Sample records for strong ca ii


    International Nuclear Information System (INIS)

    Beck, C.; Choudhary, D. P.; Rezaei, R.; Louis, R. E.


    We present a fast (<<1 s per profile) inversion code for solar Ca II lines. The code uses an archive of spectra that are synthesized prior to the inversion under the assumption of local thermodynamic equilibrium (LTE). We show that it can be successfully applied to spectrograph data or more sparsely sampled spectra from two-dimensional spectrometers. From a comparison to a non-LTE inversion of the same set of spectra, we derive a first-order non-LTE correction to the temperature stratifications derived in the LTE approach. The correction factor is close to unity up to log τ ∼ –3 and increases to values of 2.5 and 4 at log τ = –6 in the quiet Sun and the umbra, respectively

  2. Asymmetries of the solar Ca II lines

    International Nuclear Information System (INIS)

    Heasley, J.N.


    A theoretical study of the influence of propagating acoustic pulses in the solar chromosphere upon the line profiles of the Ca II resonance and infrared triplet lines has been made. The major objective has been to explain the observed asymmetries seen in the cores of the H and K lines and to predict the temporal behavior of the infrared lines caused by passing acoustic or shock pulses. The velocities in the pulses, calculated from weak shock theory, have been included consistently in the non-LTE calculations. The results of the calculations show that these lines are very sensitive to perturbations in the background atmosphere caused by the pulses. Only minor changes in the line shapes result from including the velocities consistently in the line source function calculations. The qualitative changes in the line profiles vary markedly with the strength of the shock pulses. The observed differences in the K line profiles seen on the quiet Sun can be explained in terms of a spectrum of pulses with different wavelengths and initial amplitudes in the photosphere. (Auth.)

  3. CaII Κ Imaging to Understand UV Irradiance Variability

    Indian Academy of Sciences (India)


    agencies responsible for CaII emission are: the plages, the network, and the intranet work elements. The changes in the network and intranetwork elements related to solar activity are less understood, especially because of the lack of systematic and quantitative measurements of these chromospheric features. In our earlier ...

  4. CaII Κ Imaging to Understand UV Irradiance Variability

    Indian Academy of Sciences (India)


    (NSO/Sac Peak). The main purpose of the present paper is to separate and to derive the relative intensity and area of various chromospheric features from 424 ... 2. Results and discussion. To analyze the CaII Κ spectroheliograms and to separate various chromospheric magnetic features, we have calculated histograms ...

  5. Tripeptidyl peptidase II regulates sperm function by modulating intracellular Ca(2+ stores via the ryanodine receptor.

    Directory of Open Access Journals (Sweden)

    Yuchuan Zhou

    Full Text Available Recent studies have identified Ca(2+ stores in sperm cells; however, it is not clear whether these Ca(2+ stores are functional and how they are mobilized. Here, in vitro and in vivo, we determined that tripeptidyl peptidase II antagonists strongly activated the cAMP/PKA signaling pathway that drives sperm capacitation-associated protein tyrosine phosphorylation. We demonstrated that in the absence of Ca(2+, TPIII antagonists elevated the intracellular Ca(2+ levels in sperm, resulting in a marked improvement in sperm movement, capacitation, acrosome reaction, and the in vitro fertilizing ability. This antagonist-induced release of intracellular Ca(2+ could be blocked by the inhibitors of ryanodine receptors (RyRs which are the main intracellular Ca(2+ channels responsible for releasing stored Ca(2+. Consistent with these results, indirect immunofluorescence assay using anti-RyR antibodies further validated the presence of RyR3 in the acrosomal region of mature sperm. Thus, TPPII can regulate sperm maturation by modulating intracellular Ca(2+ stores via the type 3 RyR.

  6. Catalog of strong MgII absorbers (Lawther+, 2012)

    DEFF Research Database (Denmark)

    Lawther, D.; Paarup, Troels; Schmidt, Morten L.


    Here we present a catalog of strong (rest equivalent width Wr> intervening Mg II absorbers in the SDSS Data Release 7 quasar catalog (2010AJ....139.2360S, Cat. VII/260). The intervening absorbers were found by a semi-automatic algorithm written in IDL - for details of the algorithm see section 2...... of our paper. A subset of the absorbers have been visually inspected - see the MAN_OK flag in the catalog. The number of sightlines searched, tabulated by absorber redshift, i.e. g(z), is available as an ASCII table (for S/N>8 and S/N>15). All analysis in our paper is based on the SNR>8 coverage......, and considers only sight-lines towards non-BAL quasars. Any questions regarding the catalog should be sent to Daniel Lawther (unclellama(at) (3 data files)....

  7. Flavonoid Myricetin Modulates GABAA Receptor Activity through Activation of Ca2+ Channels and CaMK-II Pathway

    Directory of Open Access Journals (Sweden)

    Xiao Hu Zhang


    Full Text Available The flavonoid myricetin is found in several sedative herbs, for example, the St. John's Wort, but its influence on sedation and its possible mechanism of action are unknown. Using patch-clamp technique on a brain slice preparation, the present study found that myricetin promoted GABAergic activity in the neurons of hypothalamic paraventricular nucleus (PVN by increasing the decay time and frequency of the inhibitory currents mediated by GABAA receptor. This effect of myricetin was not blocked by the GABAA receptor benzodiazepine- (BZ- binding site antagonist flumazenil, but by KN-62, a specific inhibitor of the Ca2+/calmodulin-stimulated protein kinase II (CaMK-II. Patch clamp and live Ca2+ imaging studies found that myricetin could increase Ca2+ current and intracellular Ca2+ concentration, respectively, via T- and L-type Ca2+ channels in rat PVN neurons and hypothalamic primary culture neurons. Immunofluorescence staining showed increased phosphorylation of CaMK-II after myricetin incubation in primary culture of rat hypothalamic neurons, and the myricetin-induced CaMK-II phosphorylation was further confirmed by Western blotting in PC-12 cells. The present results suggest that myricetin enhances GABAA receptor activity via calcium channel/CaMK-II dependent mechanism, which is distinctively different from that of most existing BZ-binding site agonists of GABAA receptor.

  8. Tracers of Chromospheric Structure. I. Observations of Ca II K and Hα in M Dwarfs (United States)

    Walkowicz, Lucianne M.; Hawley, Suzanne L.


    We report on our observing program4This paper is based on observations obtained with the Apache Point Observatory 3.5 m telescope, which is owned and operated by the Astrophysical Research Consortium. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. to capture simultaneous spectra of Ca II and Balmer lines in a sample of nearby M3 dwarfs. Our goal is to investigate the chromospheric temperature structure required to produce these lines at the observed levels. We find a strong positive correlation between instantaneous measurements of Ca II K and the Balmer lines in active stars, although these lines may not be positively correlated in time-resolved measurements. The relationship between Hα and Ca II K remains ambiguous for weak and intermediate activity stars, with Hα absorption corresponding to a range of Ca II K emission. A similar relationship is also observed between Ca II K and the higher-order Balmer lines. As our sample consists of a single spectral type, correlations between these important chromospheric tracers cannot be ascribed to continuum effects, as suggested by other authors. These data confirm prior nonsimultaneous observations of the Hα line behavior with increasing activity, showing an initial increase in the Hα absorption with increasing Ca II K emission, prior to Hα filling in and eventually becoming a pure emission line in the most active stars. We also compare our optical measurements with archival UV and X-ray measurements, finding a positive correlation between the chromospheric and coronal emission for both high and intermediate activity stars. We compare our results with previous determinations of the active fraction of low-mass stars

  9. Spectroscopic and thermal degradation behavior of Mg(II, Ca(II, Ba(II and Sr(II complexes with paracetamol drug

    Directory of Open Access Journals (Sweden)

    Moamen S. Refat


    Full Text Available Complexes of Mg(II, Ca(II, Ba(II and Sr(II with paracetamol drug were synthesized and characterized by elemental analysis, conductivity, UV–Vis, IR, and 1H NMR spectroscopy and thermal analysis, as well as screened for antimicrobial activity. The IR spectral data suggested that the ligand behaves as paracetamol behaves as a neutral bidentate ligand coordinated to the metal ions via the lone pair of electrons of nitrogen and carbonyl-O atoms of the amide group. From the microanalytical data, the stoichiometry of the complexes reacts with Mg(II, Ca(II, Ba(II and Sr(II by molar ratios (2:1 (paracetamol:metal ion. The thermal behavior (TG/DTG of the complexes was studied. The ligand and their metal complexes were screened against both of antibacterial and fungicidal activities.

  10. Ca II H and K emission from late-type stars

    International Nuclear Information System (INIS)

    Middlekoop, F.


    This thesis is based on a study of the Ca II H and K emission features of late main-sequence stars. In Chapter II it is shown that rotation periods can be determined from a modulation in the Ca II H and K signal for many stars in a broad range of spectral types. In Chapter III it is shown that a clear correlation exists between Ca II H and K emission and rotational velocity in active main-sequence stars. There is an indication for a (probably colour-dependent) critical velocity at which the Ca II H and K emission suddenly drops. Chapter IV discusses the dependence of Ca II H and K emission on the rotation rate for evolved stars. (Auth./C.F.)

  11. Intracellular angiotensin II inhibits heterologous receptor stimulated Ca2+ entry

    NARCIS (Netherlands)

    Filipeanu, CM; Brailoiu, E; Henning, RH; Deelman, LE; de Zeeuw, D; Nelemans, SA


    Recent studies show that angiotensin II (AngII) can act from within the cell, possibly via intracellular receptors pharmacologically different from typical plasma membrane AngII receptors. The role of this intracellular AngII (AngII(i)) is unclear. Besides direct effects of AngII(i) on cellular

  12. Rotation and kinematics of the premain-sequence stars in Taurus-Auriga with Ca II emission (United States)

    Hartmann, Lee W.; Soderblom, David R.; Stauffer, John R.


    Radial velocities and v sin i values for the stars in the Taurus-Auriga region that were found to have strong Ca II H and K emission by Herbig, Vrba, and Rydgren 'HVR', (1986) are reported. Most of the velocities are determined to better than 2 km/s precision. The kinematic properties of the Ca II emission stars with strong Li are found to be indistinguishable from conventional T Tauris in Taurus-Auriga, contrary to HVR. These Li-rich stars also rotate like T Tauris. Most of the stars that lack Li are probable or possible members of the Hyades, in the foreground, and are among the brightest and most active stars in that cluster for their spectral types. It is suggested following Jones and Herbig (1979), that the apparent absence of low-mass stars older than 10 Myr in Taurus-Auriga is real, and is due to the finite lifetime of the cloud.

  13. Rotation and kinematics of the premain-sequence stars in Taurus-Auriga with CA II emission (United States)

    Hartmann, Lee W.; Soderblom, David R.; Stauffer, John R.


    The authors report radial velocities and v sin i values for the stars in the Taurus-Auriga region that were found to have strong Ca II H and K emission by Herbig, Vrba, and Rydgren (HVR). Most of the velocities are determined to better than 2 km s-1 precision. The authors find the kinematic properties of the Ca II emission stars with strong Li to be indistinguishable from conventional T Tauris in Taurus-Auriga, contrary to HVR. These Li-rich stars also rotate like T Tauris. Most of the stars that lack Li are probable or possible members of the Hyades, in the foreground, and are among the brightest and most active stars in that cluster for their spectral types. The authors suggest, following Jones and Herbig, that the apparent absence of low-mass stars older than 10 Myr in Taurus-Auriga is real, and is due to the finite lifetime of the cloud.

  14. Differential Distribution of Retinal Ca2+/Calmodulin-Dependent Kinase II (CaMKII Isoforms Indicates CaMKII-β and -δ as Specific Elements of Electrical Synapses Made of Connexin36 (Cx36

    Directory of Open Access Journals (Sweden)

    Stephan Tetenborg


    Full Text Available AII amacrine cells are essential interneurons of the primary rod pathway and transmit rod-driven signals to ON cone bipolar cells to enable scotopic vision. Gap junctions made of connexin36 (Cx36 mediate electrical coupling among AII cells and between AII cells and ON cone bipolar cells. These gap junctions underlie a remarkable degree of plasticity and are modulated by different signaling cascades. In particular, Ca2+/calmodulin-dependent protein kinase II (CaMKII has been characterized as an important regulator of Cx36, capable of potentiating electrical coupling in AII cells. However, it is unclear which CaMKII isoform mediates this effect. To obtain a more detailed understanding of the isoform composition of CaMKII at retinal gap junctions, we analyzed the retinal distribution of all four CaMKII isoforms using confocal microscopy. These experiments revealed a differential distribution of CaMKII isoforms: CaMKII-α was strongly expressed in starburst amacrine cells, which are known to lack electrical coupling. CaMKII-β was abundant in OFF bipolar cells, which form electrical synapses in the outer and the inner retina. CaMKII-γ was diffusely distributed across the entire retina and could not be assigned to a specific cell type. CaMKII-δ labeling was evident in bipolar and AII amacrine cells, which contain the majority of Cx36-immunoreactive puncta in the inner retina. We double-labeled retinas for Cx36 and the four CaMKII isoforms and revealed that the composition of the CaMKII enzyme differs between gap junctions in the outer and the inner retina: in the outer retina, only CaMKII-β colocalized with Cx36-containing gap junctions, whereas in the inner retina, CaMKII-β and -δ colocalized with Cx36. This finding suggests that gap junctions in the inner and the outer retina may be regulated differently although they both contain the same connexin. Taken together, our study identifies CaMKII-β and -δ as Cx36-specific regulators in the mouse

  15. Targeted activation of the hippocampal CA2 area strongly enhances social memory. (United States)

    Smith, A S; Williams Avram, S K; Cymerblit-Sabba, A; Song, J; Young, W S


    Social cognition enables individuals to understand others' intentions. Social memory is a necessary component of this process, for without it, subsequent encounters are devoid of any historical information. The CA2 area of the hippocampus, particularly the vasopressin 1b receptor (Avpr1b) expressed there, is necessary for memory formation. We used optogenetics to excite vasopressin terminals, originating from the hypothalamic paraventricular nucleus, in the CA2 of mice. This markedly enhanced their social memory if the stimulation occurred during memory acquisition, but not retrieval. This effect was blocked by an Avpr1b antagonist. Finally, this enhanced memory is resistant to the social distraction of an introduced second mouse, important for socially navigating populations of individuals. Our results indicate the CA2 can increase the salience of social signals. Targeted pharmacotherapy with Avpr1b agonists or deep brain stimulation of the CA2 are potential avenues of treatment for those with declining social memory as in various dementias.

  16. Study of the Sextans dwarf spheroidal galaxy from the DART Ca II triplet survey

    NARCIS (Netherlands)

    Battaglia, G.; Tolstoy, E.; Helmi, A.; Irwin, M.; Parisi, P.; Hill, V.; Jablonka, P.

    We use Very Large Telescope (VLT)/Fibre Large Array Multi Element Spectrograph (FLAMES) intermediate-resolution (R˜ 6500) spectra of individual red giant branch stars in the near-infrared Ca II triplet (CaT) region to investigate the wide-area metallicity properties and internal kinematics of the

  17. Observations of the Ca II IR Triplet in High Luminosity Quasars ...

    Indian Academy of Sciences (India)

    supplement the sample presented by Martínez-Aldama et al. (2015) – allow us to confirm the constraints on physical conditions and location of the region emitting the low ionization lines, as well as the relation between. Ca II and Fe II. Key words. Quasars: general—quasars: emission lines—lines: profiles— star formation. 1.

  18. A novel mechanism for Ca2+/calmodulin-dependent protein kinase II targeting to L-type Ca2+channels that initiates long-range signaling to the nucleus. (United States)

    Wang, Xiaohan; Marks, Christian R; Perfitt, Tyler L; Nakagawa, Terunaga; Lee, Amy; Jacobson, David A; Colbran, Roger J


    Neuronal excitation can induce new mRNA transcription, a phenomenon called excitation-transcription (E-T) coupling. Among several pathways implicated in E-T coupling, activation of voltage-gated L-type Ca 2+ channels (LTCCs) in the plasma membrane can initiate a signaling pathway that ultimately increases nuclear CREB phosphorylation and, in most cases, expression of immediate early genes. Initiation of this long-range pathway has been shown to require recruitment of Ca 2+ -sensitive enzymes to a nanodomain in the immediate vicinity of the LTCC by an unknown mechanism. Here, we show that activated Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) strongly interacts with a novel binding motif in the N-terminal domain of Ca V 1 LTCC α1 subunits that is not conserved in Ca V 2 or Ca V 3 voltage-gated Ca 2+ channel subunits. Mutations in the Ca V 1.3 α1 subunit N-terminal domain or in the CaMKII catalytic domain that largely prevent the in vitro interaction also disrupt CaMKII association with intact LTCC complexes isolated by immunoprecipitation. Furthermore, these same mutations interfere with E-T coupling in cultured hippocampal neurons. Taken together, our findings define a novel molecular interaction with the neuronal LTCC that is required for the initiation of a long-range signal to the nucleus that is critical for learning and memory. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. CA-125 level as a prognostic indicator in type I and type II epithelial ovarian cancer. (United States)

    Chen, Xiaoxiang; Zhang, Jing; Cheng, Wenjun; Chang, Doo Young; Huang, Jianfei; Wang, Xuan; Jia, Lizhou; Rosen, Daniel G; Zhang, Wei; Yang, Da; Gershenson, David M; Sood, Anil K; Bast, Robert C; Liu, Jinsong


    Most patients with epithelial ovarian cancer achieve a complete clinical remission (CCR) with normal CA-125 but will still relapse and die from their disease. The present study was designed to determine whether CA-125 levels before, during, and after primary treatment provide prognostic information for both type I and type II ovarian cancer. In this retrospective study, we identified 410 patients with epithelial ovarian cancer who had achieved a CCR between 1984 and 2011. A Cox proportional hazards model and log-rank test were used to assess associations between the nadir CA-125, histotype, and prognosis. The baseline serum CA-125 concentration was higher in patients with type II ovarian cancer than in those with type I ovarian cancer (P CA-125 was an independent predictor of progression-free survival (PFS; P CA-125 of 10 U/mL or less and 13.6 and 64.6 months in those with CA-125 of 11 to 35 U/mL, respectively (P = 0.01 and P = 0.002, respectively). Histotype was an independent predictor of PFS (P = 0.041): the PFS and OS durations of the patients with type I ovarian cancer were longer than those of the patients with type II ovarian cancer (P CA-125 and histotype are predictive of PFS and OS durations in patients with ovarian cancers who experienced a CCR. Progression-free survival and OS durations were shorter in the patients with CA-125 levels of 11 to 35 U/mL and type II disease than in those with CA-125 levels of 10 U/mL or less and type I ovarian cancer.


    Energy Technology Data Exchange (ETDEWEB)

    Štěpán, Jiri [Astronomical Institute ASCR, Fričova 298, 251 65 Ondřejov (Czech Republic); Bueno, Javier Trujillo [Instituto de Astrofísica de Canarias, E-38205 La Laguna, Tenerife (Spain)


    We highlight the main results of a three-dimensional (3D) multilevel radiative transfer investigation about the solar disk-center polarization of the Ca ii 8542 Å line. First, through the use of a 3D model of the solar atmosphere, we investigate the linear polarization that occurs due to the atomic level polarization produced by the absorption and scattering of anisotropic radiation, taking into account the symmetry-breaking effects caused by its thermal, dynamic, and magnetic structure. Second, we study the contribution of the Zeeman effect to the linear and circular polarization. Finally, we show examples of the Stokes profiles produced by the joint action of the atomic level polarization and the Hanle and Zeeman effects. We find that the Zeeman effect tends to dominate the linear polarization signals only in the localized patches of opposite magnetic polarity, where the magnetic field is relatively strong and slightly inclined; outside such very localized patches, the linear polarization is often dominated by the contribution of atomic level polarization. We demonstrate that a correct modeling of this last contribution requires taking into account the symmetry-breaking effects caused by the thermal, dynamic, and magnetic structure of the solar atmosphere, and that in the 3D model used the Hanle effect in forward-scattering geometry (disk-center observation) mainly reduces the polarization corresponding to the zero-field case. We emphasize that, in general, a reliable modeling of the linear polarization in the Ca ii 8542 Å line requires taking into account the joint action of atomic level polarization and the Hanle and Zeeman effects.

  1. Electronic Structure and Oxidation State Changes in the Mn (4) Ca Cluster of Photosystem II

    Energy Technology Data Exchange (ETDEWEB)

    Yano, J.; Pushkar, Y.; Messinger, J.; Bergmann, U.; Glatzel, P.; Yachandra, V.K.; /SLAC


    Oxygen-evolving complex (Mn{sub 4}Ca cluster) of Photosystem II cycles through five intermediate states (S{sub i}-states, i = 0-4) before a molecule of dioxygen is released. During the S-state transitions, electrons are extracted from the OEC, either from Mn or alternatively from a Mn ligand. The oxidation state of Mn is widely accepted as Mn{sub 4}(III{sub 2},IV{sub 2}) and Mn{sub 4}(III,IV{sub 3}) for S{sub 1} and S{sub 2} states, while it is still controversial for the S{sub 0} and S{sub 3} states. We used resonant inelastic X-ray scattering (RIXS) to study the electronic structure of Mn{sub 4}Ca complex in the OEC. The RIXS data yield two-dimensional plots that provide a significant advantage by obtaining both K-edge pre-edge and L-edge-like spectra (metal spin state) simultaneously. We have collected data from PSII samples in the each of the S-states and compared them with data from various inorganic Mn complexes. The spectral changes in the Mn 1s2p{sub 3/2} RIXS spectra between the S-states were compared to those of the oxides of Mn and coordination complexes. The results indicate strong covalency for the electronic configuration in the OEC, and we conclude that the electron is transferred from a strongly delocalized orbital, compared to those in Mn oxides or coordination complexes. The magnitude for the S{sub 0} to S{sub 1}, and S{sub 1} to S{sub 2} transitions is twice as large as that during the S{sub 2} to S{sub 3} transition, indicating that the electron for this transition is extracted from a highly delocalized orbital with little change in charge density at the Mn atoms.

  2. New Policy Conclusions from Starting Strong II: An Update on the OECD Early Childhood Policy Reviews (United States)

    Bennett, John


    Since the start of the Organisation for Economic Co-operation and Development (OECD) thematic review of Early Childhood Education and Care (ECEC) Policy in 1998, some 20 countries across the world have been involved in the project. Recently the OECD has had a very successful launch of the report from the second round--Starting Strong II. This…

  3. Crystallization and preliminary X-ray crystallographic analysis of Ca{sup 2+}-independent and Ca{sup 2+}-dependent species of the type II antifreeze protein

    Energy Technology Data Exchange (ETDEWEB)

    Nishimiya, Yoshiyuki; Kondo, Hidemasa [Functional Protein Research Group, Research Institute of Genome-based Biofactory, National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira, Sapporo 062-8517 (Japan); Yasui, Masanori [Functional Protein Research Group, Research Institute of Genome-based Biofactory, National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira, Sapporo 062-8517 (Japan); Division of Biological Sciences, Graduate School of Science, Hokkaido University, N8W5, Kita, Sapporo 060-0808 (Japan); Sugimoto, Hiroshi [Biometal Science Laboratory, Riken SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Noro, Natsuko; Sato, Ryoko [Functional Protein Research Group, Research Institute of Genome-based Biofactory, National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira, Sapporo 062-8517 (Japan); Suzuki, Mamoru [Insititute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Miura, Ai [Functional Protein Research Group, Research Institute of Genome-based Biofactory, National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira, Sapporo 062-8517 (Japan); Tsuda, Sakae, E-mail: [Functional Protein Research Group, Research Institute of Genome-based Biofactory, National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira, Sapporo 062-8517 (Japan); Division of Biological Sciences, Graduate School of Science, Hokkaido University, N8W5, Kita, Sapporo 060-0808 (Japan)


    Crystallization and X-ray data analyses were successful for both Ca{sup 2+}-independent and Ca{sup 2+}-dependent species of the type II antifreeze protein. The resolution of the crystal was 1.35 Å for the Ca{sup 2+}-independent species, and was 1.25 and 1.06 Å for the Ca{sup 2+}-dependent species in the Ca{sup 2+}-free and -bound states, respectively. Ca{sup 2+}-independent and Ca{sup 2+}-dependent species of the type II antifreeze protein (AFP) were both crystallized using the hanging-drop vapour-diffusion method. It appeared that the crystal of the Ca{sup 2+}-independent species from Brachyosis rostratus belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 43.3, b = 48.4, c = 59.7 Å, and diffraction data were collected to 1.34 Å resolution. For the Ca{sup 2+}-dependent type II AFP species from Hypomesus nipponensis, crystallization was carried out for its Ca{sup 2+}-free and Ca{sup 2+}-bound states. 1.25 Å resolution data were collected from the crystal in the Ca{sup 2+}-free state, which exhibited P3{sub 1}21 (or P3{sub 2}21) symmetry, with unit-cell parameters a = b = 66.0, c = 50.3 Å. Data collection could be extended to 1.06 Å resolution for the crystal in the Ca{sup 2+} -bound state, which appeared to be isomorphous to the crystal in the Ca{sup 2+}-free state (unit-cell parameters a = b = 66.0, c = 49.8 Å). These data will allow us to determine the high-resolution structures of the two species of type II AFP.

  4. Ca2+/Calmodulin-Dependent Protein Kinase II in Vascular Smooth Muscle. (United States)

    Saddouk, F Z; Ginnan, R; Singer, H A


    Ca 2+ -dependent signaling pathways are central regulators of differentiated vascular smooth muscle (VSM) contractile function. In addition, Ca 2+ signals regulate VSM gene transcription, proliferation, and migration of dedifferentiated or "synthetic" phenotype VSM cells. Synthetic phenotype VSM growth and hyperplasia are hallmarks of pervasive vascular diseases including hypertension, atherosclerosis, postangioplasty/in-stent restenosis, and vein graft failure. The serine/threonine protein kinase Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous mediator of intracellular Ca 2+ signals. Its multifunctional nature, structural complexity, diversity of isoforms, and splice variants all characterize this protein kinase and make study of its activity and function challenging. The kinase has unique autoregulatory mechanisms, and emerging studies suggest that it can function to integrate Ca 2+ and reactive oxygen/nitrogen species signaling. Differentiated VSM expresses primarily CaMKIIγ and -δ isoforms. CaMKIIγ isoform expression correlates closely with the differentiated phenotype, and some studies link its function to regulation of contractile activity and Ca 2+ homeostasis. Conversely, synthetic phenotype VSM cells primarily express CaMKIIδ and substantial evidence links it to regulation of gene transcription, proliferation, and migration of VSM in vitro, and vascular hypertrophic and hyperplastic remodeling in vivo. CaMKIIδ and -γ isoforms have opposing functions at the level of cell cycle regulation, proliferation, and VSM hyperplasia in vivo. Isoform switching following vascular injury is a key step in promoting vascular remodeling. Recent availability of genetically engineered mice with smooth muscle deletion of specific isoforms and transgenics expressing an endogenous inhibitor protein (CAMK2N) has enabled a better understanding of CaMKII function in VSM and should facilitate future studies. © 2017 Elsevier Inc. All rights reserved.

  5. Oxidized CaMKII (Ca2+/Calmodulin-Dependent Protein Kinase II) Is Essential for Ventricular Arrhythmia in a Mouse Model of Duchenne Muscular Dystrophy. (United States)

    Wang, Qiongling; Quick, Ann P; Cao, Shuyi; Reynolds, Julia; Chiang, David Y; Beavers, David; Li, Na; Wang, Guoliang; Rodney, George G; Anderson, Mark E; Wehrens, Xander H T


    Duchenne muscular dystrophy patients are prone to ventricular arrhythmias, which may be caused by abnormal calcium (Ca 2+ ) homeostasis and elevated reactive oxygen species. CaMKII (Ca 2+ /calmodulin-dependent protein kinase II) is vital for normal Ca 2+ homeostasis, but excessive CaMKII activity contributes to abnormal Ca 2+ homeostasis and arrhythmias in cardiomyocytes. Reactive oxygen species induce CaMKII to become autonomously active. We hypothesized that genetic inhibition of CaMKII oxidation (ox-CaMKII) in a mouse model of Duchenne muscular dystrophy can alleviate abnormal Ca 2+ homeostasis, thus, preventing ventricular arrhythmia. The objective of this study was to test if selective loss of ox-CaMKII affects ventricular arrhythmias in the mdx mouse model of Duchenne muscular dystrophy. 5-(6)-Chloromethyl-2,7-dichlorodihydrofluorescein diacetate staining revealed increased reactive oxygen species production in ventricular myocytes isolated from mdx mice, which coincides with elevated ventricular ox-CaMKII demonstrated by Western blotting. Genetic inhibition of ox-CaMKII by knockin replacement of the regulatory domain methionines with valines (MM-VV [CaMKII M281/282V]) prevented ventricular tachycardia in mdx mice. Confocal calcium imaging of ventricular myocytes isolated from mdx :MM-VV mice revealed normalization of intracellular Ca 2+ release events compared with cardiomyocytes from mdx mice. Abnormal action potentials assessed by optical mapping in mdx mice were also alleviated by genetic inhibition of ox-CaMKII. Knockout of the NADPH oxidase regulatory subunit p47 phox normalized elevated ox-CaMKII, repaired intracellular Ca 2+ homeostasis, and rescued inducible ventricular arrhythmias in mdx mice. Inhibition of reactive oxygen species or ox-CaMKII protects against proarrhythmic intracellular Ca 2+ handling and prevents ventricular arrhythmia in a mouse model of Duchenne muscular dystrophy. © 2018 American Heart Association, Inc.

  6. Ca(2+-dependent regulation of the Ca(2+ concentration in the myometrium mitochondria. II. Ca(2+ effects on mitochondria membranes polarization and [Ca(2+](m

    Directory of Open Access Journals (Sweden)

    L. G. Babich


    Full Text Available It is known that Ca2+ accumulation in the mitochondria undergoes complex regulation by Ca2+ itself. But the mechanisms of such regulation are still discussed. In this paper we have shown that Ca ions directly or indirectly regulate the level of myometrium mitochondria membranes polarization. The additions of 100 µM Ca2+ were accompanied by depolarization of the mitochondria membranes. The following experiments were designed to study the impact of Ca2+ on the myometrium mitochondria [Ca2+]m. Isolated myometrium mitochondria were preincubated without or with 10 μM Са2+ followed by 100 μM Са2+ addition. Experiments were conducted in three mediums: without ATP and Mg2+ (0-medium, in the presence of 3 mM Mg2+ (Mg-medium and 3 mM Mg2+ + 3 mM ATP (Mg,ATP-medium. It was shown that the effects of 10 μM Са2+ addition were different in different mediums, namely in 0- and Mg-medium the [Ca2+]m values increased, whereas in Mg,ATP-medium statistically reliable changes were not registered. Preincubation of mitochondria with 10 μM Са2+ did not affect the [Ca2+]m value after the addition of 100 μM Са2+. The [Ca2+]m values after 100 μM Са2+ addition were the same in 0- and Mg,ATP-mediums and somewhat lower in Mg-medium. Preliminary incubation of mitochondria with 10 μM Са2+ in 0- and Mg-mediums reduced changes of Fluo 4 normalized fluorescence values that were induced by 100 μM Са2+ additions, but in Mg,ATP-medium such differences were not recorded. It is concluded that Са2+ exchange in myometrium mitochondria is regulated by the concentration of Ca ions as in the external medium, so in the matrix of mitochondria. The medium composition had a significant impact on the [Са2+]m values in the absence of exogenous cation. It is suggested that light increase of [Са2+]m before the addition of 100 μM Са2+ may have a positive effect on the functional activity of the mitochondria.

  7. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4874 >orf19.4874; Contig19-10215; complement(31986...2..321682); MNN3*; type II Golgi membrane protein | alpha-1, 2- mannosyltransferase; gene family MSINFLSIPRN

  8. Mechanism of Ca2+/calmodulin-dependent kinase II regulation of AMPA receptor gating

    DEFF Research Database (Denmark)

    Kristensen, Anders Skov; Jenkins, Meagan A; Banke, Tue G


    The function, trafficking and synaptic signaling of AMPA receptors are tightly regulated by phosphorylation. Ca(2+)/calmodulin-dependent kinase II (CaMKII) phosphorylates the GluA1 AMPA receptor subunit at Ser831 to increase single-channel conductance. We show that CaMKII increases the conductance....... Finally, phosphorylation of Ser831 increases the efficiency with which each subunit can activate, independent of agonist efficacy, thereby increasing the likelihood that more receptor subunits will be simultaneously activated during gating. This underlies the observation that phospho-Ser831 increases...... the frequency of openings to larger conductances rather than altering unitary conductance. Together, these findings suggest that CaMKII phosphorylation of GluA1-Ser831 decreases the activation energy for an intrasubunit conformational change that regulates the conductance of the receptor when the channel pore...

  9. Solving the conundrum of intervening strong Mg II absorbers towards gamma-ray bursts and quasars (United States)

    Christensen, L.; Vergani, S. D.; Schulze, S.; Annau, N.; Selsing, J.; Fynbo, J. P. U.; de Ugarte Postigo, A.; Cañameras, R.; Lopez, S.; Passi, D.; Cortés-Zuleta, P.; Ellison, S. L.; D'Odorico, V.; Becker, G.; Berg, T. A. M.; Cano, Z.; Covino, S.; Cupani, G.; D'Elia, V.; Goldoni, P.; Gomboc, A.; Hammer, F.; Heintz, K. E.; Jakobsson, P.; Japelj, J.; Kaper, L.; Malesani, D.; Møller, P.; Petitjean, P.; Pugliese, V.; Sánchez-Ramírez, R.; Tanvir, N. R.; Thöne, C. C.; Vestergaard, M.; Wiersema, K.; Worseck, G.


    Previous studies have shown that the incidence rate of intervening strong Mg II absorbers towards gamma-ray bursts (GRBs) were a factor of 2-4 higher than towards quasars. Exploring the similar sized and uniformly selected legacy data sets XQ-100 and XSGRB, each consisting of 100 quasar and 81 GRB afterglow spectra obtained with a single instrument (VLT/X-shooter), we demonstrate that there is no disagreement in the number density of strong Mg II absorbers with rest-frame equivalent widths W_rλ2796>1 Å towardsGRBs and quasars in the redshift range 0.1 ≲ z ≲ 5. With large and similar sample sizes, and path length coverages of Δz = 57.8 and 254.4 for GRBs and quasars, respectively, the incidences of intervening absorbers are consistent within 1σ uncertainty levels at all redshifts. For absorbers at z Digital Sky Survey (SDSS) quasar spectra, while for quasar absorbers observed with X-shooter we find an excess factor of 1.4 ± 0.2 relative to SDSS quasars. Conversely, the incidence rates agree at all redshifts with reported high-spectral-resolution quasar data, and no excess is found. The only remaining discrepancy in incidences is between SDSS Mg II catalogues and high-spectral-resolution studies. The rest-frame equivalent-width distribution also agrees to within 1σ uncertainty levels between the GRB and quasar samples. Intervening strong Mg II absorbers towards GRBs are therefore neither unusually frequent, nor unusually strong. Based on observations collected at the European Southern Observatory, Paranal, Chile, Program ID: 098.A-0055, 097.A-0036, 096.A-0079, 095.B-0811(B), 095.A-0045, 094.A-0134, 093.A-0069, 092.A-0124, 0091.C-0934, 090.A-0088, 089.A-0067, 088.A-0051, 087.A-0055, 086.A-0073, 085.A-0009 and 084.A-0260. XQ-100: 189.A-0424.

  10. The effect of Ca2+ ions and ionic strength on Mn(II) oxidation by spores of the marine Bacillus sp. SG-1 (United States)

    Toyoda, Kazuhiro; Tebo, Bradley M.


    Manganese(IV) oxides, believed to form primarily through microbial activities, are extremely important mineral phases in marine environments where they scavenge a variety of trace elements and thereby control their distributions. The presence of various ions common in seawater are known to influence Mn oxide mineralogy yet little is known about the effect of these ions on the kinetics of bacterial Mn(II) oxidation and Mn oxide formation. We examined factors affecting bacterial Mn(II) oxidation by spores of the marine Bacillus sp. strain SG-1 in natural and artificial seawater of varying ionic conditions. Ca2+ concentration dramatically affected Mn(II) oxidation, while Mg2+, Sr2+, K+, Na+ and NO3- ions had no effect. The rate of Mn(II) oxidation at 10 mM Ca2+ (seawater composition) was four or five times that without Ca2+. The relationship between Ca2+ content and oxidation rate demonstrates that the equilibrium constant is small (on the order of 0.1) and the binding coefficient is 0.5. The pH optimum for Mn(II) oxidation changed depending on the amount of Ca2+ present, suggesting that Ca2+ exerts a direct effect on the enzyme perhaps as a stabilizing bridge between polypeptide components. We also examined the effect of varying concentrations of NaCl or KNO3 (0-2000 mM) on the kinetics of Mn(II) oxidation in solutions containing 10 mM Ca2+. Mn(II) oxidation was unaffected by changes in ionic strength (I) below 0.2, but it was inhibited by increasing salt concentrations above this value. Our results suggest that the critical coagulation concentration is around 200 mM of salt (I = ca. 0.2), and that the ionic strength of seawater (I > 0.2) accelerates the precipitation of Mn oxides around the spores. Under these conditions, the aggregation of Mn oxides reduces the supply of dissolved O2 and/or Mn2+ and inhibits the Mn(II) → Mn(III) step controlling the enzymatic oxidation of Mn(II). Our results suggest that the hardness and ionic strength of the aquatic environment

  11. Ca II H and K filter photometry on the uvby system. I - The standard system

    Energy Technology Data Exchange (ETDEWEB)

    Anthony-twarog, B.J.; Twarog, B.A.; Laird, J.B.; Payne, D. (Kansas, University, Lawrence (USA) Cerro Tololo Inter-American Observatory, La Serena (Chile) Bowling Green State University, OH (USA))


    A fifth filter (fwhm = 90 A) centered on Ca II H and K has been developed for use with the standard uvby system. The filter, called Ca, is designed primarily for applications to metal-poor dwarfs and red giants, regions where the uvby metallicity index, m(l), loses some sensitivity. An index, hk, is defined by replacing v in m(l) by Ca. The effects of interstellar extinction on the index are modeled and demonstrated to be modest and relatively insensitive to spectral type. Observations of V, (b-y), and hk for 163 primary standards are detailed and transformed to the standard V and (b-y) system. A qualitative analysis using only the primary standards indicates that hk is more sensitive than m(l) over the regions of interest by about a factor of 3. 58 refs.

  12. Slender Ca ii H Fibrils Mapping Magnetic Fields in the Low Solar Chromosphere

    Energy Technology Data Exchange (ETDEWEB)

    Jafarzadeh, S.; Rutten, R. J.; Szydlarski, M. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, NO-0315 Oslo (Norway); Solanki, S. K.; Wiegelmann, T.; Riethmüller, T. L.; Noort, M. van; Barthol, P.; Gandorfer, A.; Gizon, L.; Hirzberger, J. [Max Planck Institute for Solar System Research, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany); Rodríguez, J. Blanco [Grupo de Astronomía y Ciencias del Espacio, Universidad de Valencia, E-46980 Paterna, Valencia (Spain); Iniesta, J. C. del Toro; Suárez, D. Orozco [Instituto de Astrofísica de Andalucía (CSIC), Apartado de Correos 3004, E-18080 Granada (Spain); Knölker, M. [High Altitude Observatory, National Center for Atmospheric Research, P.O. Box 3000, Boulder, CO 80307-3000 (United States); Pillet, V. Martínez [National Solar Observatory, 3665 Discovery Drive, Boulder, CO 80303 (United States); Schmidt, W., E-mail: [Kiepenheuer-Institut für Sonnenphysik, Schöneckstr. 6, D-79104 Freiburg (Germany)


    A dense forest of slender bright fibrils near a small solar active region is seen in high-quality narrowband Ca ii H images from the SuFI instrument onboard the Sunrise balloon-borne solar observatory. The orientation of these slender Ca ii H fibrils (SCF) overlaps with the magnetic field configuration in the low solar chromosphere derived by magnetostatic extrapolation of the photospheric field observed with Sunrise/IMaX and SDO/HMI. In addition, many observed SCFs are qualitatively aligned with small-scale loops computed from a novel inversion approach based on best-fit numerical MHD simulation. Such loops are organized in canopy-like arches over quiet areas that differ in height depending on the field strength near their roots.

  13. Clinical evaluation of the Byk LIA-mat CA125 II assay: discussion of a reference value. (United States)

    Bonfrer, J M; Korse, C M; Verstraeten, R A; van Kamp, G J; Hart, G A; Kenemans, P


    The Byk LIA-mat CA125 II assay was compared with the Centocor IRMA CA125 II. Serum samples studied (n = 1012) were obtained from 652 apparently healthy females, 61 pregnant women, and 299 patients with benign and malignant gynecological tumors. The CA125 II assay value at the 95th percentile of the total healthy group was 29 kU/L for the LIA-mat and 32 kU/L for the Centocor assay. For the LIA-mat assay the 95th percentile was 31 kU/L (Centocor 36 kU/L) for the group 55 years of age. By using ROC curves we found the optimal pretreatment Byk LIA-mat CA125 II value differentiating between benign and malignant ovarian tumors to be 95 kU/L. Pretreatment CA125 values > 1000 kU/L were detected in serum samples of patients with advanced epithelial ovarian cancer.

  14. Ca2+/calmodulin-dependent kinase II-dependent regulation of atrial myocyte late Na+current, Ca2+cycling, and excitability: a mathematical modeling study. (United States)

    Onal, Birce; Gratz, Daniel; Hund, Thomas J


    Atrial fibrillation (AF) affects more than three million people per year in the United States and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) in the regulation of persistent "late" Na + current ( I Na,L ) has been identified. Although I Na,L inhibition is emerging as a potential antiarrhythmic strategy in patients with AF, little is known about the mechanism linking I Na,L to atrial arrhythmogenesis. A computational approach was used to test the hypothesis that increased CaMKII-activated I Na,L in atrial myocytes disrupts Ca 2+ homeostasis, promoting arrhythmogenic afterdepolarizations. Dynamic CaMKII activity and regulation of multiple downstream targets [ I Na,L , L-type Ca 2+ current, phospholamban, and the ryanodine receptor sarcoplasmic reticulum Ca 2+ -release channel (RyR2)] were incorporated into an existing well-validated computational model of the human atrial action potential. Model simulations showed that constitutive CaMKII-dependent phosphorylation of Na v 1.5 and the subsequent increase in I Na,L effectively disrupt intracellular atrial myocyte ion homeostasis and CaMKII signaling. Specifically, increased I Na,L promotes intracellular Ca 2+ overload via forward-mode Na + /Ca 2+ exchange activity, which greatly increases RyR2 open probability beyond that observed for CaMKII-dependent phosphorylation of RyR2 alone. Increased I Na,L promotes atrial myocyte repolarization defects (afterdepolarizations and alternans) in the setting of acute β-adrenergic stimulation. We anticipate that our modeling efforts will help identify new mechanisms for atrial Na V 1.5 regulation with direct relevance for human AF. NEW & NOTEWORTHY Here, we present a novel computational model to study the effects of late Na + current ( I Na,L ) in human atrial

  15. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer

    DEFF Research Database (Denmark)

    You, Benoit; Colomban, Olivier; Heywood, Mark


    Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters....

  16. Removal of Ca(II) and Mg(II) from potassium chromate solution on Amberlite IRC 748 synthetic resin by ion exchange

    International Nuclear Information System (INIS)

    Yu Zhihui; Qi Tao; Qu Jingkui; Wang Lina; Chu Jinglong


    Experimental measurements have been made on the batch ion exchange of Ca(II) and Mg(II) from potassium chromate solution using cation exchanger of Amberlite IRC 748 as K + form. The ion exchange behavior of two alkaline-earth metals on the resin, depending on contact time, pH, temperature and resin dosage was studied. The adsorption isotherms were described by means of the Langmuir and Freundlich isotherms. For Ca(II) ion, the Langmuir model represented the adsorption process better than the Freundlich model. The maximum ion exchange capacity was found to be 47.21 mg g -1 for Ca(II) and 27.70 mg g -1 for Mg(II). The kinetic data were tested using Lagergren-first-order and pseudo-second-order kinetic models. Kinetic data correlated well with the pseudo-second-order kinetic model, indicating that the chemical adsorption was the rate-limiting step. Various thermodynamic parameters such as Gibbs free energy (ΔG o ), enthalpy (ΔH o ) and entropy (ΔS o ) were also calculated. These parameters showed that the ion exchange of Ca(II) and Mg(II) from potassium chromate solution was feasible, spontaneous and endothermic process in nature. The activation energy of ion-exchange (E a ) was determined as 12.34 kJ mol -1 for Ca(II) and 9.865 kJ mol -1 for Mg(II) according to the Arrhenius equation.

  17. Three-dimensional electromagnetic strong turbulence. II. Wave packet collapse and structure of wave packets during strong turbulence (United States)

    Graham, D. B.; Robinson, P. A.; Cairns, Iver H.; Skjaeraasen, O.


    Large-scale simulations of wave packet collapse are performed by numerically solving the three-dimensional (3D) electromagnetic Zakharov equations, focusing on individual wave packet collapses and on wave packets that form in continuously driven strong turbulence. The collapse threshold is shown to decrease as the electron thermal speed νe/c increases and as the temperature ratio Ti/Te of ions to electrons decreases. Energy lost during wave packet collapse and dissipation is shown to depend on νe/c. The dynamics of density perturbations after collapse are studied in 3D electromagnetic strong turbulence for a range of Ti/Te. The structures of the Langmuir, transverse, and total electric field components of wave packets during strong turbulence are investigated over a range of νe/c. For νe/c ≲0.17, strong turbulence is approximately electrostatic and wave packets have very similar structure to purely electrostatic wave packets. For νe/c ≳0.17, transverse modes become trapped in density wells and contribute significantly to the structure of the total electric field. At all νe/c, the Langmuir energy density contours of wave packets are predominantly oblate (pancake shaped). The transverse energy density contours of wave packets are predominantly prolate (sausage shaped), with the major axis being perpendicular to the major axes of the Langmuir component. This results in the wave packet becoming more nearly spherical as νe/c increases, and in turn generates more spherical density wells during collapse. The results obtained are compared with previous 3D electrostatic results and 2D electromagnetic results.

  18. Heme-induced Trypanosoma cruzi proliferation is mediated by CaM kinase II

    Energy Technology Data Exchange (ETDEWEB)

    Souza, C.F. [Laboratorio de Imunomodulacao e Protozoologia, Instituto Oswaldo Cruz, Fiocruz (Brazil); Carneiro, A.B.; Silveira, A.B. [Laboratorio de Sinalizacao Celular, Instituto de Bioquimica Medica, UFRJ (Brazil); Laranja, G.A.T. [Laboratorio de Interacao Tripanosomatideos e Vetores, Departamento de Bioquimica, IBRAG, UERJ, 20551-030 Rio de Janeiro (Brazil); Silva-Neto, M.A.C. [Laboratorio de Sinalizacao Celular, Instituto de Bioquimica Medica, UFRJ (Brazil); INCT, Entomologia Molecular (Brazil); Costa, S.C. Goncalves da [Laboratorio de Imunomodulacao e Protozoologia, Instituto Oswaldo Cruz, Fiocruz (Brazil); Paes, M.C., E-mail: [Laboratorio de Interacao Tripanosomatideos e Vetores, Departamento de Bioquimica, IBRAG, UERJ, 20551-030 Rio de Janeiro (Brazil); INCT, Entomologia Molecular (Brazil)


    Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted through triatomine vectors during their blood-meal on vertebrate hosts. These hematophagous insects usually ingest approximately 10 mM of heme bound to hemoglobin in a single meal. Blood forms of the parasite are transformed into epimastigotes in the crop which initiates a few hours after parasite ingestion. In a previous work, we investigated the role of heme in parasite cell proliferation and showed that the addition of heme significantly increased parasite proliferation in a dose-dependent manner . To investigate whether the heme effect is mediated by protein kinase signalling pathways, parasite proliferation was evaluated in the presence of several protein kinase (PK) inhibitors. We found that only KN-93, a classical inhibitor of calcium-calmodulin-dependent kinases (CaMKs), blocked heme-induced cell proliferation. KN-92, an inactive analogue of KN-93, was not able to block this effect. A T. cruzi CaMKII homologue is most likely the main enzyme involved in this process since parasite proliferation was also blocked when Myr-AIP, an inhibitory peptide for mammalian CaMKII, was included in the cell proliferation assay. Moreover, CaMK activity increased in parasite cells with the addition of heme as shown by immunological and biochemical assays. In conclusion, the present results are the first strong indications that CaMKII is involved in the heme-induced cell signalling pathway that mediates parasite proliferation.

  19. Resolution of strong singularities and geodesic completeness in loop quantum Bianchi-II spacetimes (United States)

    Saini, Sahil; Singh, Parampreet


    Generic resolution of singularities and geodesic completeness in the loop quantization of Bianchi-II spacetimes with arbitrary minimally coupled matter is investigated. Using the effective Hamiltonian approach, we examine two available quantizations: one based on the connection operator and second by treating extrinsic curvature as connection via gauge fixing. It turns out that for the connection based quantization, either the inverse triad modifications or imposition of weak energy condition is necessary to obtain a resolution of all strong singularities and geodesic completeness. In contrast, the extrinsic curvature based quantization generically resolves all strong curvature singularities and results in a geodesically complete effective spacetime without inverse triad modifications or energy conditions. In both the quantizations, weak curvature singularities can occur resulting from divergences in pressure and its derivatives at finite densities. These are harmless events beyond which geodesics can be extended. Our work generalizes previous results on the generic resolution of strong singularities in the loop quantization of isotropic, Bianchi-I and Kantowski–Sachs spacetimes.

  20. Ca²+/calmodulin-dependent protein kinase II (CaMKII activity and sinoatrial nodal pacemaker cell energetics.

    Directory of Open Access Journals (Sweden)

    Yael Yaniv

    Full Text Available : Ca(2+-activated basal adenylate cyclase (AC in rabbit sinoatrial node cells (SANC guarantees, via basal cAMP/PKA-calmodulin/CaMKII-dependent protein phosphorylation, the occurrence of rhythmic, sarcoplasmic-reticulum generated, sub-membrane Ca(2+ releases that prompt rhythmic, spontaneous action potentials (APs. This high-throughput signaling consumes ATP.We have previously demonstrated that basal AC-cAMP/PKA signaling directly, and Ca(2+ indirectly, regulate mitochondrial ATP production. While, clearly, Ca(2+-calmodulin-CaMKII activity regulates ATP consumption, whether it has a role in the control of ATP production is unknown.We superfused single, isolated rabbit SANC at 37°C with physiological saline containing CaMKII inhibitors, (KN-93 or autocamtide-2 Related Inhibitory Peptide (AIP, or a calmodulin inhibitor (W-7 and measured cytosolic Ca(2+, flavoprotein fluorescence and spontaneous AP firing rate. We measured cAMP, ATP and O2 consumption in cell suspensions. Graded reductions in basal CaMKII activity by KN-93 (0.5-3 µmol/L or AIP (2-10 µmol/L markedly slow the kinetics of intracellular Ca(2+ cycling, decrease the spontaneous AP firing rate, decrease cAMP, and reduce O2 consumption and flavoprotein fluorescence. In this context of graded reductions in ATP demand, however, ATP also becomes depleted, indicating reduced ATP production.CaMKII signaling, a crucial element of normal automaticity in rabbit SANC, is also involved in SANC bioenergetics.


    Energy Technology Data Exchange (ETDEWEB)

    Rapoport, Sharon; Onken, Christopher A.; Schmidt, Brian P.; Tucker, Brad E. [Research School of Astronomy and Astrophysics, Australian National University, Weston Creek, ACT 2611 (Australia); Wyithe, J. Stuart B. [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); Levan, Andrew J. [Department of Physics, University of Warwick, Coventry CV4 7AL (United Kingdom)


    Sixty percent of gamma-ray bursts (GRBs) reveal strong Mg II absorbing systems, which is a factor of {approx}2 times the rate seen along lines of sight to quasars. Previous studies argue that the discrepancy in the strong Mg II covering factor is most likely to be the result of either quasars being obscured due to dust or the consequence of many GRBs being strongly gravitationally lensed. We analyze observations of quasars that show strong foreground Mg II absorption. We find that GRB lines of sight pass closer to bright galaxies than would be expected for random lines of sight within the impact parameter expected for strong Mg II absorption. While this cannot be explained by obscuration in the GRB sample, it is a natural consequence of gravitational lensing. Upon examining the particular configurations of galaxies near a sample of GRBs with strong Mg II absorption, we find several intriguing lensing candidates. Our results suggest that lensing provides a viable contribution to the observed enhancement of strong Mg II absorption along lines of sight to GRBs, and we outline the future observations required to test this hypothesis conclusively.

  2. 76 FR 22809 - Safety Zone; Bay Ferry II Maritime Security Exercise; San Francisco Bay, San Francisco, CA (United States)


    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2011-0196] RIN 1625-AA00 Safety Zone; Bay Ferry II Maritime Security Exercise; San Francisco Bay, San Francisco, CA AGENCY... Security Exercise; San Francisco Bay, San Francisco, CA. (a) Location. The limits of this safety zone...

  3. Analysis and calibration of CaII triplet spectroscopy of red giant branch stars from VLT/FLAMES observations

    NARCIS (Netherlands)

    Battaglia, G.; Irwin, M.; Tolstoy, E.; Hill, V.; Helmi, A.; Letarte, B.; Jablonka, P.


    We demonstrate that low-resolution Ca II triplet (CaT) spectroscopic estimates of the overall metallicity ([Fe/H]) of individual red giant branch (RGB) stars in two nearby dwarf spheroidal galaxies (dSphs) agree to +/- 0.1-0.2 dex with detailed high-resolution spectroscopic determinations for the

  4. Spectroscopic (FT-IR, FT-Raman, 1H, 13C NMR, UV/VIS), thermogravimetric and antimicrobial studies of Ca(II), Mn(II), Cu(II), Zn(II) and Cd(II) complexes of ferulic acid (United States)

    Kalinowska, M.; Piekut, J.; Bruss, A.; Follet, C.; Sienkiewicz-Gromiuk, J.; Świsłocka, R.; Rzączyńska, Z.; Lewandowski, W.


    The molecular structure of Mn(II), Cu(II), Zn(II), Cd(II) and Ca(II) ferulates (4-hydroxy-3-methoxycinnamates) was studied. The selected metal ferulates were synthesized. Their composition was established by means of elementary and thermogravimetric analysis. The following spectroscopic methods were used: infrared (FT-IR), Raman (FT-Raman), nuclear magnetic resonance (13C, 1H NMR) and ultraviolet-visible (UV/VIS). On the basis of obtained results the electronic charge distribution in studied metal complexes in comparison with ferulic acid molecule was discussed. The microbiological study of ferulic acid and ferulates toward Escherichia coli, Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa, Staphylococcus aureus and Proteus vulgaris was done.

  5. Rat vas deferens SERCA2 is modulated by Ca{sup 2+}/calmodulin protein kinase II-mediated phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, J.B.R.; Muzi-Filho, H. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Valverde, R.H.F. [Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Quintas, L.E.M. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Noel, F. [Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Einicker-Lamas, M. [Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil); Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Rio de Janeiro, RJ (Brazil); Cunha, V.M.N. [Programa de Farmacologia e Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ (Brazil)


    Ca{sup 2+} pumps are important players in smooth muscle contraction. Nevertheless, little information is available about these pumps in the vas deferens. We have determined which subtype of sarco(endo)plasmic reticulum Ca{sup 2+}-ATPase isoform (SERCA) is expressed in rat vas deferens (RVD) and its modulation by calmodulin (CaM)-dependent mechanisms. The thapsigargin-sensitive Ca{sup 2+}-ATPase from a membrane fraction containing the highest SERCA levels in the RVD homogenate has the same molecular mass (∼115 kDa) as that of SERCA2 from the rat cerebellum. It has a very high affinity for Ca{sup 2+} (Ca{sub 0.5} = 780 nM) and a low sensitivity to vanadate (IC{sub 50} = 41 µM). These facts indicate that SERCA2 is present in the RVD. Immunoblotting for CaM and Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) showed the expression of these two regulatory proteins. Ca{sup 2+} and CaM increased serine-phosphorylated residues of the 115-kDa protein, indicating the involvement of CaMKII in the regulatory phosphorylation of SERCA2. Phosphorylation is accompanied by an 8-fold increase of thapsigargin-sensitive Ca{sup 2+} accumulation in the lumen of vesicles derived from these membranes. These data establish that SERCA2 in the RVD is modulated by Ca{sup 2+} and CaM, possibly via CaMKII, in a process that results in stimulation of Ca{sup 2+} pumping activity.

  6. JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants. (United States)

    Sundqvist, Emilie; Buck, Dorothea; Warnke, Clemens; Albrecht, Eva; Gieger, Christian; Khademi, Mohsen; Lima Bomfim, Izaura; Fogdell-Hahn, Anna; Link, Jenny; Alfredsson, Lars; Søndergaard, Helle Bach; Hillert, Jan; Oturai, Annette B; Hemmer, Bernhard; Hemme, Bernhard; Kockum, Ingrid; Olsson, Tomas


    JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15)) and controls (OR = 0.53, p = 2×10(-5)). In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006), and controls (OR = 2.69, p = 1×10(-5)). The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4) and OR = 1.58, p = 0.03 respectively for these haplotypes). HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays the

  7. JC polyomavirus infection is strongly controlled by human leucocyte antigen class II variants.

    Directory of Open Access Journals (Sweden)

    Emilie Sundqvist


    Full Text Available JC polyomavirus (JCV carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA, instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR = 0.42, p = 7×10(-15 and controls (OR = 0.53, p = 2×10(-5. In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR = 1.63, p = 0.006, and controls (OR = 2.69, p = 1×10(-5. The German dataset confirmed these findings (OR = 0.54, p = 1×10(-4 and OR = 1.58, p = 0.03 respectively for these haplotypes. HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and

  8. Strong-pinning regimes by spherical inclusions in anisotropic type-II superconductors (United States)

    Willa, R.; Koshelev, A. E.; Sadovskyy, I. A.; Glatz, A.


    The current-carrying capacity of type-II superconductors is decisively determined by how well material defect structures can immobilize vortex lines. In order to gain deeper insights into the fundamental pinning mechanisms, we have explored the case of vortex trapping by randomly distributed spherical inclusions using large-scale simulations of the time-dependent Ginzburg–Landau equations. We find that for a small density of particles having diameters of two coherence lengths, the vortex lattice preserves its structure and the critical current j c decays with the magnetic field following a power-law {B}-α with α ≈ 0.66, which is consistent with predictions of strong-pinning theory. For a higher density of particles and/or larger inclusions, the lattice becomes progressively more disordered and the exponent smoothly decreases down to α ≈ 0.3. At high magnetic fields, all inclusions capture a vortex and the critical current decays faster than {B}-1 as would be expected by theory. In the case of larger inclusions with a diameter of four coherence lengths, the magnetic-field dependence of the critical current is strongly affected by the ability of inclusions to capture multiple vortex lines. We found that at small densities, the fraction of inclusions trapping two vortex lines rapidly grows within narrow field range leading to a peak in j c(B)-dependence within this range. With increasing inclusion density, this peak transforms into a plateau, which then smooths out. Using the insights gained from simulations, we determine the limits of applicability of strong-pinning theory and provide different routes to describe vortex pinning beyond those bounds.

  9. Strong-pinning regimes by spherical inclusions in anisotropic type-II superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Willa, R.; Koshelev, A. E.; Sadovskyy, I. A.; Glatz, A.


    The current-carrying capacity of type-II superconductors is decisively determined by how well material defect structures can immobilize vortex lines. In order to gain deeper insights into intrinsic pinning mechanisms, we have explored the case of vortex trapping by randomly distributed spherical inclusions using large-scale simulations of the time-dependent Ginzburg-Landau equations. We find that for a small density of particles having diameters of two coherence lengths, the vortex lattice preserves its structure and the critical current jc decays with the magnetic field following a power-law B-a with a ~ 0:66, which is consistent with predictions of strong pinning theory. For higher density of particles and/or larger inclusions, the lattice becomes progressively more disordered and the exponent smoothly decreases down to a ~ 0:3. At high magnetic fields, all inclusions capture a vortex and the critical current decays faster than B-1 as would be expected by theory. In the case of larger inclusions with diameter of four coherence length, the magnetic-field dependence of the critical current is strongly affected by the ability of inclusions to capture multiple vortex lines. We found that at small densities, the fraction of inclusions trapping two vortex lines rapidly grows within narrow field range leading to a shallow peak in jc(B)-dependence within this range. With increasing inclusion density, this peak transforms into a plateau, which then smooths out. Using the insights gained from simulations, we determine the limits of applicability of strong pinning theory and provide different routes to describe vortex pinning beyond those bounds.

  10. Theoretical basal Ca II fluxes for late-type stars: results from magnetic wave models with time-dependent ionization and multi-level radiation treatments (United States)

    Fawzy, Diaa E.; Stȩpień, K.


    In the current study we present ab initio numerical computations of the generation and propagation of longitudinal waves in magnetic flux tubes embedded in the atmospheres of late-type stars. The interaction between convective turbulence and the magnetic structure is computed and the obtained longitudinal wave energy flux is used in a self-consistent manner to excite the small-scale magnetic flux tubes. In the current study we reduce the number of assumptions made in our previous studies by considering the full magnetic wave energy fluxes and spectra as well as time-dependent ionization (TDI) of hydrogen, employing multi-level Ca II atomic models, and taking into account departures from local thermodynamic equilibrium. Our models employ the recently confirmed value of the mixing-length parameter α=1.8. Regions with strong magnetic fields (magnetic filling factors of up to 50%) are also considered in the current study. The computed Ca II emission fluxes show a strong dependence on the magnetic filling factors, and the effect of time-dependent ionization (TDI) turns out to be very important in the atmospheres of late-type stars heated by acoustic and magnetic waves. The emitted Ca II fluxes with TDI included into the model are decreased by factors that range from 1.4 to 5.5 for G0V and M0V stars, respectively, compared to models that do not consider TDI. The results of our computations are compared with observations. Excellent agreement between the observed and predicted basal flux is obtained. The predicted trend of Ca II emission flux with magnetic filling factor and stellar surface temperature also agrees well with the observations but the calculated maximum fluxes for stars of different spectral types are about two times lower than observations. Though the longitudinal MHD waves considered here are important for chromosphere heating in high activity stars, additional heating mechanism(s) are apparently present.

  11. Methodology to obtain exchange properties of the calcite surface-Application to major and trace elements: Ca(II), HCO3-, and Zn(II)

    International Nuclear Information System (INIS)

    Tertre, E.; Beaucaire, C.; Juery, A.; Ly, J.; Tertre, E.; Beaucaire, C.; Juery, A.; Ly, J.


    Sorption of inorganic elements onto carbonate minerals has been intensively described in the literature by two reaction steps: (1) a first one rapid and completed within a few hours and (2) a second one slower, eventually irreversible, and occurring at a constant rate. The first step is often attributed to an ion-exchange process, but its reversibility is rarely investigated. Consequently, discrimination of the global sorption phenomenon into two different mechanisms is not always justified. In this study, we investigated, by batch experiments, both sorption and desorption of Ca(II), HCO 3 - , and Zn(II), radiolabeled with isotopes 45 Ca(II), H 14 CO 3 - , and 65 Zn(II), respectively, onto synthetic pure calcite. Solutions were pre-equilibrated with atmospheric p(CO 2 ) and saturated with respect to calcite. Therefore, our purpose was to: (1) obtain experimental distribution coefficients of major elements (Ca(II) and HCO 3 - ) and a trace element (Zn(II)) onto calcite from sorption and desorption experiments, (2) test the validity of a first-occurring ion-exchange process generally noted in the literature, by calculating distribution coefficients for the 'sole' exchange process, and (3) quantify the amounts of Ca(II), HCO 3 - , and Zn(II) sorbed on the calcite surface by the sole 'exchange process' and compare them with surface crystallochemical data. Ca(II) or HCO 3 - sorption experimental data suggest that a significant fraction of these two elements was sorbed irreversibly onto or in the calcite. By using a method based on isotopic ratios, the Ca(II) or HCO 3 - concentrations, which are reversibly adsorbed on the calcite, have been quantified. These concentrations are respectively estimated at 4. 0 ± 2. 0 * 10 -4 and 7. 0 ± 1. 5 * 10 -4 mol/kg. The obtained Ca(II) surface concentration value is one order of magnitude lower than the one obtained from isotopic measurement by former authors [Geochim. Cosmochim. Acta 55 (1991) 1549; Geochim. Cosmochim. Acta 51

  12. Atriopeptin II and 8-bromo-cGMP lower Ca2+ in cultured aortic smooth muscle cells

    International Nuclear Information System (INIS)

    Cornwell, T.L.; Rashatwar, S.S.; Lincoln, T.M.


    Atriopeptin II (ANP) or 8-Bromo-cGMP (8-Br-cGMP) decreased the levels of intracellular Ca 2+ in Angiotensin II- (Ang) or K + -stimulated cultured rat aortic smooth muscle cells. Cytoplasmic Ca 2+ , measured by fura-2 fluorescence, was maximal at 30 to 60 sec following the addition of either Ang or KCl. Pretreatment of smooth muscle cells with ANP or 8-Br-cGMP diminished peak levels of Ca 2+ in response to Ang or KCl. Because the source of Ca 2+ mobilized by KCl was extracellular while that mobilized by Ang was intracellular, these results suggested that ANP and 8-Br-cGMP did not inhibit the mobilization of Ca 2+ . This was further supported by studies on the effects of ANP and 8-Br-cGMP on inositol polyphosphate production in cells labelled with 3 H-inositol. Ang, but not KCl, produced time-dependent increases in inositol polyphosphates. On the other hand, they have observed that cGMP-dependent protein kinase (cGPK), but not cAMP-dependent protein kinase, caused a 4-fold stimulation of Ca 2+ ATPase activity in crude microsomal fractions from cultured rat aortic smooth muscle cells. These results suggest that ANP and 8-Br-cGMP may lower Ca 2+ mobilized by Ang or KCl by enhancing Ca 2+ efflux or resequestration possibly through the stimulation of a Ca 2+ ATPase pump

  13. Strongly perturbed Rydberg series originating from KrII 4p45s ionic states

    International Nuclear Information System (INIS)

    Petrov, I.D.; Demekhin, Ph.V.; Lagutin, B.M.; Sukhorukov, V.L.; Kammer, S.; Mickat, S.; Schartner, K.-H.; Ehresmann, A.; Klumpp, S.; Werner, L.; Schmoranzer, H.


    Photoionization cross-sections for the 4p 4 ( 3 P) 5s 4 P 5/2,3/2,1/2 satellites and 4s, 4p main levels of Kr II in the exciting-photon energy range between 28.48 and 28.70-bar eV with extremely narrow bandwidth (1.7-bar meV at 28.55-bar eV) of the monochromatized synchrotron radiation were measured utilizing the photon-induced fluorescence spectroscopy. The observed resonances were assigned to the 4p 4 5s( 4 P 1/2 )n p and 4p 4 5s( 2 P 3/2 )n p Rydberg series on the basis of calculations performed with taking into account core relaxation and interaction between many resonances and many continua. The calculation shows that the resonance structure in the photoionization channels exists due to 4p 4 ( 1 D) 5s 2 D 5/2 6p 3/2 promoter state which also strongly perturbs the above Rydberg series.

  14. Scanning tunneling spectroscopy studies of Bi2Sr2CaCu2O8+x from the strongly underdoped to strongly overdoped regime (United States)

    Slezak, James


    Using atomically resolved scanning tunneling microscopy (STS), we investigate the electronic structure Bi2Sr2CaCu2O8+x across a range of doping levels from x ˜ 0.1 up to as high as ˜0.23, with significant changes in electronic structure observed above p˜0.21. New sample preparation processes [1] were used to produce heavily overdoped crystals suitable for the imaging of various forms of electronic heterogeneity. The evolution of the gap map δ(r), coherence peak height map A(r), the inelastic tunneling signatures φ(r), and the quasiparticle interference LDOS modulations, as well as their interrelations across this range of doping levels, will be presented. Additional authors: J. Lee, M. Wang, Laboratory of Atomic and Solid State Physics, Department of Physics, Cornell University, Ithaca, NY 14853, U.S.A; K. Fujita, Department of Advanced Materials Science, University of Tokyo, Tokyo 113-0033, Japan; H. Eisaki, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Central 2, Umezono, Tsukuba, Ibaraki 305-8568; S. Uchida, Department of Physics, University of Tokyo, Tokyo 113-0033; and J. C. Davis, Laboratory of Atomic and Solid State Physics, Department of Physics, Cornell University. [1] J. Slezak, K. Fujita, J. C. Davis, in preparation (2005)

  15. Mixed ligand complexes of alkaline earth metals: Part XII. Mg(II, Ca(II, Sr(II and Ba(II complexes with 5-chlorosalicylaldehyde and salicylaldehyde or hydroxyaromatic ketones

    Directory of Open Access Journals (Sweden)



    Full Text Available The reactions of alkaline earth metal chlorides with 5-chlorosalicylaldehyde and salicylaldehyde, 2-hydroxyacetophenone or 2-hydroxypropiophenone have been carried out in 1 : 1 : 1 mole ratio and the mixed ligand complexes of the type MLL’(H2O2 (where M = Mg(II, Ca(II, Sr(II and Ba(II, HL = 5-chlorosalicylaldehyde and HL’ = salicylaldehyde, 2-hydroxyacetophenone or 2-hydroxypropiophenone have been isolated. These complexes were characterized by TLC, conductance measurements, IR and 1H-NMR spectra.

  16. Ca(2+) currents and voltage responses in Type I and Type II hair cells of the chick embryo semicircular canal. (United States)

    Masetto, Sergio; Zampini, Valeria; Zucca, Giampiero; Valli, Paolo


    Type I and Type II hair cells, and Type II hair cells located in different zones of the semicircular canal crista, express different patterns of voltage-dependent K channels, each one specifically shaping the hair cell receptor potential. We report here that, close to hatching, chicken embryo semicircular canal Type I and Type II hair cells express a similar voltage-dependent L-type calcium current (I(Ca)), whose main features are: activation above -60 mV, fast activation kinetics, and scarce inactivation. I(Ca) should be already active at rest in Zone 1 Type II hair cells, whose resting membrane potential was on average slightly less negative than -60 mV. Conversely, I(Ca) would not be active at rest in Type II hair cells from Zone 2 and 3, nor in Type I hair cells, since their resting membrane potential was significantly more negative than -60 mV. However, even small depolarising currents would activate I(Ca) steadily in Zone 2 and 3 Type II hair cells, but not in Type I hair cells because of the robust repolarising action of their specific array of K(+) currents. The implications of the present findings in the afferent discharge are discussed.

