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Sample records for sorting receptor vsr-ps1

  1. The Arabidopsis Vacuolar Sorting Receptor1 Is Required for Osmotic Stress-Induced Abscisic Acid Biosynthesis

    KAUST Repository

    Wang, Zhen-Yu; Gehring, Christoph A; Zhu, Jianhua; Li, Feng-Min; Zhu, Jian-Kang; Xiong, Liming

    2014-01-01

    Osmotic stress activates the biosynthesis of the phytohormone abscisic acid (ABA) through a pathway that is rate limited by the carotenoid cleavage enzyme 9-cis-epoxycarotenoid dioxygenase (NCED). To understand the signal transduction mechanism underlying the activation of ABA biosynthesis, we performed a forward genetic screen to isolate mutants defective in osmotic stress regulation of the NCED3 gene. Here, we identified the Arabidopsis (Arabidopsis thaliana) Vacuolar Sorting Receptor1 (VSR1) as a unique regulator of ABA biosynthesis. The vsr1 mutant not only shows increased sensitivity to osmotic stress, but also is defective in the feedback regulation of ABA biosynthesis by ABA. Further analysis revealed that vacuolar trafficking mediated by VSR1 is required for osmotic stress-responsive ABA biosynthesis and osmotic stress tolerance. Moreover, under osmotic stress conditions, the membrane potential, calcium flux, and vacuolar pH changes in the vsr1 mutant differ from those in the wild type. Given that manipulation of the intracellular pH is sufficient to modulate the expression of ABA biosynthesis genes, including NCED3, and ABA accumulation, we propose that intracellular pH changes caused by osmotic stress may play a signaling role in regulating ABA biosynthesis and that this regulation is dependent on functional VSR1.

  2. The Arabidopsis Vacuolar Sorting Receptor1 Is Required for Osmotic Stress-Induced Abscisic Acid Biosynthesis

    KAUST Repository

    Wang, Zhen-Yu

    2014-11-21

    Osmotic stress activates the biosynthesis of the phytohormone abscisic acid (ABA) through a pathway that is rate limited by the carotenoid cleavage enzyme 9-cis-epoxycarotenoid dioxygenase (NCED). To understand the signal transduction mechanism underlying the activation of ABA biosynthesis, we performed a forward genetic screen to isolate mutants defective in osmotic stress regulation of the NCED3 gene. Here, we identified the Arabidopsis (Arabidopsis thaliana) Vacuolar Sorting Receptor1 (VSR1) as a unique regulator of ABA biosynthesis. The vsr1 mutant not only shows increased sensitivity to osmotic stress, but also is defective in the feedback regulation of ABA biosynthesis by ABA. Further analysis revealed that vacuolar trafficking mediated by VSR1 is required for osmotic stress-responsive ABA biosynthesis and osmotic stress tolerance. Moreover, under osmotic stress conditions, the membrane potential, calcium flux, and vacuolar pH changes in the vsr1 mutant differ from those in the wild type. Given that manipulation of the intracellular pH is sufficient to modulate the expression of ABA biosynthesis genes, including NCED3, and ABA accumulation, we propose that intracellular pH changes caused by osmotic stress may play a signaling role in regulating ABA biosynthesis and that this regulation is dependent on functional VSR1.

  3. Expression analysis of Arabidopsis vacuolar sorting receptor 3 reveals a putative function in guard cells.

    Science.gov (United States)

    Avila, Emily L; Brown, Michelle; Pan, Songqin; Desikan, Radhika; Neill, Steven J; Girke, Thomas; Surpin, Marci; Raikhel, Natasha V

    2008-01-01

    Vacuolar sorting receptors (VSRs) are responsible for the proper targeting of soluble cargo proteins to their destination compartments. The Arabidopsis genome encodes seven VSRs. In this work, the spatio-temporal expression of one of the members of this gene family, AtVSR3, was determined by RT-PCR and promoter::reporter gene fusions. AtVSR3 was expressed specifically in guard cells. Consequently, a reverse genetics approach was taken to determine the function of AtVSR3 by using RNA interference (RNAi) technology. Plants expressing little or no AtVSR3 transcript had a compressed life cycle, bolting approximately 1 week earlier and senescing up to 2 weeks earlier than the wild-type parent line. While the development and distribution of stomata in AtVSR3 RNAi plants appeared normal, stomatal function was altered. The guard cells of mutant plants did not close in response to abscisic acid treatment, and the mean leaf temperatures of the RNAi plants were on average 0.8 degrees C lower than both wild type and another vacuolar sorting receptor mutant, atvsr1-1. Furthermore, the loss of AtVSR3 protein caused the accumulation of nitric oxide and hydrogen peroxide, signalling molecules implicated in the regulation of stomatal opening and closing. Finally, proteomics and western blot analyses of cellular proteins isolated from wild-type and AtVSR3 RNAi leaves showed that phospholipase Dgamma, which may play a role in abscisic acid signalling, accumulated to higher levels in AtVSR3 RNAi guard cells. Thus, AtVSR3 may play an important role in responses to plant stress.

  4. Bicaudal-D1 regulates the intracellular sorting and signalling of neurotrophin receptors.

    Science.gov (United States)

    Terenzio, Marco; Golding, Matthew; Russell, Matthew R G; Wicher, Krzysztof B; Rosewell, Ian; Spencer-Dene, Bradley; Ish-Horowicz, David; Schiavo, Giampietro

    2014-07-17

    We have identified a new function for the dynein adaptor Bicaudal D homolog 1 (BICD1) by screening a siRNA library for genes affecting the dynamics of neurotrophin receptor-containing endosomes in motor neurons (MNs). Depleting BICD1 increased the intracellular accumulation of brain-derived neurotrophic factor (BDNF)-activated TrkB and p75 neurotrophin receptor (p75(NTR)) by disrupting the endosomal sorting, reducing lysosomal degradation and increasing the co-localisation of these neurotrophin receptors with retromer-associated sorting nexin 1. The resulting re-routing of active receptors increased their recycling to the plasma membrane and altered the repertoire of signalling-competent TrkB isoforms and p75(NTR) available for ligand binding on the neuronal surface. This resulted in attenuated, but more sustained, AKT activation in response to BDNF stimulation. These data, together with our observation that Bicd1 expression is restricted to the developing nervous system when neurotrophin receptor expression peaks, indicate that BICD1 regulates neurotrophin signalling by modulating the endosomal sorting of internalised ligand-activated receptors. © 2014 The Authors.

  5. 4PS/insulin receptor substrate (IRS)-2 is the alternative substrate of the insulin receptor in IRS-1-deficient mice.

    Science.gov (United States)

    Patti, M E; Sun, X J; Bruening, J C; Araki, E; Lipes, M A; White, M F; Kahn, C R

    1995-10-20

    Insulin receptor substrate-1 (IRS-1) is the major cytoplasmic substrate of the insulin and insulin-like growth factor (IGF)-1 receptors. Transgenic mice lacking IRS-1 are resistant to insulin and IGF-1, but exhibit significant residual insulin action which corresponds to the presence of an alternative high molecular weight substrate in liver and muscle. Recently, Sun et al. (Sun, X.-J., Wang, L.-M., Zhang, Y., Yenush, L. P., Myers, M. G., Jr., Glasheen, E., Lane, W.S., Pierce, J. H., and White, M. F. (1995) Nature 377, 173-177) purified and cloned 4PS, the major substrate of the IL-4 receptor-associated tyrosine kinase in myeloid cells, which has significant structural similarity to IRS-1. To determine if 4PS is the alternative substrate of the insulin receptor in IRS-1-deficient mice, we performed immunoprecipitation, immunoblotting, and phosphatidylinositol (PI) 3-kinase assays using specific antibodies to 4PS. Following insulin stimulation, 4PS is rapidly phosphorylated in liver and muscle, binds to the p85 subunit of PI 3-kinase, and activates the enzyme. Insulin stimulation also results in the association of 4PS with Grb 2 in both liver and muscle. In IRS-1-deficient mice, both the phosphorylation of 4PS and associated PI 3-kinase activity are enhanced, without an increase in protein expression. Immunodepletion of 4PS from liver and muscle homogenates removes most of the phosphotyrosine-associated PI 3-kinase activity in IRS-1-deficient mice. Thus, 4PS is the primary alternative substrate, i.e. IRS-2, which plays a major role in physiologic insulin signal transduction via both PI 3-kinase activation and Grb 2/Sos association. In IRS-1-deficient mice, 4PS/IRS-2 provides signal transduction to these two major pathways of insulin signaling.

  6. A library of 7TM receptor C-terminal tails - Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, A.; Sondergaard, B.P.; Ersbøll, Bjarne Kjær

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor...... only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK1 receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  7. A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP)

    DEFF Research Database (Denmark)

    Heydorn, Arne; Søndergaard, Birgitte P; Ersbøll, Bjarne

    2004-01-01

    Adaptor and scaffolding proteins determine the cellular targeting, the spatial, and thereby the functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, and downstream effectors and the adaptors determine post-signaling events such as receptor...... only a single receptor tail, i.e. the beta(2)-adrenergic receptor, whereas N-ethylmaleimide-sensitive factor bound 11 of the tail-fusion proteins. Of the two proteins proposed to target receptors for lysosomal degradation, sorting nexin 1 (SNX1) bound 10 and the C-terminal domain of G protein...... the expected nanomolar affinities for interaction with SNX1. Truncations of the NK(1) receptor revealed that an extended binding epitope is responsible for the interaction with both SNX1 and G protein-coupled receptor-associated sorting protein as well as with N-ethylmaleimide-sensitive factor. It is concluded...

  8. Regulation of P2Y1 receptor traffic by sorting Nexin 1 is retromer independent.

    Science.gov (United States)

    Nisar, Shaista; Kelly, Eamonn; Cullen, Pete J; Mundell, Stuart J

    2010-04-01

    The activity and traffic of G-protein coupled receptors (GPCRs) is tightly controlled. Recent work from our laboratory has shown that P2Y(1) and P2Y(12) responsiveness is rapidly and reversibly modulated in human platelets and that the underlying mechanism requires receptor trafficking as an essential part of this process. However, little is known about the molecular mechanisms underlying P2Y receptor traffic. Sorting nexin 1 (SNX1) has been shown to regulate the endosomal sorting of cell surface receptors either to lysosomes where they are downregulated or back to the cell surface. These functions may in part be due to interactions of SNX1 with the mammalian retromer complex. In this study, we investigated the role of SNX1 in P2Y receptor trafficking. We show that P2Y(1) receptors recycle via a slow recycling pathway that is regulated by SNX1, whereas P2Y(12) receptors return to the cell surface via a rapid route that is SNX1 independent. SNX1 inhibition caused a dramatic increase in the rate of P2Y(1) receptor recycling, whereas inhibition of Vps26 and Vps35 known to be present in retromer had no effect, indicating that SNX1 regulation of P2Y(1) receptor recycling is retromer independent. In addition, inhibition of SNX4, 6 and 17 proteins did not affect P2Y(1) receptor recycling. SNX1 has also been implicated in GPCR degradation; however, we provide evidence that P2Y receptor degradation is SNX1 independent. These data describe a novel function of SNX1 in the regulation of P2Y(1) receptor recycling and suggest that SNX1 plays multiple roles in endocytic trafficking of GPCRs.

  9. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-κB ligand (RANKL) expression in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-01-01

    Highlights: ► MH7A cells and CD4 + T cells expressed S1P1 and RANKL. ► S1P increased RANKL expression in MH7A cells and CD4 + T cells. ► The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-κB ligand (RANKL) in RA synoviocytes and CD4 + T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4 + T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4 + T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-α in MH7A cells and CD4 + T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4 + T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  10. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  11. GABA(A receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin.

    Directory of Open Access Journals (Sweden)

    Yuji Yoshiike

    Full Text Available Advanced age and mutations in the genes encoding amyloid precursor protein (APP and presenilin (PS1 are two serious risk factors for Alzheimer's disease (AD. Finding common pathogenic changes originating from these risks may lead to a new therapeutic strategy. We observed a decline in memory performance and reduction in hippocampal long-term potentiation (LTP in both mature adult (9-15 months transgenic APP/PS1 mice and old (19-25 months non-transgenic (nonTg mice. By contrast, in the presence of bicuculline, a GABA(A receptor antagonist, LTP in adult APP/PS1 mice and old nonTg mice was larger than that in adult nonTg mice. The increased LTP levels in bicuculline-treated slices suggested that GABA(A receptor-mediated inhibition in adult APP/PS1 and old nonTg mice was upregulated. Assuming that enhanced inhibition of LTP mediates memory decline in APP/PS1 mice, we rescued memory deficits in adult APP/PS1 mice by treating them with another GABA(A receptor antagonist, picrotoxin (PTX, at a non-epileptic dose for 10 days. Among the saline vehicle-treated groups, substantially higher levels of synaptic proteins such as GABA(A receptor alpha1 subunit, PSD95, and NR2B were observed in APP/PS1 mice than in nonTg control mice. This difference was insignificant among PTX-treated groups, suggesting that memory decline in APP/PS1 mice may result from changes in synaptic protein levels through homeostatic mechanisms. Several independent studies reported previously in aged rodents both an increased level of GABA(A receptor alpha1 subunit and improvement of cognitive functions by long term GABA(A receptor antagonist treatment. Therefore, reduced LTP linked to enhanced GABA(A receptor-mediated inhibition may be triggered by aging and may be accelerated by familial AD-linked gene products like Abeta and mutant PS1, leading to cognitive decline that is pharmacologically treatable at least at this stage of disease progression in mice.

  12. Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis.

    Science.gov (United States)

    Dai, Lan; Liu, Yixuan; Xie, Lei; Wu, Xia; Qiu, Lihua; Di, Wen

    2017-09-26

    Sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) signaling pathway has been implicated in a variety of pathological processes of ovarian cancer. However, the function of this axis in ovarian cancer angiogenesis remains incompletely defined. Here we provided the first evidence that SphK1/S1P/S1PR 1/3 pathway played key roles in ovarian cancer angiogenesis. The expression level of SphK1, but not SphK2, was closely correlated with the microvascular density (MVD) of ovarian cancer tissue. In vitro , the angiogenic potential and angiogenic factor secretion of ovarian cancer cells could be attenuated by SphK1, but not SphK2, blockage and were restored by the addition of S1P. Moreover, in these cells, we found S1P stimulation induced the angiogenic factor secretion via S1PR 1 and S1PR 3 , but not S1PR 2 . Furthermore, inhibition of S1PR 1/3 , but not S1PR 2 , attenuated the angiogenic potential and angiogenic factor secretion of the cells. in vivo , blockage of SphK or S1PR 1/3 could attenuate ovarian cancer angiogenesis and inhibit angiogenic factor expression in mouse models. Collectively, the current study showed a novel role of SphK1/S1P/S1PR 1/3 axis within the ovarian cancer, suggesting a new target to block ovarian cancer angiogenesis.

  13. The insulin receptor substrate-1-related 4PS substrate but not the interleukin-2R gamma chain is involved in interleukin-13-mediated signal transduction.

    Science.gov (United States)

    Wang, L M; Michieli, P; Lie, W R; Liu, F; Lee, C C; Minty, A; Sun, X J; Levine, A; White, M F; Pierce, J H

    1995-12-01

    Interleukin-13 (IL-13) induced a potent mitogenic response in IL-3-dependent TF-1 cells and DNA synthesis to a lesser extent in MO7E and FDC-P1 cells. IL-13 stimulation of these lines, like IL-4 and insulin-like growth factor-1 (IGF-1), resulted in tyrosine phosphorylation of a 170-kD substrate. The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Anti-4PS serum readily detected the 170-kD substrate in lysates from both TF-1 and FDC-P1 cells stimulated with IL-13 or IL-4. These data provide evidence that IL-13 induces tyrosine phosphorylation of the 4PS substrate, providing an essential interface between the IL-13 receptor and signaling molecules containing SH2 domains. IL-13 and IL-4 stimulation of murine L cell fibroblasts, which endogenously express the IL-4 receptor (IL-4R alpha) and lack expression of the IL-2 receptor gamma subunit (IL-2R gamma), resulted in tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)/4PS. Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. These results indicate that IL-13 does not use the IL-2R gamma subunit in its receptor complex and that expression of IL-2R gamma enhances, but is not absolutely required for mediating IL-4-induced tyrosine phosphorylation of IRS-1/4PS.

  14. Technical design study. BESSY VSR. Variable pulse length Storage Ring. Upgrade of BESSY II

    International Nuclear Information System (INIS)

    2015-06-01

    BESSY-VSR is a novel approach to create in the Storage Ring BESSY II long and short photon pulses simultaneously for all beam lines through a pair of superconducting bunch compression cavities. Pulse-picking schemes will allow each individual user to freely switch between high average flux for X-ray spectroscopy, microscopy and scattering and picosecond pulses up to 500 MHz repetition rate for dynamic studies. Thus BESSY-VSR preserves the present average brilliance of BESSY II and adds the new capability of user accessible picosecond pulses at high repetition rate. In addition, high intensities for THz radiation with intrinsic synchronization of THz and X-ray pulses can be extracted from BESSY-VSR. For the scientific challenges of quantum materials for energy, future information technologies and basic energy science BESSY-VSR is the multi-user Synchrotron Radiation facility that allows with the flexible switching between high repetition rate for picosecond dynamics and high average brightness to move classical 3rd generation Synchrotron Radiation science from the observation of static properties and their quantum mechanical description towards the function and the control of materials properties, technologically relevant switching processes and chemical dynamics and kinetics on the picosecond time scale. Strategic relevance of BESSY-VSR for science with photons BESSY-VSR creates for the highly productive Synchrotron Radiation community a uniquely attractive multi user storage ring adding the soft X-ray picosecond dynamics at MHz repetition rate. In particular investigations on reversible dynamics and switching in molecular systems and materials are accessible in a non destructive way. The investigations with X-rays from BESSY-VSR are highly complementary and compatible to dynamic studies conducted by users with optical lasers at their home universities and laboratories. Technologically, the employed superconducting bunch compression cavities in BESSY-VSR are a

  15. Technical design study. BESSY VSR. Variable pulse length Storage Ring. Upgrade of BESSY II

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    BESSY-VSR is a novel approach to create in the Storage Ring BESSY II long and short photon pulses simultaneously for all beam lines through a pair of superconducting bunch compression cavities. Pulse-picking schemes will allow each individual user to freely switch between high average flux for X-ray spectroscopy, microscopy and scattering and picosecond pulses up to 500 MHz repetition rate for dynamic studies. Thus BESSY-VSR preserves the present average brilliance of BESSY II and adds the new capability of user accessible picosecond pulses at high repetition rate. In addition, high intensities for THz radiation with intrinsic synchronization of THz and X-ray pulses can be extracted from BESSY-VSR. For the scientific challenges of quantum materials for energy, future information technologies and basic energy science BESSY-VSR is the multi-user Synchrotron Radiation facility that allows with the flexible switching between high repetition rate for picosecond dynamics and high average brightness to move classical 3rd generation Synchrotron Radiation science from the observation of static properties and their quantum mechanical description towards the function and the control of materials properties, technologically relevant switching processes and chemical dynamics and kinetics on the picosecond time scale. Strategic relevance of BESSY-VSR for science with photons BESSY-VSR creates for the highly productive Synchrotron Radiation community a uniquely attractive multi user storage ring adding the soft X-ray picosecond dynamics at MHz repetition rate. In particular investigations on reversible dynamics and switching in molecular systems and materials are accessible in a non destructive way. The investigations with X-rays from BESSY-VSR are highly complementary and compatible to dynamic studies conducted by users with optical lasers at their home universities and laboratories. Technologically, the employed superconducting bunch compression cavities in BESSY-VSR are a

  16. JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes.

    Science.gov (United States)

    Yin, T; Tsang, M L; Yang, Y C

    1994-10-28

    Interleukin (IL)-4 and IL-9 regulate the proliferation of T lymphocytes through interactions with their receptors. Previous studies have shown that unknown tyrosine kinases are involved in the proliferative signaling triggered by IL-4 and IL-9. Here we show that IL-4 and IL-9 induce overlapping (170, 130, and 125 kilodalton (kDa)) and distinct (45 and 88/90 kDa, respectively) protein tyrosine phosphorylation in T lymphocytes. We further identify the 170-kDa tyrosine-phosphorylated protein as 4PS/insulin receptor substrate-1-like (IRS-1L) protein and 130-kDa protein as JAK1 kinase. Furthermore, we demonstrate for the first time that JAK1 forms complexes with the IL-4 receptor and 4PS/IRS-1L protein following ligand-receptor interaction. In addition, we demonstrate that IL-9, but not IL-4, induced tyrosine phosphorylation of Stat 91 transcriptional factor. The overlapping and distinct protein tyrosine phosphorylation and activation of the same JAK1 kinase in T lymphocytes strongly suggests that IL-4 and IL-9 share the common signal transduction pathways and that the specificity for each cytokine could be achieved through the unique tyrosine-phosphorylated proteins triggered by individual cytokines.

  17. Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1 Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Henrik H Hansen

    Full Text Available One of the major histopathological hallmarks of Alzheimer's disease (AD is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1 receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP and presenilin-1 (PS1 are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E and 'Swedish' mutation variant (hAPPSwe/PS1ΔE9 of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c., or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.. In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.

  18. Development of public acceptance and market success with very small nuclear power reactors (VSR)

    International Nuclear Information System (INIS)

    Lang, P

    2008-01-01

    This paper presents a case for public acceptance of very small nuclear reactors (VSR) as a socially welcomed, locally produced source of energy. It is argued that the subconscious associations and emotional responses that the public makes with size and appearance will often outweigh technical or economic advantages as the determining factor in their ultimate acceptance or rejection of a new power plant. The unique technical features of VSR effectively refute the three most commonly cited reasons for opposing nuclear power: cost, safety, and waste management. VSR also address the demands of environmentalists for small-scale, clean distributed energy production. (author)

  19. Calculation of coupled bunch effects in the synchrotron light source BESSY VSR

    Energy Technology Data Exchange (ETDEWEB)

    Ruprecht, Martin

    2016-02-22

    In the scope of this thesis, the strength of coupled bunch instabilities (CBIs) driven by longitudinal monopole higher order modes (HOMs) and transverse dipole and quadrupole HOMs is evaluated for the upgrade project BESSY Variable Pulse Length Storage Ring (BESSY VSR) at Helmholtz-Zentrum Berlin fuer Materialien und Energie GmbH (HZB), based on analytic calculations and tracking simulations, and compared to the performance of an active bunch-by-bunch feedback (BBFB). Algorithms for tracking codes are derived, and a semi-empirical formula for the estimation of transverse quadrupole CBIs is presented. CBI studies are an integral part of the benchmarking of the cavity models for BESSY VSR and have been accompanying and influencing their entire design process. Based on the BESSY VSR cavity model with highly advanced HOM damping, beam stability is likely to be reached with a BBFB system, independent of the bunch fill pattern. Additionally, measurements of CBIs have been performed at BESSY II and the Metrology Light Source of the Physikalisch-Technische Bundesanstalt (MLS), where the longitudinal long range impedance was characterized. Transient beam loading is evaluated by means of analytic formulas and new experimentally verified tracking codes. For the baseline bunch fill pattern of BESSY VSR, it is shown that the particular setup of cavity frequencies amplifies the transient effect on the long bunch, limiting its elongation and potentially resulting in increased Touschek losses.

  20. Interaction of the E. coli DNA G:T-mismatch endonuclease (vsr protein) with oligonucleotides containing its target sequence.

    Science.gov (United States)

    Turner, D P; Connolly, B A

    2000-12-15

    The Escherichia coli vsr endonuclease recognises G:T base-pair mismatches in double-stranded DNA and initiates a repair pathway by hydrolysing the phosphate group 5' to the incorrectly paired T. The enzyme shows a preference for G:T mismatches within a particular sequence context, derived from the recognition site of the E. coli dcm DNA-methyltransferase (CC[A/T]GG). Thus, the preferred substrate for the vsr protein is (CT[A/T]GG), where the underlined T is opposed by a dG base. This paper provides quantitative data for the interaction of the vsr protein with a number of oligonucleotides containing G:T mismatches. Evaluation of specificity constant (k(st)/K(D); k(st)=rate constant for single turnover, K(D)=equilibrium dissociation constant) confirms vsr's preference for a G:T mismatch within a hemi-methylated dcm sequence, i.e. the best substrate is a duplex (both strands written in the 5'-3' orientation) composed of CT[A/T]GG and C(5Me)C[T/A]GG. Conversion of the mispaired T (underlined) to dU or the d(5Me)C to dC gave poorer substrates. No interaction was observed with oligonucleotides that lacked a G:T mismatch or did not possess a dcm sequence. An analysis of the fraction of active protein, by "reverse-titration" (i.e. adding increasing amounts of DNA to a fixed amount of protein followed by gel-mobility shift analysis) showed that less than 1% of the vsr endonuclease was able to bind to the substrate. This was confirmed using "competitive titrations" (where competitor oligonucleotides are used to displace a (32)P-labelled nucleic acid from the vsr protein) and burst kinetic analysis. This result is discussed in the light of previous in vitro and in vivo data which indicate that the MutL protein may be needed for full vsr activity. Copyright 2000 Academic Press.

  1. Sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis is involved in liver fibrosis-associated angiogenesis.

    Science.gov (United States)

    Yang, Le; Yue, Shi; Yang, Lin; Liu, Xin; Han, Zhen; Zhang, Yuanyuan; Li, Liying

    2013-07-01

    Sphingosine kinase (SphK)/sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) axis is involved in multiple biological processes, including liver fibrosis. Angiogenesis is an important pathophysiological process closely associated with liver fibrosis; however, the functional role of SphK/S1P/S1PR in this process remains incompletely defined. Bile duct ligation or carbon tetrachloride was used to induce liver fibrosis in mice. Human fibrotic samples were obtained from livers of patients undergoing liver transplantation. S1P levels in the liver were examined by HPLC. Expression of angiogenic markers, including angiopoietin 1, CD31, vascular cell adhesion molecule-1, and von Willebrand factor, was characterized by immunofluorescence, real-time RT-PCR, and Western blot in the fibrotic liver and primary mouse hepatic stellate cells (HSCs). SphK inhibitor (SKI) or S1PR antagonists were administered intraperitoneally in mice. S1P levels in the liver were closely correlated with mRNA expression of angiogenic markers. Ang1 is expressed in activated HSCs of the fibrotic liver and in primary HSCs. In HSCs, by using specific antagonists or siRNAs, we demonstrated S1P stimulation induced Ang1 expression via S1PR1 and S1PR3. In vivo, S1P reduction by SKI inhibited angiogenesis in fibrotic mice. Furthermore, S1PR1/3 antagonist significantly blocked upregulation of angiogenic markers in the injured liver, and attenuated the extent of liver fibrosis, while S1PR2 antagonist had no effect on angiogenesis, supporting the key role of S1PR1 and S1PR3 in angiogenesis underlying liver fibrosis process. SphK1/S1P/S1PR1/3 axis plays a crucial role in the angiogenic process required for fibrosis development, which may represent an effective therapeutic strategy for liver fibrosis. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. The vacuolar transport of aleurain-GFP and 2S albumin-GFP fusions is mediated by the same pre-vacuolar compartments in tobacco BY-2 and Arabidopsis suspension cultured cells.

    Science.gov (United States)

    Miao, Yansong; Li, Kwun Yee; Li, Hong-Ye; Yao, Xiaoqiang; Jiang, Liwen

    2008-12-01

    Soluble proteins reach vacuoles because they contain vacuolar sorting determinants (VSDs) that are recognized by vacuolar sorting receptor (VSR) proteins. Pre-vacuolar compartments (PVCs), defined by VSRs and GFP-VSR reporters in tobacco BY-2 cells, are membrane-bound intermediate organelles that mediate protein traffic from the Golgi apparatus to the vacuole in plant cells. Multiple pathways have been demonstrated to be responsible for vacuolar transport of lytic enzymes and storage proteins to the lytic vacuole (LV) and the protein storage vacuole (PSV), respectively. However, the nature of PVCs for LV and PSV pathways remains unclear. Here, we used two fluorescent reporters, aleurain-GFP and 2S albumin-GFP, that represent traffic of lytic enzymes and storage proteins to LV and PSV, respectively, to study the PVC-mediated transport pathways via transient expression in suspension cultured cells. We demonstrated that the vacuolar transport of aleurain-GFP and 2S albumin-GFP was mediated by the same PVC populations in both tobacco BY-2 and Arabidopsis suspension cultured cells. These PVCs were defined by the seven GFP-AtVSR reporters. In wortmannin-treated cells, the vacuolated PVCs contained the mRFP-AtVSR reporter in their limiting membranes, whereas the soluble aleurain-GFP or 2S albumin-GFP remained in the lumen of the PVCs, indicating a possible in vivo relationship between receptor and cargo within PVCs.

  3. Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

    Science.gov (United States)

    Chen, Buxin; Dores, Michael R.; Grimsey, Neil; Canto, Isabel; Barker, Breann L.; Trejo, JoAnn

    2011-01-01

    Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs. PMID:21965661

  4. PsOr1, a potential target for RNA interference-based pest management.

    Science.gov (United States)

    Zhao, Y Y; Liu, F; Yang, G; You, M S

    2011-02-01

    Insect pests cause billions of dollars in agricultural losses, and attempts to kill them have resulted in growing threats from insecticide resistance, dietary pesticide pollution and environmental destruction. New approaches to control refractory insect pests are therefore needed. The host-plant preferences of insect pests rely on olfaction and are mediated via a seven transmembrane-domain odorant receptor (Or) family. The present study reports the cloning and characterization of PsOr1, the first candidate member of the Or gene family from Phyllotreta striolata, a devastating beetle pest that causes damage worldwide. PsOr1 is remarkably well conserved with respect to other insect orthologues, including DmOr83b from Drosophila melanogaster. These insect orthologues form an essential non-conventional Or sub-family and may play an important and generalized role in insect olfaction. We designed double-stranded (ds) RNA directly against the PsOr1 gene and exploited RNA interference (RNAi) to control P. striolata. The chemotactic behavioural measurements showed that adult beetles were unable to sense the attractant or repellent odour stimulus after microinjection of dsRNA against PsOr1. Reverse Transcription (RT)-PCR analysis showed specific down-regulation of mRNA transcript levels for this gene. Furthermore, host-plant preference experiments confirmed that silencing PsOr1 by RNAi treatment impaired the host-plant preferences of P. striolata for cruciferous vegetables. These results demonstrate that this insect control approach of using RNAi to target PsOr1 and its orthologues might be effective in blocking host-plant-seeking behaviours in diverse insect pests. The results also support the theory that this unique receptor type plays an essential general role in insect olfaction. © 2010 Fujian Agriculture and Forestry University. Insect Molecular Biology © 2010 The Royal Entomological Society.

  5. Plaque deposition dependent decrease in 5-HT2A serotonin receptor in AbetaPPswe/PS1dE9 amyloid overexpressing mice

    DEFF Research Database (Denmark)

    Holm, Peter; Ettrup, Anders; Klein, Anders B

    2010-01-01

    -HT2A receptor regulation in double transgenic AbetaPPswe/PS1dE9 mice which display excess production of Abeta and age-dependent increase in amyloid plaques. Three different age-groups, 4-month-old, 8- month-old, and 11-month-old were included in the study. [3H]-MDL100907, [3H]-escitalopram, and [11C...

  6. Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression.

    Science.gov (United States)

    Kasikara, Canan; Kumar, Sushil; Kimani, Stanley; Tsou, Wen-I; Geng, Ke; Davra, Viralkumar; Sriram, Ganapathy; Devoe, Connor; Nguyen, Khanh-Quynh N; Antes, Anita; Krantz, Allen; Rymarczyk, Grzegorz; Wilczynski, Andrzej; Empig, Cyril; Freimark, Bruce; Gray, Michael; Schlunegger, Kyle; Hutchins, Jeff; Kotenko, Sergei V; Birge, Raymond B

    2017-06-01

    Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K-dependent endogenous ligands, Protein S (ProS), and growth arrest-specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity. In the present study, we utilized TAM-IFNγR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express wild-type TAM receptors and show that although each receptor can promote PS-mediated efferocytosis, AKT-mediated chemoresistance, as well as upregulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor-mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 and Annexin V, demonstrating the existence of a PS/PS receptor (i.e., TAM receptor)/PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1-based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to upregulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on cancer cells. Mol Cancer Res; 15(6); 753-64. ©2017 AACR

  7. PTP1B targets the endosomal sorting machinery

    DEFF Research Database (Denmark)

    Stuible, Matthew; Abella, Jasmine V; Feldhammer, Matthew

    2010-01-01

    Dephosphorylation and endocytic down-regulation are distinct processes that together control the signaling output of a variety of receptor tyrosine kinases (RTKs). PTP1B can directly dephosphorylate several RTKs, but it can also promote activation of downstream pathways through largely unknown...... mechanisms. These positive signaling functions likely contribute to the tumor-promoting effect of PTP1B in mouse cancer models. Here, we have identified STAM2, an endosomal protein involved in sorting activated RTKs for lysosomal degradation, as a substrate of PTP1B. PTP1B interacts with STAM2 at defined...... phosphotyrosine sites, and knockdown of PTP1B expression augments STAM2 phosphorylation. Intriguingly, manipulating the expression and phosphorylation state of STAM2 did not have a general effect on epidermal growth factor (EGF)-induced EGF receptor trafficking, degradation, or signaling. Instead, phosphorylated...

  8. Sorting by the cytoplasmic domain of the amyloid precursor protein binding receptor SorLA

    DEFF Research Database (Denmark)

    Nielsen, Morten S; Gustafsen, Camilla; Madsen, Peder

    2007-01-01

    -formation with the amyloid precursor protein it downregulates generation of Alzheimer's disease-associated Abeta-peptide. The receptor is mainly located in vesicles, suggesting a function in protein sorting and transport. Here we examined SorLA's trafficking using full-length and chimeric receptors and find that its...

  9. PsVPS1, a dynamin-related protein, is involved in cyst germination and soybean infection of Phytophthora sojae.

    Directory of Open Access Journals (Sweden)

    Delong Li

    Full Text Available Plant pathogens secrete effector proteins to suppress plant immunity. However, the mechanism by which oomycete pathogens deliver effector proteins during plant infection remains unknown. In this report, we characterized a Phytophthora sojae vps1 gene. This gene encodes a homolog of the Saccharomyces cerevisiae vacuolar protein sorting gene vps1 that mediates budding of clathrin-coated vesicles from the late Golgi, which are diverted from the general secretory pathway to the vacuole. PsVPS1-silenced mutants were generated using polyethylene glycol-mediated protoplast stable transformation and were viable but had reduced extracellular protein activity. The PsVPS1-silenced mutants showed impaired hyphal growth, and the shapes of the vacuoles were highly fragmented. Silencing of PsVPS1 affected cyst germination as well as the polarized growth of germinated cysts. Silenced mutants showed impaired invasion of susceptible soybean plants regardless of wounding. These results suggest that PsVPS1 is involved in vacuole morphology and cyst development. Moreover, it is essential for the virulence of P. sojae and extracellular protein secretion.

  10. TREM2 Overexpression has No Improvement on Neuropathology and Cognitive Impairment in Aging APPswe/PS1dE9 Mice.

    Science.gov (United States)

    Jiang, Teng; Wan, Yu; Zhang, Ying-Dong; Zhou, Jun-Shan; Gao, Qing; Zhu, Xi-Chen; Shi, Jian-Quan; Lu, Huan; Tan, Lan; Yu, Jin-Tai

    2017-03-01

    Previously, we showed that overexpression of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific immune receptor, in the brain of a middle-aged (7 months old) APPswe/PS1dE9 mice could ameliorate Alzheimer's disease (AD)-related neuropathology by enhancement of microglial amyloid-β (Aβ) phagocytosis. Since AD is an age-related neurodegenerative disorder, it is critical to assess the efficacy of TREM2 overexpression in aging animals with an advanced disease stage. In vivo, we employed a lentiviral strategy to overexpress TREM2 in the brain of aging (18 months old) APPswe/PS1dE9 mice, and observed its efficacy on AD-related neuropathology and cognitive functions. Afterwards, we directly isolated microglia from middle-aged and aging APPswe/PS1dE9 mice and determined effects of TREM2 overexpression on microglial Aβ phagocytosis and Aβ-binding receptors expression in vitro. In aging APPswe/PS1dE9 mice, TREM2 overexpression has no beneficial effect on AD-related neuropathology and spatial cognitive functions. Of note, in vitro experiments showed a significant reduction of Aβ phagocytosis in microglia from aging APPswe/PS1dE9 mice, possibly attributing to the declined expression of Aβ-binding receptors. Meanwhile, this phagocytic deficit in microglia from aging APPswe/PS1dE9 mice cannot be rescued by TREM2 overexpression. Taken together, our study shows that TREM2 overexpression fails to provide neuroprotection in aging APPswe/PS1dE9 mice, possibly attributing to deficits in microglial Aβ phagocytosis at the late-stage of disease progression. These findings indicate that TREM2-mediated protection in AD is at least partially dependent on the reservation of microglial phagocytic functions, emphasizing the importance of early therapeutic interventions for this devastating disease.

  11. Semi-automatic characterization and simulation of VCSEL devices for high speed VSR communications

    Science.gov (United States)

    Pellevrault, S.; Toffano, Z.; Destrez, A.; Pez, M.; Quentel, F.

    2006-04-01

    Very short range (VSR) high bit rate optical fiber communications are an emerging market dedicated to local area networks, digital displays or board to board interconnects within real time calculators. In this technology, a very fast way to exchange data with high noise immunity and low-cost is needed. Optical multimode graded index fibers are used here because they have electrical noise immunity and are easier to handle than monomode fibers. 850 nm VCSEL are used in VSR communications because of their low cost, direct on-wafer tests, and the possibility of manufacturing VCSEL arrays very easily compared to classical optical transceivers using edge-emitting laser diodes. Although much research has been carried out in temperature modeling on VCSEL emitters, few studies have been devoted to characterizations over a very broad range of temperatures. Nowadays, VCSEL VSR communications tend to be used in severe environments such as space, avionics and military equipments. Therefore, a simple way to characterize VCSEL emitters over a broad range of temperature is required. In this paper, we propose a complete characterization of the emitter part of 2.5 Gb/s opto-electrical transceiver modules operating from -40°C to +120°C using 850 nm VCSELs. Our method uses simple and semi-automatic measurements of a given set of chosen device parameters in order to make fast and efficient simulations.

  12. Activity-dependent ubiquitination of GluA1 mediates a distinct AMPA receptor endocytosis and sorting pathway.

    Science.gov (United States)

    Schwarz, Lindsay A; Hall, Benjamin J; Patrick, Gentry N

    2010-12-08

    The accurate trafficking of AMPA receptors (AMPARs) to and from the synapse is a critical component of learning and memory in the brain, whereas dysfunction of AMPAR trafficking is hypothesized to be an underlying mechanism of Alzheimer's disease. Previous work has shown that ubiquitination of integral membrane proteins is a common posttranslational modification used to mediate endocytosis and endocytic sorting of surface proteins in eukaryotic cells. Here we report that mammalian AMPARs become ubiquitinated in response to their activation. Using a mutant of GluA1 that is unable to be ubiquitinated at lysines on its C-terminus, we demonstrate that ubiquitination is required for internalization of surface AMPARs and their trafficking to the lysosome in response to the AMPAR agonist AMPA but not for internalization of AMPARs in response to the NMDA receptor agonist NMDA. Through overexpression or RNA interference-mediated knockdown, we identify that a specific E3 ligase, Nedd4-1 (neural-precursor cell-expressed developmentally downregulated gene 4-1), is necessary for this process. Finally, we show that ubiquitination of GluA1 by Nedd4-1 becomes more prevalent as neurons mature. Together, these data show that ubiquitination of GluA1-containing AMPARs by Nedd4-1 mediates their endocytosis and trafficking to the lysosome. Furthermore, these results provide insight into how hippocampal neurons regulate AMPAR trafficking and degradation with high specificity in response to differing neuronal signaling cues and suggest that changes to this pathway may occur as neurons mature.

  13. Antagonist of peroxisome proliferator-activated receptor γ induces cerebellar amyloid-β levels and motor dysfunction in APP/PS1 transgenic mice

    International Nuclear Information System (INIS)

    Du, Jing; Sun, Bing; Chen, Kui; Fan, Li; Wang, Zhao

    2009-01-01

    Recent evidences show that peroxisome proliferator-activated receptor γ (PPARγ) is involved in the modulation of the amyloid-β (Aβ) cascade causing Alzheimer's disease (AD) and treatment with PPARγ agonists protects against AD pathology. However, the function of PPARγ steady-state activity in Aβ cascade and AD pathology remains unclear. In this study, an antagonist of PPARγ, GW9662, was injected into the fourth ventricle of APP/PS1 transgenic mice to inhibit PPARγ activity in cerebellum. The results show that inhibition of PPARγ significantly induced Aβ levels in cerebellum and caused cerebellar motor dysfunction in APP/PS1 transgenic mice. Moreover, GW9662 treatment markedly decreased the cerebellar levels of insulin-degrading enzyme (IDE), which is responsible for the cellular degradation of Aβ. Since cerebellum is spared from significant Aβ accumulation and neurotoxicity in AD patients and animal models, these findings suggest a crucial role of PPARγ steady-state activity in protection of cerebellum against AD pathology.

  14. Differential effects of EGFR ligands on endocytic sorting of the receptor

    DEFF Research Database (Denmark)

    Roepstorff, Kirstine; Grandal, Michael Vibo; Henriksen, Lasse

    2009-01-01

    signalling and is a more potent mitogen than EGF. In addition to EGF and TGF-alpha, five EGFR ligands have been identified. Although many of these ligands are upregulated in cancers, very little is known about their effect on EGFR trafficking. We have compared the effect of six different ligands on endocytic...... trafficking of EGFR. We find that, whereas they all stimulate receptor internalization, they have very diverse effects on endocytic sorting. Heparin-binding EGF-like growth factor and Betacellulin target all EGFRs for lysosomal degradation. In contrast, TGF-alpha and epiregulin lead to complete receptor...

  15. Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1.

    Science.gov (United States)

    Szewczyk, Bernadeta; Kotarska, Katarzyna; Daigle, Mireille; Misztak, Paulina; Sowa-Kucma, Magdalena; Rafalo, Anna; Curzytek, Katarzyna; Kubera, Marta; Basta-Kaim, Agnieszka; Nowak, Gabriel; Albert, Paul R

    2014-11-01

    The effect of stress on the mRNA and protein level of the 5-HT1A receptor and two of its key transcriptional modulators, NUDR and Freud-1, was examined in the prefrontal cortex (PFC) and hippocampus (Hp) using rodent models: olfactory bulbectomy (OB) and prenatal stress (PS) in male and female rats; chronic mild stress in male rats (CMS) and pregnancy stress. In PFC, CMS induced the most widespread changes, with significant reduction in both mRNA and protein levels of NUDR, 5-HT1A receptor and in Freud-1 mRNA; while in Hp 5-HT1A receptor and Freud-1 protein levels were also decreased. In male, but not female OB rats PFC Freud-1 and 5-HT1A receptor protein levels were reduced, while in Hp 5-HT1A receptor, Freud-1 and NUDR mRNA's but not protein were reduced. In PS rats PFC 5-HT1A receptor protein was reduced more in females than males; while in Hp Freud-1 protein was increased in females. In pregnancy stress, PFC NUDR, Freud-1 and 5-HT1A protein receptor levels were reduced, and in HP 5-HT1A receptor protein levels were also reduced; in HP only NUDR and Freud-1 mRNA levels were reduced. Overall, CMS and stress during pregnancy produced the most salient changes in 5-HT1A receptor and transcription factor expression, suggesting a primary role for altered transcription factor expression in chronic regulation of 5-HT1A receptor expression. By contrast, OB (in males) and PS (in females) produced gender-specific reductions in PFC 5-HT1A receptor protein levels, suggesting a role for post-transcriptional regulation. These and previous data suggest that chronic stress might be a key regulator of NUDR/Freud-1 gene expression.

  16. IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View.

    Science.gov (United States)

    Keegan, Achsah D; Zamorano, Jose; Keselman, Aleksander; Heller, Nicola M

    2018-01-01

    In this historical perspective, written in honor of Dr. William E. Paul, we describe the initial discovery of one of the dominant substrates for tyrosine phosphorylation stimulated by IL-4. We further describe how this "IL-4-induced phosphorylated substrate" (4PS) was characterized as a member of the insulin receptor substrate (IRS) family of large adaptor proteins that link IL-4 and insulin receptors to activation of the phosphatidyl-inositol 3' kinase pathway as well as other downstream signaling pathways. The relative contribution of the 4PS/IRS pathway to the early models of IL-4-induced proliferation and suppression of apoptosis are compared to our more recent understanding of the complex interplay between positive and negative regulatory pathways emanating from members of the IRS family that impact allergic responses.

  17. IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View

    Directory of Open Access Journals (Sweden)

    Achsah D. Keegan

    2018-05-01

    Full Text Available In this historical perspective, written in honor of Dr. William E. Paul, we describe the initial discovery of one of the dominant substrates for tyrosine phosphorylation stimulated by IL-4. We further describe how this “IL-4-induced phosphorylated substrate” (4PS was characterized as a member of the insulin receptor substrate (IRS family of large adaptor proteins that link IL-4 and insulin receptors to activation of the phosphatidyl-inositol 3′ kinase pathway as well as other downstream signaling pathways. The relative contribution of the 4PS/IRS pathway to the early models of IL-4-induced proliferation and suppression of apoptosis are compared to our more recent understanding of the complex interplay between positive and negative regulatory pathways emanating from members of the IRS family that impact allergic responses.

  18. Sorting Tubules Regulate Blood-Brain Barrier Transcytosis

    Directory of Open Access Journals (Sweden)

    Roberto Villaseñor

    2017-12-01

    Full Text Available Transcytosis across the blood-brain barrier (BBB regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB. A monovalent construct (sFab sorted for transcytosis was localized to intracellular tubules, whereas a bivalent construct (dFab sorted for degradation formed clusters with impaired transport along tubules. Manipulating tubule biogenesis by overexpressing the small GTPase Rab17 increased dFab transport into tubules and induced its transcytosis in BECs. We propose that sorting tubules regulate transcytosis in BECs and may be a general mechanism for receptor-mediated transport across the BBB.

  19. ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs.

    Science.gov (United States)

    Ren, Kun; Lu, Yan-Ju; Mo, Zhong-Cheng; -Liu, Xing; Tang, Zhen-Li; Jiang, Yue; Peng, Xiao-Shan; Li, Li; Zhang, Qing-Hai; Yi, Guang-Hui

    2017-05-01

    Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway.

  20. Functional characterization of calcineurin homologs PsCNA1/PsCNB1 in Puccinia striiformis f. sp. tritici using a host-induced RNAi system.

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    Full Text Available Calcineurin plays a key role in morphogenesis, pathogenesis and drug resistance in most fungi. However, the function of calcineurin genes in Puccinia striiformis f. sp. tritici (Pst is unclear. We identified and characterized the calcineurin genes PsCNA1 and PsCNB1 in Pst. Phylogenetic analyses indicate that PsCNA1 and PsCNB1 form a calcium/calmodulin regulated protein phosphatase belonging to the calcineurin heterodimers composed of subunits A and B. Quantitative RT-PCR analyses revealed that both PsCNA1 and PsCNB1 expression reached their maximum in the stage of haustorium formation, which is one day after inoculation. Using barely stripe mosaic virus (BSMV as a transient expression vector in wheat, the expression of PsCNA1 and PsCNB1 in Pst was suppressed, leading to slower extension of fungal hyphae and reduced production of urediospores. The immune-suppressive drugs cyclosporin A and FK506 markedly reduced the germination rates of urediospores, and when germination did occur, more than two germtubes were produced. These results suggest that the calcineurin signaling pathway participates in stripe rust morphogenetic differentiation, especially the formation of haustoria during the early stage of infection and during the production of urediospores. Therefore PsCNA1 and PsCNB1 can be considered important pathogenicity genes involved in the wheat-Pst interaction.

  1. PsHint1, associated with the G-protein α subunit PsGPA1, is required for the chemotaxis and pathogenicity of Phytophthora sojae.

    Science.gov (United States)

    Zhang, Xin; Zhai, Chunhua; Hua, Chenlei; Qiu, Min; Hao, Yujuan; Nie, Pingping; Ye, Wenwu; Wang, Yuanchao

    2016-02-01

    Zoospore chemotaxis to soybean isoflavones is essential in the early stages of infection by the oomycete pathogen Phytophthora sojae. Previously, we have identified a G-protein α subunit encoded by PsGPA1 which regulates the chemotaxis and pathogenicity of P. sojae. In the present study, we used affinity purification to identify PsGPA1-interacting proteins, including PsHint1, a histidine triad (HIT) domain-containing protein orthologous to human HIT nucleotide-binding protein 1 (HINT1). PsHint1 interacted with both the guanosine triphosphate (GTP)- and guanosine diphosphate (GDP)-bound forms of PsGPA1. An analysis of the gene-silenced transformants revealed that PsHint1 was involved in the chemotropic response of zoospores to the isoflavone daidzein. During interaction with a susceptible soybean cultivar, PsHint1-silenced transformants displayed significantly reduced infectious hyphal extension and caused a strong cell death in plants. In addition, the transformants displayed defective cyst germination, forming abnormal germ tubes that were highly branched and exhibited apical swelling. These results suggest that PsHint1 not only regulates chemotaxis by interacting with PsGPA1, but also participates in a Gα-independent pathway involved in the pathogenicity of P. sojae. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  2. The overexpressed human 46-kDa mannose 6-phosphate receptor mediates endocytosis and sorting of β-glucuronidase

    International Nuclear Information System (INIS)

    Watanabe, H.; Grubb, J.H.; Sly, W.S.

    1990-01-01

    The authors studied the function of the human small (46-kDa) mannose 6-phosphate receptor (SMPR) in transfected mouse L cells that do not express the larger insulin-like growth factor II/mannose 6-phosphate receptor. Cells overexpressing human SMPR were studied for enzyme binding to cell surface receptors, for binding to intracellular receptors in permeabilized cells, and for receptor-mediated endocytosis of recombinant human β-glucuronidase. Specific binding to human SMPR in permeabilized cells showed a pH optimum between pH 6.0 and pH 6.5. Binding was significant in the present of EDTA but was enhanced by added divalent cations. Up to 2.3% of the total functional receptor could be detected on the cell surface by enzyme binding. They present experiments showing that at very high levels of overexpression, and at pH 6.5, human SMPR mediated the endocytosis of β-glucuronidase. At pH 7.5, the rate of endocytosis was only 14% the rate seen at pH 6.5. Cells overexpressing human SMPR also showed reduced secretion of newly synthesized β-glucuronidase when compared to cells transfected with vector only, suggesting that overexpressed human SMPR can participate in sorting of newly synthesized β-glucuronidase and partially correct the sorting defect in mouse L cells that do not express the insulin-like growth factor II/mannose 6-phosphate receptor

  3. Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1-phosphate (S1P)/S1P3 signaling axis.

    Science.gov (United States)

    Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji

    2015-10-01

    Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-β is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF-β/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1-phosphate (S1P)/S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF-β/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3(-/-) mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13(+) chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3(-/-) mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-β type II receptor-dependent manner, and S1P3 was found to be required for TGF-β-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Loss of GABAergic inputs in APP/PS1 mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Tutu Oyelami

    2014-04-01

    Full Text Available Alzheimer's disease (AD is characterized by symptoms which include seizures, sleep disruption, loss of memory as well as anxiety in patients. Of particular importance is the possibility of preventing the progressive loss of neuronal projections in the disease. Transgenic mice overexpressing EOFAD mutant PS1 (L166P and mutant APP (APP KM670/671NL Swedish (APP/PS1 develop a very early and robust Amyloid pathology and display synaptic plasticity impairments and cognitive dysfunction. Here we investigated GABAergic neurotransmission, using multi-electrode array (MEA technology and pharmacological manipulation to quantify the effect of GABA Blockers on field excitatory postsynaptic potentials (fEPSP, and immunostaining of GABAergic neurons. Using MEA technology we confirm impaired LTP induction by high frequency stimulation in APPPS1 hippocampal CA1 region that was associated with reduced alteration of the pair pulse ratio after LTP induction. Synaptic dysfunction was also observed under manipulation of external Calcium concentration and input-output curve. Electrophysiological recordings from brain slice of CA1 hippocampus area, in the presence of GABAergic receptors blockers cocktails further demonstrated significant reduction in the GABAergic inputs in APP/PS1 mice. Moreover, immunostaining of GAD65 a specific marker for GABAergic neurons revealed reduction of the GABAergic inputs in CA1 area of the hippocampus. These results might be linked to increased seizure sensitivity, premature death and cognitive dysfunction in this animal model of AD. Further in depth analysis of GABAergic dysfunction in APP/PS1 mice is required and may open new perspectives for AD therapy by restoring GABAergic function.

  5. Regulation of Hippocampal Cannabinoid CB1 Receptor Actions by Adenosine A1 Receptors and Chronic Caffeine Administration: Implications for the Effects of Δ9-Tetrahydrocannabinol on Spatial Memory

    OpenAIRE

    Sousa, Vasco C; Assaife-Lopes, Natália; Ribeiro, Joaquim A; Pratt, Judith A; Brett, Ros R; Sebastião, Ana M

    2010-01-01

    Abstract The cannabinoid CB1 receptor-mediated modulation of ?-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A1 receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A1 receptors localized in GABAergic cells do not directly influence GABA release. CB1 and A1 receptors are the main targets for the effects of two of the most heavily consumed ps...

  6. α-Taxilin interacts with sorting nexin 4 and participates in the recycling pathway of transferrin receptor.

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakane

    Full Text Available Membrane traffic plays a crucial role in delivering proteins and lipids to their intracellular destinations. We previously identified α-taxilin as a binding partner of the syntaxin family, which is involved in intracellular vesicle traffic. α-Taxilin is overexpressed in tumor tissues and interacts with polymerized tubulin, but the precise function of α-taxilin remains unclear. Receptor proteins on the plasma membrane are internalized, delivered to early endosomes and then either sorted to the lysosome for degradation or recycled back to the plasma membrane. In this study, we found that knockdown of α-taxilin induced the lysosomal degradation of transferrin receptor (TfnR, a well-known receptor which is generally recycled back to the plasma membrane after internalization, and impeded the recycling of transferrin. α-Taxilin was immunoprecipitated with sorting nexin 4 (SNX4, which is involved in the recycling of TfnR. Furthermore, knockdown of α-taxilin decreased the number and length of SNX4-positive tubular structures. We report for the first time that α-taxilin interacts with SNX4 and plays a role in the recycling pathway of TfnR.

  7. The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling.

    Science.gov (United States)

    Beitner-Johnson, D; Blakesley, V A; Shen-Orr, Z; Jimenez, M; Stannard, B; Wang, L M; Pierce, J; LeRoith, D

    1996-04-19

    The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein which we have previously shown to become rapidly tyrosine phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) in NIH-3T3 cells. In order to further characterize the role of Crk in the IGF-I signaling pathway, NIH-3T3 and 293 cells were stably transfected with an expression vector containing the Crk cDNA. The various resultant 3T3-Crk clones expressed Crk at approximately 2-15-fold higher levels than parental 3T3 cells. In 3T3-Crk cells, Crk immunoreactivity was detected in insulin receptor substrate-1 (IRS-1) immunoprecipitates. Stimulation with IGF-I resulted in a dissociation of Crk protein from IRS-1. In contrast, the association of the related adaptor protein Grb2 with IRS-1 was enhanced by IGF-I stimulation. Similar results were obtained in stably transfected 293-Crk cells, which express both IRS-1 and the IRS-1-related signaling protein 4PS. In these cells, IRS-1 and 4PS both associated with Crk, and this association was also decreased by IGF-I treatment, whereas the association of Grb2 with IRS-1 and 4PS was enhanced by IGF-I. Overexpression of Crk also enhanced IGF-I-induced mitogenesis of NIH-3T3 cells, as measured by [3H]thymidine incorporation. The levels of IGF-I-induced mitogenesis were proportional to the level of Crk expression. These results suggest that Crk is a positive effector of IGF-I signaling, and may mediate its effects via interaction with IRS-1 and/or 4PS.

  8. A lipid receptor sorts polyomavirus from the endolysosome to the endoplasmic reticulum to cause infection.

    Directory of Open Access Journals (Sweden)

    Mengding Qian

    2009-06-01

    Full Text Available The mechanisms by which receptors guide intracellular virus transport are poorly characterized. The murine polyomavirus (Py binds to the lipid receptor ganglioside GD1a and traffics to the endoplasmic reticulum (ER where it enters the cytosol and then the nucleus to initiate infection. How Py reaches the ER is unclear. We show that Py is transported initially to the endolysosome where the low pH imparts a conformational change that enhances its subsequent ER-to-cytosol membrane penetration. GD1a stimulates not viral binding or entry, but rather sorting of Py from late endosomes and/or lysosomes to the ER, suggesting that GD1a binding is responsible for ER targeting. Consistent with this, an artificial particle coated with a GD1a antibody is transported to the ER. Our results provide a rationale for transport of Py through the endolysosome, demonstrate a novel endolysosome-to-ER transport pathway that is regulated by a lipid, and implicate ganglioside binding as a general ER targeting mechanism.

  9. Multifunctional Receptor Stabilin-1 in Homeostasis and Disease

    Directory of Open Access Journals (Sweden)

    Julia Kzhyshkowska

    2010-01-01

    Full Text Available The multifunctional scavenger receptor stabilin-1 (STAB1, FEEL-1, CLEVER-1, KIAA0246 is expressed on tissue macrophages and sinusoidal endothelial cells in healthy organisms, and its expression on both macrophages and different subtypes of endothelial cells is induced during chronic inflammation and tumor progression. Stabilin-1 is a type-1 transmembrane receptor that mediates endocytic and phagocytic clearance of “unwanted-self” components, intracellular sorting of the endogenously synthesized chitinase-like protein SI-CLP, and transcytosis of the growth hormone family member placental lactogen. The central sorting station for stabilin-1 trafficking seems to be the trans-Golgi network (TGN. Transport of stabilin-1 in the TGN requires interaction with GGA adaptors that bind to the classical DDSLL motif and a novel acidic cluster in its cytoplasmic tail. Degradation of stabilin-1 seems to depend on the interaction with sorting nexin 17. However, the mechanisms keeping stabilin-1 on the cell surface remain to be identified. This issue deserves specific attention due to the growing amount of data indicating that function of stabilin-1 in cell adhesion events is essential for inflammation and metastasis. Taking into consideration the complexity of stabilin-1—mediated processes, investigation of stabilin-1 functions in the animal models, as well as mathematic modeling of intracellular trafficking and extracellular contact, would enable prediction of stabilin-1 behavior in complex biological systems and would open perspectives for therapeutic targeting of stabilin-1 pathways in chronic inflammation and carcinogenesis.

  10. Influence of retrospective sorting on image quality in respiratory correlated computed tomography

    International Nuclear Information System (INIS)

    Guckenberger, Matthias; Weininger, Markus; Wilbert, Juergen; Richter, Anne; Baier, Kurt; Krieger, Thomas; Polat, Buelent; Flentje, Michael

    2007-01-01

    Purpose: To evaluate the influence of retrospective sorting on image quality in four-dimensional respiratory correlated CT. Materials and methods: Twelve patients with intrapulmonary tumors were examined using a 24-slice CT-scanner in helical mode. Images were reconstructed after retrospective sorting based on five algorithms: amplitude-based sorting with definition of peak-exhalation and peak-inhalation separately/locally for all breathing cycles (LAS) and globally for the time of image acquisition (GAS). Drifts of the breathing signal were corrected in dc-GAS. In phase-based (PS) and cycle-based (CS) algorithm the projections were sorted relative to time. Motion artifacts were scored by a radiologist. The tumor volumes were measured using automatic image segmentation. Results: Averaged over all breathing phases, LAS and PS achieved significantly improved image quality and lowest tumor volume variability compared to GAS, dc-GAS and CS. Imaging redundancy of 5 s was not sufficient for GAS and dc-GAS: missing corresponding amplitude positions in one or several breathing cycles resulted in incomplete reconstruction of peak-ventilation images in 11/12 and 10/12 patients with GAS and dc-GAS, respectively. Limiting the analysis to mid-ventilation phases showed GAS and dc-GAS as the most reliable algorithms. Conclusions: LAS and PS are suggested as a compromise between image quality and radiation dose

  11. Defining the minimal structural requirements for partial agonism at the type I myo-inositol 1,4,5-trisphosphate receptor.

    Science.gov (United States)

    Wilcox, R A; Fauq, A; Kozikowski, A P; Nahorski, S R

    1997-02-03

    The novel synthetic analogues D-3-fluoro-myo-inositol 1,5-bisphosphate-4-phosphorothioate, [3F-Ins(1,5)P2-4PS], D-3-fluoro-myo-inositol 1,4-bisphosphate-5-phosphorothioate [3F-Ins(1,4)P2-5PS], and D-3-fluoro-myo-inositol 1-phosphate-4,5-bisphosphorothioate [3F-Ins(1)P-(4,5)PS2] were utilised to define the structure-activity relationships which could produce partial agonism at the Ca2+ mobilising myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor. Based on prior structure-activity data we hypothesised that the minimal structural requirements for lns(1,4,5)P3 receptor partial agonism, were phosphorothioate substitution of the crucial vicinal 4,5-bisphosphate pair accompanied by another structural perturbation, such fluorination of 3-position of the myo-inositol ring. All the analogues fully displaced [3H]Ins(1,4,5)P3 from a single Ins(1,4,5)P3 binding site in pig cerebellar membranes [3F-Ins(1,5)P2-4PS (1C50 = 26 nM), 3F-Ins(1,4)P2-5PS (IC50 = 80 nM) and 3F-Ins(1)P-(4,5)PS2 (IC50 = 109 nM) cf. Ins(1,4,5)P3 (IC50 = 11 nM)]. In contrast, 3F-Ins(1,5)P2-4PS (IC50 = 424 nM) and 3F-Ins(1,4)P2-5PS (IC50 = 3579 nM) were weak full agonists at the Ca2+ mobilising Ins(1,4,5)P3 receptor of permeabilised SH-SY5Y neuroblastoma cells, being respectively 4- and 36-fold less potent than Ins(1,4,5)P3 (EC50 = 99 nM). While 3F-Ins(1)P-(4,5)PS2 (EC50 = 11345 nM) was a partial agonist releasing only 64.3 +/- 1.9% of the Ins(1,4,5)P3-sensitive intracellular Ca2+ pools. 3F-Ins(1)P-(4,5)PS2 was unique among the Ins(1,4,5)P3 receptor partial agonists so far identified in having a relatively high affinity for the Ins(1,4,5)P3 binding site, accompanied by a significant loss of intrinsic activity for Ca2+ mobilisation. This improved affinity was probably due to the retention of the 1-position phosphate, which enhances interaction with the Ins-(1,4,5)P3 receptor. 3F-Ins(1)P-(4,5)PS2 may be an important lead compound for the development of efficient Ins(1,4,5)P3 receptor antagonists.

  12. 3VSR: Three Valued Secure Routing for Vehicular Ad Hoc Networks using Sensing Logic in Adversarial Environment

    Directory of Open Access Journals (Sweden)

    Muhammad Sohail

    2018-03-01

    Full Text Available Today IoT integrate thousands of inter networks and sensing devices e.g., vehicular networks, which are considered to be challenging due to its high speed and network dynamics. The goal of future vehicular networks is to improve road safety, promote commercial or infotainment products and to reduce the traffic accidents. All these applications are based on the information exchange among nodes, so not only reliable data delivery but also the authenticity and credibility of the data itself are prerequisite. To cope with the aforementioned problem, trust management come up as promising candidate to conduct node’s transaction and interaction management, which requires distributed mobile nodes cooperation for achieving design goals. In this paper, we propose a trust-based routing protocol i.e., 3VSR (Three Valued Secure Routing, which extends the widely used AODV (Ad hoc On-demand Distance Vector routing protocol and employs the idea of Sensing Logic-based trust model to enhance the security solution of VANET (Vehicular Ad-Hoc Network. The existing routing protocol are mostly based on key or signature-based schemes, which off course increases computation overhead. In our proposed 3VSR, trust among entities is updated frequently by means of opinion derived from sensing logic due to vehicles random topologies. In 3VSR the theoretical capabilities are based on Dirichlet distribution by considering prior and posterior uncertainty of the said event. Also by using trust recommendation message exchange, nodes are able to reduce computation and routing overhead. The simulated results shows that the proposed scheme is secure and practical.

  13. 3VSR: Three Valued Secure Routing for Vehicular Ad Hoc Networks using Sensing Logic in Adversarial Environment.

