °C for 2 h. The alloy that experiences the solution treatment of 310 °C × 4 h + 340 °C × 28 h + 460 °C × 2 h exhibits the highest strength and the best plasticity among all the solution-treated alloys. Therefore, the optimal solution treatment is 310 °C × 4 h + 340 °C × 28 h + 460 °C × 2 h. The residual second phases in the alloy that experiences the optimal solution treatment are confirmed to be the Mg2Sn phase and the MgSnSr phase which are related to their relatively high thermal stability. The ultimate tensile strength and the elongation to rupture of the as-solutionized alloy are 238 MPa and 12%, respectively, about 25 MPa and 2.4% higher than the counterparts of the as-cast alloy.

  18. Inhibition of thalamic excitability by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol: a selective role for delta-GABA(A) receptors.

    PubMed

    Herd, Murray B; Foister, Nicola; Chandra, Dev; Peden, Dianne R; Homanics, Gregg E; Brown, Verity J; Balfour, David J K; Lambert, Jeremy J; Belelli, Delia

    2009-03-01

    The sedative and hypnotic agent 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP) is a GABA(A) receptor (GABA(A)R) agonist that preferentially activates delta-subunit-containing GABA(A)Rs (delta-GABA(A)Rs). To clarify the role of delta-GABA(A)Rs in mediating the sedative actions of THIP, we utilized mice lacking the alpha(1)- or delta-subunit in a combined electrophysiological and behavioural analysis. Whole-cell patch-clamp recordings were obtained from ventrobasal thalamic nucleus (VB) neurones at a holding potential of -60 mV. Application of bicuculline to wild-type (WT) VB neurones revealed a GABA(A)R-mediated tonic current of 92 +/- 19 pA, which was greatly reduced (13 +/- 5 pA) for VB neurones of delta(0/0) mice. Deletion of the delta- but not the alpha(1)-subunit dramatically reduced the THIP (1 mum)-induced inward current in these neurones (WT, -309 +/- 23 pA; delta(0/0), -18 +/- 3 pA; alpha(1) (0/0), -377 +/- 45 pA). Furthermore, THIP selectively decreased the excitability of WT and alpha(1) (0/0) but not delta(0/0) VB neurones. THIP did not affect the properties of miniature inhibitory post-synaptic currents in any of the genotypes. No differences in rotarod performance and locomotor activity were observed across the three genotypes. In WT mice, performance of these behaviours was impaired by THIP in a dose-dependent manner. The effect of THIP on rotarod performance was blunted for delta(0/0) but not alpha(1) (0/0) mice. We previously reported that deletion of the alpha(1)-subunit abolished synaptic GABA(A) responses of VB neurones. Therefore, collectively, these findings suggest that extrasynaptic delta-GABA(A)Rs vs. synaptic alpha(1)-subunit-containing GABA(A)Rs of thalamocortical neurones represent an important molecular target underpinning the sedative actions of THIP. PMID:19302153

  19. GENOTOXICITY OF 2,4,5-TRICHLOROPHENOXYACETIC ACID BIODEGRADATION PRODUCTS IN THE SALMONELLA REVERSION AND LAMBDA PROPHAGE-INDUCTION BIOASSAYS

    EPA Science Inventory

    The herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), is still an environmental hazard because of its persistent nature even though its use was outlawed in this country in the 1960's. n order to eliminate the contamination created by 2,4,5-T application, storage, and dispos...

  20. 4-(3,7-Dimethyl-4-oxo-4,5-dihydro­isoxazolo[4,5-d]pyridazin-5-yl)benzene­sulfonamide

    PubMed Central

    Asiri, Abdullah M.; Faidallah, Hassan M.; Al-Youbi, Abdulrahman O.; Obaid, Abdullah.Y.; Ng, Seik Weng

    2011-01-01

    The nine-membered fused-ring system of the title pyridazine derivative, C13H12N4O4S, is approximately planar (r.m.s. deviation 0.027 Å), and the benzene ring of the phenyl­sulfamide substituent is aligned at 43.5 (1)° to the fused-ring system. The amine group of the sulfonamide substituent forms an N—H⋯O hydrogen bond to the ketonic O atom of two neigboring mol­ecules to generate a chain running along the c axis. PMID:22059027

  1. Creep behaviour of Cu-30 percent Zn at intermediate temperatures

    NASA Technical Reports Server (NTRS)

    Raj, S. V.

    1991-01-01

    The present, intermediate-temperature (573-823 K) range investigation of creep properties for single-phase Cu-30 percent Zn alpha-brass observed inverse, linear, and sigmoidal primary-creep transients above 573 K under stresses that yield minimum creep rates in the 10 to the -7th to 2 x 10 to the -4th range; normal primary creep occurred in all other conditions. In conjunction with a review of the pertinent literature, a detailed analysis of these data suggests that no clearly defined, classes M-to-A-to-M transition exists in this alloy notwithstanding the presence of both classes' characteristics under nominally similar stresses and temperatures.

  2. IET. Aerial view of project, 95 percent complete. Camera facing ...

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

    IET. Aerial view of project, 95 percent complete. Camera facing east. Left to right: stack, duct, mobile test cell building (TAN-624), four-rail track, dolly. Retaining wall between mobile test building and shielded control building (TAN-620) just beyond. North of control building are tank building (TAN-627) and fuel-transfer pump building (TAN-625). Guard house at upper right along exclusion fence. Construction vehicles and temporary warehouse in view near guard house. Date: June 6, 1955. INEEL negative no. 55-1462 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

  3. A Sensitive Technique Using Atomic Force Microscopy to Measure the Low Earth Orbit Atomic Oxygen Erosion of Polymers

    NASA Technical Reports Server (NTRS)

    deGroh, Kim K.; Banks, Bruce A.; Clark, Gregory W.; Hammerstrom, Anne M.; Youngstrom, Erica E.; Kaminski, Carolyn; Fine, Elizabeth S.; Marx, Laura M.

    2001-01-01

    Polymers such as polyimide Kapton and Teflon FEP (fluorinated ethylene propylene) are commonly used spacecraft materials due to their desirable properties such as flexibility, low density, and in the case of FEP low solar absorptance and high thermal emittance. Polymers on the exterior of spacecraft in the low Earth orbit (LEO) environment are exposed to energetic atomic oxygen. Atomic oxygen erosion of polymers occurs in LEO and is a threat to spacecraft durability. It is therefore important to understand the atomic oxygen erosion yield (E, the volume loss per incident oxygen atom) of polymers being considered in spacecraft design. Because long-term space exposure data is rare and very costly, short-term exposures such as on the shuttle are often relied upon for atomic oxygen erosion determination. The most common technique for determining E is through mass loss measurements. For limited duration exposure experiments, such as shuttle experiments, the atomic oxygen fluence is often so small that mass loss measurements can not produce acceptable uncertainties. Therefore, a recession measurement technique has been developed using selective protection of polymer samples, combined with postflight atomic force microscopy (AFM) analysis, to obtain accurate erosion yields of polymers exposed to low atomic oxygen fluences. This paper discusses the procedures used for this recession depth technique along with relevant characterization issues. In particular, a polymer is salt-sprayed prior to flight, then the salt is washed off postflight and AFM is used to determine the erosion depth from the protected plateau. A small sample was salt-sprayed for AFM erosion depth analysis and flown as part of the Limited Duration Candidate Exposure (LDCE-4,-5) shuttle flight experiment on STS-51. This sample was used to study issues such as use of contact versus non-contact mode imaging for determining recession depth measurements. Error analyses were conducted and the percent probable

  4. Hypervalent iodine(iii)-promoted N-incorporation into N-aryl vinylogous carbamates to quinoxaline diesters: access to 1,4,5,8-tetraazaphenanthrene.

    PubMed

    Sagar, A; Vidaycharan, Shinde; Shinde, Anand H; Sharada, Duddu S

    2016-04-26

    A novel oxidative N-incorporation strategy for synthesis of quinoxaline diesters under metal-free conditions is described for the first time. The mild reaction conditions allow for this transformation via the formation of two C(sp(2))-N bonds utilizing cheaply available NaN3 as the N-atom source. N-Aryl vinylogous carbamates in this study undergo azidation at enamino C(sp(2))-H selectively. The robustness of this strategy is further demonstrated by the synthesis of a valuable 1,4,5,8-tetraazaphenanthrene derivative using a mild and convenient approach. PMID:27050385

  5. Performance of six 4. 5 m SSC (Superconducting Super Collider) dipole model magnets

    SciTech Connect

    Willen, E.; Dahl, P.; Cottingham, J.; Garber, M.; Ghosh, A.; Goodzeit, C.; Green, A.; Herrera, J.; Kahn, S.; Kelly, E.

    1986-01-01

    Six 4.5 m long dipole models for the proposed Superconducting Super Collider have been successfully tested. The magnets are cold-iron (and cold bore) 1-in-1 dipoles, wound with current density-graded high homogeneity NbTi cable in a two-layer cos theta coil of 40 mm inner diameter. The coil is prestressed by 15 mm wide stainless steel collars, and mounted in a circular, split iron yoke of 267 mm outer diameter, supported in a cylindrical yoke containment vessel. At 4.5 K the magnets reached a field of about 6.6 T with little training, or the short sample limit of the conductor, and in subcooled (2.6 - 2.4 K) liquid, 8 T was achieved. The allowed harmonics were close to the predicted values, and the unallowed harmonics small. The sextupole trim coil operated well above the required current with little training.

  6. Performance of three 4. 5 m dipoles for SSC reference design D

    SciTech Connect

    Dahl, P.; Cottingham, J.; Fernow, R.; Garber, M.; Ghosh, A.; Goodzeit, C.; Greene, A.; Herrera, J.; Kahn, S.; Kelly, E.

    1985-01-01

    Three 4.5 m long dipoles for Reference Design D of the proposed Superconducting Super Collider have been successfully tested. The magnets are cold-iron (and cold bore) 1-in-1 dipoles, wound with current density-graded high homogeneity NbTi cable in a two-layer cos theta coil of 40 mm inner diameter. The coil is prestressed by 15 mm wide stainless steel collars, and mounted in a circular, split iron yoke of 267 mm outer diameter, supported in a cylindrical yoke containment vessel. At 4.5 K the magnets reached a field of about 6.6T with little training, or the short sample limit of the conductor, and in subcooled (2.6 to 2.4 K) liquid, 8T was achieved. The allowed harmonics were close to the predicted values, and the unallowed harmonics small. The sextupole trim coil operated at eight times the required current without training.

  7. Heterogeneous Hadean hafnium: evidence of continental crust at 4.4 to 4.5 ga.

    PubMed

    Harrison, T M; Blichert-Toft, J; Müller, W; Albarede, F; Holden, P; Mojzsis, S J

    2005-12-23

    The long-favored paradigm for the development of continental crust is one of progressive growth beginning at approximately 4 billion years ago (Ga). To test this hypothesis, we measured initial 176Hf/177Hf values of 4.01- to 4.37-Ga detrital zircons from Jack Hills, Western Australia. epsilonHf (deviations of 176Hf/177Hf from bulk Earth in parts per 10(4)) values show large positive and negative deviations from those of the bulk Earth. Negative values indicate the development of a Lu/Hf reservoir that is consistent with the formation of continental crust (Lu/Hf approximately 0.01), perhaps as early as 4.5 Ga. Positive epsilon(Hf) deviations require early and likely widespread depletion of the upper mantle. These results support the view that continental crust had formed by 4.4 to 4.5 Ga and was rapidly recycled into the mantle. PMID:16293721

  8. Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts.

    PubMed

    Lebensohn, Andres M; Ma, Le; Ho, Hsin-Yi Henry; Kirschner, Marc W

    2006-01-01

    Xenopus egg cytoplasmic extracts have been used to study a variety of complex cellular processes. Given their amenability to biochemical manipulation and physiological balance of regulatory proteins, these extracts are an ideal system to dissect signal transduction pathways leading to actin assembly. We have developed methods to study Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts. In this chapter, we describe detailed procedures to prepare Xenopus egg extracts, Cdc42, and PI(4,5)P2 for use in actin assembly experiments. We also describe a fluorometric pyrene actin assay for quantitative kinetic analysis of actin polymerization and a microscopic rhodamine actin assay for quick measurement of actin rearrangements in extracts. Finally we provide a protocol for immunodepletion of proteins and discuss the use of immunodepletion and rescue experiments for functional analysis of components in the extracts. PMID:16472657

  9. Synthesis and antifungal activity of 2-hydroxy-4,5-methylenedioxyaryl ketones as analogues of kakuol.

    PubMed

    Musso, Loana; Dallavalle, Sabrina; Merlini, Lucio; Farina, Gandolfina

    2010-04-01

    In a study aiming to determine the structural elements essential to the antifungal activity of kakuol, we synthesized a series of 2-hydroxy-4,5-methylenedioxyaryl ketones, and we assayed their in vitro antifungal activity. The most sensitive target organisms to the action of these class of compounds were Phytophthora infestans, Phytium ultimum, Cercospora beticola, Cladosporium cucumerinum, and Rhizoctonia solani. Most of the analogs showed a remarkable in vitro activity, and some of them appeared significantly more effective than the natural product. The biological activity was mainly affected by introducing structural modification on the carbonyl moiety of the natural-product molecule. In particular, compound 5a, bearing a C=C bond conjugated to the C=O group, was found active with a MIC value of 10 microg ml(-1) against Cladosporium cucumerinum. The results suggest that 2-hydroxy-4,5-methylenedioxyaryl ketones can be considered promising candidates in the development of new antifungal compounds. PMID:20397224

  10. Constructions of Optimal (v,{4,5,6},1,Q)-OOCs

    NASA Astrophysics Data System (ADS)

    Li, Xiyang; Fan, Pingzhi; Wu, Dianhua

    Optical code-division multiple-access (OCDMA) is a promising technique for multimedia transmission in fiber-optic local-area networks (LANs). Variable-weight optical orthogonal codes (OOCs) can be used for OCDMA networks supporting multiple quality of services (QoS). Most constructions for optimal variable-weight OOCs have focused on the case where the number of distinct Hamming weights of all codewords is equal to two, and the codewords of weight 3 are normally included. In this letter, four explicit constructions of optimal (v,{4,5,6},1,Q)-OOCs are presented, and more new optimal (v,{4,5,6},1,Q)-OOCs are obtained via recursive constructions. These improve the existing results on optimal variable-weight OOCs with at least three distinct Hamming weights and minimum Hamming weight 4.

  11. Ballooning-mirror instability and internally driven Pc 4--5 wave events

    SciTech Connect

    Cheng, C.Z.; Qian, Q.; Takahashi, K.; Lui, A.T.Y.

    1994-03-01

    A kinetic-MHD field-aligned eigenmode stability analysis of low frequency ballooning-mirror instabilities has been performed for anisotropic pressure plasma sin the magnetosphere. The ballooning mode is mainly a transverse wave driven unstable by pressure gradient in the bad curvature region. The mirror mode with a dominant compressional magnetic field perturbation is excited when the product of plasma beta and pressure anisotropy (P{sub {perpendicular}}/P{sub {parallel}} > 1) is large. From the AMPTE/CCE particle and magnetic field data observed during Pc 4--5 wave events the authors compute the ballooning-mirror instability parameters and perform a correlation study with the theoretical instability threshold. They find that compressional Pc 5 waves approximately satisfy the ballooning-mirror instability condition, and transverse Pc 4--5 waves are probably related to resonant ballooning instabilities with small pressure anisotropy.

  12. Backside optimization for improving avalanche breakdown behavior of 4.5 kV IGBT

    NASA Astrophysics Data System (ADS)

    Xiaoli, Tian; Jiang, Lu; Yuan, Teng; Wenliang, Zhang; Shuojin, Lu; Yangjun, Zhu

    2015-03-01

    The static avalanche breakdown behavior of 4.5 kV high-voltage IGBT is studied by theory analysis and experiment. The avalanche breakdown behaviors of the 4.5 kV IGBTs with different backside structures are investigated and compared by using the curve tracer. The results show that the snap back behavior of the breakdown waveform is related to the bipolar PNP gain, which leads to the deterioration of the breakdown voltage. There are two ways to optimize the backside structure, one is increasing the implant dose of the N+ buffer layer, the other is decreasing the implant dose of the P+ collector layer. It is found that the optimized structure is effective in suppressing the snap back behavior and improving the breakdown characteristic of high voltage IGBT. Project supported by the National Major Science and Technology Special Project of China (No. 2011ZX02503-003).

  13. 4,5-Bis(dimethylamino)quinolines: proton sponge versus azine behavior.

    PubMed

    Dyablo, Olga V; Shmoilova, Elena A; Pozharskii, Alexander F; Ozeryanskii, Valery A; Burov, Oleg N; Starikova, Zoya A

    2012-08-17

    Two first representatives, 5 and 6, of the still unknown 4,5-bis(dimethylamino)quinoline have been synthesized and studied. While the former, being protonated either at the peri-NMe(2) groups or at the ring nitrogen, has been shown to display properties of both a proton sponge and azine, its counterpart 6 behaves exclusively as azine giving only a quinolinium salt. PMID:22860688

  14. Synthesis of oxazolo[4,5-c]quinoline TRPV1 antagonists.

    PubMed

    Voight, Eric A; Daanen, Jerome F; Kort, Michael E

    2010-12-17

    An efficient synthesis of 2-amino-oxazolo[4,5-c]quinoline TRPV1 antagonists is described via a thiourea formation/carbodiimide cyclization sequence. Synthetic route optimization eliminates intermediate isolations and facilitates the rapid preparation of a series of novel pentacyclic TRPV1 antagonists. From this series, compound (S)-4 was identified as a potent and selective ligand for the TRPV1 ion channel. PMID:21090730

  15. Analysis of cellular phosphatidylinositol (3,4,5)-trisphosphate levels and distribution using confocal fluorescent microscopy.

    PubMed

    Palmieri, Michelle; Nowell, Cameron J; Condron, Melanie; Gardiner, James; Holmes, Andrew B; Desai, Jayesh; Burgess, Antony W; Catimel, Bruno

    2010-11-01

    We have developed an immunocytochemistry method for the semiquantitative detection of phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) at the cell plasma membrane. This protocol combines the use of a glutathione S-transferase-tagged pleckstrin homology (PH) domain of the general phosphoinositides-1 receptor (GST-GRP1PH) with fluorescence confocal microscopy and image segmentation using cell mask software analysis. This methodology allows the analysis of PI(3,4,5)P3 subcellular distribution in resting and epidermal growth factor (EGF)-stimulated HEK293T cells and in LIM1215 (wild-type phosphoinositide 3-kinase (PI3K)) and LIM2550 (H1047R mutation in PI3K catalytic domain) colonic carcinoma cells. Formation of PI(3,4,5)P3 was observed 5min following EGF stimulation and resulted in an increase of the membrane/cytoplasm fluorescence ratio from 1.03 to 1.53 for HEK293T cells and from 2.2 to 3.3 for LIM1215 cells. Resting LIM2550 cells stained with GST-GRP1PH had an elevated membrane/cytoplasm fluorescence ratio of 9.8, suggesting constitutive PI3K activation. The increase in the membrane/cytoplasm fluorescent ratio was inhibited in a concentration-dependent manner by the PI3K inhibitor LY294002. This cellular confocal imaging assay can be used to directly assess the effects of PI3K mutations in cancer cell lines and to determine the potential specificity and effectiveness of PI3K inhibitors in cancer cells. PMID:20599646

  16. Development of a 4.5 K Pulse Tube Cryocooler for Superconducting Electronics

    NASA Astrophysics Data System (ADS)

    Nast, Ted; Olson, Jeff; Champagne, Patrick; Mix, Jack; Evtimov, Bobby; Roth, Eric; Collaco, Andre

    2008-03-01

    Lockheed Martin's (LM) Advanced Technology Center (ATC) has developed a four stage pulse tube cryocooler (stirling-type pulse tube system) to provide cooling at 4.5 K for superconducting digital electronics communications programs. These programs utilize superconducting niobium integrated circuits [1, 2]. A prior ATC 4 stage unit has provided cooling to 3.8 K. [3] The relatively high cooling loads for the present program led us to a new design which improves the 4.5 K power efficiency over prior systems. This design includes a unique pulse tube approach using both He-3 and He-4 working gas in two compression spaces. The compressor utilizes our standard moving magnet linear motor, clearance seal and flexure bearing system. The system is compact, lightweight and reliable and utilizes our aerospace cooler technology to provide unlimited lifetime. The unit is a proof of concept, but the construction is at an engineering model level. Follow on activities for improvements of performance and more compact packaging and future production for ground based communication systems is anticipated. This paper presents the experimental results at various cooling conditions. Primary results are shown for HYPRES cooling requirements and data is also included at lower cooling loads that may be required for future space missions. The system provides a maximum of 42 mW @ 4.5 K and a no load temperature of 3 K. The majority of this work was subcontracted by HYPRES and funded by the Army and Navy. A small part of this effort to obtain data at lower cooling loads (1-10 mW @ 4.5 K) was funded by LM internal funds.

  17. Investigation of 4,5-epoxymorphinan degradation during analysis by HPLC.

    PubMed

    Quarry, Mary Ann; Sebastian, Dolores S; Diana, Frank

    2002-08-22

    Compounds of the 4,5-epoxymorphinan series have been shown to degrade in solution to the corresponding 2,2'-dimers when stored in amber glass HPLC vials. A colorant in the glass has been shown to catalyze the degradation. Although amber glass is routinely used to protect solutions from light degradation, it should not be used without evaluating its effect on sample stability. PMID:12151069

  18. Deterministic methods in radiation transport. A compilation of papers presented February 4--5, 1992

    SciTech Connect

    Rice, A.F.; Roussin, R.W.

    1992-06-01

    The Seminar on Deterministic Methods in Radiation Transport was held February 4--5, 1992, in Oak Ridge, Tennessee. Eleven presentations were made and the full papers are published in this report, along with three that were submitted but not given orally. These papers represent a good overview of the state of the art in the deterministic solution of radiation transport problems for a variety of applications of current interest to the Radiation Shielding Information Center user community.

  19. Effects of lindane, paraquat, toxaphene, and 2,4,5-trichlorophenoxyacetic acid on mallard embryo development

    USGS Publications Warehouse

    Hoffman, D.J.; Eastin, W.C., Jr.

    1982-01-01

    The effects were determined of externally treating mallard (Anas platyrhynchos) eggs with two insecticides (lindane and toxaphene) and two herbicides (paraquat and 2,4,5-T) with formulations and concentrations similar to field applications. Paraquat was the most embryotoxic of the four compounds regardless of the type of vehicle. The LC50 for paraquat was 1.5 lb of active ingredient/ acre in aqueous emulsion and 0.1 lb/acre in the oil vehicle. The other compounds had LC50's that were several orders of magnitude higher. Both paraquat and toxaphene caused some mortality at 1/2 of the field level of application. Paraquat impaired growth and was slightly teratogenic at 1/2 of the field level of application, but required higher concentrations (1.5 to 3 times the field level) to produce brain and visceral defects. Lindane was teratogenic, resulting in multiple defects but only at doses that were greater than five times the field level of application. Toxaphene resulted in defects of the joints at doses close to or exceeding the LC50. The herbicide 2,4,5-T resulted in few toxic effects and relatively few abnormal survivors with gross defects. The overall embryotoxicity with either vehicle was paraquat > lindane > toxaphene > 2,4,5-T on a lb per acre basis. However the potential hazard at exposures of up to five times the field level of application was paraquat > toxaphene; neither lindane nor 2,4,5-T constituted much of a hazard. Both paraquat and lindane were more toxic on a lb-peracre basis when administered in oil vehicle but only paraquat represented a potential hazard at five times the field level of application.

  20. Long-life vibration-free 4.5 K sorption cooler for space applications.

    PubMed

    Burger, J F; ter Brake, H J M; Holland, H J; Meijer, R J; Veenstra, T T; Venhorst, G C F; Lozano-Castelló, D; Coesel, M; Sirbi, A

    2007-06-01

    A breadboard 4.5 K helium sorption cooler for use in vibration-sensitive space missions was developed and successfully tested. This type of cooler has no moving parts and is, therefore, essentially vibration-free. The absence of moving parts also simplifies scaling down of the cooler to small sizes, and it contributes to achieving a very long lifetime. In addition, the cooler operates with limited dc's so that hardly any electromagnetic interference is generated. This cooler is a favorite option for future missions such as ESA's Darwin mission, a space interferometer in which the sensitive optics and detectors can hardly accept any vibration. The system design consists of a hydrogen stage cooling from 80 to 14.5 K and a helium stage establishing 5 mW at 4.5 K. Both stages use microporous activated carbon as the adsorption material. The two cooler stages need about 3.5 W of total input power and are heat sunk at two passive radiators at temperatures of about 50 and 80 K-radiators which are constructed at the cold side of the spacecraft. We developed, built, and tested a demonstrator of the helium cooler. This demonstrator has four sorption compressor cells in two compressor stages. Test experiments on this cooler showed that it performs within all specifications imposed by ESA. The cooler delivered 4.5 mW at 4.5 K with a long-term temperature stability of 1 mK and an input power of 1.96 W. So far, the cooler has operated continuously for a period of 2.5 months and has not shown any sign of performance degradation. PMID:17614633

  1. Atomic polarizabilities

    SciTech Connect

    Safronova, M. S.; Mitroy, J.; Clark, Charles W.; Kozlov, M. G.

    2015-01-22

    The atomic dipole polarizability governs the first-order response of an atom to an applied electric field. Atomic polarization phenomena impinge upon a number of areas and processes in physics and have been the subject of considerable interest and heightened importance in recent years. In this paper, we will summarize some of the recent applications of atomic polarizability studies. A summary of results for polarizabilities of noble gases, monovalent, and divalent atoms is given. The development of the CI+all-order method that combines configuration interaction and linearized coupled-cluster approaches is discussed.

  2. Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels.

    PubMed

    Trebak, Mohamed; Lemonnier, Loic; DeHaven, Wayne I; Wedel, Barbara J; Bird, Gary S; Putney, James W

    2009-02-01

    The canonical transient receptor potential (TRPC) proteins have been recognized as key players in calcium entry pathways activated through phospholipase-C-coupled receptors. While it is clearly demonstrated that members of the TRPC3/6/7 subfamily are activated by diacylglycerol, the mechanism by which phospholipase C activates members of the TRPC1/4/5 subfamily remains a mystery. In this paper, we provide evidence for both negative and positive modulatory roles for membrane polyphosphoinositides in the regulation of TRPC5 channels. Depletion of polyphosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PIP2) through inhibition of phosphatidylinositol 4-kinase activates calcium entry and membrane currents in TRPC5-expressing but not in TRPC3- or TRPC7-expressing cells. Inclusion of polyphosphatidylinositol 4-phosphate or PIP2, but not phosphatidylinositol 3,4,5-trisphosphate, in the patch pipette inhibited TRPC5 currents. Paradoxically, depletion of PIP2 with a directed 5-phosphatase strategy inhibited TRPC5. Furthermore, when the activity of single TRPC5 channels was examined in excised patches, the channels were robustly activated by PIP2. These findings indicate complex functions for regulation of TRPC5 by PIP2, and we propose that membrane polyphosphoinositides may have at least two distinct functions in regulating TRPC5 channel activity. PMID:18665391

  3. The co-chaperones Fkbp4/5 control Argonaute2 expression and facilitate RISC assembly

    PubMed Central

    Martinez, Natalia J.; Chang, Hao-Ming; Borrajo, Jacob de Riba; Gregory, Richard I.

    2013-01-01

    Argonaute2 (Ago2) protein and associated microRNAs (miRNAs) or small interfering RNAs (siRNAs) form the RNA-induced silencing complex (RISC) for target messenger RNA cleavage and post-transcriptional gene silencing. Although Ago2 is essential for RISC activity, the mechanism of RISC assembly is not well understood, and factors controlling Ago2 protein expression are largely unknown. A role for the Hsc70/Hsp90 chaperone complex in loading small RNA duplexes into the RISC has been demonstrated in cell extracts, and unloaded Ago2 is unstable and degraded by the lysosome in mammalian cells. Here we identify the co-chaperones Fkbp4 and Fkbp5 as Ago2-associated proteins in mouse embryonic stem cells. Pharmacological inhibition of this interaction using FK506 or siRNA-mediated Fkbp4/5 depletion leads to decreased Ago2 protein levels. We find FK506 treatment inhibits, whereas Fkbp4/5 overexpression promotes, miRNA-mediated stabilization of Ago2 expression. Simultaneous treatment with a lysosome inhibitor revealed the accumulation of unloaded Ago2 complexes in FK506-treated cells. We find that, consistent with unloaded miRNAs being unstable, FK506 treatment also affects miRNA abundance, particularly nascent miRNAs. Our results support a role for Fkbp4/5 in RISC assembly. PMID:24049110

  4. On the nature of bright compact radio sources at z>4.5

    NASA Astrophysics Data System (ADS)

    Coppejans, Rocco; Frey, Sándor; Cseh, Dávid; Müller, Cornelia; Paragi, Zsolt; Falcke, Heino; Gabányi, Krisztina É.; Gurvits, Leonid I.; An, Tao; Titov, Oleg

    2016-09-01

    High-redshift radio-loud quasars are used to, among other things, test the predictions of cosmological models, set constraints on black hole growth in the early universe and understand galaxy evolution. Prior to this paper, 20 extragalactic radio sources at redshifts above 4.5 have been imaged with very long baseline interferometry (VLBI). Here we report on observations of an additional ten z > 4.5 sources at 1.7 and 5 GHz with the European VLBI Network (EVN), thereby increasing the number of imaged sources by 50 per cent. Combining our newly observed sources with those from the literature, we create a substantial sample of 30 z > 4.5 VLBI sources, allowing us to study the nature of these objects. Using spectral indices, variability and brightness temperatures, we conclude that of the 27 sources with sufficient information to classify, the radio emission from one source is from star formation, 13 are flat-spectrum radio quasars and 13 are steep-spectrum sources. We also argue that the steep-spectrum sources are off-axis (unbeamed) radio sources with rest-frame self-absorption peaks at or below GHz frequencies and that these sources can be classified as gigahertz peaked-spectrum (GPS) and megahertz peaked-spectrum (MPS) sources.

  5. Computational research on memory effects in AlPO4-5 nanoporous material

    NASA Astrophysics Data System (ADS)

    Gulín-González, J.; Demontis, P.; Navas Conyedo, E.; Suffritti, G. B.

    2012-06-01

    Reversible amorphization and memory effects of both dense and open frameworks have received a great attention due to their prospective industrial applications. In this paper, the results of a computational study related to phase transition and memory effects in AlPO4-5 nanoporous material at high external pressure is presented. The behavior of the AlPO4-5 unit cell at high external pressures was studied by energy minimization techniques using classical potentials. A combination of interatomic potentials was used to describe the crystalline structure of the aluminophosphate. According to simulation's result a decrease of crystalline order is observed at a pressure about 3.5 GPa. The behavior of the simulated infrared spectra of compressed structures is an unambiguous evidence of structural disorder. Also, an abrupt change in the slope of the unit cell volume vs. pressure curve was obtained. At P≤3.5 GPa the process was found reversible. Contrary to what has been reported in other aluminosilicate systems the final crystalline state of AlPO4-5 at the highest simulated pressure was not amorphous. According to our knowledge this is the first evidence of a reversible first-order crystal-crystal phase transition in AlPO- family materials. This result could be important in future industrial and catalytic applications of these materials.

  6. Evolution of the dendritic morphology with the solidification velocity in rapidly solidified Al-4.5wt.%Cu droplets

    NASA Astrophysics Data System (ADS)

    Bedel, M.; Reinhart, G.; Gandin, Ch-A.; Bogno, A.-A.; Nguyen-Thi, H.; Henein, H.

    2015-06-01

    The microstructure morphology of Al-4.5wt.%Cu droplets formed by the Impulse Atomization technique is investigated. Three-dimensional reconstructions by synchrotron X- ray micro-tomography of several droplets reveal different morphologies in droplets of similar diameter and produced in the same batch. Moreover, microstructural features also indicate that the development of the dendrite arms occurs in some droplets along <111> crystallographic axes instead of the usual <100> directions observed in conventional casting for the same alloy. It has been observed that such an unusual growth direction of the dendrites is directly related to the solidification velocity. We underpin these results by carrying out comparisons with a solidification model. Predictions are used to discuss the change of dendrite growth direction, as well as the existence of a dendrite growth direction range for a given type of droplets. In addition, the effect of the droplet size and the cooling gas on the dendrite growth direction range observed experimentally is also investigated by using the model.

  7. Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change.

    PubMed Central

    Milburn, Christine C; Deak, Maria; Kelly, Sharon M; Price, Nick C; Alessi, Dario R; Van Aalten, Daan M F

    2003-01-01

    Protein kinase B (PKB/Akt) is a key regulator of cell growth, proliferation and metabolism. It possesses an N-terminal pleckstrin homology (PH) domain that interacts with equal affinity with the second messengers PtdIns(3,4,5)P3 and PtdIns(3,4)P2, generated through insulin and growth factor-mediated activation of phosphoinositide 3-kinase (PI3K). The binding of PKB to PtdIns(3,4,5)P3/PtdIns(3,4)P2 recruits PKB from the cytosol to the plasma membrane and is also thought to induce a conformational change that converts PKB into a substrate that can be activated by the phosphoinositide-dependent kinase 1 (PDK1). In this study we describe two high-resolution crystal structures of the PH domain of PKBalpha in a noncomplexed form and compare this to a new atomic resolution (0.98 A, where 1 A=0.1 nm) structure of the PH domain of PKBalpha complexed to Ins(1,3,4,5)P4, the head group of PtdIns(3,4,5)P3. Remarkably, in contrast to all other PH domains crystallized so far, our data suggest that binding of Ins(1,3,4,5)P4 to the PH domain of PKB, induces a large conformational change. This is characterized by marked changes in certain residues making up the phosphoinositide-binding site, formation of a short a-helix in variable loop 2, and a movement of variable loop 3 away from the lipid-binding site. Solution studies with CD also provided evidence of conformational changes taking place upon binding of Ins(1,3,4,5)P4 to the PH domain of PKB. Our data provides the first structural insight into the mechanism by which the interaction of PKB with PtdIns(3,4,5)P3/PtdIns(3,4)P2 induces conformational changes that could enable PKB to be activated by PDK1. PMID:12964941

  8. A 99 percent purity molecular sieve oxygen generator

    NASA Technical Reports Server (NTRS)

    Miller, G. W.

    1991-01-01

    Molecular sieve oxygen generating systems (MSOGS) have become the accepted method for the production of breathable oxygen on military aircraft. These systems separate oxygen for aircraft engine bleed air by application of pressure swing adsorption (PSA) technology. Oxygen is concentrated by preferential adsorption in nitrogen in a zeolite molecular sieve. However, the inability of current zeolite molecular sieves to discriminate between oxygen and argon results in an oxygen purity limitations of 93-95 percent (both oxygen and argon concentrate). The goal was to develop a new PSA process capable of exceeding the present oxygen purity limitations. A novel molecular sieve oxygen concentrator was developed which is capable of generating oxygen concentrations of up to 99.7 percent directly from air. The process is comprised of four absorbent beds, two containing a zeolite molecular sieve and two containing a carbon molecular sieve. This new process may find use in aircraft and medical breathing systems, and industrial air separation systems. The commercial potential of the process is currently being evaluated.

  9. 2,4,5-Triphenyl-1-(prop-2-en-1-yl)-1H-imidazole.

    PubMed

    Akkurt, Mehmet; Mohamed, Shaaban K; Marzouk, Adel A E; Abbasov, V M; Santoyo-Gonzalez, Francisco

    2013-06-01

    In the title compound, C24H20N2, one of the ring C atoms and one of the ring N atoms are disordered over two sets of sites in a 0.615 (3):0.385 (3) ratio. The two parts of the disordered imidazole ring adopt an envelope conformation, with the undisordered ring N atom as the flap, displaced by -0.118 (6) and 0.226 (7) Å, respectively, in the two disorder components from the plane through the other ring atoms. The crystal structure features C-H⋯N hydrogen bonds and C-H⋯π inter-actions, which lead to the formation of infinite chains along [010]. PMID:23795140

  10. Crystal structure of 4,5-dinitro-1 H-imidazole

    DOE PAGESBeta

    Windler, G. Kenneth; Scott, Brian L.; Tomson, Neil C.; Leonard, Philip W.

    2015-01-01

    Here, the title compound, C3H2N4O4, forms crystals with two molecules in the asymmetric unit which are conformationally similar. With the exception of the O atoms of the nitro groups, the molecules are essentially planar. In the crystal, adjacent molecules are associated by N—H...N hydrogen bonds involving the imidazole N—H donors and N-atom acceptors of the unsaturated nitrogen of neighboring rings, forming layers parallel to (010).

  11. 4.1N binding regions of inositol 1,4,5-trisphosphate receptor type 1.

    PubMed

    Fukatsu, Kazumi; Bannai, Hiroko; Inoue, Takafumi; Mikoshiba, Katsuhiko

    2006-04-01

    Zhang et al. and Maximov et al. [S. Zhang, A. Mizutani, C. Hisatsune, T. Higo, H. Bannai, T. Nakayama, M. Hattori, and K. Mikoshiba, Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized Madin-Darby canine kidney cells, J. Biol. Chem. 278 (2003) 4048-4056; A. Maximov, T. S. Tang, and I. Bezprozvanny, Association of the type 1 inositol (1,4,5)-trisphosphate receptor with 4.1N protein in neurons, Mol. Cell. Neurosci. 22 (2003) 271-283.] reported that 4.1N is a binding partner of inositol 1,4,5-trisphosphate receptor type 1 (IP(3)R1), however the binding site of IP(3)R1 differed: the former determined the C-terminal 14 amino acids of the cytoplasmic tail (CTT14aa) as the binding site, while the latter assigned another segment, cytoplasmic tail middle 1 (CTM1). To solve this discrepancy, we performed immunoprecipitation and found that both the segments had binding activity to 4.1N. Both segments also interfered the 4.1N-regulated IP(3)R1 diffusion in neuronal dendrites. However, IP(3)R1 lacking the CTT14aa (IP(3)R1-DeltaCTT14aa) does not bind to 4.1N [S. Zhang, A. Mizutani, C. Hisatsune, T. Higo, H. Bannai, T. Nakayama, M. Hattori, and K. Mikoshiba, Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized Madin-Darby canine kidney cells, J. Biol. Chem. 278 (2003) 4048-4056.] and its diffusion constant is larger than that of IP(3)R1 full-length in neuronal dendrites [K. Fukatsu, H. Bannai, S. Zhang, H. Nakamura, T. Inoue, and K. Mikoshiba, Lateral diffusion of inositol 1,4,5-trisphosphate receptor type 1 is regulated by actin filaments and 4.1N in neuronal dendrites, J. Biol. Chem. 279 (2004) 48976-48982.]. We conclude that both the CTT14aa and CTM1 sequences can bind to 4.1N in peptide fragment forms. However, we propose that the responsible binding site for 4.1N binding in full-length tetramer form of IP

  12. Preparation, GIAO NMR Calculations and Acidic Properties of Some Novel 4,5-dihydro-1H-1,2,4-triazol-5-one Derivatives with Their Antioxidant Activities

    PubMed Central

    Yüksek, Haydar; Alkan, Muzaffer; Cakmak, Ismail; Ocak, Zafer; Bahçeci, Şule; Calapoğlu, Mustafa; Elmastaş, Mahfuz; Kolomuç, Ali; Aksu, Havva

    2008-01-01

    Six novel 3-alkyl(aryl)-4-(p-nitrobenzoylamino)-4,5-dihydro-1H-1,2,4-triazol-5- ones (2a-f) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H- 1,2,4-triazol-5-ones (1a-f) with p-nitrobenzoyl chloride and characterized by elemental analyses and IR, 1H-NMR, 13C-NMR and UV spectral data. The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as acetone, isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide, and the half-neutralization potential values and the corresponding pKa values were determined for all cases. Thus, the effects of solvents and molecular structure upon acidity were investigated. In addition, isotropic 1H and 13C nuclear magnetic shielding constants of compounds 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound has been optimized using the 6-311G basis set. Theoretical values were compared to the experimental data. Furthermore, these new compounds and five recently reported 3-alkyl-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3a–c,e,f) were screened for their antioxidant activities. PMID:19325716

  13. One Percent Strömvil Photometry in M 67

    NASA Astrophysics Data System (ADS)

    Philip, A. G. D.; Boyle, R. P.; Janusz, R.