  17. Transverse Oscillations in Slender Ca ii H Fibrils Observed with Sunrise/SuFI

    Energy Technology Data Exchange (ETDEWEB)

    Jafarzadeh, S. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, NO-0315 Oslo (Norway); Solanki, S. K.; Gafeira, R.; Noort, M. van; Barthol, P.; Gandorfer, A.; Gizon, L.; Hirzberger, J.; Riethmüller, T. L. [Max Planck Institute for Solar System Research, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany); Rodríguez, J. Blanco [Grupo de Astronomía y Ciencias del Espacio, Universidad de Valencia, E-46980 Paterna, Valencia (Spain); Iniesta, J. C. del Toro; Suárez, D. Orozco [Instituto de Astrofísica de Andalucía (CSIC), Apartado de Correos 3004, E-18080 Granada (Spain); Knölker, M. [High Altitude Observatory, National Center for Atmospheric Research, P.O. Box 3000, Boulder, CO 80307-3000 (United States); Schmidt, W., E-mail: [Kiepenheuer-Institut für Sonnenphysik, Schöneckstr. 6, D-79104 Freiburg (Germany)


    We present observations of transverse oscillations in slender Ca ii H fibrils (SCFs) in the lower solar chromosphere. We use a 1 hr long time series of high- (spatial and temporal-) resolution seeing-free observations in a 1.1 Å wide passband covering the line core of Ca ii H 3969 Å from the second flight of the Sunrise balloon-borne solar observatory. The entire field of view, spanning the polarity inversion line of an active region close to the solar disk center, is covered with bright, thin, and very dynamic fine structures. Our analysis reveals the prevalence of transverse waves in SCFs with median amplitudes and periods on the order of 2.4 ± 0.8 km s{sup −1} and 83 ± 29 s, respectively (with standard deviations given as uncertainties). We find that the transverse waves often propagate along (parts of) the SCFs with median phase speeds of 9 ± 14 km s{sup −1}. While the propagation is only in one direction along the axis in some of the SCFs, propagating waves in both directions, as well as standing waves are also observed. The transverse oscillations are likely Alfvénic and are thought to be representative of magnetohydrodynamic kink waves. The wave propagation suggests that the rapid high-frequency transverse waves, often produced in the lower photosphere, can penetrate into the chromosphere with an estimated energy flux of ≈15 kW m{sup −2}. Characteristics of these waves differ from those reported for other fibrillar structures, which, however, were observed mainly in the upper solar chromosphere.

  18. The hTAF II 68-TEC fusion protein functions as a strong transcriptional activator. (United States)

    Kim, Sol; Lee, Hye Jin; Jun, Hee Jung; Kim, Jungho


    Human extraskeletal myxoid chondrosarcoma (EMC) is caused by a chromosomal translocation that involves TEC (translocated in extraskeletal myxoid chondrosarcoma), and either EWS (Ewing's sarcoma) or hTAF(II)68 (human TATA-binding protein-associated factor II 68), which generates EWS-TEC or hTAF(II)68-TEC fusion proteins, respectively. Although there has been a great deal of progress in characterizing EWS-TEC, there is relatively little known about the biological function of hTAF(II)68-TEC. We have examined the functional consequences of the fusion of the amino terminal domain (NTD) of hTAF(II)68 to TEC in EMC. The chimeric gene encodes a nuclear protein that binds DNA with the same sequence specificity as parental TEC. Nuclear localization of hTAF(II)68-TEC was dependent on the DNA binding domain, and we identified a cluster of basic amino acids in the DNA binding domain, KRRR, that specifically mediate the nuclear localization of hTAF(II)68-TEC. The transactivation activity of hTAF(II)68-TEC was higher than TEC towards a known target promoter that contained several TEC binding sites. Finally, deletion analysis of hTAF(II)68-TEC indicated that the hTAF(II)68 NTD, and the AF1 and AF2 domains of hTAF(II)68-TEC are necessary for full transactivation potential. These results suggest that the oncogenic effect of the t(9;17) translocation may be due to the hTAF(II)68-TEC chimeric protein and that fusion of the hTAF(II)68 NTD to the TEC protein produces a gain of function chimeric product. (c) 2008 Wiley-Liss, Inc.


    Directory of Open Access Journals (Sweden)



    Full Text Available A new Ca(II coordination polymer has been obtained by reaction of Ca(ClO42·H2O with 3-amino-2-pyrazinecarboxylic acid in CH3CH2OH/H2O. It was characterized by IR, 1HNMR, thermal analysis and X-ray single crystal diffraction analysis. X-ray analysis reveals that each Ca(II center is seven-coordination with a N2O5 distorted pentagonal bipyramidal coordination environment. The Ca(II ions are linked through the O atoms of 3-amino-2-pyrazinecarboxylic acid ligands to form 1D chain structure. And then a 3D network structure is constructed by hydrogen bonds and π-π stacking. The antitumor activity of 3-amino-2-pyrazinecarboxylic acid ligand and its Ca(II coordination polymer against human intestinal adenocarcinoma HCT-8 cells, lung adenocarcinoma HCT-116 cells and human lung adenocarcinoma A549 cells line have been investigated.

  20. Kinetic and thermodynamic studies of the Co(II) and Ni(II) ions removal from aqueous solutions by Ca-Mg phosphates. (United States)

    Ivanets, A I; Srivastava, V; Kitikova, N V; Shashkova, I L; Sillanpää, M


    The aim of this work was to study the sorption kinetics and thermodynamics of Co(II) and Ni(II) from aqueous solutions by sorbents on the basis of hydrogen (PD-1) and tertiary (PD-2) Ca-Mg phosphates depending on the solution temperature and sorbents chemical composition. Kinetic studies of adsorption of Co(II) and Ni(II) ions onto samples of phosphate sorbents were performed in batch experiment at the temperatures 288, 303, 318 and 333 K. The sorbent dose was fixed at 10 g L -1 , initial pH value 2.6, and contact time varied from 5 to 600 min. The kinetics of Co(II) and Ni(II) adsorption were analyzed by using pseudo-first order, pseudo-second order and intraparticle diffusion models. Thermodynamic parameters (ΔG°, ΔH° and ΔS°) for the sorption of Co(II) and Ni(II) were determined using the Gibbs-Helmholtz equation. The calculated kinetic parameters and corresponding correlation coefficients revealed that Co(II) and Ni(II) uptake process followed the pseudo-second order rate expression. Thermodynamic studies confirmed the spontaneous and endothermic nature of removal process which indicate that sorption of Co(II) and Ni(II) ions onto both phosphate sorbents is favoured at higher temperatures and has the chemisorptive mechanism. The data thus obtained would be useful for practical application of the low cost and highly effective Ca-Mg phosphate sorbents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Physical conditions in CaFe interstellar clouds


    Gnacinski, P.; Krogulec, M.


    Interstellar clouds that exhibit strong Ca I and Fe I lines were called CaFe clouds. The ionisation equilibrium equations were used to model the column densities of Ca II, Ca I, K I, Na I, Fe I and Ti II in CaFe clouds. The chemical composition of CaFe clouds is that of the Solar System and no depletion of elements onto dust grains is seen. The CaFe clouds have high electron densities n=1 cm^-3 that leads to high column densities of neutral Ca and Fe.

  2. Synthesis, Crystal Structure, and Cytotoxic Activity of a Novel Eight-Coordinated Dinuclear Ca(II-Schiff Base Complex

    Directory of Open Access Journals (Sweden)

    Xi-Shi Tai


    Full Text Available A novel eight-coordinated dinuclear Ca(II complex, [Ca2(L2(H2O10]·H2O (L = 4-formylbenzene-1,3-disulfonate-3-pyridinecarboxylic hydrazone (1, was synthesized by the reaction of 3-pyridinecarboxylic hydrazide, disodium 4-formylbenzene-1,3-disulfonate, and Ca(ClO42·4H2O in ethanol-water solution (v:v = 3:1 at 50 °C. Complex 1 was characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and X-ray single crystal diffraction analysis. Dinuclear Ca(II complex 1 belongs to triclinic, space group P-1 with a = 7.186(3 Å, b = 11.978(5 Å, c = 12.263(5 Å, α = 90.318(5°, β = 91.922(5°, γ = 96.797(5°, V = 1047.5(8 Å3, Z = 1, Dc = 1.685 mg·m−3, μ = 0.572 mm−1, F(000 = 552, and final R1 = 0.0308, ωR2 = 0.0770. Dinuclear Ca(II molecules form a 1D chained structure by π–π stacking interaction. The 1D chains form a 3D framework structure by the π–π stacking interaction and hydrogen bonds. The in vitro cytotoxic activity activity of 1 against HL-60 and MLTC-1 was also investigated.

  3. Synthesis, spectroscopic and thermal studies of Mg(II), Ca(II), Sr(II) and Ba(II) diclofenac sodium complexes as anti-inflammatory drug and their protective effects on renal functions impairment and oxidative stress (United States)

    El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.


    The main task of our present study is the preparation of newly complexes of Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac which succeeded to great extent in alleviating the side effects of diclofenac alone and ameliorating the kidney function parameters and antioxidant capacities with respect to diclofenac treated group alone. The Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac have been synthesized and characterized using infrared, electronic and 1H NMR spectral, thermogravimetric and conductivity measurements. The diclofenac ligand has been found to act as bidentate chelating agent. Diclofenac complexes coordinate through the oxygen's of the carboxyl group. The molar ratio chelation is 1:2 (M2+-dic) with general formula [M(dic)2(H2O)2]ṡnH2O. Antibacterial screening of the alkaline earth metal complexes against Escherichia coli (Gram - ve), Bacillus subtilis (Gram + ve) and anti-fungal (Asperagillus oryzae, Asperagillus niger, Asperagillus flavus) were investigated. The kidney functions in male albino rats were ameliorated upon treatment with metal complexes of dic, which are represented by decreasing the levels of urea and uric acid to be located within normal values. The other looks bright spot in this article is the assessment of antioxidant defense system including SOD, CAT and MDA with the help of Sr2+, Mg2+ and Ca2+-dic complexes. The hormones related to kidney functions and stresses have been greatly ameliorated in groups treated with dic complexes in comparable with dic treated group.

  4. Effect of carticaine on the sarcoplasmic reticulum Ca2+-adenosine triphosphatase. II. Cations dependence. (United States)

    Takara, Delia; Sánchez, Gabriel A; Toma, Augusto F; Bonazzola, Patricia; Alonso, Guillermo L


    Ca2+-ATPase is a major intrinsic protein in the sarcoplasmic reticulum (SR) from skeletal muscles. It actively transports Ca2+ from the cytoplasm to the SR lumen, reducing cytoplasmic [Ca2+] to promote muscle relaxation. Carticaine is a local anesthetic widely used in operative dentistry. We previously showed that carticaine inhibits SR Ca2+-ATPase activity and the coupled Ca(2+) uptake by isolated SR vesicles, and increases the rate of Ca2+ efflux from preloaded vesicles. We also found that these effects were antagonized by divalent cations, and concluded that they were mainly due to the direct interaction of carticaine with the Ca2+-ATPase protein. Here we present additional results on the modulation of the above effects of carticaine by Ca2+ and Mg2+. The activating effect of Ca2+ on the ATPase activity is competitively inhibited by carticaine, indicating a decreased Ca2+ binding to the high affinity Ca2+ transport sites. The activating effect of Mg2+ on the phosphorylation of Ca2+-ATPase by orthophosphate is also inhibited by carticaine. The anesthetic does not affect the reaction mechanism of the cations acting as cofactors of ATP in the catalytic site. On the basis of the present and our previous results, we propose a model that describes the effect of carticaine on the Ca2+-ATPase cycle.

  5. Urotensin II induction of neonatal cardiomyocyte hypertrophy involves the CaMKII/PLN/SERCA 2a signaling pathway. (United States)

    Shi, Hongtao; Han, Qinghua; Xu, Jianrong; Liu, Wenyuan; Chu, Tingting; Zhao, Li


    Although studies have shown that Urotensin II (UII) can induce cardiomyocyte hypertrophy and UII-induced cardiomyocyte hypertrophy model has been widely used for hypertrophy research, but its precise mechanism remains unknown. Recent researches have demonstrated that UII-induced cardiomyocyte hypertrophy has a relationship with the changes of intracellular Ca(2+) concentration. Therefore, the aim of this study was to investigate the mechanisms of cardiomyocyte hypertrophy induced by UII and to explore whether the calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated up-regulating of phospholamban (PLN) Thr17-phosphorylation signaling pathway contributed to UII-induced cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were stimulated for 48h with UII. Cell size, protein/DNA contents and intracellular Ca(2+) were determined. Phosphorylated and total forms of CaMKII, PLN and the total amount of serco/endo-plasmic reticulum ATPases (SERCA 2a) were quantified by western blot. The responses of cardiomyocytes to UII were also evaluated after pretreatment with the CaMKII inhibitor, KN-93. These results showed that UII increased cell size, protein/DNA ratio and intracellular Ca(2+), consistent with a hypertrophic response. Furthermore, the phosphorylation of CaMKII and its downstream target PLN (Thr17), SERCA 2a levels were up-regulated by UII treatment. Conversely, treatment with KN-93 reversed all those effects of UII. Taken together, the results suggest that UII can induce cardiomyocyte hypertrophy through CaMKII-mediated up-regulating of PLN Thr17-phosphorylation signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. New 3D gas density maps of NaI and CaII interstellar absorption within 300 pc (United States)

    Welsh, B. Y.; Lallement, R.; Vergely, J.-L.; Raimond, S.


    Aims: We present new high resolution (R > 50 000) absorption measurements of the NaI doublet (5889-5895 Å) along 482 nearby sight-lines, in addition to 807 new measurements of the CaII K (3933 Å) absorption line. We have combined these new data with previously reported measurements to produce a catalog of absorptions towards a total of 1857 early-type stars located within 800 pc of the Sun. Using these data we have determined the approximate 3-dimensional spatial distribution of neutral and partly ionized interstellar gas density within a distance-cube of 300 pc from the Sun. Methods: All newly recorded spectra were analyzed by means of a multi-component line profile-fitting program, in most cases using simultaneous fits to the line doublets. Normalized absorption profiles were fitted by varying the velocity, doppler width and column density for all intervening interstellar clouds. The resulting total column densities were then used in conjunction with the Hipparcos distances of the target stars to construct inversion maps of the 3D spatial density distribution of the NaI and CaII bearing gas. Results: A plot of the equivalent width of NaI versus distance reveals a wall of neutral gas at ~80 pc that can be associated with the boundary wall to the central rarefied Local Cavity region. In contrast, a similar plot for the equivalent width of CaII shows no sharply increasing absorption at 80 pc, but instead we observe a slowly increasing value of CaII equivalent width with increasing sight-line distance sampled. Low values for the volume density of NaI (nNaI values in the range 10-8 >nNaI > 10-10 cm-3 are found for sight-lines with distance >300 pc. Both high and low values of the volume density of CaII (nCaII) are found for sight-lines 100 pc a value of nCaII ~ 10-9 cm-3 is typical for most sight-lines, indicating that the distribution of CaII bearing gas is fairly uniform throughout the general ISM. Our three maps of the 3D spatial distribution of local neutral Na


    International Nuclear Information System (INIS)

    Batcheldor, D.; Mandalou, J.; Axon, D.; Valluri, M.; Merritt, D.


    The relations observed between supermassive black holes and their host galaxies suggest a fundamental link in the processes that cause these two objects to evolve. A more comprehensive understanding of these relations could be gained by increasing the number of supermassive black hole mass (M . ) measurements. This can be achieved, in part, by continuing to model the stellar dynamics at the centers of galactic bulges using data of the highest possible spatial resolution. Consequently, we present here an atlas of galaxies in the Space Telescope Imaging Spectrograph (STIS) data archive that may have spectra suitable for new M . estimates. Archived STIS G750M data for all non-barred galactic bulges are co-aligned and combined, where appropriate, and the radial signal-to-noise ratios calculated. The line-of-sight velocity distributions from the Ca II triplet are then determined using a maximum penalized likelihood method. We find 19 out of 42 galaxies may provide useful new M . estimates since they are found to have data that is comparable in quality with data that has been used in the past to estimate M . . However, we find no relation between the signal-to-noise ratio in the previously analyzed spectra and the uncertainties of the black hole masses derived from the spectra. We also find that there is a very limited number of appropriately observed stellar templates in the archive from which to estimate the effects of template mismatching

  8. Application of Central Composite Design in the Adsorption of Ca(II on Metakaolin Zeolite

    Directory of Open Access Journals (Sweden)

    Upenyu Guyo


    Full Text Available Metakaolin zeolite-A was synthesized from thermally activated kaolin clay and characterized by Fourier Transform Infrared Spectroscopy and X-Ray Diffraction Spectroscopy. The effects of pH (2–10, contact time (10–180 min, initial concentration (5–120 mgL−1, and dosage (0.1–2 g and their interactions were investigated using response surface methodology following a central composite design. Optimum removal (87.70% was obtained at pH 6, contact time 180 min, initial concentration 40.0 mgL−1, and adsorbent dosage 1.0 g by Excel Solver using the GRG solving method. The adsorption data fitted best to the Langmuir model with correlation coefficient R2=0.993 and Chi-square value χ2=4.76. The Freundlich isotherm gave a correlation coefficient R2=0.933 and χ2=37.91. The adsorption process followed the pseudo-second-order model. The calculated thermodynamic parameters showed that the adsorption process was endothermic and not thermodynamically spontaneous. The studied zeolite-A can therefore be used as a promising adsorbent for the removal of Ca(II ions from aqueous solutions.

  9. Complete Call-by-Value Calculi of Control Operators II: Strong Termination


    Hasegawa, Ryu


    We provide characterization of the strong termination property of the CCV lambda-mu calculus introduced in the first part of the series of the paper. The calculus is complete with respect to the standard CPS semantics. The union-intersection type systems for the calculus is developed in the previous paper. We characterize the strong normalizability of terms of the calculus in terms of the CPS semantics and typeability.

  10. Non-LTE profiles of strong solar lines (United States)

    Schneeberger, T. J.; Beebe, H. A.


    The complete linearization method is applied to the formation of strong lines in the solar atmosphere. Transitions in Na(I), Mg(I), Ca(I), Mg(II), and Ca(II) are computed with a standard atmosphere and microturbulent velocity model. The computed profiles are compared to observations at disk center.

  11. Highly controlled orientation of CaBi4Ti4O15 using a strong magnetic field (United States)

    Suzuki, Tohru S.; Kimura, Masahiko; Shiratsuyu, Kosuke; Ando, Akira; Sakka, Yoshio; Sakabe, Yukio


    The texture of feeble magnetic ceramics can be controlled by a strong magnetic field. When the magnetic susceptibility of the c axis is smaller than that of the other axes, the c axis aligns perpendicular to the magnetic field; however, the direction is randomly oriented on the plane perpendicular to the magnetic field. The authors demonstrate in this letter that a highly controlled texture in bismuth titanate, which has a c-axis susceptibility smaller than the other axes, can be achieved using a two-step magnetic field procedure. This highly controlled orientation is effective for improving the electromechanical coupling coefficient.

  12. Departures from predicted type II behavior in dirty strong-coupling superconductors

    International Nuclear Information System (INIS)

    Park, J.C.; Neighbor, J.E.; Shiffman, C.A.


    Calorimetric measurements of the Ginsburg-Landau parameters for Pb-Sn and Pb-Bi alloys show good agreement with the calculations of Rainer and Bergmann for kappa 1 (t)/kappa 1 (1). However, the calculations of Rainer and Usadel for kappa 2 (t)/kappa 2 (1) substantially underestimate the enhancements due to strong-coupling. (Auth.)

  13. Ca II triplet spectroscopy of RGB stars in NGC 6822: kinematics and metallicities (United States)

    Swan, J.; Cole, A. A.; Tolstoy, E.; Irwin, M. J.


    We present a detailed analysis of the chemistry and kinematics of red giants in the dwarf irregular galaxy NGC 6822. Spectroscopy at ≈8500 Å was acquired for 72 red giant stars across two fields using FORS2 at the VLT. Line-of-sight extinction was individually estimated for each target star to accommodate the variable reddening across NGC 6822. The mean radial velocity was found to be = -52.8 ± 2.2 km s-1 with dispersion σv = 24.1 km s-1, in agreement with other studies. Ca II triplet equivalent widths were converted into [Fe/H] metallicities using a V magnitude proxy for surface gravity. The average metallicity was = -0.84 ± 0.04 with dispersion σ = 0.31 dex and interquartile range 0.48. Our assignment of individual reddening values makes our analysis more sensitive to spatial variations in metallicity than previous studies. We divide our sample into metal-rich and metal-poor stars; the former were found to cluster towards small radii with the metal-poor stars more evenly distributed across the galaxy. The velocity dispersion of the metal-poor stars was found to be higher than that of the metal-rich stars (σ _{v_MP}=27.4 km s-1; σ _{v_MR}=21.1 km s-1); combined with the age-metallicity relation this indicates that the older populations have either been dynamically heated during their lifetimes or were born in a less disc-like distribution than the younger stars.. The low ratio vrot/σv suggests that within the inner 10 arcmin, NGC 6822's stars are dynamically decoupled from the H I gas, and possibly distributed in a thick disc or spheroid structure.

  14. Strong Isotopic Effect in Phase II of Dense Solid Hydrogen and Deuterium


    Geneste, Grégory; Torrent, Marc; Bottin, François; Loubeyre, Paul


    Quantum nuclear zero-point motions in solid H$_2$ and D$_2$ under pressure are investigated at 80 K up to 160 GPa by first-principles path-integral molecular dynamics calculations. Molecular orientations are well-defined in phase II of D$_2$, while solid H$_2$ exhibits large and very asymmetric angular quantum fluctuations in this phase, with possible rotation in the (bc) plane, making it difficult to associate a well-identified single classical structure. The mechanism for the transition to ...

  15. Strong Isotope Effect in Phase II of Dense Solid Hydrogen and Deuterium (United States)

    Geneste, Grégory; Torrent, Marc; Bottin, François; Loubeyre, Paul


    Quantum nuclear zero-point motions in solid H2 and D2 under pressure are investigated at 80 K up to 160 GPa by first-principles path-integral molecular dynamics calculations. Molecular orientations are well defined in phase II of D2, while solid H2 exhibits large and very asymmetric angular quantum fluctuations in this phase, with possible rotation in the (bc) plane, making it difficult to associate a well-identified single classical structure. The mechanism for the transition to phase III is also described. Existing structural data support this microscopic interpretation.

  16. Large Negative Thermal Expansion and Anomalous Behavior on Compression in Cubic ReO 3 -Type A II B IV F 6 : CaZrF 6 and CaHfF 6

    Energy Technology Data Exchange (ETDEWEB)

    Hancock, Justin C.; Chapman, Karena W.; Halder, Gregory J.; Morelock, Cody R.; Kaplan, Benjamin S.; Gallington, Leighanne C.; Bongiorno, Angelo; Han, Chu; Zhou, Si; Wilkinson, Angus P.


    CaZrF6 and CaHfF6 display much stronger negative thermal expansion (NTE) (alpha(L100 K) similar to -18 and -22 ppm K-1, respectively) than ZrW2O8 and other corner-shared framework structures. Their NTE is comparable to that reported for framework solids containing multiatom bridges, such as metal cyanides and metal-organic frameworks. However, they are formable as ceramics, transparent over a wide wavelength range and can be handled in air; these characteristics can be beneficial for applications. The NTE of CaZrF6 is strongly temperature-dependent, and first-principles calculations show that it is largely driven by vibrational modes below similar to 150 cm(-1). CaZrF6 is elastically soft with a bulk modulus (K-300K) of 37 GPa and, upon compression, starts to disorder at similar to 400 MPa. The strong NTE of CaZrF6, which remains cubic to <10 K, contrasts with cubic CoZrF6, which only displays modest NTE above its rhombohedral to cubic phase transition at similar to 270 K. CaZrF6 and CaHfF6 belong to a large and compositionally diverse family of materials, A(II)B(IV)F(6), providing for a detailed exploration of the chemical and structural factors controlling NTE and many opportunities for the design of controlled thermal expansion materials.

  17. A Butterfly Diagram and Carrington Maps for Century-long CA II K Spectroheliograms from The Kodaikanal Observatory (United States)

    Chatterjee, Subhamoy; Banerjee, Dipankar; Ravindra, B.


    The century-long (1907-2007) Ca II K spectroheliograms from the Kodaikanal Solar Observatory (KSO) are calibrated, processed, and analyzed to follow the evolution of the bright on-disc structures called plages, possible representatives of magnetic activity on the Sun. This is the longest data set studied in Ca II K to date, covering about 9.5 cycles of 11 yr periods. Plages are segmented with area ≥slant 1 {{arcmin}}2 using global thresholds for individual full disc images and subsequent application of a morphological closing operation. The plage index is calculated and is seen to have a close positive correlation with the fractional disc area covered by plages. The newly generated plage area cycle (from KSO) was compared with the same from the Mount Wilson Observatory (correlation 95.6%) for the overlapping years, I.e., 1915-2000. This study illustrates the time-latitude distribution of plage centroids by rendering a butterfly diagram (as observed for sunspots). The 3D visualization of the diagram shows one-to-one mapping between plage location, time, and area. This work further delineates the positional correlation between magnetic patches and plage regions through the comparison of synoptic maps derived from both KSO Ca II K images and space-based full disc line-of-sight magnetograms. Regular synoptic magnetograms from ground-based observatories are available only after 1970s. Thus the long term Ca II K data from KSO can be used as a proxy for estimating magnetic activity locations and their strengths at earlier times.

  18. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.6778 >orf19.6778; Contig19-10254; complement(10843...2..112394); DRS2*; membrane-spanning Ca-ATPase (P- type); gene family MSNYNRTDNSKSNANPNPNANPNNPFSDNANNLIDLDL

  19. Efficient biosorption of lead(II) and cadmium(II) ions from aqueous solutions by functionalized cell with intracellular CaCO3 mineral scaffolds. (United States)

    Ma, Xiaoming; Cui, Weigang; Yang, Lin; Yang, Yuanyuan; Chen, Huifeng; Wang, Kui


    The functionalized Saccharomyces cerevisiae cell with biogenic intracellular CaCO3 mineral scaffold, synthesized via a simple and environmentally friendly approach, was efficient for removing lead (II) and cadmium (II) ions from aqueous solutions. The CaCO3 mineral scaffold could promote the uptake of the heavy metal ions and increase the biosorption capabilities of the adsorbent. Compared with the Freundlich isotherm, Langmuir model more fitted the equilibrium data. The maximum removal capacity of functionalized cells for Pb(II) and Cd(II) was 116.69 and 42.63mgg(-1), respectively. Further investigation showed that the adsorbent had high removal efficiency for trace amount of heavy metal ions. Adsorption data were modeled using the pseudo-first-order, pseudo-second-order and intra-particle diffusion kinetics equations. The results indicated that pseudo-second-order kinetic equation and intra-particle diffusion model could better describe the adsorption kinetics. The heavy metal ions might be removed by functionalized cells via membrane transport of metal ions and precipitation transformation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Physicochemical impact studies of gamma rays on "aspirin" analgesics drug and its metal complexes in solid form: Synthesis, spectroscopic and biological assessment of Ca(II), Mg(II), Sr(II) and Ba(II) aspirinate complexes (United States)

    Refat, Moamen S.; Sharshar, T.; Elsabawy, Khaled M.; Heiba, Zein K.


    Metal aspirinate complexes, M2(Asp)4, where M is Mg(II), Ca(II), Sr(II) or Ba(II) are formed by refluxed of aspirin (Asp) with divalent non-transition metal ions of group (II) and characterized by elemental analysis and spectroscopic measurements (infrared, electronic, 1H NMR, Raman, X-ray powder diffraction and scanning electron microscopy). Elemental analysis of the chelates suggests the stoichiometry is 1:2 (metal:ligand). Infrared spectra of the complexes agree with the coordination to the central metal atom through three donation sites of two oxygen atoms of bridge bidentate carboxylate group and oxygen atom of sbnd Cdbnd O of acetyl group. Infrared spectra coupled with the results of elemental analyzes suggested a distorted octahedral structure for the M(II) aspirinate complexes. Gamma irradiation was tested as a method for stabilization of aspirin as well as their complexes. The effect of gamma irradiation, with dose of 80 Gy, on the properties of aspirinate complexes was studied. The aspirinate chelates have been screened for their in vitro antibacterial activity against four bacteria, gram-positive (Bacillus subtilis and Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) and two strains of fungus (Aspergillus flavus and Candida albicans). The metal chelates were shown to possess more antibacterial activity than the free aspirin chelate.

  1. Intracellular angiotensin II elicits Ca2+ increases in A7r5 vascular smooth muscle cells

    NARCIS (Netherlands)

    Filipeanu, CM; Brailoiu, E; Kok, JW; Henning, RH; De Zeeuw, D; Nelemans, SA


    Recent studies show that angiotensin II can act within the cell, possibly via intracellular receptors pharmacologically different from typical plasma membrane angiotensin II receptors. The signal transduction of intracellular angiotensin LI is unclear. Therefore. we investigated the effects of

  2. An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy. (United States)

    Lach-Trifilieff, Estelle; Minetti, Giulia C; Sheppard, KellyAnn; Ibebunjo, Chikwendu; Feige, Jerome N; Hartmann, Steffen; Brachat, Sophie; Rivet, Helene; Koelbing, Claudia; Morvan, Frederic; Hatakeyama, Shinji; Glass, David J


    The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings.

  3. Cyclometalated Ruthenium(II) Anthraquinone Complexes Exhibit Strong Anticancer Activity in Hypoxic Tumor Cells. (United States)

    Zeng, Leli; Chen, Yu; Huang, Huaiyi; Wang, Jinquan; Zhao, Donglei; Ji, Liangnian; Chao, Hui


    Hypoxia is the critical feature of the tumor microenvironment that is known to lead to resistance to many chemotherapeutic drugs. Six novel ruthenium(II) anthraquinone complexes were designed and synthesized; they exhibit similar or superior cytotoxicity compared to cisplatin in hypoxic HeLa, A549, and multidrug-resistant (A549R) tumor cell lines. Their anticancer activities are related to their lipophilicity and cellular uptake; therefore, these physicochemical properties of the complexes can be changed by modifying the ligands to obtain better anticancer candidates. Complex 1, the most potent member of the series, is highly active against hypoxic HeLa cancer cells (IC50 =0.53 μM). This complex likely has 46-fold better activity than cisplatin (IC50 =24.62 μM) in HeLa cells. This complex tends to accumulate in the mitochondria and the nucleus of hypoxic HeLa cells. Further mechanistic studies show that complex 1 induced cell apoptosis during hypoxia through multiple pathways, including those of DNA damage, mitochondrial dysfunction, and the inhibition of DNA replication and HIF-1α expression, making it an outstanding candidate for further in vivo studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


    Directory of Open Access Journals (Sweden)

    Nicoleta IANOVICI


    Full Text Available Această cercetare prezintă date obţinute prin prelevarea polenului de la patru specii (Plantago lanceolata, Plantago major, Ambrosia artemisiifolia, Tilia cordata şi testarea viabilităţii acestuia prin tratare cu TTC. Aceste date preliminare sunt insuficiente pentru a da o concluzie specifică. Oricum, se poate spune că viabilitatea polenului poate fi un parametru reprezentativ pentru a stabili care plante sunt mai bine adaptate mediului urban. Modificarea viabilităţii polenului indică prezenţa gazelor cu caracter poluant, rezultate mai ales din traficul rutier, la toate cele patru specii. Polenul de Plantago lanceolata şi Tilia cordata ar putea fi folosit ca bio-indicator al calităţii aerului într-un ecosistem urban.

  5. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.7258 >orf19.7258; Contig19-2507; 88880..89851; DDI1*; response to DNA alkyl...ation; MQLTISLDHSGDIISVDVPDSLCLEDFKAYLSAETGLEASVQVLKFNGRELVGNATLSELQIHDNDLLQLSKKQVA

  6. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.7549 >orf19.7549; Contig19-2518; complement(3667.....5844); PMT5*; dolichyl-phosphate-mannose-protein mannosyltransferase; gene family MTKELPSGYFQGPFRPYKTFQPSLTE

  7. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.3852 >orf19.3852; Contig19-10193; complement(6245.....8632); ; putative alpha-1,2-mannosidase; MNFILTIIFLISNYLLVVESVAIKNLYSYLSLHKKDNAGDSSNDVFKNVDLFYGTDKNGHMFPGIT

  8. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.7030 >orf19.7030; Contig19-10262; complement(71490.....72194); CCW14*(CCW14); cell wall mannoprotein | secretory Stress Response protein; MASFLKISTLIAIVSTLQTTLAA

  9. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4475 >orf19.4475; Contig19-10206; complement(34852.....36294); MNT4; putative mannosyltransferase; MISFISLRRRKLISILAIFTIFILSGSIIGYYNGHHHIIKMVENYTPDDFQNSITALTNKFD

  10. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.1036 >orf19.1036; Contig19-10087; 26898..28745; MNS1*; mann...osyl- oligosaccharide 1,2-alpha-mannosidase; MSFSFGINNISKGNNTYKDKPAGGALPLFYKDKVPAFHPAHTSKNKKRILMLLK

  11. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4175 >orf19.4175; Contig19-10200; complement(34037.....36262); TOK1*; outward-rectifier potassium channel; MGFHAPLNGSSKNSKSSAFASFDSASVMQIVNKAKDKIVPDAQFHQTITDQGIR

  12. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.1969 >orf19.1969; Contig19-10137; complement(91851.....92666); CCW14*; cell wall mannoprotein involved in cell stress response; MLVLVIALVFLKSILATPPACFLSCINEIAHDC

  13. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.5917.3 >orf19.5917.3; Contig19-10236; join(118231.....118503,119407..119817); YRA1*; RNA annealing protein; MSASLDKSLDDIISSNKKTFKSKRPGAKFGAKGGNRVGKKIGGTNNNKKPIAK

  14. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.849 >orf19.849; Contig19-10076; complement(119209.....121755); MNN4*; regulator of cell wall mannosyl phosphorylation; gene family MPRLKRALLSPKLFVKSILLFTIVYTIYLS

  15. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4362 >orf19.4362; Contig19-10203; complement(28509.....29618); MSP1*; 40 kDa putative membrane-spanning ATPase; MINKLKIDFGKFKIDLKLLGDLFVLAGAGLSVYYILNTILNDYLDNTVK

  16. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.851 >orf19.851; Contig19-10076; 128258..130774; MN...N41*; regulator of cell wall mannosyl phosphorylation; gene family MFIIRRSRGILLLVSIVVFNLIVLSLFQFTPIDNYVIGNKY

  17. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.2768 >orf19.2768; Contig19-10158; complement(22521...7..228684); AMS1*; vacuolar alpha mannosidase; MGYDNINLQPNFKPIDHLYDDRLRQFTDTGGQFHNLNLPKFYDIHRQEIHDLKSWKVPDDS

  18. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4765 >orf19.4765; Contig19-10215; complement(92513.....93172); CCW12*; cell wall mannoprotein; MQFQTLLVVAGSLVASTLAVNSTVTEHHTTEITITHCSDNKCATSVAPAVQSVNTVTIEGVVTEYT

  19. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.1011 >orf19.1011; Contig19-10083; complement(4999.....6981); MNN2*; alpha-1,2-mannosyltransferase; MFQQLTYRLRLFRRRHKYIFINSIFLSVIIIFLIYSYWSNLPAEDNSAIINEKGTYHRSLWE

  20. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4600.1 >orf19.4600.1; Contig19-10212; complement(7...5938..76216); DPM3*; dolichol-phosphate-mannose synthase; MTKATETGLTIFALSAIYFALITGVIPTPAKIHDEILPYLPWWGLVTFGSYALSTLGWGIVTFKDKEHKYKELKIQIEEAKDFYKTKGIDLD*

  1. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.5164 >orf19.5164; Contig19-10219; complement(75211.....76965); ECM39*; alpha-1,6- mannosyltransferase; MYRYNKVLDATLIALVSFHLVISPFTKVEESFNIQAIHDILKFGIFPLETIDNYDHKQ

  2. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.2881 >orf19.2881; Contig19-10162; complement(27312.....30302); MNN42*; involved in mannose metabolism and cell wall synthesis; MSNTIPQYFIRIFNLIFSARRKNFQLALISGLLF

  3. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.2370 >orf19.2370; Contig19-10147; complement(50671..52716); DSL1*; ER-to-golgi transport; MPSIEQQLEDQELYLKDIEQNINKTLSKINKTTLENDNDFRKQFEEIPQDSNTTESN

  4. Mechanically induced strong red emission in samarium ions doped piezoelectric semiconductor CaZnOS for dynamic pressure sensing and imaging (United States)

    Wang, Wei; Peng, Dengfeng; Zhang, Hanlu; Yang, Xiaohong; Pan, Caofeng


    Piezoelectric semiconductor with optical, electrical and mechanical multifunctions has great potential applications in future optoelectronic devices. The rich properties and applications mainly encompass the intrinsic structures and their coupling effects. Here, we report that lanthanide ions doped piezoelectric semiconductor CaZnOS:Sm3+ showing strong red emission induced by dynamic mechanical stress. Under moderate mechanical load, the doped piezoelectric semiconductor exhibits strong visible red emission to the naked eyes even under the day light. A flexible dynamic pressure sensor device is fabricated based on the prepared CaZnOS:Sm3+ powders. The mechanical-induced emission properties of the device are investigated by the optical fiber spectrometer. The linear characteristic emissions are attributed to the 4G5/2→6H5/2 (566 nm), 4G5/2→6H7/2 (580-632 nm), 4G5/2→6H9/2 (653-673 nm) and 4G5/2→6H11/2 (712-735 nm) f-f transitions of Sm3+ ions. The integral emission intensity is proportional to the value of applied pressure. By using the linear relationship between integrated emission intensity and the dynamic pressure, the real-time pressure distribution is visualized and recorded. Our results highlight that the incorporation of lanthanide luminescent ions into piezoelectric semiconductors as smart materials could be applied into the flexible mechanical-optical sensor device without additional auxiliary power, which has great potential for promising applications such as mapping of personalized handwriting, smart display, and human machine interface.

  5. Inhibitions of late INa and CaMKII act synergistically to prevent ATX-II-induced atrial fibrillation in isolated rat right atria. (United States)

    Liang, Faquan; Fan, Peidong; Jia, Jessie; Yang, Suya; Jiang, Zhan; Karpinski, Serge; Kornyeyev, Dmytro; Pagratis, Nikos; Belardinelli, Luiz; Yao, Lina


    Increases in late Na(+) current (late INa) and activation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII) are associated with atrial arrhythmias. CaMKII also phosphorylates Nav1.5, further increasing late INa. The combination of a CaMKII inhibitor with a late INa inhibitor may be superior to each compound alone to suppress atrial arrhythmias. Therefore, we investigated the effect of a CaMKII inhibitor in combination with a late INa inhibitor on anemone toxin II (ATX-II, a late INa enhancer)-induced atrial arrhythmias. Rat right atrial tissue was isolated and preincubated with either the CaMKII inhibitor autocamtide-2-related inhibitory peptide (AIP), the late INa inhibitor GS458967, or both, and then exposed to ATX-II. ATX-II increased diastolic tension and caused fibrillation of isolated right atrial tissue. AIP (0.3μmol/L) and 0.1μmol/L GS458967 alone inhibited ATX-II-induced arrhythmias by 20±3% (mean±SEM, n=14) and 34±5% (n=13), respectively, whereas the two compounds in combination inhibited arrhythmias by 81±4% (n=10, pATX-induced increase of diastolic tension. Consistent with the mechanical and electrical data, 0.3μmol/L AIP and 0.1μmol/L GS458967 each inhibited ATX-II-induced CaMKII phosphorylation by 23±3% and 32±4%, whereas the combination of both compounds inhibited CaMKII phosphorylation completely. The effects of an enhanced late INa to induce arrhythmic activity and activation of CaMKII in atria are attenuated synergistically by inhibitors of late INa and CaMKII. Copyright © 2016 Elsevier Ltd. All rights reserved.


    NARCIS (Netherlands)



    We present optical absorption spectroscopy of the Ca II K and H lines along the sight line to the quasar PKS 0837-120, which lies in the direction of a high-velocity cloud (HVC) detected in H I 21-cm emission at V(LSR) = + 105 km s-1. Our data show Ca II absorption due to the HVC as well as a lower

  7. Synthesis, Structural Characterization, and Antitumor Activity of a Ca(II Coordination Polymer Based on 1,6-Naphthalenedisulfonate and 4,4′-Bipyridyl

    Directory of Open Access Journals (Sweden)

    Xishi Tai


    Full Text Available A novel Ca(II coordination polymer, [CaL(4,4′-bipyridyl(H2O4]n (L = 1,6-naphthalenedisulfonate, was synthesized by reaction of calcium perchlorate with 1,6-naphthalenedisulfonic acid disodium salt and 4,4′-bipyridyl in CH3CH2OH/H2O. It was characterized by elemental analysis, IR, molar conductivity and thermogravimetric analysis. X-ray crystallography reveals that the Ca(II coordination polymer belongs to the orthorhombic system, with space group P212121. The geometry of the Ca(II ion is a distorted CaNO6 pengonal bipyramid, arising from its coordination by four water molecules, one nitrogen atom of 4,4′-bipyridyl molecule, and two oxygen atoms from two L ligands. The complex molecules form a helical chain by self-assembly. The antitumor activity of 1,6-naphthalenedisulfonic acid disodium salt and the Ca(II coordination polymer against human hepatoma smmc-7721 cell line and human lung adenocarcinoma A549 cell line reveals that the Ca(II coordination polymer inhibits cell growth of human lung adenocarcinoma A549 cell line with IC50 value of 27 μg/mL, and is more resistive to human lung adenocarcinoma A549 cell line as compared to 1,6-naphthalenedisulfonic acid disodium salt.

  8. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.1390; >1pmi0 1 440 2 441 0.0 ... gb|EAK95509.1| hypot...hetical protein CaO19.1390 [Candida albicans SC5314] ... emb|CAA57548.1| mannose-6-phosphate isomeras...e [Candida ... albicans] pir||S55354 mannose-6-phosphate isomerase (EC ... - yeast (C...andida albicans) sp|P34948|MANA_CANAL ... Mannose-6-phosphate isomerase (Phosphomann

  9. A study of the cavity polariton under strong excitation:dynamics and nonlinearities in II-VI micro-cavities

    International Nuclear Information System (INIS)

    Muller, Markus


    This work contains an experimental study of the photoluminescence dynamics of cavity polaritons in strong coupling micro-cavities based on II-VI semiconductor compounds. The small exciton size and the strong exciton binding energy in these materials allowed us to study the strong coupling regime between photon and exciton up to high excitation densities, exploring the linear and non-linear emission regimes. Our main experimental techniques are picosecond time-resolved and angular photoluminescence spectroscopy. In the linear regime and for a negative photon-exciton detuning, we observe a suppression of the polariton relaxation by the emission of acoustic phonons leading to a non-equilibrium polariton distribution on the lower branch. This 'bottleneck' effect, which has already been described for polaritons in bulk semiconductors, results from the pronounced photon like character of the polaritons near k(parallel) = 0 in this configuration. At high excitation densities, non-linear relaxation processes, namely final state stimulation of the relaxation and polariton-polariton scattering, bypass this bottleneck giving rise to a very rapid relaxation down to the bottom of the band. We show that this dramatic change in the relaxation dynamics is finally responsible of the super-linear increase of the polariton emission from these states. (author) [fr

  10. Observations of the Ca ${\\rm\\tiny II} $ IR Triplet in High Luminosity ...

    Indian Academy of Sciences (India)

    Abstract. We present a new spectroscopic sample of 11 quasars at intermediate redshift observed with the Infrared Spectrometer and Array Camera (ISAAC) on the ESO Very Large Telescope (VLT), covering O I 8446 and the Ca I I triplet 8498, 8542, 8662. The new observations – that supplement the sample presented by ...

  11. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4769; Contig19-10215; join(105865..106689,106749.....107408); IPT1*; necessary for synthesis of mannose-(inositol-P)2-ceramide (M(IP)2C) | inositolphosphotransfe

  12. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.6996 >orf19.6996; Contig19-2500; 87694..89670; MNT44*; alpha-1,3- mann...osyltransferase involved in adding the 4th and 5th mannose residues of O-linked glycans;

  13. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.7450 >orf19.7450; Contig19-2514; 103272..104363; B...NI5*; may localize to mother-bud neck in a septin-dependent manner | similar to mammalian homer porteins; MP

  14. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.3449; >1chc0 2 68 535 601 5e-19 ... ref|XP_429145.1| ...PREDICTED: similar to Potassium/sodium hyperpolarization-activated ... cyclic nucleotide-gated channe...l 1 (Brain cyclic ... nucleotide gated channel 1) (BCNG-1) [Gallus gallus] ... Length = 67 ... Qu

  15. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.3622 >orf19.3622; Contig19-10184; complement(58884..60170); ANP1*; 8 | Golgi mannosyltransferase required for protein glycosylation; MFYSLRTLIISIVIGIIT

  16. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.1665 >orf19.1665; Contig19-10123; 125727..127022; ...KTR1*(KRE2); alpha-1,2-mannosyltransferase involved in n-linked and o-linked glycosylation; MASTRSNARLIRFGIF

  17. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.2937; >1u02A 1 220 11 247 4e-27 ... gb|EAL02637.1| hy....10454 [Candida ... albicans SC5314] gb|AAA34356.1| phosphomannomutase ... [Candida albicans] ...sp|P31353|PMM_CANAL ... Phosphomannomutase (PMM) ... Length = 237 ...

  18. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.1042; Contig19-10087; complement(35388..36236); PO...R1*(OMP2); porin|voltage-dependent anion channel(VDAC); >1o08A 3 187 2 193 2e-06 ... ref|ZP_00163152.1| COG0546

  19. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4442 >orf19.4442; Contig19-10205; 58921..60603; ALG9*; mann...osyltransferase that catalyzes the transfer of mannose from Dol-P-Man to lipid-linked oligosacchari

  20. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.3111; >1eb6A 4 175 45 228 4e-34 ... gb|AAC00525.1| pH...8 kDa fibrinogen ... binding mannoprotein) ... Length = 184 ... Query: 45 ... SSCNATQYNQLSTGLQEAQLLA

  1. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.1042 >orf19.1042; Contig19-10087; complement(35388.....36236); POR1*(OMP2); porin|voltage-dependent anion channel(VDAC); MAPAAYSDLSKASNDLINKDFYHLSTAAVDVKTVAPNGVT

  2. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.3734 >orf19.3734; Contig19-10190; 27973..30552; ; ...voltage-gated protein/chloride channel involved in intracellular iron metabolism; gene family MRSRFFGKVHDTFI

  3. Monoclonal antibody against brain calmodulin-dependent protein kinase type II detects putative conformational changes induced by Ca2+-calmodulin

    International Nuclear Information System (INIS)

    LeVine, H. III; Su, J.L.; Sahyoun, N.E.


    A mouse monoclonal IgG1 antibody has been generated against the soluble form of the calmodulin-dependent protein kinase type II. This antibody recognizes both the soluble and cytoskeletal forms of the enzyme, requiring Ca 2+ for the interaction. Other divalent cations such as Zn 2+ , Mn 2+ , Cd 2+ , Co 2+ , and Ni 2+ will substitute for Ca 2+ , while Mg 2+ and Ba 2+ will not. The antibody reacts with both the α- and β-subunits on Western blots in a similar Ca 2+ -dependent fashion but with a lower sensitivity. The affinity of the antibody for the kinase is 0.13 nM determined by displacement of 125 I Bolton-Hunter-labeled kinase with unlabeled enzyme. Calmodulin and antibody reciprocally potentiate each other's interaction with the enzyme. This is illustrated both by direct binding studies and by a decrease of the K/sub m app/ for calmodulin and an increase in the V/sub max/ for the autophosphorylation reaction of the enzyme. The antibody thus appears to recognize and stabilize a conformation of the kinase which favors calmodulin binding although it does not itself activate the kinase in the absence of calmodulin. Since the M/sub r/ 30,000 catalytic fragment of the kinase is not immunoreactive, either the antibody combining site of the kinase must be present in the noncatalytic portion of the protein along with the calmodulin binding site or proteolysis interferes with the putative Ca 2+ -dependent conformational change. Thus, monoclonal antibodies can be useful tools in elucidating the mechanism by which Ca 2+ and calmodulin act on the kinase molecule


    Directory of Open Access Journals (Sweden)

    Siti Sulastri


    Full Text Available In this research, adsorption of Ca(II, Pb(II and Ag(I in aqueous solution onto sulfonato-silica hybrid (SSH prepared from rice hull ash (RHA has been studied. The preparation of SSH adsorbent was carried out by oxidation of mercapto-silica hybrid (MSH with hydrogen peroxide (H2O2 solution 33%. MSH was prepared, via sol-gel process, by adding 3 M hydrochloric acid solution to mixture of sodium silicate (Na2SiO3 solution and 3(trimethoxysilyl-1-propanthiol (MPTS to reach pH of 7.0. Solution of Na2SiO3 was generated from destruction of RHA with sodium hydroxide solution followed with heating at 500 °C for 30 min. The SSH produced was characterized with Fourier transform infrared (FTIR spectroscopy, X-ray diffraction (XRD analyzer, energy dispersive X-ray (EDX spectroscopy and determination of ion-exchange capacity for sodium ion (Na+. The adsorption of Ag(I and Ca(II were conducted in a batch system in various concentrations for one hour. The adsorbent ion was calculated based on difference of concentrations before and after adsorption process determined using atomic absorbance spectrophotometric (AAS method. The adsorption character was evaluated using model of isotherm Langmuir and Freundlich adsorption to calculate the capacity, constants and energy of adsorption. Result of characterization by EDX and FTIR showed qualitatively that SSH has been successfully synthesized which were indicated by appearance of characteristic absorbance of functional group namely silanol (Si-OH, siloxane (Si-O-Si, methylene (-CH2- and disappearance of mercapto group (SH. The XRD data showed amorphous structure of SSH, similar to silica gel (SG and MSH. The study of adsorption thermodynamics showed that oxidation of MSH into SSH increases the ion-exchange capacity for Na+ from 0.123 to 0.575 mmol/g. The change in functional group from silanol to mercapto and from mercapto to sulfonato increases the adsorption capacity of Ca(II. However, the capacity order of

  5. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4208; >1h2iA 3 181 58 235 3e-63 ... gb|EAK92048.1| po...tential dsDNA break repair annealing factor [Candida albicans ... SC5314] gb|EAK92025.1| potential ds...DNA break repair ... annealing factor [Candida albicans SC5314] ... Length = 178 ... Query: 58 ... F

  6. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.1665; >1s4nB 10 338 100 429 e-135 ... gb|EAL02954.1| ...19.9234 [Candida ... albicans SC5314] emb|CAA67930.1| putative mannosyl ... transferase [Candi...da albicans] sp|Q00310|KRE2_CANAL ... Glycolipid ... (Alpha-1,2-mannosyltransferase) ... Length = 330 ... Query: 100 PDSYTLNDKIKATFVTLARNSDLYSL

  7. ORF Sequence: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.4769; Contig19-10215; join(105865..106689,106749.....107408); IPT1*; necessary for synthesis of mannose-(inositol-P)2-ceramide (M(IP)2C) | inositolphosphotransfe...rase 1 ... >orf19.4769; Contig19-10215; join(105865..106689,106749..107408); IPT1*; necessary for synthesis of mann...ose-(inositol-P)2-ceramide (M(IP)2C) | inositolphosphotransferase 1 | mannosy

  8. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.6190; >1yp2A 12 408 1 337 5e-34 ... gb|EAK91704.1| GDP-mann...ose pyrophosphorylase [Candida albicans SC5314] ... sp|O93827|MPG1_CANAL Mannose-1-phosphate ... ... ... guanyltransferase (ATP-mannose-1-phosphate ... guanylyltransferase) (GDP-mannose pyrophospho...rylase) ... (CASRB1) dbj|BAA34807.1| GDP-mannose pyrophosphorylase ...

  9. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.5880; >1o50A 5 138 57 197 1e-07 ... gb|EAL04384.1| li...kely voltage-gated chloride channel fragment [Candida albicans ... SC5314] gb|EAL04229.1| likely volt...age-gated chloride ... channel fragment [Candida albicans SC5314] ... Length = 141 ... Query: 577

  10. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available Ca19AnnotatedDec2004aaSeq orf19.5171; >1t9fA 5 173 343 526 2e-50 ... gb|EAK98013.1| h...9.12638 [Candida ... albicans SC5314] gb|AAC31119.1| protein ... mannosyltransferase 1 [Candid...a albicans] ... sp|O74189|PMT1_CANAL Dolichyl-phosphate-mannose--protein ... mann

  11. ORF Alignment: Ca19AnnotatedDec2004aaSeq [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available chizosaccharomyces pombe] ref|NP_594201.1| spindle poison ... sensitivity related protein. [Schizosac...charomyces pombe] ... pir||T11624 spindle poison sensitivity protein - fis...inger protein | spindle poison sensitivity related protein; >1rgoA 8 70 40 92 2e-04 ... emb|CAB16391.1| scp3 [S... Ca19AnnotatedDec2004aaSeq orf19.7385; Contig19-2513; 105328..106833; LEE1*; zinc f

  12. Association of Plages with Sunspots: A Multi-Wavelength Study Using Kodaikanal Ca ii K and Greenwich Sunspot Area Data

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Sudip; Chatterjee, Subhamoy; Banerjee, Dipankar, E-mail: [Indian Institute of Astrophysics, Koramangala, Bangalore 560034 (India)


    Plages are the magnetically active chromospheric structures prominently visible in the Ca ii K line (3933.67 Å). A plage may or may not be associated with a sunspot, which is a magnetic structure visible in the solar photosphere. In this study we explore this aspect of association of plages with sunspots using the newly digitized Kodaikanal Ca ii K plage data and the Greenwich sunspot area data. Instead of using the plage index or fractional plage area and its comparison with the sunspot number, we use, to our knowledge for the first time, the individual plage areas and compare them with the sunspot area time series. Our analysis shows that these two structures, formed in two different layers, are highly correlated with each other on a timescale comparable to the solar cycle. The area and the latitudinal distributions of plages are also similar to those of sunspots. Different area thresholdings on the “butterfly diagram” reveal that plages of area ≥4 arcmin{sup 2} are mostly associated with a sunspot in the photosphere. Apart from this, we found that the cyclic properties change when plages of different sizes are considered separately. These results may help us to better understand the generation and evolution of the magnetic structures in different layers of the solar atmosphere.

  13. The importance of occupancy rather than affinity of CaVβ subunits for the calcium channel I–II linker in relation to calcium channel function (United States)

    Butcher, Adrian J; Leroy, Jérôme; Richards, Mark W; Pratt, Wendy S; Dolphin, Annette C


    The CaVβ subunits of voltage-gated calcium channels regulate the trafficking and biophysical properties of these channels. We have taken advantage of mutations in the tyrosine residue within the alpha interaction domain (AID) in the I–II linker of CaV2.2 which reduce, but do not abolish, the binding of β1b to the AID of CaV2.2. We have found that the mutation Y388S decreased the affinity of CaVβ1b binding to the CaV2.2 I–II linker from 14 to 329 nm. However, the Y388S mutation had no effect on current density and cell surface expression of CaV2.2/α2δ-2/β1b channels expressed in human embryonic kidney tsA-201 cells, when equivalent proportions of cDNA were used. Furthermore, despite the 24-fold reduced affinity of CaVβ1b for the Y388S I–II linker of CaV2.2, all the key features of modulation as well as trafficking by CaVβ subunits remained intact. This is in contrast to the much more marked effect of the W391A mutation, which abolished interaction with the CaV2.2 I–II linker, and very markedly affected the trafficking of the channels. However, using the Xenopus oocyte expression system, where expression levels can be accurately titrated, when CaVβ1b cDNA was diluted 50-fold, all evidence of interaction with CaV2.2 Y388S was lost, although wild-type CaV2.2 was still normally modulated by the reduced concentration of β1b. These results indicate that high affinity interaction with the α1 subunit is not necessary for any of the modulatory effects of CaVβ subunits, but occupancy of the interaction site is important, and this will occur, despite the reduced affinity, if the CaVβ subunit is present in sufficient excess. PMID:16627564

  14. The importance of occupancy rather than affinity of CaV(beta) subunits for the calcium channel I-II linker in relation to calcium channel function. (United States)

    Butcher, Adrian J; Leroy, Jérôme; Richards, Mark W; Pratt, Wendy S; Dolphin, Annette C


    The Ca(V)beta subunits of voltage-gated calcium channels regulate the trafficking and biophysical properties of these channels. We have taken advantage of mutations in the tyrosine residue within the alpha interaction domain (AID) in the I-II linker of Ca(V)2.2 which reduce, but do not abolish, the binding of beta1b to the AID of Ca(V)2.2. We have found that the mutation Y388S decreased the affinity of Ca(V)beta1b binding to the Ca(V)2.2 I-II linker from 14 to 329 nm. However, the Y388S mutation had no effect on current density and cell surface expression of Ca(V)2.2/alpha2delta-2/beta1b channels expressed in human embryonic kidney tsA-201 cells, when equivalent proportions of cDNA were used. Furthermore, despite the 24-fold reduced affinity of Ca(V)beta1b for the Y388S I-II linker of Ca(V)2.2, all the key features of modulation as well as trafficking by Ca(V)beta subunits remained intact. This is in contrast to the much more marked effect of the W391A mutation, which abolished interaction with the Ca(V)2.2 I-II linker, and very markedly affected the trafficking of the channels. However, using the Xenopus oocyte expression system, where expression levels can be accurately titrated, when Ca(V)beta1b cDNA was diluted 50-fold, all evidence of interaction with Ca(V)2.2 Y388S was lost, although wild-type Ca(V)2.2 was still normally modulated by the reduced concentration of beta1b. These results indicate that high affinity interaction with the alpha1 subunit is not necessary for any of the modulatory effects of Ca(V)beta subunits, but occupancy of the interaction site is important, and this will occur, despite the reduced affinity, if the Ca(V)beta subunit is present in sufficient excess.

  15. Curcumin Attenuates Opioid Tolerance and Dependence by Inhibiting Ca2+/Calmodulin-Dependent Protein Kinase II α Activity (United States)

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena


    Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca2+/calmodulin-dependent protein kinase II α (CaMKIIα), a protein kinase that has been previously proposed to be critical for opioid tolerance and dependence. In this study, we used state-of-the-art polymeric formulation technology to produce poly(lactic-co-glycolic acid) (PLGA)-curcumin nanoparticles (nanocurcumin) to overcome the drug’s poor solubility and bioavailability, which has made it extremely difficult for studying in vivo pharmacological actions of curcumin. We found that PLGA-curcumin nanoparticles reduced the dose requirement by 11- to 33-fold. Pretreatment with PLGA-curcumin (by mouth) prevented the development of opioid tolerance and dependence in a dose-dependent manner, with ED50 values of 3.9 and 3.2 mg/kg, respectively. PLGA-curcumin dose-dependently attenuated already-established opioid tolerance (ED50 = 12.6 mg/kg p.o.) and dependence (ED50 = 3.1 mg/kg p.o.). Curcumin or PLGA-curcumin did not produce antinociception by itself or affect morphine (1–10 mg/kg) antinociception. Moreover, we found that the behavioral effects of curcumin on opioid tolerance and dependence correlated with its inhibition of morphine-induced CaMKIIα activation in the brain. These results suggest that curcumin may attenuate opioid tolerance and dependence by suppressing CaMKIIα activity. PMID:25515789

  16. Conditioned taste aversion and Ca/calmodulin-dependent kinase II in the parabrachial nucleus of rats

    Czech Academy of Sciences Publication Activity Database

    Křivánek, Jiří


    Roč. 76, č. 1 (2001), s. 46-56 ISSN 1074-7427 R&D Projects: GA AV ČR IAA7011706 Institutional research plan: CEZ:AV0Z5011922 Keywords : calcium/calmodulin-dependent kinase II * conditioned taste aversion * parabrachial nucleus of rat Subject RIV: FH - Neurology Impact factor: 1.830, year: 2001

  17. Simvastatin pretreatment protects cerebrum from neuronal injury by decreasing the expressions of phosphor-CaMK II and AQP4 in ischemic stroke rats. (United States)

    Zhu, Min-xia; Lu, Chao; Xia, Chun-mei; Qiao, Zhong-wei; Zhu, Da-nian


    Excitotoxicity and cytotoxic edema are the two major factors resulting in neuronal injury during brain ischemia and reperfusion. Ca2+/calmodulin-dependent protein kinase II (CaMK II), the downstream signal molecular of N-methyl-D-aspartate receptors (NMDARs), is a mediator in the excitotoxicity. Aquaporin 4 (AQP4), expressed mainly in the brain, is an important aquaporin to control the flux of water. In a previous study, we had reported that pretreatment of simvastatin protected the cerebrum from ischemia and reperfusion injury by decreasing neurological deficit score and infarct area (Zhu et al. PLoS One 7:e51552, 2012). The present study used a middle cerebral artery occlusion (MCAO) model to further explore the pleiotropic effect of simvastatin via CaMK II and AQP4. The results showed that simvastatin reduced degenerated cells and brain edema while decreasing the protein expressions of phosphor-CaMK II and AQP4, and increasing the ratios of Bcl-2/Bax, which was independent of cholesterol-lowering effect. Immunocomplexes formed between the subunit of NMDARs-NR3A and AQP4 were detected for the first time. It was concluded that simvastatin could protect the cerebrum from neuronal excitotoxicity and cytotoxic edema by downregulating the expressions of phosphor-CaMK II and AQP4, and that the interaction between NR3A and AQP4 might provide the base for AQP4 involving in the signaling pathways mediated by NMDARs.

  18. Spectroscopy at the solar limb. I. Average off-limb profiles and Doppler shifts of Ca II H (United States)

    Beck, C. A. R.; Rezaei, R.


    Aims: We present constraints on the thermodynamical structure of the chromosphere from ground-based observations of the Ca ii H line profile near and off the solar limb. Methods: We obtained a slit-spectrograph data set of the Ca ii H line with a high signal-to-noise ratio in a field of view extending 20'' across the limb. We analyzed the spectra for the characteristic properties of average and individual off-limb spectra. We used various tracers of the Doppler shifts, such as the location of the absorption core, the ratio of the two emission peaks H2V and H2R, and intensity images at a fixed wavelength. Results: The average off-limb profiles show a smooth variation with increasing limb distance. The line width increases up to a height of about 2 Mm above the limb. The profile shape is fairly symmetric with nearly identical H2V and H2R intensities; at a height of 5 Mm, it changes into a single Gaussian without emission peaks. We find that all off-limb spectra show large Doppler shifts that fluctuate on the smallest resolved spatial scales. The variation is more prominent in cuts parallel to the solar limb than on those perpendicular to it. As far as individual structures can be unequivocally identified at our spatial resolution, we find a specific relation between intensity enhancements and Doppler shifts: elongated brightenings are often flanked all along their extension by velocities in opposite directions. Conclusions: The average off-limb spectra of Ca ii H present a good opportunity to test static chromospheric atmosphere models because they lack the photospheric contribution that is present in disk-center spectra. We suggest that the observed relation between intensity enhancements and Doppler shifts could be caused by waves propagating along the surfaces of flux tubes: an intrinsic twist of the flux tubes or a wave propagation inclined to the tube axis would cause a helical shape of the Doppler excursions, visible as opposite velocity at the sides of the

  19. Turbulence measurements in the vicinity of a strong polar jet during POLSTRACC/GWLCYCLE II/SALSA, 2016 (United States)

    Bramberger, Martina; Dörnbrack, Andreas; Rapp, Markus; Gemsa, Steffen; Raynor, Kevin


    In January 2016, the combined POLar STRAtosphere in a Changing Climate (POLSTRACC), Investigation of the life cycle of gravity waves (GW-LCYCLE) II and Seasonality of Air mass transport and origin in the Lowermost Stratosphere (SALSA) campaign, shortly abbreviated as PGS, took place in Kiruna, Sweden. During this campaign, on 31 January 2016, a strong polar jet with horizontal wind speeds up to 100 m/s was located above northern Great Britain. The research flight PGS12 lead the High Altitude LOng range (HALO) aircraft right above the jet streak of this polar jet, a region which is known from theoretical studies for prevalent turbulence. Here, we present a case study in which high-resolution in-situ aircraft measurements are employed to analyse and quantify turbulence in the described region with parameters such as e.g. turbulent kinetic energy and the eddy dissipation rate. This analysis is supported by idealized numerical simulations to determine involved processes for the generation of turbulence. Complementing, forecasts and operational analyses of the integrated forecast system (IFS) of the European Centre for Medium-Range Weather Forecasts (ECMWF) are used to thoroughly analyze the meteorological situation.

  20. Variation of Supergranule Parameters with Solar Cycles: Results from Century-long Kodaikanal Digitized Ca ii K Data

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Subhamoy; Mandal, Sudip; Banerjee, Dipankar, E-mail: [Indian Institute of Astrophysics, Koramangala, Bangalore 560034 (India)


    The Ca ii K spectroheliograms spanning over a century (1907–2007) from Kodaikanal Solar Observatory, India, have recently been digitized and calibrated. Applying a fully automated algorithm (which includes contrast enhancement and the “Watershed method”) to these data, we have identified the supergranules and calculated the associated parameters, such as scale, circularity, and fractal dimension. We have segregated the quiet and active regions and obtained the supergranule parameters separately for these two domains. In this way, we have isolated the effect of large-scale and small-scale magnetic fields on these structures and find a significantly different behavior of the supergranule parameters over solar cycles. These differences indicate intrinsic changes in the physical mechanism behind the generation and evolution of supergranules in the presence of small-scale and large-scale magnetic fields. This also highlights the need for further studies using solar dynamo theory along with magneto-convection models.

  1. Delayed intrinsic activation of an NMDA-independent CaM-kinase II in a critical time window is necessary for late consolidation of an associative memory. (United States)

    Wan, Huimin; Mackay, Beth; Iqbal, Hassan; Naskar, Souvik; Kemenes, György


    Calcium/calmodulin-dependent kinases (CaM-kinases) are central to various forms of long-term memory (LTM) in a number of evolutionarily diverse organisms. However, it is still largely unknown what contributions specific CaM-kinases make to different phases of the same specific type of memory, such as acquisition, or early, intermediate, and late consolidation of associative LTM after classical conditioning. Here, we investigated the involvement of CaM-kinase II (CaMKII) in different phases of associative LTM induced by single-trial reward classical conditioning in Lymnaea, a well established invertebrate experimental system for studying molecular mechanisms of learning and memory. First, by using a general CaM-kinase inhibitor, KN-62, we found that CaM-kinase activation was necessary for acquisition and late consolidation, but not early or intermediate consolidation or retrieval of LTM. Then, we used Western blot-based phosphorylation assays and treatment with CaMKIINtide to identify CaMKII as the main CaM-kinase, the intrinsic activation of which, in a critical time window ( approximately 24 h after learning), is central to late consolidation of LTM. Additionally, using MK-801 and CaMKIINtide we found that acquisition was dependent on both NMDA receptor and CaMKII activation. However, unlike acquisition, CaMKII-dependent late memory consolidation does not require the activation of NMDA receptors. Our new findings support the notion that even apparently stable memory traces may undergo further molecular changes and identify NMDA-independent intrinsic activation of CaMKII as a mechanism underlying this "lingering consolidation." This process may facilitate the preservation of LTM in the face of protein turnover or active molecular processes that underlie forgetting.

  2. Direct Detection of Oxygen Ligation to the Mn4Ca Cluster of Photosystem II by X-ray Emission Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Pushkar, Yulia; Long, Xi; Glatzel, Pieter; Brudvig, Gary W.; Dismukes, G. Charles; Collins, Terrence J.; Yachandra, Vittal K.; Yano, Junko; Bergmann, Uwe


    Ligands play critical roles during the catalytic reactions in metalloproteins through bond formation/breaking, protonation/deprotonation, and electron/spin delocalization. While there are well-defined element-specific spectroscopic handles, such as X-ray spectroscopy and EPR, to follow the chemistry of metal catalytic sites in a large protein matrix, directly probing particular ligand atoms like C, N, and O is challenging due to their abundance in the protein. FTIR/Raman and ligand-sensitive EPR techniques such as ENDOR and ESEEM have been applied to study metal-ligand interactions. X-ray absorption spectroscopy (XAS) can also indirectly probe the ligand environment; its element-specificity allows us to focus only on the catalytic metal site, and EXAFS and XANES provide metal-ligand distances, coordination numbers, and symmetry of ligand environments. However, the information is limited, since one cannot distinguish among ligand elements with similar atomic number (i.e. C, N. and O). As an alternative and a more direct method to probe the specific metal-ligand chemistry in the protein matrix, we investigated the application of X-ray emission spectroscopy (XES). Using this technique we have identified the oxo-bridging ligands of the Mn{sub 4}Ca complex of photosystem II (PS II), a multisubunit membrane protein, that catalyzes the water oxidizing reaction. The catalytic mechanism has been studied intensively by Mn XAS. The fundamental question of this reaction, however, is how the water molecules are ligated to the Mn{sub 4}Ca cluster and how the O-O bond formation occurs before the evolution of O{sub 2}. This implies that it is necessary to follow the chemistry of the oxygen ligands in order to understand the mechanism.

  3. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer: data from CALYPSO trial (a GINECO-GCIG study). (United States)

    You, Benoit; Colomban, Olivier; Heywood, Mark; Lee, Chee; Davy, Margaret; Reed, Nicholas; Pignata, Sandro; Varsellona, Nenzi; Emons, Günter; Rehman, Khalid; Steffensen, Karina Dahl; Reinthaller, Alexander; Pujade-Lauraine, Eric; Oza, Amit


    Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters. Data from CALYPSO phase III trial comparing 2 carboplatin-based regimens in ROC patients were analyzed. Based on population kinetic approach, serum [CA-125] concentration-time profiles during first 50 treatment days were fit to a semi-mechanistic model with following parameters: "d[CA-125]/dt=(KPROD∗exp (BETA∗t))∗Effect-KELIM∗[CA-125]" with time, t; tumor growth rate, BETA; CA-125 tumor production rate, KPROD; CA-125 elimination rate, KELIM and K-dependent treatment indirect Effect. The predictive values of kinetic parameters were tested regarding progression-free survival (PFS) against other reported prognostic factors. Individual CA-125 kinetic profiles from 895 patients were modeled. Three kinetic parameters categorized by medians had predictive values using univariate analyses: K; KPROD and KELIM (all PCA-125 response (favoring carboplatin-paclitaxel arm), treatment arm, platinum free-interval, measurable lesions and KELIM (HR=0.53; 95% CI 0.45-0.61; PCA-125 kinetics in ROC patients enables understanding of the time-change components during chemotherapy. The contradictory surrogacy of GCIG-defined CA-125 response was confirmed. The modeled CA-125 elimination rate KELIM, potentially assessable in routine, may have promising predictive value regarding PFS. Further validation of this predictive marker is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Acute effects of taurine on sarcoplasmic reticulum Ca2+ accumulation and contractility in human type I and type II skeletal muscle fibers. (United States)

    Dutka, T L; Lamboley, C R; Murphy, R M; Lamb, G D


    Taurine occurs in high concentrations in muscle and is implicated in numerous physiological processes, yet its effects on many aspects of contractility remain unclear. Using mechanically skinned segments of human vastus lateralis muscle fibers, we characterized the effects of taurine on sarcoplasmic reticulum (SR) Ca2+ accumulation and contractile apparatus properties in type I and type II fibers. Prolonged myoplasmic exposure (>10 min) to taurine substantially increased the rate of accumulation of Ca2+ by the SR in both fiber types, with no change in the maximum amount accumulated; no such effect was found with carnosine. SR Ca2+ accumulation was similar with 10 or 20 mM taurine, but was significantly slower at 5 mM taurine. Cytoplasmic taurine (20 mM) had no detectable effects on the responsiveness of the Ca2+ release channels in either fiber type. Taurine caused a small increase in Ca2+ sensitivity of the contractile apparatus in type I fibers, but type II fibers were unaffected; maximum Ca(2+)-activated force was unchanged in both cases. The effects of taurine on SR Ca2+ accumulation (1) only became apparent after prolonged cytoplasmic exposure, and (2) persisted for some minutes after complete removal of taurine from the cytoplasm, consistent with the hypothesis that the effects were due to an action of taurine from inside the SR. In summary, taurine potentiates the rate of SR Ca2+ uptake in both type I and type II human fibers, possibly via an action from within the SR lumen, with the degree of potentiation being significantly reduced at low physiological taurine levels. Copyright © 2014 the American Physiological Society.