    Science.gov (United States)

    Sohail, Muhammad; Wang, Liangmin

    2018-03-14

    Today IoT integrate thousands of inter networks and sensing devices e.g., vehicular networks, which are considered to be challenging due to its high speed and network dynamics. The goal of future vehicular networks is to improve road safety, promote commercial or infotainment products and to reduce the traffic accidents. All these applications are based on the information exchange among nodes, so not only reliable data delivery but also the authenticity and credibility of the data itself are prerequisite. To cope with the aforementioned problem, trust management come up as promising candidate to conduct node's transaction and interaction management, which requires distributed mobile nodes cooperation for achieving design goals. In this paper, we propose a trust-based routing protocol i.e., 3VSR (Three Valued Secure Routing), which extends the widely used AODV (Ad hoc On-demand Distance Vector) routing protocol and employs the idea of Sensing Logic-based trust model to enhance the security solution of VANET (Vehicular Ad-Hoc Network). The existing routing protocol are mostly based on key or signature-based schemes, which off course increases computation overhead. In our proposed 3VSR, trust among entities is updated frequently by means of opinion derived from sensing logic due to vehicles random topologies. In 3VSR the theoretical capabilities are based on Dirichlet distribution by considering prior and posterior uncertainty of the said event. Also by using trust recommendation message exchange, nodes are able to reduce computation and routing overhead. The simulated results shows that the proposed scheme is secure and practical.

  14. Differential effects of BDNF and neurotrophin 4 (NT4) on endocytic sorting of TrkB receptors.

    Science.gov (United States)

    Proenca, Catia C; Song, Minseok; Lee, Francis S

    2016-08-01

    Neurotrophins are a family of growth factors playing key roles in the survival, development, and function of neurons. The neurotrophins brain-derived neurotrophic factor (BDNF) and NT4 both bind to and activate TrkB receptors, however, they mediate distinct neuronal functions. The molecular mechanism of how TrkB activation by BDNF and NT4 leads to diverse outcomes is unknown. Here, we report that BDNF and NT4 lead to differential endocytic sorting of TrkB receptors resulting in diverse biological functions in cultured cortical neurons. Fluorescent microscopy and surface biotinylation experiments showed that both neurotrophins stimulate internalization of TrkB with similar kinetics. Exposure to BDNF for 2-3 h reduced the surface pool of TrkB receptors to half, whereas a longer treatment (4-5 h) with NT4 was necessary to achieve a similar level of down-regulation. Although BDNF and NT4 induced TrkB phosphorylation with similar intensities, BDNF induced more rapid ubiquitination and degradation of TrkB than NT4. Interestingly, TrkB receptor ubiquitination by these ligands have substantially different pH sensitivities, resulting in varying degrees of receptor ubiquitination at lower pH levels. Consequently, NT4 was capable of maintaining longer sustained downstream signaling activation that correlated with reduced TrkB ubiquitination at endosomal pH. Thus, by leading to altered endocytic trafficking itineraries for TrkB receptors, BDNF and NT4 elicit differential TrkB signaling in terms of duration, intensity, and specificity, which may contribute to their functional differences in vivo. The neurotrophins, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4), both bind to and activate TrkB receptors, however, they mediate distinct neuronal functions. Here, we propose that BDNF and NT4 lead to differential endocytic sorting of TrkB receptors resulting in diverse biological functions. BDNF induces more rapid ubiquitination and degradation of TrkB than NT4

  15. Development of a reactor thermalhydraulic experiment databank(SORTED1)

    International Nuclear Information System (INIS)

    Bang, Young Seck; Kim, Eun Kyoung; Kim, Hho Jung; Lee, Sang Yong

    1994-01-01

    The recent trend in thermalhydraulic safety analysis of nuclear power plant shows the best-estimate and probabilistic approaches, therefore, the verification of the best-estimate code based on the applicable experiment data has been required. The present study focused on developing a simple databank, SORTED1, to be effectively used for code verification. The development of SORTED1 includes a data collection from the various sources including ENCOUNTER, which is the reactor safety data bank of U.S. Nuclear Regulatory Commission, a reorganization of collected resources suitable for requirements of SORTED1 database management system (DBMS), and a development of a simple DBMS. The SORTED1 is designed in Unix environment with graphic user interface to improve a user convenience and has a capability to provide the test related information. The currently registered data in SORTED1 cover 759 thermalhydraulic tests including LOFT, Semiscale, etc

  16. Enrichment of putative pancreatic progenitor cells from mice by sorting for prominin1 (CD133) and platelet-derived growth factor receptor beta.

    Science.gov (United States)

    Hori, Yuichi; Fukumoto, Miki; Kuroda, Yoshikazu

    2008-11-01

    Success in islet transplantation-based therapies for type 1 diabetes mellitus and an extreme shortage of pancreatic islets have motivated recent efforts to develop renewable sources of islet-replacement tissue. Although pancreatic progenitor cells hold a promising potential, only a few attempts have been made at the prospective isolation of pancreatic stem/progenitor cells, because of the lack of specific markers and the development of effective cell culture methods. We found that prominin1 (also known as CD133) recognized the undifferentiated epithelial cells, whereas platelet-derived growth factor receptor beta (PDGFRbeta) was expressed on the mesenchymal cells in the mouse embryonic pancreas. We then developed an isolation method for putative stem/progenitor cells by flow cytometric cell sorting and characterized their potential for differentiation to pancreatic tissue using both in vitro and in vivo protocols. Flow cytometry and the subsequent reverse transcription-polymerase chain reaction and microarray analysis revealed pancreatic epithelial progenitor cells to be highly enriched in the prominin1(high)PDGFRbeta(-) cell population. During in vivo differentiation, these cell populations were able to differentiate into endocrine, exocrine, and ductal tissues, including the formation of an insulin-producing cell cluster. We established the prospective isolation of putative pancreatic epithelial progenitor cells by sorting for prominin1 and PDGFRbeta. Since this strategy is based on the cell surface markers common to human and rodents, these findings may lead to the development of new strategies to derive transplantable islet-replacement tissues from human pancreatic stem/progenitor cells. Disclosure of potential conflicts of interest is found at the end of this article.

  17. Ligand recognition and domain structure of Vps10p, a vacuolar protein sorting receptor in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Jørgensen, M U; Emr, S D; Winther, Jakob R.

    1999-01-01

    Vp10p is a receptor that sorts several different vacuolar proteins by cycling between a late Golgi compartment and the endosome. The cytoplasmic tail of Vps10p is necessary for the recycling, whereas the lumenal domain is predicted to interact with the soluble ligands. We have studied ligand bind...

  18. A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

    Science.gov (United States)

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-02-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. © 2016 Yamamoto, Yako, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Polarized expression of the GFP-tagged rat V(1a) vasopressin receptor.

    Science.gov (United States)

    Campos, D M; Reyes, C E; Sarmiento, J; Navarro, J; González, C B

    2001-11-30

    We investigated the targeting of the V(1a) receptor fused with the green fluorescence protein (V(1a)R-GFP) in polarized MDCK cells. Cells expressing V(1a)R-GFP displayed binding to vasopressin (AVP) and AVP-induced calcium responses, similar to cells expressing the wild-type V1a receptor. Interestingly, as with the wild-type V(1a)R, V(1a)R-GFP is preferentially distributed in the basolateral side of MDCK cells as monitored by confocal microscopy. Furthermore, AVP induced internalization of GFP-tagged receptors. Therefore, the GFP-tagged V(1a) receptor retains all the sorting signals of the wild-type receptor and offers an excellent system to elucidate the mechanisms of cell trafficking of V(1a) receptors.

  20. Characterization of cucurbita maxima phloem serpin-1 (CmPS-1). A developmentally regulated elastase inhibitor.

    Science.gov (United States)

    Yoo, B C; Aoki, K; Xiang, Y; Campbell, L R; Hull, R J; Xoconostle-Cázares, B; Monzer, J; Lee, J Y; Ullman, D E; Lucas, W J

    2000-11-10

    We report on the molecular, biochemical, and functional characterization of Cucurbita maxima phloem serpin-1 (CmPS-1), a novel 42-kDa serine proteinase inhibitor that is developmentally regulated and has anti-elastase properties. CmPS-1 was purified to near homogeneity from C. maxima (pumpkin) phloem exudate and, based on microsequence analysis, the cDNA encoding CmPS-1 was cloned. The association rate constant (k(a)) of phloem-purified and recombinant His(6)-tagged CmPS-1 for elastase was 3.5 +/- 1.6 x 10(5) and 2.7 +/- 0.4 x 10(5) m(-)(1) s(-)(1), respectively. The fraction of complex-forming CmPS-1, X(inh), was estimated at 79%. CmPS-1 displayed no detectable inhibitory properties against chymotrypsin, trypsin, or thrombin. The elastase cleavage sites within the reactive center loop of CmPS-1 were determined to be Val(347)-Gly(348) and Val(350)-Ser(351) with a 3:2 molar ratio. In vivo feeding assays conducted with the piercing-sucking aphid, Myzus persicae, established a close correlation between the developmentally regulated increase in CmPS-1 within the phloem sap and the reduced ability of these insects to survive and reproduce on C. maxima. However, in vitro feeding experiments, using purified phloem CmPS-1, failed to demonstrate a direct effect on aphid survival. Likely roles of this novel phloem serpin in defense against insects/pathogens are discussed.

  1. Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum.

    Science.gov (United States)

    Uesaka, Naofumi; Abe, Manabu; Konno, Kohtarou; Yamazaki, Maya; Sakoori, Kazuto; Watanabe, Takaki; Kao, Tzu-Huei; Mikuni, Takayasu; Watanabe, Masahiko; Sakimura, Kenji; Kano, Masanobu

    2018-02-21

    Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16. Progranulin derived from PCs acts retrogradely onto its putative receptor Sort1 on CFs. This effect is independent of semaphorin 3A, another retrograde signaling molecule that counteracts CF synapse elimination. We propose that progranulin-Sort1 signaling strengthens and maintains developing CF inputs, and may contribute to selection of single "winner" CFs that survive synapse elimination. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.

    Science.gov (United States)

    Lee, Ju-Hyun; Yu, W Haung; Kumar, Asok; Lee, Sooyeon; Mohan, Panaiyur S; Peterhoff, Corrinne M; Wolfe, Devin M; Martinez-Vicente, Marta; Massey, Ashish C; Sovak, Guy; Uchiyama, Yasuo; Westaway, David; Cuervo, Ana Maria; Nixon, Ralph A

    2010-06-25

    Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autophagosome clearance during macroautophagy are prevented as a result of a selective impairment of autolysosome acidification and cathepsin activation. These deficits are caused by failed PS1-dependent targeting of the v-ATPase V0a1 subunit to lysosomes. N-glycosylation of the V0a1 subunit, essential for its efficient ER-to-lysosome delivery, requires the selective binding of PS1 holoprotein to the unglycosylated subunit and the Sec61alpha/oligosaccharyltransferase complex. PS1 mutations causing early-onset AD produce a similar lysosomal/autophagy phenotype in fibroblasts from AD patients. PS1 is therefore essential for v-ATPase targeting to lysosomes, lysosome acidification, and proteolysis during autophagy. Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets.

  3. Prognostic significance of cytosolic pS2 content in ovarian tumors

    International Nuclear Information System (INIS)

    Raigoso, P.; Allende, T.; Zeidan, N.; Llana, B.; Bernardo, L.; Roiz, C.; Tejuca, S.; Vazquez, J.; Lamelas, M.L.

    2002-01-01

    Aim: pS2 is an estrogen regulated peptide which has been associated with a good prognosis an with a more favorable response to treatment in breast cancer patients. In ovarian tumors, the expression of pS2 was demonstrated at both mRNA and protein levels. In addition, it has been showed significant association of pS2 with mucinous differentiation or well differentiation grade of the tumors. However, it is little know about the prognostic significance of the pS2 content in ovarian carcinomas. The aims of the present work were to analyze the cytosolic pS2 content in benign and malignant ovarian tumors, its relationship with clinico-pathologic parameters, steroid receptor status, and prognostic significance. Material and Methods: We analysed the cytosolic concentrations of pS2 in 91 specimen ovarian tissues by an immunoradiometric assay (ELSA-pS2, CIS, France). The tissues were 8 normal ovaries, 43 benign tumors and 40 malignant ovarian tumors. The same ovarian tissues processed to pS2 were analyzed to Estrogen (ER) and Progesterone (PgR) Receptor status. These steroid receptors were quantified biochemically following commercial ELISA method (ABBOTT Diagnostics, Germany). The relationship between cytosolic content and clinico-pathologic factors was examined by the Mann-Whitney or Kruskall-Wallis test. Correlation between steroid receptors and pS2 content was calculated with the Spearman test. Survival curves were calculated using the Kaplan-Meier method and compared by the log-rank test. Differences were considered significant at 5% probability level. Results: pS2 could be detected in 30 cases (32.9%) with values ranged from 0.04 to 89 ng/mg prt. Only one normal ovary showed detectable levels of pS2 and there were not differences in cytosolic content between benign and malignant ovarian tumors. The pS2 levels were only associated to mucinous differentiation in both benign and malignant ovarian tumors (p=0.029 and p=0.015, respectively). Significantly higher

  4. Involvement of Gβγ subunits of Gi protein coupled with S1P receptor on multivesicular endosomes in F-actin formation and cargo sorting into exosomes.

    Science.gov (United States)

    Kajimoto, Taketoshi; Mohamed, Nesma Nabil Ibrahim; Badawy, Shaymaa Mohamed Mohamed; Matovelo, Shubi Ambwene; Hirase, Mitsuhiro; Nakamura, Shunsuke; Yoshida, Daisuke; Okada, Taro; Ijuin, Takeshi; Nakamura, Shun-Ichi

    2018-01-05

    Exosomes play a critical role in cell-to-cell communication by delivering cargo molecules to recipient cells. However, the mechanism underlying the generation of the exosomal multivesicular endosome (MVE) is one of the mysteries in the field of endosome research. Although sphingolipid metabolites such as ceramide and sphingosine 1-phosphate (S1P) are known to play important roles in MVE formation and maturation, the detailed molecular mechanisms are still unclear. Here, we show that Rho family GTPases, including Cdc42 and Rac1, are constitutively activated on exosomal MVEs and are regulated by S1P signaling as measured by fluorescence resonance energy transfer (FRET)-based conformational changes. Moreover, we detected S1P signaling-induced filamentous actin (F-actin) formation. A selective inhibitor of Gβγ subunits, M119, strongly inhibited both F-actin formation on MVEs and cargo sorting into exosomal intralumenal vesicles of MVEs, both of which were fully rescued by the simultaneous expression of constitutively active Cdc42 and Rac1. Our results shed light on the mechanism underlying exosomal MVE maturation and inform the understanding of the physiological relevance of continuous activation of the S1P receptor and subsequent downstream G protein signaling to Gβγ subunits/Rho family GTPases-regulated F-actin formation on MVEs for cargo sorting into exosomal intralumenal vesicles. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Different pathways of [3H]inositol phosphate formation mediated by α 1a- and α 1b-adrenergic receptors

    International Nuclear Information System (INIS)

    Wilson, K.M.; Minneman, K.P.

    1990-01-01

    The types of inositol phosphates (InsPs) formed in response to activation of alpha 1-adrenergic receptor subtypes were determined in collagenase-dispersed renal cells and hepatocytes by high pressure liquid chromatography separation. In hepatocytes, which contain only the alpha 1b subtype, norepinephrine stimulated rapid (10-s) formation of [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4)P3 and slower (5-min) formation of Ins(1,4)P2 and Ins(1)P. Selective inactivation of alpha 1b receptors by chloroethylclonidine almost completely blocked the effects of norepinephrine in hepatocytes. In renal cells, which contain both alpha 1a and alpha 1b receptors in a 60:40 ratio, norepinephrine did not significantly increase the size of any peaks until 5 min after agonist activation. At this time, only a peak eluting with Ins(1)P and one eluting shortly after Ins(1,4)P2 were significantly elevated. Incubation with norepinephrine for 2 h caused small but significant increases in peaks co-eluting with Ins(1)P and Ins(1,4,5)P3 in renal cells; however, only the increase in Ins(1)P was inhibited by chloroethylclonidine pretreatment. Extraction under neutral conditions suggested that cyclic InsPs may be the primary compounds formed in response to norepinephrine in renal cells. Removal of extracellular Ca2+ caused a 60% reduction in the InsP response to norepinephrine in renal cells but had no effect in hepatocytes. These results suggest that activation of alpha 1a and alpha 1b receptor subtypes results in formation of different InsPs and that the response to alpha 1a activation may require influx of extracellular Ca2+

  6. Rab21, a Novel PS1 Interactor, Regulates γ-Secretase Activity via PS1 Subcellular Distribution.

    Science.gov (United States)

    Sun, Zhenzhen; Xie, Yujie; Chen, Yintong; Yang, Qinghu; Quan, Zhenzhen; Dai, Rongji; Qing, Hong

    2018-05-01

    γ-Secretase has been a therapeutical target for its key role in cleaving APP to generate β-amyloid (Aβ), the primary constituents of senile plaques and a hallmark of Alzheimer's disease (AD) pathology. Recently, γ-secretase-associating proteins showed promising role in specifically modulating APP processing while sparing Notch signaling; however, the underlying mechanism is still unclear. A co-immunoprecipitation (Co-IP) coupled with mass spectrometry proteomic assay for Presenilin1 (PS1, the catalytic subunit of γ-secretase) was firstly conducted to find more γ-secretase-associating proteins. Gene ontology analysis of these results identified Rab21 as a potential PS1 interacting protein, and the interaction between them was validated by reciprocal Co-IP and immunofluorescence assay. Then, molecular and biochemical methods were used to investigate the effect of Rab21 on APP processing. Results showed that overexpression of Rab21 enhanced Aβ generation, while silencing of Rab21 reduced the accumulation of Aβ, which resulted due to change in γ-secretase activity rather than α- or β-secretase. Finally, we demonstrated that Rab21 had no effect on γ-secretase complex synthesis or metabolism but enhanced PS1 endocytosis and translocation to late endosome/lysosome. In conclusion, we identified a novel γ-secretase-associating protein Rab21 and illustrate that Rab21 promotes γ-secretase internalization and translocation to late endosome/lysosome. Moreover, silencing of Rab21 decreases the γ-secretase activity in APP processing thus production of Aβ. All these results open new gateways towards the understanding of γ-secretase-associating proteins in APP processing and make inhibition of Rab21 a promising strategy for AD therapy.

  7. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

    International Nuclear Information System (INIS)

    Toba, Junya; Nikkuni, Miyu; Ishizeki, Masato; Yoshii, Aya; Watamura, Naoto; Inoue, Takafumi; Ohshima, Toshio

    2016-01-01

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  8. T cell receptor zeta allows stable expression of receptors containing the CD3gamma leucine-based receptor-sorting motif

    DEFF Research Database (Denmark)

    Dietrich, J; Geisler, C

    1998-01-01

    The leucine-based motif in the T cell receptor (TCR) subunit CD3gamma constitutes a strong internalization signal. In fully assembled TCR this motif is inactive unless phosphorylated. In contrast, the motif is constitutively active in CD4/CD3gamma and Tac/CD3gamma chimeras independently of phosph......The leucine-based motif in the T cell receptor (TCR) subunit CD3gamma constitutes a strong internalization signal. In fully assembled TCR this motif is inactive unless phosphorylated. In contrast, the motif is constitutively active in CD4/CD3gamma and Tac/CD3gamma chimeras independently...... of phosphorylation and leads to rapid internalization and sorting of these chimeras to lysosomal degradation. Because the TCRzeta chain rescues incomplete TCR complexes from lysosomal degradation and allows stable surface expression of fully assembled TCR, we addressed the question whether TCRzeta has the potential...... to mask the CD3gamma leucine-based motif. By studying CD4/CD3gamma and CD16/CD3gamma chimeras, we found that CD16/CD3gamma chimeras associated with TCRzeta. The CD16/CD3gamma-TCRzeta complexes were stably expressed at the cell surface and had a low spontaneous internalization rate, indicating...

  9. Prions amplify through degradation of the VPS10P sorting receptor sortilin.

    Science.gov (United States)

    Uchiyama, Keiji; Tomita, Mitsuru; Yano, Masashi; Chida, Junji; Hara, Hideyuki; Das, Nandita Rani; Nykjaer, Anders; Sakaguchi, Suehiro

    2017-06-01

    Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells.

  10. Multiple pathways for vacuolar sorting of yeast proteinase A

    DEFF Research Database (Denmark)

    Westphal, V; Marcusson, E G; Winther, Jakob R.

    1996-01-01

    The sorting of the yeast proteases proteinase A and carboxypeptidase Y to the vacuole is a saturable, receptor-mediated process. Information sufficient for vacuolar sorting of the normally secreted protein invertase has in fusion constructs previously been found to reside in the propeptide...

  11. Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies.

    Directory of Open Access Journals (Sweden)

    Véronique Pons

    2008-09-01

    Full Text Available After internalization, ubiquitinated signaling receptors are delivered to early endosomes. There, they are sorted and incorporated into the intralumenal invaginations of nascent multivesicular bodies, which function as transport intermediates to late endosomes. Receptor sorting is achieved by Hrs--an adaptor--like protein that binds membrane PtdIns3P via a FYVE motif-and then by ESCRT complexes, which presumably also mediate the invagination process. Eventually, intralumenal vesicles are delivered to lysosomes, leading to the notion that EGF receptor sorting into multivesicular bodies mediates lysosomal targeting. Here, we report that Hrs is essential for lysosomal targeting but dispensable for multivesicular body biogenesis and transport to late endosomes. By contrast, we find that the PtdIns3P-binding protein SNX3 is required for multivesicular body formation, but not for EGF receptor degradation. PtdIns3P thus controls the complementary functions of Hrs and SNX3 in sorting and multivesicular body biogenesis.

  12. Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma.

    Science.gov (United States)

    Rodriguez, A M; Graef, A J; LeVine, D N; Cohen, I R; Modiano, J F; Kim, J-H

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs. S1P/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA). Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used. This was a retrospective case series and in vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography/mass spectrometry. S1P signaling was evaluated by intracellular Ca(2+) mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining. Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1 , decreased S1P1 protein expression and induced apoptosis of HSA cells. S1P/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  13. Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.

    Directory of Open Access Journals (Sweden)

    Kaipeng Huang

    Full Text Available The accumulation of glomerular extracellular matrix (ECM is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1-sphingosine 1- phosphate (S1P signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG and simultaneously inhibited S1P2 receptor-mediated FN overproduction. Further, BBR also obviously suppressed the activation of NF-κB induced by HG, which was accompanied by reduced S1P2 receptor and FN expression. Taken together, our findings suggest that BBR reduces FN expression by acting on the S1P2 receptor in the mesangium under diabetic condition. The role of BBR in S1P2 receptor expression regulation could closely associate with its inhibitory effect on NF-κB activation.

  14. ARF6 and GASP-1 are post-endocytic sorting proteins selectively involved in the intracellular trafficking of dopamine D2 receptors mediated by GRK and PKC in transfected cells

    Science.gov (United States)

    Cho, DI; Zheng, M; Min, C; Kwon, KJ; Shin, CY; Choi, HK; Kim, KM

    2013-01-01

    Background and Purpose GPCRs undergo both homologous and heterologous regulatory processes in which receptor phosphorylation plays a critical role. The protein kinases responsible for each pathway are well established; however, other molecular details that characterize each pathway remain unclear. In this study, the molecular mechanisms that determine the differences in the functional roles and intracellular trafficking between homologous and PKC-mediated heterologous internalization pathways for the dopamine D2 receptor were investigated. Experimental Approach All of the S/T residues located within the intracellular loops of D2 receptor were mutated, and the residues responsible for GRK- and PKC-mediated internalization were determined in HEK-293 cells and SH-SY5Y cells. The functional role of receptor internalization and the cellular components that determine the post-endocytic fate of internalized D2 receptors were investigated in the transfected cells. Key Results T134, T225/S228/S229 and S325 were involved in PKC-mediated D2 receptor desensitization. S229 and adjacent S/T residues mediated the PKC-dependent internalization of D2 receptors, which induced down-regulation and desensitization. S/T residues within the second intracellular loop and T225 were the major residues involved in GRK-mediated internalization of D2 receptors, which induced receptor resensitization. ARF6 mediated the recycling of D2 receptors internalized in response to agonist stimulation. In contrast, GASP-1 mediated the down-regulation of D2 receptors internalized in a PKC-dependent manner. Conclusions and Implications GRK- and PKC-mediated internalizations of D2 receptors occur through different intracellular trafficking pathways and mediate distinct functional roles. Distinct S/T residues within D2 receptors and different sorting proteins are involved in the dissimilar regulation of D2 receptors by GRK2 and PKC. PMID:23082996

  15. Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling*

    Science.gov (United States)

    McGarvey, Jennifer C.; Xiao, Kunhong; Bowman, Shanna L.; Mamonova, Tatyana; Zhang, Qiangmin; Bisello, Alessandro; Sneddon, W. Bruce; Ardura, Juan A.; Jean-Alphonse, Frederic; Vilardaga, Jean-Pierre; Puthenveedu, Manojkumar A.; Friedman, Peter A.

    2016-01-01

    The G protein-coupled parathyroid hormone receptor (PTHR) regulates mineral-ion homeostasis and bone remodeling. Upon parathyroid hormone (PTH) stimulation, the PTHR internalizes into early endosomes and subsequently traffics to the retromer complex, a sorting platform on early endosomes that promotes recycling of surface receptors. The C terminus of the PTHR contains a type I PDZ ligand that binds PDZ domain-containing proteins. Mass spectrometry identified sorting nexin 27 (SNX27) in isolated endosomes as a PTHR binding partner. PTH treatment enriched endosomal PTHR. SNX27 contains a PDZ domain and serves as a cargo selector for the retromer complex. VPS26, VPS29, and VPS35 retromer subunits were isolated with PTHR in endosomes from cells stimulated with PTH. Molecular dynamics and protein binding studies establish that PTHR and SNX27 interactions depend on the PDZ recognition motif in PTHR and the PDZ domain of SNX27. Depletion of either SNX27 or VPS35 or actin depolymerization decreased the rate of PTHR recycling following agonist stimulation. Mutating the PDZ ligand of PTHR abolished the interaction with SNX27 but did not affect the overall rate of recycling, suggesting that PTHR may directly engage the retromer complex. Coimmunoprecipitation and overlay experiments show that both intact and mutated PTHR bind retromer through the VPS26 protomer and sequentially assemble a ternary complex with PTHR and SNX27. SNX27-independent recycling may involve N-ethylmaleimide-sensitive factor, which binds both PDZ intact and mutant PTHRs. We conclude that PTHR recycles rapidly through at least two pathways, one involving the ASRT complex of actin, SNX27, and retromer and another possibly involving N-ethylmaleimide-sensitive factor. PMID:27008860

  16. In vivo intracellular pH measurements in tobacco and Arabidopsis reveal an unexpected pH gradient in the endomembrane system.

    Science.gov (United States)

    Martinière, Alexandre; Bassil, Elias; Jublanc, Elodie; Alcon, Carine; Reguera, Maria; Sentenac, Hervé; Blumwald, Eduardo; Paris, Nadine

    2013-10-01

    The pH homeostasis of endomembranes is essential for cellular functions. In order to provide direct pH measurements in the endomembrane system lumen, we targeted genetically encoded ratiometric pH sensors to the cytosol, the endoplasmic reticulum, and the trans-Golgi, or the compartments labeled by the vacuolar sorting receptor (VSR), which includes the trans-Golgi network and prevacuoles. Using noninvasive live-cell imaging to measure pH, we show that a gradual acidification from the endoplasmic reticulum to the lytic vacuole exists, in both tobacco (Nicotiana tabacum) epidermal (ΔpH -1.5) and Arabidopsis thaliana root cells (ΔpH -2.1). The average pH in VSR compartments was intermediate between that of the trans-Golgi and the vacuole. Combining pH measurements with in vivo colocalization experiments, we found that the trans-Golgi network had an acidic pH of 6.1, while the prevacuole and late prevacuole were both more alkaline, with pH of 6.6 and 7.1, respectively. We also showed that endosomal pH, and subsequently vacuolar trafficking of soluble proteins, requires both vacuolar-type H(+) ATPase-dependent acidification as well as proton efflux mediated at least by the activity of endosomal sodium/proton NHX-type antiporters.

  17. An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells

    Science.gov (United States)

    Wei, Tingyi; Chen, Wen; Wang, Xiukun; Zhang, Man; Chen, Jiayu; Zhu, Songcheng; Chen, Long; Yang, Dandan; Wang, Guiying; Jia, Wenwen; Yu, Yangyang; Duan, Tao; Wu, Minjuan; Liu, Houqi; Gao, Shaorong; Kang, Jiuhong

    2015-01-01

    The maturation of induced pluripotent stem cells (iPS) is one of the limiting steps of somatic cell reprogramming, but the underlying mechanism is largely unknown. Here, we reported that knockdown of histone deacetylase 2 (HDAC2) specifically promoted the maturation of iPS cells. Further studies showed that HDAC2 knockdown significantly increased histone acetylation, facilitated TET1 binding and DNA demethylation at the promoters of iPS cell maturation-related genes during the transition of pre-iPS cells to a fully reprogrammed state. We also found that HDAC2 competed with TET1 in the binding of the RbAp46 protein at the promoters of maturation genes and knockdown of TET1 markedly prevented the activation of these genes. Collectively, our data not only demonstrated a novel intrinsic mechanism that the HDAC2-TET1 switch critically regulates iPS cell maturation, but also revealed an underlying mechanism of the interplay between histone acetylation and DNA demethylation in gene regulation. PMID:25934799

  18. PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

    Energy Technology Data Exchange (ETDEWEB)

    Toba, Junya; Nikkuni, Miyu [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ishizeki, Masato [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Yoshii, Aya; Watamura, Naoto [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Inoue, Takafumi [Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan); Ohshima, Toshio, E-mail: ohshima@waseda.jp [Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, 162-8480 Japan (Japan)

    2016-05-13

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice. -- Highlights: •Phosphorylation level of CRMP2 increased in the cerebellum of APP/PS1 mice. •p35 protein levels increased in the cerebellum of APP/PS1 mice. •Pioglitazone treatment improved cerebellar dysfunction of APP/PS1 mice.

  19. Contribution of defective PS recognition and efferocytosis to chronic inflammation and autoimmunity

    Directory of Open Access Journals (Sweden)

    Stanley Gititu Kimani

    2014-11-01

    Full Text Available Rapid and efficient clearance of apoptotic cells results in elimination of auto-antigens and provides a strong anti-inflammatory and immunosuppressive signal to prevent autoimmunity. While professional and non-professional phagocytes utilize a wide array of surface receptors to recognize apoptotic cells, recognition of phosphatidylserine (PS on apoptotic cells by PS receptors on phagocytes is emblematic signal for efferocytosis in metazoans. PS-dependent efferocytosis is associated with production of anti-inflammatory factors such as IL-10 and TGF-β that function, in part, to maintain tolerance to auto-antigens. In contrast, when apoptotic cells fail to be recognized and processed for degradation, auto-antigens persist, which can trigger immune activation leading to autoantibody production and autoimmunity. Despite the fact that genetic mouse models clearly demonstrate that loss of PS receptors can lead to age-dependent autoimmune diseases reminiscent of systemic lupus erythematosus (SLE, link between PS and defective clearance in chronic inflammation and human autoimmunity is not well delineated. In this hypothesis and theory, we review emerging questions developing in the field that may be of relevance to SLE and human autoimmunity.

  20. On the crystallization behavior of syndiotactic-b-atactic polystyrene stereodiblock copolymers, atactic/syndiotactic polystyrene blends, and aPS/sPS blends modified with sPS-b-aPS

    Energy Technology Data Exchange (ETDEWEB)

    Annunziata, Liana, E-mail: liana.annunziatta@univ-rennes1.fr [Organométalliques et Catalyse, UMR 6226 Sciences Chimiques CNRS, Université de Rennes 1, Campus de Beaulieu, F-35042 Rennes Cedex (France); Monasse, Bernard, E-mail: bernard.monasse@mines-paristech.fr [Mines-ParisTech, CEMEF, Centre de Mise en Forme des Matériaux, UMR CNRS 7635, Sophia Antipolis (France); Rizzo, Paola; Guerra, Gaetano [Dipartimento di Chimica e Biologia, Università degli studi di Salerno, Via Ponte don Melillo, I-84084 Fisciano, SA (Italy); Duc, Michel [Total Petrochemicals Research Feluy, Zone Industrielle Feluy C, B-7181 Seneffe (Belgium); Carpentier, Jean-François, E-mail: jean-francois.carpentier@univ-rennes1.fr [Organométalliques et Catalyse, UMR 6226 Sciences Chimiques CNRS, Université de Rennes 1, Campus de Beaulieu, F-35042 Rennes Cedex (France)

    2013-09-16

    Crystallization and morphological features of syndiotactic-b-atactic polystyrene stereodiblock copolymers (sPS-b-aPS), atactic/syndiotactic polystyrene blends (aPS/sPS), and aPS/sPS blends modified with sPS-b-aPS, with different compositions in aPS and sPS, have been investigated using differential scanning calorimetry (DSC), polarized light optical microscopy (POM) and wide angle X-ray diffraction (WAXRD) techniques. For comparative purposes, the properties of parent pristine sPS samples were also studied. WAXRD analyses revealed for all the samples, independently from their composition (aPS/sPS ratio) and structure (blends, block copolymers, blends modified with block copolymers), the same polymorphic β form of sPS. The molecular weight of aPS and sPS showed opposite effects on the crystallization of 50:50 aPS/sPS blends: the lower the molecular weight of aPS, the slower the crystallization while the lower the molecular weight of sPS, the faster the crystallization. DSC studies performed under both isothermal and non-isothermal conditions, independently confirmed by POM studies, led to a clear trend for the crystallization rate at a given sPS/aPS ratio (ca. 50:50 and 20:80): sPS homopolymers > sPS-b-aPS block copolymers ∼sPS/aPS blends modified with sPS-b-aPS copolymers > sPS/aPS blends. Interestingly, sPS-b-aPS block copolymers not only crystallized faster than blends, but also affected positively the crystallization behavior of blends. At 50:50 sPS/aPS ratio, blends (Blend-2), block copolymers (Cop-1) and blends modified with block copolymers (Blend-2-mod) crystallized via spherulitic crystalline growth controlled by an interfacial process. In all cases, an instantaneous nucleation was observed. The density of nuclei in block copolymers (160,000−190,000 nuclei mm{sup −3}) was always higher than that in blends and modified blends (30,000−60,000 nuclei mm{sup −3}), even for quite different sPS/aPS ratio. At 20:80 sPS/aPS ratio, the block copolymers

  1. Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Han, Kun; Jia, Ning; Li, Ji; Yang, Li; Min, Lian-Qiu

    2013-09-01

    The objective of this study was to investigate the effects of varying doses of caffeine on memory impairment and the expression of brain neurotrophic derived factor (BNDF) and TrkB in PS1/APP double transgenic mouse models. PS1/APP double transgenic mice were administered 0.3 ml/day of saline, 1.5 mg/day of caffeine or 0.75 mg/day of caffeine for eight weeks. A water maze test and western blotting were used to determine the memory capability and expression of hippocampal BNDF and TrkB of the mice. The results demonstrated that 0.75 mg/day and 1.5 mg/day doses of caffeine significantly increased memory capability and the expression of hippocampal BDNF and TrkB in PS1/APP mice with a dose-response effect. The results suggested that chronic caffeine treatment may reverse memory impairment in PS1/APP transgenic mice, and BDNF and its receptor TrkB, may be involved in this process.

  2. A paralogous decoy protects Phytophthora sojae apoplastic effector PsXEG1 from a host inhibitor.

    Science.gov (United States)

    Ma, Zhenchuan; Zhu, Lin; Song, Tianqiao; Wang, Yang; Zhang, Qi; Xia, Yeqiang; Qiu, Min; Lin, Yachun; Li, Haiyang; Kong, Liang; Fang, Yufeng; Ye, Wenwu; Wang, Yan; Dong, Suomeng; Zheng, Xiaobo; Tyler, Brett M; Wang, Yuanchao

    2017-02-17

    The extracellular space (apoplast) of plant tissue represents a critical battleground between plants and attacking microbes. Here we show that a pathogen-secreted apoplastic xyloglucan-specific endoglucanase, PsXEG1, is a focus of this struggle in the Phytophthora sojae -soybean interaction. We show that soybean produces an apoplastic glucanase inhibitor protein, GmGIP1, that binds to PsXEG1 to block its contribution to virulence. P. sojae , however, secretes a paralogous PsXEG1-like protein, PsXLP1, that has lost enzyme activity but binds to GmGIP1 more tightly than does PsXEG1, thus freeing PsXEG1 to support P. sojae infection. The gene pair encoding PsXEG1 and PsXLP1 is conserved in many Phytophthora species, and the P. parasitica orthologs PpXEG1 and PpXLP1 have similar functions. Thus, this apoplastic decoy strategy may be widely used in Phytophthora pathosystems. Copyright © 2017, American Association for the Advancement of Science.

  3. The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond

    Directory of Open Access Journals (Sweden)

    Fubito Nakatsu

    2014-11-01

    Full Text Available The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane. Adaptor protein (AP-1, a member of the AP complex family, which includes the ubiquitously expressed AP-1A and the epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network and/or at the recycling endosomes. A growing body of evidence, especially from studies using model organisms and animals, demonstrates that the AP-1-mediated polarized sorting supports the development and physiology of multi-cellular units as functional organs and tissues (e.g., cell fate determination, inflammation and gut immune homeostasis. Furthermore, a possible involvement of AP-1B in the pathogenesis of human diseases, such as Crohn’s disease and cancer, is now becoming evident. These data highlight the significant contribution of AP-1 complexes to the physiology of multicellular organisms, as master regulators of polarized sorting in epithelial cells.

  4. The Pan-STARRS PS1 Image Processing Pipeline

    Science.gov (United States)

    Magnier, E.

    The Pan-STARRS PS1 Image Processing Pipeline (IPP) performs the image processing and data analysis tasks needed to enable the scientific use of the images obtained by the Pan-STARRS PS1 prototype telescope. The primary goals of the IPP are to process the science images from the Pan-STARRS telescopes and make the results available to other systems within Pan-STARRS. It also is responsible for combining all of the science images in a given filter into a single representation of the non-variable component of the night sky defined as the "Static Sky". To achieve these goals, the IPP also performs other analysis functions to generate the calibrations needed in the science image processing, and to occasionally use the derived data to generate improved astrometric and photometric reference catalogs. It also provides the infrastructure needed to store the incoming data and the resulting data products. The IPP inherits lessons learned, and in some cases code and prototype code, from several other astronomy image analysis systems, including Imcat (Kaiser), the Sloan Digital Sky Survey (REF), the Elixir system (Magnier & Cuillandre), and Vista (Tonry). Imcat and Vista have a large number of robust image processing functions. SDSS has demonstrated a working analysis pipeline and large-scale databasesystem for a dedicated project. The Elixir system has demonstrated an automatic image processing system and an object database system for operational usage. This talk will present an overview of the IPP architecture, functional flow, code development structure, and selected analysis algorithms. Also discussed is the HW highly parallel HW configuration necessary to support PS1 operational requirements. Finally, results are presented of the processing of images collected during PS1 early commissioning tasks utilizing the Pan-STARRS Test Camera #3.

  5. LS1 Report: PS beams are back!

    CERN Multimedia

    Katarina Anthony & Anaïs Schaeffer

    2014-01-01

    For the first time in over 15 months, there are beams back in the PS. Making their first tour of the accelerator today, 20 June, their injection marks the end of weeks of cold checkouts and hardware commissioning in the PS.   The CERN Control Centre (CCC) is back in business: people gather to restart the LHC injectors, today the PS. Since hardware commissioning was wrapped up on 23 May, the Operations Group (BE-OP) has been conducting cold checkouts on the PS. This involves switching on all of the machine's systems, verifying that they respond to commands by OP and ensuring they are calibrated to beam timings. "These verifications were done, in part, during the hardware commissioning dry runs," says Rende Steerenberg, PS section leader. "But the cold checkouts are on a much larger scale, as we act as if there is beam in the whole machine. We placed a full load on the controls system, cooling, networks, etc. in order to setup the accelerator in the most realis...

  6. Chronic caffeine treatment reverses memory impairment and the expression of brain BNDF and TrkB in the PS1/APP double transgenic mouse model of Alzheimer’s disease

    Science.gov (United States)

    HAN, KUN; JIA, NING; LI, JI; YANG, LI; MIN, LIAN-QIU

    2013-01-01

    The objective of this study was to investigate the effects of varying doses of caffeine on memory impairment and the expression of brain neurotrophic derived factor (BNDF) and TrkB in PS1/APP double transgenic mouse models. PS1/APP double transgenic mice were administered 0.3 ml/day of saline, 1.5 mg/day of caffeine or 0.75 mg/day of caffeine for eight weeks. A water maze test and western blotting were used to determine the memory capability and expression of hippocampal BNDF and TrkB of the mice. The results demonstrated that 0.75 mg/day and 1.5 mg/day doses of caffeine significantly increased memory capability and the expression of hippocampal BDNF and TrkB in PS1/APP mice with a dose-response effect. The results suggested that chronic caffeine treatment may reverse memory impairment in PS1/APP transgenic mice, and BDNF and its receptor TrkB, may be involved in this process. PMID:23900282

  7. Synthesis of NiPS3 and CoPS and its hydrogen storage capacity

    International Nuclear Information System (INIS)

    Ismail, N.; Madian, M.; El-Meligi, A.A.

    2014-01-01

    Highlights: • Preparation of NiPS 3 and CoPS using solid state reaction. • Characterization of compounds using XRD, TEM, SEM and IR. • Measuring the compounds thermal stability. • Estimation of the hydrogen storage capacity. -- Abstract: Prepared CoPS and NiPS 3 are studied as new materials for hydrogen energy storage. Single phase of CoPS and NiPS 3 were grown separately in evacuated silicatube via solid state reaction at 650 °C with controlled heating rate 1 °C/min. X-ray diffraction patterns confirm the formation of the desired compounds. Both CoPS and NiPS 3 exhibited high thermal stability up to 700 °C and 630 °C, respectively. The morphology of the prepared samples was investigated using scanning electron microscopy and folded sheets appeared in the transmission electron microscopy. The samples were exposed to 20 bar applied hydrogen pressure at 80 K. Both compounds appear to have feasible hydrogen storage capacity. CoPS was capable to adsorb 1.7 wt% while NiPS 3 storage capacity reached 1.2 wt%

  8. TRAM is involved in IL-18 signaling and functions as a sorting adaptor for MyD88.

    Directory of Open Access Journals (Sweden)

    Hidenori Ohnishi

    Full Text Available MyD88, a Toll/interleukin-1 receptor homology (TIR domain-containing adaptor protein, mediates signals from the Toll-like receptors (TLR or IL-1/IL-18 receptors to downstream kinases. In MyD88-dependent TLR4 signaling, the function of MyD88 is enhanced by another TIR domain-containing adaptor, Mal/TIRAP, which brings MyD88 to the plasma membrane and promotes its interaction with the cytosolic region of TLR4. Hence, Mal is recognized as the "sorting adaptor" for MyD88. In this study, a direct interaction between MyD88-TIR and another membrane-sorting adaptor, TRAM/TICAM-2, was demonstrated in vitro. Cell-based assays including RNA interference experiments and TRAM deficient mice revealed that the interplay between MyD88 and TRAM in cells is important in mediating IL-18 signal transduction. Live cell imaging further demonstrated the co-localized accumulation of MyD88 and TRAM in the membrane regions in HEK293 cells. These findings suggest that TRAM serves as the sorting adaptor for MyD88 in IL-18 signaling, which then facilitates the signal transduction. The binding sites for TRAM are located in the TIR domain of MyD88 and actually overlap with the binding sites for Mal. MyD88, the multifunctional signaling adaptor that works together with most of the TLR members and with the IL-1/IL-18 receptors, can interact with two distinct sorting adaptors, TRAM and Mal, in a conserved manner in a distinct context.

  9. Activation of nicotinic α(7) acetylcholine receptor enhances long term potentation in wild type mice but not in APP(swe)/PS1ΔE9 mice

    DEFF Research Database (Denmark)

    Söderman, Andreas; Mikkelsen, Jens D; West, Mark J

    2011-01-01

    the effect of the partial α(7) nAChR agonist SSR180711 on hippocampal slice preparations from normal wild type (Wt) and APP(swe)/PS1ΔE9 transgenic (Tg) mice. In the hippocampal slices from the 6 months old Wt mice, the application of both nicotine (5μM) and SSR180711 (300nM) resulted in a significant...... enhancement of LTP expressed in area CA1. However, in the Tg mice the application of SSR180711 did not result in an increase in LTP beyond control levels. The amount of binding of the α(7) nAChR ligand 125-I-α-bungarotoxin was not different between in Tg and Wt mice. These findings indicate that the α(7) n......AChR is functionally blocked in the hippocampal neurons, downstream of the α(7) nAChR, and that this is likely due to an interaction between the receptor and Aβ, which leads to changes in LTP....

  10. Perbandingan Kecepatan Gabungan Algoritma Quick Sort dan Merge Sort dengan Insertion Sort, Bubble Sort dan Selection Sort

    OpenAIRE

    Al Rivan, Muhammad Ezar

    2017-01-01

    Ordering is one of the process done before doing data processing. The sorting algorithm has its own strengths and weaknesses. By taking strengths of each algorithm then combined can be a better algorithm. Quick Sort and Merge Sort are algorithms that divide the data into parts and each part divide again into sub-section until one element. Usually one element join with others and then sorted by. In this experiment data divide into parts that have size not more than threshold. This part then so...

  11. [Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes].

    Science.gov (United States)

    Bao, X H; Li, H X; Tao, J; Li, X M; Yang, Y N; Ma, Y T; Chen, B D

    2016-05-24

    To study the role and mechanism of sphingosine-1-phosphate (S1P)/ sphingosine-1-phosphate receptor 1(S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes. Neonatal rat cardiomyocytes were isolated and cultured, then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy. Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning. Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected: (1) IPost group (hypoxia+ postconditioning); (2) IPost+ S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost); (3) IPost+ W-146+ S1P group (cells in IPost+ W-146+ S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min); (4) IPost+ PD98059+ S1P group (cells in IPost+ S1P group were pretreated with MAPK antagonist PD98059 (125 μmol/L) for 20 min); (5) IPost+ LY-294002+ S1P group (cells in IPost+ S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min). Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot. (1)Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90±4.49)% group compared with normal control group (7.97±2.18)%, which could be significantly reduced in IPost group (15.90±1.77)% (all PS1P and IPost+ S1P+ LY-294002 groups than in IPost and IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 group (all PS1P and IPost+ S1P+ LY-294002 group than in IPost and IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 group (all PS1P+ W-146 and IPost+ S1P+ PD98059 groups. p-ERK1/2 and p-Akt levels in IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 were similar as in IPost group. S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and

  12. Fluorescence analysis of the Hansenula polymorpha peroxisomal targeting signal-1 receptor, Pex5p

    NARCIS (Netherlands)

    Boteva, R.; Koek, A.; Visser, N.V.; Visser, A.J.W.G.; Krieger, E.; Zlateva, T.; Veenhuis, M.; Klei, van der I.

    2003-01-01

    Correct sorting of newly synthesized peroxisomal matrix proteins is dependent on a peroxisomal targeting signal (PTS). So far two PTSs are known. PTS1 consists of a tripeptide that is located at the extreme C terminus of matrix proteins and is specifically recognized by the PTS1-receptor Pex5p. We

  13. Targeting the SphK1/S1P/S1PR1 Axis That Links Obesity, Chronic Inflammation, and Breast Cancer Metastasis.

    Science.gov (United States)

    Nagahashi, Masayuki; Yamada, Akimitsu; Katsuta, Eriko; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P; Hait, Nitai C; Allegood, Jeremy C; Tsuchida, Junko; Yuza, Kizuki; Nakajima, Masato; Abe, Manabu; Sakimura, Kenji; Milstien, Sheldon; Wakai, Toshifumi; Spiegel, Sarah; Takabe, Kazuaki

    2018-04-01

    Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here, we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), which mediates cancer pathogenesis. A high-fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors. Targeting the SphK1/S1P/S1PR1 axis with FTY720/fingolimod attenuated key proinflammatory cytokines, macrophage infiltration, and tumor progression induced by obesity. S1P produced in the lung premetastatic niche by tumor-induced SphK1 increased macrophage recruitment into the lung and induced IL6 and signaling pathways important for lung metastatic colonization. Conversely, FTY720 suppressed IL6, macrophage infiltration, and S1P-mediated signaling pathways in the lung induced by a high-fat diet, and it dramatically reduced formation of metastatic foci. In tumor-bearing mice, FTY720 similarly reduced obesity-related inflammation, S1P signaling, and pulmonary metastasis, thereby prolonging survival. Taken together, our results establish a critical role for circulating S1P produced by tumors and the SphK1/S1P/S1PR1 axis in obesity-related inflammation, formation of lung metastatic niches, and breast cancer metastasis, with potential implications for prevention and treatment. Significance: These findings offer a preclinical proof of concept that signaling by a sphingolipid may be an effective target to prevent obesity-related breast cancer metastasis. Cancer Res; 78(7); 1713-25. ©2018 AACR . ©2018 American Association for Cancer Research.

  14. LS1 Report: PS Booster prepares for beam

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    With Linac2 already up and running, the countdown to beam in the LHC has begun! The next in line is the PS Booster, which will close up shop to engineers early next week. The injector will be handed over to the Operations Group who are tasked with getting it ready for active duty.   Taken as we approach the end of LS1 activities, this image shows where protons will soon be injected from Linac2 into the four PS Booster rings. Over the coming two months, the Operations Group will be putting the Booster's new elements through their paces. "Because of the wide range of upgrades and repairs carried out in the Booster, we have a very full schedule of tests planned for the machine," says Bettina Mikulec, PS Booster Engineer in Charge. "We will begin with cold checks; these are a wide range of tests carried out without beam, including system tests with power on/off and with varying settings, as well as verification of the controls system and timings." Amon...

  15. Algorithm 426 : Merge sort algorithm [M1

    NARCIS (Netherlands)

    Bron, C.

    1972-01-01

    Sorting by means of a two-way merge has a reputation of requiring a clerically complicated and cumbersome program. This ALGOL 60 procedure demonstrates that, using recursion, an elegant and efficient algorithm can be designed, the correctness of which is easily proved [2]. Sorting n objects gives

  16. Mice with Sort1 deficiency display normal cognition but elevated anxiety-like behavior.

    Science.gov (United States)

    Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Luo, Hai-Yun; Bobrovskaya, Larisa; Zhou, Xin-Fu

    2016-07-01

    Exposure to stressful life events plays a central role in the development of mood disorders in vulnerable individuals. However, the mechanisms that link mood disorders to stress are poorly understood. Brain-derived neurotrophic factor (BDNF) has long been implicated in positive regulation of depression and anxiety, while its precursor (proBDNF) recently showed an opposing effect on such mental illnesses. P75(NTR) and sortilin are co-receptors of proBDNF, however, the role of these receptors in mood regulation is not established. Here, we aimed to investigate the role of sortilin in regulating mood-related behaviors and its role in the proBDNF-mediated mood abnormality in mice. We found that sortilin was up-regulated in neocortex (by 78.3%) and hippocampus (by 111%) of chronically stressed mice as assessed by western blot analysis. These changes were associated with decreased mobility in the open field test and increased depression-like behavior in the forced swimming test. We also found that sortilin deficiency in mice resulted in hyperlocomotion in the open field test and increased anxiety-like behavior in both the open field and elevated plus maze tests. No depression-like behavior in the forced swimming test and no deficit in spatial cognition in the Morris water maze test were found in the Sort1-deficient mice. Moreover, the intracellular and extracellular levels of mature BDNF and proBDNF were not changed when sortilin was absent in vivo and in vitro. Finally, we found that both WT and Sort1-deficient mice injected with proBDNF in lateral ventricle displayed increased depression-like behavior in the forced swimming test but not anxiety-like behaviors in the open field and elevated plus maze tests. The present study suggests that sortilin functions as a negative regulator of mood performance and can be a therapeutic target for the treatment of mental illness. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  17. Binar Sort: A Linear Generalized Sorting Algorithm

    OpenAIRE

    Gilreath, William F.

    2008-01-01

    Sorting is a common and ubiquitous activity for computers. It is not surprising that there exist a plethora of sorting algorithms. For all the sorting algorithms, it is an accepted performance limit that sorting algorithms are linearithmic or O(N lg N). The linearithmic lower bound in performance stems from the fact that the sorting algorithms use the ordering property of the data. The sorting algorithm uses comparison by the ordering property to arrange the data elements from an initial perm...

  18. N-hexanoyl-L-homoserine lactone-degrading Pseudomonas aeruginosa PsDAHP1 protects zebrafish against Vibrio parahaemolyticus infection.

    Science.gov (United States)

    Vinoj, Gopalakrishnan; Jayakumar, Rengarajan; Chen, Jiann-Chu; Withyachumnarnkul, Boonsirm; Shanthi, Sathappan; Vaseeharan, Baskaralingam

    2015-01-01

    Four strains of N-hexanoyl-L-homoserine lactone (AHL)-degrading Pseudomonas spp., named PsDAHP1, PsDAHP2, PsDAHP3, and PsDAHP4 were isolated and identified from the intestine of Fenneropenaeus indicus. PsDAHP1 showed the highest AHL-degrading activity among the four isolates. PsDAHP1 inhibited biofilm-forming exopolysaccharide and altered cell surface hydrophobicity of virulent green fluorescent protein (GFP)-tagged Vibrio parahaemolyticus DAHV2 (GFP-VpDAHV2). Oral administration of PsDAHP1 significantly reduced zebrafish mortality caused by GFP-VpDAHV2 challenge, and inhibited colonisation of GFP-VpDAHV2 in the gills and intestine of zebrafish as evidence by confocal laser scanning microscope and selective plating. Furthermore, zebrafish receiving PsDAHP1-containing feed had increased phagocytic cells of its leucocytes, increased serum activities of superoxide dismutase and lysozyme. The results suggest that Pseudomonas aeruginosa PsDAHP1 could protect zebrafish from V. parahaemolyticus infection by inhibiting biofilm formation and enhancing defence mechanisms of the fish. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. LazySorted: A Lazily, Partially Sorted Python List

    Directory of Open Access Journals (Sweden)

    Naftali Harris

    2015-06-01

    Full Text Available LazySorted is a Python C extension implementing a partially and lazily sorted list data structure. It solves a common problem faced by programmers, in which they need just part of a sorted list, like its middle element (the median, but sort the entire list to get it. LazySorted presents them with the abstraction that they are working with a fully sorted list, while actually only sorting the list partially with quicksort partitions to return the requested sub-elements. This enables programmers to use naive "sort first" algorithms but nonetheless attain linear run-times when possible. LazySorted may serve as a drop-in replacement for the built-in sorted function in most cases, and can sometimes achieve run-times more than 7 times faster.

  20. Assignment of Alzheimer's presenilin-2 (PS-2) gene to 1q42.1 by fluorescence in situ hybridization.

    Science.gov (United States)

    Takano, T; Sahara, N; Yamanouchi, Y; Mori, H

    1997-01-17

    Presenilin-2 (PS-2) was suggested to be localized on 1q31-42 based on linkage analysis and cDNA cloning. The final identification of PS-2 as the causal gene for early-onset familial Alzheimer's disease in Voga-German pedigrees was concluded based on the point mutation found in the candidate cDNA isolated from this familial AD. We present evidence of its physical genome mapping of PS-2 on chromosome 1q42.1 by fluorescence in situ hybridization method.

  1. Disease-Causing Mutations in BEST1 Gene Are Associated with Altered Sorting of Bestrophin-1 Protein

    Science.gov (United States)

    Doumanov, Jordan A.; Zeitz, Christina; Gimenez, Paloma Dominguez; Audo, Isabelle; Krishna, Abhay; Alfano, Giovanna; Diaz, Maria Luz Bellido; Moskova-Doumanova, Veselina; Lancelot, Marie-Elise; Sahel, José-Alain; Nandrot, Emeline F.; Bhattacharya, Shomi S.

    2013-01-01

    Mutations in BEST1 gene, encoding the bestrophin-1 (Best1) protein are associated with macular dystrophies. Best1 is predominantly expressed in the retinal pigment epithelium (RPE), and is inserted in its basolateral membrane. We investigated the cellular localization in polarized MDCKII cells of disease-associated Best1 mutant proteins to study specific sorting motifs of Best1. Real-time PCR and western blots for endogenous expression of BEST1 in MDCK cells were performed. Best1 mutant constructs were generated using site-directed mutagenesis and transfected in MDCK cells. For protein sorting, confocal microscopy studies, biotinylation assays and statistical methods for quantification of mislocalization were used. Analysis of endogenous expression of BEST1 in MDCK cells revealed the presence of BEST1 transcript but no protein. Confocal microscopy and quantitative analyses indicate that transfected normal human Best1 displays a basolateral localization in MDCK cells, while cell sorting of several Best1 mutants (Y85H, Q96R, L100R, Y227N, Y227E) was altered. In contrast to constitutively active Y227E, constitutively inactive Y227F Best1 mutant localized basolaterally similar to the normal Best1 protein. Our data suggest that at least three basolateral sorting motifs might be implicated in proper Best1 basolateral localization. In addition, non-phosphorylated tyrosine 227 could play a role for basolateral delivery. PMID:23880862

  2. A 1.375-approximation algorithm for sorting by transpositions.

    Science.gov (United States)

    Elias, Isaac; Hartman, Tzvika

    2006-01-01

    Sorting permutations by transpositions is an important problem in genome rearrangements. A transposition is a rearrangement operation in which a segment is cut out of the permutation and pasted in a different location. The complexity of this problem is still open and it has been a 10-year-old open problem to improve the best known 1.5-approximation algorithm. In this paper, we provide a 1.375-approximation algorithm for sorting by transpositions. The algorithm is based on a new upper bound on the diameter of 3-permutations. In addition, we present some new results regarding the transposition diameter: we improve the lower bound for the transposition diameter of the symmetric group and determine the exact transposition diameter of simple permutations.

  3. The PrPS4 type structure and a filled variant: the compounds TbPS4 and LiEuPS4

    International Nuclear Information System (INIS)

    Joergens, S.; Alili, L.; Mewis, A.

    2005-01-01

    Colourless single crystals of TbPS 4 (a = 10.696(2), c = 19.053(4) Aa) were obtained by reaction of the elements (750 C; 30 h). The compound crystallizes with the PrPS 4 type structure (I4 1 /acd; Z = 16). The structure consists of isolated PS 4 tetrahedra each surrounded by four Tb 3+ cations. Both crystallographically different Tb 3+ cations are coordinated by eight sulfur atoms which are part of four PS 4 tetrahedra. Orange single crystals of LiEuPS 4 (a = 11.498(2), c = 19.882(4) Aa) were prepared by reaction of Eu and P with Li 2 S 4 (700 C; 20 h). The crystal structure corresponds to the PrPS 4 type, in which tubes running along [001] are occupied by Li atoms, which are surrounded by four S atoms in strongly distorted tetrahedra. LiS 4 and PS 4 tetrahedra are connected via common edges into alternating chains. (orig.)

  4. Characterization of in vivo MRI detectable thalamic amyloid plaques from APP/PS1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Dhenain, M. [URA CEA CNRS 2210, I2BM, SHFJ, 4 Place du General Leclerc, 91401 Orsay Cedex (France); Dhenain, M.; El Tannir El Tayara, N.; Wu, T.D.; Volk, A.; Quintana, C. [U759 INSERM, Centre Universitaire, Laboratoire 112, 91405 Orsay Cedex (France); Dhenain, M.; El Tannir El Tayara, N.; Wu, T.D.; Volk, A.; Quintana, C. [Institut Curie, Centre Universitaire, Laboratoire 112, 91405 Orsay Cedex (France); Guegan, M.; Delatour, B. [Instituto de Microelectronica de Madrid-CSIC, 8, Isaac Newton, 28760 Tres Cantos, Madrid (Spain)

    2009-07-01

    Amyloid deposits are one of the hallmarks of Alzheimer's disease. Recent studies, in transgenic mice modeling Alzheimer's disease showed that, using in vivo, contrast agent-free, MRI, thalamic amyloid plaques are more easily detected than other plaques of the brain. Our study evaluated the characteristics of these thalamic plaques in a large population of APP/PS1, PS1 and C57BL/6 mice. Thalamic spots were detected in all mice but with different frequency and magnitude. Hence, the prevalence and size of the lesions were higher in APP/PS1 mice. However, even in APP/PS1 mice, thalamic spots did not occur in all the old animals. In APP/PS1 mice, spots detection was related to high iron and calcium load within amyloid plaques and thus reflects the ability of such plaque to capture large amounts of minerals. Interestingly, calcium and iron was also detected in extra-thalamic plaques but with a lower intensity. Hypointense lesions in the thalamus were not associated with the iron load in the tissue surrounding the plaques, nor with micro-hemorrhages, inflammation, or a neuro-degenerative context. (authors)

  5. A discrimination model in waste plastics sorting using NIR hyperspectral imaging system.

    Science.gov (United States)

    Zheng, Yan; Bai, Jiarui; Xu, Jingna; Li, Xiayang; Zhang, Yimin

    2018-02-01

    Classification of plastics is important in the recycling industry. A plastic identification model in the near infrared spectroscopy wavelength range 1000-2500 nm is proposed for the characterization and sorting of waste plastics using acrylonitrile butadiene styrene (ABS), polystyrene (PS), polypropylene (PP), polyethylene (PE), polyethylene terephthalate (PET), and polyvinyl chloride (PVC). The model is built by the feature wavelengths of standard samples applying the principle component analysis (PCA), and the accuracy, property and cross-validation of the model were analyzed. The model just contains a simple equation, center of mass coordinates, and radial distance, with which it is easy to develop classification and sorting software. A hyperspectral imaging system (HIS) with the identification model verified its practical application by using the unknown plastics. Results showed that the identification accuracy of unknown samples is 100%. All results suggested that the discrimination model was potential to an on-line characterization and sorting platform of waste plastics based on HIS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells.

    Science.gov (United States)

    Livide, Gabriella; Patriarchi, Tommaso; Amenduni, Mariangela; Amabile, Sonia; Yasui, Dag; Calcagno, Eleonora; Lo Rizzo, Caterina; De Falco, Giulia; Ulivieri, Cristina; Ariani, Francesca; Mari, Francesca; Mencarelli, Maria Antonietta; Hell, Johannes Wilhelm; Renieri, Alessandra; Meloni, Ilaria

    2015-02-01

    Rett syndrome is a monogenic disease due to de novo mutations in either MECP2 or CDKL5 genes. In spite of their involvement in the same disease, a functional interaction between the two genes has not been proven. MeCP2 is a transcriptional regulator; CDKL5 encodes for a kinase protein that might be involved in the regulation of gene expression. Therefore, we hypothesized that mutations affecting the two genes may lead to similar phenotypes by dysregulating the expression of common genes. To test this hypothesis we used induced pluripotent stem (iPS) cells derived from fibroblasts of one Rett patient with a MECP2 mutation (p.Arg306Cys) and two patients with mutations in CDKL5 (p.Gln347Ter and p.Thr288Ile). Expression profiling was performed in CDKL5-mutated cells and genes of interest were confirmed by real-time RT-PCR in both CDKL5- and MECP2-mutated cells. The only major change in gene expression common to MECP2- and CDKL5-mutated cells was for GRID1, encoding for glutamate D1 receptor (GluD1), a member of the δ-family of ionotropic glutamate receptors. GluD1 does not form AMPA or NMDA glutamate receptors. It acts like an adhesion molecule by linking the postsynaptic and presynaptic compartments, preferentially inducing the inhibitory presynaptic differentiation of cortical neurons. Our results demonstrate that GRID1 expression is downregulated in both MECP2- and CDKL5-mutated iPS cells and upregulated in neuronal precursors and mature neurons. These data provide novel insights into disease pathophysiology and identify possible new targets for therapeutic treatment of Rett syndrome.

  7. The CD3 gamma leucine-based receptor-sorting motif is required for efficient ligand-mediated TCR down-regulation

    DEFF Research Database (Denmark)

    von Essen, Marina; Menné, Charlotte; Nielsen, Bodil L

    2002-01-01

    . The other pathway is dependent on protein kinase C (PKC)-mediated activation of the CD3 gamma di-leucine-based receptor-sorting motif. Previous studies have failed to demonstrate a connection between ligand- and PKC-induced TCR down-regulation. Thus, although an apparent paradox, the dogma has been...... that ligand- and PKC-induced TCR down-regulations are not interrelated. By analyses of a newly developed CD3 gamma-negative T cell variant, freshly isolated and PHA-activated PBMC, and a mouse T cell line, we challenged this dogma and demonstrate in this work that PKC activation and the CD3 gamma di...