    2005-05-01

    The Vatican Advanced Technology Telescope on Mt. Graham is being used in a program of CCD photometry of open and globular clusters. We are using the Ströomvil System (Straižys et al. 1996), a combination of the Strömgren and Vilnius Systems. This system allows stars to be classified as to temperature, surface gravity, metallicity and reddening from the photometric measures alone. However, to make accurate estimates of the stellar parameters the photometry should be accurate to 1 or 1.5 percent. In our initial runs on the VATT we did not achieve this accuracy. The problem turned out to be scattered light in the telescope and this has now been reduced so we can do accurate photometry. Boyle has written a routine in IRAF which allows us to correct the flats for any differences. We take rotated frames and also frames which are offset in position by one third of a frame, east-west and north-south. Measures of the offset stars give us the corrections that need to be made to the flat. Robert Janusz has written a program, the CommandLog, which allows us to paste IRAF commands in the correct order to reduce measures made on a given observing run. There is an automatic version where one can test various parameters and get a set of solutions. Now we have a set of Strömvil frames in the open cluster, M 67 and we compare our color-magnitude diagram with those of BATC (Fan et al. 1996) and Vilnius (Boyle et al. 1998). A preliminary report of the M 67 photometry will be found in Laugalys et al. (2004). Here we report on a selected set of stars in the M 67 frames, those with errors 1 percent or less.

  14. Metabolic evidence for PtdIns(4,5)P2-directed phospholipase C in permeabilized plant protoplasts.

    PubMed Central

    Brearley, C A; Parmar, P N; Hanke, D E

    1997-01-01

    Comparison of the sequences of the genes encoding phospholipase C (PLC) which have been cloned to date in plants with their mammalian counterparts suggests that plant PLC is similar to PLCdelta of mammalian cells. The physiological role and mechanism of activation of PLCdelta is unclear. It has recently been shown that Ins(1,4,5)P3 may not solely be the product of PtdIns(4,5)P2-directed PLC activity. Enzyme activities capable of producing Ins(1,4,5)P3 from endogenous inositol phosphates are present in Dictyostelium and also in rat liver. Significantly it has not been directly determined whether Ins(1,4,5)P3 present in higher plants is the product of a PtdIns(4, 5)P2-directed PLC activity. Therefore we have developed an experimental strategy for the identification of d-Ins(1,4,5)P3 in higher plants. By the use of a short-term non-equilibrium labelling strategy in permeabilized plant protoplasts, coupled to the use of a 'metabolic trap' to prevent degradation of [32P]Ins(1,4,5)P3, we were able to determine the distribution of 32P in individual phosphate esters of Ins(1,4,5)P3. The [32]Ins(1,4,5)P3 identified showed the same distribution of label in individual phosphate esters as that of [32P]PtdIns(4,5)P2 isolated from the same tissue. We thus provide in vivo evidence for the action of a PtdIns(4,5)P2-directed PLC activity in plant cells which is responsible for the production of Ins(1,4,5)P3 observed here. This observation does not, however, exclude the possibility that in other cells or under different conditions Ins(1,4,5)P3 can be generated by alternative routes. PMID:9164848

  15. Increasing Phosphatidylinositol (4,5)-Bisphosphate Biosynthesis Affects Basal Signaling and Chloroplast Metabolism in Arabidopsis thaliana

    PubMed Central

    Im, Yang Ju; Smith, Caroline M.; Phillippy, Brian Q.; Strand, Deserah; Kramer, David M.; Grunden, Amy M.; Boss, Wendy F.

    2014-01-01

    One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2); this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2–3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were >2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2–4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts of genes involved in starch metabolism such as SEX1 (glucan water dikinase) and SEX4 (phosphoglucan phosphatase), DBE (debranching enzyme), MEX1 (maltose transporter), APL3 (ADP-glucose pyrophosphorylase) and glucose-6-phosphate transporter (Glc6PT) were up-regulated in the HsPIPKIα plants. Our results reveal that increasing the phosphoinositide (PI) pathway affects chloroplast carbon metabolism and suggest that InsP3 is one component of an inter-organelle signaling network regulating chloroplast metabolism. PMID:27135490

  16. Cost-Effectiveness of Thrombolysis within 4.5 Hours of Acute Ischemic Stroke in China

    PubMed Central

    Zhao, Xingquan; Liao, Xiaoling; Wang, Chunjuan; Du, Wanliang; Liu, Gaifen; Liu, Liping; Wang, Chunxue; Wang, Yilong; Wang, Yongjun

    2014-01-01

    Background Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. Methods A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. Results Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY. Conclusions Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China. PMID:25329637

  17. International Space Station Increment-4/5 Microgravity Environment Summary Report

    NASA Technical Reports Server (NTRS)

    Jules, Kenol; Hrovat, Kenneth; Kelly, Eric; McPherson, Kevin; Reckart, Timothy

    2003-01-01

    This summary report presents the results of some of the processed acceleration data measured aboard the International Space Station during the period of December 2001 to December 2002. Unlike the past two ISS Increment reports, which were increment specific, this summary report covers two increments: Increments 4 and 5, hereafter referred to as Increment-4/5. Two accelerometer systems were used to measure the acceleration levels for the activities that took place during Increment-4/5. Due to time constraint and lack of precise timeline information regarding some payload operations and station activities, not a11 of the activities were analyzed for this report. The National Aeronautics and Space Administration sponsors the Microgravity Acceleration Measurement System and the Space Acceleration Microgravity System to support microgravity science experiments which require microgravity acceleration measurements. On April 19, 2001, both the Microgravity Acceleration Measurement System and the Space Acceleration Measurement System units were launched on STS-100 from the Kennedy Space Center for installation on the International Space Station. The Microgravity Acceleration Measurement System supports science experiments requiring quasi-steady acceleration measurements, while the Space Acceleration Measurement System unit supports experiments requiring vibratory acceleration measurement. The International Space Station Increment-4/5 reduced gravity environment analysis presented in this report uses acceleration data collected by both sets of accelerometer systems: The Microgravity Acceleration Measurement System, which consists of two sensors: the low-frequency Orbital Acceleration Research Experiment Sensor Subsystem and the higher frequency High Resolution Accelerometer Package. The low frequency sensor measures up to 1 Hz, but is routinely trimmean filtered to yield much lower frequency acceleration data up to 0.01 Hz. This filtered data can be mapped to arbitrary

  18. Room temperature photoluminescence at 4.5 {mu}m from InAsN

    SciTech Connect

    Zhuang, Q.; Godenir, A. M. R.; Krier, A.; Lai, K. T.; Haywood, S. K.

    2008-03-15

    Nitrogen incorporation in InAsN epilayers grown by radio-frequency plasma-assisted molecular beam epitaxy was investigated as a function of growth conditions. Reduced growth rate, growth temperature, and arsenic flux significantly enhance the nitrogen incorporation. Optimal growth conditions allowed us to obtain high quality InAsN with nitrogen composition of up to 2.5%. The epilayers exhibit intense 4 K photoluminescence (PL) with double-peak features, which were attributed to free carrier recombination and localized carrier recombination. Strong room temperature PL emission up to a wavelength of 4.5 {mu}m is obtained.

  19. Photophysics of poly(2,3,4,5,6-pentafluorostyrene) film

    SciTech Connect

    O'Connor, D.B.; Scott, G.W. ); Coulter, D.R.; Miskowski, V.M.; Yavrouian, A. )

    1990-08-09

    The temperature-dependent steady-state emission, emission polarization anisotropy, and fluorescence kinetics of poly(2,3,4,5,6-pentafluorostyrene) film are reported. Two interconverting excited-state conformations of the chromophore have been identified. The fluorescence of the higher energy conformation results from excitation on the red edge of the polymer absorption band at temperatures below 180 K. The energy barrier for conversion of the higher energy conformer to the lower energy conformer is estimated to be E/hc = 27 {plus minus} 7 cm{sup {minus}1}. Electronic energy migration is not evident in this polymer.

  20. Accurate labeling of the light-actinide O4,5 ionization edges

    SciTech Connect

    Moore, K; der Laan, G v

    2006-08-23

    In this short article the accurate labeling of the O4,5 edges of the light actinides is addressed. The O4 and O5 edges are both contained in what is termed the ''giant resonance'' and the smaller ''pre-peak'' that is observed is a consequence of first-order perturbation by the 5d spin-orbit interaction. Thus, the small prepeak in the actinide 5d {yields} 5f transition should not be labeled the O5 peak, but rather the {Delta}S=1 peak.

  1. Towards 9 weight percent, reversible, room temperature hydrogen adsorbents: Hydrogen saturated organometallic bucky balls

    NASA Astrophysics Data System (ADS)

    Zhao, Yufeng

    2005-03-01

    A new concept for high-capacity hydrogen absorbents is introduced by first-principles calculations. Transition metal (TM) atoms bound to fullerenes are proposed as a medium for high density, room temperature, ambient pressure storage of hydrogen. TMs bind to C60 or C48B12 by charge transfer interactions to produce stable organometallic bucky balls (OBBs) and bind to multiple dihydrogen molecules through the so-called Kubas interaction [1]. A particular scandium OBB can bind as many as eleven hydrogen atoms per TM, ten of which are bound in the form of dihydrogen molecular ligands that can be adsorbed and desorbed reversibly. In this case, the calculated binding energy is around 0.3 eV/H2, which is ideal for use on-board vehicles. The theoretical maximum retrievable H2 storage density is about 9 weight percent. This work was supported by the U.S. DOE EERE, BES/MS, and BES/CS under contract No. DEAC36-99GO10337. [1] G.J. Kubas, J. Organometallic Chem. 635, 37 (2001).

  2. Crystal structure of 4,5-di­nitro-1H-imidazole

    PubMed Central

    Windler, G. Kenneth; Scott, Brian L.; Tomson, Neil C.; Leonard, Philip W.

    2015-01-01

    The title compound, C3H2N4O4, forms crystals with two mol­ecules in the asymmetric unit which are conformationally similar. With the exception of the O atoms of the nitro groups, the mol­ecules are essentially planar. In the crystal, adjacent mol­ecules are associated by N—H⋯N hydrogen bonds involving the imidazole N—H donors and N-atom acceptors of the unsaturated nitro­gen of neighboring rings, forming layers parallel to (010). PMID:26396875

  3. Crystal structure of 4,5-dinitro-1 H -imidazole

    SciTech Connect

    Windler, G. Kenneth; Scott, Brian L.; Tomson, Neil C.; Leonard, Philip W.

    2015-08-06

    The title compound, C3H2N4O4, forms crystals with two molecules in the asymmetric unit which are conformationally similar. With the exception of the O atoms of the nitro groups, the molecules are essentially planar. In the crystal, adjacent molecules are associated by N—H...N hydrogen bonds involving the imidazole N—H donors and N-atom acceptors of the unsaturated nitrogen of neighboring rings, forming layers parallel to (010).

  4. Crystal structure of 4,5-dinitro-1 H-imidazole

    SciTech Connect

    Windler, G. Kenneth; Scott, Brian L.; Tomson, Neil C.; Leonard, Philip W.

    2015-01-01

    Here, the title compound, C3H2N4O4, forms crystals with two molecules in the asymmetric unit which are conformationally similar. With the exception of the O atoms of the nitro groups, the molecules are essentially planar. In the crystal, adjacent molecules are associated by N—H...N hydrogen bonds involving the imidazole N—H donors and N-atom acceptors of the unsaturated nitrogen of neighboring rings, forming layers parallel to (010).

  5. The metabolism of gamma-2,3,4,5,6-pentachlorocyclohex-1-ene and gamma-hexachlorocyclohexane in rats.

    PubMed

    Grover, P L; Sims, P

    1965-08-01

    1. After intraperitoneal administration, gamma-hexachlorocyclohexane (Gammexane) and gamma-2,3,4,5,6-pentachlorocyclohex-1-ene were converted by rats into 2,3,5- and 2,4,5-trichlorophenol, which were excreted as free phenols and as sulphuric acid and glucuronic acid conjugates. 2. Derivatives of 2,4,5-trichlorophenol and 2,4,5-trichlorophenyl glucosiduronic acid and 2,4-dichlorophenylmercapturic acid were isolated from the urine as metabolites of gamma-2,3,4,5,6-pentachlorocyclohex-1-ene. 3. The phenolic metabolites of gamma-hexachlorocyclohexane and gamma-2,3,4,5,6-pentachlorocyclohex-1-ene isolated from urine were similar to those of 1,2,4-trichlorobenzene, which indicates that the two latter compounds are intermediates in gamma-hexachlorocyclohexane metabolism in rats. PMID:4158352

  6. The yeast transcription elongation factor Spt4/5 is a sequence-specific RNA binding protein.

    PubMed

    Blythe, Amanda J; Yazar-Klosinski, Berra; Webster, Michael W; Chen, Eefei; Vandevenne, Marylène; Bendak, Katerina; Mackay, Joel P; Hartzog, Grant A; Vrielink, Alice

    2016-09-01

    The heterodimeric transcription elongation factor Spt4/Spt5 (Spt4/5) tightly associates with RNAPII to regulate both transcriptional elongation and co-transcriptional pre-mRNA processing; however, the mechanisms by which Spt4/5 acts are poorly understood. Recent studies of the human and Drosophila Spt4/5 complexes indicate that they can bind nucleic acids in vitro. We demonstrate here that yeast Spt4/5 can bind in a sequence-specific manner to single stranded RNA containing AAN repeats. Furthermore, we show that the major protein determinants for RNA-binding are Spt4 together with the NGN domain of Spt5 and that the KOW domains are not required for RNA recognition. These findings attribute a new function to a domain of Spt4/5 that associates directly with RNAPII, making significant steps towards elucidating the mechanism behind transcriptional control by Spt4/5. PMID:27376968

  7. Expression and Distribution Pattern of Aquaporin 4, 5 and 11 in Retinas of 15 Different Species.

    PubMed

    Amann, Barbara; Kleinwort, Kristina J H; Hirmer, Sieglinde; Sekundo, Walter; Kremmer, Elisabeth; Hauck, Stefanie M; Deeg, Cornelia A

    2016-01-01

    Aquaporins (AQPs) are small integral membrane proteins with 13 members in mammals and are essential for water transport across membranes. They are found in many different tissues and cells. Currently, there are conflicting results regarding retinal aquaporin expression and subcellular localization between genome and protein analyses and among various species. AQP4, 7, 9 and 11 were described in the retina of men; whereas AQP6, 8 and 10 were earlier identified in rat retinas and AQP4, 5 and 11 in horses. Since there is a lack of knowledge regarding AQP expression on protein level in retinas of different animal models, we decided to analyze retinal cellular expression of AQP4, 5 and 11 in situ with immunohistochemistry. AQP4 was detected in all 15 explored species, AQP5 and AQP11 in 14 out of 15. Interestingly, AQP4 was unambiguously expressed in Muller glial cells, whereas AQP5 was differentially allocated among the species analyzed. AQP11 expression was Muller glial cell-specific in 50% of the animals, whereas in the others, AQP11 was detected in ganglion cell layer and at photoreceptor outer segments. Our data indicate a disparity in aquaporin distribution in retinas of various animals, especially for AQP5 and 11. PMID:27438827

  8. Analysis of Phosphatidylinositol-4,5-Bisphosphate Signaling in Cerebellar Purkinje Spines

    PubMed Central

    Brown, Sherry-Ann; Morgan, Frank; Watras, James; Loew, Leslie M.

    2008-01-01

    A 3D model was developed and used to explore dynamics of phosphatidylinositol-4,5-bisphosphate (PIP2) signaling in cerebellar Purkinje neurons. Long-term depression in Purkinje neurons depends on coincidence detection of climbing fiber stimulus evoking extracellular calcium flux into the cell and parallel fiber stimulus evoking inositol-1,4,5-trisphosphate (IP3)-meditated calcium release from the endoplasmic reticulum. Experimental evidence shows that large concentrations of IP3 are required for calcium release. This study uses computational analysis to explore how the Purkinje cell provides sufficient PIP2 to produce large amounts of IP3. Results indicate that baseline PIP2 concentration levels in the plasma membrane are inadequate, even if the model allows for PIP2 replenishment by lateral diffusion from neighboring dendrite membrane. Lateral diffusion analysis indicates apparent anomalous diffusion of PIP2 in the spiny dendrite membrane, due to restricted diffusion through spine necks. Stimulated PIP2 synthesis and elevated spine PIP2 mediated by a local sequestering protein were explored as candidate mechanisms to supply sufficient PIP2. Stimulated synthesis can indeed lead to high IP3 amplitude of long duration; local sequestration produces high IP3 amplitude, but of short duration. Simulation results indicate that local sequestration could explain the experimentally observed finely tuned timing between parallel fiber and climbing fiber activation. PMID:18487300

  9. 4.5-K Cold Box for SNS - A Successful Cooperation

    SciTech Connect

    Fleck, U.; Kurtcuoglu, K.; Urbin, J.; Howe, D.

    2004-06-23

    The US Department of Energy is constructing the next generation, accelerator-based, neutron source, the Spallation Neutron Source at the Oak Ridge National Laboratory. The superconducting LINAC requires a large custom cryogenic helium system that was specified and ordered by the Thomas Jefferson National Accelerator Laboratory. Two groups of Linde AG's engineering division teamed to design, fabricate, and deliver the 4.5-K cold box for the SNS Central He liquefier. Linde Kryotechnik AG (LK), Switzerland provided design, engineering support and the gas bearing turbine systems. Process design for 4.5 K cooling as well as 38-K shield cooling will be explained. Control logic, including turbine related logic, was specified by LK and implemented successfully by ORNL in their control system in cooperation with LK. Linde BOC Process Plants LLC, Tulsa, Oklahoma fabricated, tested and delivered the cold box. Skills and techniques specific to helium cold box fabrication will be discussed. Finally, an overview of the commissioning will be provided according to the project status.

  10. 4.5-K Cold Box for SNS — A Successful Cooperation

    NASA Astrophysics Data System (ADS)

    Fleck, U.; Urbin, J.; Kurtcuoglu, K.; Howe, D.

    2004-06-01

    The US Department of Energy is constructing the next generation, accelerator-based, neutron source, the Spallation Neutron Source at the Oak Ridge National Laboratory. The superconducting LINAC requires a large custom cryogenic helium system that was specified and ordered by the Thomas Jefferson National Accelerator Laboratory. Two groups of Linde AG's engineering division teamed to design, fabricate, and deliver the 4.5-K cold box for the SNS Central He liquefier. Linde Kryotechnik AG (LK), Switzerland provided design, engineering support and the gas bearing turbine systems. Process design for 4.5 K cooling as well as 38-K shield cooling will be explained. Control logic, including turbine related logic, was specified by LK and implemented successfully by ORNL in their control system in cooperation with LK. Linde BOC Process Plants LLC, Tulsa, Oklahoma fabricated, tested and delivered the cold box. Skills and techniques specific to helium cold box fabrication will be discussed. Finally, an overview of the commissioning will be provided according to the project status.

  11. Expression and Distribution Pattern of Aquaporin 4, 5 and 11 in Retinas of 15 Different Species

    PubMed Central

    Amann, Barbara; Kleinwort, Kristina J. H.; Hirmer, Sieglinde; Sekundo, Walter; Kremmer, Elisabeth; Hauck, Stefanie M.; Deeg, Cornelia A.

    2016-01-01

    Aquaporins (AQPs) are small integral membrane proteins with 13 members in mammals and are essential for water transport across membranes. They are found in many different tissues and cells. Currently, there are conflicting results regarding retinal aquaporin expression and subcellular localization between genome and protein analyses and among various species. AQP4, 7, 9 and 11 were described in the retina of men; whereas AQP6, 8 and 10 were earlier identified in rat retinas and AQP4, 5 and 11 in horses. Since there is a lack of knowledge regarding AQP expression on protein level in retinas of different animal models, we decided to analyze retinal cellular expression of AQP4, 5 and 11 in situ with immunohistochemistry. AQP4 was detected in all 15 explored species, AQP5 and AQP11 in 14 out of 15. Interestingly, AQP4 was unambiguously expressed in Muller glial cells, whereas AQP5 was differentially allocated among the species analyzed. AQP11 expression was Muller glial cell-specific in 50% of the animals, whereas in the others, AQP11 was detected in ganglion cell layer and at photoreceptor outer segments. Our data indicate a disparity in aquaporin distribution in retinas of various animals, especially for AQP5 and 11. PMID:27438827

  12. Genotoxicity of chryseno[4,5-bcd]thiophene and its sulfone derivative

    SciTech Connect

    Sinsheimer, J.E.; Hooberman, B.H.; Das, S.K.; Savla, P.M.; Ashe, A.J. III )

    1992-01-01

    The authors' recent syntheses of cryseno[4,5-bcd]thiophene together with its potential sulfone metabolite, chryseno[4,5-bcd]thiophene-4,4-dioxide, have made these compounds available for genotoxicity testing. Such toxicity testing is of interest as this thiophene is an isoster of the established carcinogen benzo[a]pyrene and is one of the thiaarenes which are potential environmental contaminants found in fossil fuels. Although the thiophene was less mutagenic than benzo[a]pyrene in Salmonella strains TA98 and TA100 after S9 activation, it exhibited in vivo chromosomal aberration activity equal to that of benzo[a]pyrene in the bone-marrow cells of mice. A reduced activity with Salmonella as well as in the bone-marrow cell assay for the sulfone does not support its role as the key active metabolic intermediate for the genotoxicity of the thiophene. Molecular orbital calculations would be consistent with the concept of activation through a diol-epoxide mechanism and offers an explanation for the reduced genotoxicity of the sulfone via this mechanism. These genotoxicity studies support the concern that sulfur isosters of established carcinogenic polycyclic aromatic hydrocarbons could themselves be toxic. 21 refs., 2 figs., 3 tabs.

  13. Multilayer-coated laminar grating with 16{percent} normal-incidence efficiency in the 150-{Angstrom} wavelength region

    SciTech Connect

    Seely, J. F.; Kowalski, M. P.; Cruddace, R. G.; Rife, J. C.; Osterried, K.; Kleineberg, U.; Menke, D. Hunter, W. R.

    1997-11-01

    We characterized a laminar grating with a Mo/Si multilayer coating by using synchrotron radiation and atomic force microscopy. The grating substitute had 2400 grooves/mm, 40-{Angstrom} groove depth, and 2080-{Angstrom} groove width. The microroughness of the grating substrate was 5 {Angstrom} rms. The multilayer coating was optimized to have peak normal-incidence reflectance at a wavelength near 150 {Angstrom}. For an angle of incidence of 10{degree} the peak grating efficiency was 16.3{percent} in the +1 order and 15.0{percent} in the {minus}1 order. The efficiency in the zero order was lower by a factor of 40 owing to the excellent matching of the groove depth and groove width to the wavelength of the incident radiation. By dividing the grating efficiencies by the measured reflectance of the multilayer coating, we obtained inferred groove efficiencies of 34{percent} and 32{percent} in the +1 and {minus}1 orders, respectively. {copyright} 1997 Optical Society of America

  14. Atomic supersymmetry

    NASA Technical Reports Server (NTRS)

    Kostelecky, V. Alan

    1993-01-01

    Atomic supersymmetry is a quantum-mechanical supersymmetry connecting the properties of different atoms and ions. A short description of some established results in the subject are provided and a few recent developments are discussed including the extension to parabolic coordinates and the calculation of Stark maps using supersymmetry-based models.

  15. Atomic Calligraphy

    NASA Astrophysics Data System (ADS)

    Imboden, Matthias; Pardo, Flavio; Bolle, Cristian; Han, Han; Tareen, Ammar; Chang, Jackson; Christopher, Jason; Corman, Benjamin; Bishop, David

    2013-03-01

    Here we present a MEMS based method to fabricate devices with a small number of atoms. In standard semiconductor fabrication, a large amount of material is deposited, after which etching removes what is not wanted. This technique breaks down for structures that approach the single atom limit, as it is inconceivable to etch away all but one atom. What is needed is a bottom up method with single or near single atom precision. We demonstrate a MEMS device that enables nanometer position controlled deposition of gold atoms. A digitally driven plate is swept as a flux of gold atoms passes through an aperture. Appling voltages on four comb capacitors connected to the central plate by tethers enable nanometer lateral precision in the xy plane over 15x15 sq. microns. Typical MEMS structures have manufacturing resolutions on the order of a micron. Using a FIB it is possible to mill apertures as small as 10 nm in diameter. Assuming a low incident atomic flux, as well as an integrated MEMS based shutter with microsecond response time, it becomes possible to deposit single atoms. Due to their small size and low power consumption, such nano-printers can be mounted directly in a cryogenic system at ultrahigh vacuum to deposit clean quench condensed metallic structures.

  16. PtdIns(4,5)P(2) and phospholipase C-independent Ins(1,4,5)P(3) signals induced by a nitrogen source in nitrogen-starved yeast cells.

    PubMed Central

    Bergsma, J C; Kasri, N N; Donaton, M C; De Wever, V; Tisi, R; de Winde, J H; Martegani, E; Thevelein, J M; Wera, S

    2001-01-01

    Addition of ammonium sulphate to nitrogen-depleted yeast cells resulted in a transient increase in Ins(1,4,5)P(3), with a maximum concentration reached after 7-8 min, as determined by radioligand assay and confirmed by chromatography. Surprisingly, the transient increase in Ins(1,4,5)P(3) did not trigger an increase in the concentration of intracellular calcium, as determined in vivo using the aequorin method. Similar Ins(1,4,5)P(3) signals were also observed in wild-type cells treated with the phospholipase C inhibitor 3-nitrocoumarin and in cells deleted for the only phospholipase C-encoding gene in yeast, PLC1. This showed clearly that Ins(1,4,5)P(3) was not generated by phospholipase C-dependent cleavage of PtdIns(4,5)P(2). Apart from a transient increase in Ins(1,4,5)P(3), we observed a transient increase in PtdIns(4,5)P(2) after the addition of a nitrogen source to nitrogen-starved glucose-repressed cells. Inhibition by wortmannin of the phosphatidylinositol 4-kinase, Stt4, which is involved in PtdIns(4,5)P(2) formation, did not affect the Ins(1,4,5)P(3) signal, but significantly delayed the PtdIns(4,5)P(2) signal. Moreover, wortmannin addition inhibited the nitrogen-induced activation of trehalase and the subsequent mobilization of trehalose, suggesting a role for PtdIns(4,5)P(2) in nitrogen activation of the fermentable-growth-medium-induced signalling pathway. PMID:11672425

  17. Carcinogenic 4(5)-methylimidazole found in beverages, sauces, and caramel colors: chemical properties, analysis, and biological activities.

    PubMed

    Hengel, Matt; Shibamoto, Takayuki

    2013-01-30

    Since the National Toxicology Program (NTP) identified 4(5)-methylimidazole [4(5)-MI] as a cancer causing chemical in 2007 and the State of California added it to the Proposition 65 list of compounds as a carcinogen on January 7, 2011, many researchers and regulatory agencies have become focused on the presence of 4(5)-MI in foods and beverages. 4(5)-MI has been known to form in the Maillard reaction system consisting of a sugar and ammonia-a typical caramel-color preparation method for beverages. 4(5)-MI is identified in various beverages and sauces, which are colored with caramel, as well as in caramel color itself. Analysis of 4(5)-MI is extremely difficult due to its high water solubility, but the analytical method for 4(5)-MI has progressed from conventional paper chromatography, gas chromatography, and gas chromatography-mass spectrometry to the most advanced high-performance liquid chromatography-mass spectrometry. Various studies indicate that caramel colors and carbonated beverages contain 4(5)-MI in levels ranging from 0 to around 1000 ppm and from 0 to about 500 ppm, respectively. Reports of the toxicity of 4(5)-MI at relatively high levels suggest that it may cause some adverse effects on human consumers. PMID:23294412

  18. Liquid atomization

    SciTech Connect

    Walzel, P. )

    1993-01-01

    A systematic review of different liquid atomizers is presented, accompanied by a discussion of various mechanisms of droplet formation in a gas atmosphere as a function of the liquid flow-regime and the geometry of the atomizer. Equations are presented for the calculation of the mean droplet-diameter. In many applications, details of the droplet size distribution are, also, important, e.g., approximate values of the breadth of the droplet formation are given. The efficiency of utilization of mechanical energy in droplet formation is indicated for the different types of atomizers. Atomization is used, in particular, for the following purposes: (1) atomization of fuels; (2) making granular products; (3) carrying out mass-transfer operations; and (4) coating of surfaces.

  19. cis-1,3,4,6-Tetranitrooctahydroimidazo-[4,5-d]imidazole (BCHMX), its properties and initiation reactivity.

    PubMed

    Klasovitý, Dusan; Zeman, Svatopluk; Růzicka, Ales; Jungová, Marcela; Rohác, Michal

    2009-05-30

    Using the (15)N NMR chemical shifts of nitrogen atoms in nitramino groups of cis-1,3,4,6-tetranitrooctahydroimidazo-[4,5-d]imidazole (bicyclo-HMX or BCHMX) and additional 10 nitramines, we have assessed its reactivity in detonation, under the influence of impact, and by action of electric spark. It is stated that the thermal stability of BCHMX is higher than that of 1,3,5-trinitro-1,3,5-triazinane (RDX). The longest NN bond in the BCHMX molecule (1.412(4)A) is the cause for its higher impact reactivity, which is at the level of that of penterythritol tetranitrate (PETN). In the experimentally determined detonation velocity, BCMX can be slightly better performing than RDX. From the standpoint of friction sensitivity, BCHMX is similar to 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX). Attention was also focused on the solubility-temperature dependence of BCHMX in acetone, acetonitrile, ethyl acetate, dimethyl sulfoxide, tetrahydrofurane, and nitromethane. X-ray crystallographic study of BCHMX (C(4)H(6)N(8)O(8), M(r)=294.17), has been carried out at the temperature of 150K with the following results: a=8.5430(8), b=6.9480(6), c=8.7780(8)A, alpha=90.0(7) degrees , beta=102.452(11) degrees , gamma=90.0(9) degrees , V=508.777(8)A(3), Z=2, D(x)=1.920 g cm(-3), lambda(Mo Ka)=0.71073A, micro=0.169 cm(-1), F(000)=856, final R=0.0414 for 1254 independent observed reflections. In the BCHMX crystal there were found more short contacts in the molecular crystal of BCHMX data of Gilardi creating extensive supramolecular architecture. PMID:18926628

  20. Profile of Salmonella enterica subsp. enterica (Subspecies I) Serotype 4,5,12:i:− Strains Causing Food-Borne Infections in New York City

    PubMed Central

    Agasan, Alice; Kornblum, John; Williams, George; Pratt, Chi-Chi; Fleckenstein, Phylis; Wong, Marie; Ramon, Alex

    2002-01-01

    Strains of newly emerging Salmonella enterica subsp. enterica (subspecies I) serotype 4,5,12:i:− causing food-borne infections, including a large food poisoning outbreak (n = 86) characterized by persistent diarrhea (14% bloody), abdominal pain, fever, and headache, were examined. The organisms were found in the stool samples from the patients. The biochemical profile of the organisms is consistent with that of S. enterica subsp. I serotypes, except for decreased dulcitol (13%) and increased inositol (96%) utilization. Twenty-eight percent of the strains showed resistance to streptomycin, sulfonamides, or tetracycline only; all three antimicrobial agents; or these agents either alone or in combination with ampicillin, trimethoprim, and trimethoprim-sulfamethoxazole. None of the serotype 4,5,12:i:− strains showed resistance or decreased susceptibility to chloramphenicol or ciprofloxacin. On pulsed-field gel electrophoresis (PFGE), the strains showed 11 or 12 resolvable genomic fragments with 18 banding patterns and three PFGE profile (PFP) clusters (i.e., PFP/A, PFP/B, and PFP/C). Seventy-five percent of the isolates fingerprinted were closely related (zero to three band differences; similarity [Dice] coefficient, 86 to 100%); 63% of these were indistinguishable from each other (PFP/A1). PFP/A1 was common to all strains from the outbreak and 11 hospital sources. Strains from six other hospitals shared clusters PFP/B and PFP/C. PFP/C4, of the environmental isolate, was unrelated to PFP/A and PFP/B. Nine band differences (similarity coefficient, 61%) were noted between PFP/A1 and PFP/E of the multidrug-resistant S. enterica subsp. enterica serotype Typhimurium definitive type 104 strains. Whether these emerging Salmonella strains represent a monophasic, Dul− variant of serotype Typhimurium or S. enterica subsp. enterica serotype Lagos or a distinct serotype of S. enterica subsp. I is not yet known. Some of the phenotypic and genotypic properties of the serotype

  1. Parallel synthesis of an oligomeric imidazole-4,5-dicarboxamide library.

    PubMed

    Xu, Zhigang; DiCesare, John C; Baures, Paul W

    2010-03-01

    A library of oligomeric compounds was synthesized based on the imidazole-4,5-dicarboxylic acid scaffold along with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate nonpolar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala), and were designed to be useful in screening for inhibitors of protein-protein interactions. Many of the protected and deprotected oligomers show evidence of conformational isomers persistent at room temperature in aqueous solution. A total of 317 final oligomers, out of 441 targeted compounds, were obtained in high analytical purity and of sufficient quantity to submit them for high-throughput screening as part of the NIH Roadmap. PMID:20170086

  2. Human health effects of 2,4,5-T and its toxic contaminants.

    PubMed

    Suskind, R R; Hertzberg, V S

    1984-05-11

    A clinical epidemiologic study was conducted to determine the long-term health effects of workplace exposure to the process of manufacturing the herbicide (2,4,5-trichlorophenoxy)acetic acid including contaminants such as 2,3,7,8-tetrachlorodibenzo-rho-dioxin. The population consisted of two cohorts: 204 clearly exposed and 163 not exposed. Among the exposed, clinical evidence of chloracne persisted in 55.7%. None of the not exposed experienced chloracne development. An association was found between the persistence of chloracne and the presence and severity of actinic elastosis of the skin. There is an association between exposure and the history of gastrointestinal tract ulcer. Pulmonary function values among those who were exposed and who currently smoked were lower than those who were not exposed and who currently smoked. The data assembled in the study indicate no evidence of increased risk for cardiovascular disease, hepatic disease, renal damage, or central or peripheral nervous system problems. PMID:6231388

  3. Outbreaks of monophasic Salmonella enterica serovar 4,[5],12:i:- in Luxembourg, 2006.

    PubMed

    Mossong, J; Marques, P; Ragimbeau, C; Huberty-Krau, P; Losch, S; Meyer, G; Moris, G; Strottner, C; Rabsch, W; Schneider, F

    2007-06-01

    A monophasic Salmonella enterica serovar 4,[5],12:i:- phage type DT193 emerged as the dominant serovar in Luxembourg in 2006, when it caused two major outbreaks involving 133 laboratory-confirmed human cases, 24 hospitalisations, and one death. The outbreak strain had an uncommon pulsed-field gel electrophoresis pattern STYMXB.0031 and antibiotic resistance profile ASSuT. A high proportion of cases were clustered in institutions for the elderly and in day-care centers. Strains identical to the outbreak strain were recovered from two control meals, a nappy changing table, retail sausages and caecal porcine samples at an abattoir. Locally produced pork meat is strongly suspected to have been the vehicle for the outbreaks, although the precise mechanisms remain unclear. PMID:17991400

  4. Inositol 1,4,5-trisphosphate-induced calcium release from platelet plasma membrane vesicles

    SciTech Connect

    Rengasamy, A.; Feinberg, H.

    1988-02-15

    A platelet membrane preparation, enriched in plasma membrane markers, took up /sup 45/Ca/sup 2 +/ in exchange for intravesicular Na+ and released it after the addition of inositol 1,4,5-trisphosphate (IP3). The possibility that contaminating dense tubular membrane (DTS) vesicles contributed the Ca/sup 2 +/ released by IP3 was eliminated by the addition of vanadate to inhibit Ca/sup +/-ATPase-mediated DTS Ca/sup 2 +/ sequestration and by the finding that only plasma membrane vesicles exhibit Na/sup +/-dependent Ca/sup 2 +/ uptake. Ca/sup 2 +/ released by IP3 was dependent on low extravesicular Ca/sup 2 +/ concentrations. IP3-induced Ca/sup 2 +/ release was additive to that released by Na/sup +/ addition while GTP or polyethylene glycol (PEG) had no effect. These results strongly suggest that IP3 facilitates extracellular Ca/sup 2 +/ influx in addition to release from DTS membranes.

  5. Fifth dimension of life and the 4/5 allometric scaling law for human brain.

    PubMed

    He, Ji-Huan; Zhang, Juan

    2004-01-01

    Brain cells are not spherical. The basal metabolic rate (B) of a spherical cell scales as B approximately r2, where r is the radius of the cell; that of a brain cell scales as B approximately r(d), where r is the characteristic radius of the cell and d is the fractal dimensionality of its contour. The fractal geometry of the cell leads to a 4/5 allometric scaling law for human brain, uniquely endowing humans with a 5th dimension and successfully explains why the scaling exponent varies during rest and exercise. A striking analogy between Kleiber's 3/4 law and Newton's second law is heuristically illustrated. A physical explanation is given for the 4th dimension of life for three-dimensional organisms and the 5th dimension for human brain. PMID:15563403

  6. Studying isoform-specific inositol 1,4,5-trisphosphate receptor function and regulation

    PubMed Central

    Betzenhauser, Matthew J.; Wagner, Larry E.; Won, Jong-Hak; Yule, David I.

    2011-01-01

    Inositol 1,4,5-trisphosphate receptors (InsP3R) are a family of ubiquitously expressed intracellular Ca2+ channels. Isoform-specific properties of the three family members may play a prominent role in defining the rich diversity of the spatial and temporal characteristics of intracellular Ca2+ signals. Studying the properties of the particular family members is complicated because individual receptor isoforms are typically never expressed in isolation. In this article, we discuss strategies for studying Ca2+ release through individual InsP3R family members with particular reference to methods applicable following expression of recombinant InsP3R and mutant constructs in the DT40-3KO cell line, an unambiguously null InsP3R expression system. PMID:18929664

  7. 4.5S ribonucleic acid, a novel ribosome component in the chloroplasts of flowering plants.