  5. Adenovirally delivered shRNA strongly inhibits Na+-Ca2+ exchanger expression but does not prevent contraction of neonatal cardiomyocytes. (United States)

    Hurtado, Cecilia; Ander, Bradley P; Maddaford, Thane G; Lukas, Anton; Hryshko, Larry V; Pierce, Grant N


    The cardiac Na(+)-Ca(2+) exchanger (NCX1) is the main mechanism for Ca(2+) efflux in the heart and is thought to serve an essential role in cardiac excitation-contraction (E-C) coupling. The demonstration that an NCX1 gene knock-out is embryonic lethal provides further support for this essential role. However, a recent report employing the Cre/loxP technique for cardiac specific knock-out of NCX1 has revealed that cardiac function is remarkably preserved in these mice, which survived to adulthood. This controversy highlights the necessity for further investigation of NCX1 function in the heart. In this study, we report on a novel approach for depletion of NCX1 in postnatal rat myocytes that utilizes RNA interference (RNAi), administered with high efficiency via adenoviral transfection. Depletion of NCX1 was confirmed by immunocytochemical detection, Western blots and radioisotopic assays of Na(+)-Ca(2+) exchange activity. Exchanger expression was inhibited by up to approximately 94%. Surprisingly, spontaneous beating of these cardiomyocytes was still maintained, although at a lower frequency. Electrical stimulation could elicit a normal beating rhythm, although NCX depleted cells exhibited a depressed Ca(2+) transient amplitude, a depressed rate of Ca(2+) rise and decline, elevated diastolic [Ca(2+)], and shorter action potentials. We also observed a compensatory increase in sarcolemmal Ca(2+) pump expression. Our data support an important, though non-essential, role for the NCX1 in E-C coupling in these neonatal heart cells. Furthermore, this approach provides a valuable means for assessing the role of NCX1 and could be utilized to examine other cardiac proteins in physiological and pathological studies.

  6. Radial velocities and metallicities from infrared Ca ii triplet spectroscopy of open clusters. II. Berkeley 23, King 1, NGC 559, NGC 6603, and NGC 7245 (United States)

    Carrera, R.; Casamiquela, L.; Ospina, N.; Balaguer-Núñez, L.; Jordi, C.; Monteagudo, L.


    Context. Open clusters are key to studying the formation and evolution of the Galactic disc. However, there is a deficiency of radial velocity and chemical abundance determinations for open clusters in the literature. Aims: We intend to increase the number of determinations of radial velocities and metallicities from spectroscopy for open clusters. Methods: We acquired medium-resolution spectra (R ~ 8000) in the infrared region Ca ii triplet lines (~8500 Å) for several stars in five open clusters with the long-slit IDS spectrograph on the 2.5 m Isaac Newton Telescope (Roque de los Muchachos Observatory, Spain). Radial velocities were obtained by cross-correlation fitting techniques. The relationships available in the literature between the strength of infrared Ca ii lines and metallicity were also used to derive the metallicity for each cluster. Results: We obtain ⟨Vr⟩ = 48.6 ± 3.4, -58.4 ± 6.8, 26.0 ± 4.3, and -65.3 ± 3.2 km s-1 for Berkeley 23, NGC 559, NGC 6603, and NGC 7245, respectively. We found [ Fe/H ] = -0.25 ± 0.14 and -0.15 ± 0.18 for NGC 559 and NGC 7245, respectively. Berkeley 23 has low metallicity, [ Fe/H ] = -0.42 ± 0.13, which is similar to other open clusters in the outskirts of the Galactic disc. In contrast, we derived high metallicity ([ Fe/H ] = +0.43 ± 0.15) for NGC 6603, which places this system among the most metal-rich known open clusters. To our knowledge, this is the first determination of radial velocities and metallicities from spectroscopy for these clusters, except NGC 6603, for which radial velocities had been previously determined. We have also analysed ten stars in the line of sight to King 1. Because of the large dispersion obtained in both radial velocity and metallicity, we cannot be sure that we have sampled true cluster members. Based on observations made with the 2.5 m Isaac Newton Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the

  7. Mutations in the Bacillus thuringiensis Cry1Ca toxin demonstrate the role of domain II and III in the specificity towards Spodoptera exigua larvae

    NARCIS (Netherlands)

    Herrero Sendra, S.; González-Cabrera, J.; Ferré, J.; Bakker, P.L.; Maagd, de R.A.


    Several mutants of the Bacillus thuringiensis Cry1Ca toxin affected with regard to specific activity towards Spodoptera exigua were studied. Alanine was used to replace single residues in loops 2 and 3 of domain II (mutant pPB19) and to replace residues 541-544 in domain III (mutant pPB20).

  8. OVX1, macrophage-colony stimulating factor, and CA-125-II as tumor markers for epithelial ovarian carcinoma - A critical appraisal

    NARCIS (Netherlands)

    van Haaften-Day, C; Shen, Y; Xu, FJ; Yu, YH; Berchuck, A; Havrilesky, LJ; de Bruijn, HWA; van der Zee, AGJ; Bast, RC; Hacker, NF


    BACKGROUND. Ovarian carcinoma remains the leading cause of death from gynecologic malignancy in Australia, the Netherlands, and the United States. CA-125-II, the most widely used serum marker, has limited sensitivity and specificity for detecting small-volume, early-stage disease. Therefore, a panel

  9. Rigidly linking cyclometallated Ir(iii) and Pt(ii) centres: an efficient approach to strongly absorbing and highly phosphorescent red emitters. (United States)

    Turnbull, Graeme; Williams, J A Gareth; Kozhevnikov, Valery N


    The synthesis and photophysical properties of an unprecedented tetranuclear complex are described, in which a fac-tris-cyclometallated Ir(iii) centre is rigidly connected to three cyclometallated Pt(ii) centres. The complex absorbs strongly up to ∼600 nm and emits red light with unusually high efficiency.

  10. Cytoplasmic Ca2+ signalling and reduction of mitochondrial pyridine nucleotides in adrenal glomerulosa cells in response to K+, angiotensin II and vasopressin. (United States)

    Rohács, T; Nagy, G; Spät, A


    We have examined the mitochondrial formation of NAD(P)H in rat adrenal glomerulosa cells. A short-term elevation of the K+ concentration from 3.6 to 8.4 mM induced a reversible increase in the formation of reduced pyridine nucleotides. Potassium applied after the addition of rotenone had no further effect, confirming that the redox signal was of mitochondrial origin. Inhibition of aldosterone synthesis by aminoglutethimide in K+-stimulated cells decreased the rate of decay of the NAD(P)H signal upon the termination of stimulation, indicating that the NADPH formed was consumed in aldosterone synthesis. When the NAD(P)H signal was measured simultaneously with the cytoplasmic free Ca2+ concentration ([Ca2+]i), elevation of the K+ concentration to 6.6 or 8.4 mM induced parallel increases in [Ca2+]i and NAD(P)H formation. The rates of increase and decrease of NAD(P)H were lower than for [Ca2+]i, confirming that the redox signal was secondary to the Ca2+ signal. Angiotensin II (100 pM-1 nM) induced an oscillatory NAD(P)H signal which usually returned to a lower baseline concentration, while a sustained signal with superimposed oscillations was observed at higher concentrations. Simultaneous measurements showed that NAD(P)H levels followed the [Ca2+]i pattern evoked by angiotensin II. Vasopressin (100 nM) also induced parallel oscillations of [Ca2+]i and NAD(P)H. A sustained rise in the extramitochondrial Ca2+ concentration to 1 microM induced a sustained elevation of the intramitochondrial Ca2+ concentration in permeabilized cells, as measured with rhod-2. A sustained rise in [Ca2+]i evoked by long-term stimulation with 8.4 mM K+ or 2.5 nM angiotensin II resulted in sustained NAD(P)H production. These Ca2+-dependent changes in the mitochondrial redox state support the biological response, i.e. aldosterone secretion by glomerulosa cells. PMID:9148750

  11. Single-channel L-type Ca2+ currents in chicken embryo semicircular canal type I and type II hair cells. (United States)

    Zampini, Valeria; Valli, Paolo; Zucca, Giampiero; Masetto, Sergio


    Few data are available concerning single Ca channel properties in inner ear hair cells and particularly none in vestibular type I hair cells. By using the cell-attached configuration of the patch-clamp technique in combination with the semicircular canal crista slice preparation, we determined the elementary properties of voltage-dependent Ca channels in chicken embryo type I and type II hair cells. The pipette solutions included Bay K 8644. With 70 mM Ba(2+) in the patch pipette, Ca channel activity appeared as very brief openings at -60 mV. Ca channel properties were found to be similar in type I and type II hair cells; therefore data were pooled. The mean inward current amplitude was -1.3 +/- 0.1 (SD) pA at - 30 mV (n = 16). The average slope conductance was 21 pS (n = 20). With 5 mM Ba(2+) in the patch pipette, very brief openings were already detectable at -80 mV. The mean inward current amplitude was -0.7 +/- 0.2 pA at -40 mV (n = 9). The average slope conductance was 11 pS (n = 9). The mean open time and the open probability increased significantly with depolarization. Ca channel activity was still present and unaffected when omega-agatoxin IVA (2 microM) and omega-conotoxin GVIA (3.2 microM) were added to the pipette solution. Our results show that types I and II hair cells express L-type Ca channels with similar properties. Moreover, they suggest that in vivo Ca(2+) influx might occur at membrane voltages more negative than -60 mV.

  12. The MUSCLES Treasury Survey. IV. Scaling Relations for Ultraviolet, Ca II K, and Energetic Particle Fluxes from M Dwarfs (United States)

    Youngblood, Allison; France, Kevin; Loyd, R. O. Parke; Brown, Alexander; Mason, James P.; Schneider, P. Christian; Tilley, Matt A.; Berta-Thompson, Zachory K.; Buccino, Andrea; Froning, Cynthia S.; Hawley, Suzanne L.; Linsky, Jeffrey; Mauas, Pablo J. D.; Redfield, Seth; Kowalski, Adam; Miguel, Yamila; Newton, Elisabeth R.; Rugheimer, Sarah; Segura, Antígona; Roberge, Aki; Vieytes, Mariela


    Characterizing the UV spectral energy distribution (SED) of an exoplanet host star is critically important for assessing its planet’s potential habitability, particularly for M dwarfs, as they are prime targets for current and near-term exoplanet characterization efforts and atmospheric models predict that their UV radiation can produce photochemistry on habitable zone planets different from that on Earth. To derive ground-based proxies for UV emission for use when Hubble Space Telescope (HST) observations are unavailable, we have assembled a sample of 15 early to mid-M dwarfs observed by HST and compared their nonsimultaneous UV and optical spectra. We find that the equivalent width of the chromospheric Ca II K line at 3933 Å, when corrected for spectral type, can be used to estimate the stellar surface flux in ultraviolet emission lines, including H I Lyα. In addition, we address another potential driver of habitability: energetic particle fluxes associated with flares. We present a new technique for estimating soft X-ray and >10 MeV proton flux during far-UV emission line flares (Si IV and He II) by assuming solar-like energy partitions. We analyze several flares from the M4 dwarf GJ 876 observed with HST and Chandra as part of the MUSCLES Treasury Survey and find that habitable zone planets orbiting GJ 876 are impacted by large Carrington-like flares with peak soft X-ray fluxes ≥10-3 W m-2 and possible proton fluxes ˜102-103 pfu, approximately four orders of magnitude more frequently than modern-day Earth.

  13. The MUSCLES Treasury Survey. IV. Scaling Relations for Ultraviolet, Ca ii K, and Energetic Particle Fluxes from M Dwarfs

    Energy Technology Data Exchange (ETDEWEB)

    Youngblood, Allison; France, Kevin; Loyd, R. O. Parke; Mason, James P. [Laboratory for Atmospheric and Space Physics, University of Colorado, 600 UCB, Boulder, CO 80309 (United States); Brown, Alexander [Center for Astrophysics and Space Astronomy, University of Colorado, 389 UCB, Boulder, CO 80309 (United States); Schneider, P. Christian [European Space Research and Technology Centre (ESA/ESTEC), Keplerlaan 1, 2201 AZ Noordwijk (Netherlands); Tilley, Matt A. [Department of Earth and Space Sciences, University of Washington, Box 351310, Seattle, WA 98195 (United States); Berta-Thompson, Zachory K.; Kowalski, Adam [Department of Astrophysical and Planetary Sciences, University of Colorado, 2000 Colorado Ave., Boulder, CO 80305 (United States); Buccino, Andrea; Mauas, Pablo J. D. [Dpto. de Física, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires (Argentina); Froning, Cynthia S. [Department of Astronomy/McDonald Observatory, C1400, University of Texas at Austin, Austin, TX 78712 (United States); Hawley, Suzanne L. [Astronomy Department, Box 351580, University of Washington, Seattle, WA 98195 (United States); Linsky, Jeffrey [JILA, University of Colorado and NIST, 440 UCB, Boulder, CO 80309 (United States); Redfield, Seth [Astronomy Department and Van Vleck Observatory, Wesleyan University, Middletown, CT 06459 (United States); Miguel, Yamila [Observatoire de la Cote d’Azur, Boulevard de l’Observatoire, CS 34229 F-06304 NICE Cedex 4 (France); Newton, Elisabeth R. [Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02138 (United States); Rugheimer, Sarah, E-mail: [School of Earth and Environmental Sciences, University of St. Andrews, Irvine Building, North Street, St. Andrews, KY16 9AL (United Kingdom); and others


    Characterizing the UV spectral energy distribution (SED) of an exoplanet host star is critically important for assessing its planet’s potential habitability, particularly for M dwarfs, as they are prime targets for current and near-term exoplanet characterization efforts and atmospheric models predict that their UV radiation can produce photochemistry on habitable zone planets different from that on Earth. To derive ground-based proxies for UV emission for use when Hubble Space Telescope ( HST ) observations are unavailable, we have assembled a sample of 15 early to mid-M dwarfs observed by HST and compared their nonsimultaneous UV and optical spectra. We find that the equivalent width of the chromospheric Ca ii K line at 3933 Å, when corrected for spectral type, can be used to estimate the stellar surface flux in ultraviolet emission lines, including H i Ly α . In addition, we address another potential driver of habitability: energetic particle fluxes associated with flares. We present a new technique for estimating soft X-ray and >10 MeV proton flux during far-UV emission line flares (Si iv and He ii) by assuming solar-like energy partitions. We analyze several flares from the M4 dwarf GJ 876 observed with HST and Chandra as part of the MUSCLES Treasury Survey and find that habitable zone planets orbiting GJ 876 are impacted by large Carrington-like flares with peak soft X-ray fluxes ≥10{sup −3} W m{sup −2} and possible proton fluxes ∼10{sup 2}–10{sup 3} pfu, approximately four orders of magnitude more frequently than modern-day Earth.

  14. 2,5-hexanedione (HD) treatment alters calmodulin, Ca2+/calmodulin-dependent protein kinase II, and protein kinase C in rats' nerve tissues

    International Nuclear Information System (INIS)

    Wang Qingshan; Hou Liyan; Zhang Cuili; Zhao Xiulan; Yu Sufang; Xie, Ke-Qin


    Calcium-dependent mechanisms, particularly those mediated by Ca 2+ /calmodulin (CaM)-dependent protein kinase II (CaMKII), have been implicated in neurotoxicant-induced neuropathy. However, it is unknown whether similar mechanisms exist in 2,5-hexanedione (HD)-induced neuropathy. For that, we investigated the changes of CaM, CaMKII, protein kinase C (PKC) and polymerization ratios (PRs) of NF-L, NF-M and NF-H in cerebral cortex (CC, including total cortex and some gray), spinal cord (SC) and sciatic nerve (SN) of rats treated with HD at a dosage of 1.75 or 3.50 mmol/kg for 8 weeks (five times per week). The results showed that CaM contents in CC, SC and SN were significantly increased, which indicated elevation of Ca 2+ concentrations in nerve tissues. CaMKII contents and activities were also increased in CC and were positively correlated with gait abnormality, but it could not be found in SC and SN. The increases of PKC contents and activities were also observed in SN and were positively correlated with gait abnormality. Except for that of NF-M in CC, the PRs of NF-L, NF-M and NF-H were also elevated in nerve tissues, which was consistent with the activation of protein kinases. The results suggested that CaMKII might be partly (in CC but not in SC and SN) involved in HD-induced neuropathy. CaMKII and PKC might mediate the HD neurotoxicity by altering the NF phosphorylation status and PRs

  15. Cardiac CaM Kinase II genes δ and γ contribute to adverse remodeling but redundantly inhibit calcineurin-induced myocardial hypertrophy. (United States)

    Kreusser, Michael M; Lehmann, Lorenz H; Keranov, Stanislav; Hoting, Marc-Oscar; Oehl, Ulrike; Kohlhaas, Michael; Reil, Jan-Christian; Neumann, Kay; Schneider, Michael D; Hill, Joseph A; Dobrev, Dobromir; Maack, Christoph; Maier, Lars S; Gröne, Hermann-Josef; Katus, Hugo A; Olson, Eric N; Backs, Johannes


    Ca(2+)-dependent signaling through CaM Kinase II (CaMKII) and calcineurin was suggested to contribute to adverse cardiac remodeling. However, the relative importance of CaMKII versus calcineurin for adverse cardiac remodeling remained unclear. We generated double-knockout mice (DKO) lacking the 2 cardiac CaMKII genes δ and γ specifically in cardiomyocytes. We show that both CaMKII isoforms contribute redundantly to phosphorylation not only of phospholamban, ryanodine receptor 2, and histone deacetylase 4, but also calcineurin. Under baseline conditions, DKO mice are viable and display neither abnormal Ca(2+) handling nor functional and structural changes. On pathological pressure overload and β-adrenergic stimulation, DKO mice are protected against cardiac dysfunction and interstitial fibrosis. But surprisingly and paradoxically, DKO mice develop cardiac hypertrophy driven by excessive activation of endogenous calcineurin, which is associated with a lack of phosphorylation at the auto-inhibitory calcineurin A site Ser411. Likewise, calcineurin inhibition prevents cardiac hypertrophy in DKO. On exercise performance, DKO mice show an exaggeration of cardiac hypertrophy with increased expression of the calcineurin target gene RCAN1-4 but no signs of adverse cardiac remodeling. We established a mouse model in which CaMKII's activity is specifically and completely abolished. By the use of this model we show that CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin-dependent hypertrophy. These data suggest inhibition of CaMKII but not calcineurin as a promising approach to attenuate the progression of heart failure. © 2014 American Heart Association, Inc.

  16. Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence. (United States)

    den Uil, Sjoerd H; Coupé, Veerle M H; Linnekamp, Janneke F; van den Broek, Evert; Goos, Jeroen A C M; Delis-van Diemen, Pien M; Belt, Eric J Th; van Grieken, Nicole C T; Scott, Patricia M; Vermeulen, Louis; Medema, Jan Paul; Bril, Herman; Stockmann, Hein B A C; Cormier, Robert T; Meijer, Gerrit A; Fijneman, Remond J A


    Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at risk for recurrence is an unmet clinical need. KCNQ1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with CRC liver metastases. In this study the prognostic value of KCNQ1 in stage II and stage III colon cancer patients was examined. KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. Subsequently, KCNQ1 protein expression was evaluated in an independent cohort of 386 stage II and stage III colon cancer patients by immunohistochemistry of tissue microarrays. Low KCNQ1 mRNA expression in stage II microsatellite stable (MSS) colon cancers was associated with poor disease-free survival (DFS) (P=0.025). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in stage II MSS (PKCNQ1 seemed an independent prognostic value in addition to other high-risk parameters like angio-invasion, nodal stage and microsatellite instability-status. We conclude that KCNQ1 is a promising biomarker for prediction of disease recurrence and may aid stratification of patients with stage II MSS colon cancer for adjuvant chemotherapy.

  17. Selective accumulation and strong photodynamic effects of a new photosensitizer, ATX-S10.Na (II), in experimental malignant glioma. (United States)

    Yamamoto, Junkoh; Hirano, Toru; Li, Shaoyi; Koide, Masayo; Kohno, Eiji; Inenaga, Chikanori; Tokuyama, Tsutomu; Yokota, Naoki; Yamamoto, Seiji; Terakawa, Susumu; Namba, Hiroki


    We investigated the feasibility of a novel photosensitizer, ATX-S10.Na (II), in photodynamic therapy (PDT) for glioma. First, PDT was performed in various brain tumor cell lines in vitro. Cytotoxicity depended upon both drug concentration and laser energy and the 50% inhibitory concentration ranged from 3.5 to 20 microg/ml. Next, PDT was performed in the subcutaneous and intracranial 9L tumor models in Fischer rats using ATX-S10.Na (II) and light from a 670-nm diode laser delivered by intratumoral insertion of an optical fiber. The effect of PDT on brain tumors was evaluated using magnetic resonance imaging. Sequential changes of the ATX-S10.Na (II) concentrations were also measured quantitatively by fluorospectrometry up to 12 h after intravenous administration in rats with intracranial and subcutaneous tumors. The concentration of ATX-S10.Na (II) in the brain tumor reached a maximum at 2 h after administration and the tumor/normal brain concentration ratio was as high as 131 at 8 h. Intratumoral PDT for intracranial tumors irradiated at this timing showed an obvious anti-tumor effect without severe side effects. The present study demonstrated the highly selective accumulation of ATX-S10.Na (II) in tumor tissue and its potent photodynamic effect in an experimental malignant glioma model.

  18. Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions

    NARCIS (Netherlands)

    Skates, S.J.; Horick, N.; Yu, Y.H.; Xu, F.J.; Berchuck, A.; Havrilesky, L.J.; de Bruijn, H.W.A.; van der Zee, A.G.J.; Woolas, R.P.; Jacobs, I.J.; Zhang, 27727; Bast, R.C.; Zhang, Z


    Purpose In CA-125–based ovarian cancer screening trials, overall specificity and screening sensitivity of ultrasound after an elevated CA-125 exceeded 99.6% and 70%, respectively, thereby yielding a positive predictive value (PPV) exceeding 10%. However, sensitivity for early-stage disease was only

  19. [PS II photochemical efficiency in flag leaf of wheat varieties and its adaptation to strong sun- light intensity on farmland of Xiangride in Qinghai Province, Northwest China]. (United States)

    Shi, Sheng-Bo; Chen, Wen-Jie; Shi, Rui; Li, Miao; Zhang, Huai-Gang; Sun, Ya-Nan


    Taking four wheat varieties developed by Northwest Institute of Plateau Biology, Chinese Academy of Sciences, as test materials, with the measurement of content of photosynthetic pigments, leaf area, fresh and dry mass of flag leaf, the PS II photochemistry efficiency of abaxial and adaxial surface of flag leaf and its adaptation to strong solar radiation during the period of heading stage in Xiangride region were investigated with the pulse-modulated in-vivo chlorophyll fluorescence technique. The results indicated that flag leaf angle mainly grew in horizontal state in Gaoyuan 314, Gaoyuan 363 and Gaoyuan 584, and mainly in vertical state in Gaoyuan 913 because of its smaller leaf area and larger width. Photosynthetic pigments were different among the 4 varieties, and positively correlated with intrinsic PS II photochemistry efficiencies (Fv/Fm). In clear days, especially at noon, the photosynthetic photoinhibition was more serious in abaxial surface of flag leaf due to directly facing the solar radiation, but it could recover after reduction of sunlight intensity in the afternoon, which meant that no inactive damage happened in PS II reaction centers. There were significant differences of PS II actual and maximum photochemical efficiencies at the actinic light intensity (ΦPS II and Fv'/Fm') between abaxial and adaxial surface, and their relative variation trends were on the contrary. The photochemical and non-photochemical quenching coefficients (qP and NPQ) had a similar tendency in both abaxial and adaxial surfaces. Although ΦPS II and qP were lower in adaxial surface of flag leaf, the Fv'/Fm' was significantly higher, which indicated that the potential PS II capture efficiency of excited energy was higher. The results demonstrated that process of photochemical and non-photochemical quenching could effectively dissipate excited energy caused by strong solar radiation, and there were higher adaptation capacities in wheat varieties natively cultivated in

  20. Oral administration of bisphenol A induces high blood pressure through angiotensin II/CaMKII-dependent uncoupling of eNOS. (United States)

    Saura, Marta; Marquez, Susana; Reventun, Paula; Olea-Herrero, Nuria; Arenas, María Isabel; Moreno-Gómez-Toledano, Rafael; Gómez-Parrizas, Mónica; Muñóz-Moreno, Carmen; González-Santander, Marta; Zaragoza, Carlos; Bosch, Ricardo J


    Bisphenol A (BPA) is found in human urine and fat tissue. Higher urinary BPA concentrations are associated with arterial hypertension. To shed light on the underlying mechanism, we orally administered BPA (4 nM to 400 μM in drinking water) to 8-wk-old CD11 mice over 30 d. Mice developed dosage-dependent high blood pressure (systolic 130 ± 12 vs. 170 ± 12 mmHg; EC50 0.4 μM), impairment of acetylcholine (AcH)-induced carotid relaxation (0.66 ± 0.08 vs. 0.44 ± 0.1 mm), a 1.7-fold increase in arterial angiotensin II (AngII), an 8.7-fold increase in eNOS mRNA and protein, and significant eNOS-dependent superoxide and peroxynitrite accumulation. AngII inhibition with 0.5 mg/ml losartan reduced oxidative stress and normalized blood pressure and endothelium-dependent relaxation, which suggests that AngII uncouples eNOS and contributes to the BPA-induced endothelial dysfunction by promoting oxidative and nitrosative stress. Microarray analysis of mouse aortic endothelial cells revealed a 2.5-fold increase in expression of calcium/calmodulin-dependent protein kinase II-α (CaMKII-α) in response to 10 nM BPA, with increased expression of phosphorylated-CaMKII-α in carotid rings of BPA-exposed mice, whereas CaMKII-α inhibition with 100 nM autocamptide-2-related inhibitor peptide (AIP) reduced BPA-mediated increase of superoxide. Administration of CaMKII-α inhibitor KN 93 reduced BPA-induced blood pressure and carotid blood velocity in mice, and reverted BPA-mediated carotid constriction in response to treatment with AcH. Given that CaMKII-α inhibition prevents BPA-mediated high blood pressure, our data suggest that BPA regulates blood pressure by inducing AngII/CaMKII-α uncoupling of eNOS. © FASEB.

  1. Ca²⁺/calmodulin-dependent protein kinase II contributes to hypoxic ischemic cell death in neonatal hippocampal slice cultures.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available We have recently shown that p38MAP kinase (p38MAPK stimulates ROS generation via the activation of NADPH oxidase during neonatal hypoxia-ischemia (HI brain injury. However, how p38MAPK is activated during HI remains unresolved and was the focus of this study. Ca²⁺/calmodulin-dependent protein kinase II (CaMKII plays a key role in brain synapse development, neural transduction and synaptic plasticity. Here we show that CaMKII activity is stimulated in rat hippocampal slice culture exposed to oxygen glucose deprivation (OGD to mimic the condition of HI. Further, the elevation of CaMKII activity, correlated with enhanced p38MAPK activity, increased superoxide generation from NADPH oxidase as well as necrotic and apoptotic cell death. All of these events were prevented when CaMKII activity was inhibited with KN93. In a neonatal rat model of HI, KN93 also reduced brain injury. Our results suggest that CaMKII activation contributes to the oxidative stress associated with neural cell death after HI.

  2. Phosphorylation of the PCNA binding domain of the large subunit of replication factor C by Ca2+/calmodulin-dependent protein kinase II inhibits DNA synthesis

    DEFF Research Database (Denmark)

    Maga, G; Mossi, R; Fischer, R


    Replication factor C (RF-C) is a heteropentameric protein essential for DNA replication and DNA repair. It is a molecular matchmaker required for loading of the proliferating cell nuclear antigen (PCNA) sliding clamp onto double-strand DNA and for PCNA-dependent DNA synthesis by DNA polymerases...... delta and epsilon. The DNA and PCNA binding domains of the large 140 kDa subunit of human RF-C have been recently cloned [Fotedar, R., Mossi, R., Fitzgerald, P., Rousselle, T., Maga, G., Brickner, H., Messier, H., Khastilba. S., Hübscher, U., & Fotedar, A. (1996) EMBO J. 15, 4423-4433]. Here we show...... that the PCNA binding domain is phosphorylated by the Ca2+/calmodulin-dependent protein kinase II (CaMKII), an enzyme required for cell cycle progression in eukaryotic cells. The DNA binding domain, on the other hand, is not phosphorylated. Phosphorylation by CaMKII reduces the binding of PCNA to RF-C...

  3. Electrochemical investigation of the redox couple Sm(III)/Sm(II) on a tungsten electrode in molten LiF-CaF2-SmF3

    International Nuclear Information System (INIS)

    Korenko, M.; Kubikova, B.; Stulov, Y.V.; Kuznetsov, S.A.; Ambrova, M.


    This article is focused on the electrochemical investigation (cyclic voltammetry and related studies) of the redox couple Sm(III)/Sm(II) in an eutectic LiF-CaF 2 melt containing SmF 3 . The first step of reduction for Sm(III) ions involving one electron exchange in soluble/soluble Sm(III)/Sm(II) system was found on a tungsten electrode. The study of the Sm(II)/Sm(0) electrode reaction was not feasible, due to insufficient electrochemical stability of LiF-CaF 2 . The first step was found reversible at temperatures 1,075 and 1,125 K up to polarization rate 1 V/s and at temperature 1,175 K the process was reversible at all sweep rates applied in this study. The diffusion coefficients (D) of Sm(II) and Sm(III) ions were determined by cyclic voltammetry, showing that D decreases when oxidation state increase, while the activation energy of diffusion (E a ) increases. The standard rate constants of charge transfer (k s) were calculated for the redox couple Sm(III)/Sm(II) at 1,075 and 1,125 K based on the data of cyclic voltammetry. (author)

  4. I.I. Rabi in Atomic, Molecular & Optical Physics Prize Talk: Strongly Interacting Fermi Gases of Atoms and Molecules (United States)

    Zwierlein, Martin


    Strongly interacting fermions govern physics at all length scales, from nuclear matter to modern electronic materials and neutron stars. The interplay of the Pauli principle with strong interactions can give rise to exotic properties that we do not understand even at a qualitative level. In recent years, ultracold Fermi gases of atoms have emerged as a new type of strongly interacting fermionic matter that can be created and studied in the laboratory with exquisite control. Feshbach resonances allow for unitarity limited interactions, leading to scale invariance, universal thermodynamics and a superfluid phase transition already at 17 Trapped in optical lattices, fermionic atoms realize the Fermi-Hubbard model, believed to capture the essence of cuprate high-temperature superconductors. Here, a microscope allows for single-atom, single-site resolved detection of density and spin correlations, revealing the Pauli hole as well as anti-ferromagnetic and doublon-hole correlations. Novel states of matter are predicted for fermions interacting via long-range dipolar interactions. As an intriguing candidate we created stable fermionic molecules of NaK at ultralow temperatures featuring large dipole moments and second-long spin coherence times. In some of the above examples the experiment outperformed the most advanced computer simulations of many-fermion systems, giving hope for a new level of understanding of strongly interacting fermions.

  5. Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn4CaO5-cluster in photosystem II. (United States)

    Zhang, Miao; Bommer, Martin; Chatterjee, Ruchira; Hussein, Rana; Yano, Junko; Dau, Holger; Kern, Jan; Dobbek, Holger; Zouni, Athina


    In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn 4 CaO 5 -cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn 4 CaO 5 -cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water molecules largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn 4 CaO 5 -cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn 4 CaO 5 -cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate.

  6. Strong effect of copper(II) coordination on antiproliferative activity of thiosemicarbazone-piperazine and thiosemicarbazone-morpholine hybrids. (United States)

    Bacher, Felix; Dömötör, Orsolya; Chugunova, Anastasia; Nagy, Nóra V; Filipović, Lana; Radulović, Siniša; Enyedy, Éva A; Arion, Vladimir B


    In this study, 2-formylpyridine thiosemicarbazones and three different heterocyclic pharmacophores were combined to prepare thiosemicarbazone–piperazine mPip-FTSC (HL1) and mPip-dm-FTSC (HL2), thiosemicarbazone–morpholine Morph-FTSC (HL3) and Morph-dm-FTSC (HL4), thiosemicarbazone–methylpyrrole-2-carboxylate hybrids mPyrr-FTSC (HL5) and mPyrr-dm-FTSC (HL6) as well as their copper(II) complexes [CuCl(mPipH-FTSC-H)]Cl (1 + H)Cl, [CuCl(mPipH-dm-FTSC-H)]Cl (2 + H)Cl, [CuCl(Morph-FTSC-H)] (3), [CuCl(Morph-dm-FTSC-H)] (4), [CuCl(mPyrr-FTSC-H)(H2O)] (5) and [CuCl(mPyrr-dm-FTSC-H)(H2O)] (6). The substances were characterized by elemental analysis, one- and two-dimensional NMR spectroscopy (HL1–HL6), ESI mass spectrometry, IR and UV–vis spectroscopy and single crystal X-ray diffraction (1–5). All compounds were prepared in an effort to generate potential antitumor agents with an improved therapeutic index. In addition, the effect of structural alterations with organic hybrids on aqueous solubility and copper(II) coordination ability was investigated. Complexation of ligands HL2 and HL4 with copper(II) was studied in aqueous solution by pH-potentiometry, UV–vis spectrophotometry and EPR spectroscopy. Proton dissociation processes of HL2 and HL4 were also characterized in detail and microscopic constants for the Z/E isomers were determined. While the hybrids HL5, HL6 and their copper(II) complexes 5 and 6 proved to be insoluble in aqueous solution, precluding antiproliferative activity studies, the thiosemicarbazone–piperazine and thiosemicarbazone–morpholine hybrids HL1–HL4, as well as copper(II) complexes 1–4 were soluble in water enabling cytotoxicity assays. Interestingly, the metal-free hybrids showed very low or even a lack of cytotoxicity (IC50 values > 300 μM) in two human cancer cell lines HeLa (cervical carcinoma) and A549 (alveolar basal adenocarcinoma), whereas their copper(II) complexes were cytotoxic showing IC50 values from 25.5 to 65.1

  7. Guest Induced Strong Cooperative One- and Two-Step Spin Transitions in Highly Porous Iron(II) Hofmann-Type Metal-Organic Frameworks. (United States)

    Piñeiro-López, Lucı A; Valverde-Muñoz, Francisco Javier; Seredyuk, Maksym; Muñoz, M Carmen; Haukka, Matti; Real, José Antonio


    The synthesis, crystal structure, magnetic, calorimetric, and Mössbauer studies of a series of new Hofmann-type spin crossover (SCO) metal-organic frameworks (MOFs) is reported. The new SCO-MOFs arise from self-assembly of Fe II , bis(4-pyridyl)butadiyne (bpb), and [Ag(CN) 2 ] - or [M II (CN) 4 ] 2- (M II = Ni, Pd). Interpenetration of four identical 3D networks with α-Po topology are obtained for {Fe(bpb)[Ag I (CN) 2 ] 2 } due to the length of the rod-like bismonodentate bpb and [Ag(CN) 2 ] - ligands. The four networks are tightly packed and organized in two subsets orthogonally interpenetrated, while the networks in each subset display parallel interpenetration. This nonporous material undergoes a very incomplete SCO, which is rationalized from its intricate structure. In contrast, the single network Hofmann-type MOFs {Fe(bpb)[M II (CN) 4 ]}·nGuest (M II = Ni, Pd) feature enhanced porosity and display complete one-step or two-step cooperative SCO behaviors when the pores are filled with two molecules of nitrobenzene or naphthalene that interact strongly with the pyridyl and cyano moieties of the bpb ligands via π-π stacking. The lack of these guest molecules favors stabilization of the high-spin state in the whole range of temperatures. However, application of hydrostatic pressure induces one- and two-step SCO.

  8. Effect of Ca2+/Sr2+ substitution on the electronic structure of the oxygen-evolving complex of photosystem II: a combined multifrequency EPR, 55Mn-ENDOR, and DFT study of the S2 state. (United States)

    Cox, Nicholas; Rapatskiy, Leonid; Su, Ji-Hu; Pantazis, Dimitrios A; Sugiura, Miwa; Kulik, Leonid; Dorlet, Pierre; Rutherford, A William; Neese, Frank; Boussac, Alain; Lubitz, Wolfgang; Messinger, Johannes


    The electronic structures of the native Mn(4)O(x)Ca cluster and the biosynthetically substituted Mn(4)O(x)Sr cluster of the oxygen evolving complex (OEC) of photosystem II (PSII) core complexes isolated from Thermosynechococcus elongatus, poised in the S(2) state, were studied by X- and Q-band CW-EPR and by pulsed Q-band (55)Mn-ENDOR spectroscopy. Both wild type and tyrosine D less mutants grown photoautotrophically in either CaCl(2) or SrCl(2) containing media were measured. The obtained CW-EPR spectra of the S(2) state displayed the characteristic, clearly noticeable differences in the hyperfine pattern of the multiline EPR signal [Boussac et al. J. Biol. Chem.2004, 279, 22809-22819]. In sharp contrast, the manganese ((55)Mn) ENDOR spectra of the Ca and Sr forms of the OEC were remarkably similar. Multifrequency simulations of the X- and Q-band CW-EPR and (55)Mn-pulsed ENDOR spectra using the Spin Hamiltonian formalism were performed to investigate this surprising result. It is shown that (i) all four manganese ions contribute to the (55)Mn-ENDOR spectra; (ii) only small changes are seen in the fitted isotropic hyperfine values for the Ca(2+) and Sr(2+) containing OEC, suggesting that there is no change in the overall spin distribution (electronic coupling scheme) upon Ca(2+)/Sr(2+) substitution; (iii) the changes in the CW-EPR hyperfine pattern can be explained by a small decrease in the anisotropy of at least two hyperfine tensors. It is proposed that modifications at the Ca(2+) site may modulate the fine structure tensor of the Mn(III) ion. DFT calculations support the above conclusions. Our data analysis also provides strong support for the notion that in the S(2) state the coordination of the Mn(III) ion is square-pyramidal (5-coordinate) or octahedral (6-coordinate) with tetragonal elongation. In addition, it is shown that only one of the currently published OEC models, the Siegbahn structure [Siegbahn, P. E. M. Acc. Chem. Res.2009, 42, 1871-1880, Pantazis

  9. Collapsed tetragonal phase as a strongly covalent and fully nonmagnetic state: Persistent magnetism with interlayer As-As bond formation in Rh-doped Ca0 .8Sr0 .2Fe2As2 (United States)

    Zhao, K.; Glasbrenner, J. K.; Gretarsson, H.; Schmitz, D.; Bednarcik, J.; Etter, M.; Sun, J. P.; Manna, R. S.; Al-Zein, A.; Lafuerza, S.; Scherer, W.; Cheng, J. G.; Gegenwart, P.


    A well-known feature of the CaFe2As2 -based superconductors is the pressure-induced collapsed tetragonal phase that is commonly ascribed to the formation of an interlayer As-As bond. Using detailed x-ray scattering and spectroscopy, we find that Rh-doped Ca0.8Sr0.2Fe2As2 does not undergo a first-order phase transition and that local Fe moments persist despite the formation of interlayer As-As bonds. Our density functional theory calculations reveal that the Fe-As bond geometry is critical for stabilizing magnetism and the pressure-induced drop in the c lattice parameter observed in pure CaFe2As2 is mostly due to a constriction within the FeAs planes. The collapsed tetragonal phase emerges when covalent bonding of strongly hybridized Fe 3 d and As 4 p states completely wins out over their exchange splitting. Thus the collapsed tetragonal phase is properly understood as a strong covalent phase that is fully nonmagnetic with the As-As bond forming as a by-product.

  10. Far-infrared radiation acutely increases nitric oxide production by increasing Ca{sup 2+} mobilization and Ca{sup 2+}/calmodulin-dependent protein kinase II-mediated phosphorylation of endothelial nitric oxide synthase at serine 1179

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jung-Hyun; Lee, Sangmi [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Cho, Du-Hyong [Department of Neuroscience, School of Medicine, Konkuk University, Seoul 143-701 (Korea, Republic of); Park, Young Mi [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Kang, Duk-Hee [Division of Nephrology, Department of Internal Medicine, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of); Jo, Inho, E-mail: [Department of Molecular Medicine and Ewha Medical Research Institute, Ewha Womans University Medical School, Seoul 158-710 (Korea, Republic of)


    Highlights: •Far-infrared (FIR) radiation increases eNOS-Ser{sup 1179} phosphorylation and NO production in BAEC. •CaMKII and PKA mediate FIR-stimulated increases in eNOS-Ser{sup 1179} phosphorylation. •FIR increases intracellular Ca{sup 2+} levels. •Thermo-sensitive TRPV Ca{sup 2+} channels are unlikely to be involved in the FIR-mediated eNOS-Ser{sup 1179} phosphorylation pathway. -- Abstract: Repeated thermal therapy manifested by far-infrared (FIR) radiation improves vascular function in both patients and mouse model with coronary heart disease, but its underlying mechanism is not fully understood. Using FIR as a thermal therapy agent, we investigate the molecular mechanism of its effect on endothelial nitric oxide synthase (eNOS) activity and NO production. FIR increased the phosphorylation of eNOS at serine 1179 (eNOS-Ser{sup 1179}) in a time-dependent manner (up to 40 min of FIR radiation) in bovine aortic endothelial cells (BAEC) without alterations in eNOS expression. This increase was accompanied by increases in NO production and intracellular Ca{sup 2+} levels. Treatment with KN-93, a selective inhibitor of Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) and H-89, a protein kinase A inhibitor, inhibited FIR radiation-stimulated eNOS-Ser{sup 1179} phosphorylation. FIR radiation itself also increased the temperature of culture medium. As transient receptors potential vanilloid (TRPV) ion channels are known to be temperature-sensitive calcium channels, we explore whether TRPV channels mediate these observed effects. Reverse transcription-PCR assay revealed two TRPV isoforms in BAEC, TRPV2 and TRPV4. Although ruthenium red, a pan-TRPV inhibitor, completely reversed the observed effect of FIR radiation, a partial attenuation (∼20%) was found in cells treated with Tranilast, TRPV2 inhibitor. However, ectopic expression of siRNA of TRPV2 showed no significant alteration in FIR radiation-stimulated eNOS-Ser{sup 1179} phosphorylation. This

  11. Semiconducting polymer-based nanoparticles with strong absorbance in NIR-II window for in vivo photothermal therapy and photoacoustic imaging. (United States)

    Cao, Ziyang; Feng, Liangzhu; Zhang, Guobing; Wang, Junxia; Shen, Song; Li, Dongdong; Yang, Xianzhu


    Near-infrared (NIR) light-induced photothermal therapy (PTT) has attracted much interest in recent years. In the NIR region, tissue penetration ability of the second biological near-infrared window (1000-1350 nm) is recognized to be stronger than that of the first window (650-950 nm). However, NIR light absorbers in the second NIR region (NIR-II) have been scant even though various NIR light absorbers in the first NIR region (NIR-I) have been widely explored. In this work, a thieno-isoindigo derivative-based semiconducting polymer, PBTPBF-BT, were formulated into PEGylated nanoparticles. The obtained nanoparticle NP PBTPBF-BT exhibited strong absorption in NIR-II region, inherent high photothermal conversion efficacy, and excellent photostability. The in vitro and in vivo PTT study employing 1064 nm laser in NIR-II window revealed that NP PBTPBF-BT could efficiently ablate tumor cell at a power density of 0.42 W/cm 2 (the skin tolerance threshold value). Moreover, NP PBTPBF-BT with excellent photostability exhibited enhanced photoacoustic (PA) imaging of tumor in living mice, suggesting the great probability of using NP PBTPBF-BT for in vivo PA imaging-guided PTT in the NIR-II window. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or IIIPIK3CA-Mutant ER-Positive and HER2-Negative Breast Cancer. (United States)

    Ma, Cynthia X; Suman, Vera; Goetz, Matthew P; Northfelt, Donald; Burkard, Mark E; Ademuyiwa, Foluso; Naughton, Michael; Margenthaler, Julie; Aft, Rebecca; Gray, Richard; Tevaarwerk, Amye; Wilke, Lee; Haddad, Tufia; Moynihan, Timothy; Loprinzi, Charles; Hieken, Tina; Barnell, Erica K; Skidmore, Zachary L; Feng, Yan-Yang; Krysiak, Kilannin; Hoog, Jeremy; Guo, Zhanfang; Nehring, Leslie; Wisinski, Kari B; Mardis, Elaine; Hagemann, Ian S; Vij, Kiran; Sanati, Souzan; Al-Kateb, Hussam; Griffith, Obi L; Griffith, Malachi; Doyle, Laurence; Erlichman, Charles; Ellis, Matthew J


    Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor-positive (ER + ) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA -mutant ER + breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER + breast cancer. Experimental Design: Potential eligible patients with clinical stage II/III ER + /HER2 - breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing. Patients positive for PIK3CA mutation in the tumor were eligible to start MK-2206 (150 mg orally weekly, with prophylactic prednisone) on cycle 1 day 2 (C1D2) and to receive a maximum of four 28-day cycles of combination therapy before surgery. Serial biopsies were collected at preregistration, C1D1 and C1D17. Results: Fifty-one patients preregistered and 16 of 22 with PIK3CA -mutant tumors received study drug. Three patients went off study due to C1D17 Ki67 >10% ( n = 2) and toxicity ( n = 1). Thirteen patients completed neoadjuvant therapy followed by surgery. No pCRs were observed. Rash was common. MK-2206 did not further suppress cell proliferation and did not induce apoptosis on C1D17 biopsies. Although AKT phosphorylation was reduced, PRAS40 phosphorylation at C1D17 after MK-2206 persisted. One patient acquired an ESR1 mutation at surgery. Conclusions: MK-2206 is unlikely to add to the efficacy of anastrozole alone in PIK3CA -mutant ER + breast cancer and should not be studied further in the target patient population. Clin Cancer Res; 23(22); 6823-32. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Ca2+/Calmodulin-Dependent Protein Kinase II and Androgen Signaling Pathways Modulate MEF2 Activity in Testosterone-Induced Cardiac Myocyte Hypertrophy

    Directory of Open Access Journals (Sweden)

    Javier Duran


    Full Text Available Testosterone is known to induce cardiac hypertrophy through androgen receptor (AR-dependent and -independent pathways, but the molecular underpinnings of the androgen action remain poorly understood. Previous work has shown that Ca2+/calmodulin-dependent protein kinase II (CaMKII and myocyte-enhancer factor 2 (MEF2 play key roles in promoting cardiac myocyte growth. In order to gain mechanistic insights into the action of androgens on the heart, we investigated how testosterone affects CaMKII and MEF2 in cardiac myocyte hypertrophy by performing studies on cultured rat cardiac myocytes and hearts obtained from adult male orchiectomized (ORX rats. In cardiac myocytes, MEF2 activity was monitored using a luciferase reporter plasmid, and the effects of CaMKII and AR signaling pathways on MEF2C were examined by using siRNAs and pharmacological inhibitors targeting these two pathways. In the in vivo studies, ORX rats were randomly assigned to groups that were administered vehicle or testosterone (125 mg⋅kg-1⋅week-1 for 5 weeks, and plasma testosterone concentrations were determined using ELISA. Cardiac hypertrophy was evaluated by measuring well-characterized hypertrophy markers. Moreover, western blotting was used to assess CaMKII and phospholamban (PLN phosphorylation, and MEF2C and AR protein levels in extracts of left-ventricle tissue from control and testosterone-treated ORX rats. Whereas testosterone treatment increased the phosphorylation levels of CaMKII (Thr286 and phospholambam (PLN (Thr17 in cardiac myocytes in a time- and concentration-dependent manner, testosterone-induced MEF2 activity and cardiac myocyte hypertrophy were prevented upon inhibition of CaMKII, MEF2C, and AR signaling pathways. Notably, in the hypertrophied hearts obtained from testosterone-administered ORX rats, both CaMKII and PLN phosphorylation levels and AR and MEF2 protein levels were increased. Thus, this study presents the first evidence indicating that

  14. Mouse oocytes fertilised by ICSI during in vitro maturation retain the ability to be activated after refertilisation in metaphase II and can generate Ca2+ oscillations

    Directory of Open Access Journals (Sweden)

    Pomorski Paweł


    Full Text Available Abstract Background At fertilisation, mammalian oocytes are activated by oscillations of intracellular Ca2+ ([Ca2+]i. Phospholipase Cζ, which is introduced by fertilising spermatozoon, triggers [Ca2+]i oscillations through the generation of inositol 1,4,5-triphosphate (IP3, which causes Ca2+ release by binding to IP3 receptors located on the endoplasmic reticulum (ER of the oocyte. Ability to respond to this activating stimulus develops during meiotic maturation of the oocyte. Here we examine how the development of this ability is perturbed when a single spermatozoon is introduced into the oocyte prematurely, i.e. during oocyte maturation. Results Mouse oocytes during maturation in vitro were fertilised by ICSI (intracytoplasmic sperm injection 1 – 4 h after germinal vesicle break-down (GVBD and were subsequently cultured until they reached metaphase II (MII stage. At MII stage they were fertilised in vitro for the second time (refertilisation. We observed that refertilised oocytes underwent activation with similar frequency as control oocytes, which also went through maturation in vitro, but were fertilised only once at MII stage (87% and 93%, respectively. Refertilised MII oocytes were able to develop [Ca2+]i oscillations in response to penetration by spermatozoa. We found however, that they generated a lower number of transients than control oocytes. We also showed that the oocytes, which were fertilised during maturation had a similar level of MPF activity as control oocytes, which were not subjected to ICSI during maturation, but had reduced level of IP3 receptors. Conclusion Mouse oocytes, which were experimentally fertilised during maturation retain the ability to generate repetitive [Ca2+]i transients, and to be activated after completion of maturation.

  15. Heparin cofactor II-dependent antithrombin activity of calcium spirulan. (United States)

    Hayakawa, Y; Hayashi, T; Hayashi, K; Hayashi, T; Ozawa, T; Niiya, K; Sakuragawa, N


    Calcium spirulan (Ca-SP), a novel sulfated polysaccharide isolated from the blue-green alga Spirulina platensis, enhanced the antithrombin activity of heparin cofactor II (HC II) more than 10000-fold. The apparent second-order rate constant of thrombin inhibition by HC II was calculated to be 4.2 x 10(4) M-1 min-1 in the absence of Ca-SP, and it increased in the presence of 50 micrograms/ml Ca-SP to 4.5 x 10(8) M-1 min-1. Ca-SP effectively induced the formation of a thrombin-HC II complex in plasma. In the presence of Ca-SP, both the recombinant HC II variants Lys173-->Leu and Arg 189-->His, which are defective in interactions with heparin and dermatan sulfate, respectively, inhibited thrombin in a manner similar to native rHC II. This result indicates that the binding site of HC II for Ca-SP is different from the heparin- or dermatan sulfate-binding site. When we removed the calcium from the Ca-SP, the compound did not exert any antithrombin activity. Furthermore, Na-SP, which was prepared by replacement of the calcium in Ca-SP with sodium, accelerated the antithrombin activity of HC II as Ca-SP did. We therefore suggest that the molecular conformation maintained by Ca or Na is indispensable to the antithrombin activity of Ca-SP. The HC II-dependent antithrombin activity of Ca-SP was almost totally abolished by treatment with chondroitinase AC I, heparinase or heparitinase, but not by treatment with chondroitinase ABC and chondroitinase AC II, suggesting that a heparin- or dermatan sulfate-like structure is not responsible for the activation of HC II by Ca-SP. Ca-SP is therefore thought to be a unique sulfated polysaccharide which shows a strong antithrombin effect in an exclusively HC II-dependent manner.

  16. Quantum mechanics/molecular mechanics simulation of the ligand vibrations of the water-oxidizing Mn4CaO5 cluster in photosystem II. (United States)

    Nakamura, Shin; Noguchi, Takumi


    During photosynthesis, the light-driven oxidation of water performed by photosystem II (PSII) provides electrons necessary to fix CO 2 , in turn supporting life on Earth by liberating molecular oxygen. Recent high-resolution X-ray images of PSII show that the water-oxidizing center (WOC) is composed of an Mn 4 CaO 5 cluster with six carboxylate, one imidazole, and four water ligands. FTIR difference spectroscopy has shown significant structural changes of the WOC during the S-state cycle of water oxidation, especially within carboxylate groups. However, the roles that these carboxylate groups play in water oxidation as well as how they should be properly assigned in spectra are unresolved. In this study, we performed a normal mode analysis of the WOC using the quantum mechanics/molecular mechanics (QM/MM) method to simulate FTIR difference spectra on the S 1 to S 2 transition in the carboxylate stretching region. By evaluating WOC models with different oxidation and protonation states, we determined that models of high-oxidation states, Mn(III) 2 Mn(IV) 2 , satisfactorily reproduced experimental spectra from intact and Ca-depleted PSII compared with low-oxidation models. It is further suggested that the carboxylate groups bridging Ca and Mn ions within this center tune the reactivity of water ligands bound to Ca by shifting charge via their π conjugation.

  17. Compressible Kolmogorov flow in strongly coupled dusty plasma using molecular dynamics and computational fluid dynamics. II. A comparative study (United States)

    Gupta, Akanksha; Ganesh, Rajaraman; Joy, Ashwin


    In this paper, we perform comparative studies of compressible Kolmogorov flow in the two-dimensional strongly coupled dusty plasma by means of atomistic or molecular dynamics (MD) and continuum or computational fluid dynamics (CFD) methods. Recently, using MD simulation, generation of molecular shear heat at the atomistic level is shown to reduce the average coupling strength of the system and destruct the vortical structures. To suppress the molecular heat, a novel method of a thermostat, namely, the configurational thermostat is introduced by which the microscale heat generated by the shear flow has shown to be thermostatted out efficiently without compromising the large scale vortex dynamics. While using a configurational thermostat, it has been found that the growth rate obtained from both the studies is the same with the marginal difference. To make the comparison with the continuum fluid model, we perform the same study using the generalised hydrodynamic model, wherein molecular shear heating phenomena is completely absent, however, viscous dissipation is there at the macroscale level. For this purpose, an Advanced Generalised SPECTral Code has been developed to study the linear and nonlinear aspects of the Kolmogorov flow in the incompressible and compressible limit for viscoelastic fluids. All the phenomenological parameters used in CFD simulations have been calculated from MD simulations. Code is benchmarked against the eigen value solver in the linear regime. Linear growth-rates calculated from the phenomenological fluid model is found to be close to that obtained from MD simulation for the same set of input parameters. The transition from laminar to turbulent flow has been found at a critical value of Reynolds number Rc in both the macroscopic (CFD) and microscopic (MD) simulation. Rc in MD is smaller than the one obtained by CFD simulation. In the nonlinear regime of CFD, the mode becomes unstable and vortex formation happens earlier than in MD. The

  18. Tracing N, K, Mg and Ca released from decomposing biomass to new tree growth. Part II: A model system simulating root decomposition on clearfell sites

    Energy Technology Data Exchange (ETDEWEB)

    Weatherall, A. [Macaulay Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom)]. E-mail:; Proe, M.F. [Macaulay Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom); Craig, J. [Macaulay Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom); Cameron, A.D. [School of Biological Sciences, University of Aberdeen, Cruickshank Building, St. Machar Drive AB24 3UU (United Kingdom); McKay, H.M. [Policy and Practice Division, Forestry Commission, 231 Corstorphine Road, Edinburgh EH12 7AT (United Kingdom); Midwood, A.J. [Macaulay Institute, Craigiebuckler, Aberdeen AB15 8QH (United Kingdom)


    The decomposing roots of harvested trees are a potential source of nutrients for new trees on both conventional and whole-tree harvested clearfell sites. Roots contain significant reservoirs of nutrients, but little is known about the magnitude and rate of their release. The aim of this study was to use stable isotope techniques in a model system to trace nutrients released by decomposing roots. Labelled biomass was obtained by growing Sitka spruce (Picea sitchensis (Bong.) Carr.) seedlings with a generous or poor nutrient supply containing elevated {sup 15}N, {sup 41}K, {sup 26}Mg and {sup 44}Ca. Labelled trees were re-potted in sand and in two contrasting soils types to remove them from the enriched isotope supply. After re-potting, the labelled above-ground biomass was harvested, removed and used in a separate study described previously (Part I of II). In the study described here (Part II of II), new Sitka spruce seedlings were planted alongside the labelled root systems. A full destructive harvest was undertaken after one growing season. Enriched {sup 15}N, {sup 41}K, {sup 26}Mg, and {sup 44}Ca were recovered in the new seedlings in both sand and soils. The elevated amounts of {sup 15}N, {sup 41}K, {sup 26}Mg and {sup 44}Ca recovered in new seedlings indicate that nutrients released from decomposing roots can make a direct contribution to the growth of new trees on restock sites. The success of this model system will provide guidance for the application of similar techniques in field experiments.

  19. Zebrin II Expressing Purkinje Cell Phenotype—Related and—Unrelated Cerebellar Abnormalities in Ca˅2.1 Mutant, Rolling Mouse Nagoya

    Directory of Open Access Journals (Sweden)

    Kazuhiko Sawada


    Full Text Available Rolling mouse Nagoya is an ataxic mutant mouse that carries a mutation in a gene encoding for the alpha 1A subunit of the voltage-gated P/Q-type Ca2+ channel (Ca˅2.1. This report summarizes our studies and others concerning cerebellar abnormalities in rolling mice based on chemical neuroanatomy. While there are no obvious cerebellar deformations in this mutant mouse, the altered functions of Purkinje cells can be revealed as a reduced expression of type 1 ryanodine receptor (RyR1 in all Purkinje cells uniformly throughout the cerebellum, and as an ectopic expression of tyrosine hydroxylase (TH in the Purkinje cell subsets with the zebrin II—immunopositive phenotype. As the mutated Ca˅2.1 channel is expressed at uniform levels in all Purkinje cells, its copresence with RyR1 staining suggests that a Ca˅2.1 channel dysfunction links with the expression of RyR1 in Purkinje cells of rolling mice. However, an ectopic expression of TH in the Purkinje cells is topologically related to the projection of corticotrophin-releasing factor—immunopositive climbing fibers rather than expression of the mutated Ca˅2.1 channel. On the other hand, increased levels of serotonin (5-HT in 5-HTergic fibers were revealed immunohistochemically in Purkinje cells of the vermis of rolling cerebellum. Thus, to determine whether or not cerebellar abnormalities are related to Purkinje cell populations revealed by zebrin II expression is essential for enhancing our understanding of the pathogenesis of hereditary cerebellar ataxic mutants such as rolling mice.

  20. Roles of EDTA washing and Ca{sup 2+} regulation on the restoration of anammox granules inhibited by copper(II)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zheng-Zhe; Cheng, Ya-Fei; Zhou, Yu-Huang; Buayi, Xiemuguli [Department of Environmental Science and Engineering, Hangzhou Normal University, Hangzhou 310036 (China); Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, Hangzhou Normal University, Hangzhou 310036 (China); Jin, Ren-Cun, E-mail: [Department of Environmental Science and Engineering, Hangzhou Normal University, Hangzhou 310036 (China); Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, Hangzhou Normal University, Hangzhou 310036 (China)


    Highlights: • 80.5% of the Cu in anammox granules was introduced via adsorption. • Cu(II) internalized on/into AnAOB cells plays a crucial role in toxicity. • EDTA washing contributes to the detoxification of anammox granules. • Ca{sup 2+} can stimulate the re-growth of damaged anammox consortium. - Abstract: We investigated the feasibility of using ethylene diamine tetraacetic acid (EDTA) washing followed by Ca{sup 2+} enhancement for the recovery of anammox reactors inhibited by Cu(II). Kinetic experiments and batch activity assays were employed to determine the optimal concentration of EDTA and washing time; and the performance and physiological dynamics were tracked by continuous-flow monitoring to evaluate the long-term effects. The two-step desorption process revealed that the Cu in anammox granules was primarily introduced via adsorption (approximately, 80.5%), and the portion of Cu in the dispersible layer was predominant (accounting for 71.1%). Afterwards, the Cu internalized in the cells (approximately, 14.7%) could diffuse out of the cells and be gradually washed out of the reactor over the next 20 days. The Ca{sup 2+} addition that followed led to an accelerated nitrogen removal rate recovery slope (0.1491 kgN m{sup −3} d{sup −2}) and a normal biomass growth rate (0.054 d{sup −1}). The nitrogen removal rate returned to normal levels within 90 days and gradual improvements in granular characteristics were also achieved. Therefore, this study provides a new insight that externally removing the adsorbed heavy metals followed by internally repairing the metabolic system may represent an optimal restoration strategy for anammox consortium damaged by heavy metals.


    Directory of Open Access Journals (Sweden)

    Maia ŞEVCIUC


    Full Text Available În articol este abordată problema privind mediul academic ca factor de asigurare a continuităţii şi interconexiunii dintre ciclurile învăţământului superior. În acest sens sunt analizate diferite concepte cu referire la mediul academic, sunt deduse principiile de concepere a unui mediu academic eficient, dar şi modalităţi de realizare a continuităţii şi inter­conexiunii dintre ciclurile învăţământului superior. Sunt propuse sugestii de asigurare a continuităţii şi interconexiunii dintre ciclurile învăţământului superior.ACADEMIC ENVIRONMENT AS A FACTOR IN ENSURING CONTINUITY AND INTERCONNECTION BETWEEN CYCLES OF HIGHER EDUCATIONThe article addressed academics as a factor of continuity and interconnection between cycles of higher education. In this sense analyzed different concepts with reference to academia, they are deducted design principles of an academic environment effectively, but also ways of continuity and interconnection between cycles of higher education, are proposed suggestions to ensure continuity and interconnection between cycles of higher education.

  2. The evolution of substrate specificity-associated residues and Ca(2+) -binding motifs in EF-hand-containing type II NAD(P)H dehydrogenases. (United States)

    Hao, Meng-Shu; Rasmusson, Allan G


    Most eukaryotic organisms, except some animal clades, have mitochondrial alternative electron transport enzymes that allow respiration to bypass the energy coupling in oxidative phosphorylation. The energy bypass enzymes in plants include the external type II NAD(P)H dehydrogenases (DHs) of the NDB family, which are characterized by an EF-hand domain for Ca(2+) binding. Here we investigate these plant enzymes by combining molecular modeling with evolutionary analysis. Molecular modeling of the Arabidopsis thaliana AtNDB1 with the yeast ScNDI1 as template revealed distinct similarities in the core catalytic parts, and highlighted the interaction between the pyridine nucleotide and residues correlating with NAD(P)H substrate specificity. The EF-hand domain of AtNDB1 has no counterpart in ScNDI1, and was instead modeled with Ca(2+) -binding signal transducer proteins. Combined models displayed a proximity of the AtNDB1 EF-hand domain to the substrate entrance side of the catalytic part. Evolutionary analysis of the eukaryotic NDB-type proteins revealed ancient and recent reversions between the motif observed in proteins specific for NADH (acidic type) and NADPH (non-acidic type), and that the clade of enzymes with acidic motifs in angiosperms derives from non-acidic-motif NDB-type proteins present in basal plants, fungi and protists. The results suggest that Ca(2+) -dependent external NADPH oxidation is an ancient process, indicating that it has a fundamental importance for eukaryotic cellular redox metabolism. In contrast, the external NADH DHs in plants are products of a recent expansion, mirroring the expansion of the alternative oxidase family. © 2016 Scandinavian Plant Physiology Society.

  3. Crystal structure of calcium dinickel(II iron(III tris(orthophosphate: CaNi2Fe(PO43

    Directory of Open Access Journals (Sweden)

    Said Ouaatta


    Full Text Available The title compound, CaNi2Fe(PO43, was synthesized by solid-state reactions. Its structure is closely related to that of α-CrPO4 in the space group Imma. Except for two O atoms in general positions, all atoms are located in special positions. The three-dimensional framework is built up from two types of sheets extending parallel to (100. The first sheet is made up from two edge-sharing [NiO6] octahedra, leading to the formation of [Ni2O10] double octahedra that are connected to two PO4 tetrahedra through a common edge and corners. The second sheet results from rows of corner-sharing [FeO6] octahedra and PO4 tetrahedra forming an infinite linear chain. These layers are linked together through common corners of PO4 tetrahedra and [FeO6] octahedra, resulting in an open three-dimensional framework that delimits two types of channels parallel to [100] and [010] in which the eightfold-coordinated CaII cations are located.

  4. Gentamicin blocks the ACh-induced BK current in guinea pig type II vestibular hair cells by competing with Ca²⁺ at the L-type calcium channel. (United States)

    Yu, Hong; Guo, Chang-Kai; Wang, Yi; Zhou, Tao; Kong, Wei-Jia


    Type II vestibular hair cells (VHCs II) contain big-conductance Ca²⁺-dependent K⁺ channels (BK) and L-type calcium channels. Our previous studies in guinea pig VHCs II indicated that acetylcholine (ACh) evoked the BK current by triggering the influx of Ca²⁺ ions through L-type Ca²⁺ channels, which was mediated by M2 muscarinic ACh receptor (mAChRs). Aminoglycoside antibiotics, such as gentamicin (GM), are known to have vestibulotoxicity, including damaging effects on the efferent nerve endings on VHCs II. This study used the whole-cell patch clamp technique to determine whether GM affects the vestibular efferent system at postsynaptic M2-mAChRs or the membrane ion channels. We found that GM could block the ACh-induced BK current and that inhibition was reversible, voltage-independent, and dose-dependent with an IC₅₀ value of 36.3 ± 7.8 µM. Increasing the ACh concentration had little influence on GM blocking effect, but increasing the extracellular Ca²⁺ concentration ([Ca²⁺]₀) could antagonize it. Moreover, 50 µM GM potently blocked Ca²⁺ currents activated by (-)-Bay-K8644, but did not block BK currents induced by NS1619. These observations indicate that GM most likely blocks the M2 mAChR-mediated response by competing with Ca²⁺ at the L-type calcium channel. These results provide insights into the vestibulotoxicity of aminoglycoside antibiotics on mammalian VHCs II.

  5. Predictive value of serum CA-125 levels in patients with persistent or recurrent epithelial ovarian cancer or peritoneal cancer treated with bevacizumab on a Gynecologic Oncology Group phase II trial (United States)

    Randall, Leslie M.; Sill, Michael W.; Burger, Robert A.; Monk, Bradley J.; Buening, Barbara; Sorosky, Joel I.


    Purpose To compare two methods of determining therapeutic response and disease progression - modified Gynecologic Cancer Intergroup (GCIG) criteria based on CA-125 and Radiographic Evaluation Criteria in Solid Tumors (RECIST), in a phase II trial of bevacizumab for patients with recurrent or persistent epithelial ovarian and peritoneal carcinoma.) Patients and Methods Patients were treated with bevacizumab 15 mg/kg every 21 days. Modified GCIG definitions of progression and response were retrospectively applied and compared to RECIST-defined progression and response. The prognostic significance of CA-125- and RECIST-defined responses and progressions were explored. Results Sixty-two patients were evaluable by RECIST, 59 for progression by CA-125, and 45 for response by CA-125. Median progression-free survival (PFS) by RECIST and progression-free interval (PFI) by CA-125 were 4.7 and 5.2 months respectively. However, 12.9% of those with CA-125 defined progression remained progression-free according to RECIST for at least 8 months. Thirteen of 62 patients (21%) had response by RECIST and 14/45 (31%) by CA-125. Time dependent analyses indicated that progression by CA-125 was associated with a 5.2 fold increased risk of progression by RECIST, and response by CA-125 had a 5 fold decrease in risk of progression by RECIST. Landmark and time dependent analyses showed prognostic value of responses by CA-125 and RECIST. Conclusions In this study, disease assessment by RECIST and CA-125 appear to correlate in general. However, approximately 10% of patients might demonstrate progression earlier by CA-125. PMID:22138229

  6. A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility (United States)

    Carmona, F. David; Mackie, Sarah L.; Martín, Jose-Ezequiel; Taylor, John C.; Vaglio, Augusto; Eyre, Stephen; Bossini-Castillo, Lara; Castañeda, Santos; Cid, Maria C.; Hernández-Rodríguez, José; Prieto-González, Sergio; Solans, Roser; Ramentol-Sintas, Marc; González-Escribano, M. Francisca; Ortiz-Fernández, Lourdes; Morado, Inmaculada C.; Narváez, Javier; Miranda-Filloy, José A.; Martínez-Berriochoa, Agustín; Unzurrunzaga, Ainhoa; Hidalgo-Conde, Ana; Madroñero-Vuelta, Ana B.; Fernández-Nebro, Antonio; Ordóñez-Cañizares, M. Carmen; Escalante, Begoña; Marí-Alfonso, Begoña; Sopeña, Bernardo; Magro, César; Raya, Enrique; Grau, Elena; Román, José A.; de Miguel, Eugenio; López-Longo, F. Javier; Martínez, Lina; Gómez-Vaquero, Carmen; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Díaz-López, J. Bernardino; Caminal-Montero, Luis; Martínez-Zapico, Aleida; Monfort, Jordi; Tío, Laura; Sánchez-Martín, Julio; Alegre-Sancho, Juan J.; Sáez-Comet, Luis; Pérez-Conesa, Mercedes; Corbera-Bellalta, Marc; García-Villanueva, M. Jesús; Fernández-Contreras, M. Encarnación; Sanchez-Pernaute, Olga; Blanco, Ricardo; Ortego-Centeno, Norberto; Ríos-Fernández, Raquel; Callejas, José L.; Fanlo-Mateo, Patricia; Martínez-Taboada, Víctor M.; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A.; Gianfreda, Davide; Santilli, Daniele; Ramirez, Giuseppe A.; Soriano, Alessandra; Muratore, Francesco; Pazzola, Giulia; Addimanda, Olga; Wijmenga, Cisca; Witte, Torsten; Schirmer, Jan H.; Moosig, Frank; Schönau, Verena; Franke, Andre; Palm, Øyvind; Molberg, Øyvind; Diamantopoulos, Andreas P.; Carette, Simon; Cuthbertson, David; Forbess, Lindsy J.; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; McAlear, Carol A.; Moreland, Larry; Monach, Paul A.; Pagnoux, Christian; Seo, Philip; Spiera, Robert; Sreih, Antoine G.; Warrington, Kenneth J.; Ytterberg, Steven R.; Gregersen, Peter K.; Pease, Colin T.; Gough, Andrew; Green, Michael; Hordon, Lesley; Jarrett, Stephen; Watts, Richard; Levy, Sarah; Patel, Yusuf; Kamath, Sanjeet; Dasgupta, Bhaskar; Worthington, Jane; Koeleman, Bobby P.C.; de Bakker, Paul I.W.; Barrett, Jennifer H.; Salvarani, Carlo; Merkel, Peter A.; González-Gay, Miguel A.; Morgan, Ann W.; Martín, Javier


    We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function. PMID:25817017

  7. Production of dammarane-type sapogenins in rice by expressing the dammarenediol-II synthase gene from Panax ginseng C.A. Mey. (United States)

    Huang, Zhiwei; Lin, Juncheng; Cheng, Zuxin; Xu, Ming; Huang, Xinying; Yang, Zhijian; Zheng, Jingui


    Ginsenosides are the main active ingredients in Chinese medicinal ginseng; 2,3-oxidosqualene is a precursor metabolite to ginsenosides that is present in rice. Because rice lacks a key rate-limiting enzyme (dammarenediol-II synthase, DS), rice cannot synthesize dammarane-type ginsenosides. In this study, the ginseng (Panax ginseng CA Mey.) DS gene (GenBank: AB265170.1) was transformed into rice using agrobacterium, and 64 rice transgenic plants were produced. The Transfer-DNA (T-DNA) insertion sites in homozygous lines of the T2 generation were determined by using high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR) and differed in all tested lines. One to two copies of the T-DNA were present in each transformant, and real-time PCR and Western blotting showed that the transformed DS gene could be transcribed and highly expressed. High performance liquid chromatography (HPLC) analysis showed that the dammarane-type sapogenin 20(S)-protopanaxadiol (PPD) content was 0.35-0.59 mg/g dw and the dammarane-type sapogenin 20(S)-protopanaxatriol (PPT) content was 0.23-0.43 mg/g dw in the transgenic rice. LC/MS analysis confirmed production of PPD and PPT. These results indicate that a new "ginseng rice" germplasm containing dammarane-type sapogenins has been successfully developed by transforming the ginseng DS gene into rice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Membrane events and ionic processes involved in dopamine release from tuberoinfundibular neurons. II. Effect of the inhibition of the Na+-Ca++ exchange by amiloride

    International Nuclear Information System (INIS)

    Taglialatela, M.; Amoroso, S.; Canzoniero, L.M.; Di Renzo, G.F.; Annunziato, L.