  8. Molecular determinants of the interaction between Doa1 and Hse1 involved in endosomal sorting.

    Science.gov (United States)

    Han, Seungsu; Shin, Donghyuk; Choi, Hoon; Lee, Sangho

    2014-03-28

    Yeast Doa1/Ufd3 is an adaptor protein for Cdc48 (p97 in mammal), an AAA type ATPase associated with endoplasmic reticulum-associated protein degradation pathway and endosomal sorting into multivesicular bodies. Doa1 functions in the endosomal sorting by its association with Hse1, a component of endosomal sorting complex required for transport (ESCRT) system. The association of Doa1 with Hse1 was previously reported to be mediated between PFU domain of Doa1 and SH3 of Hse1. However, it remains unclear which residues are specifically involved in the interaction. Here we report that Doa1/PFU interacts with Hse1/SH3 with a moderate affinity of 5 μM. Asn-438 of Doa1/PFU and Trp-254 of Hse1/SH3 are found to be critical in the interaction while Phe-434, implicated in ubiquitin binding via a hydrophobic interaction, is not. Small-angle X-ray scattering measurements combined with molecular docking and biochemical analysis yield the solution structure of the Doa1/PFU:Hse1/SH3 complex. Taken together, our results suggest that hydrogen bonding is a major determinant in the interaction of Doa1/PFU with Hse1/SH3. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors

    Directory of Open Access Journals (Sweden)

    Wang Cheng-Li

    2012-08-01

    Full Text Available Abstract Background The fungus of Ganoderma is a traditional medicine in Asia with a variety of pharmacological functions including anti-cancer activities. We have purified an extracellular heteropolysaccharide fraction, PS-F2, from the submerged mycelia culture of G. formosanum and shown that PS-F2 exhibits immunostimulatory activities. In this study, we investigated the molecular mechanisms of immunostimulation by PS-F2. Results PS-F2-stimulated TNF-α production in macrophages was significantly reduced in the presence of blocking antibodies for Dectin-1 and complement receptor 3 (CR3, laminarin, or piceatannol (a spleen tyrosine kinase inhibitor, suggesting that PS-F2 recognition by macrophages is mediated by Dectin-1 and CR3 receptors. In addition, the stimulatory effect of PS-F2 was attenuated in the bone marrow-derived macrophages from C3H/HeJ mice which lack functional Toll-like receptor 4 (TLR4. PS-F2 stimulation triggered the phosphorylation of mitogen-activated protein kinases JNK, p38, and ERK, as well as the nuclear translocation of NF-κB, which all played essential roles in activating TNF-α expression. Conclusions Our results indicate that the extracellular polysaccharides produced by G. formosanum stimulate macrophages via the engagement of multiple pattern-recognition receptors including Dectin-1, CR3 and TLR4, resulting in the activation of Syk, JNK, p38, ERK, and NK-κB and the production of TNF-α.

  10. Omega-conotoxin- and nifedipine-insensitive voltage-operated calcium channels mediate K(+)-induced release of pro-thyrotropin-releasing hormone-connecting peptides Ps4 and Ps5 from perifused rat hypothalamic slices.

    Science.gov (United States)

    Valentijn, K; Tranchand Bunel, D; Vaudry, H

    1992-07-01

    The rat thyrotropin-releasing hormone (TRH) precursor (prepro-TRH) contains five copies of the TRH progenitor sequence linked together by intervening sequences. Recently, we have shown that the connecting peptides prepro-TRH-(160-169) (Ps4) and prepro-TRH-(178-199) (Ps5) are released from rat hypothalamic neurones in response to elevated potassium concentrations, in a calcium-dependent manner. In the present study, the role of voltage-operated calcium channels in potassium-induced release of Ps4 and Ps5 was investigated, using a perifusion system for rat hypothalamic slices. The release of Ps4 and Ps5 stimulated by potassium (70 mM) was blocked by the inorganic ions Co2+ (2.6 mM) and Ni2+ (5 mM). In contrast, the stimulatory effect of KCl was insensitive to Cd2+ (100 microM). The dihydropyridine antagonist nifedipine (10 microM) had no effect on K(+)-evoked release of Ps4 and Ps5. Furthermore, the response to KCl was not affected by nifedipine (10 microM) in combination with diltiazem (1 microM), a benzothiazepine which increases the affinity of dihydropyridine antagonists for their receptor. The dihydropyridine agonist BAY K 8644, at concentrations as high as 1 mM, did not stimulate the basal secretion of Ps4 and Ps5. In addition, BAY K 8644 had no potentiating effect on K(+)-induced release of Ps4 and Ps5. The marine cone snail toxin omega-conotoxin, a blocker of both L- and N-type calcium channels had no effect on the release of Ps4 and Ps5 stimulated by potassium. Similarly, the omega-conopeptide SNX-111, a selective blocker of N-type calcium channels, did not inhibit the stimulatory effect of potassium. The release of Ps4 and Ps5 evoked by high K+ was insensitive to the non-selective calcium channel blocker verapamil (20 microM). Amiloride (1 microM), a putative blocker of T-type calcium channels, did not affect KCl-induced secretion of the two connecting peptides. Taken together, these results indicate that two connecting peptides derived from the pro-TRH, Ps

  11. A Myb transcription factor of Phytophthora sojae, regulated by MAP kinase PsSAK1, is required for zoospore development.

    Directory of Open Access Journals (Sweden)

    Meng Zhang

    Full Text Available PsSAK1, a mitogen-activated protein (MAP kinase from Phytophthora sojae, plays an important role in host infection and zoospore viability. However, the downstream mechanism of PsSAK1 remains unclear. In this study, the 3'-tag digital gene expression (DGE profiling method was applied to sequence the global transcriptional sequence of PsSAK1-silenced mutants during the cysts stage and 1.5 h after inoculation onto susceptible soybean leaf tissues. Compared with the gene expression levels of the recipient P. sojae strain, several candidates of Myb family were differentially expressed (up or down in response to the loss of PsSAK1, including of a R2R3-type Myb transcription factor, PsMYB1. qRT-PCR indicated that the transcriptional level of PsMYB1 decreased due to PsSAK1 silencing. The transcriptional level of PsMYB1 increased during sporulating hyphae, in germinated cysts, and early infection. Silencing of PsMYB1 results in three phenotypes: a no cleavage of the cytoplasm into uninucleate zoospores or release of normal zoospores, b direct germination of sporangia, and c afunction in zoospore-mediated plant infection. Our data indicate that the PsMYB1 transcription factor functions downstream of MAP kinase PsSAK1 and is required for zoospore development of P. sojae.

  12. The 1.4 GeV PS Booster in its tunnel.

    CERN Multimedia

    Patrice Loïez

    2002-01-01

    The PS Improvement Programme, launched as early as 1964, had a "Booster" as the key element in the quest for higher beam intensity and density. These were limited in the PS at injection of the 50 MeV proton beam from the linac by the incoherent (Laslett-) Q-shift. Boosting the linac beam to 800 MeV would raise the PS intensity limit by an order of magnitude, from 1E12 protons per pulse to 1E13. The main motivation was the supply of intense beams to the ISR. Soon, the Booster proved to be crucial for the neutral current experiment. A unique feature of the Booster are its 4 superposed rings. Its lattice is also unusual: between its 32 bending magnets, every second straight section contains a quadrupole triplet (F,D,F), while the alternate ones are drift spaces (mostly filled with essential components like septa, kickers, RF-cavities, etc.). In each picture we see one of the 16 periods. Following the direction of the beam from right to left: a bending magnet (green); an empty straight section; a bending magnet; ...

  13. Sorting Out Sorts

    OpenAIRE

    Jonathan B. Berk

    1998-01-01

    In this paper we analyze the theoretical implications of sorting data into groups and then running asset pricing tests within each group. We show that the way this procedure is implemented introduces a severe bias in favor of rejecting the model under consideration. By simply picking enough groups to sort into even the true asset pricing model can be shown to have no explanatory power within each group.

  14. Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Bing Han

    2017-03-01

    Full Text Available Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57 mice caused by chronic unpredictable mild stress (CUMS, we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

  15. Virus-induced plasma membrane aquaporin PsPIP2;1 silencing inhibits plant water transport of Pisum sativum.

    Science.gov (United States)

    Song, Juanjuan; Ye, Guoliang; Qian, Zhengjiang; Ye, Qing

    2016-12-01

    Aquaporins (AQPs) are known to facilitate water transport across cell membranes, but the role of a single AQP in regulating plant water transport, particularly in plants other than Arabidopsis remains largely unexplored. In the present study, a virus-induced gene silencing (VIGS) technique was employed to suppress the expression of a specific plasma membrane aquaporin PsPIP2;1 of Pea plants (Pisum sativum), and subsequent effects of the gene suppression on root hydraulic conductivity (Lp r ), leaf hydraulic conductivity (K leaf ), root cell hydraulic conductivity (Lp rc ), and leaf cell hydraulic conductivity (Lp lc ) were investigated, using hydroponically grown Pea plants. Compared with control plants, VIGS-PsPIP2;1 plants displayed a significant suppression of PsPIP2;1 in both roots and leaves, while the expression of other four PIP isoforms (PsPIP1;1, PsPIP1;2, PsPIP2;2, and PsPIP2;3) that were simultaneously monitored were not altered. As a consequence, significant declines in water transport of VIGS-PsPIP2;1 plants were observed at both organ and cell levels, i.e., as compared to control plants, Lp r and K leaf were reduced by 29 %, and Lp rc and Lp lc were reduced by 20 and 29 %, respectively. Our results demonstrate that PsPIP2;1 alone contributes substantially to root and leaf water transport in Pea plants, and highlight VIGS a useful tool for investigating the role of a single AQP in regulating plant water transport.

  16. Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

    Science.gov (United States)

    Yang, Weiwei; Li, Qinghua; Pan, Zhifang

    2014-01-01

    Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

  17. The Presenilin-1 ΔE9 Mutation Results in Reduced γ-Secretase Activity, but Not Total Loss of PS1 Function, in Isogenic Human Stem Cells

    Directory of Open Access Journals (Sweden)

    Grace Woodruff

    2013-11-01

    Full Text Available Presenilin 1 (PS1 is the catalytic core of γ-secretase, which cleaves type 1 transmembrane proteins, including the amyloid precursor protein (APP. PS1 also has γ-secretase-independent functions, and dominant PS1 missense mutations are the most common cause of familial Alzheimer’s disease (FAD. Whether PS1 FAD mutations are gain- or loss-of-function remains controversial, primarily because most studies have relied on overexpression in mouse and/or nonneuronal systems. We used isogenic euploid human induced pluripotent stem cell lines to generate and study an allelic series of PS1 mutations, including heterozygous null mutations and homozygous and heterozygous FAD PS1 mutations. Rigorous analysis of this allelic series in differentiated, purified neurons allowed us to resolve this controversy and to conclude that FAD PS1 mutations, expressed at normal levels in the appropriate cell type, impair γ-secretase activity but do not disrupt γ-secretase-independent functions of PS1. Thus, FAD PS1 mutations do not act as simple loss of PS1 function but instead dominantly gain an activity toxic to some, but not all, PS1 functions.

  18. Synthesis and Characterization of the Rubidium Thiophosphate Rb 6 (PS 5 )(P 2 S 10 ) and the Rubidium Silver Thiophosphates Rb 2 AgPS 4 , RbAg 5 (PS 4 ) 2 and Rb 3 Ag 9 (PS 4 ) 4

    KAUST Repository

    Alahmary, Fatimah S.; Davaasuren, Bambar; Khanderi, Jayaprakash; Rothenberger, Alexander

    2016-01-01

    The metal thiophosphates Rb2AgPS4 (2), RbAg5(PS4)2 (3), and Rb3Ag9(PS4)4 (4) were synthesized by stoichiometric reactions, whereas Rb6(PS5)(P2S10) (1) was prepared with excess amount of sulfur. The compounds crystallize as follows: 1 monoclinic, P21

  19. Crystal structure of the mixed-metal thiophosphate Nb1.18V0.82PS10

    Directory of Open Access Journals (Sweden)

    Joobin Sun

    2015-03-01

    Full Text Available The mixed-metal thiophosphate, Nb1.18V0.82PS10 (niobium vanadium phosphorus decasulfide, has been prepared though solid state reactions using an alkali-metal halide flux. The title compound is isostructural with two-dimensional Nb2PS10. [M2S12] (M = Nb or V dimers built up from two bicapped trigonal prisms and tetrahedral [PS4] units share sulfur atoms to construct 1∞[M2PS10] chains along the a axis. These chains are linked through the disulfide bonds between [PS4] units in adjacent chains to form layers parallel to the ab plane. These layers then stack on top of each other to complete the three-dimensional structure with van der Waals gaps. The M sites are occupied by 59% of Nb and 41% of V and the average M—S and M—M distances in the title compound are in between those of V2PS10 and Nb2PS10. The classical charge balance of the title compound can be represented by [(Nb/V4+]2[P5+][S2−]3[S−]7.

  20. Verification of counting sort and radix sort

    NARCIS (Netherlands)

    C.P.T. de Gouw (Stijn); F.S. de Boer (Frank); J.C. Rot (Jurriaan)

    2016-01-01

    textabstractSorting is an important algorithmic task used in many applications. Two main aspects of sorting algorithms which have been studied extensively are complexity and correctness. [Foley and Hoare, 1971] published the first formal correctness proof of a sorting algorithm (Quicksort). While

  1. Ready, steady, SORT!

    CERN Document Server

    Laëtitia Pedroso

    2010-01-01

    The selective or ecological sorting of waste is already second nature to many of us and concerns us all. As the GS Department's new awareness-raising campaign reminds us, everything we do to sort waste contributes to preserving the environment.    Placemats printed on recycled paper using vegetable-based ink will soon be distributed in Restaurant No.1.   Environmental protection is never far from the headlines, and CERN has a responsibility to ensure that the 3000 tonnes and more of waste it produces every year are correctly and selectively sorted. Materials can be given a second life through recycling and re-use, thereby avoiding pollution from landfill sites and incineration plants and saving on processing costs. The GS Department is launching a new poster campaign designed to raise awareness of the importance of waste sorting and recycling. "After conducting a survey to find out whether members of the personnel were prepared to make an effort to sort a...

  2. Striatal Dopamine D2/D3 Receptor Availability Is Associated with Executive Function in Healthy Controls but Not Methamphetamine Users.

    Directory of Open Access Journals (Sweden)

    Michael E Ballard

    Full Text Available Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence.Methamphetamine users and non-user controls (n = 18 per group completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride.The methamphetamine users displayed significantly lower striatal D2/D3 receptor availability on average than controls after controlling for age and education (p = 0.008, but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622. The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D2/D3 receptor availability among controls (r = -0.588, p = 0.010, but not methamphetamine users (r = 0.281, p = 0.258, and the group-wise interaction was significant (p = 0.030.These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls.

  3. Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    mice was not due to a more extensive cholinergic degeneration since the reduction in choline acetyltransferase activity was similar following SAP treatment in APP/PS1 mice and Wt. Interestingly, plaque load was significantly increased in SAP treated APP/PS1 mice relative to sham lesioned APP/PS1 mice....... Additionally, APP/PS1 mice treated with SAP showed a tendency towards an increased level of soluble and insoluble Aß1-40 and Aß1-42 measured in brain tissue homogenate. Our results suggest that the combination of cholinergic degeneration and Aß overexpression in the APP/PS1 mouse model results in cognitive...... decline and accelerated plaque burden. SAP treated APP/PS1 mice might thus constitute an improved model of Alzheimer's disease-like neuropathology and cognitive deficits compared to the conventional APP/PS1 model without selective removal of basal forebrain cholinergic neurons....

  4. Activity-Dependent Ubiquitination of GluA1 Mediates a Distinct AMPAR Endocytosis and Sorting Pathway

    Science.gov (United States)

    Schwarz, Lindsay A.; Hall, Benjamin J.; Patrick, Gentry N.

    2010-01-01

    The accurate trafficking of AMPA receptors (AMPARs) to and from the synapse is a critical component of learning and memory in the brain, while dysfunction of AMPAR trafficking is hypothesized to be an underlying mechanism of Alzheimer’s disease. Previous work has shown that ubiquitination of integral membrane proteins is a common post-translational modification used to mediate endocytosis and endocytic sorting of surface proteins in eukaryotic cells. Here we report that mammalian AMPARs become ubiquitinated in response to their activation. Using a mutant of GluA1 that is unable to be ubiquitinated at lysines on its carboxy-terminus, we demonstrate that ubiquitination is required for internalization of surface AMPARs and their trafficking to the lysosome in response to the AMPAR agonist AMPA, but not for internalization of AMPARs in response to the NMDA receptor (NMDAR) agonist NMDA. Through over-expression or RNAi-mediated knockdown, we identify that a specific E3 ligase, Nedd4-1, is necessary for this process. Finally, we show that ubiquitination of GluA1 by Nedd4-1 becomes more prevalent as neurons mature. Together, these data show that ubiquitination of GluA1-containing AMPARs by Nedd4-1 mediates their endocytosis and trafficking to the lysosome. Furthermore, these results provide insight into how hippocampal neurons regulate AMPAR trafficking and degradation with high specificity in response to differing neuronal signaling cues, and suggest that changes to this pathway may occur as neurons mature. PMID:21148011

  5. Lack of tau proteins rescues neuronal cell death and decreases amyloidogenic processing of APP in APP/PS1 mice.

    Science.gov (United States)

    Leroy, Karelle; Ando, Kunie; Laporte, Vincent; Dedecker, Robert; Suain, Valérie; Authelet, Michèle; Héraud, Céline; Pierrot, Nathalie; Yilmaz, Zehra; Octave, Jean-Noël; Brion, Jean-Pierre

    2012-12-01

    Lack of tau expression has been reported to protect against excitotoxicity and to prevent memory deficits in mice expressing mutant amyloid precursor protein (APP) identified in familial Alzheimer disease. In APP mice, mutant presenilin 1 (PS1) enhances generation of Aβ42 and inhibits cell survival pathways. It is unknown whether the deficient phenotype induced by concomitant expression of mutant PS1 is rescued by absence of tau. In this study, we have analyzed the effect of tau deletion in mice expressing mutant APP and PS1. Although APP/PS1/tau(+/+) mice had a reduced survival, developed spatial memory deficits at 6 months and motor impairments at 12 months, these deficits were rescued in APP/PS1/tau(-/-) mice. Neuronal loss and synaptic loss in APP/PS1/tau(+/+) mice were rescued in the APP/PS1/tau(-/-) mice. The amyloid plaque burden was decreased by roughly 50% in the cortex and the spinal cord of the APP/PS1/tau(-/-) mice. The levels of soluble and insoluble Aβ40 and Aβ42, and the Aβ42/Aβ40 ratio were reduced in APP/PS1/tau(-/-) mice. Levels of phosphorylated APP, of β-C-terminal fragments (CTFs), and of β-secretase 1 (BACE1) were also reduced, suggesting that β-secretase cleavage of APP was reduced in APP/PS1/tau(-/-) mice. Our results indicate that tau deletion had a protective effect against amyloid induced toxicity even in the presence of mutant PS1 and reduced the production of Aβ. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. The PS1 hairpin of Mcm3 is essential for viability and for DNA unwinding in vitro.

    Directory of Open Access Journals (Sweden)

    Simon K W Lam

    Full Text Available The pre-sensor 1 (PS1 hairpin is found in ring-shaped helicases of the AAA+ family (ATPases associated with a variety of cellular activities of proteins and is implicated in DNA translocation during DNA unwinding of archaeal mini-chromosome maintenance (MCM and superfamily 3 viral replicative helicases. To determine whether the PS1 hairpin is required for the function of the eukaryotic replicative helicase, Mcm2-7 (also comprised of AAA+ proteins, we mutated the conserved lysine residue in the putative PS1 hairpin motif in each of the Saccharomyces cerevisiae Mcm2-7 subunits to alanine. Interestingly, only the PS1 hairpin of Mcm3 was essential for viability. While mutation of the PS1 hairpin in the remaining MCM subunits resulted in minimal phenotypes, with the exception of Mcm7 which showed slow growth under all conditions examined, the viable alleles were synthetic lethal with each other. Reconstituted Mcm2-7 containing Mcm3 with the PS1 mutation (Mcm3(K499A had severely decreased helicase activity. The lack of helicase activity provides a probable explanation for the inviability of the mcm3(K499A strain. The ATPase activity of Mcm2-7(3K499A was similar to the wild type complex, but its interaction with single-stranded DNA in an electrophoretic mobility shift assay and its associations in cells were subtly altered. Together, these findings indicate that the PS1 hairpins in the Mcm2-7 subunits have important and distinct functions, most evident by the essential nature of the Mcm3 PS1 hairpin in DNA unwinding.

  7. Modelling of Ne-like copper X-ray laser driven by 1.2 ps short pulse and 280 ps background pulse configuration

    International Nuclear Information System (INIS)

    Demir, A.; Kenar, N.; Goktas, H.; Tallents, G.J.

    2004-01-01

    Detailed simulations of Ne-like Cu x-ray laser are undertaken using the EHYBRID code. The atomic physics data are obtained using the Cowan code. The optimization calculations are performed in terms of the intensity of background and the time separation between the background and the short pulse. The optimum value is obtained for the conditions of a Nd:glass laser with 1.2 ps pulse at 4.4 x 10 15 W cm -2 irradiance pumping a plasma pre-formed by a 280 ps duration pulse at 5.4 x 10 12 W cm -2 with peak-to-peak pulse separation set at 300 ps. X-ray resonance lines between 6 A and 15 A emitted from copper plasmas have been simulated. Free-free and free-bound emission from the Si-, Al-, Mg-, Na-, Ne- and F-like ions is calculated in the simulation. (author)

  8. Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation.

    Science.gov (United States)

    Rocha, Sandra M; Saraiva, Tatiana; Cristóvão, Ana C; Ferreira, Raquel; Santos, Tiago; Esteves, Marta; Saraiva, Cláudia; Je, Goun; Cortes, Luísa; Valero, Jorge; Alves, Gilberto; Klibanov, Alexander; Kim, Yoon-Seong; Bernardino, Liliana

    2016-06-04

    Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcγ or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase-positive neurons in the substantia nigra (SN) of mice. We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia

  9. Theoretical considerations regarding the existence of PsO and PsS+

    International Nuclear Information System (INIS)

    Farazdel, A.; Cade, P.E.

    1977-01-01

    It has been proposed from experimental studies and in analogy with hydrogen compounds that PsO may be an entity of some importance, or an intermediate, in the reaction of positronium, Ps, with aqueous oxyacid species such as H 2 PO 4 - , HSO 4 - , ClO 4 - , and NO 3 - . This communication explores the stability of PsO and PsS, or [O - :e + ] and [S - :e + ], respectively, relative to dissociation into Ps and O( 3 P) or S( 3 P) on the basis of restricted Hartree-Fock calculations for the PsO and PsS systems and certain correlation correction arguments. A reasonable lower estimate of the dissociation energy to Y+Ps of >-0.47 eV for PsO and >0.70 eV for PsS is obtained. It is suggested that a modest correlation correction to the positron affinity (PA) of O - would very probably lead to a bound state system for PsO. (Auth.)

  10. HiPS - Hierarchical Progressive Survey Version 1.0

    Science.gov (United States)

    Fernique, Pierre; Allen, Mark; Boch, Thomas; Donaldson, Tom; Durand, Daniel; Ebisawa, Ken; Michel, Laurent; Salgado, Jesus; Stoehr, Felix; Fernique, Pierre

    2017-05-01

    This document presents HiPS, a hierarchical scheme for the description, storage and access of sky survey data. The system is based on hierarchical tiling of sky regions at finer and finer spatial resolution which facilitates a progressive view of a survey, and supports multi-resolution zooming and panning. HiPS uses the HEALPix tessellation of the sky as the basis for the scheme and is implemented as a simple file structure with a direct indexing scheme that leads to practical implementations.

  11. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  12. Physics at the AD/PS/SPS (1/4)

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    Lecture 1: The CERN injector complex and beams for non-LHC physics. The various machines and beam lines in the CERN injector complex are presented, from the linacs to the SPS. Special emphasis is given to the beam lines at the PS and SPS machines: AD, North and East Areas, nTOF and CNGS and HiRadMad as well as the ion beams. A short outlook is given to possible future upgrades and projects.

  13. Perbandingan Bubble Sort dengan Insertion Sort pada Bahasa Pemrograman C dan Fortran

    OpenAIRE

    Reina, Reina; Gautama, Josef Bernadi

    2013-01-01

    Sorting is a basic algorithm studied by students of computer science major. Sorting algorithm is the basis of other algorithms such as searching algorithm, pattern matching algorithm. Bubble sort is a popular basic sorting algorithm due to its easiness to be implemented. Besides bubble sort, there is insertion sort. It is lesspopular than bubble sort because it has more difficult algorithm. This paper discusses about process time between insertion sort and bubble sort with two kinds of data. ...

  14. Crop-associated virus reduces the rooting depth of non-crop perennial native grass more than non-crop-associated virus with known viral suppressor of RNA silencing (VSR).

    Science.gov (United States)

    Malmstrom, Carolyn M; Bigelow, Patrick; Trębicki, Piotr; Busch, Anna K; Friel, Colleen; Cole, Ellen; Abdel-Azim, Heba; Phillippo, Colin; Alexander, Helen M

    2017-09-15

    As agricultural acreage expanded and came to dominate landscapes across the world, viruses gained opportunities to move between crop and wild native plants. In the Midwestern USA, virus exchange currently occurs between widespread annual Poaceae crops and remnant native perennial prairie grasses now under consideration as bioenergy feedstocks. In this region, the common aphid species Rhopalosiphum padi L. (the bird cherry-oat aphid) transmits several virus species in the family Luteoviridae, including Barley yellow dwarf virus (BYDV-PAV, genus Luteovirus) and Cereal yellow dwarf virus (CYDV-RPV and -RPS, genus Polerovirus). The yellow dwarf virus (YDV) species in these two genera share genetic similarities in their 3'-ends, but diverge in the 5'-regions. Most notably, CYDVs encode a P0 viral suppressor of RNA silencing (VSR) absent in BYDV-PAV. Because BYDV-PAV has been reported more frequently in annual cereals and CYDVs in perennial non-crop grasses, we examine the hypothesis that the viruses' genetic differences reflect different affinities for crop and non-crop hosts. Specifically, we ask (i) whether CYDVs might persist within and affect a native non-crop grass more strongly than BYDV-PAV, on the grounds that the polerovirus VSR could better moderate the defenses of a well-defended perennial, and (ii) whether the opposite pattern of effects might occur in a less defended annual crop. Because previous work found that the VSR of CYDV-RPS possessed greater silencing suppressor efficiency than that of CYDV-RPV, we further explored (iii) whether a novel grass-associated CYDV-RPS isolate would influence a native non-crop grass more strongly than a comparable CYDV-RPV isolate. In growth chamber studies, we found support for this hypothesis: only grass-associated CYDV-RPS stunted the shoots and crowns of Panicum virgatum L. (switchgrass), a perennial native North American prairie grass, whereas crop-associated BYDV-PAV (and coinfection with BYDV-PAV and CYDV-RPS) most

  15. Determination of grafting conversion degree in PS/PS-graft-POSS/POSS hybrid nanocomposites obtained through reactive processing

    International Nuclear Information System (INIS)

    Bianchi, Otavio; Repenning, Gustavo B.; Mauler, Raquel S.; Oliveira, Ricardo V.B.; Canto, Leonardo B.

    2011-01-01

    Hybrid nanocomposites of polystyrene (PS) and polyhedral oligomeric silsesquioxanes (POSS) - PS/PS-graft-POSS/POSS - with different grafting degrees were prepared by reactive melt processing using dicumyl peroxide (DCP) as initiator in the presence or absence of styrene monomer as radical transfer agent. Gel permeation chromatography (GPC) using triple-detector and proton nuclear magnetic resonance (NMR 1 H) analyses were used together to determine the conversion degree of PS-graft-POSS as a function of the reactive processing conditions adopted. GPC was employed to evaluate the effects of grafting (PS-graft-POSS) and PS chains degradation (β scission) that occur simultaneously during processing on the variation of average molecular masses and distributions for each PS/POSS sample. PS/POSS systems processed with styrene showed higher weight average molecular weights (M w ) and lower polydispersity indexes (M w /M n ), as a result of higher grafting (PS-graft-POSS) conversion (28-40%) and lower PS chain degradation level, as compared to PS/POSS systems processed without styrene in which the degree of grafting conversion was around 25-28%. (author)

  16. Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model

    Directory of Open Access Journals (Sweden)

    Jelle Praet

    2016-01-01

    Full Text Available While no definitive cure for Alzheimer's disease exists yet, currently available treatments would benefit greatly from an earlier diagnosis. It has previously been shown that Magnetization transfer contrast (MTC imaging is able to detect amyloid β plaques in old APP/PS1 mice. In the current study we investigated if MTC is also able to visualize early amyloid β (Aβ induced pathological changes. In a cross-sectional study, a comparison was made between the MT ratio of wild type (WT and APP/PS1 mice at 2, 4, 6, 8 and 24 months of age. We observed an increased MT-ratio in the cortex of 24 month old APP/PS1 mice as compared to WT mice. However, when comparing the MT-ratio of the cortex of WT mice with the MT-ratio of the APP/PS1 mice at 2, 4, 6 or 8 months of age, no significant changes could be observed. In contrast to the cortex, we consistently observed a decreased MT-ratio in the splenium of 4, 6 and 8 month old APP/PS1 mice as compared to age-matched WT mice. Lastly, the decreased MT-ratio in the splenium of APP/PS1 mice correlated to the Aβ plaque deposition, astrogliosis and microgliosis. This MT-ratio decrease did however not correlate to the myelin content. Combined, our results suggest that MTC is able to visualize early Aβ-induced changes in the splenium but not the cortex of APP/PS1 mice.

  17. Perbandingan Bubble Sort dengan Insertion Sort pada Bahasa Pemrograman C dan Fortran

    Directory of Open Access Journals (Sweden)

    Reina Reina

    2013-12-01

    Full Text Available Sorting is a basic algorithm studied by students of computer science major. Sorting algorithm is the basis of other algorithms such as searching algorithm, pattern matching algorithm. Bubble sort is a popular basic sorting algorithm due to its easiness to be implemented. Besides bubble sort, there is insertion sort. It is lesspopular than bubble sort because it has more difficult algorithm. This paper discusses about process time between insertion sort and bubble sort with two kinds of data. First is randomized data, and the second is data of descending list. Comparison of process time has been done in two kinds of programming language that is C programming language and FORTRAN programming language. The result shows that bubble sort needs more time than insertion sort does.

  18. Interaction of the deubiquitinating enzyme Ubp2 and the e3 ligase Rsp5 is required for transporter/receptor sorting in the multivesicular body pathway.

    Directory of Open Access Journals (Sweden)

    Mandy H Y Lam

    Full Text Available Protein ubiquitination is essential for many events linked to intracellular protein trafficking. We sought to elucidate the possible involvement of the S. cerevisiae deubiquitinating enzyme Ubp2 in transporter and receptor trafficking after we (this study and others established that affinity purified Ubp2 interacts stably with the E3 ubiquitin ligase Rsp5 and the (ubiquitin associated UBA domain containing protein Rup1. UBP2 interacts genetically with RSP5, while Rup1 facilitates the tethering of Ubp2 to Rsp5 via a PPPSY motif. Using the uracil permease Fur4 as a model reporter system, we establish a role for Ubp2 in membrane protein turnover. Similar to hypomorphic rsp5 alleles, cells deleted for UBP2 exhibited a temporal stabilization of Fur4 at the plasma membrane, indicative of perturbed protein trafficking. This defect was ubiquitin dependent, as a Fur4 N-terminal ubiquitin fusion construct bypassed the block and restored sorting in the mutant. Moreover, the defect was absent in conditions where recycling was absent, implicating Ubp2 in sorting at the multivesicular body. Taken together, our data suggest a previously overlooked role for Ubp2 as a positive regulator of Rsp5-mediated membrane protein trafficking subsequent to endocytosis.

  19. Genetic evidence for involvement of neuronally expressed S1P₁ receptor in nociceptor sensitization and inflammatory pain.

    Directory of Open Access Journals (Sweden)

    Norbert Mair

    2011-02-01

    Full Text Available Sphingosine-1-phosphate (S1P is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P₁ receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P₁ receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P₁ receptor. Our data show that neuronally expressed S1P₁ receptors play a significant role in regulating nociceptor function and that S1P/S1P₁ signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation.

  20. Dopamine D2-receptor SPECT with [123I]-iodobenzamide in the diagnosis of Parkinson's syndrome

    International Nuclear Information System (INIS)

    Reiche, W.; Grundmann, M.; Huber, G.

    1995-01-01

    The purpose of this study was to determine the value of the [ 123 I]IBZM D 2 -receptor SPECT in the differential diagnosis of PS. A total of 38 patients (20 females, 18 males; age 61 ± 13.3 years), with typical extrapyramidal symptoms were investigated. Twenty suffered from idiopathic and 11 from secondary PS. Seven patients in whom a neurological disease could be excluded, served as controls. SPECT data were acquired 90 min after i.v. injection of 185-200 MBq [ 123 I]IBZM. After reconstruction with a Butterworth filter (cutoff frequency 0.5) and attenuation correction (coefficient 0.12 cm -1 ) we quantify the IBZM basal ganglia uptake as ratio to the frontal D 2 -receptor-free cortex (BG/FC). The patients with idiopathic PS (IPS) and the controls revealed high and specific IBZM uptake in the basal ganglia compared to the adjacent frontal brain tissue (IPS: BG/FC = 1,44 ± 0,10; controls: BG/FC = 1.48 ± 0.10). A significant decreased striatal IBZM uptake is found in cases with secondary PS (BG/FC = 1.25 ± 0.10, t-test compared to controls and IPS). The patient group with IPS can be subdivided into patients without L-dopatherapy (BG/FC = 1.49 ± 0.07), patients with longstanding L-dopa-therapy demonstrating significantly decreased striatal IBZM uptake (BG/FC = 1.31 ± 0.04, t-test compared to controls and other IPS), which correlates pathophysiological with a reduction of free D 2 receptors, and patients with de novo PS showing a slight increased striatal IBZM uptake (BG/FC = 1.56 ± 0.05), which represents D 2 -receptor stimulation. [ 123 I]IBZM-SPECT is a sensitive and non-invasive test for striatal D 2 -receptor density and activity which permits relatively clear discrimination between idiopathic and secondary PS and yields important information for differential therapy. (orig.) [de

  1. Design and realization of sort manipulator of crystal-angle sort machine

    Science.gov (United States)

    Wang, Ming-shun; Chen, Shu-ping; Guan, Shou-ping; Zhang, Yao-wei

    2005-12-01

    It is a current tendency of development in automation technology to replace manpower with manipulators in working places where dangerous, harmful, heavy or repetitive work is involved. The sort manipulator is installed in a crystal-angle sort machine to take the place of manpower, and engaged in unloading and sorting work. It is the outcome of combing together mechanism, electric transmission, and pneumatic element and micro-controller control. The step motor makes the sort manipulator operate precisely. The pneumatic elements make the sort manipulator be cleverer. Micro-controller's software bestows some simple artificial intelligence on the sort manipulator, so that it can precisely repeat its unloading and sorting work. The combination of manipulator's zero position and step motor counting control puts an end to accumulating error in long time operation. A sort manipulator's design in the practice engineering has been proved to be correct and reliable.

  2. VizieR Online Data Catalog: RR Lyrae stars from the PS1 3π survey (Sesar+, 2017)

    Science.gov (United States)

    Sesar, B.; Hernitschek, N.; Mitrovic, S.; Ivezic, Z.; Rix, H.-W.; Cohen, J. G.; Bernard, E. J.; Grebel, E. K.; Martin, N. F.; Schlafly, E. F.; Burgett, W. S.; Draper, P. W.; Flewelling, H.; Kaiser, N.; Kudritzki, R. P.; Magnier, E. A.; Metcalfe, N.; Tonry, J. L.; Waters, C.

    2018-04-01

    Building on the work by Hernitschek+ (2016, J/ApJ/817/73), in this paper, we use the final PS1 data release (PV3) to significantly increase the completeness and purity of the PS1 sample of RR Lyrae stars. Pan-STARRS1 (PS1; Kaiser+ 2010, see II/349) is a wide-field optical/near-IR survey telescope system located at the Haleakala Observatory on the island of Maui in Hawai'i. The largest survey undertaken by the telescope, the PS1 3π survey (Chambers K.C. 2011, BAAS, 43, 113.01), has observed the entire sky north of decl. -30° in five filter bands, reaching 5σ single-epoch depths of about 22.0, 22.0, 21.9, 21.0, and 19.8mag in gP1, rP1, iP1, zP1, and yP1 bands, respectively. The uncertainty in photometric calibration of the survey is <~0.01mag, and the astrometric precision of single-epoch detections is 10mas. (4 data files).

  3. Two barcodes encoded by the type-1 PDZ and by phospho-Ser312 regulate retromer/WASH-mediated sorting of the ß1-adrenergic receptor from endosomes to the plasma membrane.

    Science.gov (United States)

    Nooh, Mohammed M; Bahouth, Suleiman W

    2017-01-01

    Recycling of the majority of agonist-internalized GPCR is dependent on a type I-PDZ "barcode" in their C-tail. The recycling of wild-type (WT) ß 1 -AR is also dependent on its default "type-1 PDZ barcode", but trafficking of the ß 1 -AR is inhibited when PKA or its substrate serine at position 312 (Ser 312 ) are inactivated. We tested the hypothesis that phospho-Ser 312 provided a second barcode for ß 1 -AR sorting from endosomes to the plasma membrane by determining the role of retromer/WASH complexes in ß 1 -AR trafficking. Recycling of WT ß 1 -AR or WT ß 2 -AR was dependent on targeting the retromer to endosomal membranes via SNX3 and rab7a, and on complexing the retromer to the WASH pentamer via the C-tail of FAM21 (FAM21 C ). These maneuvers however, did not inhibit the recycling of a phospho-Ser 312 ß 1 -AR mimic ((S312D) ß 1 -AR). Knockdown of the trans-acting PDZ protein sorting nexin27 (SNX27) inhibited the recycling of WT ß 1 -AR and WT ß 2 -AR, but had no effect on (S312D) ß 1 -AR∆PDZ or on phosphorylation of WT ß 1 -AR by PKA at Ser 312 . However, depletion of FKBP15, a FAM21 C -binding endosomal protein, selectively inhibited WT ß 1 -AR but not ß 2 -AR recycling, suggesting divergence might exist in GPCR trafficking roadmaps. These results indicate that two barcodes are involved in sorting WT ß 1 -AR out of early endosomes. The first and antecedent "barcode" was the "type-1 PDZ", followed by a second reversible "phospho-Ser 312 " verification "barcode". This organization allows tight regulation of ß 1 -AR density to signaling intensity in conditions associated with aberrant ß 1 -AR signaling such as in hypertension and heart failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Regulation of 1, 4, 5-triphosphate receptor channel gating dynamics by mutant presenilin in Alzheimer's disease cells

    Science.gov (United States)

    Wei, Fang; Li, Xiang; Cai, Meichun; Liu, Yanping; Jung, Peter; Shuai, Jianwei

    2017-06-01

    In neurons of patients with Alzheimer's disease, the intracellular Ca2+ concentration is increased by its release from the endoplasmic reticulum via the inositol 1, 4, 5-triphosphate receptor (IP3R). In this paper, we discuss the IP3R gating dynamics in familial Alzheimer's disease (FAD) cells induced with presenilin mutation PS1. By fitting the parameters of an IP3R channel model to experimental data of the open probability, the mean open time and the mean closed time of IP3R channels, in control cells and FAD mutant cells, we suggest that the interaction of presenilin mutation PS1 with IP3R channels leads the decrease in the unbinding rates of IP3 and the activating Ca2+ from IP3Rs. As a result, the increased affinities of IP3 and activating Ca2+ for IP3R channels induce the increase in the Ca2+ signal in FAD mutant cells. Specifically, the PS1 mutation decreases the IP3 dissociation rate of IP3R channels significantly in FAD mutant cells. Our results suggest possible novel targets for FAD therapeutic intervention.

  5. Synthesis and Characterization of the Rubidium Thiophosphate Rb 6 (PS 5 )(P 2 S 10 ) and the Rubidium Silver Thiophosphates Rb 2 AgPS 4 , RbAg 5 (PS 4 ) 2 and Rb 3 Ag 9 (PS 4 ) 4

    KAUST Repository

    Alahmary, Fatimah S.

    2016-02-18

    The metal thiophosphates Rb2AgPS4 (2), RbAg5(PS4)2 (3), and Rb3Ag9(PS4)4 (4) were synthesized by stoichiometric reactions, whereas Rb6(PS5)(P2S10) (1) was prepared with excess amount of sulfur. The compounds crystallize as follows: 1 monoclinic, P21/c (no. 14), a = 17.0123(7) Å, b = 6.9102(2) Å, c = 23.179(1) Å, β = 94.399(4)°; 2 triclinic, P ¯ (no. 2), a = 6.600(1) Å, b = 6.856(1) Å, c = 10.943(3) Å, α = 95.150(2)°, β = 107.338(2)°, γ = 111.383(2)°; 3 orthorhombic, Pbca (no. 61), a = 12.607(1) Å, b = 12.612(1) Å, c = 17.759(2) Å; 4 orthorhombic, Pbcm (no. 57), a = 6.3481(2) Å, b = 12.5782(4) Å, c = 35.975(1) Å. The crystal structures contain discrete units, chains, and 3D polyanionic frameworks composed of PS4 tetrahedral units arranged and connected in different manner. Compounds 1-3 melt congruently, whereas incongruent melting behavior was observed for compound 4. 1-4 are semiconductors with bandgaps between 2.3 and 2.6 eV and thermally stable up to 450 °C in an inert atmosphere. Copyright © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor.

    Science.gov (United States)

    Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto

    2013-12-01

    Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs. © 2013.

  7. Parallel sorting algorithms

    CERN Document Server

    Akl, Selim G

    1985-01-01

    Parallel Sorting Algorithms explains how to use parallel algorithms to sort a sequence of items on a variety of parallel computers. The book reviews the sorting problem, the parallel models of computation, parallel algorithms, and the lower bounds on the parallel sorting problems. The text also presents twenty different algorithms, such as linear arrays, mesh-connected computers, cube-connected computers. Another example where algorithm can be applied is on the shared-memory SIMD (single instruction stream multiple data stream) computers in which the whole sequence to be sorted can fit in the

  8. Ectopic expression of phloem motor protein pea forisome PsSEO-F1 enhances salinity stress tolerance in tobacco.

    Science.gov (United States)

    Srivastava, Vineet Kumar; Raikwar, Shailendra; Tuteja, Renu; Tuteja, Narendra

    2016-05-01

    PsSEOF-1 binds to calcium and its expression is upregulated by salinity treatment. PsSEOF - 1 -overexpressing transgenic tobacco showed enhanced salinity stress tolerance by maintaining cellular ion homeostasis and modulating ROS-scavenging pathway. Calcium (Ca(2+)) plays important role in growth, development and stress tolerance in plants. Cellular Ca(2+) homeostasis is achieved by the collective action of channels, pumps, antiporters and by Ca(2+) chelators present in the cell like calcium-binding proteins. Forisomes are ATP-independent mechanically active motor proteins known to function in wound sealing of injured sieve elements of phloem tissue. The Ca(2+)-binding activity of forisome and its role in abiotic stress signaling were largely unknown. Here we report the Ca(2+)-binding activity of pea forisome (PsSEO-F1) and its novel function in promoting salinity tolerance in transgenic tobacco. Native PsSEO-F1 promoter positively responded in salinity stress as confirmed using GUS reporter. Overexpression of PsSEO-F1 tobacco plants confers salinity tolerance by alleviating ionic toxicity and increased ROS scavenging activity which probably results in reduced membrane damage and improved yield under salinity stress. Evaluation of several physiological indices shows an increase in relative water content, electrolyte leakage, proline accumulation and chlorophyll content in transgenic lines as compared with null-segregant control. Expression of several genes involved in cellular homeostasis is perturbed by PsSEO-F1 overexpression. These findings suggest that PsSEO-F1 provides salinity tolerance through cellular Ca(2+) homeostasis which in turn modulates ROS machinery providing indirect link between Ca(2+) and ROS signaling under salinity-induced perturbation. PsSEO-F1 most likely functions in salinity stress tolerance by improving antioxidant machinery and mitigating ion toxicity in transgenic lines. This finding should make an important contribution in our better

  9. Asymmetric PS-block-(PS-co-PB)-block-PS block copolymers: morphology formation and deformation behaviour

    International Nuclear Information System (INIS)

    Adhikari, Rameshwar; Huy, Trinh An; Buschnakowski, Matthias; Michler, Goerg H; Knoll, Konrad

    2004-01-01

    Morphology formation and deformation behaviour of asymmetric styrene/butadiene triblock copolymers (total polystyrene (PS) content ∼70%) consisting of PS outer blocks held apart by a styrene-co-butadiene random copolymer block (PS-co-PB) each were investigated. The techniques used were differential scanning calorimetry, transmission electron microscopy, uniaxial tensile testing and Fourier-transform infrared spectroscopy. A significant shift of the phase behaviour relative to that of a neat symmetric triblock copolymer was observed, which can be attributed to the asymmetric architecture and the presence of PS-co-PB as a soft block. The mechanical properties and the microdeformation phenomena were mainly controlled by the nature of their solid-state morphology. Independent of morphology type, the soft phase was found to deform to a significantly higher degree of orientation when compared with the hard phase

  10. Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury

    DEFF Research Database (Denmark)

    Jansen, Pernille; Giehl, Klaus; Nyengaard, Jens R

    2007-01-01

    Neurotrophins are essential for development and maintenance of the vertebrate nervous system. Paradoxically, although mature neurotrophins promote neuronal survival by binding to tropomyosin receptor kinases and p75 neurotrophin receptor (p75(NTR)), pro-neurotrophins induce apoptosis in cultured......)/sortilin receptor complex to neuronal viability. In the developing retina, Sortilin 1 (Sort1)(-/-) mice showed reduced neuronal apoptosis that was indistinguishable from that observed in p75(NTR)-deficient (Ngfr(-/-)) mice. To our surprise, although sortilin deficiency did not affect developmentally regulated...... apoptosis of sympathetic neurons, it did prevent their age-dependent degeneration. Furthermore, in an injury protocol, lesioned corticospinal neurons in Sort1(-/-) mice were protected from death. Thus, the sortilin pathway has distinct roles in pro-neurotrophin-induced apoptotic signaling in pathological...

  11. Psühhodramaatikud annavad Pärnus eksami

    Index Scriptorium Estoniae

    2008-01-01

    29. maist kuni 1. juunini kestab Pärnus psühhodraama konverents "Geeniuste kohtumine", kus rahvusvahelise koolituse läbinud annavad eksami. Ruuda Palmquist on psühhodraama kui teadusharu rajajaid Eestis. Pärnus on kohal Rootsi Moreno Instituudi juhataja, psühhodraama lavastaja Marc Treadwell

  12. Modelling of absorption, distribution and physicochemical properties of AT1 receptor antagonists / Modelovanie absorpcie, distribúcie a fyzikálnochemických vlastnosti antagonistov AT1 receptorov

    Directory of Open Access Journals (Sweden)

    Ježko Pavol

    2015-12-01

    Full Text Available The theoretical chemistry methods were used to elucidate absorption, distribution and physicochemical properties of AT1 receptor antagonists and dual angiotensin II and endothelin A receptor antagonist (PS-433540. Computed partition coefficients (ALOGPS method studied for drugs varied between 2.98 and 6.66. Neutral compounds are described as lipophilic drugs. Telmisartan is a drug with the highest lipophilicity. The neutral forms of the studied AT1 receptor antagonists are practically insoluble in water, and their computed solubilities is in interval between 2.04 and 22.65 mg/l (ALOGpS method. The calculated pKa values for tetrazolyle moiety are in the range 3.92-5.00 and for carboxylic moiety 3.12-5.50. Telmisartan (polar surface area = 72.95 A and irbesartan (polar surface area = 87.14 A belong to the AT1 receptor antagonists with increased absorption.

  13. Sorting waves and associated eigenvalues

    Science.gov (United States)

    Carbonari, Costanza; Colombini, Marco; Solari, Luca

    2017-04-01

    The presence of mixed sediment always characterizes gravel bed rivers. Sorting processes take place during bed load transport of heterogeneous sediment mixtures. The two main elements necessary to the occurrence of sorting are the heterogeneous character of sediments and the presence of an active sediment transport. When these two key ingredients are simultaneously present, the segregation of bed material is consistently detected both in the field [7] and in laboratory [3] observations. In heterogeneous sediment transport, bed altimetric variations and sorting always coexist and both mechanisms are independently capable of driving the formation of morphological patterns. Indeed, consistent patterns of longitudinal and transverse sorting are identified almost ubiquitously. In some cases, such as bar formation [2] and channel bends [5], sorting acts as a stabilizing effect and therefore the dominant mechanism driving pattern formation is associated with bed altimetric variations. In other cases, such as longitudinal streaks, sorting enhances system instability and can therefore be considered the prevailing mechanism. Bedload sheets, first observed by Khunle and Southard [1], represent another classic example of a morphological pattern essentially triggered by sorting, as theoretical [4] and experimental [3] results suggested. These sorting waves cause strong spatial and temporal fluctuations of bedload transport rate typical observed in gravel bed rivers. The problem of bed load transport of a sediment mixture is formulated in the framework of a 1D linear stability analysis. The base state consists of a uniform flow in an infinitely wide channel with active bed load transport. The behaviour of the eigenvalues associated with fluid motion, bed evolution and sorting processes in the space of the significant flow and sediment parameters is analysed. A comparison is attempted with the results of the theoretical analysis of Seminara Colombini and Parker [4] and Stecca

  14. Effect of running exercise on the number of the neurons in the hippocampus of young transgenic APP/PS1 mice.

    Science.gov (United States)

    Jiang, Lin; Ma, Jing; Zhang, Yi; Zhou, Chun-Ni; Zhang, Lei; Chao, Feng-Lei; Chen, Lin-Mu; Jiang, Rong; Wu, Hong; Tang, Yong

    2018-08-01

    To investigate the effect of running exercise on the number of the neurons in the hippocampus of young APP/PS1 mice, twenty 6-month-old male APP/ PS1 transgenic mice were randomly divided into the APP/PS1 control (AD control) group and the APP/PS1 running (AD running) group (10 mice per group), and ten wild-type mice of the littermate were regarded as the wild-type (WT) group. The AD running mice ran on motorized treadmill machiene for 4 months, while the WT mice and AD control mice were housed in standard condition without running. Then, Morris water maze tests (MWM) were used to assess the special learning and memory abilities of mice in three groups. The stereological methods were used to quantitatively evaluate the volume of the hippocampus, CA1/2, CA3 and the dentate gyrus (DG) and count the number of the neurons in CA1/2, CA3 and DG. We found that 4-month running effectively shortened the escape latency of young APP/PS1 control mice in MWM. More importantly, 4-month running effectively increased the volumes of the hippocampus, CA1/2, CA3 and DG and increased the number of neurons in CA1/2, CA3 and DG in young APP/PS1 mice. The present results suggested that 4-month running has significant beneficial effects on the spatial learning and memory capacities of young APP/PS1 mice and could delay the progress of atrophy of hippocampus and the neuron death in CA1/2, CA3 and DG in young APP/PS1 mice. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. NaPdPS{sub 4} and RbPdPS{sub 4}: systems with infinite straight ((1)/({infinity}))[PdPS{sub 4}]{sup -} chains soluble in polar solvents and the structure of cubic RbPdPS{sub 4}{l_brace}Rb{sub 0.33}P{sub 0.4}S{sub 2.23}O{sub x}{r_brace}

    Energy Technology Data Exchange (ETDEWEB)

    Coste, Servane; Hanko, Jason; Bujoli-Doeuff, Martine; Louarn, Guy; Evain, Michel; Brec, Raymond; Alonso, Bruno; Jobic, S; Kanatzidis, Mercouri G

    2003-11-01

    The synthesis, crystal structures, chemical and spectroscopic properties of NaPdPS{sub 4}, RbPdPS{sub 4}, and RbPdPS{sub 4}{l_brace}Rb{sub 0.33}P{sub 0.4}S{sub 2.23}O{sub x}{r_brace} are described. NaPdPS{sub 4}, RbPdPS{sub 4}, are isostructural and crystallize in the tetragonal system I4/mcm with cell parameters a=7.3074(8) A, c=12.2308(14) A and a=8.2954(3) A, c=12.2284(4) A respectively. RbPdPS{sub 4}{l_brace}Rb{sub 0.33}P{sub 0.4}S{sub 2.23}O{sub x}{r_brace} is cubic, space group Pm-3n and a=12.0042(2) A. All compounds contain the same ((1)/({infinity}))[PdPS{sub 4}]{sup -} chains made of alternating square planar Pd{sup 2+} cations and tetrahedral [PS{sub 4}]{sup 3-} anions. RbPdPS{sub 4}{l_brace}Rb{sub 0.33}P{sub 0.4}S{sub 2.23}O{sub x}{r_brace} contains co-crystallized highly disordered molecular species encapsulated within [Rb{sub 8}] cubic cavities. Spectroscopic solid state {sup 31}P NMR, infrared and Raman data as well as elemental analysis suggest that these species could be S{sub n}{sup 2-} (n=3 or 4) anions and possibly cationic [P{sub 4}S{sub 6}O]{sup 6+} fragments. NaPdPS{sub 4} and RbPdPS{sub 4} exhibit exfoliative dissolution in polar solvents giving rise to solutions that show signs of complex fluid behavior.

  16. A novel cold-regulated gene from Phlox subulata, PsCor413im1, enhances low temperature tolerance in Arabidopsis.

    Science.gov (United States)

    Zhou, Aimin; Sun, Hongwei; Feng, Shuang; Zhou, Mi; Gong, Shufang; Wang, Jingang; Zhang, Shuzhen

    2018-01-08

    Low temperature stress adversely affects plant growth, development, and crop productivity. Analysis of the function of genes in the response of plants to low temperature stress is essential for understanding the mechanism of chilling and freezing tolerance. In this study, PsCor413im1, a novel cold-regulated gene isolated from Phlox subulata, was transferred to Arabidopsis to investigate its function under low temperature stress. Real-time quantitative PCR analysis revealed that PsCor413im1 expression was induced by cold and abscisic acid. Subcellular localization revealed that PsCor413im1-GFP fusion protein was localized to the periphery of the chloroplast, consistent with the localization of chloroplast inner membrane protein AtCor413im1, indicating that PsCor413im1 is a chloroplast membrane protein. Furthermore, the N-terminal of PsCor413im1 was determined to be necessary for its localization. Compared to the wild-type plants, transgenic plants showed higher germination and survival rates under cold and freezing stress. Moreover, the expression of AtCor15 in transgenic plants was higher than that in the wild-type plants under cold stress. Taken together, our results suggest that the overexpression of PsCor413im1 enhances low temperature tolerance in Arabidopsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Ilkjær, Laura; Clausen, Bettina H

    2015-01-01

    of CD11b, TNF, and IL-1Ra. Cytokine production and Aβ load were assessed in neocortical CD11b(+)(CD45(+)) microglia by flow cytometry. Whereas most microglia in aged mice produced IL-1Ra, relatively low proportions of microglia produced TNF, IL-1α, and IL-1β. However, microglial production......, however the inter-relationship between these processes is poorly understood. Here we show that % Aβ plaque load followed a sigmoidal trajectory with age in the neocortex of APPswe/PS1ΔE9 Tg mice, and correlated positively with soluble Aβ40 and Aβ42. Aβ measures were moderately correlated with mRNA levels...... of these latter cytokines was generally increased in APP/PS1 Tg mice. Microglia that phagocytosed endogenously-produced Aβ were only observed in APP/PS1 Tg mice. Differences in phagocytic index and total Aβ load were observed in microglia with specific cytokine profiles. Both phagocytic index and total Aβ load...

  18. Expectation values of the e+PsH system

    International Nuclear Information System (INIS)

    Zhang, J.-Y.; Mitroy, J.

    2007-01-01

    Close to converged energies and expectation values for e + PsH are computed using a ground-state wave function consisting of 1500 explicitly correlated Gaussians. The best estimate of the e + PsH ∞ energy was -0.810 254 hartrees, which has a binding energy of 0.021 057 hartrees against dissociation into e + +PsH. The 2γ annihilation rate was 2.7508x10 9 s -1 . Binding energies and annihilation rates are also given for the different finite-mass variants of e + PsH. Comparisons between expectation values for e + PsH and PsH provide compelling evidence that the e + PsH ground state can be regarded as consisting of a weakly bound positron orbiting the PsH ground state

  19. S1P/S1PR3 signaling mediated proliferation of pericytes via Ras/pERK pathway and CAY10444 had beneficial effects on spinal cord injury.

    Science.gov (United States)

    Tang, Hai-Bin; Jiang, Xiao-Jian; Wang, Chen; Liu, Shi-Chang

    2018-04-15

    Pericytes have long been regarded merely to maintain structural and functional integrity of blood-brain barrier (BBB). Nevertheless, it has also been identified as a component of scar-forming stromal cells after spinal cord injury (SCI). In process of enlargement of spinal cavity after SCI, the number of pericytes increased and outnumbered astrocytes. However, the mechanism of proliferation of pericytes remains unclear. Sphingosine-1-phosphate (S1P) has been reported to play important roles in the formation of glia scar, but previous studies had paid more attention to the astrocytes. The present study aimed to observe the effects of S1P and S1P receptors (S1PRs) on proliferation of pericytes and investigate the underlying mechanism. By double immunostaining, we found that the number of PDGFRβ-positive pericytes was gradually increased and sealed the cavity, which surrounded by reactive astrocytes. Moreover, the subtype of S1PR3 was found to be induced by SCI and mainly expressed on pericytes. Further, by use of CAY10444, an inhibitor of S1PR3, we showed that S1P/S1PR3 mediated the proliferation of pericytes through Ras/pERK pathway. Moreover, CAY10444 was found to have the effects of enhancing neuronal survival, alleviating glial scar formation, and improving locomotion recovery after SCI. The results suggested that S1P/S1PR3 might be a promising target for clinical therapy for SCI. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Genotype-induced changes in biophysical properties of frontal cortex lipid raft from APP/PS1 transgenic mice

    Directory of Open Access Journals (Sweden)

    Mario L Diaz

    2012-11-01

    Full Text Available Alterations in the lipid composition of lipid rafts have been demonstrated both in human brain and transgenic mouse models, and it has been postulated that aberrant lipid composition in lipid rafts is partly responsible for neuronal degeneration. In order to assess the impact of lipid changes on lipid raft functional properties, we have aimed at determining relevant physicochemical modifications in lipid rafts purified from frontal cortex of wild type (WT and APP/PS1 double transgenic mice. By means of steady-state fluorescence anisotropy analyses using two lipid soluble fluorescent probes, TMA-DPH (1-[(4-trimethyl-aminophenyl]-6-phenyl-1,3,5-hexatriene and DPH (1,6-diphenyl-1,3,5-hexatriene, we demonstrate that cortical lipid rafts from WT and APP/PS1 animals exhibit different biophysical behaviours, depending on genotype but also on age. Thus, aged APP/PS1 animals exhibited slightly more liquid-ordered lipid rafts than WT counterparts. Membrane microviscosity napp analyses demonstrate that WT lipid rafts are more fluid than APP/PS1 animals of similar age, both at the aqueous interface and hydrophobic core of the membrane. napp in APP/PS1 animals was higher for DPH than for TMA-DPH under similar experimental conditions, indicating that the internal core of the membrane is more viscous than the raft membrane at the aqueous interface. The most dramatic changes in biophysical properties of lipid rafts were observed when membrane cholesterol was depleted with methyl-beta-cyclodextrin. Overall, our results indicate that APP/PS1 genotype strongly affects physicochemical properties of lipid raft. Such alterations appear not to be homogeneous across the raft membrane axis, but rather are more prominent at the membrane plane. These changes correlate with aberrant proportions of sphingomyelin, cholesterol and saturated fatty acids, as well as polyunsaturated fatty acids, measured in lipid rafts from frontal cortex in this familial model of

  1. Anomalies in social behaviors and exploratory activities in an APPswe/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Filali, Mohammed; Lalonde, Robert; Rivest, Serge

    2011-10-24

    Alzheimer's disease is characterized by deficits in social communication, associated with generalized apathy or agitation, as well as social memory. To assess social behaviors in 6-month-old male APPswe/PS1 bigenics relative to non-transgenic controls, the 3-chamber test was used, together with open-field and elevated plus-maze tests of exploration. APPswe/PS1 mice were less willing to engage in social interaction than wild-type, avoiding an unfamiliar stimulus mouse, probably not due to generalized apathy because in both tests of exploratory activity the mutants were hyperactive. This study reveals reduced "sociability" combined with hyperactivity in an APPswe/PS1 mouse model of Alzheimer dementia. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. What is a Sorting Function?

    DEFF Research Database (Denmark)

    Henglein, Fritz

    2009-01-01

    What is a sorting function—not a sorting function for a given ordering relation, but a sorting function with nothing given? Formulating four basic properties of sorting algorithms as defining requirements, we arrive at intrinsic notions of sorting and stable sorting: A function is a sorting...... are derivable without compromising data abstraction. Finally we point out that stable sorting functions as default representations of ordering relations have the advantage of permitting linear-time sorting algorithms; inequality tests forfeit this possibility....... function if and only it is an intrinsically parametric permutation function. It is a stable sorting function if and only if it is an intrinsically stable permutation function. We show that ordering relations can be represented isomorphically as inequality tests, comparators and stable sorting functions...

  3. Two-year survival rates of anti-TNF-α therapy in psoriatic arthritis (PsA) patients with either polyarticular or oligoarticular PsA.

    Science.gov (United States)

    Iannone, F; Lopriore, S; Bucci, R; Scioscia, C; Anelli, M G; Notarnicola, A; Lapadula, G

    2015-05-01

    To evaluate the 2-year drug survival rates of the tumour necrosis factor (TNF)-α blockers adalimumab, etanercept, and infliximab in psoriatic arthritis (PsA) patients with either oligoarticular (oligo-PsA) or polyarticular PsA (poly-PsA). We studied a prospective cohort of 328 PsA patients with peripheral arthritis (213 with poly-PsA and 115 with oligo-PsA), beginning their first ever anti-TNF-α treatment with adalimumab, etanercept, or infliximab. The aim of the study was to evaluate the drug survival rates and possible baseline predictors at 2 years. After 24 months, persistence in therapy with the first anti-TNF-α blocker was not statistically different in the oligo-PsA (70.4%) and poly-PsA (65.7%) subsets. Predictors of drug discontinuation were female sex [hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.00-2.68, p = 0.04] and starting the therapy in years 2003-8 (HR 0.51, 95% CI 0.33-0.80, p = 0.003). In poly-PsA, the persistence of etanercept (68.3%) was significantly higher than that of adalimumab (51.9%, p = 0.01), whereas in oligo-PsA no significant difference was detected. In poly-PsA, the period 2003-8 was a negative predictor (HR 0.36, 95% CI 0.21-0.62, p = 0.0001) whereas in oligo-PsA female gender was a positive predictor of drug discontinuation (HR 2.08, 95% CI 1.02-4.24, p = 0.04). With regard to clinical outcomes, the best responses in terms of European League Against Rheumatism (EULAR) 'good' response or Disease Activity Score (DAS28) remission, crude or adjusted according to the LUND Efficacy indeX (LUNDEX), were seen in patients on etanercept or infliximab. Our study provides some evidence that anti-TNF-α drugs may perform differently in PsA, and that the analysis of clinical disease subsets may improve our knowledge and promote better management of PsA.

  4. Signal transduction through the IL-4 and insulin receptor families.

    Science.gov (United States)

    Wang, L M; Keegan, A; Frankel, M; Paul, W E; Pierce, J H

    1995-07-01

    Activation of tyrosine kinase-containing receptors and intracellular tyrosine kinases by ligand stimulation is known to be crucial for mediating initial and subsequent events involved in mitogenic signal transduction. Receptors for insulin and insulin-like growth factor 1 (IGF-1) contain cytoplasmic tyrosine kinase domains that undergo autophosphorylation upon ligand stimulation. Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin. A related substrate, designated 4PS, is similarly phosphorylated by insulin and IGF-1 stimulation in many hematopoietic cell types. IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Thus, they appear to act as docking substrates for a variety of signaling molecules. The majority of hematopoietic cytokines bind to receptors that do not possess intrinsic kinase activity, and these receptors have been collectively termed as members of the hematopoietin receptor superfamily. Despite their lack of tyrosine kinase domains, stimulation of these receptors has been demonstrated to activate intracellular kinases leading to tyrosine phosphorylation of multiple substrates. Recent evidence has demonstrated that activation of different members of the Janus family of tyrosine kinases is involved in mediating tyrosine phosphorylation events by specific cytokines. Stimulation of the interleukin 4 (IL-4) receptor, a member of the hematopoietin receptor superfamily, is thought to result in activation of Jak1, Jak3, and/or Fes tyrosine kinases.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. A Preliminary Study of MSD-First Radix-Sorting Methed

    OpenAIRE

    小田, 哲久

    1984-01-01

    Many kinds of sorting algorithms have been developed from the age of Punched Card System. Nowadays, any sorting algorithm can be called either (1) internal sorting methed or (2) external sorting method. Internal sorting method is used only when the number of records to be sorted (N) is not so large for the internal memory of the computer system. Larger memory space has become available with the aid of semiconductor technology. Therefore, it might be desired to develop a new internal sorting m...

