Compact versus noncompact quantum dynamics of time-dependent su(1,1)-valued Hamiltonians

International Nuclear Information System (INIS)

Penna, V.

1996-01-01

We consider the Schroedinger problem for time-dependent (TD) Hamiltonians represented by a linear combination of the compact generator and the hyperbolic generator of su(1,1). Several types of transitions, characterized by different time initial conditions on the generator coefficients, are analyzed by resorting to the harmonic oscillator model with a frequency vanishing for t→+∞. We provide examples that point out how the TD states of the transitions can be constructed either by the compact eigenvector basis or by the noncompact eigenvector basis depending on the initial conditions characterizing the frequency time behavior. Copyright copyright 1996 Academic Press, Inc

Time-dependent behavior of concrete

International Nuclear Information System (INIS)

Pfeiffer, P.A.; Tanabe, Tada-aki

1992-01-01

This paper is a condensed version of the material presented at the International Workshop on Finite Element Analysis of Reinforced Concrete, Session 4 -- Time Dependent Behavior, held at Columbia University, New York on June 3--6, 1991. Dr. P.A. Pfeiffer presented recent developments in time-dependent behavior of concrete and Professor T. Tanabe presented a review of research in Japan on time-dependent behavior of concrete. The paper discusses the recent research of time-dependent behavior of concrete in the past few years. 6 refs

Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

Science.gov (United States)

Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

2017-02-01

We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21 CIP/WAF1 )-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21 CIP/WAF1 )-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21 CIP/WAF1 )-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21 CIP/WAF1 )-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation

Science.gov (United States)

Messias, Carolina V.; Santana-Van-Vliet, Eliane; Lemos, Julia P.; Moreira, Otacilio C.; Cotta-de-Almeida, Vinicius; Savino, Wilson; Mendes-da-Cruz, Daniella Arêas

2016-01-01

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5). S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL) did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM) did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000–10000 nM) through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts. PMID:26824863

Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation.

Directory of Open Access Journals (Sweden)

Carolina V Messias

Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5. S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000-10000 nM through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts.

PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1

Energy Technology Data Exchange (ETDEWEB)

Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

2015-10-23

p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. - Highlights: • PF-4708671, a S6K1-specific inhibitor, prevents S6K1-mediated S6 phosphorylation. • However, PF-4708671 treatment often leads to apoptotic cell death. • Protective mechanism against PF-4708671-induced cell death remains to be elucidated. • PF-4708671 induced p62-dependent, autophagic Keap1 degradation-mediated Nrf2 activation. • p62-dependent Nrf2 activation protects cells from PF-4708671-mediated apoptosis.

Mutations in ash1 and trx enhance P-element-dependent silencing in Drosophila melanogaster.

Science.gov (United States)

McCracken, Allen; Locke, John

2016-08-01

In Drosophila melanogaster, the mini-w(+) transgene in Pci is normally expressed throughout the adult eye; however, when other P or KP elements are present, a variegated-eye phenotype results, indicating random w(+) silencing during development called P-element-dependent silencing (PDS). Mutant Su(var)205 and Su(var)3-7 alleles act as haplo-suppressors/triplo-enhancers of this variegated phenotype, indicating that these heterochromatic modifiers act dose dependently in PDS. Previously, we recovered a spontaneous mutation of P{lacW}ci(Dplac) called P{lacW}ci(DplacE1) (E1) that variegated in the absence of P elements, presumably due to the insertion of an adjacent gypsy element. From a screen for genetic modifiers of E1 variegation, we describe here the isolation of five mutations in ash1 and three in trx that enhance the E1 variegated phenotype in a dose-dependent and cumulative manner. These mutant alleles enhance PDS at E1, and in E1/P{lacW}ci(Dplac), but suppress position effect variegation (PEV) at In(1)w(m)(4). This opposite action is consistent with a model where ASH1 and TRX mark transcriptionally active chromatin domains. If ASH1 or TRX function is lost or reduced, heterochromatin can spread into these domains creating a sink that diverts heterochromatic proteins from other variegating locations, which then may express a suppressed phenotype.

Deficiency of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 accelerates atherogenesis in apolipoprotein E-deficient mice

International Nuclear Information System (INIS)

Akyuerek, Levent M.; Boehm, Manfred; Olive, Michelle; Zhou, Alex-Xianghua; San, Hong; Nabel, Elizabeth G.

2010-01-01

Cyclin-dependent kinase inhibitors, p21 Cip1 and p27 Kip1 , are upregulated during vascular cell proliferation and negatively regulate growth of vascular cells. We hypothesized that absence of either p21 Cip1 or p27 Kip1 in apolipoprotein E (apoE)-deficiency may increase atherosclerotic plaque formation. Compared to apoE -/- aortae, both apoE -/- /p21 -/- and apoE -/- /p27 -/- aortae exhibited significantly more atherosclerotic plaque following a high-cholesterol regimen. This increase was particularly observed in the abdominal aortic regions. Deficiency of p27 Kip1 accelerated plaque formation significantly more than p21 -/- in apoE -/- mice. This increased plaque formation was in parallel with increased intima/media area ratios. Deficiency of p21 Cip1 and p27 Kip1 accelerates atherogenesis in apoE -/- mice. These findings have significant implications for our understanding of the molecular basis of atherosclerosis associated with excessive proliferation of vascular cells.

CK1α ablation in keratinocytes induces p53-dependent, sunburn-protective skin hyperpigmentation.

Science.gov (United States)

Chang, Chung-Hsing; Kuo, Che-Jung; Ito, Takamichi; Su, Yu-Ya; Jiang, Si-Tse; Chiu, Min-Hsi; Lin, Yi-Hsiung; Nist, Andrea; Mernberger, Marco; Stiewe, Thorsten; Ito, Shosuke; Wakamatsu, Kazumasa; Hsueh, Yi-An; Shieh, Sheau-Yann; Snir-Alkalay, Irit; Ben-Neriah, Yinon

2017-09-19

Casein kinase 1α (CK1α), a component of the β-catenin destruction complex, is a critical regulator of Wnt signaling; its ablation induces both Wnt and p53 activation. To characterize the role of CK1α (encoded by Csnk1a1 ) in skin physiology, we crossed mice harboring floxed Csnk1a1 with mice expressing K14-Cre-ER T2 to generate mice in which tamoxifen induces the deletion of Csnk1a1 exclusively in keratinocytes [single-knockout (SKO) mice]. As expected, CK1α loss was accompanied by β-catenin and p53 stabilization, with the preferential induction of p53 target genes, but phenotypically most striking was hyperpigmentation of the skin, importantly without tumorigenesis, for at least 9 mo after Csnk1a1 ablation. The number of epidermal melanocytes and eumelanin levels were dramatically increased in SKO mice. To clarify the putative role of p53 in epidermal hyperpigmentation, we established K14-Cre-ER T2 CK1α/p53 double-knockout (DKO) mice and found that coablation failed to induce epidermal hyperpigmentation, demonstrating that it was p53-dependent. Transcriptome analysis of the epidermis revealed p53-dependent up-regulation of Kit ligand (KitL). SKO mice treated with ACK2 (a Kit-neutralizing antibody) or imatinib (a Kit inhibitor) abrogated the CK1α ablation-induced hyperpigmentation, demonstrating that it requires the KitL/Kit pathway. Pro-opiomelanocortin (POMC), a precursor of α-melanocyte-stimulating hormone (α-MSH), was not activated in the CK1α ablation-induced hyperpigmentation, which is in contrast to the mechanism of p53-dependent UV tanning. Nevertheless, acute sunburn effects were successfully prevented in the hyperpigmented skin of SKO mice. CK1α inhibition induces skin-protective eumelanin but no carcinogenic pheomelanin and may therefore constitute an effective strategy for safely increasing eumelanin via UV-independent pathways, protecting against acute sunburn.

Theoretical information measurement in nonrelativistic time-dependent approach

Science.gov (United States)

Najafizade, S. A.; Hassanabadi, H.; Zarrinkamar, S.

2018-02-01

The information-theoretic measures of time-dependent Schrödinger equation are investigated via the Shannon information entropy, variance and local Fisher quantities. In our calculations, we consider the two first states n = 0,1 and obtain the position Sx (t) and momentum Sp (t) Shannon entropies as well as Fisher information Ix (t) in position and momentum Ip (t) spaces. Using the Fourier transformed wave function, we obtain the results in momentum space. Some interesting features of the information entropy densities ρs (x,t) and γs (p,t), as well as the probability densities ρ (x,t) and γ (p,t) for time-dependent states are demonstrated. We establish a general relation between variance and Fisher's information. The Bialynicki-Birula-Mycielski inequality is tested and verified for the states n = 0,1.

arXiv Longitudinal double-spin asymmetry $A_1^{\\rm p}$ and spin-dependent structure function $g_1^{\\rm p}$ of the proton at small values of $x$ and $Q^2$

CERN Document Server

Aghasyan, M.; The COMPASS collaboration; Alexeev, G.D.; Amoroso, A.; Andrieux, V.; Anfimov, N.V.; Anosov, V.; Antoshkin, A.; Augsten, K.; Augustyniak, W.; Austregesilo, A.; Azevedo, C.D.R.; Badełek, B.; Balestra, F.; Ball, M.; Barth, J.; Beck, R.; Bedfer, Y.; Bernhard, J.; Bicker, K.; Bielert, E.R.; Birsa, R.; Bodlak, M.; Bordalo, P.; Bradamante, F.; Bressan, A.; Büchele, M.; Burtsev, V.E.; Chang, W.-C.; Chatterjee, C.; Chiosso, M.; Choi, I.; Chumakov, A.G.; Chung, S.-U.; Cicuttin, A.; Crespo, M.L.; Dalla Torre, S.; Dasgupta, S.S.; Dasgupta, S.; Denisov, O.Yu.; Dhara, L.; Donskov, S.V.; Doshita, N.; Dreisbach, Ch.; Dünnweber, W.; Dusaev, R.R.; Dziewiecki, M.; Efremov, A.; Eversheim, P.D.; Faessler, M.; Ferrero, A.; Finger, M.; jr.,M.Finger; Fischer, H.; Franco, C.; du Fresne von Hohenesche, N.; Friedrich, J.M.; Frolov, V.; Fuchey, E.; Gautheron, F.; Gavrichtchouk, O.P.; Gerassimov, S.; Giarra, J.; Giordano, F.; Gnesi, I.; Gorzellik, M.; Grasso, A.; Gridin, A.; Grosse Perdekamp, M.; Grube, B.; Grussenmeyer, T.; Guskov, A.; Hahne, D.; Hamar, G.; von Harrach, D.; Heinsius, F.H.; Heitz, R.; Herrmann, F.; Horikawa, N.; d'Hose, N.; Hsieh, C.-Y.; Huber, S.; Ishimoto, S.; Ivanov, A.; Iwata, T.; Jary, V.; Joosten, R.; Jörg, P.; Kabuß, E.; Kerbizi, A.; Ketzer, B.; Khaustov, G.V.; Khokhlov, Yu.A.; Kisselev, Yu.; Klein, F.; Koivuniemi, J.H.; Kolosov, V.N.; Kondo, K.; Königsmann, K.; Konorov, I.; Konstantinov, V.F.; Kotzinian, A.M.; Kouznetsov, O.M.; Kral, Z.; Krämer, M.; Kremser, P.; Krinner, F.; Kroumchtein, Z.V.; Kulinich, Y.; Kunne, F.; Kurek, K.; Kurjata, R.P.; Kuznetsov, I.I.; Kveton, A.; Lednev, A.A.; Levchenko, E.A.; Levillain, M.; Levorato, S.; Lian, Y.-S.; Lichtenstadt, J.; Longo, R.; Lyubovitskij, V.E.; Maggiora, A.; Magnon, A.; Makins, N.; Makke, N.; Mallot, G.K.; Mamon, S.A.; Marianski, B.; Martin, A.; Marzec, J.; Matoušek, J.; Matsuda, H.; Matsuda, T.; Meshcheryakov, G.V.; Meyer, M.; Meyer, W.; Mikhailov, Yu.V.; Mikhasenko, M.; Mitrofanov, E.; Mitrofanov, N.; Miyachi, Y.; Moretti, A.; Nagaytsev, A.; Nerling, F.; Neyret, D.; Nový, J.; Nowak, W.-D.; Nukazuka, G.; Nunes, A.S.; Olshevsky, A.G.; Orlov, I.; Ostrick, M.; Panzieri, D.; Parsamyan, B.; Paul, S.; Peng, J.-C.; Pereira, F.; Pešek, M.; Pešková, M.; Peshekhonov, D.V.; Pierre, N.; Platchkov, S.; Pochodzalla, J.; Polyakov, V.A.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Regali, C.; Reicherz, G.; Riedl, C.; Rogacheva, N.S.; Ryabchikov, D.I.; Rybnikov, A.; Rychter, A.; Salac, R.; Samoylenko, V.D.; Sandacz, A.; Santos, C.; Sarkar, S.; Savin, I.A.; Sawada, T.; Sbrizzai, G.; Schiavon, P.; Schmidt, K.; Schmieden, H.; Schönning, K.; Seder, E.; Selyunin, A.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Smolik, J.; Srnka, A.; Steffen, D.; Stolarski, M.; Subrt, O.; Sulc, M.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Tasevsky, M.; Tessaro, S.; Tessarotto, F.; Thiel, A.; Tomsa, J.; Tosello, F.; Tskhay, V.; Uhl, S.; Vasilishin, B.I.; Vauth, A.; Veloso, J.; Vidon, A.; Virius, M.; Wallner, S.; Weisrock, T.; Wilfert, M.; ter Wolbeek, J.; Zaremba, K.; Zavada, P.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.

2018-06-10

We present a precise measurement of the proton longitudinal double-spin asymmetry A1p and the proton spin-dependent structure function g1p at photon virtualities 0.006(GeV/c)21(GeV/c)2 in the Bjorken x range of 4×10−51p and g1p are found to be positive. It is for the first time that spin effects are found at such low values of x .

Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism.

Science.gov (United States)

Fu, Maofu; Wang, Chenguang; Rao, Mahadev; Wu, Xiaofang; Bouras, Toula; Zhang, Xueping; Li, Zhiping; Jiao, Xuanmao; Yang, Jianguo; Li, Anping; Perkins, Neil D; Thimmapaya, Bayar; Kung, Andrew L; Munoz, Alberto; Giordano, Antonio; Lisanti, Michael P; Pestell, Richard G

2005-08-19

Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor gamma-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300.

Crossed molecular beam-tunable laser determination of velocity dependence of intramultiplet mixing: K(4p2P1/2)+He →K(4p2P3/2)+He

International Nuclear Information System (INIS)

Anderson, R.W.; Goddard, T.P.; Parravano, C.; Warner, J.

1976-01-01

The velocity dependence of intramultiplet mixing, K(4p 2 P 1 / 2 ) +He→K(4p 2 P 3 / 2 )+He, has been measured over the relative velocity range v=1.3--3.4 km/sec. The cross section appears to fit a linear function Q (v) =A (v-v 0 ), where a=6.3 x 10 -4 A 2 and v 0 = 7.9 x 10 4 cm/sec. The value of A is obtained by normalization to the literature thermal average cross section. The intramultiplet mixing theory of Nikitin is modified to yield Q (v) for the process. The modified theory correctly exhibits detailed balancing, and it is normalized to provide a very good fit to the observed Q (v). The magnitude of the normalization factor, however, is larger than that predicted from recent pseudopotential calculations of the excited state potentials. The temperature dependence of intramultiplet mixing is predicted. The use of laser polarization to determine the m/subj/ dependence of the process K(4p 2 P 3 / 2 +He→K(4p 2 P 1 / 2 )+He and other collision processes of excited 2 P 3 / 2 states is examined

New results on the proton spin-dependent structure function $g^{p}_{1}$ at COMPASS with $E = 200$ GeV

CERN Document Server

Zemlyanichkina, Elena

2014-01-01

New results of the double spin asymmetry A p 1 and the spin-dependent structure function of the proton g p 1 as a function of x Bj and Q 2 will be presented. New COMPASS data on longitudinal polarized NH 3 target were collected during the year 2011 with a beam of positive muons with energy E = 200 GeV. It allows us to cover low x region down to 0 : 0025 in the range Q 2 > 1 GeV = c 2 for the first time

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.

EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

Science.gov (United States)

Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

2016-12-01

The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Dependable Real-Time Systems

Science.gov (United States)

1991-09-30

0196 or 413 545-0720 PI E-mail Address: krithi@nirvan.cs.umass.edu, stankovic(ocs.umass.edu Grant or Contract Title: Dependable Real - Time Systems Grant...Dependable Real - Time Systems " Grant or Contract Number: N00014-85-k-0398 L " Reporting Period: 1 Oct 87 - 30 Sep 91 , 2. Summary of Accomplishments ’ 2.1 Our...in developing a sound approach to scheduling tasks in complex real - time systems , (2) developed a real-time operating system kernel, a preliminary

Form-preserving Transformations for the Time-dependent Schroedinger Equation in (n + 1) Dimensions

International Nuclear Information System (INIS)

Schulze-Halberg, Axel

2006-01-01

We define a form-preserving transformation (also called point canonical transformation) for the time-dependent Schroedinger equation (TDSE) in (n+1) dimensions. The form-preserving transformation is shown to be invertible and to preserve L 2 -normalizability. We give a class of time-dependent TDSEs that can be mapped onto stationary Schroedinger equations by our form-preserving transformation. As an example, we generate a solvable, time-dependent potential of Coulombic ring-shaped type together with the corresponding exact solution of the TDSE in (3+1) dimensions. We further consider TDSEs with position-dependent (effective) masses and show that there is no form-preserving transformation between them and the conventional TDSEs, if the spatial dimension of the system is higher than one

Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice.

Science.gov (United States)

Rieck, Michael; Kremser, Christiane; Jobin, Katarzyna; Mettke, Elisabeth; Kurts, Christian; Gräler, Markus; Willecke, Klaus; Kolanus, Waldemar

2017-04-01

Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine. We, therefore, investigated whether Cers2 is involved in the regulation of S1P gradients and S1P-dependent egress into the circulation. By analyzing Cers2-deficient mice, we demonstrate that Cers2 limits the levels of S1P in thymus and blood to maintain functional S1P gradients that mediate thymocyte emigration into the circulation. This function is specific for Cers2, as we also show that Cers4 is not involved in the regulation of thymic egress. Our study identified Cers2 as an important regulator of S1P-dependent thymic egress, and thus contributes to the understanding of how S1P gradients are maintained in vivo. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

FGF1 protects neuroblastoma SH-SY5Y cells from p53-dependent apoptosis through an intracrine pathway regulated by FGF1 phosphorylation

Science.gov (United States)

Pirou, Caroline; Montazer-Torbati, Fatemeh; Jah, Nadège; Delmas, Elisabeth; Lasbleiz, Christelle; Mignotte, Bernard; Renaud, Flore

2017-01-01

Neuroblastoma, a sympathetic nervous system tumor, accounts for 15% of cancer deaths in children. In contrast to most human tumors, p53 is rarely mutated in human primary neuroblastoma, suggesting impaired p53 activation in neuroblastoma. Various studies have shown correlations between fgf1 expression levels and both prognosis severity and tumor chemoresistance. As we previously showed that fibroblast growth factor 1 (FGF1) inhibited p53-dependent apoptosis in neuron-like PC12 cells, we initiated the study of the interaction between the FGF1 and p53 pathways in neuroblastoma. We focused on the activity of either extracellular FGF1 by adding recombinant rFGF1 in media, or of intracellular FGF1 by overexpression in human SH-SY5Y and mouse N2a neuroblastoma cell lines. In both cell lines, the genotoxic drug etoposide induced a classical mitochondrial p53-dependent apoptosis. FGF1 was able to inhibit p53-dependent apoptosis upstream of mitochondrial events in SH-SY5Y cells by both extracellular and intracellular pathways. Both rFGF1 addition and etoposide treatment increased fgf1 expression in SH-SY5Y cells. Conversely, rFGF1 or overexpressed FGF1 had no effect on p53-dependent apoptosis and fgf1 expression in neuroblastoma N2a cells. Using different FGF1 mutants (that is, FGF1K132E, FGF1S130A and FGF1S130D), we further showed that the C-terminal domain and phosphorylation of FGF1 regulate its intracrine anti-apoptotic activity in neuroblastoma SH-SY5Y cells. This study provides the first evidence for a role of an intracrine growth factor pathway on p53-dependent apoptosis in neuroblastoma, and could lead to the identification of key regulators involved in neuroblastoma tumor progression and chemoresistance. PMID:29048426

Darboux transformations for the time-dependent nonhomogeneous Burgers equation in (1+1) dimensions

International Nuclear Information System (INIS)

Schulze-Halberg, Axel; Manuel Carballo Jimenez, Juan

2009-01-01

We extend the formalism of nth order Darboux transformations to the time-dependent nonhomogeneous Burgers equation (NBE) in (1+1) dimensions. Similar to the Schroedinger case, our Darboux transformation retains the form of the NBE, while changing the nonhomogeneous term. The transformed solution of the NBE and the corresponding transformed nonhomogeneity are given in closed form. Furthermore, properties of the transformation are discussed and an application is given.

Time-dependent pH sensing phenomena using CdSe/ZnS quantum dots in EIS structure.

Science.gov (United States)

Kumar, Pankaj; Maikap, Siddheswar; Prakash, Amit; Tien, Ta-Chang

2014-04-12

Time-dependent pH sensing phenomena of the core-shell CdSe/ZnS quantum dot (QD) sensors in EIS (electrolyte insulator semiconductor) structure have been investigated for the first time. The quantum dots are immobilized by chaperonin GroEL protein, which are observed by both atomic force microscope and scanning electron microscope. The diameter of one QD is approximately 6.5 nm. The QDs are not oxidized over a long time and core-shell CdSe/ZnS are confirmed by X-ray photon spectroscopy. The sensors are studied for sensing of hydrogen ions concentration in different buffer solutions at broad pH range of 2 to 12. The QD sensors show improved sensitivity (38 to 55 mV/pH) as compared to bare SiO2 sensor (36 to 23 mV/pH) with time period of 0 to 24 months, owing to the reduction of defects in the QDs. Therefore, the differential sensitivity of the QD sensors with respect to the bare SiO2 sensors is improved from 2 to 32 mV/pH for the time period of 0 to 24 months. After 24 months, the sensitivity of the QD sensors is close to ideal Nernstian response with good linearity of 99.96%. Stability and repeatability of the QD sensors show low drift (10 mV for 10 cycles) as well as small hysteresis characteristics (sensor is very useful for future human disease diagnostics.

p53-dependent inhibition of TrxR1 contributes to the tumor-specific induction of apoptosis by RITA.