    PubMed Central

    Bowman, C M; Dyer, T A

    1979-01-01

    A species of low-molecular-weight ribosomal RNA, referred to as '4.5S rRNA', was found in addition to 5S rRNA in the large subunit of chloroplast ribosomes of a wide range of flowering plants. It was shown by sequence analysis that several variants of this RNA may occur in a plant. Furthermore, although in most flowering plants the predominant variant contains about 100 nucleotides, in the broad bean it has less than 80. It seems, therefore, to be much more diverse in size and sequence than the other ribosomal RNA species. Like 5S rRNA , it does not contain modified nucleotides and it is also unusual in having an unphosphorylated 5'-end. It is apparently neither a homologue of cytosol 5.8S rRNA nor a fragment of 23S rRNA. Images Fig. 1. Fig. 3. Fig. 4. PMID:540035

  8. Crystal structure of phenyl 2,4,5-tri­chloro­benzene­sulfonate

    PubMed Central

    Riley, Sean; Staples, Richard J.; Biros, Shannon M.; Ngassa, Felix N.

    2016-01-01

    The title compound, C12H7Cl3O3S, was synthesized via a nucleophilic substitution reaction between phenol and 2,4,5-tri­chloro­benzene­sulfonyl chloride. The two aryl rings are oriented gauche to one another around the sulfonate S—O bond, with a C—S—O—C torsion angle of −70.68 (16)°, and the two rings are inclined to one another by 72.40 (7)°. In the crystal, mol­ecules are linked via various C—Cl⋯π inter­actions, forming ribbons propagating along [100]. Neighboring ribbons are linked by a weak C—Cl⋯π inter­action, forming layers parallel to (010). PMID:27308043

  9. Synthesis of CORONA 5 (Ti-4.5Al-5Mo-1.5Cr)

    NASA Astrophysics Data System (ADS)

    Froes, F. H.; Highberger, W. T.

    1980-05-01

    The synthesis of CORONA 5 (Ti-4.5Al-5Mo-1.5Cr) is described from the viewpoints of alloy chemistry and microstructure. Lenticular alpha is shown to maximize fracture resistance parameters, while a globular alpha optimizes hightemperature flow characteristics. The processing and application of CORONA 5 as forging, plate, sheet and powder metallurgy products are presented. The weldability of the alloy is described and potential use of the alloy for engine applications discussed. The improved mechanical property behavior over the "workhorse" Ti-6Al-4V alloy combined with cost-effective production should result in use of CORONA 5 in many applications. Future developments for CORONA 5 are suggested both in terms of further mechanical property optimization and in light of the economics of producing the alloy.

  10. Complex self-assembly of pyrimido[4,5-d]pyrimidine nucleoside supramolecular structures

    NASA Astrophysics Data System (ADS)

    Zhao, Hang; Guo, Xiurong; He, Shiliang; Zeng, Xin; Zhou, Xinglong; Zhang, Chaoliang; Hu, Jing; Wu, Xiaohua; Xing, Zhihua; Chu, Liangyin; He, Yang; Chen, Qianming

    2014-01-01

    Supramolecular self-assembly is not only one of the chemical roots of biological structure but is also drawing attention in different industrial fields. Here we study the mechanism of the formation of a complex flower-shaped supramolecular structure of pyrimido[4,5-d]pyrimidine nucleosides by dynamic light scattering, scanning electron microscopy, differential scanning calorimetry, nuclear magnetic resonance and X-ray analysis. Upon removing the hydroxyl group of sugars, different flower-shaped superstructures can be produced. These works demonstrate that complex self-assembly can indeed be attained through hierarchical non-covalent interactions of single molecules. Furthermore, chimerical structures built from molecular recognition by these monomers indicate their potential in other fields if combined with other chemical entities.

  11. Inositol 1,4,5‐trisphosphate receptors and their protein partners as signalling hubs

    PubMed Central

    Taylor, Colin W.

    2016-01-01

    Abstract Inositol 1,4,5‐trisphosphate receptors (IP3Rs) are expressed in nearly all animal cells, where they mediate the release of Ca2+ from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca2+ signals allows selective regulation of diverse physiological responses. Interactions of IP3Rs with other proteins contribute to the specificity and speed of Ca2+ signalling pathways, and to their capacity to integrate information from other signalling pathways. In this review, we provide a comprehensive survey of the proteins proposed to interact with IP3Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP3Rs, facilitate their regulation by multiple signalling pathways and direct the Ca2+ that they release to specific targets. We suggest that IP3Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca2+ signals. PMID:26830355

  12. Preliminary toxicology study of 3,6-diamino-1,2,4,5-tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The calculated acute oral LD 30/50 (lethal dose for 50% of the animals occurring within 30 days after compound administration) value for 3,6-diamino-1,2,4,5-tetrazine (DATZ) was 863 mg/kg in rats. According to classical guidelines, DATZ would be considered slightly to moderately toxic for rats. The calculated acute oral LD {sub 30/50} value was 2,288 mg/kg in mice and would be considered slightly to moderately toxic for mice. Skin application studies using rabbits demonstrated DATZ to be a nonirritant. The eye study using rabbits disclosed DATZ to be a very mild irritant. The sensitization study using guinea pigs did not show DATZ to have potential sensitizing properties.

  13. Preliminary toxicology study of 3,6-diamino-1,2,4,5-tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The calculated acute oral LD 30/50 (lethal dose for 50% of the animals occurring within 30 days after compound administration) value for 3,6-diamino-1,2,4,5-tetrazine (DATZ) was 863 mg/kg in rats. According to classical guidelines, DATZ would be considered slightly to moderately toxic for rats. The calculated acute oral LD [sub 30/50] value was 2,288 mg/kg in mice and would be considered slightly to moderately toxic for mice. Skin application studies using rabbits demonstrated DATZ to be a nonirritant. The eye study using rabbits disclosed DATZ to be a very mild irritant. The sensitization study using guinea pigs did not show DATZ to have potential sensitizing properties.

  14. Potential GPS user architecture for the NASA Space Station based on Landsat 4/5 experience

    NASA Technical Reports Server (NTRS)

    Korenstein, David A.

    1987-01-01

    A Landsat 4/5 GPS system is described which uses an inertial reference attitude control system and precision real-time ephemeris generation to achieve precision earth pointing. The system has application to the validation of the use of GPS for the low earth orbit navigation of the Space Station. The present system consists of a receiver/processor assembly (R/PA), an L-band GPS antenna, a precision oscillator, and the Landsat computer. The R/PA is integrated with a GPS receiver which selects, acquires, tracks, times, and decodes navigation signals from GPS satellites in order to derive ephemerides. Ephemeris estimates were found to be accurate to better than 50 meters.

  15. Human cardiac phospholipase D activity is tightly controlled by phosphatidylinositol 4,5-bisphosphate.

    PubMed

    Kurz, Thomas; Kemken, Dorit; Mier, Kenneth; Weber, Isabel; Richardt, Gert

    2004-02-01

    Phospholipase D (PLD) plays a central role in receptor-mediated breakdown of choline phospholipids and formation of phosphatidic acid (PA), an important regulator of cardiac function. However, specific mechanisms that regulate myocardial PLD activity remain largely unknown, particularly in the human heart. We hypothesized that phosphatidylinositol 4,5-bisphosphate (PIP2), best known as substrate for phospholipase C (PLC) isozymes, plays a critical role in regulating myocardial PLD activity. We examined the effect of PIP2 on human myocardial PLD activity in vitro by utilizing a fluorescence HPLC assay. PIP2 increased 10-fold the maximal activity of a partially solubilized PLD from human atrial myocardium. PIP2-stimulated PLD activity was accompanied by a consecutive increase in diacylglycerol, indicating dephosphorylation of PA by PA phosphohydrolase. Likewise, phosphatidylinositol 3,4,5-trisphosphate, which is produced from PIP2 by phosphatidylinositol 3-kinase, increased PLD activity with about the same potency but with somewhat lower efficacy. In contrast, other phospholipids were ineffective, indicating that the action of PIP2 on PLD is highly specific. Neomycin, a high-affinity ligand of PIP2, inhibited PLD activity in human atrial myocardium, but had no effect on the activity of partially solubilized enzyme. The addition of PIP2 restored the sensitivity of solubilized PLD to neomycin inhibition, indicating that neomycin inhibits PLD activity by binding to endogenous PIP2. Our results demonstrate a critical role for PIP2 in human cardiac PLD activity and suggest that PIP2 synthesis (by phosphatidylinositol 4-phosphate 5-kinase) and hydrolysis (by PIP2-specific PLC) could be important determinants in regulating PLD signal transduction in the human heart. PMID:14871550

  16. Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system

    PubMed Central

    Duan, Shi-Yue; Ge, Xue-Mei; Lu, Nan; Wu, Fei; Yuan, Weien; Jin, Tuo

    2012-01-01

    A chemically dynamic spermine-based polymer: polyspermine imidazole-4, 5-amide (PSIA, Mw > 7 kDa) was designed, synthesized, and evaluated in terms of its ability to deliver nucleic acids. This polymer was made from an endogenous monomer professionally condensing genes in sperms, spermine, and a known safety drug metabolite, imidazole-4, 5-dicarboxylic acid, through a bis-amide bond conjugated with the imidazole ring. This polymer can condense pDNA at a W/W ratio above 10 to form polyplexes (100–200 nm in diameter), which is consistent with the observation by transmission electron microscopy (TEM), and the zeta potential was in the range of 10–20 mV. The pDNA packaged polymer was stable in phosphate buffer solution (PBS) at pH 7.4 (simulated body fluid) while the polyplexes were releasing pDNA into the solution at pH 5.8 (simulated endo-lysosomes) due to the degradation of the bis-amide linkages in response to changes in pH values. PSIA-polyplexes were able to achieve efficient cellular uptake and luciferase gene silencing by co-transfection of pDNA and siRNA in COS-7 cells and HepG2 cells with negligible cytotoxicity. Biodistribution of Rhodamine B-labeled PSIA-polyplexes after being systemically injected in BALB/c nude-mice showed that the polyplexes circulated throughout the body, accumulated mainly in the kidney at 4 hours of sample administration, and moved to the liver and spleen after 24 hours. All the results suggested that PSIA offered a promising example to balance the transfection efficiency and toxicity of a synthetic carrier system for the delivery of therapeutic nucleic acids. PMID:22888236

  17. THE NATURE OF EXTREMELY RED H - [4.5] > 4 GALAXIES REVEALED WITH SEDS AND CANDELS

    SciTech Connect

    Caputi, K. I.; Dunlop, J. S.; McLure, R. J.; Cirasuolo, M.; Huang, J.-S.; Fazio, G. G.; Ashby, M. L. N.; Castellano, M.; Fontana, A.; Almaini, O.; Bell, E. F.; Dickinson, M.; Donley, J. L.; Ferguson, H. C.; Grogin, N. A.; Koekemoer, A. M.; Faber, S. M.; Kocevski, D. D.; Koo, D. C.; and others

    2012-05-01

    We have analyzed a sample of 25 extremely red H - [4.5] > 4 galaxies, selected using 4.5 {mu}m data from the Spitzer SEDS survey and deep H-band data from the Hubble Space Telescope CANDELS survey, over {approx}180 arcmin{sup 2} of the UKIDSS Ultra-Deep Survey field. Our aim is to investigate the nature of this rare population of mid-infrared (mid-IR) sources that display such extreme near-to-mid-IR colors. Using up to 17-band photometry (U through 8.0 {mu}m), we have studied in detail their spectral energy distributions, including possible degeneracies in the photometric redshift/internal extinction (z{sub phot}-A{sub V} ) plane. Our sample appears to include sources of very different nature. Between 45% and 75% of them are dust-obscured, massive galaxies at 3 < z{sub phot} < 5. All of the 24 {mu}m detected sources in our sample are in this category. Two of these have S(24 {mu}m)>300 {mu}Jy, which at 3 < z{sub phot} < 5 suggests that they probably host a dust-obscured active galactic nucleus. Our sample also contains four highly obscured (A{sub V} > 5) sources at z{sub phot} < 1. Finally, we analyze in detail two z{sub phot} {approx} 6 galaxy candidates, and discuss their plausibility and implications. Overall, our red galaxy sample contains the tip of the iceberg of a larger population of z > 3 galaxies to be discovered with the future James Webb Space Telescope.

  18. Pulsations in magnetic field and ion flux observed at L = 4. 5 on August 5, 1972

    SciTech Connect

    Engebretson, M.J.; Cahill, L.J. Jr.; Williams, D.J.

    1983-01-01

    After the unusually strong compression of the earth's magnetosphere associated with the August 1972 geomagnetic storm, large amplitude ULF pulsations were observed for several hours in space by Explorer 45 magnetic field and particle instruments near L = 4.5 and at magnetic observatories on the ground over a large range of latitudes. Spectral analysis of Explorer 45 magnetometer data suggests that a compressional mode oscillation coupled to a transverse mode oscillation. Enhancements in amplitude of a 300-s period wave near 0040 UT August 5 coincide with an intensification of 100- to 1000-Hz magnetic and electric field oscillations and with the appearance of enhancements of fluxes of energetic ions. During this period the ion pitch angle distribution in each available energy channel (24--300 keV) followed a periodic sequence, apparently synchronized with the magnetic pulsations, from normal trappping (highest fluxes near 90/sup 0/ and lowest near 0/sup 0/ and 180/sup 0/) to a nearly isotropic particle distribution. During the transitions the particle flux near 90/sup 0/ pitch angle was alternately larger earthward of the satellite (before isotropy) and larger radially outward from the satellite (after isotropy). Intense field-aligned fluxes of lower energy ions (E< or =5 keV) were observed periodically throughout the interval. Possible configurations of the magnetosphere consistent with the wave and particle observations are discussed, the most likely candidate being the presence of a wavelike boundary near the satellite. It is possible that the satellite sensed the low-latitude boundary layer at L = 4.5 during this period of extreme magnetospheric compression.

  19. Stereopsis Results at 4.5 Years of Age in the Infant Aphakia Treatment Study

    PubMed Central

    Hartmann, E. Eugenie; Stout, Ann U.; Lynn, Michael J.; Yen, Kimberly G.; Kruger, Stacey J.; Lambert, Scott R.

    2014-01-01

    Purpose To determine whether stereopsis of infants treated for monocular cataracts varies with the type of optical correction used. Design Randomized prospective clinical trial Methods The Infant Aphakia Treatment Study randomized 114 patients with unilateral cataracts at age 1 to 7 months to either primary intraocular lens (IOL) or contact lens correction. At 4.5 years of age a masked examiner assessed stereopsis on these patients using three different tests: 1) Frisby; 2) Randot Preschool; and 3) Titmus fly. Results Twenty-eight patients (25%) had a positive response to at least one of the stereopsis tests. There was no statistically significant difference in stereopsis between the two treatment groups. Frisby (contact lens, 6 (11%); IOL, 7 (13%); p=0.99), Randot (contact lens, 3 (6%); IOL, 1 (2%); p=0.62) or Titmus: (contact lens, 8 (15%); IOL, 13 (23%); p=0.34). The median age at surgery for patients with stereopsis was younger than for those without stereopsis (1.2 versus 2.4 months; p=0.002). The median visual acuity for patients with stereopsis was better than for those without stereopsis (20/40 vs. 20/252; p=0.0003). Conclusion The type of optical correction did not influence stereopsis outcomes. However, two other factors did: age at surgery and visual acuity in the treated eye at age 4.5 years. Early surgery for unilateral congenital cataract and the presence of visual acuity better than or equal to 20/40 appear to be more important than the type of initial optical correction used for the development of stereopsis. PMID:25261241

  20. CLONING AND CHARACTERIZATION OF A CHROMOSOMAL DNA REGION REQUIRED FOR GROWTH ON 2,4,5-T BY PSEUDOMONAS CEPACIA AC1100

    EPA Science Inventory

    A series of spontaneous 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) nonmetabolizing mutants of Pseudomonas cepacia AC1100 were characterized to be defective in either 2,4,5-T uptake or conversion of this compound to 2,4,5-trichlorophenol (2,4,5-TCP). Two of these mutants, RHC22 a...

  1. CLONING AND CHARACTERIZATION OF A CHROMOSOMAL DNA REGION REQUIRED FOR GROWTH ON 2,4,5-T BY PSEUDOMONAS CEPACIA AC1100

    EPA Science Inventory

    A series of spontaneous 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) nonmetaolizing mutants of Pseudomonas cepacia AC1100 were characterized to be defective in either 2,4,5-T uptake or conversion of this compound to 2,4,5-trichlorophenol (2,4,5TCP). wo of these mutants, RHC22 and ...

  2. Integrin adhesion and force coupling are independently regulated by localized PtdIns(4,5)2 synthesis

    PubMed Central

    Legate, Kyle R; Takahashi, Seiichiro; Bonakdar, Navid; Fabry, Ben; Boettiger, David; Zent, Roy; Fässler, Reinhard

    2011-01-01

    The 90-kDa isoform of the lipid kinase PIP kinase Type I γ (PIPKIγ) localizes to focal adhesions (FAs), where it provides a local source of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Although PtdIns(4,5)P2 regulates the function of several FA-associated molecules, the role of the FA-specific pool of PtdIns(4,5)P2 is not known. We report that the genetic ablation of PIPKIγ specifically from FAs results in defective integrin-mediated adhesion and force coupling. Adhesion defects in cells deficient in FA-PtdIns(4,5)P2 synthesis are corrected within minutes while integrin–actin force coupling remains defective over a longer period. Talin and vinculin, but not kindlin, are less efficiently recruited to new adhesions in these cells. These data demonstrate that the specific depletion of PtdIns(4,5)P2 from FAs temporally separates integrin–ligand binding from integrin–actin force coupling by regulating talin and vinculin recruitment. Furthermore, it suggests that force coupling relies heavily on locally generated PtdIns(4,5)P2 rather than bulk membrane PtdIns(4,5)P2. PMID:21926969

  3. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  4. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  5. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  6. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  7. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  8. Vacuum ultraviolet laser induced fluorescence on a Si atomic beam

    NASA Technical Reports Server (NTRS)

    O'Brian, T. R.; Lawler, J. E.

    1991-01-01

    A broadly applicable vacuum ultraviolet experiment is described for measuring radiative lifetimes of neutral and singly-ionized atoms in a beam environment to 5-percent accuracy using laser induced fluorescence. First results for neutral Si are reported.

  9. Acting Atoms.

    ERIC Educational Resources Information Center

    Farin, Susan Archie

    1997-01-01

    Describes a fun game in which students act as electrons, protons, and neutrons. This activity is designed to help students develop a concrete understanding of the abstract concept of atomic structure. (DKM)

  10. Kinetic Atom.

    ERIC Educational Resources Information Center

    Wilson, David B.

    1981-01-01

    Surveys the research of scientists like Joule, Kelvin, Maxwell, Clausius, and Boltzmann as it comments on the basic conceptual issues involved in the development of a more precise kinetic theory and the idea of a kinetic atom. (Author/SK)

  11. Newton's Atom

    NASA Astrophysics Data System (ADS)

    Chaney, Andrea; Espinosa, James; Espinosa, James

    2006-10-01

    At the turn of the twentieth century, physicists and chemists were developing atomic models. Some of the phenomena that they had to explain were the periodic table, the stability of the atom, and the emission spectra. Niels Bohr is known as making the first modern picture that accounted for these. Unknown to much of the physics community is the work of Walter Ritz. His model explained more emission spectra and predates Bohr's work. We will fit several spectra using Ritz's magnetic model for the atom. The problems of stability and chemical periodicity will be shown to be challenges that this model has difficulty solving, but we will present some potentially useful adaptations to the Ritzian atom that can account for them.

  12. Synthesis of 5-chloro-4,5-diaryl-. delta. /sup 3/-1,3-oxazolin-2-ones

    SciTech Connect

    Bal'on, Ya.G.; Smirnov, V.A.

    1987-09-20

    During an attempt at the synthesis of the oxazoles by the reactions of the oxazolines (I) with phosphorus pentachloride the authors obtained the 5-chloro-4,5-diaryl-..delta../sup 3/-1,3-oxazolin-2-ones instead of the expected 4,5-diaryl-2-chlorooxazoles. As electrophiles, these compounds are active in nucleophilic addition and substitution reactions. Thus, in their reaction with methanol the 4,5-dimethoxy-4,5-diaryl-1,3-oxazolidin-2-ones are formed with quantitative yields. When heated they are easily converted into 5-methoxy-4,5-diaryl-..delta..-1,3-oxazolin-2-ones. The compositions and structures were proved by IR and PMR spectroscopy and elemental analysis.

  13. Ca(2+) signals mediated by Ins(1,4,5)P(3)-gated channels in rat ureteric myocytes.

    PubMed Central

    Boittin, F X; Coussin, F; Morel, J L; Halet, G; Macrez, N; Mironneau, J

    2000-01-01

    Localized Ca(2+)-release signals (puffs) and propagated Ca(2+) waves were characterized in rat ureteric myocytes by confocal microscopy. Ca(2+) puffs were evoked by photorelease of low concentrations of Ins(1,4,5)P(3) from a caged precursor and by low concentrations of acetylcholine; they were also observed spontaneously in Ca(2+)-overloaded myocytes. Ca(2+) puffs showed some variability in amplitude, time course and spatial spread, suggesting that Ins(1,4,5)P(3)-gated channels exist in clusters containing variable numbers of channels and that within these clusters a variable number of channels can be recruited. Immunodetection of Ins(1,4,5)P(3) receptors revealed the existence of several spots of fluorescence in the confocal cell sections, supporting the existence of clusters of Ins(1,4,5)P(3) receptors. Strong Ins(1,4,5)P(3) photorelease and high concentrations of acetylcholine induced Ca(2+) waves that originated from an initiation site and propagated in the whole cell by spatial recruitment of neighbouring Ca(2+)-release sites. Both Ca(2+) puffs and Ca(2+) waves were blocked selectively by intracellular applications of heparin and an anti-Ins(1,4,5)P(3)-receptor antibody, but were unaffected by ryanodine and intracellular application of an anti-ryanodine receptor antibody. mRNAs encoding for the three subtypes of Ins(1,4,5)P(3) receptor and subtype 3 of ryanodine receptor were detected in these myocytes, and the maximal binding capacity of [(3)H]Ins(1,4,5)P(3) was 10- to 12-fold higher than that of [(3)H]ryanodine. These results suggest that Ins(1,4,5)P(3)-gated channels mediate a continuum of Ca(2+) signalling in smooth-muscle cells expressing a high level of Ins(1,4,5)P(3) receptors and no subtypes 1 and 2 of ryanodine receptors. PMID:10861244

  14. A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate.

    PubMed

    Iwasaki, Hirohide; Murata, Yoshimichi; Kim, Youngjun; Hossain, Md Israil; Worby, Carolyn A; Dixon, Jack E; McCormack, Thomas; Sasaki, Takehiko; Okamura, Yasushi

    2008-06-10

    Phosphatidylinositol lipids play diverse physiological roles, and their concentrations are tightly regulated by various kinases and phosphatases. The enzymatic activity of Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP), recently identified as a member of the PTEN (phosphatase and tensin homolog deleted on chromosome 10) family of phosphatidylinositol phosphatases, is regulated by its own voltage-sensor domain in a voltage-dependent manner. However, a detailed mechanism of Ci-VSP regulation and its substrate specificity remain unknown. Here we determined the in vitro substrate specificity of Ci-VSP by measuring the phosphoinositide phosphatase activity of the Ci-VSP cytoplasmic phosphatase domain. Despite the high degree of identity shared between the active sites of PTEN and Ci-VSP, Ci-VSP dephosphorylates not only the PTEN substrate, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], but also, unlike PTEN, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Enzymatic action on PI(4,5)P2 removes the phosphate at position 5 of the inositol ring, resulting in the production of phosphatidylinositol 4-phosphate [PI(4)P]. The active site Cys-X(5)-Arg (CX(5)R) sequence of Ci-VSP differs with that of PTEN only at amino acid 365 where a glycine residue in Ci-VSP is replaced by an alanine in PTEN. Ci-VSP with a G365A mutation no longer dephosphorylates PI(4,5)P2 and is not capable of inducing depolarization-dependent rundown of a PI(4,5)P2-dependent potassium channel. These results indicate that Ci-VSP is a PI(3,4,5)P3/PI(4,5)P2 phosphatase that uniquely functions in the voltage-dependent regulation of ion channels through regulation of PI(4,5)P2 levels. PMID:18524949

  15. Cold Atoms

    NASA Astrophysics Data System (ADS)

    Bellac, Michel Le

    2014-11-01

    This chapter and the following one address collective effects of quantum particles, that is, the effects which are observed when we put together a large number of identical particles, for example, electrons, helium-4 or rubidium-85 atoms. We shall see that quantum particles can be classified into two categories, bosons and fermions, whose collective behavior is radically different. Bosons have a tendency to pile up in the same quantum state, while fermions have a tendency to avoid each other. We say that bosons and fermions obey two different quantum statistics, the Bose-Einstein and the Fermi-Dirac statistics, respectively. Temperature is a collective effect, and in Section 5.1 we shall explain the concept of absolute temperature and its relation to the average kinetic energy of molecules. We shall describe in Section 5.2 how we can cool atoms down thanks to the Doppler effect, and explain how cold atoms can be used to improve the accuracy of atomic clocks by a factor of about 100. The effects of quantum statistics are prominent at low temperatures, and atom cooling will be used to obtain Bose-Einstein condensates at low enough temperatures, when the atoms are bosons.

  16. Quantum mechanics/molecular mechanics studies on the mechanism of action of cofactor pyridoxal 5'-phosphate in ornithine 4,5-aminomutase.

    PubMed

    Pang, Jiayun; Scrutton, Nigel S; Sutcliffe, Michael J

    2014-09-01

    A computational study was performed on the experimentally elusive cyclisation step in the cofactor pyridoxal 5'-phosphate (PLP)-dependent D-ornithine 4,5-aminomutase (OAM)-catalysed reaction. Calculations using both model systems and a combined quantum mechanics/molecular mechanics approach suggest that regulation of the cyclic radical intermediate is achieved through the synergy of the intrinsic catalytic power of cofactor PLP and the active site of the enzyme. The captodative effect of PLP is balanced by an enzyme active site that controls the deprotonation of both the pyridine nitrogen atom (N1) and the Schiff-base nitrogen atom (N2). Furthermore, electrostatic interactions between the terminal carboxylate and amino groups of the substrate and Arg297 and Glu81 impose substantial "strain" energy on the orientation of the cyclic intermediate to control its trajectory. In addition the "strain" energy, which appears to be sensitive to both the number of carbon atoms in the substrate/analogue and the position of the radical intermediates, may play a key role in controlling the transition of the enzyme from the closed to the open state. Our results provide new insights into several aspects of the radical mechanism in aminomutase catalysis and broaden our understanding of cofactor PLP-dependent reactions. PMID:25048616

  17. Spectral approach to finite Reynolds number effects on Kolmogorov's 4/5 law in isotropic turbulence

    NASA Astrophysics Data System (ADS)

    Tchoufag, J.; Sagaut, P.; Cambon, C.

    2012-01-01

    The Kolmogorov's 4/5 law is often considered as the sole exact relationship of inertial range statistics. Its asymptotic character, however, has been evidenced, investigating the finite Reynolds number (FRN) effect for the third-order structure function S3(r) (e.g., for longitudinal velocity increments with r separation length) using variants of the Kármán-Howarth equation in physical space. Similar semi-empirical fits were proposed for the maximum of the normalized structure function, C3 = -maxrS3(r)/(ɛr), expressing C3 - 4/5 as a power law of the Taylor-based Reynolds number. One of the most complete studies in this domain is by Antonia and Burratini [J. Fluid Mech. 550, 175 (2006)]. Considering that these studies are based on a model for the unsteady second-order structure function S2(r,t), with no explicit model for the third-order structure function itself, we propose to revisit the FRN effect by a spectral approach, in the line of Qian [Phys. Rev. E 55, 337 (1997), Phys. Rev. E 60, 3409 (1999)]. The spectral transfer term T(k,t), from which S3(r,t) is derived by an exact quadrature, is directly calculated by solving the Lin equation for the energy spectrum E(k,t), closed by a standard triadic (or three-point) theory, here Eddy Damped Quasi Normal Markovian. We show that the best spectral approach to the FRN effect is found by separately investigating the negative (largest scales) and positive (smaller scales) bumps of the transfer term, and not only by looking at the maximum of the spectral flux or maxk ∫k∞T(p ,t)dp→ɛ. In the forced case, previous results are well reproduced, with Reynolds numbers as high as Reλ = 5 000 to nearly recover the 4/5 value. In the free decay case, the general trend is recovered as well, with an even higher value of Reλ = 50 000, but the EDQNM plots are systematically below those in Antonia and Burattini [J. Fluid Mech. 550, 175 (2006)]. This is explained by the sensitivity to initial data for E(k) in solving the Lin

  18. Aldolase A Ins(1,4,5)P3-binding domains as determined by site-directed mutagenesis.

    PubMed Central

    Baron, C B; Tolan, D R; Choi, K H; Coburn, R F

    1999-01-01

    We substituted neutral amino acids for some positively charged residues (R42, K107, K146, R148 and K229) that line the active site of aldolase A in an effort to determine binding sites for inositol 1, 4,5-trisphosphate. In addition, D33 (involved in carbon-carbon bond cleavage) was mutated. K229A and D33S aldolases showed almost no catalytic activity, but Ins(1,4,5)P(3) binding was similar to that determined with the use of wild-type aldolase A. R42A, K107A, K146R and R148A had markedly decreased affinities for Ins(1,4,5)P(3) binding, increased EC(50) values for Fru(1,6)P(2)-evoked release of bound Ins(1,4,5)P(3) and increased K(i) values for Ins(1,4, 5)P(3)-evoked inhibition of aldolase activity. K146Q (positive charge removal) had essentially no catalytic activity and could not bind Ins(1,4,5)P(3). Computer-simulated docking of Ins(1,4,5)P(3) in the aldolase A structure was consistent with electrostatic binding of Ins(1,4,5)P(3) to K107, K146, R148, R42, R303 and backbone nitrogens, as has been reported for Fru(1,6)P(2) binding. Results indicate that Ins(1,4,5)P(3) binding occurs at the active site and is not dependent on having a catalytically active enzyme; they also suggest that there is competition between Ins(1,4,5)P(3) and Fru(1, 6)P(2) for binding. Although Ins(1,4,5)P(3) binding to aldolase involved electrostatic interactions, the aldolase A Ins(1,4, 5)P(3)-binding domain did not show other similarities to pleckstrin homology domains or phosphotyrosine-binding domains known to bind Ins(1,4,5)P(3) in other proteins. PMID:10417347

  19. Biosensors to measure inositol 1,4,5-trisphosphate concentration in living cells with spatiotemporal resolution.

    PubMed

    Remus, Timothy P; Zima, Aleksey V; Bossuyt, Julie; Bare, Dan J; Martin, Jody L; Blatter, Lothar A; Bers, Donald M; Mignery, Gregory A

    2006-01-01

    Phosphoinositides participate in many signaling cascades via phospholipase C stimulation, which hydrolyzes phosphatidylinositol 4,5-bisphosphate, producing second messengers diacylglycerol and inositol 1,4,5-trisphosphate (InsP3). Destructive chemical approaches required to measure [InsP3] limit spatiotemporal understanding of subcellular InsP3 signaling. We constructed novel fluorescence resonance energy transfer-based InsP3 biosensors called FIRE (fluorescent InsP3-responsive element) by fusing plasmids encoding the InsP3-binding domain of InsP3 receptors (types 1-3) between cyan fluorescent protein and yellow fluorescent protein sequences. FIRE was expressed and characterized in COS-1 cells, cultured neonatal cardiac myocytes, and incorporated into an adenoviral vector for expression in adult cardiac ventricular myocytes. FIRE-1 exhibits an approximately 11% increase in the fluorescence ratio (F530/F480) at saturating [InsP3] (apparent K(d) = 31.3 +/- 6.7 nm InsP3). In COS-1 cells, neonatal rat cardiac myocytes and adult cat ventricular myocytes FIRE-1 exhibited comparable dynamic range and a 10% increase in donor (cyan fluorescent protein) fluorescence upon bleach of yellow fluorescent protein, indicative of fluorescence resonance energy transfer. In FIRE-1 expressing ventricular myocytes endothelin-1, phenylephrine, and angiotensin II all produced rapid and spatially resolved increases in [InsP3] using confocal microscopy (with free [InsP3] rising to approximately 30 nm). Local entry of intracellular InsP3 via membrane rupture by a patch pipette (containing InsP3)in myocytes expressing FIRE-1 allowed detailed spatiotemporal monitoring of intracellular InsP3 diffusion. Both endothelin-1-induced and direct InsP3 application (via pipette rupture) revealed that InsP3 diffusion into the nucleus occurs with a delay and blunted rise of [InsP3] versus cytosolic [InsP3]. These new biosensors allow studying InsP3 dynamics at high temporal and spatial resolution that

  20. Hydrogeodeformation field in the Caucasus related to the preparation of Tbilisi earthquakes (M>4.5)

    NASA Astrophysics Data System (ADS)

    Aliev, A.; Bendukidze, G.; Biagi, P. F.; Chelidze, T.; Devidze, M.; Garalov, B.; Melikadze, G.; Vartanian, G.

    2003-04-01

    Here we present the relation between the variations of the underground water level in boreholes and the deformation processes associated with the occurrence of Tbilisi earthquakes with Mge4.5. The hydrogeodeformation field (HGDF) has been pointed out on the basis of the data collected in networks located in Armenia, Azerbaijan, Georgia and Russia. The boreholes are uniformly distributed in the Caucasus and they cover all the main geological blocks of the region; their depth ranges from 250 m to 3.500 m. On the basis of the water variations related to the gravity tides, a preliminary calibration of the boreholes was carried out at the purpose to evaluate the sensitivity and to normalize the hydrodynamic signals. The hydrodynamical and hydrochemical data have been processed by means of spectral analyses to separate the disturbance background field from the valid signals. The processed data cover the period 1999-2002 in which 3 earthquakes (Mge4.5) occurred in Tbilisi at December 14, 2000, January 03, 2001 and April 25, 2002. The formation of an extension zone in the eastern Caucasus and of a compression zone in the western Georgia and northern Caucasus was observed 3 months before the April 2002 earthquake. The boundary between these 2 zones was along a well known sub horizontal fault. The largest deformation gradient was observed in a zone that is the joint of deep faults. This zone is the place where the previous earthquake was generated. After the earthquake occurrence, the zone of the largest gradient migrated towards East and the residual HGDF could be considered as source of the Ujarma earthquake (August 2002). Thus, HGDF seems to indicate a migration of the deformation field along the slope of the Greater Caucasus 3 months prior the earthquake. Another observation is that before the earthquakes, when the deformation reaches its critical value, the natural pattern of tidal variations in each observation point was disturbed. The period of the perturbation (from

  1. 4-[5-(4-Formyl­phen­oxy)pent­oxy]benzaldehyde

    PubMed Central

    Balić, Tomislav; Marković, Berislav; Balić, Ivana

    2012-01-01

    In the title compound, C20H19O4, the benzene rings, linked via five methyl­ene C atoms, form a dihedral angle of 77.28 (6)°. In the crystal, mol­ecules are linked via pairs of weak C—H⋯O inter­actions [graph set R 2 2(6)] into dimers that are further connected by additional weak C—H⋯O interactions [graph sets R 2 2(14), R 2 2(26) and R 2 2(6)]. PMID:22969559

  2. Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphatase.

    PubMed

    Ho, Melisa W Y; Yang, Xiaonian; Carew, Mark A; Zhang, Tong; Hua, Len; Kwon, Yong-Uk; Chung, Sung-Kee; Adelt, Stephan; Vogel, Günter; Riley, Andrew M; Potter, Barry V L; Shears, Stephen B

    2002-03-19

    Regulation of Cl(-) channel conductance by Ins(3,4,5,6)P(4) provides receptor-dependent control over salt and fluid secretion, cell volume homeostasis, and electrical excitability of neurones and smooth muscle. Ignorance of how Ins(3,4,5,6)P(4) is synthesized has long hindered our understanding of this signaling pathway. We now show Ins(3,4,5,6)P(4) synthesis by Ins(1,3,4,5,6)P(5) 1-phosphatase activity by an enzyme previously characterized as an Ins(3,4,5,6)P(4) 1-kinase. Rationalization of these phenomena with a ligand binding model unveils Ins(1,3,4)P(3) as not simply an alternative kinase substrate, but also an activator of Ins(1,3,4,5,6)P(5) 1-phosphatase. Stable overexpression of the enzyme in epithelial monolayers verifies its physiological role in elevating Ins(3,4,5,6)P(4) levels and inhibiting secretion. It is exceptional for a single enzyme to catalyze two opposing signaling reactions (1-kinase/1-phosphatase) under physiological conditions. Reciprocal coordination of these opposing reactions offers an alternative to general doctrine that intracellular signals are regulated by integrating multiple, distinct phosphatases and kinases. PMID:11909533

  3. Removal of 2,4,5-trichlorophenol by bacterial isolates from the secondary sludge of pulp and paper mill.

    PubMed

    Karn, Santosh Kr; Reddy, M Sudhakara

    2013-09-01

    2,4,5-trichlorophenol (2,4,5-TCP) mineralizing bacteria were isolated from the secondary sludge of pulp and paper industry. These isolates used 2,4,5-TCP as a source of carbon and energy and were capable of degrading this compound, as indicated by stoichimetric release of chloride and biomass formation. Based on 16S rRNA sequence analysis, these bacteria were identified as Kocuria sp. (CL2), Bacillus pumillus (CL5), Pseudomonas stutzeri (CL7). HPLC analysis revealed that these isolates were able to degrade 2,4,5-TCP at higher concentrations (600 mg/l or 3.0 mM). A consortia of these isolates completely removed 2,4,5-TCP from the sludge obtained from pulp and paper mill within 2 weeks when supplemented at a rate of 100 mg l(-1) . Bacterial consortium also significantly reduced absorbable organic halogen (AOX) and extractable organic halogen (EOX) by 61% and 63%, respectively from the sludge. These isolates have high potential to remove 2,4,5-TCP and may be used for remediation of pulp paper mill waste containing 2,4,5-TCP. PMID:22961799

  4. Iraq challenges sanctions, offers 4.5 million b/d developable capacity

    SciTech Connect

    Stauffer, T.R.

    1995-04-10

    The prospective oil deals of the century were unveiled last month in Baghdad at the unlikely venue of the first international oil conference in Iraq in decades. In a dramatic twist Iraq detailed 33 oil fields that are now open for joint development with foreign partners. The productive capacity of the listed fields totals some 4.5 million b/d, and the underlying proved reserves exceed 50 billion bbl--equal to more than US and Canadian reserves combined. Reversing its prior compulsive secretiveness concerning oil affairs, the government cleared at the highest level the proposal to publicize the available resources and to offer corroborative detail. ``Four and a half million b/d is an awful lot of oil,`` noted one foreign oilman who was loath to be quoted because his company feared possible reprisals in the US. The economic bait was both clear and enticing. Iraq chose the public forum to signal to the world the gains that could accrue to the first countries that break with the US over continuing the sanctions. The paper discusses the political impacts, the substantial offerings, exploitation costs, and bypassing sanctions.