    In the present study we investigated the effect of amiloride, a rather specific inhibitor of the membrane Na+-Ca++ exchange system, on the release of endogenous dopamine (DA) and previously taken-up [3H]DA from tuberoinfundibular dopaminergic neurons. Amiloride (300 microM) stimulated either endogenous DA or [3H]DA release. Amiloride-induced stimulation of [3H]DA release was prevented in a Ca++-free plus ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid medium. Amiloride, at the same concentration, reinforced both high K+- and electrically-induced stimulation of [3H]DA release. These results are explained on the basis of the ability of amiloride in blocking the Na+-Ca++ exchange system, therefore causing an elevation of intracellular Ca++ levels in resting conditions, and a further accumulation of Ca++ ions after high K+- or electrically elicited opening of voltage-operated channels specific for Ca++ ions. The enhanced intracellular Ca++ availability may trigger the stimulation of neurotransmitter release. In addition, amiloride was able to block in a dose-dependent manner (70-300 microM) the ouabain-induced [3H]DA release, suggesting that, when intracellular concentrations of Na+ are increased by the blockade of Na+,K+-adenosine triphosphatase the Na+-Ca+;+ exchange carrier reverses its resting mode of operation, mediating the influx of extracellular Ca++ ions. Amiloride, by blocking the Na+-Ca++ exchange mechanism, prevents the ouabain-elicited entrance of extracellular Ca++ ions, therefore inhibiting [3H]DA release stimulated by the cardioactive glycoside. Collectively, the results of the present study seem to be compatible with the idea that the Na+-Ca++ exchange mechanism is involved in the regulation of [3H]DA release from tuberoinfundibular dopaminergic neurons, through the regulation of Ca++ movements across the plasma membrane

  9. Ca2+ induced surfactant secretion in alveolar type II cultures isolated from the H-2Kb-tsA58 transgenic mouse

    NARCIS (Netherlands)

    Jennings, Paul; Bertocchi, Cristina; Frick, Manfred; Haller, Thomas; Pfaller, Walter; Dietl, Paul


    BACKGROUND/AIMS: There is a need for the development of transgenic mice to elucidate molecular mechanisms in surfactant secretion. However at present very little is known about the regulation of surfactant exocytosis in murine alveolar type II (AT II) cells. METHODS: We brought AT II cells isolated

  10. Strong and weak lensing united: II. The cluster mass distribution of the most X-ray luminous cluster RX J1347.5-1145

    Energy Technology Data Exchange (ETDEWEB)

    Bradač, M.; Erben, T.; Schneider, P.; Hildebrandt, H.; Lombardi, M.; Schirmer, M.; Miralles, J. -M.; Clowe, D.; Schindler, S.


    We have shown that the cluster-mass reconstruction method which combines strong and weak gravitational lensing data, developed in the first paper in the series, successfully reconstructs the mass distribution of a simulated cluster. In this paper we apply the method to the ground-based high-quality multi-colour data of RX J1347.5-1145 , the most X-ray luminous cluster to date. A new analysis of the cluster core on very deep, multi-colour data analysis of VLT/FORS data reveals many more arc candidates than previously known for this cluster. The combined strong and weak lensing reconstruction confirms that the cluster is indeed very massive. If the redshift and identification of the multiple-image system as well as the redshift estimates of the source galaxies used for weak lensing are correct, we determine the enclosed cluster mass in a cylinder to M(<360 h -1 kpc)= (1.2± 0.3) x 1015 M. In addition the reconstructed mass distribution follows the distribution found with independent methods (X-ray measurements, SZ). With higher resolution (e.g. HST imaging data) more reliable multiple imaging information can be obtained and the reconstruction can be improved to accuracies greater than what is currently possible with weak and strong lensing techniques.

  11. Strong and Weak Lensing United II: the Cluster Mass Distribution of the Most X-ray Luminous Cluster RX J1347.5-1145

    Energy Technology Data Exchange (ETDEWEB)

    Bradac, M.


    We have shown that the cluster-mass reconstruction method which combines strong and weak gravitational lensing data, developed in the first paper in the series, successfully reconstructs the mass distribution of a simulated cluster. In this paper we apply the method to the ground-based high-quality multi-colour data of RX J1347.5-1145, the most X-ray luminous cluster to date. A new analysis of the cluster core on very deep, multi-colour data analysis of VLT/FORS data reveals many more arc candidates than previously known for this cluster. The combined strong and weak lensing reconstruction confirms that the cluster is indeed very massive. If the redshift and identification of the multiple-image system as well as the redshift estimates of the source galaxies used for weak lensing are correct, we determine the enclosed cluster mass in a cylinder to M(< 360h{sup -1}kpc) = (1.2 {+-} 0.3) x 10{sup 15}M{circle_dot}. In addition the reconstructed mass distribution follows the distribution found with independent methods (X-ray measurements, SZ). With higher resolution (e.g. HST imaging data) more reliable multiple imaging information can be obtained and the reconstruction can be improved to accuracies greater than what is currently possible with weak and strong lensing techniques.

  12. Dumbbells of five-connected Ge atoms and superconductivity in CaGe3. (United States)

    Schnelle, Walter; Ormeci, Alim; Wosylus, Aron; Meier, Katrin; Grin, Yuri; Schwarz, Ulrich


    CaGe(3) has been synthesized at high-pressure, high-temperature conditions. The atomic pattern comprises intricate germanium layers of condensed moleculelike dimers. Below T(c) = 6.8 K, type II superconductivity with moderately strong electron-phonon coupling is observed.

  13. A Mouse Monoclonal Antibody against Dengue Virus Type 1 Mochizuki Strain Targeting Envelope Protein Domain II and Displaying Strongly Neutralizing but Not Enhancing Activity (United States)

    Kotaki, Tomohiro; Konishi, Eiji


    Dengue fever and its more severe form, dengue hemorrhagic fever, are major global concerns. Infection-enhancing antibodies are major factors hypothetically contributing to increased disease severity. In this study, we generated 26 monoclonal antibodies (MAbs) against the dengue virus type 1 Mochizuki strain. We selected this strain because a relatively large number of unique and rare amino acids were found on its envelope protein. Although most MAbs showing neutralizing activities exhibited enhancing activities at subneutralizing doses, one MAb (D1-IV-7F4 [7F4]) displayed neutralizing activities without showing enhancing activities at lower concentrations. In contrast, another MAb (D1-V-3H12 [3H12]) exhibited only enhancing activities, which were suppressed by pretreatment of cells with anti-FcγRIIa. Although antibody engineering revealed that antibody subclass significantly affected 7F4 (IgG3) and 3H12 (IgG1) activities, neutralizing/enhancing activities were also dependent on the epitope targeted by the antibody. 7F4 recognized an epitope on the envelope protein containing E118 (domain II) and had a neutralizing activity 10- to 1,000-fold stronger than the neutralizing activity of previously reported human or humanized neutralizing MAbs targeting domain I and/or domain II. An epitope-blocking enzyme-linked immunosorbent assay (ELISA) indicated that a dengue virus-immune population possessed antibodies sharing an epitope with 7F4. Our results demonstrating induction of these antibody species (7F4 and 3H12) in Mochizuki-immunized mice may have implications for dengue vaccine strategies designed to minimize induction of enhancing antibodies in vaccinated humans. PMID:24049185

  14. Influence of Ca/Mg ratio on phytoextraction properties of Salix viminalis. II. Secretion of low molecular weight organic acids to the rhizosphere. (United States)

    Magdziak, Z; Kozlowska, M; Kaczmarek, Z; Mleczek, M; Chadzinikolau, T; Drzewiecka, K; Golinski, P


    A hydroponic experiment in a phytotron was performed to investigate the effect of two different Ca/Mg ratios (4:1 and 1:10) and trace element ions (Cd, Cu, Pb and Zn) in solution on the efficiency of low molecular weight organic acid (LMWOA) formation in Salix viminalis rhizosphere. Depending on the Ca/Mg ratio and presence of selected trace elements at 0.5mM concentration, the amount and kind of LMWOAs in the rhizosphere were significantly affected. In physiological 4:1 Ca/Mg ratio the following complex of acids was observed: malonic (Pb, Zn), citric, lactic, maleic and succinic (Zn) acids. Under 1:10 Ca/Mg ratio, citric (Cd, Zn), maleic and succinic (Cd, Cu, Pb, Zn) acids were seen. Additionally, high accumulation of zinc and copper in all systems was observed, with the exception of those where one of the metals was at higher concentration. Summing up, the results indicate a significant role of LMWOAs in Salix phytoremediation abilities. Both effects can be modulated depending on the mutual Ca/Mg ratio. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Ruthenium(II) Complexes with 2-Phenylimidazo[4,5-f][1,10]phenanthroline Derivatives that Strongly Combat Cisplatin-Resistant Tumor Cells (United States)

    Zeng, Leli; Chen, Yu; Liu, Jiangping; Huang, Huaiyi; Guan, Ruilin; Ji, Liangnian; Chao, Hui


    Cisplatin was the first metal-based therapeutic agent approved for the treatment of human cancers, but its clinical activity is greatly limited by tumor drug resistance. This work utilized the parent complex [Ru(phen)2(PIP)]2+ (1) to develop three Ru(II) complexes (2-4) with different positional modifications. These compounds exhibited similar or superior cytotoxicities compared to cisplatin in HeLa, A549 and multidrug-resistant (A549R) tumor cell lines. Complex 4, the most potent member of the series, was highly active against A549R cancer cells (IC50 = 0.8 μM). This complex exhibited 178-fold better activity than cisplatin (IC50 = 142.5 μM) in A549R cells. 3D multicellular A549R tumor spheroids were also used to confirm the high proliferative and cytotoxic activity of complex 4. Complex 4 had the greatest cellular uptake and had a tendency to accumulate in the mitochondria of A549R cells. Further mechanistic studies showed that complex 4 induced A549R cell apoptosis via inhibition of thioredoxin reductase (TrxR), elevated intracellular ROS levels, mitochondrial dysfunction and cell cycle arrest, making it an outstanding candidate for overcoming cisplatin resistance.

  16. Lunar highland rocks - Element partitioning among minerals. II - Electron microprobe analyses of Al, P, Ca, Ti, Cr, Mn and Fe in olivine (United States)

    Smith, J. V.; Hansen, E. C.; Steele, I. M.


    Lunar olivines from anorthosites, granulitic impactites, and rocks in the Mg-rich plutonic trend were subjected to electron probe measurements for Al, P, Ca, Ti, Cr and Mn, which show that the FeO/MnO ratio for lunar olivines lies between 80 and 110 with little difference among the rock types. The low values of Ca in lunar olivines indicate slow cooling to subsolidus temperatures, with blocking temperatures of about 750 C for 67667 and 1000 C for 60255,73-alpha determined by the Finnerty and Boyd (1978) experiments. An important paradox is noted in the low Ti content of Fe-rich olivines from anorthosites, although both Ti and Fe tend to become enriched in liquid during fractional distillation. Except for Ca and Mn, olivine from anorthosites has lower minor element values than other rock types. Formation from a chemically distinct system is therefore implied.

  17. Sarcoplasmic reticulum Ca2+ uptake rate and endogenous content in MHC I and MHC II fibres of human skeletal muscle following prolonged exercise in highly trained

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Nielsen, Jens Steen

    no differences in eSR content between the fibre types before exercise and no change with exhaustive exercise. The loading time was 17% slower in MHC II fibres (13.4 ± 0.2 vs 15.7 ± 0.2 sec, MHCI and MHCII respectively). However, the maximum loading capacity was higher in MHC II fibres. Following exercise the SR...

  18. Some thiazine dyes as redox indicators in the estimations of U(VI), Mo(VI), V(V), Cr(VI) and Cu(II) with Fe(II) in strong phosphoric acid medium

    International Nuclear Information System (INIS)

    Krishna Murty, N.; Satyanarayana, V.


    U(VI) and Mo(VI) in 11.5-12.5M, Cr(VI) in 8.5 10.3M and V(V) and V(IV) in 10.5 12.0M phosphoric acid medium can be estimated with Fe(II) visually using azure A, azure B, azure C, toluidine blue and new methylene blue. (author)

  19. The TRPC1 CA2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes (United States)

    The transient receptor potential canonical channel-1 (TRPC1) is a Ca2+ permeable channel found in key metabolic organs and tissues, including the hypothalamus, adipose tissue, and skeletal muscle, making it a likely candidate for the regulation of cellular energy metabolism. However, the exact role ...

  20. Excitonic condensation of strongly correlated electrons: the case of Pr.sub.0.5./sub. Ca.sub.0.5./sub. CoO.sub.3./sub..

    Czech Academy of Sciences Publication Activity Database

    Kuneš, Jan; Augustinský, Pavel


    Roč. 90, č. 23 (2014), "235112-1"-"235112-5" ISSN 1098-0121 R&D Projects: GA ČR GA13-25251S Institutional support: RVO:68378271 Keywords : excitonic condensation * strongly correlated electrons * cobaltites Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.736, year: 2014


    Energy Technology Data Exchange (ETDEWEB)

    Huang, Kuang-Han; Bradač, Maruša; Hoag, Austin; Cain, Benjamin; Lubin, L. M.; Knight, Robert I. [University of California Davis, 1 Shields Avenue, Davis, CA 95616 (United States); Lemaux, Brian C. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Ryan, R. E. Jr.; Brammer, Gabriel B. [Aix Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille) UMR 7326, F-13388 Marseille (France); Castellano, Marco; Amorin, Ricardo; Fontana, Adriano; Merlin, Emiliano [INAF—Osservatorio Astronomico di Roma Via Frascati 33, I-00040 Monte Porzio Catone (Italy); Schmidt, Kasper B. [Department of Physics, University of California, Santa Barbara, CA 93106 (United States); Schrabback, Tim [Argelander-Institut für Astronomie, Auf Dem Hügel 71, D-53121 Bonn (Germany); Treu, Tommaso [Department of Physics and Astronomy, UCLA, Los Angeles, CA 90095 (United States); Gonzalez, Anthony H. [Department of Astronomy, University of Florida, 211 Bryant Space Science Center, Gainesville, FL 32611 (United States); Linden, Anja von der, E-mail:, E-mail: [Department of Physics, Stanford University, 382 Via Pueblo Mall, Stanford, CA 94305 (United States)


    We study the stellar population properties of the IRAC-detected 6 ≲ z ≲ 10 galaxy candidates from the Spitzer UltRa Faint SUrvey Program. Using the Lyman Break selection technique, we find a total of 17 galaxy candidates at 6 ≲ z ≲ 10 from Hubble Space Telescope images (including the full-depth images from the Hubble Frontier Fields program for MACS 1149 and MACS 0717) that have detections at signal-to-noise ratios  ≥ 3 in at least one of the IRAC 3.6 and 4.5 μm channels. According to the best mass models available for the surveyed galaxy clusters, these IRAC-detected galaxy candidates are magnified by factors of ∼1.2–5.5. Due to the magnification of the foreground galaxy clusters, the rest-frame UV absolute magnitudes M{sub 1600} are between −21.2 and −18.9 mag, while their intrinsic stellar masses are between 2 × 10{sup 8}M{sub ⊙} and 2.9 × 10{sup 9}M{sub ⊙}. We identify two Lyα emitters in our sample from the Keck DEIMOS spectra, one at z{sub Lyα} = 6.76 (in RXJ 1347) and one at z{sub Lyα} = 6.32 (in MACS 0454). We find that 4 out of 17 z ≳ 6 galaxy candidates are favored by z ≲ 1 solutions when IRAC fluxes are included in photometric redshift fitting. We also show that IRAC [3.6]–[4.5] color, when combined with photometric redshift, can be used to identify galaxies which likely have strong nebular emission lines or obscured active galactic nucleus contributions within certain redshift windows.

  2. Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice. (United States)

    Moriguchi, Shigeki; Tanaka, Tomoya; Tagashira, Hideaki; Narahashi, Toshio; Fukunaga, Kohji


    Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice. OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0mg/kg p.o.) from 10 days after operation with or without gavestinel (10mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR). The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Sunifiram also restored hippocampal LTP injured in OBX mice without treatment with gavestinel. By contrast, sunifiram treatment did not ameliorate the depressive behaviors assessed by tail suspension task in OBX mice. Notably, sunifiram treatment restored CaMKIIα (Thr-286) autophosphorylation and GluR1 (Ser-831) phosphorylation in the hippocampal CA1 region from OBX mice to the levels of control mice. Likewise, sunifiram treatment improved PKCα (Ser-657) autophosphorylation and NR1 (Ser-896) phosphorylation to the control levels. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel. However, sunifiram treatment did not affect the phosphorylation of CaMKIV (Thr-196) and ERK. Taken together, sunifiram ameliorates OBX-induced deficits of memory-related behaviors and impaired LTP in the hippocampal CA1 region via stimulation of glycine-binding site of NMDAR. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Performance of ROMA based on Architect CA 125 II and HE4 values in Chinese women presenting with a pelvic mass: A multicenter prospective study. (United States)

    Shen, Fengxian; Lu, Shiming; Peng, Yibing; Yang, Fan; Chen, Yan; Lin, Yingying; Yang, Chen; Wu, Li; Li, Huijun; Zheng, Yijie


    We evaluated the performance of human epididymis protein 4 (HE4), cancer antigen 125(CA 125) and Risk of Ovarian Malignancy Algorithm (ROMA) in distinguishing between benign and malignant pelvic masses in Chinese women. From April to December 2012, women with a pelvic mass scheduled to have surgery were enrolled in a prospective, multi-center study conducted in 5 different regions in China. Preoperative serum concentrations of HE4 and CA 125 were examined and ROMA was calculated. A total of 684 women with a pelvic mass were included, of which 482 were diagnosed with benign conditions and 202 were diagnosed with malignant ovarian tumors. At cutoffs of 7.4% and 25.3% for ROMA, the sensitivities and specificities were 85.6% and 81.7% for all patients, 85.7% and 81.5% for premenopausal women, and 85.6% and 83.9% for postmenopausal women, respectively. The ROC-AUC of ROMA was significantly better than that of HE4 (P=0.0003) or CA 125 (P<0.0001) for all malignant diseases (including EOC, Non-EOC, LMP, metastases and other pelvic malignancy with no involvement of the ovaries) compared with benign diseases for all patients. We demonstrated the efficiency of ROMA in the distinction of ovarian cancers from benign disease in a multiple-regions Chinese population, especially in premenopausal women. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression

    Directory of Open Access Journals (Sweden)

    Hasegawa Shunsuke


    Full Text Available Abstract Background Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII in learning, memory and long-term potentiation (LTP. However, previous studies have also shown that alpha-CaMKII (+/- heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes. Results We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/- heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression. Conclusion Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects

  5. ISORROPIA II: a computationally efficient thermodynamic equilibrium model for K+─Ca²+─Mg²+─NH4+─Na+─SO4²-─NO3-─Cl-─H2O aerosols

    Directory of Open Access Journals (Sweden)

    C. Fountoukis


    Full Text Available This study presents ISORROPIA II, a thermodynamic equilibrium model for the K+–Ca2+–Mg2+–NH4+–Na+–SO42−–NO3−–Cl−–H2O aerosol system. A comprehensive evaluation of its performance is conducted against water uptake measurements for laboratory aerosol and predictions of the SCAPE2 thermodynamic module over a wide range of atmospherically relevant conditions. The two models agree well, to within 13% for aerosol water content and total PM mass, 16% for aerosol nitrate and 6% for aerosol chloride and ammonium. Largest discrepancies were found under conditions of low RH, primarily from differences in the treatment of water uptake and solid state composition. In terms of computational speed, ISORROPIA II was more than an order of magnitude faster than SCAPE2, with robust and rapid convergence under all conditions. The addition of crustal species does not slow down the thermodynamic calculations (compared to the older ISORROPIA code because of optimizations in the activity coefficient calculation algorithm. Based on its computational rigor and performance, ISORROPIA II appears to be a highly attractive alternative for use in large scale air quality and atmospheric transport models.

  6. Strong enhancement of the chemiluminescence of the Cu(II)-H2O2 system on addition of carbon nitride quantum dots, and its application to the detection of H2O2 and glucose. (United States)

    Hallaj, Tooba; Amjadi, Mohammad; Song, Zhenlun; Bagheri, Robabeh


    The authors report that carbon nitride quantum dots (CN QDs) exert a strong enhancing effect on the Cu(II)/H 2 O 2 chemiluminescent system. Chemiluminescence (CL) intensity is enhanced by CN QDs by a factor of ~75, while other carbon nanomaterials have a much weaker effect. The possible mechanism of the effect was evaluated by recording fluorescence and CL spectra and by examining the effect of various radical scavengers. Emitting species was found to be excited-state CN QDs that produce green CL peaking at 515 nm. The new CL system was applied to the sensitive detection of H 2 O 2 and glucose (via glucose oxidase-catalyzed formation of H 2 O 2 ) with detection limits (3σ) of 10 nM for H 2 O 2 and 100 nM for glucose. The probe was employed for glucose determination in human plasma samples with satisfactory results. Graphical abstract The effect of carbon nitride quantum dots (CN QDs) on Cu(II)-H 2 O 2 chemiluminescence reaction was studied and the new CL system was applied for sensitive detection of glucose based on the glucose oxidase (GOx)-catalyzed formation of H 2 O 2 .

  7. Filling the gap. Human cranial remains from Gombore II (Melka Kunture, Ethiopia; ca. 850 ka) and the origin of Homo heidelbergensis. (United States)

    Profico, Antonio; Di Vincenzo, Fabio; Gagliardi, Lorenza; Piperno, Marcello; Manzi, Giorgio


    African archaic humans dated to around 1,0 Ma share morphological affinities with Homo ergaster and appear distinct in cranio-dental morphology from those of the Middle Pleistocene that are referred to Homo heidelbergensis. This observation suggests a taxonomic and phylogenetic discontinuity in Africa that ranges across the Matuyama/Brunhes reversal (780 ka). Yet, the fossil record between roughly 900 and 600 ka is notoriously poor. In this context, the Early Stone Age site of Gombore II, in the Melka Kunture formation (Upper Awash, Ethiopia), provides a privileged case-study. In the Acheulean layer of Gombore II, somewhat more recent than 875 ±10 ka, two large cranial fragments were discovered in 1973 and 1975 respectively: a partial left parietal (Melka Kunture 1) and a right portion of the frontal bone (Melka Kunture 2), which probably belonged to the same cranium. We present here the first detailed description and computer-assisted reconstruction of the morphology of the cranial vault pertaining to these fossil fragments. Our analysis suggest that the human fossil specimen from Gombore II fills a phenetic gap between Homo ergaster and Homo heidelbergensis. This appears in agreement with the chronology of such a partial cranial vault, which therefore represents at present one of the best available candidates (if any) for the origin of Homo heidelbergensis in Africa.

  8. Effect of hydrogen on the behavior of metals II - Hydrogen embrittlement of titanium alloy TV13CA - effect of oxygen - comparison with non-alloyed titanium

    International Nuclear Information System (INIS)

    Arditty, Jean-Pierre


    The effect of oxygen on the hydrogen embrittlement of non-alloyed titanium and the metastable β titanium alloy, TV13 CA, was studied during dynamic mechanical tests, the concentrations considered varying from 1000 to 5000 ppm (oxygen) and from 0 to 5000 ppm (hydrogen) respectively. TV13 CA alloy has a very high solubility for hydrogen. The establishment of a temperature range and a rate of deformation region in which the embrittlement of the alloy is maximum leads to the conclusion that an embrittlement mechanism occurs involving the dragging and accumulation of hydrogen by dislocations. This is the case for all annealings effected in the medium temperature range, which, by favoring the re-establishment of the stable two-phase α + β state of the alloy, produce hardening. The same is true for oxygen which, in addition to hardening the alloy by the solid solution effect, tends to increase its instability and, in consequence, favors the decomposition of the β phase. Nevertheless oxygen concentrations of up to 1500 ppm contribute to increasing the mechanical resistance without catastrophically reducing the deformation capacity. In the case of non-alloyed titanium, the hardening effect also leads to an increase in E 0.2p c and R, and to a reduction in the deformation capacity. Nevertheless, hydrogen is only very slightly soluble at room temperature and a distribution of the hydride phase linked to the thermal history of the sample predominates. Thus a fine acicular structure obtained from the β phase by quenching, enables an alloy having a good mechanical resistance to be conserved even when large quantities of hydrogen are present; the deformation capacity remains small. On the other hand, when the hydride phase separates the metallic phase into large grains, a very small elongation leads to a breakdown in mechanical resistance. (author) [fr

  9. Role of Synthesis Method on Luminescence Properties of Europium(II, III) Ions in β-Ca2SiO4: Probing Local Site and Structure. (United States)

    Mani, Rajaboopathi; Jiang, Huaidong; Gupta, Santosh Kumar; Li, Ziqing; Duan, Xiulan


    The europium ion probes the symmetry disorder in the crystal structure, although the distortion due to charge compensation in the case of aliovalent dopant remains interesting, especially preparation involves low and high temperatures. This work studies the preparation of the β-Ca 2 SiO 4 (from here on C 2 S) particle from Pechini (C 2 SP) and hydrothermal (C 2 SH) methods, and its luminescence variance upon doping with Eu 2+ and Eu 3+ ions. The blue shift of the charge-transfer band (CTB) in the excitation spectra indicates a larger Eu 3+ -O 2- distance in Eu 3+ doped C 2 SH. The changes in vibrational frequencies due to stretching and bending vibrations in the FTIR and the Raman spectra and binding energy shift in the XPS analysis confirmed the distorted SiO 4 4- tetrahedra in C 2 SH. The high hydrothermal temperature and pressure produce distortion, which leads to symmetry lowering although doping of aliovalent ion may slightly change the position of the Ca atoms. The increasing asymmetry ratio value from C 2 SP to C 2 SH clearly indicates that the europium ion stabilized in a more distorted geometry. It is also supported by Judd-Ofelt analysis. The concentration quenching and site-occupancy of Eu 3+ ions in two nonequivalent sites of C 2 S were discussed. The charge state and concentration of europium ions in C 2 SP and C 2 SH were determined using X-ray photoelectron spectroscopy measurements. The C 2 S particles were studied by X-ray powder diffraction, FTIR, Raman, BET surface area, TGA/DTA, electron microscopy, XPS, and luminescence spectroscopy. The impact of citrate ion on the morphology and particle size of C 2 SH has been hypothesized on the basis of the microscopy images. This study provides insights that are needed for further understanding the structure of C 2 S and thereby improves the applications in optical and biomedical areas and cement hydration.


    Directory of Open Access Journals (Sweden)

    Natalia BURLACU


    Full Text Available În procesul de elaborare a unui sistem de management al activității antreprenoriale în sfera serviciilor este necesar de a fi luate în considerare caracteristicile social-psihologice ale antreprenoriatului, care țin de specificul evoluției istorice a țării, tradițiile naționale, caracteristicile economiei naționale la etapa actuală, de politica și de cultura societății. O astfel de abordare ar putea adapta instrumentele managementului la specificul schimbărilor de ordin regional sau industrial. Activitatea de antreprenoriat în sectorul serviciilor va permite asigurarea cu locuri de muncă a unei mari părți a populației, întrucât dispune de o capacitate mare de absorbție a muncii.ENTREPRENEURSHIP SERVICES AS A FACTOR OF ECONOMIC GROWTH UNDER MARKET CONDITIONSIn the process of the services area entrepreneurial activity management system development it is necessary to take into consideration the socio-psychological characteristics of entrepreneurship, which are close related to the specificity of the historical country evolution, the national traditions, the main characteristics and the current economic situation, as well as the politics and cultural aspects of the Moldavian society. Such an approach could be realized by the means of management tools, accorded to the specific regional or industrial changes. Entrepreneurship in the service sector will create jobs for a large proportion of the population, as it has a high capacity of work absorption.

  11. Determination of activities of human carbonic anhydrase II inhibitors ...

    African Journals Online (AJOL)

    Purpose: To evaluate the activities of new curcumin analogs as carbonic anhydrase II (CA-II) inhibitor. Methods: Carbonic anhydrase II (CA-II) inhibition was determined by each ligand capability to inhibit the esterase activity of CA-II using 4-NPA as a substrate in 96-well plates. Dimethyl sulfoxide was used to dissolve each ...

  12. CaMKII in the Cardiovascular System: Sensing Redox States (United States)

    Erickson, Jeffrey R.; He, B. Julie; Grumbach, Isabella M.; Anderson, Mark E


    The multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease. CaMKII is a multimeric serine-threonine kinase that is initially activated by binding calcified calmodulin (Ca2+/CaM). Under conditions of sustained exposure to elevated Ca2+/CaM CaMKII transitions into a Ca2+/CaM-autonomous enzyme by two distinct but parallel processes. Autophosphorylation of threonine 287 in the CaMKII regulatory domain ‘traps’ CaMKII into an open configuration even after Ca2+/CaM unbinding. More recently, our group identified a pair of methionines (281/282) in the CaMKII regulatory domain that undergo a partially reversible oxidation which, like autophosphorylation, prevents CaMKII from inactivating after Ca2+/CaM unbinding. Here we review roles of CaMKII in cardiovascular disease with an eye to understanding how CaMKII may act as a transduction signal to connect pro-oxidant conditions into specific downstream pathological effects that are relevant to rare and common forms of cardiovascular disease. PMID:21742790

  13. Investigation of a Ca2+ channel α2δ ligand for the treatment of interstitial cystitis: results of a randomized, double-blind, placebo controlled phase II trial. (United States)

    Nickel, J Curtis; Crossland, Anna; Davis, Edward; Haab, François; Mills, Ian W; Rovner, Eric; Scholfield, David; Crook, Tim


    We investigated PD-0299685, a Ca(2+) channel α2δ ligand, for interstitial cystitis pain in a randomized, double-blind, placebo controlled phase IIa study. Patients with interstitial cystitis/bladder pain syndrome received 30 or 60 mg PD-0299685 daily or placebo for 12 weeks. Primary end points were change in average daily worst pain severity score (on an 11-point numerical rating scale) and change in Interstitial Cystitis Symptom Index score from baseline to week 12. Secondary end points included global response assessment, micturition and urgency episode frequency per 24 hours and mean voided volume per micturition. Incidence of adverse events was also assessed. Of 161 patients 54 received 30 mg PD-0299685 daily, 55 received 60 mg PD-0299685 daily and 52 received placebo. At week 12 the 60 mg dose produced a clinically significant reduction in daily worst pain severity score from baseline compared to placebo (treatment difference [90% CI] -0.82 [-1.72, 0.08]). A greater proportion of patients taking 60 mg PD-0299685 daily demonstrated improvement in global response assessment. PD-0299685 had no clinically significant effect on the Interstitial Cystitis Symptom Index score or urinary end points. More patients discontinued due to treatment related adverse events with 30 or 60 mg PD-0299685 daily than with the placebo. PD-0299685 failed to demonstrate positive proof of concept for the treatment of pain and other urinary end points associated with interstitial cystitis/bladder pain syndrome. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Autonomous CaMKII Mediates Both LTP and LTD Using a Mechanism for Differential Substrate Site Selection

    Directory of Open Access Journals (Sweden)

    Steven J. Coultrap


    Full Text Available Traditionally, hippocampal long-term potentiation (LTP of synaptic strength requires Ca2+/calmodulin (CaM-dependent protein kinase II (CaMKII and other kinases, whereas long-term depression (LTD requires phosphatases. Here, we found that LTD also requires CaMKII and its phospho-T286-induced “autonomous” (Ca2+-independent activity. However, whereas LTP is known to induce phosphorylation of the AMPA-type glutamate receptor (AMPAR subunit GluA1 at S831, LTD instead induced CaMKII-mediated phosphorylation at S567, a site known to reduce synaptic GluA1 localization. GluA1 S831 phosphorylation by “autonomous” CaMKII was further stimulated by Ca2+/CaM, as expected for traditional substrates. By contrast, GluA1 S567 represents a distinct substrate class that is unaffected by such stimulation. This differential regulation caused GluA1 S831 to be favored by LTP-type stimuli (strong but brief, whereas GluA1 S567 was favored by LTD-type stimuli (weak but prolonged. Thus, requirement of autonomous CaMKII in opposing forms of plasticity involves distinct substrate classes that are differentially regulated to enable stimulus-dependent substrate-site preference.

  15. Isotopic abundance measurements of K and Ca using a wide-dispersion multi-collector mass spectrometer and low-fractionation ionisation techniques (United States)

    Fletcher, I. R.; Maggi, A. L.; Rosman, K. J. R.; McNaughton, N. J.


    Procedures have been established for routine high-precision isotopic analyses of all aspects of the K-Ca isotopic system, for virtually any natural sample, using a set of 40K + 43Ca + 46Ca spikes and a VG354 (Multi-II) mass spectrometer. Loading samples as KI and CaI2 on triple (or double) filament arrays results in reduced mass fractionation, approximately as expected from Rayleigh distillation theory. For K, this improves the fractionation (or 41K anomaly) detection limit to ~0.8[per mille sign]/amu for single analyses. For Ca, the reduced fractionation renders data insensitive to the choice of fractionation law used for internal corrections. The 2[sigma] reproducibility of normalised 40Ca/44Ca data (expressed as [epsilon]Ca) is ~4, approximately twice the theoretical limits, but for measurements of natural fractionation ([delta]44/42Ca) it is ~0.4[per mille sign], about five times theoretical. These measurement procedures yield an atomic weight for the Ca standard which is consistent with the IUPAC value, and provide strong support for a reduced uncertainty (by a factor of two). A value of 40.078 ± 0.002 would include all known isotopic fractionations in natural and commercial materials. Analyses of four Nerita marine mollusc samples from a wide geographic (and water temperature) range failed to detect any thermally controlled Ca isotope fractionation ([delta]44/42Ca) corresponding to the observed [delta]18O variations.

  16. Strong Bisimilarity of Simple Process Algebras

    DEFF Research Database (Denmark)

    Srba, Jirí


    We study bisimilarity and regularity problems of simple process algebras. In particular, we show PSPACE-hardness of the following problems: (i) strong bisimilarity of Basic Parallel Processes (BPP), (ii) strong bisimilarity of Basic Process Algebra (BPA), (iii) strong regularity of BPP, and (iv) ...

  17. Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors. (United States)

    Angapelly, Srinivas; Ramya, P V Sri; Angeli, Andrea; Del Prete, Sonia; Capasso, Clemente; Arifuddin, Mohammed; Supuran, Claudiu T


    A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (K I s in the range of 0.50-50.5nM), hCA IX (K I s of 1.8-228.5nM), and hCA XII (K I s of 3.5-96.2nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure-activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. El sitio Bajo del Coypar II: Las evidencias más tempranas (CA. 1000 AP del proceso agropastoril en la Puna Meridional Argentina (Antofagasta de la Sierra, Catamarca

    Directory of Open Access Journals (Sweden)

    Silvina Vigliani


    Full Text Available El sitio Bajo del Coypar II (BC II es un conjunto de estructuras de pequeñas dimensiones ubicado sobre una saliente de la ladera de los cerros del Coypar, frente y alrededor del cual se distribuye una gran superficie de campos de cultivo prehispánicos, (Bajo del Coypar I de aproximadamente 1000 ha. En un trabajo anterior se postuló que este amplio sistema de producción agrícola se originó hacia el final del proceso regional tardío (ca. 1300 AP en asociación con el crecimiento del principal centro habitacional de la región, La Alumbrera (Olivera, 1994 y que luego fue apropiado y ampliado por el Incario. En el presente trabajo se plantean tres objetivos generales: conocer el tipo de actividades que se realizaban en el conjunto de estructuras de BC II, establecer la asociación que había entre este conjunto de estructuras y el sistema de producción agrícola e identificar posibles cambios en el uso del espacio a lo largo del tiempo. En un principio se pensó que Bajo del Coypar II formaba parte de la ampliación del espacio productivo implementada por el Imperio Incaico. Las investigaciones llevadas a cabo en el mismo permitieron determinar que efectivamente hacia las etapas más tardías y en asociación con el Incario había una estrecha relación con el sector agrícola, evidenciado en una alta frecuencia de vasijas para el almacenaje y/o el procesamiento de sustancias secas. Sin embargo, también revelaron ocupaciones más tempranas vinculadas a grupos o unidades domésticas con un desarrollo creciente de las prácticas agrícolas. De este modo, la actividad agro-pastoril fue, en este sector de la Puna meridional, mucho más temprana de lo que pensábamos.

  19. <strong>Neuroeconomics and Health Economicsstrong>/>

    DEFF Research Database (Denmark)

    Larsen, Torben


    activation of Amygdala - a key center in our emotional arousal (limbic system) - as shaped in the elder stone-age with many acute threats. II. In general, the Hawthorne-effect of management is explained as the result of supportive job-relations reinforcing the homeostatic properties of the limbic system...... with de-stressing benefits as reduced anxiety, less use of stimulants and a reduction of blood pressure which in all increase life-expectancy. Conclusion: Neuroeconomics helps economists to identify dominant health economic interventions that may be overlooked by traditional discipålines   [i] This part...

  20. <strong>Neuroeconomics and behavioral health economicsstrong>/>

    DEFF Research Database (Denmark)

    Larsen, Torben


    dissemination of relaxation procedures is evident in industrialized countries since about 1970 both inside the medical healthcare system and as NGO-settings in a market-alike competition. However, a serious barrier to the dissemination of meditative de-stressing is the lack of general knowledge of the action...... for explanation of the neural dynamics of normal decision making. Secondly, the literature is reviewed for evidence on hypothesized applications of NeM in behavioral health. Results I. The present bias as documented by neuroeconomic game-trials is explained by NeM as rooted in the basal activation of Amygdala...... - a key center in our emotional arousal (limbic system) - as shaped in the elder stone-age with many acute threats. II. In general, the Hawthorne-effect of human-relations management is explained as the result of supportive job-relations relaxing Amygdala for better emotional integration...

  1. <strong>Neuroeconomics and behavioral health economicsstrong>/>

    DEFF Research Database (Denmark)

    Larsen, Torben


    - a key center in our emotional arousal (limbic system) - as shaped in the elder stone-age with many acute threats. II. In general, the Hawthorne-effect of human-relations management is explained as the result of supportive job-relations relaxing Amygdala for better emotional integration...... some are rooted in the religious tradition while other aim to be post-religious. Medical meditation across settings combines savings on health care costs with de-stressing benefits as reduced anxiety, less use of stimulants and a reduction of blood pressure which in all increase life...... is met by a meso-strategy aiming the formation of an international, multidisciplinary network which might organize regional workshops for representatives for all involved parties in order to prepare local implementation projects.   Regarding de-stressing by medical meditation a relatively fast...

  2. Sensing mechanisms involved in Ca2+ and Mg2+ homeostasis

    NARCIS (Netherlands)

    Ferre, S.; Hoenderop, J.G.J.; Bindels, R.J.M.


    Calcium (Ca(2+)) and magnesium (Mg(2+)) ions are involved in many vital physiological functions. In the human body, Ca(2+) and Mg(2+) homeostatic systems rely on three components: (i) tissues (re)absorbing or storing Ca(2+) and Mg(2+), mainly kidney, intestine, and bone; (ii) hormones that modulate

  3. Testing strong interaction theories

    International Nuclear Information System (INIS)

    Ellis, J.


    The author discusses possible tests of the current theories of the strong interaction, in particular, quantum chromodynamics. High energy e + e - interactions should provide an excellent means of studying the strong force. (W.D.L.)

  4. Isospin effects in {sup 40,48}Ca+{sup 40,48}Ca collisions

    Energy Technology Data Exchange (ETDEWEB)

    Henzl, V., E-mail: henzl@mit.ed [MSU-NSCL, 1 Cyclotron, East Lansing MI, 48824 (United States); Henzlova, D.; Kilburn, M. [MSU-NSCL, 1 Cyclotron, East Lansing MI, 48824 (United States); Verde, G. [INFN, Sezione di Catania. 64 Via S. Sofia, I-95123, Catania (Italy); Brown, D. [MSU-NSCL, 1 Cyclotron, East Lansing MI, 48824 (United States); Chbihi, A. [GANIL, CEA et IN2P3-CNRS, B.P. 5027, F-14076 Caen Cedex (France); Coupland, D. [MSU-NSCL, 1 Cyclotron, East Lansing MI, 48824 (United States); Elson, J. [Departments of Chemistry and Physics, Washington University, St. Louis, MO 63130 (United States); Famiano, M. [Western Michigan University, 2229 Everett Tower, Kalamazoo, MI 49008-5252 (United States); Herlitzius, C. [MSU-NSCL, 1 Cyclotron, East Lansing MI, 48824 (United States); Hudan, S. [Indiana Univ. Cyclotron Facility, 2401 Milo B. Sampson Lane, Bloomington, IN 47405-4001 (United States); Lee, J.; Lukyanov, S.; Lynch, W.; Rogers, A.; Sanetullaev, A. [MSU-NSCL, 1 Cyclotron, East Lansing MI, 48824 (United States); Sobotka, L. [Departments of Chemistry and Physics, Washington University, St. Louis, MO 63130 (United States); Souza, R.T. de [Indiana Univ. Cyclotron Facility, 2401 Milo B. Sampson Lane, Bloomington, IN 47405-4001 (United States); Sun, Z.Y.; Tsang, B. [MSU-NSCL, 1 Cyclotron, East Lansing MI, 48824 (United States)


    The isospin dependence of two proton correlations is studied in {sup 40}Ca+{sup 40}Ca and {sup 48}Ca+{sup 48}Ca collisions at E/A=80MeV. Measurements were performed with the HiRA detector array complemented by the 4pi Ball at NSCL. We observe a strong isospin dependence of the pp-correlation functions; however the emitting source radius extracted using the imaging technique yields no sensitivity to the isospin of the reaction system. We interpret this result as a consequence of smaller fraction of fast proton emission in the neutron rich {sup 48}Ca system.

  5. Isospin effects in 40,48Ca+40,48Ca collisions

    International Nuclear Information System (INIS)

    Henzl, V.; Henzlova, D.; Kilburn, M.; Verde, G.; Brown, D.; Chbihi, A.; Coupland, D.; Elson, J.; Famiano, M.; Herlitzius, C.; Hudan, S.; Lee, J.; Lukyanov, S.; Lynch, W.; Rogers, A.; Sanetullaev, A.; Sobotka, L.; Souza, R.T. de; Sun, Z.Y.; Tsang, B.


    The isospin dependence of two proton correlations is studied in 40 Ca+ 40 Ca and 48 Ca+ 48 Ca collisions at E/A=80MeV. Measurements were performed with the HiRA detector array complemented by the 4π Ball at NSCL. We observe a strong isospin dependence of the pp-correlation functions; however the emitting source radius extracted using the imaging technique yields no sensitivity to the isospin of the reaction system. We interpret this result as a consequence of smaller fraction of fast proton emission in the neutron rich 48 Ca system.

  6. Strongly correlating liquids and their isomorphs


    Pedersen, Ulf R.; Gnan, Nicoletta; Bailey, Nicholas P.; Schröder, Thomas B.; Dyre, Jeppe C.


    This paper summarizes the properties of strongly correlating liquids, i.e., liquids with strong correlations between virial and potential energy equilibrium fluctuations at constant volume. We proceed to focus on the experimental predictions for strongly correlating glass-forming liquids. These predictions include i) density scaling, ii) isochronal superposition, iii) that there is a single function from which all frequency-dependent viscoelastic response functions may be calculated, iv) that...

  7. Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. (United States)

    Temperini, Claudia; Cecchi, Alessandro; Scozzafava, Andrea; Supuran, Claudiu T


    Thiazide and high ceiling diuretics were recently shown to inhibit all mammalian isoforms of carbonic anhydrase (CA, EC with a very different profile as compared to classical inhibitors, such as acetazolamide, methazolamide, and ethoxzolamide. Some of these structurally related compounds have a very different behavior against the widespread isozyme CA II, with chlorthalidone, trichloromethiazide, and furosemide being efficient inhibitors against CA II (K(I)s of 65-138 nM), whereas indapamide is a much weaker one (K(I) of 2520 nM). Furthermore, some of these diuretics are quite efficient (low nanomolar) inhibitors of other isoforms, for example, chlorthalidone against hCA VB, VII, IX, and XIII; indapamide against CA VII, IX, XII, and XIII, trichloromethiazide against CA VII and IX, and furosemide against CA I and XIV. Examining the four X-ray crystal structures of their CA II adducts, we observed several (2-3) active site water molecules interacting with the chlorthalidone, trichloromethiazide, and furosemide scaffolds which may be responsible for this important difference of activity. Indeed, indapamide bound to CA II has no interactions with active site water molecules. Chlorthalidone bound within the CA II active site is in an enolic (lactimic) tautomeric form, with the enolic OH also participating in two strong hydrogen bonds with Asn67 and a water molecule. The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications.

  8. Strong interaction phenomenology

    International Nuclear Information System (INIS)

    Giffon, M.


    A brief review of high energy hadronic data (Part I)is followed by an introduction to the standard (Weinberg Salam Glashow) model of electroweak interactions and its extension to the hadrons (Part II). Rudiments of QCD and of the parton model area given in Part III together with a quick review of the spectroscopy of heavy flavours whereas Part IV is devoted to the introduction to deep inelastic scattering and to the so-called EMC effects. (author)

  9. Autoantibodies Against Carbonic Anhydrase I and II in Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ahmet Menteşe


    Full Text Available Objective: Cancer, one of the principal causes of death, is a global social health problem. Autoantibodies developed against the organism’s self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA I and II autoantibodies have been shown in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been explained. The aim of this study was to evaluate CA I and II autoantibodies in patients with acute myeloid leukemia (AML and to provide a novel perspective regarding the autoimmune basis of the disease. Materials and Methods: Anti-CA I and II antibody levels were investigated using ELISA in serum samples from 30 patients with AML and 30 healthy peers. Results: Anti-CA I and II antibody titers in the AML group were significantly higher compared with the control group (p=0.0001 and 0.018, respectively. A strong positive correlation was also determined between titers of anti-CA I and II antibodies (r=0.613, p=0.0001. Conclusion: Our results suggest that these autoantibodies may be involved in the pathogenesis of AML. More extensive studies are now needed to reveal the entire mechanism.

  10. Treatment of Ruptured Ovarian Endometrioma with Extremely High CA 125, Moderately High CA 19-9 and CA 15-3 Level

    Directory of Open Access Journals (Sweden)

    Muzeyyen Duran


    Full Text Available In this case report, a ruptured ovarian endometrioma with a very high CA-125 level, moderately elevated CA 19-9, and CA 15-3 levels is presented. A 20 years old patient, complaining from pelvic pain, 5 cm adnexial mass was detected on left side. Biochemical examination was revealed very high CA-125 value (2556IU/ml, moderately elevated CA 19-9 (134IU/ml, and CA 15-3 (65IU/ml values. Laparoscopy was done and a ruptured ovarian endometrioma of 5 cm was seen during operation. After the total excision of the cyst, tumor markers fell rapidly. Very high CA-125 value, moderately elevated CA19-9, and CA 15-3 values can be seen in cases with ruptured endometrioma. In young patients, endometrioma must be considered firstly and laparoscopy should be applied instead of more invasive methods unless there was any finding or strong suspicion about malignancy.

  11. Application of strong phosphoric acid to radiochemistry

    International Nuclear Information System (INIS)

    Terada, Kikuo


    Not only inorganic and organic compounds but also natural substrances, such as accumulations in soil, are completely decomposed and distilled by heating with strong phosphoric acid for 30 to 50 minutes. As applications of strong phosphoric acid to radiochemistry, determination of uranium and boron by use of solubilization effect of this substance, titration of uranyl ion by use of sulfuric iron (II) contained in this substance, application to tracer experiment, and determination of radioactive ruthenium in environmental samples are reviewed. Strong phosphoric acid is also applied to activation analysis, for example, determination of N in pyrographite with iodate potassium-strong phosphoric acid method, separation of Os and Ru with sulfuric cerium (IV) - strong phosphoric acid method or potassium dechromate-strong phosphoric acid method, analysis of Se, As and Sb rocks and accumulations with ammonium bromide, sodium chloride and sodium bromide-strong phosphoric acid method. (Kanao, N.)

  12. Inhibition of endogenous heat shock protein 70 attenuates inducible nitric oxide synthase induction via disruption of heat shock protein 70/Na(+) /H(+) exchanger 1-Ca(2+) -calcium-calmodulin-dependent protein kinase II/transforming growth factor β-activated kinase 1-nuclear factor-κB signals in BV-2 microglia. (United States)

    Huang, Chao; Lu, Xu; Wang, Jia; Tong, Lijuan; Jiang, Bo; Zhang, Wei


    Inducible nitric oxide synthase (iNOS) critically contributes to inflammation and host defense. The inhibition of heat shock protein 70 (Hsp70) prevents iNOS induction in lipopolysaccharide (LPS)-stimulated macrophages. However, the role and mechanism of endogenous Hsp70 in iNOS induction in microglia remains unclear. This study addresses this issue in BV-2 microglia, showing that Hsp70 inhibition or knockdown prevents LPS-induced iNOS protein expression and nitric oxide production. Real-time PCR experiments showed that LPS-induced iNOS mRNA transcription was blocked by Hsp70 inhibition. Further studies revealed that the inhibition of Hsp70 attenuated LPS-stimulated nuclear translocation and phosphorylation of nuclear factor (NF)-κB as well as the degradation of inhibitor of κB (IκB)-α and phosphorylation of IκB kinase β (IKKβ). This prevention effect of Hsp70 inhibition on IKKβ-NF-κB activation was found to be dependent on the Ca(2+) /calcium-calmodulin-dependent protein kinase II (CaMKII)/transforming growth factor β-activated kinase 1 (TAK1) signals based on the following observations: 1) chelation of intracellular Ca(2+) or inhibition of CaMKII reduced LPS-induced increases in TAK1 phosphorylation and 2) Hsp70 inhibition reduced LPS-induced increases in CaMKII/TAK1 phosphorylation, intracellular pH value, [Ca(2+) ]i , and CaMKII/TAK1 association. Mechanistic studies showed that Hsp70 inhibition disrupted the association between Hsp70 and Na(+) /H(+) exchanger 1 (NHE1), which is an important exchanger responsible for Ca(2+) influx in LPS-stimulated cells. These studies demonstrate that the inhibition of endogenous Hsp70 attenuates the induction of iNOS, which likely occurs through the disruption of NHE1/Hsp70-Ca(2+) -CaMKII/TAK1-NF-κB signals in BV-2 microglia, providing further insight into the functions of Hsp70 in the CNS. © 2015 Wiley Periodicals, Inc.

  13. New anticancer drug candidates sulfonamides as selective hCA IX or hCA XII inhibitors. (United States)

    Gul, Halise Inci; Yamali, Cem; Sakagami, Hiroshi; Angeli, Andrea; Leitans, Janis; Kazaks, Andris; Tars, Kaspars; Ozgun, Dilan Ozmen; Supuran, Claudiu T


    In this study, new 4-[3-(aryl)-5-substitutedphenyl-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamides (19-36) were synthesized and evaluated their cytotoxic/anticancer and CA inhibitory effects. According to results obtained, the compounds 34 (4-[5-(2,3,4-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl] benzensulfonamide, Potency-Selectivity Expression (PSE) = 141) and 36 (4-[5-(3,4,5-trimethoxyphenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide, PSE = 54.5) were found the leader anticancer compounds with the highest PSE values. In CA inhibitory studies, the compounds 36 and 24 (4-[5-(3,4,5-trimethoxyphenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-yl]benzensulfonamide) were found the leader CA inhibitors depending on selectivity ratios. The compound 36 was a selective inhibitor of hCA XII isoenzyme (hCA I/hCA XII = 1250 and hCA II/hCA XII = 224) while the compound 24 was a selective inhibitor of hCA IX isoenzyme (hCA I/hCA IX = 161 and hCA II/hCA IX = 177). The compounds 24, 34, and 36 can be considered to develop new anticancer drug candidates. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. A new oxidimetric reagent: potassium dichromate in a strong phosphoric acid medium--VII. Photometric titration of vanadium(IV) and of cerium(III) alone and in mixtures with iroN(II). (United States)

    Rao, G G; Rao, P K


    Vanadium(IV) can be accurately titrated with potassium dichromate in media containing phosphoric acid of 3-12M concentration: the change in absorption of vanadium(IV) is followed in the region 660 mmicro using a red filter. It is more convenient to carry out the titration in 3M phosphoric acid because at higher concentrations chloride, nitrate, cerium(III) and manganese(II) may interfere. Photoelcetric titration is more convenient than potentiometric because the former can be made in a 3M phosphoric acid medium, whereas the latter is possible only in 12M phosphoric acid. The simultaneous differential photometric titration of iron(II) and vanadium(IV) is also possible. Conditions have been found for the photometric titration of cerium(III) and of cerium(III) plus iron(II). The titration is carried out (at 450 mmicro or with a blue filter) in about 10.5M phosphoric acid. Application of the method to a cerium mineral is considered.

  15. Impact of seawater [Ca

    NARCIS (Netherlands)

    Mewes, A.; Langer, G.; Thoms, S.; Nehrke, G.; Reichart, G.J.; de Nooijer, L.J.; Bijma, J.


    Mg / Ca ratios in foraminiferal tests are routinely used as paleotemperature proxies, but on long timescales, they also hold the potential to reconstruct past seawater Mg / Ca. The impact of both temperature and seawater Mg / Ca on Mg incorporation in Foraminifera has been quantified by a number of

  16. CA-125 blood test (United States)

    Ovarian cancer - CA-125 test ... CA-125 is a protein that is found more in ovarian cancer cells than in other cells. This ... ovarian cancer . The test is useful if the CA-125 level was high when the cancer was first ...

  17. Strongly Correlated Topological Insulators (United States)


    Strongly Correlated Topological Insulators In the past year, the grant was used for work in the field of topological phases, with emphasis on finding...surface of topological insulators. In the past 3 years, we have started a new direction, that of fractional topological insulators. These are which a topologically nontrivial quasi-flat band is fractionally filled and then subject to strong interactions. The views, opinions and/or

  18. Strong Cosmic Censorship (United States)

    Isenberg, James


    The Hawking-Penrose theorems tell us that solutions of Einstein's equations are generally singular, in the sense of the incompleteness of causal geodesics (the paths of physical observers). These singularities might be marked by the blowup of curvature and therefore crushing tidal forces, or by the breakdown of physical determinism. Penrose has conjectured (in his `Strong Cosmic Censorship Conjecture`) that it is generically unbounded curvature that causes singularities, rather than causal breakdown. The verification that ``AVTD behavior'' (marked by the domination of time derivatives over space derivatives) is generically present in a family of solutions has proven to be a useful tool for studying model versions of Strong Cosmic Censorship in that family. I discuss some of the history of Strong Cosmic Censorship, and then discuss what is known about AVTD behavior and Strong Cosmic Censorship in families of solutions defined by varying degrees of isometry, and discuss recent results which we believe will extend this knowledge and provide new support for Strong Cosmic Censorship. I also comment on some of the recent work on ``Weak Null Singularities'', and how this relates to Strong Cosmic Censorship.

  19. Electronic structures and magnetism of CaFeAsH and CaFeAsF

    International Nuclear Information System (INIS)

    Wang Guangtao; Shi Xianbiao; Liu Haipeng; Liu Qingbo


    We studied the electronic structures, magnetism, and Fermi surface (FS) nesting of CaFeAsH and CaFeAsF by first-principles calculations. In the nonmagnetic (NM) states, we found strong FS nesting, which induces magnetic instability and a spin density wave (SDW). Our calculations indicate that the ground state of CaFeAsH and CaFeAsF is the stripe antiferromagnetic state. The calculated bare susceptibility χ 0 (q) peaked at the M-point and was clearly suppressed and became slightly incommensurate with both electron doping and hole doping for both materials. (author)

  20. Ca adsorption on dickite, Sericite and quartz. Dickite, sericite oyobi sekiei ni taisuru Ca no kyuchaku

    Energy Technology Data Exchange (ETDEWEB)

    Matsuoka, Isao; Nozawa, Miki (Tohoku Univ., Sendai, (Japan). Faculty of Engineering)


    Ca adsorbing characteristics of dickite were studied to clarify the possibility of clay minerals on selective Ca activation. Ca adsorption on hydrogenated dickite was compared with those of Na {sup +} and K {sup +} and further, the comparison was made for adsorption of Ca and these ikns on quartz and hydrogenated sericite. Ca adsorption on quartz which is thought to be caused by the negative charge of broken bond, depends strongly on pH and for pH of 7 or more, Ca acts strongly on any quartz surface. Moreover, when Na {sup +} or K {sup +} coexists, the effect of coexisting ion on Ca adsorption does not result any difference. On the contrary, Ca adsorption on sericite is mainly caused by the exchanging adsorption with H {sup +} and Ca saturated adsortion does not depend on pH in the range of 4-10pH. But Na {sup +} adsorption does not reach the saturation for lower pH unless Na {sup +} of sufficient concentration exists. 13 refs., 16 figs.

  1. Inhibition of PaCaMKII-E isoform in the dorsal unpaired median neurosecretory cells of cockroach reduces nicotine- and clothianidin-induced currents. (United States)

    List, Olivier; Calas-List, Delphine; Taillebois, Emiliane; Juchaux, Marjorie; Heuland, Emilie; Thany, Steeve H


    Cellular responses to Ca(2+) require intermediary proteins such as calcium/calmodulin-dependent protein kinase II (CaMKII), which transduces the signal into downstream effects. We recently demonstrated that the cockroach genome encodes five different CaMKII isoforms, and only PaCaMKII-E isoform is specifically expressed in the dorsal unpaired median neurosecretory cells. In the present study, using antisense oligonucleotides, we demonstrated that PaCaMKII-E isoform inhibition reduced nicotine-induced currents through α-bungarotoxin-sensitive and -insensitive nicotinic acetylcholine receptor subtypes. Specifically, PaCaMKII-E isoform is sufficient to repress nicotinic current amplitudes as a result of its depression by antisense oligonucleotides. Similar results were found using the neonicotinoid insecticide clothianidin, which acted as a full agonist of dorsal unpaired median neuron nicotinic acetylcholine receptors. Clothianidin current amplitudes are strongly reduced under bath application of PaCaMKII-E antisense oligonucleotides but no significant results are found with α-bungarotoxin co-applied, demonstrating that CaMKII-E isoform affects nicotine currents through α-bungarotoxin-sensitive and -insensitive receptor subtypes whereas clothianidin currents are reduced via α-bungarotoxin-insensitive receptors. In addition, we found that intracellular calcium increase induced by nicotine and clothianidin were reduced by PaCaMKII-E antisense oligonucleotides, demonstrating that intracellular calcium increase induced by nicotine and clothianidin are affected by PaCaMKII-E inhibition. Cellular responses to Ca(2+) require intermediary proteins such as calcium/calmodulin-dependent protein kinase II (CaMKII). We recently demonstrated that the cockroach genome encodes five different CaMKII isoforms and only PaCaMKII-E isoform was specifically expressed in the dorsal unpaired median neurosecretory cells. Here we show that specific inhibition of PaCaMKII-E isoform is

  2. Strong Arcwise Connectedness


    Espinoza, Benjamin; Gartside, Paul; Kovan-Bakan, Merve; Mamatelashvili, Ana


    A space is `n-strong arc connected' (n-sac) if for any n points in the space there is an arc in the space visiting them in order. A space is omega-strong arc connected (omega-sac) if it is n-sac for all n. We study these properties in finite graphs, regular continua, and rational continua. There are no 4-sac graphs, but there are 3-sac graphs and graphs which are 2-sac but not 3-sac. For every n there is an n-sac regular continuum, but no regular continuum is omega-sac. There is an omega-sac ...

  3. Abortion: Strong's counterexamples fail

    DEFF Research Database (Denmark)

    Di Nucci, Ezio


    This paper shows that the counterexamples proposed by Strong in 2008 in the Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's basic idea is that there are cases--for example, terminally ill patients--where killing an adult human being is prima facie seriously morally......'s scenarios have some valuable future or admitted that killing them is not seriously morally wrong. Finally, if "valuable future" is interpreted as referring to objective standards, one ends up with implausible and unpalatable moral claims....

  4. A strong comeback

    International Nuclear Information System (INIS)

    Marier, D.


    This article presents the results of a financial rankings survey which show a strong economic activity in the independent energy industry. The topics of the article include advisor turnover, overseas banks, and the increase in public offerings. The article identifies the top project finance investors for new projects and restructurings and rankings for lenders

  5. Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task. (United States)

    Martig, Adria K; Mizumori, Sheri J Y


    Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicate DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N = 9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N = 167) and CA3 (N = 94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps by maintaining place field stability selectively in CA1/CA2. Copyright © 2009 Wiley-Liss, Inc.

  6. Synthesis of a ruthenium(II) bipyridyl complex coordinated by a functionalized Schiff base ligand: characterization, spectroscopic and isothermal titration calorimetry measurements of M2+ binding and sensing (M2+=Ca2+, Mg2+). (United States)

    Dixit, Namrata; Mishra, Lallan; Mustafi, Sourajit M; Chary, Kandala V R; Houjou, Hirohiko


    Bis-[methylsalicylidine-4'benzoic acid]-ethylene (LH2) complexed with cis-Ru(bpy)2Cl(2).2H2O provides a complex of composition [Ru(bpy)2L].2NH4PF6 (1), which has been characterized spectroscopically. Its binding behaviour towards Mg2+ and Ca2+ ions is monitored using 1H NMR titration, isothermal titration calorimetry (ITC) and luminescence microscopy. The luminescent ruthenium complex binds Ca2+ in a more selective manner as compared to Mg2+.

  7. Role of Ca++ in Shoot Gravitropism. [avena (United States)

    Rayle, D. L.


    A cornerstone in the argument that Ca(2+) levels may regulate growth is the finding the EGTA promotes straight growth. The usual explanation for these results is that Ca(2+) chelation from cell walls results in wall loosening and thus accelerated straight growth. The ability of frozen-thawed Avena coleoptile tissue (subjected to 15g tension) to extend in response to EGTA and Quin II was examined. The EGTA when applied in weakly buffered (i.e., 0.1mM) neutral solutions initiates rapid extension. When the buffer strength is increased, similar concentrations of EGTA produce no growth response. This implies when EGTA liberated protons are released upon Ca(2+) chelation they can either initiate acid growth (low buffer conditions) or if consumed (high buffer conditions) have no effect. Thus Ca(2+) chelation in itself apparently does not result in straight growth.

  8. Sequestration of chelated copper by structural Fe(II): Reductive decomplexation and transformation of Cu{sup II}-EDTA

    Energy Technology Data Exchange (ETDEWEB)

    He, Hongping [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Wu, Deli, E-mail: [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Zhao, Linghui [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China); Luo, Cong [School of Civil and Environmental Engineering, Georgia Institute of Technology, GA 30332 (United States); Dai, Chaomeng; Zhang, Yalei [State Key Laboratory of Pollution Control and Resources Reuse, School of Environmental Science & Engineering, Tongji University, Shanghai 200092 (China)


    Highlights: • Structural Fe(II) was found to reveal high sequestration potential in various chelated copper. • Chelated copper was reduced to Cu(0) and Cu{sub 2}O by =Fe(II), whcih was oxidized to Fe{sub 2}O{sub 3}·H{sub 2}O. • Both electron transfer and surface =Fe(II) were found to be crucial during chelated copper reduction. • The indispensible role of reductive decomplexation was identified in chelated copper sequestration. - Abstract: Chelated coppers, such as Cu{sup II}-EDTA, are characteristically refractory and difficult to break down because of their high stability and solubility. Cu{sup II}–EDTA sequestration by structural Fe(II) (=Fe(II)) was investigated intensively in this study. Up to 101.21 mgCu(II)/gFe(II) was obtained by =Fe(II) in chelated copper sequestration under near neutral pH condition (pH 7.70). The mechanism of Cu{sup II}-EDTA sequestration by =Fe(II) was concluded as follows: 3Cu{sup II}–EDTA + 7=Fe(II) + 9H{sub 2}O → Cu(0) ↓ + Cu{sub 2}O ↓ (the major product) + 2Fe{sub 2}O{sub 3}·H{sub 2}O ↓ + 3Fe{sup II}–EDTA +14H{sup +} Novel results strongly indicate that Cu{sup II} reductive transformation induced by surface =Fe(II) was mainly responsible for chelated copper sequestration. Cu(0) generation was initially facilitated, and subsequent reduction of Cu(II) into Cu(I) was closely combined with the gradual increase of ORP (Oxidation-Reduction Potential). Cu-containing products were inherently stable, but Cu{sub 2}O would be reoxidized to Cu(II) with extra-aeration, resulting in the release of copper, which was beneficial to Cu reclamation. Concentration diminution of Cu{sup II}–EDTA within the electric double layer and competitive adsorption were responsible for the negative effects of Ca{sup 2+}, Mg{sup 2+}. By generating vivianite, PO{sub 4}{sup 3−} was found to decrease surface =Fe(II) content. This study is among the first ones to identify the indispensible role of reductive decomplexation in chelated copper

  9. Defect chemistry and oxygen transport of (La0.6Sr0.4 − xMx)0.99Co0.2Fe0.8O3 − δ, M = Ca (x = 0.05, 0.1), Ba (x = 0.1, 0.2), Sr: Part II: Oxygen transport

    DEFF Research Database (Denmark)

    Dalslet, Bjarke Thomas; Søgaard, Martin; Hendriksen, Peter Vang


    , the findings on the defect chemistry were reported, while the oxygen transport properties are reported here in part II. In the investigated material series, the amount of divalent dopant has been kept constant, while Sr ions have been substituted with Ca ions (smaller ionic radius) or Ba ions (larger ionic...... radius). The size difference induces different strains into the crystal structure in each composition. The possibility of simple relationships between various crystal strain parameters and the transport properties were analyzed. Oxygen pump controlled permeation experiments and a surface sensitive...


    International Development Research Centre (IDRC) Digital Library (Canada)

    et des enfants d'Afrique. INITIATIVE CONCERTÉE. Innovation pour la santé des mères et des enfants d'Afrique. Centre de recherches pour le développement international. CP Box 8500 Ottawa ON Canada K1G 3H9. Téléphone : +1 613 236 6163 • Télécopieur : +1 613 657 7749 |

  11. Strong Electroweak Symmetry Breaking

    CERN Document Server

    Grinstein, Benjamin


    Models of spontaneous breaking of electroweak symmetry by a strong interaction do not have fine tuning/hierarchy problem. They are conceptually elegant and use the only mechanism of spontaneous breaking of a gauge symmetry that is known to occur in nature. The simplest model, minimal technicolor with extended technicolor interactions, is appealing because one can calculate by scaling up from QCD. But it is ruled out on many counts: inappropriately low quark and lepton masses (or excessive FCNC), bad electroweak data fits, light scalar and vector states, etc. However, nature may not choose the minimal model and then we are stuck: except possibly through lattice simulations, we are unable to compute and test the models. In the LHC era it therefore makes sense to abandon specific models (of strong EW breaking) and concentrate on generic features that may indicate discovery. The Technicolor Straw Man is not a model but a parametrized search strategy inspired by a remarkable generic feature of walking technicolor,...

  12. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)


    ABSTRACT. The manganese (II), cobalt (II), nickel (II) and copper (II) complexes of N, N' – bis(benzoin)ethylenediiminato have been prepared and characterized by infrared, elemental analysis, conductivity measurements and solubility. The potentiometric, and elemental analyses studies of the complexes revealed 1:1 ...

  13. CaMKII: linking heart failure and arrhythmias (United States)

    Swaminathan, Paari Dominic; Purohit, Anil; Hund, Thomas J; Anderson, Mark E


    Understanding relationships between heart failure and arrhythmias, important causes of suffering and sudden death, remains an unmet goal for biomedical researchers and physicians. Evidence assembled over the last decade supports a view that activation of the multifunctional Ca2+ and calmodulin-dependent protein kinase II (CaMKII) favors myocardial dysfunction and cell membrane electrical instability. CaMKII activation follows increases in intracellular Ca2+ or oxidation, upstream signals with the capacity to transition CaMKII into a Ca2+ and calmodulin-independeant, constitutively active enzyme. Constitutively active CaMKII appears poised to participate in disease pathways by catalyzing the phosphorylation of classes of protein targets important for excitation-contraction coupling and cell survival, including ion channels and Ca2+ homeostatic proteins, and transcription factors that drive hypertrophic and inflammatory gene expression. This rich diversity of downstream targets helps to explain the potential for CaMKII to simultaneously affect mechanical and electrical properties of heart muscle cells. Proof of concept studies from a growing number of investigators show that CaMKII inhibition is beneficial for improving myocardial performance and reducing arrhythmias. Here we review the molecular physiology of CaMKII, discuss CaMKII actions at key cellular targets and results of animal models of myocardial hypertrophy, dysfunction and arrhythmias that suggest CaMKII inhibition may benefit myocardial function while reducing arrhythmias. PMID:22679140


    Directory of Open Access Journals (Sweden)

    Shahdevi Nandar Kurniawan


    Full Text Available Ca2+ signaling functions to regulate many cellular processes. Dynamics of Ca2+ signaling or homeostasis is regulated by the interaction between ON and OFF reactions that control Ca2+ flux in both the plasma membrane and internal organelles such as the endoplasmic reticulum (ER and mitochondria. External stimuli activate the ON reactions, which include Ca2+ into the cytoplasm either through channels in the plasma membrane or from internal storage like in ER. Most of the cells utilize both channels/sources, butthere area few cells using an external or internal source to control certain processes. Most of the Ca2+ entering the cytoplasm adsorbed to the buffer, while a smaller part activate effect or to stimulate cellular processes. Reaction OFF is pumping of cytoplasmic Ca2+ using a combination mechanism of mitochondrial and others. Changes in Ca2+ signal has been detected in various tissues isolated from animals induced into diabetes as well as patients with diabetes. Ca2+ signal interference is also found in sensory neurons of experimental animals with diabetes. Ca2+ signaling is one of the main signaling systems in the cell.