  6. The EARP Complex and Its Interactor EIPR-1 Are Required for Cargo Sorting to Dense-Core Vesicles.

    Directory of Open Access Journals (Sweden)

    Irini Topalidou

    2016-05-01

    Full Text Available The dense-core vesicle is a secretory organelle that mediates the regulated release of peptide hormones, growth factors, and biogenic amines. Dense-core vesicles originate from the trans-Golgi of neurons and neuroendocrine cells, but it is unclear how this specialized organelle is formed and acquires its specific cargos. To identify proteins that act in dense-core vesicle biogenesis, we performed a forward genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We previously reported the identification of two conserved proteins that interact with the small GTPase RAB-2 to control normal dense-core vesicle cargo-sorting. Here we identify several additional conserved factors important for dense-core vesicle cargo sorting: the WD40 domain protein EIPR-1 and the endosome-associated recycling protein (EARP complex. By assaying behavior and the trafficking of dense-core vesicle cargos, we show that mutants that lack EIPR-1 or EARP have defects in dense-core vesicle cargo-sorting similar to those of mutants in the RAB-2 pathway. Genetic epistasis data indicate that RAB-2, EIPR-1 and EARP function in a common pathway. In addition, using a proteomic approach in rat insulinoma cells, we show that EIPR-1 physically interacts with the EARP complex. Our data suggest that EIPR-1 is a new interactor of the EARP complex and that dense-core vesicle cargo sorting depends on the EARP-dependent trafficking of cargo through an endosomal sorting compartment.

  7. Machine-learned Identification of RR Lyrae Stars from Sparse, Multi-band Data: The PS1 Sample

    Science.gov (United States)

    Sesar, Branimir; Hernitschek, Nina; Mitrović, Sandra; Ivezić, Željko; Rix, Hans-Walter; Cohen, Judith G.; Bernard, Edouard J.; Grebel, Eva K.; Martin, Nicolas F.; Schlafly, Edward F.; Burgett, William S.; Draper, Peter W.; Flewelling, Heather; Kaiser, Nick; Kudritzki, Rolf P.; Magnier, Eugene A.; Metcalfe, Nigel; Tonry, John L.; Waters, Christopher

    2017-05-01

    RR Lyrae stars may be the best practical tracers of Galactic halo (sub-)structure and kinematics. The PanSTARRS1 (PS1) 3π survey offers multi-band, multi-epoch, precise photometry across much of the sky, but a robust identification of RR Lyrae stars in this data set poses a challenge, given PS1's sparse, asynchronous multi-band light curves (≲ 12 epochs in each of five bands, taken over a 4.5 year period). We present a novel template fitting technique that uses well-defined and physically motivated multi-band light curves of RR Lyrae stars, and demonstrate that we get accurate period estimates, precise to 2 s in > 80 % of cases. We augment these light-curve fits with other features from photometric time-series and provide them to progressively more detailed machine-learned classification models. From these models, we are able to select the widest (three-fourths of the sky) and deepest (reaching 120 kpc) sample of RR Lyrae stars to date. The PS1 sample of ˜45,000 RRab stars is pure (90%) and complete (80% at 80 kpc) at high galactic latitudes. It also provides distances that are precise to 3%, measured with newly derived period-luminosity relations for optical/near-infrared PS1 bands. With the addition of proper motions from Gaia and radial velocity measurements from multi-object spectroscopic surveys, we expect the PS1 sample of RR Lyrae stars to become the premier source for studying the structure, kinematics, and the gravitational potential of the Galactic halo. The techniques presented in this study should translate well to other sparse, multi-band data sets, such as those produced by the Dark Energy Survey and the upcoming Large Synoptic Survey Telescope Galactic plane sub-survey.

  8. Neurobeachin regulates neurotransmitter receptor trafficking to synapses

    NARCIS (Netherlands)

    Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

    2013-01-01

    The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

  9. L-3-n-Butylphthalide Regulates Proliferation, Migration, and Differentiation of Neural Stem Cell In Vitro and Promotes Neurogenesis in APP/PS1 Mouse Model by Regulating BDNF/TrkB/CREB/Akt Pathway.

    Science.gov (United States)

    Lei, Hui; Zhang, Yu; Huang, Longjian; Xu, Shaofeng; Li, Jiang; Yang, Lichao; Wang, Ling; Xing, Changhong; Wang, Xiaoliang; Peng, Ying

    2018-05-04

    Alzheimer's disease (AD) is characterized by extracellular accumulation of β-amyloid peptides (Aβ) and intracellular neurofibrillary tangles, along with cognitive decline and neurodegeneration. The cognitive deficit is considered to be due to the dysfunction of hippocampal neurogenesis. Although L-3-n-butylphthalide (L-NBP) has been shown beneficial effects in multiple AD animal models, the underlying molecular mechanisms are still elusive. In this study, we investigated the effects of L-NBP on neurogenesis both in vitro and in vivo. L-NBP promoted proliferation and migration of neural stem cells and induced neuronal differentiation in vitro. In APP/PS1 mice, L-NBP induced neurogenesis in the dentate gyrus and improved cognitive functions. In addition, L-NBP significantly increased the expressions of BDNF and NGF, tyrosine phosphorylation of its cognate receptor, and phosphorylation of Akt as well as CREB at Ser133 in the hippocampus of APP/PS1 mice. These results indicated that L-NBP might stimulate the proliferation, migration, and differentiation of hippocampal neural stem cells and reversed cognitive deficits in APP/PS1 mice. BDNF/TrkB/CREB/Akt signaling pathway might be involved.

  10. Inhibition of TRAIL-induced apoptosis and forced internalization of TRAIL receptor 1 by adenovirus proteins.

    Science.gov (United States)

    Tollefson, A E; Toth, K; Doronin, K; Kuppuswamy, M; Doronina, O A; Lichtenstein, D L; Hermiston, T W; Smith, C A; Wold, W S

    2001-10-01

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis through two receptors, TRAIL-R1 (also known as death receptor 4) and TRAIL-R2 (also known as death receptor 5), that are members of the TNF receptor superfamily of death domain-containing receptors. We show that human adenovirus type 5 encodes three proteins, named RID (previously named E3-10.4K/14.5K), E3-14.7K, and E1B-19K, that independently inhibit TRAIL-induced apoptosis of infected human cells. This conclusion was derived from studies using wild-type adenovirus, adenovirus replication-competent mutants that lack one or more of the RID, E3-14.7K, and E1B-19K genes, and adenovirus E1-minus replication-defective vectors that express all E3 genes, RID plus E3-14.7K only, RID only, or E3-14.7K only. RID inhibits TRAIL-induced apoptosis when cells are sensitized to TRAIL either by adenovirus infection or treatment with cycloheximide. RID induces the internalization of TRAIL-R1 from the cell surface, as shown by flow cytometry and indirect immunofluorescence for TRAIL-R1. TRAIL-R1 was internalized in distinct vesicles which are very likely to be endosomes and lysosomes. TRAIL-R1 is degraded, as indicated by the disappearance of the TRAIL-R1 immunofluorescence signal. Degradation was inhibited by bafilomycin A1, a drug that prevents acidification of vesicles and the sorting of receptors from late endosomes to lysosomes, implying that degradation occurs in lysosomes. RID was also shown previously to internalize and degrade another death domain receptor, Fas, and to prevent apoptosis through Fas and the TNF receptor. RID was shown previously to force the internalization and degradation of the epidermal growth factor receptor. E1B-19K was shown previously to block apoptosis through Fas, and both E1B-19K and E3-14.7K were found to prevent apoptosis through the TNF receptor. These findings suggest that the receptors for TRAIL, Fas ligand, and TNF play a role in limiting virus

  11. Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein

    DEFF Research Database (Denmark)

    Järås, Marcus; Johnels, Petra; Hansen, Nils Gunder

    2010-01-01

    stem cells could be prospectively separated. In addition, by generating an anti-IL1RAP antibody, we provide proof of concept that IL1RAP can be used as a target on CML CD34(+)CD38(-) cells to induce antibody-dependent cell-mediated cytotoxicity. This study thus identifies IL1RAP as a unique cell...... will require full eradication of Ph chromosome-positive (Ph(+)) CML stem cells. Here we used gene-expression profiling to identify IL-1 receptor accessory protein (IL1RAP) as up-regulated in CML CD34(+) cells and also in cord blood CD34(+) cells as a consequence of retroviral BCR/ABL1 expression. To test...... whether IL1RAP expression distinguishes normal (Ph(-)) and leukemic (Ph(+)) cells within the CML CD34(+)CD38(-) cell compartment, we established a unique protocol for conducting FISH on small numbers of sorted cells. By using this method, we sorted cells directly into drops on slides to investigate...

  12. Sex-sorting sperm using flow cytometry/cell sorting.

    Science.gov (United States)

    Garner, Duane L; Evans, K Michael; Seidel, George E

    2013-01-01

    The sex of mammalian offspring can be predetermined by flow sorting relatively pure living populations of X- and Y-chromosome-bearing sperm. This method is based on precise staining of the DNA of sperm with the nucleic acid-specific fluorophore, Hoechst 33342, to differentiate between the subpopulations of X- and Y-sperm. The fluorescently stained sperm are then sex-sorted using a specialized high speed sorter, MoFlo(®) SX XDP, and collected into biologically supportive media prior to reconcentration and cryopreservation in numbers adequate for use with artificial insemination for some species or for in vitro fertilization. Sperm sorting can provide subpopulations of X- or Y-bearing bovine sperm at rates in the 8,000 sperm/s range while maintaining; a purity of 90% such that it has been applied to cattle on a commercial basis. The sex of offspring has been predetermined in a wide variety of mammalian species including cattle, swine, horses, sheep, goats, dogs, cats, deer, elk, dolphins, water buffalo as well as in humans using flow cytometric sorting of X- and Y-sperm.

  13. Fine-tuning of T-cell development by the CD3γ di-leucine-based TCR-sorting motif

    DEFF Research Database (Denmark)

    Lauritsen, Jens Peter Holst; Boding, Lasse; Buus, Terkild B

    2015-01-01

    The CD3γ di-leucine-based (diL) receptor-sorting motif plays a central role in TCR down-regulation and in clonal expansion of virus-specific T cells. However, the role of the CD3γ diL motif in T-cell development is not known. In this study, we show that protein kinase C-induced TCR down-regulatio......The CD3γ di-leucine-based (diL) receptor-sorting motif plays a central role in TCR down-regulation and in clonal expansion of virus-specific T cells. However, the role of the CD3γ diL motif in T-cell development is not known. In this study, we show that protein kinase C-induced TCR down...

  14. Genomic differentiation among two strains of the PS1 clade isolated from geographically separated marine habitats

    KAUST Repository

    Jimenez Infante, Francy M.

    2014-05-22

    Using dilution-to-extinction cultivation, we isolated a strain affiliated with the PS1 clade from surface waters of the Red Sea. Strain RS24 represents the second isolate of this group of marine Alphaproteobacteria after IMCC14465 that was isolated from the East (Japan) Sea. The PS1 clade is a sister group to the OCS116 clade, together forming a putatively novel order closely related to Rhizobiales. While most genomic features and most of the genetic content are conserved between RS24 and IMCC14465, their average nucleotide identity (ANI) is < 81%, suggesting two distinct species of the PS1 clade. Next to encoding two different variants of proteorhodopsin genes, they also harbor several unique genomic islands that contain genes related to degradation of aromatic compounds in IMCC14465 and in polymer degradation in RS24, possibly reflecting the physicochemical differences in the environment they were isolated from. No clear differences in abundance of the genomic content of either strain could be found in fragment recruitment analyses using different metagenomic datasets, in which both genomes were detectable albeit as minor part of the communities. The comparative genomic analysis of both isolates of the PS1 clade and the fragment recruitment analysis provide first insights into the ecology of this group. © 2014 Federation of European Microbiological Societies.

  15. Role of sphingosine 1-phosphate (S1P and effects of fingolimod, an S1P receptor 1 functional antagonist in lymphocyte circulation and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Kenji Chiba

    2014-11-01

    Full Text Available Sphingosine 1-phosphate (S1P, a multi-functional phospholipid mediator, is generated from sphingosine by sphingosine kinases and binds to five known G protein-coupled S1P receptors (S1P1, S1P2, S1P3, S1P4, and S1P5. It is widely accepted that S1P receptor 1 (S1P1 plays an essential role in lymphocyte egress from the secondary lymphoid organs (SLO and thymus, because lymphocyte egress from these organs to periphery is at extremely low levels in mice lacking lymphocytic S1P1. Fingolimod hydrochloride (FTY720 is a first-in-class, orally active S1P1 functional antagonist which was discovered by chemical modification of a natural product, myriocin. Since FTY720 has a structure closely related to sphingosine, the phosphorylated FTY720 (FTY720-P is converted by sphingosine kinases and binds 4 types of S1P receptors. FTY720-P strongly induces down-regulation of S1P1 by internalization and degradation of this receptor and acts as a functional antagonist at S1P1. Consequently, FTY720 inhibits S1P1-dependent lymphocyte egress from the SLO and thymus to reduce circulating lymphocytes including autoreactive Th17 cells, and is highly effective in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. In relapsing remitting MS patients, oral FTY720 shows a superior efficacy when compared to intramuscular interferon-β-1a. Based on these data, it is presumed that modulation of the S1P-S1P1 axis provides an effective therapy for autoimmune diseases including MS.

  16. GSK3 beta forms a tetrameric complex with endogenous PS1-CTF/NTF and beta-catenin. Effects of the D257/D385A and FAD-linked mutations.

    Science.gov (United States)

    Tesco, G; Tanzi, R E

    2000-01-01

    We have previously shown that the endogenous C-terminal fragment of presenilin 1 co-immunoprecipitates with endogenous beta-catenin. Since PS1 has been suggested to be involved in beta-catenin stabilization, we further investigated whether GSK3 beta, responsible for beta-catenin phosphorylation and degradation, is part of the PS1/beta-catenin complex. In naïve H4 and CHO cells, PS1 co-immunoprecipitated with both endogenous beta-catenin and GSK3 beta. In addition, GSK3 beta endogenously binds to the PS1-CTF/NTF complex and beta-catenin in naïve CHO cells. GSK3 beta also co-immunoprecipitated with PS1 full length in CHO cell lines overexpressing PS1 wild type. Given that it has been recently shown that PS1 mutations of aspartate 257 or 385 result in prevention of PS1 endoproteolysis and inhibition of gamma-secretase activity, we also tested whether PS1 endoproteolysis is required for beta-catenin/GSK3 beta/PS1 binding and whether PS1 FAD-linked mutations affect GSK3 beta recruitment in the PS1/beta-catenin complex. GSK3 beta was detected in PS1 immunoprecipitates from H4 cell lines overexpressing PS1 wild type, delta E10, A286E, L246V and in CHO cell lines overexpressing aspartate or M146L mutations. The latter data show that the absence of PS1 endoproteolysis (D257A/D385A and delta E10) or the presence of PS1-FAD mutations does not interfere with beta-catenin/GSK3 beta/PS1 complex formation.

  17. Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy.

    Science.gov (United States)

    Gao, Yuanzheng; Guo, Xiuming; Santostefano, Katherine; Wang, Yanlin; Reid, Tammy; Zeng, Desmond; Terada, Naohiro; Ashizawa, Tetsuo; Xia, Guangbin

    2016-08-01

    Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1.

  18. Psychometric properties of the OARSI/OMERACT osteoarthritis pain and functional impairment scales: ICOAP, KOOS-PS and HOOS-PS.

    Science.gov (United States)

    Ruyssen-Witrand, A; Fernandez-Lopez, C J; Gossec, L; Anract, P; Courpied, J P; Dougados, M

    2011-01-01

    To evaluate the psychometric properties of the OARSI-OMERACT questionnaires in comparison to the existing validated scales. Consecutive hip or knee osteoarthritis patients consulting in an orthopedic department were enrolled in the study. Data collected were pain using the Intermittent and Constant Osteoarthritis Pain (ICOAP), a Numeric Rating Scale (NRS), the Western Ontario McMaster Universities' Osteoarthritis Index (WOMAC) pain subscale, the Lequesne pain subscale; functional impairment using the Knee disability and Osteoarthritis Outcome Score-Physical Function Shortform (KOOS-PS), the Hip disability and Osteoarthritis Outcome Score-Physical Function Shortform (HOOS-PS), a NRS, the WOMAC function sub-scale, the Lequesne function subscale. Validity was assessed by calculating the Spearman's correlation coefficient between all the scales. Reliability was assessed in out-patients with stable disease comparing the data collected within 2 weeks using the intra-class correlation coefficient (ICC). Responsiveness was assessed on the data from hospitalised patients prior to and 12 weeks after a total joint replacement (TJR) using the standardised response mean. Three hundred patients (mean age=68 years, females=62%, hip OA=57%) were included. There was a moderate to good correlation between ICOAP, KOOS-PS, HOOS-PS and the WOMAC, NRS and Lequesne scales. Reliability of the ICOAP hip OA HOOS-PS and KOOS-PS was good (ICC range 0.80-0.81) whereas it was moderate for knee ICOAP (ICC=0.65). Responsiveness of the ICOAP, KOOS-PS and HOOS-PS 12 weeks after TJR was comparable to responsiveness of other scales (SRM range: 0.54-1.82). The psychometric properties of the ICOAP, KOOS-PS and HOOS-PS were comparable to those of the WOMAC, Lequesne and NRS.

  19. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    International Nuclear Information System (INIS)

    Waser, Beatrice; Reubi, Jean Claude

    2014-01-01

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  20. PS1-10bzj: A FAST, HYDROGEN-POOR SUPERLUMINOUS SUPERNOVA IN A METAL-POOR HOST GALAXY

    Energy Technology Data Exchange (ETDEWEB)

    Lunnan, R.; Chornock, R.; Berger, E.; Milisavljevic, D.; Drout, M.; Sanders, N. E.; Challis, P. M.; Czekala, I.; Foley, R. J.; Fong, W.; Kirshner, R. P.; Leibler, C.; Marion, G. H.; Narayan, G. [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Huber, M. E. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); McCrum, M.; Smartt, S. J. [Astrophysics Research Centre, School of Mathematics and Physics, Queen' s University Belfast, Belfast BT7 1NN (United Kingdom); Rest, A. [Space Telescope Science Institute, 3700 San Martin Dr., Baltimore, MD 21218 (United States); Roth, K. C. [Gemini Observatory, 670 N. Aohoku Place, Hilo, HI 96720 (United States); Scolnic, D., E-mail: rlunnan@cfa.harvard.edu [Department of Physics and Astronomy, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 (United States); and others

    2013-07-10

    We present observations and analysis of PS1-10bzj, a superluminous supernova (SLSN) discovered in the Pan-STARRS Medium Deep Survey at a redshift z = 0.650. Spectroscopically, PS1-10bzj is similar to the hydrogen-poor SLSNe 2005ap and SCP 06F6, though with a steeper rise and lower peak luminosity (M{sub bol} {approx_equal} -21.4 mag) than previous events. We construct a bolometric light curve, and show that while PS1-10bzj's energetics were less extreme than previous events, its luminosity still cannot be explained by radioactive nickel decay alone. We explore both a magnetar spin-down and circumstellar interaction scenario and find that either can fit the data. PS1-10bzj is located in the Extended Chandra Deep Field South and the host galaxy is imaged in a number of surveys, including with the Hubble Space Telescope. The host is a compact dwarf galaxy (M{sub B} Almost-Equal-To -18 mag, diameter {approx}< 800 pc), with a low stellar mass (M{sub *} Almost-Equal-To 2.4 Multiplication-Sign 10{sup 7} M{sub Sun }), young stellar population ({tau}{sub *} Almost-Equal-To 5 Myr), and a star formation rate of {approx}2-3 M{sub Sun} yr{sup -1}. The specific star formation rate is the highest seen in an SLSN host so far ({approx}100 Gyr{sup -1}). We detect the [O III] {lambda}4363 line, and find a low metallicity: 12 + (O/H) = 7.8 {+-} 0.2 ({approx_equal} 0.1 Z{sub Sun }). Together, this indicates that at least some of the progenitors of SLSNe come from young, low-metallicity populations.

  1. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

    2014-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  2. Sorting a distribution theory

    CERN Document Server

    Mahmoud, Hosam M

    2011-01-01

    A cutting-edge look at the emerging distributional theory of sorting Research on distributions associated with sorting algorithms has grown dramatically over the last few decades, spawning many exact and limiting distributions of complexity measures for many sorting algorithms. Yet much of this information has been scattered in disparate and highly specialized sources throughout the literature. In Sorting: A Distribution Theory, leading authority Hosam Mahmoud compiles, consolidates, and clarifies the large volume of available research, providing a much-needed, comprehensive treatment of the

  3. VizieR Online Data Catalog: Gaia-PS1-SDSS (GPS1) proper motion catalog (Tian+, 2017)

    Science.gov (United States)

    Tian, H.-J.; Gupta, P.; Sesar, B.; Rix, H.-W.; Martin, N. F.; Liu, C.; Goldman, B.; Platais, I.; Kudritzki, R.-P.; Waters, C. Z.

    2018-02-01

    In order to construct proper motions, we analyze and model catalog positions from four different imaging surveys, as discussed below. Gaia DR1 is based on observations collected between 2014 July 25 and 2015 September 16. PS1 observations were collected between 2010 and 2014. The SDSS DR9 data used here were obtained in the years between 2000 and 2008. The images from 2MASS were taken between 1997 and 2001. (1 data file).

  4. The color tuning of PS-b-P2VP lamellar films with changing the alkyl chain length of 1-iodoalkanes.

    Science.gov (United States)

    Shin, Sung-Eui; Kim, Su-Young; Shin, Dong-Myung

    2011-05-01

    Photonic crystals with tunability in the visible or near-infrared region have drawn increasing attention for controlling and processing light for the active components of future display. We prepared polystyrene-b-poly(2-vinyl pyridine) (PS-b-P2VP) lamellar films which is hydrophobic block-hydrophilic polyelectrolyte block polymer of 57 kg/mol-b-57 kg/mol. The lamellar stacks, which is alternating layer of hydrophilic and hydrophobic moiety of PS-b-P2VP, are obtained by exposing the spin coated film under chloroform vapor. The band gaps of the lamellar films interestingly varied after immersion into the quaternizing solvents containing 5 wt% of iodomethane, iodoethane, 1-iodobutane, 1-iodopentane, 1-iodohexane and 1-iodooctane solubilized in n-hexane. The iodoalkanes reacted with pyridine groups in PS-b-P2VP and generated the alkyl pyridinium salts readily. The degree of quaternization, alkyl chain length of iodoalkane and the salt water concentration affects the spacing of layer structure of PS-b-P2VP. The iodomethane and iodohexane produced similar band gaps and salt concentration dependence. These results are very much dependent on the hydrophobic-hydrophilic characters of PS-b-P2VP lamellar surface.

  5. Tradeoffs Between Branch Mispredictions and Comparisons for Sorting Algorithms

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Moruz, Gabriel

    2005-01-01

    Branch mispredictions is an important factor affecting the running time in practice. In this paper we consider tradeoffs between the number of branch mispredictions and the number of comparisons for sorting algorithms in the comparison model. We prove that a sorting algorithm using O(dnlog n......) comparisons performs Omega(nlogd n) branch mispredictions. We show that Multiway MergeSort achieves this tradeoff by adopting a multiway merger with a low number of branch mispredictions. For adaptive sorting algorithms we similarly obtain that an algorithm performing O(dn(1+log (1+Inv/n))) comparisons must...... perform Omega(nlogd (1+Inv/n)) branch mispredictions, where Inv is the number of inversions in the input. This tradeoff can be achieved by GenericSort by Estivill-Castro and Wood by adopting a multiway division protocol and a multiway merging algorithm with a low number of branch mispredictions....

  6. Efficient biotransformation of herbicide diuron by bacterial strain Micrococcus sp. PS-1.

    Science.gov (United States)

    Sharma, Priyanka; Chopra, Adity; Cameotra, Swaranjit Singh; Suri, C Raman

    2010-11-01

    A Gram-positive, Micrococcus sp. strain PS-1 capable of utilizing phenylurea herbicide diuron as a sole carbon source at a high concentration (up to 250 ppm) was isolated from diuron storage site by selective enrichment study. The taxonomic characterization with 16S rRNA gene sequencing (1,477 bp) identified PS-1 as a member of Micrococcus sp. It was studied for the degradation of diuron and a range of its analogues (monuron, linuron, monolinuron, chlortoluron and fenuron). The shake flasks experiments demonstrated fast degradation of diuron (up to 96% at 250 ppm within 30 h incubation) with the addition of small quantity (0.01%) of non-ionic detergent. The relative degradation profile by the isolate was in the order of fenuron > monuron > diuron > linuron > monolinuron > chlortoluron. Further, the biochemical characterization of catabolic pathway by spectroscopic and chromatographic techniques demonstrated that the degradation proceeded via formation of dealkylated metabolites to form 3,4-dichloroaniline (3,4-DCA). It was the major metabolite formed, associated with profound increase in degradation kinetics in presence of appropriate additive.

  7. The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs

    Directory of Open Access Journals (Sweden)

    Chunman Li

    2017-10-01

    Full Text Available G-protein-coupled receptors (GPCRs constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.

  8. Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

    Science.gov (United States)

    Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2014-01-01

    Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

  9. Monoclonal antibody 1.6.1 against human MPL receptor allows HSC enrichment of CB and BM CD34(+)CD38(-) populations.

    Science.gov (United States)

    Petit Cocault, Laurence; Fleury, Maud; Clay, Denis; Larghero, Jérôme; Vanneaux, Valérie; Souyri, Michèle

    2016-04-01

    Thrombopoietin (TPO) and its receptor Mpl (CD110) play a crucial role in the regulation of hematopoietic stem cells (HSCs). Functional study of Mpl-expressing HSCs has, however, been hampered by the lack of efficient monoclonal antibodies, explaining the very few data available on Mpl(+) HSCs during human embryonic development and after birth. Investigating the main monoclonal antibodies used so far to sort CD110(+) cells from cord blood (CB) and adult bone marrow (BM), we found that only the recent monoclonal antibody 1.6.1 engineered by Immunex Corporation was specific. Using in vitro functional assays, we found that this antibody can be used to sort a CD34(+)CD38(-)CD110(+) population enriched in hematopoietic progenitor stem cells, both in CB and in adult BM. In vivo injection into NSG mice further indicated that the CB CD34(+)CD38(-)CD110(+) population is highly enriched in HSCs compared with both CD34(+)CD38(-)CD110(-) and CD34(+)CD38(-) populations. Together our results validate MAb1.6.1 as an important tool, which has so far been lacking, in the HSC field. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  10. Pressure Monitoring Using Hybrid fs/ps Rotational CARS

    Science.gov (United States)

    Kearney, Sean P.; Danehy, Paul M.

    2015-01-01

    We investigate the feasibility of gas-phase pressure measurements at kHz-rates using fs/ps rotational CARS. Femtosecond pump and Stokes pulses impulsively prepare a rotational Raman coherence, which is then probed by a high-energy 6-ps pulse introduced at a time delay from the Raman preparation. Rotational CARS spectra were recorded in N2 contained in a room-temperature gas cell for pressures from 0.1 to 3 atm and probe delays ranging from 10-330 ps. Using published self-broadened collisional linewidth data for N2, both the spectrally integrated coherence decay rate and the spectrally resolved decay were investigated as means for detecting pressure. Shot-averaged and single-laser-shot spectra were interrogated for pressure and the accuracy and precision as a function of probe delay and cell pressure are discussed. Single-shot measurement accuracies were within 0.1 to 6.5% when compared to a transducer values, while the precision was generally between 1% and 6% of measured pressure for probe delays of 200 ps or more, and better than 2% as the delay approached 300 ps. A byproduct of the pressure measurement is an independent but simultaneous measurement of the gas temperature.

  11. Modeling of drug-mediated CYP3A4 induction by using human iPS cell-derived enterocyte-like cells

    International Nuclear Information System (INIS)

    Negoro, Ryosuke; Takayama, Kazuo; Nagamoto, Yasuhito; Sakurai, Fuminori; Tachibana, Masashi; Mizuguchi, Hiroyuki

    2016-01-01

    Many drugs have potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in small intestinal enterocytes. Therefore, a model that can accurately evaluate drug-mediated CYP3A4 induction is urgently needed. In this study, we overlaid Matrigel on the human induced pluripotent stem cells-derived enterocyte-like cells (hiPS-ELCs) to generate the mature hiPS-ELCs that could be applied to drug-mediated CYP3A4 induction test. By overlaying Matrigel in the maturation process of enterocyte-like cells, the gene expression levels of intestinal markers (VILLIN, sucrase-isomaltase, intestine-specific homeobox, caudal type homeobox 2, and intestinal fatty acid-binding protein) were enhanced suggesting that the enterocyte-like cells were maturated by Matrigel overlay. The percentage of VILLIN-positive cells in the hiPS-ELCs found to be approximately 55.6%. To examine the CYP3A4 induction potential, the hiPS-ELCs were treated with various drugs. Treatment with dexamethasone, phenobarbital, rifampicin, or 1α,25-dihydroxyvitamin D3 resulted in 5.8-fold, 13.4-fold, 9.8-fold, or 95.0-fold induction of CYP3A4 expression relative to that in the untreated controls, respectively. These results suggest that our hiPS-ELCs would be a useful model for CYP3A4 induction test. - Highlights: • The hiPS-ELCs were matured by Matrigel overlay. • The hiPS-ELCs expressed intestinal nuclear receptors, such as PXR, GR and VDR. • The hiPS-ELC is a useful model for the drug-mediated CYP3A4 induction test.

  12. Modeling of drug-mediated CYP3A4 induction by using human iPS cell-derived enterocyte-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Negoro, Ryosuke [Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan); Takayama, Kazuo [Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan); The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX), Kyoto University, Kyoto 606-8302 (Japan); Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085 (Japan); Nagamoto, Yasuhito [Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan); Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085 (Japan); Sakurai, Fuminori [Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan); Laboratory of Regulatory Sciences for Oligonucleotide Therapeutics, Clinical Drug Development Project, Graduate School of Pharmaceutical Sciences, Osaka University Osaka 565-0871 (Japan); Tachibana, Masashi [Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan); Mizuguchi, Hiroyuki, E-mail: mizuguch@phs.osaka-u.ac.jp [Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan); Laboratory of Hepatocyte Regulation, National Institute of Biomedical Innovation, Health and Nutrition, Osaka 567-0085 (Japan); Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565-0871 (Japan)

    2016-04-15

    Many drugs have potential to induce the expression of drug-metabolizing enzymes, particularly cytochrome P450 3A4 (CYP3A4), in small intestinal enterocytes. Therefore, a model that can accurately evaluate drug-mediated CYP3A4 induction is urgently needed. In this study, we overlaid Matrigel on the human induced pluripotent stem cells-derived enterocyte-like cells (hiPS-ELCs) to generate the mature hiPS-ELCs that could be applied to drug-mediated CYP3A4 induction test. By overlaying Matrigel in the maturation process of enterocyte-like cells, the gene expression levels of intestinal markers (VILLIN, sucrase-isomaltase, intestine-specific homeobox, caudal type homeobox 2, and intestinal fatty acid-binding protein) were enhanced suggesting that the enterocyte-like cells were maturated by Matrigel overlay. The percentage of VILLIN-positive cells in the hiPS-ELCs found to be approximately 55.6%. To examine the CYP3A4 induction potential, the hiPS-ELCs were treated with various drugs. Treatment with dexamethasone, phenobarbital, rifampicin, or 1α,25-dihydroxyvitamin D3 resulted in 5.8-fold, 13.4-fold, 9.8-fold, or 95.0-fold induction of CYP3A4 expression relative to that in the untreated controls, respectively. These results suggest that our hiPS-ELCs would be a useful model for CYP3A4 induction test. - Highlights: • The hiPS-ELCs were matured by Matrigel overlay. • The hiPS-ELCs expressed intestinal nuclear receptors, such as PXR, GR and VDR. • The hiPS-ELC is a useful model for the drug-mediated CYP3A4 induction test.

  13. Cannabinoid Receptor 2 Participates in Amyloid-β Processing in a Mouse Model of Alzheimer's Disease but Plays a Minor Role in the Therapeutic Properties of a Cannabis-Based Medicine.

    Science.gov (United States)

    Aso, Ester; Andrés-Benito, Pol; Carmona, Margarita; Maldonado, Rafael; Ferrer, Isidre

    2016-01-01

    The endogenous cannabinoid system represents a promising therapeutic target to modify neurodegenerative pathways linked to Alzheimer's disease (AD). The aim of the present study was to evaluate the specific contribution of CB2 receptor to the progression of AD-like pathology and its role in the positive effect of a cannabis-based medicine (1:1 combination of Δ9-tetrahidrocannabinol and cannabidiol) previously demonstrated to be beneficial in the AβPP/PS1 transgenic model of the disease. A new mouse strain was generated by crossing AβPP/PS1 transgenic mice with CB2 knockout mice. Results show that lack of CB2 exacerbates cortical Aβ deposition and increases the levels of soluble Aβ40. However, CB2 receptor deficiency does not affect the viability of AβPP/PS1 mice, does not accelerate their memory impairment, does not modify tau hyperphosphorylation in dystrophic neurites associated to Aβ plaques, and does not attenuate the positive cognitive effect induced by the cannabis-based medicine in these animals. These findings suggest a minor role for the CB2 receptor in the therapeutic effect of the cannabis-based medicine in AβPP/PS1 mice, but also constitute evidence of a link between CB2 receptor and Aβ processing.

  14. Eletronic system for search of particles with 1-0.1 ps lifetime

    International Nuclear Information System (INIS)

    Bobkov, S.G.; Kantserov, V.A.; Pershin, A.S.

    1986-01-01

    The algorithms for search of short-lived particleswith 1-0.1 ps lifetime in a vertex detector based on drift chambers are considered. Electronics supply of such selecting by means ofthe suggested algorithms is described. The algorithms for useful event selecting in electron detectors are developed by pp-interaction simulation using the Monte-Carlo method. Events of two types are simulated: charm particle generation with theirfurther decay and interactions without charm particle generation. Two-dimensional interaction pattern is cnsidered. Some algorithms for data processing by the selecting systems (trigger systems) are developed. For all algorithms the event is considered to be useful, if more than one vertex is determined. The algorithms are based on geometrical relations for one-vertex events. Systematic deviation from these relations means that the event is multivertex

  15. GGA1 regulates signal-dependent sorting of BACE1 to recycling endosomes, which moderates Aβ production

    Science.gov (United States)

    Toh, Wei Hong; Chia, Pei Zhi Cheryl; Hossain, Mohammed Iqbal; Gleeson, Paul A.

    2018-01-01

    The diversion of the membrane-bound β-site amyloid precursor protein–(APP) cleaving enzyme (BACE1) from the endolysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the sorting nexin 4 (SNX4)-mediated, signal-independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the DXXLL-motif sequence DISLL in the cytoplasmic tail of BACE1. The phosphomimetic S498D BACE1 mutant was trafficked to recycling endosomes at a faster rate compared with wild-type BACE1 or the nonphosphorylatable S498A mutant. The rapid transit of BACE1 S498D from early endosomes was coupled with reduced levels of amyloid precursor protein processing and Aβ production, compared with the S498A mutant. We show that the adaptor, GGA1, and retromer are essential to mediate rapid trafficking of phosphorylated BACE1 to recycling endosomes. In addition, the BACE1 DISLL motif is phosphorylated and regulates endosomal trafficking, in primary neurons. Therefore, post-translational phosphorylation of DISLL enhances the exit of BACE1 from early endosomes, a pathway mediated by GGA1 and retromer, which is important in regulating Aβ production. PMID:29142073

  16. Wage Sorting Trends

    DEFF Research Database (Denmark)

    Bagger, Jesper; Vejlin, Rune Majlund; Sørensen, Kenneth Lykke

    Using a population-wide Danish Matched Employer-Employee panel from 1980-2006, we document a strong trend towards more positive assortative wage sorting. The correlation between worker and firm fixed effects estimated from a log wage regression increases from -0.07 in 1981 to .14 in 2001. The non......Using a population-wide Danish Matched Employer-Employee panel from 1980-2006, we document a strong trend towards more positive assortative wage sorting. The correlation between worker and firm fixed effects estimated from a log wage regression increases from -0.07 in 1981 to .14 in 2001....... The nonstationary wage sorting pattern is not due to compositional changes in the labor market, primarily occurs among high wage workers, and comprises 41 percent of the increase in the standard deviation of log real wages between 1980 and 2006. We show that the wage sorting trend is associated with worker...

  17. Flow sorting in aquatic ecology

    Directory of Open Access Journals (Sweden)

    Marcus Reckermann

    2000-06-01

    Full Text Available Flow sorting can be a very helpful tool in revealing phytoplankton and bacterial community structure and elaborating specific physiological parameters of isolated species. Droplet sorting has been the most common technique. Despite the high optical and hydro-dynamic stress for the cells to be sorted, many species grow in culture subsequent to sorting. To date, flow sorting has been applied to post-incubation separation in natural water samples to account for group-specific physiological parameters (radiotracer-uptake rates, to the production of clonal or non-clonal cultures from mixtures, to the isolaton of cell groups from natural assemblages for molecular analyses, and for taxonomic identification of sorted cells by microscopy. The application of cell sorting from natural water samples from the Wadden Sea, including different cryptophytes, cyanobacteria and diatoms, is shown, as well as the establishment of laboratory cultures from field samples. The optional use of a red laser to account for phycocyanine-rich cells is also discussed.

  18. ps-ro Fuzzy Open(Closed Functions and ps-ro Fuzzy Semi-Homeomorphism

    Directory of Open Access Journals (Sweden)

    Pankaj Chettri

    2015-11-01

    Full Text Available The aim of this paper is to introduce and characterize some new class of functions in a fuzzy topological space termed as ps-ro fuzzy open(closed functions, ps-ro fuzzy pre semiopen functions and ps-ro fuzzy semi-homeomorphism. The interrelation among these concepts and also their relations with the parallel existing concepts are established. It is also shown with the help of examples that these newly introduced concepts are independent of the well known existing allied concepts.

  19. Ore sorting

    International Nuclear Information System (INIS)

    Hawkins, A.P.; Richards, A.W.

    1982-01-01

    In an ore sorting apparatus, ore particles are bombarded with neutrons in a chamber and sorted by detecting radiation emitted by isotopes of elements, such as gold, forming or contained in the particles, using detectors and selectively controlling fluid jets. The isotopes can be selectively recognised by their radiation characteristics. In an alternative embodiment, shorter life isotopes are formed by neutron bombardment and detection of radiation takes place immediately adjacent the region of bombardment

  20. External parallel sorting with multiprocessor computers

    International Nuclear Information System (INIS)

    Comanceau, S.I.

    1984-01-01

    This article describes methods of external sorting in which the entire main computer memory is used for the internal sorting of entries, forming out of them sorted segments of the greatest possible size, and outputting them to external memories. The obtained segments are merged into larger segments until all entries form one ordered segment. The described methods are suitable for sequential files stored on magnetic tape. The needs of the sorting algorithm can be met by using the relatively slow peripheral storage devices (e.g., tapes, disks, drums). The efficiency of the external sorting methods is determined by calculating the total sorting time as a function of the number of entries to be sorted and the number of parallel processors participating in the sorting process

  1. Last PS magnet refurbished

    CERN Multimedia

    2009-01-01

    PS Magnet Refurbishment Programme Completed. The 51st and final refurbished magnet was transported to the PS on Tuesday 3 February. The repair and consolidation work on the PS started back in 2003 when two magnets and a busbar connection were found to be faulty during routine high-voltage tests. The cause of the fault was a combination of age and radiation on electrical insulation. After further investigation the decision was taken to overhaul half of the PS’s 100 magnets to reduce the risk of a similar fault. As from 20 February the PS ring will start a five-week test programme to be ready for operation at the end of March.

  2. ALGORITHM FOR SORTING GROUPED DATA

    Science.gov (United States)

    Evans, J. D.

    1994-01-01

    It is often desirable to sort data sets in ascending or descending order. This becomes more difficult for grouped data, i.e., multiple sets of data, where each set of data involves several measurements or related elements. The sort becomes increasingly cumbersome when more than a few elements exist for each data set. In order to achieve an efficient sorting process, an algorithm has been devised in which the maximum most significant element is found, and then compared to each element in succession. The program was written to handle the daily temperature readings of the Voyager spacecraft, particularly those related to the special tracking requirements of Voyager 2. By reducing each data set to a single representative number, the sorting process becomes very easy. The first step in the process is to reduce the data set of width 'n' to a data set of width '1'. This is done by representing each data set by a polynomial of length 'n' based on the differences of the maximum and minimum elements. These single numbers are then sorted and converted back to obtain the original data sets. Required input data are the name of the data file to read and sort, and the starting and ending record numbers. The package includes a sample data file, containing 500 sets of data with 5 elements in each set. This program will perform a sort of the 500 data sets in 3 - 5 seconds on an IBM PC-AT with a hard disk; on a similarly equipped IBM PC-XT the time is under 10 seconds. This program is written in BASIC (specifically the Microsoft QuickBasic compiler) for interactive execution and has been implemented on the IBM PC computer series operating under PC-DOS with a central memory requirement of approximately 40K of 8 bit bytes. A hard disk is desirable for speed considerations, but is not required. This program was developed in 1986.

  3. Development of sorting system control using LABVIEW

    International Nuclear Information System (INIS)

    Azraf Azman; Mohd Arif Hamzah; Noriah Mod Ali; John Konsoh; Mohd Idris Taib; Maslina Mohd Ibrahim; Nor Arymaswati Abdullah; Abu Bakar Mhd Ghazali

    2005-01-01

    The development of the Personnel Dosimeter Sorting System, proposed by the Secondary Standard Dosimetry Laboratory (SSDL) is to enhance the system or work flow in preparing the personnel dosimeter. The main objective of the system is to reduce stamping error, time and cost. The Personnel Dosimeter Sorting System is a semi-automatic system with an interfacing method using the Advantec 32 bit PCI interface card of 64 digital input and output. The system is integrated with the Labview version 7.1 programming language to control the sorting system and operation. (Author)

  4. The Q sort theory and technique.

    Science.gov (United States)

    Nyatanga, L

    1989-10-01

    This paper is based on the author's experience of using the Q sort technique with BA Social Sciences (BASS) students, and the community psychiatric nursing (CPN, ENB No 811 course). The paper focuses on two main issues: 1. The theoretical assumptions underpinning the Q Sort technique. Carl Rogers' self theory and some of the values of humanistic psychology are summarised. 2. The actual technique procedure and meaning of results are highlighted. As the Q Sort technique is potentially useful in a variety of sittings some of which are listed in this paper, the emphasis has deliberately been placed in understanding the theoretical underpinning and the operationalisation (sensitive interpretation) of the theory to practice.

  5. YXQN Reduces Alzheimer’s Disease-Like Pathology and Cognitive Decline in APPswePS1dE9 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Xiaowan Wang

    2017-05-01

    Full Text Available Alzheimer’s disease (AD is the world’s most common form of dementia, in which aggregation of amyloid-β (Aβ is the hallmark. Unfortunately, few medicines have succeeded to completely cure AD. Yangxue Qingnao (YXQN is a Chinese traditional medicine, and its pharmacological effect is improving cerebral blood flow. In this study, we firstly demonstrated that YXQN reduced AD-like pathology and cognitive impairment in APPswePS1dE9 (APP/PS1 mice with 2 months administration. Our data showed that YXQN substantially ameliorated behavioral defects in 10-month old APP/PS1 mice using Morris Water Maze and Y-maze tests, in which the cognitive ability of YXQN high-dose group approaches to wild type mice. Next, we focused on the brain pathological alterations in the YXQN group by three experiments, including thioflavin-S, congo-red, and Aβ-immunohistochemistry staining. The results demonstrated that the high-dose of YXQN dramatically suppressed amyloid plaques in the hippocampus and cortex of APP/PS1 mice, which showed a 47–72% reduction in plaque deposits, relative to the vehicle group. In addition, our data verified that YXQN decreased the cerebral amyloid load by attenuating β-secretase BACE1 and γ-secretase PS1 in the pathological processing of APP, and promoting the level of α-secretase ADAM10 in the physiological processing of APP to generate more sAPPα, which combats amyloidosis formation, and also carries out neurotropic and neuroprotective effect. Taken together, our results strongly suggest that YXQN could be a potential medicine for AD, and provide new evidence for further AD drug research and development.

  6. Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice.

    Science.gov (United States)

    Cheng, David; Low, Jac Kee; Logge, Warren; Garner, Brett; Karl, Tim

    2014-08-01

    Patients suffering from Alzheimer's disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces. Hallmark pathological changes in AD include the aggregation of amyloid-β (Aβ), tau protein hyperphosphorylation as well as pronounced neurodegeneration, neuroinflammation, neurotoxicity and oxidative damage. The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents. Thus we determined the therapeutic-like effects of chronic CBD treatment (20 mg/kg, daily intraperitoneal injections for 3 weeks) on the APPswe/PS1∆E9 (APPxPS1) transgenic mouse model for AD in a number of cognitive tests, including the social preference test, the novel object recognition task and the fear conditioning paradigm. We also analysed the impact of CBD on anxiety behaviours in the elevated plus maze. Vehicle-treated APPxPS1 mice demonstrated impairments in social recognition and novel object recognition compared to wild type-like mice. Chronic CBD treatment reversed these cognitive deficits in APPxPS1 mice without affecting anxiety-related behaviours. This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model. Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.

  7. Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

    Science.gov (United States)

    Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

    2014-07-01

    The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Chemotherapy and quality of life in NSCLC PS 2 patients

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Strøm, Hans H; Sundstrøm, Stein H

    2009-01-01

    , fatigue, dyspnea, sleeping problems and appetite loss in comparison to the PS 0/1 group. CONCLUSIONS: PS 2 NSCLC patients seem to achieve valuable HRQOL benefits from platinum-based combination therapy. Prospective clinical studies with predefined HRQOL outcomes in PS 2 patients are needed to confirm...

  9. Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels

    Directory of Open Access Journals (Sweden)

    Stephan eKratzer

    2013-07-01

    Full Text Available Corticotropin-releasing hormone (CRH plays an important role in a substantial number of patients with stress-related mental disorders, such as anxiety disorders and depression. CRH has been shown to increase neuronal excitability in the hippocampus, but the underlying mechanisms are poorly understood. The effects of CRH on neuronal excitability were investigated in acute hippocampal brain slices. Population spikes (PS and field excitatory postsynaptic potentials (fEPSP were evoked by stimulating Schaffer-collaterals and recorded simultaneously from the somatic and dendritic region of CA1 pyramidal neurons. CRH was found to increase PS amplitudes (mean  Standard error of the mean; 231.8  31.2% of control; n=10 while neither affecting fEPSPs (104.3 ± 4.2%; n=10 nor long-term potentiation (LTP. However, when Schaffer-collaterals were excited via action potentials (APs generated by stimulation of CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 ± 3.6%; n=8 and the magnitude of LTP in the CA1 region. Experiments in slices from transgenic mice revealed that the effect on PS amplitude is mediated exclusively by CRH receptor 1 (CRHR1 expressed on glutamatergic neurons. The effects of CRH on PS were dependent on phosphatase-2B, L- and T-type calcium channels and voltage-gated potassium channels but independent on intracellular Ca2+-elevation. In patch-clamp experiments, CRH increased the frequency and decay times of APs and decreased currents through A-type and delayed-rectifier potassium channels. These results suggest that CRH does not affect synaptic transmission per se, but modulates voltage-gated ion currents important for the generation of APs and hence elevates by this route overall neuronal activity.

  10. Effects of short-term Western diet on cerebral oxidative stress and diabetes related factors in APP x PS1 knock-in mice.

    Science.gov (United States)

    Studzinski, Christa M; Li, Feng; Bruce-Keller, Annadora J; Fernandez-Kim, Sun Ok; Zhang, Le; Weidner, Adam M; Markesbery, William R; Murphy, M Paul; Keller, Jeffrey N

    2009-02-01

    A chronic high fat Western diet (WD) promotes a variety of morbidity factors although experimental evidence for short-term WD mediating brain dysfunction remains to be elucidated. The amyloid precursor protein and presenilin-1 (APP x PS1) knock-in mouse model has been demonstrated to recapitulate some key features of Alzheimer's disease pathology, including amyloid-beta (Abeta) pathogenesis. In this study, we placed 1-month-old APP x PS1 mice and non-transgenic littermates on a WD for 4 weeks. The WD resulted in a significant elevation in protein oxidation and lipid peroxidation in the brain of APP x PS1 mice relative to non-transgenic littermates, which occurred in the absence of increased Abeta levels. Altered adipokine levels were also observed in APP x PS1 mice placed on a short-term WD, relative to non-transgenic littermates. Taken together, these data indicate that short-term WD is sufficient to selectively promote cerebral oxidative stress and metabolic disturbances in APP x PS1 knock-in mice, with increased oxidative stress preceding alterations in Abeta. These data have important implications for understanding how WD may potentially contribute to brain dysfunction and the development of neurodegenerative disorders such as Alzheimer's disease.

  11. Energy and expectation values of the PsH system

    International Nuclear Information System (INIS)

    Mitroy, J.

    2006-01-01

    Close to converged energies and expectation values for PsH are computed using a ground state wave function consisting of 1800 explicitly correlated gaussians. The best estimate of the Ps ∞ H energy was -0.789 196 740 hartree which is the lowest variational energy to date. The 2γ annihilation rate for Ps ∞ H was 2.471 78x10 9 s -1

  12. Simple sorting algorithm test based on CUDA

    OpenAIRE

    Meng, Hongyu; Guo, Fangjin

    2015-01-01

    With the development of computing technology, CUDA has become a very important tool. In computer programming, sorting algorithm is widely used. There are many simple sorting algorithms such as enumeration sort, bubble sort and merge sort. In this paper, we test some simple sorting algorithm based on CUDA and draw some useful conclusions.

  13. Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.

    Science.gov (United States)

    Janota, C S; Brites, D; Lemere, C A; Brito, M A

    2015-09-16

    Vascular and glial involvement in the development of neurodegenerative disorders, such as Alzheimer's disease (AD), and age-related brain vulnerabilities have been suggested. Therefore, we sought to: (i) investigate which vascular and glial events are evident in ageing and/or AD, (ii) to establish the temporal evolution of vascular and glial changes in AD-like and wild-type (WT) mice and (iii) to relate them to amyloid-β (Aβ) peptide accumulation. We examined immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice along ageing and disease progression (young-adulthood, middle- and old-age). Ageing resulted in the increase in receptor for advanced glycation endproducts expression, as well as the entrance of thrombin and albumin in hippocampal parenchyma. In contrast, the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both regions, was only related to AD pathogenesis. Hypovascularization was affected by both ageing and AD in the hippocampus, but resulted from the interaction between both factors in the cortex. Astrogliosis was a result of AD in hippocampus and of both factors in cortex, while microgliosis was associated with fibrillar amyloid plaques in AD-like mice and with the interaction between both factors in each of the studied regions. In sum, these data show that senile plaques precede vascular and glial alterations only in hippocampus, whereas in cortex, vascular and glial alterations, namely the loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. Hence, this study points to vascular and glial events that co-exist in AD pathogenesis and age-related brain vulnerabilities. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Cocaine Disrupts Histamine H3 Receptor Modulation of Dopamine D1 Receptor Signaling: σ1-D1-H3 Receptor Complexes as Key Targets for Reducing Cocaine's Effects

    Science.gov (United States)

    Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric

    2014-01-01

    The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455

  15. Cholesterol depletion induces dynamic confinement of the G-protein coupled serotonin(1A) receptor in the plasma membrane of living cells.

    Science.gov (United States)

    Pucadyil, Thomas J; Chattopadhyay, Amitabha

    2007-03-01

    Cholesterol is an essential constituent of eukaryotic membranes and plays a crucial role in membrane organization, dynamics, function, and sorting. It is often found distributed non-randomly in domains or pools in biological and model membranes and is thought to contribute to a segregated distribution of membrane constituents. Signal transduction events mediated by seven transmembrane domain G-protein coupled receptors (GPCRs) are the primary means by which cells communicate with and respond to their external environment. We analyzed the role of cholesterol in the plasma membrane organization of the G-protein coupled serotonin(1A) receptor by fluorescence recovery after photobleaching (FRAP) measurements with varying bleach spot sizes. Our results show that lateral diffusion parameters of serotonin(1A) receptors in normal cells are consistent with models describing diffusion of molecules in a homogenous membrane. Interestingly, these characteristics are altered in cholesterol-depleted cells in a manner that is consistent with dynamic confinement of serotonin(1A) receptors in the plasma membrane. Importantly, analysis of ligand binding and downstream signaling of the serotonin(1A) receptor suggests that receptor function is affected in a significantly different manner when intact cells or isolated membranes are depleted of cholesterol. These results assume significance in the context of interpreting effects of cholesterol depletion on diffusion characteristics of membrane proteins in particular, and cholesterol-dependent cellular processes in general.

  16. Heteroreceptor Complexes Formed by Dopamine D1, Histamine H3, and N-Methyl-D-Aspartate Glutamate Receptors as Targets to Prevent Neuronal Death in Alzheimer's Disease.

    Science.gov (United States)

    Rodríguez-Ruiz, Mar; Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Mallol, Josefa; Cortés, Antonio; Lluís, Carme; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Franco, Rafael

    2017-08-01

    Alzheimer's disease (AD) is a neurodegenerative disorder causing progressive memory loss and cognitive dysfunction. Anti-AD strategies targeting cell receptors consider them as isolated units. However, many cell surface receptors cooperate and physically contact each other forming complexes having different biochemical properties than individual receptors. We here report the discovery of dopamine D 1 , histamine H 3 , and N-methyl-D-aspartate (NMDA) glutamate receptor heteromers in heterologous systems and in rodent brain cortex. Heteromers were detected by co-immunoprecipitation and in situ proximity ligation assays (PLA) in the rat cortex where H 3 receptor agonists, via negative cross-talk, and H 3 receptor antagonists, via cross-antagonism, decreased D 1 receptor agonist signaling determined by ERK1/2 or Akt phosphorylation, and counteracted D 1 receptor-mediated excitotoxic cell death. Both D 1 and H 3 receptor antagonists also counteracted NMDA toxicity suggesting a complex interaction between NMDA receptors and D 1 -H 3 receptor heteromer function. Likely due to heteromerization, H 3 receptors act as allosteric regulator for D 1 and NMDA receptors. By bioluminescence resonance energy transfer (BRET), we demonstrated that D 1 or H 3 receptors form heteromers with NR1A/NR2B NMDA receptor subunits. D 1 -H 3 -NMDA receptor complexes were confirmed by BRET combined with fluorescence complementation. The endogenous expression of complexes in mouse cortex was determined by PLA and similar expression was observed in wild-type and APP/PS1 mice. Consistent with allosteric receptor-receptor interactions within the complex, H 3 receptor antagonists reduced NMDA or D 1 receptor-mediated excitotoxic cell death in cortical organotypic cultures. Moreover, H 3 receptor antagonists reverted the toxicity induced by ß 1-42 -amyloid peptide. Thus, histamine H 3 receptors in D 1 -H 3 -NMDA heteroreceptor complexes arise as promising targets to prevent neurodegeneration.

  17. Layers in sorting practices: Sorting out patients with potential cancer

    DEFF Research Database (Denmark)

    Møller, Naja Holten; Bjørn, Pernille

    2011-01-01

    for a particular patient. Due to the limited resources within the Danish healthcare system, initiating cancer pathways for all patients with a remote suspicion of cancer would crash the system, as it would be impossible for healthcare professionals to commit to the prescribed schedules and times defined...... they show that sorting patients before initiating a standardized cancer pathway is not a simple process of deciding on a predefined category that will stipulate particular dates and times. Instead, these informal sorting mechanisms show that the process of sorting patients prior to diagnosis......In the last couple of years, widespread use of standardized cancer pathways has been seen across a range of countries, including Denmark, to improve prognosis of cancer patients. In Denmark, standardized cancer pathways take the form of guidelines prescribing well-defined sequences where steps...

  18. Evidence for the effect of serotonin receptor 1A gene (HTR1A) polymorphism on tractability in Thoroughbred horses.

    Science.gov (United States)

    Hori, Y; Tozaki, T; Nambo, Y; Sato, F; Ishimaru, M; Inoue-Murayama, M; Fujita, K

    2016-02-01

    Tractability, or how easily animals can be trained and controlled, is an important behavioural trait for the management and training of domestic animals, but its genetic basis remains unclear. Polymorphisms in the serotonin receptor 1A gene (HTR1A) have been associated with individual variability in anxiety-related traits in several species. In this study, we examined the association between HTR1A polymorphisms and tractability in Thoroughbred horses. We assessed the tractability of 167 one-year-old horses reared at a training centre for racehorses using a questionnaire consisting of 17 items. A principal components analysis of answers contracted the data to five principal component (PC) scores. We genotyped two non-synonymous single nucleotide polymorphisms (SNPs) in the horse HTR1A coding region. We found that one of the two SNPs, c.709G>A, which causes an amino acid change at the intracellular region of the receptor, was significantly associated with scores of four of five PCs in fillies (all Ps Horses carrying an A allele at c.709G>A showed lower tractability. This result provides the first evidence that a polymorphism in a serotonin-related gene may affect tractability in horses with the effect partially different depending on sex. © 2015 Stichting International Foundation for Animal Genetics.

  19. Angiotensin II stimulates basolateral 50-pS K channels in the thick ascending limb.

    Science.gov (United States)

    Wang, Mingxiao; Luan, Haiyan; Wu, Peng; Fan, Lili; Wang, Lijun; Duan, Xinpeng; Zhang, Dandan; Wang, Wen-Hui; Gu, Ruimin

    2014-03-01

    We used the patch-clamp technique to examine the effect of angiotensin II (ANG II) on the basolateral K channels in the thick ascending limb (TAL) of the rat kidney. Application of ANG II increased the channel activity and the current amplitude of the basolateral 50-pS K channel. The stimulatory effect of ANG II on the K channels was completely abolished by losartan, an inhibitor of type 1 angiotensin receptor (AT1R), but not by PD123319, an AT2R antagonist. Moreover, inhibition of phospholipase C (PLC) and protein kinase C (PKC) also abrogated the stimulatory effect of ANG II on the basolateral K channels in the TAL. This suggests that the stimulatory effect of ANG II on the K channels was induced by activating PLC and PKC pathways. Western blotting demonstrated that ANG II increased the phosphorylation of c-Src at tyrosine residue 416, an indication of c-Src activation. This effect was mimicked by PKC stimulator but abolished by calphostin C. Moreover, inhibition of NADPH oxidase (NOX) also blocked the effect of ANG II on c-Src tyrosine phosphorylation. The role of Src-family protein tyrosine kinase (SFK) in mediating the effect of ANG II on the basolateral K channel was further suggested by the experiments in which inhibition of SFK abrogated the stimulatory effect of ANG II on the basolateral 50-pS K channel. We conclude that ANG II increases basolateral 50-pS K channel activity via AT1R and that activation of AT1R stimulates SFK by a PLC-PKC-NOX-dependent mechanism.

  20. The Container Problem in Bubble-Sort Graphs

    Science.gov (United States)

    Suzuki, Yasuto; Kaneko, Keiichi

    Bubble-sort graphs are variants of Cayley graphs. A bubble-sort graph is suitable as a topology for massively parallel systems because of its simple and regular structure. Therefore, in this study, we focus on n-bubble-sort graphs and propose an algorithm to obtain n-1 disjoint paths between two arbitrary nodes in time bounded by a polynomial in n, the degree of the graph plus one. We estimate the time complexity of the algorithm and the sum of the path lengths after proving the correctness of the algorithm. In addition, we report the results of computer experiments evaluating the average performance of the algorithm.

  1. Chip-based droplet sorting

    Energy Technology Data Exchange (ETDEWEB)

    Beer, Neil Reginald; Lee, Abraham; Hatch, Andrew

    2017-11-21

    A non-contact system for sorting monodisperse water-in-oil emulsion droplets in a microfluidic device based on the droplet's contents and their interaction with an applied electromagnetic field or by identification and sorting.

  2. PS1-12sk IS A PECULIAR SUPERNOVA FROM A He-RICH PROGENITOR SYSTEM IN A BRIGHTEST CLUSTER GALAXY ENVIRONMENT

    International Nuclear Information System (INIS)

    Sanders, N. E.; Soderberg, A. M.; Foley, R. J.; Chornock, R.; Milisavljevic, D.; Margutti, R.; Drout, M. R.; Moe, M.; Berger, E.; Brown, W. R.; Lunnan, R.; Smartt, S. J.; Fraser, M.; Kotak, R.; Magill, L.; Smith, K. W.; Wright, D.; Huang, K.; Urata, Y.; Mulchaey, J. S.

    2013-01-01

    We report on our discovery and observations of the Pan-STARRS1 supernova (SN) PS1-12sk, a transient with properties that indicate atypical star formation in its host galaxy cluster or pose a challenge to popular progenitor system models for this class of explosion. The optical spectra of PS1-12sk classify it as a Type Ibn SN (SN Ibn; cf. SN 2006jc), dominated by intermediate-width (3 × 10 3 km s –1 ) and time variable He I emission. Our multi-wavelength monitoring establishes the rise time dt ∼ 9-23 days and shows an NUV-NIR spectral energy distribution with temperature ∼> 17 × 10 3 K and a peak magnitude of M z = –18.88 ± 0.02 mag. SN Ibn spectroscopic properties are commonly interpreted as the signature of a massive star (17-100 M ☉ ) explosion within an He-enriched circumstellar medium. However, unlike previous SNe Ibn, PS1-12sk is associated with an elliptical brightest cluster galaxy, CGCG 208–042 (z = 0.054) in cluster RXC J0844.9+4258. The expected probability of an event like PS1-12sk in such environments is low given the measured infrequency of core-collapse SNe in red-sequence galaxies compounded by the low volumetric rate of SN Ibn. Furthermore, we find no evidence of star formation at the explosion site to sensitive limits (Σ Hα ∼ –3 M ☉ yr –1 kpc –2 ). We therefore discuss white dwarf binary systems as a possible progenitor channel for SNe Ibn. We conclude that PS1-12sk represents either a fortuitous and statistically unlikely discovery, evidence for a top-heavy initial mass function in galaxy cluster cooling flow filaments, or the first clue suggesting an alternate progenitor channel for SNe Ibn.

  3. Additive estrogenic effects of mixtures of frequently used UV filters on pS2-gene transcription in MCF-7 cells

    International Nuclear Information System (INIS)

    Heneweer, Marjoke; Muusse, Martine; Berg, Martin van den; Sanderson, J. Thomas

    2005-01-01

    In order to protect consumers from ultraviolet (UV) radiation and enhance light stability of the product, three to eight UV filters are usually added to consumer sunscreen products. High lipophilicity of the UV filters has been shown to cause bioaccumulation in fish and humans, leading to environmental levels of UV filters that are similar to those of PCBs and DDT. In this paper, estrogen-regulated pS2 gene transcription in the human mammary tumor cell line MCF-7 was used as a measure of estrogenicity of four individual UV filters. Since humans are exposed to more than one UV filter at a time, an equipotent binary mixture of 2-hydroxy-4-methoxy-benzophenone (BP-3) and its metabolite 2,4-dihydroxy benzophenone (BP-1), as well as an equipotent multi-component mixture of BP-1, BP-3, octyl methoxy cinnamate (OMC) and 3-(4-methylbenzylidene) camphor (4-MBC), were also evaluated for their ability to induce pS2 gene transcription in order to examine additivity. An estrogen receptor-mediated mechanism of action was expected for all UV filters. Therefore, our null-hypothesis was that combined estrogenic responses, measured as increased pS2 gene transcription in MCF-7 cells after exposure to mixtures of UV filters, are additive, according to a concentration-addition model. Not all UV filters produced a full concentration-response curve within the concentration range tested (100 nM-1 μM). Therefore, instead of using EC 50 values for comparison, the concentration at which each compound caused a 50% increase of basal pS2 gene transcription was defined as the C50 value for that compound and used to calculate relative potencies. For comparison, the EC 50 value of a compound is the concentration at which the compound elicits an effect that is 50% of its maximal effect. Individual UV filters increased pS2 gene transcription concentration-dependently with C50 values of 0.12 μM, 0.5 μM, 1.9 μM, and 1.0 μM for BP-1, BP-3, 4-MBC and OMC, respectively. Estradiol (E2) had a C50

  4. Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor 2 Axis Can Promote Mouse and Human Primary Mast Cell Angiogenic Potential through Upregulation of Vascular Endothelial Growth Factor-A and Matrix Metalloproteinase-2

    Directory of Open Access Journals (Sweden)

    Alena Chumanevich

    2016-01-01

    Full Text Available Mast cells (MC are present in most vascularized tissues around the vasculature likely exerting immunomodulatory functions. Endowed with diverse mediators, resident MC represent first-line fine-tuners of local microenvironment. Sphingosine-1-phosphate (S1P functions as a pluripotent signaling sphingolipid metabolite in health and disease. S1P formation occurs at low levels in resting MC and is upregulated upon activation. Its export can result in type 2 S1P receptor- (S1PR2- mediated stimulation of MC, further fueling inflammation. However, the role of S1PR2 ligation in proangiogenic vascular endothelial growth factor- (VEGF- A and matrix metalloproteinase- (MMP- 2 release from MC is unknown. Using a preclinical MC-dependent model of acute allergic responses and in vitro stimulated primary mouse bone marrow-derived MC (BMMC or human primary skin MC, we report that S1P signaling resulted in substantial amount of VEGF-A release. Similar experiments using S1pr2-deficient mice or BMMC or selective S1P receptor agonists or antagonists demonstrated that S1P/S1PR2 ligation on MC is important for VEGF-A secretion. Further, we show that S1P stimulation triggered transcriptional upregulation of VEGF-A and MMP-2 mRNA in human but not in mouse MC. S1P exposure also triggered MMP-2 secretion from human MC. These studies identify a novel proangiogenic axis encompassing MC/S1P/S1PR2 likely relevant to inflammation.