  5. Geological Mapping Uses Landsat 4-5TM Satellite Data in Manlai Soum of Omnogovi Aimag

    NASA Astrophysics Data System (ADS)

    Norovsuren, B.

    2014-12-01

    Author: Bayanmonkh N1, Undram.G1, Tsolmon.R2, Ariunzul.Ya1, Bayartungalag B31 Environmental Research Information and Study Center 2NUM-ITC-UNESCO Space Science and Remote Sensing International Laboratory, National University of Mongolia 3Geology and Hydrology School, Korea University KEY WORDS: geology, mineral resources, fracture, structure, lithologyABSTRACTGeologic map is the most important map for mining when it does exploration job. In Mongolia geological map completed by Russian geologists which is done by earlier technology. Those maps doesn't satisfy for present requirements. Thus we want to study improve geological map which includes fracture, structural map and lithology use Landsat TM4-5 satellite data. If we can produce a geological map from satellite data with more specification then geologist can explain or read mineralogy very easily. We searched all methodology and researches of every single element of geological mapping. Then we used 3 different remote sensing methodologies to produce structural and lithology and fracture map based on geographic information system's softwares. There can be found a visible lithology border improvement and understandable structural map and we found fracture of the Russian geological map has a lot of distortion. The result of research geologist can read mineralogy elements very easy and discovered 3 unfound important elements from satellite image.

  6. Formation of carcinogenic 4(5)-methylimidazole in caramel model systems: a role of sulphite.

    PubMed

    Lee, Kwang-Geun; Jang, Haewon; Shibamoto, Takayuki

    2013-02-15

    Aqueous caramel model systems consisted the D-glucose/NH(3)/sulphite were heated at 100°C for 2 h and amounts of carcinogenic 4(5)-methylimidazole (4-MI) formed were determined. The amount formed ranged from 7.0 to 155.0 ppm. A system with 0.1 M sulphite yielded the greatest amount of 4-MI, which was 54% more than that yielded from a system without sulphite. When the amount of sulphite increased over 0.1 M, the amount of 4-MI reduced. The greatest reduction was achieved with 0.2 M sulphite by 68% compared to 0 M sulphite, suggesting that sulphite plays an important role in the formation of carcinogenic 4-MI in caramel colour. Also, a system with 0.1 M sulphite yielded the most intense caramel colour but the other levels of sulphite did not change the colour intensity significantly. Sulphite contributed slightly to the level of flavour chemicals evaluated using pyrazine formation. The results suggest that sulphite addition at appropriate amount reduces 4-MI formation in caramel colour without sacrificing flavour and colour formation. PMID:23194510

  7. A map of dust reddening to 4.5 kpc from Pan-STARRS1

    SciTech Connect

    Schlafly, E. F.; Rix, H.-W.; Martin, N. F.; Green, G.; Finkbeiner, D. P.; Jurić, M.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Magnier, E. A.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.; Draper, P. W.; Metcalfe, N.; Price, P. A.; Stubbs, C. W.

    2014-07-01

    We present a map of the dust reddening to 4.5 kpc derived from Pan-STARRS1 stellar photometry. The map covers almost the entire sky north of declination –30° at a resolution of 7'-14', and is based on the estimated distances and reddenings to more than 500 million stars. The technique is designed to map dust in the Galactic plane, where many other techniques are stymied by the presence of multiple dust clouds at different distances along each line of sight. This reddening-based dust map agrees closely with the Schlegel et al. (SFD) far-infrared emission-based dust map away from the Galactic plane, and the most prominent differences between the two maps stem from known limitations of SFD in the plane. We also compare the map with Planck, finding likewise good agreement in general at high latitudes. The use of optical data from Pan-STARRS1 yields reddening uncertainty as low as 25 mmag E(B – V).

  8. A new FPGA with 4/5-input LUT and optimized carry chain

    NASA Astrophysics Data System (ADS)

    Zhidong, Mao; Liguang, Chen; Yuan, Wang; Jinmei, Lai

    2012-07-01

    A new LUT and carry structure embedded in the configurable logic block of an FPGA is proposed. The LUT is designed to support both 4-input and 5-input structures, which can be configured by users according to their needs without increasing interconnect resources. We also develop a new carry chain structure with an optimized critical path. Finally a newly designed configurable scan-chain is inserted. The circuit is fabricated in 0.13 μm 1P8M 1.2/2.5/3.3 V logic CMOS process. The test results show a correct function of 4/5-input LUT and scan-chain, and a speedup in carry performance of nearly 3 times over current architecture in the same technology at the cost of an increase in total area of about 72.5%. Our results also show that the logic utilization of this work is better than that of a Virtex II/Virtex 4/Virtex 5/Virtex 6/Virtex 7 FPGA when implemented using only 4-LUT and better than that of a Virtex II/Virtex 4 FPGA when implemented using only 5-LUT.

  9. Acoustic Receptivity of Mach 4.5 Boundary Layer with Leading- Edge Bluntness

    NASA Technical Reports Server (NTRS)

    Malik, Mujeeb R.; Balakumar, Ponnampalam

    2007-01-01

    Boundary layer receptivity to two-dimensional slow and fast acoustic waves is investigated by solving Navier-Stokes equations for Mach 4.5 flow over a flat plate with a finite-thickness leading edge. Higher order spatial and temporal schemes are employed to obtain the solution whereby the flat-plate leading edge region is resolved by providing a sufficiently refined grid. The results show that the instability waves are generated in the leading edge region and that the boundary-layer is much more receptive to slow acoustic waves (by almost a factor of 20) as compared to the fast waves. Hence, this leading-edge receptivity mechanism is expected to be more relevant in the transition process for high Mach number flows where second mode instability is dominant. Computations are performed to investigate the effect of leading-edge thickness and it is found that bluntness tends to stabilize the boundary layer. Furthermore, the relative significance of fast acoustic waves is enhanced in the presence of bluntness. The effect of acoustic wave incidence angle is also studied and it is found that the receptivity of the boundary layer on the windward side (with respect to the acoustic forcing) decreases by more than a factor of 4 when the incidence angle is increased from 0 to 45 deg. However, the receptivity coefficient for the leeward side is found to vary relatively weakly with the incidence angle.

  10. Csátalja, the largest H4-5 chondrite from Hungary

    NASA Astrophysics Data System (ADS)

    Kovács, János; Sajó, István; Márton, Zsuzsanna; Jáger, Viktor; Hegedüs, Tibor; Berecz, Tibor; Tóth, Tamás; Gyenizse, Péter; Podobni, András

    2015-01-01

    We report here for the first time the composition and mineralogical studies on a new meteorite, which was found in August 2012 near the village of Csátalja, Hungary (46°0'21''N; 18°59'27'E). The Csátalja meteorite is classified as a H4-5 ordinary chondrite with shock stage S2 and a degree of weathering W1 and the total mass is 15 kg. The Csátalja meteorite is characterized by well-defined chondrules composed either of olivine or pyroxene. X-ray diffractogram shows the primary phases olivine, pyroxene, kamacite, and albite. Metal particles were extracted from the bulk powdered samples exhibit only kamacite and small amounts of the intergrowth taenite/kamacite. Raman spectra of forsterite indicate that Csátalja meteorite suffered from relatively low shock pressure regime. The texture of chondrules varies from nonporphyritic (e.g., barred olivine, radial pyroxene) to porphyritic ones (e.g., granular olivine as well as olivine pyroxene). The meteorite name has not yet approved by the Nomenclature Committee of the Meteoritical Society.

  11. Activationless charge transport across 4.5 to 22 nm in molecular electronic junctions

    PubMed Central

    Yan, Haijun; Bergren, Adam Johan; McCreery, Richard; Della Rocca, Maria Luisa; Martin, Pascal; Lafarge, Philippe; Lacroix, Jean Christophe

    2013-01-01

    In this work, we bridge the gap between short-range tunneling in molecular junctions and activated hopping in bulk organic films, and greatly extend the distance range of charge transport in molecular electronic devices. Three distinct transport mechanisms were observed for 4.5–22-nm-thick oligo(thiophene) layers between carbon contacts, with tunneling operative when d < 8 nm, activated hopping when d > 16 nm for high temperatures and low bias, and a third mechanism consistent with field-induced ionization of highest occupied molecular orbitals or interface states to generate charge carriers when d = 8–22 nm. Transport in the 8–22-nm range is weakly temperature dependent, with a field-dependent activation barrier that becomes negligible at moderate bias. We thus report here a unique, activationless transport mechanism, operative over 8–22-nm distances without involving hopping, which severely limits carrier mobility and device lifetime in organic semiconductors. Charge transport in molecular electronic junctions can thus be effective for transport distances significantly greater than the 1–5 nm associated with quantum-mechanical tunneling. PMID:23509271

  12. Activationless charge transport across 4.5 to 22 nm in molecular electronic junctions.

    PubMed

    Yan, Haijun; Bergren, Adam Johan; McCreery, Richard; Della Rocca, Maria Luisa; Martin, Pascal; Lafarge, Philippe; Lacroix, Jean Christophe

    2013-04-01

    In this work, we bridge the gap between short-range tunneling in molecular junctions and activated hopping in bulk organic films, and greatly extend the distance range of charge transport in molecular electronic devices. Three distinct transport mechanisms were observed for 4.5-22-nm-thick oligo(thiophene) layers between carbon contacts, with tunneling operative when d < 8 nm, activated hopping when d > 16 nm for high temperatures and low bias, and a third mechanism consistent with field-induced ionization of highest occupied molecular orbitals or interface states to generate charge carriers when d = 8-22 nm. Transport in the 8-22-nm range is weakly temperature dependent, with a field-dependent activation barrier that becomes negligible at moderate bias. We thus report here a unique, activationless transport mechanism, operative over 8-22-nm distances without involving hopping, which severely limits carrier mobility and device lifetime in organic semiconductors. Charge transport in molecular electronic junctions can thus be effective for transport distances significantly greater than the 1-5 nm associated with quantum-mechanical tunneling. PMID:23509271

  13. Phosphatidylinositol-4,5-Bisphosphate Enhances Anionic Lipid Demixing by the C2 Domain of PKCα

    PubMed Central

    Egea-Jiménez, Antonio L.; Fernández-Martínez, Ana M.; Pérez-Lara, Ángel; de Godos, Ana; Corbalán-García, Senena; Gómez-Fernández, Juan C.

    2014-01-01

    The C2 domain of PKCα (C2α) induces fluorescence self-quenching of NBD-PS in the presence of Ca2+, which is interpreted as the demixing of phosphatidylserine from a mixture of this phospholipid with phosphatidylcholine. Self-quenching of NBD-PS was considerably increased when phosphatidylinositol-4,5-bisphosphate (PIP2) was present in the membrane. When PIP2 was the labeled phospholipid, in the form of TopFluor-PIP2, fluorescence self-quenching induced by the C2 domain was also observed, but this was dependent on the presence of phosphatidylserine. An independent indication of the phospholipid demixing effect given by the C2α domain was obtained by using 2H-NMR, since a shift of the transition temperature of deuterated phosphatidylcholine was observed as a consequence of the addition of the C2α domain, but only in the presence of PIP2. The demixing induced by the C2α domain may have a physiological significance since it means that the binding of PKCα to membranes is accompanied by the formation of domains enriched in activating lipids, like phosphatidylserine and PIP2. The formation of these domains may enhance the activation of the enzyme when it binds to membranes containing phosphatidylserine and PIP2. PMID:24763383

  14. Novel Phosphotidylinositol 4,5-Bisphosphate Binding Sites on Focal Adhesion Kinase.

    PubMed

    Feng, Jun; Mertz, Blake

    2015-01-01

    Focal adhesion kinase (FAK) is a protein tyrosine kinase that is ubiquitously expressed, recruited to focal adhesions, and engages in a variety of cellular signaling pathways. Diverse cellular responses, such as cell migration, proliferation, and survival, are regulated by FAK. Prior to activation, FAK adopts an autoinhibited conformation in which the FERM domain binds the kinase domain, blocking access to the activation loop and substrate binding site. Activation of FAK occurs through conformational change, and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2) are known to facilitate this process. PIP2 binding alters the autoinhibited conformation of the FERM and kinase domains and subsequently exposes the activation loop to phosphorylation. However, the detailed molecular mechanism of PIP2 binding and its role in FAK activation remain unclear. In this study, we conducted coarse-grained molecular dynamics simulations to investigate the binding of FAK to PIP2. Our simulations identified novel areas of basic residues in the kinase domain of FAK that potentially undergo transient binding to PIP2 through electrostatic attractions. Our investigation provides a molecular picture of PIP2-initiated FAK activation and introduces promising new pathways for future studies of FAK regulation. PMID:26186725

  15. Future Climate Data from RCP 4.5 and Occurrence of Malaria in Korea

    PubMed Central

    Kwak, Jaewon; Noh, Huiseong; Kim, Soojun; Singh, Vijay P.; Hong, Seung Jin; Kim, Duckgil; Lee, Keonhaeng; Kang, Narae; Kim, Hung Soo

    2014-01-01

    Since its reappearance at the Military Demarcation Line in 1993, malaria has been occurring annually in Korea. Malaria is regarded as a third grade nationally notifiable disease susceptible to climate change. The objective of this study is to quantify the effect of climatic factors on the occurrence of malaria in Korea and construct a malaria occurrence model for predicting the future trend of malaria under the influence of climate change. Using data from 2001–2011, the effect of time lag between malaria occurrence and mean temperature, relative humidity and total precipitation was investigated using spectral analysis. Also, a principal component regression model was constructed, considering multicollinearity. Future climate data, generated from RCP 4.5 climate change scenario and CNCM3 climate model, was applied to the constructed regression model to simulate future malaria occurrence and analyze the trend of occurrence. Results show an increase in the occurrence of malaria and the shortening of annual time of occurrence in the future. PMID:25321875

  16. The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate

    PubMed Central

    Nilius, Bernd; Mahieu, Frank; Prenen, Jean; Janssens, Annelies; Owsianik, Grzegorz; Vennekens, Rudi; Voets, Thomas

    2006-01-01

    Transient receptor potential (TRP) channel, melastatin subfamily (TRPM)4 is a Ca2+-activated monovalent cation channel that depolarizes the plasma membrane and thereby modulates Ca2+ influx through Ca2+-permeable pathways. A typical feature of TRPM4 is its rapid desensitization to intracellular Ca2+ ([Ca2+]i). Here we show that phosphatidylinositol 4,5-biphosphate (PIP2) counteracts desensitization to [Ca2+]i in inside-out patches and rundown of TRPM4 currents in whole-cell patch-clamp experiments. PIP2 shifted the voltage dependence of TRPM4 activation towards negative potentials and increased the channel's Ca2+ sensitivity 100-fold. Conversely, activation of the phospholipase C (PLC)-coupled M1 muscarinic receptor or pharmacological depletion of cellular PIP2 potently inhibited currents through TRPM4. Neutralization of basic residues in a C-terminal pleckstrin homology (PH) domain accelerated TRPM4 current desensitization and strongly attenuated the effect of PIP2, whereas mutations to the C-terminal TRP box and TRP domain had no effect on the PIP2 sensitivity. Our data demonstrate that PIP2 is a strong positive modulator of TRPM4, and implicate the C-terminal PH domain in PIP2 action. PLC-mediated PIP2 breakdown may constitute a physiologically important brake on TRPM4 activity. PMID:16424899

  17. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels

    PubMed Central

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-01-01

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1–KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4–S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  18. Reactions of organyl and silyl alanes with 1,3,4,5,6-pentamethyl-2-aminoborazine.

    PubMed

    Fan, Maomin; Duesler, Eileen N; Nöth, Heinrich; Paine, Robert T

    2010-03-15

    The reactions of (Me(3)Si)(3)Al, Me(3)Al, Et(3)Al, and i-Bu(3)Al with 1,3,4,5,6-pentamethyl-2-aminoborazine have been examined. An amine alane adduct (Me(3)Si)(3)Al.NH(2)B(3)(Me)(2)N(3)Me(3) (1) and several elimination products [(Me(3)Si)(2)AlN(H)B(3)(Me)(2)N(3)Me(3)](2) (2), [(Me(3)SiAl)(4)(Me(3)SiN)(3)NH] (3), [Me(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (4), [Et(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (5), and [i-Bu(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (6) have been isolated. Compounds 1, 2, 4-6 have been spectroscopically characterized, and single crystal X-ray diffraction structure determinations have been completed for 1-4 and 6. The molecular chemistry provides insight into the reaction of Me(3)Al and 1,3,5-N-trimethyl-2,4,6-B-triaminoborazine that, upon pyrolysis, produces AlN/BN composite ceramic materials. PMID:20158196

  19. Absolute configuration of 2-sec-butyl-4,5-dihydrothiazole in male mouse urine.

    PubMed

    Cavaggioni, Andrea; Mucignat-Caretta, Carla; Zagotto, Giuseppe

    2003-11-01

    The absolute configuration of 2-sec-butyl-4,5-dihydrothiazole (DHT) in urine of adult male mice was determined through chiral trifluoroacetyl derivative capillary chromatography by comparing the retention time with synthetic standards. (S)-DHT was extracted from fresh urine, while neither (R)-DHT nor the racemization of (S)-DHT were detected. We can conclude that DHT in urine possesses the S configuration, although we cannot exclude a minor component in the R configuration. (S)-DHT was then characterized for binding to the complex of major urinary proteins of male mouse urine (MUP) and for a behavioral response, the competitive scent marking behavior (countermarking). The binding constant of (S)-DHT to MUP (determined by competitive displacement) was 8.2 +/- 0.6 microM (mean +/- SD) and was 10.5 +/- 0.6 microM for R-DHT, thus excluding a relevant difference in binding. (S)-DHT modified countermarking in a peculiar way. Male mice were slow in countermarking urinary spots streaked 2 days earlier and on top of which (S)-DHT was added shortly before the test. This response was not seen when adding (S)-DHT to freshly streaked urinary spots or to clean paper. Unlike (S)-DHT, (R)-DHT prompted countermarking rather than delaying it. We can further conclude that (S)-DHT in male mouse urine is an aversive chemosignal for countermarking. PMID:14654447

  20. 2-Aminoethoxydiphenyl borate, a inositol 1,4,5-triphosphate receptor inhibitor, prevents atrial fibrillation.

    PubMed

    Xiao, Junjie; Liang, Dandan; Zhao, Hong; Liu, Ying; Zhang, Hong; Lu, Xiaowei; Liu, Yi; Li, Jun; Peng, Luying; Chen, Yi-Han

    2010-07-01

    The expression of the inositol 1,4,5-triphosphate receptor (IP3R) is upregulated and the function of IP3R also increases during atrial fibrillation (AF). 2-Aminoethoxydiphenyl borate (2-APB) is a membrane-permeable inhibitor of IP3R. However, the effect of 2-APB on AF is unknown. The aim of the present study is to explore the effects of 2-APB on AF. In vitro rabbit heart models of ischemia-, stretch- and cholinergic agitation-induced AF were developed. Fura-2-acetoxymethyl (Fura-2-AM) and Mg2+-Fura-2-AM were used to monitor alterations of intracellular Ca2+ and ATP, respectively, in HL-1 cells, an atrial muscle cell line, under chemical ischemia or cholinergic agitation. The results showed that inhibition of IP3R significantly reduced the incidence and its probability of being sustained in all three types of AF. IP3R inhibition ameliorated the cytoplasmic Ca2+ overload and energy compromise resulting from chemical ischemia or cholinergic agitation. Thus, IP3R inhibition may be a novel target for AF treatment, and IP3R may be an important molecule in the context of different kinds of AF. PMID:20472714

  1. Structural and Theoretical Investigation of Anhydrous 3,4,5-Triacetoxybenzoic Acid

    PubMed Central

    Carvalho, Paulo S.; Almeida, Leonardo R.; Araújo Neto, João H.; Medina, Ana Carolina Q. D.; Menezes, Antonio C. S.; Sousa, José E. F.; Oliveira, Solemar S.; Camargo, Ademir J.; Napolitano, Hamilton B.

    2016-01-01

    A comprehensive investigation of anhydrous form of 3,4,5-Triacetoxybenzoic acid (TABA) is reported. Single crystal X-ray diffraction, Thermal analysis, Fourier Transform Infrared spectroscopy (FTIR) and DFT calculations were applied for TABA characterization. This anhydrous phase crystallizes in the triclinic P1¯ space group (Z' = 1) and its packing shows a supramolecular motif in a classical R22(4) ring formed by acid-acid groups association. The phase stability is accounted in terms of supramolecular architecture and its thermal behaviour. Conformation search at B3LYP/6-311++G(2d,p) level of theory shows the existence of three stable conformers and the most stable conformation was found experimentally. The reactivity of TABA was investigated using the molecular orbital theory and molecular electrostatic potential. The calculation results were used to simulate the infrared spectrum. There is a good agreement between calculated and experimental IR spectrum, which allowed the assignment of the normal vibrational modes PMID:27355378

  2. Preparations, structures and properties of heterobimetallic complexes based on tetrahydrofuran-2,3,4,5-tetracarboxylate

    NASA Astrophysics Data System (ADS)

    Jia, Tian-Jing; Li, Shu-Mu; Cao, Wei; Li, Li-Cun; Zheng, Xiang-Jun; Yuan, Da-Qiang

    2013-05-01

    Transition heterobimetallic metal-organic frameworks based on tetrahydrofuran-2,3,4,5-tetracarboxylicate (FTA), namely [M(H2O)6][Cu2M(FTA)2(H2O)2]·4H2O [M=Mn (1), Co (2)], and [CuZn(FTA)(H2O)5]·H2O (3) have been synthesized and characterized. Single-crystal X-ray diffraction indicates that complexes 1 and 2 are isomorphic. In 1 and 2, FTA ligand links the metal ions to a 2-D wave-like negative-charged layer with a topology of {4;62}2{4;63;82}2{6}. They possess 1-D channels with [M(H2O)6]2+ and lattice water molecules enclathrated. While in the complex 3, Cu2+ and Zn2+ ions are bridged by FTA to a 2-D neutral layer structure with a {8}2{84;122} topology. Magnetic properties of 1-3 were analyzed in connection with their structures, which show that there exist weak antiferromagnetic interactions between metal ions.

  3. Molecular Mapping of Wheat: Major Genes and Rearrangements in Homoeologous Groups 4, 5, and 7

    PubMed Central

    Nelson, J. C.; Sorrells, M. E.; Van-Deynze, A. E.; Lu, Y. H.; Atkinson, M.; Bernard, M.; Leroy, P.; Faris, J. D.; Anderson, J. A.

    1995-01-01

    A molecular-marker linkage map of hexaploid wheat (Triticum aestivum L. em. Thell) provides a framework for integration with the classical genetic map and a record of the chromosomal rearrangements involved in the evolution of this crop species. We have constructed restriction fragment length polymorphism (RFLP) maps of the A-, B-, and D-genome chromosomes of homoeologous groups 4, 5, and 7 of wheat using 114 F(7) lines from a synthetic X cultivated wheat cross and clones from 10 DNA libraries. Chromosomal breakpoints for known ancestral reciprocal translocations involving these chromosomes and for a known pericentric inversion on chromosome 4A were localized by linkage and aneuploid analysis. Known genes mapped include the major vernalization genes Vrn1 and Vrn3 on chromosome arms 5AL and 5DL, the red-coleoptile gene Rc1 on 7AS, and presumptively the leaf-rust (Puccinia recondita f.sp. tritici) resistance gene Lr34 on 7DS and the kernel-hardness gene Ha on 5DS. RFLP markers previously obtained for powdery-mildew (Blumeria graminis f.sp. tritici) resistance genes Pm2 and Pm1 were localized on chromosome arms 5DS and 7AL. PMID:8647405

  4. Investigations of shot reproducibility for the SMP diode at 4.5 MV.

    SciTech Connect

    Bennett, Nichelle; Crain, Marlon D.; Droemer, Darryl W.; Gignac, Raymond Edward; Lare, Gregory A.; Molina, Isidro; Obregon, Rafael; Smith, Chase C.; Wilkins, Frank Lee; Welch, Dale Robert; Cordova, Steve Ray; Gallegos, M.; Johnston, Mark D.; Kiefer, Mark Linden; Leckbee, Joshua J.; Nielsen, Daniel Scott; Oliver, Bryan Velten; Renk, Timothy Jerome; Romero, Tobias; Webb, Timothy Jay; Ziska, Derek Raymond

    2013-11-01

    In experiments conducted on the RITS-6 accelerator, the SMP diode exhibits sig- ni cant shot-to-shot variability. Speci cally, for identical hardware operated at the same voltage, some shots exhibit a catastrophic drop in diode impedance. A study is underway to identify sources of shot-to-shot variations which correlate with diode impedance collapse. To remove knob emission as a source, only data from a shot series conducted with a 4.5-MV peak voltage are considered. The scope of this report is limited to sources of variability which occur away from the diode, such as power ow emission and trajectory changes, variations in pulsed power, dustbin and transmission line alignment, and di erent knob shapes. We nd no changes in the transmission line hardware, alignment, or hardware preparation methods which correlate with impedance collapse. However, in classifying good versus poor shots, we nd that there is not a continuous spectrum of diode impedance behavior but that the good and poor shots can be grouped into two distinct impedance pro les. This result forms the basis of a follow-on study focusing on the variability resulting from diode physics. 3

  5. Design and Operating Features of the ITER 4.5 K Cryoplant

    SciTech Connect

    Kalinine, V.; Haange, R.; Shatil, N.; Millet, F.; Jager, B.; Briend, P.; Crispel, S.; Dauguet, P.

    2004-06-23

    The main cryogenic users of ITER are the superconducting magnet system and the cryogenic vacuum pumps. The magnet system consists of 18 toroidal field and six poloidal field coils and the central solenoid coils. The cryogenic vacuum pumps contain eight pumps for the vacuum vessel, up to four pumps for the neutral beam injectors and two for the tokamak cryostat.The paper presents the current design status of the ITER cryoplant and its operating features that allow stable and flexible operation for different plasma pulsing scenarios and transient operating modes including cool-down and coil quench. The LHe plant operates in a combined liquefaction / refrigeration mode. Liquefied helium is used for the coil current leads and for cool-down of the cryopumps after their regeneration at 80 K. The operating temperature of the LHe plant can vary in the range of 4.3 K to 4.5 K to satisfy different cooling demands of various plasma scenarios. The LHe plant is designed for a large variation ratio of refrigeration to liquefaction in order to facilitate filling of the coils with a large amount of supercritical helium after a standard cool-down or specific cool-down mode following a fast energy discharge.

  6. Inositol 1,4,5-Trisphosphate Signaling Regulates Mating Behavior in Caenorhabditis elegans MalesD⃞

    PubMed Central

    Gower, Nicholas J. D.; Walker, Denise S.; Baylis, Howard A.

    2005-01-01

    Complex behavior requires the coordinated action of the nervous system and nonneuronal targets. Male mating in Caenorhabditis elegans consists of a series of defined behavioral steps that lead to the physiological outcomes required for successful impregnation. We demonstrate that signaling mediated by inositol 1,4,5-trisphosphate (IP3) is required at several points during mating. Disruption of IP3 receptor (itr-1) function results in dramatic loss of male fertility, due to defects in turning behavior (during vulva location), spicule insertion and sperm transfer. To elucidate the signaling pathways responsible, we knocked down the six C. elegans genes encoding phospholipase C (PLC) family members. egl-8, which encodes PLC-β, functions in spicule insertion and sperm transfer. itr-1 and egl-8 are widely expressed in the male reproductive system. An itr-1 gain-of-function mutation rescues infertility caused by egl-8 RNA interference, indicating that egl-8 and itr-1 function together as central components of the signaling events controlling sperm transfer. PMID:15958491

  7. Future climate data from RCP 4.5 and occurrence of malaria in Korea.

    PubMed

    Kwak, Jaewon; Noh, Huiseong; Kim, Soojun; Singh, Vijay P; Hong, Seung Jin; Kim, Duckgil; Lee, Keonhaeng; Kang, Narae; Kim, Hung Soo

    2014-01-01

    Since its reappearance at the Military Demarcation Line in 1993, malaria has been occurring annually in Korea. Malaria is regarded as a third grade nationally notifiable disease susceptible to climate change. The objective of this study is to quantify the effect of climatic factors on the occurrence of malaria in Korea and construct a malaria occurrence model for predicting the future trend of malaria under the influence of climate change. Using data from 2001-2011, the effect of time lag between malaria occurrence and mean temperature, relative humidity and total precipitation was investigated using spectral analysis. Also, a principal component regression model was constructed, considering multicollinearity. Future climate data, generated from RCP 4.5 climate change scenario and CNCM3 climate model, was applied to the constructed regression model to simulate future malaria occurrence and analyze the trend of occurrence. Results show an increase in the occurrence of malaria and the shortening of annual time of occurrence in the future. PMID:25321875

  8. Synthesis of New Thiazolo[4,5-d]pyrimidines as Corticotropin Releasing Factor Modulators

    PubMed Central

    Kuppast, Bhimanna; Spyridaki, Katerina; Lynch, Christophina; Hu, Yueshan; Liapakis, George; Davies, Gareth E.; Fahmy, Hesham

    2015-01-01

    Corticotropin-releasing factor (CRF) is a neurohormone that plays a crucial role in integrating the body’s overall response to stress. It appears necessary and sufficient for the organism to mount functional, physiological and endocrine responses to stressors. CRF is released in response to various triggers such as chronic stress. The role of CRF and its involvement in these neurological disorders suggest that new drugs that can target the CRF function or bind to its receptors may represent a new development of neuropsychiatric medicines to treat various stress-related disorders including depression, anxiety and addictive disorders. Based on pharmacophore of the CRF1 receptor antagonists, a new series of thiazolo[4,5-d] pyrimidines were synthesized as Corticotropin-releasing factor (CRF) receptor modulators and the prepared compounds carry groups shown to produce optimum binding affinity to CRF receptors. Twenty two compounds were evaluated for their CRF1 receptor binding affinity in HEK 293 cell lines and two compounds 5o and 5s showed approximately 25% binding affinity to CRF1 receptors. Selected compounds (5c and 5f) were also evaluated for their effect on expression of genes associated with depression and anxiety disorders such as CRF1, CREB, MAO-A, SERT, NPY, DatSLC6a3, and DBH and significant upregulation of CRF1 mRNA has been observed with compound 5c. PMID:25059547

  9. Structure-based discovery of substituted 4,5'-bithiazoles as novel DNA gyrase inhibitors.

    PubMed

    Brvar, Matjaž; Perdih, Andrej; Renko, Miha; Anderluh, Gregor; Turk, Dušan; Solmajer, Tom

    2012-07-26

    Bacterial DNA gyrase is a well-established and validated target for the development of novel antibacterials. Starting from the available structural information about the binding of the natural product inhibitor, clorobiocin, we identified a novel series of 4'-methyl-N(2)-phenyl-[4,5'-bithiazole]-2,2'-diamine inhibitors of gyrase B with a low micromolar inhibitory activity by implementing a two-step structure-based design procedure. This novel class of DNA gyrase inhibitors was extensively investigated by various techniques (differential scanning fluorimetry, surface plasmon resonance, and microscale thermophoresis). The binding mode of the potent inhibitor 18 was revealed by X-ray crystallography, confirming our initial in silico binding model. Furthermore, the high resolution of the complex structure allowed for the placement of the Gly97-Ser108 flexible loop, thus revealing its role in binding of this class of compounds. The crystal structure of the complex protein G24 and inhibitor 18 provides valuable information for further optimization of this novel class of DNA gyrase B inhibitors. PMID:22731783

  10. Intracellular localization of human Ins(1,3,4,5,6)P5 2-kinase

    PubMed Central

    Brehm, Maria A.; Schenk, Tobias M. H.; Zhou, Xuefei; Fanick, Werner; Lin, Hongying; Windhorst, Sabine; Nalaskowski, Marcus M.; Kobras, Mario; Shears, Stephen B.; Mayr, Georg W.

    2007-01-01

    InsP6 is an intracellular signal with several proposed functions that is synthesized by IP5K [Ins(1,3,4,5,6)P5 2-kinase]. In the present study, we overexpressed EGFP (enhanced green fluorescent protein)–IP5K fusion proteins in NRK (normal rat kidney), COS7 and H1299 cells. The results indicate that there is spatial microheterogeneity in the intracellular localization of IP5K that could also be confirmed for the endogenous enzyme. This may facilitate changes in InsP6 levels at its sites of action. For example, overexpressed IP5K showed a structured organization within the nucleus. The kinase was preferentially localized in euchromatin and nucleoli, and co-localized with mRNA. In the cytoplasm, the overexpressed IP5K showed locally high concentrations in discrete foci. The latter were attributed to stress granules by using mRNA, PABP [poly(A)-binding protein] and TIAR (TIA-1-related protein) as markers. The incidence of stress granules, in which IP5K remained highly concentrated, was further increased by puromycin treatment. Using FRAP (fluorescence recovery after photobleaching) we established that IP5K was actively transported into the nucleus. By site-directed mutagenesis we identified a nuclear import signal and a peptide segment mediating the nuclear export of IP5K. PMID:17705785

  11. Design of a 4.5 MJ/1 MW sectored toroidal superconducting energy storage magnet

    NASA Astrophysics Data System (ADS)

    Bhunia, Uttam; Akhter, Javed; Nandi, Chinmay; Pal, Gautam; Saha, Subimal

    2014-09-01

    A 4.5 MJ/1 MW superconducting magnetic energy storage (SMES) system is being developed at VECC centre, Kolkata. The magnet system consists of the cryostat and coil assembly comprising eight superconducting solenoid coils made of custom-made NbTi based Rutherford-type cable and arranged in toroidal fashion with finite inter-sector gap. Since the strong electromagnetic force distributed to the coil is asymmetric and non-uniform in nature, a precise 3-D finite element analysis (FEA) has been carried out to design a mechanically stable coil and support structure under various operational scenarios. The results reveal that maximum stress developed on coil and its support structure is below allowable stress limit. Extensive transient analysis has also been carried out to evaluate transient loss and assess the feasibility of using helium re-condensation technology with commercially available cryo-refrigerators. Finally, quench protection scenario has also been discussed suitable for this toroidal-type SMES system. The article investigates the design concept of the cryostat and coil assembly.

  12. Performance appraisal of VAS radiometry for GOES-4, -5 and -6

    NASA Technical Reports Server (NTRS)

    Chesters, D.; Robinson, W. D.

    1983-01-01

    The first three VISSR Atmospheric Sounders (VAS) were launched on GOES-4, -5, and -6 in 1980, 1981 and 1983. Postlaunch radiometric performance is assessed for noise, biases, registration and reliability, with special attention to calibration and problems in the data processing chain. The postlaunch performance of the VAS radiometer meets its prelaunch design specifications, particularly those related to image formation and noise reduction. The best instrument is carried on GOES-5, currently operational as GOES-EAST. Single sample noise is lower than expected, especially for the small longwave and large shortwave detectors. Detector to detector offsets are correctable to within the resolution limits of the instrument. Truncation, zero point and droop errors are insignificant. Absolute calibration errors, estimated from HIRS and from radiation transfer calculations, indicate moderate, but stable biases. Relative calibration errors from scanline to scanline are noticeable, but meet sounding requirements for temporarily and spatially averaged sounding fields of view. The VAS instrument is a potentially useful radiometer for mesoscale sounding operations. Image quality is very good. Soundings derived from quality controlled data meet prelaunch requirements when calculated with noise and bias resistant algorithms.

  13. Phosphatidylinositol 4,5-bisphosphate (PIP2) controls magnesium gatekeeper TRPM6 activity

    PubMed Central

    Xie, Jia; Sun, Baonan; Du, Jianyang; Yang, Wenzhong; Chen, Hsiang-Chin; Overton, Jeffrey D.; Runnels, Loren W.; Yue, Lixia

    2011-01-01

    TRPM6 is crucial for human Mg2+ homeostasis as patients carrying TRPM6 mutations develop hypomagnesemia and secondary hypocalcemia (HSH). However, the activation mechanism of TRPM6 has remained unknown. Here we demonstrate that phosphatidylinositol-4,5-bisphophate (PIP2) controls TRPM6 activation and Mg2+ influx. Stimulation of PLC-coupled M1-receptors to deplete PIP2 potently inactivates TRPM6. Translocation of over-expressed 5-phosphatase to cell membrane to specifically hydrolyze PIP2 also completely inhibits TRPM6. Moreover, depolarization-induced-activation of the voltage-sensitive-phosphatase (Ci-VSP) simultaneously depletes PIP2 and inhibits TRPM6. PLC-activation induced PIP2-depletion not only inhibits TRPM6, but also abolishes TRPM6-mediated Mg2+ influx. Furthermore, neutralization of basic residues in the TRP domain leads to nonfunctional or dysfunctional mutants with reduced activity by PIP2, suggesting that they are likely to participate in interactions with PIP2. Our data indicate that PIP2 is required for TRPM6 channel function; hydrolysis of PIP2 by PLC-coupled hormones/agonists may constitute an important pathway for TRPM6 gating, and perhaps Mg2+ homeostasis. PMID:22180838

  14. Reactivity and synthetic applications of 4,5-dicyanopyridazine: an overview.

    PubMed

    Alfini, Renzo; Cecchi, Marco; Giomi, Donatella

    2010-03-01

    Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA) reactions, 4,5-dicyanopyridazine (DCP) showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2p electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systemsthrough pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles. In addition an unprecedented reactivity of DCP as a very reactive heterocyclic electrophile at the C-4 carbon was also evidenced: by changing the experimental conditions, cyanopyrrolyl- and cyanoindolyl-pyridazines were obtained through reactions of pyrrole and indole systems as carbon nucleophiles in formal SNAr2 processes where a CN group of DCP acts as leaving group. Thus, careful control of the reaction conditions allows exploitation of both pathways for the synthesis of different classes of heterocyclic derivatives. PMID:20336010

  15. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels.

    PubMed

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-05-21

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1-KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4-S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  16. Phosphatidylinositol 4,5-bisphosphate Directs Spermatid Cell Polarity and Exocyst Localization in Drosophila

    PubMed Central

    Fabian, Lacramioara; Wei, Ho-Chun; Rollins, Janet; Noguchi, Tatsuhiko; Blankenship, J. Todd; Bellamkonda, Kishan; Polevoy, Gordon; Gervais, Louis; Guichet, Antoine; Fuller, Margaret T.