  15. Plasmons in strong superconductors

    International Nuclear Information System (INIS)

    Baldo, M.; Ducoin, C.


    We present a study of the possible plasmon excitations that can occur in systems where strong superconductivity is present. In these systems the plasmon energy is comparable to or smaller than the pairing gap. As a prototype of these systems we consider the proton component of Neutron Star matter just below the crust when electron screening is not taken into account. For the realistic case we consider in detail the different aspects of the elementary excitations when the proton, electron components are considered within the Random-Phase Approximation generalized to the superfluid case, while the influence of the neutron component is considered only at qualitative level. Electron screening plays a major role in modifying the proton spectrum and spectral function. At the same time the electron plasmon is strongly modified and damped by the indirect coupling with the superfluid proton component, even at moderately low values of the gap. The excitation spectrum shows the interplay of the different components and their relevance for each excitation modes. The results are relevant for neutrino physics and thermodynamical processes in neutron stars. If electron screening is neglected, the spectral properties of the proton component show some resemblance with the physical situation in high-T c superconductors, and we briefly discuss similarities and differences in this connection. In a general prospect, the results of the study emphasize the role of Coulomb interaction in strong superconductors.

  16. Origins of mass-dependent and mass-independent Ca isotope variations in meteoritic components and meteorites (United States)

    Bermingham, K. R.; Gussone, N.; Mezger, K.; Krause, J.


    The Ca isotope composition of meteorites and their components may vary due to mass-dependent and/or -independent isotope effects. In order to evaluate the origin of these effects, five amoeboid olivine aggregates (AOAs), three calcium aluminum inclusions (CAIs), five chondrules (C), a dark inclusion from Allende (CV3), two dark fragments from North West Africa 753 (NWA 753; R3.9), and a whole rock sample of Orgueil (CI1) were analyzed. This is the first coupled mass-dependent and -independent Ca isotope dataset to include AOAs, a dark inclusion, and dark fragments. Where sample masses permit, Ca isotope data are reported with corresponding petrographic analyses and rare earth element (REE) relative abundance patterns. The CAIs and AOAs are enriched in light Ca isotopes (δ44/40Ca -5.32 to +0.72, where δ44/40Ca is reported relative to SRM 915a). Samples CAI 5 and AOA 1 have anomalous Group II REE patterns. These REE and δ44/40Ca data suggest that the CAI 5 and AOA 1 compositions were set via kinetic isotope fractionation during condensation and evaporation. The remaining samples show mass-dependent Ca isotope variations which cluster between δ44/40Ca +0.53 and +1.59, some of which are coupled with unfractionated REE abundance patterns. These meteoritic components likely formed through the coaccretion of the evaporative residue and condensate following Group II CAI formation or their chemical and isotopic signatures were decoupled (e.g., via nebular or parent-body alteration). The whole rock sample of Orgueil has a δ44/40Ca +0.67 ± 0.18 which is in agreement with most published data. Parent-body alteration, terrestrial alteration, and variable sampling of Ca-rich meteoritic components can have an effect on δ44/40Ca compositions in whole rock meteorites. Samples AOA 1, CAI 5, C 2, and C 4 display mass-independent 48/44Ca anomalies (ε48/44Ca +6 to +12) which are resolved from the standard composition. Other samples measured for these effects (AOA 5, CAI 1, CAI 2


    Energy Technology Data Exchange (ETDEWEB)

    Marinello, M. [Universidade Federal de Itajubá, Rua Doutor Pereira Cabral 1303, 37500-903, Itajubá, MG (Brazil); Rodríguez-Ardila, A.; Garcia-Rissmann, A. [Laboratório Nacional de Astrofísica, Rua Estados Unidos 154, Itajubá, MG, 37504-364 (Brazil); Sigut, T. A. A. [The University of Western Ontario, London, ON N6A 3K7 (Canada); Pradhan, A. K., E-mail: [McPherson Laboratory, The Ohio State University, 140 W. 18th Ave., Columbus, OH 43210-1173 (United States)


    We present a study of Fe ii emission in the near-infrared region (NIR) for 25 active galactic nuclei (AGNs) to obtain information about the excitation mechanisms that power it and the location where it is formed. We employ an NIR Fe ii template derived in the literature and find that it successfully reproduces the observed Fe ii spectrum. The Fe ii bump at 9200 Å detected in all objects studied confirms that Lyα fluorescence is always present in AGNs. The correlation found between the flux of the 9200 Å bump, the 1 μm lines, and the optical Fe ii implies that Lyα fluorescence plays an important role in Fe ii production. We determined that at least 18% of the optical Fe ii is due to this process, while collisional excitation dominates the production of the observed Fe ii. The line profiles of Fe ii λ10502, O i λ11287, Ca ii λ8664, and Paβ were compared to gather information about the most likely location where they are emitted. We found that Fe ii, O i and Ca ii have similar widths and are, on average, 30% narrower than Paβ. Assuming that the clouds emitting the lines are virialized, we show that the Fe ii is emitted in a region twice as far from the central source than Paβ. The distance, though, strongly varies: from 8.5 light-days for NGC 4051 to 198.2 light-days for Mrk 509. Our results reinforce the importance of the Fe ii in the NIR to constrain critical parameters that drive its physics and the underlying AGN kinematics, as well as more accurate models aimed at reproducing this complex emission.

  18. Strong-coupling approximations

    International Nuclear Information System (INIS)

    Abbott, R.B.


    Standard path-integral techniques such as instanton calculations give good answers for weak-coupling problems, but become unreliable for strong-coupling. Here we consider a method of replacing the original potential by a suitably chosen harmonic oscillator potential. Physically this is motivated by the fact that potential barriers below the level of the ground-state energy of a quantum-mechanical system have little effect. Numerically, results are good, both for quantum-mechanical problems and for massive phi 4 field theory in 1 + 1 dimensions. 9 references, 6 figures

  19. Strong interaction and QFD

    International Nuclear Information System (INIS)

    Ebata, T.


    With an assumed weak multiplet structure for bosonic hadrons, which is consistent with the ΔI = 1/2 rule, it is shown that the strong interaction effective hamiltonian is compatible with the weak SU(2) x U(1) gauge transformation. Especially the rho-meson transforms as a triplet under SU(2)sub(w), and this is the origin of the rho-photon analogy. It is also shown that the existence of the non-vanishing Cabibbo angle is a necessary condition for the absence of the exotic hadrons. (orig.)

  20. PIK3CA (United States)

    Ilic, Nina; Birsoy, Kıvanç; Aguirre, Andrew J; Kory, Nora; Pacold, Michael E; Singh, Shambhavi; Moody, Susan E; DeAngelo, Joseph D; Spardy, Nicole A; Freinkman, Elizaveta; Weir, Barbara A; Tsherniak, Aviad; Cowley, Glenn S; Root, David E; Asara, John M; Vazquez, Francisca; Widlund, Hans R; Sabatini, David M; Hahn, William C


    Oncogenic PIK3CA mutations are found in a significant fraction of human cancers, but therapeutic inhibition of PI3K has only shown limited success in clinical trials. To understand how mutant PIK3CA contributes to cancer cell proliferation, we used genome scale loss-of-function screening in a large number of genomically annotated cancer cell lines. As expected, we found that PIK3CA mutant cancer cells require PIK3CA but also require the expression of the TCA cycle enzyme 2-oxoglutarate dehydrogenase (OGDH). To understand the relationship between oncogenic PIK3CA and OGDH function, we interrogated metabolic requirements and found an increased reliance on glucose metabolism to sustain PIK3CA mutant cell proliferation. Functional metabolic studies revealed that OGDH suppression increased levels of the metabolite 2-oxoglutarate (2OG). We found that this increase in 2OG levels, either by OGDH suppression or exogenous 2OG treatment, resulted in aspartate depletion that was specifically manifested as auxotrophy within PIK3CA mutant cells. Reduced levels of aspartate deregulated the malate-aspartate shuttle, which is important for cytoplasmic NAD + regeneration that sustains rapid glucose breakdown through glycolysis. Consequently, because PIK3CA mutant cells exhibit a profound reliance on glucose metabolism, malate-aspartate shuttle deregulation leads to a specific proliferative block due to the inability to maintain NAD + /NADH homeostasis. Together these observations define a precise metabolic vulnerability imposed by a recurrently mutated oncogene.

  1. Saccharin Sulfonamides as Inhibitors of Carbonic Anhydrases I, II, VII, XII, and XIII

    Directory of Open Access Journals (Sweden)

    Vaida Morkūnaitė


    Full Text Available A series of modified saccharin sulfonamides have been designed as carbonic anhydrase (CA inhibitors and synthesized. Their binding to CA isoforms I, II, VII, XII, and XIII was measured by the fluorescent thermal shift assay (FTSA and isothermal titration calorimetry (ITC. Saccharin bound the CAs weakly, exhibiting the affinities of 1–10 mM for four CAs except CA I where binding could not be detected. Several sulfonamide-bearing saccharines exhibited strong affinities of 1–10 nM towards particular CA isoforms. The functional group binding Gibbs free energy additivity maps are presented which may provide insights into the design of compounds with increased affinity towards selected CAs.

  2. Strong Coupling Holography

    CERN Document Server

    Dvali, Gia


    We show that whenever a 4-dimensional theory with N particle species emerges as a consistent low energy description of a 3-brane embedded in an asymptotically-flat (4+d)-dimensional space, the holographic scale of high-dimensional gravity sets the strong coupling scale of the 4D theory. This connection persists in the limit in which gravity can be consistently decoupled. We demonstrate this effect for orbifold planes, as well as for the solitonic branes and string theoretic D-branes. In all cases the emergence of a 4D strong coupling scale from bulk holography is a persistent phenomenon. The effect turns out to be insensitive even to such extreme deformations of the brane action that seemingly shield 4D theory from the bulk gravity effects. A well understood example of such deformation is given by large 4D Einstein term in the 3-brane action, which is known to suppress the strength of 5D gravity at short distances and change the 5D Newton's law into the four-dimensional one. Nevertheless, we observe that the ...

  3. MicroRNA-145 suppresses ROS-induced Ca{sup 2+} overload of cardiomyocytes by targeting CaMKIIδ

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Min-Ji [Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Jang, Jin-Kyung [College of Pharmacy, Sookmyung Women’s University, 52 HyoChangWon-Gil, Yongsan-ku, Seoul 140-742 (Korea, Republic of); Ham, Onju; Song, Byeong-Wook; Lee, Se-Yeon [Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Lee, Chang Yeon; Park, Jun-Hee [Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University, 50 Yonsei-ro, Seodamun-gu, Seoul 120-759 (Korea, Republic of); Lee, Jiyun; Seo, Hyang-Hee [Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Choi, Eunhyun [Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Jeon, Woo-min [Department of Animal Resource, Sahmyook University, Seoul 139-742 (Korea, Republic of); Hwang, Hye Jin [Cardiovascular Research Institute, Yonsei University College of Medicine, 250 Seongsanno, Seodamun-gu, Seoul 120-752 (Korea, Republic of); Shin, Hyun-Taek [College of Pharmacy, Sookmyung Women’s University, 52 HyoChangWon-Gil, Yongsan-ku, Seoul 140-742 (Korea, Republic of); and others


    Highlights: •CaMKIIδ mediates H{sub 2}O{sub 2}-induced Ca{sup 2+} overload in cardiomyocytes. •miR-145 can inhibit Ca{sup 2+} overload. •A luciferase assay confirms that miR-145 functions as a CaMKIIδ-targeting miRNA. •Overexpression of miR-145 regulates CaMKIIδ-related genes and ameliorates apoptosis. -- Abstract: A change in intracellular free calcium (Ca{sup 2+}) is a common signaling mechanism of reperfusion-induced cardiomyocyte death. Calcium/calmodulin dependent protein kinase II (CaMKII) is a critical regulator of Ca{sup 2+} signaling and mediates signaling pathways responsible for functions in the heart including hypertrophy, apoptosis, arrhythmia, and heart disease. MicroRNAs (miRNA) are involved in the regulation of cell response, including survival, proliferation, apoptosis, and development. However, the roles of miRNAs in Ca{sup 2+}-mediated apoptosis of cardiomyocytes are uncertain. Here, we determined the potential role of miRNA in the regulation of CaMKII dependent apoptosis and explored its underlying mechanism. To determine the potential roles of miRNAs in H{sub 2}O{sub 2}-mediated Ca{sup 2+} overload, we selected and tested 6 putative miRNAs that targeted CaMKIIδ, and showed that miR-145 represses CaMKIIδ protein expression and Ca{sup 2+} overload. We confirmed CaMKIIδ as a direct downstream target of miR-145. Furthermore, miR-145 regulates Ca{sup 2+}-related signals and ameliorates apoptosis. This study demonstrates that miR-145 regulates reactive oxygen species (ROS)-induced Ca{sup 2+} overload in cardiomyocytes. Thus, miR-145 affects ROS-mediated gene regulation and cellular injury responses.

  4. Phosphorylation and activation of nuclear Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP-N/PPM1E) by Ca{sup 2+}/calmodulin-dependent protein kinase I (CaMKI)

    Energy Technology Data Exchange (ETDEWEB)

    Onouchi, Takashi [Department of Life Sciences, Faculty of Agriculture, Kagawa University, Miki-cho, Kagawa 761-0795 (Japan); Sueyoshi, Noriyuki, E-mail: [Department of Life Sciences, Faculty of Agriculture, Kagawa University, Miki-cho, Kagawa 761-0795 (Japan); Ishida, Atsuhiko [Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima 739-8521 (Japan); Kameshita, Isamu [Department of Life Sciences, Faculty of Agriculture, Kagawa University, Miki-cho, Kagawa 761-0795 (Japan)


    Highlights: Black-Right-Pointing-Pointer CaMKP-N/PPM1E underwent proteolytic processing and translocated to cytosol. Black-Right-Pointing-Pointer The proteolysis was effectively inhibited by the proteasome inhibitors. Black-Right-Pointing-Pointer Ser-480 of zebrafish CaMKP-N was phosphorylated by cytosolic CaMKI. Black-Right-Pointing-Pointer Phosphorylation-mimic mutants of CaMKP-N showed enhanced activity. Black-Right-Pointing-Pointer These results suggest that CaMKP-N is regulated by CaMKI. -- Abstract: Nuclear Ca{sup 2+}/calmodulin-dependent protein kinase phosphatase (CaMKP-N/PPM1E) is an enzyme that dephosphorylates and downregulates multifunctional Ca{sup 2+}/calmodulin-dependent protein kinases (CaMKs) as well as AMP-dependent protein kinase. In our previous study, we found that zebrafish CaMKP-N (zCaMKP-N) underwent proteolytic processing and translocated to cytosol in a proteasome inhibitor-sensitive manner. In the present study, we found that zCaMKP-N is regulated by phosphorylation at Ser-480. When zCaMKP-N was incubated with the activated CaMKI, time-dependent phosphorylation of the enzyme was observed. This phosphorylation was significantly reduced when Ser-480 was replaced by Ala, suggesting that CaMKI phosphorylates Ser-480 of zCaMKP-N. Phosphorylation-mimic mutants, S480D and S480E, showed higher phosphatase activities than those of wild type and S480A mutant in solution-based phosphatase assay using various substrates. Furthermore, autophosphorylation of CaMKII after ionomycin treatment was more severely attenuated in Neuro2a cells when CaMKII was cotransfected with the phosphorylation-mimic mutant of zCaMKP-N than with the wild-type or non-phosphorylatable zCaMKP-N. These results strongly suggest that phosphorylation of zCaMKP-N at Ser-480 by CaMKI activates CaMKP-N catalytic activity and thereby downregulates multifunctional CaMKs in the cytosol.

  5. LIGO: The strong belief

    CERN Multimedia

    Antonella Del Rosso


    Twenty years of designing, building and testing a number of innovative technologies, with the strong belief that the endeavour would lead to a historic breakthrough. The Bulletin publishes an abstract of the Courier’s interview with Barry Barish, one of the founding fathers of LIGO.   The plots show the signals of gravitational waves detected by the twin LIGO observatories at Livingston, Louisiana, and Hanford, Washington. (Image: Caltech/MIT/LIGO Lab) On 11 February, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo collaborations published a historic paper in which they showed a gravitational signal emitted by the merger of two black holes. These results come after 20 years of hard work by a large collaboration of scientists operating the two LIGO observatories in the US. Barry Barish, Linde Professor of Physics, Emeritus at the California Institute of Technology and former Director of the Global Design Effort for the Internat...

  6. Enhanced biosorption of transition metals by living Chlorella vulgaris immobilized in Ca-alginate beads. (United States)

    Ahmad, Ashfaq; Bhat, A H; Buang, Azizul


    In this study freely suspended and Ca-alginate immobilized C. vulgaris cells were used for the biosorption of Fe(II), Mn(II), and Zn(II) ions, from the aqueous solution. Experimental data showed that biosorption capacity of algal cells was strongly dependent on the operational condition such as pH, initial metal ions concentration, dosages, contact time and temperature. The maximum biosorption of Fe(II) 43.43, Mn(II) 40.98 and Zn(II) 37.43 mg/g was achieved with Ca-alginate immobilized algal cells at optimum pH of 6.0, algal cells dosage 0.6 g/L, and contact time of 450 min at room temperature. The biosorption efficiency of freely suspended and immobilized C. vulgaris cells for heavy metals removal from the industrial wastewater was validated. Modeling of biosorption kinetics showed good agreements with pseudo-second-order. Langmuir and D-R isotherm models exhibited the best fit of experimental data. The thermodynamic parameters (ΔG°, ΔH°, and ΔS°) revealed that the biosorption of considered metal ions was feasible, spontaneous and exothermic at 25-45°C. The SEM showed porous morphology which greatly helps in the biosorption of heavy metals. The Fourier transform infrared spectrophotometer (FTIR) and X-rays Photon Spectroscopy (XPS) data spectra indicated that the functional groups predominately involved in the biosorption were C-N, -OH, COO-, -CH, C=C, C=S and -C-. These results shows that immobilized algal cells in alginate beads could potentially enhance the biosorption of considered metal ions than freely suspended cells. Furthermore, the biosorbent has significantly removed heavy metals from industrial wastewater at the optimized condition.

  7. John Strong (1941 - 2006)

    CERN Multimedia

    Wickens, F

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

  8. Stirring Strongly Coupled Plasma

    CERN Document Server

    Fadafan, Kazem Bitaghsir; Rajagopal, Krishna; Wiedemann, Urs Achim


    We determine the energy it takes to move a test quark along a circle of radius L with angular frequency w through the strongly coupled plasma of N=4 supersymmetric Yang-Mills (SYM) theory. We find that for most values of L and w the energy deposited by stirring the plasma in this way is governed either by the drag force acting on a test quark moving through the plasma in a straight line with speed v=Lw or by the energy radiated by a quark in circular motion in the absence of any plasma, whichever is larger. There is a continuous crossover from the drag-dominated regime to the radiation-dominated regime. In the crossover regime we find evidence for significant destructive interference between energy loss due to drag and that due to radiation as if in vacuum. The rotating quark thus serves as a model system in which the relative strength of, and interplay between, two different mechanisms of parton energy loss is accessible via a controlled classical gravity calculation. We close by speculating on the implicati...

  9. Strong-interaction nonuniversality

    International Nuclear Information System (INIS)

    Volkas, R.R.; Foot, R.; He, X.; Joshi, G.C.


    The universal QCD color theory is extended to an SU(3) 1 direct product SU(3) 2 direct product SU(3) 3 gauge theory, where quarks of the ith generation transform as triplets under SU(3)/sub i/ and singlets under the other two factors. The usual color group is then identified with the diagonal subgroup, which remains exact after symmetry breaking. The gauge bosons associated with the 16 broken generators then form two massive octets under ordinary color. The interactions between quarks and these heavy gluonlike particles are explicitly nonuniversal and thus an exploration of their physical implications allows us to shed light on the fundamental issue of strong-interaction universality. Nonuniversality and weak flavor mixing are shown to generate heavy-gluon-induced flavor-changing neutral currents. The phenomenology of these processes is studied, as they provide the major experimental constraint on the extended theory. Three symmetry-breaking scenarios are presented. The first has color breaking occurring at the weak scale, while the second and third divorce the two scales. The third model has the interesting feature of radiatively induced off-diagonal Kobayashi-Maskawa matrix elements

  10. Early events elicited by bombesin and structurally related peptides in quiescent Swiss 3T3 cells. II. Changes in Na+ and Ca2+ fluxes, Na+/K+ pump activity, and intracellular pH

    International Nuclear Information System (INIS)

    Mendoza, S.A.; Schneider, J.A.; Lopez-Rivas, A.; Sinnett-Smith, J.W.; Rozengurt, E.


    The amphibian tetradecapeptide, bombesin, and structurally related peptides caused a marked increase in ouabain-sensitive 86 Rb + uptake (a measure of Na + /K + pump activity) in quiescent Swiss 3T3 cells. This effect occurred within seconds after the addition of the peptide and appeared to be mediated by an increase in Na + entry into the cells. The effect of bombesin on Na + entry and Na + /K + pump activity was concentration dependent with half-maximal stimulation occurring at 0.3-0.4 nM. The structurally related peptides litorin, gastrin-releasing peptide, and neuromedin B also stimulated ouabain-sensitive 86 Rb + uptake; the relative potencies of these peptides in stimulating the Na + /K + pump were comparable to their potencies in increasing DNA synthesis. Bombesin increased Na + influx, at least in part, through an Na + /H + antiport. The peptide augmented intracellular pH and this effect was abolished in the absence of extracellular Na + . In addition to monovalent ion transport, bombesin and the structurally related peptides rapidly increased the efflux of 45 Ca 2+ from quiescent Swiss 3T3 cells. This Ca 2+ came from an intracellular pool and the efflux was associated with a 50% decrease in total intracellular Ca 2+ . The peptides also caused a rapid increase in cytosolic free calcium concentration. Prolonged pretreatment of Swiss 3T3 cells with phorbol dibutyrate, which causes a loss of protein kinase C activity, greatly decreased the stimulation of 86 Rb + uptake and Na + entry by bombesin implicating this phosphotransferase system in the mediation of part of these responses to bombesin. Since some activation of monovalent ion transport by bombesin was seen in phorbol dibutyrate-pretreated cells, it is likely that the peptide also stimulates monovalent ion transport by a second mechanism

  11. Raman spectroscopy of DNA-metal complexes. II. The thermal denaturation of DNA in the presence of Sr2+, Ba2+, Mg2+, Ca2+, Mn2+, Co2+, Ni2+, and Cd2+.


    Duguid, J G; Bloomfield, V A; Benevides, J M; Thomas, G J


    Differential scanning calorimetry, laser Raman spectroscopy, optical densitometry, and pH potentiometry have been used to investigate DNA melting profiles in the presence of the chloride salts of Ba2+, Sr2+, Mg2+, Ca2+, Mn2+, Co2+, Ni2+, and Cd2+. Metal-DNA interactions have been observed for the molar ratio [M2+]/[PO2-] = 0.6 in aqueous solutions containing 5% by weight of 160 bp mononucleosomal calf thymus DNA. All of the alkaline earth metals, plus Mn2+, elevate the melting temperature of ...

  12. CAED Document Repository (United States)

    Compliance Assurance and Enforcement Division Document Repository (CAEDDOCRESP) provides internal and external access of Inspection Records, Enforcement Actions, and National Environmental Protection Act (NEPA) documents to all CAED staff. The respository will also include supporting documents, images, etc.

  13. The many phases of CaC{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Konar, Sumit; Nylén, Johanna; Svensson, Gunnar; Bernin, Diana; Edén, Mattias [Department of Materials and Environmental Chemistry, Stockholm University, SE-10691 Stockholm (Sweden); Ruschewitz, Uwe [Department of Chemistry, University of Cologne, Greinstrasse 6, 50939 Cologne (Germany); Häussermann, Ulrich, E-mail: [Department of Materials and Environmental Chemistry, Stockholm University, SE-10691 Stockholm (Sweden)


    Polymorphic CaC{sub 2} was prepared by reacting mixtures of CaH{sub 2} and graphite with molar ratios between 1:1.8 and 1:2.2 at temperatures between 700 and 1400 °C under dynamic vacuum. These conditions provided a well controlled, homogeneous, chemical environment and afforded products with high purity. The products, which were characterized by powder X-ray diffraction, solid state NMR and Raman spectroscopy, represented mixtures of the three known polymorphs, tetragonal CaC{sub 2}-I and monoclinic CaC{sub 2}-II and -III. Their proportion is dependent on the nominal C/CaH{sub 2} ratio of the reaction mixture and temperature. Reactions with excess carbon produced a mixture virtually free from CaC{sub 2}-I, whereas high temperatures (above 1100 °C) and C-deficiency favored the formation of CaC{sub 2}-I. From first principles calculations it is shown that CaC{sub 2}-I is dynamically unstable within the harmonic approximation. This indicates that existing CaC{sub 2}-I is structurally/dynamically disordered and may possibly even occur as slightly carbon-deficient phase CaC{sub 2-δ}. It is proposed that monoclinic II is the ground state of CaC{sub 2} and polymorph III is stable at temperatures above 200 °C. Tetragonal I represents a metastable, heterogeneous, phase of CaC{sub 2}. It is argued that a complete understanding of the occurrence of three room temperature modifications of CaC{sub 2} will require a detailed characterization of compositional and structural heterogeneities within the high temperature form CaC{sub 2}-IV, which is stable above 450 °C. The effect of high pressure on the stability of the monoclinic forms of CaC{sub 2} was studied in a diamond anvil cell using Raman spectroscopy. CaC{sub 2}-II and -III transform into tetragonal CaC{sub 2}-I at about 4 and 1GPa, respectively. - Graphical abstract: The famous tetragonal form of CaC{sub 2}, CaC{sub 2}-I, is dynamically unstable. Why does it exist? Display Omitted - Highlights: • Critical review

  14. The other side of cardiac Ca2+ signaling: transcriptional control

    Directory of Open Access Journals (Sweden)

    Alejandro eDomínguez-Rodríquez


    Full Text Available Ca2+ is probably the most versatile signal transduction element used by all cell types. In the heart, it is essential to activate cellular contraction in each heartbeat. Nevertheless Ca2+ is not only a key element in excitation-contraction coupling (EC coupling, but it is also a pivotal second messenger in cardiac signal transduction, being able to control processes such as excitability, metabolism, and transcriptional regulation. Regarding the latter, Ca2+ activates Ca2+-dependent transcription factors by a process called excitation-transcription coupling (ET coupling. ET coupling is an integrated process by which the common signaling pathways that regulate EC coupling activate transcription factors. Although ET coupling has been extensively studied in neurons and other cell types, less is known in cardiac muscle. Some hints have been found in studies on the development of cardiac hypertrophy, where two Ca2+-dependent enzymes are key actors: Ca2+/Calmodulin kinase II (CaMKII and phosphatase calcineurin, both of which are activated by the complex Ca2+/ /Calmodulin. The question now is how ET coupling occurs in cardiomyocytes, where intracellular Ca2+ is continuously oscillating. In this focused review, we will draw attention to location of Ca2+ signaling: intranuclear ([Ca2+]n or cytoplasmic ([Ca2+]c, and the specific ionic channels involved in the activation of cardiac ET coupling. Specifically, we will highlight the role of the 1,4,5 inositol triphosphate receptors (IP3Rs in the elevation of [Ca2+]n levels, which are important to locally activate CaMKII, and the role of transient receptor potential channels canonical (TRPCs in [Ca2+]c, needed to activate calcineurin.

  15. Ca isotopes in refractory inclusions

    International Nuclear Information System (INIS)

    Niederer, F.R.; Papanastassiou, D.A.


    We report measurements of the absolute isotope abundance of Ca in Ca-Al-rich inclusions from the Allende and Leoville meteorites. Improved high precision measurements are reported also for 46 Ca. We find that nonlinear isotope effects in Ca are extremely rare in these inclusions. The absence of nonlinear effects in Ca, except for the effects in FUN inclusions, is in sharp contrast to the endemic effects in Ti. One fine-grained inclusion shows an excess of 46 Ca of (7 +- 1) per mille, which is consistent with addition of only 46 Ca or of an exotic (*) component with 46 Ca* approx. 48 Ca*. FUN inclusion EK-1-4-1 shows a small 46 Ca excess of (3.3 +- 1.0) per mille; this confirms that the exotic Ca components in EK-1-4-1 were even more deficient in 46 Ca relative to 48 Ca than is the case for normal Ca. The Ca in the Ca-Al-rich inclusions shows mass dependent isotope fractionation effects which have a range from -3.8 to +6.7 per mille per mass unit difference. This range is a factor of 20 wider than the range previously established for bulk meteorites and for terrestrial and lunar samples. Ca and Mg isotope fractionation effects in the Ca-Al-rich inclusions are common and attributed to kinetic isotope effects. (author)

  16. The role of the coordination defect: A new structural description of four fluorite-related sesquioxide minerals, bixbyite (Mn 2O 3), braunite (Mn 7SiO 12), braunite II (CaMn 14SiO 24), parwelite (Mn 10Sb 2As 2Si 2O 24), and their structural relationships (United States)

    Bevan, D. J. M.; Martin, R. L.


    The anion-deficient, fluorite-related structures of the manganese-based minerals bixbyite (Mn 2O 3), braunite (Mn 7SiO 12), braunite II (CaMn 14SiO 24) and parwelite (Mn 10Sb 2As 2Si 2O 24) are reinterpreted in terms of the coordination defect (CD) theory to gain new insights into their structural interrelationships. CDs are extended, octahedral defects centred by an anion vacancy and including its immediate atomic environment: it is represented as □ M4O 6, where the symbol □ is the anion vacancy. The bixbyite motif is a CD dimer (two edge-sharing octahedra), and this motif repeats, by further edge-sharing, around the 2-fold screw axes of the cubic structure. These same dimers are present in each of the other structures, but the presence of Si 4+ in braunite and braunite II, together with that of other foreign cations such as As 5+ and Sb 5+ in parwelite, leads to different juxtapositions of these motifs. Moreover, the structure of braunite, Mn 2+(Mn 3+) 6SiO 12, reflects the clustering of 12 Mn 3+-centred octahedra (MnO 6) around a central SiO 4 tetrahedron to generate a structure for the [(Mn 3+) 6SiO 12] 2- anion which is almost identical to that of the well-known cuboctahedral structure of the PO 4-centred heteropolytungstate anion, [(W 6+) 12PO 40] 3-. The structure of braunite II, [Ca(Mn 3+) 14SiO 24], is simply an intergrowth of slabs of bixbyite- and braunite-type structures, linked by the CaO 8 cubes of the latter. Our various analyses of the reported structure of parwelite in terms of the only possible vacancy assignment have led to some apparent anomalies. We report briefly on these, and have decided to seek confirmation of the reported structure as a consequence. Despite the increasing complexity of these structures, there are clear and defining relationships in the distribution of CDs. The assumption of a close relationship to the fluorite parent in all these structures is based on the observation that the cation sub-lattices are essentially face

  17. Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.

    Directory of Open Access Journals (Sweden)

    Peter Rellos


    Full Text Available Long-term potentiation (LTP, a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM-dependent kinase II (CaMKII. CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.

  18. Synthesis, characterization, computational studies, antimicrobial activities and carbonic anhydrase inhibitor effects of 2-hydroxy acetophenone-N-methyl p-toluenesulfonylhydrazone and its Co(II), Pd(II), Pt(II) complexes (United States)

    Özbek, Neslihan; Alyar, Saliha; Memmi, Burcu Koçak; Gündüzalp, Ayla Balaban; Bahçeci, Zafer; Alyar, Hamit


    2-Hydroxyacetophenone-N-methyl p-toluenesulfonylhydrazone (afptsmh) derived from p-toluenesulfonicacid-1-methylhydrazide (ptsmh) and its Co(II), Pd(II), Pt(II) complexes were synthesized for the first time. Synthesized compounds were characterized by spectroscopic methods (FT-IR, 1Hsbnd 13C NMR, LC-MS, UV-vis), magnetic susceptibility and conductivity measurements. 1H and 13C shielding tensors for crystal structure of ligand were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The vibrational band assignments were performed at B3LYP/6-311++G(d,p) theory level combined with scaled quantum mechanics force field (SQMFF) methodology. The antibacterial activities of synthesized compounds were studied against some Gram positive and Gram negative bacteria by using microdilution and disc diffusion methods. In vitro enzyme inhibitory effects of the compounds were measured by UV-vis spectrophotometer. The enzyme activities against human carbonic anhydrase II (hCA II) were evaluated as IC50 (the half maximal inhibitory concentration) values. It was found that afptsmh and its metal complexes have inhibitory effects on hCA II isoenzyme. General esterase activities were determined using alpha and beta naphtyl acetate substrates (α- and β-NAs) of Drosophila melanogaster (D. melanogaster). Activity results show that afptsmh does not strongly affect the bacteria strains and also shows poor inhibitory activity against hCAII isoenzyme whereas all complexes posses higher biological activities.

  19. Preparation of 45Ca(HDEHP)n and (CaH1502)2 samples for liquid scintillation counting, compared to 45caCl2 results

    International Nuclear Information System (INIS)

    Rodriguez, L.; Arcos, J. M. los; Grau Malonda, A.


    A procedure for preparation of liquid scintillation counting organic samples of the Di-2-ethylhexyl phosphate calcium complex and the 2-ethylhexanoate calcium salt, labelled with 45Ca, is described. The chemical quench, the counting stability and spectral evolution of both compounds is studied in six scintillators,Toluene-alcohol, Dioxane-naphtalene, Hi safe II, Ultimate-Gold and Instagel, and compared to results obtained from a commercial solution of 4 5CaCl2. (Author) 7 refs

  20. Evaluation of Preoperative Serum Levels of CA 125 and Expression of p53 in Ovarian Neoplasms: A Prospective Clinicopathological Study in a Tertiary Care Hospital. (United States)

    Tiwari, Ranjan Kumar; Saha, Kaushik; Mukhopadhyay, Debasis; Datta, Chhanda; Chatterjee, Uttara; Ghosh, Tarun Kumar


    To assess the preoperative serum levels of CA 125 with its diagnostic role and to evaluate the p53 expression in patients of primary ovarian neoplasms. We also wished to judge their relationship with other parameters like clinical staging and histopathologic tumor type. The present study was conducted on 86 patients during the study period of 2.5 years. Preoperative CA 125 levels were evaluated by an automated immunoassay analyzer. p53 expression was judged immunohistochemically with pre-diluted monoclonal antibody. An objective scoring was done depending on distinct nuclear immunopositivity. Median value of preoperative CA 125 levels was 32 U/mL in benign surface epithelial-stromal tumors (BSEST), 53 U/mL in borderline surface epithelial-stromal tumors (BOT), 346 U/mL in malignant surface epithelial-stromal tumors (MSEST) and 560 U/mL in serous adenocarcinomas (SAC). Most of ovarian tumors were in the FIGO stage I (64 cases, 74.4%), but higher stages (II, III, IV) were observed mostly in MSESTs. SACs displayed the maximum p53 expression. Considering the cut-off value of more than 35 U/mL in CA 125 levels, the sensitivity to diagnose MSESTs was 94.7%. Preoperative CA 125 levels strongly and positively correlated with FIGO staging and p53 expression. Similarly p53 expression strongly and positively correlated with FIGO staging and histopathological categories. Higher values of preoperative CA 125 levels and higher expression p53 are associated with MSESTs and BOTs especially of serous type. They strongly correlate with each other and with tumor stage. But there is no serum CA 125 concentration that can clearly differentiate benign and malignant ovarian masses.

  1. A strongly coupled quark-gluon plasma

    Energy Technology Data Exchange (ETDEWEB)

    Shuryak, Edward [Department of Physics and Astronomy, University at Stony Brook, NY 11794 (United States)


    Successful description of robust collective flow phenomena at RHIC by ideal hydrodynamics, recent observations of bound c-barc,q-barq states on the lattice, and other theoretical developments indicate that QGP produced at RHIC, and probably in a wider temperature region T{sub c} < T < 4T{sub c}, is not a weakly coupled quasiparticle gas as believed previously. We discuss how strong the interaction is and why it seems to generate hundreds of binary channels with bound states, surviving well inside the QGP phase. We in particular discuss their effect on pressure and viscosity. We conclude by reviewing the similar phenomena for other 'strongly coupled systems', such as (i) strongly coupled supersymmetric theories studied via Maldacena duality; (ii) trapped ultra-cold atoms with very large scattering length, tuned to Feschbach resonances.

  2. Inflationary Magnetogenesis without the Strong Coupling Problem II

    DEFF Research Database (Denmark)

    J. Z. Ferreira, Ricardo; Kumar Jain, Rajeev; Sloth, Martin Snoager


    Recent observational claims of magnetic fields stronger than $10^{-16}$ G in the extragalactic medium motivate a new look for their origin in the inflationary magnetogenesis models. In this work we shall review the constraints on the simplest gauge invariant model $f^2(\\phi)F_{\\mu \

  3. βCaMKII plays a nonenzymatic role in hippocampal synaptic plasticity and learning by targeting αCaMKII to synapses. (United States)

    Borgesius, Nils Z; van Woerden, Geeske M; Buitendijk, Gabrielle H S; Keijzer, Nanda; Jaarsma, Dick; Hoogenraad, Casper C; Elgersma, Ype


    The calcium/calmodulin-dependent kinase type II (CaMKII) holoenzyme of the forebrain predominantly consists of heteromeric complexes of the αCaMKII and βCaMKII isoforms. Yet, in contrast to αCaMKII, the role of βCaMKII in hippocampal synaptic plasticity and learning has not been investigated. Here, we compare two targeted Camk2b mouse mutants to study the role of βCaMKII in hippocampal function. Using a Camk2b(-/-) mutant, in which βCaMKII is absent, we show that both hippocampal-dependent learning and Schaffer collateral-CA1 long-term potentiation (LTP) are highly dependent upon the presence of βCaMKII. We further show that βCaMKII is required for proper targeting of αCaMKII to the synapse, indicating that βCaMKII regulates the distribution of αCaMKII between the synaptic pool and the adjacent dendritic shaft. In contrast, localization of αCaMKII, hippocampal synaptic plasticity and learning were unaffected in the Camk2b(A303R) mutant, in which the calcium/calmodulin-dependent activation of βCaMKII is prevented, while the F-actin binding and bundling property is preserved. This indicates that the calcium/calmodulin-dependent kinase activity of βCaMKII is fully dispensable for hippocampal learning, LTP, and targeting of αCaMKII, but implies a critical role for the F-actin binding and bundling properties of βCaMKII in synaptic function. Together, our data provide compelling support for a model of CaMKII function in which αCaMKII and βCaMKII act in concert, but with distinct functions, to regulate hippocampal synaptic plasticity and learning.

  4. Biomarker CA125

    DEFF Research Database (Denmark)

    Kargo, Anette Stolberg

    be detected months before symptoms arise and recurrence is visible on imaging. Therefore, biochemical detection of potential relapse by CA125 assessment can cause significant distress. A decision aid (DA) is a tool that provides information and describes advantages and disadvantages of a specific intervention...... patient organisations and cancer societies. First, a focus group of seven former OC patients was performed followed by a quantitative rating of the DA pilot version. The DA was adapted accordingly and then tested in 14 OC patients with recurrence using a structured interview guide (alpha testing). A final...... agreed that the DA prepared them to make a better decision and helped them reflecting on their concerns regarding CA125. Conclusion: The DA was useful in decision making regarding monitoring CA125 during follow up after OC. The majority of participants indicated that the DA was helpful in clarifying...

  5. New fluorescent reagents specific for Ca2+-binding proteins

    International Nuclear Information System (INIS)

    Ben-Hail, Danya; Lemelson, Daniela; Israelson, Adrian; Shoshan-Barmatz, Varda


    Highlights: ► New reagents specifically inhibit the activity of Ca 2+ -dependent proteins. ► FITC-Ru and EITC-Ru allow for mechanism-independent probing of Ca 2+ -binding proteins. ► Changes in reagents fluorescence allow characterization of protein Ca 2+ -binding properties. -- Abstract: Ca 2+ carries information pivotal to cell life and death via its interactions with specific binding sites in a protein. We previously developed a novel photoreactive reagent, azido ruthenium (AzRu), which strongly inhibits Ca 2+ -dependent activities. Here, we synthesized new fluorescent ruthenium-based reagents containing FITC or EITC, FITC-Ru and EITC-Ru. These reagents were purified, characterized and found to specifically interact with and markedly inhibit Ca 2+ -dependent activities but not the activity of Ca 2+ -independent reactions. In contrast to many reagents that serve as probes for Ca 2+ , FITC-Ru and EITC-Ru are the first fluorescent divalent cation analogs to be synthesized and characterized that specifically bind to Ca 2+ -binding proteins and inhibit their activity. Such reagents will assist in characterizing Ca 2+ -binding proteins, thereby facilitating better understanding of the function of Ca 2+ as a key bio-regulator.

  6. Meiosis, egg activation, and nuclear envelope breakdown are differentially reliant on Ca2+, whereas germinal vesicle breakdown is Ca2+ independent in the mouse oocyte (United States)

    Tombes, R. M.; Simerly, C.; Borisy, G. G.; Schatten, G.


    During early development, intracellular Ca2+ mobilization is not only essential for fertilization, but has also been implicated during other meiotic and mitotic events, such as germinal vesicle breakdown (GVBD) and nuclear envelope breakdown (NEBD). In this study, the roles of intracellular and extracellular Ca2+ were examined during meiotic maturation and reinitiation at parthenogenetic activation and during first mitosis in a single species using the same methodologies. Cumulus-free metaphase II mouse oocytes immediately resumed anaphase upon the induction of a large, transient Ca2+ elevation. This resumption of meiosis and associated events, such as cortical granule discharge, were not sensitive to extracellular Ca2+ removal, but were blocked by intracellular Ca2+ chelators. In contrast, meiosis I was dependent on external Ca2+; in its absence, the formation and function of the first meiotic spindle was delayed, the first polar body did not form and an interphase-like state was induced. GVBD was not dependent on external Ca2+ and showed no associated Ca2+ changes. NEBD at first mitosis in fertilized eggs, on the other hand, was frequently, but not always associated with a brief Ca2+ transient and was dependent on Ca2+ mobilization. We conclude that GVBD is Ca2+ independent, but that the dependence of NEBD on Ca2+ suggests regulation by more than one pathway. As cells develop from Ca(2+)-independent germinal vesicle oocytes to internal Ca(2+)-dependent pronuclear eggs, internal Ca2+ pools increase by approximately fourfold.

  7. Skeletal muscle Ca(2+)-independent kinase activity increases during either hypertrophy or running (United States)

    Fluck, M.; Waxham, M. N.; Hamilton, M. T.; Booth, F. W.


    Spikes in free Ca(2+) initiate contractions in skeletal muscle cells, but whether and how they might signal to transcription factors in skeletal muscles of living animals is unknown. Since previous studies in non-muscle cells have shown that serum response factor (SRF) protein, a transcription factor, is phosphorylated rapidly by Ca(2+)/calmodulin (CaM)-dependent protein kinase after rises in intracellular Ca(2+), we measured enzymatic activity that phosphorylates SRF (designated SRF kinase activity). Homogenates from 7-day-hypertrophied anterior latissimus dorsi muscles of roosters had more Ca(2+)-independent SRF kinase activity than their respective control muscles. However, no differences were noted in Ca(2+)/CaM-dependent SRF kinase activity between control and trained muscles. To determine whether the Ca(2+)-independent and Ca(2+)/CaM-dependent forms of Ca(2+)/CaM-dependent protein kinase II (CaMKII) might contribute to some of the SRF kinase activity, autocamtide-3, a synthetic substrate that is specific for CaMKII, was employed. While the Ca(2+)-independent form of CaMKII was increased, like the Ca(2+)-independent form of SRF kinase, no alteration in CaMKII occurred at 7 days of stretch overload. These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII. To determine whether this adaptation was specific to the exercise type (i.e., hypertrophy), similar measurements were made in the white vastus lateralis muscle of rats that had completed 2 wk of voluntary running. Although Ca(2+)-independent SRF kinase was increased, no alteration occurred in Ca(2+)/CaM-dependent SRF kinase activity. Thus any role of Ca(2+)-independent SRF kinase signaling has downstream modulators specific to the exercise phenotype.

  8. Metode de atracţie şi localizare a faunei utile în agrocenoza culturii de piersic ca factor biologic de control al densităţii speciilor dăunătoare

    Directory of Open Access Journals (Sweden)

    Mihai BATCO


    Full Text Available The use of such biorational means as nectariferous plants (Eruca sativa, Fagopyrum esculentum, Phacelia tanacetifolia, Satureja hortensis, Lobulalaria maritima, Dracocephalum moldavica and lawn grasses, protein-carbohydrate compositions and methyl salicylate as factors influencing the beneficial fauna in peach orchard agrocenosis has contributed to the attraction and location of 26 species of Encyrtidae belonging to 19 genera. The species capable to influence the numeric dynamics of economically important species such as oriental moth (Grapholita molesta Busck, peach twig borer (Anarsia lineatella Z, San Jose scale (Diaspidiotus perniciosus Comst., fruit apple scale (Eulecanium coryli L. were nominated. Encyrtidae species whose hosts are potential pests of peach trees, as well as hyperparasite species and parasites of beneficial predatory insects were registered. The stages for timely application of biorational means for useful fauna in the peach orchard agrocenosis during the vegetation period were established. Rezumat. Aplicarea mijloacelor bioraţionale precum culturile nectarifere (Eruca sativa, Fagopyrum esculentum, Phacelia tanacetifolia, Satureja hortensis, Lobulalaria maritima, Dracocephalum moldavica şi iarba de gazon, compoziţiile proteico-glucidice şi metilsalicilatul ca factori de influenţă asupra faunei benefice în agrocenoza culturii de piersic au contribuit la atracţia şi localizarea a 26 specii de Encyrtidae, care se atribuie la 19 genuri. Sunt nominalizate speciile capabile de a influenţa dinamica numerică a speciilor economic importante, aşa ca molia orientală (Grapholita molesta Busck, molia vărgată (Anarsia lineatella Z, păduchele din San Jose (Diaspidiotus perniciosus Comst., păduchele ţestos fals al mărului (Eulecanium coryli L.. Au fost semnalate specii de Encyrtidae ale căror gazde sunt dăunători potenţiali ai piersicului şi de asemenea specii hiperparazite şi paraziţi ai insectelor pr

  9. Synthesis of Al₂Ca Dispersoids by Powder Metallurgy Using a Mg-Al Alloy and CaO Particles. (United States)

    Fujita, Junji; Umeda, Junko; Kondoh, Katsuyoshi


    The elemental mixture of Mg-6 wt %Al-1 wt %Zn-0.3 wt %Mn (AZ61B) alloy powder and CaO particles was consolidated by an equal-channel angular bulk mechanical alloying (ECABMA) process to form a composite precursor. Subsequently, the precursor was subjected to a heat treatment to synthesize fine Al₂Ca particles via a solid-state reaction between the Mg-Al matrix and CaO additives. Scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS) and electron probe micro-analysis on the precursor indicated that 4.7-at % Al atoms formed a supersaturated solid solution in the α-Mg matrix. Transmission electron microscopy-EDS and X-ray diffraction analyses on the AZ61B composite precursor with 10-vol % CaO particles obtained by heat treatment confirmed that CaO additives were thermally decomposed in the Mg-Al alloy, and the solid-soluted Ca atoms diffused along the α-Mg grain boundaries. Al atoms also diffused to the grain boundaries because of attraction to the Ca atoms resulting from a strong reactivity between Al and Ca. As a result, needle-like (Mg,Al)₂Ca intermetallics were formed as intermediate precipitates in the initial reaction stage during the heat treatment. Finally, the precipitates were transformed into spherical Al₂Ca particles by the substitution of Al atoms for Mg atoms in (Mg,Al)₂Ca after a long heat treatment.

  10. Up-regulation of Ca2+/CaMKII/CREB signaling in salicylate-induced tinnitus in rats. (United States)

    Zhao, Jiuhan; Wang, Biao; Wang, Xiaohong; Shang, Xiuli


    The purpose of the study was to investigate the changes of Ca 2+ /calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-D-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p salicylate administration causes tinnitus symptoms and elevates Ca 2+ /CaMKII/CREB signaling pathway in auditory cortex cells. Our study likely provides a new understanding of the development of tinnitus.

  11. Topological organization of CA3-to-CA1 excitation. (United States)

    Hongo, Yoshie; Ogawa, Koichi; Takahara, Yuji; Takasu, Keiko; Royer, Sebastien; Hasegawa, Minoru; Sakaguchi, Gaku; Ikegaya, Yuji


    The CA1-projecting axons of CA3 pyramidal cells, called Schaffer collaterals, constitute one of the major information flow routes in the hippocampal formation. Recent anatomical studies have revealed the non-random structural connectivity between CA3 and CA1, but little is known regarding the functional connectivity (i.e. how CA3 network activity is functionally transmitted downstream to the CA1 network). Using functional multi-neuron calcium imaging of rat hippocampal slices, we monitored the spatiotemporal patterns of spontaneous CA3 and CA1 burst activity under pharmacological GABAergic blockade. We found that spatially clustered CA3 activity patterns were transformed into layered CA1 activity sequences. Specifically, synchronized bursts initiated from multiple hot spots in CA3 ensembles, and CA1 neurons located deeper in the pyramidal cell layer were recruited during earlier phases of the burst events. The order of these sequential activations was maintained across the bursts, but the sequence velocity varied depending on the inter-burst intervals. Thus, CA3 axons innervate CA1 neurons in a highly topographical fashion. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Evaluation of the medtronic exponent self-expanding carotid stent system with the medtronic guardwire temporary occlusion and aspiration system in the treatment of carotid stenosis: combined from the MAVErIC (Medtronic AVE Self-expanding CaRotid Stent System with distal protection In the treatment of Carotid stenosis) I and MAVErIC II trials. (United States)

    Higashida, Randall T; Popma, Jeffrey J; Apruzzese, Patricia; Zimetbaum, Peter


    Embolic protection devices and improved stent technology have advanced the endovascular treatment of carotid artery disease. A combined analysis was performed of the MAVErIC (Medtronic AVE Self-expanding CaRotid Stent System with distal protection) I and II trials to evaluate the safety and feasibility of this system among patients at high risk for surgical endarterectomy. Four hundred ninety-eight patients were enrolled in the MAVErIC I (99 patients) and MAVErIC II (399 patients) studies from June 2001 to October 2004. The results were pooled for statistical analysis of a common primary end point, the 365-day rate of major adverse events. Clinical follow-up took place at 30 days, 6 months, and 365 days postprocedure. The 365-day major adverse event rate, defined as death, stroke, or myocardial infarction within 30 days, and death, ipsilateral stroke, or myocardial infarction from days 31 to 365 was 12.5%. The incidence of neurological death through 365 days was 1.1%. The 30-day major adverse event rate was 5.4%. Subgroup analyses showed no notable differences in the 365-day major adverse event rate for symptomatic patients compared with asymptomatic patients. Treatment of carotid artery disease with carotid artery stenting with a self-expanding stent and distal embolic protection results in a low 30-day adverse event rate, including the occurrence of stroke in patients at high risk for carotid endarterectomy.

  13. Raman spectroscopy of DNA-metal complexes. II. The thermal denaturation of DNA in the presence of Sr2+, Ba2+, Mg2+, Ca2+, Mn2+, Co2+, Ni2+, and Cd2+. (United States)

    Duguid, J G; Bloomfield, V A; Benevides, J M; Thomas, G J


    Differential scanning calorimetry, laser Raman spectroscopy, optical densitometry, and pH potentiometry have been used to investigate DNA melting profiles in the presence of the chloride salts of Ba2+, Sr2+, Mg2+, Ca2+, Mn2+, Co2+, Ni2+, and Cd2+. Metal-DNA interactions have been observed for the molar ratio [M2+]/[PO2-] = 0.6 in aqueous solutions containing 5% by weight of 160 bp mononucleosomal calf thymus DNA. All of the alkaline earth metals, plus Mn2+, elevate the melting temperature of DNA (Tm > 75.5 degrees C), whereas the transition metals Co2+, Ni2+, and Cd2+ lower Tm. Calorimetric (delta Hcal) and van't Hoff (delta HVH) enthalpies of melting range from 6.2-8.7 kcal/mol bp and 75.6-188.6 kcal/mol cooperative unit, respectively, and entropies from 17.5 to 24.7 cal/K mol bp. The average number of base pairs in a cooperative melting unit () varied from 11.3 to 28.1. No dichotomy was observed between alkaline earth and transition DNA-metal complexes for any of the thermodynamic parameters other than their effects on Tm. These results complement Raman difference spectra, which reveal decreases in backbone order, base unstacking, distortion of glycosyl torsion angles, and rupture of hydrogen bonds, which occur after thermal denaturation. Raman difference spectroscopy shows that transition metals interact with the N7 atom of guanine in duplex DNA. A broader range of interaction sites with single-stranded DNA includes ionic phosphates, the N1 and N7 atoms of purines, and the N3 atom of pyrimidines. For alkaline earth metals, very little interaction was observed with duplex DNA, whereas spectra of single-stranded complexes are very similar to those of melted DNA without metal. However, difference spectra reveal some metal-specific perturbations at 1092 cm-1 (nPO2-), 1258 cm-1 (dC, dA), and 1668 cm-1 (nC==O, dNH2 dT, dG, dC). Increased spectral intensity could also be observed near 1335 cm-1 (dA, dG) for CaDNA. Optical densitometry, employed to detect DNA

  14. Selective Extraction of Co(II in the Presence of Mn(II, Ni(II and Cu(II Using Salting-out Phase Separation Method

    Directory of Open Access Journals (Sweden)

    A M Shafiqul Alam


    Full Text Available Extraction of Co(II in the presence of Mn(II, Ni(II and Cu(II has been studied using the mixture of 2-propanol with water upon the addition of CaCl2 in the concentration range of 3.0 – 5.0 mol dm-3 (M. Co(II was extracted selectively to the extent of 80% into the 2-propanol phase at 5.0 M CaCl2. The percent of extraction of other transition metal ions, for example Mn(II, Ni(II and Cu(II was much lower than that of Co(II, but they were stripped in the aqueous phase upon addition of CaCl2. Therefore, selective extraction of Co(II from these metal ions was attained by using the mixture of water and 2-propanol. Co(II was extracted as CoCl42- from the aqueous phase into the 2-propanol phase through the formation of ion pair, Ca2+ - CoCl42-. A mechanism is proposed to explain the extraction.

  15. CaCDPK15 positively regulates pepper responses to Ralstonia solanacearum inoculation and forms a positive-feedback loop with CaWRKY40 to amplify defense signaling (United States)

    Shen, Lei; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Cheng, Wei; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Mou, Shaoliang; Liu, Zhiqin; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin


    CaWRKY40 is a positive regulator of pepper (Capsicum annum) response to Ralstonia solanacearum inoculation (RSI), but the underlying mechanism remains largely unknown. Here, we functionally characterize CaCDPK15 in the defense signaling mediated by CaWRKY40. Pathogen-responsive TGA, W, and ERE boxes were identified in the CaCDPK15 promoter (pCaCDPK15), and pCaCDPK15-driven GUS expression was significantly enhanced in response to RSI and exogenously applied salicylic acid, methyl jasmonate, abscisic acid, and ethephon. Virus-induced gene silencing (VIGS) of CaCDPK15 significantly increased the susceptibility of pepper to RSI and downregulated the immunity-associated markers CaNPR1, CaPR1, and CaDEF1. By contrast, transient CaCDPK15 overexpression significantly activated hypersensitive response associated cell death, upregulated the immunity-associated marker genes, upregulated CaWRKY40 expression, and enriched CaWRKY40 at the promoters of its targets genes. Although CaCDPK15 failed to interact with CaWRKY40, the direct binding of CaWRKY40 to pCaCDPK15 was detected by chromatin immunoprecipitation, which was significantly potentiated by RSI in pepper plants. These combined results suggest that RSI in pepper induces CaCDPK15 and indirectly activates downstream CaWRKY40, which in turn potentiates CaCDPK15 expression. This positive-feedback loop would amplify defense signaling against RSI and efficiently activate strong plant immunity. PMID:26928570

  16. Expression of CA-IX is associated with advanced stage tumors and poor survival in oral squamous cell carcinoma patients. (United States)

    Pérez-Sayáns, Mario; Suárez-Peñaranda, José Manuel; Pilar, Gayoso-Diz; Supuran, Claudiu T; Pastorekova, Silvia; Barros-Angueira, Francisco; Gándara-Rey, José Manuel; García-García, Abel


    Carbonic anhydrases (CAs), a group of ubiquitously expressed metalloenzymes, are involved in numerous physiological and pathological processes, including tumorigenicity. Specifically, CA-IX has been primarily found in hypoxic tumor tissues. This is a retrospective study of tumors from the Tissue Bank of the Pathology Department of the University Hospital of Santiago de Compostela. We selected 50 oral squamous cell carcinomas (OSCCs) using Tissue Microarray (TMA) technology. The immunohistochemical study was performed to determine CA-IX expression. The resulting data were subject to statistical analysis and survival curves. Of the 50 cases, 23 were detected in early stages (I and II) and 27 in advanced stages (III and IV). In the first year, almost 50% of patients in stages III-IV died, which contrasted with those patients in initial stages who registered a survival rate of 80% (P = 0.019). Regarding the expression of CA-IX, nine cases (18%) were negative, 18 cases (36%) were moderate, while 23 cases (46%) were intense. Tumors in stages I-II showed a positivity of 52.6%; however, in advanced stages, the percentage reached 95.5% (P = 0.002). Regarding CA-IX expression and survival, patients with tumors with strong staining had a lower average survival time (13.8 months) than patients with negative or weak-moderate staining (33.4 and 32.8 months, respectively), log-rank=6.1, P value=0.0484. Early diagnosis of these tumors is essential to improve patient survival. CA-IX expression augments with increasing tumor stage, probably related with the degree of hypoxia; thus, its measurement can be used as a prognostic factor. © 2012 John Wiley & Sons A/S.

  17. Ca2+ current versus Ca2+ channel cooperativity of exocytosis. (United States)

    Matveev, Victor; Bertram, Richard; Sherman, Arthur


    Recently there has been significant interest and progress in the study of spatiotemporal dynamics of Ca(2+) that triggers exocytosis at a fast chemical synapse, which requires understanding the contribution of individual calcium channels to the release of a single vesicle. Experimental protocols provide insight into this question by probing the sensitivity of exocytosis to Ca(2+) influx. While varying extracellular or intracellular Ca(2+) concentration assesses the intrinsic biochemical Ca(2+) cooperativity of neurotransmitter release, varying the number of open Ca(2+) channels using pharmacological channel block or the tail current titration probes the cooperativity between individual Ca(2+) channels in triggering exocytosis. Despite the wide use of these Ca(2+) sensitivity measurements, their interpretation often relies on heuristic arguments. Here we provide a detailed analysis of the Ca(2+) sensitivity measures probed by these experimental protocols, present simple expressions for special cases, and demonstrate the distinction between the Ca(2+) current cooperativity, defined by the relationship between exocytosis rate and the whole-terminal Ca(2+) current magnitude, and the underlying Ca(2+) channel cooperativity, defined as the average number of channels involved in the release of a single vesicle. We find simple algebraic expressions that show that the two are different but linearly related. Further, we use three-dimensional computational modeling of buffered Ca(2+) diffusion to analyze these distinct Ca(2+) cooperativity measures, and demonstrate the role of endogenous Ca(2+) buffers on such measures. We show that buffers can either increase or decrease the Ca(2+) current cooperativity of exocytosis, depending on their concentration and the single-channel Ca(2+) current.

  18. Reaction of tin(iv) phthalocyanine dichloride with decamethylmetallocenes (M = CrII and CoII). Strong magnetic coupling of spins in (Cp*2Co+){SnIVCl2(Pc˙3-)}˙-·2C6H4Cl2. (United States)

    Konarev, Dmitri V; Troyanov, Sergey I; Shestakov, Alexander F; Yudanova, Evgeniya I; Otsuka, Akihiro; Yamochi, Hideki; Kitagawa, Hiroshi; Lyubovskaya, Rimma N


    The reaction of tin(iv) phthalocyanine dichloride {Sn IV Cl 2 (Pc 2- )} with decamethylmetallocenes (Cp* 2 M, M = Co, Cr) has been studied. Decamethylcobaltocene reduces Sn IV Cl 2 (Pc 2- ) to form the (Cp* 2 Co + ){Sn IV Cl 2 (Pc˙ 3- )}˙ - ·2C 6 H 4 Cl 2 (1) complex. The negative charge of {Sn IV Cl 2 (Pc˙ 3- )}˙ - is delocalized over the Pc macrocycle providing the alternation of the C-N(imine) bonds, the appearance of new bands in the NIR range and a strong blue shift of both the Soret and Q-bands in the spectrum of 1. The magnetic moment of 1 is equal to 1.68μ B at 300 K, indicating the contribution of one S = 1/2 spin of the Pc˙ 3- macrocycles. These macrocycles form closely packed double stacks in 1 with effective π-π interactions providing strong antiferromagnetic coupling of spins at a Weiss temperature of -80 K. Decamethylchromocene initially also reduces Sn IV Cl 2 (Pc 2- ) to form the [(Cp* 2 Cr + ){Sn VI Cl 2 (Pc˙ 3- )}˙ - complex but further reaction between the ions is observed. This reaction is accompanied by the substitution of one Cp* ligand of Cp* 2 Cr by chloride anions originating from {Sn IV Cl 2 (Pc˙ 3- )}˙ - to form the complex {(Cp*CrCl 2 )(Sn IV (μ-Cl)(Pc 2- ))}·C 6 H 4 Cl 2 (2) in which the (Cp*CrCl 2 ) and {Sn IV (Pc 2- )} species are bonded through the μ-bridged Cl - anion. According to the DFT calculations, this reaction proceeds via an intermediate [(Cp* 2 CrCl)(SnClPc)] complex.

  19. Quantum electrodynamics of strong fields

    International Nuclear Information System (INIS)

    Greiner, W.


    Quantum Electrodynamics of Strong Fields provides a broad survey of the theoretical and experimental work accomplished, presenting papers by a group of international researchers who have made significant contributions to this developing area. Exploring the quantum theory of strong fields, the volume focuses on the phase transition to a charged vacuum in strong electric fields. The contributors also discuss such related topics as QED at short distances, precision tests of QED, nonperturbative QCD and confinement, pion condensation, and strong gravitational fields In addition, the volume features a historical paper on the roots of quantum field theory in the history of quantum physics by noted researcher Friedrich Hund

  20. Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain

    Directory of Open Access Journals (Sweden)

    Norifumi Shioda


    Full Text Available Ca2+/calmodulin (CaM-dependent protein kinase II (CaMKII, a multifunctional serine (Ser/threonine (Thr protein kinase, regulates diverse activities related to Ca2+-mediated neuronal plasticity in the brain, including synaptic activity and gene expression. Among its regulators, protein phosphatase-1 (PP1, a Ser/Thr phosphatase, appears to be critical in controlling CaMKII-dependent neuronal signaling. In postsynaptic densities (PSDs, CaMKII is required for hippocampal long-term potentiation (LTP, a cellular process correlated with learning and memory. In response to Ca2+ elevation during hippocampal LTP induction, CaMKIIα, an isoform that translocates from the cytosol to PSDs, is activated through autophosphorylation at Thr286, generating autonomous kinase activity and a prolonged Ca2+/CaM-bound state. Moreover, PP1 inhibition enhances Thr286 autophosphorylation of CaMKIIα during LTP induction. By contrast, CaMKII nuclear import is regulated by Ser332 phosphorylation state. CaMKIIδ3, a nuclear isoform, is dephosphorylated at Ser332 by PP1, promoting its nuclear translocation, where it regulates transcription. In this review, we summarize physio-pathological roles of CaMKII/PP1 signaling in neurons. CaMKII and PP1 crosstalk and regulation of gene expression is important for neuronal plasticity as well as survival and/or differentiation.

  1. Hippocampal area CA2: an emerging modulatory gateway in the hippocampal circuit. (United States)

    Benoy, Amrita; Dasgupta, Ananya; Sajikumar, Sreedharan


    The hippocampus is a critical brain region for the formation of declarative memories. While social memory had long been attributed to be a function of the hippocampus, it is only of late that the area CA2 of the hippocampus was demarcated as essential for social memory formation. In addition to this distinct role, CA2 possesses unique molecular, structural and physiological characteristics compared to the other CA regions-CA1 and CA3, and the dentate gyrus (DG). CA2 pyramidal neurons are positioned at a location between CA1 and CA3, receiving inputs from CA3 and DG, in addition to forming a powerful disynaptic circuit with direct input from the entorhinal cortical layer II neurons. CA2 also receives direct inputs from the hypothalamic regions and displays a unique expression pattern for receptors for neuromodulators. The location, inputs, and molecular signatures of the area CA2 point to the possibility that CA2 serves as a modulatory gateway that processes information from the entorhinal cortex and CA3, before relaying them onto CA1, the major output of the hippocampus. This review discusses recent findings regarding plasticity and neuromodulation in the CA2 region of the hippocampus, and how this may have the potential to influence plasticity in connecting circuits, and thereby memory and behaviour.

  2. CA 125 in ovarian cancer

    NARCIS (Netherlands)

    van der Burg, M. E.; Lammes, F. B.; Verweij, J.


    The serum tumour marker CA 125 is useful in the management of ovarian cancer, although it has its limitations. Approximately 85% of the ovarian cancer patients have an increased serum CA 125 at the start of treatment. There is a good correlation between the course of CA 125 and the clinical response

  3. Strong WW Interaction at LHC

    Energy Technology Data Exchange (ETDEWEB)

    Pelaez, Jose R


    We present a brief pedagogical introduction to the Effective Electroweak Chiral Lagrangians, which provide a model independent description of the WW interactions in the strong regime. When it is complemented with some unitarization or a dispersive approach, this formalism allows the study of the general strong scenario expected at the LHC, including resonances.

  4. Strong-back safety latch

    International Nuclear Information System (INIS)

    DeSantis, G.N.


    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch

  5. Strong-back safety latch

    Energy Technology Data Exchange (ETDEWEB)

    DeSantis, G.N.


    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch.

  6. Towards ultracold RbCa molecules (United States)

    Kleinert, Michaela; Whitson, Hayley; Parsagian, Alexandria


    Ultracold heteronuclear molecules have seen increasing interest in the scientific community over the last few years. By controlling their ro-vibrational energy levels, ultracold molecules can be used for high precision spectroscopy, to study cold collisions with rich internal dynamics, as model systems for condensed matter physics, and as qubits in quantum information processing. We study the novel combination RbCa. In addition to a permanent electric dipole moment, it also possesses a permanent magnetic dipole moment. This makes it an ideal candidate to study strong long-range dipole-dipole interactions. We are currently in the process of adding a Ca MOT to our existing Rb MOT and will discuss our current and future efforts toward our goal of creating, for the first time, ultracold RbCa molecules. Molecules, once created, will be detected through resonantly enhanced multi-photon ionization (REMPI). We have also performed ab initio calculations to determine the electronic energy levels of RbCa, and calculated Franck-Condon factors between the ground and several excited states

  7. Structural Changes in the Mn4Ca Cluster and the Mechanism of Photosynthetic Water Splitting

    Energy Technology Data Exchange (ETDEWEB)

    Pushkar, Y.; Yano, J.; Sauer, K.; Boussac, A.; Yachandra, V.K.


    Photosynthetic water oxidation, where water is oxidized to dioxygen, is a fundamental chemical reaction that sustains the biosphere. This reaction is catalyzed by a Mn4Ca complex in the photosystem II (PS II) oxygen-evolving complex (OEC): a multiproteinassembly embedded in the thylakoid membranes of green plants, cyanobacteria, and algae. The mechanism of photosynthetic water oxidation by the Mn4Ca cluster in photosystem II is the subject of much debate, although lacking structural characterization of the catalytic intermediates. Biosynthetically exchanged Ca/Sr-PS II preparations and x-ray spectroscopy, including extended x-ray absorption fine structure (EXAFS), allowed us to monitor Mn-Mn and Ca(Sr)-Mn distances in the four intermediate S states, S0 through S3, of the catalytic cycle that couples the one-electron photochemistry occurring at the PS II reaction center with the four-electron water-oxidation chemistry taking place at the Mn4Ca(Sr) cluster. We have detected significant changes in the structure of the complex, especially in the Mn-Mn and Ca(Sr)-Mn distances, on the S2-to-S3 and S3-to-S0 transitions. These results implicate the involvement of at least one common bridging oxygen atom between the Mn-Mn and Mn-Ca(Sr) atoms in the O-O bond formation. Because PS II cannot advance beyond the S2 state in preparations that lack Ca(Sr), these results show that Ca(Sr) is one of the critical components in the mechanism of the enzyme. The results also show that Ca is not just a spectator atom involved in providing a structural framework, but is actively involved in the mechanism of water oxidation and represents a rare example of a catalytically active Ca cofactor.

  8. Hippocampal CA1 pyramidal cells form functionally distinct sublayers


    Mizuseki, Kenji; Diba, Kamran; Pastalkova, Eva; Buzsáki, György


    Summary Hippocampal CA1 pyramidal neurons have frequently been regarded as a homogeneous cell population in biophysical, pharmacological and modeling studies. Here we report robust differences between pyramidal neurons residing in the deep and superficial CA1 sublayers in the rat. Compared to their superficial peers, deep pyramidal cells fired at higher rates, burst more frequently, were more likely to have place fields and were more strongly modulated by slow oscillations of sleep. Both deep...

  9. Titanium: light, strong, and white (United States)

    Woodruff, Laurel; Bedinger, George


    Titanium (Ti) is a strong silver-gray metal that is highly resistant to corrosion and is chemically inert. It is as strong as steel but 45 percent lighter, and it is twice as strong as aluminum but only 60 percent heavier. Titanium dioxide (TiO2) has a very high refractive index, which means that it has high light-scattering ability. As a result, TiO2 imparts whiteness, opacity, and brightness to many products. ...Because of the unique physical properties of titanium metal and the whiteness provided by TiO2, titanium is now used widely in modern industrial societies.