  5. PS Main Control Room (partial view)

    CERN Multimedia

    1974-01-01

    Jean-Pierre Potier (turning buttons) and Bertran Frammery (telephoning) on shift. The 26 GeV Synchrotron and later also its related machines (Linacs 1,2,3; PS-Booster; LEP-Injector Linacs and Electron-Positron Accumulator; Antiproton Accumulator, Antiproton Collector, Low Energy Antiproton Ring and more recently Antiproton Decelerator) were all controlled from the PS control room situated on the Meyrin site. The SPS and LEP were controlled from a separat control centre on the Prevessin site. In 2005 all controls were transferred to the Prevessin centre.

  6. Mutations in AtPS1 (Arabidopsis thaliana parallel spindle 1 lead to the production of diploid pollen grains.

    Directory of Open Access Journals (Sweden)

    Isabelle d'Erfurth

    2008-11-01

    Full Text Available Polyploidy has had a considerable impact on the evolution of many eukaryotes, especially angiosperms. Indeed, most--if not all-angiosperms have experienced at least one round of polyploidy during the course of their evolution, and many important crop plants are current polyploids. The occurrence of 2n gametes (diplogametes in diploid populations is widely recognised as the major source of polyploid formation. However, limited information is available on the genetic control of diplogamete production. Here, we describe the isolation and characterisation of the first gene, AtPS1 (Arabidopsis thaliana Parallel Spindle 1, implicated in the formation of a high frequency of diplogametes in plants. Atps1 mutants produce diploid male spores, diploid pollen grains, and spontaneous triploid plants in the next generation. Female meiosis is not affected in the mutant. We demonstrated that abnormal spindle orientation at male meiosis II leads to diplogamete formation. Most of the parent's heterozygosity is therefore conserved in the Atps1 diploid gametes, which is a key issue for plant breeding. The AtPS1 protein is conserved throughout the plant kingdom and carries domains suggestive of a regulatory function. The isolation of a gene involved in diplogamete production opens the way for new strategies in plant breeding programmes and progress in evolutionary studies.

  7. Algorithm Sorts Groups Of Data

    Science.gov (United States)

    Evans, J. D.

    1987-01-01

    For efficient sorting, algorithm finds set containing minimum or maximum most significant data. Sets of data sorted as desired. Sorting process simplified by reduction of each multielement set of data to single representative number. First, each set of data expressed as polynomial with suitably chosen base, using elements of set as coefficients. Most significant element placed in term containing largest exponent. Base selected by examining range in value of data elements. Resulting series summed to yield single representative number. Numbers easily sorted, and each such number converted back to original set of data by successive division. Program written in BASIC.

  8. Selection Signatures in the First Exon of Paralogous Receptor Kinase Genes from the Sym2 Region of the Pisum sativum L. Genome

    Directory of Open Access Journals (Sweden)

    Anton S. Sulima

    2017-11-01

    Full Text Available During the initial step of the symbiosis between legumes (Fabaceae and nitrogen-fixing bacteria (rhizobia, the bacterial signal molecule known as the Nod factor (nodulation factor is recognized by plant LysM motif-containing receptor-like kinases (LysM-RLKs. The fifth chromosome of barrel medic (Medicago truncatula Gaertn. contains a cluster of paralogous LysM-RLK genes, one of which is known to participate in symbiosis. In the syntenic region of the pea (Pisum sativum L. genome, three genes have been identified: PsK1 and PsSym37, two symbiosis-related LysM-RLK genes with known sequences, and the unsequenced PsSym2 gene which presumably encodes a LysM-RLK and is associated with increased selectivity to certain Nod factors. In this work, we identified a new gene encoding a LysM-RLK, designated as PsLykX, within the Sym2 genomic region. We sequenced the first exons (corresponding to the protein receptor domain of PsSym37, PsK1, and PsLykX from a large set of pea genotypes of diverse origin. The nucleotide diversity of these fragments was estimated and groups of haplotypes for each gene were revealed. Footprints of selection pressure were detected via comparative analyses of SNP distribution across the first exons of these genes and their homologs MtLYK2, MtLYK3, and MtLYK4 from M. truncatula retrieved from the Medicago Hapmap project. Despite the remarkable similarity among all the studied genes, they exhibited contrasting selection signatures, possibly pointing to diversification of their functions. Signatures of balancing selection were found in LysM1-encoding parts of PsSym37 and PsK1, suggesting that the diversity of these parts may be important for pea LysM-RLKs. The first exons of PsSym37 and PsK1 displayed signatures of purifying selection, as well as MtLYK2 of M. truncatula. Evidence of positive selection affecting primarily LysM domains was found in all three investigated M. truncatula genes, as well as in the pea gene PsLykX. The data

  9. Acoustic bubble sorting for ultrasound contrast agent enrichment.

    Science.gov (United States)

    Segers, Tim; Versluis, Michel

    2014-05-21

    An ultrasound contrast agent (UCA) suspension contains encapsulated microbubbles with a wide size distribution, with radii ranging from 1 to 10 μm. Medical transducers typically operate at a single frequency, therefore only a small selection of bubbles will resonate to the driving ultrasound pulse. Thus, the sensitivity can be improved by narrowing down the size distribution. Here, we present a simple lab-on-a-chip method to sort the population of microbubbles on-chip using a traveling ultrasound wave. First, we explore the physical parameter space of acoustic bubble sorting using well-defined bubble sizes formed in a flow-focusing device, then we demonstrate successful acoustic sorting of a commercial UCA. This novel sorting strategy may lead to an overall improvement of the sensitivity of contrast ultrasound by more than 10 dB.

  10. ScanSort{sup SM} at Whiteshell Laboratories for sorting of experimental cesium pond soil

    Energy Technology Data Exchange (ETDEWEB)

    Downey, H., E-mail: heath.downey@amecfw.com [Amec Foster Wheeler, Portland, ME (United States)

    2015-07-01

    The ScanSort{sup SM} soil sorting system is a unique and efficient radiological instrument used for measuring and sorting bulk soils and volumetric materials. The system performs automatic radioassay and segregation of preconditioned material using a gamma spectroscopy system mounted above a conveyor belt. It was deployed to the Whiteshell Laboratories site to process the excavated soils generated during the decommissioning of the former Experimental Cesium Pond. The ScanSort{sup SM} system was utilized to segregate material with Cs-137 concentrations above the established site unrestricted release and restricted site reuse levels as well as demonstrated the ability to accurately determine the radioactivity concentrations of the radiologically-impacted material and to confidently segregate volumes of that material for appropriate final disposition. (author)

  11. PS Booster - Festive colloquium

    CERN Multimedia

    2012-01-01

    A festive colloquium will be held to celebrate the 40th anniversary of the PS Booster on Friday, 28 September at 2 p.m. in the CERN council chamber. The meeting will be open to everybody. Read more on the PS Booster in the CERN Bulletin and in the CERN Courier.

  12. Sigma-1 receptor agonists directly inhibit Nav1.2/1.4 channels.

    Directory of Open Access Journals (Sweden)

    Xiao-Fei Gao

    Full Text Available (+-SKF 10047 (N-allyl-normetazocine is a prototypic and specific sigma-1 receptor agonist that has been used extensively to study the function of sigma-1 receptors. (+-SKF 10047 inhibits K(+, Na(+ and Ca2+ channels via sigma-1 receptor activation. We found that (+-SKF 10047 inhibited Na(V1.2 and Na(V1.4 channels independently of sigma-1 receptor activation. (+-SKF 10047 equally inhibited Na(V1.2/1.4 channel currents in HEK293T cells with abundant sigma-1 receptor expression and in COS-7 cells, which barely express sigma-1 receptors. The sigma-1 receptor antagonists BD 1063,BD 1047 and NE-100 did not block the inhibitory effects of (+-SKF-10047. Blocking of the PKA, PKC and G-protein pathways did not affect (+-SKF 10047 inhibition of Na(V1.2 channel currents. The sigma-1 receptor agonists Dextromethorphan (DM and 1,3-di-o-tolyl-guanidine (DTG also inhibited Na(V1.2 currents through a sigma-1 receptor-independent pathway. The (+-SKF 10047 inhibition of Na(V1.2 currents was use- and frequency-dependent. Point mutations demonstrated the importance of Phe(1764 and Tyr(1771 in the IV-segment 6 domain of the Na(V1.2 channel and Phe(1579 in the Na(V1.4 channel for (+-SKF 10047 inhibition. In conclusion, our results suggest that sigma-1 receptor agonists directly inhibit Na(V1.2/1.4 channels and that these interactions should be given special attention for future sigma-1 receptor function studies.

  13. Clopidogrel, a P2Y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Analia E Garcia

    Full Text Available The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS-induced arthritis model with four groups of rats: 1 untreated, 2 clopidogrel-treated, 3 PG-PS-induced, and 4 PG-PS-induced and clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-inflammatory cytokines (IL-1 beta, interferon (IFN gamma, and IL-6, an elevated neutrophil blood count and an increased circulating platelet count. Plasma levels of IL-10 were significantly lower in the PG-PS+clopidogrel group compared to the PG-PS group. Plasma levels of platelet factor 4 (PF4 were elevated in both the PG-PS and the PG-PS+clopidogrel groups, however PF4 levels showed no difference upon clopidogrel treatment, suggesting that the pro- inflammatory effect of clopidogrel may be due to its action on cells other than platelets. Histology indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation, blood vessel proliferation, subsynovial fibrosis and cartilage erosion upon treatment with clopidogrel in PG-PS-induced arthritis animals. In summary, animals treated with clopidogrel showed a pro-inflammatory effect in the PG-PS-induced arthritis animal model, which might not be mediated by platelets. Elucidation of the mechanism of clopidogrel-induced cell responses is important to understand the role of the P2Y12 receptor in inflammation.

  14. Clopidogrel, a P2Y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritis.

    Science.gov (United States)

    Garcia, Analia E; Mada, Sripal R; Rico, Mario C; Dela Cadena, Raul A; Kunapuli, Satya P

    2011-01-01

    The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS)-induced arthritis model with four groups of rats: 1) untreated, 2) clopidogrel-treated, 3) PG-PS-induced, and 4) PG-PS-induced and clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-inflammatory cytokines (IL-1 beta, interferon (IFN) gamma, and IL-6), an elevated neutrophil blood count and an increased circulating platelet count. Plasma levels of IL-10 were significantly lower in the PG-PS+clopidogrel group compared to the PG-PS group. Plasma levels of platelet factor 4 (PF4) were elevated in both the PG-PS and the PG-PS+clopidogrel groups, however PF4 levels showed no difference upon clopidogrel treatment, suggesting that the pro- inflammatory effect of clopidogrel may be due to its action on cells other than platelets. Histology indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation, blood vessel proliferation, subsynovial fibrosis and cartilage erosion upon treatment with clopidogrel in PG-PS-induced arthritis animals. In summary, animals treated with clopidogrel showed a pro-inflammatory effect in the PG-PS-induced arthritis animal model, which might not be mediated by platelets. Elucidation of the mechanism of clopidogrel-induced cell responses is important to understand the role of the P2Y12 receptor in inflammation.

  15. Symmetry of dipositronium Ps2

    International Nuclear Information System (INIS)

    Schrader, D.M.

    2004-01-01

    We work out the complete symmetry and spin problem for diatomic positronium Ps 2 for the ground and singly excited states of zero orbital angular momentum. The general form of the wave function for each state is given, with due regard to charge conjugation parity. Annihilation rates are discussed, and correlations to dissociation products are deduced. We indicate how the approach is extensible to larger aggregates: i.e., PsPs n , n>2

  16. PhySortR: a fast, flexible tool for sorting phylogenetic trees in R.

    Science.gov (United States)

    Stephens, Timothy G; Bhattacharya, Debashish; Ragan, Mark A; Chan, Cheong Xin

    2016-01-01

    A frequent bottleneck in interpreting phylogenomic output is the need to screen often thousands of trees for features of interest, particularly robust clades of specific taxa, as evidence of monophyletic relationship and/or reticulated evolution. Here we present PhySortR, a fast, flexible R package for classifying phylogenetic trees. Unlike existing utilities, PhySortR allows for identification of both exclusive and non-exclusive clades uniting the target taxa based on tip labels (i.e., leaves) on a tree, with customisable options to assess clades within the context of the whole tree. Using simulated and empirical datasets, we demonstrate the potential and scalability of PhySortR in analysis of thousands of phylogenetic trees without a priori assumption of tree-rooting, and in yielding readily interpretable trees that unambiguously satisfy the query. PhySortR is a command-line tool that is freely available and easily automatable.

  17. EGFRvIII escapes down-regulation due to impaired internalization and sorting to lysosomes

    DEFF Research Database (Denmark)

    Grandal, Michael V; Zandi, Roza; Pedersen, Mikkel W

    2007-01-01

    . Moreover, internalized EGFRvIII is recycled rather than delivered to lysosomes. EGFRvIII binds the ubiquitin ligase c-Cbl via Grb2, whereas binding via phosphorylated tyrosine residue 1045 seems to be limited. Despite c-Cbl binding, the receptor fails to become effectively ubiquitinylated. Thus, our...... results suggest that the long lifetime of EGFRvIII is caused by inefficient internalization and impaired sorting to lysosomes due to lack of effective ubiquitinylation....

  18. Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon.

    Science.gov (United States)

    Baño Otalora, Beatriz; Popovic, Natalija; Gambini, Juan; Popovic, Miroljub; Viña, José; Bonet-Costa, Vicent; Reiter, Russel J; Camello, Pedro Javier; Rol, Maria Ángeles; Madrid, Juan Antonio

    2012-08-01

    Alzheimer disease (AD) is a neurodegenerative disorder that primarily causes β-amyloid accumulation in the brain, resulting in cognitive and behavioral deficits. AD patients, however, also suffer from severe circadian rhythm disruptions, and the underlying causes are still not fully known. Patients with AD show reduced systemic melatonin levels. This may contribute to their symptoms, since melatonin is an effective chronobiotic and antioxidant with neuroprotective properties. Here, the authors critically assessed the effects of long-term melatonin treatment on circadian system function, hippocampal oxidative stress, and spatial memory performance in the APPswe/PS1 double transgenic (Tg) mouse model of AD. To test if melatonin MT1/MT2 receptor activation, alone, was involved, the authors chronically treated some mice with the selective MT1/MT2 receptor agonist ramelteon. The results indicate that many of the circadian and behavioral parameters measured, including oxidative stress markers, were not significantly affected in these AD mice. During the day, though, Tg controls (Tg-CON) showed significantly higher mean activity and body temperature (BT) than wild-type (WT) mice. Overall, BT rhythm amplitude was significantly lower in Tg than in WT mice. Although melatonin treatment had no effect, ramelteon significantly reduced the amplitude of the BT rhythm in Tg mice. Towards the end of the experiment, Tg mice treated with ramelteon (Tg-RAM) showed significantly higher circadian rhythm fragmentation than Tg-CON and reduced circadian BT rhythm strength. The free-running period (τ) for the BT and locomotor activity (LA) rhythms of Tg-CON was RAM compared with Tg-CON animals. These results suggest that not all aspects of the circadian system are affected in the APPswe/PS1 mice. Therefore, care should be taken when extending the results obtained in Tg mice to develop new therapies in humans. This study also revealed the complexity in the therapeutic actions of melatonin

  19. Sorting out Downside Beta

    NARCIS (Netherlands)

    G.T. Post (Thierry); P. van Vliet (Pim); S.D. Lansdorp (Simon)

    2009-01-01

    textabstractDownside risk, when properly defined and estimated, helps to explain the cross-section of US stock returns. Sorting stocks by a proper estimate of downside market beta leads to a substantially larger cross-sectional spread in average returns than sorting on regular market beta. This

  20. Clinical and Patient-reported Outcomes in Patients with Psoriatic Arthritis (PsA) by Body Surface Area Affected by Psoriasis: Results from the Corrona PsA/Spondyloarthritis Registry.

    Science.gov (United States)

    Mease, Philip J; Karki, Chitra; Palmer, Jacqueline B; Etzel, Carol J; Kavanaugh, Arthur; Ritchlin, Christopher T; Malley, Wendi; Herrera, Vivian; Tran, Melody; Greenberg, Jeffrey D

    2017-08-01

    Psoriatic arthritis (PsA) is commonly comorbid with psoriasis; the extent of skin lesions is a major contributor to psoriatic disease severity/burden. We evaluated whether extent of skin involvement with psoriasis [body surface area (BSA) > 3% vs ≤ 3%] affects overall clinical and patient-reported outcomes (PRO) in patients with PsA. Using the Corrona PsA/Spondyloarthritis Registry, patient characteristics, disease activity, and PRO at registry enrollment were assessed for patients with PsA aged ≥ 18 years with BSA > 3% versus ≤ 3%. Regression models were used to evaluate associations of BSA level with outcome [modified minimal disease activity (MDA), Health Assessment Questionnaire (HAQ) score, patient-reported pain and fatigue, and the Work Productivity and Activity Impairment questionnaire score]. Adjustments were made for age, sex, race, body mass index, disease duration, and history of biologics, disease-modifying antirheumatic drug, and prednisone use. This analysis included 1240 patients with PsA with known BSA level (n = 451, BSA > 3%; n = 789, BSA ≤ 3%). After adjusting for potential confounding variables, patients with BSA > 3% versus ≤ 3% had greater patient-reported pain and fatigue and higher HAQ scores (p = 2.33 × 10 -8 , p = 0.002, and p = 1.21 × 10 -7 , respectively), were 1.7× more likely not to be in modified MDA (95% CI 1.21-2.41, p = 0.002), and were 2.1× more likely to have overall work impairment (1.37-3.21, p = 0.0001). These Corrona Registry data show that substantial skin involvement (BSA > 3%) is associated with greater PsA disease burden, underscoring the importance of assessing and effectively managing psoriasis in patients with PsA because this may be a contributing factor in PsA severity.

  1. A faster 1.375-approximation algorithm for sorting by transpositions.

    Science.gov (United States)

    Cunha, Luís Felipe I; Kowada, Luis Antonio B; Hausen, Rodrigo de A; de Figueiredo, Celina M H

    2015-11-01

    Sorting by Transpositions is an NP-hard problem for which several polynomial-time approximation algorithms have been developed. Hartman and Shamir (2006) developed a 1.5-approximation [Formula: see text] algorithm, whose running time was improved to O(nlogn) by Feng and Zhu (2007) with a data structure they defined, the permutation tree. Elias and Hartman (2006) developed a 1.375-approximation O(n(2)) algorithm, and Firoz et al. (2011) claimed an improvement to the running time, from O(n(2)) to O(nlogn), by using the permutation tree. We provide counter-examples to the correctness of Firoz et al.'s strategy, showing that it is not possible to reach a component by sufficient extensions using the method proposed by them. In addition, we propose a 1.375-approximation algorithm, modifying Elias and Hartman's approach with the use of permutation trees and achieving O(nlogn) time.

  2. Three Sorts of Naturalism

    DEFF Research Database (Denmark)

    Fink, Hans

    2006-01-01

    In "Two sorts of Naturalism" John McDowell is sketching his own sort of naturalism in ethics as an alternative to "bald naturalism". In this paper I distinguish materialist, idealist and absolute conceptions of nature and of naturalism in order to provide a framework for a clearer understanding...

  3. PS1-12sk IS A PECULIAR SUPERNOVA FROM A He-RICH PROGENITOR SYSTEM IN A BRIGHTEST CLUSTER GALAXY ENVIRONMENT

    Energy Technology Data Exchange (ETDEWEB)

    Sanders, N. E.; Soderberg, A. M.; Foley, R. J.; Chornock, R.; Milisavljevic, D.; Margutti, R.; Drout, M. R.; Moe, M.; Berger, E.; Brown, W. R.; Lunnan, R. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Smartt, S. J.; Fraser, M.; Kotak, R.; Magill, L.; Smith, K. W.; Wright, D. [Astrophysics Research Centre, School of Maths and Physics, Queens University, Belfast BT7 1NN (United Kingdom); Huang, K. [Academia Sinica Institute of Astronomy and Astrophysics, Taipei 106, Taiwan (China); Urata, Y. [Institute of Astronomy, National Central University, Chung-Li 32054, Taiwan (China); Mulchaey, J. S., E-mail: nsanders@cfa.harvard.edu [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); and others

    2013-05-20

    We report on our discovery and observations of the Pan-STARRS1 supernova (SN) PS1-12sk, a transient with properties that indicate atypical star formation in its host galaxy cluster or pose a challenge to popular progenitor system models for this class of explosion. The optical spectra of PS1-12sk classify it as a Type Ibn SN (SN Ibn; cf. SN 2006jc), dominated by intermediate-width (3 Multiplication-Sign 10{sup 3} km s{sup -1}) and time variable He I emission. Our multi-wavelength monitoring establishes the rise time dt {approx} 9-23 days and shows an NUV-NIR spectral energy distribution with temperature {approx}> 17 Multiplication-Sign 10{sup 3} K and a peak magnitude of M{sub z} = -18.88 {+-} 0.02 mag. SN Ibn spectroscopic properties are commonly interpreted as the signature of a massive star (17-100 M{sub Sun }) explosion within an He-enriched circumstellar medium. However, unlike previous SNe Ibn, PS1-12sk is associated with an elliptical brightest cluster galaxy, CGCG 208-042 (z = 0.054) in cluster RXC J0844.9+4258. The expected probability of an event like PS1-12sk in such environments is low given the measured infrequency of core-collapse SNe in red-sequence galaxies compounded by the low volumetric rate of SN Ibn. Furthermore, we find no evidence of star formation at the explosion site to sensitive limits ({Sigma}{sub H{alpha}} {approx}< 2 Multiplication-Sign 10{sup -3} M{sub Sun} yr{sup -1} kpc{sup -2}). We therefore discuss white dwarf binary systems as a possible progenitor channel for SNe Ibn. We conclude that PS1-12sk represents either a fortuitous and statistically unlikely discovery, evidence for a top-heavy initial mass function in galaxy cluster cooling flow filaments, or the first clue suggesting an alternate progenitor channel for SNe Ibn.

  4. Enhancement of Selection, Bubble and Insertion Sorting Algorithm

    OpenAIRE

    Muhammad Farooq Umar; Ehsan Ullah Munir; Shafqat Ali Shad; Muhammad Wasif Nisar

    2014-01-01

    In everyday life there is a large amount of data to arrange because sorting removes any ambiguities and make the data analysis and data processing very easy, efficient and provides with cost less effort. In this study a set of improved sorting algorithms are proposed which gives better performance and design idea. In this study five new sorting algorithms (Bi-directional Selection Sort, Bi-directional bubble sort, MIDBiDirectional Selection Sort, MIDBidirectional bubble sort and linear insert...

  5. Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal-anchored receptors.

    Science.gov (United States)

    Becker, Thomas; Pfannschmidt, Sylvia; Guiard, Bernard; Stojanovski, Diana; Milenkovic, Dusanka; Kutik, Stephan; Pfanner, Nikolaus; Meisinger, Chris; Wiedemann, Nils

    2008-01-04

    The translocase of the outer membrane (TOM complex) is the central entry gate for nuclear-encoded mitochondrial precursor proteins. All Tom proteins are also encoded by nuclear genes and synthesized as precursors in the cytosol. The channel-forming beta-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly machinery (SAM complex). A further outer membrane protein, Mim1, plays a less defined role in assembly of Tom40 into the TOM complex. The three receptors Tom20, Tom22, and Tom70 are anchored in the outer membrane by a single transmembrane alpha-helix, located at the N terminus in the case of Tom20 and Tom70 (signal-anchored) or in the C-terminal portion in the case of Tom22 (tail-anchored). Insertion of the precursor of Tom22 into the outer membrane requires pre-existing Tom receptors while the import pathway of the precursors of Tom20 and Tom70 is only poorly understood. We report that Mim1 is required for efficient membrane insertion and assembly of Tom20 and Tom70, but not Tom22. We show that Mim1 associates with SAM(core) components to a large SAM complex, explaining its role in late steps of the assembly pathway of Tom40. We conclude that Mim1 is not only required for biogenesis of the beta-barrel protein Tom40 but also for membrane insertion and assembly of signal-anchored Tom receptors. Thus, Mim1 plays an important role in the efficient assembly of the mitochondrial TOM complex.

  6. Effect of P/S ratio (0.5 vs 0.9) on hepatic LDL transport at three levels of dietary cholesterol in cynomolgus macaques

    International Nuclear Information System (INIS)

    Hunt, C.E.; Funk, G.M.; Turley, S.D.; Spady, D.K.; Dietschy, J.M.

    1990-01-01

    Interaction between dietary polyunsaturated to saturated (P/S) fatty acid ratio and cholesterol (C) was studied in 6 groups of male cynomolgus macaques fed diets (oleic acid constant) for 72 weeks as follows (C mg/Cal-P/S): (1), 0.06 - 0.5; (2), 0.06-0.9, (3), 0.28-0.5; (4), 0.28-0.9; (5), 2,35-0.5; (6), 2,35-0.9. Plasma C was proportional to dietary C and was affected significantly by P/S in 1 and 2 only. Mean plasma C (mg/dl) at 72 weeks was: (1) 158; (2) 117; (3) 320; (4) 284; (5) 602; (6) 601. LDL-C was significantly higher in (1) than in (2) (90 vs 65 mg/dl). In vivo LDL turnover studies showed that LDL clearance was suppressed by excess dietary C and by saturated fats in low C diets. Receptor-independent clearance was relatively constant. Hepatic LDL transport was determined after injection of 125I-cellobiose-LDL. Hepatic LDL-C uptake was greater in (2) than in (1). LDL-C synthesis was reduced in (4) and (6) compared to (3) and (5), respectively. The authors conclude that (i) hepatic LDL receptor activity is altered by degree of saturation in dietary triglycerides when dietary C is minimal and (ii) saturated triglycerides enhance LDL-C synthesis when dietary C is ample in this model

  7. IRS-1: essential for insulin- and IL-4-stimulated mitogenesis in hematopoietic cells.

    Science.gov (United States)

    Wang, L M; Myers, M G; Sun, X J; Aaronson, S A; White, M; Pierce, J H

    1993-09-17

    Although several interleukin-3 (IL-3)-dependent cell lines proliferate in response to IL-4 or insulin, the 32D line does not. Insulin and IL-4 sensitivity was restored to 32D cells by expression of IRS-1, the principal substrate of the insulin receptor. Although 32D cells possessed receptors for both factors, they lacked the IRS-1--related protein, 4PS, which becomes phosphorylated by tyrosine in insulin- or IL-4--responsive lines after stimulation. These results indicate that factors that bind unrelated receptors can use similar mitogenic signaling pathways in hematopoietic cells and that 4PS and IRS-1 are functionally similar proteins that are essential for insulin- and IL-4--induced proliferation.

  8. Early-Life Stress Does Not Aggravate Spatial Memory or the Process of Hippocampal Neurogenesis in Adult and Middle-Aged APP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Lianne Hoeijmakers

    2018-03-01

    Full Text Available Life-time experiences are thought to influence the risk to develop the neurodegenerative disorder Alzheimer’s disease (AD. In particular, early-life stress (ES may modulate the onset and progression of AD. There is recent evidence by our group and others that AD-related neuropathological progression and the associated neuroimmune responses are modulated by ES in the classic APPswe/PS1dE9 mouse model for AD. We here extend our previous study on ES mediated modulation of neuropathology and neuroinflammation and address in the same cohort of mice whether ES accelerates and/or aggravates AD-induced cognitive decline and alterations in the process of adult hippocampal neurogenesis (AHN, a form of brain plasticity. Chronic ES was induced by limiting bedding and nesting material during the first postnatal week and is known to induce cognitive deficits by 4 months in wild type (WT mice. The onset of cognitive decline in APP/PS1 mice generally starts around 6 months of age. We here tested mice at ages 2–4 months to study acceleration and at ages 8–10 months for aggravation of the APP/PS1 phenotype. ES-exposed WT and APP/PS1 mice were able to perform the object recognition (ORT and location tasks (OLT at 2 months of age. Interestingly, at 3 months, ES induced impairments in the performance of the OLT in WT, but not in APP/PS1 mice. APP/PS1 mice exhibited alterations in hippocampal cell proliferation and differentiation, but ES exposure did not further change this. At 9 months, APP/PS1 mice exhibited impaired performance in the Morris Water Maze (MWM task, as well as reductions in markers of the AHN process, which were not further modulated by ES exposure. In addition, we observed a so far unreported hyperactivity in ES-exposed mice at 8 months of age, which hampered assessment of cognitive functions in the ORT and OLT. In conclusion, while ES has been reported to modulate AD neuropathology and neuroinflammation before, it failed to accelerate or

  9. Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease

    Science.gov (United States)

    Kim, Hye Yun; Kim, Hyunjin V.; Yoon, Jin H.; Kang, Bo Ram; Cho, Soo Min; Lee, Sejin; Kim, Ji Yoon; Kim, Joo Won; Cho, Yakdol; Woo, Jiwan; Kim, YoungSoo

    2014-01-01

    Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages. PMID:25502280

  10. Generation of the SCN1A epilepsy mutation in hiPS cells using the TALEN technique

    Science.gov (United States)

    Chen, Wanjuan; Liu, Jingxin; Zhang, Longmei; Xu, Huijuan; Guo, Xiaogang; Deng, Sihao; Liu, Lipeng; Yu, Daiguan; Chen, Yonglong; Li, Zhiyuan

    2014-06-01

    Human induced pluripotent stem cells (iPSC) can be used to understand the pathological mechanisms of human disease. These cells are a promising source for cell-replacement therapy. However, such studies require genetically defined conditions. Such genetic manipulations can be performed using the novel Transcription Activator-Like Effector Nucleases (TALENs), which generate site-specific double-strand DNA breaks (DSBs) with high efficiency and precision. Combining the TALEN and iPSC methods, we developed two iPS cell lines by generating the point mutation A5768G in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1 α subunit. The engineered iPSC maintained pluripotency and successfully differentiated into neurons with normal functional characteristics. The two cell lines differ exclusively at the epilepsy-susceptibility variant. The ability to robustly introduce disease-causing point mutations in normal hiPS cell lines can be used to generate a human cell model for studying epileptic mechanisms and for drug screening.

  11. Sortilin 1 Loss-of-Function Protects Against Cholestatic Liver Injury by Attenuating Hepatic Bile Acid Accumulation in Bile Duct Ligated Mice.

    Science.gov (United States)

    Li, Jibiao; Woolbright, Benjamin L; Zhao, Wen; Wang, Yifeng; Matye, David; Hagenbuch, Bruno; Jaeschke, Hartmut; Li, Tiangang

    2018-01-01

    Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid (BA) metabolism. This study further investigated the role of Sort1 in modulating BA detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 knockout (KO) mice had attenuated liver injury 24 h after bile duct ligation (BDL), which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger BA pool size than sham-operated wildtype (WT) mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic BA accumulation and smaller BA pool size. After 14 days BDL, Sort1 KO mice showed significantly lower hepatic BA concentration and reduced expression of inflammatory and fibrotic marker genes, but similar degree of liver fibrosis compared with WT mice. Unbiased quantitative proteomics revealed that Sort1 KO mice had increased hepatic BA sulfotransferase 2A1, but unaltered phase-I BA metabolizing cytochrome P450s or phase-III BA efflux transporters. Consistently, Sort1 KO mice showed elevated plasma sulfated taurocholate after BDL. Finally, we found that liver Sort1 was repressed after BDL, which may be due to BA activation of farnesoid x receptor. In conclusion, we report a role of Sort1 in the regulation of hepatic BA detoxification and cholestatic liver injury in mice. The mechanisms underlying increased hepatic BA elimination in Sort1 KO mice after BDL require further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. CellSort: a support vector machine tool for optimizing fluorescence-activated cell sorting and reducing experimental effort.

    Science.gov (United States)

    Yu, Jessica S; Pertusi, Dante A; Adeniran, Adebola V; Tyo, Keith E J

    2017-03-15

    High throughput screening by fluorescence activated cell sorting (FACS) is a common task in protein engineering and directed evolution. It can also be a rate-limiting step if high false positive or negative rates necessitate multiple rounds of enrichment. Current FACS software requires the user to define sorting gates by intuition and is practically limited to two dimensions. In cases when multiple rounds of enrichment are required, the software cannot forecast the enrichment effort required. We have developed CellSort, a support vector machine (SVM) algorithm that identifies optimal sorting gates based on machine learning using positive and negative control populations. CellSort can take advantage of more than two dimensions to enhance the ability to distinguish between populations. We also present a Bayesian approach to predict the number of sorting rounds required to enrich a population from a given library size. This Bayesian approach allowed us to determine strategies for biasing the sorting gates in order to reduce the required number of enrichment rounds. This algorithm should be generally useful for improve sorting outcomes and reducing effort when using FACS. Source code available at http://tyolab.northwestern.edu/tools/ . k-tyo@northwestern.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  13. Delay-line cables for the fast bumpers in the PS.

    CERN Multimedia

    CERN PhotoLab

    1976-01-01

    For 'continuous transfer' to the SPS, the beam accelerated in the PS is shaved off over several turns, so as to form a continuous sequence of bunches several times the length of the PS circumference. Fast bumpers, powered in a 'staircase' way, displace the PS beam stepwise towards the ejection septum. Each step lasts 2.1 microsec and the cable drums in this picture contain some of the bumper delay-lines of altogether 10 km.

  14. Obesity and Hepatic Steatosis Are Associated with Elevated Serum Amyloid Beta in Metabolically Stressed APPswe/PS1dE9 Mice.

    Directory of Open Access Journals (Sweden)

    Feng-Shiun Shie

    Full Text Available Diabesity-associated metabolic stresses modulate the development of Alzheimer's disease (AD. For further insights into the underlying mechanisms, we examine whether the genetic background of APPswe/PS1dE9 at the prodromal stage of AD affects peripheral metabolism in the context of diabesity. We characterized APPswe/PS1dE9 transgenic mice treated with a combination of high-fat diet with streptozotocin (HFSTZ in the early stage of AD. HFSTZ-treated APPswe/PS1dE9 transgenic mice exhibited worse metabolic stresses related to diabesity, while serum β-amyloid levels were elevated and hepatic steatosis became apparent. Importantly, two-way analysis of variance shows a significant interaction between HFSTZ and genetic background of AD, indicating that APPswe/PS1dE9 transgenic mice are more vulnerable to HFSTZ treatment. In addition, body weight gain, high hepatic triglyceride, and hyperglycemia were positively associated with serum β-amyloid, as validated by Pearson's correlation analysis. Our data suggests that the interplay between genetic background of AD and HFSTZ-induced metabolic stresses contributes to the development of obesity and hepatic steatosis. Alleviating metabolic stresses including dysglycemia, obesity, and hepatic steatosis could be critical to prevent peripheral β-amyloid accumulation at the early stage of AD.

  15. Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

    International Nuclear Information System (INIS)

    Zou, Yang; Liu, Fa-Ying; Liu, Huai; Wang, Feng; Li, Wei; Huang, Mei-Zhen; Huang, Yan; Yuan, Xiao-Qun; Xu, Xiao-Yun; Huang, Ou-Ping; He, Ming

    2014-01-01

    The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively

  16. Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yang; Liu, Fa-Ying; Liu, Huai; Wang, Feng [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Li, Wei [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Huang, Mei-Zhen [Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); Huang, Yan; Yuan, Xiao-Qun [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Xu, Xiao-Yun [Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); Huang, Ou-Ping, E-mail: huangouping@gmail.com [Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); He, Ming, E-mail: jxhm56@hotmail.com [Department of Pharmacology and Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang 330006 (China)

    2014-03-15

    The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively

  17. Genomic differentiation among two strains of the PS1 clade isolated from geographically separated marine habitats

    KAUST Repository

    Jimenez Infante, Francy M.; Ngugi, David; Alam, Intikhab; Rashid, Mamoon; Ba Alawi, Wail; Kamau, Allan; Bajic, Vladimir B.; Stingl, Ulrich

    2014-01-01

    Using dilution-to-extinction cultivation, we isolated a strain affiliated with the PS1 clade from surface waters of the Red Sea. Strain RS24 represents the second isolate of this group of marine Alphaproteobacteria after IMCC14465 that was isolated

  18. Surface acoustic wave actuated cell sorting (SAWACS).

    Science.gov (United States)

    Franke, T; Braunmüller, S; Schmid, L; Wixforth, A; Weitz, D A

    2010-03-21

    We describe a novel microfluidic cell sorter which operates in continuous flow at high sorting rates. The device is based on a surface acoustic wave cell-sorting scheme and combines many advantages of fluorescence activated cell sorting (FACS) and fluorescence activated droplet sorting (FADS) in microfluidic channels. It is fully integrated on a PDMS device, and allows fast electronic control of cell diversion. We direct cells by acoustic streaming excited by a surface acoustic wave which deflects the fluid independently of the contrast in material properties of deflected objects and the continuous phase; thus the device underlying principle works without additional enhancement of the sorting by prior labelling of the cells with responsive markers such as magnetic or polarizable beads. Single cells are sorted directly from bulk media at rates as fast as several kHz without prior encapsulation into liquid droplet compartments as in traditional FACS. We have successfully directed HaCaT cells (human keratinocytes), fibroblasts from mice and MV3 melanoma cells. The low shear forces of this sorting method ensure that cells survive after sorting.

  19. Real-life experience of using conventional disease-modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA). Retrospective analysis of the efficacy of methotrexate, sulfasalazine, and leflunomide in PsA in comparison to spondyloarthritides other than PsA and literature review of the use of conventional DMARDs in PsA

    Science.gov (United States)

    Roussou, Euthalia; Bouraoui, Aicha

    2017-01-01

    Objective With the aim of assessing the response to treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) used in patients with psoriatic arthritis (PsA), data on methotrexate, sulfasalazine (SSZ), and leflunomide were analyzed from baseline and subsequent follow-up (FU) questionnaires completed by patients with either PsA or other spondyloarthritides (SpAs). Material and Methods A single-center real-life retrospective analysis was performed by obtaining clinical data via questionnaires administered before and after treatment. The indices used were erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Function Index (BASFI), wellbeing (WB), and treatment effect (TxE). The indices measured at baseline were compared with those measured on one occasion in a FU visit at least 1 year later. Results A total of 73 patients, 51 with PsA (mean age 49.8±12.8 years; male-to-female ratio [M:F]=18:33) and 22 with other SpAs (mean age 50.6±16 years; M:F=2:20), were studied. BASDAI, BASFI, and WB displayed consistent improvements during FU assessments in both PsA patients and controls in comparison to baseline values. SSZ exhibited better efficacy as confirmed by TxE in both PsA patients and controls. ESR and CRP displayed no differences in either the PsA or the SpA group between the cases before and after treatment. Conclusion Real-life retrospective analysis of three DMARDs used in PsA (and SpAs other than PsA) demonstrated that all three DMARDs that were used brought about improvements in BASDAI, BASFI, TxE, and WB. However, the greatest improvements at FU were seen with SSZ use in both PsA and control cohorts. PMID:28293446

  20. Cache-Aware and Cache-Oblivious Adaptive Sorting

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf; Moruz, Gabriel

    2005-01-01

    Two new adaptive sorting algorithms are introduced which perform an optimal number of comparisons with respect to the number of inversions in the input. The first algorithm is based on a new linear time reduction to (non-adaptive) sorting. The second algorithm is based on a new division protocol...... for the GenericSort algorithm by Estivill-Castro and Wood. From both algorithms we derive I/O-optimal cache-aware and cache-oblivious adaptive sorting algorithms. These are the first I/O-optimal adaptive sorting algorithms....

  1. Proceedings of the workshop on the PS-spin collider

    International Nuclear Information System (INIS)

    Mori, Yoshiharu

    1993-05-01

    This volume is a record of the PS-Spin Collider Workshop which was held at KEK, Jan. 31-Feb.1, 1992. As a future project of the KEK 12-GeV proton synchrotron (KEK-PS), the hadron collider (PS-Collider), has been under discussion. Originally, the PSC was designed for heavy ion beam collisions with the energy range of 5-7 GeV/u. If polarized protons are accelerated in PSC, 19 x 19 GeV collisions are possible. This workshop was proposed to bring together interested experimentalists and accelerator physicists to discuss the case that could be made for polarization physics and the technical feasibility at the PS Spin Collider. More than 30 physicists participated in the workshop and very interesting and useful discussions took place. (author)

  2. TIM-1 Promotes Hepatitis C Virus Cell Attachment and Infection.

    Science.gov (United States)

    Wang, Jing; Qiao, Luhua; Hou, Zhouhua; Luo, Guangxiang

    2017-01-15

    Human TIM and TAM family proteins were recently found to serve as phosphatidylserine (PS) receptors which promote infections by many different viruses, including dengue virus, West Nile virus, Ebola virus, Marburg virus, and Zika virus. In the present study, we provide substantial evidence demonstrating that TIM-1 is important for efficient infection by hepatitis C virus (HCV). The knockdown of TIM-1 expression significantly reduced HCV infection but not HCV RNA replication. Likewise, TIM-1 knockout in Huh-7.5 cells remarkably lowered HCV cell attachment and subsequent HCV infection. More significantly, the impairment of HCV infection in the TIM-1 knockout cells could be restored completely by ectopic expression of TIM-1 but not TIM-3 or TIM-4. Additionally, HCV infection and cell attachment were inhibited by PS but not by phosphatidylcholine (PC), demonstrating that TIM-1-mediated enhancement of HCV infection is PS dependent. The exposure of PS on the HCV envelope was confirmed by immunoprecipitation of HCV particles with a PS-specific monoclonal antibody. Collectively, these findings demonstrate that TIM-1 promotes HCV infection by serving as an attachment receptor for binding to PS exposed on the HCV envelope. TIM family proteins were recently found to enhance infections by many different viruses, including several members of the Flaviviridae family. However, their importance in HCV infection has not previously been examined experimentally. The TIM family proteins include three members in humans: TIM-1, TIM-3, and TIM-4. The findings derived from our studies demonstrate that TIM-1, but not TIM-3 or TIM-4, promotes HCV infection by functioning as an HCV attachment factor. Knockout of the TIM-1 gene resulted in a remarkable reduction of HCV cell attachment and infection. PS-containing liposomes blocked HCV cell attachment and subsequent HCV infection. HCV particles could also be precipitated with a PS-specific monoclonal antibody. These findings suggest that TIM-1

  3. An Unsupervised Online Spike-Sorting Framework.

    Science.gov (United States)

    Knieling, Simeon; Sridharan, Kousik S; Belardinelli, Paolo; Naros, Georgios; Weiss, Daniel; Mormann, Florian; Gharabaghi, Alireza

    2016-08-01

    Extracellular neuronal microelectrode recordings can include action potentials from multiple neurons. To separate spikes from different neurons, they can be sorted according to their shape, a procedure referred to as spike-sorting. Several algorithms have been reported to solve this task. However, when clustering outcomes are unsatisfactory, most of them are difficult to adjust to achieve the desired results. We present an online spike-sorting framework that uses feature normalization and weighting to maximize the distinctiveness between different spike shapes. Furthermore, multiple criteria are applied to either facilitate or prevent cluster fusion, thereby enabling experimenters to fine-tune the sorting process. We compare our method to established unsupervised offline (Wave_Clus (WC)) and online (OSort (OS)) algorithms by examining their performance in sorting various test datasets using two different scoring systems (AMI and the Adamos metric). Furthermore, we evaluate sorting capabilities on intra-operative recordings using established quality metrics. Compared to WC and OS, our algorithm achieved comparable or higher scores on average and produced more convincing sorting results for intra-operative datasets. Thus, the presented framework is suitable for both online and offline analysis and could substantially improve the quality of microelectrode-based data evaluation for research and clinical application.

  4. PS-Modules over Ore Extensions and Skew Generalized Power Series Rings

    Directory of Open Access Journals (Sweden)

    Refaat M. Salem

    2015-01-01

    Full Text Available A right R-module MR is called a PS-module if its socle, SocMR, is projective. We investigate PS-modules over Ore extension and skew generalized power series extension. Let R be an associative ring with identity, MR a unitary right R-module, O=Rx;α,δ Ore extension, MxO a right O-module, S,≤ a strictly ordered additive monoid, ω:S→EndR a monoid homomorphism, A=RS,≤,ω the skew generalized power series ring, and BA=MS,≤RS,≤, ω the skew generalized power series module. Then, under some certain conditions, we prove the following: (1 If MR is a right PS-module, then MxO is a right PS-module. (2 If MR is a right PS-module, then BA is a right PS-module.

  5. Receptor oligomerization in family B1 of G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

    2012-01-01

    , the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

  6. Data Sorting Using Graphics Processing Units

    Directory of Open Access Journals (Sweden)

    M. J. Mišić

    2012-06-01

    Full Text Available Graphics processing units (GPUs have been increasingly used for general-purpose computation in recent years. The GPU accelerated applications are found in both scientific and commercial domains. Sorting is considered as one of the very important operations in many applications, so its efficient implementation is essential for the overall application performance. This paper represents an effort to analyze and evaluate the implementations of the representative sorting algorithms on the graphics processing units. Three sorting algorithms (Quicksort, Merge sort, and Radix sort were evaluated on the Compute Unified Device Architecture (CUDA platform that is used to execute applications on NVIDIA graphics processing units. Algorithms were tested and evaluated using an automated test environment with input datasets of different characteristics. Finally, the results of this analysis are briefly discussed.

  7. Big Five Measurement via Q-Sort

    Directory of Open Access Journals (Sweden)

    Chris D. Fluckinger

    2014-08-01

    Full Text Available Socially desirable responding presents a difficult challenge in measuring personality. I tested whether a partially ipsative measure—a normatively scored Q-sort containing traditional Big Five items—would produce personality scores indicative of less socially desirable responding compared with Likert-based measures. Across both instructions to respond honestly and in the context of applying for a job, the Q-sort produced lower mean scores, lower intercorrelations between dimensions, and similar validity in predicting supervisor performance ratings to Likert. In addition, the Q-sort produced a more orthogonal structure (but not fully orthogonal when modeled at the latent level. These results indicate that the Q-sort method did constrain socially desirable responding. Researchers and practitioners should consider Big Five measurement via Q-sort for contexts in which high socially desirable responding is expected.

  8. Magnet sorting algorithms

    International Nuclear Information System (INIS)

    Dinev, D.

    1996-01-01

    Several new algorithms for sorting of dipole and/or quadrupole magnets in synchrotrons and storage rings are described. The algorithms make use of a combinatorial approach to the problem and belong to the class of random search algorithms. They use an appropriate metrization of the state space. The phase-space distortion (smear) is used as a goal function. Computational experiments for the case of the JINR-Dubna superconducting heavy ion synchrotron NUCLOTRON have shown a significant reduction of the phase-space distortion after the magnet sorting. (orig.)

  9. Online sorting of recovered wood waste by automated XRF-technology: part II. Sorting efficiencies.

    Science.gov (United States)

    Hasan, A Rasem; Solo-Gabriele, Helena; Townsend, Timothy

    2011-04-01

    Sorting of waste wood is an important process practiced at recycling facilities in order to detect and divert contaminants from recycled wood products. Contaminants of concern include arsenic, chromium and copper found in chemically preserved wood. The objective of this research was to evaluate the sorting efficiencies of both treated and untreated parts of the wood waste stream, and metal (As, Cr and Cu) mass recoveries by the use of automated X-ray fluorescence (XRF) systems. A full-scale system was used for experimentation. This unit consisted of an XRF-detection chamber mounted on the top of a conveyor and a pneumatic slide-way diverter which sorted wood into presumed treated and presumed untreated piles. A randomized block design was used to evaluate the operational conveyance parameters of the system, including wood feed rate and conveyor belt speed. Results indicated that online sorting efficiencies of waste wood by XRF technology were high based on number and weight of pieces (70-87% and 75-92% for treated wood and 66-97% and 68-96% for untreated wood, respectively). These sorting efficiencies achieved mass recovery for metals of 81-99% for As, 75-95% for Cu and 82-99% of Cr. The incorrect sorting of wood was attributed almost equally to deficiencies in the detection and conveyance/diversion systems. Even with its deficiencies, the system was capable of producing a recyclable portion that met residential soil quality levels established for Florida, for an infeed that contained 5% of treated wood. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Photo-fermentational hydrogen production of Rhodobacter sp. KKU-PS1 isolated from an UASB reactor

    Directory of Open Access Journals (Sweden)

    Thitirut Assawamongkholsiri

    2015-05-01

    Conclusions: KKU-PS1 can produce hydrogen from at least 8 types of organic acids. By optimizing pH and temperature, a maximal hydrogen production by this strain was obtained. Additionally, by optimizing the light intensity, Rm was increased by approximately two fold and the lag phase of hydrogen production was shortened.

  11. Sequence control of phase separation and dewetting in PS/PVME blend thin films by changing molecular weight of PS.

    Science.gov (United States)

    Xia, Tian; Qin, Yaping; Huang, Yajiang; Huang, Ting; Xu, Jianhui; Li, Youbing

    2016-11-28

    The morphology evolution mechanism of polystyrene (PS)/poly (vinyl methyl ether) (PVME) blend thin films with different PS molecular weights (M w ) was studied. It was found that the morphology evolution was closely related to the molecular weight asymmetry between PS and PVME. In the film where M w (PS) ≈ M w (PVME), dewetting happened at the interface between the bottom layer and substrate after SD phase separation. While in the film where M w (PS) > M w (PVME), dewetting happened at the interface between the middle PS/PVME blend layer and bottom PVME layer near the substrate prior to phase separation. The different sequences of phase separation and dewetting and different interface for dewetting occurrence were studied by regarding the competitive effects of viscoelasticity contrast between polymer components and preferential wetting between PVME and the substrate. The viscoelastic nature of the PS component played a crucial role in the sequence of phase separation and dewetting.

  12. Pengembangan Algoritma Pengurutan SMS (Scan, Move, And Sort)

    OpenAIRE

    Lubis, Denni Aprilsyah

    2015-01-01

    Sorting has been a profound area for the algorithmic researchers. And many resources are invested to suggest a more working sorting algorithm. For this purpose many existing sorting algorithms were observed in terms of the efficiency of the algorithmic complexity. Efficient sorting is important to optimize the use of other algorithms that require sorted lists to work correctly. sorting has been considered as a fundamental problem in the study of algorithms that due to many reas...

  13. Dynamic colloidal sorting on a magnetic bubble lattice

    Science.gov (United States)

    Tierno, Pietro; Soba, Alejandro; Johansen, Tom H.; Sagués, Francesc

    2008-11-01

    We use a uniaxial garnet film with a magnetic bubble lattice to sort paramagnetic colloidal particles with different diameters, i.e., 1.0 and 2.8μm. We apply an external magnetic field which precesses around an axis normal to the film with a frequency Ω =62.8s-1 and intensity 3120A/m bubbles while the others are transported through the array. We complement the experimental measurements with numerical simulations to explore the sorting capability for particles with different magnetic moments.

  14. Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential markers of antiphospholipid syndrome.

    Science.gov (United States)

    Vlagea, Alexandru; Gil, Antonio; Cuesta, Maria V; Arribas, Florencia; Diez, Jesús; Lavilla, Paz; Pascual-Salcedo, Dora

    2013-06-01

    The antiphospholipid antibodies present in antiphospholipid syndrome (APS) are directed at a number of phospholipid-binding proteins: β2 glycoprotein I (β2GPI), prothrombin, and so on. Antibodies directed at β2GPI are accepted as a classification criterion for APS, while the presence of antiprothrombin antibodies is not. In the present article, we investigated the possible role of antiphosphatidylserine/prothrombin antibodies (aPS/PT) as marker of APS on a cohort of 295 individuals with APS (95 primary APS and 45 secondary APS) and APS-related diseases. We found aPS/PT to be highly associated with venous thrombosis (immunoglobulin G [IgG] aPS/PT odds ratio [OR], 7.44; 95% confidence interval [CI], 3.97-13.92 and IgM aPS/PT OR, 2.54; 95% CI, 1.35-4.77) and obstetric abnormalities (IgG aPS/PT OR, 2.37; 95% CI, 1.04-5.43), but not with arterial thrombosis. A very high degree of concordance between the concentration of aPS/PT and lupus anticoagulant activity was demonstrated. Therefore, we support the inclusion of aPS/PT determination as second-level assay to confirm APS classification.

  15. Unsupervised spike sorting based on discriminative subspace learning.

    Science.gov (United States)

    Keshtkaran, Mohammad Reza; Yang, Zhi

    2014-01-01

    Spike sorting is a fundamental preprocessing step for many neuroscience studies which rely on the analysis of spike trains. In this paper, we present two unsupervised spike sorting algorithms based on discriminative subspace learning. The first algorithm simultaneously learns the discriminative feature subspace and performs clustering. It uses histogram of features in the most discriminative projection to detect the number of neurons. The second algorithm performs hierarchical divisive clustering that learns a discriminative 1-dimensional subspace for clustering in each level of the hierarchy until achieving almost unimodal distribution in the subspace. The algorithms are tested on synthetic and in-vivo data, and are compared against two widely used spike sorting methods. The comparative results demonstrate that our spike sorting methods can achieve substantially higher accuracy in lower dimensional feature space, and they are highly robust to noise. Moreover, they provide significantly better cluster separability in the learned subspace than in the subspace obtained by principal component analysis or wavelet transform.

  16. Word Sorts for General Music Classes

    Science.gov (United States)

    Cardany, Audrey Berger

    2015-01-01

    Word sorts are standard practice for aiding children in acquiring skills in English language arts. When included in the general music classroom, word sorts may aid students in acquiring a working knowledge of music vocabulary. The author shares a word sort activity drawn from vocabulary in John Lithgow's children's book "Never Play…

  17. A Sequence of Sorting Strategies.

    Science.gov (United States)

    Duncan, David R.; Litwiller, Bonnie H.

    1984-01-01

    Describes eight increasingly sophisticated and efficient sorting algorithms including linear insertion, binary insertion, shellsort, bubble exchange, shakersort, quick sort, straight selection, and tree selection. Provides challenges for the reader and the student to program these efficiently. (JM)

  18. The IRS-1 signaling system.

    Science.gov (United States)

    Myers, M G; Sun, X J; White, M F

    1994-07-01

    Insulin-receptor substrate 1 (IRS-1) is a principal substrate of the receptor tyrosine kinase for insulin and insulin-like growth factor 1, and a substrate for a tyrosine kinase activated by interleukin 4. IRS-1 undergoes multisite tyrosine phosphorylation and mediates downstream signals by 'docking' various proteins that contain Src homology 2 domains. IRS-1 appears to be a unique molecule; however, 4PS, a protein found mainly in hemopoietic cells, may represent another member of this family.

  19. The role of GABA-A and mitochondrial diazepam-binding inhibitor receptors on the effects of neurosteroids on food intake in mice.

    Science.gov (United States)

    Reddy, D S; Kulkarni, S K

    1998-06-01

    The present studies were undertaken to investigate the neuroactive steroidal modulation of feeding behavior and possible involvement of gamma-aminobutyric acid type-A (GABA-A) and mitochondrial diazepam binding inhibitor (DBI) receptors (MDR) in food-deprived male mice. Allopregnanolone (0.5-2 mg/kg), a neurosteroid, progesterone (1-10 mg/kg), a neurosteroid precursor, and 4'-chlordiazepam (0.25-1 mg/kg), a specific high affinity MDR agonist, produced a dose-dependent hyperphagic effects. In contrast, neurosteroids pregnenolone sulfate (PS) (1-10 mg/kg) and dehydroepiandrosterone sulfate (DHEAS) (1-10 mg/kg) produced a hypophagic effect, in a dose-dependent manner. The allopregnanolone-, progesterone- and 4'-chlordiazepam-induced hyperphagic effect was blocked by picrotoxin (1 mg/kg), a GABA-A chloride channel antagonist, but not by flumazenil (2 mg/kg), a benzodiazepine (BZD) antagonist. The 4'-chlordiazepam-induced hyperphagic effect was prevented by pretreatment with PK11195 (2 mg/kg), a selective partial MDR antagonist. The hypophagic effect of DHEAS (10 mg/kg) was reversed by dizocilpine (10 microg/kg), an NMDA receptor antagonist, but resistant to muscimol (0.1 mg/kg), a selective GABA-A receptor agonist. In contrast, the PS (10 mg/kg)-induced hypophagic response was resistant to dizocilpine, but sensitive to muscimol (0.1 mg/kg). Both the sulfated neurosteroids PS and DHEAS also reversed the hyperphagic effect of allopregnanolone. In addition, the BZD agonist triazolam (0.05-0.25 mg/kg) also produced a flumazenil- and picrotoxin-sensitive hyperphagic effects, thereby suggesting the changes in feeding behavior by neurosteroids represent GABA-A receptor mediated hyperphagic action. Although the possible antistress or anxiolytic actions of neurosteroids may confound the hyperphagia, behavioral effects observed were specific to food because the mice were adopted to the test environment and diet, and of a possible variation between various neurosteroids in the

  20. Structure and function of the Juxta membrane domain of the human epidermal growth factor receptor by NMR spectroscopy

    International Nuclear Information System (INIS)

    Choowongkomon, Kiattawee; Carlin, Cathleen; Sonnichsen, Frank D.

    2005-10-01

    The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family involved in the regulation of cellular proliferation and differentiation. Its juxta membrane domain (JX), the region located between the transmembrane and kinase domains, plays important roles in receptor trafficking since both basolateral sorting in polarized epithelial cells and lysosomal sorting signals are identified in this region. In order to understand the regulation of these signals, we characterized the structural properties of recombinant JX domain in dodecyl phosphocholine detergent (DPC) by nuclear magnetic resonance (NMR) spectroscopy. In DPC micelles, structures derived from NMR data showed three amphipathic, helical segments. Two equivalent average structural models on the surface of micelles were obtained that differ only in the relative orientation between the first and second helices. Our data suggests that the activity of sorting signals may be regulated by their membrane association and restricted accessibility in the intact receptor

  1. Fixing the Sorting Algorithm for Android, Java and Python

    NARCIS (Netherlands)

    C.P.T. de Gouw (Stijn); F.S. de Boer (Frank)

    2015-01-01

    htmlabstractTim Peters developed the Timsort hybrid sorting algorithm in 2002. TimSort was first developed for Python, a popular programming language, but later ported to Java (where it appears as java.util.Collections.sort and java.util.Arrays.sort). TimSort is today used as the default sorting

  2. Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA.

    Science.gov (United States)

    Santos, Helena; Eusébio, Mónica; Borges, Joana; Gonçalves, Diana; Ávila-Ribeiro, Pedro; Faria, Daniela Santos; Lopes, Carina; Rovisco, João; Águeda, Ana; Nero, Patrícia; Valente, Paula; Cravo, Ana Rita; Santos, Maria José

    2017-01-01

    Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating adalimumab (ADA), with short- and long-term disease duration and to evaluate the potential effect of concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) between June 2008-June 2016 who received ADA for ≥3 months. Psoriatic Arthritis Response Criteria (PsARC) response, tender and swollen joint count, inflammatory parameters, patient (PtGA) and physician global assessment (PhGA), Disease Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability Index (HAQ-DI) were compared between patients with PsA) and those with ≥5 years of disease duration (late PsA). Time to achieving PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA patients treated with ADA, 126 had information on disease duration (earlyPsA, n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs 62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs 1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and lower PhGA (6.3 vs 21.9; PPsA, respectively. Early PsA patients obtained PsARC response more rapidly than late PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant glucocorticoids had no effect on PsARC response over 2 years of follow-up. Persistence on ADA was similar in both groups. Conclusion Early PsA patients had a greater chance of improvement after ADA therapy and better functional outcome, and

  3. IMPLEMENTATION OF SERIAL AND PARALLEL BUBBLE SORT ON FPGA

    Directory of Open Access Journals (Sweden)

    Dwi Marhaendro Jati Purnomo

    2016-06-01

    Full Text Available Sorting is common process in computational world. Its utilization are on many fields from research to industry. There are many sorting algorithm in nowadays. One of the simplest yet powerful is bubble sort. In this study, bubble sort is implemented on FPGA. The implementation was taken on serial and parallel approach. Serial and parallel bubble sort then compared by means of its memory, execution time, and utility which comprises slices and LUTs. The experiments show that serial bubble sort required smaller memory as well as utility compared to parallel bubble sort. Meanwhile, parallel bubble sort performed faster than serial bubble sort

  4. Electron Spin Resonance studies on PS, PP and PS/PP blends under gamma irradiation

    International Nuclear Information System (INIS)

    Reyes, J.; Claro, M.; Albano, C.; Venezuela Central University, Caracas; Moronta, D.

    2002-01-01

    Complete text of publication follows. Electron Spin Resonance (ESR) studies on Polystyrene (PS), Polypropylene (PP) and their mixtures at compositions of 80/20 with and without a compatibilizer (SBS in block), 7.5 wt.%, irradiated with gamma rays from a Cobalt-60 source with a dose rate of 4.8 KGy/h at integral doses of radiation of 10, 25, 50, 60, 70, 400, 800 and 1300 KGy in the presence of air and at room temperature (RT) are reported. The dependence of resonance line width, Hpp; resonance line shapes K, and radical concentration, S, with the integral dose of irradiation is investigated. The nature of the free radicals after ten days of air storage is discussed. The free radical concentration, the double integral of the resonance line, S, has been estimated at room temperature, RT, for a group of single lines, characterized by the same giromagnetic, g, value by direct numerical double integration. In the samples studied no spectrum of 0 kGy of integral dose was observed. The concentration of radicals, S, observed when the integral radiation doses was increased, presents a maximum value in the PP samples at high doses (70-1300 kGy) and minimum values in the PS samples with the same doses. This shows that the PP degrades at a faster rate than the PS, owing to the presence of the bencenic ring in the latter. In the PS/PP mixtures studied with and without compatibilizer, the values of the radical concentration is found between the observed values in the homopolymers, being closer to the PS, which might imply that the presence of PS decays the degradation process of the PP in the mixture

  5. Cs0.49NbPS6

    Directory of Open Access Journals (Sweden)

    Hoseop Yun

    2011-01-01

    Full Text Available The quaternary thiophosphate, Cs0.49NbPS6, caesium hexathioniobiophosphate(V, has been synthesized by the reactive halide flux method. The title compound is isotypic with Rb0.46TaPS6 and is made up of a bicapped trigonal–biprismatic [Nb2S12] unit and a tetrahedral [PS4] group. The [Nb2S12] units linked by the [PS4] tetrahedra form infinite chains, yielding a three-dimensional network with rather large van der Waals gaps along the c axis in which the disordered Cs+ ions reside. The electrons released by the Cs atoms are transferred to the pairwise niobium metal site and there are substantial intermetallic Nb—Nb bonding interactions. This leads to a significant decrease of the intermetallic distance in the title compound compared to that in TaPS6. The classical charge balance of the title compound may be represented as [Cs+]0.49[Nb4.51+][P5+][S2−]4[S22−].

  6. Automatic spike sorting using tuning information.

    Science.gov (United States)

    Ventura, Valérie

    2009-09-01

    Current spike sorting methods focus on clustering neurons' characteristic spike waveforms. The resulting spike-sorted data are typically used to estimate how covariates of interest modulate the firing rates of neurons. However, when these covariates do modulate the firing rates, they provide information about spikes' identities, which thus far have been ignored for the purpose of spike sorting. This letter describes a novel approach to spike sorting, which incorporates both waveform information and tuning information obtained from the modulation of firing rates. Because it efficiently uses all the available information, this spike sorter yields lower spike misclassification rates than traditional automatic spike sorters. This theoretical result is verified empirically on several examples. The proposed method does not require additional assumptions; only its implementation is different. It essentially consists of performing spike sorting and tuning estimation simultaneously rather than sequentially, as is currently done. We used an expectation-maximization maximum likelihood algorithm to implement the new spike sorter. We present the general form of this algorithm and provide a detailed implementable version under the assumptions that neurons are independent and spike according to Poisson processes. Finally, we uncover a systematic flaw of spike sorting based on waveform information only.