Science.gov (United States)

Hedström, Elisabeth; Eriksson, Sofi; Zawacka-Pankau, Joanna; Arnér, Elias S J; Selivanova, Galina

2009-11-01

Thioredoxin reductase 1 (TrxR1) is a key regulator in many redox-dependent cellular pathways, and is often overexpressed in cancer. Several studies have identified TrxR1 as a potentially important target for anticancer therapy. The low molecular weight compound RITA (NSC 652287) binds p53 and induces p53-dependent apoptosis. Here we found that RITA also targets TrxR1 by non-covalent binding, followed by inhibition of its activity in vitro and by inhibition of TrxR activity in cancer cells. Interestingly, a novel approximately 130 kDa form of TrxR1, presumably representing a stable covalently linked dimer, and an increased generation of reactive oxygen species (ROS) were induced by RITA in cancer cells in a p53-dependent manner. Similarly, the gold-based TrxR inhibitor auranofin induced apoptosis related to oxidative stress, but independently of p53 and without apparent induction of the approximately 130 kDa form of TrxR1. In contrast to the effects observed in cancer cells, RITA did not inhibit TrxR or ROS formation in normal fibroblasts (NHDF). The inhibition of TrxR1 can sensitize tumor cells to agents that induce oxidative stress and may directly trigger cell death. Thus, our results suggest that a unique p53-dependent effect of RITA on TrxR1 in cancer cells might synergize with p53-dependent induction of pro-apoptotic genes and oxidative stress, thereby leading to a robust induction of cancer cell death, without affecting non-transformed cells.

The MX/G/1 queue with queue length dependent service times

Directory of Open Access Journals (Sweden)

Bong Dae Choi

2001-01-01

Full Text Available We deal with the MX/G/1 queue where service times depend on the queue length at the service initiation. By using Markov renewal theory, we derive the queue length distribution at departure epochs. We also obtain the transient queue length distribution at time t and its limiting distribution and the virtual waiting time distribution. The numerical results for transient mean queue length and queue length distributions are given.

Measurement of time dependent B$0\\atop{d}$ $\\bar{B}$$0\\atop{d}$ mixing parameter using opposite side lepton and D* meson in p$\\bar{p}$ collisions at √s = 1.8 TeV

Energy Technology Data Exchange (ETDEWEB)

Vandenbrink, Stephan Christopher [Univ. of Pittsburgh, PA (United States)

1998-01-13

This thesis presents the results from the investigation of time dependent B$0\\atop{d}$ $\\bar{B}$$0\\atop{d}$ mixing in B → lepton X, B$0\\atop{d}$ → D^*- → $\\bar{D}$⁰ π^-, $\\bar{D}$⁰ → K⁺ π^- channel in p$\\bar{p}$ collisions at √s = 1.8 TeV using 110 pb^-1 data collected with the CDF detector at the Fermilab Tevatron Collider. The $\\bar{D}$⁰ vertex is reconstructed. The B$0\\atop{d}$ decay length is estimated using the distance from the primary vertex to the measured position of the D⁰ vertex. The B⁰ momentum is estimated using the D⁰ momentum and a kinematic correction factor from Monte Carlo. With the dilution floating, ΔM_d = 0.55 ±$0.15\\atop{0.16}$ (stat) ± 0.06 (syst)ps^-1 is measured.

Arecoline-induced phosphorylated p53 and p21(WAF1) protein expression is dependent on ATM/ATR and phosphatidylinositol-3-kinase in clone-9 cells.

Science.gov (United States)

Chou, Wen-Wen; Guh, Jinn-Yuh; Tsai, Jung-Fa; Hwang, Chi-Ching; Chiou, Shean-Jaw; Chuang, Lea-Yea

2009-06-01

Betel-quid use is associated with liver cancer whereas its constituent arecoline is cytotoxic, genotoxic, and induces p53-dependent p21(WAF1) protein expression in Clone-9 cells (rat hepatocytes). The ataxia telangiectasia mutated (ATM)/rad3-related (ATR)-p53-p21(WAF1) and the phosphatidylinositol-3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathways are involved in the DNA damage response and the pathogenesis of cancers. Thus, we studied the role of ATM/ATR and PI3K in arecoline-induced p53 and p21(WAF1) protein expression in Clone-9 cells. We found that arecoline (0.5 mM) activated the ATM/ATR kinase at 30 min. The arecoline-activated ATM/ATR substrate contained p-p53Ser15. Moreover, arecoline only increased the levels of the p-p53Ser6, p-p53Ser15, and p-p53Ser392 phosphorylated p53 isoforms among the known isoforms. ATM shRNA attenuated arecoline-induced p-p53Ser15 and p21(WAF1) at 24 h. Arecoline (0.5 mM) increased phosphorylation levels of p-AktSer473 and p-mTORSer2448 at 30-60 min. Dominant-negative PI3K plasmids attenuated arecoline-induced p21(WAF1), but not p-p53Ser15, at 24 h. Rapamycin attenuated arecoline-induced phosphrylated p-p53Ser15, but not p21(WAF1), at 24 h. ATM shRNA, but not dominant-negative PI3K plasmids, attenuated arecoline-induced p21(WAF1) gene transcription. We conclude that arecoline activates the ATM/ATR-p53-p21(WAF1) and the PI3K/Akt-mTOR-p53 pathways in Clone-9 cells. Arecoline-induced phosphorylated p-p53Ser15 expression is dependent on ATM whereas arecoline-induced p21(WAF1) protein expression is dependent on ATM and PI3K. Moreover, p21(WAF1) gene is transcriptionally induced by arecoline-activated ATM. (c) 2009 Wiley-Liss, Inc.

Field dependence of T1 for hyperpolarized [1-13C]pyruvate

DEFF Research Database (Denmark)

Chattergoon, N.; Martnez-Santiesteban, F.; Handler, W. B.

2013-01-01

conformation and properties of the dissolution media such as buffer composition, solution pH, temperature and magnetic field. We have measured the magnetic field dependence of the spin–lattice relaxation time of hyperpolarized [1-13C]pyruvate using field-cycled relaxometry. [1-13C]pyruvate was hyperpolarized...

Involvement of histidine residues in the pH-dependent β-galactoside binding activity of human galectin-1.

Science.gov (United States)

Hiramatsu, Hirotsugu; Takeuchi, Katsuyuki; Takeuchi, Hideo

2013-04-02

The pH dependence of the β-galactoside binding activity of human galectin-1 (hGal-1) was investigated by fluorescence spectroscopy using lactose as a ligand. The obtained binding constant Kb was 2.94 ± 0.10 mM(-1) at pH 7.5. The Kb value decreased at acidic pH with a midpoint of transition at pH 6.0 ± 0.1. To elucidate the molecular mechanism of the pH dependence, we investigated the structures of hGal-1 and its two His mutants (H44Q and H52Q) using fluorescence, circular dichroism, UV absorption, and UV resonance Raman spectroscopy. Analysis of the spectra has shown that the pKa values of His44 and His52 are 5.7 ± 0.2 and 6.3 ± 0.1, respectively. The protonation of His52 below pH 6.3 induces a small change in secondary structure and partly reduces the galactoside binding activity. On the other hand, the protonation of His44 below pH 5.7 exerts a cation-π interaction with Trp68 and largely diminishes the galactoside binding activity. With reference to the literature X-ray structures at pH 7.0 and 5.6, protonated His52 is proposed to move slightly away from the galactoside-binding region with a partial unfolding of the β-strand containing His52. On the other hand, protonated His44 becomes unable to form a hydrogen bond with galactoside and additionally induces a reorientation and/or displacement of Trp68 through cation-π interaction, leading to a loosening of the galactoside-binding pocket. These structural changes associated with His protonation are likely to be the origin of the pH dependence of the galactoside binding activity of hGal-1.

FANCA and FANCC modulate TLR and p38 MAPK-dependent expression of IL-1β in macrophages.

Science.gov (United States)

Garbati, Michael R; Hays, Laura E; Keeble, Winifred; Yates, Jane E; Rathbun, R Keaney; Bagby, Grover C

2013-10-31

Hematopoietic stem and progenitor cells with inactivated Fanconi anemia (FA) genes, FANCA and FANCC, are hypersensitive to inflammatory cytokines. One of these, tumor necrosis factor α (TNF-α), is also overproduced by FA mononuclear phagocytes in response to certain Toll-like receptor (TLR) agonists, creating an autoinhibitory loop that may contribute to the pathogenesis of progressive bone marrow (BM) failure and selection of TNF-α-resistant leukemic stem cell clones. In macrophages, the TNF-α overproduction phenotype depends on p38 mitogen-activated protein kinase (MAPK), an enzyme also known to induce expression of other inflammatory cytokines, including interleukin 1β (IL-1β). Reasoning that IL-1β might be involved in a like autoinhibitory loop, we determined that (1) TLR activation of FANCA- and FANCC-deficient macrophages induced overproduction of both TNF-α and IL-1β in a p38-dependent manner; (2) exposure of Fancc-deficient BM progenitors to IL-1β potently suppressed the expansion of multipotent progenitor cells in vitro; and (3) although TNF-α overexpression in FA cells is controlled posttranscriptionally by the p38 substrate MAPKAPK-2, p38-dependent overproduction of IL-1β is controlled transcriptionally. We suggest that multiple inflammatory cytokines overproduced by FANCA- and FANCC-deficient mononuclear phagocytes may contribute to the progressive BM failure that characterizes FA, and that to achieve suppression of this proinflammatory state, p38 is a more promising molecular therapeutic target than either IL-1β or TNF-α alone.

Polycomb Group Protein PHF1 Regulates p53-dependent Cell Growth Arrest and Apoptosis*

Science.gov (United States)

Yang, Yang; Wang, Chenji; Zhang, Pingzhao; Gao, Kun; Wang, Dejie; Yu, Hongxiu; Zhang, Ting; Jiang, Sirui; Hexige, Saiyin; Hong, Zehui; Yasui, Akira; Liu, Jun O.; Huang, Haojie; Yu, Long

2013-01-01

Polycomb group protein PHF1 is well known as a component of a novel EED-EZH2·Polycomb repressive complex 2 complex and plays important roles in H3K27 methylation and Hox gene silencing. PHF1 is also involved in the response to DNA double-strand breaks in human cells, promotes nonhomologous end-joining processes through interaction with Ku70/Ku80. Here, we identified another function of PHF1 as a potential p53 pathway activator in a pathway screen using luminescence reporter assay. Subsequent studies showed PHF1 directly interacts with p53 proteins both in vivo and in vitro and co-localized in nucleus. PHF1 binds to the C-terminal regulatory domain of p53. Overexpression of PHF1 elevated p53 protein level and prolonged its turnover. Knockdown of PHF1 reduced p53 protein level and its target gene expression both in normal state and DNA damage response. Mechanically, PHF1 protects p53 proteins from MDM2-mediated ubiquitination and degradation. Furthermore, we showed that PHF1 regulates cell growth arrest and etoposide-induced apoptosis in a p53-dependent manner. Finally, PHF1 expression was significantly down-regulated in human breast cancer samples. Taken together, we establish PHF1 as a novel positive regulator of the p53 pathway. These data shed light on the potential roles of PHF1 in tumorigenesis and/or tumor progression. PMID:23150668

Algebraic time-dependent variational approach to dynamical calculations

International Nuclear Information System (INIS)

Shi, S.; Rabitz, H.

1988-01-01

A set of time-dependent basis states is obtained with a group of unitary transformations generated by a Lie algebra. Applying the time-dependent variational principle to the trial function subspace constructed from the linear combination of the time-dependent basis states gives rise to a set of ''classical'' equations of motion for the group parameters and the expansion coefficients from which the time evolution of the system state can be determined. The formulation is developed for a general Lie algebra as well as for the commonly encountered algebra containing homogeneous polynominal products of the coordinate Q and momentum P operators (or equivalently the boson creation a/sup dagger/ and annihilation a operators) of order 0, 1, and 2. Explicit expressions for the transition amplitudes are derived by virtue of the cannonical transformation properties of the unitary transformation. The applicability of the present formalism in a variety of problems is implied by two illustrative examples: (a) a parametric amplifier; (b) the collinear collision of an atom with a Morse oscillator

Unexpected dependence on pH of NO release from Paracoccus pantotrophus cytochrome cd1

International Nuclear Information System (INIS)

Sam, Katharine A.; Tolland, John D.; Fairhurst, Shirley A.; Higham, Christopher W.; Lowe, David J.; Thorneley, Roger N.F.; Allen, James W.A.; Ferguson, Stuart J.

2008-01-01

A previous study of nitrite reduction by Paracoccus pantotrophus cytochrome cd 1 at pH 7.0 identified early reaction intermediates. The c-heme rapidly oxidised and nitrite was reduced to NO at the d 1 -heme. A slower equilibration of electrons followed, forming a stable complex assigned as 55% cFe(III)d 1 Fe(II)-NO and 45% cFe(II)d 1 Fe(II)-NO + . No catalytically competent NO release was observed. Here we show that at pH 6.0, a significant proportion of the enzyme undergoes turnover and releases NO. An early intermediate, which was previously overlooked, is also identified; enzyme immediately following product release is a candidate. However, even at pH 6.0 a considerable fraction of the enzyme remains bound to NO so another component is required for full product release. The kinetically stable product formed at the end of the reaction differs significantly at pH 6.0 and 7.0, as does its rate of formation; thus the reaction is critically dependent on pH

Reversible pH-dependent activation/inactivation of CF(1-ATPase of spinach chloroplasts

Directory of Open Access Journals (Sweden)

A. P. Khomochkin

2017-08-01

Full Text Available The aim of the work was to study the reverse pH-dependent regulation of the enzymatic activity of the catalytic part of ATP synthase (EC 3.6.3.14 of chloroplast – coupling factor CF1. It was shown that the short-term incubation of isolated CF1 in the media with pH 4.5 or 3.5 leads to inactivation of Ca2+-ATPase, which is rapidly (t1/2 ~ 1 min restored in the medium containing 0.5-10 mM bicarbonate at pH 7.8. After acid treatment, the rate of Mg2+-ATPase reaction was also stimulated in the presence of 1 mM bicarbonate (рН 7.8; 37 °С. The increase in Ca2+– and Mg2+-АТР activity of CF1 associated with the addition of NaHCO3 solution was completely eliminated after the introduction of 50 mM acetazolamide – a specific inhibitor of carbonic anhydrase. The obtained results suggest the existence of the bound bicarbonate in the CF1 structure, which apparently participates in proton transfer.

The pH-dependent adsorption of tributyltin to charcoals and soot

International Nuclear Information System (INIS)

Fang Liping; Borggaard, Ole K.; Marcussen, Helle; Holm, Peter E.; Bruun Hansen, Hans Christian

2010-01-01

Widespread use of tributyltin (TBT) poses a serious environmental problem. Adsorption by black carbon (BC) may strongly affect its behavior. The adsorption of TBT to well characterized soot and two charcoals with specific surface area in the range of 62-111 m 2 g -1 have been investigated with main focus on pH effects. The charcoals but not soot possess acidic functional groups. TBT adsorption reaches maximum at pH 6-7 for charcoals, and at pH > 6 for soot. Soot has between 1.5 and 15 times higher adsorption density (0.09-1.77 μmol m -2 ) than charcoals, but charcoals show up to 17 times higher sorption affinities than soot. TBT adsorption is successfully described by a new pH-dependent dual Langmuir model considering electrostatic and hydrophobic adsorption, and pH effects on TBT speciation and BC surface charge. It is inferred that strong sorption of the TBTOH species to BC may affect TBT toxicity. - Tributyltin adsorption to black carbon increases at increasing pH but charcoal exhibits electrostatic and hydrophobic adsorption, whereas soot only adsorbs hydrophobically.

FANCA and FANCC modulate TLR and p38 MAPK–dependent expression of IL-1β in macrophages

Science.gov (United States)

Garbati, Michael R.; Hays, Laura E.; Keeble, Winifred; Yates, Jane E.; Rathbun, R. Keaney

2013-01-01

Hematopoietic stem and progenitor cells with inactivated Fanconi anemia (FA) genes, FANCA and FANCC, are hypersensitive to inflammatory cytokines. One of these, tumor necrosis factor α (TNF-α), is also overproduced by FA mononuclear phagocytes in response to certain Toll-like receptor (TLR) agonists, creating an autoinhibitory loop that may contribute to the pathogenesis of progressive bone marrow (BM) failure and selection of TNF-α–resistant leukemic stem cell clones. In macrophages, the TNF-α overproduction phenotype depends on p38 mitogen-activated protein kinase (MAPK), an enzyme also known to induce expression of other inflammatory cytokines, including interleukin 1β (IL-1β). Reasoning that IL-1β might be involved in a like autoinhibitory loop, we determined that (1) TLR activation of FANCA- and FANCC-deficient macrophages induced overproduction of both TNF-α and IL-1β in a p38-dependent manner; (2) exposure of Fancc-deficient BM progenitors to IL-1β potently suppressed the expansion of multipotent progenitor cells in vitro; and (3) although TNF-α overexpression in FA cells is controlled posttranscriptionally by the p38 substrate MAPKAPK-2, p38-dependent overproduction of IL-1β is controlled transcriptionally. We suggest that multiple inflammatory cytokines overproduced by FANCA- and FANCC-deficient mononuclear phagocytes may contribute to the progressive BM failure that characterizes FA, and that to achieve suppression of this proinflammatory state, p38 is a more promising molecular therapeutic target than either IL-1β or TNF-α alone. PMID:24046015

Final COMPASS results on the spin-dependent structure functions $g_1^p$ and $g_1^d$ in the deep-inelastic and nonperturbative regions

CERN Document Server

Badelek, Barbara

2018-01-01

This paper summarizes the COMPASS Collaboration legacy on measurements of the proton and deuteron spin-dependent structure functions, $g_1^p$ and $g_1^d$ at $Q^2 1$ (GeV/c)$^2$. In both regions and at the lowest measured $x, g^d_1 (x)$ is consistent with zero while $g^p_1 (x)$ is positive. This is the first time that the spin effects are observed at such low values of $x$. The NLO QCD fit of $g_1$ world data gives well constrained quark helicity distributions; gluons are poorly determined. Quark helicity contribution to nucleon spin is $0.26 < \\Delta \\Sigma < 0.36$. From the COMPASS data alone the Bjorken sum rule is verified to $9\\%$ accuracy and the extracted flavour-singlet axial charge is $a_0 (Q^2 = 3 (\\text{GeV/}c)^2) = 0.32 \\pm 0.02_{stat.} \\pm 0.04_{syst.} \\pm 0.05_{evol.}$.

Final COMPASS results on the spin-dependent structure functions $g_1^p$ and $g_1^d$ in the deep-inelastic and nonperturbative regions

CERN Document Server

Badelek, Barbara

2017-01-01

This paper summarizes the COMPASS Collaboration legacy on measurements of the proton and deuteron spin-dependent structure functions, $g_1^p$ and $g_1^d$ at $Q^2 1$ (GeV/c)$^2$. In both regions and at the lowest measured $x, g^d_1 (x)$ is consistent with zero while $g^p_1 (x)$ is positive. This is the first time that the spin effects are observed at such low values of $x$. The NLO QCD fit of $g_1$ world data gives well constrained quark helicity distributions; gluons are poorly determined. Quark helicity contribution to nucleon spin is $0.26 < \\Delta \\Sigma < 0.36$. From the COMPASS data alone the Bjorken sum rule is verified to $9\\%$ accuracy and the extracted flavour-singlet axial charge is $a_0 (Q^2 = 3 (\\text{GeV/}c)^2) = 0.32 \\pm 0.02_{stat.} \\pm 0.04_{syst.} \\pm 0.05_{evol.}$.

First measurement of the helicity-dependent vector gamma)vector(p)->p eta differential cross-section

CERN Document Server

Ahrens, J; Aulenbacher, K; Beck, R; Drechsel, D; Von Harrach, D; Heid, E; Altieri, S; Annand, J R M; Anton, G; Bradtke, C; Görtz, S; Harmsen, J; Braghieri, A; D'Hose, N; Dutz, H; Grabmayr, P; Hansen, K; Hasegawa, S; Hasegawa, T; Helbing, K; Holvoet, H; Van Hoorebeke, L; Horikawa, N; Iwata, T; Jahn, O; Jennewein, P; Kageya, T; Kiel, B; Klein, F; Kondratiev, R; Kossert, K; Krimmer, J; Lang, M; Lannoy, B; Leukel, R; Lisin, V; Matsuda, T; McGeorge, J C; Meier, A; Menze, D; Meyer, Werner T; Michel, T; Naumann, J; Panzeri, A; Pedroni, P; Pinelli, T; Preobrajenski, I; Radtke, E; Reichert, E; Reicherz, G; Rohlof, C; Rosner, G; Ryckbosch, D; Sauer, M C; Schoch, B; Schumacher, M; Seitz, B; Speckner, T; Takabayashi, N; Tamas, G; Thomas, A; Van De Vyver, R; Wakai, A; Weihofen, W; Wissmann, F; Zapadtka, F; Zeitler, G

2003-01-01

The helicity dependence of the vector(gamma)vector(p)->p eta reaction has been measured for the first time at a center-of-mass angle theta sup * subeta=70 in the photon energy range from 780 MeV to 790 MeV. The experiment, performed at the Mainz microtron MAMI, used a 4 pi-detector system, a circularly polarized, tagged photon beam, and a longitudinally polarized frozen-spin target. The helicity 3/2 cross-section is found to be small and the results for helicity 1/2 agree with predictions from the MAID analysis. (orig.)

Vitamin E δ-tocotrienol induces p27(Kip1-dependent cell-cycle arrest in pancreatic cancer cells via an E2F-1-dependent mechanism.