    International Nuclear Information System (INIS)

    Chen, Hsin-Wei; Lee, Typhoon; Lee, Der-Chuen; Chen, Jiang-Chang


    Precise determinations of 48 Ca anomalies in Allende calcium–aluminum-rich inclusions (CAIs) are reported in this work. There are endemic positive 48 Ca/ 44 Ca anomalies in all analyzed CAIs after normalization to 42 Ca/ 44 Ca, and it is clearly shown that there is no simple correlation between 48 Ca/ 44 Ca and 50 Ti/ 48 Ti anomalies, in agreement with Jungck et al. Compared to the 48 Ca/ 44 Ca versus 50 Ti/ 48 Ti correlation line defined by differentiated meteorites, reported by Chen et al., the CAIs plot to elevated 50 Ti/ 48 Ti. Assuming the 48 Ca/ 44 Ca anomalies of both CAIs and differentiated meteorites came from the same source, excess 50 Ti anomalies in CAIs can be calculated by subtracting the part associated with 48 Ca/ 44 Ca. These excesses show a linear correlation with 138 La anomalies, a neutrino-process nuclide. According to current stellar nucleosynthetic models, we therefore suggest that the solar system 48 Ca, 50 Ti, and 138 La isotopic variations are made of mixtures between grains condensed from ejecta of neutron-rich accretion-induced SNe Ia and the O/Ne–O/C zone of core-collapse SNe II

  11. Cross talk between β subunits, intracellular Ca2+ signaling, and SNAREs in the modulation of CaV 2.1 channel steady-state inactivation. (United States)

    Serra, Selma Angèlica; Gené, Gemma G; Elorza-Vidal, Xabier; Fernández-Fernández, José M


    Modulation of Ca V 2.1 channel activity plays a key role in interneuronal communication and synaptic plasticity. SNAREs interact with a specific synprint site at the second intracellular loop (LII-III) of the Ca V 2.1 pore-forming α 1A subunit to optimize neurotransmitter release from presynaptic terminals by allowing secretory vesicles docking near the Ca 2+ entry pathway, and by modulating the voltage dependence of channel steady-state inactivation. Ca 2+ influx through Ca V 2.1 also promotes channel inactivation. This process seems to involve Ca 2+ -calmodulin interaction with two adjacent sites in the α 1A carboxyl tail (C-tail) (the IQ-like motif and the Calmodulin-Binding Domain (CBD) site), and contributes to long-term potentiation and spatial learning and memory. Besides, binding of regulatory β subunits to the α interaction domain (AID) at the first intracellular loop (LI-II) of α 1A determines the degree of channel inactivation by both voltage and Ca 2+ . Here, we explore the cross talk between β subunits, Ca 2+ , and syntaxin-1A-modulated Ca V 2.1 inactivation, highlighting the α 1A domains involved in such process. β 3 -containing Ca V 2.1 channels show syntaxin-1A-modulated but no Ca 2+ -dependent steady-state inactivation. Conversely, β 2a -containing Ca V 2.1 channels show Ca 2+ -dependent but not syntaxin-1A-modulated steady-state inactivation. A LI-II deletion confers Ca 2+ -dependent inactivation and prevents modulation by syntaxin-1A in β 3 -containing Ca V 2.1 channels. Mutation of the IQ-like motif, unlike CBD deletion, abolishes Ca 2+ -dependent inactivation and confers modulation by syntaxin-1A in β 2a -containing Ca V 2.1 channels. Altogether, these results suggest that LI-II structural modifications determine the regulation of Ca V 2.1 steady-state inactivation either by Ca 2+ or by SNAREs but not by both. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and

  12. TRPC3-mediated Ca2+ influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts. (United States)

    Kitajima, Naoyuki; Watanabe, Kunihiro; Morimoto, Sachio; Sato, Yoji; Kiyonaka, Shigeki; Hoshijima, Masahiko; Ikeda, Yasuhiro; Nakaya, Michio; Ide, Tomomi; Mori, Yasuo; Kurose, Hitoshi; Nishida, Motohiro


    Dilated cardiomyopathy (DCM) is a myocardial disorder that is characterized by dilation and dysfunction of the left ventricle (LV). Accumulating evidence has implicated aberrant Ca(2+) signaling and oxidative stress in the progression of DCM, but the molecular details are unknown. In the present study, we report that inhibition of the transient receptor potential canonical 3 (TRPC3) channels partially prevents LV dilation and dysfunction in muscle LIM protein-deficient (MLP (-/-)) mice, a murine model of DCM. The expression level of TRPC3 and the activity of Ca(2+)/calmodulin-dependent kinase II (CaMKII) were increased in MLP (-/-) mouse hearts. Acitivity of Rac1, a small GTP-binding protein that participates in NADPH oxidase (Nox) activation, and the production of reactive oxygen species (ROS) were also increased in MLP (-/-) mouse hearts. Treatment with pyrazole-3, a TRPC3 selective inhibitor, strongly suppressed the increased activities of CaMKII and Rac1, as well as ROS production. In contrast, activation of TRPC3 by 1-oleoyl-2-acetyl-sn-glycerol (OAG), or by mechanical stretch, induced ROS production in rat neonatal cardiomyocytes. These results suggest that up-regulation of TRPC3 is responsible for the increase in CaMKII activity and the Nox-mediated ROS production in MLP (-/-) mouse cardiomyocytes, and that inhibition of TRPC3 is an effective therapeutic strategy to prevent the progression of DCM. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Average [O II]nebular emission associated with Mg II absorbers: Dependence on Fe II absorption (United States)

    Joshi, Ravi; Srianand, Raghunathan; Petitjean, Patrick; Noterdaeme, Pasquier


    We investigate the effect of Fe II equivalent width (W2600) and fibre size on the average luminosity of [O II]λλ3727,3729 nebular emission associated with Mg II absorbers (at 0.55 ≤ z ≤ 1.3) in the composite spectra of quasars obtained with 3 and 2 arcsec fibres in the Sloan Digital Sky Survey. We confirm the presence of strong correlations between [O II] luminosity (L_{[O II]}) and equivalent width (W2796) and redshift of Mg II absorbers. However, we show L_{[O II]} and average luminosity surface density suffers from fibre size effects. More importantly, for a given fibre size the average L_{[O II]} strongly depends on the equivalent width of Fe II absorption lines and found to be higher for Mg II absorbers with R ≡W2600/W2796 ≥0.5. In fact, we show the observed strong correlations of L_{[O II]} with W2796 and z of Mg II absorbers are mainly driven by such systems. Direct [O II] detections also confirm the link between L_{[O II]} and R. Therefore, one has to pay attention to the fibre losses and dependence of redshift evolution of Mg II absorbers on W2600 before using them as a luminosity unbiased probe of global star formation rate density. We show that the [O II] nebular emission detected in the stacked spectrum is not dominated by few direct detections (i.e., detections ≥3σ significant level). On an average the systems with R ≥0.5 and W2796 ≥2Å are more reddened, showing colour excess E(B - V) ˜ 0.02, with respect to the systems with R <0.5 and most likely traces the high H I column density systems.

  14. 2IrrigatioIi)Division

    African Journals Online (AJOL)

    assftssed using Njoro .ya. • >. • .-. ,. ,,- ... i'deVices 'were 'insiailed ii{ej"s'tilt"ioni aliitii'ooa I cana(.whiie;-Goa i ca~ai· stations,."were left as a ..... Estimates of discharge were based on visual " dQ .,,;, Change of discharge caused by a unit inspection ...

  15. The SNAP Strong Lens Survey

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, P.


    Basic considerations of lens detection and identification indicate that a wide field survey of the types planned for weak lensing and Type Ia SNe with SNAP are close to optimal for the optical detection of strong lenses. Such a ''piggy-back'' survey might be expected even pessimistically to provide a catalogue of a few thousand new strong lenses, with the numbers dominated by systems of faint blue galaxies lensed by foreground ellipticals. After sketching out our strategy for detecting and measuring these galaxy lenses using the SNAP images, we discuss some of the scientific applications of such a large sample of gravitational lenses: in particular we comment on the partition of information between lens structure, the source population properties and cosmology. Understanding this partitioning is key to assessing strong lens cosmography's value as a cosmological probe.

  16. Strong coupling phase in QED

    International Nuclear Information System (INIS)

    Aoki, Ken-ichi


    Existence of a strong coupling phase in QED has been suggested in solutions of the Schwinger-Dyson equation and in Monte Carlo simulation of lattice QED. In this article we recapitulate the previous arguments, and formulate the problem in the modern framework of the renormalization theory, Wilsonian renormalization. This scheme of renormalization gives the best understanding of the basic structure of a field theory especially when it has a multi-phase structure. We resolve some misleading arguments in the previous literature. Then we set up a strategy to attack the strong phase, if any. We describe a trial; a coupled Schwinger-Dyson equation. Possible picture of the strong coupling phase QED is presented. (author)

  17. Thermoelectric properties of antiperovskite calcium oxides Ca3PbO and Ca3SnO (United States)

    Okamoto, Y.; Sakamaki, A.; Takenaka, K.


    We report the thermoelectric properties of polycrystalline samples of Ca3Pb1-xBixO (x = 0, 0.1, 0.2) and Ca3SnO, both crystallizing in a cubic antiperovskite-type structure. The Ca3SnO sample shows metallic resistivity and its thermoelectric power approaches 100 μV K-1 at room temperature, resulting in the thermoelectric power factor of Ca3SnO being larger than that of Ca3Pb1-xBixO. On the basis of Hall and Sommerfeld coefficients, the Ca3SnO sample is found to be a p-type metal with a carrier density of ˜1019 cm-3, a mobility of ˜80 cm2 V-1 s-1, both comparable to those in degenerated semiconductors, and a moderately large hole carrier effective mass. The coexistence of moderately high mobility and large effective mass observed in Ca3SnO, as well as possible emergence of a multivalley electronic structure with a small band gap at low-symmetry points in k-space, suggests that the antiperovskite Ca oxides have strong potential as a thermoelectric material.

  18. Weak and strong typicality in quantum systems. (United States)

    Santos, Lea F; Polkovnikov, Anatoli; Rigol, Marcos


    We study the properties of mixed states obtained from eigenstates of many-body lattice Hamiltonians after tracing out part of the lattice. Two scenarios emerge for generic systems: (i) The diagonal entropy becomes equivalent to the thermodynamic entropy when a few sites are traced out (weak typicality); and (ii) the von Neumann (entanglement) entropy becomes equivalent to the thermodynamic entropy when a large fraction of the lattice is traced out (strong typicality). Remarkably, the results for few-body observables obtained with the reduced, diagonal, and canonical density matrices are very similar to each other, no matter which fraction of the lattice is traced out. Hence, for all physical quantities studied here, the results in the diagonal ensemble match the thermal predictions.

  19. The promise of CaMKII inhibition for heart disease : preventing heart failure and arrhythmias

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Edwards, Andrew G.; McCulloch, Andrew D.; Brown, Joan Heller

    Introduction: Calcium-calmodulin-dependent protein kinase II (CaMKII) has emerged as a central mediator of cardiac stress responses which may serve several critical roles in the regulation of cardiac rhythm, cardiac contractility and growth. Sustained and excessive activation of CaMKII during

  20. Accessing the nuclear symmetry energy in Ca+Ca collisions

    Directory of Open Access Journals (Sweden)

    Chbihi A.


    Full Text Available The status of the analysis of the INDRA-VAMOS experiement performed at GANIL, using the reactions 40,48Ca+40,48Ca reactions at 35AMeV, are presented. Isotopic distributions of fragments produced in multifragmentation events provide information on the importance of the surface term contribution in the symmetry energy by comparison to AMD predictions.

  1. Strong Decomposition of Random Variables

    DEFF Research Database (Denmark)

    Hoffmann-Jørgensen, Jørgen; Kagan, Abram M.; Pitt, Loren D.


    A random variable X is stongly decomposable if X=Y+Z where Y=Φ(X) and Z=X-Φ(X) are independent non-degenerated random variables (called the components). It is shown that at least one of the components is singular, and we derive a necessary and sufficient condition for strong decomposability...

  2. Strong interaction at finite temperature

    Indian Academy of Sciences (India)

    Abstract. We review two methods discussed in the literature to determine the effective parameters of strongly interacting particles as they move through a heat bath. The first one is the general method of chiral perturbation theory, which may be readily applied to this problem. The other is the method of thermal QCD sum rules ...

  3. Strong-strong beam-beam simulation on parallel computer

    Energy Technology Data Exchange (ETDEWEB)

    Qiang, Ji


    The beam-beam interaction puts a strong limit on the luminosity of the high energy storage ring colliders. At the interaction points, the electromagnetic fields generated by one beam focus or defocus the opposite beam. This can cause beam blowup and a reduction of luminosity. An accurate simulation of the beam-beam interaction is needed to help optimize the luminosity in high energy colliders.

  4. Strong-strong beam-beam simulation on parallel computer

    International Nuclear Information System (INIS)

    Qiang, Ji


    The beam-beam interaction puts a strong limit on the luminosity of the high energy storage ring colliders. At the interaction points, the electromagnetic fields generated by one beam focus or defocus the opposite beam. This can cause beam blowup and a reduction of luminosity. An accurate simulation of the beam-beam interaction is needed to help optimize the luminosity in high energy colliders

  5. CaII Κ Imaging to Understand UV Irradiance Variability

    Indian Academy of Sciences (India)


    Jan 27, 2016 ... To identify and understand the underlying physical mechanisms of total solar and UV irradiance variability and to estimate the contribution of various chromospheric features to UV irradiance, detailed analysis of spatially resolved data is required. The various chromospheric features have been segregated ...


    African Journals Online (AJOL)

    bivalent Co, Ni, Cu and Zn complexes with Schiff base ligand: Experimental and DFT calculations. Bull. Chem. Soc. Ethiop. 2017, 31, 159-170. 4. Esmaielzadeh, S.; Zare, Z.; Azimian, L. Synthesis, physical characterization, antibacterial activity and thermodynamic studies of five coordinate cobalt(III) Schiff base complexes.

  7. Ca II 8542 angstrom brightenings induced by a solar microflare

    Czech Academy of Sciences Publication Activity Database

    Kuckein, C.; Diercke, A.; Manrique, T.; Gonzalez Manrique, S. J.; Verma, M.; Loehner-Boettcher, J.; Socas-Navarro, H.; Balthasar, H.; Sobotka, Michal; Denker, C.


    Roč. 608, December (2017), A117/1-A117/13 E-ISSN 1432-0746 R&D Projects: GA MŠk(CZ) 7E13003 EU Projects: European Commission(XE) 312495 - SOLARNET Institutional support: RVO:67985815 Keywords : Sun * photosphere * chromosphere Subject RIV: BN - Astronomy , Celestial Mechanics, Astrophysics OBOR OECD: Astronomy (including astrophysics,space science) Impact factor: 5.014, year: 2016

  8. Strong Convergence for Hybrid Implicit S-Iteration Scheme of Nonexpansive and Strongly Pseudocontractive Mappings

    Directory of Open Access Journals (Sweden)

    Shin Min Kang


    Full Text Available Let K be a nonempty closed convex subset of a real Banach space E, let S:K→K be nonexpansive, and let  T:K→K be Lipschitz strongly pseudocontractive mappings such that p∈FS∩FT=x∈K:Sx=Tx=x and x-Sy≤Sx-Sy and x-Ty≤Tx-Ty for all x, y∈K. Let βn be a sequence in 0, 1 satisfying (i ∑n=1∞βn=∞; (ii limn→∞⁡βn=0. For arbitrary x0∈K, let xn be a sequence iteratively defined by xn=Syn, yn=1-βnxn-1+βnTxn, n≥1. Then the sequence xn converges strongly to a common fixed point p of S and T.

  9. PREFACE: Strongly correlated electron systems Strongly correlated electron systems (United States)

    Saxena, Siddharth S.; Littlewood, P. B.


    This special section is dedicated to the Strongly Correlated Electron Systems Conference (SCES) 2011, which was held from 29 August-3 September 2011, in Cambridge, UK. SCES'2011 is dedicated to 100 years of superconductivity and covers a range of topics in the area of strongly correlated systems. The correlated electronic and magnetic materials featured include f-electron based heavy fermion intermetallics and d-electron based transition metal compounds. The selected papers derived from invited presentations seek to deepen our understanding of the rich physical phenomena that arise from correlation effects. The focus is on quantum phase transitions, non-Fermi liquid phenomena, quantum magnetism, unconventional superconductivity and metal-insulator transitions. Both experimental and theoretical work is presented. Based on fundamental advances in the understanding of electronic materials, much of 20th century materials physics was driven by miniaturisation and integration in the electronics industry to the current generation of nanometre scale devices. The achievements of this industry have brought unprecedented advances to society and well-being, and no doubt there is much further to go—note that this progress is founded on investments and studies in the fundamentals of condensed matter physics from more than 50 years ago. Nevertheless, the defining challenges for the 21st century will lie in the discovery in science, and deployment through engineering, of technologies that can deliver the scale needed to have an impact on the sustainability agenda. Thus the big developments in nanotechnology may lie not in the pursuit of yet smaller transistors, but in the design of new structures that can revolutionise the performance of solar cells, batteries, fuel cells, light-weight structural materials, refrigeration, water purification, etc. The science presented in the papers of this special section also highlights the underlying interest in energy-dense materials, which

  10. Penetrating Internet Information Services (IIS).

    African Journals Online (AJOL)



    Dec 1, 2013 ... by default. On IIS 5.0 however, unless the Internet Printing Protocol function is in use, administrators are strongly encouraged to remove the ISAPI application mapping for .printer resources. The ISAPI mappings can be defined for the entire or an individual web site from the IIS management console snap-in.

  11. Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload. (United States)

    Li, Wei; Wang, Yue-peng; Gao, Ling; Zhang, Peng-pai; Zhou, Qing; Xu, Quan-fu; Zhou, Zhi-wen; Guo, Kai; Chen, Ren-hua; Yang, Huang-tian; Li, Yi-gang


    To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca(2+) overload in ventricular myocytes and to explore the underlying mechanisms. Hydrogen peroxide (H2O2, 200 μmol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na(+) and Ca(2+) currents were examined using whole-cell recording in myocytes. H2O2 markedly prolonged Ca(2+) transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 μmol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 μmol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca(2+)]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na(+) current (I(Na,L)) and L-type Ca(2+) current (I(Ca,L)) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol. Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca(2+) overload through inhibition of I(Na,L)/I(Ca,L), reduction of ROS generation, and prevention of CaMKII activation.

  12. Pb II

    African Journals Online (AJOL)

    Windows User

    ., 2009) biomaterials. However, the ..... reported for various microorganisms by various researchers (Gong et al., 2005). At biomass ... the increase in initial Pb (II) was also observed for removal of Pb (II) by loofa sponge immobilized Aspergillus.

  13. Strongly correlated systems experimental techniques

    CERN Document Server

    Mancini, Ferdinando


    The continuous evolution and development of experimental techniques is at the basis of any fundamental achievement in modern physics. Strongly correlated systems (SCS), more than any other, need to be investigated through the greatest variety of experimental techniques in order to unveil and crosscheck the numerous and puzzling anomalous behaviors characterizing them. The study of SCS fostered the improvement of many old experimental techniques, but also the advent of many new ones just invented in order to analyze the complex behaviors of these systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. The volume presents a representative collection of the modern experimental techniques specifically tailored for the analysis of strongly correlated systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognize...

  14. Strongly Correlated Systems Theoretical Methods

    CERN Document Server

    Avella, Adolfo


    The volume presents, for the very first time, an exhaustive collection of those modern theoretical methods specifically tailored for the analysis of Strongly Correlated Systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognized main contributors. The exposition has a clear pedagogical cut and fully reports on the most relevant case study where the specific technique showed to be very successful in describing and enlightening the puzzling physics of a particular strongly correlated system. The book is intended for advanced graduate students and post-docs in the field as textbook and/or main reference, but also for other researchers in the field who appreciates consulting a single, but comprehensive, source or wishes to get acquainted, in a as painless as po...

  15. Strongly correlated systems numerical methods

    CERN Document Server

    Mancini, Ferdinando


    This volume presents, for the very first time, an exhaustive collection of those modern numerical methods specifically tailored for the analysis of Strongly Correlated Systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and material science, belong to this class of systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognized main contributors. The exposition has a clear pedagogical cut and fully reports on the most relevant case study where the specific technique showed to be very successful in describing and enlightening the puzzling physics of a particular strongly correlated system. The book is intended for advanced graduate students and post-docs in the field as textbook and/or main reference, but also for other researchers in the field who appreciate consulting a single, but comprehensive, source or wishes to get acquainted, in a as painless as possi...

  16. Strongly nonlinear oscillators analytical solutions

    CERN Document Server

    Cveticanin, Livija


    This book provides the presentation of the motion of pure nonlinear oscillatory systems and various solution procedures which give the approximate solutions of the strong nonlinear oscillator equations. The book presents the original author’s method for the analytical solution procedure of the pure nonlinear oscillator system. After an introduction, the physical explanation of the pure nonlinearity and of the pure nonlinear oscillator is given. The analytical solution for free and forced vibrations of the one-degree-of-freedom strong nonlinear system with constant and time variable parameter is considered. Special attention is given to the one and two mass oscillatory systems with two-degrees-of-freedom. The criteria for the deterministic chaos in ideal and non-ideal pure nonlinear oscillators are derived analytically. The method for suppressing chaos is developed. Important problems are discussed in didactic exercises. The book is self-consistent and suitable as a textbook for students and also for profess...

  17. Intense Shock Waves and Strongly Coupled Plasmas (United States)

    Fortov, Vladimir


    The report presents the recent results of experimental investigations of equations of state, compositions, thermodynamical and transport properties, electrical conductivity and opacity of strongly coupled plasmas generated by intense shock and rarefaction waves. The experimental methods for generation of high energy densities in matter, drivers for shock waves and fast diagnostic tools are discussed. Application of intense shock waves to solid and porous targets generates nonideal plasmas in megabar-gigabar pressure range. Compression of plasma by a series of reverberating shock waves allows us to decrease irreversible heating effects. To increase the irreversibility effects and to generate high temperature plasma states the experiments on shock compression of porous samples (fine metal powder, aerogels) were performed. The adiabatic expansion of matter initially compressed by intense shocks up to megabars allows investigating the intermediate region between the solid and vapor phase of nonideal plasmas, including the metal-insulator transition phase and the high temperature saturation curve with critical points of metals. The shock-wave-induced non-equilibrium phenomena at fast melting, spallation and adiabatic condensation are analyzed in the framework of the interspinodal decomposition model. The spall strength of single and polycrystal metals at extremely fast deformation produced by fast shock waves is discussed. The ``pressure ionization'' phenomena in hydrogen, helium, argon, xenon, krypton, neon, iodine, silica, sulfur, fullerenes, and some metals are analyzed on the base of multiple shock compression experiments. For some simple metals (Li, Na, Ca) the effect of ``dielectrization'' as a result of multiple shock compression are discussed.

  18. Flavour Democracy in Strong Unification

    CERN Document Server

    Abel, S A; Abel, Steven; King, Steven


    We show that the fermion mass spectrum may naturally be understood in terms of flavour democratic fixed points in supersymmetric theories which have a large domain of attraction in the presence of "strong unification". Our approach provides an alternative to the approximate Yukawa texture zeroes of the Froggatt-Nielsen mechanism. We discuss a particular model based on a broken gauged $SU(3)_L\\times SU(3)_R$ family symmetry which illustrates our approach.

  19. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  20. Intracellular calcium oscillations in strongly metastatic human breast and prostate cancer cells: control by voltage-gated sodium channel activity. (United States)

    Rizaner, Nahit; Onkal, Rustem; Fraser, Scott P; Pristerá, Alessandro; Okuse, Kenji; Djamgoz, Mustafa B A


    The possible association of intracellular Ca 2+ with metastasis in human cancer cells is poorly understood. We have studied Ca 2+ signaling in human prostate and breast cancer cell lines of strongly versus weakly metastatic potential in a comparative approach. Intracellular free Ca 2+ was measured using a membrane-permeant fluorescent Ca 2+ -indicator dye (Fluo-4 AM) and confocal microscopy. Spontaneous Ca 2+ oscillations were observed in a proportion of strongly metastatic human prostate and breast cancer cells (PC-3M and MDA-MB-231, respectively). In contrast, no such oscillations were observed in weakly/non metastatic LNCaP and MCF-7 cells, although a rise in the resting Ca 2+ level could be induced by applying a high-K + solution. Various parameters of the oscillations depended on extracellular Ca 2+ and voltage-gated Na + channel activity. Treatment with either tetrodotoxin (a general blocker of voltage-gated Na + channels) or ranolazine (a blocker of the persistent component of the channel current) suppressed the Ca 2+ oscillations. It is concluded that the functional voltage-gated Na + channel expression in strongly metastatic cancer cells makes a significant contribution to generation of oscillatory intracellular Ca 2+ activity. Possible mechanisms and consequences of the Ca 2+ oscillations are discussed.

  1. Rates for some reactions involving 42Ca and 44Ca

    International Nuclear Information System (INIS)

    Cheng, C.W.; King, J.D.


    Ground-state reaction rates have been deduced from recent cross section measurements for the 42 CA(α, n) 45 Ti, 42 Ca(p, γ) 43 Sc, and 44 Ca(p, n) 44 Sc reactions. Comparison of these rates with those calculated from a statistical model of nuclear reactions. (Woosley et al) shows good agreement for the first two, but the 44 Ca(p, n) rate is more than a factor of 2 less than the theoretical prediction. Stellar reaction rates have been derived from the ground-state rates by multiplying the ground-state rates by the ratio of stellar to ground-state rates given by the statistical model. Both ground-state and stellar rates have been represented by analytic functions of the temperature. The role of these reactions in the approach to quasi-equilibrium during explosive silicon burning is discussed

  2. Atoms in strong laser fields

    International Nuclear Information System (INIS)

    L'Huillier, A.


    When a high-power laser focuses into a gas of atoms, the electromagnetic field becomes of the same magnitude as the Coulomb field which binds a 1s electron in a hydrogen atom. 3 highly non-linear phenomena can happen: 1) ATI (above threshold ionization): electrons initially in the ground state absorb a large number of photons, many more than the minimum number required for ionization; 2) multiple ionization: many electrons can be emitted one at a time, in a sequential process, or simultaneously in a mechanism called direct or non-sequential; and 3) high order harmonic generation (HHG): efficient photon emission in the extreme ultraviolet range, in the form of high-order harmonics of the fundamental laser field can occur. The theoretical problem consists in solving the time dependent Schroedinger equation (TDSE) that describes the interaction of a many-electron atom with a laser field. A number of methods have been proposed to solve this problem in the case of a hydrogen atom or a single-active electron atom in a strong laser field. A large effort is presently being devoted to go beyond the single-active approximation. The understanding of the physics of the interaction between atoms and strong laser fields has been provided by a very simple model called ''simple man's theory''. A unified view of HHG, ATI, and non-sequential ionization, originating from the simple man's model and the strong field approximation, expressed in terms of electrons trajectories or quantum paths is slowly emerging. (A.C.)

  3. Strongly Interacting Light Dark Matter

    Directory of Open Access Journals (Sweden)

    Sebastian Bruggisser, Francesco Riva, Alfredo Urbano


    Full Text Available In the presence of approximate global symmetries that forbid relevant interactions, strongly coupled light Dark Matter (DM can appear weakly coupled at small energy and generate a sizable relic abundance. Fundamental principles like unitarity restrict these symmetries to a small class, where the leading interactions are captured by effective operators up to dimension-8. Chiral symmetry, spontaneously broken global symmetries and non-linearly realized supersymmetry are examples of this. Their DM candidates (composite fermions, pseudo Nambu-Goldstone Bosons and Goldstini are interesting targets for LHC missing-energy searches.

  4. Strongly interacting light dark matter

    International Nuclear Information System (INIS)

    Bruggisser, Sebastian; Riva, Francesco; Urbano, Alfredo


    In the presence of approximate global symmetries that forbid relevant interactions, strongly coupled light Dark Matter (DM) can appear weakly coupled at small-energy and generate a sizable relic abundance. Fundamental principles like unitarity restrict these symmetries to a small class, where the leading interactions are captured by effective operators up to dimension-8. Chiral symmetry, spontaneously broken global symmetries and non-linearly realized supersymmetry are examples of this. Their DM candidates (composite fermions, pseudo-Nambu-Goldstone Bosons and Goldstini) are interesting targets for LHC missing-energy searches.

  5. Rydberg atoms in strong fields

    International Nuclear Information System (INIS)

    Kleppner, D.; Tsimmerman, M.


    Experimental and theoretical achievements in studying Rydberg atoms in external fields are considered. Only static (or quasistatic) fields and ''one-electron'' atoms, i.e. atoms that are well described by one-electron states, are discussed. Mainly behaviour of alkali metal atoms in electric field is considered. The state of theoretical investigations for hydrogen atom in magnetic field is described, but experimental data for atoms of alkali metals are presented as an illustration. Results of the latest experimental and theoretical investigations into the structure of Rydberg atoms in strong fields are presented

  6. Scalar strong interaction hadron theory

    CERN Document Server

    Hoh, Fang Chao


    The scalar strong interaction hadron theory, SSI, is a first principles' and nonlocal theory at quantum mechanical level that provides an alternative to low energy QCD and Higgs related part of the standard model. The quark-quark interaction is scalar rather than color-vectorial. A set of equations of motion for mesons and another set for baryons have been constructed. This book provides an account of the present state of a theory supposedly still at its early stage of development. This work will facilitate researchers interested in entering into this field and serve as a basis for possible future development of this theory.

  7. Strong Plate, Weak Slab Dichotomy (United States)

    Petersen, R. I.; Stegman, D. R.; Tackley, P.


    Models of mantle convection on Earth produce styles of convection that are not observed on Earth.Moreover non-Earth-like modes, such as two-sided downwellings, are the de facto mode of convection in such models.To recreate Earth style subduction, i.e. one-sided asymmetric recycling of the lithosphere, proper treatment of the plates and plate interface are required. Previous work has identified several model features that promote subduction. A free surface or pseudo-free surface and a layer of material with a relatively low strength material (weak crust) allow downgoing plates to bend and slide past overriding without creating undue stress at the plate interface. (Crameri, et al. 2012, GRL)A low viscosity mantle wedge, possibly a result of slab dehydration, decouples the plates in the system. (Gerya et al. 2007, Geo)Plates must be composed of material which, in the case of the overriding plate, are is strong enough to resist bending stresses imposed by the subducting plate and yet, as in the case of the subducting plate, be weak enough to bend and subduct when pulled by the already subducted slab. (Petersen et al. 2015, PEPI) Though strong surface plates are required for subduction such plates may present a problem when they encounter the lower mantle.As the subducting slab approaches the higher viscosity, lower mantle stresses are imposed on the tip.Strong slabs transmit this stress to the surface.There the stress field at the plate interface is modified and potentially modifies the style of convection. In addition to modifying the stress at the plate interface, the strength of the slab affects the morphology of the slab at the base of the upper mantle. (Stegman, et al 2010, Tectonophysics)Slabs that maintain a sufficient portion of their strength after being bent require high stresses to unbend or otherwise change their shape.On the other hand slabs that are weakened though the bending process are more amenable to changes in morphology. We present the results of

  8. Targeting the CaMKII/ERK Interaction in the Heart Prevents Cardiac Hypertrophy (United States)

    Cipolletta, Ersilia; Rusciano, Maria Rosaria; Maione, Angela Serena; Santulli, Gaetano; Sorriento, Daniela; Del Giudice, Carmine; Ciccarelli, Michele; Franco, Antonietta; Crola, Catherine; Campiglia, Pietro; Sala, Marina; Gomez-Monterrey, Isabel; De Luca, Nicola; Trimarco, Bruno; Iaccarino, Guido; Illario, Maddalena


    Aims Activation of Ca2+/Calmodulin protein kinase II (CaMKII) is an important step in signaling of cardiac hypertrophy. The molecular mechanisms by which CaMKII integrates with other pathways in the heart are incompletely understood. We hypothesize that CaMKII association with extracellular regulated kinase (ERK), promotes cardiac hypertrophy through ERK nuclear localization. Methods and Results In H9C2 cardiomyoblasts, the selective CaMKII peptide inhibitor AntCaNtide, its penetratin conjugated minimal inhibitory sequence analog tat-CN17β, and the MEK/ERK inhibitor UO126 all reduce phenylephrine (PE)-mediated ERK and CaMKII activation and their interaction. Moreover, AntCaNtide or tat-CN17β pretreatment prevented PE induced CaMKII and ERK nuclear accumulation in H9C2s and reduced the hypertrophy responses. To determine the role of CaMKII in cardiac hypertrophy in vivo, spontaneously hypertensive rats were subjected to intramyocardial injections of AntCaNtide or tat-CN17β. Left ventricular hypertrophy was evaluated weekly for 3 weeks by cardiac ultrasounds. We observed that the treatment with CaMKII inhibitors induced similar but significant reduction of cardiac size, left ventricular mass, and thickness of cardiac wall. The treatment with CaMKII inhibitors caused a significant reduction of CaMKII and ERK phosphorylation levels and their nuclear localization in the heart. Conclusion These results indicate that CaMKII and ERK interact to promote activation in hypertrophy; the inhibition of CaMKII-ERK interaction offers a novel therapeutic approach to limit cardiac hypertrophy. PMID:26110816

  9. Targeting the CaMKII/ERK Interaction in the Heart Prevents Cardiac Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Ersilia Cipolletta

    Full Text Available Activation of Ca2+/Calmodulin protein kinase II (CaMKII is an important step in signaling of cardiac hypertrophy. The molecular mechanisms by which CaMKII integrates with other pathways in the heart are incompletely understood. We hypothesize that CaMKII association with extracellular regulated kinase (ERK, promotes cardiac hypertrophy through ERK nuclear localization.In H9C2 cardiomyoblasts, the selective CaMKII peptide inhibitor AntCaNtide, its penetratin conjugated minimal inhibitory sequence analog tat-CN17β, and the MEK/ERK inhibitor UO126 all reduce phenylephrine (PE-mediated ERK and CaMKII activation and their interaction. Moreover, AntCaNtide or tat-CN17β pretreatment prevented PE induced CaMKII and ERK nuclear accumulation in H9C2s and reduced the hypertrophy responses. To determine the role of CaMKII in cardiac hypertrophy in vivo, spontaneously hypertensive rats were subjected to intramyocardial injections of AntCaNtide or tat-CN17β. Left ventricular hypertrophy was evaluated weekly for 3 weeks by cardiac ultrasounds. We observed that the treatment with CaMKII inhibitors induced similar but significant reduction of cardiac size, left ventricular mass, and thickness of cardiac wall. The treatment with CaMKII inhibitors caused a significant reduction of CaMKII and ERK phosphorylation levels and their nuclear localization in the heart.These results indicate that CaMKII and ERK interact to promote activation in hypertrophy; the inhibition of CaMKII-ERK interaction offers a novel therapeutic approach to limit cardiac hypertrophy.

  10. Studies of highly ionized atoms using internal conversion: 197Au, 57Fe; electric monopole transitions in 40Ca, 42Ca, and 44Ca

    International Nuclear Information System (INIS)

    Ulrickson, M.A.


    By using heavy-ion reactions, highly ionized electronic states of atoms may be produced. The interaction between excited nuclear levels and the surrounding atomic electrons via internal conversion allows the nucleus to be used as a probe of the electronic structure of the highly ionized atoms. Studies of such atoms were undertaken for strongly internally converted nuclear levels in 197 Au and 57 Fe. The nuclear levels were Coulomb excited by using 16 O and 32 S beams. Simultaneous measurement of the lifetime of the 77-keV state of 197 Au in both neutral gold atoms and gold atoms with mean charge +10 resulted in a measured change in the internal conversion coefficient of Δalpha/alpha equals - 1.7 +- 3.0)10 -3 . This result is consistent with calculations using a Hartree-Fock--Slater program. Measurements of the electric monopole strengths for 0 + → 0 + transitions were undertaken to determine the amount of core-deformation in calcium nuclei. The E0 strengths for the decays of the 0 + states at 5.21 MeV in 40 C, 1.84 MeV in 42 Ca, and 1.88 MeV in 44 Ca were observed. The branching ratios for the subsequent E0 pair decays were measured by observing the coincident annihilation radiation from the e + member of the pair in coincidence with protons feeding the state in the cases of 42 Ca and 44 Ca, and by observing the actual coincident e + --e - pair together with protons feeding the state in the case of 40 Ca. The resulting E0 strengths (rho less than or equal to 0.06, rho = 0.34 +- 0.03, rho = 0.30 +- 0.10 for 40 Ca, 42 Ca, and 44 Ca respectively) agree with theoretical descriptions

  11. Correlation of CA-125 with different stages of endometriosis

    Directory of Open Access Journals (Sweden)

    Runa Laila


    Full Text Available This study was conducted to evaluate the association of serum cancer antigen (CA-125 level with the severity of pelvic endometriosis. Seventy diagnosed cases of pelvic endometriosis were included in this study. The CA-125 level was estimated in all these patients, cutoff value of the serum CA-125 level was considered 35.0 U/mL. The correlations between serum CA-125 and different stages of endometriosis were evaluated by linear regression analysis. In Stage I of endometriosis, the mean serum CA-125 level was 21.8 ± 15.1 U/mL, in Stage II 26.0 ± 17.3 U/mL, in Stage III 83.2 ± 48.9 U/mL and in Stage IV 117.0 ± 41.6 U/mL. A significant positive correlation (r=0.729; p=0.001 was found between the serum CA-125 and different stages of endometriosis.

  12. Coping with Asymmetric Channel Losses in CSMA/CA

    DEFF Research Database (Denmark)

    Paramanathan, Achuthan; Roetter, Daniel Enrique Lucani; Fitzek, Frank


    Inspired by the discrepancy between past theoretical analysis and real measurements for high-load scenarios for intersession network coding, we pinpoint and analyze the source of this discrepancy in wireless networks implementing a CSMA/CA medium access scheme. Our analysis shows that CSMA/CA is ......) confirm the sensitivity of the CSMA/CA scheme in real implementations, and (ii) shows that our adaptive protocol provides a simple, yet potent mechanism to cope with asymmetric channel losses and ultimately to enhance end-to-end throughput in high-load scenarios.......Inspired by the discrepancy between past theoretical analysis and real measurements for high-load scenarios for intersession network coding, we pinpoint and analyze the source of this discrepancy in wireless networks implementing a CSMA/CA medium access scheme. Our analysis shows that CSMA....../CA is very sensitive to asymmetric channel losses caused by channel conditions. Leveraging this analysis, we present an adaptive channel priority protocol that copes with asymmetric channel losses while being compatible with CSMA/CA. We implement this protocol and perform real-life measurements that (i...

  13. Spatial information is preferentially processed by the distal part of CA3: implication for memory retrieval. (United States)

    Flasbeck, Vera; Atucha, Erika; Nakamura, Nozomu H; Yoshida, Motoharu; Sauvage, Magdalena M


    For the past decades, CA3 was considered as a single functional entity. However, strong differences between the proximal (close to the dentate gyrus) and the distal (close to CA2) parts of CA3 in terms of connectivity patterns, gene expression and electrophysiological properties suggest that it is not the case. We recently showed that proximal CA3 (together with distal CA1) preferentially deals with non-spatial information [1]. In contrast to proximal CA3, distal CA3 mainly receives and predominantly projects to spatially tuned areas. Here, we tested if distal CA3 preferentially processes spatial information, which would suggest a segregation of the spatial information along the proximodistal axis of CA3. We used a high-resolution imaging technique based on the detection of the expression of the immediate-early gene Arc, commonly used to map activity in the medial temporal lobe. We showed that distal CA3 is strongly recruited in a newly designed delayed nonmatching-to-location task with high memory demands in rats, while proximal CA3 is not. These results indicate a functional segregation of CA3 that mirrors the one reported in CA1, and suggest the existence of a distal CA3- proximal CA1 spatial subnetwork. These findings bring further evidence for the existence of 'specialized' spatial and non-spatial subnetworks segregated along the proximodistal axis of the hippocampus and put forward the 'segregated' view of information processing in the hippocampus as a reasonable alternative to the well-accepted 'integrated' view, according to which spatial and non-spatial information are systematically integrated in the hippocampus to form episodic memory. Copyright © 2018. Published by Elsevier B.V.

  14. Carbonic anhydrase II confers resistance to deltamethrin in Culex pipiens pallens. (United States)

    Ye, Wenyun; Zhang, Cheng; Xu, Na; Sun, Yan; Ma, Lei; Shen, Bo; Zhou, Dan; Zhu, Changliang


    Carbonic anhydrases (CAs) are metabolic enzymes that regulate the physiological equilibrium in a variety of organisms. In this study, we investigated the function of CA II in Culex pipiens pallens using real-time quantitative polymerase chain reaction and double-stranded RNA injection. CA II transcripts were more abundant in the deltamethrin-susceptible strain than the deltamethrin-resistant strain. The activities of metabolic enzymes increased when the CA II expression was silenced. These findings suggest CA II regulates deltamethrin resistance by altering metabolic enzyme activity, and could serve as a potential genetic marker for monitoring deltamethrin resistance in mosquitoes. © 2017 Wiley Periodicals, Inc.

  15. Study on the diagnostic value of determination of changes of serum CA125 and CA19-9 levels in patients with endometriosis

    International Nuclear Information System (INIS)

    Liu Aimin


    Objective: To explore the diagnostic value of determination of changes of serum CA125 and CA19-9 levels in patients with endometriosis. Methods: Serum CA125 and CA19-9 levels were determined with RIA in 45 patients with endometriosis and 40 controls. Results: Serum levels of CA125 and CA19-9 in patients with endometriosis (89.63 ± 30.16u/ml and 95.62±43.67u/ml respectively) were significantly higher than those (16.26±6.37u/ml and 20.26±8.25u/ml respectively) in controls (P<0. 001). Sensitivity of CA125 for diagnosis of endometriosis was 77.78% and that of CA19-9 was 62.22%, while the specificity was 92.50% and 90.00% respectively. If we only took the patients with both markers elevated as being diagnostically positive, the sensitivity would naturally be lower (57.78%) but the specificity would be 100%. Levels of the markers were significantly higher in stage III, IV patients than those in patients with stage I, II disease (P<0.01). Conclusion: Combined determination of serum CA125 and CA19-9 levels were of highly specific diagnostic value in patients with endometriosis. (authors)

  16. Activity-Dependent Phosphorylation by CaMKIIδ Alters the Ca2+ Affinity of the Multi-C2-Domain Protein Otoferlin

    Directory of Open Access Journals (Sweden)

    Sandra Meese


    Full Text Available Otoferlin is essential for fast Ca2+-triggered transmitter release from auditory inner hair cells (IHCs, playing key roles in synaptic vesicle release, replenishment and retrieval. Dysfunction of otoferlin results in profound prelingual deafness. Despite its crucial role in cochlear synaptic processes, mechanisms regulating otoferlin activity have not been studied to date. Here, we identified Ca2+/calmodulin-dependent serine/threonine kinase II delta (CaMKIIδ as an otoferlin binding partner by pull-downs from chicken utricles and reassured interaction by a co-immunoprecipitation with heterologously expressed proteins in HEK cells. We confirmed the expression of CaMKIIδ in rodent IHCs by immunohistochemistry and real-time PCR. A proximity ligation assay indicates close proximity of the two proteins in rat IHCs, suggesting that otoferlin and CaMKIIδ also interact in mammalian IHCs. In vitro phosphorylation of otoferlin by CaMKIIδ revealed ten phosphorylation sites, five of which are located within C2-domains. Exchange of serines/threonines at phosphorylated sites into phosphomimetic aspartates reduces the Ca2+ affinity of the recombinant C2F domain 10-fold, and increases the Ca2+ affinity of the C2C domain. Concordantly, we show that phosphorylation of otoferlin and/or its interaction partners are enhanced upon hair cell depolarization and blocked by pharmacological CaMKII inhibition. We therefore propose that otoferlin activity is regulated by CaMKIIδ in IHCs.

  17. Identification of peptides in wheat germ hydrolysate that demonstrate calmodulin-dependent protein kinase II inhibitory activity. (United States)

    Kumrungsee, Thanutchaporn; Akiyama, Sayaka; Guo, Jian; Tanaka, Mitsuru; Matsui, Toshiro


    Hydrolysis of wheat germ by proteases resulted in bioactive peptides that demonstrated an inhibitory effect against the vasoconstrictive Ca(2+)-calmodulin (CaM)-dependent protein kinase II (CaMK II). The hydrolysate by thermolysin (1.0wt%, 5h) showed a particularly potent CaMK II inhibition. As a result of mixed mode high-performance liquid chromatography of thermolysin hydrolysate with pH elution gradient ranging between 4.8 and 8.9, the fraction eluted at pH 8.9 was the most potent CaMK II inhibitor. From this fraction, Trp-Val and Trp-Ile were identified as CaMK II inhibitors. In Sprague-Dawley rats, an enhanced aortic CaMK II activity by 1μM phenylephrine was significantly (p<0.05) suppressed by 15-min incubation with 300μM Trp-Val or Trp-Ile. On the basis of Ca(2+)-chelating fluorescence and CaMK II activity assays, it was concluded that Trp-Val and Trp-Ile competed with Ca(2+)-CaM complex to bind to CaMK II with Ki values of 5.4 and 3.6μM, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Characterization and lead(II), cadmium(II), nickel(II) biosorption of dried marine brown macro algae Cystoseira barbata. (United States)

    Yalçın, Sibel; Sezer, Semih; Apak, Reşat


    The objectives of this research are to identify the functional groups and determine corresponding pK (a) values of the acidic sites on dried brown algae Cystoseira barbata using FTIR and potentiometric titrations, and to investigate the biosorption ability of biomass towards divalent nickel, cadmium, and lead ions. Adsorption was studied as a function of solution pH and contact time, and experimental data were evaluated by the Langmuir isotherm model. CaCl(2) pretreatment was applied to the sorbent for enhancing the metal uptake capacity. The effect of solution pH on biosorption equilibrium was investigated in the pH range of 1.5-5.0. Individual as well as competitive adsorption capacity of the sorbent were studied for metal cations and mixtures. The retention of the tested metal ions was mostly influenced from pH in the range of 1.5-2.5, then stayed almost constant up to 5.0, while Ni(II) uptake showed the highest variation with pH. Potentiometric titrations were performed to find the number of strong and weak acidic groups and their acidity constants. The density of strong and weak acidic functional groups in the biomass were found to be 0.9 and 2.26 mmol/g, respectively. The FTIR spectra of the sorbent samples indicated various functionalities on the biomass surface including carboxyl, hydroxyl, and amino and sulphonate groups which are responsible for the binding of metal ions. The capacity of the biomass for single metal ions (around 1 mmol/g) was increased to 1.3 mmol/g in competitive adsorption, Pb(II) showing the highest Langmuir intensity constant. Considering its extremely high abundance and low cost, C. barbata may be potentially important in metal ion removal from contaminated water and industrial effluents.

  19. EDITORIAL: Strongly correlated electron systems Strongly correlated electron systems (United States)

    Ronning, Filip; Batista, Cristian


    Strongly correlated electrons is an exciting and diverse field in condensed matter physics. This special issue aims to capture some of that excitement and recent developments in the field. Given that this issue was inspired by the 2010 International Conference on Strongly Correlated Electron Systems (SCES 2010), we briefly give some history in order to place this issue in context. The 2010 International Conference on Strongly Correlated Electron Systems was held in Santa Fe, New Mexico, a reunion of sorts from the 1989 International Conference on the Physics of Highly Correlated Electron Systems that also convened in Santa Fe. SCES 2010—co-chaired by John Sarrao and Joe Thompson—followed the tradition of earlier conferences, in this century, hosted by Buzios (2008), Houston (2007), Vienna (2005), Karlsruhe (2004), Krakow (2002) and Ann Arbor (2001). Every three years since 1997, SCES has joined the International Conference on Magnetism (ICM), held in Recife (2000), Rome (2003), Kyoto (2006) and Karlsruhe (2009). Like its predecessors, SCES 2010 topics included strongly correlated f- and d-electron systems, heavy-fermion behaviors, quantum-phase transitions, non-Fermi liquid phenomena, unconventional superconductivity, and emergent states that arise from electronic correlations. Recent developments from studies of quantum magnetism and cold atoms complemented the traditional subjects and were included in SCES 2010. 2010 celebrated the 400th anniversary of Santa Fe as well as the birth of astronomy. So what's the connection to SCES? The Dutch invention of the first practical telescope and its use by Galileo in 1610 and subsequent years overturned dogma that the sun revolved about the earth. This revolutionary, and at the time heretical, conclusion required innovative combinations of new instrumentation, observation and mathematics. These same combinations are just as important 400 years later and are the foundation of scientific discoveries that were discussed

  20. Astragalus Granule Prevents Ca2+ Current Remodeling in Heart Failure by the Downregulation of CaMKII

    Directory of Open Access Journals (Sweden)

    Sinai Li


    Full Text Available Background. Astragalus was broadly used for treating heart failure (HF and arrhythmias in East Asia for thousands of years. Astragalus granule (AG, extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca2+ current (ICa-L in HF mice by the downregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII. Methods. HF mice were induced by thoracic aortic constriction (TAC. After 4 weeks of AG treatment, cardiac function and QT interval were evaluated. Single cardiac ventricular myocyte was then isolated and whole-cell patch clamp was used to record action potential (AP and ICa-L. The expressions of L-type calcium channel alpha 1C subunit (Cav1.2, CaMKII, and phosphorylated protein kinase A (p-PKA were examined by western blot. Results. The failing heart manifested distinct electrical remodeling including prolonged repolarization time and altered ICa-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak ICa-L, accelerated ICa-L inactivation, and positive frequency-dependent ICa-L facilitation. In addition, AG treatment suppressed the overexpression of CaMKII, but not p-PKA, in the failing heart. Conclusion. AG treatment protected the failing heart against electrical remodeling and ICa-L remodeling by downregulating CaMKII.

  1. Sonoma County, CA, 2013 Lidar (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Sonoma County Vegetation Mapping and LiDAR Consortium retained WSI to provide lidar and Orthophoto data and derived products in Sonoma County, CA. A classified LAS...

  2. Physics of Strongly Coupled Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Kraeft, Wolf-Dietrich [Universitat Rostock (Germany)


    Strongly coupled plasmas (or non-ideal plasmas) are multi-component charged many-particle systems, in which the mean value of the potential energy of the system is of the same order as or even higher than the mean value of the kinetic energy. The constituents are electrons, ions, atoms and molecules. Dusty (or complex) plasmas contain still mesoscopic (multiply charged) particles. In such systems, the effects of strong coupling (non-ideality) lead to considerable deviations of physical properties from the corresponding properties of ideal plasmas, i.e., of plasmas in which the mean kinetic energy is essentially larger than the mean potential energy. For instance, bound state energies become density dependent and vanish at higher densities (Mott effect) due to the interaction of the pair with the surrounding particles. Non-ideal plasmas are of interest both for general scientific reasons (including, for example, astrophysical questions), and for technical applications such as inertially confined fusion. In spite of great efforts both experimentally and theoretically, satisfactory information on the physical properties of strongly coupled plasmas is not at hand for any temperature and density. For example, the theoretical description of non-ideal plasmas is possible only at low densities/high temperatures and at extremely high densities (high degeneracy). For intermediate degeneracy, however, numerical experiments have to fill the gap. Experiments are difficult in the region of 'warm dense matter'. The monograph tries to present the state of the art concerning both theoretical and experimental attempts. It mainly includes results of the work performed in famous Russian laboratories in recent decades. After outlining basic concepts (chapter 1), the generation of plasmas is considered (chapter 2, chapter 3). Questions of partial (chapter 4) and full ionization (chapter 5) are discussed including Mott transition and Wigner crystallization. Electrical and

  3. Angiotensin II disrupts inhibitory avoidance memory retrieval. (United States)

    Bonini, Juliana S; Bevilaqua, Lia R; Zinn, Carolina G; Kerr, Daniel S; Medina, Jorge H; Izquierdo, Iván; Cammarota, Martín


    The brain renin-angiotensin system (RAS) is involved in learning and memory, but the actual role of angiotensin II (A(II)) and its metabolites in this process has been difficult to comprehend. This has been so mainly due to procedural issues, especially the use of multi-trial learning paradigms and the utilization of pre-training intracerebroventricular infusion of RAS-acting compounds. Here, we specifically analyzed the action of A(II) in aversive memory retrieval using a hippocampal-dependent, one-trial, step-down inhibitory avoidance task (IA) in combination with stereotaxically localized intrahippocampal infusion of drugs. Rats bilaterally implanted with infusion cannulae aimed to the CA1 region of the dorsal hippocampus were trained in IA and tested for memory retention 24 h later. We found that when given into CA1 15 min before IA memory retention test, A(II), but not angiotensin IV or angiotensin(1-7) induced a dose-dependent and reversible amnesia without altering locomotor activity, exploratory behavior or anxiety state. The effect of A(II) was blocked in a dose-dependent manner by the A(II)-type 2 receptor (AT(2)) antagonist PD123319 but not by the A(II)-type 1 receptor (AT(1)) antagonist losartan. By themselves, neither PD123319 nor losartan had any effect on memory expression. Our data indicate that intra-CA1 A(II) hinders retrieval of avoidance memory through a process that involves activation of AT(2) receptors.

  4. Competition from Cu(II), Zn(II) and Cd(II) in Pb(II) binding to Suwannee River Fulvic Acid

    NARCIS (Netherlands)

    Chakraborty, P.; Chakrabarti, C.L.


    This is a study of trace metal competition in the complexation of Pb(II) by well-characterized humic substances, namely Suwannee River Fulvic Acid (SRFA) in model solutions. It was found that Cu(II) seems to compete with Pb(II) for strong binding sites of SRFA when present at the same concentration

  5. Strongly coupled dust coulomb clusters

    International Nuclear Information System (INIS)

    Juan Wentau; Lai Yingju; Chen Mingheng; I Lin


    The structures and motions of quasi-2-dimensional strongly coupled dust Coulomb clusters with particle number N from few to hundreds in a cylindrical rf plasma trap are studied and compared with the results from the molecular dynamic simulation using more ideal models. Shell structures with periodic packing in different shells and intershell rotational motion dominated excitations are observed at small N. As N increases, the boundary has less effect, the system recovers to the triangular lattice with isotropic vortex type cooperative excitations similar to an infinite N system except the outer shell region. The above generic behaviors are mainly determined by the system symmetry and agree with the simulation results. The detailed interaction form causes minor effect such as the fine structure of packing

  6. Probability densities in strong turbulence (United States)

    Yakhot, Victor


    In this work we, using Mellin’s transform combined with the Gaussian large-scale boundary condition, calculate probability densities (PDFs) of velocity increments P(δu,r), velocity derivatives P(u,r) and the PDF of the fluctuating dissipation scales Q(η,Re), where Re is the large-scale Reynolds number. The resulting expressions strongly deviate from the Log-normal PDF P(δu,r) often quoted in the literature. It is shown that the probability density of the small-scale velocity fluctuations includes information about the large (integral) scale dynamics which is responsible for the deviation of P(δu,r) from P(δu,r). An expression for the function D(h) of the multifractal theory, free from spurious logarithms recently discussed in [U. Frisch, M. Martins Afonso, A. Mazzino, V. Yakhot, J. Fluid Mech. 542 (2005) 97] is also obtained.

  7. Characterization of sulfur mustard resistant keratinocyte cell line HaCaT/SM. (United States)

    Wolf, Markus; Siegert, Markus; Rothmiller, Simone; Scheithauer, Nina; Strobelt, Romano; Steinritz, Dirk; Worek, Franz; Thiermann, Horst; Schmidt, Annette


    The cell line HaCaT/SM was derived from the human keratinocyte cell line HaCaT. HaCaT/SM cells display a high resistance against sulfur mustard (SM). Intention of the presented study was to determine the cellular and molecular differences between HaCaT/SM and HaCaT so as to evaluate which changes might be responsible for being resistant against SM. Both cell lines HaCaT and HaCaT/SM were analyzed with respect to their cell growth, nuclei perimeter, clonogenicity and secretion profile. Moreover DNA alkylation pattern under presence of SM was investigated. In comparison to HaCaT, the HaCaT/SM showed a significant smaller nuclei perimeter. For DNA alkylation a significant difference was observed over time. The clonogenicity of HaCaT/SM was increased to 150%. The secretion profile of these cells demonstrated a strong increase of ANG, PDGF-AA, TIMP1, TIMP2, and a decrease of AREG, CCL5, CXC1, CXC2/3, CXCL6, CXCL7, CXCL8, CXCL10, MIF, Trappin-1. The sulfur mustard (SM) resistant cell line HaCaT/SM demonstrates a wide range of significant differences to their origin cell line HaCaT. These differences might be responsible to provide resistance against SM and might also be useful to establish treatment concepts for humans after SM exposure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Enhanced emission of CaNb2O6: Sm 3 phosphor by codoping Na+ ...

    Indian Academy of Sciences (India)

    Energy transfer between Nb 2 O 6 2 − group and Sm 3 + ion was observed and analysed via luminescence properties. The luminous mechanism was explained by energy level scheme and energy transfer process in CaNb 2 O 6 : x Sm 3 + phosphor. The strong excitation band peaking at ∼407 nm indicated that the CaNb ...

  9. Preparation of 45Ca(HDEHP)n and (CaH{sub 1}50{sub 2})2 samples for liquid scintillation counting, compared to 45caCl{sub 2} results; Preparacion de Ca (HDEHP)n y (C{sub 8}H{sub 1}50{sub 2})2 marcados con 45Ca y estudio comparativo con 4 5ca Cl2 en medidas por centelleo liquido

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, L.; Arcos, J. M. los; Grau Malonda, A.


    A procedure for preparation of liquid scintillation counting organic samples of the Di-2-ethylhexyl phosphate calcium complex and the 2-ethylhexanoate calcium salt, labelled with 45Ca, is described. The chemical quench, the counting stability and spectral evolution of both compounds is studied in six scintillators,Toluene-alcohol, Dioxane-naphtalene, Hi safe II, Ultimate-Gold and Instagel, and compared to results obtained from a commercial solution of 4 5CaCl2. (Author) 7 refs.

  10. Parallel activation of field CA2 and dentate gyrus by synaptically elicited perforant path volleys. (United States)

    Bartesaghi, Renata; Gessi, Tiziana


    Previous studies showed that dorsal psalterium (PSD) volleys to the entorhinal cortex (ENT) activated in layer II perforant path neurons projecting to the dentate gyrus. The discharge of layer II neurons was followed by the sequential activation of the dentate gyrus (DG), field CA3, field CA1. The aim of the present study was to ascertain whether in this experimental model field, CA2, a largely ignored sector, is activated either directly by perforant path volleys and/or indirectly by recurrent hippocampal projections. Field potentials evoked by single-shock PSD stimulation were recorded in anesthetized guinea pigs from ENT, DG, fields CA2, CA1, and CA3. Current source-density (CSD) analysis was used to localize the input/s to field CA2. The results showed the presence in field CA2 of an early population spike superimposed on a slow wave (early response) and of a late and smaller population spike, superimposed on a slow wave (late response). CSD analysis during the early CA2 response showed a current sink in stratum lacunosum-moleculare, followed by a sink moving from stratum radiatum to stratum pyramidale, suggesting that this response represented the activation and discharge of CA2 pyramidal neurons, mediated by perforant path fibers to this field. CSD analysis during the late response showed a current sink in middle stratum radiatum of CA2 followed by a sink moving from inner stratum radiatum to stratum pyramidale, suggesting that this response was mediated by Schaffer collaterals from field CA3. No early population spike was evoked in CA3. However, an early current sink of small magnitude was evoked in stratum lacunosum-moleculare of CA3, suggesting the presence of synaptic currents mediated by perforant path fibers to this field. The results provide novel information about the perforant path system, by showing that dorsal psalterium volleys to the entorhinal cortex activate perforant path neurons that evoke the parallel discharge of granule cells and CA2

  11. Influence of initial CaO/SiO2 ratio on the hydration of rice husk ash-Ca(OH2 and sugar cane bagasse ash-Ca(OH2 pastes

    Directory of Open Access Journals (Sweden)

    Lourdes Maria Silva de Souza


    Full Text Available This work presents the results of a study on the hydration of pastes containing calcium hydroxide and either rice husk ash (RHA or sugar cane bagasse ash (SCBA in various initial CaO/SiO2 molar ratios. The products of the reactions were characterized by thermal analyses X-ray diffraction, and scanning electron microscopy. In the case of the RHA pastes, the product was composed of CaO-SiO2-H2O (type I C-S-H or CaO-SiO2-H2O (type II C-S-H according to the CaO/SiO2 ratio of the mixture. In contrast, in the case of the SBCA pastes, the product was composed primarily of CaO-SiO2-H2O that differed from both the previous types; the product also contained inclusions of calcium aluminate hydrates.

  12. Ca2+-activated force-generating properties of mammalian skeletal muscle fibres: histochemically identified single peeled rabbit fibres. (United States)

    Donaldson, S K


    Single peeled (sarcolemma removed) rabbit skeletal muscle fibres, identified histochemically from their myofibrillar ATPase and oxidative staining patterns, were characterized according to their Ca2+-activated steady-state force-generating properties at normal intracellular pH (7.0) and under acidotic (pH 6.5) conditions. Maximum force-generating capacity of each fibre was assessed by measuring steady-state isometric force generation at saturating Ca2+ concentration at both pH values. The Ca2+ sensitivity of each fibre was ascertained by determining the percentage of maximum force generated at each of several subsaturating Ca2+ concentrations at both pH values. Fibres were selected from soleus, tibialis anterior and adductor magnus muscles. At subsaturating Ca2+ concentrations only two functional groups of fibres were distinguishable, corresponding to the histochemical classifications type I and type II. Type I fibres were more sensitive to Ca2+ and less depressed by acidosis than type II fibres in the subsaturating range of Ca2+ concentrations. At saturating Ca2+ concentrations, the acidotic depression of maximum force was significantly less for type I fibres than type II nonoxidative fibres regardless of their muscle of origin. Type II oxidative fibre maximum force properties depended upon the muscle of origin and demonstrated subgroups of these fibres that were different from type II nonoxidative fibres and similar to type I fibres.

  13. Ca isotopic geochemistry of an Antarctic aquatic system (United States)

    Lyons, W. Berry; Bullen, Thomas D.; Welch, Kathleen A.


    The McMurdo Dry Valleys, Antarctica, are a polar desert ecosystem. The hydrologic system of the dry valleys is linked to climate with ephemeral streams that flow from glacial melt during the austral summer. Past climate variations have strongly influenced the closed-basin, chemically stratified lakes on the valley floor. Results of previous work point to important roles for both in-stream processes (e.g., mineral weathering, precipitation and dissolution of salts) and in-lake processes (e.g., mixing with paleo-seawater and calcite precipitation) in determining the geochemistry of these lakes. These processes have a significant influence on calcium (Ca) biogeochemistry in this aquatic ecosystem, and thus variations in Ca stable isotope compositions of the waters can aid in validating the importance of these processes. We have analyzed the Ca stable isotope compositions of streams and lakes in the McMurdo Dry Valleys. The results validate the important roles of weathering of aluminosilicate minerals and/or CaCO3 in the hyporheic zone of the streams, and mixing of lake surface water with paleo-seawater and precipitation of Ca-salts during cryo-concentration events to form the deep lake waters. The lakes in the McMurdo Dry Valleys evolved following different geochemical pathways, evidenced by their unique, nonsystematic Ca isotope signatures.

  14. Strong Ideal Convergence in Probabilistic Metric Spaces

    Indian Academy of Sciences (India)

    In the present paper we introduce the concepts of strongly ideal convergent sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and establish some basic facts. Next, we define the strong ideal limit points and the strong ideal cluster points of a sequence in this ...

  15. Strong ideal convergence in probabilistic metric spaces

    Indian Academy of Sciences (India)

    In the present paper we introduce the concepts of strongly ideal convergent sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and establish some basic facts. Next, we define the strong ideal limit points and the strong ideal cluster points of a sequence in this ...


    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hsin-Wei; Lee, Typhoon; Lee, Der-Chuen; Chen, Jiang-Chang, E-mail: [Institute of Earth Sciences, Academia Sinica, Taipei, Taiwan, ROC (China)


    Precise determinations of {sup 48}Ca anomalies in Allende calcium–aluminum-rich inclusions (CAIs) are reported in this work. There are endemic positive {sup 48}Ca/{sup 44}Ca anomalies in all analyzed CAIs after normalization to {sup 42}Ca/{sup 44}Ca, and it is clearly shown that there is no simple correlation between {sup 48}Ca/{sup 44}Ca and {sup 50}Ti/{sup 48}Ti anomalies, in agreement with Jungck et al. Compared to the {sup 48}Ca/{sup 44}Ca versus {sup 50}Ti/{sup 48}Ti correlation line defined by differentiated meteorites, reported by Chen et al., the CAIs plot to elevated {sup 50}Ti/{sup 48}Ti. Assuming the {sup 48}Ca/{sup 44}Ca anomalies of both CAIs and differentiated meteorites came from the same source, excess {sup 50}Ti anomalies in CAIs can be calculated by subtracting the part associated with {sup 48}Ca/{sup 44}Ca. These excesses show a linear correlation with {sup 138}La anomalies, a neutrino-process nuclide. According to current stellar nucleosynthetic models, we therefore suggest that the solar system {sup 48}Ca, {sup 50}Ti, and {sup 138}La isotopic variations are made of mixtures between grains condensed from ejecta of neutron-rich accretion-induced SNe Ia and the O/Ne–O/C zone of core-collapse SNe II.

  17. Vortex-lattice states at strong magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Akera, H.; MacDonald, A.H.; Girvin, S.M. (Department of Physics, Indiana University, Bloomington, Indiana (USA)); Norman, M.R. (Materials Science Division, Argonne National Laboratory, Argonne, Illinois (USA))


    At strong magnetic fields, Landau quantization invalidates the semiclassical approximations which underly the Ginzburg-Landau (GL) theory of the mixed states of type-II superconductors. We have solved the {ital microscopic} mean-field equations for the case of a two-dimensional electron system in the strong magnetic-field limit. For delta-function attractive interactions there exist {ital n}+1 pairing channels in the {ital n}th Landau level. For {ital n}{gt}0, two channels share the maximum {ital T}{sub {ital c}}, and the order parameter differs markedly from expectations based on GL theory.

  18. Remnants of strong tidal interactions

    International Nuclear Information System (INIS)

    Mcglynn, T.A.


    This paper examines the properties of stellar systems that have recently undergone a strong tidal shock, i.e., a shock which removes a significant fraction of the particles in the system, and where the shocked system has a much smaller mass than the producer of the tidal field. N-body calculations of King models shocked in a variety of ways are performed, and the consequences of the shocks are investigated. The results confirm the prediction of Jaffe for shocked systems. Several models are also run where the tidal forces on the system are constant, simulating a circular orbit around a primary, and the development of tidal radii under these static conditions appears to be a mild process which does not dramatically affect material that is not stripped. The tidal radii are about twice as large as classical formulas would predict. Remnant density profiles are compared with a sample of elliptical galaxies, and the implications of the results for the development of stellar populations and galaxies are considered. 38 refs

  19. John Strong - 1941-2006

    CERN Document Server


    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on 31 July, a few days before his 65th birthday. John started his career and obtained his PhD in a group from Westfield College, initially working on experiments at Rutherford Appleton Laboratory (RAL). From the early 1970s onwards, however, his research was focused on experiments in CERN, with several particularly notable contributions. The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras (a type of television camera) to record the sparks in the spark chambers. This highly automated system allowed Omega to be used in a similar way to bubble chambers. He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems. In these experiments the Westfield group joined forces with Italian colleagues to measure the form factors of the pion and the kaon, and the lifetime of some of the newly discovered charm particles. Such h...

  20. Strong seismic ground motion propagation

    International Nuclear Information System (INIS)

    Seale, S.; Archuleta, R.; Pecker, A.; Bouchon, M.; Mohammadioun, G.; Murphy, A.; Mohammadioun, B.


    At the McGee Creek, California, site, 3-component strong-motion accelerometers are located at depths of 166 m, 35 m and 0 m. The surface material is glacial moraine, to a depth of 30.5 m, overlying homfels. Accelerations were recorded from two California earthquakes: Round Valley, M L 5.8, November 23, 1984, 18:08 UTC and Chalfant Valley, M L 6.4, July 21, 1986, 14:42 UTC. By separating out the SH components of acceleration, we were able to determine the orientations of the downhole instruments. By separating out the SV component of acceleration, we were able to determine the approximate angle of incidence of the signal at 166 m. A constant phase velocity Haskell-Thomson model was applied to generate synthetic SH seismograms at the surface using the accelerations recorded at 166 m. In the frequency band 0.0 - 10.0 Hz, we compared the filtered synthetic records to the filtered surface data. The onset of the SH pulse is clearly seen, as are the reflections from the interface at 30.5 m. The synthetic record closely matches the data in amplitude and phase. The fit between the synthetic accelerogram and the data shows that the seismic amplification at the surface is a result of the contrast of the impedances (shear stiffnesses) of the near surface materials

  1. Large magnetoresistance in La-Ca-Mn-O films

    International Nuclear Information System (INIS)

    Chen, L.H.; Jin, S.; Tiefel, T.H.; Ramesh, R.; Schurig, D.


    A very large magnetoresistance value in excess of 10 6 % has been obtained at 110 K, H = 6 T in La-Ca-Mn-O thin films epitaxially grown on LaAlO 3 substrates by pulsed laser deposition. The as-deposited film exhibits a substantial magnetoresistance value of 39,000%, which is further improved by heat treatment. A strong dependence of the magnetoresistance on film thickness was observed, with the value reduced by orders of magnitude when the film is made thicker than ∼2,000 angstrom. This behavior is interpreted in terms of lattice strain in the La-Ca-Mn-O films

  2. Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia (United States)

    Vincent, Kevin P.; McCulloch, Andrew D.; Edwards, Andrew G.


    Calcium/calmodulin-dependent protein kinase II (CaMKII) activity has been shown to contribute to arrhythmogenesis in a remarkably broad range of cardiac pathologies. Several of these involve significant structural and electrophysiologic remodeling, whereas others are due to specific channelopathies, and are not typically associated with arrhythmogenic changes to protein expression or cellular and tissue structure. The ability of CaMKII to contribute to arrhythmia across such a broad range of phenotypes suggests one of two interpretations regarding the role of CaMKII in cardiac arrhythmia: (1) some CaMKII-dependent mechanism is a common driver of arrhythmia irrespective of the specific etiology of the disease, or (2) these different etiologies expose different mechanisms by which CaMKII is capable of promoting arrhythmia. In this review, we dissect the available mechanistic evidence to explore these two possibilities and discuss how the various molecular actions of CaMKII promote arrhythmia in different pathophysiologic contexts. PMID:24994983

  3. Copper (II)

    African Journals Online (AJOL)


    ABSTRACT: A Schiff base was prepared from the reaction of 2 - amino - 3 – methylbutanoic acid and 2, 4 - pentanedione. The reaction of the prepared Schiff base with ethanolic solution of copper (II) chloride formed diaquo bis( N – 2 – amino – 3 - methylbutyl - 2, 4 - pentanedionato) copper (II) complex. The Schiff base is ...

  4. Altered Ca2+ kinetics associated with α-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution.

    Directory of Open Access Journals (Sweden)

    Stewart I Head

    Full Text Available Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i an increased rate of decay of the twitch transient; (ii a fourfold increase in the rate of SR Ca2+ leak; (iii a threefold increase in the rate of SR Ca2+ pumping; and (iv enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments

  5. Strongly interacting photons and atoms

    International Nuclear Information System (INIS)

    Alge, W.