  7. Liver X receptor α and farnesoid X receptor are major transcriptional regulators of OATP1B1.

    Science.gov (United States)

    Meyer Zu Schwabedissen, Henriette E; Böttcher, Kerstin; Chaudhry, Amarjit; Kroemer, Heyo K; Schuetz, Erin G; Kim, Richard B

    2010-11-01

    Organic anion transporting polypeptide 1B1 (OATP1B1) is a liver-enriched transporter involved in the hepatocellular uptake of many endogenous molecules and several structurally divergent drugs in clinical use. Although OATP1B1 coding region polymorphisms are known to make an impact on substrate drug disposition in humans, little is known regarding the mechanisms underlying the transcriptional regulation of this transporter. In this study, we note that messenger RNA (mRNA) expression of OATP1B1 in a large human liver bank exhibited marked interindividual variability that was not associated with coding region polymorphisms. Accordingly, we hypothesized that such variability in expression is reflective of nuclear receptor-mediated transcriptional regulation of this transporter. We tested prototypical ligands for the nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), liver X receptor (LXR) α, and farnesoid X receptor (FXR) in a human hepatoma-derived cell line and noted induction of OATP1B1 mRNA when the cells were treated with LXRα or FXR ligands. To confirm a direct role for LXRα and FXR to OATP1B1 expression, we performed detailed promoter analysis and cell-based reporter gene assays resulting in the identification of two functional FXR response elements and one LXRα response element. The direct interaction between nuclear receptors with the identified response elements was assessed using chromatin immunoprecipitation assays. Using isolated primary human hepatocytes, we show that LXRα or FXR agonists, but not PXR or CAR agonists, are capable of OATP1B1 induction. We note that OATP1B1 transcriptional regulation is under dual nuclear receptor control through the oxysterol sensing LXRα and the bile acid sensor FXR. Accordingly, the interplay between OATP1B1 and nuclear receptors may play an important and heretofore unrecognized role during cholestasis, drug-induced liver injury, and OATP1B1 induction-related drug interactions.

  8. Dielectrophoretic focusing integrated pulsed laser activated cell sorting

    Science.gov (United States)

    Zhu, Xiongfeng; Kung, Yu-Chun; Wu, Ting-Hsiang; Teitell, Michael A.; Chiou, Pei-Yu

    2017-08-01

    We present a pulsed laser activated cell sorter (PLACS) integrated with novel sheathless size-independent dielectrophoretic (DEP) focusing. Microfluidic fluorescence activated cell sorting (μFACS) systems aim to provide a fully enclosed environment for sterile cell sorting and integration with upstream and downstream microfluidic modules. Among them, PLACS has shown a great potential in achieving comparable performance to commercial aerosol-based FACS (>90% purity at 25,000 cells sec-1). However conventional sheath flow focusing method suffers a severe sample dilution issue. Here we demonstrate a novel dielectrophoresis-integrated pulsed laser activated cell sorter (DEP-PLACS). It consists of a microfluidic channel with 3D electrodes laid out to provide a tunnel-shaped electric field profile along a 4cmlong channel for sheathlessly focusing microparticles/cells into a single stream in high-speed microfluidic flows. All focused particles pass through the fluorescence detection zone along the same streamline regardless of their sizes and types. Upon detection of target fluorescent particles, a nanosecond laser pulse is triggered and focused in a neighboring channel to generate a rapidly expanding cavitation bubble for precise sorting. DEP-PLACS has achieved a sorting purity of 91% for polystyrene beads at a throughput of 1,500 particle/sec.

  9. Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice.

    Science.gov (United States)

    Gu, G; Zhang, W; Li, M; Ni, J; Wang, P

    2015-04-16

    The ability to selectively control the differentiation of neural stem cells (NSCs) into cholinergic neurons in vivo would be an important step toward cell replacement therapy. First, green fluorescent protein (GFP)-NSCs were induced to differentiate into cholinergic neuron-like cells (CNLs) with retinoic acid (RA) pre-induction followed by nerve growth factor (NGF) induction. Then, these CNLs were transplanted into bilateral hippocampus of APP/PS1 transgenic mice. Behavioral parameters showed by Morris water maze (MWM) tests and the percentages of GFP-labeled cholinergic neurons of CNL transplanted mice were compared with those of controls. Brain levels of choline acetyltransferase (ChAT) mRNA and proteins were analyzed by quantitative real-time PCR and Western blotting, ChAT activity and acetylcholine (ACh) concentration were also evaluated by ChAT activity and ACh concentration assay kits. Immunofluorescence analysis showed that 80.3±1.5% NSCs differentiated into CNLs after RA pre-induction followed by NGF induction in vitro. Three months after transplantation, 82.4±6.3% CNLs differentiated into cholinergic neurons in vivo. APP/PS1 mice transplanted with CNLs showed a significant improvement in learning and memory ability compared with control groups at different time points. Furthermore, CNLs transplantation dramatically increased in the expressions of ChAT mRNA and protein, as well ChAT activity and ACh concentration in APP/PS1 mice. Our findings support the prospect of using NSC-derived CNLs in developing therapies for Alzheimer's disease (AD). Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. SPS and PS Experiments Committee

    CERN Multimedia

    CERN. Geneva

    2004-01-01

    OPEN SESSION: 09:00 Status report of NA58 / COMPASS: A. Magnon 09:40 Status report of PS212 / DIRAC: L. Tausher 10:10 PS212 / DIRAC Addendum: L. Nemenov CLOSED SESSION on Tuesday, 27 April 2004 after the open session, Main Building, 6th floor conference room

  11. The orphan nuclear receptor LRH-1 and ERα activate GREB1 expression to induce breast cancer cell proliferation.

    Directory of Open Access Journals (Sweden)

    Ashwini L Chand

    Full Text Available BACKGROUND: Liver Receptor Homolog 1 (LRH-1, NR5A2 is an orphan nuclear receptor that is over-expressed in cancers in tissues such as the breast, colon and pancreas. LRH-1 plays important roles in embryonic development, steroidogenesis and cholesterol homeostasis. In tumor cells, LRH-1 induces proliferation and cell cycle progression. High LRH-1 expression is demonstrated in breast cancers, positively correlating with ERα status and aromatase activity. LRH-1 dependent cellular mechanisms in breast cancer epithelial cells are poorly defined. Hence in the present study we investigated the actions of LRH-1 in estrogen receptor α (ERα positive breast cancer cells. RESULTS: The study aimed to investigate LRH-1 dependent mechanisms that promote breast cancer proliferation. We identified that LRH-1 regulated the expression of Growth Regulation by Estrogen in Breast Cancer 1 (GREB1 in MCF-7 and MDA-MB-231 cells. Over-expression of LRH-1 increased GREB1 mRNA levels while knockdown of LRH-1 reduced its expression. GREB1 is a well characterised ERα target gene, with three estrogen response elements (ERE located on its promoter. Chromatin immunoprecipitation studies provided evidence of the co-localisation of LRH-1 and ERα at all three EREs. With electrophoretic mobility shift assays, we demonstrated direct binding of LRH-1 to EREs located on GREB1 and Trefoil Factor 1 (TFF1, pS2 promoters. LRH-1 and ERα co-operatively activated transcription of ERE luciferase reporter constructs suggesting an overlap in regulation of target genes in breast cancer cells. Over-expression of LRH-1 resulted in an increase in cell proliferation. This effect was more pronounced with estradiol treatment. In the presence of ICI 182,780, an ERα antagonist, LRH-1 still induced proliferation. CONCLUSIONS: We conclude that in ER-positive breast cancer cells, LRH-1 promotes cell proliferation by enhancing ERα mediated transcription of target genes such as GREB-1. Collectively

  12. Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6

    Directory of Open Access Journals (Sweden)

    Ke Geng

    2017-11-01

    Full Text Available The Tyro3, Axl, and Mertk (TAM receptors are homologous type I receptor tyrosine kinases that have critical functions in the clearance of apoptotic cells in multicellular organisms. TAMs are activated by their endogenous ligands, growth arrest-specific 6 (Gas6, and protein S (Pros1, that function as bridging molecules between externalized phosphatidylserine (PS on apoptotic cells and the TAM ectodomains. However, the molecular mechanisms by which Gas6/Pros1 promote TAM activation remains elusive. Using TAM/IFNγR1 reporter cell lines to monitor functional TAM activity, we found that Gas6 activity was exquisitely dependent on vitamin K-mediated γ-carboxylation, whereby replacing vitamin K with anticoagulant warfarin, or by substituting glutamic acid residues involved in PS binding, completely abrogated Gas6 activity as a TAM ligand. Furthermore, using domain and point mutagenesis, Gas6 activity also required both an intact Gla domain and intact EGF-like domains, suggesting these domains function cooperatively in order to achieve TAM activation. Despite the requirement of γ-carboxylation and the functional Gla domain, non-γ-carboxylated Gas6 and Gla deletion/EGF-like domain deletion mutants still retained their ability to bind TAMs and acted as blocking decoy ligands. Finally, we found that distinct sources of PS-positive cells/vesicles (including apoptotic cells, calcium-induced stressed cells, and exosomes bound Gas6 and acted as cell-derived or exosome-derived ligands to activate TAMs. Taken together, our findings indicate that PS is indispensable for TAM activation by Gas6, and by inference, provides new perspectives on how PS, regulates TAM receptors and efferocytosis.

  13. Altered cell cycle-related gene expression in brain and lymphocytes from a transgenic mouse model of Alzheimer's disease [amyloid precursor protein/presenilin 1 (PS1)].

    Science.gov (United States)

    Esteras, Noemí; Bartolomé, Fernando; Alquézar, Carolina; Antequera, Desireé; Muñoz, Úrsula; Carro, Eva; Martín-Requero, Ángeles

    2012-09-01

    Cumulative evidence indicates that aberrant re-expression of many cell cycle-related proteins and inappropriate neuronal cell cycle control are critical events in Alzheimer's disease (AD) pathogenesis. Evidence of cell cycle activation in post-mitotic neurons has also been observed in murine models of AD, despite the fact that most of these mice do not show massive loss of neuronal bodies. Dysfunction of the cell cycle appears to affect cells other than neurons, as peripheral cells, such as lymphocytes and fibroblasts from patients with AD, show an altered response to mitogenic stimulation. We sought to determine whether cell cycle disturbances are present simultaneously in both brain and peripheral cells from the amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD, in order to validate the use of peripheral cells from patients not only to study cell cycle abnormalities as a pathogenic feature of AD, but also as a means to test novel therapeutic approaches. By using cell cycle pathway-specific RT(2)Profiler™ PCR Arrays, we detected changes in a number of cell cycle-related genes in brain as well as in lymphocytes from APP/PS1 mice. Moreover, we found enhanced 5'-bromo-2'-deoxyuridine incorporation into DNA in lymphocytes from APP/PS1 mice, and increased expression of the cell proliferation marker proliferating cell nuclear antigen (PCNA), and the cyclin-dependent kinase (CDK) inhibitor Cdkn2a, as detected by immunohistochemistry in cortical neurons of the APP/PS1 mice. Taken together, the cell cycle-related changes in brain and blood cells reported here support the mitosis failure hypothesis in AD and validate the use of peripheral cells as surrogate tissue to study the molecular basis of AD pathogenesis. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  14. Science and technology of kernels and TRISO coated particle sorting

    International Nuclear Information System (INIS)

    Nothnagel, G.

    2006-09-01

    The ~1mm diameter TRISO coated particles, which form the elemental units of PBMR nuclear fuel, has to be close to spherical in order to best survive damage during sphere pressing. Spherical silicon carbide layers further provide the strongest miniature pressure vessels for fission product retention. To make sure that the final product contains particles of acceptable shape, 100% of kernels and coated particles have to be sorted on a surface-ground sorting table. Broken particles, twins, irregular (odd) shapes and extreme ellipsoids have to be separated from the final kernel and coated particle batches. Proper sorting of particles is an extremely important step in quality fuel production as the final failure fraction depends sensitively on the quality of sorting. After sorting a statistically significant sample of the sorted product is analysed for sphericity, which is defined as the ratio of maximum to minimum diameter, as part of a standard QC test to ensure conformance to German specifications. In addition a burn-leach test is done on coated particles (before pressing) and fuel spheres (after pressing) to ensure adherence to failure specifications. Because of the extreme importance of particle sorting for assurance of fuel quality it is essential to have an in-depth understanding of the capabilities and limitations of particle sorting. In this report a systematic scientific rationale is developed, from fundamental principles, to provide a basis for understanding the relationship between product quality and sorting parameters. The principles and concepts, developed in this report, will be of importance when future sorting tables (or equivalents) are to be designed. A number of new concepts and methodologies are developed to assist with equivalence validation of any two sorting tables. This is aimed in particular towards quantitative assessment of equivalence between current QC tables (closely based on the original NUKEM parameters, except for the driving mechanism

  15. Data parallel sorting for particle simulation

    Science.gov (United States)

    Dagum, Leonardo

    1992-01-01

    Sorting on a parallel architecture is a communications intensive event which can incur a high penalty in applications where it is required. In the case of particle simulation, only integer sorting is necessary, and sequential implementations easily attain the minimum performance bound of O (N) for N particles. Parallel implementations, however, have to cope with the parallel sorting problem which, in addition to incurring a heavy communications cost, can make the minimun performance bound difficult to attain. This paper demonstrates how the sorting problem in a particle simulation can be reduced to a merging problem, and describes an efficient data parallel algorithm to solve this merging problem in a particle simulation. The new algorithm is shown to be optimal under conditions usual for particle simulation, and its fieldwise implementation on the Connection Machine is analyzed in detail. The new algorithm is about four times faster than a fieldwise implementation of radix sort on the Connection Machine.

  16. RF Scenarios for Pb54+ Ions in the PS2

    CERN Document Server

    Benedikt, M; Hancock, S; CERN. Geneva. AB Department

    2008-01-01

    This note analyses some of the rf scenarios that are presently being considered for lead ions in the PS2. An earlier note principally concerning protons [1] highlighted the problem of the large revolution frequency swing of ions in the PS2 and the issue of bunching factor with direct injection from the LEIR machine. We present solutions based on additional rf systems in LEIR and consider the 40 MHz principal rf system proposed for the PS2 in the earlier work to have switchable tuning ranges to cover the large frequency swing required.

  17. Stochastic Model of Vesicular Sorting in Cellular Organelles

    Science.gov (United States)

    Vagne, Quentin; Sens, Pierre

    2018-02-01

    The proper sorting of membrane components by regulated exchange between cellular organelles is crucial to intracellular organization. This process relies on the budding and fusion of transport vesicles, and should be strongly influenced by stochastic fluctuations, considering the relatively small size of many organelles. We identify the perfect sorting of two membrane components initially mixed in a single compartment as a first passage process, and we show that the mean sorting time exhibits two distinct regimes as a function of the ratio of vesicle fusion to budding rates. Low ratio values lead to fast sorting but result in a broad size distribution of sorted compartments dominated by small entities. High ratio values result in two well-defined sorted compartments but sorting is exponentially slow. Our results suggest an optimal balance between vesicle budding and fusion for the rapid and efficient sorting of membrane components and highlight the importance of stochastic effects for the steady-state organization of intracellular compartments.

  18. Application of visible spectroscopy in waste sorting

    Science.gov (United States)

    Spiga, Philippe; Bourely, Antoine

    2011-10-01

    Today, waste recycling, (bottles, papers...), is a mechanical operation: the waste are crushed, fused and agglomerated in order to obtain new manufactured products (e.g. new bottles, clothes ...). The plastics recycling is the main application in the color sorting process. The colorless plastics recovered are more valuable than the colored plastics. Other emergent applications are in the paper sorting, where the main goal is to sort dyed paper from white papers. Up to now, Pellenc Selective Technologies has manufactured color sorting machines based on RGB cameras. Three dimensions (red, green and blue) are no longer sufficient to detect low quantities of dye in the considered waste. In order to increase the efficiency of the color detection, a new sorting machine, based on visible spectroscopy, has been developed. This paper presents the principles of the two approaches and their difference in terms of sorting performance, making visible spectroscopy a clear winner.

  19. File list: ALL.PSC.50.AllAg.iPS_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.PSC.50.AllAg.iPS_cells mm9 All antigens Pluripotent stem cell iPS cells SRX9773...1,SRX035985,SRX1090869 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.PSC.50.AllAg.iPS_cells.bed ...

  20. LEADIR-PS: providing unprecedented SMR safety and economics

    Energy Technology Data Exchange (ETDEWEB)

    Hart, R.S., E-mail: N2i2@xplornet.ca [Northern Nuclear Industries Incorporated, Cambridge, ON (Canada)

    2015-07-01

    Northern Nuclear Industries Incorporated (N{sup 2} I{sup 2}) is developing Small Modular Reactors (SMRs) called LEADIR-PS, an acronym for LEAD-cooled Integral Reactor-Passively Safe. LEADIR-PS integrates proven technologies including TRISO fuel, Pebble Bed core and graphite moderator, with molten lead coolant in an integral pool type reactor configuration to achieve unprecedented safety and economics. Plants under development are LEADIR-PS30, producing 30 MWth, LEADIR-PS100 producing 100 MWth and LEADIR-PS300 producing 300 MWth that are focused on serving the energy demands of areas with a small electrical grid and/or process heat applications. A plant consisting of six LEADIR-PS300 reactor modules serving a common turbine-generator, called the LEADIR-PS Six-Pack, is focused on serving areas with higher energy demands and a robust electricity grid. The Gen{sup +} I LEADIR-PS plants are inherently/passively safe. There is no potential for a Loss Of Coolant Accident, a reactivity transient without shutdown, a loss of heat sink, or hydrogen generation. No active systems or operator actions are required to assure safety. The unprecedented safety of LEADIR-PS reactors avoids large exclusion radius and demanding evacuation plan requirements. LEADIR-PS, with steam conditions of 370 {sup o}C and 12 MPa can serve over 85% of the world's non-transportation process heat demands. In Canada, the electricity and process heat demands, ranging from those of remote communities and the oil sands to densely populated areas can be served by LEADIR-PS. (author)

  1. The PS complex as proton pre-injector for the LHC - design and implementation report

    International Nuclear Information System (INIS)

    Benedikt, M.; Blas, A.; Borburgh, J.

    2000-01-01

    The LHC will be supplied with protons from the pre-injector chain comprising Linac2, PS Booster and PS. These accelerators have undergone a major upgrading programme during the last five years so as to meet the stringent requirements of the LHC. This implies that many high-intensity bunches of small emittance and tight spacing (25 ns) be available at the PS extraction energy (26 GeV/c). The upgrading project involved an increase of Linac2 current, new RF systems in the PS Booster and the PS, raising the PS Booster energy from 1 to 1.4 GeV, two-batch filling of the PS, and the installation of high-resolution beam profile measurement devices. With the project entering its final phase and most of the newly installed hardware now being operational, the emphasis switches to producing the nominal LHC beam and tackling the associated beam physics problems. This report describes all the hardware changes related to the upgrading project. (orig.)

  2. Homologous histamine H1 receptor desensitization results in reduction of H1 receptor agonist efficacy

    NARCIS (Netherlands)

    Leurs, R; Smit, M J; Bast, A; Timmerman, H

    1991-01-01

    Prolonged exposure of the guinea-pig intestinal longitudinal smooth muscle to histamine caused homologous desensitization of the H1 receptor, which led to reduced H1 receptor-mediated production of [3H]inositol phosphates as well as to reduced H1 agonist-induced contractions. [3H]Mepyramine binding

  3. High-throughput microfluidic mixing and multiparametric cell sorting for bioactive compound screening.

    Science.gov (United States)

    Young, Susan M; Curry, Mark S; Ransom, John T; Ballesteros, Juan A; Prossnitz, Eric R; Sklar, Larry A; Edwards, Bruce S

    2004-03-01

    HyperCyt, an automated sample handling system for flow cytometry that uses air bubbles to separate samples sequentially introduced from multiwell plates by an autosampler. In a previously documented HyperCyt configuration, air bubble separated compounds in one sample line and a continuous stream of cells in another are mixed in-line for serial flow cytometric cell response analysis. To expand capabilities for high-throughput bioactive compound screening, the authors investigated using this system configuration in combination with automated cell sorting. Peptide ligands were sampled from a 96-well plate, mixed in-line with fluo-4-loaded, formyl peptide receptor-transfected U937 cells, and screened at a rate of 3 peptide reactions per minute with approximately 10,000 cells analyzed per reaction. Cell Ca(2+) responses were detected to as little as 10(-11) M peptide with no detectable carryover between samples at up to 10(-7) M peptide. After expansion in culture, cells sort-purified from the 10% highest responders exhibited enhanced sensitivity and more sustained responses to peptide. Thus, a highly responsive cell subset was isolated under high-throughput mixing and sorting conditions in which response detection capability spanned a 1000-fold range of peptide concentration. With single-cell readout systems for protein expression libraries, this technology offers the promise of screening millions of discrete compound interactions per day.

  4. A Model Vision of Sorting System Application Using Robotic Manipulator

    Directory of Open Access Journals (Sweden)

    Maralo Sinaga

    2010-08-01

    Full Text Available Image processing in today’s world grabs massive attentions as it leads to possibilities of broaden application in many fields of high technology. The real challenge is how to improve existing sorting system in the Moduler Processing System (MPS laboratory which consists of four integrated stations of distribution, testing, processing and handling with a new image processing feature. Existing sorting method uses a set of inductive, capacitive and optical sensors do differentiate object color. This paper presents a mechatronics color sorting system solution with the application of image processing. Supported by OpenCV, image processing procedure senses the circular objects in an image captured in realtime by a webcam and then extracts color and position information out of it. This information is passed as a sequence of sorting commands to the manipulator (Mitsubishi Movemaster RV-M1 that does pick-and-place mechanism. Extensive testing proves that this color based object sorting system works 100% accurate under ideal condition in term of adequate illumination, circular objects’ shape and color. The circular objects tested for sorting are silver, red and black. For non-ideal condition, such as unspecified color the accuracy reduces to 80%.

  5. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

    Science.gov (United States)

    Zhao, Lan-Xue; Ge, Yan-Hui; Xiong, Cai-Hong; Tang, Ling; Yan, Ying-Hui; Law, Ping-Yee; Qiu, Yu; Chen, Hong-Zhuan

    2018-03-06

    M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

  6. VizieR Online Data Catalog: Gravitational waves from known pulsars (Aasi+, 2014)

    Science.gov (United States)

    Aasi, J.; Abadie, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Accadia, T.; Acernese, F.; Adams, C.; Adams, T.; Adhikari, R. X.; Affeldt, C.; Agathos, M.; Aggarwal, N.; Aguiar, O. D.; Ajith, P.; Allen, B.; Allocca, A.; Ceron, E. A.; Amariutei, D.; Anderson, R. A.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C.; Areeda, J.; Ast, S.; Aston, S. M.; Astone, P.; Aufmuth, P.; Aulbert, C.; Austin, L.; Aylott, B. E.; Babak, S.; Baker, P. T.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barker, D.; Barnum, S. H.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J.; Bauchrowitz, J.; Bauer, Th. S.; Bebronne, M.; Behnke, B.; Bejger, M.; Beker, M. G.; Bell, A. S.; Bell, C.; Belopolski, I.; Bergmann, G.; Berliner, J. M.; Bersanetti, D.; Bertolini, A.; Bessis, D.; Betzwieser, J.; Beyersdorf, P. T.; Bhadbhade, T.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Bitossi, M.; Bizouard, M. A.; Black, E.; Blackburn, J. K.; Blackburn, L.; Blair, D.; Blom, M.; Bock, O.; Bodiya, T. P.; Boer, M.; Bogan, C.; Bo, Nd C.; Bondu, F.; Bonelli, L.; Bonnand, R.; Bork, R.; Born, M.; Boschi, V.; Bose, S.; Bosi, L.; Bowers, J.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brannen, C. A.; Brau, J. E.; Breyer, J.; Briant, T.; Bridges, D. O.; Brillet, A.; Brinkmann, M.; Brisson, V.; Britzger, M.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Bruckner, F.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Calderon Bustillo, J.; Calloni, E.; Camp, J. B.; Campsie, P.; Cannon, K. C.; Canuel, B.; Cao, J.; Capano, C. D.; Carbognani, F.; Carbone, L.; Caride, S.; Castiglia, A.; Caudill, S.; Cavaglia, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C.; Cesarini, E.; Chakraborty, R.; Chalermsongsak, T.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Chen, X.; Chen, Y.; Chincarini, A.; Chiummo, A.; Cho, H. S.; Chow, J.; Christensen, N.; Chu, Q.; Chua, S. S. Y.; Chung, S.; Ciani, G.; Clara, F.; Clark, D. E.; Clark, J. A.; Cleva, F.; Coccia, E.; Cohadon, P.-F.; Colla, A.; Colombini, M.; Constancio, M. Jr; Conte, A.; Conte, R.; Cook, D.; Corbitt, T. R.; Cordier, M.; Cornish, N.; Corsi, A.; Costa, C. A.; Coughlin, M. W.; Coulon, J.-P.; Countryman, S.; Couvares, P.; Coward, D. M.; Cowart, M.; Coyne, D. C.; Craig, K.; Creighton, J. D. E.; Creighton, T. D.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dahl, K.; Dal Canton, T.; Damjanic, M.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Dattilo, V.; Daudert, B.; Daveloza, H.; Davier, M.; Davies, G. S.; Daw, E. J.; Day, R.; Dayanga, T.; De Rosa, R.; Debreczeni, G.; Degallaix, J.; Del Pozzo, W.; Deleeuw, E.; Deleglise, S.; Denker, T.; Dent, T.; Dereli, H.; Dergachev, V.; Derosa, R.; Desalvo, R.; Dhurandhar, S.; di Fiore, L.; di Lieto, A.; di Palma, I.; di, Virgilio A.; Diaz, M.; Dietz, A.; Dmitry, K.; Donovan, F.; Dooley, K. L.; Doravari, S.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Dumas, J.-C.; Dwyer, S.; Eberle, T.; Edwards, M.; Effler, A.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Endroczi, G.; Essick, R.; Etzel, T.; Evans, K.; Evans, M.; Evans, T.; Factourovich, M.; Fafone, V.; Fairhurst, S.; Fang, Q.; Farinon, S.; Farr, B.; Farr, W.; Favata, M.; Fazi, D.; Fehrmann, H.; Feldbaum, D.; Ferrante, I.; Ferrini, F.; Fidecaro, F.; Finn, L. S.; Fiori, I.; Fisher, R.; Flaminio, R.; Foley, E.; Foley, S.; Forsi, E.; Fotopoulos, N.; Fournier, J.-D.; Franco, S.; Frasca, S.; Frasconi, F.; Frede, M.; Frei, M.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fujimoto, M.-K.; Fulda, P.; Fyffe, M.; Gair, J.; Gammaitoni, L.; Garcia, J.; Garufi, F.; Gehrels, N.; Gemme, G.; Genin, E.; Gennai, A.; Gergely, L.; Ghosh, S.; Giaime, J. A.; Giampanis, S.; Giardina, K. D.; Giazotto, A.; Gil-Casanova, S.; Gill, C.; Gleason, J.; Goetz, E.; Goetz, R.; Gondan, L.; Gonzalez, G.; Gordon, N.; Gorodetsky, M. L.; Gossan, S.; Gossler, S.; Gouaty, R.; Graef, C.; Graff, P. B.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Griffo, C.; Groot, P.; Grote, H.; Grover, K.; Grunewald, S.; Guidi, G. M.; Guido, C.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hall, B.; Hall, E.; Hammer, D.; Hammond, G.; Hanke, M.; Hanks, J.; Hanna, C.; Hanson, J.; Harms, J.; Harry, G. M.; Harry, I. W.; Harstad, E. D.; Hartman, M. T.; Haughian, K.; Hayama, K.; Heefner, J.; Heidmann, A.; Heintze, M.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Holt, K.; Holtrop, M.; Hong, T.; Hooper, S.; Horrom, T.; Hosken, D. J.; Hough, J.; Howell, E. J.; Hu, Y.; Hua, Z.; Huang, V.; Huerta, E. A.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh, M.; Huynh-Dinh, T.; Iafrate, J.; Ingram, D. R.; Inta, R.; Isogai, T.; Ivanov, A.; Iyer, B. R.; Izumi, K.; Jacobson, M.; James, E.; Jang, H.; Jang, Y. J.; Jaranowski, P.; Jimenez-Forteza, F.; Johnson, W. W.; Jones, D.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; K, H.; Kalmus, P.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kasprzack, M.; Kasturi, R.; Katsavounidis, E.; Katzman, W.; Kaufer, H.; Kaufman, K.; Kawabe, K.; Kawamura, S.; Kawazoe, F.; Kefelian, F.; Keitel, D.; Kelley, D. B.; Kells, W.; Keppel, D. G.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, B. K.; Kim, C.; Kim, K.; Kim, N.; Kim, W.; Kim, Y.-M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimen, Ko S.; Kline, J.; Koehlenbeck, S.; Kokeyama, K.; Kondrashov, V.; Koranda, S.; Korth, W. Z.; Kowalska, I.; Kozak, D.; Kremin, A.; Kringel, V.; Krishnan, B.; Krolak, A.; Kucharczyk, C.; Kudla, S.; Kuehn, G.; Kumar, A.; Kumar, P.; Kumar, R.; Kurdyumov, R.; Kwee, P.; Landry, M.; Lantz, B.; Larson, S.; Lasky, P. D.; Lawrie, C.; Lazzarini, A.; Le Roux, A.; Leaci, P.; Lebigot, E. O.; Lee, C.-H.; Lee, H. K.; Lee, H. M.; Lee, J.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levine, B.; Lewis, J. B.; Lhuillier, V.; Li, T. G. F.; Lin, A. C.; Littenberg, T. B.; Litvine, V.; Liu, F.; Liu, H.; Liu, Y.; Liu, Z.; Lloyd, D.; Lockerbie, N. A.; Lockett, V.; Lodhia, D.; Loew, K.; Logue, J.; Lombardi, A. L.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J.; Luan, J.; Lubinski, M. J.; Luck, H.; Lundgren, A. P.; MacArthur, J.; MacDonald, E.; Machenschalk, B.; Macinnis, M.; MacLeod, D. M.; Magana-Sandoval, F.; Mageswaran, M.; Mailand, K.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Manca, G. M.; Mandel, I.; Mandic, V.; Mangano, V.; Mantovani, M.; Marchesoni, F.; Marion, F.; Marka, S.; Marka, Z.; Markosyan, A.; Maros, E.; Marque, J.; Martelli, F.; Martin, I. W.; Martin, R. M.; Martinelli, L.; Martynov, D.; Marx, J. N.; Mason, K.; Masserot, A.; Massinger, T. J.; Matichard, F.; Matone, L.; Matzner, R. A.; Mavalvala, N.; May, G.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McGuire, S. C.; McIntyre, G.; McIver, J.; Meacher, D.; Meadors, G. D.; Mehmet, M.; Meidam, J.; Meier, T.; Melatos, A.; Mendell, G.; Mercer, R. A.; Meshkov, S.; Messenger, C.; Meyer, M. S.; Miao, H.; Michel, C.; Mikhailov, E. E.; Milano, L.; Miller, J.; Minenkov, Y.; Mingarelli, C. M. F.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moe, B.; Mohan, M.; Mohapatra, S. R. P.; Mokler, F.; Moraru, D.; Moreno, G.; Morgado, N.; Mori, T.; Morriss, S. R.; Mossavi, K.; Mours, B.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Munch, J.; Murphy, D.; Murray, P. G.; Mytidis, A.; Nagy, M. F.; Nanda, Kumar D.; Nardecchia, I.; Nash, T.; Naticchioni, L.; Nayak, R.; Necula, V.; Nelemans, G.; Neri, I.; Neri, M.; Newton, G.; Nguyen, T.; Nishida, E.; Nishizawa, A.; Nitz, A.; Nocera, F.; Nolting, D.; Normandin, M. E.; Nuttall, L. K.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oppermann, P.; O'Reilly, B.; Ortega Larcher, W.; O'Shaughnessy, R.; Osthelder, C.; Ottaway, D. J.; Ottens, R. S.; Ou, J.; Overmier, H.; Owen, B. J.; Padilla, C.; Pai, A.; Palomba, C.; Pan, Y.; Pankow, C.; Paoletti, F.; Paoletti, R.; Papa, M. A.; Paris, H.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Pedraza, M.; Peiris, P.; Penn, S.; Perreca, A.; Phelps, M.; Pichot, M.; Pickenpack, M.; Piergiovanni, F.; Pierro, V.; Pinard, L.; Pindor, B.; Pinto, I. M.; Pitkin, M.; Poeld, J.; Poggiani, R.; Poole, V.; Poux, C.; Predoi, V.; Prestegard, T.; Price, L. R.; Prijatelj, M.; Principe, M.; Privitera, S.; Prix, R.; Prodi, G. A.; Prokhorov, L.; Puncken, O.; Punturo, M.; Puppo, P.; Quetschke, V.; Quintero, E.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Racz, I.; Radkins, H.; Raffai, P.; Raja, S.; Rajalakshmi, G.; Rakhmanov, M.; Ramet, C.; Rapagnani, P.; Raymond, V.; Re, V.; Reed, C. M.; Reed, T.; Regimbau, T.; Reid, S.; Reitze, D. H.; Ricci, F.; Riesen, R.; Riles, K.; Robertson, N. A.; Robinet, F.; Rocchi, A.; Roddy, S.; Rodriguez, C.; Rodruck, M.; Roever, C.; Rolland, L.; Rollins, J. G.; Romano, J. D.; Romano, R.; Romanov, G.; Romie, J. H.; Rosinska, D.; Rowan, S.; Rudiger, A.; Ruggi, P.; Ryan, K.; Salemi, F.; Sammut, L.; Sandberg, V.; Sanders, J.; Sannibale, V.; Santiago-Prieto, I.; Saracco, E.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Savage, R.; Schilling, R.; Schnabel, R.; Schofield, R. M. S.; Schreiber, E.; Schuette, D.; Schulz, B.; Schutz, B. F.; Schwinberg, P.; Scott, J.; Scott, S. M.; Seifert, F.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sergeev, A.; Shaddock, D.; Shah, S.; Shahriar, M. S.; Shaltev, M.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sidery, T. L.; Siellez, K.; Siemens, X.; Sigg, D.; Simakov, D.; Singer, A.; Singer, L.; Sintes, A. M.; Skelton, G. R.; Slagmolen, B. J. J.; Slutsky, J.; Smith, J. R.; Smith, M. R.; Smith, R. J. E.; Smith-Lefebvre, N. D.; Soden, K.; Son, E. J.; Sorazu, B.; Souradeep, T.; Sperandio, L.; Staley, A.; Steinert, E.; Steinlechner, J.; Steinlechner, S.; Steplewski, S.; Stevens, D.; Stochino, A.; Stone, R.; Strain, K. A.; Straniero, N.; Strigin, S.; Stroeer, A. S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Susmithan, S.; Sutton, P. J.; Swinkels, B.; Szeifert, G.; Tacca, M.; Talukder, D.; Tang, L.; Tanner, D. B.; Tarabrin, S. P.; Taylor, R.; Ter Braack, A. P. M.; Thirugnanasambandam, M. P.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, V.; Tokmakov, K. V.; Tomlinson, C.; Toncelli, A.; Tonelli, M.; Torre, O.; Torres, C. V.; Torrie, C. I.; Travasso, F.; Traylor, G.; Tse, M.; Ugolini, D.; Unnikrishnan, C. S.; Vahlbruch, H.; Vajente, G.; Vallisneri, M.; van den Brand, J. F. J.; van den Broeck, C.; van der Putten, S.; van der Sluys, M. V.; van Heijningen, J.; van Veggel, A. A.; Vass, S.; Vasuth, M.; Vaulin, R.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Verkindt, D.; Verma, S.; Vetrano, F.; Vicere, A.; Vincent-Finley, R.; Vinet, J.-Y.; Vitale, S.; Vlcek, B.; Vo, T.; Vocca, H.; Vorvick, C.; Vousden, W. D.; Vrinceanu, D.; Vyachanin, S. P.; Wade, A.; Wade, L.; Wade, M.; Waldman, S. J.; Walker, M.; Wallace, L.; Wan, Y.; Wang, J.; Wang, M.; Wang, X.; Wanner, A.; Ward, R. L.; Was, M.; Weaver, B.; Wei, L.-W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.; Wessels, P.; West, M.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Wibowo, S.; Wiesner, K.; Wilkinson, C.; Williams, L.; Williams, R.; Williams, T.; Willis, J. L.; Willke, B.; Wimmer, M.; Winkelmann, L.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Yablon, J.; Yakushin, I.; Yamamoto, H.; Yancey, C. C.; Yang, H.; Yeaton-Massey, D.; Yoshida, S.; Yum, H.; Yvert, M.; Zadrozny, A.; Zanolin, M.; Zendri, J.-P.; Zhang, F.; Zhang, L.; Zhao, C.; Zhu, H.; Zhu, X. J.; Zotov, N.; Zucker, M. E.; Zweizig, J.; Buchner, S.; Cognard, I.; Corongiu, A.; D'Amico, N.; Espinoza, C. M.; Freire, P. C. C.; Gotthelf, E. V.; Guillemot, L.; Hessels, J. W. T.; Hobbs, G. B.; Kramer, M.; Lyne, A. G.; Marshall, F. E.; Possenti, A.; Ransom, S. M.; Ray, P. S.; Roy, J.; Stappers, B. W.; VIRGO Collaboration

    2017-06-01

    In this paper we have used calibrated data from the Virgo second (Aasi et al. 2012CQGra..29o5002A) and fourth science runs (VSR2 and VSR4) and the LIGO sixth science run (S6). Virgo's third science run (VSR3) was relatively insensitive in comparison with VSR4 and has not been included in this analysis. This was partially because Virgo introduced monolithic mirror suspensions prior to VSR4 which improved sensitivity in the low-frequency range. During S6, the two LIGO 4 km detectors at Hanford, Washington (LHO/H1), and Livingston, Louisiana (LLO/L1), were running in an enhanced configuration (Adhikari et al. 2006, Enhanced LIGO, Tech. Rep. LIGO-T060156-v01, California Institute of Technology, Massachusetts Institute of Technology, https://dcc.ligo.org/LIGO-T060156-v1/public) over that from the previous S5 run (Abbott et al. 2009RPPh...72g6901A). (1 data file).

  7. Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016.

    Science.gov (United States)

    Orbai, Ana-Maria; de Wit, Maarten; Mease, Philip J; Callis Duffin, Kristina; Elmamoun, Musaab; Tillett, William; Campbell, Willemina; FitzGerald, Oliver; Gladman, Dafna D; Goel, Niti; Gossec, Laure; Hoejgaard, Pil; Leung, Ying Ying; Lindsay, Chris; Strand, Vibeke; van der Heijde, Désirée M; Shea, Bev; Christensen, Robin; Coates, Laura; Eder, Lihi; McHugh, Neil; Kalyoncu, Umut; Steinkoenig, Ingrid; Ogdie, Alexis

    2017-10-01

    To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda. The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

  8. Parallel integer sorting with medium and fine-scale parallelism

    Science.gov (United States)

    Dagum, Leonardo

    1993-01-01

    Two new parallel integer sorting algorithms, queue-sort and barrel-sort, are presented and analyzed in detail. These algorithms do not have optimal parallel complexity, yet they show very good performance in practice. Queue-sort designed for fine-scale parallel architectures which allow the queueing of multiple messages to the same destination. Barrel-sort is designed for medium-scale parallel architectures with a high message passing overhead. The performance results from the implementation of queue-sort on a Connection Machine CM-2 and barrel-sort on a 128 processor iPSC/860 are given. The two implementations are found to be comparable in performance but not as good as a fully vectorized bucket sort on the Cray YMP.

  9. Sorting live stem cells based on Sox2 mRNA expression.

    Directory of Open Access Journals (Sweden)

    Hans M Larsson

    Full Text Available While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES and neural stem cells (NSC. One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB(+SSEA1(+ cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB(+ cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB(- cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner.

  10. Magnetic behavior of MnPS3 phases intercalated by [Zn2L]2+ (LH2: macrocyclic ligand obtained by condensation of 2-hydroxy-5-methyl-1,3-benzenedicarbaldehyde and 1,2-diaminobenzene)

    International Nuclear Information System (INIS)

    Spodine, E.; Valencia-Galvez, P.; Fuentealba, P.; Manzur, J.; Ruiz, D.; Venegas-Yazigi, D.; Paredes-Garcia, V.; Cardoso-Gil, R.; Schnelle, W.; Kniep, R.

    2011-01-01

    The intercalation of the cationic binuclear macrocyclic complex [Zn 2 L] 2+ (LH 2 : macrocyclic ligand obtained by the template condensation of 2-hydroxy-5-methyl-1,3-benzenedicarbaldehyde and 1,2-diaminobenzene) was achieved by a cationic exchange process, using K 0.4 Mn 0.8 PS 3 as a precursor. Three intercalated materials were obtained and characterized: (Zn 2 L) 0.05 K 0.3 Mn 0.8 PS 3 (1), (Zn 2 L) 0.1 K 0.2 Mn 0.8 PS 3 (2) and (Zn 2 L) 0.05 K 0.3 Mn 0.8 PS 3 (3), the latter phase being obtained by an assisted microwave radiation process. The magnetic data permit to estimate the Weiss temperature θ of ∼-130 K for (1); ∼-155 K for (2) and ∼-130 K for (3). The spin canting present in the potassium precursor remains unperturbed in composite (3), and spontaneous magnetization is observed under 50 K in both materials. However composites (1) and (2) do not present this spontaneous magnetization at low temperatures. The electronic properties of the intercalates do not appear to be significantly altered. The reflectance spectra of the intercalated phases (1), (2) and (3) show a gap value between 1.90 and 1.80 eV, lower than the value observed for the K 0.4 Mn 0.8 PS 3 precursor of 2.8 eV. -- Graphical Abstract: Microwave assisted synthesis was used to obtain an intercalated MnPS 3 phase with a binuclear Zn(II) macrocyclic complex. A comparative magnetic study of the composites obtained by assisted microwave and traditional synthetic methods is reported. Display Omitted Highlights: → A rapid and efficient preparation of intercalated MnPS 3 composites by assisted microwave synthesis is described. → The exchange of potassium ions of the precursor by the macrocyclic Zn(II) complex is partial. → The composite obtained by assisted microwave synthesis retains the spontaneous magnetization, observed in the low temperature range of the magnetic susceptibility of the potassium precursor. → The materials obtained by the conventional method loose the spontaneous

  11. Psychopharmacology of 5-HT1A receptors

    International Nuclear Information System (INIS)

    Cowen, Philip J.

    2000-01-01

    Serotonin 1A (5-HT 1A ) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT 1A receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT 1A receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT 1A receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT 1A receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT 1A receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT 1A autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT 1A receptor antagonists

  12. The PS Booster hits 40

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    Many accelerators’ "round" birthdays are being celebrated at CERN these days – the PS turned 50 in 2009, the SPS was 35 in 2011, and this year it's the turn of the PS Booster to mark its 40th anniversary. Originally designed to accelerate 1013 protons to 800 MeV, it has far exceeded its initial design performance over the years.   The PS Booster in the 1970s. Imagine the scene: a group of accelerator physicists staring expectantly at a monitor, when suddenly a shout of joy goes up as a signal flickers across the screen. Does that sound familiar? Well, turn the clock back 40 years (longer hair, wider trouser legs) and you have the situation at the PS Booster on 26 May 1972. On that day, beam was injected into the Booster for the first time. “It was a real buzz,” says Heribert Koziol, then Chairman of the Running-in Committee. “We were very happy – and also a little relieved – when the beam finally...

  13. The PS locomotive runs again

    CERN Multimedia

    2001-01-01

    Over forty years ago, the PS train entered service to steer the magnets of the accelerator into place... ... a service that was resumed last Tuesday. Left to right: Raymond Brown (CERN), Claude Tholomier (D.B.S.), Marcel Genolin (CERN), Gérard Saumade (D.B.S.), Ingo Ruehl (CERN), Olivier Carlier (D.B.S.), Patrick Poisot (D.B.S.), Christian Recour (D.B.S.). It is more than ten years since people at CERN heard the rumbling of the old PS train's steel wheels. Last Tuesday, the locomotive came back into service to be tested. It is nothing like the monstrous steel engines still running on conventional railways -just a small electric battery-driven vehicle employed on installing the magnets for the PS accelerator more than 40 years ago. To do so, it used the tracks that run round the accelerator. In fact, it is the grandfather of the LEP monorail. After PS was commissioned in 1959, the little train was used more and more rarely. This is because magnets never break down, or hardly ever! In fact, the loc...

  14. β-asarone improves learning and memory and reduces Acetyl Cholinesterase and Beta-amyloid 42 levels in APP/PS1 transgenic mice by regulating Beclin-1-dependent autophagy.

    Science.gov (United States)

    Deng, Minzhen; Huang, Liping; Ning, Baile; Wang, Nanbu; Zhang, Qinxin; Zhu, Caixia; Fang, Yongqi

    2016-12-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, and studies have suggested that β-asarone has pharmacological effects on beta-amyloid (Aβ) injected in the rat hippocampus. However, the effect of β-asarone on autophagy in the APP/PS1 transgenic mouse is unreported. APP/PS1 transgenic mice were randomly divided into six groups (n=10/group): an untreated group, an Aricept-treated group, a 3-MA-treated group, a rapamycin-treated group, an LY294002-treated group, a β-asarone-treated group. The control group consisted of wild-type C57BL/6 mice. All treatments were administered to the mice for 30 days. Spatial learning and memory were assessed by water maze, passive avoidance, and step-down tests. AChE and Aβ 42 levels in the hippocampus were determined by ELISA. p-Akt, p-mTOR, and LC3B expression were detected by flow cytometry. The expression of p-Akt, p-mTOR, Beclin-1, and p62 proteins was assessed by western blot. Changes in autophagy were viewed using a transmission electron microscope. APP and Beclin-1 mRNA levels were measured by Real-Time PCR. The learning and memory of APP/PS1 transgenic mice were improved significantly after β-asarone treatment compared with the untreated group. In addition, β-asarone treatment reduced AChE and Aβ 42 levels, increased p-mTOR and p62 expression, decreased p-Akt, Beclin-1, and LC3B expression, decreased the number of autophagosomes and reduced APP mRNA and Beclin-1 mRNA levels compared with the untreated group. That is, β-asarone treatment can improve the learning and memory abilities of APP/PS1 transgenic mouse by inhibiting Beclin-1-dependent autophagy via the PI3K/Akt/mTOR pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. The Multifaceted Effects of Polysaccharides Isolated from Dendrobium huoshanense on Immune Functions with the Induction of Interleukin-1 Receptor Antagonist (IL-1ra) in Monocytes

    Science.gov (United States)

    Lin, Juway; Chang, Ya-Jen; Yang, Wen-Bin; Yu, Alice L.; Wong, Chi-Huey

    2014-01-01

    Dendrobium huoshanense is a valuable and versatile Chinese herbal medicine with the anecdotal claims of cancer prevention and anti-inflammation. However, its immunological activities are limited to in vitro studies on a few cytokines and immune cell functions. First, we investigated the effects of polysaccharides isolated from DH (DH-PS) on inducing a panel of cytokines/chemokines in mice in vivo and human in vitro. We found that DH polysaccharides (DH-PS) induced TH1, TH2, inflammatory cytokines and chemokines in mouse in vivo and human cells in vitro. Secondly, we demonstrated that DH-PS expanded mouse splenocytes in vivo including CD4+ T cells, CD8+ T cells, B cells, NK cells, NKT cells, monocytes/macrophages, granulocytes and regulatory T cells. Notably, DH-PS induced an anti-inflammatory molecule, IL-1ra, in mouse and human immune cells, especially monocytes. The serum level of IL-1ra elicited by the injection of DH-PS was over 10 folds of IL-1β, suggesting that DH-PS-induced anti-inflammatory activities might over-ride the inflammatory ones mediated by IL-1β. The signaling pathways of DH-PS-induced IL-1ra production was shown to involve ERK/ELK, p38 MAPK, PI3K and NFκB. Finally, we observed that IL-1ra level induced by DH-PS was significantly higher than that by F3, a polysaccharide extract isolated from another popular Chinese herbal medicine, Ganoderma lucidum. These results indicated that DH-PS might have potential applications for ameliorating IL-1-induced pathogenic conditions. PMID:24705413

  16. The multifaceted effects of polysaccharides isolated from Dendrobium huoshanense on immune functions with the induction of interleukin-1 receptor antagonist (IL-1ra in monocytes.

    Directory of Open Access Journals (Sweden)

    Juway Lin

    Full Text Available Dendrobium huoshanense is a valuable and versatile Chinese herbal medicine with the anecdotal claims of cancer prevention and anti-inflammation. However, its immunological activities are limited to in vitro studies on a few cytokines and immune cell functions. First, we investigated the effects of polysaccharides isolated from DH (DH-PS on inducing a panel of cytokines/chemokines in mice in vivo and human in vitro. We found that DH polysaccharides (DH-PS induced TH1, TH2, inflammatory cytokines and chemokines in mouse in vivo and human cells in vitro. Secondly, we demonstrated that DH-PS expanded mouse splenocytes in vivo including CD4(+ T cells, CD8(+ T cells, B cells, NK cells, NKT cells, monocytes/macrophages, granulocytes and regulatory T cells. Notably, DH-PS induced an anti-inflammatory molecule, IL-1ra, in mouse and human immune cells, especially monocytes. The serum level of IL-1ra elicited by the injection of DH-PS was over 10 folds of IL-1β, suggesting that DH-PS-induced anti-inflammatory activities might over-ride the inflammatory ones mediated by IL-1β. The signaling pathways of DH-PS-induced IL-1ra production was shown to involve ERK/ELK, p38 MAPK, PI3K and NFκB. Finally, we observed that IL-1ra level induced by DH-PS was significantly higher than that by F3, a polysaccharide extract isolated from another popular Chinese herbal medicine, Ganoderma lucidum. These results indicated that DH-PS might have potential applications for ameliorating IL-1-induced pathogenic conditions.

  17. UCSD SORT Test (U-SORT): Examination of a newly developed organizational skills assessment tool for severely mentally ill adults.

    Science.gov (United States)

    Tiznado, Denisse; Mausbach, Brent T; Cardenas, Veronica; Jeste, Dilip V; Patterson, Thomas L

    2010-12-01

    The present investigation examined the validity of a new cognitive test intended to assess organizational skills. Participants were 180 middle-aged or older participants with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder. Participants' organizational skills were measured using our newly developed University of California, San Diego Sorting Test (U-SORT), a performance-based test of organizational ability in which subjects sort objects (e.g., battery, pens) from a "junk drawer" into "keep" versus "trash" piles. Significant correlations between U-SORT scores and theoretically similar constructs (i.e. functional capacity, cognitive functioning, and clinical symptoms) were acceptable (mean r = 0.34), and weak correlations were found between U-SORT scores and theoretically dissimilar constructs (e.g., health symptoms, social support, gender; mean r = 0.06 ). The correlation between assessment scores provides preliminary support for the U-SORT test as a brief, easily transportable, reliable, and valid measure of functioning for this population.

  18. Sphingosine-1-Phosphate Signaling in Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Li, Yuan; Lindbom, Bengt Johansson

    2017-01-01

    primary non-responders or lose responsiveness during maintenance treatment. A new class of small molecules, sphingosine-1-phosphate (S1P) receptor modulators, has recently shown efficacy in IBD. Here we provide an overview of the mechanism of action of this novel treatment principle in the context...... of intestinal inflammation. The remarkable impact of therapeutic modulation of the S1P/S1P receptor axis reflects the complexity of the pathogenesis of IBD and the fact that S1P receptor modulation may be a logical therapeutic approach for the future management of IBD....

  19. Categorizing Variations of Student-Implemented Sorting Algorithms

    Science.gov (United States)

    Taherkhani, Ahmad; Korhonen, Ari; Malmi, Lauri

    2012-01-01

    In this study, we examined freshmen students' sorting algorithm implementations in data structures and algorithms' course in two phases: at the beginning of the course before the students received any instruction on sorting algorithms, and after taking a lecture on sorting algorithms. The analysis revealed that many students have insufficient…

  20. On the Construction of Sorted Reactive Systems

    DEFF Research Database (Denmark)

    Birkedal, Lars; Debois, Søren; Hildebrandt, Thomas

    2008-01-01

    We develop a theory of sorted bigraphical reactive systems. Every application of bigraphs in the literature has required an extension, a sorting, of pure bigraphs. In turn, every such application has required a redevelopment of the theory of pure bigraphical reactive systems for the sorting at hand...... bigraphs. Technically, we give our construction for ordinary reactive systems, then lift it to bigraphical reactive systems. As such, we give also a construction of sortings for ordinary reactive systems. This construction is an improvement over previous attempts in that it produces smaller and much more...

  1. Lorentz violating p-form gauge theories in superspace

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Sudhaker [Indian Institute of Technology Kharagpur, Centre for Theoretical Studies, Kharagpur (India); Shah, Mushtaq B.; Ganai, Prince A. [National Institute of Technology, Department of Physics, Srinagar, Kashmir (India)

    2017-03-15

    Very special relativity (VSR) keeps the main features of special relativity but breaks rotational invariance due to an intrinsic preferred direction. We study the VSR-modified extended BRST and anti-BRST symmetry of the Batalin-Vilkovisky (BV) actions corresponding to the p = 1, 2, 3-form gauge theories. Within the VSR framework, we discuss the extended BRST invariant and extended BRST and anti-BRST invariant superspace formulations for these BV actions. Here we observe that the VSR-modified extended BRST invariant BV actions corresponding to the p = 1, 2, 3-form gauge theories can be written in a manifestly covariant manner in a superspace with one Grassmann coordinate. Moreover, two Grassmann coordinates are required to describe the VSR-modified extended BRST and extended anti-BRST invariant BV actions in a superspace. These results are consistent with the Lorentz-invariant (special relativity) formulation. (orig.)

  2. Implementation of Serial and Parallel Bubble Sort on Fpga

    OpenAIRE

    Purnomo, Dwi Marhaendro Jati; Arinaldi, Ahmad; Priyantini, Dwi Teguh; Wibisono, Ari; Febrian, Andreas

    2016-01-01

    Sorting is common process in computational world. Its utilization are on many fields from research to industry. There are many sorting algorithm in nowadays. One of the simplest yet powerful is bubble sort. In this study, bubble sort is implemented on FPGA. The implementation was taken on serial and parallel approach. Serial and parallel bubble sort then compared by means of its memory, execution time, and utility which comprises slices and LUTs. The experiments show that serial bubble sort r...

  3. Gender-Specific Hippocampal Dysrhythmia and Aberrant Hippocampal and Cortical Excitability in the APPswePS1dE9 Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Anna Papazoglou

    2016-01-01

    Full Text Available Alzheimer’s disease (AD is a multifactorial disorder leading to progressive memory loss and eventually death. In this study an APPswePS1dE9 AD mouse model has been analyzed using implantable video-EEG radiotelemetry to perform long-term EEG recordings from the primary motor cortex M1 and the hippocampal CA1 region in both genders. Besides motor activity, EEG recordings were analyzed for electroencephalographic seizure activity and frequency characteristics using a Fast Fourier Transformation (FFT based approach. Automatic seizure detection revealed severe electroencephalographic seizure activity in both M1 and CA1 deflection in APPswePS1dE9 mice with gender-specific characteristics. Frequency analysis of both surface and deep EEG recordings elicited complex age, gender, and activity dependent alterations in the theta and gamma range. Females displayed an antithetic decrease in theta (θ and increase in gamma (γ power at 18-19 weeks of age whereas related changes in males occurred earlier at 14 weeks of age. In females, theta (θ and gamma (γ power alterations predominated in the inactive state suggesting a reduction in atropine-sensitive type II theta in APPswePS1dE9 animals. Gender-specific central dysrhythmia and network alterations in APPswePS1dE9 point to a functional role in behavioral and cognitive deficits and might serve as early biomarkers for AD in the future.

  4. Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

    Science.gov (United States)

    Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

    2013-01-01

    Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

  5. Immunocytochemical Characterization of Alzheimer Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

    Directory of Open Access Journals (Sweden)

    Iván Carrera

    2013-01-01

    Full Text Available APP/PS1 double-transgenic mouse models of Alzheimer’s disease (AD, which overexpress mutated forms of the gene for human amyloid precursor protein (APP and presenilin 1 (PS1, have provided robust neuropathological hallmarks of AD-like pattern at early ages. This study characterizes immunocytochemical patterns of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this novel vaccine, a new approach has been taken to circumvent past failures by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol. Our findings showed that administration of amyloid-β1−42 (Aβ and sphingosine-1-phosphate emulsified in liposome complex (EB101 to APP/PS1 mice before onset of Aβ deposition (7 weeks of age and/or at an older age (35 weeks of age is effective in halting the progression and clearing the AD-like neuropathological hallmarks. Passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus in the brain of treated mice was notably reduced. These results demonstrate that immunization with EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.

  6. A cargo-sorting DNA robot.

    Science.gov (United States)

    Thubagere, Anupama J; Li, Wei; Johnson, Robert F; Chen, Zibo; Doroudi, Shayan; Lee, Yae Lim; Izatt, Gregory; Wittman, Sarah; Srinivas, Niranjan; Woods, Damien; Winfree, Erik; Qian, Lulu

    2017-09-15

    Two critical challenges in the design and synthesis of molecular robots are modularity and algorithm simplicity. We demonstrate three modular building blocks for a DNA robot that performs cargo sorting at the molecular level. A simple algorithm encoding recognition between cargos and their destinations allows for a simple robot design: a single-stranded DNA with one leg and two foot domains for walking, and one arm and one hand domain for picking up and dropping off cargos. The robot explores a two-dimensional testing ground on the surface of DNA origami, picks up multiple cargos of two types that are initially at unordered locations, and delivers them to specified destinations until all molecules are sorted into two distinct piles. The robot is designed to perform a random walk without any energy supply. Exploiting this feature, a single robot can repeatedly sort multiple cargos. Localization on DNA origami allows for distinct cargo-sorting tasks to take place simultaneously in one test tube or for multiple robots to collectively perform the same task. Copyright © 2017, American Association for the Advancement of Science.

  7. Gamma Transition Jump for PS2

    CERN Document Server

    Bartmann, W; Métral, E; Möhl, D; Peggs, S

    2008-01-01

    The PS2, which is proposed as a replacement for the existing ~50-year old PS accelerator, is presently considered to be a normal conducting synchrotron with an injection kinetic energy of 4 GeV and a maximum energy of 50 GeV. One of the possible lattices (FODO option) foresees crossing of transition energy near 10 GeV. Since the phase-slip-factor $\\eta$ becomes very small near transition energy, many intensity dependent effects can take place in both longitudinal and transverse planes. The aim of the present paper is on the one hand to scale the gamma transition jump, used since 1973 in the PS, to the projected PS2 and on the other hand based on these results the analysis of the implementation and feasibility of a gamma transition jump scheme in a conventional FODO lattice.

  8. Quantum lower bound for sorting

    OpenAIRE

    Shi, Yaoyun

    2000-01-01

    We prove that \\Omega(n log(n)) comparisons are necessary for any quantum algorithm that sorts n numbers with high success probability and uses only comparisons. If no error is allowed, at least 0.110nlog_2(n) - 0.067n + O(1) comparisons must be made. The previous known lower bound is \\Omega(n).

  9. iPS-Cinderella Story in Cell Biology

    Directory of Open Access Journals (Sweden)

    Editorial

    2010-01-01

    Full Text Available As we step through the frontiers of modern Science, we are all witnesses to the Cinderella story repeating itself in the form of the iPS. The process of re-programming adult somatic cells to derive Induced Pluripotent stem cells (iPS with the wand of transcription factors and then differentiating them back to adult somatic cells resembles the transformation of Cinderella from a Cinder girl to princess and back to a Cinder girl after the ball; but the iPS-Cinderella is the most fascinating thing ever in cell biology!From the day iPS first made its headlines when it was first produced by Shinya Yamanaka at Kyoto University in Japan, Stem Cell scientists all over the world are re- doing their experiments so far done using other sources like embryonic and adult Stem cells with the iPS cells exploring their potential to the fullest. A Stem Cell science news page without this magic word of iPS is difficult to imagine these days and Scientists have been successful in growing most of the adult Cell types from iPS cells.iPS cells was the key to solve the problems of Immune rejection and Immunosupression required when using other allogeneic Stem cell types which had baffled scientists previously. But the issues raised by scientists about the use of viruses and Oncogenes in producing iPS cells were made groundless when scientists in February 2008 published the discovery of a technique that could remove oncogenes after the induction of pluripotency and now it is possible to induce pluripotency using plasmid transfection, piggyback transposon system and piggyback transposon system combined with a non viral vector system. The word of the day is pIPS which are protein-induced Pluripotent stem cells which are iPS cells that were generated without any genetic alteration of the adult cell. This research by the group of Sheng Ding in La Jolla, California made public in April 2009 showed that the generation of poly-arginine anchors was sufficient to induce

  10. Sub One-Hundred-PS Pyroelectric Detector Research and Evaluation Program at LASL

    International Nuclear Information System (INIS)

    McLellan, E.J.; Stotlar, S.C.

    1978-01-01

    Preliminary devices have been designed and evaluated with 1 ns and 90 ps FWHM CO 2 laser pulses. Good agreement between calculated and measured values of falltime and voltage responsivity has been obtained. The female SMA to male BNC connector appears to be the most desirable easily available package for sub-one-hundred ps CO 2 laser pulses. A new detector with an expected risetime of 13 ps has been designed

  11. Gamma-secretase activity of presenilin 1 regulates acetylcholine muscarinic receptor-mediated signal transduction

    DEFF Research Database (Denmark)

    Popescu, Bogdan O; Cedazo-Minguez, Angel; Benedikz, Eirikur

    2004-01-01

    , we studied the effect of two other FAD PS1 mutants (M146V and L250S) and two dominant negative PS1 mutants (D257A and D385N) on basal and carbachol-stimulated phosphoinositide (PI) hydrolysis and intracellular calcium concentrations ([Ca2+]i) in SH-SY5Y neuroblastoma cells. We found a significant...

  12. New age radiometric ore sorting - the elegant solution

    International Nuclear Information System (INIS)

    Gordon, H.P.; Heuer, T.

    2000-01-01

    Radiometric ore sorting technology and application are described in two parts. Part I reviews the history of radiometric sorting in the minerals industry and describes the latest developments in radiometric sorting technology. Part II describes the history, feasibility study and approach used in the application of the new technology at Rossing Uranium Limited. There has been little progress in the field of radiometric sorting since the late 1970s. This has changed with the development of a high capacity radiometric sorter designed to operate on low-grade ore in the +75mm / -300mm size fraction. This has been designed specifically for an application at Rossing. Rossing has a long history in radiometric sorting dating back to 1968 when initial tests were conducted on the Rossing prospect. Past feasibility studies concluded that radiometric sorting would not conclusively reduce the unit cost of production unless sorting was used to increase production levels. The current feasibility study shows that the application of new radiometric sorter technology makes sorting viable without increasing production, and significantly more attractive with increased production. A pilot approach to confirm sorter performance is described. (author)

  13. Determination of HIV-1 co-receptor usage.

    Science.gov (United States)

    Cavarelli, Mariangela; Scarlatti, Gabriella

    2014-01-01

    Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly the β-chemokine receptor 5 (CCR5) and the α-chemokine receptor 4 (CXCR4). Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. In this chapter, methods to determine the co-receptor usage of HIV-1 variants are described.

  14. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

    International Nuclear Information System (INIS)

    Pires, L.A.; Hegg, R.; Freitas, F.R.; Tavares, E.R.; Almeida, C.P.; Baracat, E.C.; Maranhão, R.C.

    2012-01-01

    Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

  15. Effects of Specific Multi-Nutrient Enriched Diets on Cerebral Metabolism, Cognition and Neuropathology in AβPPswe-PS1dE9 Mice

    Science.gov (United States)

    Jansen, Diane; Zerbi, Valerio; Arnoldussen, Ilse A. C.; Wiesmann, Maximilian; Rijpma, Anne; Fang, Xiaotian T.; Dederen, Pieter J.; Mutsaers, Martina P. C.; Broersen, Laus M.; Lütjohann, Dieter; Miller, Malgorzata; Joosten, Leo A. B.; Heerschap, Arend; Kiliaan, Amanda J.