    2010-01-01

    During spermiogenesis, Drosophila melanogaster spermatids coordinate their elongation in interconnected cysts that become highly polarized, with nuclei localizing to one end and sperm tail growth occurring at the other. Remarkably little is known about the signals that drive spermatid polarity and elongation. Here we identify phosphoinositides as critical regulators of these processes. Reduction of plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) by low-level expression of the PIP2 phosphatase SigD or mutation of the PIP2 biosynthetic enzyme Skittles (Sktl) results in dramatic defects in spermatid cysts, which become bipolar and fail to fully elongate. Defects in polarity are evident from the earliest stages of elongation, indicating that phosphoinositides are required for establishment of polarity. Sktl and PIP2 localize to the growing end of the cysts together with the exocyst complex. Strikingly, the exocyst becomes completely delocalized when PIP2 levels are reduced, and overexpression of Sktl restores exocyst localization and spermatid cyst polarity. Moreover, the exocyst is required for polarity, as partial loss of function of the exocyst subunit Sec8 results in bipolar cysts. Our data are consistent with a mechanism in which localized synthesis of PIP2 recruits the exocyst to promote targeted membrane delivery and polarization of the elongating cysts. PMID:20237161

  17. Dislocation distributions in an Al-4. 5% Mg alloy during superplastic deformation

    SciTech Connect

    Li, F.; Roberts, W.T.; Bate, P.S. . IRC in Materials for High Performance Applications)

    1993-10-01

    Superplasticity has been studied actively for several decades. Many models of the phenomenon have been proposed, in most of which normal dislocation glide has either not been considered or been considered only as an accommodation process to maintain continuity during grain boundary sliding. Although evidence of dislocation activity during superplastic deformation has been observed several times by TEM studies following deformation, the published results appear to be inconsistent and occasionally contradict themselves, and so are unable to provide systematic and convincing evidence for the development of any theoretical model. A major experimental problem associated with those results is the delay between unloading and quenching the specimens from the high testing temperatures. Dislocations can be lost by relaxation and annealing during the unloading and also during the preparation of TEM thin foils. A facility was developed to preserve the high temperature deformation microstructure for consequent TEM examination by quenching and aging under constant stress. This technique and some preliminary results are given elsewhere. The work presented here is from a more comprehensive TEM study of the dislocation distributions in an Al-4.5%Mg alloy developed during deformation at an elevated temperature and a range of strain rates.

  18. Superplasticity and the development of dislocation structures in an Al-4.5% Mg alloy

    SciTech Connect

    Li, F.; Roberts, W.T.; Bate, P.S.

    1996-01-01

    The mechanical behavior and development of microstructure in tension of an Al-4.5% Mg alloy at temperatures from 450 to 570C and strain rates from 10{sup {minus}6} to 10{sup {minus}2} s{sup {minus}1} has been investigated. High strain rate sensitivities, up to m = 0.7, but relatively small elongations, between 120 and 280%, were observed. A single activation energy for deformation, close to reported values for self diffusion in aluminium, was obtained over the temperature and strain rate range used, and the strain rate and stress could be related using a hyperbolic sine function at constant strain. Tensile specimens were quenched and aged under stress to preserve the dislocation structures for examination by transmission electron microscopy. The dislocation structures observed showed a gradual and systematic change between regimes of power law creep at higher strain rates and diffusional creep at lower strain rates, and in the superplastic regime there was a tendency for small grains to be free of dislocations. Many of the dislocations had Burgers vectors inclined at about 45{degree} to the stress axis, which suggests that they were active directly in response to the applied stress rather than as the result of a relaxation process accommodating grain boundary sliding.

  19. Performance appraisal of VAS radiometry for GOES-4, -5 and -6

    NASA Astrophysics Data System (ADS)

    Chesters, D.; Robinson, W. D.

    1983-12-01

    The first three VISSR Atmospheric Sounders (VAS) were launched on GOES-4, -5, and -6 in 1980, 1981 and 1983. Postlaunch radiometric performance is assessed for noise, biases, registration and reliability, with special attention to calibration and problems in the data processing chain. The postlaunch performance of the VAS radiometer meets its prelaunch design specifications, particularly those related to image formation and noise reduction. The best instrument is carried on GOES-5, currently operational as GOES-EAST. Single sample noise is lower than expected, especially for the small longwave and large shortwave detectors. Detector to detector offsets are correctable to within the resolution limits of the instrument. Truncation, zero point and droop errors are insignificant. Absolute calibration errors, estimated from HIRS and from radiation transfer calculations, indicate moderate, but stable biases. Relative calibration errors from scanline to scanline are noticeable, but meet sounding requirements for temporarily and spatially averaged sounding fields of view. The VAS instrument is a potentially useful radiometer for mesoscale sounding operations. Image quality is very good. Soundings derived from quality controlled data meet prelaunch requirements when calculated with noise and bias resistant algorithms.

  20. Dual Effect of Phosphatidyl (4,5)-Bisphosphate PIP2 on Shaker K+ Channels*

    PubMed Central

    Abderemane-Ali, Fayal; Es-Salah-Lamoureux, Zeineb; Delemotte, Lucie; Kasimova, Marina A.; Labro, Alain J.; Snyders, Dirk J.; Fedida, David; Tarek, Mounir; Baró, Isabelle; Loussouarn, Gildas

    2012-01-01

    Phosphatidylinositol (4,5)-bisphosphate (PIP2) is a phospholipid of the plasma membrane that has been shown to be a key regulator of several ion channels. Functional studies and more recently structural studies of Kir channels have revealed the major impact of PIP2 on the open state stabilization. A similar effect of PIP2 on the delayed rectifiers Kv7.1 and Kv11.1, two voltage-gated K+ channels, has been suggested, but the molecular mechanism remains elusive and nothing is known on PIP2 effect on other Kv such as those of the Shaker family. By combining giant-patch ionic and gating current recordings in COS-7 cells, and voltage-clamp fluorimetry in Xenopus oocytes, both heterologously expressing the voltage-dependent Shaker channel, we show that PIP2 exerts 1) a gain-of-function effect on the maximal current amplitude, consistent with a stabilization of the open state and 2) a loss-of-function effect by positive-shifting the activation voltage dependence, most likely through a direct effect on the voltage sensor movement, as illustrated by molecular dynamics simulations. PMID:22932893

  1. Synthesis of new thiazolo[4,5-d]pyrimidines as Corticotropin releasing factor modulators.

    PubMed

    Kuppast, Bhimanna; Spyridaki, Katerina; Lynch, Christophina; Hu, Yueshan; Liapakis, George; Davies, Gareth E; Fahmy, Hesham

    2014-01-01

    Corticotropin-releasing factor (CRF) is a neurohormone that plays a crucial role in integrating the body's overall response to stress. It appears necessary and sufficient for the organism to mount functional, physiological and endocrine responses to stressors. CRF is released in response to various triggers such as chronic stress. The role of CRF and its involvement in these neurological disorders suggest that new drugs that can target the CRF function or bind to its receptors may represent a new development of neuropsychiatric medicines to treat various stress-related disorders including depression, anxiety and addictive disorders. Based on pharmacophore of the CRF1 receptor antagonists, a new series of thiazolo[4,5-d] pyrimidines were synthesized as Corticotropin-releasing factor (CRF) receptor modulators and the prepared compounds carry groups shown to produce optimum binding affinity to CRF receptors. Twenty two compounds were evaluated for their CRF1 receptor binding affinity in HEK 293 cell lines and two compounds 5o and 5s showed approximately 25% binding affinity to CRF1 receptors. Selected compounds (5c and 5f) were also evaluated for their effect on expression of genes associated with depression and anxiety disorders such as CRF1, CREB1, MAO-A, SERT, NPY, DatSLC6a3, and DBH and significant upregulation of CRF1 mRNA has been observed with compound 5c. PMID:25059547

  2. Phosphatidylinositol 4,5-bisphosphate phospholipase C and phosphomonoesterase in Dunaliella salina membranes

    SciTech Connect

    Einspahr, K.J.; Peeler, T.C.; Thompson, G.A. Jr. )

    1989-07-01

    In comparison with other cell organelles, the Dunaliella salina plasma membrane was found to be highly enriched in phospholipase C activity toward exogenous ({sup 3}H)phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}). Based on release of ({sup 3}H)inositol phosphates, the plasma membrane exhibited a PIP{sub 2}-phospholipase C activity nearly tenfold higher than the nonplasmalemmal, nonchloroplast bottom phase (BP) membrane fraction and 47 times higher than the chloroplast membrane fraction. The majority of phospholipase activity was clearly of a phospholipase C nature since over 80% of ({sup 3}H)inositol phosphates released were recovered as ({sup 3}H)inositol trisphosphate (IP{sub 3}). These results suggest a plausible mechanism for the rapid breakdown of PIP{sub 2} and phosphatidylinositol 4-phosphate (PIP) following hypoosmotic shock. The authors have also examined some of the in vitro characteristics of the plasma membrane phospholipase C activity and have found it to be calcium sensitive, reaching maximal activity at 10 micromolar free (Ca{sup 2+}). They also report here that 100 micromolar GTP{gamma}S stimulates phospholipase C activity over a range of free (Ca{sup 2+}). Together, these results provide evidence that the plasma membrane PIP{sub 2}-phospholipase C of D. salina may be subject to Ca{sup 2+} and G-protein regulation.

  3. Cloning and expression of a cDNA encoding human inositol 1,4,5-trisphosphate 3-kinase C.

    PubMed Central

    Dewaste, V; Pouillon, V; Moreau, C; Shears, S; Takazawa, K; Erneux, C

    2000-01-01

    Inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase catalyses the phosphorylation of Ins(1,4,5)P(3) to Ins(1,3,4,5)P(4). cDNAs encoding two isoenzymes of Ins(1,4,5)P(3) 3-kinase (3-kinases A and B) have been described previously. In the present study, we report the cloning of a full-length 2052 bp cDNA encoding a third human isoenzyme of the Ins(1,4,5)P(3) 3-kinase family, referred to as isoform C. This novel enzyme has a calculated molecular mass of 75. 207 kDa and a K(m) for Ins(1,4,5)P(3) of 6 microM. Northern-blot analysis showed the presence of a transcript of approx. 3.9 kb in various human tissues. Inositol trisphosphate 3-kinase C demonstrates enzymic activity when expressed in DH5alphaF' bacteria or COS-7 cells. Calcium alone decreases the Ins(1,4,5)P(3) 3-kinase activity of the 3-kinase C isoenzyme in transfected COS-7 cells. This inhibitory effect is reversed in the presence of calmodulin. The recombinant bacterial 3-kinase C can be adsorbed on calmodulin-Sepharose in the presence of calcium. The present data show that Ins(1,4,5)P(3) 3-kinase C: (i) shares a conserved catalytic domain of about 275 amino acids with the two other mammalian isoforms, (ii) could be purified on a calmodulin-Sepharose column and (iii) could be distinguished from the A and B isoenzymes by the effects of calcium and of calmodulin. PMID:11085927

  4. Atomic research

    NASA Technical Reports Server (NTRS)

    Hadaway, James B.; Connatser, Robert; Cothren, Bobby; Johnson, R. B.

    1993-01-01

    Work performed by the University of Alabama in Huntsville's (UAH) Center for Applied Optics (CAO) entitled Atomic Research is documented. Atomic oxygen (AO) effects on materials have long been a critical concern in designing spacecraft to withstand exposure to the Low Earth Orbit (LEO) environment. The objective of this research effort was to provide technical expertise in the design of instrumentation and experimental techniques for analyzing materials exposed to atomic oxygen in accelerated testing at NASA/MSFC. Such testing was required to answer fundamental questions concerning Space Station Freedom (SSF) candidate materials and materials exposed to atomic oxygen aboard the Long-Duration Exposure Facility (LDEF). The primary UAH task was to provide technical design, review, and analysis to MSFC in the development of a state-of-the-art 5eV atomic oxygen beam facility required to simulate the RAM-induced low earth orbit (LEO) AO environment. This development was to be accomplished primarily at NASA/MSFC. In support of this task, contamination effects and ultraviolet (UV) simulation testing was also to be carried out using NASA/MSFC facilities. Any materials analysis of LDEF samples was to be accomplished at UAH.

  5. Actuated atomizer

    NASA Technical Reports Server (NTRS)

    Tilton, Charles (Inventor); Weiler, Jeff (Inventor); Palmer, Randall (Inventor); Appel, Philip (Inventor)

    2008-01-01

    An actuated atomizer is adapted for spray cooling or other applications wherein a well-developed, homogeneous and generally conical spray mist is required. The actuated atomizer includes an outer shell formed by an inner ring; an outer ring; an actuator insert and a cap. A nozzle framework is positioned within the actuator insert. A base of the nozzle framework defines swirl inlets, a swirl chamber and a swirl chamber. A nozzle insert defines a center inlet and feed ports. A spool is positioned within the coil housing, and carries the coil windings having a number of turns calculated to result in a magnetic field of sufficient strength to overcome the bias of the spring. A plunger moves in response to the magnetic field of the windings. A stop prevents the pintle from being withdrawn excessively. A pintle, positioned by the plunger, moves between first and second positions. In the first position, the head of the pintle blocks the discharge passage of the nozzle framework, thereby preventing the atomizer from discharging fluid. In the second position, the pintle is withdrawn from the swirl chamber, allowing the atomizer to release atomized fluid. A spring biases the pintle to block the discharge passage. The strength of the spring is overcome, however, by the magnetic field created by the windings positioned on the spool, which withdraws the plunger into the spool and further compresses the spring.

  6. Characteristics of Salmonella enterica Serovar 4,[5],12:i:- as a Monophasic Variant of Serovar Typhimurium

    PubMed Central

    Ido, Noriko; Lee, Ken-ichi; Iwabuchi, Kaori; Izumiya, Hidemasa; Uchida, Ikuo; Kusumoto, Masahiro; Iwata, Taketoshi; Ohnishi, Makoto; Akiba, Masato

    2014-01-01

    Salmonella enterica subspecies enterica serovar 4,[5],12:i:- (S. 4,[5]12:i:-) is believed to be a monophasic variant of S. enterica serovar Typhimurium (S. Typhimurium). This study was conducted to corroborate this hypothesis and to identify the molecular and phenotypic characteristics of the S. 4,[5]12:i:- isolates in Japan. A total of 51 S. 4,[5]12:i:- isolates derived from humans, cattle, swine, chickens, birds, meat (pork), and river water in 15 prefectures in Japan between 2000 and 2010 were analyzed. All the S. 4,[5],12:i:- isolates were identified as S. Typhimurium by two different polymerase chain reactions (PCR) for identification of S. Typhimurium. Of the 51 S. 4,[5],12:i:- isolates, 39 (76.5%) harbored a 94-kb virulence plasmid, which is known to be specific for S. Typhimurium. These data suggest that the S. 4,[5],12:i:- isolates are monophasic variants of S. Typhimurium. The flagellar phase variation is induced by three adjacent genes (fljA, fljB, and hin) in the chromosome. The results of PCR mapping of this region and comparative genomic hybridization analysis suggested that the deletion of the fljAB operon and its flanking region was the major genetic basis of the monophasic phenotype of S. 4,[5],12:i:-. The fljAB operon and hin gene were detectable in eight of the S. 4,[5],12:i:- isolates with common amino acid substitutions of A46T in FljA and R140L in Hin. The introduction of these mutations into S. Typhimurium isolates led to the loss of selectability of isolates expressing the phase 2 H antigen. These data suggested that a point mutation was the genetic basis, at least in part, of the S. 4,[5],12:i:- isolates. The results of phenotypic analysis suggested that the S. 4,[5],12:i:- isolates in Japan consist of multiple distinct clones. This is the first detailed characterization of the S. 4,[5],12:i:- isolates derived from various sources across Japan. PMID:25093666

  7. Pedestrian Deaths in U.S. Projected to Jump 10 Percent

    MedlinePlus

    ... now account for 15 percent of all motor vehicle crash-related deaths, compared with 11 percent a ... as vulnerable when they're hit by a vehicle, the researchers pointed out. SOURCE: Governors Highway Safety ...

  8. Just 6 Percent of Chest Pain Cases in ER Are Life-Threatening

    MedlinePlus

    ... Percent of Chest Pain Cases in ER Are Life-Threatening: Study Muscle strains, anxiety, gastrointestinal issues often ... than 6 percent of these patients suffer from life-threatening conditions such as a heart attack. Most ...

  9. High-performance hybrid buffer layer using 1,4,5,8,9,11-hexaazatriphenylenehexacarbonitrile/molybdenum oxide in inverted top-emitting organic light-emitting diodes.

    PubMed

    Park, Cheol Hwee; Lee, Hyun Jun; Hwang, Ju Hyun; Kim, Kyu Nyun; Shim, Yong Sub; Jung, Sun-Gyu; Park, Chan Hyuk; Park, Young Wook; Ju, Byeong-Kwon

    2015-03-25

    A high-performance 1,4,5,8,9,11-hexaazatriphenylenehexacarbonitrile (HATCN)/molybdenum oxide (MoO3) hybrid buffer layer with high hole-injection efficiency and superior plasma resistance under the sputtering process was developed. The HATCN enhances the hole-injection efficiency, and the MoO3 effectively protects the underlying organic layers from plasma damage during deposition by sputtering. This improves the characteristics of inverted top-emitting organic light-emitting diodes using a top transparent conductive oxide electrode. The device using the hybrid buffer layer showed the highest electroluminescence characteristics among devices with other buffer layers. The high hole-injection efficiency of HATCN was shown by the J-F curve of hole-only devices, and the plasma protection performance of MoO3 was shown by atomic force microscope surface morphology images of the buffer layer film after O2 plasma treatment. PMID:25761363

  10. Synthesis, characterization and intramolecular proton transfer of 3,3";-dihydroxy-4,4";-[5-methyl-1,3-phenylenebis(nitrilomethylidyne)]-bis-phenol

    NASA Astrophysics Data System (ADS)

    Eshtiagh-Hosseini, Hossein; Beyramabadi, S. Ali; Morsali, Ali; Mirzaei, Masoud; Chegini, Hamed; Elahi, Morteza; Naseri, Mohammad Ali

    2014-08-01

    A newly synthesized Schiff base, 3,3";-dihydroxy-4,4";-[5-methyl-1,3-phenylenebis(nitrilomethylidyne)]-bis-phenol, was characterized experimentally. Its geometries optimization, tautomerization, assignment of the IR bands and NMR chemical shifts were calculated by using density functional theory (DFT) method. In addition, the atoms in molecules (AIM) analysis was employed for investigation of its tautomerization. Four possible tautomers of the investigated Schiff base were optimized in both of the gas and solution phases. The Schiff base has no planar structure, but each of the benzene rings is in a separate plane. In the most stable tautomer, the phenolic protons of the two sbnd OH groups are engaged in the intramolecular-hydrogen bond with the azomethine nitrogens. Good consistency between the theoretical and experimental results confirms validity of the optimized geometry. Also, kinetics and mechanism of the intramolecular-proton transfer of the studied Schiff base was demonstrated theoretically.

  11. Atom Interferometry

    SciTech Connect

    Kasevich, Mark

    2008-05-08

    Atom de Broglie wave interferometry has emerged as a tool capable of addressing a diverse set of questions in gravitational and condensed matter physics, and as an enabling technology for advanced sensors in geodesy and navigation. This talk will review basic principles, then discuss recent applications and future directions. Scientific applications to be discussed include measurement of G (Newton's constant), tests of the Equivalence Principle and post-Newtonian gravity, and study of the Kosterlitz-Thouless phase transition in layered superfluids. Technology applications include development of precision gyroscopes and gravity gradiometers. The talk will conclude with speculative remarks looking to the future: Can atom interference methods be used to detect gravity waves? Can non-classical (entangled/squeezed state) atom sources lead to meaningful sensor performance improvements?

  12. Atom Interferometry

    SciTech Connect

    Mark Kasevich

    2008-05-07

    Atom de Broglie wave interferometry has emerged as a tool capable of addressing a diverse set of questions in gravitational and condensed matter physics, and as an enabling technology for advanced sensors in geodesy and navigation. This talk will review basic principles, then discuss recent applications and future directions. Scientific applications to be discussed include measurement of G (Newton’s constant), tests of the Equivalence Principle and post-Newtonian gravity, and study of the Kosterlitz-Thouless phase transition in layered superfluids. Technology applications include development of precision gryoscopes and gravity gradiometers. The talk will conclude with speculative remarks looking to the future: Can atom interference methods be sued to detect gravity waves? Can non-classical (entangled/squeezed state) atom sources lead to meaningful sensor performance improvements?

  13. Atom Interferometry

    ScienceCinema

    Mark Kasevich

    2010-01-08

    Atom de Broglie wave interferometry has emerged as a tool capable of addressing a diverse set of questions in gravitational and condensed matter physics, and as an enabling technology for advanced sensors in geodesy and navigation. This talk will review basic principles, then discuss recent applications and future directions. Scientific applications to be discussed include measurement of G (Newton?s constant), tests of the Equivalence Principle and post-Newtonian gravity, and study of the Kosterlitz-Thouless phase transition in layered superfluids. Technology applications include development of precision gryoscopes and gravity gradiometers. The talk will conclude with speculative remarks looking to the future: Can atom interference methods be sued to detect gravity waves? Can non-classical (entangled/squeezed state) atom sources lead to meaningful sensor performance improvements?

  14. Interconversion of inositol (1,4,5)-trisphosphate to inositol (1,3,4,5)-tetrakisphosphate and (1,3,4)-trisphosphate in permeabilized adrenal glomerulosa cells is calcium-sensitive and ATP-dependent

    SciTech Connect

    Rossier, M.F.; Dentand, I.A.; Lew, P.D.; Capponi, A.M.; Vallotton, M.B.

    1986-08-29

    The metabolism of (/sub 3/H)inositol (1,4,5)-trisphosphate was followed in permeabilized bovine adrenal glomerulosa cells. At low Ca++ concentration (pCa = 7.2), more than 90% of (/sub 3/H)inositol (1,4,5)-trisphosphate had disappeared within 2 min, while two other metabolites, (/sub 3/H)inositol (1,3,4)-trisphosphate and (/sub 3/H)inositol (1,3,4,5)-tetrakisphosphate appeared progressively. At higher Ca++ concentrations (pCa = 5.7 and 4.8), the formation of these two metabolites was markedly increased, but completely abolished if the medium was ATP-depleted. The peak levels for the generation of (/sub 3/H)inositol (1,3,4,5)-tetrakisphosphate (1 min) preceded those of (3H)inositol (1,3,4)-trisphosphate and were closely correlated. These results suggest that, in adrenal glomerulosa cells, the isomer inositol (1,3,4)-trisphosphate is generated from inositol (1,4,5)-trisphosphate via a calcium-sensitive and ATP-dependent phosphorylation/dephosphorylation pathway involving the formation of inositol (1,3,4,5)-tetrakisphosphate.

  15. Synthesis, preclinical evaluation and antidepressant activity of 5-substituted phenyl-3-(thiophen-2-yl)-4, 5-dihydro-1H-pyrazole-1-carbothioamides

    PubMed Central

    Mathew, Bijo; Suresh, Jerad; Anbazhagan, S.

    2014-01-01

    A series of phenyl-3-(thiophen-2-yl)-4, 5-dihydro-1H-pyrazole-1-carbothioamides (TTa-TTg) were synthesized by the ring closure reaction of phenyl-1-(thiophen-2-yl) prop-2-en-1-ones with thiosemicarbazide in alcoholic basic medium. All the final derivatives were evaluated for their antidepressant and neurotoxicity screening. The structures of the compounds were characterized by IR, 1H NMR, 13C NMR, Mass and elemental analyses. Preclinical evaluation of the compounds were ascertained by in silico toxicity, blood-brain barrier and human oral absorption prediction. In this series, 5-(4-hydroxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1 carbothioamide (TTg) reduced immobility time 61.17 and 62.05 % in both force swimming and tail suspension test respectively at 10 mg/kg dose level when compared to the standard Imipramine without influencing the baseline locomotion. Moreover it was observed that the titled scaffold possessing electron withdrawing chlorine atom in the 4th position of aromatic ring of the scaffold also showed good the antidepressant activity. In conclusion, the behavioural investigation revealed that thiophene based pyrazolines having a carbothioamide tail unit in the N1 position may be therapeutically useful as potential antidepressant medications. PMID:26417270

  16. Investigation of Effectiveness of a Wing Equipped with a 50-percent-chord Sliding Flap, a 30-percent-chord Slotted Flap, and a 30-percent-chord Slat in Deflecting Propeller Slipstreams Downward for Vertical Take-off

    NASA Technical Reports Server (NTRS)

    Kuhn, Richard E

    1957-01-01

    Results are presented of an investigation of the effectiveness of a wing equipped with a 50-percent-chord sliding flap and a 30-percent-chord slotted flap in deflecting a propeller slipstream downward for vertical take-off. Tests were conducted at zero forward speed in a large room and included the effects of flap deflection, proximity to the ground, a leading-edge slat, and end plates. A turning angle of about 70 degrees and a resultant force of about 100 percent of the thrust were achieved near the ground. Out of the ground-effect region, the turning angle was also about 70 degrees but the resultant force was reduced to about 86 percent of the thrust.

  17. 30 CFR 57.22236 - Actions at 1.0 percent methane (VI mines).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 1.0 percent methane (VI mines). 57.22236 Section 57.22236 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... percent methane (VI mines). If methane reaches 1.0 percent in the mine atmosphere, all persons other...

  18. 30 CFR 57.22236 - Actions at 1.0 percent methane (VI mines).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Actions at 1.0 percent methane (VI mines). 57.22236 Section 57.22236 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... percent methane (VI mines). If methane reaches 1.0 percent in the mine atmosphere, all persons other...

  19. 30 CFR 57.22236 - Actions at 1.0 percent methane (VI mines).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Actions at 1.0 percent methane (VI mines). 57.22236 Section 57.22236 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... percent methane (VI mines). If methane reaches 1.0 percent in the mine atmosphere, all persons other...

  20. 30 CFR 57.22236 - Actions at 1.0 percent methane (VI mines).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Actions at 1.0 percent methane (VI mines). 57.22236 Section 57.22236 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... percent methane (VI mines). If methane reaches 1.0 percent in the mine atmosphere, all persons other...

  1. 12 CFR 741.4 - Insurance premium and one percent deposit.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Insurance premium and one percent deposit. 741... Insurance premium and one percent deposit. (a) Scope. This section implements the requirements of Section... a deposit by each insured credit union in an amount equaling one percent of its insured shares...

  2. 49 CFR 173.182 - Barium azide-50 percent or more water wet.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Barium azide-50 percent or more water wet. 173.182 Section 173.182 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... Class 1 and Class 7 § 173.182 Barium azide—50 percent or more water wet. Barium azide—50 percent or...

  3. 49 CFR 173.182 - Barium azide-50 percent or more water wet.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Barium azide-50 percent or more water wet. 173.182 Section 173.182 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... Class 1 and Class 7 § 173.182 Barium azide—50 percent or more water wet. Barium azide—50 percent or...

  4. 49 CFR 173.182 - Barium azide-50 percent or more water wet.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Barium azide-50 percent or more water wet. 173.182 Section 173.182 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... Class 1 and Class 7 § 173.182 Barium azide—50 percent or more water wet. Barium azide—50 percent or...

  5. 49 CFR 173.182 - Barium azide-50 percent or more water wet.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Barium azide-50 percent or more water wet. 173.182 Section 173.182 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... Class 1 and Class 7 § 173.182 Barium azide—50 percent or more water wet. Barium azide—50 percent or...

  6. 49 CFR 173.182 - Barium azide-50 percent or more water wet.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Barium azide-50 percent or more water wet. 173.182 Section 173.182 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS... Class 1 and Class 7 § 173.182 Barium azide—50 percent or more water wet. Barium azide—50 percent or...

  7. 30 CFR 57.22236 - Actions at 1.0 percent methane (VI mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 1.0 percent methane (VI mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22236 Actions at 1.0 percent methane (VI mines). If methane reaches 1.0 percent in the mine atmosphere, all persons other...

  8. 30 CFR 57.22233 - Actions at 0.5 percent methane (I-C mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.5 percent methane (I-C mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22233 Actions at 0.5 percent methane (I-C mines). If methane reaches 0.5 percent in the mine atmosphere, ventilation...

  9. 30 CFR 57.22239 - Actions at 2.0 percent methane (IV mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 2.0 percent methane (IV mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22239 Actions at 2.0 percent methane (IV mines). If methane reaches 2.0 percent in the mine atmosphere, all persons other...

  10. Structural, photophysical and magnetic properties of transition metal complexes based on the dipicolylamino-chloro-1,2,4,5-tetrazine ligand.

    PubMed

    Nazarenko, Iuliia; Pop, Flavia; Sun, Qinchao; Hauser, Andreas; Lloret, Francesc; Julve, Miguel; El-Ghayoury, Abdelkrim; Avarvari, Narcis

    2015-05-21

    The ligand 3-chloro-6-dipicolylamino-1,2,4,5-tetrazine (Cl-TTZ-dipica) , prepared by the direct reaction between 3,6-dichloro-1,2,4,5-tetrazine and di(2-picolyl)-amine, afforded a series of four neutral transition metal complexes formulated as [Cl-TTZ-dipica-MCl2]2, with M = Zn(II), Cd(II), Mn(II) and Co(II), when reacted with the corresponding metal chlorides. The dinuclear structure of the isostructural complexes was disclosed by single crystal X-ray analysis, clearly indicating the formation of [M(II)-(μ-Cl)2M(II)] motifs and the involvement of the amino nitrogen atom in semi-coordination with the metal centers, thus leading to distorted octahedral coordination geometries. Moreover, the chlorine atoms, either coordinated to the metal or as a substituent on the tetrazine ring, engage respectively in specific anion-π intramolecular and intermolecular interactions with the electron-poor tetrazine units in the solid state, thus controlling the supramolecular architecture. Modulation of the emission properties is observed in the case of the Zn(II) and Cd(II) complexes when compared to the free ligand. A striking difference is observed in the magnetic properties of the Mn(II) and Co(II) complexes. An antiferromagnetic coupling takes place in the dimanganese(II) compound (J = -1.25 cm(-1)) while the Co(II) centers are ferromagnetically coupled in the corresponding complex (J = +0.55 cm(-1)), the spin Hamiltonian being defined as H = -JSA·SB. PMID:25868861

  11. Role of Phosphatidylinositol 4,5-Bisphosphate in Regulating EHD2 Plasma Membrane Localization

    PubMed Central

    Simone, Laura C.; Caplan, Steve; Naslavsky, Naava

    2013-01-01

    The four mammalian C-terminal Eps15 homology domain-containing proteins (EHD1-EHD4) play pivotal roles in endocytic membrane trafficking. While EHD1, EHD3 and EHD4 associate with intracellular tubular/vesicular membranes, EHD2 localizes to the inner leaflet of the plasma membrane. Currently, little is known about the regulation of EHD2. Thus, we sought to define the factors responsible for EHD2’s association with the plasma membrane. The subcellular localization of endogenous EHD2 was examined in HeLa cells using confocal microscopy. Although EHD partner proteins typically mediate EHD membrane recruitment, EHD2 was targeted to the plasma membrane independent of two well-characterized binding proteins, syndapin2 and EHBP1. Additionally, the EH domain of EHD2, which facilitates canonical EHD protein interactions, was not required to direct overexpressed EHD2 to the cell surface. On the other hand, several lines of evidence indicate that the plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) plays a crucial role in regulating EHD2 subcellular localization. Pharmacologic perturbation of PIP2 metabolism altered PIP2 plasma membrane distribution (as assessed by confocal microscopy), and caused EHD2 to redistribute away from the plasma membrane. Furthermore, overexpressed EHD2 localized to PIP2-enriched vacuoles generated by active Arf6. Finally, we show that although cytochalasin D caused actin microfilaments to collapse, EHD2 was nevertheless maintained at the plasma membrane. Intriguingly, cytochalasin D induced relocalization of both PIP2 and EHD2 to actin aggregates, supporting a role of PIP2 in controlling EHD2 subcellular localization. Altogether, these studies emphasize the significance of membrane lipid composition for EHD2 subcellular distribution and offer new insights into the regulation of this important endocytic protein. PMID:24040268

  12. Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine.

    PubMed

    Kim, Dojung; Lee, Young-Joo; Ryu, Heui-Young; Lee, Jin-Hee; Kim, Hyun-Kyung; Kim, Eunhee; Moon, Jae-Dong; Chang, Dong Deuk; Yoon, Hae-Seong

    2013-01-01

    Heterocyclic amines (HCAs) are naturally produced during common cooking processes for meats and fish. HCAs are metabolized by various enzymes, including cytochromes P450, N-acetyl transferases, and sulfotransferases, and their bioactivated metabolites are considered to bind to DNA or protein to show carcinogenic effects. More than 20 HCAs have been identified, of which 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as 'reasonably anticipated to be a human carcinogen' to develop cancers in breast, colon and prostate. The purpose of this study was to evaluate human exposure levels of PhIP and to understand the role of genetic polymorphisms of enzymes on PhIP metabolism. Urine samples were collected from subjects (n = 100) before 3-day meat-restricted diets. Subjects consumed grilled chicken, and their blood and urine were collected before and after the administration of the chickens to investigate genetic polymorphisms and PhIP levels. The mean PhIP levels were 4.22 ± 0.12, 0.61 ± 0.19 and 22.64 ± 1.00 pg ml(-1) in urine under normal conditions and before and after chicken administration, respectively. Among 21 Single-nucleotide polymorphisms (SNP) of CYP1A1, CYP1A2, NATs and UGTs investigated in this study, genotypic groups of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P < 0.05). These results suggest that genetic polymorphisms might affect PhIP metabolism, which could improve understanding of populations subject to PhIP-derived health risk. PMID:22131055

  13. Inositol 1,4,5-tripshosphate receptor, calcium signaling and polyglutamine expansion disorders

    PubMed Central

    Bezprozvanny, Ilya

    2016-01-01

    Huntington’s disease (HD), spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) are autosomal-dominant neurodegenerative disorders. HD is caused by polyglutamine (polyQ) expansion (exp) in the amino-terminal region of a protein huntingtin (Htt) and primarily affects medium spiny striatal neurons (MSN). SCA2 is caused by a polyQ expansion in the amino-terminal region of a cytosolic protein ataxin-2 (Atxn2) and primarily affects cerebellar Purkinje neurons. SCA3 is caused by a polyQ expansion in the carboxy-terminal portion of a cytosolic protein ataxin-3 (Atxn3) and primarily affects dentate and pontine nuclei and substantia nigra. The reasons for neuronal dysfunction and death in HD, SCA2 and SCA3 remain poorly understood and no cure is available for the patients. My laboratory discovered that mutant Huntingtin, ataxin-2 and ataxin-3 proteins specifically binds to the carboxy-terminal region of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1), an intracellular Ca2+ release channel. Moreover, we found that association with IP3R1 causes sensitization of IP3R1 to activation by IP3 in planar lipid bilayers and in neuronal cells. These results suggested that deranged neuronal Ca2+ signaling might play an important role in pathogenesis of HD, SCA2 and SCA3. In support of this idea, we demonstrated a connection between abnormal Ca2+ signaling and neuronal cell death in experimnts with HD, SCA2 and SCA3 transgenic mouse models. Based on these results I propose that IP3R and other Ca2+ signaling proteins should be considered as potential therapeutic targets for treatment of HD, SCA2 and SCA3. PMID:22353486

  14. Proteolytic fragmentation of inositol 1,4,5-trisphosphate receptors: a novel mechanism regulating channel activity?

    PubMed

    Wang, Liwei; Alzayady, Kamil J; Yule, David I

    2016-06-01

    Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are a family of ubiquitously expressed intracellular Ca(2+) release channels. Regulation of channel activity by Ca(2+) , nucleotides, phosphorylation, protein binding partners and other cellular factors is thought to play a major role in defining the specific spatiotemporal characteristics of intracellular Ca(2+) signals. These properties are, in turn, believed pivotal for the selective and specific physiological activation of Ca(2+) -dependent effectors. IP3 Rs are also substrates for the intracellular cysteine proteases, calpain and caspase. Cleavage of the IP3 R has been proposed to play a role in apoptotic cell death by uncoupling regions important for IP3 binding from the channel domain, leaving an unregulated leaky Ca(2+) pore. Contrary to this hypothesis, we demonstrate following proteolysis that N- and C-termini of IP3 R1 remain associated, presumably through non-covalent interactions. Further, we show that complementary fragments of IP3 R1 assemble into tetrameric structures and retain their ability to be regulated robustly by IP3 . While peptide continuity is clearly not necessary for IP3 -gating of the channel, we propose that cleavage of the IP3 R peptide chain may alter other important regulatory events to modulate channel activity. In this scenario, stimulation of the cleaved IP3 R may support distinct spatiotemporal Ca(2+) signals and activation of specific effectors. Notably, in many adaptive physiological events, the non-apoptotic activities of caspase and calpain are demonstrated to be important, but the substrates of the proteases are poorly defined. We speculate that proteolytic fragmentation may represent a novel form of IP3 R regulation, which plays a role in varied adaptive physiological processes. PMID:26486785

  15. Preparations, structures and properties of heterobimetallic complexes based on tetrahydrofuran-2,3,4,5-tetracarboxylate

    SciTech Connect

    Jia, Tian-Jing; Li, Shu-Mu; Cao, Wei; Li, Li-Cun; Zheng, Xiang-Jun; Yuan, Da-Qiang

    2013-05-01

    Transition heterobimetallic metal-organic frameworks based on tetrahydrofuran-2,3,4,5-tetracarboxylicate (FTA), namely [M(H₂O)₆][Cu₂M(FTA)₂(H₂O)₂]·4H₂O [M=Mn (1), Co (2)], and [CuZn(FTA)(H₂O)₅]·H₂O (3) have been synthesized and characterized. Single-crystal X-ray diffraction indicates that complexes 1 and 2 are isomorphic. In 1 and 2, FTA ligand links the metal ions to a 2-D wave-like negative-charged layer with a topology of (4;6²)₂(4;6³;8²)₂(6). They possess 1-D channels with [M(H₂O)₆]²⁺ and lattice water molecules enclathrated. While in the complex 3, Cu²⁺ and Zn²⁺ ions are bridged by FTA to a 2-D neutral layer structure with a (8)₂(8⁴;12²) topology. Magnetic properties of 1–3 were analyzed in connection with their structures, which show that there exist weak antiferromagnetic interactions between metal ions. - Graphical abstract: Three heterobimetallic MOFs were constructed through the size-selectivity of TFA coordination sites for different transition metal ions based on the concept of “Hard and Soft Acids and Bases”. Highlights: • Complexes 1 and 3 contain 2-D wave-like negative-charged layers. • Complex 2 is a 2-D neutral layer structure with a (8)₂(8⁴;12²) topology. • Complexes 1–3 are the first example of heterobimetallic MOFs based on FTA. • The coordination sites of FTA show size-selectivity to metal ions.

  16. Regulation of Inositol 1,4,5-Trisphosphate Receptor Function During Mouse Oocyte Maturation

    PubMed Central

    Wakai, Takuya; Vanderheyden, Veerle; Yoon, Sook-Young; Cheon, Banyoon; Zhang, Nan; Parys, Jan B.; Fissore, Rafael A.