    This thesis contains the main results of the research topics I have pursued during the my PhD studies at the University of Innsbruck and partly in collaboration with the Institut d' Optique in Orsay, France. It is divided into three parts. The first and largest part discusses the possibility of using strong standing waves as a tool to cool and trap neutral atoms in optical cavities. This is very important in the field of nonlinear optics where several successful experiments with cold atoms in cavities have been performed recently. A discussion of the optical parametric oscillator in a regime where the nonlinearity dominates the evolution is the topic of the second part. We investigated mainly the statistical properties of the cavity output of the three interactive cavity modes. Very recently a system has been proposed which promises fantastic properties. It should exhibit a giant Kerr nonlinearity with negligible absorption thus leading to a photonic turnstile device based on cold atoms in cavity. We have shown that this model suffers from overly simplistic assumptions and developed several more comprehensive approaches to study the behavior of this system. Apart from the division into three parts of different contents the thesis is divided into publications, supplements and invisible stuff. The intention of the supplements is to reach researchers which work in related areas and provide them with more detailed information about the concepts and the numerical tools we used. It is written especially for diploma and PhD students to give them a chance to use the third part of our work which is actually the largest one. They consist of a large number of computer programs we wrote to investigate the behavior of the systems in parameter regions where no hope exists to solve the equations analytically. (author)

  6. Topics in strong Langmuir turbulence

    International Nuclear Information System (INIS)

    Skoric, M.M.


    This thesis discusses certain aspects of the turbulence of a fully ionised non-isothermal plasma dominated by the Langmuir mode. Some of the basic properties of strongly turbulent plasmas are reviewed. In particular, interest is focused on the state of Langmuir turbulence, that is the turbulence of a simple externally unmagnetized plasma. The problem of the existence and dynamics of Langmuir collapse is discussed, often met as a non-linear stage of the modulational instability in the framework of the Zakharov equations (i.e. simple time-averaged dynamical equations). Possible macroscopic consequences of such dynamical turbulent models are investigated. In order to study highly non-linear collapse dynamics in its advanced stage, a set of generalized Zakharov equations are derived. Going beyond the original approximation, the author includes the effects of higher electron non-linearities and a breakdown of slow-timescale quasi-neutrality. He investigates how these corrections may influence the collapse stabilisation. Recently, it has been realised that the modulational instability in a Langmuir plasma will be accompanied by the collisionless-generation of a slow-timescale magnetic field. Accordingly, a novel physical situation has emerged which is investigated in detail. The stability of monochromatic Langmuir waves in a self-magnetized Langmuir plasma, is discussed, and the existence of a novel magneto-modulational instability shown. The wave collapse dynamics is investigated and a physical interpretation of the basic results is given. A problem of the transient analysis of an interaction of time-dependent electromagnetic pulses with linear cold plasma media is investigated. (Auth.)

  7. Promoting Strong Written Communication Skills (United States)

    Narayanan, M.


    The reason that an improvement in the quality of technical writing is still needed in the classroom is due to the fact that universities are facing challenging problems not only on the technological front but also on the socio-economic front. The universities are actively responding to the changes that are taking place in the global consumer marketplace. Obviously, there are numerous benefits of promoting strong written communication skills. They can be summarized into the following six categories. First, and perhaps the most important: The University achieves learner satisfaction. The learner has documented verbally, that the necessary knowledge has been successfully acquired. This results in learner loyalty that in turn will attract more qualified learners.Second, quality communication lowers the cost per pupil, consequently resulting in increased productivity backed by a stronger economic structure and forecast. Third, quality communications help to improve the cash flow and cash reserves of the university. Fourth, having high quality communication enables the university to justify the need for high costs of tuition and fees. Fifth, better quality in written communication skills result in attracting top-quality learners. This will lead to happier and satisfied learners, not to mention greater prosperity for the university as a whole. Sixth, quality written communication skills result in reduced complaints, thus meaning fewer hours spent on answering or correcting the situation. The University faculty and staff are thus able to devote more time on scholarly activities, meaningful research and productive community service. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate.Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., & Winter, J. (1997). Mastering change: Learning the lessons of the enterprise.London: Department for Education and Employment. Buzzel, Robert D., and Bradley T. Gale. (1987

  8. Postsynaptic GABA(B Receptors Contribute to the Termination of Giant Depolarizing Potentials in CA3 Neonatal Rat Hippocampus

    Directory of Open Access Journals (Sweden)

    Ilgam Khalilov


    Full Text Available During development, hippocampal CA3 network generates recurrent population bursts, so-called Giant Depolarizing Potentials (GDPs. GDPs are characterized by synchronous depolarization and firing of CA3 pyramidal cells followed by afterhyperpolarization (GDP-AHP. Here, we explored the properties of GDP-AHP in CA3 pyramidal cells using gramicidin perforated patch clamp recordings from neonatal rat hippocampal slices. We found that GDP-AHP occurs independently of whether CA3 pyramidal cells fire action potentials (APs or remain silent during GDPs. However, the amplitude of GDP-AHP increased with the number of APs the cells fired during GDPs. The reversal potential of the GDP-AHP was close to the potassium equilibrium potential. During voltage-clamp recordings, current-voltage relationships of the postsynaptic currents activated during GDP-AHP were characterized by reversal near the potassium equilibrium potential and inward rectification, similar to the responses evoked by the GABA(B receptor agonists. Finally, the GABA(B receptor antagonist CGP55845 strongly reduced GDP-AHP and prolonged GDPs, eventually transforming them to the interictal and ictal-like discharges. Together, our findings suggest that the GDP-AHP involves two mechanisms: (i postsynaptic GABA(B receptor activated potassium currents, which are activated independently on whether the cell fires or not during GDPs; and (ii activity-dependent, likely calcium activated potassium currents, whose contribution to the GDP-AHP is dependent on the amount of firing during GDPs. We propose that these two complementary inhibitory postsynaptic mechanisms cooperate in the termination of GDP.

  9. Ca2+ signalling and early embryonic patterning during zebrafish development. (United States)

    Webb, Sarah E; Miller, Andrew L


    1. It has been proposed that Ca2+ signalling, in the form of pulses, waves and steady gradients, may play a crucial role in key pattern-forming events during early vertebrate development. 2. With reference to the embryo of the zebrafish (Danio rerio), herein we review the Ca2+ transients reported from the cleavage to segmentation periods. This time-window includes most of the major pattern-forming events of early development, which transform a single-cell zygote into a complex multicellular embryo with established primary germ layers and body axes. 3. Data are presented to support our proposal that intracellular Ca2+ waves are an essential feature of embryonic cytokinesis and that propagating intercellular Ca2+ waves (both long and short range) may play a crucial role in: (i) the establishment of the embryonic periderm and the coordination of cell movements during epiboly, convergence and extension; (ii) the establishment of the basic embryonic axes and germ layers; and (iii) definition of the morphological boundaries of specific tissue domains and embryonic structures, including future organ anlagen. 4. The potential downstream targets of these Ca2+ transients are also discussed, as well as how they may integrate with other pattern-forming signalling pathways known to modulate early developmental events.

  10. Vibrational spectroscopic study of poldervaartite CaCa[SiO3(OH)(OH) (United States)

    Frost, Ray L.; López, Andrés; Scholz, Ricardo; Lima, Rosa Malena Fernandes


    We have studied the mineral poldervaartite CaCa[SiO3(OH)(OH)] which forms a series with its manganese analogue olmiite CaMn[SiO3(OH)](OH) using a range of techniques including scanning electron microscopy, thermogravimetric analysis, Raman and infrared spectroscopy. Chemical analysis shows the mineral is reasonably pure and contains only calcium and manganese with low amounts of Al and F. Thermogravimetric analysis proves the mineral decomposes at 485 °C with a mass loss of 7.6% compared with the theoretical mass loss of 7.7%. A strong Raman band at 852 cm-1 is assigned to the SiO stretching vibration of the SiO3(OH) units. Two Raman bands at 914 and 953 cm-1 are attributed to the antisymmetric vibrations. Intense prominent peaks observed at 3487, 3502, 3509, 3521 and 3547 cm-1 are assigned to the OH stretching vibration of the SiO3(OH) units. The observation of multiple OH bands supports the concept of the non-equivalence of the OH units. Vibrational spectroscopy enables a detailed assessment of the molecular structure of poldervaartite.

  11. Sub-barrier fusion and transfers in the 40Ca + 58,64Ni systems

    Directory of Open Access Journals (Sweden)

    Bourgin D.


    Full Text Available Fusion cross sections have been measured in the 40Ca + 58Ni and 40Ca + 64Ni systems at energies around and below the Coulomb barrier. The 40Ca beam was delivered by the XTU Tandem accelerator of the Laboratori Nazionali di Legnaro and evaporation residues were measured at very forward angles with the LNL electrostatic beam deflector. Coupled-channels calculations were performed which highlight possible strong effects of neutron transfers on the fusion below the barrier in the 40Ca + 64Ni system. Microscopic time-dependent Hartree-Fock calculations have also been performed for both systems. Preliminary results are shown.

  12. Effects of Ca antagonists on Ca fluxes in resistance vessels

    International Nuclear Information System (INIS)

    Cauvin, C.; Saida, K.; van Breemen, C.


    Researchers have examined contractions and 45 Ca fluxes induced by norepinephrine (NE) and 80 mM potassium (high K) depolarization and their inhibition by dilitazem in rabbit mesenteric resistance vessels. Contraction induced by both NE and high K depended almost completely on extracellular Ca. Dose-response curves for diltiazem inhibition of NE (10(-5) M) and high K contractions showed ED50 values of 1 X 10(-8) and 6 X 10(-7) M, respectively, indicating that the receptor-operated channel (ROC) was more sensitive than the potential-operated channel (POC) to the action of diltiazem. Diltiazem (10(-6) M) was shown to inhibit NE- and 80 mM K-stimulated 45 Ca influx effectively by 87 +/- 15 and 85 +/- 10%, respectively. Comparison of these data to those obtained from aorta suggest that although the sensitivity of the POC is approximately the same in aorta and mesenteric resistance vessels, the sensitivity of the ROC is much greater in the latter. This increased sensitivity is paralleled by a greatly decreased role of intracellular Ca release in NE contraction in mesenteric resistance vessels

  13. Total synthesis of all stereoisomers of eudesm-II-en-4-ol

    NARCIS (Netherlands)

    Kesselmans, R.P.W.


    In this thesis the total synthesis of all stereoisomers of eudesm-11-en-4-ol e.g. selin-11-en-4α-ol <strong>I> , intermedeol <strong>II> , neointermedeol <strong>III> , paradisiol <strong>IV> , amiteol

  14. CaMKII inhibition promotes neuronal apoptosis by transcriptionally upregulating Bim expression. (United States)

    Zhao, Yiwei; Zhu, Lin; Yu, Shaojun; Zhu, Jing; Wang, Chong


    The effects of Ca/calmodulin-dependent protein kinase II (CaMKII) on neuronal apoptosis are complex and contradictory, and the underlying mechanisms remain unclear. Bcl-2-interacting mediator of cell death (Bim) is an important proapoptotic protein under many physiological and pathophysiological conditions. However, there is no evidence that CaMKII and Bim are mechanistically linked in neuronal apoptosis. In this study, we showed that CaMKII inhibition by the inhibitors KN-62 and myristoylated autocamtide-2-related inhibitory peptide promoted apoptosis in cerebellar granule neurons in a dose-dependent manner. CaMKII inhibition increased Bim protein and messenger RNA levels. The expression of early growth response factor-1, a transcription factor of Bim, was also induced by CaMKII inhibitors. These data suggested that CaMKII repressed the transcriptional expression of Bim. Moreover, knockdown of Bim using small interfering RNAs attenuated the proapoptotic effects of CaMKII inhibition. Taken together, this is the first report to show that CaMKII inhibition transcriptionally upregulates Bim expression to promote neuronal apoptosis, providing new insights into the proapoptotic mechanism of CaMKII inhibition.

  15. Bound states in strongly correlated magnetic and electronic systems

    International Nuclear Information System (INIS)

    Trebst, S.


    A novel strong coupling expansion method to calculate two-particle spectra of quantum lattice models is developed. The technique can be used to study bosonic and fermionic models and in principle it can be applied to systems in any dimension. A number of strongly correlated magnetic and electronic systems are examined including the two-leg spin-half Heisenberg ladder, the dimerized Heisenberg chain with a frustrating next-nearest neighbor interaction, coupled Heisenberg ladders, and the one-dimensional Kondo lattice model. In the various models distinct bound states are found below the two-particle continuum. Quantitative calculations of the dispersion, coherence length and binding energy of these bound states are used to describe spectroscopic experiments on (Ca,La) 14 Cu 24 O 41 and NaV 2 O 5 . (orig.)

  16. Level and evaluation of tumor marker CA-125 in ovarian cancer patients in Khyber Pakhtunkhwa, Pakistan. (United States)

    Ahmad, Bashir; Nawaz, Seema; Ali, Sajid; Bashir, Shumaila; Mahmood, Nourin; Gul, Bushra


    Due to the increase in morbidity and mortality rate, cancer has become an alarming threat to the human population worldwide. Since cancer is a progressive disorder, timely diagnosis is necessary to prevent/stop cancer from progressing to a severe stage. In Khyber Paktunkhwa, Pakistan, many tumors are diagnosed with endoscopy and biopsy; rare studies exist regarding the diagnosis and evaluation of ovarian cancer, based on tumor markers like CA-125. The objectives of this study were to investigate and evaluate levels of CA-125 in hospitalized ovarian cancer patients. In this study, a total of 63 admitted patients having ovarian cancer by biopsy were included. The level of CA-125 was determined in the blood of these patients using ELISA technique. Out of 63 patients, the level of CA-125 was high in 52% . The affected individuals were more in the group of 40-60 and the level of CA-125 was comparatively higher in patients having moderately differentiated histology than those having well differentiated and poorly differentiated tumor histology. Moreover, the highest level of CA-125 was present among the patients having serous subtype of carcinoma and the common stage of carcinoma was stage II followed by stage III, I and IV. CA-125 level was high in more than 50% of the total patients. Moreover, CA-125 elevation was more common in serous subtype and stage II cancer patients.

  17. Spins, moments and charge radii beyond $^{48}$Ca

    CERN Multimedia

    Neyens, G; Rajabali, M M; Hammen, M; Blaum, K; Froemmgen, N E; Garcia ruiz, R F; Kreim, K D; Budincevic, I

    Laser spectroscopy of $^{49-54}$Ca is proposed as a continuation of the experimental theme initiated with IS484 “Ground-state properties of K-isotopes from laser and $\\beta$-NMR spectroscopy” and expanded in INTC-I-117 “Moments, Spins and Charge Radii Beyond $^{48}$Ca.” It is anticipated that the charge radii of these isotopes can show strong evidence for the existence of a sub-shell closure at N=32 and could provide a first tentative investigation into the existence of a shell effect at N=34. Furthermore the proposed experiments will simultaneously provide model-independent measurements of the spins, magnetic moments and quadrupole moments of $^{51,53}$Ca permitting existing and future excitation spectra to be pinned to firm unambiguous ground states.

  18. CA125 in ovarian cancer

    DEFF Research Database (Denmark)

    Duffy, M J; Bonfrer, J M; Kulpa, J


    value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal...

  19. Tissue expression of CA 125 in benign and malignant lesions of ovary and fallopian tube: a comparison with CA 19-9 and CEA. (United States)

    Neunteufel, W; Breitenecker, G


    Sections of formalin-fixed and paraffin-embedded tissue specimens of 11 normal ovaries and tubes, 13 tubo-ovarian abscesses, 3 tubal carcinomas, and 115 ovarian tumors were investigated by immunohistochemistry. CA 125 and CA 19-9 were demonstrated with monoclonal antibodies, CEA with polyclonal antibodies. The tissue expression was visualized by the avidin-biotin method. In the germinal epithelium of all ovaries no tumor marker was confirmed. In 4 out of 11 tubes the epithelium was CA 125 positive, in 2 out of 11 cases CA 19-9 positive. Nine out of 13 tubo-ovarian abscesses were CA 125 and 5 out of 13 were CA 19-9 positive in their epithelium. Elevated serum levels of these markers might be due to expression via the epithelial cell of the inflamed tube. All normal and inflammatory adnexal tissues were CEA negative. In serous tumors and undifferentiated carcinomas, CA 125 was most frequently confirmed (85 and 70%, respectively). All mucinous tumors were CA 125 negative. The most frequently confirmed tumor marker was CA 19-9 (77%). In endometrioid tumors, CEA was most frequent (44%). In 42% of the borderline tumors and carcinomas only one marker was demonstrated, in 7% none. Here, immunohistochemistry may indicate the most adequate marker. Tumor marker expression was markedly heterogenous: tumor areas with strong, weak, and no reaction were adjacent. The tumor markers revealed no specificity for malignancy or disease.

  20. Control of ciliary motility by Ca2+: Integration of Ca2+-dependent functions and targets for Ca2+ action

    International Nuclear Information System (INIS)

    Evans, T.C.


    To identify functions that regulate Ca 2+ -induced ciliary reversal in Paramecium, mutants defective in terminating depolarization-induced backward swimming were selected. Six independent recessive mutations (k-shy) comprising two complementation groups, k-shyA and k-shyB, were identified. All mutants exhibited prolonged backward swimming in depolarizing solutions. Voltage clamp studies revealed that mutant Ca 2+ current amplitudes were reduced, but could be restored to wild type levels by EGTA injection. The recovery of the mutant Ca 2+ current from Ca 2+ -dependent inactivation, and the decay of the Ca 2+ -dependent K + and Ca 2+ -dependent Na + currents after depolarization were slow in k-shy compared to wild type. To identify protein targets of Ca 2+ action, ciliary proteins that interact with calmodulin (CaM) were characterized. With a 125 I-CaM blot assay, several CaM-binding proteins were identified including axonemal, soluble, and membrane-bound polypeptides. Competitive displacement studies with unlabeled Paramecium CaM, bovine CaM, and troponinC suggested that both protein types bind CaM with high affinity and specificity. To examine the presence of CaM-binding sites in intact axonemes, a filtration binding assay was developed

  1. Ca isotopic fractionation patterns in forest ecosystems (United States)

    Kurtz, A. C.; Takagi, K.


    Calcium stable isotope ratios are an emerging tracer of the biogeochemical cycle of Ca that are just beginning to see significant application to forest ecosystems. The primary source of isotopic fractionation in these systems is discrimination against light Ca during uptake by plant roots. Cycling of vegetation-fractionated Ca establishes isotopically distinct Ca pools within a forest ecosystem. In some systems, the shallow soil exchangeable Ca pool is isotopically heavy relative to Ca inputs. This has been explained by preferential removal of light Ca from the soil. In other systems, the soil exchange pool is isotopically light relative to inputs, which is explained by recycling of plant-fractionated light Ca back into soil. Thus vegetation uptake of light Ca has been called on to account for both isotopically heavy and light Ca in the shallow soil exchange pools. We interpret patterns in ecosystem δ44Ca with the aid of a simple box model of the forest Ca cycle. We suggest that the δ44Ca of exchangeable Ca in the shallow soil pool primarily reflects the relative magnitude of three key fluxes in a forest Ca cycle, 1) the flux of external Ca into the system via weathering or atmospheric deposition, 2) the uptake flux of Ca from soils into the vegetation pool, and 3) the return flux of Ca to shallow soils via remineralization of leaf litter. Two observations that emerge from our model may aid in the application of Ca isotopes to provide insight into the forest Ca cycle. First, regardless of the magnitude of both vegetation Ca uptake and isotopic fractionation, the δ44Ca of the soil exchange pool will equal the input δ44Ca unless the plant uptake and remineralization fluxes are out of balance. A second observation is that the degree to which the shallow soil exchange pool δ44Ca can differ from the input ratio is controlled by the relative rates of biological uptake and external Ca input. Significant differences between soil exchange and input δ44Ca are seen only

  2. Control of temperature and aqueous Mg2+/Ca2+ ratio on the (trans-)formation of ikaite (United States)

    Purgstaller, B.; Dietzel, M.; Baldermann, A.; Mavromatis, V.


    The calcium carbonate hexahydrate mineral ikaite (CaCO3 ṡ 6 H2O) has been documented in aquatic environments at near-freezing temperatures. An increase of the prevailing temperature in the depositional environment, results in the transformation of natural ikaite into less soluble calcium carbonate phases occasionally leaving calcite pseudomorphs in the sediments, which are considered as an indicator for primary cold water temperatures. Detailed understanding on the physicochemical parameters controlling ikaite (trans-)formation however, such as temperature and reactive solution chemical composition, are still under debate. In order to study the formation of ikaite, we conducted precipitation experiments under controlled physicochemical conditions (pH = 8.3 ± 0.1; T = 6, 12, and 18 ± 0.1 °C) at defined aqueous molar Mg/Ca ratios. The transformation of ikaite into anhydrous calcium carbonate polymorphs was investigated in solution and at air exposure. The obtained results reveal the formation of ikaite at temperatures up to 12 °C, whereas Mg-rich amorphous calcium carbonate precipitated at 18 °C. In contact with the reactive solution ikaite transformed into aragonite at aqueous molar Mg2+/Ca2+ ratios of ≥14. In contrast, ikaite separated from the Mg-rich solution and exposed to air transformed in all cases into calcite/vaterite. The herein obtained temperature limit of ≤12 for ikaite formation is significantly higher than formerly expected and most probably caused by (i) the high saturation degree of the solution with respect to ikaite and (ii) the slow dehydration of the aqueous Ca2+ ion at low temperatures. This result questions the suitability of calcite pseudomorphs (i.e. glendonites) as a proxy for near-freezing temperatures. Moreover, our findings show that the CaCO3 polymorph formed from ikaite is strongly controlled by the physicochemical conditions, such as aqueous molar Mg2+/Ca2+ ratio of the reactive fluid and H2O availability throughout the

  3. Emission-Line Studies of Young Stars. II. The Herbig Ae/Be Stars (United States)

    Hamann, Fred; Persson, S. E.


    We present optical emission-line data for a sample of 32 Herbig Ae/Be stars. Many of the Herbig stars have line spectra similar to the "classical" (strong Hα) T Tauri stars. The Herbig stars with the most T Tauri-like characteristics are the ones that also have direct evidence for outflow in their spectra, e.g., P Cygni profiles or broad or blueshifted forbidden lines. Among the similarities derived from the Ca II triplet lines are space densities of ≳1011-3, column densities of Nβ ≳ 1021 cm-3, and optically thick emitting areas that can be several times larger than the stars. The triplet line profiles also suggest similar dynamical environments. Some Herbig stars have the distinctive Ca II triplet signature observed in the T Tauri stars, where 8498 Å has the largest peak height but the narrowest width of the three. We interpret this in terms of increasing velocities and decreasing triplet source functions outward through the emitting gas. Based on these similarities we suggest that the models developed for classical T Tauri star winds/envelopes could also apply to many of the Herbig stars. We favor the model discussed in our accompanying paper on the T Tauri stars; e.g., where the strong and broad emission lines form in dense turbulent regions that are generated at a star-accretion disk boundary layer and reside primarily near the disk plane. This conflicts with previous models of Herbig star envelopes that invoke the star as the driving force behind the winds and dense line-emitting gas. We also estimate the Ca II emissivity from dense envelopes near hot stars using photoionization calculations. We find that the Ca II lines of most Herbig stars could form very near the photosphere. Therefore, the T Tauri star models of dense turbulent envelopes near the star might apply directly. However, the early B stars require more extended high-density regions. Their sometimes double-peaked line profiles and general spectral similarity to the classical Be stars

  4. Calmodulin Kinase II Interacts with the Dopamine Transporter C Terminus to Regulate Amphetamine-Induced Reverse Transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion


    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d......Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound...

  5. Application value of combined measurement of serum sTn, CA242, CA19-9 and CEA in the diagnosis of gastroenterological neoplasm

    International Nuclear Information System (INIS)

    Zhang Wanzhong; Chen Zhizhou; Fan Zhenfu


    To determine the application value of four serum tumor markers sTn, CA242, CA 19-9 and CEA in the diagnosis of gastroenterological neoplasm, the serum sTn, CA242, CA19-9 and CEA in 30 normal adult controls and 60 patients with gastroenterological neoplasm were measured by IRMA. The results showed that the serum sTn, CA242, CA19-9 and CEA levels in patients with gastric carcinoma or colorectal carcinoma were much higher than those in control group (P<0.01). The serum CEA, CA19-9 and CA242 levels in patients with colorectal carcinoma were significantly higher than those in patients with gastric carcinoma (P<0.01), but the serum sTn level in the former was markedly lower (P<0.01) than that in the latter. The sensitivity of tumor marker increased with the progress of clinical stages, with a considerably higher sensitivity for stage IV compared with stage I-II (P<0.01). The combined test of four tumor markers could be more sensitive than single test in detecting gastric carcinoma and colorectal carcinoma (P<0.05). Four tumor markers are useful for diagnosing gastroenterological neoplasm, and the combined measurement of 4 tumor markers could increase the sensitivity of detecting gastric carcinoma. (authors)

  6. Ca II H and K Filter Photometry on the UVBY System. II. The Catalog of Observations (United States)

    Twarog, Bruce A.; Anthony-Twarog, Barbara J.


    A catalog of photometry of 1990 stars on the Caby system is presented. The sample includes stars covering an extensive range in spectral type, luminosity class, and metallicity, as well as apparent magnitude. The hk indices are on the standard system defined in Anthony-Twarog et al. (1991), while the V and (b -y) indices have been transformed to the system of Olsen (1993; hereafter referred to as 093), superseding the values in the original catalog of standard stars. Extensive comparisons to three earlier u V by catalogs with a large degree of overlap are made and the residual trends discussed. The qualitative sensitivity of the hk index as a function of temperature is illustrated for the primary spectral ranges.

  7. Ablation of Ca(V2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

    Directory of Open Access Journals (Sweden)

    Robert Theodor Mallmann

    Full Text Available Voltage-gated Ca(V2.1 (P/Q-type Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V2.1 mouse models. Global Ca(V2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V2.1 in the adult murine forebrain.


    Chen, Chung-Ho; Greenawalt, John W.; Lehninger, Albert L.


    Mitochondria isolated from the hepatopancreas of the blue crab Callinectes sapidus show up to 12-fold stimulation of respiration on addition of Ca2+, which is accompanied by Ca2+ accumulation (Ca2+:site = 1.9) and H+ ejection (H+:Ca2+ = 0.85). Sr2+ and Mn2+ are also accumulated; Mg2+ is not. A strongly hypertonic medium (383 mosM), Mg2+, and phosphate are required for maximal Ca2+ uptake. Ca2+ uptake takes precedence over oxidative phosphorylation of ADP for respiratory energy. Once Ca2+ is accumulated by the crab mitochondria, it is stable and only very slowly released, even by uncoupling agents. ATP hydrolysis also supports Ca2+ uptake. Respiration-inhibited crab hepatopancreas mitochondria show both high-affinity and low-affinity Ca2+-binding sites, which are inactive in the presence of uncoupling agents. Crab hepatopancreas mitochondria have an enormous capacity for accumulation of Ca2+, up to 5,500 ng-atoms Ca2+ per mg protein, with an equivalent amount of phosphate. Freshly isolated mitochondria contain very large amounts of Ca2+, Mg2+, phosphate, K+, and Na+; their high Ca2+ content is a reflection of the vary large amount of extra-mitochondrial Ca2+ in the whole tissue. Electron microscopy of crab mitochondria loaded with Ca2+ and phosphate showed large electron-dense deposits, presumably of precipitated calcium phosphate. They consisted of bundles of needle-like crystals, whereas Ca2+-loaded rat liver mitochondria show only amorphous deposits of calcium phosphate under similar conditions. The very pronounced capacity of crab hepatopancreas mitochondria for transport of Ca2+ appears to be adapted to a role in the storage and release of Ca2+ during the molting cycle of this crustacean. PMID:4827906

  9. Analysis of Distinct Roles of CaMKK Isoforms Using STO-609-Resistant Mutants in Living Cells. (United States)

    Fujiwara, Yuya; Hiraoka, Yuri; Fujimoto, Tomohito; Kanayama, Naoki; Magari, Masaki; Tokumitsu, Hiroshi


    To assess the isoform specificity of the Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK)-mediated signaling pathway using a CaMKK inhibitor (STO-609) in living cells, we have established A549 cell lines expressing STO-609-resistant mutants of CaMKK isoforms. Following serial mutagenesis studies, we have succeeded in obtaining an STO-609-resistant CaMKKα mutant (Ala292Thr/Leu233Phe) and a CaMKKβ mutant (Ala328Thr/Val269Phe), which showed sensitivity to STO-609 that was 2-3 orders of magnitude lower without an appreciable effect on kinase activity or CaM requirement. These results are consistent with the results obtained for CaMKK activities in the extracts of A549 cells stably expressing the mutants of CaMKK isoforms. Ionomycin-induced 5'-AMP-activated protein kinase (AMPK) phosphorylation at Thr172 in A549 cells expressing either the wild-type or the STO-609-resistant mutant of CaMKKα was completely suppressed by STO-609 treatment but resistant to the inhibitor in the presence of the CaMKKβ mutant (Ala328Thr/Val269Phe). This result strongly suggested that CaMKKβ is responsible for ionomycin-induced AMPK activation, which supported previous reports. In contrast, ionomycin-induced CaMKIV phosphorylation at Thr196 was resistant to STO-609 treatment in A549 cells expressing STO-609-resistant mutants of both CaMKK isoforms, indicating that both CaMKK isoforms are capable of phosphorylating and activating CaMKIV in living cells. Considering these results together, STO-609-resistant CaMKK mutants developed in this study may be useful for distinguishing CaMKK isoform-mediated signaling pathways in combination with the use of an inhibitor compound.

  10. Regulation of CaMKII signaling in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Mariya Yordanova Mollova


    Full Text Available Heart failure (HF is a major cause of death in the developed countries. (Murray and Lopez, 1996;Koitabashi and Kass, 2012. Adverse cardiac remodeling that precedes heart muscle dysfunction is characterized by a myriad of molecular changes affecting the cardiomyocyte. Among these, alterations in protein kinase pathways play often an important mediator role since they link upstream pathologic stress signaling with downstream regulatory programs and thus affect both the structural and functional integrity of the heart muscle. In the context of cardiac disease, a profound understanding for the overriding mechanisms that regulate protein kinase activity (protein-protein interactions, post-translational modifications, or targeting via anchoring proteins is crucial for the development of specific and effective pharmacological treatment strategies targeting the failing myocardium.In this review, we focus on several mechanisms of upstream regulation of Ca2+/Calmodulin-dependent kinase II (CaM Kinase II, CaMKII that play a relevant pathophysiological role in the development and progression of cardiovascular disease; precise targeting of these mechanisms might therefore represent novel and promising tools for prevention and treatment of HF.

  11. Strong nonlinear current-voltage behaviour in perovskite-derivative calcium copper titanate. (United States)

    Chung, Sung-Yoon; Kim, Il-Doo; Kang, Suk-Joong L


    The discovery of a giant dielectric constant of 10(5) in CaCu(3)Ti(4)O(12) has increased interest in this perovskite-type oxide. Here we demonstrate that, in addition to high permittivity, CaCu(3)Ti(4)O(12) has remarkably strong nonlinear current-voltage characteristics without the addition of any dopants. An intrinsic electrostatic barrier at the grain boundaries is responsible for the unusual nonlinear behaviour. The nonlinear coefficient of CaCu(3)Ti(4)O(12) reaches a value of 900, which is even greater than that of the varistor material ZnO. As a result, CaCu(3)Ti(4)O(12) may lead to efficient switching and gas-sensing devices.

  12. Modeling CaMKII in cardiac physiology: from molecule to tissue

    Directory of Open Access Journals (Sweden)

    Birce eOnal


    Full Text Available Post-translational modification of membrane proteins (e.g. ion channels, receptors by protein kinases is an essential mechanism for control of excitable cell function. Importantly, loss of temporal and/or spatial control of ion channel post-translational modification is common in congenital and acquired forms of cardiac disease and arrhythmia. The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII regulates a number of diverse cellular functions in heart, including excitation-contraction coupling, gene transcription, and apoptosis. Dysregulation of CaMKII signaling has been implicated in human and animal models of disease. Understanding of CaMKII function has been advanced by mathematical modeling approaches well-suited to the study of complex biological systems. Early kinetic models of CaMKII function in the brain characterized this holoenzyme as a bistable molecular switch capable of storing information over a long period of time. Models of CaMKII activity have been incorporated into models of the cell and tissue (particularly in the heart to predict the role of CaMKII in regulating organ function. Disease models that incorporate CaMKII overexpression clearly demonstrate a link between its excessive activity and arrhythmias associated with congenital and acquired heart disease. This review aims at discussing systems biology approaches that have been applied to analyze CaMKII signaling from the single molecule to intact cardiac tissue. In particular, efforts to use computational biology to provide new insight into cardiac disease mechanisms are emphasized.

  13. Calcium dysregulation in atrial fibrillation: the role of CaMKII

    Directory of Open Access Journals (Sweden)

    Jordi eHeijman


    Full Text Available Atrial fibrillation (AF is the most frequently encountered clinical arrhythmia and is associated with increased morbidity and mortality. Ectopic activity and reentry are considered major arrhythmogenic mechanisms contributing to the initiation and maintenance of AF. In addition, AF is self-reinforcing through progressive electrical and structural remodeling which stabilize the arrhythmia and make it more difficult to treat. Recent research has suggested an important role for Ca2+-dysregulation in AF. Ca2+-handling abnormalities may promote ectopic activity, conduction abnormalities facilitating reentry, and AF-related remodeling. In this review article, we summarize the Ca2+-handling derangements occurring in AF and discuss their impact on fundamental arrhythmogenic mechanisms. We focus in particular on the role of the multifunctional Ca2+/calmodulin-dependent protein kinase type-II (CaMKII, which acts as a major link between Ca2+-dysregulation and arrhythmogenesis. CaMKII expression and activity are increased in AF and promote arrhythmogenesis through phosphorylation of various targets involved in cardiac electrophysiology and excitation-contraction coupling. We discuss the implications for potential novel therapeutic strategies for AF based on CaMKII and Ca2+-handling abnormalities.

  14. Oxidized CaMKII causes cardiac sinus node dysfunction in mice (United States)

    Swaminathan, Paari Dominic; Purohit, Anil; Soni, Siddarth; Voigt, Niels; Singh, Madhu V.; Glukhov, Alexey V.; Gao, Zhan; He, B. Julie; Luczak, Elizabeth D.; Joiner, Mei-ling A.; Kutschke, William; Yang, Jinying; Donahue, J. Kevin; Weiss, Robert M.; Grumbach, Isabella M.; Ogawa, Masahiro; Chen, Peng-Sheng; Efimov, Igor; Dobrev, Dobromir; Mohler, Peter J.; Hund, Thomas J.; Anderson, Mark E.


    Sinus node dysfunction (SND) is a major public health problem that is associated with sudden cardiac death and requires surgical implantation of artificial pacemakers. However, little is known about the molecular and cellular mechanisms that cause SND. Most SND occurs in the setting of heart failure and hypertension, conditions that are marked by elevated circulating angiotensin II (Ang II) and increased oxidant stress. Here, we show that oxidized calmodulin kinase II (ox-CaMKII) is a biomarker for SND in patients and dogs and a disease determinant in mice. In wild-type mice, Ang II infusion caused sinoatrial nodal (SAN) cell oxidation by activating NADPH oxidase, leading to increased ox-CaMKII, SAN cell apoptosis, and SND. p47–/– mice lacking functional NADPH oxidase and mice with myocardial or SAN-targeted CaMKII inhibition were highly resistant to SAN apoptosis and SND, suggesting that ox-CaMKII–triggered SAN cell death contributed to SND. We developed a computational model of the sinoatrial node that showed that a loss of SAN cells below a critical threshold caused SND by preventing normal impulse formation and propagation. These data provide novel molecular and mechanistic information to understand SND and suggest that targeted CaMKII inhibition may be useful for preventing SND in high-risk patients. PMID:21785215

  15. Optimizing the structure of Tetracyanoplatinate(II)

    DEFF Research Database (Denmark)

    Dohn, Asmus Ougaard; Møller, Klaus Braagaard; Sauer, Stephan P. A.


    The geometry of tetracyanoplatinate(II) (TCP) has been optimized with density functional theory (DFT) calculations in order to compare different computational strategies. Two approximate scalar relativistic methods, i.e. the scalar zeroth-order regular approximation (ZORA) and non-relativistic ca...

  16. Evaluation of Transvaginal Ultrasound plus CA-125 Measurement and Prophylactic Salpingo-Oophorectomy in Women at Different Risk Levels of Ovarian Cancer: The Modena Study Group Cohort Study. (United States)

    Cortesi, Laura; De Matteis, Elisabetta; Toss, Angela; Marchi, Isabella; Medici, Veronica; Contu, Giannina; Xholli, Anjeza; Grandi, Giovanni; Cagnacci, Angelo; Federico, Massimo


    To evaluate the effectiveness of transvaginal ultrasound (TVU) and serum CA-125 measurement in women at different risk of developing ovarian cancer/fallopian tube cancer (OC/FTC) and the incidence of primary peritoneal cancer (PPC) after risk-reducing salpingo-oophorectomy (RRSO). Between 2002 and 2014, 661 women at different risk of OC/FTC/PPC due to a family history or BRCA1/2 gene mutation were offered TVU and CA-125 measurement or RRSO as prevention strategies. The detection rate of OC/FTC/PPC was evaluated, and the sensitivity and specificity for CA-125 measurement and TVU were calculated. Survival and event analysis was performed for diagnosed patients. After a median follow-up of 112 months, 12 OC/FTC/PPC cases were detected (2.6/1,000 persons/year). The screening sensitivity was 70%, with 73% for BRCA carriers. Six (50%) of 12 cancers were stage I or II. Among 41 women who underwent RRSO, 2 BRCA1 carriers developed a PPC (4.9%). At 61-month follow-up, overall and event-free survival were 75 and 64%, respectively. The cancer detection rate in women with BRCA mutation or a strong family history supports the effectiveness of our surveillance program for early diagnosis. Screening for women at lower risk of OC/FTC is not recommended. A residual risk of PPC after RRSO remains for BRCA1 carriers. © 2017 S. Karger AG, Basel.

  17. Atoms and clusters in strong laser fields

    NARCIS (Netherlands)

    Marchenko, T.


    This thesis describes experimental and theoretical studies on the interaction of strong infrared laser fields with atoms and atomic clusters. Part I provides an overview of the main strong-field phenomena in atoms, molecules and clusters and describes the state-of-the-art in strong-field science.

  18. 78 FR 15710 - Strong Sensitizer Guidance (United States)


    ... definition of ``strong sensitizer'' found at 16 CFR 1500.3(c)(5). The Commission is proposing to revise the supplemental definition of ``strong sensitizer'' due to advancements in the science of sensitization that have... document is intended to clarify the ``strong sensitizer'' definition, assist manufacturers in understanding...

  19. Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. (United States)

    Fraser, Heather; Belardinelli, Luiz; Wang, Lianguo; Light, Peter E; McVeigh, Jeffrey J; Clanachan, Alexander S


    Cardiac pathologies are associated with increased late INa that contributes to the dysregulation of ion homeostasis and causes electrical and contractile dysfunction. This study was designed to test the hypothesis that an increased late sodium channel current (INa) leads to Ca2+ overload and left ventricular (LV) dysfunction, and thereby inhibition of late INa (e.g., by ranolazine) improves Ca2+ homeostasis and reduces LV dysfunction. Intracellular Ca2+ ([Ca2+]i) and LV function were measured simultaneously in rat isolated perfused hearts. Augmentation of late INa with sea anemone toxin-II (ATX-II, 12 nM) increased diastolic [Ca2+]i (d[Ca2+]i), and impaired LV mechanical function, but had no effect on [Ca2+]i transient amplitude. Although ranolazine (4 and 9 microM), an inhibitor of late INa, had no direct effects on d[Ca2+]i or LV function, it significantly reduced the deleterious effects of ATX-II. Global ischemia increased d[Ca2+]i and inhibited Ca2+ transient amplitude. During reperfusion, Ca2+ transient amplitude recovered fully, but d[Ca2+]i remained elevated and LV function was depressed, indicative of Ca2+ overload. Ranolazine (9 microM) reduced d[Ca2+]i accumulation during ischemia as well as reperfusion and improved recovery of LV function. These results show that augmentation of late INa with ATX-II or by ischemia is associated with diastolic Ca2+ overload and LV dysfunction. The beneficial effects of ranolazine in reducing Ca2+ overload and LV mechanical dysfunction during ischemia/reperfusion is consistent with the inhibition of late INa mechanism of action.

  20. Highly active and durable Ca-doped Ce-SBA-15 catalyst for biodiesel production

    International Nuclear Information System (INIS)

    Thitsartarn, Warintorn; Maneerung, Thawatchai; Kawi, Sibudjing


    In this work, Ca-doped Ce-incorporated SBA-15 (Ca/CeS) catalyst was successfully synthesized by using direct synthesis of Ce-incorporated SBA-15 followed by impregnation of CaO (calcium oxide). The maximum Si/Ce molar ratio that Ce atoms can be incorporated successfully into the mesoporous framework was found to be 5 (CeS-5). After the impregnation of 30 wt. % Ca, the obtained 30Ca/CeS-5 catalysts showed the superior catalytic performance for transesterification reaction of palm oil with methanol and also the higher catalytic activity as compared to other supported catalysts, i.e. CaO/CeO 2 and CaO–CeO 2 /SBA-15. This can be attributed to the well-dispersion of CaO on the CeS-5 support surface. Furthermore, it was found that the leaching of Si, Ce and Ca from the catalyst into biodiesel produced was negligible (i.e. <1 ppm after 7 cycles), indicating the strong interaction between CaO and CeS-5 support. As a result, the 30Ca/CeS-5 catalyst can be reused at least 15 cycles with insignificant decrease in catalytic activity, offering the efficient CaO-based catalyst for biodiesel production. - Highlights: • Mesoporous Ca-based catalyst was successfully developed for biodiesel production. • Catalyst exhibited high activity towards transesterification (FAME yield > 98%). • Catalyst can be effectively re-used at least 15 cycles. • Extremely low catalyst contaminant (<1 ppm) was presented

  1. Muscle-Type Specific Autophosphorylation of CaMKII Isoforms after Paced Contractions

    Directory of Open Access Journals (Sweden)

    Wouter Eilers


    Full Text Available We explored to what extent isoforms of the regulator of excitation-contraction and excitation-transcription coupling, calcium/calmodulin protein kinase II (CaMKII contribute to the specificity of myocellular calcium sensing between muscle types and whether concentration transients in its autophosphorylation can be simulated. CaMKII autophosphorylation at Thr287 was assessed in three muscle compartments of the rat after slow or fast motor unit-type stimulation and was compared against a computational model (CaMuZclE coupling myocellular calcium dynamics with CaMKII Thr287 phosphorylation. Qualitative differences existed between fast- (gastrocnemius medialis and slow-type muscle (soleus for the expression pattern of CaMKII isoforms. Phospho-Thr287 content of δA CaMKII, associated with nuclear functions, demonstrated a transient and compartment-specific increase after excitation, which contrasted to the delayed autophosphorylation of the sarcoplasmic reticulum-associated βM CaMKII. In soleus muscle, excitation-induced δA CaMKII autophosphorylation demonstrated frequency dependence (P = 0.02. In the glycolytic compartment of gastrocnemius medialis, CaMKII autophosphorylation after excitation was blunted. In silico assessment emphasized the importance of mitochondrial calcium buffer capacity for excitation-induced CaMKII autophosphorylation but did not predict its isoform specificity. The findings expose that CaMKII autophosphorylation with paced contractions is regulated in an isoform and muscle type-specific fashion and highlight properties emerging for phenotype-specific regulation of CaMKII.

  2. Regulation of Ca(2+) signaling in rat bile duct epithelia by inositol 1,4,5-trisphosphate receptor isoforms. (United States)

    Hirata, Keiji; Dufour, Jean-François; Shibao, Kazunori; Knickelbein, Roy; O'Neill, Allison F; Bode, Hans-Peter; Cassio, Doris; St-Pierre, Marie V; Larusso, Nicholas F; Leite, M Fatima; Nathanson, Michael H


    Cytosolic Ca(2+) (Ca(i)(2+)) regulates secretion of bicarbonate and other ions in the cholangiocyte. In other cell types, this second messenger acts through Ca(2+) waves, Ca(2+) oscillations, and other subcellular Ca(2+) signaling patterns, but little is known about the subcellular organization of Ca(2+) signaling in cholangiocytes. Therefore, we examined Ca(2+) signaling and the subcellular distribution of Ca(2+) release channels in cholangiocytes and in a model cholangiocyte cell line. The expression and subcellular distribution of inositol 1,4,5-trisphosphate (InsP(3)) receptor (InsP(3)R) isoforms and the ryanodine receptor (RyR) were determined in cholangiocytes from normal rat liver and in the normal rat cholangiocyte (NRC) polarized bile duct cell line. Subcellular Ca(2+) signaling in cholangiocytes was examined by confocal microscopy. All 3 InsP(3)R isoforms were expressed in cholangiocytes, whereas RyR was not expressed. The type III InsP(3)R was the most heavily expressed isoform at the protein level and was concentrated apically, whereas the type I and type II isoforms were expressed more uniformly. The type III InsP(3)R was expressed even more heavily in NRC cells but was concentrated apically in these cells as well. Adenosine triphosphate (ATP), which increases Ca(2+) via InsP(3) in cholangiocytes, induced Ca(2+) oscillations in both cholangiocytes and NRC cells. Acetylcholine (ACh) induced apical-to-basal Ca(2+) waves. In conclusion, Ca(2+) signaling in cholangiocytes occurs as polarized Ca(2+) waves that begin in the region of the type III InsP(3)R. Differential subcellular localization of InsP(3)R isoforms may be an important molecular mechanism for the formation of Ca(2+) waves and oscillations in cholangiocytes. Because Ca(i)(2+) is in part responsible for regulating ductular secretion, these findings also may have implications for the molecular basis of cholestatic disorders.

  3. CaMKIIdelta isoforms differentially affect calcium handling but similarly regulate HDAC/MEF2 transcriptional responses. (United States)

    Zhang, Tong; Kohlhaas, Michael; Backs, Johannes; Mishra, Shikha; Phillips, William; Dybkova, Nataliya; Chang, Shurong; Ling, Haiyun; Bers, Donald M; Maier, Lars S; Olson, Eric N; Brown, Joan Heller


    The delta(B) and delta(C) splice variants of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), which differ by the presence of a nuclear localization sequence, are both expressed in cardiomyocytes. We used transgenic (TG) mice and CaMKII expression in cardiomyocytes to test the hypothesis that the CaMKIIdelta(C) isoform regulates cytosolic Ca(2+) handling and the delta(B) isoform, which localizes to the nucleus, regulates gene transcription. Phosphorylation of CaMKII sites on the ryanodine receptor (RyR) and on phospholamban (PLB) were increased in CaMKIIdelta(C) TG. This was associated with markedly enhanced sarcoplasmic reticulum (SR) Ca(2+) spark frequency and decreased SR Ca(2+) content in cardiomyocytes. None of these parameters were altered in TG mice expressing the nuclear-targeted CaMKIIdelta(B). In contrast, cardiac expression of either CaMKIIdelta(B) or delta(C) induced transactivation of myocyte enhancer factor 2 (MEF2) gene expression and up-regulated hypertrophic marker genes. Studies using rat ventricular cardiomyocytes confirmed that CaMKIIdelta(B) and delta(C) both regulate MEF2-luciferase gene expression, increase histone deacetylase 4 (HDAC4) association with 14-3-3, and induce HDAC4 translocation from nucleus to cytoplasm, indicating that either isoform can stimulate HDAC4 phosphorylation. Finally, HDAC4 kinase activity was shown to be increased in cardiac homogenates from either CaMKIIdelta(B) or delta(C) TG mice. Thus CaMKIIdelta isoforms have similar effects on hypertrophic gene expression but disparate effects on Ca(2+) handling, suggesting distinct roles for CaMKIIdelta isoform activation in the pathogenesis of cardiac hypertrophy versus heart failure.

  4. Molecular evolution and functional divergence of the Ca(2+ sensor protein in store-operated Ca(2+ entry: stromal interaction molecule.

    Directory of Open Access Journals (Sweden)

    Xinjiang Cai


    Full Text Available Receptor-mediated Ca(2+ signaling in many non-excitable cells initially induces Ca(2+ release from intracellular Ca(2+ stores, followed by Ca(2+ influx across the plasma membrane. Recent findings have suggested that stromal interaction molecules (STIMs function as the Ca(2+ sensor to detect changes of Ca(2+ content in the intracellular Ca(2+ stores. Human STIMs and invertebrate STIM share several functionally important protein domains, but diverge significantly in the C-terminus. To better understand the evolutionary significance of STIM activity, phylogenetic analysis of the STIM protein family was conducted after extensive database searching. Results from phylogeny and sequence analysis revealed early adaptation of the C-terminal divergent domains in Urochordata, before the expansion of STIMs in Vertebrata. STIMs were subsequently subjected to one round of gene duplication as early as in the Euteleostomi lineage in vertebrates, with a second round of fish-specific gene duplication. After duplication, STIM-1 and STIM-2 molecules appeared to have undergone purifying selection indicating strong evolutionary constraints within each group. Furthermore, sequence analysis of the EF-hand Ca(2+ binding domain and the SAM domain, together with functional divergence studies, identified critical regions/residues likely underlying functional changes, and provided evidence for the hypothesis that STIM-1 and STIM-2 might have developed distinct functional properties after duplication.

  5. Copper (II)

    African Journals Online (AJOL)


    Bhardwaj C. N., and Singh V. R., (1994), Synthesis and characterization of thallium (I) complexes of biologically active benzothiazolines, Indian Journal Chemistry 33(3): 423 - 425. Chakraborty H., Paul N., and Rahman M. L., (1994), Catalytic activities of Schiff bases aquo complexes of Cu (II) in the hydrolysis of amino acid ...

  6. Determination of Sr and Ca sources in small tropical catchments (La Selva, Costa Rica) - A comparison of Sr and Ca isotopes (United States)

    Wiegand, B. A.; Schwendenmann, L.


    SummaryA comparative study of Sr and Ca isotopes was conducted to assess solute sources and effects of biogeochemical processes on surface water and groundwater in four small tropical catchments located at La Selva Biological Station, Costa Rica. Variable concentrations of dissolved Sr2+ and Ca2+ in the catchments are related to mixing of waters from different origin. Three catchments are influenced by high-solute bedrock groundwater, while another catchment is primarily supplied by local recharge. 87Sr/86Sr ratios were employed to discriminate contributions from mineral weathering and atmospheric sources. Solutes in bedrock groundwater have a predominant geogenic origin, whereas local recharge is characterized by low-solute inputs from rainwater and minor in situ weathering releases from nutrient-depleted soils. Bedrock groundwater contributes more than 60% of dissolved Sr2+ to surface discharge in the Salto, Saltito, and Arboleda catchments, whereas the Taconazo catchment receives more than 95% of dissolved Sr2+ from rainwater. δ44/40Ca values of dissolved Ca2+ vary greatly in the catchments, mainly as a result of heterogeneous Ca isotope compositions of the contributing sources. Based on differences in δ44/40Ca values, two distinct bedrock groundwaters discharging at the Salto and the Arboleda catchments are suggested. Effects of biological processes in the plant-soil system on solute generation in the catchments are indicated by variable Ca/Sr ratios. However, these effects cannot clearly be assessed by Ca isotopes due to the strong heterogeneity of δ44/40Ca values of Ca2+ sources and high Ca2+ concentrations in bedrock groundwater.

  7. Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src.

    Directory of Open Access Journals (Sweden)

    Silviya R Stateva

    Full Text Available Src family non-receptor tyrosine kinases play a prominent role in multiple cellular processes, including: cell proliferation, differentiation, cell survival, stress response, and cell adhesion and migration, among others. And when deregulated by mutations, overexpression, and/or the arrival of faulty incoming signals, its hyperactivity contributes to the development of hematological and solid tumors. c-Src is a prototypical member of this family of kinases, which is highly regulated by a set of phosphorylation events. Other factor contributing to the regulation of Src activity appears to be mediated by the Ca2+ signal generated in cells by different effectors, where the Ca2+-receptor protein calmodulin (CaM plays a key role. In this report we demonstrate that CaM directly interacts with Src in both Ca2+-dependent and Ca2+-independent manners in vitro and in living cells, and that the CaM antagonist N-(6-aminohexyl-5-chloro-1-naphthalenesulfonamide (W-7 inhibits the activation of this kinase induced by the upstream activation of the epidermal growth factor receptor (EGFR, in human carcinoma epidermoide A431 cells, and by hydrogen peroxide-induced oxidative stress, in both A431 cells and human breast adenocarcinoma SK-BR-3 cells. Furthermore, we show that the Ca2+/CaM complex strongly activates the auto-phosphorylation and tyrosine kinase activity of c-Src toward exogenous substrates, but most relevantly and for the first time, we demonstrate that Ca2+-free CaM (apo-CaM exerts a far higher activatory action on Src auto-phosphorylation and kinase activity toward exogenous substrates than the one exerted by the Ca2+/CaM complex. This suggests that a transient increase in the cytosolic concentration of free Ca2+ is not an absolute requirement for CaM-mediated activation of Src in living cells, and that a direct regulation of Src by apo-CaM could be inferred.


    International Nuclear Information System (INIS)

    Chen, Hsin-Wei; Lee, Typhoon; Lee, Der-Chuen; Shen, Jason Jiun-San; Chen, Jiang-Chang


    Isotopic heterogeneities of 48 Ca have been found in numerous bulk meteorites that are correlated with 50 Ti and 54 Cr anomalies among differentiated planetary bodies, and the results suggest that a rare subset of neutron-rich Type Ia supernova (nSN Ia) was responsible for contributing these neutron-rich iron-group isotopes into the solar system (SS). The heterogeneity of these isotopes found in differentiated meteorites indicates that the isotopic compositions of the bulk SS are not uniform, and there are significant amounts of nSNe Ia dust incompletely mixed with the rest of SS materials during planetary formation. Combined with the data of now-extinct short-lived nuclide 60 Fe, which can be produced more efficiently from an nSN Ia than a Type II supernova ejecta, the observed planetary-scale isotopic heterogeneity probably reflects a late input of stellar dust grains with neutron-rich nuclear statistical equilibrium nuclides into the early SS.

  9. Application of 17% EDTA Enhances Diffusion of (45)Ca-labeled OH(-) and Ca(2+) in Primary Tooth Root Canal. (United States)

    Ximenes, Marcos; Cavalcanti Taguchi, Carolina Mayumi; Triches, Thaisa Cezaria; Sartori, Neimar; Pereira Dias, Luis Alberto; de Araujo, Elaine Bortoleti; Cardoso, Mariane


    Proper cleaning of the root canal is key to the success of endodontic treatment as it allows more effective diffusion of medication throughout the dentinal tubules. The aim of this in vitro study was to investigate the efficacy of 17% ethylenediaminetetraacetic acid (EDTA) in enhancing diffusion of hydroxyl (OH(-)) and calcium ions (Ca(2+)) throughout the root canal in primary teeth. The canals of 25 primary tooth roots were cleaned with endodontic files and 1% sodium hypochlorite. Three groups (G) were then established: GI, in which final irrigation was performed with 1% sodium hypochlorite; GII, in which 17% EDTA was used; and GIII, in which no irrigation was performed. The roots canals in GI and GII were filled with a calcium hydroxide-based paste labeled with the radioisotope calcium-45. Diffusion of OH(-) was detected with pH strips and Ca(2+) analyzed by measuring radioactivity in counts per min. Group II differed statistically from the other groups in diffusion of OH(-) at 24 hr (p<0.05), but no significant difference among groups was found at the day 7 evaluation; GII also differed statistically from the other groups in diffusion of Ca(2+) at 24 hr (p<0.05). These results suggest that application of 17% EDTA in primary tooth enhances diffusion of OH(-) and Ca(2+).

  10. Novel platinum(II) and palladium(II) complexes with cyclin-dependent kinase inhibitors: Synthesis, characterization and antitumour activity

    Czech Academy of Sciences Publication Activity Database

    Szüčová, Lucie; Trávníček, Zdeněk; Zatloukal, Marek; Popa, Igor


    Roč. 14, č. 2 (2006), s. 479-491 ISSN 0968-0896 R&D Projects: GA ČR GA203/04/1168 Institutional research plan: CEZ:AV0Z50380511 Keywords : Platinum(II) * Palladium(II) * Cyclin-dependent kinase inhibitors Subject RIV: CA - Inorganic Chemistry Impact factor: 2.624, year: 2006

  11. The diagnostic value of determination of serum GOLPH3 associated with CA125, CA19.9 in patients with ovarian cancer. (United States)

    Fan, H-Y; Duan, D-M; Liu, Y-F


    To evaluate the value of three tumor markers serum Golgi phosphoprotein-3 (GOLPH3), cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19.9) in the diagnosis and postoperative evaluation of ovarian cancer by detecting these three markers. A total of 187 patients were studied and included in the ovarian cancer group, benign pelvic mass group, and the normal control group. The levels of serum Golgi phosphoprotein-3 (GOLPH3), cancer antigen 125 (CA125) and cancer antigen 199 (CA19.9) were detected, respectively, and their effects on the diagnosis, evaluation, pathology typing and staging of ovarian cancer were measured. The sensitivity of the detection of ovarian cancer by GOLPH3 combined with CA125 and CA19.9 was higher than that by a single marker (pserum GOLPH3 in patients with serous and endometrioid carcinoma was significantly higher than that in patients with mucinous carcinoma, clear-cell carcinoma and germ cell tumor (pserum GOLPH3 level between patients with ovarian malignancies at stage III-IV and those at stage I-II (p>0.05). The levels of serum GOLPH3, CA125 and CA19.9 in patients with ovarian malignancies after surgery were significantly lower than those before surgery (p<0.05). The combined detection by GOLPH3, CA125, and CA19.9 may improve the diagnosis rate of ovarian epithelial cancer. GOLPH3, as a new ovarian cancer tumor marker used in clinical diagnosis, is expected to become an important indicator for the early diagnosis of ovarian cancer and the determination of clinical surgery efficacy.

  12. Improved recovery of trace amounts of gold (III), palladium (II) and platinum (IV) from large amounts of associated base metals using anion-exchange resins

    Energy Technology Data Exchange (ETDEWEB)

    Matsubara, I. [Lab. of Chemistry, Tokyo Women' s Medical Univ. (Japan); Takeda, Y.; Ishida, K. [Lab. of Chemistry, Nippon Medical School, Kawasaki-shi, Kanagawa-ken (Japan)


    The adsorption and desorption behaviors of gold (III), palladium (II) and platinum (IV) were surveyed in column chromatographic systems consisting of one of the conventional anion-exchange resins of large ion-exchange capacity and dilute thiourea solutions. The noble metals were strongly adsorbed on the anion-exchange resins from dilute hydrochloric acid, while most base metals did not show any marked adsorbability. These facts made it possible to separate the noble metals from a large quantity of base metals such as Ag (I), Al (III), Co (II), Cu (II), Fe (III), Mn (II), Ni (II), Pb (II), and Zn (II). Although it used to be very difficult to desorb the noble metals from the resins used, the difficulty was easily overcome by use of dilute thiourea solutions as an eluant. In the present study, as little as 1.00 {mu}g of the respective noble metals was quantitatively separated and recovered from as much as ca. 10 mg of a number of metals on a small column by elution with a small amount of dilute thiourea solution. The present systems should be applicable to the separation, concentration and recovery of traces of the noble metals from a number of base metals coexisting in a more extended range of amounts and ratios. (orig.)

  13. The effect of the host lattice on the optical properties of Bi3+in Ca1-xO:Bi and Ca1-x(OH)2:Bi phosphors (United States)

    Yousif, A.; Jafer, R. M.; Som, S.; Swart, H. C.


    The present work refers to the structural and luminescence changes in Ca1-xO:Bi (x = 0.5%) phosphor due to the reaction of the Ca1-xO: Bi (x = 0.5%) phosphor with atmospheric air. The X-ray diffraction (XRD) patterns of the as-annealed sample (at 1200 °C) showed the characteristic peaks of CaO, while high-intensity peaks of Ca(OH)2 were also observed for the same samples that were kept in the air after annealing. Indicating that mixed phases of Ca1-xO:Bi (x = 0.5%) and Ca(OH)2:Bi were present in the exposed samples. It was clear that the observed optical properties (excitation and emission) of the Bi3+ depended strongly on the reaction of the CaO with the environment due to the host lattice structure changes and therefore a big challenge for practical applications.

  14. Magnetism in Ca 2 CoOsO 6 and Ca 2 NiOsO 6 : Unraveling the Mystery of Superexchange Interactions between 3d and 5d Ions

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, Ryan; Samanta, Kartik; Saha Dasgupta, Tanusri; Xiong, Jie; Freeland, John W.; Haskel, Daniel; Woodward, Patrick M.


    In order to rationalize and predict the behavior of compounds containing 5d transition metal ions, an understanding of the local moments and superexchange interactions from which their magnetic properties are derived is necessary. The magnetic and electrical properties of the ferrimagnetic double perovskites Ca2CoOsO6 and Ca2NiOsO6 studied here provide critical insight toward that goal. First-principles density functional theory (DFT) calculations indicate, and experimental measurements confirm, that the Os(VI) moments are directed antiparallel to the Co/Ni moments. X-ray magnetic circular dichroism (XMCD) measurements reveal that the orbital moment on osmium has a magnitude that is approximately 30% of the spin moment, and the two contributions oppose each other. Both the size and direction of the orbital moment are confirmed by the DFT calculations. The size of the Os(VI) total moment is predicted to be 0.6-0.7 μB by DFT calculations. The ferrimagnetic ground state is stabilized by strong antiferromagnetic coupling between the d2 Os(VI) ion and the d8/d7 Ni(II)/Co(II) ion. Not only does the observation of antiferromagnetic coupling violate the Goodenough-Kanamori rules, but also it is unusual in that it becomes stronger as the Os-O-Co/Ni bond angle decreases. This unusual behavior is shown to arise predominantly from coupling between Os t2g orbitals and Ni/Co eg orbitals, mediated by the intervening oxide ion. We further find that both compounds are spin-orbit assisted Mott insulators.

  15. A simple method for the accurate determination of free [Ca] in Ca-EGTA solutions. (United States)

    Bers, D M


    A simple method for the accurate determination of free [Ca] in ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA)-buffered Ca solutions is described. This method is useful for calibration of Ca macro- and microelectrodes to low free [Ca] and should improve the reliability of calculated free [Ca] in more complex solutions. Briefly, free [Ca] in Ca-EGTA solutions is measured with a Ca electrode, bound Ca is calculated, and Scatchard and double-reciprocal plots are resolved for the total [EGTA] and the apparent Ca-EGTA association constant (K'Ca) in the solutions used. The free [Ca] is then recalculated using the determined parameters, giving a more accurate knowledge of the free [Ca] in these solutions and providing an accurate calibration curve for the Ca electrode. These solutions can then be used to calibrate other Ca electrodes (e.g., Ca microelectrodes) or the calibrated Ca electrode can be used to measure free [Ca] in solutions containing multiple metal ligands. This method allows determination of free [Ca], K'Ca, and total [EGTA] in the actual solutions used regardless of pH, temperature, or ionic strength. It does not require accurate knowledge of K'Ca or EGTA purity and circumvents many potential errors due to assumption of binding parameters. K'Ca was found to be 2.45 +/- 0.04 X 10(6) M-1 in 100 mM KCl, 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, and 1 mM EGTA at pH 7.00 and 23 degrees C. Total [EGTA] varied with supplier but was always less than quoted.

  16. Biochemical and Spectroscopic Observation of Mn(II) Sequestration from Bacterial Mn(II) Transport Machinery by Calprotectin. (United States)

    Hadley, Rose C; Gagnon, Derek M; Brophy, Megan Brunjes; Gu, Yu; Nakashige, Toshiki G; Britt, R David; Nolan, Elizabeth M


    Human calprotectin (CP, S100A8/S100A9 oligomer) is a metal-sequestering host-defense protein that prevents bacterial acquisition of Mn(II). In this work, we investigate Mn(II) competition between CP and two solute-binding proteins that Staphylococcus aureus and Streptococcus pneumoniae, Gram-positive bacterial pathogens of significant clinical concern, use to obtain Mn(II) when infecting a host. Biochemical and electron paramagnetic resonance (EPR) spectroscopic analyses demonstrate that CP outcompetes staphylococcal MntC and streptococcal PsaA for Mn(II). This behavior requires the presence of excess Ca(II) ions, which enhance the Mn(II) affinity of CP. This report presents new spectroscopic evaluation of two Mn(II) proteins important for bacterial pathogenesis, direct observation of Mn(II) sequestration from bacterial Mn(II) acquisition proteins by CP, and molecular insight into the extracellular battle for metal nutrients that occurs during infection.

  17. Caveolae-specific activation loop between CaMKII and L-type Ca2+channel aggravates cardiac hypertrophy in α1-adrenergic stimulation. (United States)

    Tonegawa, Kota; Otsuka, Wataru; Kumagai, Shohei; Matsunami, Sachi; Hayamizu, Nao; Tanaka, Shota; Moriwaki, Kazumasa; Obana, Masanori; Maeda, Makiko; Asahi, Michio; Kiyonari, Hiroshi; Fujio, Yasushi; Nakayama, Hiroyuki


    Activation of CaMKII induces a myriad of biological processes and plays dominant roles in cardiac hypertrophy. Caveolar microdomain contains many calcium/calmodulin-dependent kinase II (CaMKII) targets, including L-type Ca 2+ channel (LTCC) complex, and serves as a signaling platform. The location of CaMKII activation is thought to be critical; however, the roles of CaMKII in caveolae are still elusive due to lack of methodology for the assessment of caveolae-specific activation. Our aim was to develop a novel tool for the specific analysis of CaMKII activation in caveolae and to determine the functional role of caveolar CaMKII in cardiac hypertrophy. To assess the caveolae-specific activation of CaMKII, we generated a fusion protein composed of phospholamban and caveolin-3 (cPLN-Cav3) and GFP fusion protein with caveolin-binding domain fused to CaMKII inhibitory peptide (CBD-GFP-AIP), which inhibits CaMKII activation specifically in caveolae. Caveolae-specific activation of CaMKII was detected using phosphospecific antibody for PLN (Thr 17 ). Furthermore, adenoviral overexpression of LTCC β 2a -subunit (β 2a ) in NRCMs showed its constitutive phosphorylation by CaMKII, which induces hypertrophy, and that both phosphorylation and hypertrophy are abolished by CBD-GFP-AIP expression, indicating that β 2a phosphorylation occurs specifically in caveolae. Finally, β 2a phosphorylation was observed after phenylephrine stimulation in β 2a -overexpressing mice, and attenuation of cardiac hypertrophy after chronic phenylephrine stimulation was observed in nonphosphorylated mutant of β 2a -overexpressing mice. We developed novel tools for the evaluation and inhibition of caveolae-specific activation of CaMKII. We demonstrated that phosphorylated β 2a dominantly localizes to caveolae and induces cardiac hypertrophy after α 1 -adrenergic stimulation in mice. NEW & NOTEWORTHY While signaling in caveolae is thought to be important in cardiac hypertrophy, direct evidence

  18. Dimensionality and magnetic interactions in CaFe2As2: An ab initio study

    International Nuclear Information System (INIS)

    Tompsett, D.A.; Lonzarich, G.G.


    We present detailed electronic structure calculations for CaFe 2 As 2 . We investigate in particular the 'collapsed' tetragonal and orthorhombic regions of the temperature-pressure phase diagram and find properties that distinguish CaFe 2 As 2 from other Fe-pnictide compounds. In contrast to the tetragonal phase of other Fe-pnictides the electronic structure in the 'collapsed' tetragonal phase of CaFe 2 As 2 is found to be strongly 3D. By an analysis of the non-interacting susceptibility, χ 0 (q), of CaFe 2 As 2 and LaFePO we discuss the role of magnetic interactions in iron-pnictides. From this we propose an intuitive explanation for the outstanding question relating to why the predicted antiferromagnetic moment depends strongly on coordinate relaxation and the choice of correlation functional.

  19. Role of a Water Network around the Mn4CaO5 Cluster in Photosynthetic Water Oxidation: A Fourier Transform Infrared Spectroscopy and Quantum Mechanics/Molecular Mechanics Calculation Study. (United States)

    Nakamura, Shin; Ota, Kai; Shibuya, Yuichi; Noguchi, Takumi


    Photosynthetic water oxidation takes place at the Mn4CaO5 cluster in photosystem II. Around the Mn4CaO5 cluster, a hydrogen bond network is formed by several water molecules, including four water ligands. To clarify the role of this water network in the mechanism of water oxidation, we investigated the effects of the removal of Ca(2+) and substitution with metal ions on the vibrations of water molecules coupled to the Mn4CaO5 cluster by means of Fourier transform infrared (FTIR) difference spectroscopy and quantum mechanics/molecular mechanics (QM/MM) calculations. The OH stretching vibrations of nine water molecules forming a network between D1-D61 and YZ were calculated using the QM/MM method. On the the calculated normal modes, a broad positive feature at 3200-2500 cm(-1) in an S2-minus-S1 FTIR spectrum was attributed to the vibrations of strongly hydrogen-bonded OH bonds of water involving the vibrations of water ligands to a Mn ion and the in-phase coupled vibration of a water network connected to YZ, while bands in the 3700-3500 cm(-1) region were assigned to the coupled vibrations of weakly hydrogen-bonded OH bonds of water. All the water bands were lost upon Ca(2+) depletion and Ba(2+) substitution, which inhibit the S2 → S3 transition, indicating that a solid water network was broken by these treatments. By contrast, Sr(2+) substitution slightly altered the water bands around 3600 cm(-1), reflecting minor modification in water interactions, consistent with the retention of water oxidation activity with a decreased efficiency. These results suggest that the water network around the Mn4CaO5 cluster plays an essential role in the water oxidation mechanism particularly in a concerted process of proton transfer and water insertion during the S2 → S3 transition.

  20. Exploring B/Ca as a pH proxy in bivalves: relationships between Mytilus californianus B/Ca and environmental data from the northeast Pacific

    Directory of Open Access Journals (Sweden)

    N. Shimizu


    Full Text Available A distinct gap in our ability to understand changes in coastal biology that may be associated with recent ocean acidification is the paucity of directly measured ocean environmental parameters at coastal sites in recent decades. Thus, many researchers have turned to sclerochronological reconstructions of water chemistry to document the historical seawater environment. In this study, we explore the relationships between B/Ca and pH to test the feasibility of B/Ca measured on the ion probe as a pH proxy in the California mussel, Mytilus californianus. Heterogeneity in a range of ion microprobe standards is assessed, leading to reproducible B/Ca ratios at the 5% level. The B/Ca data exhibit large excursions during winter months, which are particularly pronounced during the severe winters of 2004–2005 and 2005–2006. Furthermore, B/Ca ratios are offset in different parts of the skeleton that calcified at the same time. We compare the M. californianus B/Ca record to directly measured environmental data during mussel growth from the period of 1999–2009 to examine whether seawater chemistry or temperature plays a role in controlling shell B/Ca. A suite of growth rate models based on measured temperature are compared to the B/Ca data to optimise the potential fit of B/Ca to pH. Despite sampling conditions that were well-suited to testing a pH control on B/Ca, including a close proximity to an environmental record, a distinct change in pH at the sampling locale, and a growth model designed to optimise the correlations between seawater pH and shell B/Ca, we do not see a strong correlations between pH and shell B/Ca (maximum coefficient of determination, r2, of 0.207. Instead, our data indicate a strong biological control on B/Ca as observed in some other carbonate-forming organisms.