    2013-01-01

    Recent studies have focused on the use of multi-nutrient dietary interventions in search of alternatives for the treatment and prevention of Alzheimer's disease (AD). In this study we investigated to which extent long-term consumption of two specific multi-nutrient diets can modulate AD-related etiopathogenic mechanisms and behavior in 11-12-month-old AβPPswe-PS1dE9 mice. Starting from 2 months of age, male AβPP-PS1 mice and wild-type littermates were fed either a control diet, the DHA+EPA+UMP (DEU) diet enriched with uridine monophosphate (UMP) and the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), or the Fortasyn® Connect (FC) diet enriched with the DEU diet plus phospholipids, choline, folic acid, vitamins and antioxidants. We performed behavioral testing, proton magnetic resonance spectroscopy, immunohistochemistry, biochemical analyses and quantitative real-time PCR to gain a better understanding of the potential mechanisms by which these multi-nutrient diets exert protective properties against AD. Our results show that both diets were equally effective in changing brain fatty acid and cholesterol profiles. However, the diets differentially affected AD-related pathologies and behavioral measures, suggesting that the effectiveness of specific nutrients may depend on the dietary context in which they are provided. The FC diet was more effective than the DEU diet in counteracting neurodegenerative aspects of AD and enhancing processes involved in neuronal maintenance and repair. Both diets elevated interleukin-1β mRNA levels in AβPP-PS1 and wild-type mice. The FC diet additionally restored neurogenesis in AβPP-PS1 mice, decreased hippocampal levels of unbound choline-containing compounds in wild-type and AβPP-PS1 animals, suggesting diminished membrane turnover, and decreased anxiety-related behavior in the open field behavior. In conclusion, the current data indicate that specific multi-nutrient diets can influence AD

  16. Effects of specific multi-nutrient enriched diets on cerebral metabolism, cognition and neuropathology in AβPPswe-PS1dE9 mice.

    Directory of Open Access Journals (Sweden)

    Diane Jansen

    Full Text Available Recent studies have focused on the use of multi-nutrient dietary interventions in search of alternatives for the treatment and prevention of Alzheimer's disease (AD. In this study we investigated to which extent long-term consumption of two specific multi-nutrient diets can modulate AD-related etiopathogenic mechanisms and behavior in 11-12-month-old AβPPswe-PS1dE9 mice. Starting from 2 months of age, male AβPP-PS1 mice and wild-type littermates were fed either a control diet, the DHA+EPA+UMP (DEU diet enriched with uridine monophosphate (UMP and the omega-3 fatty acids docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA, or the Fortasyn® Connect (FC diet enriched with the DEU diet plus phospholipids, choline, folic acid, vitamins and antioxidants. We performed behavioral testing, proton magnetic resonance spectroscopy, immunohistochemistry, biochemical analyses and quantitative real-time PCR to gain a better understanding of the potential mechanisms by which these multi-nutrient diets exert protective properties against AD. Our results show that both diets were equally effective in changing brain fatty acid and cholesterol profiles. However, the diets differentially affected AD-related pathologies and behavioral measures, suggesting that the effectiveness of specific nutrients may depend on the dietary context in which they are provided. The FC diet was more effective than the DEU diet in counteracting neurodegenerative aspects of AD and enhancing processes involved in neuronal maintenance and repair. Both diets elevated interleukin-1β mRNA levels in AβPP-PS1 and wild-type mice. The FC diet additionally restored neurogenesis in AβPP-PS1 mice, decreased hippocampal levels of unbound choline-containing compounds in wild-type and AβPP-PS1 animals, suggesting diminished membrane turnover, and decreased anxiety-related behavior in the open field behavior. In conclusion, the current data indicate that specific multi-nutrient diets can

  17. Electrophysical properties of PMN-PT-PS-PFN:Li ceramics

    Directory of Open Access Journals (Sweden)

    R. Skulski

    2013-01-01

    Full Text Available We present the technology of obtaining and the electrophysical properties of a multicomponent material 0.61PMN-0.20PT-0.09PS-0.1PFN:Li (PMN-PT-PS-PFN:Li. The addition of PFN into PMN-PT decreases the temperature of final sintering which is very important during technological process (addition of Li decreases electric conductivity of PFN. Addition of PS i.e., PbSnO3 (which is unstable in ceramic form permits to shift the temperature of the maximum of dielectric permittivity. One-step method of obtaining ceramic samples from oxides and carbonates has been used. XRD, microstructure, scanning calorimetry measurements and the main dielectric, ferroelectric and electromechanical properties have been investigated for the obtained samples.

  18. A Comparison of Card-sorting Analysis Methods

    DEFF Research Database (Denmark)

    Nawaz, Ather

    2012-01-01

    This study investigates how the choice of analysis method for card sorting studies affects the suggested information structure for websites. In the card sorting technique, a variety of methods are used to analyse the resulting data. The analysis of card sorting data helps user experience (UX......) designers to discover the patterns in how users make classifications and thus to develop an optimal, user-centred website structure. During analysis, the recurrence of patterns of classification between users influences the resulting website structure. However, the algorithm used in the analysis influences...... the recurrent patterns found and thus has consequences for the resulting website design. This paper draws an attention to the choice of card sorting analysis and techniques and shows how it impacts the results. The research focuses on how the same data for card sorting can lead to different website structures...

  19. Effect of corticotropin-releasing factor receptor antagonist on psychologically suppressed masculine sexual behavior in rats.

    Science.gov (United States)

    Miwa, Yoshiji; Nagase, Keiko; Oyama, Nobuyuki; Akino, Hironobu; Yokoyama, Osamu

    2011-03-01

    Corticotropin-releasing factor (CRF) coordinates various responses of the body to stress, and CRF receptors are important targets of treatment for stress-related disorders. To investigate the effect of a nonselective CRF receptor antagonist, astressin, on suppression of masculine sexual behavior by psychological stress in rats. First, we investigated the influence of psychological stress, induced 2 hours per day for three consecutive days, on sexual behavior. Then, rats were divided into 4 groups: a control group, an astressin administration group (A), a psychological stress loading group (PS), and a psychological stress loading and astressin administration group (PS + A). The rats were exposed to sham or psychological stress for three consecutive days. After the last stress loading, the rats were injected with vehicle or astressin, and their sexual behavior was observed. We also measured serum levels of adrenocorticotropic hormone (ACTH). The effects of astressin on sexual behavior and serum levels of ACTH in rats affected by psychological stress were determined. Sexual behavior was reduced after psychological stress loading. The PS rats had significantly longer mount, intromission, and ejaculation latencies and lower ejaculation frequency than did the control, A, and PS + A rats. The intromission latency and ejaculation frequency in the PS + A rats did not achieve the level observed in the controls. There was no significant difference in these parameters between the control and A rats. Serum ACTH levels were significantly lower in PS + A rats than in PS rats. Psychologically suppressed masculine sexual behavior could be partially recovered with astressin administration in rats. These data provide a rationale for the further study of CRF receptor antagonists as novel agents for treating psychological sexual disorders. © 2010 International Society for Sexual Medicine.

  20. A real-time spike sorting method based on the embedded GPU.

    Science.gov (United States)

    Zelan Yang; Kedi Xu; Xiang Tian; Shaomin Zhang; Xiaoxiang Zheng

    2017-07-01

    Microelectrode arrays with hundreds of channels have been widely used to acquire neuron population signals in neuroscience studies. Online spike sorting is becoming one of the most important challenges for high-throughput neural signal acquisition systems. Graphic processing unit (GPU) with high parallel computing capability might provide an alternative solution for increasing real-time computational demands on spike sorting. This study reported a method of real-time spike sorting through computing unified device architecture (CUDA) which was implemented on an embedded GPU (NVIDIA JETSON Tegra K1, TK1). The sorting approach is based on the principal component analysis (PCA) and K-means. By analyzing the parallelism of each process, the method was further optimized in the thread memory model of GPU. Our results showed that the GPU-based classifier on TK1 is 37.92 times faster than the MATLAB-based classifier on PC while their accuracies were the same with each other. The high-performance computing features of embedded GPU demonstrated in our studies suggested that the embedded GPU provide a promising platform for the real-time neural signal processing.

  1. Magnetic Sorting of the Regolith on the Moon: Lunar Swirls

    Science.gov (United States)

    Pieters, C. M.; Garrick-Bethell, I.; Hemingway, D.

    2014-12-01

    All of the mysterious albedo features on the Moon called "lunar swirls" are associated with magnetic anomalies, but not all magnetic anomalies are associated with lunar swirls [1]. It is often hypothesized that the albedo markings are tied to immature regolith on the surface, perhaps due to magnetic shielding of the solar wind and prevention of normal space weathering of the soil. Although interaction of the solar wind with the surface at swirls is indeed affected by the local magnetic field [2], this does not appear to result in immature soils on the surface. Calibrated spectra from the Moon Mineralogy Mapper [M3] (in image format) demonstrate that the high albedo markings for swirls are simply not consistent with immature regolith as is now understood from detailed analyses of lunar samples [eg 3]. However, M3 data show that the high albedo features of swirls are distinct and quite different from normal soils (in both the highlands and the mare). They allexhibit a flatter continuum across the near-infrared, but the actual band strength of ferrous minerals shows little (if any) deviation [4]. Recent analyses of magnetic field direction at swirls [5] mimic the observed albedo patterns (horizontal surface fields in bright areas, vertical surface fields in dark lanes). When coupled with the optical properties of magnetic separates of lunar soils [6] and our knowledge that the magnetic component of the soil results from space weathering [3,6], we propose a new and very simple explanation for these enigmatic albedo markings: the lunar swirls result from magnetic sorting of a well developed regolith. With time, normal gardening of the soil over a magnetic anomaly causes some of the dark magnetic component of the soil to be gradually removed from regions (high albedo areas) and accumulated in others (dark lanes). We are modeling predicted sorting rates using realistic rates of dust production. If this mechanism is tenable, only the origin of these magnetic anomalies

  2. Enhanced personal protection system for the PS

    CERN Multimedia

    Caroline Duc

    2013-01-01

    During the first long shutdown (LS1) a new safety system will be installed in the primary beam areas of the PS complex in order to bring the standard of personnel radiation protection at the PS into line with that of the LHC.   Pierre Ninin, deputy group leader of GS-ASE and responsible for the installation of the new PS complex safety system, in front of a new access control system. The LHC access control systems are state-of-the-art, whereas those of the injection chain accelerators were running the risk of becoming obsolete. For the past two years a project to upgrade the access and safety systems of the first links in the LHC accelerator chain has been underway to bring them into compliance with nuclear safety standards. These systems provide the personnel with automatic protection by limiting access to hazardous areas and by ensuring that nobody is present in the areas when the accelerator is in operation. By the end of 2013, the project teams will ha...

  3. 6. Algorithms for Sorting and Searching

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 3. Algorithms - Algorithms for Sorting and Searching. R K Shyamasundar. Series Article ... Author Affiliations. R K Shyamasundar1. Computer Science Group, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005, India ...

  4. Three Sorts of Naturalism

    OpenAIRE

    Fink, Hans

    2006-01-01

    In "Two sorts of Naturalism" John McDowell is sketching his own sort of naturalism in ethics as an alternative to "bald naturalism". In this paper I distinguish materialist, idealist and absolute conceptions of nature and of naturalism in order to provide a framework for a clearer understanding of what McDowell's own naturalism amounts to. I argue that nothing short of an absolute naturalism will do for a number of McDowell's own purposes, but that it is far from obvious that this is his posi...

  5. The importin α subunit PsIMPA1 mediates the oxidative stress response and is required for the pathogenicity of Phytophthora sojae.

    Science.gov (United States)

    Yang, Xinyu; Ding, Fa; Zhang, Lei; Sheng, Yuting; Zheng, Xiaobo; Wang, Yuanchao

    2015-09-01

    The sensing of extracellular signals and their transduction into an appropriate response are crucial for the survival and virulence of plant pathogens. Eukaryotic plant pathogens must overcome the obstacles posed by nuclear membranes to manipulate gene expression to adapt to the host challenge. A highly sophisticated mechanism is the use of importins to transport proteins into the nucleus. In this study, we identified a conserved importin α gene, PsIMPA1, in Phytophthora sojae that was differentially expressed during the life cycle of this soybean pathogen. PsIMPA1 expression was lowest in zoospores and cysts but relatively consistent during the other life cycle stages, except for a slight increase at 6h post infection. Silenced mutants Psimpa1 had a decreased growth rate, an aberrant mycelial morphology, and a severely impaired ability to form oospores and sporangia. In addition, the Psimpa1 mutants exhibited reduced pathogenicity compared to the wild type. 3,3-Diaminobenzidine (DAB) staining and in vitro hydrogen peroxide tolerance assays showed that the scavenging of reactive oxygen species by these mutants was significantly impaired. Taken together, these results indicate that PsIMPA1 regulates multiple processes during the life cycle of P. sojae. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. AβPP/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging.

    Science.gov (United States)

    Ordoñez-Gutierrez, Lara; Fernandez-Perez, Ivan; Herrera, Jose Luis; Anton, Marta; Benito-Cuesta, Irene; Wandosell, Francisco

    2016-09-06

    Cerebellar pathology has been related to presenilin 1 mutations in certain pedigrees of familial Alzheimer's disease. However, cerebellum tissue has not been intensively analyzed in transgenic models of mutant presenilins. Furthermore, the effect of the sex of the mice was not systematically analyzed, despite the fact that important gender differences in the evolution of the disease in the human population have been described. We analyzed whether the progression of amyloidosis in a double transgenic mouse, AβPP/PS1, is susceptible to aging and differentially affects males and females. The accumulation of amyloid in the cerebellum differentially affects males and females of the AβPP/PS1 transgenic line, which was found to be ten-fold higher in 15-month-old females. Amyloid-β accumulation was more evident in the molecular layer of the cerebellum, but glia reaction was only observed in the granular layer of the older mice. The sex divergence was also observed in other neuronal, survival, and autophagic markers. The cerebellum plays an important role in the evolution of the pathology in this transgenic mouse model. Sex differences could be crucial for a complete understanding of this disease. We propose that the human population could be studied in this way. Sex-specific treatment strategies in human populations could show a differential response to the therapeutic approach.

  7. Package-friendly piezoresistive pressure sensors with on-chip integrated packaging-stress-suppressed suspension (PS3) technology

    International Nuclear Information System (INIS)

    Wang, Jiachou; Li, Xinxin

    2013-01-01

    An on-chip integrated packaging-stress-suppressed suspension (PS 3 ) technology for a packaging-stress-free pressure sensor is proposed and developed. With a MIS (microholes interetch and sealing) micromachining process implemented only from the front-side of a single-side polished (111) silicon wafer, a compact cantilever-shaped PS 3 is on-chip integrated surrounding a piezoresistive pressure-sensing structure to provide a packaging-process/substrate-friendly method for low-cost but high-performance sensor applications. With the MIS process, the chip size of the PS 3 -enclosed pressure sensor is as small as 0.8 mm × 0.8 mm. Compared with a normal pressure sensor without PS 3 (but with an identical pressure-sensing structure), the proposed pressure sensor has the same sensitivity of 0.046 mV kPa −1 (3.3 V) −1 . However, without using the thermal compensation technique, a temperature coefficient of offset of only 0.016% °C −1 FS is noted for the sensor with PS 3 , which is about 15 times better than that for the sensor without PS 3 . Featuring effective isolation and elimination of the influence from packaging stress, the PS 3 technique is promising to be widely used for packaging-friendly mechanical sensors. (paper)

  8. Application of radix sorting in high energy physics experiment

    International Nuclear Information System (INIS)

    Chen Xuan; Gu Minhao; Zhu Kejun

    2012-01-01

    In the high energy physics experiments, there are always requirements to sort the large scale of experiment data. To meet the demand, this paper introduces one radix sorting algorithms, whose sub-sort is counting sorting and time complex is O (n), based on the characteristic of high energy physics experiment data that is marked by time stamp. This paper gives the description, analysis, implementation and experimental result of the sorting algorithms. (authors)

  9. NK-1 receptor antagonists as anti-cancer drugs

    Indian Academy of Sciences (India)

    The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, ...

  10. A new receptor tyrosine kinase inhibitor, icotinib, for patients with lung adenocarcinoma cancer without indication for chemotherapy.

    Science.gov (United States)

    Zheng, Xiao; Liu, Guan; Wang, Shengye; Zhang, Yunli; Bao, Wenlong; Deng, Dehou; Mao, Weiming; Fang, Meiyu

    2014-10-01

    Epidermal growth factor receptor (EGFR) is an important therapeutic target in lung cancer. Gefitinib and erlotinib, two reversible EGFR receptor tyrosine kinases inhibitors (TKIs), have been approved for the treatment of patients with metastatic non small-cell lung cancer. Icotinib, which is a selective EGFR-TKI, provides a similar efficacy to gefitinib. The present study aimed to investigate the survival and safety of icotinib in patients with lung adenocarcinoma with a poor performance status (PS). A total of 42 cases of lung adenocarcinoma, including 35 females and 7 males, were enrolled. Icotinib was used as the first-line of treatment due to poor PS of the patient or a more advanced age. Icotinib (125 mg) was orally administered three times per day. The overall response rate and disease control rates were 33.3 and 85.7%, respectively. The median survival time was 13.0 months (95% CI, 5.6-20.4), The median progression-free survival time was 7.0 months, and the 1-year survival rate was 71.4%. A total of 79% of patients had an improved PS following icotinib treatment. Grade 1 to 2 rashes and diarrhea were the most frequent side effects. One patient succumbed during the study due to interstitial pneumonia. In conclusion, this is the first study indicating that patients with lung adenocarcinoma and poor PS may benefit from first-line icotinib therapy, but should be cautious of the occurrence of interstitial lung disease.

  11. Engineering a Cache-Oblivious Sorting Algorithm

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf; Vinther, Kristoffer

    2007-01-01

    This paper is an algorithmic engineering study of cache-oblivious sorting. We investigate by empirical methods a number of implementation issues and parameter choices for the cache-oblivious sorting algorithm Lazy Funnelsort, and compare the final algorithm with Quicksort, the established standard...

  12. Unraveling the mechanisms underlying the rapid vascular effects of steroids: sorting out the receptors and the pathways.

    Science.gov (United States)

    Feldman, Ross D; Gros, Robert

    2011-07-01

    Aldosterone, oestrogens and other vasoactive steroids are important physiological and pathophysiological regulators of cardiovascular and metabolic function. The traditional view of the cardiovascular actions of these vasoactive steroids has focused on their roles as regulators of transcription via activation of their 'classical' receptors [mineralocorticoid receptors (MR) and oestrogen receptors (ER)]. However, based on a series of observations going back more than half a century, scientists have speculated that a range of steroids, including oestrogen and aldosterone, might have effects on regulation of smooth muscle contractility, cell growth and differentiation that are too rapid to be accounted for by transcriptional regulation. Recent studies performed in our laboratories (and those of others) have begun to elucidate the mechanism of rapid steroid-mediated cardiometabolic regulation. GPR30, now designated as GPER-1 (http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=22), a newly characterized 'orphan receptor', has been implicated in mediating the rapid effects of estradiol and most recently those of aldosterone. Studies to date have taught us that to understand the rapid vascular mechanisms of steroids, one must (i) know which vascular 'compartment' the steroid is acting; (ii) know which receptor the steroid hormone is activating; and (iii) not assume the receptor specificity of a steroid receptor ligand based solely on its selectivity for its traditional 'transcriptional' steroid receptor. Our newfound appreciation of the rapid effects of steroids such as aldosterone and oestrogens opens up a new vista for advancing our understanding of the biology and pathobiology of vascular regulation. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  13. Beyond iPS!

    Directory of Open Access Journals (Sweden)

    Editorial

    2012-01-01

    Full Text Available It’s undoubtedly a jubilant moment for scientists and clinicians working in the stem cell arena as Prof. Gurdon and Prof. Shinya Yamanaka have been chosen for the Nobel Prize in Physiology & Medicine this year. The mystery of cell biology is something unfathomable and probably the work of this duo as well as the other scientists, who have put their hands on in- vitro de-differentiation have opened our eyes to a new window or a new paradigm in cell biology. The iPS invention has brought a lot of hope in terms of potential direct benefits to treat several diseases, which have no definite options at the moment. But, we envisage that several spin-offs could come out of this invention and one very significant spin-off finding recently witnessed is the finding by Prof. Masaharu Seno and his team of researchers at the Okayama University, Japan (Chen L, et al. 2012, PLoS ONE 7(4:e33544.doi:10.1371/journal.pone.0033544. According to Prof. Seno, mouse iPS cells (miPS when cultured in the conditioned medium derived from cancer cell lines, differentiate into cancer stem cells (CSCs. While differentiating into CSCs, they do retain the potential to develop endothelial progenitor cells. Several questions arise here: 1.Are these miPS derived CSCs really pluripotent, even if the terminal differentiation destined to specific phenotypes? 2.Shouldn’t the Cancer Stem Cells be termed as cancer progenitor cells, as till date they are considered to be producing only cancer cells but not pluripotent to yield other types of normal tissues? The spin-offs could be infinite as the process of differentiation and de-differentiation happening due to trillions of signals and pathways, most still remaining not-so-well understood. A special mention should be made to Prof. Shinya Yamanaka as he has several sterling qualities to be a role-model for budding scientists. Apart from his passion for science, which made him shift his career from orthopedics to a cell biologist, his

  14. Sorting cells of the microalga Chlorococcum littorale with increased triacylglycerol productivity.

    Science.gov (United States)

    Cabanelas, Iago Teles Dominguez; van der Zwart, Mathijs; Kleinegris, Dorinde M M; Wijffels, René H; Barbosa, Maria J

    2016-01-01

    Despite extensive research in the last decades, microalgae are still only economically feasible for high valued markets. Strain improvement is a strategy to increase productivities, hence reducing costs. In this work, we focus on microalgae selection: taking advantage of the natural biological variability of species to select variations based on desired characteristics. We focused on triacylglycerol (TAG), which have applications ranging from biodiesel to high-value omega-3 fatty-acids. Hence, we demonstrated a strategy to sort microalgae cells with increased TAG productivity. 1. We successfully identified sub-populations of cells with increased TAG productivity using Fluorescence assisted cell sorting (FACS). 2. We sequentially sorted cells after repeated cycles of N-starvation, resulting in five sorted populations (S1-S5). 3. The comparison between sorted and original populations showed that S5 had the highest TAG productivity [0.34 against 0.18 g l(-1) day(-1) (original), continuous light]. 4. Original and S5 were compared in lab-scale reactors under simulated summer conditions confirming the increased TAG productivity of S5 (0.4 against 0.2 g l(-1) day(-1)). Biomass composition analyses showed that S5 produced more biomass under N-starvation because of an increase only in TAG content and, flow cytometry showed that our selection removed cells with lower efficiency in producing TAGs. All combined, our results present a successful strategy to improve the TAG productivity of Chlorococcum littorale, without resourcing to genetic manipulation or random mutagenesis. Additionally, the improved TAG productivity of S5 was confirmed under simulated summer conditions, highlighting the industrial potential of S5 for microalgal TAG production.

  15. The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

    DEFF Research Database (Denmark)

    Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja

    2015-01-01

    We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes......, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress...

  16. Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis.

    Science.gov (United States)

    Harris, Richard A; Tindale, Lauren; Lone, Asad; Singh, Olivia; Macauley, Shannon L; Stanley, Molly; Holtzman, David M; Bartha, Robert; Cumming, Robert C

    2016-02-10

    Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-β. In vivo (1)H-magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here

  17. Development of a new approach based on midwave infrared spectroscopy for post-consumer black plastic waste sorting in the recycling industry.

    Science.gov (United States)

    Rozenstein, Offer; Puckrin, Eldon; Adamowski, Jan

    2017-10-01

    Waste sorting is key to the process of waste recycling. Exact identification of plastic resin and wood products using Near Infrared (NIR, 1-1.7µm) sensing is currently in use. Yet, dark targets characterized by low reflectance, such as black plastics, are hard to identify by this method. Following the recent success of Midwave Infrared (MWIR, 3-12µm) measurements to identify coloured plastic polymers, the aim of this study was to assess whether this technique is applicable to sorting black plastic polymers and wood products. We performed infrared reflectance contact measurements of 234 plastic samples and 29 samples of wood and paper products. Plastic samples included black, coloured and transparent Polyethylene Terephthalate (PET), Polyethylene (PE), Polyvinyl Chloride (PVC), Polypropylene (PP), Polylactic acid (PLA) and Polystyrene (PS). The spectral signatures of the black and coloured plastic samples were compared with clear plastic samples and signatures documented in the literature to identify the polymer spectral features in the presence of coloured material. This information was used to determine the spectral bands that best suit the sorting of black plastic polymers. The main NIR-MWIR absorption features of wood, cardboard and paper were identified as well according to the spectral measurements. Good agreement was found between our measurements and the absorption features documented in the literature. The new approach using MWIR spectral features appears to be useful for black plastics as it overcomes some of the limitations in the NIR region to identify them. The main limitation of this technique for industrial applications is the trade-off between the signal-to-noise ratio of the sensor operating in standoff mode and the speed at which waste is moved under the sensor. This limitation can be resolved by reducing the system's spectral resolution to 16cm -1 , which allows for faster spectra acquisition while maintaining a reasonable signal-to-noise ratio

  18. Transplantation of Human Menstrual Blood-Derived Mesenchymal Stem Cells Alleviates Alzheimer’s Disease-Like Pathology in APP/PS1 Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Yongjia Zhao

    2018-04-01

    Full Text Available Extracellular β-amyloid (Aβ plaques and neurofibrillary tangles (NFTs are the pathological hallmarks of Alzheimer’s disease (AD. Mesenchymal stem cells (MSCs have shown therapeutic efficacy in many neurodegenerative diseases, including AD. Human menstrual blood-derived stem cells (MenSCs are a novel source of MSCs advantageous for their higher proliferation rate and because they are easy to obtain without ethical concerns. Although MenSCs have exhibited therapeutic efficacy in some diseases, their effects on AD remain elusive. In the present study, we showed that intracerebral transplantation of MenSCs dramatically improved the spatial learning and memory of APP/PS1 mice. In addition, MenSCs significantly ameliorated amyloid plaques and reduced tau hyperphosphorylation in APP/PS1 mice. Remarkably, we also found that intracerebral transplantation of MenSCs markedly increased several Aβ degrading enzymes and modulated a panel of proinflammatory cytokines associated with an altered microglial phenotype, suggesting an Aβ degrading and anti-inflammatory impact of MenSCs in the brains of APP/PS1 mice. In conclusion, these findings suggest that MenSCs are a promising therapeutic candidate for AD.

  19. Buoyancy-activated cell sorting using targeted biotinylated albumin microbubbles.

    Directory of Open Access Journals (Sweden)

    Yu-Ren Liou

    Full Text Available Cell analysis often requires the isolation of certain cell types. Various isolation methods have been applied to cell sorting, including fluorescence-activated cell sorting and magnetic-activated cell sorting. However, these conventional approaches involve exerting mechanical forces on the cells, thus risking cell damage. In this study we applied a novel isolation method called buoyancy-activated cell sorting, which involves using biotinylated albumin microbubbles (biotin-MBs conjugated with antibodies (i.e., targeted biotin-MBs. Albumin MBs are widely used as contrast agents in ultrasound imaging due to their good biocompatibility and stability. For conjugating antibodies, biotin is conjugated onto the albumin MB shell via covalent bonds and the biotinylated antibodies are conjugated using an avidin-biotin system. The albumin microbubbles had a mean diameter of 2 μm with a polydispersity index of 0.16. For cell separation, the MDA-MB-231 cells are incubated with the targeted biotin-MBs conjugated with anti-CD44 for 10 min, centrifuged at 10 g for 1 min, and then allowed 1 hour at 4 °C for separation. The results indicate that targeted biotin-MBs conjugated with anti-CD44 antibodies can be used to separate MDA-MB-231 breast cancer cells; more than 90% of the cells were collected in the MB layer when the ratio of the MBs to cells was higher than 70:1. Furthermore, we found that the separating efficiency was higher for targeted biotin-MBs than for targeted avidin-incorporated albumin MBs (avidin-MBs, which is the most common way to make targeted albumin MBs. We also demonstrated that the recovery rate of targeted biotin-MBs was up to 88% and the sorting purity was higher than 84% for a a heterogenous cell population containing MDA-MB-231 cells (CD44(+ and MDA-MB-453 cells (CD44-, which are classified as basal-like breast cancer cells and luminal breast cancer cells, respectively. Knowing that the CD44(+ is a commonly used cancer

  20. 100-ps framing-camera tube

    International Nuclear Information System (INIS)

    Kalibjian, R.

    1978-01-01

    The optoelectronic framing-camera tube described is capable of recording two-dimensional image frames with high spatial resolution in the <100-ps range. Framing is performed by streaking a two-dimensional electron image across narrow slits. The resulting dissected electron line images from the slits are restored into framed images by a restorer deflector operating synchronously with the dissector deflector. The number of framed images on the tube's viewing screen equals the number of dissecting slits in the tube. Performance has been demonstrated in a prototype tube by recording 135-ps-duration framed images of 2.5-mm patterns at the cathode. The limitation in the framing speed is in the external drivers for the deflectors and not in the tube design characteristics. Faster frame speeds in the <100-ps range can be obtained by use of faster deflection drivers

  1. Physics with primary beams of the KEK-PS

    International Nuclear Information System (INIS)

    Tanaka, Kazuhiro; Yoshii, Masahito

    1993-08-01

    The 12-GeV Proton Synchrotron (PS) at the National Laboratory for High Energy Physics (KEK) has provided great opportunities to high-energy-physics and related communities as a unique high-energy hadron machine, since its operation in 1976. Activities of the KEK-PS are indispensable for the rapid development in the field. Six experimental subjects are proposed in this Report; (1) media effects in φ meson decay, (2) multifragmentation in high-energy reactions, (3) mechanism of high-energy reactions by means of radio-chemical methods, (4) physics with polarized high-energy neutrons, (5) physics with polarized high-energy deuterons, and (6) hypernucleus with high-energy heavy-ion beams. As a summary, new facilities (a new injector, a new beamline and a new experimental area) and physics programs with primary beams, proposed in this Report are themselves unique and valuable. Moreover, technical developments and physics outcomes stimulated with those new facilities are indispensable for future plans of the KEK-PS. (J.P.N.)

  2. Cloning the interleukin 1 receptor from human T cells

    International Nuclear Information System (INIS)

    Sims, J.E.; Acres, R.B.; Grubin, C.E.; McMahan, C.J.; Wignall, J.M.; March, C.J.; Dower, S.K.

    1989-01-01

    cDNA clones of the interleukin 1 (IL-1) receptor expressed in a human T-cell clone have been isolated by using a murine IL-1 receptor cDNA as a probe. The human and mouse receptors show a high degree of sequence conservation. Both are integral membrane proteins possessing a single membrane-spanning segment. Similar to the mouse receptor, the human IL-1 receptor contains a large cytoplasmic region and an extracellular, IL-1 binding portion composed of three immunoglobulin-like domains. When transfected into COS cells, the human IL-1 receptor cDNA clone leads to expression of two different affinity classes of receptors, with K a values indistinguishable from those determined for IL-1 receptors in the original T-cell clone. An IL-1 receptor expressed in human dermal fibroblasts has also been cloned and sequenced and found to be identical to the IL-1 receptor expressed in T cells

  3. Neurokinin-1 receptor activation in globus pallidus

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2009-10-01

    Full Text Available The undecapeptide substance P has been demonstrated to modulate neuronal activity in a number of brain regions by acting on neurokinin-1 receptors. Anatomical studies revealed a moderate level of neurokinin-1 receptor in rat globus pallidus. To determine the electrophysiological effects of neurokinin-1 receptor activation in globus pallidus, whole-cell patch-clamp recordings were performed in the present study. Under current-clamp recordings, neurokinin-1 receptor agonist, [Sar9, Met(O211] substance P (SM-SP at 1 μM, depolarized globus pallidus neurons and increased their firing rate. Consistently, SM-SP induced an inward current under voltage-clamp recording. The depolarization evoked by SM-SP persisted in the presence of tetrodotoxin, glutamate and GABA receptor antagonists, indicating its direct postsynaptic effects. The neurokinin-1 receptor antagonist, SR140333B, could block SM-SP-induced depolarization. Further experiments showed that suppression of potassium conductance was the predominant ionic mechanism of SM-SP-induced depolarization. To determine if neurokinin-1 receptor activation exerts any effects on GABAergic and glutamatergic neurotransmission, the action of SM-SP on synaptic currents was studied. SM-SP significantly increased the frequency of spontaneous inhibitory postsynaptic currents, but only induced a transient increase in the frequency of miniature inhibitory postsynaptic currents. No change was observed in both spontaneous and miniature excitatory postsynaptic currents. Based on the direct excitatory effects of SM-SP on pallidal neurons, we hypothesize that neurokinin-1 receptor activation in globus pallidus may be involved in the beneficial effect of substance P in Parkinson’s disease.

  4. Look into the PS Main Control Room (partial view)

    CERN Multimedia

    1974-01-01

    Jean-Pierre Potier at work. The 26 GeV Synchrotron and later also its related machines (Linacs 1,2,3; PS-Booster, LEP-Injector Linacs and Electron-Positron Accumulator; Antiproton Accumulator, Antiproton Collector, Low Energy Antiproton Ring and more recently Antiproton Decelerator) were all controlled from the PS control room situated at the Meyrin site. The SPS and LEP were controlled from a separat control centre on the Prevessin site. In 2005 all controls were transferred to the Prevessin centre.

  5. On the Directly and Subdirectly Irreducible Many-Sorted Algebras

    Directory of Open Access Journals (Sweden)

    Climent Vidal J.

    2015-03-01

    Full Text Available A theorem of single-sorted universal algebra asserts that every finite algebra can be represented as a product of a finite family of finite directly irreducible algebras. In this article, we show that the many-sorted counterpart of the above theorem is also true, but under the condition of requiring, in the definition of directly reducible many-sorted algebra, that the supports of the factors should be included in the support of the many-sorted algebra. Moreover, we show that the theorem of Birkhoff, according to which every single-sorted algebra is isomorphic to a subdirect product of subdirectly irreducible algebras, is also true in the field of many-sorted algebras.

  6. Chemical resistance of core-shell particles (PS/PMMA) polymerized by seeded suspension

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Luiz Fernando Belchior; Machado, Ricardo Antonio Francisco, E-mail: ricardo.machado@ufsc.br [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Departamento de Engenharia de Materiais; Gonçalves, Odinei Hess [Universidade Técnológica Federal do Paraná(UTFPR), Campo Mourão, PR (Brazil); Marangoni, Cintia [Universidade Federal de Santa Catarina (UFSC), Blumenau, SC (Brazil); Motz, Günter [Lehrstuhl Keramische Werkstoffe, Universität Bayreuth (Germany)

    2017-07-01

    Core-shell particles were produced on seeded suspension polymerization by using polystyrene (PS) as polymer core, or seed, and methyl methacrylate (MMA) as the shell forming monomer. Two synthesis routes were evaluated by varying the PS seed conversion before MMA addition. The main purpose of this work was to investigate the influence of synthesis routes on the morphology and chemical resistance of the resulting particles. {sup 1}H NMR spectroscopy showed that the use of PS seeds with lower conversion led to the formation of higher amount of poly(styrene-co-MMA). The copolymer acted as a compatibilizer, decreasing the interfacial energy between both homopolymers. As a consequence, a larger amount of reduced PMMA cluster were formed, as was revealed by TEM measurements. Samples in this system showed enhanced resistance to cyclohexane attack compared with pure PS, with a PS extraction of only 37% after 54 hours test. (author)

  7. Chemical resistance of core-shell particles (PS/PMMA polymerized by seeded suspension

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Belchior Ribeiro

    2017-09-01

    Full Text Available Abstract Core-shell particles were produced on seeded suspension polymerization by using polystyrene (PS as polymer core, or seed, and methyl methacrylate (MMA as the shell forming monomer. Two synthesis routes were evaluated by varying the PS seed conversion before MMA addition. The main purpose of this work was to investigate the influence of synthesis routes on the morphology and chemical resistance of the resulting particles. 1H NMR spectroscopy showed that the use of PS seeds with lower conversion led to the formation of higher amount of poly(styrene-co-MMA. The copolymer acted as a compatibilizer, decreasing the interfacial energy between both homopolymers. As a consequence, a larger amount of reduced PMMA cluster were formed, as was revealed by TEM measurements. Samples in this system showed enhanced resistance to cyclohexane attack compared with pure PS, with a PS extraction of only 37% after 54 hours test.

  8. A Longitudinal Study of Cognition, Proton MR Spectroscopy and Synaptic and Neuronal Pathology in Aging Wild-type and AβPPswe-PS1dE9 Mice

    Science.gov (United States)

    Jansen, Diane; Zerbi, Valerio; Janssen, Carola I. F.; Dederen, Pieter J. W. C.; Mutsaers, Martina P. C.; Hafkemeijer, Anne; Janssen, Anna-Lena; Nobelen, Cindy L. M.; Veltien, Andor; Asten, Jack J.; Heerschap, Arend; Kiliaan, Amanda J.

    2013-01-01

    Proton magnetic resonance spectroscopy (1H MRS) is a valuable tool in Alzheimer’s disease research, investigating the functional integrity of the brain. The present longitudinal study set out to characterize the neurochemical profile of the hippocampus, measured by single voxel 1H MRS at 7 Tesla, in the brains of AβPPSswe-PS1dE9 and wild-type mice at 8 and 12 months of age. Furthermore, we wanted to determine whether alterations in hippocampal metabolite levels coincided with behavioral changes, cognitive decline and neuropathological features, to gain a better understanding of the underlying neurodegenerative processes. Moreover, correlation analyses were performed in the 12-month-old AβPP-PS1 animals with the hippocampal amyloid-β deposition, TBS-T soluble Aβ levels and high-molecular weight Aβ aggregate levels to gain a better understanding of the possible involvement of Aβ in neurochemical and behavioral changes, cognitive decline and neuropathological features in AβPP-PS1 transgenic mice. Our results show that at 8 months of age AβPPswe-PS1dE9 mice display behavioral and cognitive changes compared to age-matched wild-type mice, as determined in the open field and the (reverse) Morris water maze. However, there were no variations in hippocampal metabolite levels at this age. AβPP-PS1 mice at 12 months of age display more severe behavioral and cognitive impairment, which coincided with alterations in hippocampal metabolite levels that suggest reduced neuronal integrity. Furthermore, correlation analyses suggest a possible role of Aβ in inflammatory processes, synaptic dysfunction and impaired neurogenesis. PMID:23717459

  9. The role of waste sorting in the South African gold-mining industry

    International Nuclear Information System (INIS)

    Freer, J.S.; Boehme, R.C.

    1985-01-01

    The absolute potential for sorting waste from run-of-mine Witwatersrand gold ores normally lies between 60 and 90 per cent by mass. At present, the practical potential lies between 40 and 50 per cent. Yet few mines achieve a waste rejection of even 30 per cent. The average waste rejection for industry, including underground sorting, fell from 19,6 per cent in 1959 to 10,1 per cent in 1983, as industry moved from labour-intensive, multistage comminution, incorporating washing, screening, and sorting, to single-stage run-of-mine milling. Most of the sorting is still being done by hand; yet photometric and radiometric sorting machines of high capacity are available. More recently, a sorter based on neutron activation and the subsequent isomeric radioactive decay of gold itself was designed. This paper examines the case for an increased role for sorting in the South African gold-mining industry brought about by the increasing cost of power for milling and the possibility of extracting gold from low-grade reject fractions by heap leaching

  10. Enhanced personal protection at the PS

    CERN Multimedia

    Samuel Morier Genoud

    2013-01-01

    Pictures 03, 06, 07 08 : Pierre Ninin, deputy group leader of GS-ASE and responsible for the installation of the new PS complex safety system, in front of a new access control system.Pictures 10, 12 ,13 : View of Building 271, the future control centre of the new PS complex safety system.

  11. Psychopharmacology of 5-HT{sub 1A} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Cowen, Philip J

    2000-07-01

    Serotonin{sub 1A} (5-HT{sub 1A}) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT{sub 1A} receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT{sub 1A} receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT{sub 1A} receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT{sub 1A} receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT{sub 1A} receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT{sub 1A} autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT{sub 1A} receptor antagonists.

  12. The PS will soon be back in operation

    CERN Multimedia

    2006-01-01

    The PS's power supply system is undergoing repairs for the accelerator to restart on 26 June. The AB Department's Power Converter Group is working flat out with Siemens to return the PS's power supply system to working order. A problem appeared on the insulation of the power cables of the rotor of the rotating machine (photo) which supplies power to the PS magnets. To prevent more significant damage to the rotating machine, the AB Department, with the approval of the CERN Management, decided to shut down the PS which had started running on 15 May. Everything is being done to restart the accelerator on 26 June. The PS's rotating machine comprises a motor coupled to a generator. The generator's rotor acts like a flywheel, supplying high-power pulses of 40 to 50 megawatts to the PS magnets. The 6 megawatt motor drives the installation at 1000 revolutions per minute and compensates only for variations in speed. It is an essential interface since it would be hard to imagine connecting such an electrical charge, p...

  13. Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4.

    Science.gov (United States)

    Tietjen, Gregory T; Gong, Zhiliang; Chen, Chiu-Hao; Vargas, Ernesto; Crooks, James E; Cao, Kathleen D; Heffern, Charles T R; Henderson, J Michael; Meron, Mati; Lin, Binhua; Roux, Benot; Schlossman, Mark L; Steck, Theodore L; Lee, Ka Yee C; Adams, Erin J

    2014-04-15

    Recognition of phosphatidylserine (PS) lipids exposed on the extracellular leaflet of plasma membranes is implicated in both apoptotic cell removal and immune regulation. The PS receptor T cell immunoglobulin and mucin-domain-containing molecule 4 (Tim4) regulates T-cell immunity via phagocytosis of both apoptotic (high PS exposure) and nonapoptotic (intermediate PS exposure) activated T cells. The latter population must be removed at lower efficiency to sensitively control immune tolerance and memory cell population size, but the molecular basis for how Tim4 achieves this sensitivity is unknown. Using a combination of interfacial X-ray scattering, molecular dynamics simulations, and membrane binding assays, we demonstrate how Tim4 recognizes PS in the context of a lipid bilayer. Our data reveal that in addition to the known Ca(2+)-coordinated, single-PS binding pocket, Tim4 has four weaker sites of potential ionic interactions with PS lipids. This organization makes Tim4 sensitive to PS surface concentration in a manner capable of supporting differential recognition on the basis of PS exposure level. The structurally homologous, but functionally distinct, Tim1 and Tim3 are significantly less sensitive to PS surface density, likely reflecting the differences in immunological function between the Tim proteins. These results establish the potential for lipid membrane parameters, such as PS surface density, to play a critical role in facilitating selective recognition of PS-exposing cells. Furthermore, our multidisciplinary approach overcomes the difficulties associated with characterizing dynamic protein/membrane systems to reveal the molecular mechanisms underlying Tim4's recognition properties, and thereby provides an approach capable of providing atomic-level detail to uncover the nuances of protein/membrane interactions.

  14. Order-sorted Algebraic Specifications with Higher-order Functions

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth

    1995-01-01

    This paper gives a proposal for how order-sorted algebraic specification languages can be extended with higher-order functions. The approach taken is a generalisation to the order-sorted case of an approach given by Mller, Tarlecki and Wirsing for the many-sorted case. The main idea in the proposal...

  15. Sorting and sustaining cooperation

    DEFF Research Database (Denmark)

    Vikander, Nick

    2013-01-01

    This paper looks at cooperation in teams where some people are selfish and others are conditional cooperators, and where lay-offs will occur at a fixed future date. I show that the best way to sustain cooperation prior to the lay-offs is often in a sorting equilibrium, where conditional cooperators...... can identify and then work with one another. Changes to parameters that would seem to make cooperation more attractive, such as an increase in the discount factor or the fraction of conditional cooperators, can reduce equilibrium cooperation if they decrease a selfish player's incentive to sort....

  16. Minor psychiatric disorders among nurses university faculties Disturbios psíquicos menores en enfermeros docentes universitarios Distúrbios psíquicos menores em enfermeiros docentes de universidades

    Directory of Open Access Journals (Sweden)

    Juliana Petri Tavares

    2012-02-01

    Full Text Available This cross-sectional study addresses 130 nursing faculty members in federal universities from Rio Grande do Sul, Brazil. It investigated the psychological demands and decision latitude (the Demand-Control Model by Karasek and their association with Minor Psychological Disorders (MPDs. The Brazilian versions of the Self-Report-Questionnaire-20 and the Job Stress Scale were used. MPDs were prevalent in 20% of the studied individuals. After adjusting for potential confounders, the chances of participants presenting mental disorders were higher in the quadrant 'active strain jobs' (OR=14.23, 95% CI 1.55 to 130.73, followed by the 'high strain jobs' quadrant (OR=10.05, 95% CI 1.23 to 82.44, compared to nursing professors classified in the 'low strain jobs' quadrant. We conclude that high psychological demands and low control over work can cause disorders in nursing professors, among them, MPDs.Estudio epidemiológico seccional entre 130 enfermeros docentes de las universidades federales del estado de Rio Grande do Sul, en Brasil, que tuvo como objetivo investigar la demanda psicológica y el control del trabajo (Modelo Demanda-Control de Karasek y sus asociaciones con Disturbios Psíquicos Menores. Se utilizaron las versiones brasileñas del Self-Report-Questionnaire-20 y del Job Stress Scale. La prevalencia de Disturbios Psíquicos Menores fue del 20,1%. Después de ajustar los posibles factores de confusión, las posibilidades de trastornos psíquicos fueron mayores en el cuadrante Trabajo Activo (OR=14,13; IC95%=1,55-130,73, seguido del cuadrante Alta exigencia (OR=10,05; IC95%=1,23-82,44, en comparación con los enfermeros docentes del cuadrante Baja Exigencia. Se concluyó que la alta demanda psicológica y el bajo control del trabajo pueden provocar daños a la salud, entre ellos los Disturbios Psíquicos Menores en enfermeros docentes.Trata-se de estudo epidemiológico seccional, incluindo 130 enfermeiros docentes das Universidades Federais do

  17. Back to work for the PS

    CERN Multimedia

    2006-01-01

    On 22 June, the PS's rotating machine started turning again for the first time since its enforced shutdown one month ago (see Bulletin No. 23-24/2006) - and the PS was back in operation the very next day! A team from Siemens worked their socks off, 6 days a week for one month (including public holidays), to repair the electrical power supply in collaboration with the AB/PO Group's Main Power Converters (MPC) Section. The generator's faulty rotor was dismantled and replaced by the renovated spare rotor. The multitude of electrical and mechanical connections together with the sheer weight of the rotor (80 tonnes) made this an extremely complex job. The AB/PO Group used the shutdown to test a back-up solution for the PS power supply. The accelerator was directly wired up to the 18 kV electrical network via a 13 MVA transformer, installed at the end of the 1970s but never used. This solution succeeded in bringing the PS back into operation but at limited energy and frequency. Just 14 GeV could be achieved, whic...

  18. A Simple Deep Learning Method for Neuronal Spike Sorting

    Science.gov (United States)

    Yang, Kai; Wu, Haifeng; Zeng, Yu

    2017-10-01

    Spike sorting is one of key technique to understand brain activity. With the development of modern electrophysiology technology, some recent multi-electrode technologies have been able to record the activity of thousands of neuronal spikes simultaneously. The spike sorting in this case will increase the computational complexity of conventional sorting algorithms. In this paper, we will focus spike sorting on how to reduce the complexity, and introduce a deep learning algorithm, principal component analysis network (PCANet) to spike sorting. The introduced method starts from a conventional model and establish a Toeplitz matrix. Through the column vectors in the matrix, we trains a PCANet, where some eigenvalue vectors of spikes could be extracted. Finally, support vector machine (SVM) is used to sort spikes. In experiments, we choose two groups of simulated data from public databases availably and compare this introduced method with conventional methods. The results indicate that the introduced method indeed has lower complexity with the same sorting errors as the conventional methods.

  19. Effect of PS-K on long-term survival of primary lung cancer patients treated with radiation

    International Nuclear Information System (INIS)

    Okazaki, Atsushi; Nakajima, Nobuaki; Hayakawa, Kazushige; Saito, Yoshihiro; Mitomo, Osamu; Niibe, Hideo

    1984-01-01

    The effect of PS-K on long-term survival of primary lung cancer patients irradiated over 60 Gy through 1977 to 1982 was studied. PS-K was administrated orally 3.0 g, daily or intermittently in the pattern of 2 weeks per a month on patients of positive PPD skin test. All cases irradiated over 60 Gy were 174 (Group A) containing 62 cases with PS-K (Group B) and 112 cases without PS-K (Group C). Of group B, 44 cases were administrated within a month after curative irradiation (Group B1), 7 cases were administrated on time maintaining long-term good condition after irradiation (Group B2) and 11 cases were administrated after recognition of recurrence or metastasis (Group B3). Following results were obtained. 1. Obvious prolongation of survivals was recognized in the patients with PS-K after irradiation. (1) The cumulative 5 years survival rates of Group A, B 1 and C were 11.0%, 28.8% and 4.8%, respectively. (2) The cumulative 5 years survival rates of stage I,11 were 45.7% with PS-K and 10.7% without PS-K. (3) The cumulative 5 years survival rates of 21 cases matched age, sex, stage, histological type and tumor dose with and without PS-K were 37.8% and 7.2%. (4) In Group B 2, 5 cases out of 7 cases have been alived, but in Group B 3, satisfactory long-term survivals ware not obtained. 2. The necessary conditions which obtain long-term survival with PS-K were thought to be follows. One is that the tumor is brought almost to vanish by irradiation. Another is that the condition of host is superior to that of tumor in host-tumor relationship. 3. The possibility of intermittent administration of PS-K was suggested. (author)

  20. Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization.

    Science.gov (United States)

    Nisar, Shaista P; Cunningham, Margaret; Saxena, Kunal; Pope, Robert J; Kelly, Eamonn; Mundell, Stuart J

    2012-07-13

    We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y(12) receptor (P2Y(12)R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y(12)R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y(12)R internalization. In vitro and prior to agonist stimulation P2Y(12)R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization.

  1. CRF1 receptor-deficiency increases cocaine reward.

    Science.gov (United States)

    Contarino, Angelo; Kitchener, Pierre; Vallée, Monique; Papaleo, Francesco; Piazza, Pier-Vincenzo

    2017-05-01

    Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF 1 receptor-deficient (CRF 1 -/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF 1 -/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF 1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF 1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF 1 -/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF 1 -/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF 1 -/- mice by exogenous corticosterone does not affect CRF 1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF 1 receptor in cocaine reward, independently of the closely related HPA axis activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Denni Algorithm An Enhanced Of SMS (Scan, Move and Sort) Algorithm

    Science.gov (United States)

    Aprilsyah Lubis, Denni; Salim Sitompul, Opim; Marwan; Tulus; Andri Budiman, M.

    2017-12-01

    Sorting has been a profound area for the algorithmic researchers, and many resources are invested to suggest a more working sorting algorithm. For this purpose many existing sorting algorithms were observed in terms of the efficiency of the algorithmic complexity. Efficient sorting is important to optimize the use of other algorithms that require sorted lists to work correctly. Sorting has been considered as a fundamental problem in the study of algorithms that due to many reasons namely, the necessary to sort information is inherent in many applications, algorithms often use sorting as a key subroutine, in algorithm design there are many essential techniques represented in the body of sorting algorithms, and many engineering issues come to the fore when implementing sorting algorithms., Many algorithms are very well known for sorting the unordered lists, and one of the well-known algorithms that make the process of sorting to be more economical and efficient is SMS (Scan, Move and Sort) algorithm, an enhancement of Quicksort invented Rami Mansi in 2010. This paper presents a new sorting algorithm called Denni-algorithm. The Denni algorithm is considered as an enhancement on the SMS algorithm in average, and worst cases. The Denni algorithm is compared with the SMS algorithm and the results were promising.

  3. Increased Alzheimer's disease-like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy.

    Science.gov (United States)

    Joshi, Gururaj; Gan, Kok Ann; Johnson, Delinda A; Johnson, Jeffrey A

    2015-02-01

    The presence of senile plaques is one of the major pathologic hallmarks of the brain with Alzheimer's disease (AD). The plaques predominantly contain insoluble amyloid β-peptide, a cleavage product of the larger amyloid precursor protein (APP). Two enzymes, named β and γ secretase, generate the neurotoxic amyloid-β peptide from APP. Mature APP is also turned over endogenously by autophagy, more specifically by the endosomal-lysosomal pathway. A defective lysosomal system is known to be pathogenic in AD. Modulation of NF-E2 related factor 2 (Nrf2) has been shown in several neurodegenerative disorders, and Nrf2 has become a potential therapeutic target for various neurodegenerative disorders, including AD, Parkinson's disease, and amyotrophic lateral sclerosis. In the current study, we explored the effect of genetic ablation of Nrf2 on APP/Aβ processing and/or aggregation as well as changes in autophagic dysfunction in APP/PS1 mice. There was a significant increase in inflammatory response in APP/PS1 mice lacking Nrf2. This was accompanied by increased intracellular levels of APP, Aβ (1-42), and Aβ (1-40), without a change total full-length APP. There was a shift of APP and Aβ into the insoluble fraction, as well as increased poly-ubiquitin conjugated proteins in mice lacking Nrf2. APP/PS1-mediated autophagic dysfunction is also enhanced in Nrf2-deficient mice. Finally, neurons in the APP/PS1/Nrf2-/- mice had increased accumulation of multivesicular bodies, endosomes, and lysosomes. These outcomes provide a better understanding of the role of Nrf2 in modulating autophagy in an AD mouse model and may help design better Nrf2 targeted therapeutics that could be efficacious in the treatment of AD. Published by Elsevier Inc.

  4. Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Tanya L Medley

    Full Text Available BACKGROUND: Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes. OBJECTIVE: We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha and the canonical Wnt pathway in this process. METHODS: Embryoid bodies (EBs derived from iPS cells were differentiated into cardiomyocytes and were exposed either to 24 h normoxia or transient hypoxia followed by a further 13 days of normoxic culture. RESULTS: At 14 days of differentiation, 59 ± 2% of normoxic EBs were beating, whilst transient hypoxia abolished beating at 14 days and EBs appeared immature. Hypoxia induced a significant increase in Brachyury and islet-1 mRNA expression, together with reduced troponin C expression. Collectively, these data suggest that transient and sustained hypoxia inhibits maturation of differentiating cardiomyocytes. Compared to normoxia, hypoxia increased HIF-1alpha, Wnt target and ligand genes in EBs, as well as accumulation of HIF-1alpha and beta-catenin in nuclear protein extracts, suggesting involvement of the Wnt/beta-catenin pathway. CONCLUSION: Hypoxia impairs cardiomyocyte differentiation and activates Wnt signaling in undifferentiated iPS cells. Taken together the study suggests that oxygenation levels play a critical role in cardiomyocyte differentiation and suggest that hypoxia may play a role in early cardiogenesis.

  5. The solution space of sorting by DCJ.

    Science.gov (United States)

    Braga, Marília D V; Stoye, Jens

    2010-09-01

    In genome rearrangements, the double cut and join (DCJ) operation, introduced by Yancopoulos et al. in 2005, allows one to represent most rearrangement events that could happen in multichromosomal genomes, such as inversions, translocations, fusions, and fissions. No restriction on the genome structure considering linear and circular chromosomes is imposed. An advantage of this general model is that it leads to considerable algorithmic simplifications compared to other genome rearrangement models. Recently, several works concerning the DCJ operation have been published, and in particular, an algorithm was proposed to find an optimal DCJ sequence for sorting one genome into another one. Here we study the solution space of this problem and give an easy-to-compute formula that corresponds to the exact number of optimal DCJ sorting sequences for a particular subset of instances of the problem. We also give an algorithm to count the number of optimal sorting sequences for any instance of the problem. Another interesting result is the demonstration of the possibility of obtaining one optimal sorting sequence by properly replacing any pair of consecutive operations in another optimal sequence. As a consequence, any optimal sorting sequence can be obtained from one other by applying such replacements successively, but the problem of finding the shortest number of replacements between two sorting sequences is still open.

  6. High-precision calculation of loosely bound states of LiPs+ and NaPs+

    International Nuclear Information System (INIS)

    Yamashita, Takuma; Kino, Yasushi

    2015-01-01

    A positronic alkali atom would be the first step to investigate behavior of a positronium(Ps) in an external field from atoms/molecules because the system can be regarded as a simple three-body system using model potentials reflecting electron orbitals of the ion core. In order to precisely determine binding energies and structures of positronic alkali atoms (LiPs + and NaPs + ), we improve the model potential so as to reproduce highly excited atomic energy levels of alkali atoms (Li and Na). The polarization potential included by the model potential is expanded in terms of Gaussian functions to finely determine a short range part of the potential which has been assumed to be a simple form. We find better reproducibility not only of atomic levels of the alkali atoms but also of the dipole polarizability of the core ion than previous works. We construct a model potential between a positron and an ion core based on the model potential between the valence electron and ion core. Binding energies associated with a dissociation of the alkali ion core and positronium, and interparticle distances are recalculated. Our results show slightly deeper bound than other previous studies. (paper)

  7. α1b-Adrenergic Receptor Localization and Relationship to the D1-Dopamine Receptor in the Rat Nucleus Accumbens.

    Science.gov (United States)

    Mitrano, Darlene A; Jackson, Kelsey; Finley, Samantha; Seeley, Allison

    2018-02-10

    The α1-adrenergic receptors1ARs) have been implicated in numerous actions of the brain, including attention and wakefulness. Additionally, they have been identified as contributing to disorders of the brain, such as drug addiction, and recent work has shown a role of these receptors in relapse to psychostimulants. While some functionality is known, the actual subcellular localization of the subtypes of the α1ARs remains to be elucidated. Further, their anatomical relationship to receptors for other neurotransmitters, such as dopamine (DA), remains unclear. Therefore, using immunohistochemistry and electron microscopy techniques, this study describes the subcellular localization of the α1b-adrenergic receptor1bAR), the subtype most tied to relapse behaviors, as well as its relationship to the D1-dopamine receptor (D1R) in both the shell and core of the rat nucleus accumbens (NAc). Overall, α1bARs were found in unmyelinated axons and axon terminals with some labeling in dendrites. In accordance with other studies of the striatum, the D1R was found mainly in dendrites and spines; therefore, colocalization of the D1R with the α1bAR was rare postsynaptically. However, in the NAc shell, when the receptors were co-expressed in the same neuronal elements there was a trend for both receptors to be found on the plasma membrane, as opposed to the intracellular compartment. This study provides valuable anatomical information about the α1bAR and its relationship to the D1R and the regulation of DA and norepinephrine (NE) neurotransmission in the brain which have been examined previously. Published by Elsevier Ltd.

  8. The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

    Science.gov (United States)

    Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

    2012-01-01

    The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

  9. EDH 'Millionaire' in PS Division

    CERN Multimedia

    2001-01-01

    Christmas cheer! Left to right: Gerard Lobeau receives a bottle of Champagne from Derek Mathieson and Jurgen De Jonghe in recognition of EDH's millionth document. At 14:33 on Monday 3 December a technician in PS division, Gerard Lobeau, unwittingly became part of an important event in the life of CERN's Electronic Document Handling system (EDH). While ordering some pieces of aluminum for one of the PS's 10Mhz RF cavities, he created EDH document number 1,000,000. To celebrate the event Derek Mathieson (EDH Project Leader) and Jurgen De Jonghe (Original EDH Project Leader) presented Mr Lobeau with a bottle of champagne. As with 93% of material requests, Mr Lobeau's order was delivered within 24 hours. 'I usually never win anything' said Mr Lobeau as he accepted his prize, 'I initially though there may have been a problem with EDH when the document number had so many zeros in it, and was then surprised to get a phone call from you a few minutes later.' The EDH team had been monitoring the EDH document number ...

  10. Particle Transport and Size Sorting in Bubble Microstreaming Flow

    Science.gov (United States)

    Thameem, Raqeeb; Rallabandi, Bhargav; Wang, Cheng; Hilgenfeldt, Sascha

    2014-11-01

    Ultrasonic driving of sessile semicylindrical bubbles results in powerful steady streaming flows that are robust over a wide range of driving frequencies. In a microchannel, this flow field pattern can be fine-tuned to achieve size-sensitive sorting and trapping of particles at scales much smaller than the bubble itself; the sorting mechanism has been successfully described based on simple geometrical considerations. We investigate the sorting process in more detail, both experimentally (using new parameter variations that allow greater control over the sorting) and theoretically (incorporating the device geometry as well as the superimposed channel flow into an asymptotic theory). This results in optimized criteria for size sorting and a theoretical description that closely matches the particle behavior close to the bubble, the crucial region for size sorting.

  11. Phosphorene-directed self-assembly of asymmetric PS-b-PMMA block copolymer for perpendicularly-oriented sub-10 nm PS nanopore arrays

    Science.gov (United States)

    Zhang, Ziming; Zheng, Lu; Khurram, Muhammad; Yan, Qingfeng

    2017-10-01

    Few-layer black phosphorus, also known as phosphorene, is a new two-dimensional material which is of enormous interest for applications, mainly in electronics and optoelectronics. Herein, we for the first time employ phosphorene for directing the self-assembly of asymmetric polystyrene-block-polymethylmethacrylate (PS-b-PMMA) block copolymer (BCP) thin film to form the perpendicular orientation of sub-10 nm PS nanopore arrays in a hexagonal fashion normal to the interface. We experimentally demonstrate that none of the PS and PMMA blocks exhibit preferential affinity to the phosphorene-modified surface. Furthermore, the perpendicularly-oriented PS nanostructures almost stay unchanged with the variation of number of layers of few-layer phosphorene nanoflakes between 15-30 layers. Differing from the neutral polymer brushes which are widely used for chemical modification of the silicon substrate, phosphorene provides a novel physical way to control the interfacial interactions between the asymmetric PS-b-PMMA BCP thin film and the silicon substrate. Based on our results, it is possible to build a new scheme for producing sub-10 nm PS nanopore arrays oriented perpendicularly to the few-layer phosphorene nanoflakes. Furthermore, the nanostructural microdomains could serve as a promising nanolithography template for surface patterning of phosphorene nanoflakes.

  12. Phosphorene-directed self-assembly of asymmetric PS-b-PMMA block copolymer for perpendicularly-oriented sub-10 nm PS nanopore arrays.

    Science.gov (United States)

    Zhang, Ziming; Zheng, Lu; Khurram, Muhammad; Yan, Qingfeng

    2017-10-20

    Few-layer black phosphorus, also known as phosphorene, is a new two-dimensional material which is of enormous interest for applications, mainly in electronics and optoelectronics. Herein, we for the first time employ phosphorene for directing the self-assembly of asymmetric polystyrene-block-polymethylmethacrylate (PS-b-PMMA) block copolymer (BCP) thin film to form the perpendicular orientation of sub-10 nm PS nanopore arrays in a hexagonal fashion normal to the interface. We experimentally demonstrate that none of the PS and PMMA blocks exhibit preferential affinity to the phosphorene-modified surface. Furthermore, the perpendicularly-oriented PS nanostructures almost stay unchanged with the variation of number of layers of few-layer phosphorene nanoflakes between 15-30 layers. Differing from the neutral polymer brushes which are widely used for chemical modification of the silicon substrate, phosphorene provides a novel physical way to control the interfacial interactions between the asymmetric PS-b-PMMA BCP thin film and the silicon substrate. Based on our results, it is possible to build a new scheme for producing sub-10 nm PS nanopore arrays oriented perpendicularly to the few-layer phosphorene nanoflakes. Furthermore, the nanostructural microdomains could serve as a promising nanolithography template for surface patterning of phosphorene nanoflakes.

  13. Performance of a dual-process PVD/PS tungsten coating structure under deuterium ion irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyunmyung; Lee, Ho Jung; Kim, Sung Hwan [Department of Nuclear and Quantum Engineering, KAIST, Daejeon (Korea, Republic of); Song, Jae-Min [Department of Nuclear Engineering, Seoul National University, Seoul (Korea, Republic of); Jang, Changheui, E-mail: chjang@kaist.ac.kr [Department of Nuclear and Quantum Engineering, KAIST, Daejeon (Korea, Republic of)

    2016-11-01

    Highlights: • D{sup +} irradiation performance of a dual-process PVD/PS W coating was evaluated. • Low-energy plasmas exposure of 100 eV D{sup +} with 1.17 × 10{sup 21} D/s{sup −1} m{sup 2} flux was applied. • After D ion irradiation, flakes were observed on the surface of the simple PS coating. • While, sub-μm size protrusions were observed for dual-process PVD/PS W coating. • Height of D spike in depth profile was lower for dual-process PVD/PS W coating. - Abstract: A dual-process coating structure was developed on a graphite substrate to improve the performance of the coating structure under anticipated operating condition of fusion devices. A thin multilayer W/Mo coating (6 μm) was deposited by physical vapor deposition (PVD) method with a variation of Mo interlayer thickness on plasma spray (PS) W coating (160 μm) of a graphite substrate panel. The dual-process PVD/PS W coatings then were exposed to 3.08 × 10{sup 24} D m{sup −2} of 100 eV D ions with a flux of 1.71 × 10{sup 21} D m{sup −2} s{sup −1} in an electron cyclotron resonance (ECR) chamber. After irradiation, surface morphology and D depth profiles of the dual-process coating were analyzed and compared to those of the simple PS W coating. Both changes in surface morphology and D retention were strongly dependent on the microstructure of surface coating. Meanwhile, the existence of Mo interlayer seemed to have no significant effect on the retention of deuterium.