Directory of Open Access Journals (Sweden)

Pamela J Hodul

Full Text Available Vitamin E δ-tocotrienol has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we demonstrated that δ-tocotrienol exerted significant cell growth inhibition pancreatic ductal cancer (PDCA cells without affecting normal human pancreatic ductal epithelial cell growth. We also showed that δ-tocotrienol-induced growth inhibition occurred concomitantly with G(1 cell-cycle arrest and increased p27(Kip1 nuclear accumulation. This finding is significant considering that loss of nuclear p27(Kip1 expression is a well-established adverse prognostic factor in PDCA. Furthermore, δ-tocotrienol inactivated RAF-MEK-ERK signaling, a pathway known to suppress p27(Kip1 expression. To determine whether p27(Kip1 induction is required for δ-tocotrienol inhibition of PDCA cell proliferation, we stably silenced the CDKN1B gene, encoding p27(Kip1, in MIAPaCa-2 PDCA cells and demonstrated that p27(Kip1 silencing suppressed cell-cycle arrest induced by δ-tocotrienol. Furthermore, δ-tocotrienol induced p27(Kip1 mRNA expression but not its protein degradation. p27(Kip1 gene promoter activity was induced by δ-tocotrienol through the promoter's E2F-1 binding site, and this activity was attenuated by E2F-1 depletion using E2F-1 small interfering RNA. Finally, decreased proliferation, mediated by Ki67 and p27(Kip1 expression by δ-tocotrienol, was confirmed in vivo in a nude mouse xenograft pancreatic cancer model. Our findings reveal a new mechanism, dependent on p27(Kip1 induction, by which δ-tocotrienol can inhibit proliferation in PDCA cells, providing a new rationale for p27(Kip1 as a biomarker for δ-tocotrienol efficacy in pancreatic cancer prevention and therapy.

Single Machine Scheduling and Due Date Assignment with Past-Sequence-Dependent Setup Time and Position-Dependent Processing Time

Directory of Open Access Journals (Sweden)

Chuan-Li Zhao

2014-01-01

Full Text Available This paper considers single machine scheduling and due date assignment with setup time. The setup time is proportional to the length of the already processed jobs; that is, the setup time is past-sequence-dependent (p-s-d. It is assumed that a job's processing time depends on its position in a sequence. The objective functions include total earliness, the weighted number of tardy jobs, and the cost of due date assignment. We analyze these problems with two different due date assignment methods. We first consider the model with job-dependent position effects. For each case, by converting the problem to a series of assignment problems, we proved that the problems can be solved in On4 time. For the model with job-independent position effects, we proved that the problems can be solved in On3 time by providing a dynamic programming algorithm.

On $L^p$ Estimates for the Time-Dependent Schrodinger Operator on $L^2$

CERN Document Server

Mortad, M H

2006-01-01

Let L denote the time-dependent Schrodinger operator in n space variables. We consider a variety of Lebesgue norms for functions u on R^{n+1}, and prove or disprove estimates for such norms of u in terms of the L^2-norms of u and Lu. The results have implications for self-adjo intness of operators of the form L+V where V is a multiplication operator. The proofs are based mainly on the Strichartz-type inequalities.

Time-dependent Bragg diffraction by multilayer gratings

International Nuclear Information System (INIS)

André, Jean-Michel; Jonnard, Philippe

2016-01-01

Time-dependent Bragg diffraction by multilayer gratings working by reflection or by transmission is investigated. The study is performed by generalizing the time-dependent coupled-wave theory previously developed for one-dimensional photonic crystals (André J-M and Jonnard P 2015 J. Opt. 17 085609) and also by extending the Takagi–Taupin approach of the dynamical theory of diffraction. The indicial response is calculated. It presents a time delay with a transient time that is a function of the extinction length for reflection geometry and of the extinction length combined with the thickness of the grating for transmission geometry. (paper)

p18(Hamlet) mediates different p53-dependent responses to DNA-damage inducing agents.

Science.gov (United States)

Lafarga, Vanesa; Cuadrado, Ana; Nebreda, Angel R

2007-10-01

Cells organize appropriate responses to environmental cues by activating specific signaling networks. Two proteins that play key roles in coordinating stress responses are the kinase p38alpha (MAPK14) and the transcription factor p53 (TP53). Depending on the nature and the extent of the stress-induced damage, cells may respond by arresting the cell cycle or by undergoing cell death, and these responses are usually associated with the phosphorylation of particular substrates by p38alpha as well as the activation of specific target genes by p53. We recently characterized a new p38alpha substrate, named p18(Hamlet) (ZNHIT1), which mediates p53-dependent responses to different genotoxic stresses. Thus, cisplatin or UV light induce stabilization of the p18(Hamlet) protein, which then enhances the ability of p53 to bind to and activate the promoters of pro-apoptotic genes such as NOXA and PUMA leading to apoptosis induction. In a similar way, we report here that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A).

Time-dependent Hartree approximation and time-dependent harmonic oscillator model

International Nuclear Information System (INIS)

Blaizot, J.P.

1982-01-01

We present an analytically soluble model for studying nuclear collective motion within the framework of the time-dependent Hartree (TDH) approximation. The model reduces the TDH equations to the Schroedinger equation of a time-dependent harmonic oscillator. Using canonical transformations and coherent states we derive a few properties of the time-dependent harmonic oscillator which are relevant for applications. We analyse the role of the normal modes in the time evolution of a system governed by TDH equations. We show how these modes couple together due to the anharmonic terms generated by the non-linearity of the theory. (orig.)

ENERGY-DEPENDENT TIME LAGS IN THE SEYFERT 1 GALAXY NGC 4593

International Nuclear Information System (INIS)

Sriram, K.; Agrawal, V. K.; Rao, A. R.

2009-01-01

We investigate the energy-time lag dependence of the source NGC 4593 using XMM-Newton/EPIC pn data. We found that the time lag dependency is linear in nature with respect to the logarithm of different energy bands. We also investigate the frequency-dependent time lags and identify that at some frequency range (5 x 10 -5 Hz to 2 x 10 -4 Hz) the X-ray emission is highly coherent, mildly frequency dependent, and very strongly energy dependent. These observations can be explained in the framework of the thermal Comptonization process, and they indicate a truncated accretion disk very close to the black hole. We discuss the plausible spectral state to explain the phenomenon and conclude that the observed properties bear a close resemblance to the intermediate state or the steep power-law state, found in galactic black hole sources.

Role of individual histidines in the pH-dependent global stability of human chloride intracellular channel 1.

Science.gov (United States)

Achilonu, Ikechukwu; Fanucchi, Sylvia; Cross, Megan; Fernandes, Manuel; Dirr, Heini W

2012-02-07

Chloride intracellular channel proteins exist in both a soluble cytosolic form and a membrane-bound form. The mechanism of conversion between the two forms is not properly understood, although one of the contributing factors is believed to be the variation in pH between the cytosol (~7.4) and the membrane (~5.5). We systematically mutated each of the three histidine residues in CLIC1 to an alanine at position 74 and a phenylalanine at positions 185 and 207. We examined the effect of the histidine-mediated pH dependence on the structure and global stability of CLIC1. None of the mutations were found to alter the global structure of the protein. However, the stability of H74A-CLIC1 and H185F-CLIC1, as calculated from the equilibrium unfolding data, is no longer dependent on pH because similar trends are observed at pH 7.0 and 5.5. The crystal structures show that the mutations result in changes in the local hydrogen bond coordination. Because the mutant total free energy change upon unfolding is not different from that of the wild type at pH 7.0, despite the presence of intermediates that are not seen in the wild type, we propose that it may be the stability of the intermediate state rather than the native state that is dependent on pH. On the basis of the lower stability of the intermediate in the H74A and H185F mutants compared to that of the wild type, we conclude that both His74 and His185 are involved in triggering the pH changes to the conformational stability of wild-type CLIC1 via their protonation, which stabilizes the intermediate state.

Kinetic study of time-dependent fixation of U{sup VI} on biochar

Energy Technology Data Exchange (ETDEWEB)

Ashry, A. [Division of Agricultural and Environmental Sciences, School of Biosciences, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD (United Kingdom); Radiation Protection Department, Nuclear Research Centre, Egyptian Atomic Energy Authority, Cairo (Egypt); Bailey, E.H., E-mail: liz.bailey@nottingham.ac.uk [Division of Agricultural and Environmental Sciences, School of Biosciences, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD (United Kingdom); Chenery, S.R.N. [British Geological Survey, Nicker Hill, Keyworth, Nottingham NG12 5GG (United Kingdom); Young, S.D. [Division of Agricultural and Environmental Sciences, School of Biosciences, University of Nottingham, Sutton Bonington, Leicestershire LE12 5RD (United Kingdom)

2016-12-15

Biochar, a by-product from the production of biofuel and syngas by gasification, was tested as a material for adsorption and fixation of U{sup VI} from aqueous solutions. A batch experiment was conducted to study the factors that influence the adsorption and time-dependent fixation on biochar at 20 °C, including pH, initial concentration of U{sup VI} and contact time. Uranium (U{sup VI}) adsorption was highly dependent on pH but adsorption on biochar was high over a wide range of pH values, from 4.5 to 9.0, and adsorption strength was time-dependent over several days. The experimental data for pH > 7 were most effectively modelled using a Freundlich adsorption isotherm coupled to a reversible first order kinetic equation to describe the time-dependent fixation of U{sup VI} within the biochar structure. Desorption experiments showed that U{sup VI} was only sparingly desorbable from the biochar with time and isotopic dilution with {sup 233}U{sup VI} confirmed the low, or time-dependent, lability of adsorbed {sup 238}U{sup VI}. Below pH 7 the adsorption isotherm trend suggested precipitation, rather than true adsorption, may occur. However, across all pH values (4.5-9) measured saturation indices suggested precipitation was possible: autunite below pH 6.5 and either swartzite, liebigite or bayleyite above pH 6.5.

Observation of π- B meson charge-flavor correlations and measurement of time dependent B⁰$\\bar{B}$⁰ mixing in p$\\bar{p}$ collisions

Energy Technology Data Exchange (ETDEWEB)

Maksimovic, Peter [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

1998-02-01

We present a study of time dependent B⁰-$\\bar{B}$⁰ mixing in p$\\bar{p}$ collisions at 1.8 TeV using 110 pb^-1 collected with the CDF detector at the Fermilab Tevatron Collider. B mesons are partially reconstructed using the semileptonic decays B⁰→l⁺D^*-X and B⁺→l⁺$\\bar{D}$⁰X (and their charge conjugates). B meson-charged pion correlations are used in order to determine the flavor of the B meson at t=0. Such correlations are expected to arise from pions produced in the fragmentation chain and also from B** decays. We measure the efficiency and purity of this flavor tagging method for both charged and neutral B mesons.

The pH-dependent adsorption of tributyltin to charcoals and soot

Energy Technology Data Exchange (ETDEWEB)

Fang Liping, E-mail: fang@life.ku.d [Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C (Denmark); Borggaard, Ole K.; Marcussen, Helle; Holm, Peter E.; Bruun Hansen, Hans Christian [Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C (Denmark)

2010-12-15

Widespread use of tributyltin (TBT) poses a serious environmental problem. Adsorption by black carbon (BC) may strongly affect its behavior. The adsorption of TBT to well characterized soot and two charcoals with specific surface area in the range of 62-111 m{sup 2} g{sup -1} have been investigated with main focus on pH effects. The charcoals but not soot possess acidic functional groups. TBT adsorption reaches maximum at pH 6-7 for charcoals, and at pH > 6 for soot. Soot has between 1.5 and 15 times higher adsorption density (0.09-1.77 {mu}mol m{sup -2}) than charcoals, but charcoals show up to 17 times higher sorption affinities than soot. TBT adsorption is successfully described by a new pH-dependent dual Langmuir model considering electrostatic and hydrophobic adsorption, and pH effects on TBT speciation and BC surface charge. It is inferred that strong sorption of the TBTOH species to BC may affect TBT toxicity. - Tributyltin adsorption to black carbon increases at increasing pH but charcoal exhibits electrostatic and hydrophobic adsorption, whereas soot only adsorbs hydrophobically.

Accurate, Fast and Cost-Effective Diagnostic Test for Monosomy 1p36 Using Real-Time Quantitative PCR

Directory of Open Access Journals (Sweden)

Pricila da Silva Cunha

2014-01-01

Full Text Available Monosomy 1p36 is considered the most common subtelomeric deletion syndrome in humans and it accounts for 0.5–0.7% of all the cases of idiopathic intellectual disability. The molecular diagnosis is often made by microarray-based comparative genomic hybridization (aCGH, which has the drawback of being a high-cost technique. However, patients with classic monosomy 1p36 share some typical clinical characteristics that, together with its common prevalence, justify the development of a less expensive, targeted diagnostic method. In this study, we developed a simple, rapid, and inexpensive real-time quantitative PCR (qPCR assay for targeted diagnosis of monosomy 1p36, easily accessible for low-budget laboratories in developing countries. For this, we have chosen two target genes which are deleted in the majority of patients with monosomy 1p36: PRKCZ and SKI. In total, 39 patients previously diagnosed with monosomy 1p36 by aCGH, fluorescent in situ hybridization (FISH, and/or multiplex ligation-dependent probe amplification (MLPA all tested positive on our qPCR assay. By simultaneously using these two genes we have been able to detect 1p36 deletions with 100% sensitivity and 100% specificity. We conclude that qPCR of PRKCZ and SKI is a fast and accurate diagnostic test for monosomy 1p36, costing less than 10 US dollars in reagent costs.

Prospects for time-dependent asymmetries at LHCb

CERN Document Server

INSPIRE-00260500

2012-01-01

LHCb is already providing leading measurements of time-dependent CP asymmetries with 1 fb$^{-1}$ of data. With the LHCb detector, and further one with the LHCb upgrade, very high-precision time-dependent CP measurements are expected to stringently test the CKM paradigm and to the search for possible small NP effects. A review of the current precision and the prospects for these time-dependent quantities with the LHCb and LHCb upgraded detectors are summarised in this paper.

Uniform in N global well-posedness of the time-dependent Hartree-Fock-Bogoliubov equations in R^{1+1}

Science.gov (United States)

Chong, Jacky Jia Wei

2018-04-01

We prove the global well-posedness of the time-dependent Hartree-Fock-Bogoliubov (TDHFB) equations in R^{1+1} with two-body interaction potential of the form N^{-1}v_N(x) = N^{β -1} v(N^β x) where v≥0 is a sufficiently regular radial function, i.e., v \\in L^1(R)\\cap C^∞ (R) . In particular, using methods of dispersive PDEs similar to the ones used in Grillakis and Machedon (Commun Partial Differ Equ 42:24-67, 2017), we are able to show for any scaling parameter β >0 the TDHFB equations are globally well-posed in some Strichartz-type spaces independent of N, cf. (Bach et al. in The time-dependent Hartree-Fock-Bogoliubov equations for Bosons, 2016. arXiv:1602.05171).

Analysis of time-dependent changes in Bitemarks on Styrofoam sheets

Directory of Open Access Journals (Sweden)

Djeapragassam Parimala

2015-01-01

Full Text Available Context: The scope of Bitemarks in forensic dentistry is widening as they help the forensic expert in identifying the perpetuator in medicolegal cases. The greatest challenge in Bitemarks analysis is the time-dependent changes produced in Bitemark patterns on various substrates at the scene of the crime. Aims: To analyze the time-dependent changes in Bitemarks on Styrofoam sheets. Settings and Design: Single centered prospective study. Materials and Methods: Twenty-five subjects were randomly chosen, and dental casts prepared. Then test bites were registered on Styrofoam sheets, overlays prepared from these test bites on subsequent days (day 1, 2, 3, 4 and checked for matching accuracy. Statistical Analysis Used: The data were analyzed using Kruskal-Wallis ANOVA to compare the overlays from dental stone cast with test bites on Styrofoam sheets on subsequent days. Results: The P value was found to be 1 which is statistically not significant implying that there were no significant time-dependent changes in the pattern of Bitemarks. Conclusions: There were no time-dependent changes in the pattern of Bitemarks on Styrofoam sheets hence they serve as better materials than Bitemarks on human skin or food substrates obtained from the scene of the crime.

Recombinant mouse PAP has pH-dependent ectonucleotidase activity and acts through A(1-adenosine receptors to mediate antinociception.

Directory of Open Access Journals (Sweden)

Nathaniel A Sowa

Full Text Available Prostatic acid phosphatase (PAP is expressed in nociceptive neurons and functions as an ectonucleotidase. When injected intraspinally, the secretory isoforms of human and bovine PAP protein have potent and long-lasting antinociceptive effects that are dependent on A(1-adenosine receptor (A(1R activation. In this study, we purified the secretory isoform of mouse (mPAP using the baculovirus expression system to determine if recombinant mPAP also had antinociceptive properties. We found that mPAP dephosphorylated AMP, and to a much lesser extent, ADP at neutral pH (pH 7.0. In contrast, mPAP dephosphorylated all purine nucleotides (AMP, ADP, ATP at an acidic pH (pH 5.6. The transmembrane isoform of mPAP had similar pH-dependent ectonucleotidase activity. A single intraspinal injection of mPAP protein had long-lasting (three day antinociceptive properties, including antihyperalgesic and antiallodynic effects in the Complete Freund's Adjuvant (CFA inflammatory pain model. These antinociceptive effects were transiently blocked by the A(1R antagonist 8-cyclopentyl-1, 3-dipropylxanthine (CPX, suggesting mPAP dephosphorylates nucleotides to adenosine to mediate antinociception just like human and bovine PAP. Our studies indicate that PAP has species-conserved antinociceptive effects and has pH-dependent ectonucleotidase activity. The ability to metabolize nucleotides in a pH-dependent manner could be relevant to conditions like inflammation where tissue acidosis and nucleotide release occur. Lastly, our studies demonstrate that recombinant PAP protein can be used to treat chronic pain in animal models.

Kinetic study of time-dependent fixation of U"V"I on biochar

International Nuclear Information System (INIS)

Ashry, A.; Bailey, E.H.; Chenery, S.R.N.; Young, S.D.

2016-01-01

Biochar, a by-product from the production of biofuel and syngas by gasification, was tested as a material for adsorption and fixation of U"V"I from aqueous solutions. A batch experiment was conducted to study the factors that influence the adsorption and time-dependent fixation on biochar at 20 °C, including pH, initial concentration of U"V"I and contact time. Uranium (U"V"I) adsorption was highly dependent on pH but adsorption on biochar was high over a wide range of pH values, from 4.5 to 9.0, and adsorption strength was time-dependent over several days. The experimental data for pH > 7 were most effectively modelled using a Freundlich adsorption isotherm coupled to a reversible first order kinetic equation to describe the time-dependent fixation of U"V"I within the biochar structure. Desorption experiments showed that U"V"I was only sparingly desorbable from the biochar with time and isotopic dilution with "2"3"3U"V"I confirmed the low, or time-dependent, lability of adsorbed "2"3"8U"V"I. Below pH 7 the adsorption isotherm trend suggested precipitation, rather than true adsorption, may occur. However, across all pH values (4.5-9) measured saturation indices suggested precipitation was possible: autunite below pH 6.5 and either swartzite, liebigite or bayleyite above pH 6.5.

Thymocyte apoptosis induced by p53-dependent and independent pathways

International Nuclear Information System (INIS)

Clarke, A.R.; Purdie, C.A.; Harrison, D.J.; Morris, R.G.; Bird, C.C.; Hooper, M.L.; Wyllie, A.H.

1993-01-01

The authors studied the dependence of apoptosis on p53 expression in cells from the thymus cortex. Short-term thymocyte cultures were prepared from mice constitutively heterozygous or homozygous for a deletion in the p53 gene introduced into the germ line after gene targeting. Wild-type thymocytes readily undergo apoptosis after treatment with ionizing radiation, the glucocorticoid methylprednisolone, or etoposide (an inhibitor of topoisomerase II), or after Ca 2+ -dependent activation by phorbol ester and a calcium ionophore. In contrast, homozygous null p53 thymocytes are resistant to induction of apoptosis by radiation or etoposide, but retain normal sensitivity to glucocorticoid and calcium. The time-dependent apoptosis that occurs in untreated cultures is unaffected by p53 status. Cells heterozygous for p53 deletion are partially resistant to radiation and etoposide. Results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage. (Author)

Rosiglitazone attenuates NF-κB-dependent ICAM-1 and TNF-α production caused by homocysteine via inhibiting ERK1/2/p38MAPK activation

International Nuclear Information System (INIS)

Bai, Yong-Ping; Liu, Yu-Hui; Chen, Jia; Song, Tao; You, Yu; Tang, Zhen-Yan; Li, Yuan-Jian; Zhang, Guo-Gang

2007-01-01

Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-κB) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-κB-mediated sICAM-1, TNF-α production and the possible involvement of ERK 1/2 /p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-α in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-κB inhibitor; PD98059, MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK 1/2 /p38MAPK pathway and NF-κB activity in HUVECs. The results show that Hcy activated both ERK 1/2 /p38MAPK pathway and NF-κB-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK 1/2 /p38MAPK phosphorylation, suggesting that Hcy-induced ERK 1/2 /p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-κB activation was mediated by activation of ERK 1/2 /p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-κB-mediated sICAM-1 and TNF-α production induced by Hcy via inhibition of ERK 1/2 /p38MAPK pathway

Time-dependent AdS backgrounds from S-branes

Energy Technology Data Exchange (ETDEWEB)

Deger, Nihat Sadik, E-mail: sadik.deger@boun.edu.tr [Department of Mathematics, Bogazici University, Bebek, 34342, Istanbul (Turkey); Feza Gursey Center for Physics and Mathematics, Bogazici University, Kandilli, 34684, Istanbul (Turkey)

2016-11-10

We construct time and radial dependent solutions that describe p-branes in chargeless S-brane backgrounds. In particular, there are some new M5- and D3-branes among our solutions which have AdS limits and contain a cosmological singularity as well. We also find a time-dependent version of the dyonic membrane configuration in 11-dimensions by applying a Lunin–Maldacena deformation to our new M5-brane solution.

Time-dependent embedding

OpenAIRE

Inglesfield, J. E.

2007-01-01

A method of solving the time-dependent Schr\\"odinger equation is presented, in which a finite region of space is treated explicitly, with the boundary conditions for matching the wave-functions on to the rest of the system replaced by an embedding term added on to the Hamiltonian. This time-dependent embedding term is derived from the Fourier transform of the energy-dependent embedding potential, which embeds the time-independent Schr\\"odinger equation. Results are presented for a one-dimensi...

Propeptides are sufficient to regulate organelle-specific pH-dependent activation of furin and proprotein convertase 1/3.