    2011-01-01

    At the time of fertilization, an increase in the intracellular Ca2+ concentration ([Ca2+]i) underlies egg activation and initiation of development in all species studied to date. The inositol 1,4,5-trisphosphate receptor (IP3R1), which is mostly located in the endoplasmic reticulum (ER) mediates the majority of this Ca2+ release. The sensitivity of IP3R1, i.e. its Ca2+ releasing capability, is increased during oocyte maturation so that the optimum [Ca2+]i response concurs with fertilization, which in mammals occurs at metaphase of second meiosis. Multiple IP3R1 modifications affect its sensitivity, including phosphorylation, sub-cellular localization and ER Ca2+ concentration ([Ca2+]ER). Here we evaluated using mouse oocytes how each of these factors affected IP3R1 sensitivity. The capacity for IP3-induced Ca2+ release markedly increased at the germinal vesicle breakdown stage, although oocytes only acquire the ability to initiate fertilization-like oscillations at later stages of maturation. The increase in IP3R1 sensitivity was underpinned by an increase in [Ca2+]ER and receptor phosphorylation(s) but not by changes in IP3R1 cellular distribution, as inhibition of the former factors reduced Ca2+ release, whereas inhibition of the latter had no impact. Therefore, the results suggest that the regulation of [Ca2+]ER and IP3R1 phosphorylation during maturation enhance IP3R1 sensitivity rendering oocytes competent to initiate oscillations at the expected time of fertilization. The temporal discrepancy between the initiation of changes in IP3R1 sensitivity and acquisition of mature oscillatory capacity suggest that other mechanisms that regulate Ca2+ homeostasis also shape the pattern of oscillations in mammalian eggs. PMID:21465476

  17. Mechanism of protein kinase C activation by phosphatidylinositol 4,5-bisphosphate

    SciTech Connect

    Lee, Myungho; Bell, R.M. )

    1991-01-29

    The mechanism of protein kinase C (PKC) activation by phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol (PI) was investigated by using Triton X-100 mixed micellar methods. The activation of PKC by PIP{sub 2}, for which maximal activity was 60% of that elicited by sn-1,2-diacylglycerol (DAG), was similar to activation by DAG in several respects: (1) activation by PIP{sub 2} and DAG required phosphatidylserine (PS) as a phospholipid cofactor, (2) PIP{sub 2} and DAG reduced the concentration of Ca{sup 2+} and PS required for activation, (3) the concentration dependences of activation by PIP{sub 2} and DAG depended on the concentration of PS, and (4) PIP{sub 2} and DAG complemented one another to achieve maximal activation. On the other hand, PIP{sub 2} activation of the PKC differed from activation by DAG in several respects. With increasing concentrations of PIP{sub 2}, (1) the optimal concentration of PS required was constant at 12 mol%, (2) the maximal activity at 12 mol% PS increased, and (3) the cooperativity for PS decreased. PIP{sub 2} did not inhibit ({sup 3}H)phorbol 12,13-dibutyrate (PDBu) binding of PKC at saturating levels of PS; however, at subsaturating levels of PS, PIP{sub 2} enhanced ({sup 3}H)PDBu binding by acting as a phospholipid cofactor. PIP did not function as an activator but served as a phospholipid cofactor in the presence of PS. These data establish that PIP{sub 2}, PIP, and PI can function to spare, in part, the PS phospholipid cofactor requirement of PKC, and they demonstrate that PIP{sub 2} but not PIP and PI can function as a lipid activator of PKC by mechanisms distinct from those of DAG and phorbol esters.

  18. Phosphatidylinositol 4,5-bisphosphate competitively inhibits phorbol ester binding to protein kinase C

    SciTech Connect

    Chauhan, A.; Cauhan, V.P.S.; Deshmukh, D.S.; Brokerhoff, H. )

    1989-06-13

    Calcium phospholipid dependent protein kinase C (PKC) is activated by diacylglycerol (DG) and by phorbol esters and is recognized to be the phorbol ester receptor of cells; DG displaces phorbol ester competitively from PKC. A phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}), can also activate PKC in the presence of phosphatidylserine (PS) and Ca{sup 2+} with a K{sub PIP{sub 2}} of 0.04 mol %. Preliminary experiments have suggested a common binding site for PIP{sub 2} and DG on PKC. Here, the authors investigate the effect of PIP{sub 2} on phorbol ester binding to PKC in a mixed micellar assay. In the presence of 20 mol % PS, PIP{sub 2} inhibited specific binding of ({sup 3}H)phorbol 12,13-dibutyrate (PDBu) in a dose-dependent fashion up to 85% at 1 mol %. Inhibition of binding was more pronounced with PIP{sub 2} than with DG. Scatchard analysis indicated that the decrease in binding of PDBu in the presence of PIP{sub 2} is the result of an altered affinity for the phorbol ester rather than of a change in maximal binding. The plot of apparent dissociation constants (K{sub d{prime}}) against PIP{sub 2} concentration was linear over a range of 0.01-1 mol % with a K{sub i} of 0.043 mol % and confirmed the competitive nature of inhibition between PDBu and PIP{sub 2}. Competition between PIP{sub 2} and phorbol ester could be determined in a liposomal assay system also. These results indicate that PIP{sub 2}, DG, and phorbol ester all compete for the same activator-receiving region on the regulatory moiety of protein kinase C, and they lend support to the suggestion that PIP{sub 2} is a primary activator of the enzyme.

  19. Thermodynamics of lanthanide and uranyl complexes with tetrahydrofuran-2,3,4,5-tetracarboxylic acid (THFTCA).

    SciTech Connect

    Morss, L. R.; Nash, K. L.; Tennessee Technological Univ.

    2000-01-01

    We present the results of an investigation of the thermochemistry of the complexation of La{sup 3+} Nd{sup 3+}, Eu{sup 3+}, Dy{sup 3+}, Tm{sup 3+}, and UO{sub 2}{sup 2+} by tetrahydrofuran-2,3,4,5-tetracarboxylic acid (THFTCA). This predisposed structural analog to oxydiacetic acid (ODA) has been previously shown both to exhibit greater sensitivity to lanthanide cation radius than complexes with the unconstrained ODA and to form anomalously weak complexes with UO{sub 2}{sup 2+}. Our purpose is to interpret these observations in terms of the balance between enthalpy and entropy contributions to the overall complexation thermodynamics. Enthalpies have been calculated from titration calorimetry experiments both for the protonation of the free ligand and for the formation of selected 1:1 and 1:2 complexes in pH 2-3 acidic media (I = 0.1 M). The complexation entropies for the lanthanide complexes have been calculated using the previously reported stability constants for the MH{sub 2}L{sup +}, MHL, and M(H{sub 2}L){sup 2-}. The stability constants for the uranyl complexes have been determined by potentiometric titration and these values used to calculate the thermodynamic parameters. Complexation enthalpies for the 1:1 lanthanide-THFTCA complexes (MH{sub 2}L{sup +} species) are nearly identical to those of the lanthanide ODA complexes. Therefore, the size-selectivity observed in the lanthanide-THFTCA complexes arises from the complexation entropy. The comparative weakness of the uranyl complexes with THFTCA also is accounted for thermodynamically in the entropy term. Calculations based on an electrostatic model for complexation entropy and molecular mechanics modeling are used to help interpret the experimental results.

  20. The 18 May 2012 (Ms 4.5) Chapala Lake, Jalisco, Mexico Earthquake

    NASA Astrophysics Data System (ADS)

    Yamamoto, J.; Espindola, J. M.

    2015-12-01

    The central part of Jalisco, Mexico has experienced at different times the occurrence of low magnitude earthquakes series. Although the effect of these earthquakes have been limited to relatively small areas have caused general alarm within the population and even in some cases true catastrophes (e.g. San Cristobal 1875). These groups of earthquakes that have lasted for weeks and even months have greater importance because they affect the most populous state area including the capital city of Guadalajara. An extraordinary example of these series of earthquakes occurred on 8 may 1912 that lasted until September. In the first 18 days 64 events were felt by residents of Guadalajara. Since then, there has been a relative seismic activity calm in the region. This paper analyzes the earthquake of May 18, 2012 (03:07 UT) occurred at the West edge of Lake Chapala. While it's an event of low magnitude (4.5 Ms) it has the importance of having occurred just 60 km to the South of Guadalajara and for which instrumental data of first quality is available. The focus of the earthquake was located at 20.30 ° N and 103.49 ° W at a depth of 0 km using arrivals of P and S waves at 16 regional seismic stations. However, by the errors of localization inherent in the method focus could be in a range of 0 to 5 km deep. The mechanism of failure using the polarities of the first arrivals favors a clear faulting of dip slip type along a plane with strike = 227 °, Dip = 80 °, and Rake = 93 °. Waveforms analysis is being used to corroborate these results.

  1. Morphological evaluation of eccentric sets guide-plates of dcp-l 4.5 mm

    PubMed Central

    Borges, José Humberto de Souza; da Silva Filho, Antonio Lisboa; Pereira Neto, Francisco; Daher, Walter Rodrigo; de Mesquita, Alessandro Queiroz; Freitas, Anderson

    2012-01-01

    Objective To carry out isolated and comparative evaluations of the measurements of the set eccentric guide plates used in 4.5mm surgical implants, and to determine the effect of these measurements on compression strength. Methods Four eccentric guides, four large dynamic compression plates (L-DCP) from four local manufacturers, and a Vonder® 200 mm caliper brand were used. Five standard parameter measurements were created for the set eccentric guide-plate, which were identified as A to E. Four sets were made, using materials of the same factory, and identified as groups I to IV. The analyses were performed by measuring all the parameters from a ventral view of the plate, with the eccentric guide placed in the plate hole. Results Groups I and II showed the same values for all the parameters. All the groups showed the same measurements for E = 8.15 e B = 3.60. Group III: A = 8.10mm, C = 3.25mm, D = 1.25mm. Group IV: A = 7.00mm, C = 3.10mm, D = 0.30mm. Maximum compression force was (F Max.): Group I 80.58 N, Group. II: F Max. 81.63 N, Group. III: F Max. 36.32N, Group. IV: F Max. 37.52N Conclusion The measurements evaluated show a lack of standardization in the manufacture of orthopedic instruments and its effects on the values for compression strength. Level of Evidence: Level III, analytical study. PMID:24453573

  2. A WHITE LIGHT MEGAFLARE ON THE dM4.5e STAR YZ CMi

    SciTech Connect

    Kowalski, Adam F.; Hawley, Suzanne L.; Wisniewski, John P.; Hilton, Eric J.; Holtzman, Jon A.

    2010-05-01

    On UT 2009 January 16, we observed a white light megaflare on the dM4.5e star YZ CMi as part of a long-term spectroscopic flare-monitoring campaign to constrain the spectral shape of optical flare continuum emission. Simultaneous U-band photometric and 3350-9260 A spectroscopic observations were obtained during 1.3 hr of the flare decay. The event persisted for more than 7 hr and at flare peak, the U-band flux was almost 6 mag brighter than in the quiescent state. The properties of this flare mark it as one of the most energetic and longest-lasting white light flares ever to be observed on an isolated low-mass star. We present the U-band flare energetics and a flare continuum analysis. For the first time, we show convincingly with spectra that the shape of the blue continuum from 3350 A to 4800 A can be represented as a sum of two components: a Balmer continuum as predicted by the Allred et al. radiative hydrodynamic flare models and a T{approx} 10,000 K blackbody emission component as suggested by many previous studies of the broadband colors and spectral distributions of flares. The areal coverage of the Balmer continuum and blackbody emission regions vary during the flare decay, with the Balmer continuum emitting region always being significantly ({approx}3-16 times) larger. These data will provide critical constraints for understanding the physics underlying the mysterious blue continuum radiation in stellar flares.

  3. Chronic alteration in phosphatidylinositol 4,5-bisphosphate levels regulates capsaicin and mustard oil responses

    PubMed Central

    Patil, Mayur J.; Belugin, Sergei; Akopian, Armen N.

    2011-01-01

    There is an agreement that acute (in minutes) hydrolysis and accumulation of phosphatidylinositol 4,5-bisphosphate (PIP2) modulate TRPV1 and TRPA1 activities. Since inflammation results in PIP2 depletion, persisting for long periods (hours-to-days) in pain models and in clinic, we examined whether chronic depletion and accumulation of PIP2 affects capsaicin and mustard oil responses. In addition we also wanted to evaluate whether the effects of PIP2 depend on TRPV1 and TRPA1 co-expression, and whether the PIP2 actions vary in expression cells versus sensory neurons. Chronic PIP2 production was stimulated by over-expression of phosphatidylinositol-4-phosphate-5-kinase, while PIP2-specific phospholipid 5′-phosphatase was selected to reduce plasma membrane levels of PIP2. Our results demonstrate that capsaicin (100 nM; CAP) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in PIP2 levels in wild-type (WT) or TRPA1 null-mutant sensory neurons, as well as CHO cells expressing TRPV1 alone or with TRPA1. However, low concentrations of CAP (20 nM) produced a higher response after PIP2 depletion in cells containing TRPV1 alone, but not TRPV1 together with TRPA1. Mustard oil (25 μM; MO) responses were also not affected by PIP2 in WT sensory neurons and cells co-expressing TRPA1 and TRPV1. In contrast, PIP2 reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of PIP2 on TRPA1 activity depends on presence of the TRPV1 channel and cell type (CHO vs. sensory neurons). In summary, chronic alterations in PIP2 levels regulate magnitude of CAP and MO responses, as well as MO-tachyphylaxis. This regulation depends on co-expression profile of TRPA1 and TRPV1 and cell type. PMID:21337373

  4. Structural Studies of Inositol 1,4,5-Trisphosphate Receptor COUPLING LIGAND BINDING TO CHANNEL GATING

    SciTech Connect

    Chan, Jenny; Yamazaki, Haruka; Ishiyama, Noboru; Seo, Min-Duk; Mal, Tapas K.; Michikawa, Takayuki; Mikoshiba, Katsuhiko; Ikura, Mitsuhiko

    2010-11-22

    The three isoforms of the inositol 1,4,5-trisphosphate receptor (IP{sub 3}R) exhibit distinct IP{sub 3} sensitivities and cooperativities in calcium (Ca{sup 2+}) channel function. The determinants underlying this isoform-specific channel gating mechanism have been localized to the N-terminal suppressor region of IP3R. We determined the 1.9 {angstrom} crystal structure of the suppressor domain from type 3 IP{sub 3}R (IP{sub 3}R3{sub SUP}, amino acids 1-224) and revealed structural features contributing to isoform-specific functionality of IP{sub 3}R by comparing it with our previously determined structure of the type 1 suppressor domain (IP{sub 3}R1{sub SUP}). The molecular surface known to associate with the ligand binding domain (amino acids 224-604) showed marked differences between IP{sub 3}R3{sub SUP} and IP{sub 3}R1{sub SUP}. Our NMR and biochemical studies showed that three spatially clustered residues (Glu-20, Tyr-167, and Ser-217 in IP{sub 3}R1 and Glu-19, Trp-168, and Ser-218 in IP{sub 3}R3) within the N-terminal suppressor domains of IP{sub 3}R1{sub SUP} and IP{sub 3}R3{sub SUP} interact directly with their respective C-terminal fragments. Together with the accompanying paper (Yamazaki, H., Chan, J., Ikura, M., Michikawa, T., and Mikoshiba, K. (2010) J. Biol. Chem. 285, 36081-36091), we demonstrate that the single aromatic residue in this region (Tyr-167 in IP{sub 3}R1 and Trp-168 in IP{sub 3}R3) plays a critical role in the coupling between ligand binding and channel gating.

  5. Nonlinear finite element analysis of anular lesions in the L4/5 intervertebral disc.

    PubMed

    Little, J P; Adam, C J; Evans, J H; Pettet, G J; Pearcy, M J

    2007-01-01

    Degenerate intervertebral discs exhibit both material and structural changes. Structural defects (lesions) develop in the anulus fibrosus with age. While degeneration has been simulated in numerous previous studies, the effects of structural lesions on disc mechanics are not well known. In this study, a finite element model (FEM) of the L4/5 intervertebral disc was developed in order to study the effects of anular lesions and loss of hydrostatic pressure in the nucleus pulposus on the disc mechanics. Models were developed to simulate both healthy and degenerate discs. Degeneration was simulated with either rim, radial or circumferential anular lesions and by equating nucleus pressure to zero. The anulus fibrosus ground substance was represented as a nonlinear incompressible material using a second-order polynomial, hyperelastic strain energy equation. Hyperelastic material parameters were derived from experimentation on sheep discs. Endplates were assumed to be rigid, and annulus lamellae were assumed to be vertical in the unloaded state. Loading conditions corresponding to physiological ranges of rotational motion were applied to the models and peak rotation moments compared between models. Loss of nucleus pulposus pressure had a much greater effect on the disc mechanics than the presence of anular lesions. This indicated that the development of anular lesions alone (prior to degeneration of the nucleus) has minimal effect on disc mechanics, but that disc stiffness is significantly reduced by the loss of hydrostatic pressure in the nucleus. With the degeneration of the nucleus, the outer innervated anulus or surrounding osteo-ligamentous anatomy may therefore experience increased strains. PMID:17383659

  6. Protein kinase Cζ exhibits constitutive phosphorylation and phosphatidylinositol-3,4,5-triphosphate-independent regulation

    PubMed Central

    Tobias, Irene S.; Kaulich, Manuel; Kim, Peter K.; Simon, Nitya; Jacinto, Estela; Dowdy, Steven F.; King, Charles C.; Newton, Alexandra C.

    2016-01-01

    Atypical protein kinase C (aPKC) isoenzymes are key modulators of insulin signalling, and their dysfunction correlates with insulin-resistant states in both mice and humans. Despite the engaged interest in the importance of aPKCs to type 2 diabetes, much less is known about the molecular mechanisms that govern their cellular functions than for the conventional and novel PKC isoenzymes and the functionally-related protein kinase B (Akt) family of kinases. Here we show that aPKC is constitutively phosphorylated and, using a genetically-encoded reporter for PKC activity, basally active in cells. Specifically, we show that phosphorylation at two key regulatory sites, the activation loop and turn motif, of the aPKC PKCζ in multiple cultured cell types is constitutive and independently regulated by separate kinases: ribosome-associated mammalian target of rapamycin complex 2 (mTORC2) mediates co-translational phosphorylation of the turn motif, followed by phosphorylation at the activation loop by phosphoinositide-dependent kinase-1 (PDK1). Live cell imaging reveals that global aPKC activity is constitutive and insulin unresponsive, in marked contrast to the insulin-dependent activation of Akt monitored by an Akt-specific reporter. Nor does forced recruitment to phosphoinositides by fusing the pleckstrin homology (PH) domain of Akt to the kinase domain of PKCζ alter either the phosphorylation or activity of PKCζ. Thus, insulin stimulation does not activate PKCζ through the canonical phosphatidylinositol-3,4,5-triphosphate-mediated pathway that activates Akt, contrasting with previous literature on PKCζ activation. These studies support a model wherein an alternative mechanism regulates PKCζ-mediated insulin signalling that does not utilize conventional activation via agonist-evoked phosphorylation at the activation loop. Rather, we propose that scaffolding near substrates drives the function of PKCζ. PMID:26635352

  7. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit

    PubMed Central

    Pronk, Sander; Páll, Szilárd; Schulz, Roland; Larsson, Per; Bjelkmar, Pär; Apostolov, Rossen; Shirts, Michael R.; Smith, Jeremy C.; Kasson, Peter M.; van der Spoel, David; Hess, Berk; Lindahl, Erik

    2013-01-01

    Motivation: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. Results: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. Availability: GROMACS is an open source and free software available from http://www.gromacs.org. Contact: erik.lindahl@scilifelab.se Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23407358

  8. 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation

    PubMed Central

    Racine, Christopher; Ward, Dakota; Anestis, Dianne K.; Ferguson, Travis; Preston, Deborah; Rankin, Gary O.

    2014-01-01

    Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined. PMID:25402648

  9. Chronic alteration in phosphatidylinositol 4,5-biphosphate levels regulates capsaicin and mustard oil responses.

    PubMed

    Patil, Mayur J; Belugin, Sergei; Akopian, Armen N

    2011-06-01

    There is an agreement that acute (in minutes) hydrolysis and accumulation of phosphatidylinositol 4,5-bisphosphate (PIP(2) ) modulate TRPV1 and TRPA1 activities. Because inflammation results in PIP(2) depletion, persisting for long periods (hours to days) in pain models and in the clinic, we examined whether chronic depletion and accumulation of PIP(2) affect capsaicin (CAP) and mustard oil (MO) responses. In addition, we wanted to evaluate whether the effects of PIP(2) depend on TRPV1 and TRPA1 coexpression and whether the PIP(2) actions vary in expression cells vs. sensory neurons. Chronic PIP(2) production was stimulated by overexpression of phosphatidylinositol-4-phosphate-5-kinase, and PIP(2) -specific phospholipid 5'-phosphatase was selected to reduce plasma membrane levels of PIP(2) . Our results demonstrate that CAP (100 nM) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in PIP(2) levels in wild-type (WT) or TRPA1 null-mutant sensory neurons as well as CHO cells expressing TRPV1 alone or with TRPA1. However, low concentrations of CAP (20 nM) produced a higher response after PIP(2) depletion in cells containing TRPV1 alone but not TRPV1 together with TRPA1. MO (25 μM) responses were also not affected by PIP(2) in WT sensory neurons and cells coexpressing TRPA1 and TRPV1. In contrast, PIP(2) reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of PIP(2) on TRPA1 activity depends on presence of the TRPV1 channel and cell type (CHO vs. sensory neurons). In summary, chronic alterations in PIP(2) levels regulate magnitude of CAP and MO responses as well as MO tachyphylaxis. This regulation depends on coexpression profile of TRPA1 and TRPV1 and cell type. PMID:21337373

  10. Searching for Organics Preserved in 4.5 Billion Year Old Salt

    NASA Technical Reports Server (NTRS)

    Zolensky, Michael E.; Fries, M.; Steele, A.; Bodnar, R.

    2012-01-01

    Our understanding of early solar system fluids took a dramatic turn a decade ago with the discovery of fluid inclusion-bearing halite (NaCl) crystals in the matrix of two freshly fallen brecciated H chondrite falls, Monahans and Zag. Both meteorites are regolith breccias, and contain xenolithic halite (and minor admixed sylvite -- KCl, crystals in their regolith lithologies. The halites are purple to dark blue, due to the presence of color centers (electrons in anion vacancies) which slowly accumulated as 40K (in sylvite) decayed over billions of years. The halites were dated by K-Ar, Rb-Sr and I-Xe systematics to be 4.5 billion years old. The "blue" halites were a fantastic discovery for the following reasons: (1) Halite+sylvite can be dated (K is in sylvite and will substitute for Na in halite, Rb substitutes in halite for Na, and I substitutes for Cl). (2) The blue color is lost if the halite dissolves on Earth and reprecipitates (because the newly-formed halite has no color centers), so the color serves as a "freshness" or pristinity indicator. (3) Halite frequently contains aqueous fluid inclusions. (4) Halite contains no structural oxygen, carbon or hydrogen, making them ideal materials to measure these isotopic systems in any fluid inclusions. (5) It is possible to directly measure fluid inclusion formation temperatures, and thus directly measure the temperature of the mineralizing aqueous fluid. In addition to these two ordinary chondrites halite grains have been reliably reported in several ureilites, an additional ordinary chondrite (Jilin), and in the carbonaceous chondrite (Murchison), although these reports were unfortunately not taken seriously. We have lately found additional fluid inclusions in carbonates in several additional carbonaceous chondrites. Meteoritic aqueous fluid inclusions are apparently relatively widespread in meteorites, though very small and thus difficult to analyze.

  11. Detection and quantification of 4(5)-methylimidazole in cooked meat.

    PubMed

    Karim, Faris; Smith, J Scott

    2015-02-01

    4(5)-Methylimidazole (4-MeI) is a nitrogen-containing heterocyclic compound found in class III and IV ammoniated caramel colors, a group of additives widely used in the food industry. A suspected carcinogen and neurotoxin and efforts are underway to limit its presence in foods. Several methods have been developed to detect and quantitate 4-MeI in different food matrices, including roasted coffee, beer, soft drinks, and soy sauce; however, no methods are available to measure 4-MeI in cooked meat and meat products containing lipids and high levels of interfering nitrogen compounds, such as amino acids and peptides. A rapid method using 0.1 M sodium acetate buffer (pH 5) as an extraction solvent followed by derivatization with isobutylchloroformate and gas chromatograph mass-spectrometry was developed to quantify 4-MeI in cooked meat products with added caramel colors containing 4-MeI. Selected ion monitoring mode was used to monitor 4-MeI ions fragments. In the 8 commercial meat products tested, 4-MeI levels ranged from 0.041 to 1.015 mg/kg, with recovery of 94.76% to 103.94%. In addition, a matrix-matched calibration performed by analyzing a spiked cooked meat sample indicated no significant difference (P > 0.05), which means the meat matrix had no effect on the developed method. This method proved useful in analyzing 4-MeI in meat products with added caramel color containing 4-MeI. PMID:25603986

  12. Near Zero Emissions at 50 Percent Thermal Efficiency

    SciTech Connect

    None, None

    2012-12-31

    Detroit Diesel Corporation (DDC) has successfully completed a 10 year DOE sponsored heavy-duty truck engine program, hereafter referred to as the NZ-50 program. This program was split into two major phases. The first phase was called Near-Zero Emission at 50 Percent Thermal Efficiency, and was completed in 2007. The second phase was initiated in 2006, and this phase was named Advancements in Engine Combustion Systems to Enable High-Efficiency Clean Combustion for Heavy-Duty Engines. This phase was completed in September, 2010. The key objectives of the NZ-50 program for this first phase were to: Quantify thermal efficiency degradation associated with reduction of engine-out NOx emissions to the 2007 regulated level of ~1.1 g/hp-hr. Implement an integrated analytical/experimental development plan for improving subsystem and component capabilities in support of emerging engine technologies for emissions and thermal efficiency goals of the program. Test prototype subsystem hardware featuring technology enhancements and demonstrate effective application on a multi-cylinder, production feasible heavy-duty engine test-bed. Optimize subsystem components and engine controls (calibration) to demonstrate thermal efficiency that is in compliance with the DOE 2005 Joule milestone, meaning greater than 45% thermal efficiency at 2007 emission levels. Develop technology roadmap for meeting emission regulations of 2010 and beyond while mitigating the associated degradation in engine fuel consumption. Ultimately, develop technical prime-path for meeting the overall goal of the NZ-50 program, i.e., 50% thermal efficiency at 2010 regulated emissions. These objectives were successfully met during the course of the NZ-50 program. The most noteworthy achievements in this program are summarized as follows: Demonstrated technologies through advanced integrated experiments and analysis to achieve the technical objectives of the NZ-50 program with 50.2% equivalent thermal efficiency under

  13. Homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system at ER-PM junctions.

    PubMed

    Chang, Chi-Lun; Liou, Jen

    2016-08-01

    The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca(2+) signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca(2+) from the endoplasmic reticulum (ER) store to the cytosol to activate Ca(2+)-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca(2+) must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca(2+). Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca(2+) influx across the PM is required to refill the ER Ca(2+) store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca(2+) signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca(2+) signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occur, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca(2+) signaling, including the ER Ca(2+) sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26924250

  14. Injector Design Tool Improvements: User's manual for FDNS V.4.5

    NASA Technical Reports Server (NTRS)

    Chen, Yen-Sen; Shang, Huan-Min; Wei, Hong; Liu, Jiwen

    1998-01-01

    The major emphasis of the current effort is in the development and validation of an efficient parallel machine computational model, based on the FDNS code, to analyze the fluid dynamics of a wide variety of liquid jet configurations for general liquid rocket engine injection system applications. This model includes physical models for droplet atomization, breakup/coalescence, evaporation, turbulence mixing and gas-phase combustion. Benchmark validation cases for liquid rocket engine chamber combustion conditions will be performed for model validation purpose. Test cases may include shear coaxial, swirl coaxial and impinging injection systems with combinations LOXIH2 or LOXISP-1 propellant injector elements used in rocket engine designs. As a final goal of this project, a well tested parallel CFD performance methodology together with a user's operation description in a final technical report will be reported at the end of the proposed research effort.

  15. 2-Amino-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile.

    PubMed

    Khan, Ashraf Y; Fathima, Nikhath; Kalashetti, Mallikarjun B; Begum, Noor Shahina; Khazi, I M

    2012-10-01

    In the title compound, C(10)H(12)N(2)S, the thio-phene ring is essentially planar (r.m.s. deviation = 0.0290 Å). The two C atoms of the cyclo-hexene ring (at positions 6 and 7) are disordered over two sets of sites in a 0.810 (5):0.190 (5) ratio. The cyclo-hexene rings in both the major and minor occupancy conformers adopt a half-chair conformation. In the crystal, there are two types of N-H⋯N inter-action. One of these results in centrosymmetric head-to-head dimers corresponding to an R(2) (2)(12) graph-set motif and the other forms a 20-membered macrocyclic ring involving six mol-ecules. PMID:23125792

  16. Translocation between membranes and cytosol of p42IP4, a specific inositol 1,3,4,5-tetrakisphosphate/phosphatidylinositol 3,4, 5-trisphosphate-receptor protein from brain, is induced by inositol 1,3,4,5-tetrakisphosphate and regulated by a membrane-associated 5-phosphatase.

    PubMed

    Stricker, R; Adelt, S; Vogel, G; Reiser, G

    1999-10-01

    The highly conserved 42-kDa protein, p42IP4 was identified recently from porcine brain. It has also been identified similarly in bovine, rat and human brain as a protein with two pleckstrin homology domains that binds Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 with high affinity and selectivity. The brain-specific p42IP4 occurs both as membrane-associated and cytosolic protein. Here, we investigate whether p42IP4 can be translocated from membranes by ligand interaction. p42IP4 is released from cerebellar membranes by incubation with Ins(1,3,4,5)P4. This dissociation is concentration-dependent (> 100 nM), occurs within a few minutes and and is ligand-specific. p42IP4 specifically associates with PtdIns(3, 4,5)P3-containing lipid vesicles and can dissociate from these vesicles by addition of Ins(1,3,4,5)P4. p42IP4 is only transiently translocated from the membranes as Ins(1,3,4,5)P4 can be degraded by a membrane-associated 5-phosphatase to Ins(1,3,4)P3. Then, p42IP4 re-binds to the membranes from which it can be re-released by re-addition of Ins(1,3,4,5)P4. Thus, Ins(1,3,4,5)P4 specifically induces the dissociation from membranes of a PtdIns(3,4,5)P3 binding protein that can reversibly re-associate with the membranes. Quantitative analysis of the inositol phosphates in rat brain tissue revealed a concentration of Ins(1,3,4,5)P4 comparable to that required for p42IP4 translocation. Thus, in vivo p42IP4 might interact with membranes in a ligand-controlled manner and be involved in physiological processes induced by the two second messengers Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3. PMID:10504414

  17. Optimization of the catalytic asymmetric addition of nitroalkanes to cyclic enones with trans-4,5-methano-L-proline.

    PubMed

    Hanessian, Stephen; Shao, Zhihui; Warrier, Jayakumar S

    2006-10-12

    [reaction: see text] The conjugate addition of symmetrical 2-nitroalkanes to 2-cycloalkenones catalyzed by trans-4,5-methano-l-proline proceeds with >99% ee and excellent chemical yields. 1-Nitroalkanes afford diastereomeric syn/anti products that can be separated with good individual enantioselectivities. Proline hydroxamic acid and its trans-4,5-methano -l-proline hydroxamic acid are also effective organocatalysts in the addition of 2-nitropropane to 2-cyclohexenone (75% and 81% ee, respectively). PMID:17020303

  18. Conformation of 4.5S RNA in the signal recognition particle and on the 30S ribosomal subunit

    PubMed Central

    GU, SHAN-QING; JÖCKEL, JOHANNES; BEINKER, PHILIPP; WARNECKE, JENS; SEMENKOV, YURI P.; RODNINA, MARINA V.; WINTERMEYER, WOLFGANG

    2005-01-01

    The signal recognition particle (SRP) from Escherichia coli consists of 4.5S RNA and protein Ffh. It is essential for targeting ribosomes that are translating integral membrane proteins to the translocation pore in the plasma membrane. Independently of Ffh, 4.5S RNA also interacts with elongation factor G (EF-G) and the 30S ribosomal subunit. Here we use a cross-linking approach to probe the conformation of 4.5S RNA in SRP and in the complex with the 30S ribosomal subunit and to map the binding site. The UV-activatable cross-linker p-azidophenacyl bromide (AzP) was attached to positions 1, 21, and 54 of wild-type or modified 4.5S RNA. In SRP, cross-links to Ffh were formed from AzP in all three positions in 4.5S RNA, indicating a strongly bent conformation in which the 5′ end (position 1) and the tetraloop region (including position 54) of the molecule are close to one another and to Ffh. In ribosomal complexes of 4.5S RNA, AzP in both positions 1 and 54 formed cross-links to the 30S ribosomal subunit, independently of the presence of Ffh. The major cross-linking target on the ribosome was protein S7; minor cross-links were formed to S2, S18, and S21. There were no cross-links from 4.5S RNA to the 50S subunit, where the primary binding site of SRP is located close to the peptide exit. The functional role of 4.5S RNA binding to the 30S subunit is unclear, as the RNA had no effect on translation or tRNA translocation on the ribosome. PMID:16043501

  19. Synthesis and biological activities of some new 4,5-dihydro-1H-1,2,4-triazol-5-ones.

    PubMed

    Demirbas, A; Johansson, C B; Duman, N; Ikizler, A A

    1996-01-01

    The reactions of 3-alkyl(aryl)-4-phenylamino-4,5-dihydro-1H-1,2,4-triazol-5-ones with appropriate alkyl halides via sodio derivatives were studied and the corresponding 1-alkyl-3-alkyl(aryl)-4-phenylamino-4,5-dihydro-1H-1,2,4-traizol-5 -ones were synthesized. Next, the new compounds were tested for their in vitro antimicrobial activities. PMID:8960286

  20. Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

    PubMed Central

    Ayoup, Mohammed Salah; Cordes, David B; Slawin, Alexandra M Z

    2015-01-01

    Summary Palladium catalysed carbonylation reactions using the meta- and para-iodo derivatives of all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane (4) are illustrated as the start point for a variety of functional group interconversions. The resultant benzaldehyde and benzoic acids offer novel building blocks for further derivatisation and facilitate the incorporation of the facially polarised all-cis-1,2,4,5-tetrafluorocyclohexane motif into more advanced molecular scaffolds. PMID:26877788

  1. Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients.

    PubMed

    Windhorst, Sabine; Minge, Daniel; Bähring, Robert; Hüser, Svenja; Schob, Claudia; Blechner, Christine; Lin, Hong-Ying; Mayr, Georg W; Kindler, Stefan

    2012-03-01

    Inositol-1,4,5-trisphosphate 3-kinase-A (itpka) accumulates in dendritic spines and seems to be critically involved in synaptic plasticity. The protein possesses two functional activities: it phosphorylates inositol-1,4,5-trisphosphate (Ins(1,4,5)P(3)) and regulates actin dynamics by its F-actin bundling activity. To assess the relevance of these activities for neuronal physiology, we examined the effects of altered itpka levels on cell morphology, Ins(1,4,5)P(3) metabolism and dendritic Ca(2+) signaling in hippocampal neurons. Overexpression of itpka increased the number of dendritic protrusions by 71% in immature primary neurons. In mature neurons, however, the effect of itpka overexpression on formation of dendritic spines was weaker and depletion of itpka did not alter spine density and synaptic contacts. In synaptosomes of mature neurons itpka loss resulted in decreased duration of Ins(1,4,5)P(3) signals and shorter Ins(1,4,5)P(3)-dependent Ca(2+) transients. At synapses of itpka deficient neurons the levels of Ins(1,4,5)P(3)-5-phosphatase (inpp5a) and sarcoplasmic/endoplasmic reticulum calcium ATPase pump-2b (serca2b) were increased, indicating that decreased duration of Ins(1,4,5)P(3) and Ca(2+) signals results from compensatory up-regulation of these proteins. Taken together, our data suggest a dual role for itpka. In developing neurons itpka has a morphogenic effect on dendrites, while the kinase appears to play a key role in shaping Ca(2+) transients at mature synapses. PMID:22120525

  2. The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size.

    PubMed

    Planas-Paz, Lara; Orsini, Vanessa; Boulter, Luke; Calabrese, Diego; Pikiolek, Monika; Nigsch, Florian; Xie, Yang; Roma, Guglielmo; Donovan, Adriana; Marti, Patricia; Beckmann, Nicolau; Dill, Michael T; Carbone, Walter; Bergling, Sebastian; Isken, Andrea; Mueller, Matthias; Kinzel, Bernd; Yang, Yi; Mao, Xiaohong; Nicholson, Thomas B; Zamponi, Raffaella; Capodieci, Paola; Valdez, Reginald; Rivera, Daniel; Loew, Andreas; Ukomadu, Chinweike; Terracciano, Luigi M; Bouwmeester, Tewis; Cong, Feng; Heim, Markus H; Forbes, Stuart J; Ruffner, Heinz; Tchorz, Jan S

    2016-05-01

    LGR4/5 receptors and their cognate RSPO ligands potentiate Wnt/β-catenin signalling and promote proliferation and tissue homeostasis in epithelial stem cell compartments. In the liver, metabolic zonation requires a Wnt/β-catenin signalling gradient, but the instructive mechanism controlling its spatiotemporal regulation is not known. We have now identified the RSPO-LGR4/5-ZNRF3/RNF43 module as a master regulator of Wnt/β-catenin-mediated metabolic liver zonation. Liver-specific LGR4/5 loss of function (LOF) or RSPO blockade disrupted hepatic Wnt/β-catenin signalling and zonation. Conversely, pathway activation in ZNRF3/RNF43 LOF mice or with recombinant RSPO1 protein expanded the hepatic Wnt/β-catenin signalling gradient in a reversible and LGR4/5-dependent manner. Recombinant RSPO1 protein increased liver size and improved liver regeneration, whereas LGR4/5 LOF caused the opposite effects, resulting in hypoplastic livers. Furthermore, we show that LGR4(+) hepatocytes throughout the lobule contribute to liver homeostasis without zonal dominance. Taken together, our results indicate that the RSPO-LGR4/5-ZNRF3/RNF43 module controls metabolic liver zonation and is a hepatic growth/size rheostat during development, homeostasis and regeneration. PMID:27088858

  3. Synthesis, biological evaluation and molecular docking studies of 2-amino-3,4,5-trimethoxyaroylindole derivatives as novel anticancer agents.