  14. AAV-mediated overexpression of the CB1 receptor in the mPFC of adult rats alters cognitive flexibility, social behavior and emotional reactivity

    Directory of Open Access Journals (Sweden)

    Matthias eKlugmann

    2011-07-01

    Full Text Available The endocannabinoid (ECB system is strongly involved in the regulation of cognitive processing and emotional behavior and evidence indicates that ECB signaling might affect these behavioral abilities by modulations of prefrontal cortical functions. The aim of the present study was to examine the role of the CB1 receptor in the medial prefrontal cortex (mPFC on cognitive flexibility and emotional behavior. Therefore, the CB1 receptor was overexpressed by adeno-associated virus (AAV vector-mediated gene transfer specifically in the mPFC of adult Wistar rats. Animals were then tested in different anxiety-related paradigms for emotional reactivity (e.g. elevated plus maze (EPM, light/dark emergence test (EMT, social interaction and the attentional set shift task (ASST - an adaptation of the human Wisconsin card sorting test - for cognitive abilities and behavioral flexibility. A subtle increase in exploratory behavior was found in CB1 receptor overexpressing animals (CB1-R compared to empty vector injected controls (Empty in the EMT and EPM, although general locomotor activity did not differ between the groups. During social interaction testing, social contact behavior towards the unknown conspecific was found to be decreased, whereas social withdrawal was increased in CB1-R animals and they showed an inadequate increase in exploratory behavior compared to control animals. In the ASST, impaired reversal learning abilities were detected in CB1-R animals compared to controls, indicating reduced behavioral flexibility. In conclusion, upregulation of the CB1 receptor specifically in the rat mPFC induces alterations in emotional reactivity, leads to inadequate social behavior and impairs cognitive flexibility. These findings might be relevant for neuropsychiatric disorders, since higher cortical CB1 receptor expression levels as well as similar behavioral impairments as observed in the present study have been described in schizophrenic patients.

  15. Efficient programming of human eye conjunctiva-derived induced pluripotent stem (ECiPS) cells into definitive endoderm-like cells.

    Science.gov (United States)

    Massumi, Mohammad; Hoveizi, Elham; Baktash, Parvaneh; Hooti, Abdollah; Ghazizadeh, Leili; Nadri, Samad; Pourasgari, Farzaneh; Hajarizadeh, Athena; Soleimani, Masoud; Nabiuni, Mohammad; Khorramizadeh, Mohammad R

    2014-03-10

    Due to pluripotency of induced pluripotent stem (iPS) cells, and the lack of immunological incompatibility and ethical issues, iPS cells have been considered as an invaluable cell source for future cell replacement therapy. This study was aimed first at establishment of novel iPS cells, ECiPS, which directly reprogrammed from human Eye Conjunctiva-derived Mesenchymal Stem Cells (EC-MSCs); second, comparing the inductive effects of Wnt3a/Activin A biomolecules to IDE1 small molecule in derivation of definitive endoderm (DE) from the ECiPS cells. To that end, first, the EC-MSCs were transduced by SOKM-expressing lentiviruses and characterized for endogenous expression of embryonic markers Then the established ECiPS cells were induced to DE formation by Wnt3a/Activin A or IDE1. Quantification of GSC, Sox17 and Foxa2 expression, as DE-specific markers, in both mRNA and protein levels revealed that induction of ECiPS cells by either Wnt3a/Activin A or IDE1 could enhance the expression level of the genes; however the levels of increase were higher in Wnt3a/Activin A induced ECiPS-EBs than IDE1 induced cells. Furthermore, the flow cytometry analyses showed no synergistic effect between Activin A and Wnt3a to derive DE-like cells from ECiPS cells. The comparative findings suggest that although both Wnt3a/Activin A signaling and IDE1 molecule could be used for differentiation of iPS into DE cells, the DE-inducing effect of Wnt3a/Activin A was statistically higher than IDE1. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Comparative, validity and responsiveness of the HOOS-PS and KOOS-PS to the WOMAC physical function subscale in total joint replacement for osteoarthritis

    DEFF Research Database (Denmark)

    Davis, A M; Perruccio, A V; Canizares, M

    2009-01-01

    OBJECTIVE: To evaluate the internal consistency of the Hip disability and Osteoarthritis Outcome Score-Physical Function Short-form (HOOS-PS) and the Knee injury and Osteoarthritis Outcome Score-Physical Function Short-form (KOOS-PS) in total hip replacement (THR) and total knee (TKR) replacement....... Construct validity and responsiveness were compared to the Western Ontario McMaster Universities' Osteoarthritis Index (WOMAC) Likert 3.0 physical function (PF) subscale and the PF excluding the items in the short measures (PF-exclusions). METHODS: Participants completed the full HOOS or KOOS, measures...... of fatigue, anxiety, depression and the Chronic Pain Grade (CPG) pre-surgery and the HOOS or KOOS 6 months post-surgery. Internal consistency for the HOOS-PS and KOOS-PS was calculated using Cronbach's alpha. For construct validity, it was hypothesized that correlations between the HOOS-PS or KOOS-PS and PF...

  17. Distinct pathways mediate the sorting of tail-anchored proteins to the plastid outer envelope.

    Directory of Open Access Journals (Sweden)

    Preetinder K Dhanoa

    Full Text Available BACKGROUND: Tail-anchored (TA proteins are a distinct class of membrane proteins that are sorted post-translationally to various organelles and function in a number of important cellular processes, including redox reactions, vesicular trafficking and protein translocation. While the molecular targeting signals and pathways responsible for sorting TA proteins to their correct intracellular destinations in yeasts and mammals have begun to be characterized, relatively little is known about TA protein biogenesis in plant cells, especially for those sorted to the plastid outer envelope. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the biogenesis of three plastid TA proteins, including the 33-kDa and 34-kDa GTPases of the translocon at the outer envelope of chloroplasts (Toc33 and Toc34 and a novel 9-kDa protein of unknown function that we define here as an outer envelope TA protein (OEP9. Using a combination of in vivo and in vitro assays we show that OEP9 utilizes a different sorting pathway than that used by Toc33 and Toc34. For instance, while all three TA proteins interact with the cytosolic OEP chaperone/receptor, AKR2A, the plastid targeting information within OEP9 is distinct from that within Toc33 and Toc34. Toc33 and Toc34 also appear to differ from OEP9 in that their insertion is dependent on themselves and the unique lipid composition of the plastid outer envelope. By contrast, the insertion of OEP9 into the plastid outer envelope occurs in a proteinaceous-dependent, but Toc33/34-independent manner and membrane lipids appear to serve primarily to facilitate normal thermodynamic integration of this TA protein. CONCLUSIONS/SIGNIFICANCE: Collectively, the results provide evidence in support of at least two sorting pathways for plastid TA outer envelope proteins and shed light on not only the complex diversity of pathways involved in the targeting and insertion of proteins into plastids, but also the molecular mechanisms that underlie

  18. Event shape sorting

    International Nuclear Information System (INIS)

    Kopecna, Renata; Tomasik, Boris

    2016-01-01

    We propose a novel method for sorting events of multiparticle production according to the azimuthal anisotropy of their momentum distribution. Although the method is quite general, we advocate its use in analysis of ultra-relativistic heavy-ion collisions where a large number of hadrons is produced. The advantage of our method is that it can automatically sort out samples of events with histograms that indicate similar distributions of hadrons. It takes into account the whole measured histograms with all orders of anisotropy instead of a specific observable (e.g., v 2 , v 3 , q 2 ). It can be used for more exclusive experimental studies of flow anisotropies which are then more easily compared to theoretical calculations. It may also be useful in the construction of mixed-events background for correlation studies as it allows to select events with similar momentum distribution. (orig.)

  19. 80 kV electrostatic wire septum for AmPS

    International Nuclear Information System (INIS)

    Linden, A. van der; Bijleveld, J.H.M.; Rookhuizen, H.B.; Bruinsma, P.J.T.; Heine, E.; Lassing, P.; Prins, E.

    1992-01-01

    The Amsterdam Pulse Stretcher (AmPS) ring aims at a 100% duty cycle operation by means of slow extraction of injected electron beam pulses of 2.1 μs. In the extraction process of the AmPS, the extracted beam is intercepted from the circulating beam by the 1 m long electrostatic wire septum. For a bending angle of 4.4 mrad the maximum anode voltage is 80 kV. Care has been given to the electric field distribution at the entrance and exit of the septum and to the insulators, required to support the anode. Prototype tests have been successful up to an anode voltage of 120 kV. (R.P.) 9 refs.; 5 figs

  20. P2X1 receptors and the endothelium

    Directory of Open Access Journals (Sweden)

    LS Harrington

    2005-03-01

    Full Text Available Adenosine triphosphate (ATP is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted that ATP induces a bi-phasic response in arteries, inducing contraction via the P2X and P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y receptors located on the endothelium. However, a number of recent studies have placed P2X1 receptors on the endothelium of some arteries. The use of a specific P2X1 receptor ligand, a, b methylene ATP has demonstrated that P2X1 receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is therefore dependant on its location, inducing contraction when located on the smooth muscle cells, and dilation when expressed on the endothelium, comparable to that of P2Y receptors.

  1. Optimal Time-Space Trade-Offs for Non-Comparison-Based Sorting

    DEFF Research Database (Denmark)

    Pagh, Rasmus; Pagter, Jacob Illeborg

    2002-01-01

    We study the problem of sorting n integers of w bits on a unit-cost RAM with word size w, and in particular consider the time-space trade-off (product of time and space in bits) for this problem. For comparison-based algorithms, the time-space complexity is known to be Θ(n2). A result of Beame...... shows that the lower bound also holds for non-comparison-based algorithms, but no algorithm has met this for time below the comparison-based Ω(nlgn) lower bound.We show that if sorting within some time bound &Ttilde; is possible, then time T = O(&Ttilde; + nlg* n) can be achieved with high probability...... using space S = O(n2/T + w), which is optimal. Given a deterministic priority queue using amortized time t(n) per operation and space nO(1), we provide a deterministic algorithm sorting in time T = O(n(t(n) + lg* n)) with S = O(n2/T + w). Both results require that w ≤ n1-Ω(1). Using existing priority...

  2. Stronger Dopamine D1 Receptor-Mediated Neurotransmission in Dyskinesia.

    Science.gov (United States)

    Farré, Daniel; Muñoz, Ana; Moreno, Estefanía; Reyes-Resina, Irene; Canet-Pons, Júlia; Dopeso-Reyes, Iria G; Rico, Alberto J; Lluís, Carme; Mallol, Josefa; Navarro, Gemma; Canela, Enric I; Cortés, Antonio; Labandeira-García, José L; Casadó, Vicent; Lanciego, José L; Franco, Rafael

    2015-12-01

    Radioligand binding assays to rat striatal dopamine D1 receptors showed that brain lateralization of the dopaminergic system were not due to changes in expression but in agonist affinity. D1 receptor-mediated striatal imbalance resulted from a significantly higher agonist affinity in the left striatum. D1 receptors heteromerize with dopamine D3 receptors, which are considered therapeutic targets for dyskinesia in parkinsonian patients. Expression of both D3 and D1-D3 receptor heteromers were increased in samples from 6-hydroxy-dopamine-hemilesioned rats rendered dyskinetic by treatment with 3, 4-dihydroxyphenyl-L-alanine (L-DOPA). Similar findings were obtained using striatal samples from primates. Radioligand binding studies in the presence of a D3 agonist led in dyskinetic, but not in lesioned or L-DOPA-treated rats, to a higher dopamine sensitivity. Upon D3-receptor activation, the affinity of agonists for binding to the right striatal D1 receptor increased. Excess dopamine coming from L-DOPA medication likely activates D3 receptors thus making right and left striatal D1 receptors equally responsive to dopamine. These results show that dyskinesia occurs concurrently with a right/left striatal balance in D1 receptor-mediated neurotransmission.

  3. KEGS Discovery of 9 Supernova Candidates in the K2 Campaign 17 field with Pan-STARRS PS1

    Science.gov (United States)

    Smith, K. W.; Rest, A.; Tucker, B. E.; Garnavich, P. M.; Margheim, S.; Kasen, D.; Olling, R.; Shaya, E.; Narayan, G.; Villar, A.; Forster, F.; Mushotzky, R.; Zenteno, A.; James, D.; Smith, R. Chris; Dotson, J. L.; Barentsen, G.; Gully-Santiago, M.; Smartt, S. J.; Wright, D. E.; Huber, M.; Chambers, K. C.; Flewelling, H.; Willman, M.; Schultz, A.; Magnier, E.; Waters, C.; Bulger, J.; Wainscoat, R. J.

    2018-05-01

    We report the following transients discovered by Pan-STARRS1 during a targeted search of the Kepler Campaign 17 field as part of the K2 Extragalactic Survey (KEGS) for Transients (see http://www.mso.anu.edu.au/kegs/ ) Information on the Pan-STARRS Survey for Transients is available at http://star.pst.qub.ac.uk/ps1threepi/ (see Huber et al. ATel #7153).

  4. Reduction of Aflatoxins in Apricot Kernels by Electronic and Manual Color Sorting

    Directory of Open Access Journals (Sweden)

    Rosanna Zivoli

    2016-01-01

    Full Text Available The efficacy of color sorting on reducing aflatoxin levels in shelled apricot kernels was assessed. Naturally-contaminated kernels were submitted to an electronic optical sorter or blanched, peeled, and manually sorted to visually identify and sort discolored kernels (dark and spotted from healthy ones. The samples obtained from the two sorting approaches were ground, homogenized, and analysed by HPLC-FLD for their aflatoxin content. A mass balance approach was used to measure the distribution of aflatoxins in the collected fractions. Aflatoxin B1 and B2 were identified and quantitated in all collected fractions at levels ranging from 1.7 to 22,451.5 µg/kg of AFB1 + AFB2, whereas AFG1 and AFG2 were not detected. Excellent results were obtained by manual sorting of peeled kernels since the removal of discolored kernels (2.6%–19.9% of total peeled kernels removed 97.3%–99.5% of total aflatoxins. The combination of peeling and visual/manual separation of discolored kernels is a feasible strategy to remove 97%–99% of aflatoxins accumulated in naturally-contaminated samples. Electronic optical sorter gave highly variable results since the amount of AFB1 + AFB2 measured in rejected fractions (15%–18% of total kernels ranged from 13% to 59% of total aflatoxins. An improved immunoaffinity-based HPLC-FLD method having low limits of detection for the four aflatoxins (0.01–0.05 µg/kg was developed and used to monitor the occurrence of aflatoxins in 47 commercial products containing apricot kernels and/or almonds commercialized in Italy. Low aflatoxin levels were found in 38% of the tested samples and ranged from 0.06 to 1.50 μg/kg for AFB1 and from 0.06 to 1.79 μg/kg for total aflatoxins.

  5. The LLL compact 10-ps streak camera

    International Nuclear Information System (INIS)

    Thomas, S.W.; Houghton, J.W.; Tripp, G.R.; Coleman, L.W.

    1975-01-01

    The 10-ps streak camera has been redesigned to simplify its operation, reduce manufacturing costs, and improve its appearance. The electronics have been simplified, a film indexer added, and a contacted slit has been evaluated. Data support a 10-ps resolution. (author)

  6. PS, SL and LHC Auditoria change names

    CERN Multimedia

    2003-01-01

    Following the replacement of the PS, SL and LHC Divisions by the AB and AT Divisions, the Auditoria are also changing their names. PS Auditorium is renamed AB Meyrin SL Auditorium is renamed AB Prévessin LHC Auditorium is renamed AT

  7. Computer modeling of Cannabinoid receptor type 1

    Directory of Open Access Journals (Sweden)

    Sapundzhi Fatima

    2018-01-01

    Full Text Available Cannabinoid receptors are important class of receptors as they are involved in various physiological processes such as appetite, pain-sensation, mood, and memory. It is important to design receptor-selective ligands in order to treat a particular disorder. The aim of the present study is to model the structure of cannabinoid receptor CB1 and to perform docking between obtained models and known ligands. Two models of CBR1 were prepared with two different methods (Modeller of Chimera and MOE. They were used for docking with GOLD 5.2. It was established a high correlation between inhibitory constant Ki of CB1 cannabinoid ligands and the ChemScore scoring function of GOLD, which concerns both models. This suggests that the models of the CB1 receptors obtained could be used for docking studies and in further investigation and design of new potential, selective and active cannabinoids with the desired effects.

  8. Disturbed neuronal ER-Golgi sorting of unassembled glycine receptors suggests altered subcellular processing is a cause of human hyperekplexia.

    Science.gov (United States)

    Schaefer, Natascha; Kluck, Christoph J; Price, Kerry L; Meiselbach, Heike; Vornberger, Nadine; Schwarzinger, Stephan; Hartmann, Stephanie; Langlhofer, Georg; Schulz, Solveig; Schlegel, Nadja; Brockmann, Knut; Lynch, Bryan; Becker, Cord-Michael; Lummis, Sarah C R; Villmann, Carmen

    2015-01-07

    Recent studies on the pathogenic mechanisms of recessive hyperekplexia indicate disturbances in glycine receptor (GlyR) α1 biogenesis. Here, we examine the properties of a range of novel glycine receptor mutants identified in human hyperekplexia patients using expression in transfected cell lines and primary neurons. All of the novel mutants localized in the large extracellular domain of the GlyR α1 have reduced cell surface expression with a high proportion of receptors being retained in the ER, although there is forward trafficking of glycosylated subpopulations into the ER-Golgi intermediate compartment and cis-Golgi compartment. CD spectroscopy revealed that the mutant receptors have proportions of secondary structural elements similar to wild-type receptors. Two mutants in loop B (G160R, T162M) were functional, but none of those in loop D/β2-3 were. One nonfunctional truncated mutant (R316X) could be rescued by coexpression with the lacking C-terminal domain. We conclude that a proportion of GlyR α1 mutants can be transported to the plasma membrane but do not necessarily form functional ion channels. We suggest that loop D/β2-3 is an important determinant for GlyR trafficking and functionality, whereas alterations to loop B alter agonist potencies, indicating that residues here are critical elements in ligand binding. Copyright © 2015 the authors 0270-6474/15/350422-16$15.00/0.

  9. Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells.

    Science.gov (United States)

    Amoh, Yasuyuki; Kanoh, Maho; Niiyama, Shiro; Hamada, Yuko; Kawahara, Katsumasa; Sato, Yuichi; Hoffman, Robert M; Katsuoka, Kensei

    2009-08-01

    The optimal source of stem cells for regenerative medicine is a major question. Embryonic stem (ES) cells have shown promise for pluripotency but have ethical issues and potential to form teratomas. Pluripotent stem cells have been produced from skin cells by either viral-, plasmid- or transposon-mediated gene transfer. These stem cells have been termed induced pluripotent stem cells or iPS cells. iPS cells may also have malignant potential and are inefficiently produced. Embryonic stem cells may not be suited for individualized therapy, since they can undergo immunologic rejection. To address these fundamental problems, our group is developing hair follicle pluripotent stem (hfPS) cells. Our previous studies have shown that mouse hfPS cells can differentiate to neurons, glial cells in vitro, and other cell types, and can promote nerve and spinal cord regeneration in vivo. hfPS cells are located above the hair follicle bulge in what we have termed the hfPS cell area (hfPSA) and are nestin positive and keratin 15 (K-15) negative. Human hfPS cells can also differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In the present study, human hfPS cells were transplanted in the severed sciatic nerve of the mouse where they differentiated into glial fibrillary-acidic-protein (GFAP)-positive Schwann cells and promoted the recovery of pre-existing axons, leading to nerve generation. The regenerated nerve recovered function and, upon electrical stimulation, contracted the gastrocnemius muscle. The hfPS cells can be readily isolated from the human scalp, thereby providing an accessible, autologous and safe source of stem cells for regenerative medicine that have important advantages over ES or iPS cells. (c) 2009 Wiley-Liss, Inc.

  10. New free-release and sorting monitors developed for NPP A-1 decommissioning, Slovakia - 59071

    International Nuclear Information System (INIS)

    Slavik, Ondrej; Listjak, Martin; Kravar, Kamil; Slaninka, Alojz; Pely, Igor

    2012-01-01

    A pilot free-release monitoring post with a 600 L container monitor was developed and metrological tested within the 2. stage of NPP A1 decommissioning project. In order to reduce the volume of contaminated soil monitoring a conceptual design of fast sorting loader shovel monitor (loader's spoon) was proposed and tested within the project as well. The free-release monitoring post makes use of a pair of electrically cooled lead shielded semiconductor detectors placed into a mounting rack ensuring measurements in either horizontal (container monitoring) or vertical (drum monitoring) counting geometry. For evaluation of measured HPGe spectra the Canberra -Packard ISOCS detection efficiency calculation code was used. A loader is used to change the measured side of the 600 L container. For metrological certification of this monitor a special prototype test container with 24 rod sources inside a regular grid was necessary to design and to use. The mentioned above vertical counting geometry together with an additional drum rotator ensures standard free release monitoring of materials in 200 l rotating drums. Successful metrological qualification of the both counting geometries at SMU Bratislava showed 20 % accuracy class. A pair of NaI(Tl) detectors and a measurement and navigation frame ensuring loader shovel fixation in counting position are used for the fast sorting monitoring. The navigation of loader and its shovel to the counting geometry should be as fast as possible. The monitored results shall be indicated by a prompt light indication system (apart from storing on HDD). MCNP 5 calculation code was used for assessment of gross gamma 137 Cs detection efficiency. The estimated MDA for a pair of 2'' x 2'' Na(Tl) detectors and 30 s acquisition time is about 90 Bq/kg. However, due to the counting geometry deviations from calculated values the uncertainty of measurements can be relatively high. Hence, the system is applicable for sorting monitoring only. (authors)

  11. Sorting and selection in posets

    DEFF Research Database (Denmark)

    Daskalakis, Constantinos; Karp, Richard M.; Mossel, Elchanan

    2011-01-01

    from two decades ago by Faigle and Turán. In particular, we present the first algorithm that sorts a width-$w$ poset of size $n$ with query complexity $O(n(w+\\log n))$ and prove that this query complexity is asymptotically optimal. We also describe a variant of Mergesort with query complexity $O......(wn\\log\\frac{n}{w})$ and total complexity $O(w^{2}n\\log\\frac{n}{w})$; an algorithm with the same query complexity was given by Faigle and Turán, but no efficient implementation of that algorithm is known. Both our sorting algorithms can be applied with negligible overhead to the more general problem of reconstructing transitive......Classical problems of sorting and searching assume an underlying linear ordering of the objects being compared. In this paper, we study these problems in the context of partially ordered sets, in which some pairs of objects are incomparable. This generalization is interesting from a combinatorial...

  12. The GPRC6A Receptor displays Constitutive Internalization and Sorting to the Slow Recycling Pathway

    DEFF Research Database (Denmark)

    Jacobsen, Stine Engesgaard; Ammendrup-Johnsen, Ina; Jansen, Anna Mai

    2017-01-01

    The class C G protein-coupled receptor GPRC6A is a putative nutrient sensing receptor and represents a possible new drug target in metabolic disorders. However, the specific physiological role of this receptor has yet to be identified, and the mechanisms regulating its activity and cell surface...... availability also remain enigmatic. In the present study, we investigated the trafficking properties of GPRC6A by use of both a classical antibody feeding internalization assay in which cells were visualized using confocal microscopy and a novel internalization assay that is based on real-time measurements...... slow recycling pathway, which may be responsible for ensuring a persistent pool of GPRC6A receptors at the cell surface despite chronic agonist exposure. Distinct trafficking pathways have been reported for several of the class C receptors, and our results thus substantiate that non...

  13. Sorting processes with energy-constrained comparisons*

    Science.gov (United States)

    Geissmann, Barbara; Penna, Paolo

    2018-05-01

    We study very simple sorting algorithms based on a probabilistic comparator model. In this model, errors in comparing two elements are due to (1) the energy or effort put in the comparison and (2) the difference between the compared elements. Such algorithms repeatedly compare and swap pairs of randomly chosen elements, and they correspond to natural Markovian processes. The study of these Markov chains reveals an interesting phenomenon. Namely, in several cases, the algorithm that repeatedly compares only adjacent elements is better than the one making arbitrary comparisons: in the long-run, the former algorithm produces sequences that are "better sorted". The analysis of the underlying Markov chain poses interesting questions as the latter algorithm yields a nonreversible chain, and therefore its stationary distribution seems difficult to calculate explicitly. We nevertheless provide bounds on the stationary distributions and on the mixing time of these processes in several restrictions.

  14. Psühhodraama - spontaansuse kool / Taimi Elenurm

    Index Scriptorium Estoniae

    Elenurm, Taimi

    2010-01-01

    Viinis ja New Yorgis tegutsenud psühhiaatri Jakob Levy Moreno loodud psühhodraamast, mis võimaldab rollimängu kaudu näha ennast läbi teiste silmade, aga ka vabaneda pingetest andes võimaluse käituda teisiti kui tavaelus

  15. Syntheses of 7-Substituted α-Cyperone Derivatives for Selective Sigma-1 Receptor over Cannabinoid-1 Receptor Binding Affinities

    Energy Technology Data Exchange (ETDEWEB)

    Park, Juyoung; Shin, Younggyun; Yoon, Sunghwa [Ajou Univ., Suwon (Korea, Republic of); Kim, Keewon; Kwon, Youngbae [ChonBuk National Univ., Jeonju (Korea, Republic of)

    2013-11-15

    We have successfully synthesized seven α-cyperone derivatives and found that the presence of a hydrogen bond donor/acceptor groups at the C7 position of α-cyperone significantly affects specificity and potency of CB{sub 1} receptor binding affinity over sigma-1 receptor binding affinity. In particular, the presence of the amino moiety at the C7 position of α-cyperone is beneficial for binding to sigmia-1 receptor. The molecular mechanism of compound 8 involved in the high binding affinity to sigma-1 receptor is under investigation. We first synthesized α-cyperone 1 by following the previously reported synthetic routes.15-19 In brief, azeotropic imination of (+)-dihydrocarvone and (R)-(+)-1-phenylethylamine followed by alkylation with a slight excess of ethyl vinyl ketone (EVK) in THF at 40 .deg. C produced the Micheal adduct. The resulting adduct was hydrolyzed and then treated with sodium methoxide at room temperature to give an easily separable mixture of α-cyperone 1 and its side product. Flash chromatography resulted in pure α-cyperone 1 in a 30% yield from (+)-dihydrocarvone.

  16. Effect of early exposure to different feed presentations on feed sorting of dairy calves.

    Science.gov (United States)

    Miller-Cushon, E K; Bergeron, R; Leslie, K E; Mason, G J; Devries, T J

    2013-07-01

    This study examined how early exposure to different feed presentations affects development of feed sorting in dairy calves. Twenty Holstein bull calves were exposed for the first 8 wk of life to 1 of 2 feed presentation treatments: concentrate and chopped grass hay (haylage, 21.5% high-moisture corn, and 16.0% protein supplement) in wk 12 to 13. Intake was recorded daily and calves were weighed twice a week. Fresh feed and orts were sampled on d 1 to 4 of wk 6, 8, 9, 11, 12, and 13 for analysis of feed sorting, which was assessed through nutrient analysis for the MIX diet and particle size analysis for the TMR. The particle separator had 3 screens (19, 8, and 1.18mm) producing long, medium, short, and fine particle fractions. Sorting of nutrients or particle fractions was calculated as the actual intake as a percentage of predicted intake; values >100% indicate sorting for, whereas values <100% indicate sorting against. Feed presentation did not affect dry matter intake or growth. Prior to weaning, all calves selected in favor of hay; MIX calves consumed more neutral detergent fiber (NDF) than predicted (103.6%) and less nonfiber carbohydrates (NFC) than predicted (92.6%), and COM calves consumed, as a percentage of dry matter intake, 40.3% hay (vs. 30% offered rate). In wk 8, calves fed COM consumed more NFC than calves fed MIX (1.0 vs. 0.95kg/d) and less NDF (0.43 vs. 0.54kg/d), indicating greater selection in favor of concentrate. However, when provided the MIX diet, calves previously fed COM did not sort, whereas calves previously fed MIX consumed more NFC intake than predicted (103.2%) and less NDF intake than predicted (97.6%). Calves previously fed MIX maintained increased sorting after transition to the novel TMR, sorting against long particles (86.5%) and for short (101.8%) and fine (101.2%) particles. These results indicate that initially providing dairy calves with solid feeds as separate components, compared with as a mixed ration, reduces the extent of

  17. Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes.

    Science.gov (United States)

    Stone, Matthew B; Shelby, Sarah A; Núñez, Marcos F; Wisser, Kathleen; Veatch, Sarah L

    2017-02-01

    Diverse cellular signaling events, including B cell receptor (BCR) activation, are hypothesized to be facilitated by domains enriched in specific plasma membrane lipids and proteins that resemble liquid-ordered phase-separated domains in model membranes. This concept remains controversial and lacks direct experimental support in intact cells. Here, we visualize ordered and disordered domains in mouse B lymphoma cell membranes using super-resolution fluorescence localization microscopy, demonstrate that clustered BCR resides within ordered phase-like domains capable of sorting key regulators of BCR activation, and present a minimal, predictive model where clustering receptors leads to their collective activation by stabilizing an extended ordered domain. These results provide evidence for the role of membrane domains in BCR signaling and a plausible mechanism of BCR activation via receptor clustering that could be generalized to other signaling pathways. Overall, these studies demonstrate that lipid mediated forces can bias biochemical networks in ways that broadly impact signal transduction.

  18. Chemokine receptor expression by inflammatory T cells in EAE

    DEFF Research Database (Denmark)

    Mony, Jyothi Thyagabhavan; Khorooshi, Reza; Owens, Trevor

    2014-01-01

    Chemokines direct cellular infiltration to tissues, and their receptors and signaling pathways represent targets for therapy in diseases such as multiple sclerosis (MS). The chemokine CCL20 is expressed in choroid plexus, a site of entry of T cells to the central nervous system (CNS). The CCL20...... receptor CCR6 has been reported to be selectively expressed by CD4(+) T cells that produce the cytokine IL-17 (Th17 cells). Th17 cells and interferon-gamma (IFNγ)-producing Th1 cells are implicated in induction of MS and its animal model experimental autoimmune encephalomyelitis (EAE). We have assessed...... whether CCR6 identifies specific inflammatory T cell subsets in EAE. Our approach was to induce EAE, and then examine chemokine receptor expression by cytokine-producing T cells sorted from CNS at peak disease. About 7% of CNS-infiltrating CD4(+) T cells produced IFNγ in flow cytometric cytokine assays...

  19. Serotonin type-1A receptor imaging in depression

    International Nuclear Information System (INIS)

    Drevets, Wayne C.; Frank, Ellen; Price, Julie C.; Kupfer, David J.; Greer, Phil J.; Mathis, Chester

    2000-01-01

    Regional 5-hydroxytryptamine 1A (5-HT 1A ) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl- 11 C]WAY-100635 {[ 11 C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide}. The mean 5-HT 1A receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT 1A receptor BP are consistent with in vivo evidence that 5-HT 1A receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT 1A receptor expression in primary mood disorders

  20. MODELING WORK OF SORTING STATION USING UML

    Directory of Open Access Journals (Sweden)

    O. V. Gorbova

    2014-12-01

    Full Text Available Purpose. The purpose of this paper is the construction of methods and models for the graphical representation process of sorting station, using the unified modeling language (UML. Methodology. Methods of graph theory, finite automata and the representation theory of queuing systems were used as the methods of investigation. A graphical representation of the process was implemented with using the Unified Modeling Language UML. The sorting station process representation is implemented as a state diagram and actions through a set of IBM Rational Rose. Graphs can show parallel operation of sorting station, the parallel existence and influence of objects process and the transition from one state to another. The IBM Rational Rose complex allows developing a diagram of work sequence of varying degrees of detailing. Findings. The study has developed a graphical representation method of the process of sorting station of different kind of complexity. All graphical representations are made using the UML. They are represented as a directed graph with the states. It is clear enough in the study of the subject area. Applying the methodology of the representation process, it allows becoming friendly with the work of any automation object very fast, and exploring the process during algorithms construction of sorting stations and other railway facilities. This model is implemented with using the Unified Modeling Language (UML using a combination of IBM Rational Rose. Originality. The representation process of sorting station was developed by means of the Unified Modeling Language (UML use. Methodology of representation process allows creating the directed graphs based on the order of execution of the works chain, objects and performers of these works. The UML allows visualizing, specifying, constructing and documenting, formalizing the representation process of sorting station and developing sequence diagrams of works of varying degrees of detail. Practical

  1. Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer's disease-related pathologies in APPswe/PS1dE9 transgenic mice.

    Science.gov (United States)

    Tsai-Teng, Tzeng; Chin-Chu, Chen; Li-Ya, Lee; Wan-Ping, Chen; Chung-Kuang, Lu; Chien-Chang, Shen; Chi-Ying, Huang F; Chien-Chih, Chen; Shiao, Young-Ji

    2016-06-27

    The fruiting body of Hericium erinaceus has been demonstrated to possess anti-dementia activity in mouse model of Alzheimer's disease and people with mild cognitive impairment. However, the therapeutic potential of Hericium erinaceus mycelia on Alzheimer's disease remains unclear. In this study, the effects of erinacine A-enriched Hericium erinaceus mycelia (HE-My) on the pathological changes in APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease are studied. After a 30 day oral administration to 5 month-old female APPswe/PS1dE9 transgenic mice, we found that HE-My and its ethanol extracts (HE-Et) attenuated cerebral Aβ plaque burden. It's worth noting that the attenuated portion of a plaque is the non-compact structure. The level of insulin-degrading enzyme was elevated by both HE-My and HE-Et in cerebral cortex. On the other hand, the number of plaque-activated microglia and astrocytes in cerebral cortex and hippocampus were diminished, the ratio of nerve growth factor (NGF) to NGF precursor (proNGF) was increased and hippocampal neurogenesis was promoted after these administrations. All the mentioned benefits of these administrations may therefore improve the declined activity of daily living skill in APPswe/PS1dE9 transgenic mice. These results highlight the therapeutic potential of HE-My and HE-Et on Alzheimer's disease. Therefore, the effective components of HE-My and HE-Et are worth to be developed to become a therapeutic drug for Alzheimer's disease.

  2. The chitinase C gene PsChiC from Pseudomonas sp. and its synergistic effects on larvicidal activity

    Directory of Open Access Journals (Sweden)

    Wanfang Zhong

    2015-09-01

    Full Text Available Pseudomonas sp. strain TXG6-1, a chitinolytic gram-negative bacterium, was isolated from a vegetable field in Taixing city, Jiangsu Province, China. In this study, a Pseudomonas chitinase C gene (PsChiC was isolated from the chromosomal DNA of this bacterium using a pair of specific primers. The PsChiC gene consisted of an open reading frame of 1443 nucleotides and encoded 480 amino acid residues with a calculated molecular mass of 51.66 kDa. The deduced PsChiC amino acid sequence lacked a signal sequence and consisted of a glycoside hydrolase family 18 catalytic domain responsible for chitinase activity, a fibronectin type III-like domain (FLD and a C-terminal chitin-binding domain (ChBD. The amino acid sequence of PsChiCshowed high sequence homology (> 95% with chitinase C from Serratia marcescens. SDS-PAGE showed that the molecular mass of chitinase PsChiC was 52 kDa. Chitinase assays revealed that the chitobiosidase and endochitinase activities of PsChiCwere 51.6- and 84.1-fold higher than those of pET30a, respectively. Although PsChiC showed little insecticidal activity towards Spodoptera litura larvae, an insecticidal assay indicated that PsChiC increased the insecticidal toxicity of SpltNPV by 1.78-fold at 192 h and hastened death. These results suggest that PsChiC from Pseudomonas sp. could be useful in improving the pathogenicity of baculoviruses.

  3. Huperzine A alleviates synaptic deficits and modulates amyloidogenic and nonamyloidogenic pathways in APPswe/PS1dE9 transgenic mice.

    Science.gov (United States)

    Wang, Ying; Tang, Xi Can; Zhang, Hai Yan

    2012-02-01

    Huperzine A (HupA) is a potent acetylcholinesterase inhibitor (AChEI) used in the treatment of Alzheimer's disease (AD). Recently, HupA was shown to be active in modulating the nonamyloidogenic metabolism of β-amyloid precursor protein (APP) in APP-transfected human embryonic kidney cell line (HEK293swe). However, in vivo research concerning the mechanism of HupA in APP transgenic mice has not yet been fully elucidated. The present study indicates that the loss of dendritic spine density and synaptotagmin levels in the brain of APPswe/presenilin-1 (PS1) transgenic mice was significantly ameliorated by chronic HupA treatment and provides evidence that this neuroprotection was associated with reduced amyloid plaque burden and oligomeric β-amyloid (Aβ) levels in the cortex and hippocampus of APPswe/PS1dE9 transgenic mice. Our findings further demonstrate that the amelioration effect of HupA on Aβ deposits may be mediated, at least in part, by regulation of the compromised expression of a disintegrin and metalloprotease 10 (ADAM10) and excessive membrane trafficking of β-site APP cleavage enzyme 1 (BACE1) in these transgenic mice. In addition, extracellular signal-regulated kinases 1/2 (Erk1/2) phosphorylation may also be partially involved in the effect of HupA on APP processing. In conclusion, our work for the first time demonstrates the neuroprotective effect of HupA on synaptic deficits in APPswe/PS1dE9 transgenic mice and further clarifies the potential pharmacological targets for this protective effect, in which modulation of nonamyloidogenic and amyloidogenic APP processing pathways may be both involved. These findings may provide adequate evidence for the clinical and experimental benefits gained from HupA treatment. Copyright © 2011 Wiley Periodicals, Inc.

  4. Cloning of Plasmodium falciparum by single-cell sorting.

    Science.gov (United States)

    Miao, Jun; Li, Xiaolian; Cui, Liwang

    2010-10-01

    Malaria parasite cloning is traditionally carried out mainly by using the limiting dilution method, which is laborious, imprecise, and unable to distinguish multiply-infected RBCs. In this study, we used a parasite engineered to express green fluorescent protein (GFP) to evaluate a single-cell sorting method for rapidly cloning Plasmodium falciparum. By dividing a two-dimensional scattergram from a cell sorter into 17 gates, we determined the parameters for isolating singly-infected erythrocytes and sorted them into individual cultures. Pre-gating of the engineered parasites for GFP allowed the isolation of almost 100% GFP-positive clones. Compared with the limiting dilution method, the number of parasite clones obtained by single-cell sorting was much higher. Molecular analyses showed that parasite isolates obtained by single-cell sorting were highly homogenous. This highly efficient single-cell sorting method should prove very useful for cloning both P. falciparum laboratory populations from genetic manipulation experiments and clinical samples. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Cloning of Plasmodium falciparum by single-cell sorting

    Science.gov (United States)

    Miao, Jun; Li, Xiaolian; Cui, Liwang

    2010-01-01

    Malaria parasite cloning is traditionally carried out mainly by using the limiting dilution method, which is laborious, imprecise, and unable to distinguish multiply-infected RBCs. In this study, we used a parasite engineered to express green fluorescent protein (GFP) to evaluate a single-cell sorting method for rapidly cloning Plasmodium falciparum. By dividing a two dimensional scattergram from a cell sorter into 17 gates, we determined the parameters for isolating singly-infected erythrocytes and sorted them into individual cultures. Pre-gating of the engineered parasites for GFP allowed the isolation of almost 100% GFP-positive clones. Compared with the limiting dilution method, the number of parasite clones obtained by single-cell sorting was much higher. Molecular analyses showed that parasite isolates obtained by single-cell sorting were highly homogenous. This highly efficient single-cell sorting method should prove very useful for cloning both P. falciparum laboratory populations from genetic manipulation experiments and clinical samples. PMID:20435038

  6. Ps 22 in Gospels’ interpretation of Passion

    Directory of Open Access Journals (Sweden)

    Sylwester Jędrzejewski

    2012-09-01

    Full Text Available Ps 22 is a piece of artistically high poetry, clear images and metaphors, historical and prophetic references. The conviction of biblical scholars that the New Testament writers has recognized in Ps 22 prophetic witness of passion, accompanies the Church from its beginnings. The words of Jesus on the cross, taken from Ps 22: 2, have a character of lamentable re-symbolization of the prayer of Israel. These words establish a theological answer in the form of suitable credo as well. Dramatic question “why?” is connected with a proclamation and identification “My God”. The personal experience of oppression and death is included by Jesus in the history of his nation and in the experience of God. Ps 22 in the Gospels’ passion context becomes a proclamation form of prayer and a very personal, expressed in such dramatic circumstances confession of the faith.

  7. Passive sorting of capsules by deformability

    Science.gov (United States)

    Haener, Edgar; Juel, Anne

    We study passive sorting according to deformability of liquid-filled ovalbumin-alginate capsules. We present results for two sorting geometries: a straight channel with a half-cylindrical obstruction and a pinched flow fractioning device (PFF) adapted for use with capsules. In the half-cylinder device, the capsules deform as they encounter the obstruction, and travel around the half-cylinder. The distance from the capsule's centre of mass to the surface of the half-cylinder depends on deformability, and separation between capsules of different deformability is amplified by diverging streamlines in the channel expansion downstream of the obstruction. We show experimentally that capsules can be sorted according to deformability with their downstream position depending on capillary number only, and we establish the sensitivity of the device to experimental variability. In the PFF device, particles are compressed against a wall using a strong pinching flow. We show that capsule deformation increases with the intensity of the pinching flow, but that the downstream capsule position is not set by deformation in the device. However, when using the PFF device like a T-Junction, we achieve improved sorting resolution compared to the half-cylinder device.

  8. Disruption of sorting nexin 5 causes respiratory failure associated with undifferentiated alveolar epithelial type I cells in mice.

    Directory of Open Access Journals (Sweden)

    Sun-Kyoung Im

    Full Text Available Sorting nexin 5 (Snx5 has been posited to regulate the degradation of epidermal growth factor receptor and the retrograde trafficking of cation-independent mannose 6-phosphate receptor/insulin-like growth factor II receptor. Snx5 has also been suggested to interact with Mind bomb-1, an E3 ubiquitin ligase that regulates the activation of Notch signaling. However, the in vivo functions of Snx5 are largely unknown. Here, we report that disruption of the Snx5 gene in mice (Snx5(-/- mice resulted in partial perinatal lethality; 40% of Snx5(-/- mice died shortly after birth due to cyanosis, reduced air space in the lungs, and respiratory failure. Histological analysis revealed that Snx5(-/- mice exhibited thickened alveolar walls associated with undifferentiated alveolar epithelial type I cells. In contrast, alveolar epithelial type II cells were intact, exhibiting normal surfactant synthesis and secretion. Although the expression levels of surfactant proteins and saturated phosphatidylcholine in the lungs of Snx5(-/- mice were comparable to those of Snx5(+/+ mice, the expression levels of T1α, Aqp5, and Rage, markers for distal alveolar epithelial type I cells, were significantly decreased in Snx5 (-/- mice. These results demonstrate that Snx5 is necessary for the differentiation of alveolar epithelial type I cells, which may underlie the adaptation to air breathing at birth.

  9. Preliminary Astrometric Results from the PS1 Demo Month and Routine Survey Operations

    Science.gov (United States)

    2010-09-01

    with the  2MASS  catalog 3 to  produce preliminary astrometric solutions.  Using these  coordinates, the NOFS astrometric pipeline correlates PS1...objects with other catalogs (USNO‐B1.0, SDSS, Tycho‐2,  2MASS , etc.) so that unique star identification numbers can  be assigned across all catalogs. This...correlated  pair, and the standard deviation for these pairings is about  0.3 arcsec.  Whereas the  2MASS  catalog error for a brighter  star is believed to be

  10. On Sorting Genomes with DCJ and Indels

    Science.gov (United States)

    Braga, Marília D. V.

    A previous work of Braga, Willing and Stoye compared two genomes with unequal content, but without duplications, and presented a new linear time algorithm to compute the genomic distance, considering double cut and join (DCJ) operations, insertions and deletions. Here we derive from this approach an algorithm to sort one genome into another one also using DCJ, insertions and deletions. The optimal sorting scenarios can have different compositions and we compare two types of sorting scenarios: one that maximizes and one that minimizes the number of DCJ operations with respect to the number of insertions and deletions.

  11. PS1/γ-Secretase-Mediated Cadherin Cleavage Induces β-Catenin Nuclear Translocation and Osteogenic Differentiation of Human Bone Marrow Stromal Cells

    Directory of Open Access Journals (Sweden)

    Danielle C. Bonfim

    2016-01-01

    Full Text Available Bone marrow stromal cells (BMSCs are considered a promising tool for bone bioengineering. However, the mechanisms controlling osteoblastic commitment are still unclear. Osteogenic differentiation of BMSCs requires the activation of β-catenin signaling, classically known to be regulated by the canonical Wnt pathway. However, BMSCs treatment with canonical Wnts in vitro does not always result in osteogenic differentiation and evidence indicates that a more complex signaling pathway, involving cadherins, would be required to induce β-catenin signaling in these cells. Here we showed that Wnt3a alone did not induce TCF activation in BMSCs, maintaining the cells at a proliferative state. On the other hand, we verified that, upon BMSCs osteoinduction with dexamethasone, cadherins were cleaved by the PS1/γ-secretase complex at the plasma membrane, and this event was associated with an enhanced β-catenin translocation to the nucleus and signaling. When PS1/γ-secretase activity was inhibited, the osteogenic process was impaired. Altogether, we provide evidence that PS1/γ-secretase-mediated cadherin cleavage has as an important role in controlling β-catenin signaling during the onset of BMSCs osteogenic differentiation, as part of a complex signaling pathway responsible for cell fate decision. A comprehensive map of these pathways might contribute to the development of strategies to improve bone repair.

  12. Serotonin type-1A receptor imaging in depression

    Energy Technology Data Exchange (ETDEWEB)

    Drevets, Wayne C. E-mail: drevets@pet.upmc.edu; Frank, Ellen; Price, Julie C.; Kupfer, David J.; Greer, Phil J.; Mathis, Chester

    2000-07-01

    Regional 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl-{sup 11}C]WAY-100635 {l_brace}[{sup 11}C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide{r_brace}. The mean 5-HT{sub 1A} receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT{sub 1A} receptor BP are consistent with in vivo evidence that 5-HT{sub 1A} receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT{sub 1A} receptor expression in primary mood disorders.

  13. Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists.

    Directory of Open Access Journals (Sweden)

    Gunnar Kleinau

    Full Text Available Trace amine-associated receptors (TAAR are rhodopsin-like G-protein-coupled receptors (GPCR. TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR, phenylethylamine (PEA, octopamine (OA, but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1 and 2 (ADRB2 have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR octopamine (OAR, ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes.

  14. Cannabinoid receptor type-1: breaking the dogmas [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Arnau Busquets Garcia

    2016-05-01

    Full Text Available The endocannabinoid system (ECS is abundantly expressed in the brain. This system regulates a plethora of physiological functions and is composed of cannabinoid receptors, their endogenous ligands (endocannabinoids, and the enzymes involved in the metabolism of endocannabinoids. In this review, we highlight the new advances in cannabinoid signaling, focusing on a key component of the ECS, the type-1 cannabinoid receptor (CB1. In recent years, the development of new imaging and molecular tools has demonstrated that this receptor can be distributed in many cell types (e.g., neuronal or glial cells and intracellular compartments (e.g., mitochondria. Interestingly, cellular and molecular effects are differentially mediated by CB1 receptors according to their specific localization (e.g., glutamatergic or GABAergic neurons. Moreover, this receptor is expressed in the periphery, where it can modulate periphery-brain connections. Finally, the better understanding of the CB1 receptor structure led researchers to propose interesting and new allosteric modulators. Thus, the advances and the new directions of the CB1 receptor field will provide new insights and better approaches to profit from its interesting therapeutic profile.

  15. Magnethophoretic sorting of fluid catalytic cracking particles

    NARCIS (Netherlands)

    Solsona, Miguel; Nieuwelink, A. E.; Odijk, Mathieu; Meirer, Florian; Abelmann, Leon; Olthuis, Wouter; Weckhuysen, Bert M.; van den Berg, Albert; Lee, Abraham; DeVoe, Don

    2017-01-01

    We demonstrate an on-chip particle activity sorter, focused on iron concentration and based on magnetophoresis. This device was used for fast sorting of stepwise homogenously distributed [Fe]s. The preliminary results are very encouraging. We show that we can sort particles on magnetic moment, with

  16. Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases.

    Science.gov (United States)

    Johnston, J A; Wang, L M; Hanson, E P; Sun, X J; White, M F; Oakes, S A; Pierce, J H; O'Shea, J J

    1995-12-01

    The signaling molecules insulin receptor substrate (IRS)-1 and the newly described IRS-2 (4PS) molecule are major insulin and interleukin 4 (IL-4)-dependent phosphoproteins. We report here that IL-2, IL-7, and IL-15, as well as IL-4, rapidly stimulate the tyrosine phosphorylation of IRS-1 and IRS-2 in human peripheral blood T cells, NK cells, and in lymphoid cell lines. In addition, we show that the Janus kinases, JAK1 and JAK3, associate with IRS-1 and IRS-2 in T cells. Coexpression studies demonstrate that these kinases can tyrosine-phosphorylate IRS-2, suggesting a possible mechanism by which cytokine receptors may induce the tyrosine phosphorylation of IRS-1 and IRS-2. We further demonstrate that the p85 subunit of phosphoinositol 3-kinase associates with IRS-1 in response to IL-2 and IL-4 in T cells. Therefore, these data indicate that IRS-1 and IRS-2 may have important roles in T lymphocyte activation not only in response to IL-4, but also in response to IL-2, IL-7, and IL-15.

  17. Improvement of spatial memory function in APPswe/PS1dE9 mice after chronic inhibition of phosphodiesterase type 4D.

    Science.gov (United States)

    Sierksma, A S R; van den Hove, D L A; Pfau, F; Philippens, M; Bruno, O; Fedele, E; Ricciarelli, R; Steinbusch, H W M; Vanmierlo, T; Prickaerts, J

    2014-02-01

    Phosphodiesterase type 4 inhibitors (PDE4-Is) have received increasing attention as cognition-enhancers and putative treatment strategies for Alzheimer's disease (AD). By preventing cAMP breakdown, PDE4-Is can enhance intracellular signal transduction and increase the phosphorylation of cAMP response element-binding protein (CREB) and transcription of proteins related to synaptic plasticity and associated memory formation. Unfortunately, clinical development of PDE4-Is has been seriously hampered by emetic side effects. The new isoform-specific PDE4D-I, GEBR-7b, has shown to have beneficial effects on memory at non-emetic doses. The aim of the current study was to investigate chronic cognition-enhancing effects of GEBR-7b in a mouse model of AD. To this extent, 5-month-old (5M) APPswe/PS1dE9 mice received daily subcutaneous injections with GEBR-7b (0.001 mg/kg) or vehicle for a period of 3 weeks, and were tested on affective and cognitive behavior at 7M. We demonstrated a cognition-enhancing potential in APPswe/PS1dE9 mice as their spatial memory function at 7M in the object location test was improved by prior GEBR-7b treatment. APPswe/PS1dE9 mice displayed lower levels of CREB phosphorylation, which remained unaltered after chronic GEBR-7b treatment, and higher levels of tau in the hippocampus. Hippocampal brain-derived neurotrophic factor levels and synaptic densities were not different between experimental groups and no effects were observed on hippocampal GSK3β and tau phosphorylation or Aβ levels. In conclusion, GEBR-7b can enhance spatial memory function in the APPswe/PS1dE9 mouse model of AD. Although the underlying mechanisms of its cognition-enhancing potential remain to be elucidated, PDE4D inhibition appears an interesting novel therapeutic option for cognitive deficits in AD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. National flow cytometry and sorting research resource. Annual progress report, July, 1, 1994--June 30, 1995, Year 12

    Energy Technology Data Exchange (ETDEWEB)

    Jett, J.H.

    1995-04-27

    Research progress utilizing flow cytometry is described. Topics include: rapid kinetics flow cytometry; characterization of size determinations for small DNA fragments; statistical analysis; energy transfer measurements of molecular confirmation in micelles; and enrichment of Mus spretus chromosomes by dual parameter flow sorting and identification of sorted fractions by fluorescence in-situ hybridization onto G-banded mouse metaphase spreads.

  19. Effect Of IGF-1 On Expression Of Gh Receptor, IGF-1, IGF-1 ...

    African Journals Online (AJOL)

    ... and the skin expression of growth hormone receptor (GHR), insulin-like growth factor1 (IGF-1), insulin-like growth factor receptor (IGF- R), KAP3.2 and KAP6-1 mRNA were measured by RT-PCR. The results indicated that IGF-1 could degrade GHR gene expression, have no effect of IGF-1 and IGF-1R gene expression, ...

  20. A many-sorted calculus based on resolution and paramodulation

    CERN Document Server

    Walther, Christoph

    1987-01-01

    A Many-Sorted Calculus Based on Resolution and Paramodulation emphasizes the utilization of advantages and concepts of many-sorted logic for resolution and paramodulation based automated theorem proving.This book considers some first-order calculus that defines how theorems from given hypotheses by pure syntactic reasoning are obtained, shifting all the semantic and implicit argumentation to the syntactic and explicit level of formal first-order reasoning. This text discusses the efficiency of many-sorted reasoning, formal preliminaries for the RP- and ?RP-calculus, and many-sorted term rewrit

  1. Ophthalmic antihistamines and H1-H4 receptors.

    Science.gov (United States)

    Wade, Laurie; Bielory, Leonard; Rudner, Shara

    2012-10-01

    Antihistamines exert pharmacologic effects by binding to four histamine receptors (H1-H4) at different affinities, producing variable effects depending on the receptor they predominantly bind to. This review's purpose is to determine the relative potency of antihistamines by comparing their binding affinities to these receptors. Studies on binding affinities of antihistamines to histamine receptors were reviewed and the dissociation constant for inhibitor binding (Ki) analyzed to determine the most and least potent antihistamine for each receptor. We retrieved the binding affinities for nineteen antihistamines. For H1 receptors, pyrilamine exhibited the highest affinity (Ki = 0.8 nM), and thioperamide the lowest (Ki = 280, 000 nM). For H2 receptors, ranitidine exhibited the highest affinity (Ki = 187 nM), and olopatadine the lowest (Ki = 100 ,000 nM). For the recently discovered H3 and H4 receptors, thioperamide exhibited the highest affinity (Ki = 1.1 nM), and olopatadine exhibited the lowest (Ki = 79 ,400 nM), to H3. Data on binding affinities to the H4 receptor exist for: ketotifen, pheniramine, ranitidine, cimetidine and thioperamide. Of these, thioperamide exhibited the highest affinity (Ki = 27 nM), whereas cimetidine and ranitidine exhibited the lowest affinity (Ki = >10, 000 nM) for H4 receptors. This review summarizes the relative potency of antihistamines based on their binding affinities to the four histamine receptors. Although data on binding affinities of antihistamines to the H4 receptor are sparse, it is apparent that further research on these histamine subtypes may open new venues for more direct treatment with a higher therapeutic efficacy on allergic disorders including those affecting the ocular surface.

  2. Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.

    Science.gov (United States)

    Chevalier, Adrien S; Chaumont, François

    2015-05-01

    Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. An empirical study on SAJQ (Sorting Algorithm for Join Queries

    Directory of Open Access Journals (Sweden)

    Hassan I. Mathkour

    2010-06-01

    Full Text Available Most queries that applied on database management systems (DBMS depend heavily on the performance of the used sorting algorithm. In addition to have an efficient sorting algorithm, as a primary feature, stability of such algorithms is a major feature that is needed in performing DBMS queries. In this paper, we study a new Sorting Algorithm for Join Queries (SAJQ that has both advantages of being efficient and stable. The proposed algorithm takes the advantage of using the m-way-merge algorithm in enhancing its time complexity. SAJQ performs the sorting operation in a time complexity of O(nlogm, where n is the length of the input array and m is number of sub-arrays used in sorting. An unsorted input array of length n is arranged into m sorted sub-arrays. The m-way-merge algorithm merges the sorted m sub-arrays into the final output sorted array. The proposed algorithm keeps the stability of the keys intact. An analytical proof has been conducted to prove that, in the worst case, the proposed algorithm has a complexity of O(nlogm. Also, a set of experiments has been performed to investigate the performance of the proposed algorithm. The experimental results have shown that the proposed algorithm outperforms other Stable–Sorting algorithms that are designed for join-based queries.

  4. Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.

    Science.gov (United States)

    Harding, Peter J; Attrill, Helen; Boehringer, Jonas; Ross, Simon; Wadhams, George H; Smith, Eleanor; Armitage, Judith P; Watts, Anthony

    2009-02-01

    Neurotensin receptor 1 (NTS1), a Family A G-protein coupled receptor (GPCR), was expressed in Escherichia coli as a fusion with the fluorescent proteins eCFP or eYFP. A fluorophore-tagged receptor was used to study the multimerization of NTS1 in detergent solution and in brain polar lipid bilayers, using fluorescence resonance energy transfer (FRET). A detergent-solubilized receptor was unable to form FRET-competent complexes at concentrations of up to 200 nM, suggesting that the receptor is monomeric in this environment. When reconstituted into a model membrane system at low receptor density, the observed FRET was independent of agonist binding, suggesting constitutive multimer formation. In competition studies, decreased FRET in the presence of untagged NTS1 excludes the possibility of fluorescent protein-induced interactions. A simulation of the experimental data indicates that NTS1 exists predominantly as a homodimer, rather than as higher-order multimers. These observations suggest that, in common with several other Family A GPCRs, NTS1 forms a constitutive dimer in lipid bilayers, stabilized through receptor-receptor interactions in the absence of other cellular signaling components. Therefore, this work demonstrates that well-characterized model membrane systems are useful tools for the study of GPCR multimerization, allowing fine control over system composition and complexity, provided that rigorous control experiments are performed.

  5. Redetermination of AgNb2PS10 revealing a silver deficiency

    Directory of Open Access Journals (Sweden)

    Hoseop Yun

    2009-08-01

    Full Text Available In comparison with a previous crystallographic study [Goh et al. (2002. J. Solid State Chem. 168, 119–125] of the title compound, silver diniobium tris(disulfide tetrathiophosphate(V, that reports a full occupation of the silver position and isotropic displacement parameters for the atoms, the current redetermination reveals a silver deficiency with a site-occupation factor of 0.88 (1 and reports all atoms with anisotropic displacement parameters. The structure of Ag0.88Nb2PS10 is composed of ∞1[Nb2PS10] chains, which are built up from pairs of distorted bicapped trigonal-prismatic [NbS8] polyhedra forming [Nb2S12] dimers and of tetrahedral [PS4] groups. These chains are connected via the statistically disordered Ag+ ions, forming double layers. Adjacent layers are stacked solely through van der Waals forces into a three-dimensional structure. Short and long Nb—Nb distances [2.880 (1 and 3.770 (2 Å, respectively] alternate along the chain and S22− and S2− anionic species are observed.

  6. Updating the Psoriatic Arthritis (PsA) Core Domain Set

    DEFF Research Database (Denmark)

    Orbai, Ana-Maria; de Wit, Maarten; Mease, Philip J

    2017-01-01

    OBJECTIVE: To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). METHODS: At OMERACT 2016, research...... conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. RESULTS: We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted...... and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health...

  7. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain.

    Science.gov (United States)

    Wang, H Y; Paul, W E; Keegan, A D

    1996-02-01

    IL-4 binds to a cell surface receptor complex that consists of the IL-4 binding protein (IL-4R alpha) and the gamma chain of the IL-2 receptor complex (gamma c). The receptors for IL-4 and IL-2 have several features in common; both use the gamma c as a receptor component, and both activate the Janus kinases JAK-1 and JAK-3. In spite of these similarities, IL-4 evokes specific responses, including the tyrosine phosphorylation of 4PS/IRS-2 and the induction of CD23. To determine whether sequences within the cytoplasmic domain of the IL-4R alpha specify these IL-4-specific responses, we transplanted the insulin IL-4 receptor motif (I4R motif) of the huIL-4R alpha to the cytoplasmic domain of a truncated IL-2R beta. In addition, we transplanted a region that contains peptide sequences shown to block Stat6 binding to DNA. We analyzed the ability of cells expressing these IL-2R-IL-4R chimeric constructs to respond to IL-2. We found that IL-4 function could be transplanted to the IL-2 receptor by these regions and that proliferative and differentiative functions can be induced by different receptor sequences.

  8. β-arrestins negatively control human adrenomedullin type 1-receptor internalization.

    Science.gov (United States)

    Kuwasako, Kenji; Kitamura, Kazuo; Nagata, Sayaka; Sekiguchi, Toshio; Danfeng, Jiang; Murakami, Manabu; Hattori, Yuichi; Kato, Johji

    2017-05-27

    Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful variety of protective effects against multiorgan damage through the AM type 1 receptor (AM 1 receptor), which consists of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2). Two β-arrestin (β-arr) isoforms, β-arr-1 and β-arr-2, play a central role in the agonist-induced internalization of many receptors for receptor resensitization. Notably, β-arr-biased agonists are now being tested in phase II clinical trials, targeting acute pain and acute heart failure. Here, we examined the effects of β-arr-1 and β-arr-2 on human AM 1 receptor internalization. We constructed a V5-tagged chimera in which the cytoplasmic C-terminal tail (C-tail) of CLR was replaced with that of the β 2 -adrenergic receptor (β 2 -AR), and it was transiently transfected into HEK-293 cells that stably expressed RAMP2. The cell-surface expression and internalization of the wild-type or chimeric receptor were quantified by flow cytometric analysis. The [ 125 I]AM binding and the AM-induced cAMP production of these receptors were also determined. Surprisingly, the coexpression of β-arr-1 or -2 resulted in significant decreases in AM 1 receptor internalization without affecting AM binding and signaling prior to receptor internalization. Dominant-negative (DN) β-arr-1 or -2 also significantly decreased AM-induced AM 1 receptor internalization. In contrast, the AM-induced internalization of the chimeric AM 1 receptor was markedly augmented by the cotransfection of β-arr-1 or -2 and significantly reduced by the coexpression of DN-β-arr-1 or -2. These results were consistent with those seen for β 2 -AR. Thus, both β-arrs negatively control AM 1 receptor internalization, which depends on the C-tail of CLR. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Comparison of spike-sorting algorithms for future hardware implementation.

    Science.gov (United States)

    Gibson, Sarah; Judy, Jack W; Markovic, Dejan

    2008-01-01

    Applications such as brain-machine interfaces require hardware spike sorting in order to (1) obtain single-unit activity and (2) perform data reduction for wireless transmission of data. Such systems must be low-power, low-area, high-accuracy, automatic, and able to operate in real time. Several detection and feature extraction algorithms for spike sorting are described briefly and evaluated in terms of accuracy versus computational complexity. The nonlinear energy operator method is chosen as the optimal spike detection algorithm, being most robust over noise and relatively simple. The discrete derivatives method [1] is chosen as the optimal feature extraction method, maintaining high accuracy across SNRs with a complexity orders of magnitude less than that of traditional methods such as PCA.

  10. Administration of Bifidobacterium breve PS12929 and Lactobacillus salivarius PS12934, Two Strains Isolated from Human Milk, to Very Low and Extremely Low Birth Weight Preterm Infants: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Laura Moles

    2015-01-01

    Full Text Available The preterm infant gut has been described as immature and colonized by an aberrant microbiota. Therefore, the use of probiotics is an attractive practice in hospitals to try to reduce morbidity and mortality in this population. The objective of this pilot study was to elucidate if administration of two probiotic strains isolated from human milk to preterm infants led to their presence in feces. In addition, the evolution of a wide spectrum of immunological compounds, including the inflammatory biomarker calprotectin, in both blood and fecal samples was also assessed. For this purpose, five preterm infants received two daily doses (~109 CFU of a 1 : 1 mixture of Bifidobacterium breve PS12929 and Lactobacillus salivarius PS12934. Bacterial growth was detected by culture-dependent techniques in all the fecal samples. The phylum Firmicutes dominated in nearly all fecal samples while L. salivarius PS12934 was detected in all the infants at numerous sample collection points and B. breve PS12929 appeared in five fecal samples. Finally, a noticeable decrease in the fecal calprotectin levels was observed along time.

  11. Administration of Bifidobacterium breve PS12929 and Lactobacillus salivarius PS12934, two strains isolated from human milk, to very low and extremely low birth weight preterm infants: a pilot study.

    Science.gov (United States)

    Moles, Laura; Escribano, Esperanza; de Andrés, Javier; Montes, María Teresa; Rodríguez, Juan M; Jiménez, Esther; Sáenz de Pipaón, Miguel; Espinosa-Martos, Irene

    2015-01-01

    The preterm infant gut has been described as immature and