Science.gov (United States)

Dillon, Stephanie L; Williamson, Danielle M; Elferich, Johannes; Radler, David; Joshi, Rajendra; Thomas, Gary; Shinde, Ujwal

2012-10-12

The proprotein convertases (PCs) furin and proprotein convertase 1/3 (PC1) cleave substrates at dibasic residues along the eukaryotic secretory/endocytic pathway. PCs are evolutionarily related to bacterial subtilisin and are synthesized as zymogens. They contain N-terminal propeptides (PRO) that function as dedicated catalysts that facilitate folding and regulate activation of cognate proteases through multiple-ordered cleavages. Previous studies identified a histidine residue (His69) that functions as a pH sensor in the propeptide of furin (PRO(FUR)), which regulates furin activation at pH~6.5 within the trans-Golgi network. Although this residue is conserved in the PC1 propeptide (PRO(PC1)), PC1 nonetheless activates at pH~5.5 within the dense core secretory granules. Here, we analyze the mechanism by which PRO(FUR) regulates furin activation and examine why PRO(FUR) and PRO(PC1) differ in their pH-dependent activation. Sequence analyses establish that while both PRO(FUR) and PRO(PC1) are enriched in histidines when compared with cognate catalytic domains and prokaryotic orthologs, histidine content in PRO(FUR) is ~2-fold greater than that in PRO(PC1), which may augment its pH sensitivity. Spectroscopy and molecular dynamics establish that histidine protonation significantly unfolds PRO(FUR) when compared to PRO(PC1) to enhance autoproteolysis. We further demonstrate that PRO(FUR) and PRO(PC1) are sufficient to confer organelle sensing on folding and activation of their cognate proteases. Swapping propeptides between furin and PC1 transfers pH-dependent protease activation in a propeptide-dictated manner in vitro and in cells. Since prokaryotes lack organelles and eukaryotic PCs evolved from propeptide-dependent, not propeptide-independent prokaryotic subtilases, our results suggest that histidine enrichment may have enabled propeptides to evolve to exploit pH gradients to activate within specific organelles. Copyright © 2012 Elsevier Ltd. All rights reserved.

MODICO, 1-D Time-Dependent 1 Group, 2 Group Neutron Diffusion with Delayed Neutron Precursors

International Nuclear Information System (INIS)

Camiciola, P.; Cundari, D.; Montagnini, B.

1992-01-01

1 - Description of program or function: The program solves the 1-D time-dependent one and two group coarse-mesh neutron diffusion equations, coupled with the equations for the delayed-neutron precursor, in plane geometry. 2 - Method of solution: The program is based on a simple coarse-mesh cubic approximation formula for the spatial behaviour of the flux inside each interval. An implicit scheme (the time-integrated method) is used for the advancement of the solution. The resulting (block three-diagonal) matrix is inverted at each time step by Thomas' method. 3 - Restrictions on the complexity of the problem: Number of coarse- mesh intervals LE 80; number of material regions LE 10; number of delayed-neutron precursor groups LE 10. Typical mesh sizes range from 5 cm to 20 cm; typical step length (non-prompt critical transients) ranges from 0.005 to 0.1 seconds

Clinical significance of cyclin-dependent kinase inhibitor p27Kip1 expression and proliferation in non-Hodgkin's lymphoma

DEFF Research Database (Denmark)

Møller, Michael Boe; Skjødt, Karsten; Mortensen, Leif Spange

1999-01-01

The cyclin-dependent kinase inhibitor p27Kip1 is a negative cell cycle regulator linking extracellular growth-regulatory signals to the cell cycle machinery in G1. We investigated the pattern and prognostic value of p27Kip1 expression in a population-based group of 203 non-Hodgkin's lymphoma (NHL...... between p27Kip1 and Ki-67 expression. Low expression of p27Kip1, defined as nuclear p27Kip1 expression in lymphomas behaved differently as those with low p27Kip1...... expression tended to do better. Likewise, a high proliferation rate (Ki-67 >40%) was associated with poor survival in indolent and aggressive lymphomas. Multivariate analysis using the proportional hazards model showed that only p27Kip1, and not Ki-67, maintained independent prognostic significance...

Transportin-1-dependent YB-1 nuclear import

International Nuclear Information System (INIS)

Mordovkina, Daria A.; Kim, Ekaterina R.; Buldakov, Ilya A.; Sorokin, Alexey V.; Eliseeva, Irina A.; Lyabin, Dmitry N.; Ovchinnikov, Lev P.

2016-01-01

The DNA/RNA-binding protein YB-1 (Y-box binding protein 1) performs multiple functions both in the cytoplasm and the nucleus of the cell. Generally localized to the cytoplasm, under certain conditions YB-1 is translocated to the nucleus. Here we report for the first time a transport factor that mediates YB-1 nuclear import – transportin-1. The YB-1/transportin-1 complex can be isolated from HeLa cell extract. Nuclear import of YB-1 and its truncated form YB-1 (1-219) in in vitro transport assay was diminished in the presence of a competitor substrate and ceased in the presence of transportin-1 inhibitor M9M. Inhibitors of importin β1 had no effect on YB-1 transport. Furthermore, transport of YB-1 (P201A/Y202A) and YB-1 (1–219) (P201A/Y202A) bearing inactivating mutations in the transportin-1-dependent nuclear localization signal was practically abolished. Together, these results indicate that transportin-1 mediates YB-1 nuclear translocation. - Highlights: • Transportin-1 mediates YB-1 nuclear import. • YB-1 nuclear translocation is diminished in the presence of transportin-1 inhibitors. • Mutations in the PY motif of YB-1 NLS prevent its translocation to the nucleus.

Phase diagrams of a nonequilibrium mixed spin-1/2 and spin-2 Ising ferrimagnetic system under a time-dependent oscillating magnetic field

International Nuclear Information System (INIS)

Keskin, M.; Canko, O.; Gueldal, S.

2009-01-01

We present phase diagrams for a nonequilibrium mixed spin-1/2 and spin-2 Ising ferrimagnetic system on a square lattice in the presence of a time dependent oscillating external magnetic field. We employ the Glauber transition rates to construct the mean-field dynamical equations. The time variation of the average magnetizations and the thermal behavior of the dynamic magnetizations are investigated, extensively. The nature (continuous or discontinuous) of the transitions is characterized by studying the thermal behaviors of the dynamic magnetizations. The dynamic phase transition points are obtained and the phase diagrams are presented in two different planes. Phase diagrams contain paramagnetic (p) and ferrimagnetic (i) phases, and one coexistence or mixed phase region, namely the i+p, that strongly depend on interaction parameters. The system exhibits the dynamic tricritical point and the reentrant behaviors.

Phase diagrams of a nonequilibrium mixed spin-1/2 and spin-2 Ising ferrimagnetic system under a time-dependent oscillating magnetic field

Energy Technology Data Exchange (ETDEWEB)

Keskin, M., E-mail: keskin@erciyes.edu.t [Department of Physics, Erciyes University, 38039 Kayseri (Turkey); Canko, O. [Department of Physics, Erciyes University, 38039 Kayseri (Turkey); Gueldal, S. [Institute of Science, Erciyes University, 38039 Kayseri (Turkey)

2009-12-14

We present phase diagrams for a nonequilibrium mixed spin-1/2 and spin-2 Ising ferrimagnetic system on a square lattice in the presence of a time dependent oscillating external magnetic field. We employ the Glauber transition rates to construct the mean-field dynamical equations. The time variation of the average magnetizations and the thermal behavior of the dynamic magnetizations are investigated, extensively. The nature (continuous or discontinuous) of the transitions is characterized by studying the thermal behaviors of the dynamic magnetizations. The dynamic phase transition points are obtained and the phase diagrams are presented in two different planes. Phase diagrams contain paramagnetic (p) and ferrimagnetic (i) phases, and one coexistence or mixed phase region, namely the i+p, that strongly depend on interaction parameters. The system exhibits the dynamic tricritical point and the reentrant behaviors.

Accelerated turnover of taste bud cells in mice deficient for the cyclin-dependent kinase inhibitor p27Kip1

Directory of Open Access Journals (Sweden)

Perna Marla K

2011-04-01

Full Text Available Abstract Background Mammalian taste buds contain several specialized cell types that coordinately respond to tastants and communicate with sensory nerves. While it has long been appreciated that these cells undergo continual turnover, little is known concerning how adequate numbers of cells are generated and maintained. The cyclin-dependent kinase inhibitor p27Kip1 has been shown to influence cell number in several developing tissues, by coordinating cell cycle exit during cell differentiation. Here, we investigated its involvement in the control of taste cell replacement by examining adult mice with targeted ablation of the p27Kip1 gene. Results Histological and morphometric analyses of fungiform and circumvallate taste buds reveal no structural differences between wild-type and p27Kip1-null mice. However, when examined in functional assays, mutants show substantial proliferative changes. In BrdU incorporation experiments, more S-phase-labeled precursors appear within circumvallate taste buds at 1 day post-injection, the earliest time point examined. After 1 week, twice as many labeled intragemmal cells are present, but numbers return to wild-type levels by 2 weeks. Mutant taste buds also contain more TUNEL-labeled cells and 50% more apoptotic bodies than wild-type controls. In normal mice, p27 Kip1 is evident in a subset of receptor and presynaptic taste cells beginning about 3 days post-injection, correlating with the onset of taste cell maturation. Loss of gene function, however, does not alter the proportions of distinct immunohistochemically-identified cell types. Conclusions p27Kip1 participates in taste cell replacement by regulating the number of precursor cells available for entry into taste buds. This is consistent with a role for the protein in timing cell cycle withdrawal in progenitor cells. The equivalence of mutant and wild-type taste buds with regard to cell number, cell types and general structure contrasts with the hyperplasia

Analysis of cavity effect on space- and time-dependent fast and thermal neutron energy spectra

International Nuclear Information System (INIS)

Kudo, Katsuhisa; Narita, Masakuni; Ozawa, Yasutomo.

1975-01-01

The effects of the presence of a central cavity on the space- and time-dependent neutron energy spectra in both thermal and fast neutron systems are analyzed theoretically with use made of the multi-group one-dimensional time-dependent Ssub(n) method. The thermal neutron field is also analyzed for the case of a fundamental time eigenvalue problem with the time-dependent P 1 approximation. The cavity radius is variable, and the system radius for graphite is 120 cm and for the other materials 7 cm. From the analysis of the time-dependent Ssub(n) calculations in the non-multiplying systems of polythene, light water and graphite, cavity heating is the dominant effect for the slowing-down spectrum in the initial period following fast neutron burst, and when the slowing-down spectrum comes into the thermal energy region, cavity heating shifts to cavity cooling. In the multiplying system of 235 U, cavity cooling also takes place as the spectrum approaches equilibrium after the fast neutron burst is injected. The mechanism of cavity cooling is explained analytically for the case of thermal neutron field to illustrate its physical aspects, using the time-dependent P 1 approximation. An example is given for the case of light water. (auth.)

First measurement of the helicity-dependent (vector)({gamma})(vector)(p){yields}p{eta} differential cross-section

Energy Technology Data Exchange (ETDEWEB)

Ahrens, J.; Arends, H.J.; Aulenbacher, K.; Beck, R.; Drechsel, D.; Harrach, D. van; Heid, E. [Institut fuer Kernphysik, Universitaet Mainz, D-55099 Mainz (Germany); Altieri, S. [INFN, Sezione di Pavia, I-27100 Pavia (Italy); Dipartimento di Fisica Nucleare e Teorica, Universita di Pavia, I-27100 Pavia (Italy); Annand, J.R.M. [Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Anton, G. [Physikalisches Institut, Universitaet Erlangen-Nuernberg, D-91058 Erlangen (Germany); Bradtke, C.; Goertz, S.; Harmsen, J. [Institut fuer Experimentalphysik, Ruhr-Universitaet Bochum, D-44801 Bochum (Germany); Braghieri, A. [INFN, Sezione di Pavia, I-27100 Pavia (Italy); d' Hose, N. [CEA Saclay, DSM/DAPNIA/SPhN, F-91191 Gif-sur-Yvette Cedex (France); Dutz, H. [Physikalisches Institut, Universitaet Bonn, D-53115 Bonn (Germany); Grabmayr, P. [Physikalisches Institut, Universitaet Tuebingen, D-72076 Tuebingen (Germany); Hansen, K. [Department of Physics, University of Lund, Lund (Sweden); Hasegawa, S. [Department of Physics, Nagoya University, Chikusa-ku, Nagoya (Japan); Hasegawa, T. [Faculty of Engineering, Miyazaki University, Miyazaki (Japan); Helbing, K.; Holvoet, H.; Van Hoorebeke, L.; Horikawa, N.; Iwata, T.; Jahn, O.; Jennewein, P.; Kageya, T.; Kiel, B.; Klein, F.; Kondratiev, R.; Kossert, K.; Krimmer, J.; Lang, M.; Lannoy, B.; Leukel, R.; Lisin, V.; Matsuda, T.; McGeorge, J.C.; Meier, A.; Menze, D.; Meyer, W.; Michel, T.; Naumann, J.; Panzeri, A.; Pedroni, P.; Pinelli, T.; Preobrajenski, I.; Radtke, E.; Reichert, E.; Reicherz, G.; Rohlof, Ch.; Rosner, G.; Ryckbosch, D.; Sauer, M.; Schoch, B.; Schumacher, M.; Seitz, B.; Speckner, T.; Takabayashi, N.; Tamas, G.; Thomas, A.; Van de Vyver, R.; Wakai, A.; Weihofen, W.; Wissmann, F.; Zapadtka, F.; Zeitler, G.

2003-06-01

The helicity dependence of the (vector)({gamma})(vector)(p){yields}p{eta} reaction has been measured for the first time at a center-of-mass angle {theta}{sup *}{sub {eta}}=70 in the photon energy range from 780 MeV to 790 MeV. The experiment, performed at the Mainz microtron MAMI, used a 4{pi}-detector system, a circularly polarized, tagged photon beam, and a longitudinally polarized frozen-spin target. The helicity 3/2 cross-section is found to be small and the results for helicity 1/2 agree with predictions from the MAID analysis. (orig.)

Pharmacokinetics of colon-specific pH and time-dependent flurbiprofen tablets.

Science.gov (United States)

Vemula, Sateesh Kumar; Veerareddy, Prabhakar Reddy; Devadasu, Venkat Ratnam

2015-09-01

Present research deals with the development of compression-coated flurbiprofen colon-targeted tablets to retard the drug release in the upper gastro intestinal system, but progressively release the drug in the colon. Flurbiprofen core tablets were prepared by direct compression method and were compression coated using sodium alginate and Eudragit S100. The formulation is optimized based on the in vitro drug release study and further evaluated by X-ray imaging and pharmacokinetic studies in healthy humans for colonic delivery. The optimized formulation showed negligible drug release (4.33 ± 0.06 %) in the initial lag period followed by progressive release (100.78 ± 0.64 %) for 24 h. The X-ray imaging in human volunteers showed that the tablets reached the colon without disintegrating in the upper gastrointestinal tract. The C max of colon-targeted tablets was 12,374.67 ng/ml at T max 10 h, where as in case of immediate release tablets the C max was 15,677.52 ng/ml at T max 3 h, that signifies the ability of compression-coated tablets to target the colon. Development of compression-coated tablets using combination of time-dependent and pH-sensitive approaches was suitable to target the flurbiprofen to colon.

Time-dependent effect of p-Aminophenol (PAP) toxicity in renal slices and development of oxidative stress

International Nuclear Information System (INIS)

Harmon, R. Christopher; Terneus, Marcus V.; Kiningham, Kinsley K.; Valentovic, Monica

2005-01-01

p-Aminophenol (PAP), a metabolite of acetaminophen, is nephrotoxic. This study investigated PAP-mediated changes as a function of time that occur prior to loss of membrane integrity. Experiments further evaluated the development of oxidative stress by PAP. Renal slices from male Fischer 344 (F344) rats (N = 4-6) were exposed to 0.1, 0.25, and 0.5 mM PAP for 15-120 min under oxygen and constant shaking at 37 o C. Pyruvate-stimulated gluconeogenesis, adenine nucleotide levels, and total glutathione (GSH) levels were diminished in a concentration- and time-dependent manner prior to detection of a rise in lactate dehydrogenase (LDH) leakage. Glutathione disulfide (GSSG) levels were increased by PAP suggesting the induction of oxidative stress. Western blot analysis confirmed a rise in 4-hydroxynonenal (4-HNE)-adducted proteins in tissues exposed to 0.1 and 0.25 mM PAP for 90 min. The appearance of 4-HNE-adducted proteins at the 0.1 mM concentration of PAP occurred prior to development of increased LDH leakage. Pretreatment with 1 mM glutathione (GSH) for 30 min only partially reduced PAP toxicity as LDH values were less severely depleted relative to tissues not pretreated with GSH. In contrast, pretreatment for 15 min with 2 mM ascorbic acid completely protected against PAP toxicity. Further studies showed that ascorbic acid pretreatment prevented PAP-mediated depletion of GSH. In summary, PAP rapidly depletes GSH and adenine nucleotides and inhibits gluconeogenesis prior to a rise in LDH leakage. PAP induces oxidative stress as indicated by an increase in GSSG and 4-HNE-adducted proteins. Ascorbic acid pretreatment prevents PAP toxicity by maintaining GSH status

KCNE5 induces time- and voltage-dependent modulation of the KCNQ1 current

DEFF Research Database (Denmark)

Angelo, Kamilla; Jespersen, Thomas; Grunnet, Morten

2002-01-01

The function of the KCNE5 (KCNE1-like) protein has not previously been described. Here we show that KCNE5 induces both a time- and voltage-dependent modulation of the KCNQ1 current. Interaction of the KCNQ1 channel with KCNE5 shifted the voltage activation curve of KCNQ1 by more than 140 mV in th...... the I(Ks) current in certain parts of the mammalian heart....

First measurement of the helicity dependence for the {gamma}p{yields}p{pi} reaction

Energy Technology Data Exchange (ETDEWEB)

Ahrens, J.; Arends, H.J.; Beck, R.; Heid, E.; Jahn, O.; Jennewein, P.; Lang, M.; Martinez-Fabregate, M.; Rost, M.; Tamas, G.; Thomas, A. [Universitaet Mainz, Institut fuer Kernphysik, Mainz (Germany); Altieri, S.; Panzeri, A.; Pinelli, T. [INFN, Sezione di Pavia, Pavia (Italy); Universita di Pavia, Dipartimento di Fisica Nucleare e Teorica, Pavia (Italy); Annand, J.R.M.; McGeorge, J.C.; Rosner, G. [University of Glasgow, Department of Physics and Astronomy, Glasgow (United Kingdom); Blackston, M.A.; Weller, H.R. [Duke University, Department of Physics, Durham (United States); Bradtke, C.; Dutz, H.; Klein, F.; Rohlof, C. [Universitaet Bonn, Physikalisches Institut, Bonn (Germany); Braghieri, A.; Pedroni, P. [INFN, Sezione di Pavia, Pavia (Italy); Hose, N. d' [CEA Saclay, DSM/DAPNIA/SPhN, Gif-sur-Yvette Cedex (France); Fix, A. [Tomsk Polytechnic University, Laboratory of Mathematical Physics, Tomsk (Russian Federation); Goertz, S.; Meyer, W.; Reicherz, G. [Ruhr-Universitaet Bochum, Insitut fuer Experimentalphysik, Bochum (Germany); Grabmayr, P. [Universitaet Tuebingen, Physikalisches Institut, Tuebingen (Germany); Hasegawa, S.; Iwata, T. [Nagoya University, Department of Physics, Chikusa-ku, Nagoya (Japan); Holvoet, H.; Lannoy, B.; Ryckbosch, D.; Van de Vyver, R. [Universiteit Gent, Subatomaire en Stralingsfysica, Gent (Belgium); Horikawa, N. [Nagoya University, CIRSE, Chikusa-ku, Nagoya (Japan); Kondratiev, R.; Lisin, V. [Academy of Science, INR, Moscow (Russian Federation); Preobrajenski, I. [Universitaet Mainz, Institut fuer Kernphysik, Mainz (Germany); Academy of Science, INR, Moscow (Russian Federation); Rostomyan, T. [Universiteit Gent, Subatomaire en Stralingsfysica, Gent (Belgium); INFN, Sezione di Pavia, Pavia (Italy); Schumacher, M.; Seitz, B.; Zapadtka, F. [Universitaet Goettingen, II.Physikalisches Institut, Goettingen (Germany)

2007-10-15

The helicity dependence of the total cross-section and the invariant-mass distributions in the (p{pi}{sup {+-}}) and ({pi}{sup +}{pi}{sup -}) final states for the {gamma}p{yields}p{pi}{sup +}{pi}{sup -} reaction have been measured for the first time at incident photon energies from 400 to 800 MeV. The measurement was performed with the large-acceptance detector DAPHNE at the tagged photon beam facility of the MAMI accelerator in Mainz. Although this channel is found to be predominantly excited by the intermediate production of a {delta}{pi} state, both the measured unpolarized and the helicity-dependent observables are generally not well described by the existing theoretical models. (orig.)