    PubMed

    Patel, Vijay K; Rajak, Harish

    2016-05-01

    A series of novel 2-amino-3,4,5 trimethoxyaroylindole derivatives was synthesized and evaluated against selected human cancer cell lines of breast (MCF-7) and colon (HT-29). Introduction of an amino group at the C-2 position on ring A of 3,4,5-trimethoxyaroylindole derivatives resulted in novel compounds, i.e., 2-amino-3,4,5-trimethoxyaroylindole derivatives exhibiting excellent cytotoxic activity against human cancer cell lines. Substitution with methoxy group at R(6) in 2-amino-3,4,5-trimethoxyaroylindole 5d exhibited excellent cytotoxic activity against MCF-7 (0.013μM) and colon HT-29 (0.143μM) indicating slightly higher potency than Combretastatin A-4. Molecular modeling studies of 2-amino-3,4,5-trimethoxyaroylindole derivatives have similar structural alignment as colchicine in protein (PDB code: 1SA0) and exhibited hydrogen bond interaction between para position of 3,4,5-trimethoxyphenyl ring with CYS 241 and N-H molecule of indole ring with Val 315 of receptor molecule. PMID:27040661

  4. Characterization of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid-degrading fungi in Vietnamese soils.

    PubMed

    Itoh, Kazuhito; Kinoshita, Masahiro; Morishita, Shigeyuki; Chida, Masateru; Suyama, Kousuke

    2013-04-01

    Sixty-nine fungal strains were isolated countrywide from 10 Vietnamese soils, in areas both with and without a history of exposure to Agent Orange, and their degrading activities on the phenoxy acid herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), as well as related compounds, were examined. Among taxonomically various fungi, 45, 12 and 4% of the isolates degraded phenoxyacetic acid (PA), 2,4-D and 2,4,5-T, respectively. While the PA-degrading fungi were distributed to all sites and among many genera, the 2,4-D-degraders were found only in order Eurotiales in class Eurotiomycetes. All of the 2,4,5-T-degrading fungal strains were phylogenetically close to Eupenicillium spp. and were isolated from southern Vietnam. As a degradation intermediate, the corresponding phenol compounds were detected in some strains. The degradation substrate spectrum for 26 compounds of Eupenicillium spp. strains including 2,4,5-T-degraders and -non-degraders seemed to be related to phylogenetic similarity and soil sampling location of the isolates. These results suggest that the heavily contaminated environments enhanced the adaptation of the phylogenetic group of Eupenicillium spp. toward to obtain the ability to degrade 2,4,5-T. PMID:23167922

  5. Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes.

    PubMed

    Goñi, Guillermina M; Epifano, Carolina; Boskovic, Jasminka; Camacho-Artacho, Marta; Zhou, Jing; Bronowska, Agnieszka; Martín, M Teresa; Eck, Michael J; Kremer, Leonor; Gräter, Frauke; Gervasio, Francesco Luigi; Perez-Moreno, Mirna; Lietha, Daniel

    2014-08-01

    Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the players involved are known; however, mechanistically, FAK activation is not understood. Here, using a multidisciplinary approach, including biochemical, biophysical, structural, computational, and cell biology approaches, we provide a detailed view of a multistep activation mechanism of FAK initiated by phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Interestingly, the mechanism differs from canonical NRTK activation and is tailored to the dual catalytic and scaffolding function of FAK. We find PI(4,5)P2 induces clustering of FAK on the lipid bilayer by binding a basic region in the regulatory 4.1, ezrin, radixin, moesin homology (FERM) domain. In these clusters, PI(4,5)P2 induces a partially open FAK conformation where the autophosphorylation site is exposed, facilitating efficient autophosphorylation and subsequent Src recruitment. However, PI(4,5)P2 does not release autoinhibitory interactions; rather, Src phosphorylation of the activation loop in FAK results in release of the FERM/kinase tether and full catalytic activation. We propose that PI(4,5)P2 and its generation in focal adhesions by the enzyme phosphatidylinositol 4-phosphate 5-kinase type Iγ are important in linking integrin signaling to FAK activation. PMID:25049397

  6. Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes

    PubMed Central

    Goñi, Guillermina M.; Epifano, Carolina; Boskovic, Jasminka; Camacho-Artacho, Marta; Zhou, Jing; Bronowska, Agnieszka; Martín, M. Teresa; Eck, Michael J.; Kremer, Leonor; Gräter, Frauke; Gervasio, Francesco Luigi; Perez-Moreno, Mirna; Lietha, Daniel

    2014-01-01

    Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the players involved are known; however, mechanistically, FAK activation is not understood. Here, using a multidisciplinary approach, including biochemical, biophysical, structural, computational, and cell biology approaches, we provide a detailed view of a multistep activation mechanism of FAK initiated by phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Interestingly, the mechanism differs from canonical NRTK activation and is tailored to the dual catalytic and scaffolding function of FAK. We find PI(4,5)P2 induces clustering of FAK on the lipid bilayer by binding a basic region in the regulatory 4.1, ezrin, radixin, moesin homology (FERM) domain. In these clusters, PI(4,5)P2 induces a partially open FAK conformation where the autophosphorylation site is exposed, facilitating efficient autophosphorylation and subsequent Src recruitment. However, PI(4,5)P2 does not release autoinhibitory interactions; rather, Src phosphorylation of the activation loop in FAK results in release of the FERM/kinase tether and full catalytic activation. We propose that PI(4,5)P2 and its generation in focal adhesions by the enzyme phosphatidylinositol 4-phosphate 5-kinase type Iγ are important in linking integrin signaling to FAK activation. PMID:25049397

  7. GATA4-mediated cardiac hypertrophy induced by D-myo-inositol 1,4,5-tris-phosphate

    SciTech Connect

    Zhu Zhiming . E-mail: zhuzming@mail.dph-fsi.com; Zhu Shanjun; Liu Daoyan; Yu Zengping; Yang Yongjian; Giet, Markus van der; Tepel, Martin . E-mail: Martin.Tepel@charite.de

    2005-12-16

    We evaluated the effects of D-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. D-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, {beta}-myosin heavy chain, and {alpha}-actin. The administration of D-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that D-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of D-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that D-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway.

  8. Phospholipid-binding sites of phosphatase and tensin homolog (PTEN): exploring the mechanism of phosphatidylinositol 4,5-bisphosphate activation.

    PubMed

    Wei, Yang; Stec, Boguslaw; Redfield, Alfred G; Weerapana, Eranthie; Roberts, Mary F

    2015-01-16

    The lipid phosphatase activity of the tumor suppressor phosphatase and tensin homolog (PTEN) is enhanced by the presence of its biological product, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). This enhancement is suggested to occur via the product binding to the N-terminal region of the protein. PTEN effects on short-chain phosphoinositide (31)P linewidths and on the full field dependence of the spin-lattice relaxation rate (measured by high resolution field cycling (31)P NMR using spin-labeled protein) are combined with enzyme kinetics with the same short-chain phospholipids to characterize where PI(4,5)P2 binds on the protein. The results are used to model a discrete site for a PI(4,5)P2 molecule close to, but distinct from, the active site of PTEN. This PI(4,5)P2 site uses Arg-47 and Lys-13 as phosphate ligands, explaining why PTEN R47G and K13E can no longer be activated by that phosphoinositide. Placing a PI(4,5)P2 near the substrate site allows for proper orientation of the enzyme on interfaces and should facilitate processive catalysis. PMID:25429968

  9. Effect of Various Food Additives on the Levels of 4(5)-Methylimidazole in a Soy Sauce Model System.

    PubMed

    Lee, Sumin; Lee, Jung-Bin; Hwang, Junho; Lee, Kwang-Geun

    2016-01-01

    In this study, the effect of food additives such as iron sulfate, magnesium sulfate, zinc sulfate, citric acid, gallic acid, and ascorbic acid on the reduction of 4(5)-methylimidazole (4(5)-MI) was investigated using a soy sauce model system. The concentration of 4(5)-MI in the soy sauce model system with 5% (v/v) caramel colorant III was 1404.13 μg/L. The reduction rate of 4(5)-MI level with the addition of 0.1M additives followed in order: iron sulfate (81%) > zinc sulfate (61%) > citric acid (40%) > gallic acid (38%) > ascorbic acid (24%) > magnesium sulfate (13%). Correlations between 4(5)-MI levels and the physicochemical properties of soy sauce, including the amount of caramel colorant, pH value, and color differences, were determined. The highest correlations were found between 4(5)-MI levels and the amount of caramel colorant and pH values (r(2) = 0.9712, r(2) = 0.9378). The concentration of caramel colorants in 8 commercial soy sauces were estimated, and ranged from 0.01 to 1.34% (v/v). PMID:26661512

  10. Atomic forces between noble gas atoms, alkali ions, and halogen ions for surface interactions

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Outlaw, R. A.; Heinbockel, J. H.

    1988-01-01

    The components of the physical forces between noble gas atoms, alkali ions, and halogen ions are analyzed and a data base developed from analysis of the two-body potential data, the alkali-halide molecular data, and the noble gas crystal and salt crystal data. A satisfactory global fit to this molecular and crystal data is then reproduced by the model to within several percent. Surface potentials are evaluated for noble gas atoms on noble gas surfaces and salt crystal surfaces with surface tension neglected. Within this context, the noble gas surface potentials on noble gas and salt crystals are considered to be accurate to within several percent.

  11. Formation of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate from inositol 1,3,4,5-tetrakisphosphate and their pathways of degradation in RBL-2H3 cells

    SciTech Connect

    Cunha-Melo, J.R.; Dean, N.M.; Ali, H.; Beaven, M.A.

    1988-10-05

    Previous studies with antigen-stimulated rat basophilic leukemia (RBL-2H3) cells indicated the formation of multiple isomers of each of the various categories of inositol phosphates. The identities of the different isomers have been elucidated by selective labeling of (3H)inositol 1,3,4,5-tetrakisphosphate with (32P)phosphate in the 3'-or 4',5'-positions and by following the metabolism of different radiolabeled inositol phosphates in extracts of RBL-2H3 cells. We report here that inositol 1,3,4,5-tetrakisphosphate, when incubated with the membrane fraction of extracts of RBL-2H3 cells, was converted to inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate. Further dephosphorylation of the inositol polyphosphates proceeded rapidly in whole extracts of cells, although the process was significantly retarded when ATP (2 mM) levels were maintained by an ATP-regenerating system. The degradation of inositol 1,4,5-trisphosphate proceeded with the sequential formation of inositol 1,4-bisphosphate, the inositol 4-monophosphate (with smaller amounts of the 1-monophosphate), and finally inositol. Inositol 1,3,4-trisphosphate, on the other hand, was converted to inositol 1,3-bisphosphate and inositol 3,4-bisphosphate and subsequently to inositol 4-monophosphate and inositol 1-monophosphate (stereoisomeric forms were undetermined). The possible implications of the apparent interconversion between inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in regulating histamine secretion in the RBL-2H3 cells are discussed.

  12. Quantum-chemical insight into structure-reactivity relationship in 4,5,6,7-tetrahalogeno-1H-benzimidazoles: a combined X-ray, DSC, DFT/QTAIM, Hirshfeld surface-based, and molecular docking approach.

    PubMed

    Latosińska, Jolanta Natalia; Latosińska, Magdalena; Maurin, Jan Krzysztof; Orzeszko, Andrzej; Kazimierczuk, Zygmunt

    2014-03-20

    The weak interaction patterns in 4,5,6,7-tetrahalogeno-1H-benzimidazoles, protein kinase CK2 inhibitors, in solid state are studied by the X-ray method and quantum chemistry calculations. The crystal structures of 4,5,6,7-tetrachloro- and 4,5,6,7-tetrabromo-1H-benzimidazole are determined by X-ray diffraction and refined to a final R-factor of 3.07 and 3.03%, respectively, at room temperature. The compound 4,5,6,7-tetrabromo-1H-benzimidazole, which crystallizes in the I41/a space group, is found to be isostructural with previously studied 4,5,6,7-tetraiodo-1H-benzimidazole in contrast to 4,5,6,7-tetrachloro-1H-benzimidazole, which crystallizes as triclinic P1̅ with 4 molecules in elementary unit. For 4,5,6,7-tetrachloro-1H-benzimidazole, differential scanning calorimetry (DSC) revealed a second order glassy phase transition at Tg = 95°/106° (heating/cooling), an indication of frozen disorder. The lack of 3D isostructurality found in all 4,5,6,7-tetrahalogeno-1H-benzimidazoles is elucidated on the basis of the intra- and intermolecular interactions (hydrogen bonding, van der Waals contacts, and C-H···π interactions). The topological Bader's Quantum Theory of Atoms in Molecules (QTAIM) and Spackman's Hirshfeld surface-based approaches reveal equilibration of electrostatic matching and dispersion van der Waals interactions between molecules consistent with the crystal site-symmetry. The weakening of van der Waals forces accompanied by increasing strength of the hydrogen bond (N-H···N) result in a decrease in the crystal site-symmetry and a change in molecular packing in the crystalline state. Crystal packing motifs were investigated with the aid of Hirshfeld surface fingerprint plots. The ordering 4,5,6,7-tetraiodo > 4,5,6,7-tetrabromo > 4,5,6,7-tetrachloro > 4,5,6,7-tetrafluoro reflects not only a decrease in crystal symmetry but also increase in chemical reactivity (electronic activation), which could explain some changes in biological activity of

  13. The Microstructure, Creep, and Tensile Behavior for Ti-5Al-45Nb (Atomic Percent) Fully- β Alloy

    NASA Astrophysics Data System (ADS)

    Cowen, C. J.; Boehlert, C. J.

    2007-11-01

    The microstructure, tensile, and creep behavior of a Ti-5Al-45Nb (at. pct) alloy was evaluated. The main objective of processing and characterizing this alloy was to obtain the constituent properties of a fully- β Ti-Al-Nb alloy to aid in modeling the tensile and creep properties of two-phase orthorhombic + body-centered-cubic (O + bcc) alloys. A second objective was to compare the tensile and creep behavior of this fully- β alloy to that for two-phase O + bcc alloys. This alloy exhibited a single-phase microstructure, containing the disordered bcc phase ( β), after all the processing and heat treatments performed. This alloy was easily fabricated and workable; however, its creep resistance was significantly worse than that for fully-O and two-phase O + bcc alloys. The alloy exhibited little strain hardening along with a room-temperature yield strength (YS) of 545 MPa, an ultimate tensile stress (UTS) of 559 MPa, a Young’s modulus (E) of 86 GPa, and a tensile elongation to failure of 25 pct. Extensive surface slip was evident on the deformed material. Its room-temperature tensile properties were quite similar to those for a fully- β Ti-12Al-38Nb microstructure (YS = 553 MPa, UTS = 566 MPa, E = 84, and ɛ f > 27 pct). Thus, the room-temperature tensile properties and behavior of fully- β Ti-Al-Nb microstructures containing 50 at. pct Ti are not sensitive to compositional variations between 5 to 12 at. pct Al and 38 to 45 at. pct Nb.

  14. The mass function of black holes 14.5: comparison of models with observations

    NASA Astrophysics Data System (ADS)

    Natarajan, Priyamvada; Volonteri, Marta

    2012-05-01

    In this paper, we compare the observationally derived black hole mass function (BHMF) of luminous (>1045-1046 erg s-1) broad-line quasars (BLQSOs) at 1 < z < 4.5 drawn from the Sloan Digital Sky Survey (SDSS) presented by Kelly et al., with models of merger-driven black hole (BH) growth in the context of standard hierarchical structure formation models. In these models, we explore two distinct black hole seeding prescriptions at the highest redshifts: 'light seeds'- remnants of Population III stars and 'massive seeds' that form from the direct collapse of pre-galactic discs. The subsequent merger triggered mass build-up of the black hole population is tracked over cosmic time under the assumption of a fixed accretion rate as well as rates drawn from the distribution derived by Merloni & Heinz. Four model snapshots at z= 1.25, 2, 3.25 and 4.25 are compared with the SDSS-derived BHMFs of BLQSOs. We find that the light seed models fall short of reproducing the observationally derived mass function of BLQSOs at MBH > 109 M⊙ throughout the redshift range; the massive seed models with a fixed accretion rate of 0.3 Edd, or with accretion rates drawn from the Merloni & Heinz distribution provide the best fit to the current observational data at z > 2, although they overestimate the high-mass end of the mass function at lower redshifts. At low redshifts, a drastic drop in the accretion rate is observed and this is explained as arising due to the diminished gas supply available due to consumption by star formation or changes in the geometry of the inner feeding regions. Therefore, the overestimate at the high-mass end of the black hole mass function for the massive seed models can be easily modified, as the accretion rate is likely significantly lower at these epochs than what we assume. For the Merloni & Heinz model, examining the Eddington ratio distributions fEdd, we find that they are almost uniformly sampled from fEdd= 10-2 to 1 at z≃ 1, while at high redshift

  15. The environmental impact of 4(5)-methylbenzotriazole from aircraft deicing operations

    NASA Astrophysics Data System (ADS)

    Cornell, Jeffrey Scott

    2002-01-01

    Hundreds of millions of gallons of aircraft deicer fluid (ADF) are applied to aircraft and runway surfaces annually. Recently public and regulatory attention has forced the air transport industry and military aviation community to examine the environmental impacts of aircraft deicing operations (ADOs), and to seek a balance between flight safety and environmental impact. Little data exists which is useful to evaluate the impact of ADF additives. 4(5)-methylbenzotriazole (MeBT) is used in a variety of industrial and commercial fluids to inhibit metal corrosion; it is a standard additive to most common ADF (approx. 0.5%). This MeBT component is actually a mixture of two isomers: 4-methylbenzotriazole (4-MeBT) and 5-methylbenzotriazole (5-MeBT). A significant amount of MeBT enters the natural environment through aircraft deicing operations. Research was conducted to address important data gaps impacting the ability to assess the environmental impact of MeBT and ADOs. Matrixed toxicity studies were conducted to determine the effect of different additives on ADF ecotoxicity. Aerobic liquid batch-fed microcosms were employed to investigate how MeBT affects the toxicity of wastewater containing ADF, describe how MeBT affects the aerobic biodegradation of propylene glycol (PG), and determine the biodegradability of MeBT. Field samples from contaminated areas were collected and analyzed for comparison. Cell energy production and electron transport assays were conducted to determine if MeBT was capable of disrupting oxidative phosphorylation via uncoupling, as its chemical structure would suggest. MicrotoxRTM studies indicated MeBT was toxic to test bacteria below 10 mg/L. C. dubia and P. promelas , however, were less sensitive to MeBT than bacteria but more sensitive to other ADF additives. The effect of MeBT on PG biodegradation was complex and concentration-dependent. Cell yield and PG biodegradation rates generally decreased with increasing reactor MeBT concentration

  16. Bimodal regulation of an Elk subfamily K+ channel by phosphatidylinositol 4,5-bisphosphate

    PubMed Central

    Li, Xiaofan; Anishkin, Andriy; Liu, Hansi; van Rossum, Damian B.; Chintapalli, Sree V.; Sassic, Jessica K.; Gallegos, David; Pivaroff-Ward, Kendra

    2015-01-01

    Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates Shaker K+ channels and voltage-gated Ca2+ channels in a bimodal fashion by inhibiting voltage activation while stabilizing open channels. Bimodal regulation is conserved in hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, but voltage activation is enhanced while the open channel state is destabilized. The proposed sites of PIP2 regulation in these channels include the voltage-sensor domain (VSD) and conserved regions of the proximal cytoplasmic C terminus. Relatively little is known about PIP2 regulation of Ether-á-go-go (EAG) channels, a metazoan-specific family of K+ channels that includes three gene subfamilies, Eag (Kv10), Erg (Kv11), and Elk (Kv12). We examined PIP2 regulation of the Elk subfamily potassium channel human Elk1 to determine whether bimodal regulation is conserved within the EAG K+ channel family. Open-state stabilization by PIP2 has been observed in human Erg1, but the proposed site of regulation in the distal C terminus is not conserved among EAG family channels. We show that PIP2 strongly inhibits voltage activation of Elk1 but also stabilizes the open state. This stabilization produces slow deactivation and a mode shift in voltage gating after activation. However, removal of PIP2 has the net effect of enhancing Elk1 activation. R347 in the linker between the VSD and pore (S4–S5 linker) and R479 near the S6 activation gate are required for PIP2 to inhibit voltage activation. The ability of PIP2 to stabilize the open state also requires these residues, suggesting an overlap in sites central to the opposing effects of PIP2 on channel gating. Open-state stabilization in Elk1 requires the N-terminal eag domain (PAS domain + Cap), and PIP2-dependent stabilization is enhanced by a conserved basic residue (K5) in the Cap. Our data shows that PIP2 can bimodally regulate voltage gating in EAG family channels, as has been proposed for Shaker and HCN channels. PIP2 regulation

  17. Gas Phase Chromatography of some Group 4, 5, and 6 Halides

    SciTech Connect

    Sylwester, Eric Robert

    1998-10-01

    Gas phase chromatography using The Heavy Element Volatility Instrument (HEVI) and the On Line Gas Apparatus (OLGA III) was used to determine volatilities of ZrBr{sub 4}, HfBr{sub 4}, RfBr{sub 4}, NbBr{sub 5}, TaOBr{sub 3}, HaCl{sub 5}, WBr{sub 6}, FrBr, and BiBr{sub 3}. Short-lived isotopes of Zr, Hf, Rf, Nb, Ta, Ha, W, and Bi were produced via compound nucleus reactions at the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory and transported to the experimental apparatus using a He gas transport system. The isotopes were halogenated, separated from the other reaction products, and their volatilities determined by isothermal gas phase chromatography. Adsorption Enthalpy ({Delta}H{sub a}) values for these compounds were calculated using a Monte Carlo simulation program modeling the gas phase chromatography column. All bromides showed lower volatility than molecules of similar molecular structures formed as chlorides, but followed similar trends by central element. Tantalum was observed to form the oxybromide, analogous to the formation of the oxychloride under the same conditions. For the group 4 elements, the following order in volatility and {Delta}H{sub a} was observed: RfBr{sub 4} > ZrBr{sub 4} > HfBr{sub 4}. The {Delta}H{sub a} values determined for the group 4, 5, and 6 halides are in general agreement with other experimental data and theoretical predictions. Preliminary experiments were performed on Me-bromides. A new measurement of the half-life of {sup 261}Rf was performed. {sup 261}Rf was produced via the {sup 248}Cm({sup 18}O, 5n) reaction and observed with a half-life of 74{sub -6}{sup +7} seconds, in excellent agreement with the previous measurement of 78{sub -6}{sup +11} seconds. We recommend a new half-life of 75{+-}7 seconds for {sup 261}Rf based on these two measurements. Preliminary studies in transforming HEVI from an isothermal (constant temperature) gas phase chromatography instrument to a thermochromatographic (variable temperature

  18. Stretch increases inositol 1,4,5-trisphosphate concentration in airway epithelial cells.

    PubMed

    Felix, J A; Woodruff, M L; Dirksen, E R

    1996-03-01

    Mechanical stimulation of airway epithelial cells with a microprobe leads to an increase in cytoplasmic [Ca2+] that appears to be due, in part, to release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive stores (Boitano et al., Science 258:292[1992]). To investigate whether intracellular IP3 concentration ([IP3]i) increases in response to mechanical stimulation, we grew confluent monolayers from rabbit tracheal mucosal explants on flexible substrates and measured [IP3]i after stretching the substrate. The effect of stretch on [IP3]i was measured in the presence of Li+, an inhibitor of IP3 degradation. In unstretched cells, IP3 measured approximately 5.1 pmol/10(6) cells, from which we estimated [IP3]i to be 1.8 microM. Addition of Li+ had no effect on resting [IP3]i. When the flexible cell support was stretched to increase its surface area by 13%, mean [IP3]i increased about 3-fold with a half-time of approximately 1 s. The increased [IP3]i was maintained in a plateau phase for approximately 8 s and then decayed to near the unstretched level over the next 10 s, despite the sustained application of stretch. A transient stretch (0.5 s) induced a similar rate of increase and peak [IP3]i; however, [IP3]i subsided without a plateau phase. The magnitude of the [IP3]i increase was proportional to stimulus intensity between 0 and 13% increase in substrate surface area. In addition, dissociated airway epithelial cells were exposed to hypotonic solution to induce cell swelling. [IP3]i increased about 4-fold above control levels after 10 s of exposure to hypotonic solution. Basal [IP3]i of dissociated cells in isotonic solution was estimated to be 0.7 microM. These results are consistent with mechanical stimulation leading to phospholipase C synthesis of IP3, which mediates intracellular and intercellular Ca2+ signaling. PMID:8845181

  19. Probing the regulation of TASK potassium channels by PI(4,5)P2 with switchable phosphoinositide phosphatases

    PubMed Central

    Lindner, Moritz; Leitner, Michael G; Halaszovich, Christian R; Hammond, Gerald R V; Oliver, Dominik

    2011-01-01

    Abstract TASK channels are background K+ channels that contribute to the resting conductance in many neurons. A key feature of TASK channels is the reversible inhibition by Gq-coupled receptors, thereby mediating the dynamic regulation of neuronal activity by modulatory transmitters. The mechanism that mediates channel inhibition is not fully understood. While it is clear that activation of Gαq is required, the immediate signal for channel closure remains controversial. Experimental evidence pointed to either phospholipase C (PLC)-mediated depletion of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) as the cause for channel closure or to a direct inhibitory interaction of active Gαq with the channel. Here, we address the role of PI(4,5)P2 for G-protein-coupled receptor (GPCR)-mediated TASK inhibition by using recently developed genetically encoded tools to alter phosphoinositide (PI) concentrations in the living cell. When expressed in CHO cells, TASK-1- and TASK-3-mediated currents were not affected by depletion of plasma membrane PI(4,5)P2 either via the voltage-activated phosphatase Ci-VSP or via chemically triggered recruitment of a PI(4,5)P2-5′-phosphatase. Depletion of both PI(4,5)P2 and PI(4)P via membrane recruitment of a novel engineered dual-specificity phosphatase also did not inhibit TASK currents. In contrast, each of these methods produced robust inhibition of the bona fide PI(4,5)P2-dependent channel KCNQ4. Efficient depletion of PI(4,5)P2 and PI(4)P was further confirmed with a fluorescent phosphoinositide sensor. Moreover, TASK channels recovered normally from inhibition by co-expressed muscarinic M1 receptors when resynthesis of PI(4,5)P2 was prevented by depletion of cellular ATP. These results demonstrate that TASK channel activity is independent of phosphoinositide concentrations within the physiological range. Consequently, Gq-mediated inhibition of TASK channels is not mediated by depletion of PI(4,5)P2. PMID:21540350

  20. Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors.

    PubMed

    Wong, Albert; Grubb, David R; Cooley, Nicola; Luo, Jieting; Woodcock, Elizabeth A

    2013-01-01

    Autophagy is a process that removes damaged proteins and organelles and is of particular importance in terminally differentiated cells such as cardiomyocytes, where it has primarily a protective role. We investigated the involvement of inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3)) and its receptors in autophagic responses in neonatal rat ventricular myocytes (NRVM). Treatment with the IP(3)-receptor (IP(3)-R) antagonist 2-aminoethoxydiphenyl borate (2-APB) at 5 or 20 μmol/L resulted in an increase in autophagosome content, defined as puncta labeled by antibody to microtubule associated light chain 3 (LC3). 2-APB also increased autophagic flux, indicated by heightened LC3II accumulation, which was further enhanced by bafilomycin (10nmol/L). Expression of Ins(1,4,5)P(3) 5-phosphatase (IP(3)-5-Pase) to deplete Ins(1,4,5)P(3) also increased LC3-labeled puncta and LC3II content, suggesting that Ins(1,4,5)P(3) inhibits autophagy. The IP(3)-R can act as an inhibitory scaffold sequestering the autophagic effector, beclin-1 to its ligand binding domain (LBD). Expression of GFP-IP(3)-R-LBD inhibited autophagic signaling and furthermore, beclin-1 co-immunoprecipitated with the IP(3)-R-LBD. A mutant GFP-IP(3)-R-LBD with reduced ability to bind Ins(1,4,5)P(3) bound beclin-1 and inhibited autophagy similarly to the wild type sequence. These data provide evidence that Ins(1,4,5)P(3) and IP(3)-R act as inhibitors of autophagic responses in cardiomyocytes. By suppressing autophagy, IP(3)-R may contribute to cardiac pathology. PMID:23137780

  1. Atomic rivals

    SciTech Connect

    Goldschmidt, B.

    1990-01-01

    This book is a memoir of rivalries among the Allies over the bomb, by a participant and observer. Nuclear proliferation began in the uneasy wartime collaboration of the United States, England, Canada, and Free France to produce the atom bomb. Through the changes of history, a young French chemist had a role in almost every act of this international drama. This memoir is based on Goldschmidt's own recollections, interviews with other leading figures, and 3,000 pages of newly declassified documents in Allied archives. From his own start as Marie Curie's lab assistant, Goldschmidt's career was closely intertwined with Frances complicated rise to membership in the nuclear club. As a refugee from the Nazis, he became part of the wartime nuclear energy project in Canada and found himself the only French scientist to work (although briefly) on the American atom bomb project.

  2. Atomic arias

    NASA Astrophysics Data System (ADS)

    Crease, Robert P.

    2009-01-01

    The American composer John Adams uses opera to dramatize controversial current events. His 1987 work Nixon in China was about the landmark meeting in 1972 between US President Richard Nixon and Chairman Mao Zedong of China; The Death of Klinghoffer (1991) was a musical re-enactment of an incident in 1985 when Palestinian terrorists kidnapped and murdered a wheelchair-bound Jewish tourist on a cruise ship. Adams's latest opera, Doctor Atomic, is also tied to a controversial event: the first atomic-bomb test in Alamogordo, New Mexico, on 16 June 1945. The opera premièred in San Francisco in 2005, had a highly publicized debut at the Metropolitan Opera in New York in 2008, and will have another debut on 25 February - with essentially the same cast - at the English National Opera in London.

  3. A combined solid-state NMR and synchrotron x-ray diffraction powder study on the structure of the antioxidant(+)-catechin 4.5 hydrate.

    SciTech Connect

    Harper, J. K.; Doebbler, J. A.; Jaccques, E.; Grant, D. M.; Von Dreele, R. B.; Univ. of Utah

    2010-03-10

    Analyses combining X-ray powder diffraction (XRD) and solid-state NMR (SSNMR) data can now provide crystal structures in challenging powders that are inaccessible by traditional methods. The flavonoid catechin is an ideal candidate for these methods, as it has eluded crystallographic characterization despite extensive study. Catechin was first described nearly two centuries ago, and its powders exhibit numerous levels of hydration. Here, synchrotron XRD data provide all heavy-atom positions in (+)-catechin 4.5-hydrate and establish the space group as C2. SSNMR data ({sup 13}C tensor and {sup 1}H/{sup 13}C correlation) complete the conformation by providing catechin's five OH hydrogen orientations. Since 1903, this phase has been erroneously identified as a 4.0 hydrate, but XRD and density data establish that this discrepancy is due to the facile loss of the water molecule located at a Wyckoff special position in the unit cell. A final improvement to heavy-atom positions is provided by a geometry optimization of bond lengths and valence angles with XRD torsion angles held constant. The structural enhancement in this final structure is confirmed by the significantly improved fit of computed {sup 13}C tensors to experimental data.

  4. Atomic physics

    SciTech Connect

    Livingston, A.E.; Kukla, K.; Cheng, S.

    1995-08-01

    In a collaboration with the Atomic Physics group at Argonne and the University of Toledo, the Atomic Physics group at the University of Notre Dame is measuring the fine structure transition energies in highly-charged lithium-like and helium-like ions using beam-foil spectroscopy. Precise measurements of 2s-2p transition energies in simple (few-electron) atomic systems provide stringent tests of several classes of current atomic- structure calculations. Analyses of measurements in helium-like Ar{sup 16+} have been completed, and the results submitted for publication. A current goal is to measure the 1s2s{sup 3}S{sub 1} - 1s2p{sup 3}P{sub 0} transition wavelength in helium-like Ni{sup 26+}. Measurements of the 1s2s{sup 2}S{sub 1/2} - 1s2p{sup 2}P{sub 1/2,3/2} transition wavelengths in lithium-like Kr{sup 33+} is planned. Wavelength and lifetime measurements in copper-like U{sup 63+} are also expected to be initiated. The group is also participating in measurements of forbidden transitions in helium-like ions. A measurement of the lifetime of the 1s2s{sup 3}S{sub 1} state in Kr{sup 34+} was published recently. In a collaboration including P. Mokler of GSI, Darmstadt, measurements have been made of the spectral distribution of the 2E1 decay continuum in helium-like Kr{sup 34+}. Initial results have been reported and further measurements are planned.

  5. Synthesis, structure and antimicrobial evaluation of new 3,3a,4,5-tetrahydro-2H-benzo[g]indazol-2-yl-thiazol-4(5H)-ones

    NASA Astrophysics Data System (ADS)

    Gautam, Deepika; Chaudhary, R. P.

    2015-01-01

    The reaction of semicarbazide or thiosemicarbazide with 2-arylidene-1-tetralones under alkaline condition affords 3,3a,4,5-tetrahydro-2H-benzo[g]indazole-2-carbo(thio)amides as a mixture of cis and trans diastereoisomers of 3-H and 3a-H. The synthesis of new indazolyl-thiazol-4(5H)-ones from the condensation of cis isomer and α-halo acids is reported. A DFT study along with X-ray single crystal data of a representative compound is presented. All the eight newly synthesised indazolyl-thiazol-4(5H)-ones were screened for their antibacterial and antifungal activities and some compounds have shown promising activities.

  6. Synthesis, structure and antimicrobial evaluation of new 3,3a,4,5-tetrahydro-2H-benzo[g]indazol-2-yl-thiazol-4(5H)-ones.

    PubMed

    Gautam, Deepika; Chaudhary, R P

    2015-01-25

    The reaction of semicarbazide or thiosemicarbazide with 2-arylidene-1-tetralones under alkaline condition affords 3,3a,4,5-tetrahydro-2H-benzo[g]indazole-2-carbo(thio)amides as a mixture of cis and trans diastereoisomers of 3-H and 3a-H. The synthesis of new indazolyl-thiazol-4(5H)-ones from the condensation of cis isomer and α-halo acids is reported. A DFT study along with X-ray single crystal data of a representative compound is presented. All the eight newly synthesised indazolyl-thiazol-4(5H)-ones were screened for their antibacterial and antifungal activities and some compounds have shown promising activities. PMID:25064506

  7. Synthesis, structures, and properties of 1,2,4,5-benzenetetrathiolate linked group 10 metal complexes.

    PubMed

    Arumugam, Kuppuswamy; Shaw, Mohamed C; Chandrasekaran, P; Villagrán, Dino; Gray, Thomas G; Mague, Joel T; Donahue, James P

    2009-11-16

    Dimetallic compounds [(P-P)M(S(2)C(6)H(2)S(2))M(P-P)] (M = Ni, Pd; P-P = chelating bis(phosphine), 3a-3f) are prepared from O=CS(2)C(6)H(2)S(2)C=O or (n)Bu(2)SnS(2)C(6)H(2)S(2)Sn(n)Bu(2), which are protected forms of 1,2,4,5-benzenetetrathiolate. Selective monodeprotections of O=CS(2)C(6)H(2)S(2)C=O or (n)Bu(2)SnS(2)C(6)H(2)S(2)Sn(n)Bu(2) lead to [(P-P)Ni(S(2)C(6)H(2)S(2)C=O)] or [(P-P)Ni(S(2)C(6)H(2)S(2)Sn(n)Bu(2))]; the former is used to prepare trimetallic compounds [(dcpe)Ni(S(2)C(6)H(2)S(2))M(S(2)C(6)H(2)S(2))Ni(dcpe)] (M = Ni (6a) or Pt (6b); dcpe = 1,2-bis(dicyclohexylphosphino)ethane). Compounds 3a-3f are redox active and display two oxidation processes, of which the first is generally reversible. Dinickel compound [(dcpe)Ni(S(2)C(6)H(2)S(2))Ni(dcpe)] (3d) reveals two reversible oxidation waves with DeltaE(1/2) = 0.66 V, corresponding to K(c) of 1.6 x 10(11) for the mixed valence species. Electrochemical behavior is unstable to repeated scanning in the presence of [Bu(4)N][PF(6)] electrolyte but indefinitely stable with Na[BArF(24)] (BArF(24) = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate), suggesting that the radical cation generated by oxidation is vulnerable to reaction with PF(6)(-). Chemical oxidation of 3d with [Cp(2)Fe][BArF(24)] leads to formation of [3d][BArF(24)]. Structural identification of [3d][BArF(24)] reveals appreciable shortening and lengthening of C-S and C-C bond distances, respectively, within the tetrathioarene fragment compared to charge-neutral 3d, indicating this to be the redox active moiety. Attempted oxidation of [(dppb)Ni(S(2)C(6)H(2)S(2))Ni(dppb)] (3c) (dppb = 1,2-bis(diphenylphosphino)benzene) with AgBArF(24) produces [[(dppb)Ni(S(2)C(6)H(2)S(2))Ni(dppb)](2)(mu-Ag(2))][BArF(24)](2), [4c][BArF(24)](2), in which no redox chemistry has occurred. Crystal structures of bis(disulfide)-linked compounds [(P-P)Ni(S(2)C(6)H(2)(mu-S(2))(2)C(6)H(2)S(2))Ni(P-P)] are reported. Near IR spectroscopy upon cationic [3d](+) and neutral 6a

  8. Prevalence and Characterization of Monophasic Salmonella Serovar 1,4,[5],12:i:- of Food Origin in China

    PubMed Central

    Yang, Xiaojuan; Wu, Qingping; Zhang, Jumei; Huang, Jiahui; Guo, Weipeng; Cai, Shuzhen

    2015-01-01

    Salmonella enterica subsp. enterica serovar 1,4,[5],12:i:- is a monophasic variant of Salmonella Typhimurium, which has recently been recognized as an emerging cause of infection worldwide. This bacterium has also ranked among the four most frequent serovars causing human salmonellosis in China. However, there are no reports on its contamination in Chinese food. Serotyping, polymerase chain reaction, antibiotic resistance, virulotyping, and multilocus sequence typing (MLST) assays were used to investigate the prevalence of this serological variant in food products in China, and to determine phenotypic and genotypic difference of monophasic isolates and Salmonella Typhimurium isolated over the same period. Salmonella 1,4,[5],12:i:- was prevalent in various food sources, including beef, pork, chicken, and pigeon. The study also confirmed the high prevalence (53.8%) of resistance to ampicillin, streptomycin, sulfonamides, and tetracycline in Salmonella 1,4,[5],12:i:-, which was higher than that in Salmonella Typhimurium. Moreover, Salmonella 1,4,[5],12:i:- isolates in our study were different from Salmonella Typhimurium isolates by the absence of three plasmid-borne genes (spvC, pefA, and rck) and the presence of gipA in all isolates. All Salmonella 1,4,[5],12:i:- isolates demonstrated MLST pattern ST34. Genomic deletions within the fljBA operon and surrounding genes were only found in Salmonella 1,4,[5],12:i:- isolates, with all isolates containing a deletion of fljB. However, hin and iroB were identified in all Salmonella 1,4,[5],12:i:- isolates. Three different deletion profiles were observed and two of them were different from the reported Salmonella 1,4,[5],12:i:- clones from Spain, America, and Italy, which provided some new evidence on the independent evolution of the multiple successful monophasic clones from Salmonella Typhimurium ancestors. This study is the first report of Salmonella 1,4,[5],12:i:- in food products from China. The data are more

  9. Prevalence and Characterization of Monophasic Salmonella Serovar 1,4,[5],12:i:- of Food Origin in China.

    PubMed

    Yang, Xiaojuan; Wu, Qingping; Zhang, Jumei; Huang, Jiahui; Guo, Weipeng; Cai, Shuzhen

    2015-01-01

    Salmonella enterica subsp. enterica serovar 1,4,[5],12:i:- is a monophasic variant of Salmonella Typhimurium, which has recently been recognized as an emerging cause of infection worldwide. This bacterium has also ranked among the four most frequent serovars causing human salmonellosis in China. However, there are no reports on its contamination in Chinese food. Serotyping, polymerase chain reaction, antibiotic resistance, virulotyping, and multilocus sequence typing (MLST) assays were used to investigate the prevalence of this serological variant in food products in China, and to determine phenotypic and genotypic difference of monophasic isolates and Salmonella Typhimurium isolated over the same period. Salmonella 1,4,[5],12:i:- was prevalent in various food sources, including beef, pork, chicken, and pigeon. The study also confirmed the high prevalence (53.8%) of resistance to ampicillin, streptomycin, sulfonamides, and tetracycline in Salmonella 1,4,[5],12:i:-, which was higher than that in Salmonella Typhimurium. Moreover, Salmonella 1,4,[5],12:i:- isolates in our study were different from Salmonella Typhimurium isolates by the absence of three plasmid-borne genes (spvC, pefA, and rck) and the presence of gipA in all isolates. All Salmonella 1,4,[5],12:i:- isolates demonstrated MLST pattern ST34. Genomic deletions within the fljBA operon and surrounding genes were only found in Salmonella 1,4,[5],12:i:- isolates, with all isolates containing a deletion of fljB. However, hin and iroB were identified in all Salmonella 1,4,[5],12:i:- isolates. Three different deletion profiles were observed and two of them were different from the reported Salmonella 1,4,[5],12:i:- clones from Spain, America, and Italy, which provided some new evidence on the independent evolution of the multiple successful monophasic clones from Salmonella Typhimurium ancestors. This study is the first report of Salmonella 1,4,[5],12:i:- in food products from China. The data are more

  10. Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate

    PubMed Central

    Gerber, Pehuén Pereyra; Cabrini, Mercedes; Jancic, Carolina; Paoletti, Luciana; Banchio, Claudia; von Bilderling, Catalina; Sigaut, Lorena; Pietrasanta, Lía I.; Duette, Gabriel; Freed, Eric O.; de Saint Basile, Genevieve; Moita, Catarina Ferreira; Moita, Luis Ferreira; Amigorena, Sebastian; Benaroch, Philippe; Geffner, Jorge

    2015-01-01

    During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55Gag is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4+ T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, therefore controlling Pr55Gag membrane association. Rab27a also controls PI(4,5)P2 levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55Gag with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication. PMID:25940347

  11. Role of Phosphatidylinositol(4,5)bisphosphate Organization in Membrane Transport by the Unc104 Kinesin Motor

    PubMed Central

    Klopfenstein, Dieter R.; Tomishige, Michio; Stuurman, Nico; Vale, Ronald D.