  1. Cu(II), Zn(II)

    African Journals Online (AJOL)

    stereochemistry has been suggested to Zn(II), Cd(II) and Hg(II) complexes. The thermal analysis data provided the kinetic parameters as order of decomposition reaction, activation energy and frequency factor. All theoretical calculations of the ligand and the Cu(II) and Zn(II) complexes were made using Gaussian 03 rev.

  2. Evolution and functional diversity of the Calcium Binding Proteins (CaBPs

    Directory of Open Access Journals (Sweden)

    Lee P Haynes


    Full Text Available The mammalian central nervous system (CNS exhibits a remarkable ability to process, store and transfer information. Key to these activities is the use of highly regulated and unique patterns of calcium signals encoded by calcium channels and decoded by families of specific calcium-sensing proteins. The largest family of eukaryotic calcium sensors are those related to the small EF-hand containing protein calmodulin (CaM. In order to maximise the usefulness of calcium as a signalling species and to permit the evolution and fine tuning of the mammalian CNS, families of related proteins have arisen that exhibit characteristic calcium binding properties and tissue-, cellular- and sub-cellular distribution profiles. The Calcium Binding Proteins (CaBPs represent one such family of vertebrate specific calmodulin like proteins that have emerged in recent years as important regulators of essential neuronal target proteins. Bioinformatic analyses indicate that the CaBPs consist of two subfamilies and that the ancestral members of these are CaBP1 and CaBP8. The CaBPs have distinct intracellular localisations based on different targeting mechanisms including a novel type-II transmembrane domain in CaBPs 7 and 8. Recent work has led to the identification of new target interactions and possible functions for the CaBPs suggesting that they have multiple physiological roles with relevance for the normal functioning of the CNS.

  3. Distinct Roles for Dorsal CA3 and CA1 in Memory for Sequential Nonspatial Events (United States)

    Farovik, Anja; Dupont, Laura M.; Eichenbaum, Howard


    Previous studies have suggested that dorsal hippocampal areas CA3 and CA1 are both involved in representing sequences of events that compose unique episodes. However, it is uncertain whether the contribution of CA3 is restricted to spatial information, and it is unclear whether CA1 encodes order per se or contributes by an active maintenance of…

  4. 46 CFR 7.130 - Point Conception, CA to Point Sur, CA. (United States)


    ... 46 Shipping 1 2010-10-01 2010-10-01 false Point Conception, CA to Point Sur, CA. 7.130 Section 7.130 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Pacific Coast § 7.130 Point Conception, CA to Point Sur, CA. (a) A line drawn from the...

  5. 46 CFR 7.125 - Point Vincente, CA to Point Conception, CA. (United States)


    ... 46 Shipping 1 2010-10-01 2010-10-01 false Point Vincente, CA to Point Conception, CA. 7.125 Section 7.125 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY PROCEDURES APPLICABLE TO THE PUBLIC BOUNDARY LINES Pacific Coast § 7.125 Point Vincente, CA to Point Conception, CA. (a) A line drawn from...

  6. In vitro effects of estrogen and progesterone containing drugs on human erythrocyte carbonic anhydrase I and II isozymes in women smokers and nonsmokers

    Directory of Open Access Journals (Sweden)

    Mine Islimye Taskin


    Conclusion: The results of the current study provide important information to clinicians about how to consider the possible adverse effects of these drugs which are produced as a result of inhibition of CA I and CA II enzyme. Clinicians should take into consideration the side effects caused by CA I and CA II enzyme inhibition when prescribing these drugs in the treatment of different clinical conditions, especially in women who smoke.

  7. Evaluation of I/Ca ratios in benthic foraminifera from the Peruvian oxygen minimum zone as proxy for redox conditions in the ambient water masses (United States)

    Glock, N.; Liebetrau, V.; Eisenhauer, A.


    Tropical oxygen minimum zones (OMZs) are most important areas of oxygen depletion in today´s oceans and nutrient cycling in these regions has a large socio-economic impact because they account for about 17% of the global commercial fish catches(1). Possibly increasing magnitude and area of oxygen depletion in these regions, might endanger rich pelagic fish habitats in the future threatening the global marine food supply. By the use of a quantitative redox proxy in OMZs, reconstruction of the temporal variation in OMZ extension eventually providing information about past and future changes in oxygenation and the anthropogenic role in the recent trend of expanding OMZs(2). Recent work has shown that iodine/calcium (I/Ca) ratios in marine carbonates are a promising proxy for ambient oxygen concentration(3). Our study explores the correlation of I/Ca ratios in four benthic foraminiferal species (three calcitic, one aragonitic) from the Peruvian OMZ to bottom water oxygen concentrations ([O2]BW) and evaluates foraminiferal I/Ca ratios as a possible redox proxy for the ambient water masses. Our results show that all species have a positive trend in the I/Ca ratios as a function of [O2]BW. Only for the aragonitic species Hoeglundina elegans this trend is not significant. The highest significance has been found for Uvigerina striata (I/Ca = 0.032(±0.004).[O2]BW + 0.29(±0.03), R² = 0.61, F = 75, P solutions, (ii) a species dependency of the I/Ca-[O2]BW relationship which is either related to a strong vital effect or toa species dependency on the calcification depth within sediment, and (iii) the inter-test variability of I/Ca between different specimens from the same species and habitat. (1): FAO FishStat: Fisheries and aquaculture software. In: FAO Fisheries and Aquaculture Department[online]. Rome. Updated 28 Nov. 2013. (2): Stramma et al.: Expanding Oxygen-Minimum Zones in the Tropical Oceans, Science, 320, 655-658, 2008. (3): Lu et al.: Iodine to calcium ratios in

  8. Atom collisions in a strong electromagnetic field

    International Nuclear Information System (INIS)

    Smirnov, V.S.; Chaplik, A.V.


    It is shown that the long-range part of interatomic interaction is considerably altered in a strong electromagnetic field. Instead of the van der Waals law the potential asymptote can best be described by a dipole-dipole R -3 law. Impact broadening and the line shift in a strong nonresonant field are calculated. The possibility of bound states of two atoms being formed in a strong light field is discussed

  9. Labeling the human skeleton with {sup 41}Ca to assess changes in bone calcium metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Denk, E.; Hurrell, R.F.; Walczyk, T. [Institute of Food Science and Nutrition, ETH Zurich, Laboratory of Human Nutrition, Zuerich (Switzerland); Hillegonds, D.; Vogel, J. [Lawrence Livermore National Laboratory, Center for Accelerator Mass Spectrometry, Livermore, CA (United States); Synal, A. [Paul Scherrer Institute/ETH Zurich, Laboratory of Particle Physics, Zuerich (Switzerland); Geppert, C.; Wendt, K. [Johannes Gutenberg University, Institute of Physics, Mainz (Germany); Fattinger, K. [University Hospital Bern, Department of General Internal Medicine, Inselspital, Bern (Switzerland); Hennessy, C.; Berglund, M. [Institute for Reference Materials and Measurements (IRMM), European Commission Joint Research Centre, Geel (Belgium)


    Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using {sup 41}Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary {sup 41}Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of {sup 41}Ca (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary {sup 41}Ca/{sup 40}Ca isotope ratios up to 700 days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary {sup 41}Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) {sup 41}Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary {sup 41}Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the {sup 41}Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary {sup 41}Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated {sup 41}Ca/{sup 40}Ca isotope ratios in urine were significantly lower than the observed {sup 41}Ca/{sup 40}Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying

  10. Angiotensin-2-mediated Ca2+ signaling in the retinal pigment epithelium: role of angiotensin-receptor-associated-protein and TRPV2 channel.

    Directory of Open Access Journals (Sweden)

    Rene Barro-Soria

    Full Text Available Angiotensin II (AngII receptor (ATR is involved in pathologic local events such as neovascularisation and inflammation including in the brain and retina. The retinal pigment epithelium (RPE expresses ATR in its AT1R form, angiotensin-receptor-associated protein (Atrap, and transient-receptor-potential channel-V2 (TRPV2. AT1R and Atrap co-localize to the basolateral membrane of the RPE, as shown by immunostaining. Stimulation of porcine RPE (pRPE cells by AngII results in biphasic increases in intracellular free Ca(2+inhibited by losartan. Xestospongin C (xest C and U-73122, blockers of IP3R and PLC respectively, reduced AngII-evoked Ca(2+response. RPE cells from Atrap(-/- mice showed smaller AngII-evoked Ca(2+peak (by 22% and loss of sustained Ca(2+elevation compared to wild-type. The TRPV channel activator cannabidiol (CBD at 15 µM stimulates intracellular Ca(2+-rise suggesting that porcine RPE cells express TRPV2 channels. Further evidence supporting the functional expression of TRPV2 channels comes from experiments in which 100 µM SKF96365 (a TRPV channel inhibitor reduced the cannabidiol-induced Ca(2+-rise. Application of SKF96365 or reduction of TRPV2 expression by siRNA reduced the sustained phase of AngII-mediated Ca(2+transients by 53%. Thus systemic AngII, an effector of the local renin-angiotensin system stimulates biphasic Ca(2+transients in the RPE by releasing Ca(2+from cytosolic IP3-dependent stores and activating ATR/Atrap and TRPV2 channels to generate a sustained Ca(2+elevation.

  11. GPR55 agonist lysophosphatidylinositol and lysophosphatidylcholine inhibit endothelial cell hyperpolarization via GPR-independent suppression of Na+-Ca2+exchanger and endoplasmic reticulum Ca2+refilling. (United States)

    Bondarenko, Alexander I; Montecucco, Fabrizio; Panasiuk, Olga; Sagach, Vadim; Sidoryak, Nataliya; Brandt, Karim J; Mach, François


    Lysophosphatidylinositol (LPI) and lysophosphatidylcholine (LPC) are lipid signaling molecules that induce endothelium-dependent vasodilation. In addition, LPC suppresses acetylcholine (Ach)-induced responses. We aimed to determine the influence of LPC and LPI on hyperpolarizing responses in vitro and in situ endothelial cells (EC) and identify the underlying mechanisms. Using patch-clamp method, we show that LPI and LPC inhibit EC hyperpolarization to histamine and suppress Na + /Ca 2+ exchanged (NCX) currents in a concentration-dependent manner. The inhibition is non-mode-specific and unaffected by intracellular GDPβS infusion and tempol, a superoxide dismutase mimetic. In excised mouse aorta, LPI strongly inhibits the sustained and the peak endothelial hyperpolarization induced by Ach, but not by SKA-31, an opener of Ca 2+ -dependent K + channels of intermediate and small conductance. The hyperpolarizing responses to consecutive histamine applications are strongly reduced by NCX inhibition. In a Ca 2+ -re-addition protocol, bepridil, a NCX inhibitor, and KB-R7943, a blocker of reversed NCX, inhibit the hyperpolarizing responses to Ca 2+ -re-addition following Ca 2+ stores depletion. These finding indicate that LPC and LPI inhibit endothelial hyperpolarization to Ach and histamine independently of G-protein coupled receptors and superoxide anions. Reversed NCX is critical for ER Ca 2+ refilling in EC. The inhibition of NCX by LPI and LPC underlies diminished endothelium-dependent responses and endothelial dysfunction accompanied by increased levels of these lipids in the blood. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Multiple Ca2+ sensors in secretion

    DEFF Research Database (Denmark)

    Walter, Alexander M; Groffen, Alexander J; Sørensen, Jakob Balslev


    Regulated neurotransmitter secretion depends on Ca(2+) sensors, C2 domain proteins that associate with phospholipids and soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) complexes to trigger release upon Ca(2+) binding. Ca(2+) sensors are thought to prevent spontaneous...... fusion at rest (clamping) and to promote fusion upon Ca(2+) activation. At least eight, often coexpressed, Ca(2+) sensors have been identified in mammals. Accumulating evidence suggests that multiple Ca(2+) sensors interact, rather than work autonomously, to produce the complex secretory response...... observed in neurons and secretory cells. In this review, we present several working models to describe how different sensors might be arranged to mediate synchronous, asynchronous and spontaneous neurotransmitter release. We discuss the scenario that different Ca(2+) sensors typically act on one shared...

  13. Evaluation of in vitro effects of some analgesic drugs on erythrocyte and recombinant carbonic anhydrase I and II. (United States)

    Gökçe, Başak; Gençer, Nahit; Arslan, Oktay; Turkoğlu, Sumeyye Aydogan; Alper, Meltem; Köçkar, Feray


    The in vitro effects of the injectable form of analgesic drugs, dexketoprofen trometamol, dexamethasone sodium phosphate, metamizole sodium, diclofenac sodium, thiocolchicoside, on the activity of purified human carbonic anhydrase I and II were evaluated. The effect of these drugs on erythrocyte hCA I and hCA II was compared to recombinant hCA I and hCA II expressed in Ecoli. IC(50) values of the drugs that caused inhibition were determined by means of activity percentage diagrams. The IC(50) concentrations of dexketoprofen trometamol and dexamethasone sodium phosphate on hCA I were 683 μM and 4250 μM and for hCA II 950 μM and 6200 μM respectively. Conversely, the enzyme activity was increased by diflofenac sodium. In addition, thiocolchicoside has not any affect on hCA I and hCA II. The effect of these drugs on erythrocyte hCA I and hCA II were consistent with the inhibition of recombinant enzymes.

  14. Direct mobilisation of lysosomal Ca2+ triggers complex Ca2+ signals. (United States)

    Kilpatrick, Bethan S; Eden, Emily R; Schapira, Anthony H; Futter, Clare E; Patel, Sandip


    Accumulating evidence implicates acidic organelles of the endolysosomal system as mobilisable stores of Ca(2+) but their relationship to the better-characterised endoplasmic reticulum (ER) Ca(2+) store remains unclear. Here we show that rapid osmotic permeabilisation of lysosomes evokes prolonged, spatiotemporally complex Ca(2+) signals in primary cultured human fibroblasts. These Ca(2+) signals comprised an initial response that correlated with lysosomal disruption and secondary long-lasting spatially heterogeneous Ca(2+) oscillations that required ER-localised inositol trisphosphate receptors. Electron microscopy identified extensive membrane contact sites between lysosomes and the ER. Mobilisation of lysosomal Ca(2+) stores is thus sufficient to evoke ER-dependent Ca(2+) release probably through lysosome-ER membrane contact sites, and akin to the proposed mechanism of action of the Ca(2+) mobilising messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Our data identify functional and physical association of discrete Ca(2+) stores important for the genesis of Ca(2+) signal complexity.

  15. Streptomyces clavuligerus shows a strong association between TCA cycle intermediate accumulation and clavulanic acid biosynthesis. (United States)

    Ramirez-Malule, Howard; Junne, Stefan; Nicolás Cruz-Bournazou, Mariano; Neubauer, Peter; Ríos-Estepa, Rigoberto


    Clavulanic acid (CA) is produced by Streptomyces clavuligerus (S. clavuligerus) as a secondary metabolite. Knowledge about the carbon flux distribution along the various routes that supply CA precursors would certainly provide insights about metabolic performance. In order to evaluate metabolic patterns and the possible accumulation of tricarboxylic acid (TCA) cycle intermediates during CA biosynthesis, batch and subsequent continuous cultures with steadily declining feed rates were performed with glycerol as the main substrate. The data were used to in silico explore the metabolic capabilities and the accumulation of metabolic intermediates in S. clavuligerus. While clavulanic acid accumulated at glycerol excess, it steadily decreased at declining dilution rates; CA synthesis stopped when glycerol became the limiting substrate. A strong association of succinate, oxaloacetate, malate, and acetate accumulation with CA production in S. clavuligerus was observed, and flux balance analysis (FBA) was used to describe the carbon flux distribution in the network. This combined experimental and numerical approach also identified bottlenecks during the synthesis of CA in a batch and subsequent continuous cultivation and demonstrated the importance of this type of methodologies for a more advanced understanding of metabolism; this potentially derives valuable insights for future successful metabolic engineering studies in S. clavuligerus.

  16. Co(II), Ni(II) and Zn(II)

    Indian Academy of Sciences (India)


    161. Synthesis, characterisation and electrochemical behaviour of. Cu(II), Co(II), Ni(II) and Zn(II) complexes derived from acetylacetone and p-anisidine and their antimicrobial activity. N RAMAN*, V MUTHURAJ, S RAVICHANDRAN and. A KULANDAISAMY. Department of Chemistry, VHNSN College, Virudhunagar 626 001 ...

  17. Preoperative serum levels of ca 72-4, cea, ca 19-9, and Alpha-fetoprotein in patients with gastric cancer Níveis séricos pré-operatórios de CA 72-4, CEA, CA 19-9 e Alfa-fetoproteína em pacientes com câncer gástrico

    Directory of Open Access Journals (Sweden)

    Rejane Mattar


    Full Text Available INTRODUCTION: The clinical importance of preoperative serum levels of CA 72-4, carcinoembryonic antigen (CEA, CA 19-9, and alpha-fetoprotein (AFP was prospectively evaluated in 44 patients with gastric cancer. METHOD: The serum tumor marker levels were determined by commercial radioimmunoassay kits. Positivity for CA 72-4 (>4 U/mL, CEA (>5 ng/mL, CA 19-9 (>37 U/mL, and AFP (>10 ng/mL were correlated according to the stage, histology, and lymph node metastasis. RESULTS AND DISCUSSION: CA 72-4 showed a higher positivity rate for gastric cancer (47.7% than CEA (25%, CA 19-9 (25%, and AFP (0%. The combination of CA 72-4 with CEA and CA 19-9 increased the sensitivity to 61.4%. The positivity rates of CA 72-4 in patients at stages I and II (initial disease and in patients at stages III and IV (advanced disease were 9% and 60.6%, respectively (P INTRODUÇÃO: A importância clínica dos níveis séricos pré-operatórios de CA 72-4, antígeno carcinoembrionário (CEA, CA 19-9 e alfa-fetoproteína (AFPfoi avaliada prospectivamente em 44 pacientes com câncer gástrico. MÉTODOS: Os marcadores tumorais foram quantificados com o emprego de kits comerciais de radioimunoensaio. A positividade dos marcadores, CA 72-4 (>4 U/ml, CEA (>5 ng/ml, CA 19-9 (>37 U/ml e AFP (>10 ng/ml, foi correlacionada com o estágio da doença, a histologia do tumor e comprometimento de linfonodo. RESULTADOS E DISCUSSÃO: O marcador CA 72-4 apresentou maior positividade para o câncer gástrico (47,7% que CEA (25%, CA 19-9 (25% e AFP (0%. A associação de CA 72-4, CEA e CA 19-9 aumentou a sensibilidade para 61,4%. A positividade do CA 72-4 nos pacientes com estágios I e II (Doença Inicial e nos pacientes com estágios III e IV (Doença Avançada foi de 9 e 60,6%, respectivamente (p<0,005. Não foi observada correlação entre os níveis séricos de CEA e CA 19-9 com o estágio do câncer gástrico. O CA 72-4 apresentou tendência de sugerir comprometimento de linfonodo, mas n

  18. Synthesis and characterisation of alkaline earth bis(diphenylphosphano)metallocene complexes and heterobimetallic alkaline earth metal/platinum(II) complexes [Ae(thf)(x)(η5-C5H4PPh2)2Pt(Me)2] (Ae = Ca, Sr, Ba). (United States)

    Daniels, Daisy P; Deacon, Glen B; Harakat, Dominique; Jaroschik, Florian; Junk, Peter C


    A series of alkaline earth metallocene complexes carrying the diphenylphosphanocyclopentadienyl ligand, [Ae(L)(x)(η(5)-C(5)H(4)PPh(2))(2)] (Ae = Ca, L = thf, x = 1 (6a); Ae = Ca, L = dme, x = 1 (6b); Ae = Sr, L = thf, x = 1 (7); Ae = Ba, L = thf, x = 1 (8a); Ae = Ba, L = dme, x = 2 (8b)), were prepared by redox transmetallation/protolysis from the free metals, diphenylmercury and diphenylphosphanocyclopentadiene. These complexes were characterised using multinuclear NMR spectroscopy and two by single crystal X-ray diffraction. [Ca(dme)(η(5)-C(5)H(4)PPh(2))(2)] (6b) is a discrete neutral monomeric eight coordinate molecule in which the phosphorus atoms are not coordinated to the calcium ion and the larger barium analogue, ten-coordinate [Ba(dme)(2)(η(5)-C(5)H(4)PPh(2))(2)] (8b), has an extremely bent sandwich structure due to the two dme ligands attached to the metal. Bimetallic complexes, [Ae(thf)(x)(η(5)-C(5)H(4)PPh(2))(2)Pt(Me)(2)].(solv) (Ae = Ca, L = thf, x = 2, solv = 1.5thf (9); Ae = Sr, L = thf, x = 3, solv = 1.5thf (10); Ae = Ba, L = thf, x = 3, solv = thf (11)) were obtained by reaction of the homometallic complexes with [Pt(cod)(Me)(2)]. The crystal structures of [Ca(thf)(2)(η(5)-C(5)H(4)PPh(2))(2)Pt(Me)(2)].1.5thf (9), [Sr(thf)(3)(η(5)-C(5)H(4)PPh(2))(2)Pt(Me)(2)].1.5thf (10) and [Ba(thf)(3)(η(5)-C(5)H(4)PPh(2))(2)Pt(Me)(2)].thf (11) show the eight (calcium) and nine coordinate (strontium and barium) fragments acting as a chelating metalloligand attached to the square planar platinum through the phosphorus donor atoms. The solution chemistry of these bimetallic complexes has been investigated by NMR spectroscopy, electro-spray ionisation mass spectrometry and conductivity experiments which indicate that the bimetallic compounds persist in solution.

  19. Host material induced hyperfine structure of F{sup +} centres EPR spectra in CaS

    Energy Technology Data Exchange (ETDEWEB)

    Seeman, Viktor, E-mail:; Dolgov, Sergei; Maaroos, Aarne


    The hyperfine structure (HFS) of F{sup +} centres in CaS single crystals due to the interaction with {sup 33}S and {sup 43}Ca nuclei was observed in EPR spectra for the first time. Angular variations of the HFS were measured for rotation of magnetic field in {100} and {110} crystallographic planes. Using measured orientation-dependent EPR spectra and the EPR NMR program, the parameters of the spin Hamiltonian were determined. In case of {sup 33}S nucleus there is a strong dependence of the F{sup +} centre EPR spectrum on the quadrupole term whereas for {sup 43}Ca nucleus this dependence is insignificant.

  20. Muscle-Type Specific Autophosphorylation of CaMKII Isoforms after Paced Contractions

    NARCIS (Netherlands)

    Eilers, W.; Gevers, W.; van Overbeek, D.; de Haan, A.; Jaspers, R.T.; Hilbers, P.A.; van Riel, A.C.R.; Flueck, M.


    We explored to what extent isoforms of the regulator of excitation-contraction and excitation-transcription coupling, calcium/calmodulin protein kinase II (CaMKII) contribute to the specificity of myocellular calcium sensing between muscle types and whether concentration transients in its

  1. Analytical and clinical evaluation of an electrochemiluminescence immunoassay for the determination of CA 125

    NARCIS (Netherlands)

    H.E. van Ingen (Erik); D.W. Chan (Daniel); W. Hubl; H. Miyachi; R. Molina (Rafael); L. Pitzel; A. Ruibal; J.C. Rymer; I. Domke (Ingrid)


    textabstractThe CA 125 II assay on the Elecsys(R) 2010 analyzer was evaluated in an international multicenter trial. Imprecision studies yielded within-run CVs of 0.8-3.3% and between-day CVs of 2.4-10.9%; CVs for total imprecision in the manufacturer's laboratory were

  2. Ca2+/cation antiporters (CaCA: Identification, characterization and expression profiling in bread wheat (Triticum aestivum L.

    Directory of Open Access Journals (Sweden)

    Mehak Taneja


    Full Text Available The Ca2+/cation antiporters (CaCA superfamily proteins play vital function in Ca2+ ion homeostasis, which is an important event during development and defense response. Molecular characterization of these proteins has been performed in certain plants, but they are still not characterized in Triticum aestivum (bread wheat. Herein, we identified thirty four TaCaCA superfamily proteins, which were classified into TaCAX, TaCCX, TaNCL and TaMHX protein families based on their structural organization and evolutionary relation with earlier reported proteins. Since the T. aestivum comprises an allohexaploid genome, TaCaCA genes were derived from each A, B and D subgenome and homeologous chromosome (HC, except chromosome-group 1. Majority of genes were derived from more than one HCs in each family that were considered as homeologous genes (HGs due to their high similarity with each other. These HGs showed comparable gene and protein structures in terms of exon/intron organization and domain architecture. Majority of TaCaCA proteins comprised two Na_Ca_ex domains. However, TaNCLs consisted of an additional EF-hand domain with calcium binding motifs. Each TaCaCA protein family consisted of about ten transmembrane and two α-repeat regions with specifically conserved signature motifs except TaNCL, which had single α-repeat. Variable expression of most of the TaCaCA genes during various developmental stages suggested their specified role in development. However, constitutively high expression of a few genes like TaCAX1-A and TaNCL1-B indicated their role throughout the plant growth and development. The modulated expression of certain genes during biotic (fungal infections and abiotic stresses (heat, drought, salt suggested their role in stress response. Majority of TaCCX and TaNCL family genes were found highly affected during various abiotic stresses. However the role of individual gene needs to be established. The present study unfolded the opportunity

  3. Ca2+/Cation Antiporters (CaCA): Identification, Characterization and Expression Profiling in Bread Wheat (Triticum aestivum L.). (United States)

    Taneja, Mehak; Tyagi, Shivi; Sharma, Shailesh; Upadhyay, Santosh Kumar


    The Ca 2+ /cation antiporters (CaCA) superfamily proteins play vital function in Ca 2+ ion homeostasis, which is an important event during development and defense response. Molecular characterization of these proteins has been performed in certain plants, but they are still not characterized in Triticum aestivum (bread wheat). Herein, we identified 34 TaCaCA superfamily proteins, which were classified into TaCAX, TaCCX, TaNCL, and TaMHX protein families based on their structural organization and evolutionary relation with earlier reported proteins. Since the T. aestivum comprises an allohexaploid genome, TaCaCA genes were derived from each A, B, and D subgenome and homeologous chromosome (HC), except chromosome-group 1. Majority of genes were derived from more than one HCs in each family that were considered as homeologous genes (HGs) due to their high similarity with each other. These HGs showed comparable gene and protein structures in terms of exon/intron organization and domain architecture. Majority of TaCaCA proteins comprised two Na_Ca_ex domains. However, TaNCLs consisted of an additional EF-hand domain with calcium binding motifs. Each TaCaCA protein family consisted of about 10 transmembrane and two α-repeat regions with specifically conserved signature motifs except TaNCL, which had single α-repeat. Variable expression of most of the TaCaCA genes during various developmental stages suggested their specified role in development. However, constitutively high expression of a few genes like TaCAX1-A and TaNCL1-B indicated their role throughout the plant growth and development. The modulated expression of certain genes during biotic (fungal infections) and abiotic stresses (heat, drought, salt) suggested their role in stress response. Majority of TaCCX and TaNCL family genes were found highly affected during various abiotic stresses. However, the role of individual gene needs to be established. The present study unfolded the opportunity for detail

  4. Synaptic Remodeling in the Dentate Gyrus, CA3, CA1, Subiculum, and Entorhinal Cortex of Mice: Effects of Deprived Rearing and Voluntary Running

    Directory of Open Access Journals (Sweden)

    Andrea T. U. Schaefers


    Full Text Available Hippocampal cell proliferation is strongly increased and synaptic turnover decreased after rearing under social and physical deprivation in gerbils (Meriones unguiculatus. We examined if a similar epigenetic effect of rearing environment on adult neuroplastic responses can be found in mice (Mus musculus. We examined synaptic turnover rates in the dentate gyrus, CA3, CA1, subiculum, and entorhinal cortex. No direct effects of deprived rearing on rates of synaptic turnover were found in any of the studied regions. However, adult wheel running had the effect of leveling layer-specific differences in synaptic remodeling in the dentate gyrus, CA3, and CA1, but not in the entorhinal cortex and subiculum of animals of both rearing treatments. Epigenetic effects during juvenile development affected adult neural plasticity in mice, but seemed to be less pronounced than in gerbils.

  5. Strong ideal convergence in probabilistic metric spaces

    Indian Academy of Sciences (India)

    sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and ... also important applications in nonlinear analysis [2]. The theory was brought to ..... for each t > 0 since each set on the right-hand side of the relation (3.1) belongs to I. Thus, by Definition 2.11 and the ...

  6. Large N baryons, strong coupling theory, quarks

    International Nuclear Information System (INIS)

    Sakita, B.


    It is shown that in QCD the large N limit is the same as the static strong coupling limit. By using the static strong coupling techniques some of the results of large N baryons are derived. The results are consistent with the large N SU(6) static quark model. (author)

  7. Optimization of strong and weak coordinates

    NARCIS (Netherlands)

    Swart, M.; Bickelhaupt, F.M.


    We present a new scheme for the geometry optimization of equilibrium and transition state structures that can be used for both strong and weak coordinates. We use a screening function that depends on atom-pair distances to differentiate strong coordinates from weak coordinates. This differentiation

  8. Strong decays of nucleon and delta resonances

    International Nuclear Information System (INIS)

    Bijker, R.; Leviatan, A.


    We study the strong couplings of the nucleon and delta resonances in a collective model. In the ensuing algebraic treatment we derive closed expressions for decay widths which are used to analyze the experimental data for strong decays into the pion and eta channels. (Author)

  9. Theoretical studies of strongly correlated fermions

    Energy Technology Data Exchange (ETDEWEB)

    Logan, D. [Institut Max von Laue - Paul Langevin (ILL), 38 - Grenoble (France)


    Strongly correlated fermions are investigated. An understanding of strongly correlated fermions underpins a diverse range of phenomena such as metal-insulator transitions, high-temperature superconductivity, magnetic impurity problems and the properties of heavy-fermion systems, in all of which local moments play an important role. (author).

  10. Effect of sulfation on the surface activity of CaO for N{sub 2}O decomposition

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Lingnan, E-mail: [School of Energy, Power and Mechanical Engineering, North China Electric Power University, 102206 Beijing (China); National Engineering Laboratory for Biomass Power Generation Equipment, North China Electric Power University, 102206 Beijing (China); Hu, Xiaoying, E-mail: [National Engineering Laboratory for Biomass Power Generation Equipment, North China Electric Power University, 102206 Beijing (China); Qin, Wu, E-mail: [National Engineering Laboratory for Biomass Power Generation Equipment, North China Electric Power University, 102206 Beijing (China); Dong, Changqing, E-mail: [National Engineering Laboratory for Biomass Power Generation Equipment, North China Electric Power University, 102206 Beijing (China); Yang, Yongping, E-mail: [School of Energy, Power and Mechanical Engineering, North China Electric Power University, 102206 Beijing (China)


    Graphical abstract: - Highlights: • Sulfation of CaO (1 0 0) surface greatly deactivates its surface activity for N{sub 2}O decomposition. • An increase of sulfation degree leads to a decrease of CaO surface activity for N{sub 2}O decomposition. • Sulfation from CaSO{sub 3} into CaSO{sub 4} is the crucial step for deactivating the surface activity for N{sub 2}O decomposition. • The electronic interaction CaO (1 0 0)/CaSO{sub 4} (0 0 1) interface is limited to the bottom layer of CaSO{sub 4} (0 0 1) and the top layer of CaO (1 0 0). • CaSO{sub 4} (0 0 1) and (0 1 0) surfaces show negligible catalytic ability for N{sub 2}O decomposition. - Abstract: Limestone addition to circulating fluidized bed boilers for sulfur removal affects nitrous oxide (N{sub 2}O) emission at the same time, but mechanism of how sulfation process influences the surface activity of CaO for N{sub 2}O decomposition remains unclear. In this paper, we investigated the effect of sulfation on the surface properties and catalytic activity of CaO for N{sub 2}O decomposition using density functional theory calculations. Sulfation of CaO (1 0 0) surface by the adsorption of a single gaseous SO{sub 2} or SO{sub 3} molecule forms stable local CaSO{sub 3} or CaSO{sub 4} on the CaO (1 0 0) surface with strong hybridization between the S atom of SO{sub x} and the surface O anion. The formed local CaSO{sub 3} increases the barrier energy of N{sub 2}O decomposition from 0.989 eV (on the CaO (1 0 0) surface) to 1.340 eV, and further sulfation into local CaSO{sub 4} remarkably increases the barrier energy to 2.967 eV. Sulfation from CaSO{sub 3} into CaSO{sub 4} is therefore the crucial step for deactivating the surface activity for N{sub 2}O decomposition. Completely sulfated CaSO{sub 4} (0 0 1) and (0 1 0) surfaces further validate the negligible catalytic ability of CaSO{sub 4} for N{sub 2}O decomposition.

  11. CaLB Catalyzed Conversion of ε-Caprolactone in Aqueous Medium. Part 1: Immobilization of CaLB to Microgels

    Directory of Open Access Journals (Sweden)

    Stefan Engel


    Full Text Available The enzymatic ring-opening polymerization of lactones is a method of increasing interest for the synthesis of biodegradable and biocompatible polymers. In the past it was shown that immobilization of Candida antarctica lipase B (CaLB and the reaction medium play an important role in the polymerization ability especially of medium ring size lactones like ε-caprolactone (ε-CL. We investigated a route for the preparation of compartmentalized microgels based on poly(glycidol in which CaLB was immobilized to increase its esterification ability. To find the ideal environment for CaLB, we investigated the acceptable water concentration and the accessibility for the monomer in model polymerizations in toluene and analyzed the obtained oligomers/polymers by NMR and SEC. We observed a sufficient accessibility for ε-CL to a toluene like hydrophobic phase imitating a hydrophobic microgel. Comparing free CaLB and Novozym® 435 we found that not the monomer concentration but rather the solubility of the enzyme, as well as the water concentration, strongly influences the equilibrium of esterification and hydrolysis. On the basis of these investigations, microgels of different polarity were prepared and successfully loaded with CaLB by physical entrapment. By comparison of immobilized and free CaLB, we demonstrated an effect of the hydrophobicity of the microenvironment of CaLB on its enzymatic activity.

  12. Photometric and spectroscopic monitoring of AA Tau, DN Tau, UX Tau A, T Tau, RY Tau, Lk Ca 4, and Lk Ca 7 (United States)

    Vrba, F. J.; Chugainov, P. F.; Weaver, W. B.; Stauffer, J. S.


    We report the results of a UBVRI photometric monitoring campaign for three classical T Tauri stars (AA Tau, DN Tau, and UX Tau A) and two weak emission line T Tauri stars (Lk Ca 4 and Lk Ca 7). Observations were obtained at three sites during a core observing period spanning UT 1985 October 14 through UT 1985 December 25, with additional observations continuing until UT 1986 April 6. Concurrent spectrophotometric observations were obtained for all main program stars except Lk Ca 7 and additionally for T Tau, RW Aur, and RY Tau. Periodic photometric variability, assumed to be the stars' rotation periods, were found for AA Tau, DN Tau, Lk Ca 4, and Lk Ca 7, respectively, as 8.2, 6.3, 3.4, and 5.7 days. Several U-filter flares were observed for Lk Ca 4 and Lk Ca 7, which are strongly concentrated toward phases of minimum light. Correlations are found between H-alpha line strengths and V magnitudes for AA Tau and RY Tau. An analysis of absolute color variations of classical T Tauri stars confirms that hot spots are the predominant cause of these stars' variability. Our overall results are consistent with earlier findings that long-lived cool spots are responsible for most of the variability found for weak-emission T Tauri stars, while temporal hot spots are primarily responsible for the observed variability found in classical T Tauri stars.

  13. Seismic switch for strong motion measurement (United States)

    Harben, P.E.; Rodgers, P.W.; Ewert, D.W.


    A seismic switching device is described that has an input signal from an existing microseismic station seismometer and a signal from a strong motion measuring instrument. The seismic switch monitors the signal level of the strong motion instrument and passes the seismometer signal to the station data telemetry and recording systems. When the strong motion instrument signal level exceeds a user set threshold level, the seismometer signal is switched out and the strong motion signal is passed to the telemetry system. The amount of time the strong motion signal is passed before switching back to the seismometer signal is user controlled between 1 and 15 seconds. If the threshold level is exceeded during a switch time period, the length of time is extended from that instant by one user set time period. 11 figs.

  14. Coral Cd/Ca and Mn/Ca records of ENSO variability in the Gulf of California

    Directory of Open Access Journals (Sweden)

    J. D. Carriquiry


    Full Text Available We analyzed the trace element ratios Cd/Ca and Mn/Ca in three coral colonies (Porites panamensis (1967–1989, Pavona clivosa (1967–1989 and Pavona gigantea (1979–1989 from Cabo Pulmo reef, Southern Gulf of California, Mexico, to assess the oceanographic changes caused by El Niño – Southern Oscillation (ENSO events in the Eastern Tropical North Pacific (ETNP. Interannual variations in the coral Cd/Ca and Mn/Ca ratios showed clear evidence that incorporation of Cd and Mn in the coral skeleton was influenced by ENSO conditions, but the response for each metal was controlled by different processes. The Mn/Ca ratios were significantly higher during ENSO years (p<0.05 relative to non-ENSO years for the three species of coral. In contrast, the Cd/Ca was systematically lower during ENSO years, but the difference was significant (p<0.05 only in Pavona gigantea. A decrease in the incorporation of Cd and a marked increase in Mn indicated strongly reduced vertical mixing in the Gulf of California during the mature phase of El Niño. The oceanic warming during El Niño events produces a relaxation of upwelling and a stabilization of the thermocline, which may act as a physical barrier limiting the transport of Cd from deeper waters into the surface layer. In turn, this oceanic condition can increase the residence time of particulate-Mn in surface waters, allowing an increase in the photo-reduction of particulate-Mn and the release of available Mn into the dissolved phase. These results support the use of Mn/Ca and Cd/Ca ratios in biogenic carbonates as tracers of increases in ocean stratification and trade wind weakening and/or collapse in the ETNP during ENSO episodes.

  15. The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia

    Directory of Open Access Journals (Sweden)

    Rossner Moritz


    Full Text Available Abstract Background The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD, RNA amplification, and array hybridization. Results Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. Conclusion The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel

  16. Weak transition of 44Ca

    International Nuclear Information System (INIS)

    Tauhata, L.


    A study of the nuclear core contribution to the excited nuclear states was done, along with its theoretical evaluation and interpretation, in the light nuclei region. The 727 KeV gamma ray transition between the 1885 KeV O + and 1157 KeV - 2 + states was detected, putting in evidence experimentally, the possibility of the 0 + state, characterized as core excitation, and found to be by + decay or electron capture from 44,44m Sc. The formation of the 2850 KeV state, due to 880 KeV transition from the 3667 KeV state, is re-discussed. The 564 KeV and 1684 KeV transitions from the 2850 KeV state to the 2285 KeV and 1157 KeV states, respectively, are also discussed. A new scheme is proposed for the 44 Ca excited states. (Author) [pt

  17. A novel CISD2 mutation associated with a classical Wolfram syndrome phenotype alters Ca2+ homeostasis and ER-mitochondria interactions. (United States)

    Rouzier, Cécile; Moore, David; Delorme, Cécile; Lacas-Gervais, Sandra; Ait-El-Mkadem, Samira; Fragaki, Konstantina; Burté, Florence; Serre, Valérie; Bannwarth, Sylvie; Chaussenot, Annabelle; Catala, Martin; Yu-Wai-Man, Patrick; Paquis-Flucklinger, Véronique


    Wolfram syndrome (WS) is a progressive neurodegenerative disease characterized by early-onset optic atrophy and diabetes mellitus, which can be associated with more extensive central nervous system and endocrine complications. The majority of patients harbour pathogenic WFS1 mutations, but recessive mutations in a second gene, CISD2, have been described in a small number of families with Wolfram syndrome type 2 (WFS2). The defining diagnostic criteria for WFS2 also consist of optic atrophy and diabetes mellitus, but unlike WFS1, this phenotypic subgroup has been associated with peptic ulcer disease and an increased bleeding tendency. Here, we report on a novel homozygous CISD2 mutation (c.215A > G; p.Asn72Ser) in a Moroccan patient with an overlapping phenotype suggesting that Wolfram syndrome type 1 and type 2 form a continuous clinical spectrum with genetic heterogeneity. The present study provides strong evidence that this particular CISD2 mutation disturbs cellular Ca2+ homeostasis with enhanced Ca2+ flux from the ER to mitochondria and cytosolic Ca2+ abnormalities in patient-derived fibroblasts. This Ca2+ dysregulation was associated with increased ER-mitochondria contact, a swollen ER lumen and a hyperfused mitochondrial network in the absence of overt ER stress. Although there was no marked alteration in mitochondrial bioenergetics under basal conditions, culture of patient-derived fibroblasts in glucose-free galactose medium revealed a respiratory chain defect in complexes I and II, and a trend towards decreased ATP levels. Our results provide important novel insight into the potential disease mechanisms underlying the neurodegenerative consequences of CISD2 mutations and the subsequent development of multisystemic disease. © The Author 2017. Published by Oxford University Press.

  18. Small Ca2+releases enable hour-long high-frequency contractions in midshipman swimbladder muscle. (United States)

    Nelson, Frank E; Hollingworth, Stephen; Marx, James O; Baylor, Stephen M; Rome, Lawrence C


    Type I males of the Pacific midshipman fish ( Porichthys notatus ) vibrate their swimbladder to generate mating calls, or "hums," that attract females to their nests. In contrast to the intermittent calls produced by male Atlantic toadfish ( Opsanus tau ), which occur with a duty cycle (calling time divided by total time) of only 3-8%, midshipman can call continuously for up to an hour. With 100% duty cycles and frequencies of 50-100 Hz (15°C), the superfast muscle fibers that surround the midshipman swimbladder may contract and relax as many as 360,000 times in 1 h. The energy for this activity is supported by a large volume of densely packed mitochondria that are found in the peripheral and central regions of the fiber. The remaining fiber cross section contains contractile filaments and a well-developed network of sarcoplasmic reticulum (SR) and triadic junctions. Here, to understand quantitatively how Ca 2+ is managed by midshipman fibers during calling, we measure (a) the Ca 2+ pumping-versus-pCa and force-versus-pCa relations in skinned fiber bundles and (b) changes in myoplasmic free [Ca 2+ ] (Δ[Ca 2+ ]) during stimulated activity of individual fibers microinjected with the Ca 2+ indicators Mag-fluo-4 and Fluo-4. As in toadfish, the force-pCa relation in midshipman is strongly right-shifted relative to the Ca 2+ pumping-pCa relation, and contractile activity is controlled in a synchronous, not asynchronous, fashion during electrical stimulation. SR Ca 2+ release per action potential is, however, approximately eightfold smaller in midshipman than in toadfish. Midshipman fibers have a larger time-averaged free [Ca 2+ ] during activity than toadfish fibers, which permits faster Ca 2+ pumping because the Ca 2+ pumps work closer to their maximum rate. Even with midshipman's sustained release and pumping of Ca 2+ , however, the Ca 2+ energy cost of calling (per kilogram wet weight) is less than twofold more in midshipman than in toadfish. © 2018 Nelson et al.

  19. Stable incorporation versus dynamic exchange of β subunits in a native Ca2+ channel complex. (United States)

    Campiglio, Marta; Di Biase, Valentina; Tuluc, Petronel; Flucher, Bernhard E


    Voltage-gated Ca(2+) channels are multi-subunit membrane proteins that transduce depolarization into cellular functions such as excitation-contraction coupling in muscle or neurotransmitter release in neurons. The auxiliary β subunits function in membrane targeting of the channel and modulation of its gating properties. However, whether β subunits can reversibly interact with, and thus differentially modulate, channels in the membrane is still unresolved. In the present study we applied fluorescence recovery after photobleaching (FRAP) of GFP-tagged α1 and β subunits expressed in dysgenic myotubes to study the relative dynamics of these Ca(2+) channel subunits for the first time in a native functional signaling complex. Identical fluorescence recovery rates of both subunits indicate stable interactions, distinct recovery rates indicate dynamic interactions. Whereas the skeletal muscle β1a isoform formed stable complexes with CaV1.1 and CaV1.2, the non-skeletal muscle β2a and β4b isoforms dynamically interacted with both α1 subunits. Neither replacing the I-II loop of CaV1.1 with that of CaV2.1, nor deletions in the proximal I-II loop, known to change the orientation of β relative to the α1 subunit, altered the specific dynamic properties of the β subunits. In contrast, a single residue substitution in the α interaction pocket of β1aM293A increased the FRAP rate threefold. Taken together, these findings indicate that in skeletal muscle triads the homologous β1a subunit forms a stable complex, whereas the heterologous β2a and β4b subunits form dynamic complexes with the Ca(2+) channel. The distinct binding properties are not determined by differences in the I-II loop sequences of the α1 subunits, but are intrinsic properties of the β subunit isoforms.

  20. Evidence for a modulation of neutral trehalase activity by Ca2+ and cAMP signaling pathways in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Souza A.C.


    Full Text Available Saccharomyces cerevisiae neutral trehalase (encoded by NTH1 is regulated by cAMP-dependent protein kinase (PKA and by an endogenous modulator protein. A yeast strain with knockouts of CMK1 and CMK2 genes (cmk1cmk2 and its isogenic control (CMK1CMK2 were used to investigate the role of CaM kinase II in the in vitro activation of neutral trehalase during growth on glucose. In the exponential growth phase, cmk1cmk2 cells exhibited basal trehalase activity and an activation ratio by PKA very similar to that found in CMK1CMK2 cells. At diauxie, even though both cells presented comparable basal trehalase activities, cmk1cmk2 cells showed reduced activation by PKA and lower total trehalase activity when compared to CMK1CMK2 cells. To determine if CaM kinase II regulates NTH1 expression or is involved in post-translational modulation of neutral trehalase activity, NTH1 promoter activity was evaluated using an NTH1-lacZ reporter gene. Similar ß-galactosidase activities were found for CMK1CMK2 and cmk1cmk2 cells, ruling out the role of CaM kinase II in NTH1 expression. Thus, CaM kinase II should act in concert with PKA on the activation of the cryptic form of neutral trehalase. A model for trehalase regulation by CaM kinase II is proposed whereby the target protein for Ca2+/CaM-dependent kinase II phosphorylation is not the neutral trehalase itself. The possible identity of this target protein with the recently identified trehalase-associated protein YLR270Wp is discussed.

  1. Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

    Directory of Open Access Journals (Sweden)

    Yuan Hung Lo


    Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

  2. Regulation of Ca2+ Signaling in Rat Bile Duct Epithelia by Inositol 1,4,5-Trisphosphate Receptor Isoforms (United States)

    Hirata, Keiji; Dufour, Jean-François; Shibao, Kazunori; Knickelbein, Roy; O'Neill, Allison F.; Bode, Hans-Peter; Cassio, Doris; St-Pierre, Marie V.; LaRusso, Nicholas F.; Leite, M. Fatima; Nathanson, Michael H.


    Cytosolic Ca2+ (Cai2+) regulates secretion of bicarbonate and other ions in the cholangiocyte. In other cell types, this second messenger acts through Ca2+ waves, Ca2+ oscillations, and other subcellular Ca2+ signaling patterns, but little is known about the subcellular organization of Ca2+ signaling in cholangiocytes. Therefore, we examined Ca2+ signaling and the subcellular distribution of Ca2+ release channels in cholangiocytes and in a model cholangiocyte cell line. The expression and subcellular distribution of inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) isoforms and the ryanodine receptor (RyR) were determined in cholangiocytes from normal rat liver and in the normal rat cholangiocyte (NRC) polarized bile duct cell line. Subcellular Ca2+ signaling in cholangiocytes was examined by confocal microscopy. All 3 InsP3R isoforms were expressed in cholangiocytes, whereas RyR was not expressed. The type III InsP3R was the most heavily expressed isoform at the protein level and was concentrated apically, whereas the type I and type II isoforms were expressed more uniformly. The type III InsP3R was expressed even more heavily in NRC cells but was concentrated apically in these cells as well. Adenosine triphosphate (ATP), which increases Ca2+ via InsP3 in cholangiocytes, induced Ca2+ oscillations in both cholangiocytes and NRC cells. Acetylcholine (ACh) induced apical-to-basal Ca2+ waves. In conclusion, Ca2+ signaling in cholangiocytes occurs as polarized Ca2+ waves that begin in the region of the type III InsP3R. Differential subcellular localization of InsP3R isoforms may be an important molecular mechanism for the formation of Ca2+ waves and oscillations in cholangiocytes. Because Cai2+ is in part responsible for regulating ductular secretion, these findings also may have implications for the molecular basis of cholestatic disorders. PMID:12143036

  3. PH dependent uranyl reduction by sorbed Fe(II) on montmorillonite

    International Nuclear Information System (INIS)

    Chakraborty, S.; Boivin, F.F.; Banerjee, D.; Scheinost, A.C.; Mullet, M.; Ehrhardt, J.J.; Brendle, J.; Charlet, L.


    Document available in extended abstract form only. The impact of surface bound Fe(II) in radionuclide migration as a function of pH (6.1-8.5) was studied in U(VI)-Fe(II)-montmorillonite system under a CO 2 -free anoxic (O 2 < 1 ppmv) condition using X-ray spectroscopies. The results show a rapid removal of U(VI) from the aqueous solution occurs within 1 h under experimental pH ranges, whereas the reduction is not completed after 72 h. X-ray absorption near-edge structure (XANES) spectra of U L III -edge show that 96% of the total sorbed U(VI) is reduced at pH 8.5. The reduction rate significantly decreases with decreasing specifically sorbed concentrations of Fe(II) on montmorillonite at lower pH values. The reduction kinetics followed-up by X-ray photoelectron spectroscopy (XPS) during 24 h at pH 7.5 indicates the presence of partially reduced mixed valence U 4 O 9 - like surface species also well explained by relevant pe-pH diagram. The measured redox potentials of Fe(II)/montmorillonite suspensions are controlled by Fe(II)/HFO(s) at pH 6.1 and Fe(II)/γ-FeOOH(s) at 7.5. The slow U(VI) reduction mechanism was attributed to differential reactivities of Fe(II) specifically sorbed on strong and/or weak montmorillonite surface sites. Montmorillonite is a constituent clay mineral of various soils, sediments in reducing environment and the major component of bentonite, a strong candidate for the back-fill material for the radioactive waste repository. Apart from sorption capacity, montmorillonite is also known to catalyze reduction of Cr(VI) (1), Se(IV) (2), chlorinated ethylenes, nitro-aromatic compounds (3) in presence of Fe(II). In the present contribution we investigated the reactivity of Fe(II) sorbed on montmorillonite towards U(VI) as a function of solution pH under strictly O 2 , CO 2 free atmosphere to exclude the effect of carbonate on uranium mobilization. We used higher ionic strength ionic background medium (0.05 M CaCl 2 ) to account only for the

  4. [Cation ions modulate the ACh-sensitive current in type II vestibular hair cells of guinea pigs]. (United States)

    Guo, Chang-Kai; Zhang, Song; Kong, Wei-Jia; Li, Qing-Tian; Li, Zhi-Wang


    Molecular biological studies and electrophysiological data have demonstrated that acetylcholine (ACh) is the principal cochlear and vestibular efferent neurotransmitter among mammalians. However, the functional roles of ACh in type II vestibular hair cells among mammalians are still unclear, with the exception of the well-known alpha9-containing nicotinic ACh receptor (alpha9-nAChR) in cochlear hair cells and frog saccular hair cells. In this study, the properties of the ACh-sensitive current were investigated by whole-cell patch clamp technique in isolated type II vestibular hair cells of guinea pigs. The direct effect of extracellular ACh was to induce a hyperpolarization effect in type II vestibular hair cells. Type II vestibular hair cells displayed a sustained outward current in response to the perfusion of ACh. It took about 60 s for the ACh-sensitive current to get a complete re-activation. The reversal potential of the ACh-sensitive current was (-66 +/- 8) mV, which indicated that potassium ion was the main carrier of this current. The blocking effect by the submillimolar concentration of tetraethylammonium (TEA) further indicated that extracellular ACh stimulated the calcium-dependent potassium current. Following replacement of the compartment of NaCl in the normal external solution with TrisCl, LiCl or saccharose respectively, the amplitude of the ACh-sensitive current was not affected. Blocking of the release of intracellular Ca(2+) stores by intracellular application of heparin failed to inhibit the ACh-sensitive current. Therefore, extracellular Na(+)and the inositol 1,4,5-trisphosphate (IP(3))-dependent intracellular Ca(2+)release were not involved in the activation of the ACh-sensitive current. However, the ACh-sensitive current was strongly affected by the concentration of the extracellular K(+), extracellular Ca(2+) and intracellular Mg(2+). The amplitude of the ACh- sensitive current was strongly inhibited by high concentration of extracellular K

  5. Study of giant multipole resonances in 40Ca

    International Nuclear Information System (INIS)

    Rost, H.


    In the present thesis giant resonance states in 40 Ca were studied by scattering of 104 MeV a particles on 40 Ca and by the reactions 39 K(p vector,p') 39 K and 39 K(p,α) 36 Ar. The scattered α-particles were measured at extreme forward angles (THETAsub(L) = 4 0 -16 0 C), because at forward angles the cross sections for the excitation of states with spin 0 and 1 strongly differ from those with higher spin. The aim of this experiment was first of all the study of the giant resonance region in 40 Ca on the contribution to 0 + or 1 - states. Beside the known electric giant quadrupole resonances at Esub(x) approx. equal to 18.5 MeV (25% EWSR) contributions of EO-strength at Esub(x) approx. equal to 21 MeV (6% EWSR) and indications to a (isoscalar) E1-strength at Esub(x) approx. equal to 14 MeV and Esub(x) approx. equal to 16 MeV were found. At the reactions 39 K(p vector,p') 39 K and 39 K(p,α) 36 Ar in the channels (p,p 0 ),(p,p 4 ), (p,αsub(o)), and (p,α 1 ) at incident energies at about 10 MeV (Esub(x)( 40 Ca) approx. equal to 18 MeV) resonant structures were observed. A scattering phase analysis performed for the elastic proton scattering didn't however yield quantitative results about the resonance parameter. An expansion of the cross sections by Legendre polynomials for the remaining reaction channel didn't allow a conclusion about the dominance of a certain L-value. The only indication to the connection of the observed resonant structures with the giant quadrupole resonance in 40 Ca is therefore the energetic position at about Esub(x) approx. equal to 18 MeV. Altogether the observed structures however were not very pronounced, so it can be concluded, that the excitation of the giant quadrupole resonance in 40 Ca by protons via the ground state of 39 K occurs not very strongly. (orig./HSI) [de

  6. The role of Ca2+ influx in endocytic vacuole formation in pancreatic acinar cells (United States)

    Voronina, Svetlana; Collier, David; Chvanov, Michael; Middlehurst, Ben; Beckett, Alison J.; Prior, Ian A.; Criddle, David N.; Begg, Malcolm; Mikoshiba, Katsuhiko; Sutton, Robert; Tepikin, Alexei V.


    The inducers of acute pancreatitis trigger a prolonged increase in the cytosolic Ca2+ concentration ([Ca2+]c), which is responsible for the damage to and eventual death of pancreatic acinar cells. Vacuolization is an important indicator of pancreatic acinar cell damage. Furthermore, activation of trypsinogen occurs in the endocytic vacuoles; therefore the vacuoles can be considered as ‘initiating’ organelles in the development of the cell injury. In the present study, we investigated the relationship between the formation of endocytic vacuoles and Ca2+ influx developed in response to the inducers of acute pancreatitis [bile acid taurolithocholic acid 3-sulfate (TLC-S) and supramaximal concentration of cholecystokinin-8 (CCK)]. We found that the inhibitor of STIM (stromal interaction molecule)/Orai channels, GSK-7975A, effectively suppressed both the Ca2+ influx (stimulated by inducers of pancreatitis) and the formation of endocytic vacuoles. Cell death induced by TLC-S or CCK was also inhibited by GSK-7975A. We documented the formation of endocytic vacuoles in response to store-operated Ca2+ entry (SOCE) induced by thapsigargin [TG; inhibitor of sarcoplasmic/endoplasmic reticulum (ER) Ca2+ pumps] and observed strong inhibition of TG-induced vacuole formation by GSK-7975A. Finally, we found that structurally-unrelated inhibitors of calpain suppress formation of endocytic vacuoles, suggesting that this Ca2+-dependent protease is a mediator between Ca2+ elevation and endocytic vacuole formation. PMID:25370603

  7. Role of Ca2+, membrane excitability, and Ca2+ stores in failing muscle contraction with aging. (United States)

    Payne, Anthony Michael; Jimenez-Moreno, Ramón; Wang, Zhong-Ming; Messi, María Laura; Delbono, Osvaldo


    Excitation-contraction (EC) coupling in a population of skeletal muscle fibers of aged mice becomes dependent on the presence of external Ca(2+) ions (Payne, A.M., Zheng, Z., Gonzalez, E., Wang, Z.M., Messi, M.L., Delbono, O., 2004b. External Ca(2+)-dependent excitation - contraction coupling in a population of aging mouse skeletal muscle fibers. J. Physiol. 560, 137-155.). However, the mechanism(s) underlying this process remain unknown. In this work, we examined the role of (1) extracellular Ca(2+); (2) voltage-induced influx of external Ca(2+) ions; (3) sarcoplasmic reticulum (SR) Ca(2+) depletion during repeated contractions; (4) store-operated Ca(2+) entry (SOCE); (5) SR ultrastructure; (6) SR subdomain localization of the ryanodine receptor; and (7) sarcolemmal excitability in muscle force decline with aging. These experiments show that external Ca(2+), but not Ca(2+) influx, is needed to maintain force upon repetitive fiber electrical stimulation. Decline in fiber force is associated with depressed SR Ca(2+) release. SR Ca(2+) depletion, SOCE, and the putative segregated Ca(2+) release store do not play a significant role in external Ca(2+)-dependent contraction. More importantly, a significant number of action potentials fail in senescent mouse muscle fibers subjected to a stimulation frequency. These results indicate that failure to generate action potentials accounts for decreased intracellular Ca(2+) mobilization and tetanic force in aging muscle exposed to a Ca(2+)-free medium.

  8. Ca2+ cycling in heart cells from ground squirrels: adaptive strategies for intracellular Ca2+ homeostasis.

    Directory of Open Access Journals (Sweden)

    Xiao-Chen Li

    Full Text Available Heart tissues from hibernating mammals, such as ground squirrels, are able to endure hypothermia, hypoxia and other extreme insulting factors that are fatal for human and nonhibernating mammals. This study was designed to understand adaptive mechanisms involved in intracellular Ca(2+ homeostasis in cardiomyocytes from the mammalian hibernator, ground squirrel, compared to rat. Electrophysiological and confocal imaging experiments showed that the voltage-dependence of L-type Ca(2+ current (I(Ca was shifted to higher potentials in ventricular myocytes from ground squirrels vs. rats. The elevated threshold of I(Ca did not compromise the Ca(2+-induced Ca(2+ release, because a higher depolarization rate and a longer duration of action potential compensated the voltage shift of I(Ca. Both the caffeine-sensitive and caffeine-resistant components of cytosolic Ca(2+ removal were more rapid in ground squirrels. Ca(2+ sparks in ground squirrels exhibited larger amplitude/size and much lower frequency than in rats. Due to the high I(Ca threshold, low SR Ca(2+ leak and rapid cytosolic Ca(2+ clearance, heart cells from ground squirrels exhibited better capability in maintaining intracellular Ca(2+ homeostasis than those from rats and other nonhibernating mammals. These findings not only reveal adaptive mechanisms of hibernation, but also provide novel strategies against Ca(2+ overload-related heart diseases.

  9. Subcellular distribution of glycogen and decreased tetanic Ca2+ in fatigued single intact mouse muscle fibres

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Cheng, Arthur J; Ørtenblad, Niels


    of sarcoplasmic reticulum Ca(2+) release. The aim of the present study was to test directly how the decrease in cytoplasmic free Ca(2+) ([Ca(2+)]i) during repeated tetanic contractions relates to the subcellular glycogen distribution. Single fibres of mouse flexor digitorum brevis muscles were fatigued with 70 Hz......In skeletal muscle fibres, glycogen has been shown to be stored at different subcellular locations: (i) between the myofibrils (intermyofibrillar); (ii) within the myofibrils (intramyofibrillar); and (iii) subsarcolemmal. Of these, intramyofibrillar glycogen has been implied as a critical regulator......, 350 ms tetani given at 2 s (high-intensity fatigue, HIF) or 10 s (low-intensity fatigue, LIF) intervals, while force and [Ca(2+)]i were measured. Stimulation continued until force decreased to 30% of its initial value. Fibres were then prepared for analyses of subcellular glycogen distribution...

  10. Metabolic Regulation of CaMKII Protein and Caspases in Xenopus laevis Egg Extracts* (United States)

    McCoy, Francis; Darbandi, Rashid; Chen, Si-Ing; Eckard, Laura; Dodd, Keela; Jones, Kelly; Baucum, Anthony J.; Gibbons, Jennifer A.; Lin, Sue-Hwa; Colbran, Roger J.; Nutt, Leta K.


    The metabolism of the Xenopus laevis egg provides a cell survival signal. We found previously that increased carbon flux from glucose-6-phosphate (G6P) through the pentose phosphate pathway in egg extracts maintains NADPH levels and calcium/calmodulin regulated protein kinase II (CaMKII) activity to phosphorylate caspase 2 and suppress cell death pathways. Here we show that the addition of G6P to oocyte extracts inhibits the dephosphorylation/inactivation of CaMKII bound to caspase 2 by protein phosphatase 1. Thus, G6P sustains the phosphorylation of caspase 2 by CaMKII at Ser-135, preventing the induction of caspase 2-mediated apoptotic pathways. These findings expand our understanding of oocyte biology and clarify mechanisms underlying the metabolic regulation of CaMKII and apoptosis. Furthermore, these findings suggest novel approaches to disrupt the suppressive effects of the abnormal metabolism on cell death pathways. PMID:23400775

  11. Influence of reaction products of K-getter fuel additives on commercial vanadia-based SCR catalysts Part II. Simultaneous addition of KCl, Ca(OH)(2), H3PO4 and H2SO4 in a hot flue gas at a SCR pilot-scale setup

    DEFF Research Database (Denmark)

    Castellino, Francesco; Jensen, Anker Degn; Johnsson, Jan Erik


    surface and did not proceed at the fast rates known for KCl. This fact indicates that binding K in P-K-Ca compounds is an effective way to reduce the negative influence of alkali metals on the lifetime of the vanadia-based SCR catalysts. On the other hand, P-deposition was favoured by the formation...... biomass combustion. Aerosol measurements carried out by using a SMPS and a low pressure cascade impactor have shown two distinct particle populations with volume-based mean diameters equal to 12 and 300 nm, respectively. The small particles have been associated to polyphosphoric acids formed...

  12. Facilities design for TIBER II

    International Nuclear Information System (INIS)

    Thomson, S.L.; Blevins, J.D.


    This paper describes the conceptual design of the reactor building and reactor maintenance building for the TIBER II tokamak. These buildings are strongly influenced by the reactor configuration, and their characterization allows a better understanding of the economic and technical implications of the reactor design. Key features of TIBER II that affect the facilities design are the small size and compact arrangement, the use of an external vacuum vessel, and the complete reliance on remote maintenance. The building design incorporates requirements for equipment layout, maintenance operations and equipment, safety, and contamination control. 4 figs

  13. Anticancer ruthenium(III) complex KP1019 interferes with ATP-dependent Ca2+ translocation by sarco-endoplasmic reticulum Ca2+-ATPase (SERCA). (United States)

    Sadafi, Fabrizio-Zagros; Massai, Lara; Bartolommei, Gianluca; Moncelli, Maria Rosa; Messori, Luigi; Tadini-Buoninsegni, Francesco


    Sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), a P-type ATPase that sustains Ca2+ transport and plays a major role in intracellular Ca2+ homeostasis, represents a therapeutic target for cancer therapy. Here, we investigated whether ruthenium-based anticancer drugs, namely KP1019 (indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)]), NAMI-A (imidazolium [trans-tetrachloro(1H-imidazole)(S-dimethylsulfoxide)ruthenate(III)]) and RAPTA-C ([Ru(η6-p-cymene)dichloro(1,3,5-triaza-7-phosphaadamantane)]), and cisplatin (cis-diammineplatinum(II) dichloride) might act as inhibitors of SERCA. Charge displacement by SERCA adsorbed on a solid-supported membrane was measured after ATP or Ca2+ concentration jumps. Our results show that KP1019, in contrast to the other metal compounds, is able to interfere with ATP-dependent translocation of Ca2+ ions. An IC50 value of 1 μM was determined for inhibition of calcium translocation by KP1019. Conversely, it appears that KP1019 does not significantly affect Ca2+ binding to the ATPase from the cytoplasmic side. Inhibition of SERCA at pharmacologically relevant concentrations may represent a crucial aspect in the overall pharmacological and toxicological profile of KP1019. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Strong and superstrong pulsed magnetic fields generation

    CERN Document Server

    Shneerson, German A; Krivosheev, Sergey I


    Strong pulsed magnetic fields are important for several fields in physics and engineering, such as power generation and accelerator facilities. Basic aspects of the generation of strong and superstrong pulsed magnetic fields technique are given, including the physics and hydrodynamics of the conductors interacting with the field as well as an account of the significant progress in generation of strong magnetic fields using the magnetic accumulation technique. Results of computer simulations as well as a survey of available field technology are completing the volume.

  15. Impurity screening in strongly coupled plasma systems

    CERN Document Server

    Kyrkos, S


    We present an overview of the problem of screening of an impurity in a strongly coupled one-component plasma within the framework of the linear response (LR) theory. We consider 3D, 2D and quasi-2D layered systems. For a strongly coupled plasma the LR can be determined by way of the known S(k) structure functions. In general, an oscillating screening potential with local overscreening and antiscreening regions emerges. In the case of the bilayer, this phenomenon becomes global, as overscreening develops in the layer of the impurity and antiscreening in the adjacent layer. We comment on the limitations of the LR theory in the strong coupling situation.

  16. The lambda sigma calculus and strong normalization

    DEFF Research Database (Denmark)

    Schack-Nielsen, Anders; Schürmann, Carsten

    Explicit substitution calculi can be classified into several dis- tinct categories depending on whether they are confluent, meta-confluent, strong normalization preserving, strongly normalizing, simulating, fully compositional, and/or local. In this paper we present a variant of the λσ-calculus......, which satisfies all seven conditions. In particular, we show how to circumvent Mellies counter-example to strong normalization by a slight restriction of the congruence rules. The calculus is implemented as the core data structure of the Celf logical framework. All meta-theoretic aspects of this work...

  17. Nonspatial Sequence Coding in CA1 Neurons. (United States)

    Allen, Timothy A; Salz, Daniel M; McKenzie, Sam; Fortin, Norbert J


    The hippocampus is critical to the memory for sequences of events, a defining feature of episodic memory. However, the fundamental neuronal mechanisms underlying this capacity remain elusive. While considerable research indicates hippocampal neurons can represent sequences of locations, direct evidence of coding for the memory of sequential relationships among nonspatial events remains lacking. To address this important issue, we recorded neural activity in CA1 as rats performed a hippocampus-dependent sequence-memory task. Briefly, the task involves the presentation of repeated sequences of odors at a single port and requires rats to identify each item as "in sequence" or "out of sequence". We report that, while the animals' location and behavior remained constant, hippocampal activity differed depending on the temporal context of items-in this case, whether they were presented in or out of sequence. Some neurons showed this effect across items or sequence positions (general sequence cells), while others exhibited selectivity for specific conjunctions of item and sequence position information (conjunctive sequence cells) or for specific probe types (probe-specific sequence cells). We also found that the temporal context of individual trials could be accurately decoded from the activity of neuronal ensembles, that sequence coding at the single-cell and ensemble level was linked to sequence memory performance, and that slow-gamma oscillations (20-40 Hz) were more strongly modulated by temporal context and performance than theta oscillations (4-12 Hz). These findings provide compelling evidence that sequence coding extends beyond the domain of spatial trajectories and is thus a fundamental function of the hippocampus. The ability to remember the order of life events depends on the hippocampus, but the underlying neural mechanisms remain poorly understood. Here we addressed this issue by recording neural activity in hippocampal region CA1 while rats performed a


    Directory of Open Access Journals (Sweden)

    Sri Juari Santosa


    Full Text Available This study reports the results of the elucidation of the sorption-desorption mechanism of Zn(II and Cd(II on chitin through the determination of capacity, energy, and rate constant of sorption as well as the investigation of their desorption properties in NaCl and Na2EDTA solutions. The chitin was isolated through deproteination followed by demineralization of crab (Portunus pelagicus Linn shell using NaOH solutions. The sorption of both metal ions followed the Langmuir isotherm model, resulting the sorption capacities of 3.2 x 10-4 and 2.8 x 10-4 mol g-1 for Zn(II and Cd(II, respectively, and sorption energies of 15.1 kJ mol-1 for Zn(II and 17.9 kJ mol-1 for Cd(II. It was also observed that Zn(II was sorbed slightly faster than Cd(II with first order sorption rate constants of 2.82 x 10-3 min-1 for Zn(II and 2.61 x 10-3 min-1 for Cd(II. The result of the desorption experiment showed that Cd(II and especially Zn(II could only be exchanged by Na(I after desorbing those metal ions by strong chelating agent of EDTA2-. The easier desorption of Zn(II than Cd(II by EDTA2- must be attributed by the smaller sorption energy of Zn(II and by harder acid property of Zn(II than Cd(II as EDTA2- contained hard electron donor elements.   Keywords: sorption, desorption, chitin, Zn(II, Cd(II

  19. Strong Coupling Corrections in Quantum Thermodynamics (United States)

    Perarnau-Llobet, M.; Wilming, H.; Riera, A.; Gallego, R.; Eisert, J.


    Quantum systems strongly coupled to many-body systems equilibrate to the reduced state of a global thermal state, deviating from the local thermal state of the system as it occurs in the weak-coupling limit. Taking this insight as a starting point, we study the thermodynamics of systems strongly coupled to thermal baths. First, we provide strong-coupling corrections to the second law applicable to general systems in three of its different readings: As a statement of maximal extractable work, on heat dissipation, and bound to the Carnot efficiency. These corrections become relevant for small quantum systems and vanish in first order in the interaction strength. We then move to the question of power of heat engines, obtaining a bound on the power enhancement due to strong coupling. Our results are exemplified on the paradigmatic non-Markovian quantum Brownian motion.

  20. Finding quantum effects in strong classical potentials (United States)

    Hegelich, B. Manuel; Labun, Lance; Labun, Ou Z.


    The long-standing challenge to describing charged particle dynamics in strong classical electromagnetic fields is how to incorporate classical radiation, classical radiation reaction and quantized photon emission into a consistent unified framework. The current, semiclassical methods to describe the dynamics of quantum particles in strong classical fields also provide the theoretical framework for fundamental questions in gravity and hadron-hadron collisions, including Hawking radiation, cosmological particle production and thermalization of particles created in heavy-ion collisions. However, as we show, these methods break down for highly relativistic particles propagating in strong fields. They must therefore be improved and adapted for the description of laser-plasma experiments that typically involve the acceleration of electrons. Theory developed from quantum electrodynamics, together with dedicated experimental efforts, offer the best controllable context to establish a robust, experimentally validated foundation for the fundamental theory of quantum effects in strong classical potentials.