Emission-energy dependence of ultrafast P-emission decay in ZnO from bulk to nanofilm

International Nuclear Information System (INIS)

Wakaiki, Shuji; Ichida, Hideki; Bamba, Motoaki; Kawase, Toshiki; Kawakami, Masaki; Mizoguchi, Kohji; Kim, DaeGwi; Nakayama, Masaaki; Kanematsu, Yasuo

2014-01-01

We have performed time-resolved photoluminescence (PL) spectroscopy for ZnO thin films with thicknesses of 90, 460, and 2800 nm under intense excitation condition. We clearly observed the P emission due to inelastic exciton–exciton scattering. It was found that, in the 460- and 2800-nm thick samples, the decay time of the P emission considerably depends on the detection energy inversely proportional to the group velocity of the polariton in a bulk crystal with each factor of proportionality. In contrast, the energy dependence is less remarkable in the 90-nm thick sample. The decay times are basically shortened with a decrease in the film thickness. The thickness dependence of the P-emission-decay profiles is explained by considering the crossover from the polariton modes in the 2800-nm thick sample (bulk-like film) to the exciton-/photon-like modes in the 90-nm thick sample (nanofilm). - Highlights: • We clearly observed the P-PL dynamics due to inelastic exciton–exciton scattering. • The P-PL decay times are basically shortened with a decrease in the film thickness. • The P-PL decay time depends on the detection energy in the bulk-like sample. • The energy dependence of the P-PL decay time almost disappears in the 90-nm sample. • The thickness dependence is explained by the crossover between exciton and photon

Emission-energy dependence of ultrafast P-emission decay in ZnO from bulk to nanofilm

Energy Technology Data Exchange (ETDEWEB)

Wakaiki, Shuji, E-mail: s.wakaiki@mls.eng.osaka-u.ac.jp [Department of Material and Life Science, Division of Advanced Science and Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871 (Japan); Ichida, Hideki [Department of Material and Life Science, Division of Advanced Science and Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871 (Japan); Science and Technology Entrepreneurship Laboratory, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871 (Japan); Bamba, Motoaki [Department of Physics, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 (Japan); Kawase, Toshiki; Kawakami, Masaki [Department of Applied Physics, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Mizoguchi, Kohji [Department of Physical Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen, Naka-ku, Sakai, Osaka 599-8531 (Japan); Kim, DaeGwi; Nakayama, Masaaki [Department of Applied Physics, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan); Kanematsu, Yasuo [Department of Material and Life Science, Division of Advanced Science and Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871 (Japan); Science and Technology Entrepreneurship Laboratory, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871 (Japan)

2014-08-01

We have performed time-resolved photoluminescence (PL) spectroscopy for ZnO thin films with thicknesses of 90, 460, and 2800 nm under intense excitation condition. We clearly observed the P emission due to inelastic exciton–exciton scattering. It was found that, in the 460- and 2800-nm thick samples, the decay time of the P emission considerably depends on the detection energy inversely proportional to the group velocity of the polariton in a bulk crystal with each factor of proportionality. In contrast, the energy dependence is less remarkable in the 90-nm thick sample. The decay times are basically shortened with a decrease in the film thickness. The thickness dependence of the P-emission-decay profiles is explained by considering the crossover from the polariton modes in the 2800-nm thick sample (bulk-like film) to the exciton-/photon-like modes in the 90-nm thick sample (nanofilm). - Highlights: • We clearly observed the P-PL dynamics due to inelastic exciton–exciton scattering. • The P-PL decay times are basically shortened with a decrease in the film thickness. • The P-PL decay time depends on the detection energy in the bulk-like sample. • The energy dependence of the P-PL decay time almost disappears in the 90-nm sample. • The thickness dependence is explained by the crossover between exciton and photon.

Time-dependent massless Dirac fermions in graphene

Energy Technology Data Exchange (ETDEWEB)

Khantoul, Boubakeur, E-mail: bobphys@gmail.com [Department of Mathematics, City University London, Northampton Square, London EC1V 0HB (United Kingdom); Department of Physics, University of Jijel, BP 98, Ouled Aissa, 18000 Jijel (Algeria); Fring, Andreas, E-mail: a.fring@city.ac.uk [Department of Mathematics, City University London, Northampton Square, London EC1V 0HB (United Kingdom)

2015-10-30

Using the Lewis–Riesenfeld method of invariants we construct explicit analytical solutions for the massless Dirac equation in 2+1 dimensions describing quasi-particles in graphene. The Hamiltonian of the system considered contains some explicit time-dependence in addition to one resulting from being minimally coupled to a time-dependent vector potential. The eigenvalue equations for the two spinor components of the Lewis–Riesenfeld invariant are found to decouple into a pair of supersymmetric invariants in a similar fashion as the known decoupling for the time-independent Dirac Hamiltonians. - Highlights: • An explicit analytical solution for a massless 2+1 dimensional time-dependent Dirac equation is found. • All steps of the Lewis–Riesenfeld method have been carried out.

Deoxyinosine triphosphate induces MLH1/PMS2- and p53-dependent cell growth arrest and DNA instability in mammalian cells

Science.gov (United States)

Yoneshima, Yasuto; Abolhassani, Nona; Iyama, Teruaki; Sakumi, Kunihiko; Shiomi, Naoko; Mori, Masahiko; Shiomi, Tadahiro; Noda, Tetsuo; Tsuchimoto, Daisuke; Nakabeppu, Yusaku

2016-01-01

Deoxyinosine (dI) occurs in DNA either by oxidative deamination of a previously incorporated deoxyadenosine residue or by misincorporation of deoxyinosine triphosphate (dITP) from the nucleotide pool during replication. To exclude dITP from the pool, mammals possess specific hydrolysing enzymes, such as inosine triphosphatase (ITPA). Previous studies have shown that deficiency in ITPA results in cell growth suppression and DNA instability. To explore the mechanisms of these phenotypes, we analysed ITPA-deficient human and mouse cells. We found that both growth suppression and accumulation of single-strand breaks in nuclear DNA of ITPA-deficient cells depended on MLH1/PMS2. The cell growth suppression of ITPA-deficient cells also depended on p53, but not on MPG, ENDOV or MSH2. ITPA deficiency significantly increased the levels of p53 protein and p21 mRNA/protein, a well-known target of p53, in an MLH1-dependent manner. Furthermore, MLH1 may also contribute to cell growth arrest by increasing the basal level of p53 activity. PMID:27618981

House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived epithelial cells by protease-dependent and protease-independent mechanisms

Directory of Open Access Journals (Sweden)

Timmerman J André B

2006-03-01

Full Text Available Abstract House dust mite allergens (HDM cause bronchoconstriction in asthma patients and induce an inflammatory response in the lungs due to the release of cytokines, chemokines and additional mediators. The mechanism how HDM components achieve this is largely unknown. The objective of this study was to assess whether HDM components of Dermatophagoides pteronissinus with protease activity (Der p 1 and unknown enzymatic activity (Der p 2, Der p 5 induce biological responses in a human airway-derived epithelial cell line (A549, and if so, to elucidate the underlying mechanism(s of action. A549 cells were incubated with HDM extract, Der p 1, recombinant Der p 2 and recombinant Der p 5. Cell desquamation was assessed by microscopy. The proinflammatory cytokines, IL-6 and IL-8, were measured by ELISA. Intracellular Ca2+ levels were assessed in A549 cells and in mouse fibroblasts expressing the human protease activated receptor (PAR1, PAR2 or PAR4. HDM extract, Der p 1 and Der p 5 dose-dependently increased the production of IL-6 and IL-8. Added simultaneously, Der p 1 and Der p 5 further increased the production of IL-6 and IL-8. The action of Der p 1 was blocked by cysteine-protease inhibitors, while that of Der p 5 couldn't be blocked by either serine- or cysteine protease inhibitors. Der p 5 only induced cell shrinking, whereas HDM extract and Der p1 also induced cell desquamation. Der p 2 had no effect on A549 cells. Der p 1's protease activity causes desquamation and induced the release of IL6 and IL-8 by a mechanism independent of Ca2+ mobilisation and PAR activation. Der p 5 exerts a protease-independent activation of A549 that involves Ca2+ mobilisation and also leads to the production of these cytokines. Together, our data indicate that allergens present in HDM extracts can trigger protease-dependent and protease-independent signalling pathways in A549 cells.

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.

Nardilysin controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation.

Science.gov (United States)

Kanda, Keitaro; Sakamoto, Jiro; Matsumoto, Yoshihide; Ikuta, Kozo; Goto, Norihiro; Morita, Yusuke; Ohno, Mikiko; Nishi, Kiyoto; Eto, Koji; Kimura, Yuto; Nakanishi, Yuki; Ikegami, Kanako; Yoshikawa, Takaaki; Fukuda, Akihisa; Kawada, Kenji; Sakai, Yoshiharu; Ito, Akihiro; Yoshida, Minoru; Kimura, Takeshi; Chiba, Tsutomu; Nishi, Eiichiro; Seno, Hiroshi

2018-04-19

Colon cancer is a complex disease affected by a combination of genetic and epigenetic factors. Here we demonstrate that nardilysin (N-arginine dibasic convertase; NRDC), a metalloendopeptidase of the M16 family, regulates intestinal tumorigenesis via its nuclear functions. NRDC is highly expressed in human colorectal cancers. Deletion of the Nrdc gene in ApcMin mice crucially suppressed intestinal tumor development. In ApcMin mice, epithelial cell-specific deletion of Nrdc recapitulated the tumor suppression observed in Nrdc-null mice. Moreover, epithelial cell-specific overexpression of Nrdc significantly enhanced tumor formation in ApcMin mice. Notably, epithelial NRDC controlled cell apoptosis in a gene dosage-dependent manner. In human colon cancer cells, nuclear NRDC directly associated with HDAC1, and controlled both acetylation and stabilization of p53, with alterations of p53 target apoptotic factors. These findings demonstrate that NRDC is critically involved in intestinal tumorigenesis through its epigenetic regulatory function, and targeting NRDC may lead to a novel prevention or therapeutic strategy against colon cancer.

Stochastic Landau equation with time-dependent drift

International Nuclear Information System (INIS)

Swift, J.B.; Hohenberg, P.C.; Ahlers, G.

1991-01-01

The stochastic differential equation τ 0 ∂ tA =ε(t)A-g 3 A 3 +bar f(t), where bar f(t) is Gaussian white noise, is studied for arbitrary time dependence of ε(t). In particular, cases are considered where ε(t) goes through the bifurcation of the deterministic system, which occurs at ε=0. In the limit of weak noise an approximate analytic expression generalizing earlier work of Suzuki [Phys. Lett. A 67, 339 (1978); Prog. Theor. Phys. (Kyoto) Suppl. 64, 402 (1978)] is obtained for the time-dependent distribution function P(A,t). The results compare favorably with a numerical simulation of the stochastic equation for the case of a linear ramp (both increasing and decreasing) and for a periodic time dependence of ε(t). The procedure can be generalized to an arbitrary deterministic part ∂ tA =D(A,t)+bar f(t), but the deterministic equation may then have to be solved numerically

Space dependent neutron slowing and thermalization in monatomic hydrogen gas in the P-1 approximation

International Nuclear Information System (INIS)

Musazay, M.S.

1981-01-01

A solution to the space and energy dependent neutron transport equation in the framework of the consistent P-1 approximation is sought. The transport equation for thermal neutrons in a moderator of 1/v absorption and constant scattering cross section is changed into a set of coupled partial differential equations. The space dependent part is removed by assuming a cosine shaped flux due to a cosine shaped source at a very high energy. The resulting set of strongly coupled ordinary differential equations is decoupled by assuming expansion of collision density in the powers of a leakage parameter whose coefficients are energy and absorption dependent. These energy dependent coefficients are solutions of a set of weakly coupled differential equations. Series solutions to these differential equations in powers of epsilon and 1/epsilon, where epsilon = E/kT, E being the neutron energy and kT the moderator temperature in units of energy, are found. The properties of these solutions are studied extensively. Absorption appears as a parameter in the coefficients of the series. The difficulties arising in choosing the correct form of the asymptotic solutions are resolved by comparing slowing and thermalization. The limitations on the size of the slab and on the range of absorption are included in the analysis

LHCb time-dependent results

OpenAIRE

Calvi, Marta

2011-01-01

This review reports preliminary results of time-dependent measurements of decays of $B^0$ mesons and $B^0_s$ mesons coming from the analysis of about 36 pb$^{-1}$ of data collected by the LHCb experiment during the 2010 run of the Large Hadron Collider at $\\sqrt{s}$ = 7 TeV.

LHCb time-dependent results

OpenAIRE

Calvi, Marta; Collaboration, for the LHCb

2011-01-01

This review reports preliminary results of time-dependent measurements of decays of B^0 mesons and B^0_s mesons coming from the analysis of about 36 pb^-1 of data collected by the LHCb experiment during the 2010 run of the Large Hadron Collider at sqrt(s)=7 TeV.

Histone Deacetylase Inhibitors Increase p27Kip1 by Affecting Its Ubiquitin-Dependent Degradation through Skp2 Downregulation

Directory of Open Access Journals (Sweden)

Adriana Borriello

2016-01-01

Full Text Available Histone deacetylase inhibitors (HDACIs represent an intriguing class of pharmacologically active compounds. Currently, some HDACIs are FDA approved for cancer therapy and many others are in clinical trials, showing important clinical activities at well tolerated doses. HDACIs also interfere with the aging process and are involved in the control of inflammation and oxidative stress. In vitro, HDACIs induce different cellular responses including growth arrest, differentiation, and apoptosis. Here, we evaluated the effects of HDACIs on p27Kip1, a key cyclin-dependent kinase inhibitor (CKI. We observed that HDACI-dependent antiproliferative activity is associated with p27Kip1 accumulation due to a reduced protein degradation. p27Kip1 removal requires a preliminary ubiquitination step due to the Skp2-SCF E3 ligase complex. We demonstrated that HDACIs increase p27Kip1 stability through downregulation of Skp2 protein levels. Skp2 decline is only partially due to a reduced Skp2 gene expression. Conversely, the protein decrease is more profound and enduring compared to the changes of Skp2 transcript. This argues for HDACIs effects on Skp2 protein posttranslational modifications and/or on its removal. In summary, we demonstrate that HDACIs increase p27Kip1 by hampering its nuclear ubiquitination/degradation. The findings might be of relevance in the phenotypic effects of these compounds, including their anticancer and aging-modulating activities.

V-ATPase-dependent luminal acidification is required for endocytic recycling of a yeast cell wall stress sensor, Wsc1p

Energy Technology Data Exchange (ETDEWEB)

Ueno, Kazuma; Saito, Mayu; Nagashima, Makiko; Kojima, Ai; Nishinoaki, Show [Department of Biological Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Toshima, Junko Y., E-mail: yama_jun@aoni.waseda.jp [Faculty of Science and Engineering, Waseda University, Wakamatsu-cho 2-2, Shinjuku-ku, Tokyo 162-8480 (Japan); Research Center for RNA Science, RIST, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Toshima, Jiro, E-mail: jtosiscb@rs.noda.tus.ac.jp [Department of Biological Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Research Center for RNA Science, RIST, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan)

2014-01-10

Highlights: •A targeted genome screen identified 5 gene groups affecting Wsc1p recycling. •V-ATPase-dependent luminal acidification is required for Wsc1p recycling. •Activity of V-ATPase might be required for cargo recognition by the retromer complex. -- Abstract: Wsc1p is a major cell wall sensor protein localized at the polarized cell surface. The localization of Wsc1p is maintained by endocytosis and recycling from endosomes back to the cell surface, but changes to the vacuole when cells are subjected to heat stress. Exploiting this unique property of Wsc1p, we screened for yeast single-gene deletion mutants exhibiting defects in Wsc1p trafficking. By expressing 3GFP-tagged Wsc1p in mutants with deleted genes whose function is related to intracellular trafficking, we identified 5 gene groups affecting Wsc1p trafficking, impaired respectively in endocytic internalization, multivesicular body sorting, the GARP complex, endosomal maturation/vacuolar fusion, and V-ATPase. Interestingly, deletion of the VPH1 gene, encoding the V{sub o} subunit of vacuolar-type H{sup +}-ATPase (V-ATPase), led to mis-localization of Wsc1p from the plasma membrane to the vacuole. In addition, disruption of other V-ATPase subunits (vma mutants) also caused defects of Wsc1p trafficking and vacuolar acidification similar to those seen in the vph1Δ mutant. Moreover, we found that deletion of the VPS26 gene, encoding a subunit of the retromer complex, also caused a defect in Wsc1p recycling and mis-localization of Wsc1p to the vacuole. These findings clarified the previously unidentified Wsc1p recycling pathway and requirement of V-ATPase-dependent luminal acidification for Wsc1p recycling.

V-ATPase-dependent luminal acidification is required for endocytic recycling of a yeast cell wall stress sensor, Wsc1p

International Nuclear Information System (INIS)

Ueno, Kazuma; Saito, Mayu; Nagashima, Makiko; Kojima, Ai; Nishinoaki, Show; Toshima, Junko Y.; Toshima, Jiro

2014-01-01

Highlights: •A targeted genome screen identified 5 gene groups affecting Wsc1p recycling. •V-ATPase-dependent luminal acidification is required for Wsc1p recycling. •Activity of V-ATPase might be required for cargo recognition by the retromer complex. -- Abstract: Wsc1p is a major cell wall sensor protein localized at the polarized cell surface. The localization of Wsc1p is maintained by endocytosis and recycling from endosomes back to the cell surface, but changes to the vacuole when cells are subjected to heat stress. Exploiting this unique property of Wsc1p, we screened for yeast single-gene deletion mutants exhibiting defects in Wsc1p trafficking. By expressing 3GFP-tagged Wsc1p in mutants with deleted genes whose function is related to intracellular trafficking, we identified 5 gene groups affecting Wsc1p trafficking, impaired respectively in endocytic internalization, multivesicular body sorting, the GARP complex, endosomal maturation/vacuolar fusion, and V-ATPase. Interestingly, deletion of the VPH1 gene, encoding the V o subunit of vacuolar-type H + -ATPase (V-ATPase), led to mis-localization of Wsc1p from the plasma membrane to the vacuole. In addition, disruption of other V-ATPase subunits (vma mutants) also caused defects of Wsc1p trafficking and vacuolar acidification similar to those seen in the vph1Δ mutant. Moreover, we found that deletion of the VPS26 gene, encoding a subunit of the retromer complex, also caused a defect in Wsc1p recycling and mis-localization of Wsc1p to the vacuole. These findings clarified the previously unidentified Wsc1p recycling pathway and requirement of V-ATPase-dependent luminal acidification for Wsc1p recycling

Dma1-dependent degradation of SIN proteins during meiosis in Schizosaccharomyces pombe.

Science.gov (United States)

Krapp, Andrea; Simanis, Viesturs

2014-07-15

The Schizosaccharomyces pombe septation initiation network (SIN) is required for cytokinesis during vegetative growth and for spore formation during meiosis. Regulation of the SIN during mitosis has been studied extensively, but less is known about its meiotic regulation. Here, we show that several aspects of SIN regulation differ between mitosis and meiosis. First, the presence of GTP-bound Spg1p is not the main determinant of the timing of Cdc7p and Sid1p association with the spindle pole body (SPB) during meiosis. Second, the localisation dependencies of SIN proteins differ from those in mitotic cells, suggesting a modified functional organisation of the SIN during meiosis. Third, there is stage-specific degradation of SIN components in meiosis; Byr4p is degraded after meiosis I, whereas the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second meiotic division and depends upon the ubiquitin ligase Dma1p. Finally, Dma1p-dependent degradation is not restricted to the SIN, as we show that Dma1p is needed for the degradation of Mcp6p (also known as Hrs1p) during meiosis I. Taken together, these data suggest that stage-specific targeted proteolysis plays an important role in regulating meiotic progression. © 2014. Published by The Company of Biologists Ltd.

A note on the optimal pricing strategy in the discrete-time Geo/Geo/1 queuing system with sojourn time-dependent reward

Directory of Open Access Journals (Sweden)

Doo Ho Lee

Full Text Available This work studies the optimal pricing strategy in a discrete-time Geo/Geo/1 queuing system under the sojourn time-dependent reward. We consider two types of pricing schemes. The first one is called the ex-post payment scheme where the server charges a price that is proportional to the time a customer spends in the system, and the second one is called ex-ante payment scheme where the server charges a flat price for all services. In each pricing scheme, a departing customer receives the reward that is inversely proportional to his/her sojourn time. The server should make the optimal pricing decisions in order to maximize its expected profits per time unit in each pricing scheme. This work also investigates customer's equilibrium joining or balking behavior under server's optimal pricing strategy. Numerical experiments are also conducted to validate our analysis. Keywords: Optimal pricing, Equilibrium behavior, Geo/Geo/1 queue, Sojourn time-dependent reward

Time-dependent reversal of significant intrapulmonary shunt after liver transplantation.

Science.gov (United States)

Jin, Xin; Sun, Byung Joo; Song, Jae-Kwan; Roh, Jae-Hyung; Jang, Jeong Yoon; Kim, Dae-Hee; Lim, Young-Suk; Song, Jong-Min; Kang, Duk-Hyun; Lee, Sung Gyu

2018-03-05

Although the association between intrapulmonary shunt (IPS) and liver cirrhosis is clear, data of repeated contrast echocardiography (CE) before and after liver transplantation (LT) to evaluate factors associated with IPS are limited. Hand-agitated saline was used for CE and, by assessing left-chamber opacification, IPS was classified as grade 0 to 4. Grade 3/4 constituted significant IPS and hepatopulmonary syndrome (HPS) was defined as significant IPS with the arterial partial pressure of oxygen < 70 mmHg. Before LT, 253 patients underwent CE and the frequency of significant IPS and HPS were 44% (n = 112) and 7% (n = 17), respectively. Child-Pugh score (odds ratio [OR], 1.345; 95% confidence interval [CI], 1.090 to 1.660; p = 0.006) and arterial oxygen content (OR, 0.838; 95% CI, 0.708 to 0.991; p = 0.039) were independent determinants of significant IPS, whereas direct bilirubin (OR, 1.076; 95% CI, 1.012 to 1.144; p = 0.019) was the only variable associated with HPS. Among 153 patients who underwent successful LT, repeated CE was performed in 97 (63%), which showed significant reductions in IPS grade (from 2.6 ± 1.0 to 1.2 ± 1.3, p < 0.001) and the prevalence of significant IPS (from 56% to 20%, p = 0.038). After adjustment for pre-LT IPS grade, time from LT to repeated CE presented negative linear relationship with post-LT IPS grade (r 2 = 0.366, p < 0.001) and was the only determinant of post-LT IPS grade (OR, 1.009; 95% CI, 1.003 to 1.014; p = 0.004). Repeated CE is useful to evaluate intrapulmonary vascular change before and after LT. Reversal of IPS after successful LT is time-dependent and follow-up duration should be considered for accurate assessment of IPS after LT.

PRAP1 is a novel executor of p53-dependent mechanisms in cell survival after DNA damage.