    2010-01-01

    Summary Unc104 (KIF1A) kinesin transports membrane vesicles along microtubules in lower and higher eukaryotes. Using an in vitro motility assay, we show that Unc104 uses a lipid binding pleckstrin homology (PH) domain to dock onto membrane cargo. Through its PH domain, Unc104 can transport phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2)-containing liposomes with similar properties to native vesicles. Interestingly, liposome movement by monomeric Unc104 motors shows a very steep dependence on PtdIns(4,5)P2 concentration (Hill coefficient of ~20), even though liposome binding is noncooperative. This switch-like transition for movement can be shifted to lower PtdIns(4,5)P2 concentrations by the addition of cholesterol/sphingomyelin or GM1 ganglioside/cholera toxin, conditions that produce raft-like behavior of Unc104 bound to lipid bilayers. These studies suggest that clustering of Unc104 in PtdIns(4,5)P2-containing rafts provides a trigger for membrane transport. PMID:12015984

  12. Formation of persistent organic pollutants from 2,4,5-trichlorothiophenol combustion: a density functional theory investigation.

    PubMed

    Dar, Tajwar; Shah, Kalpit; Moghtaderi, Behdad; Page, Alister J

    2016-06-01

    Polychlorinated dibenzothiophene (PCDT) and polychlorinated thianthrene (PCTA) are sulfur analogues of dioxins, such as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F). In this work, we present a detailed mechanistic and kinetic analysis of PCDT and PCTA formation from the combustion of 2,4,5-trichlorothiophenol. It is shown that the formation of these persistent organic pollutants is more favourable, both kinetically and thermodynamically, than their analogous dioxin counterparts. This is rationalised in terms of the different influences of the S-H and O-H moieties in the 2,4,5-trichlorothiophenol and 2,4,5-trichlorophenol precursors. Kinetic parameters also indicate that the yield of PCDT should exceed that of PCDD. Finally, we demonstrate here that the degree and pattern of chlorination on the 2,4,5-trichlorothiophenol precursor leads to subtle thermodynamic and kinetic changes to the PCDT/PCTA formation mechanisms. Graphical abstract Formation mechanisms of persistant organic pollutants, PCDT and PCTA, from 2,4,5-trichlorothiophenol combustion, has been investigated using density functional theory. PMID:27179803

  13. Reduced phosphatidylinositol 4,5-bisphosphate synthesis impairs inner ear Ca2+ signaling and high-frequency hearing acquisition

    PubMed Central

    Rodriguez, Laura; Simeonato, Elena; Scimemi, Pietro; Anselmi, Fabio; Calì, Bianca; Crispino, Giulia; Ciubotaru, Catalin D.; Bortolozzi, Mario; Ramirez, Fabian Galindo; Majumder, Paromita; Arslan, Edoardo; De Camilli, Pietro; Pozzan, Tullio; Mammano, Fabio

    2012-01-01

    Phosphatidylinositol phosphate kinase type 1γ (PIPKIγ) is a key enzyme in the generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and is expressed at high levels in the nervous system. Homozygous knockout mice lacking this enzyme die postnatally within 24 h, whereas PIPKIγ+/− siblings breed normally and have no reported phenotype. Here we show that adult PIPKIγ+/− mice have dramatically elevated hearing thresholds for high-frequency sounds. During the first postnatal week we observed a reduction of ATP-dependent Ca2+ signaling activity in cochlear nonsensory cells. Because Ca2+ signaling under these conditions depends on inositol-1,4,5-trisphosphate generation from phospholipase C (PLC)-dependent hydrolysis of PI(4,5)P2, we conclude that (i) PIPKIγ is primarily responsible for the synthesis of the receptor-regulated PLC-sensitive PI(4,5)P2 pool in the cell syncytia that supports auditory hair cells; (ii) spatially graded impairment of this signaling pathway in cochlear nonsensory cells causes a selective alteration in the acquisition of hearing in PIPKIγ+/− mice. This mouse model also suggests that PIPKIγ may determine the level of gap junction contribution to cochlear development. PMID:22891314

  14. Syndecan-1 interaction with the LG4/5 domain in laminin-332 is essential for keratinocyte migration.

    PubMed

    Bachy, Sophie; Letourneur, François; Rousselle, Patricia

    2008-01-01

    Laminin 5/laminin 332 (LN332) is an adhesion substrate for epithelial cells. After secretion of LN332, a regulated cleavage occurs at the carboxy-terminus of its alpha3 subunit, which releases a tandem of two globular modules named LG4/5. We show that the presence of the LG4/5 domain in precursor LN332 decreases its integrin-mediated cell adhesion properties in comparison with mature LN332. Whereas cell adhesion to the recombinant LG4/5 fragment relies solely on the heparan sulfate proteoglycan (HSPG) receptor syndecan-1, we reveal that both syndecan-1 and the alpha3beta1 integrin bind to precursor LN332. We further demonstrate that syndecan-1 mediated cell adhesion to the LG4/5 fragment and pre-LN332 allows the formation of fascin-containing protrusions, depending on the GTPases Rac and Cdc42 activation. Reducing syndecan-1 expression in normal keratinocytes prevents cell protrusions on pre-LN332 with subsequent failure of the peripheral localization of the alpha3beta1 integrin. We finally show that cell migration on pre-LN332 requires syndecan-1. Therefore, the LG4/5 domain in precursor LN332 appears to trigger intracellular signaling events, which participate in keratinocyte motility. PMID:17579341

  15. Adsorption and photodegradation kinetics of herbicide 2,4,5-trichlorophenoxyacetic acid with MgFeTi layered double hydroxides.

    PubMed

    Nguyen, Thi Kim Phuong; Beak, Min-wook; Huy, Bui The; Lee, Yong-Ill

    2016-03-01

    The calcined layered double hydroxides (cLDHs) Ti-doped and undoped MgFe for this study were prepared by co-precipitation method followed by calcination at 500 °C. The as-prepared samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Brunauer Emmett Teller (BET) and UV-Vis diffuse reflectance spectrum (DRS) techniques and tested for adsorption and photodegradation (including photocatalytic and photo-Fenton-like) of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in aqueous solutions under visible light irradiation. In the range of studied operating conditions, the as-prepared samples exhibited excellent photo-Fenton-like activity, leading to more than 80-95% degradation of 2,4,5-T at initial concentration of 100 mg L(-1) with 4 g calcined LDHs per liter, was accomplished in 360 min, while 2,4,5-T half-life time was as short as 99-182 min. The kinetics of adsorption and photodegradation of 2,4,5-T were also discussed. These results offered a green, low cost and high efficiency photocatalyst for environmental remediation. PMID:26706931

  16. Depletion of plasma membrane PtdIns(4,5)P2 reveals essential roles for phosphoinositides in flagellar biogenesis

    PubMed Central

    Wei, Ho-Chun; Rollins, Janet; Fabian, Lacramioara; Hayes, Madeline; Polevoy, Gordon; Bazinet, Christopher; Brill, Julie A.

    2011-01-01

    Summary Axonemes are microtubule-based organelles of crucial importance in the structure and function of eukaryotic cilia and flagella. Despite great progress in understanding how axonemes are assembled, the signals that initiate axoneme outgrowth remain unknown. Here, we identified phosphatidylinositol phosphates (phosphoinositides) as key regulators of early stages of axoneme outgrowth in Drosophila melanogaster spermatogenesis. In a study of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] function in developing Drosophila male germ cells, we depleted PtdIns(4,5)P2 by expression of a potent phosphoinositide phosphatase. Phosphatase expression dramatically inhibited sperm tail formation and perturbed microtubule organization in a manner reversible by co-expression of a PtdIns 4-phosphate 5-kinase. Depletion of PtdIns(4,5)P2 caused increased levels of basal body γ-tubulin and altered the distribution of proteins known to be required for axoneme assembly. Examination of PtdIns(4,5)P2-depleted spermatids by transmission electron microscopy revealed defects in basal body docking to the nuclear envelope, and in axoneme architecture and integrity of the developing flagellar axoneme and axial sheath. Our results provide the first evidence that phosphoinositides act at several steps during flagellar biogenesis, coordinately regulating microtubule and membrane organization. They further suggest that phosphoinositides play evolutionarily conserved roles in flagella and cilia, across phyla and in structurally diverse cell types. PMID:18334551

  17. Flood of August 4-5, 1943, in central West Virginia, with a summary of flood stages and discharges in West Virginia

    USGS Publications Warehouse

    Erskine, Harlan Mercer

    1951-01-01

    During the night of August 4-5, 1943, a violent thunderstorm of unusual intensity occurred in parts of Braxton, Calhoun, Gilmer, Ritchie, and Wirth Counties in the Little Kanawha River Basin in central West Virginia. Precipitation amounted to as much as 15 inches in 2 hours in some sections. As a result, many small streams and a reach of the Little Kanawha River in the vicinity of Burnsville and Gilmer reached the highest stages known. Computations based on special surveys made at suitable sites on representative small streams in the areas of intense flooding indicate that peak discharges closely approach 50 percent of the Jarvis scale. Twenty-three lives were lost on the small tributaries as numerous homes were swept away by the flood, which developed with incredible rapidity during the early morning hours. Damage estimated at $1,300,000 resulted to farm buildings, crops, land, livestock, railroads, highways, and gas- and oil-producing facilities. Considerable permanent land damage resulted from erosion and deposition of sand and gravel.

  18. Bis­(4-benzoyl-3-methyl-1-phenyl-4,5-di­hydro-1H-pyrazol-5-olato-κ2 O,O′)(methanol-κO)dioxidouranium(VI) methanol monosolvate

    PubMed Central

    Dehbi, Ouarda; Keraghel, Saida; Bouacida, Sofiane; Benghanem, Fatiha; Ourari, Ali

    2012-01-01

    In the title compound, [U(C17H13N2O2)2O2(CH3OH)]·CH3OH, the UVI ion is coordinated by seven O atoms in a distorted pentagonal–bipyramidal geometry with two 3-methyl-1-phenyl-4-benzoyl-4,5-dihydro-1H-pyrazol-5-olate groups with two O atoms in a bidentate chelating coordination mode and by three O atoms, one of which is from a methanol ligand. The crystal packing can be described by alternating layers of complex mol­ecules along the a axis. The structure is stabilized by O—H⋯N and O—H⋯O hydrogen bonding and van der Waals inter­actions. PMID:22589827

  19. Synthesis, cytotoxicity and antiviral evaluation of new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives.

    PubMed

    Briguglio, Irene; Loddo, Roberta; Laurini, Erik; Fermeglia, Maurizio; Piras, Sandra; Corona, Paola; Giunchedi, Paolo; Gavini, Elisabetta; Sanna, Giuseppina; Giliberti, Gabriele; Ibba, Cristina; Farci, Pamela; La Colla, Paolo; Pricl, Sabrina; Carta, Antonio

    2015-11-13

    Linear aromatic N-tricyclic compounds with promising antiviral activity and minimal cytotoxicity were prepared and analyzed in the last years. Specifically, the pyrido[2,3-g]quinoxalinone nucleus was found endowed with high potency against several pathogenic RNA viruses as etiological agents of important veterinary and human pathologies. Following our research program on new antiviral agents we have designed, synthesized and assayed new series of imidazo[4,5-g]quinoline and pyrido[2,3-g]quinoxalinone derivatives. Lead compounds 1-4 were further modified to enhance their antiviral activity and reduce their cytotoxicity. Thus, different substituents were introduced on N atom at position 1 or the O atom at position 2 of the leads; contextually, several groups were inserted on the nitrogen atom at position 7 of diaminoquinoline intermediates. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against RNA virus families containing single-stranded (either positive-sense (ssRNA+) or negative-sense (ssRNA-)), and double-stranded genomes (dsRNA), and against two representatives of DNA virus families. Some derivatives emerged as potential leads for further development as antiviral agents against some viruses of public health significance, such as RSV, Reo, BVDV and HCV. Particularly, compounds 4, 11b, 11c, 13c, 15a, 18 and 21 resulted active against BVDV at concentrations ranging from 1.3 to 5 μM. Compound 21 was also evaluated for its activity on the BVDV RdRp. Compound 4 was also tested as potential anti-HCV compound in a subgenomic replication assay. Molecular simulation results provided a molecular rationale for the anti-BVDV activity of these compounds. PMID:26479028

  20. Modification of molecular sieves MCM-41 and SBA-15 with covalently grafted pyromellitimide and 1,4,5,8-naphthalenediimide.

    PubMed

    Trindade, Fabiane Jesus; Rey, José Fernando Queiruga; Brochsztain, Sergio

    2012-02-15

    This article describes the covalent grafting of pyromellitimide and 1,4,5,8-naphthalenediimide, which are organic semiconductors with very interesting electro-optical properties, onto the walls of mesoporous molecular sieves. The mesoporous materials MCM-41 and SBA-15 were first treated with 3-aminopropyltriethoxysilane, generating materials with a surface coverage of primary amino groups. These materials were further reacted with either pyromellitic dianhydride or 1,4,5,8-naphthalenetetracarboxylic dianhydride, generating surface-bound pyromellitimide or 1,4,5,8-naphthalenediimide, respectively. The success of the modification reactions was confirmed by elemental and thermogravimetric analyses, X-ray diffraction patterns and infrared, reflectance and fluorescence spectroscopies. The results indicated that the mesoporous structure of the new materials was preserved after the modification reactions and that the chromophores were included inside the mesoporous channels with stacked aromatic rings. PMID:22153336

  1. Synthesis and Antifungal Activity of Natural Product-Based 6-Alkyl-2,3,4,5-tetrahydropyridines

    PubMed Central

    Dai, Liyan; Jacob, Melissa R.; Khan, Shabana I.; Khan, Ikhlas A.; Clark, Alice M.; Li, Xing-Cong

    2011-01-01

    Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a–5g) that mimic the natural piperideines that were recently identified in the fire ant venom have been synthesized. Compounds 5c–5g with the C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexadecyl-2,3,4,5-tetrahydropyridine) and 5f (6-heptadecyl-2,3,4,5-tetrahydropyridine) being the most active. Compound 5e exhibited minimum fungicidal concentrations (MFCs) of 3.8, 15.0, 7.5, and 7.5 μg/mL against Cryptococcus neoformans, Candida albicans, Candida glabrata, and Candida krusei, respectively. The antifungal activities of these compounds appear to be associated with the C-6 side chain length. This study represents the first effort to evaluate antifungal activities of synthetic analogs of the newly identified fire ant venom alkaloids. PMID:21905650

  2. 3D Cell Entrapment as a Function of the Weight Percent of Peptide-Amphiphile Hydrogels

    PubMed Central

    Scott, Carolyn M.; Forster, Colleen L.; Kokkoli, Efrosini

    2015-01-01

    The design of scaffolds which mimic the stiffness, nanofiber structure, and biochemistry of the native extra-cellular matrix (ECM) has been a major objective for the tissue engineering field. Furthermore, mimicking the innate three dimensional (3D) environment of the ECM has been shown to significantly alter cellular response compared to traditional two dimensional (2D) culture. We report the development of a self-assembling, fibronectin-mimetic, peptide-amphiphile nanofiber scaffold for 3D cell culture. To form such a scaffold, 5 mol% of a bioactive PR_g fibronectin-mimetic peptide-amphiphile was mixed with 95 mol% of a diluent peptide-amphiphile (E2) whose purpose was to neutralize electrostatic interactions, increase the gelation kinetics and promote cell survival. Atomic force microscopy verified the fibrilar structure of the gels and the mechanical properties were characterized for various weight percent (wt%) formulations of the 5 mol% PR_g - 95 mol% E2 peptide-amphiphile mixture. The 0.5 wt% formulations had an elastic modulus of 429.0 ± 21.3 Pa while the 1.0 wt% peptide-amphiphile hydrogels had an elastic modulus of 808.6 ± 38.1 Pa. The presence of entrapped cells in the gels decreased the elastic modulus and the decrease was a function of the cell loading. While both formulations supported cell proliferation, the 0.5 wt% gels supported significantly greater NIH3T3/GFP fibroblast cell proliferation throughout the gels than the 1.0 wt% gels. However, compared to the 0.5 wt% formulations, the 1.0 wt% hydrogels promoted greater increase in mRNA expression and production of fibronectin and type IV collagen ECM proteins. This study suggests that this fibronectin-mimetic scaffold holds great promise in the advance of 3D culture applications and cell therapies. PMID:25970351

  3. Domain rearrangement of SRP protein Ffh upon binding 4.5S RNA and the SRP receptor FtsY

    PubMed Central

    BUSKIEWICZ, IWONA; KUBARENKO, ANDRIY; PESKE, FRANK; RODNINA, MARINA V.; WINTERMEYER, WOLFGANG

    2005-01-01

    The signal recognition particle (SRP) mediates membrane targeting of translating ribosomes displaying a signal-anchor sequence. In Escherichia coli, SRP consists of 4.5S RNA and a protein, Ffh, that recognizes the signal peptide emerging from the ribosome and the SRP receptor at the membrane, FtsY. In the present work, we studied the interactions between the NG and M domains in Ffh and their rearrangements upon complex formation with 4.5S RNA and/or FtsY. In free Ffh, the NG and M domains are facing one another in an orientation that allows cross-linking between positions 231 in the G domain and 377 in the M domain. There are binding interactions between the two domains, as the isolated domains form a strong complex. The interdomain contacts are disrupted upon binding of Ffh to 4.5S RNA, consuming a part of the total binding energy of 4.5S RNA-Ffh association that is roughly equivalent to the free energy of domain binding to each other. In the SRP particle, the NG domain binds to 4.5S RNA in a region adjacent to the binding site of the M domain. Ffh binding to FtsY also requires a reorientation of NG and M domains. These results suggest that in free Ffh, the binding sites for 4.5S RNA and FtsY are occluded by strong domain–domain interactions which must be disrupted for the formation of SRP or the Ffh-FtsY complex. PMID:15923378

  4. Domain rearrangement of SRP protein Ffh upon binding 4.5S RNA and the SRP receptor FtsY.

    PubMed

    Buskiewicz, Iwona; Kubarenko, Andriy; Peske, Frank; Rodnina, Marina V; Wintermeyer, Wolfgang

    2005-06-01

    The signal recognition particle (SRP) mediates membrane targeting of translating ribosomes displaying a signal-anchor sequence. In Escherichia coli, SRP consists of 4.5S RNA and a protein, Ffh, that recognizes the signal peptide emerging from the ribosome and the SRP receptor at the membrane, FtsY. In the present work, we studied the interactions between the NG and M domains in Ffh and their rearrangements upon complex formation with 4.5S RNA and/or FtsY. In free Ffh, the NG and M domains are facing one another in an orientation that allows cross-linking between positions 231 in the G domain and 377 in the M domain. There are binding interactions between the two domains, as the isolated domains form a strong complex. The interdomain contacts are disrupted upon binding of Ffh to 4.5S RNA, consuming a part of the total binding energy of 4.5S RNA-Ffh association that is roughly equivalent to the free energy of domain binding to each other. In the SRP particle, the NG domain binds to 4.5S RNA in a region adjacent to the binding site of the M domain. Ffh binding to FtsY also requires a reorientation of NG and M domains. These results suggest that in free Ffh, the binding sites for 4.5S RNA and FtsY are occluded by strong domain-domain interactions which must be disrupted for the formation of SRP or the Ffh-FtsY complex. PMID:15923378

  5. Lipotoxic disruption of NHE1 interaction with PI(4,5)P2 expedites proximal tubule apoptosis

    PubMed Central

    Khan, Shenaz; Abu Jawdeh, Bassam G.; Goel, Monu; Schilling, William P.; Parker, Mark D.; Puchowicz, Michelle A.; Yadav, Satya P.; Harris, Raymond C.; El-Meanawy, Ashraf; Hoshi, Malcolm; Shinlapawittayatorn, Krekwit; Deschênes, Isabelle; Ficker, Eckhard; Schelling, Jeffrey R.

    2014-01-01

    Chronic kidney disease progression can be predicted based on the degree of tubular atrophy, which is the result of proximal tubule apoptosis. The Na+/H+ exchanger NHE1 regulates proximal tubule cell survival through interaction with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], but pathophysiologic triggers for NHE1 inactivation are unknown. Because glomerular injury permits proximal tubule luminal exposure and reabsorption of fatty acid/albumin complexes, we hypothesized that accumulation of amphipathic, long-chain acyl-CoA (LC-CoA) metabolites stimulates lipoapoptosis by competing with the structurally similar PI(4,5)P2 for NHE1 binding. Kidneys from mouse models of progressive, albuminuric kidney disease exhibited increased fatty acids, LC-CoAs, and caspase-2–dependent proximal tubule lipoapoptosis. LC-CoAs and the cytosolic domain of NHE1 directly interacted, with an affinity comparable to that of the PI(4,5)P2-NHE1 interaction, and competing LC-CoAs disrupted binding of the NHE1 cytosolic tail to PI(4,5)P2. Inhibition of LC-CoA catabolism reduced NHE1 activity and enhanced apoptosis, whereas inhibition of proximal tubule LC-CoA generation preserved NHE1 activity and protected against apoptosis. Our data indicate that albuminuria/lipiduria enhances lipotoxin delivery to the proximal tubule and accumulation of LC-CoAs contributes to tubular atrophy by severing the NHE1-PI(4,5)P2 interaction, thereby lowering the apoptotic threshold. Furthermore, these data suggest that NHE1 functions as a metabolic sensor for lipotoxicity. PMID:24531551

  6. Phosphatidylinositol (3,4,5)-Trisphosphate Activity Probes for the Labeling and Proteomic Characterization of Protein Binding Partners

    PubMed Central

    Rowland, Meng M.; Bostic, Heidi E.; Gong, Denghuang; Speers, Anna E.; Lucas, Nathan; Cho, Wonhwa; Cravatt, Benjamin F.; Best, Michael D.

    2013-01-01

    Phosphatidylinositol polyphosphate lipids, such as phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3), regulate critical biological processes, many of which are aberrant in disease. These lipids often act as site-specific ligands in interactions that enforce membrane-association of protein binding partners. Herein, we describe the development of bifunctional activity probes corresponding to the headgroup of PI(3,4,5)P3 that are effective for identifying and characterizing protein binding partners from complex samples, namely cancer cell extracts. These probes contain both a photoaffinity tag for covalent labeling of target proteins as well as a secondary handle for subsequent detection or manipulation of labeled proteins. Probes bearing different secondary tags were exploited, either by direct attachment of a fluorescent dye for optical detection or by using an alkyne that can be derivatized after protein labeling via click chemistry. First, we describe the design and modular synthetic strategy used to generate multiple probes with different reporter tags of use for characterizing probe-labeled proteins. Next, we report initial labeling studies using purified protein, the PH domain of Akt, in which probes were found to label this target, as judged by on-gel detection. Furthermore, protein labeling was abrogated by controls including competition with an unlabeled PI(3,4,5)P3 headgroup analog as well as through protein denaturation, indicating specific labeling. In addition, probes featuring different linker lengths between the PI(3,4,5)P3 headgroup and photoaffinity tag led to variations in protein labeling, indicating that a shorter linker was more effective in this case. Finally, proteomic labeling studies were performed using cell extracts, labeled proteins were observed by in-gel detection and characterized using post-labeling with biotin, affinity chromatography and identification via tandem mass spectrometry. These studies yielded a total of 265 proteins

  7. 30 CFR 57.22240 - Actions at 2.0 percent methane (V-A mines).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 2.0 percent methane (V-A mines). 57... MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22240 Actions at 2.0 percent methane (V-A mines). If methane reaches 2.0 percent in the mine atmosphere, all persons other...

  8. A Turn-on and Reversible Fluorescence Sensor for Zinc Ion Based on 4,5-Diazafluorene Schiff Base.

    PubMed

    Li, Hui; Zhang, ShuJiang; Gong, ChenLiang; Wang, JianZhi; Wang, Feng

    2016-09-01

    A new 4,5-diazafluorene-based fluorescent chemosensor has been synthesized by Schiff base condensation of 9,9-bis(3,5-dimethyl-4-aminophenyl)-4,5-diazafluorene with salicylaldehyde. The interaction of Schiff base with different metal ions has been studied over photofluorescent spectra. The results showed that Schiff base exhibited 194-fold enhancements in fluorescence at 465 nm after Zn(2+) ions. Such fluorescent responses could be detected by naked eye under UV-lamp. The complex solution (L-Zn(2+)) exhibited reversibility with EDTA. PMID:27430628

  9. Composite lead for conducting an electrical current between 75-80K and 4.5K temperatures

    DOEpatents

    Negm, Yehia; Zimmerman, George O.; Powers, Jr., Robert E.; McConeghy, Randy J.; Kaplan, Alvaro

    1994-12-27

    A composite lead is provided which electrically links and conducts a current between about 75-80K. and liquid helium temperature of about 4.5K. The composite lead may be employed singly or in multiples concurrently to provide conduction of electrical current from normal conductors and semi-conductors at room temperature to superconductors operating at 4.5K. In addition, a variety of organizationl arrangements and assemblies are provided by which the mechanical strength and electrical reliability of the composite lead is maintained.

  10. Composite lead for conducting an electrical current between 75--80K and 4. 5K temperatures

    DOEpatents

    Negm, Y.; Zimmerman, G.O.; Powers, R.E. Jr.; McConeghy, R.J.; Kaplan, A.

    1994-12-27

    A composite lead is provided which electrically links and conducts a current between about 75-80K and liquid helium temperature of about 4.5K. The composite lead may be employed singly or in multiples concurrently to provide conduction of electrical current from normal conductors and semi-conductors at room temperature to superconductors operating at 4.5K. In addition, a variety of organizational arrangements and assemblies are provided by which the mechanical strength and electrical reliability of the composite lead is maintained. 12 figures.

  11. Process for manufacturing bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene

    SciTech Connect

    Rasmussen, Paul George; Lawton, Richard Graham

    2014-06-03

    A process to manufacture substituted tetracyano-hexaazatricyclics with the substitutions occurring at the 9 and 10 hydrogens. The process begins with 2,3-dichloro-5,6-dicyanopyrazine, which is reacted to form the desired tetracyano-hexaazatricyclic. Different process embodiments enable different reaction paths to the desired tetracyano-hexaazatricyclic. Different tetracyano-hexaazatricyclic embodiments include bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene and bis(2-methoxyethoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracen- e.

  12. Implementation and comparison of a suite of heat stress metrics within the Community Land Model version 4.5

    NASA Astrophysics Data System (ADS)

    Buzan, J. R.; Oleson, K.; Huber, M.

    2014-08-01

    We implement and analyze 13 different metrics (4 moist thermodynamic quantities and 9 heat stress metrics) in the Community Land Model (CLM4.5), the land surface component of the Community Earth System Model (CESM). We call these routines the HumanIndexMod. These heat stress metrics embody three philosophical approaches: comfort, physiology, and empirically based algorithms. The metrics are directly connected to CLM4.5 BareGroundFuxesMod, CanopyFluxesMod, SlakeFluxesMod, and UrbanMod modules in order to differentiate between the distinct regimes even within one gridcell. This allows CLM4.5 to calculate the instantaneous heat stress at every model time step, for every land surface type, capturing all aspects of non-linearity in moisture-temperature covariance. Secondary modules for initialization and archiving are modified to generate the metrics as standard output. All of the metrics implemented depend on the covariance of near surface atmospheric variables: temperature, pressure, and humidity. Accurate wet bulb temperatures are critical for quantifying heat stress (used by 5 of the 9 heat stress metrics). Unfortunately, moist thermodynamic calculations for calculating accurate wet bulb temperatures are not in CLM4.5. To remedy this, we incorporated comprehensive water vapor calculations into CLM4.5. The three advantages of adding these metrics to CLM4.5 are (1) improved thermodynamic calculations within climate models, (2) quantifying human heat stress, and (3) that these metrics may be applied to other animals as well as industrial applications. Additionally, an offline version of the HumanIndexMod is available for applications with weather and climate datasets. Examples of such applications are the high temporal resolution CMIP5 archived data, weather and research forecasting models, CLM4.5 flux tower simulations (or other land surface model validation studies), and local weather station data analysis. To demonstrate the capabilities of the HumanIndexMod, we

  13. Tetrazolo(1,5-a)pyridines and furazano(4,5-b)pyridine 1-oxides

    SciTech Connect

    Lowe-Ma, C.K.; Nissan, R.A.; Wilson, W.S. )

    1990-06-08

    Tetrazolo(1,5-a)pyridines may be prepared by the reaction of azide ion with 2-chloropyridines. These tetrazolo(1,5-a)pyridines are shown to be in equilibrium with the corresponding 2-azidopyridines. Furazano(4,5-b)pyridine 1-oxides may be prepared by thermolysis of the appropriate 4-nitrotetrazolo(1,2-a)pyridines, presumably via the corresponding 2-azido-3-nitropyridines. The furazano(4,5-b)pyridine 1-oxides are found to be in equilibrium with the 3-oxides. {sup 1}H and {sup 13}C NMR are used to examine this equilibrium.

  14. Molecular design of new nitramine explosives: 1,3,5,7-tetranitro-8-(nitromethyl)-4-imidazolino[4,5-b]4-imidazolino-[4,5-e] pyridine and its N-oxide.

    PubMed

    Liu, Hui; Du, Hongchen; Wang, Guixiang; Liu, Yan; Gong, Xuedong

    2012-04-01

    Two new nitramine compounds containing pyridine, 1,3,5,7-tetranitro-8-(nitromethyl) -4-imidazolino[4,5-b]4-imidazolino-[4,5-e]pyridine and its N-oxide 1,3,5,7-tetranitro-8- (nitromethyl)-4-imidazolino[4,5-b]4-imidazolino-[4,5-e]pyridine-4-ol were proposed. Density functional theory (DFT) has been employed to study the molecular geometries, electronic structures, infrared spectra, and thermodynamic properties at the B3LYP/6-31G* level. Their detonation performances evaluated using the Kamlet-Jacobs equations with the calculated densities and heats of formation are superior to those of HMX. The predicted densities of them were ca. 2 g cm(-3), detonation velocities were over 9 km s(-1), and detonation pressures were about 40 GPa, showing that they may be potential candidates of high energy density materials (HEDMs). The natural bond orbital analysis indicated that N-NO(2) bond is the trigger bond during thermolysis process. The stability of the title compounds is slightly lower than that of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12- hexaazaisowurtzitane (CL-20). The results of this study may provide basic information for the molecular design of new HEDMs. PMID:21748326

  15. The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma membrane and viral egress

    PubMed Central

    Johnson, Kristen A.; Taghon, Geoffrey J. F.; Scott, Jordan L.; Stahelin, Robert V.

    2016-01-01

    VP40 is one of eight proteins encoded by the Ebola Virus (EBOV) and serves as the primary matrix protein, forming virus like particles (VLPs) from mammalian cells without the need for other EBOV proteins. While VP40 is required for viral assembly and budding from host cells during infection, the mechanisms that target VP40 to the plasma membrane are not well understood. Phosphatidylserine is required for VP40 plasma membrane binding, VP40 hexamer formation, and VLP egress, However, PS also becomes exposed on the outer membrane leaflet at sites of VP40 budding, raising the question of how VP40 maintains an interaction with the plasma membrane inner leaflet when PS is flipped to the opposite side. To address this question, cellular and in vitro assays were employed to determine if phosphoinositides are important for efficient VP40 localization to the plasma membrane. Cellular studies demonstrated that PI(4,5)P2 was an important component of VP40 assembly at the plasma membrane and subsequent virus like particle formation. Additionally, PI(4,5)P2 was required for formation of extensive oligomers of VP40, suggesting PS and PI(4,5)P2 have different roles in VP40 assembly where PS regulates formation of hexamers from VP40 dimers and PI(4,5)P2 stabilizes and/or induces extensive VP40 oligomerization at the plasma membrane. PMID:26753796

  16. Atomic Clocks

    NASA Astrophysics Data System (ADS)

    Wynands, Robert

    Time is a strange thing. On the one hand it is arguably the most inaccessible physical phenomenon of all: both in that it is impossible to manipulate or modify—for all we know—and in that even after thousands of years mankind's philosophers still have not found a fully satisfying way to understand it. On the other hand, no other quantity can be measured with greater precision. Today's atomic clocks allow us to reproduce the length of the second as the SI unit of time with an uncertainty of a few parts in 1016—orders of magnitude better than any other quantity. In a sense, one can say [1

  17. Three-dimensional atomic-scale imaging of impurity segregation to line defects

    PubMed

    Blavette; Cadel; Fraczkiewicz; Menand

    1999-12-17

    Clouds of impurity atoms near line defects are believed to affect the plastic deformation of alloys. Three-dimensional atom probe techniques were used to image these so-called Cottrell atmospheres directly. Ordered iron-aluminum alloys (40 atomic percent aluminum) doped with boron (400 atomic parts per million) were investigated on an atomic scale along the <001> direction. A boron enrichment was observed in the vicinity of an <001> edge dislocation. The enriched region appeared as a three-dimensional pipe 5 nanometers in diameter, tangent to the dislocation line. The dislocation was found to be boron-enriched by a factor of 50 (2 atomic percent) relative to the bulk. The local boron enrichment is accompanied by a strong aluminum depletion of 20 atomic percent. PMID:10600736

  18. Effects of thermomechanical processing on tensile and long-time creep behavior of Nb-1 percent Zr-0.1 percent C sheet

    NASA Technical Reports Server (NTRS)

    Titran, Robert H.; Uz, Mehmet

    1994-01-01

    Effects of thermomechanical processing on the mechanical properties of Nb-1 wt. percent Zr-0.1 wt. percent C, a candidate alloy for use in advanced space power systems, were investigated. Sheet bars were cold rolled into 1-mm thick sheets following single, double, or triple extrusion operations at 1900 K. All the creep and tensile specimens were given a two-step heat treatment 1 hr at 1755 K + 2 hr 1475 K prior to testing. Tensile properties were determined at 300 as well as at 1350 K. Microhardness measurements were made on cold rolled, heat treated, and crept samples. Creep tests were carried out at 1350 K and 34.5 MPa for times of about 10,000 to 19,000 hr. The results show that the number of extrusions had some effects on both the microhardness and tensile properties. However, the long-time creep behavior of the samples were comparable, and all were found to have adequate properties to meet the design requirements of advanced power systems regardless of thermomechanical history. The results are discussed in correlation with processing and microstructure, and further compared to the results obtained from the testing of Nb-1 wt. percent Zr and Nb-1 wt. percent Zr-0.06 wt. percent C alloys.

  19. Preliminary investigation of the combustion of a 50 percent pentaborane - 50 percent JP-4 fuel blend in a turbojet combustor at simulated altitude conditions

    NASA Technical Reports Server (NTRS)

    Branstetter, J Robert; Kaufman, Warner B; Gibbs, James B

    1957-01-01

    A preliminary investigation was conducted to determine the combustion characteristics of a fuel composed of 50 percent pentaborane and 50 percent JP-4 (MIL-F-5624A) by weight in a turbojet combustor. A combustor designed to fit the housing of a J33-A-23 turbojet engine was selected for convenience. The fuel was evaluated at two engine conditions simulating altitudes of 40,000 and 57,000 feet, an engine speed of 85 percent of rated rpm, and a flight Mach number of 0.6. The pentaborane blend was initially evaluated in combustors developed for pure pentaborane and diborane reported in NACA RM E53B18 and RM E52L15. The performance of the blend was unsatisfactory in these combustors. A new combustor was then developed which provided combustor efficiencies measured from 91 to 101 percent as compared with efficiencies of 92 to 94 percent previously obtained for pentaborane at comparable conditions. Additional refinements of design details are needed to obtain lower oxide deposits and a more uniform outlet temperature profile; however, the combustor is believed to incorporate some of the design principles required to obtain satisfactory over-all performance with the fuel blend investigated.

  20. A record setting amorphous silicon alloy triple-junction solar cell with 14.6{percent} initial and 12.8{percent} stable efficiencies

    SciTech Connect

    Yang, J.; Banerjee, A.; Guha, S.

    1997-02-01

    World record 14.6{percent} initial and 12.8{percent} stable conversion efficiencies have been achieved using amorphous silicon based alloy in a spectrum-splitting, triple-junction structure. This performance exceeds our previous record of 13.2{percent} initial and 11.8{percent} stable efficiencies and establishes a new milestone toward reaching the 15{percent} stable module goal. Key factors leading to this major advance include: (a) Improvement in the low bandgap amorphous silicon-germanium component cell that resulted in enhanced red response and provided desired current mismatching, (b) improvement in the pn tunnel junction between component cells by incorporating microcrystalline p and n layers in a multilayered structure that resulted in reduced optical and electrical losses, and (c) improvement in the top conducting oxide that resulted in reduced absorption and enhanced blue response without increasing the top cell thickness. Details of these advances along with light-soaking data for high efficiency cells will be discussed. {copyright} {ital 1997 American Institute of Physics.}