Science.gov (United States)

Huang, B H; Zhuo, J L; Leung, C H W; Lu, G D; Liu, J J; Yap, C T; Hooi, S C

2012-12-13

p53 has a crucial role in governing cellular mechanisms in response to a broad range of genotoxic stresses. During DNA damage, p53 can either promote cell survival by activating senescence or cell-cycle arrest and DNA repair to maintain genomic integrity for cell survival or direct cells to undergo apoptosis to eliminate extensively damaged cells. The ability of p53 to execute these two opposing cell fates depends on distinct signaling pathways downstream of p53. In this study, we showed that under DNA damage conditions induced by chemotherapeutic drugs, gamma irradiation and hydrogen peroxide, p53 upregulates a novel protein, proline-rich acidic protein 1 (PRAP1). We identified functional p53-response elements within intron 1 of PRAP1 gene and showed that these regions interact directly with p53 using ChIP assays, indicating that PRAP1 is a novel p53 target gene. The induction of PRAP1 expression by p53 may promote resistance of cancer cells to chemotherapeutic drugs such as 5-fluorouracil (5-FU), as knockdown of PRAP1 increases apoptosis in cancer cells after 5-FU treatment. PRAP1 appears to protect cells from apoptosis by inducing cell-cycle arrest, suggesting that the induction of PRAP1 expression by p53 in response to DNA-damaging agents contributes to cancer cell survival. Our findings provide a greater insight into the mechanisms underlying the pro-survival role of p53 in response to cytotoxic treatments.

Wave function for time-dependent harmonically confined electrons in a time-dependent electric field.

Science.gov (United States)

Li, Yu-Qi; Pan, Xiao-Yin; Sahni, Viraht

2013-09-21

The many-body wave function of a system of interacting particles confined by a time-dependent harmonic potential and perturbed by a time-dependent spatially homogeneous electric field is derived via the Feynman path-integral method. The wave function is comprised of a phase factor times the solution to the unperturbed time-dependent Schrödinger equation with the latter being translated by a time-dependent value that satisfies the classical driven equation of motion. The wave function reduces to that of the Harmonic Potential Theorem wave function for the case of the time-independent harmonic confining potential.

Am/Cm target glass durability dependence on pH (U). Revision 1

International Nuclear Information System (INIS)

Daniel, W.E.; Best, D.R.

1996-03-01

At the Westinghouse Savannah River Company near Aiken, South Carolina, a process is being developed to safely vitrify all of the highly radioactive americium/curium (Am/Cm) material and a portion of the other fissile actinide materials stored on site. One goal of this campaign is to provide Oak Ridge National Laboratory with the excess Am/Cm so it can be recycled as opposed to simply disposing of it as waste. The vitrification will allow safe transportation of the Am/Cm to Oak Ridge as well as safe storage once it arrives. The Am/Cm Target glass being used in this project has been specifically designed to be extremely durable in aqueous environments while it can be selectively attacked by nitric acid to recover the valuable Am and Cm isotopes. Similar glass compositions could be used for storage and retrieval of other actinides on the WSRC site. Previous reports have presented the time, temperature, and compositional dependence of the Am/Cm glass durability. This paper will show results from a pH study on the Am/Cm Target glass durability. The data indicate that the Am/Cm Target Glass durability decreases as pH decreases from a neutral reading. These findings support the extraction of the valuable isotopes from the glass using nitric acid

Actin-interacting Protein 1 Promotes Disassembly of Actin-depolymerizing Factor/Cofilin-bound Actin Filaments in a pH-dependent Manner.

Science.gov (United States)

Nomura, Kazumi; Hayakawa, Kimihide; Tatsumi, Hitoshi; Ono, Shoichiro

2016-03-04

Actin-interacting protein 1 (AIP1) is a conserved WD repeat protein that promotes disassembly of actin filaments when actin-depolymerizing factor (ADF)/cofilin is present. Although AIP1 is known to be essential for a number of cellular events involving dynamic rearrangement of the actin cytoskeleton, the regulatory mechanism of the function of AIP1 is unknown. In this study, we report that two AIP1 isoforms from the nematode Caenorhabditis elegans, known as UNC-78 and AIPL-1, are pH-sensitive in enhancement of actin filament disassembly. Both AIP1 isoforms only weakly enhance disassembly of ADF/cofilin-bound actin filaments at an acidic pH but show stronger disassembly activity at neutral and basic pH values. However, a severing-defective mutant of UNC-78 shows pH-insensitive binding to ADF/cofilin-decorated actin filaments, suggesting that the process of filament severing or disassembly, but not filament binding, is pH-dependent. His-60 of AIP1 is located near the predicted binding surface for the ADF/cofilin-actin complex, and an H60K mutation of AIP1 partially impairs its pH sensitivity, suggesting that His-60 is involved in the pH sensor for AIP1. These biochemical results suggest that pH-dependent changes in AIP1 activity might be a novel regulatory mechanism of actin filament dynamics. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Rotational dynamics account for pH-dependent relaxivities of PAMAM dendrimeric, Gd-based potential MRI contrast agents.

Science.gov (United States)

Laus, Sabrina; Sour, Angélique; Ruloff, Robert; Tóth, Eva; Merbach, André E

2005-05-06

The EPTPA5) chelate, which ensures fast water exchange in GdIII complexes, has been coupled to three different generations (5, 7, and 9) of polyamidoamine (PAMAM) dendrimers through benzylthiourea linkages (H5EPTPA = ethylenepropylenetriamine-N,N,N',N'',N''-pentaacetic acid). The proton relaxivities measured at pH 7.4 for the dendrimer complexes G5-(GdEPTPA)111, G7-(GdEPTPA)253 and G9-(GdEPTPA)1157 decrease with increasing temperature, indicating that, for the first time for dendrimers, slow water exchange does not limit relaxivity. At a given field and temperature, the relaxivity increases from G5 to G7, and then slightly decreases for G9 (r1 = 20.5, 28.3 and 27.9 mM(-1) s(-1), respectively, at 37 degrees C, 30 MHz). The relaxivities show a strong and reversible pH dependency for all three dendrimer complexes. This originates from the pH-dependent rotational dynamics of the dendrimer skeleton, which was evidenced by a combined variable-temperature and multiple-field 17O NMR and 1H relaxivity study performed at pH 6.0 and 9.9 on G5-(GdEPTPA)111. The longitudinal 17O and 1H relaxation rates of the dendrimeric complex are strongly pH-dependent, whereas they are not for the [Gd(EPTPA)(H2O)]2- monomer chelate. The longitudinal 17O and 1H relaxation rates have been analysed by the Lipari-Szabo spectral density functions and correlation times have been calculated for the global motion of the entire macromolecule (tau(gO)) and the local motion of the GdIII chelates on the surface (tau(lO)), correlated by means of an order parameter S2. The dendrimer complex G5-(GdEPTPA)111 has a considerably higher tau(gO) under acidic than under basic conditions (tau(298)gO = 4040 ps and 2950 ps, respectively), while local motions are less influenced by pH (tau(298)lO = 150 and 125 ps). The order parameter, characterizing the rigidity of the macromolecule, is also higher at pH 6.0 than at pH 9.9 (S2 = 0.43 vs 0.36, respectively). The pH dependence of the global correlation time can be

Zinc-ion-dependent acid phosphatase exhibits magnesium-ion-dependent myo-inositol-1-phosphatase activity.

Science.gov (United States)

Fujimoto, S; Okano, I; Tanaka, Y; Sumida, Y; Tsuda, J; Kawakami, N; Shimohama, S

1996-06-01

We have purified bovine brain Zn(2+)-dependent acid phosphatase (Zn(2+)-APase), which requires Zn2+ ions to hydrolyze the substrate p-nitrophenyl phosphate (pNPP) in an acidic environment. The substrate specificity and metal requirement of Zn(2+)-APase at a physiological pH was also studied. The enzyme exhibited hydrolytic activity on myo-inositol-1- and -2-monophosphates, 2'-adenosine monophosphate, 2'-guanosine monophosphate, and the alpha- and beta-glycerophosphates, glucose-1-phosphate, and fructose-6-phosphate in 50 mM Tris-HCl buffer (pH 7.4) in the presence of Mg2+ ions, but not on pNPP and phosphotyrosine. Zn2+, Mn2+ and Co2+ ions were less effective for activation. Among the above substrates, myo-inositol-1-phosphate was the most susceptible to hydrolysis by the enzyme in the presence of 3 mM Mg2+ ions. The enzyme exhibited an optimum pH at around 8 for myo-inositol-1-phosphate in the presence of 3 mM Mg2+ ions. The Mg(2+)-dependent myo-inositol-1-phosphatase activity of the enzyme was significantly inhibited by Li+ ions. The Zn(2+)-dependent p-nitrophenyl phosphatase activity and Mg(2+)-dependent myo-inositol-1-phosphatase activity of the purified enzyme fraction exhibited similar behavior on Sephadex G-100 and Mono Q colomns. These findings suggest that Zn(2+)-APase also exhibits Mg(2+)-dependent myo-inositol-1-phosphatase activity under physiological conditions.

Time-dependent Schroedinger equations with effective mass in (2 + 1) dimensions: intertwining relations and Darboux operators

International Nuclear Information System (INIS)

Cobian, Hector; Schulze-Halberg, Axel

2011-01-01

We construct Darboux transformations for time-dependent Schroedinger equations with position-dependent mass in (2 + 1) dimensions. Several examples illustrate our results, which complement and generalize former findings for the constant mass case in two spatial variables (Schulze-Halberg 2010 J. Math. Phys. 51 033521).

1-Soliton solution of the generalized Zakharov-Kuznetsov equation with nonlinear dispersion and time-dependent coefficients

International Nuclear Information System (INIS)

Biswas, Anjan

2009-01-01

In this Letter, the 1-soliton solution of the Zakharov-Kuznetsov equation with power law nonlinearity and nonlinear dispersion along with time-dependent coefficients is obtained. There are two models for this kind of an equation that are studied. The constraint relation between these time-dependent coefficients is established for the solitons to exist. Subsequently, this equation is again analysed with generalized evolution. The solitary wave ansatz is used to carry out this investigation.

SUN family proteins Sun4p, Uth1p and Sim1p are secreted from Saccharomyces cerevisiae and produced dependently on oxygen level.

Directory of Open Access Journals (Sweden)

Evgeny Kuznetsov

Full Text Available The SUN family is comprised of proteins that are conserved among various yeasts and fungi, but that are absent in mammals and plants. Although the function(s of these proteins are mostly unknown, they have been linked to various, often unrelated cellular processes such as those connected to mitochondrial and cell wall functions. Here we show that three of the four Saccharomyces cerevisiae SUN family proteins, Uth1p, Sim1p and Sun4p, are efficiently secreted out of the cells in different growth phases and their production is affected by the level of oxygen. The Uth1p, Sim1p, Sun4p and Nca3p are mostly synthesized during the growth phase of both yeast liquid cultures and colonies. Culture transition to slow-growing or stationary phases is linked with a decreased cellular concentration of Sim1p and Sun4p and with their efficient release from the cells. In contrast, Uth1p is released mainly from growing cells. The synthesis of Uth1p and Sim1p, but not of Sun4p, is repressed by anoxia. All four proteins confer cell sensitivity to zymolyase. In addition, Uth1p affects cell sensitivity to compounds influencing cell wall composition and integrity (such as Calcofluor white and Congo red differently when growing on fermentative versus respiratory carbon sources. In contrast, Uth1p is essential for cell resistance to boric acids irrespective of carbon source. In summary, our novel findings support the hypothesis that SUN family proteins are involved in the remodeling of the yeast cell wall during the various phases of yeast culture development and under various environmental conditions. The finding that Uth1p is involved in cell sensitivity to boric acid, i.e. to a compound that is commonly used as an important antifungal in mycoses, opens up new possibilities of investigating the mechanisms of boric acid's action.

Wave Functions for Time-Dependent Dirac Equation under GUP

Science.gov (United States)

Zhang, Meng-Yao; Long, Chao-Yun; Long, Zheng-Wen

2018-04-01

In this work, the time-dependent Dirac equation is investigated under generalized uncertainty principle (GUP) framework. It is possible to construct the exact solutions of Dirac equation when the time-dependent potentials satisfied the proper conditions. In (1+1) dimensions, the analytical wave functions of the Dirac equation under GUP have been obtained for the two kinds time-dependent potentials. Supported by the National Natural Science Foundation of China under Grant No. 11565009

Time-dependent switched discrete-time linear systems control and filtering

CERN Document Server

Zhang, Lixian; Shi, Peng; Lu, Qiugang

2016-01-01

This book focuses on the basic control and filtering synthesis problems for discrete-time switched linear systems under time-dependent switching signals. Chapter 1, as an introduction of the book, gives the backgrounds and motivations of switched systems, the definitions of the typical time-dependent switching signals, the differences and links to other types of systems with hybrid characteristics and a literature review mainly on the control and filtering for the underlying systems. By summarizing the multiple Lyapunov-like functions (MLFs) approach in which different requirements on comparisons of Lyapunov function values at switching instants, a series of methodologies are developed for the issues on stability and stabilization, and l2-gain performance or tube-based robustness for l∞ disturbance, respectively, in Chapters 2 and 3. Chapters 4 and 5 are devoted to the control and filtering problems for the time-dependent switched linear systems with either polytopic uncertainties or measurable time-varying...

Evaluating the Impact of Antibiotic Exposures as Time-Dependent Variables on the Acquisition of Carbapenem-Resistant Acinetobacter baumannii.

Science.gov (United States)

Munoz-Price, L Silvia; Rosa, Rossana; Castro, Jose G; Laowansiri, Panthipa; Latibeaudiere, Rachel; Namias, Nicholas; Tarima, Sergey

2016-10-01

To determine the time-dependent effect of antibiotics on the initial acquisition of carbapenem-resistant Acinetobacter baumannii. Retrospective cohort study. Forty-bed trauma ICU in Miami, FL. All consecutive patients admitted to the unit from November 1, 2010, to November 30, 2011. None. Patients underwent surveillance cultures at admission to the unit and weekly thereafter. The primary outcome was the acquisition of carbapenem-resistant A. baumannii on surveillance cultures. Daily antibiotic exposures during the time of observation were used to construct time-dependent variables, including cumulative exposures (in grams and daily observed doses [defined daily doses]). Among 360 patients, 45 (12.5%) became colonized with carbapenem-resistant A. baumannii. Adjusted Cox models showed that each additional point in the Acute Physiologic and Chronic Health Evaluation score increased the hazard by 4.8% (hazard ratio, 1.048; 95% CI, 1.010-1.087; p = 0.0124) and time-dependent exposure to carbapenems quadrupled the hazard (hazard ratio, 4.087; 95% CI, 1.873-8.920; p = 0.0004) of acquiring carbapenem-resistant A. baumannii. Additionally, adjusted Cox models determined that every additional carbapenem defined daily dose increased the hazard of acquiring carbapenem-resistant A. baumannii by 5.1% (hazard ratio, 1.051; 95% CI, 1.007-1.093; p = 0.0243). Carbapenem exposure quadrupled the hazards of acquiring A. baumannii even after controlling for severity of illness.

Time-dependent anisotropic external sources in transient 3-D transport code TORT-TD

International Nuclear Information System (INIS)

Seubert, A.; Pautz, A.; Becker, M.; Dagan, R.

2009-01-01

This paper describes the implementation of a time-dependent distributed external source in TORT-TD by explicitly considering the external source in the ''fixed-source'' term of the implicitly time-discretised 3-D discrete ordinates transport equation. Anisotropy of the external source is represented by a spherical harmonics series expansion similar to the angular fluxes. The YALINA-Thermal subcritical assembly serves as a test case. The configuration with 280 fuel rods has been analysed with TORT-TD using cross sections in 18 energy groups and P1 scattering order generated by the KAPROS code system. Good agreement is achieved concerning the multiplication factor. The response of the system to an artificial time-dependent source consisting of two square-wave pulses demonstrates the time-dependent external source capability of TORT-TD. The result is physically plausible as judged from validation calculations. (orig.)

Down-regulation of Wild-type p53-induced Phosphatase 1 (Wip1) Plays a Critical Role in Regulating Several p53-dependent Functions in Premature Senescent Tumor Cells*

Science.gov (United States)

Crescenzi, Elvira; Raia, Zelinda; Pacifico, Francesco; Mellone, Stefano; Moscato, Fortunato; Palumbo, Giuseppe; Leonardi, Antonio

2013-01-01

Premature or drug-induced senescence is a major cellular response to chemotherapy in solid tumors. The senescent phenotype develops slowly and is associated with chronic DNA damage response. We found that expression of wild-type p53-induced phosphatase 1 (Wip1) is markedly down-regulated during persistent DNA damage and after drug release during the acquisition of the senescent phenotype in carcinoma cells. We demonstrate that down-regulation of Wip1 is required for maintenance of permanent G2 arrest. In fact, we show that forced expression of Wip1 in premature senescent tumor cells induces inappropriate re-initiation of mitosis, uncontrolled polyploid progression, and cell death by mitotic failure. Most of the effects of Wip1 may be attributed to its ability to dephosphorylate p53 at Ser15 and to inhibit DNA damage response. However, we also uncover a regulatory pathway whereby suppression of p53 Ser15 phosphorylation is associated with enhanced phosphorylation at Ser46, increased p53 protein levels, and induction of Noxa expression. On the whole, our data indicate that down-regulation of Wip1 expression during premature senescence plays a pivotal role in regulating several p53-dependent aspects of the senescent phenotype. PMID:23612976

Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase.

Directory of Open Access Journals (Sweden)

Evgeny V Berdyshev

Full Text Available BACKGROUND: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P induces migration of human pulmonary artery endothelial cells (HPAECs through the activation of S1P(1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs and S1P lyase (S1PL, that regulate intracellular S1P accumulation, in HPAEC motility. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino-4-(p-Chlorophenyl Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1P(int, and attenuated S1P(ext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1P(int and potentiated motility of HPAECs to S1P(ext or serum. S1P(ext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting "inside-out" signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs. Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1P(ext or 4-deoxypyridoxine-dependent endothelial cell motility. CONCLUSIONS/SIGNIFICANCE: These results suggest S1P(ext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL.

Sphingosine 1-phosphate mediates hyperalgesia via a neutrophil-dependent mechanism.

Directory of Open Access Journals (Sweden)

Amanda Finley

Full Text Available Novel classes of pain-relieving molecules are needed to fill the void between non-steroidal anti-inflammatory agents and narcotics. We have recently shown that intraplantar administration of sphingosine 1-phosphate (S1P in rats causes peripheral sensitization and hyperalgesia through the S1P(1 receptor subtype (S1PR(1: the mechanism(s involved are largely unknown and were thus explored in the present study. Intraplantar injection of carrageenan in rats led to a time-dependent development of thermal hyperalgesia that was associated with pronounced edema and infiltration of neutrophils in paw tissues. Inhibition of 1 S1P formation with SK-I, a sphingosine kinase inhibitor, 2 S1P bioavailability with the S1P blocking antibody Sphingomab, LT1002 (but not its negative control, LT1017 or 3 S1P actions through S1PR(1 with the selective S1PR(1 antagonist, W146 (but not its inactive enantiomer, W140 blocked thermal hyperalgesia and infiltration of neutrophils. Taken together, these findings identify S1P as an important contributor to inflammatory pain acting through S1PR(1 to elicit hyperalgesia in a neutrophil-dependant manner. In addition and in further support, we demonstrate that the development of thermal hyperalgesia following intraplantar injection of S1P or SEW2871 (an S1PR(1 agonist was also associated with neutrophilic infiltration in paw tissues as these events were attenuated by fucoidan, an inhibitor of neutrophilic infiltration. Importantly, FTY720, an FDA-approved S1P receptor modulator known to block S1P-S1PR(1 signaling, attenuated carrageenan-induced thermal hyperalgesia and associated neutrophil infiltration. Targeting the S1P/S1PR(1 axis opens a therapeutic strategy for the development of novel non-narcotic anti-hyperalgesic agents.

Period1 gates the circadian modulation of memory-relevant signaling in mouse hippocampus by regulating the nuclear shuttling of the CREB kinase pP90RSK.

Science.gov (United States)

Rawashdeh, Oliver; Jilg, Antje; Maronde, Erik; Fahrenkrug, Jan; Stehle, Jörg H

2016-09-01

Memory performance varies over a 24-h day/night cycle. While the detailed underlying mechanisms are yet unknown, recent evidence suggests that in the mouse hippocampus, rhythmic phosphorylation of mitogen-activated protein kinase (MAPK) and cyclic adenosine monophosphate response element-binding protein (CREB) are central to the circadian (~ 24 h) regulation of learning and memory. We recently identified the clock protein PERIOD1 (PER1) as a vehicle that translates information encoding time of day to hippocampal plasticity. We here elaborate how PER1 may gate the sensitivity of memory-relevant hippocampal signaling pathways. We found that in wild-type mice (WT), spatial learning triggers CREB phosphorylation only during the daytime, and that this effect depends on the presence of PER1. The time-of-day-dependent induction of CREB phosphorylation can be reproduced pharmacologically in acute hippocampal slices prepared from WT mice, but is absent in preparations made from Per1-knockout (Per1(-/-) ) mice. We showed that the PER1-dependent CREB phosphorylation is regulated downstream of MAPK. Stimulation of WT hippocampal neurons triggered the co-translocation of PER1 and the CREB kinase pP90RSK (pMAPK-activated ribosomal S6 kinase) into the nucleus. In hippocampal neurons from Per1(-/-) mice, however, pP90RSK remained perinuclear. A co-immunoprecipitation assay confirmed a high-affinity interaction between PER1 and pP90RSK. Knocking down endogenous PER1 in hippocampal cells inhibited adenylyl cyclase-dependent CREB activation. Taken together, the PER1-dependent modulation of cytoplasmic-to-nuclear signaling in the murine hippocampus provides a molecular explanation for how the circadian system potentially shapes a temporal framework for daytime-dependent memory performance, and adds a novel facet to the versatility of the clock gene protein PER1. We provide evidence that the circadian clock gene Period1 (Per1) regulates CREB phosphorylation in the mouse hippocampus

SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity.

Science.gov (United States)

Lee, Soonduck; Kim, Jinsun; Jung, Samil; Li, Chengping; Yang, Young; Kim, Keun Il; Lim, Jong-Seok; Kim, Yonghwan; Cheon, Choong-Il; Lee, Myeong-Sok

2015-03-01

Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.

Excited-state absorption in tetrapyridyl porphyrins: comparing real-time and quadratic-response time-dependent density functional theory

Energy Technology Data Exchange (ETDEWEB)

Bowman, David N. [Department of Chemistry; Supercomputing Institute and Chemical Theory Center; University of Minnesota; Minneapolis; USA; Asher, Jason C. [Department of Chemistry; Supercomputing Institute and Chemical Theory Center; University of Minnesota; Minneapolis; USA; Fischer, Sean A. [William R. Wiley Environmental Molecular Sciences Laboratory; Pacific Northwest National Laboratory; P.O. Box 999; Richland; USA; Cramer, Christopher J. [Department of Chemistry; Supercomputing Institute and Chemical Theory Center; University of Minnesota; Minneapolis; USA; Govind, Niranjan [William R. Wiley Environmental Molecular Sciences Laboratory; Pacific Northwest National Laboratory; P.O. Box 999; Richland; USA

2017-01-01

<p>Threemeso-substituted tetrapyridyl porphyrins (free base, Ni(ii), and Cu(ii)) were investigated for their optical limiting (OL) capabilities using real-time (RT-), linear-response (LR-), and quadratic-response (QR-) time-dependent density functional theory (TDDFT) methods.p>

53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis.

Science.gov (United States)

Fong, Chii Shyang; Mazo, Gregory; Das, Tuhin; Goodman, Joshua; Kim, Minhee; O'Rourke, Brian P; Izquierdo, Denisse; Tsou, Meng-Fu Bryan

2016-07-02

Mitosis occurs efficiently, but when it is disturbed or delayed, p53-dependent cell death or senescence is often triggered after mitotic exit. To characterize this process, we conducted CRISPR-mediated loss-of-function screens using a cell-based assay in which mitosis is consistently disturbed by centrosome loss. We identified 53BP1 and USP28 as essential components acting upstream of p53, evoking p21-dependent cell cycle arrest in response not only to centrosome loss, but also to other distinct defects causing prolonged mitosis. Intriguingly, 53BP1 mediates p53 activation independently of its DNA repair activity, but requiring its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo. Moreover, 53BP1 can transduce prolonged mitosis to cell cycle arrest independently of the spindle assembly checkpoint (SAC), suggesting that while SAC protects mitotic accuracy by slowing down mitosis, 53BP1 and USP28 function in parallel to select against disturbed or delayed mitosis, promoting mitotic efficiency.

Time-dependent Autler-Townes spectroscopy

International Nuclear Information System (INIS)

Qamar, Sajid; Zhu, S.-Y.; Zubairy, M Suhail

2003-01-01

Autler-Townes spontaneous emission spectroscopy is revisited for a time-dependent case. We report the results of spontaneous emission spectra for nonstationary scattered light signals using the definition of the time-dependent physical spectrum. This is a rare example of problems where time-dependent spectra can be calculated exactly

Time-dependent Autler-Townes spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Qamar, Sajid [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States); Zhu, S.-Y. [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States); Zubairy, M Suhail [Institute for Quantum Studies, Department of Physics, Texas A and M University, College Station, TX 77843-4242 (United States)

2003-04-01

Autler-Townes spontaneous emission spectroscopy is revisited for a time-dependent case. We report the results of spontaneous emission spectra for nonstationary scattered light signals using the definition of the time-dependent physical spectrum. This is a rare example of problems where time-dependent spectra can be calculated exactly.

Time-dependent anisotropic distributed source capability in transient 3-d transport code tort-TD

International Nuclear Information System (INIS)

Seubert, A.; Pautz, A.; Becker, M.; Dagan, R.

2009-01-01

The transient 3-D discrete ordinates transport code TORT-TD has been extended to account for time-dependent anisotropic distributed external sources. The extension aims at the simulation of the pulsed neutron source in the YALINA-Thermal subcritical assembly. Since feedback effects are not relevant in this zero-power configuration, this offers a unique opportunity to validate the time-dependent neutron kinetics of TORT-TD with experimental data. The extensions made in TORT-TD to incorporate a time-dependent anisotropic external source are described. The steady state of the YALINA-Thermal assembly and its response to an artificial square-wave source pulse sequence have been analysed with TORT-TD using pin-wise homogenised cross sections in 18 prompt energy groups with P 1 scattering order and 8 delayed neutron groups. The results demonstrate the applicability of TORT-TD to subcritical problems with a time-dependent external source. (authors)

The temperature dependence of 1/f noise in InP

NARCIS (Netherlands)

Chen, X.Y.; Hooge, F.N.; Leijs, M.R.

1997-01-01

Noise spectra were measured on CBE grown InP samples in the frequency range from 1 Hz to 104 kHz at temperatures from 77 to 500 K. The experimental results show that llfnoise stems from the lattice scattering. The 1/f noise in InP is well characterised by a parameter CtL~,, in this temperature

Effect of Microstructure on Time Dependent Fatigue Crack Growth Behavior In a P/M Turbine Disk Alloy

Science.gov (United States)

Telesman, Ignacy J.; Gabb, T. P.; Bonacuse, P.; Gayda, J.

2008-01-01

A study was conducted to determine the processes which govern hold time crack growth behavior in the LSHR disk P/M superalloy. Nineteen different heat treatments of this alloy were evaluated by systematically controlling the cooling rate from the supersolvus solutioning step and applying various single and double step aging treatments. The resulting hold time crack growth rates varied by more than two orders of magnitude. It was shown that the associated stress relaxation behavior for these heat treatments was closely correlated with the crack growth behavior. As stress relaxation increased, the hold time crack growth resistance was also increased. The size of the tertiary gamma' in the general microstructure was found to be the key microstructural variable controlling both the hold time crack growth behavior and stress relaxation. No relationship between the presence of grain boundary M23C6 carbides and hold time crack growth was identified which further brings into question the importance of the grain boundary phases in determining hold time crack growth behavior. The linear elastic fracture mechanics parameter, Kmax, is unable to account for visco-plastic redistribution of the crack tip stress field during hold times and thus is inadequate for correlating time dependent crack growth data. A novel methodology was developed which captures the intrinsic crack driving force and was able to collapse hold time crack growth data onto a single curve.

Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae*

Science.gov (United States)

Effelsberg, Daniel; Cruz-Zaragoza, Luis Daniel; Tonillo, Jason; Schliebs, Wolfgang; Erdmann, Ralf

2015-01-01

Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD+ salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. PMID:26276932

Time-dependent Hartree-Fock calculation of the escape width of the giant monopole resonance in 16O

International Nuclear Information System (INIS)

Pacheco, J.M.; Maglione, E.; Broglia, R.A.

1988-01-01

The damping of the giant monopole resonance in 16 O is calculated within the framework of the time-dependent Hartree-Fock approximation. The strength function contains two peaks, centered at around 25 and 33 MeV, with escape widths of ∼11 and ∼2 MeV, associated with the 1p(0p) -1 and 1s(0s) -1 configurations, respectively

pH-dependent solubility of indomethacin-saccharin and carbamazepine-saccharin cocrystals in aqueous media.

Science.gov (United States)

Alhalaweh, Amjad; Roy, Lilly; Rodríguez-Hornedo, Naír; Velaga, Sitaram P

2012-09-04

Cocrystals constitute an important class of pharmaceutical solids for their remarkable ability to modulate solubility and pH dependence of water insoluble drugs. Here we show how cocrystals of indomethacin-saccharin (IND-SAC) and carbamazepine-saccharin (CBZ-SAC) enhance solubility and impart a pH-sensitivity different from that of the drugs. IND-SAC exhibited solubilities 13 to 65 times higher than IND at pH values of 1 to 3, whereas CBZ-SAC exhibited a 2 to 10 times higher solubility than CBZ dihydrate. Cocrystal solubility dependence on pH predicted from mathematical models using cocrystal K(sp), and cocrystal component K(a) values, was in excellent agreement with experimental measurements. The cocrystal solubility increase relative to drug was predicted to reach a limiting value for a cocrystal with two acidic components. This limiting value is determined by the ionization constants of cocrystal components. Eutectic constants are shown to be meaningful indicators of cocrystal solubility and its pH dependence. The two contributions to solubility, cocrystal lattice and solvation, were evaluated by thermal and solubility determinations. The results show that solvation is the main barrier for the aqueous solubility of these drugs and their cocrystals, which are orders of magnitude higher than their lattice barriers. Cocrystal increase in solubility is thus a result of decreasing the solvation barrier compared to that of the drug. This work demonstrates the favorable properties of cocrystals and strategies that facilitate their meaningful characterization.

Erratic time dependence of orbits of topologically mixing maps

International Nuclear Information System (INIS)

Xiong Jincheng.

1988-11-01

In the present paper we show that for a topologically mixing map there are considerably many points in the domain whose orbits display highly erratic time dependence, i.e., if f: X→X is a topologically mixing map where X is a compact metric space then for any increasing sequence {q i } of positive integers and any countable subset S dense in X there exists everywhere an uncountable subset C of X satisfying the conditions of (1) for any s is an element of S. There exists a subsequence {p i } of the sequence {q i } such that lim i→∞ f P 1 (y)=s for every y is an element of C, and (2) for any n>0, any n distinct points y 1 ,y 2 ,...,y n of C and any n points x 1 ,x 2 ,...,x n of X there exists a subsequence {t i } of the sequence {q i } such that lim i→∞ f t i (y j )=x j for every j=1,2,...n. (author). 4 refs

Real time process algebra with time-dependent conditions

NARCIS (Netherlands)

Baeten, J.C.M.; Middelburg, C.A.

We extend the main real time version of ACP presented in [6] with conditionals in which the condition depends on time. This extension facilitates flexible dependence of proccess behaviour on initialization time. We show that the conditions concerned generalize the conditions introduced earlier

Holographic complexity for time-dependent backgrounds

Energy Technology Data Exchange (ETDEWEB)

Momeni, Davood, E-mail: davoodmomeni78@gmail.com [Eurasian International Center for Theoretical Physics and Department of General Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Faizal, Mir, E-mail: mirfaizalmir@googlemail.com [Irving K. Barber School of Arts and Sciences, University of British Columbia, Okanagan, 3333 University Way, Kelowna, British Columbia V1V 1V7 (Canada); Department of Physics and Astronomy, University of Lethbridge, Lethbridge, Alberta, T1K 3M4 (Canada); Bahamonde, Sebastian, E-mail: sebastian.beltran.14@ucl.ac.uk [Department of Mathematics, University College London, Gower Street, London, WC1E 6BT (United Kingdom); Myrzakulov, Ratbay [Eurasian International Center for Theoretical Physics and Department of General Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan)

2016-11-10

In this paper, we will analyze the holographic complexity for time-dependent asymptotically AdS geometries. We will first use a covariant zero mean curvature slicing of the time-dependent bulk geometries, and then use this co-dimension one spacelike slice of the bulk spacetime to define a co-dimension two minimal surface. The time-dependent holographic complexity will be defined using the volume enclosed by this minimal surface. This time-dependent holographic complexity will reduce to the usual holographic complexity for static geometries. We will analyze the time-dependence as a perturbation of the asymptotically AdS geometries. Thus, we will obtain time-dependent asymptotically AdS geometries, and we will calculate the holographic complexity for such time-dependent geometries.

Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87 Cell Line

Directory of Open Access Journals (Sweden)

Allison A. Atnip

2017-02-01

Full Text Available Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87 has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h, concentration (50–1500 µM, and pH (3.0, 5.0, 7.4 on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0.

The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the mouse

Directory of Open Access Journals (Sweden)

Bayrak Aykut

2003-05-01

Full Text Available Abstract Background Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs. CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs. Method In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. Ovaries were collected from 60-day-old cycling B6D2F1/J mice (n = 16. Results Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. However, p16 staining was stronger (++ in the oocytes of all primordial, and 57.4 ± 3.1% of primary follicles compared to the remaining primary and more advanced follicles (+. Interestingly, primary follicles with weaker (+ oocyte staining for p16 had significantly larger mean follicle diameter compared to the primary and primordial follicles with stronger (++ oocyte staining (55.6 ± 2.1 vs. 32.0 ± 1.0 and 26.5 ± 0.7 μm, respectively, p Conclusions These preliminary findings suggest that the initiation of oocyte growth, which seems to lead follicle growth, is associated with diminished p16 expression in the mouse ovary. Further studies are needed to investigate the factors that regulate the expression of p16 in the oocyte, which might also govern the initiation of primordial follicle growth.

Constructing bioactive peptides with pH-dependent activities.

Science.gov (United States)

Tu, Zhigang; Volk, Melanie; Shah, Khushali; Clerkin, Kevin; Liang, Jun F

2009-08-01

Many bioactive peptides are featured by their arginine and lysine rich contents. In this study, lysine and arginine residues in lytic peptides were selectively replaced by histidines. Although resulting histidine-containing lytic peptides had decreased activity, they did show pH-dependent cytotoxicity. The activity of the constructed histidine-containing lytic peptides increased 2-8 times as the solution pH changed from 7.4 to 5.5. More importantly, these histidine-containing peptides maintain the same cell killing mechanism as their parent peptides by causing cell lysis. Both the activity and pH-sensitivity of histidine-containing peptides are tunable by adjusting histidine substitution numbers and positions. This study has presented a general strategy to create bioactive peptides with desired pH-sensitivity to meet the needs of various applications such as cancer treatments.

Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

Science.gov (United States)

Berdyshev, Evgeny V.; Gorshkova, Irina; Usatyuk, Peter; Kalari, Satish; Zhao, Yutong; Pyne, Nigel J.; Pyne, Susan; Sabbadini, Roger A.; Garcia, Joe G. N.; Natarajan, Viswanathan

2011-01-01

Background Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility. Methodology/Principal Findings Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino)-4-(p-Chlorophenyl) Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1Pint, and attenuated S1Pext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1Pint and potentiated motility of HPAECs to S1Pext or serum. S1Pext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting “inside-out” signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs). Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1Pext or 4-deoxypyridoxine-dependent endothelial cell motility. Conclusions/Significance These results suggest S1Pext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL. PMID:21304987

pH-dependent biotransformation of ionizable organic micropollutants in activated sludge.

Science.gov (United States)

Gulde, Rebekka; Helbling, Damian E; Scheidegger, Andreas; Fenner, Kathrin

2014-12-02

Removal of micropollutants (MPs) during activated sludge treatment can mainly be attributed to biotransformation and sorption to sludge flocs, whereby the latter process is known to be of minor importance for polar organic micropollutants. In this work, we investigated the influence of pH on the biotransformation of MPs with cationic-neutral speciation in an activated sludge microbial community. We performed batch biotransformation, sorption control, and abiotic control experiments for 15 MPs with cationic-neutral speciation, one control MP with neutral-anionic speciation, and two neutral MPs at pHs 6, 7, and 8. Biotransformation rate constants corrected for sorption and abiotic processes were estimated from measured concentration time series with Bayesian inference. We found that biotransformation is pH-dependent and correlates qualitatively with the neutral fraction of the ionizable MPs. However, a simple speciation model based on the assumption that only the neutral species is efficiently taken up and biotransformed by the cells tends to overpredict the effect of speciation. Therefore, additional mechanisms such as uptake of the ionic species and other more complex attenutation mechanisms are discussed. Finally, we observed that the sorption coefficients derived from our control experiments were small and showed no notable pH-dependence. From this we conclude that pH-dependent removal of polar, ionizable organic MPs in activated sludge systems is less likely an effect of pH-dependent sorption but rather of pH-dependent biotransformation. The latter has the potential to cause marked differences in the removal of polar, ionizable MPs at different operational pHs during activated sludge treatment.

TEMPS, 1-Group Time-Dependent Pulsed Source Neutron Transport

International Nuclear Information System (INIS)

Ganapol, B.D.

1988-01-01

1 - Description of program or function: TEMPS numerically determines the scalar flux as given by the one-group neutron transport equation with a pulsed source in an infinite medium. Standard plane, point, and line sources are considered as well as a volume source in the negative half-space in plane geometry. The angular distribution of emitted neutrons can either be isotropic or mono-directional (beam) in plane geometry and isotropic in spherical and cylindrical geometry. A general anisotropic scattering Kernel represented in terms of Legendre polynomials can be accommodated with a time- dependent number of secondaries given by c(t)=c 0 (t/t 0 ) β , where β is greater than -1 and less than infinity. TEMPS is designed to provide the flux to a high degree of accuracy (4-5 digits) for use as a benchmark to which results from other numerical solutions or approximations can be compared. 2 - Method of solution: A semi-analytic Method of solution is followed. The main feature of this approach is that no discretization of the transport or scattering operators is employed. The numerical solution involves the evaluation of an analytical representation of the solution by standard numerical techniques. The transport equation is first reformulated in terms of multiple collisions with the flux represented by an infinite series of collisional components. Each component is then represented by an orthogonal Legendre series expansion in the variable x/t where the distance x and time t are measured in terms of mean free path and mean free time, respectively. The moments in the Legendre reconstruction are found from an algebraic recursion relation obtained from Legendre expansion in the direction variable mu. The multiple collision series is evaluated first to a prescribed relative error determined by the number of digits desired in the scalar flux. If the Legendre series fails to converge in the plane or point source case, an accelerative transformation, based on removing the

On the underlying micromechanisms in time-dependent anelasticity in Al-(1 wt%)Cu thin films

NARCIS (Netherlands)

Bergers, L.I.J.C.; Hoefnagels, J.P.M.; Geers, M.G.D.

2017-01-01

This paper reveals potential micro mechanisms underlying time-dependent anelasticity observed in Al-(1 wt%)Cu thin films. The analyzed deformation mechanisms involve dislocation motion and interaction with solute diffusion, grain boundaries and precipitates. In order to investigate the role of these

PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

Science.gov (United States)

Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

2013-11-01

We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells. © 2013.

Space-time dependent couplings In N = 1 SUSY gauge theories: Anomalies and central functions

International Nuclear Information System (INIS)

Babington, J.; Erdmenger, J.

2005-01-01

We consider N = 1 supersymmetric gauge theories in which the couplings are allowed to be space-time dependent functions. Both the gauge and the superpotential couplings become chiral superfields. As has recently been shown, a new topological anomaly appears in models with space-time dependent gauge coupling. Here we show how this anomaly may be used to derive the NSVZ β-function in a particular, well-determined renormalisation scheme, both without and with chiral matter. Moreover we extend the topological anomaly analysis to theories coupled to a classical curved superspace background, and use it to derive an all-order expression for the central charge c, the coefficient of the Weyl tensor squared contribution to the conformal anomaly. We also comment on the implications of our results for the central charge a expected to be of relevance for a four-dimensional C-theorem. (author)

Role of Pex21p for Piggyback Import of Gpd1p and Pnc1p into Peroxisomes of Saccharomyces cerevisiae.

Science.gov (United States)

Effelsberg, Daniel; Cruz-Zaragoza, Luis Daniel; Tonillo, Jason; Schliebs, Wolfgang; Erdmann, Ralf

2015-10-16

Proteins designated for peroxisomal protein import harbor one of two common peroxisomal targeting signals (PTS). In the yeast Saccharomyces cerevisiae, the oleate-induced PTS2-dependent import of the thiolase Fox3p into peroxisomes is conducted by the soluble import receptor Pex7p in cooperation with the auxiliary Pex18p, one of two supposedly redundant PTS2 co-receptors. Here, we report on a novel function for the co-receptor Pex21p, which cannot be fulfilled by Pex18p. The data establish Pex21p as a general co-receptor in PTS2-dependent protein import, whereas Pex18p is especially important for oleate-induced import of PTS2 proteins. The glycerol-producing PTS2 protein glycerol-3-phosphate dehydrogenase Gpd1p shows a tripartite localization in peroxisomes, in the cytosol, and in the nucleus under osmotic stress conditions. We show the following: (i) Pex21p is required for peroxisomal import of Gpd1p as well as a key enzyme of the NAD(+) salvage pathway, Pnc1p; (ii) Pnc1p, a nicotinamidase without functional PTS2, is co-imported into peroxisomes by piggyback transport via Gpd1p. Moreover, the specific transport of these two enzymes into peroxisomes suggests a novel regulatory role for peroxisomes under various stress conditions. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Time-dependent friction and solvation time correlation function

International Nuclear Information System (INIS)

Samanta, Alok; Ali, Sk Musharaf; Ghosh, Swapan K

2005-01-01

We have derived a new relation between the time-dependent friction and solvation time correlation function (STCF) for non-polar fluids. The friction values calculated using this relation and simulation results on STCF for a Lennard-Jones fluid are shown to have excellent agreement with the same obtained through mode-coupling theory. Also derived is a relation between the time-dependent dielectric friction and STCF for polar fluids. Routes are thus provided to obtain the time-dependent friction (non-polar as well as dielectric) from an experimentally measured quantity like STCF, even if the interparticle interaction potential is not known

Univariate Lp and ɭ p Averaging, 0 < p < 1, in Polynomial Time by Utilization of Statistical Structure

Directory of Open Access Journals (Sweden)

John E. Lavery

2012-10-01

Full Text Available We present evidence that one can calculate generically combinatorially expensive Lp and lp averages, 0 < p < 1, in polynomial time by restricting the data to come from a wide class of statistical distributions. Our approach differs from the approaches in the previous literature, which are based on a priori sparsity requirements or on accepting a local minimum as a replacement for a global minimum. The functionals by which Lp averages are calculated are not convex but are radially monotonic and the functionals by which lp averages are calculated are nearly so, which are the keys to solvability in polynomial time. Analytical results for symmetric, radially monotonic univariate distributions are presented. An algorithm for univariate lp averaging is presented. Computational results for a Gaussian distribution, a class of symmetric heavy-tailed distributions and a class of asymmetric heavy-tailed distributions are presented. Many phenomena in human-based areas are increasingly known to be represented by data that have large numbers of outliers and belong to very heavy-tailed distributions. When tails of distributions are so heavy that even medians (L1 and l1 averages do not exist, one needs to consider using lp minimization principles with 0 < p < 1.

pH-dependent toxicity of sulphur mustard in vitro

International Nuclear Information System (INIS)

Sawyer, Thomas W.; Vair, Cory; Nelson, Peggy; Shei Yimin; Bjarnason, Stephen; Tenn, Catherine; McWilliams, Michael; Villanueva, Mercy; Burczyk, Andrew

2007-01-01

The dependence of sulphur mustard (HD) toxicity on intracellular (pH i ) and extracellular pH was examined in CHO-K1 cells. HD produced an immediate and significant concentration-dependent decline in cytosolic pH, and also inhibited the mechanisms responsible for restoring pH i to physiological values. The concentration-response of HD-induced cytosolic acidification, closely paralleled the acidification of the extracellular buffer through HD hydrolysis. A viability study was carried out in order to assess the importance of HD-induced cytosolic acidification. Cultures were exposed to HD for 1 h in media that were adjusted through a pH range (pH 5.0-10), and the 24 h LC 50 values were assessed using the viability indicator dye alamarBlue TM . The toxicity of HD was found to be dependent on extracellular pH, with a greater than eight-fold increase in LD 50 obtained in cultures treated with HD at pH 9.5, compared to those treated at pH 5.0. Assays of apoptotic cell death, including morphology, soluble DNA, caspase-3 activity and TUNEL also showed that as pH was increased, much greater HD concentrations were required to cause cell death. The modest decline in HD half-life measured in buffers of increasing pH, did not account for the protective effects of basic pH. The early event(s) that HD initiates to eventually culminate in cell death are not known. However, based on the data obtained in this study, we propose that HD causes an extracellular acidification through chemical hydrolysis and that this, in both a concentration and temporally related fashion, results in cytosolic acidification. Furthermore, HD also acts to poison the antiporter systems responsible for maintaining physiological pH i , so that the cells are unable to recover from this insult. It is this irreversible decline in pH i that initiates the cascade of events that results in HD-induced cell death

G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of Plk1.

Science.gov (United States)

Zhang, Jie; Wang, Yafang; Shen, Yanyan; He, Pengxing; Ding, Jian; Chen, Yi

2018-01-01

Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a. Detailed molecular mechanisms underlying the effect of G9a on Plk1 expression were determined by performing point mutation analysis, chromatin immunoprecipitation analysis, and luciferase reporter assay. Correlation between G9a and Plk1 expression was determined by analyzing clinical samples of patients with CRC by performing immunohistochemistry. Results: Our study is the first to report a significant positive correlation between G9a and Plk1 levels in 89 clinical samples of patients with CRC. Moreover, G9a depletion decreased Plk1 expression and suppressed CRC cell growth both in vitro and in vivo , thus confirming the significant correlation between G9a and Plk1 levels. Further, we observed that G9a-induced Plk1 regulation depended on p53 inhibition. G9a dimethylated p53 at lysine 373, which in turn increased Plk1 expression and promoted CRC cell growth. Conclusions: These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.

Time Dependent Quantum Mechanics

OpenAIRE

Morrison, Peter G.

2012-01-01

We present a systematic method for dealing with time dependent quantum dynamics, based on the quantum brachistochrone and matrix mechanics. We derive the explicit time dependence of the Hamiltonian operator for a number of constrained finite systems from this formalism. Once this has been achieved we go on to calculate the wavevector as a function of time, in order to demonstrate the use of matrix methods with respect to several concrete examples. Interesting results are derived for elliptic ...

Noisy time-dependent spectra

International Nuclear Information System (INIS)

Shore, B.W.; Eberly, J.H.

1983-01-01

The definition of a time-dependent spectrum registered by an idealized spectrometer responding to a time-varying electromagnetic field as proposed by Eberly and Wodkiewicz and subsequently applied to the spectrum of laser-induced fluorescence by Eberly, Kunasz, and Wodkiewicz is here extended to allow a stochastically fluctuating (interruption model) environment: we provide an algorithm for numerical determination of the time-dependent fluorescence spectrum of an atom subject to excitation by an intense noisy laser and interruptive relaxation

pH-dependent inhibition of K2P3.1 prolongs atrial refractoriness in whole hearts

DEFF Research Database (Denmark)

Skarsfeldt, Mark A; Jepps, Thomas A; Bomholtz, Sofia H

2016-01-01

In isolated human atrial cardiomyocytes, inhibition of K2P3.1 K(+) channels results in action potential (action potential duration (APD)) prolongation. It has therefore been postulated that K2P3.1 (KCNK3), together with K2P9.1 (KCNK9), could represent novel drug targets for the treatment of atrial...... fibrillation (AF). However, it is unknown whether these findings in isolated cells translate to the whole heart. The purposes of this study were to investigate the expression levels of KCNK3 and KCNK9 in human hearts and two relevant rodent models and determine the antiarrhythmic potential of K2P3.1 inhibition...... displayed a more uniform expression of KCNK3 between atria and ventricle. In voltage-clamp experiments, ML365 and A293 were found to be potent and selective inhibitors of K2P3.1, but at pH 7.4, they failed to prolong atrial APD and refractory period (effective refractory period (ERP)) in isolated perfused...

Radiation-induced p53 protein response in the A549 cell line is culture growth-phase dependent

Energy Technology Data Exchange (ETDEWEB)

Johnson, N.F.; Gurule, D.M.; Carpenter, T.R.

1995-12-01

One role of the p53 tumor suppressor protein has been recently revealed. Kastan, M.B. reported that p53 protein accumulates in cells exposed to ionizing radiation. The accumulation of p53 protein is in response to DNA damage, most importantly double-strand breaks, that results from exposure to ionizing radiation. The rise in cellular p53 levels is necessary for an arrest in the G{sub 1} phase of the cell cycle to provide additional time for DNA repair. The p53 response has also been demonstrated to enhance PCNA-dependent repair. p53 is thus an important regulator of the cellular response to DNA-damaging radiation. From this data, it can be concluded that the magnitude of the p53 response is not dependent on the phase of culture growth.

Temperature dependence of relaxation times in proton components of fatty acids

International Nuclear Information System (INIS)

Kuroda, Kagayaki; Iwabuchi, Taku; Saito, Kensuke; Obara, Makoto; Honda, Masatoshi; Imai, Yutaka

2011-01-01

We examined the temperature dependence of relaxation times in proton components of fatty acids in various samples in vitro at 11 tesla as a standard calibration data for quantitative temperature imaging of fat. The spin-lattice relaxation time, T 1 , of both the methylene (CH 2 ) chain and terminal methyl (CH 3 ) was linearly related to temperature (r>0.98, P 2 signal for calibration and observed the signal with 18% of CH 3 to estimate temperature. These findings suggested that separating the fatty acid components would significantly improve accuracy in quantitative thermometry for fat. Use of the T 1 of CH 2 seems promising in terms of reliability and reproducibility in measuring temperature of fat. (author)

Scheduling with time-dependent execution times

NARCIS (Netherlands)

Woeginger, G.J.

1995-01-01

We consider systems of tasks where the task execution times are time-dependent and where all tasks have some common deadline. We describe how to compute in polynomial time a schedule that minimizes the number of late tasks. This answers a question raised in a recent paper by Ho, Leung and Wei.

CEXE INCEXE, 1 Group 3-D Time-Dependent Xe Oscillations in X-Y-Z Geometry with Feedback

International Nuclear Information System (INIS)

Kern, R.; Pacino, S.

1973-01-01

1 - Description of problem or function: CEXE solves the three- dimensional xyz time-dependent xenon spatial oscillation problem using a modified one energy group theory and a nodal representation. 2 - Method of solution: CEXE solves for the spatial neutron source distribution with coupled Doppler and moderator temperature feedbacks. The time dependence of the iodine and xenon concentrations are based on the assumption of constant power during each time-step interval. 3 - Restrictions on the complexity of the problem: Maximum reactor core size representation is restricted to a nodal configuration of 19 x 19 x 10 in the x, y, z directions, respectively

Transcriptional activation of cyclin-dependent kinase inhibitor, p21waf1 gene by treatment with a differentiation inducing agent, vesnarinone in a human salivary gland cancer cell line.

Science.gov (United States)

Omotehara, F; Nakashiro, K; Uchida, D; Hino, S; Fujimori, T; Kawamata, H

2003-03-01

Recently, a new concept for cancer therapy termed "tumor dormancy therapy" has been proposed. The concept of this therapy is to prolong the survival time of cancer patients while maintaining their quality of life. We have been developing a differentiation-inducing therapy, which is included in the tumor dormancy therapy, for salivary gland cancer. In this study, we examined the effect of a differentiation-inducing drug, Vesnarinone on the growth of several cancer cells, and examined the molecular mechanism by which Vesnarinone induces the cyclin dependent kinase inhibitor, p21waf1 in the cancer cells. Vesnarinone significantly suppressed the growth of TYS (salivary gland cancer cells), PC3 (prostate cancer cells), and A431 (squamous cell cancer cells). Furthermore, Vesnarinone dose-dependently enhanced the expression of p21waf1 mRNA in TYS cells. Using the luciferase reporter assay it was found that the enhancement of p21waf1 mRNA expression by Vesnarinone was through direct transcriptional activation of the p21waf1 promoter. Thus, analyzing the molecular mechanisms of differentiation inducing drugs may lead to the development of a new therapeutic strategy for several human malignancies, including salivary gland cancer.

Coherent states of general time-dependent harmonic oscillator

Indian Academy of Sciences (India)

Abstract. By introducing an invariant operator, we obtain exact wave functions for a general time-dependent quadratic harmonic oscillator. The coherent states, both in x- and p-spaces, are calculated. We confirm that the uncertainty product in coherent state is always larger than Η/2 and is equal to the minimum of the ...

Parallel processing for a 1-D time-dependent solution to impurity rate equations for fusion plasma simulations

International Nuclear Information System (INIS)

Veerasingam, R.

1990-01-01

In fusion plasmas impurities such as carbon, oxygen or nickel can contaminate the plasma and cause degradation of the performance of a fusion device through radiation. However, impurities can also be used as diagnostics to obtain information about a plasma through spectroscopic experiments which can then be used in plasma modeling and simulations. In the past, serial algorithms have been described for either the time dependent or steady state problem. In this paper, we describe a parallel procedure adopted to solve the time-dependent problem. It can be shown that for the steady state problem a parallel procedure would not be a useful application of parallelization because a few seconds of the Central Processing Unit time on a CRAY-XMP or IBM 3090/600S would suffice to obtain the solution, while this is not the case for the time-dependent problem. In order to study the effects of low Z and high Z impurities on the final state of a plasma, time-dependent solutions are necessary. For purposes of diagnostics and comparisons with experiments, a fast turn around time of the simulations would be advantageous. We have implemented a parallel algorithm on and IBM 3090/600S and tested its performance for a typical set of fusion plasma parameters. 4 refs., 1 tab

Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.

Science.gov (United States)

Grison, Alice; Mantovani, Fiamma; Comel, Anna; Agostoni, Elena; Gustincich, Stefano; Persichetti, Francesca; Del Sal, Giannino

2011-11-01

Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKCδ, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.

A time-dependent neutron transport method of characteristics formulation with time derivative propagation

Energy Technology Data Exchange (ETDEWEB)

Hoffman, Adam J., E-mail: adamhoff@umich.edu; Lee, John C., E-mail: jcl@umich.edu

2016-02-15

A new time-dependent Method of Characteristics (MOC) formulation for nuclear reactor kinetics was developed utilizing angular flux time-derivative propagation. This method avoids the requirement of storing the angular flux at previous points in time to represent a discretized time derivative; instead, an equation for the angular flux time derivative along 1D spatial characteristics is derived and solved concurrently with the 1D transport characteristic equation. This approach allows the angular flux time derivative to be recast principally in terms of the neutron source time derivatives, which are approximated to high-order accuracy using the backward differentiation formula (BDF). This approach, called Source Derivative Propagation (SDP), drastically reduces the memory requirements of time-dependent MOC relative to methods that require storing the angular flux. An SDP method was developed for 2D and 3D applications and implemented in the computer code DeCART in 2D. DeCART was used to model two reactor transient benchmarks: a modified TWIGL problem and a C5G7 transient. The SDP method accurately and efficiently replicated the solution of the conventional time-dependent MOC method using two orders of magnitude less memory.

A time-dependent neutron transport method of characteristics formulation with time derivative propagation

International Nuclear Information System (INIS)

Hoffman, Adam J.; Lee, John C.

2016-01-01

A new time-dependent Method of Characteristics (MOC) formulation for nuclear reactor kinetics was developed utilizing angular flux time-derivative propagation. This method avoids the requirement of storing the angular flux at previous points in time to represent a discretized time derivative; instead, an equation for the angular flux time derivative along 1D spatial characteristics is derived and solved concurrently with the 1D transport characteristic equation. This approach allows the angular flux time derivative to be recast principally in terms of the neutron source time derivatives, which are approximated to high-order accuracy using the backward differentiation formula (BDF). This approach, called Source Derivative Propagation (SDP), drastically reduces the memory requirements of time-dependent MOC relative to methods that require storing the angular flux. An SDP method was developed for 2D and 3D applications and implemented in the computer code DeCART in 2D. DeCART was used to model two reactor transient benchmarks: a modified TWIGL problem and a C5G7 transient. The SDP method accurately and efficiently replicated the solution of the conventional time-dependent MOC method using two orders of magnitude less memory.

Distortion dependent intersystem crossing: A femtosecond time-resolved photoelectron spectroscopy study of benzene, toluene, and p-xylene

Directory of Open Access Journals (Sweden)

Anne B. Stephansen

2017-07-01

Full Text Available The competition between ultrafast intersystem crossing and internal conversion in benzene, toluene, and p-xylene is investigated with time-resolved photoelectron spectroscopy and quantum chemical calculations. By exciting to S2 out-of-plane symmetry breaking, distortions are activated at early times whereupon spin-forbidden intersystem crossing becomes (partly allowed. Natural bond orbital analysis suggests that the pinnacle carbon atoms distorting from the aromatic plane change hybridization between the planar Franck-Condon geometry and the deformed (boat-shaped S2 equilibrium geometry. The effect is observed to increase in the presence of methyl-groups on the pinnacle carbon-atoms, where largest extents of σ and π orbital-mixing are observed. This is fully consistent with the time-resolved spectroscopy data: Toluene and p-xylene show evidence for ultrafast triplet formation competing with internal conversion, while benzene appears to only decay via internal conversion within the singlet manifold. For toluene and p-xylene, internal conversion to S1 and intersystem crossing to T3 occur within the time-resolution of our instrument. The receiver triplet state (T3 is found to undergo internal conversion in the triplet manifold within ≈100–150 fs (toluene or ≈180–200 fs (p-xylene as demonstrated by matching rise and decay components of upper and lower triplet states. Overall, the effect of methylation is found to both increase the intersystem crossing probability and direct the molecular axis of the excited state dynamics.

Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

Science.gov (United States)

Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

2018-04-01

Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

Pseudodirect to Direct Compositional Crossover in Wurtzite GaP/InxGa1–xP Core–Shell Nanowires

KAUST Repository

Gagliano, L.

2016-11-29

Thanks to their uniqueness, nanowires allow the realization of novel semiconductor crystal structures with yet unexplored properties, which can be key to overcome current technological limits. Here we develop the growth of wurtzite GaP/InGaP core-shell nanowires with tunable indium concentration and optical emission in the visible region from 590 nm (2.1 eV) to 760 nm (1.6 eV). We demonstrate a pseudodirect (δ-δ) to direct (δ-δ) transition crossover through experimental and theoretical approach. Time resolved and temperature dependent photoluminescence measurements were used, which led to the observation of a steep change in carrier lifetime and temperature dependence by respectively one and 3 orders of magnitude in the range 0.28 ± 0.04 ≤ x ≤ 0.41 ± 0.04. Our work reveals the electronic properties of wurtzite InGaP.

Analysis of Queue-Length Dependent Vacations and P-Limited Service in BMAP/G/1/N Systems: Stationary Distributions and Optimal Control

Directory of Open Access Journals (Sweden)

A. D. Banik

2013-01-01

Full Text Available We consider a finite-buffer single server queueing system with queue-length dependent vacations where arrivals occur according to a batch Markovian arrival process (BMAP. The service discipline is P-limited service, also called E-limited with limit variation (ELV where the server serves until either the system is emptied or a randomly chosen limit of L customers has been served. Depending on the number of customers present in the system, the server will monitor his vacation times. Queue-length distributions at various epochs such as before, arrival, arbitrary and after, departure have been obtained. Several other service disciplines like Bernoulli scheduling, nonexhaustive service, and E-limited service can be treated as special cases of the P-limited service. Finally, the total expected cost function per unit time is considered to determine locally optimal values N* of N or a maximum limit L^* of L^ as the number of customers served during a service period at a minimum cost.

Evaluation of digital model accuracy and time-dependent deformation of alginate impressions.

Science.gov (United States)

Cesur, M G; Omurlu, I K; Ozer, T

2017-09-01

The aim of this study was to evaluate the accuracy of digital models produced with the three-dimensional dental scanner, and to test the dimensional stability of alginate impressions for durations of immediately (T0), 1 day (T1), and 2 days (T2). A total of sixty impressions were taken from a master model with an alginate, and were poured into plaster models in three different storage periods. Twenty impressions were directly scanned (negative digital models), after which plaster models were poured and scanned (positive digital models) immediately. The remaining 40 impressions were poured after 1 and 2 days. In total, 9 points and 11 linear measurements were used to analyze the plaster models, and negative and positive digital models. Time-dependent deformation of the alginate impressions and the accuracy of the conventional plaster models and digital models were evaluated separately. Plaster models, negative and positive digital models showed significant differences in nearly all measurements at T (0), T (1), and T (2) times (P 0.05), but they demonstrated statistically significant differences at T (2) time (P impressions is practicable method for orthodontists.

Comparing of the Reaction Time in Substance-Dependent and Non-Dependent Individuals

Directory of Open Access Journals (Sweden)

Mohammad Narimani

2012-11-01

Full Text Available Aim: The aim of this study was to compare the simple, selective, and discrimination reaction time in substance-dependent and non-dependent individuals. Method: In this causal-comparative study, the population included of 425 males (opium and crystal dependents who were referred to addiction rehabilitation centers in Tabriz. By random sampling, 16 opium dependents, 16 crystal dependents, and 16 non-dependent individuals with no history of dependency as the compare group were selected. All groups peered in age, and marital status. For gathering data, “Addicts Admit Questionnaire” and laboratory device known as the "Reaction Time Assay" have been used. Results: The results of this study showed that there are significant differences among all groups in simple reaction time, choice reaction time and reaction time to auditory stimuli, but no significant difference in discrimination reaction time and reaction time to visual stimulus observed. Conclusion: The reaction time of substance-dependent groups is slower than non-dependent groups.

Josephson-like currents in graphene for arbitrary time-dependent potential barriers

OpenAIRE

Savel'ev, Sergey E.; Hausler, Wolfgang; Hanggi, Peter

2011-01-01

From the exact solution of the Dirac-Weyl equation we find unusual currents j_y running in y-direction parallel to a time-dependent scalar potential barrier W(x,t) placed upon a monolayer of graphene, even for vanishing momentum component p_y. In their sine-like dependence on the phase difference of wave functions, describing left and right moving Dirac fermions, these currents resemble Josephson currents in superconductors, including the occurance of Shapiro steps at certain frequencies of p...

p53-dependent control of cell death by nicastrin: lack of requirement for presenilin-dependent gamma-secretase complex.

Science.gov (United States)

Pardossi-Piquard, Raphaëlle; Dunys, Julie; Giaime, Emilie; Guillot-Sestier, Marie-Victoire; St George-Hyslop, Peter; Checler, Frédéric; Alves da Costa, Cristine

2009-04-01

Nicastrin (NCT) is a component of the presenilin (PS)-dependent gamma-secretase complexes that liberate amyloid beta-peptides from the beta-Amyloid Precursor Protein. Several lines of evidence indicate that the members of these complexes could also contribute to the control of cell death. Here we show that over-expression of NCT increases the viability of human embryonic kidney (HEK293) cells and decreases staurosporine (STS)- and thapsigargin (TPS)-induced caspase-3 activation in various cell lines from human and neuronal origins by Akt-dependent pathway. NCT lowers p53 expression, transcriptional activity and promoter transactivation and reduces p53 phosphorylation. NCT-associated protection against STS-stimulated cell death was completely abolished by p53 deficiency. Conversely, the depletion of NCT drastically enhances STS-induced caspase-3 activation and p53 pathway and favored p53 nuclear translocation. We examined whether NCT protective function depends on PS-dependent gamma-secretase activity. First, a 29-amino acid deletion known to reduce NCT-dependent amyloid beta-peptide production did not affect NCT-associated protective phenotype. Second, NCT still reduces STS-induced caspase-3 activation in fibroblasts lacking PS1 and PS2. Third, the gamma-secretase inhibitor DFK167 did not affect NCT-mediated reduction of p53 activity. Altogether, our study indicates that NCT controls cell death via phosphoinositide 3-kinase/Akt and p53-dependent pathways and that this function remains independent of the activity and molecular integrity of the gamma-secretase complexes.

In vivo measurements of T1 relaxation times of 31P-metabolites in human skeletal muscle

DEFF Research Database (Denmark)

Thomsen, C; Jensen, K E; Henriksen, O

1989-01-01

The T1 relaxation times were estimated for 31P-metabolites in human skeletal muscle. Five healthy volunteers were examined in a 1.5 Tesla wholebody imaging system using an inversion recovery pulse sequence. The calculated T1 relaxation times ranged from 5.517 sec for phosphocreatine to 3.603 sec...

Chk1 inhibition activates p53 through p38 MAPK in tetraploid cancer cells.

Science.gov (United States)

Vitale, Ilio; Senovilla, Laura; Galluzzi, Lorenzo; Criollo, Alfredo; Vivet, Sonia; Castedo, Maria; Kroemer, Guido

2008-07-01

We have previously shown that tetraploid cancer cells succumb through a p53-dependent apoptotic pathway when checkpoint kinase 1 (Chk1) is depleted by small interfering RNAs (siRNAs) or inhibited with 7-hydroxystaurosporine (UCN-01). Here, we demonstrate that Chk1 inhibition results in the activating phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK). Depletion of p38 MAPK by transfection with a siRNA targeting the alpha isoform of p38 MAPK (p38alpha MAPK) abolishes the phosphorylation of p53 on serines 15 and 46 that is induced by Chk1 knockdown. The siRNA-mediated downregulation and pharmacological inhibition of p38alpha MAPK (with SB 203580) also reduces cell death induced by Chk1 knockdown or UCN-01. These results underscore the role of p38 MAPK as a pro-apoptotic kinase in the p53-dependant pathway for the therapeutic elimination of polyploidy cells.

Exactly solvable quantum state reduction models with time-dependent coupling

International Nuclear Information System (INIS)

Brody, Dorje C; Constantinou, Irene C; Dear, James D C; Hughston, Lane P

2006-01-01

A closed-form solution to the energy-based stochastic Schroedinger equation with a time-dependent coupling is obtained. The solution is algebraic in character, and is expressed directly in terms of independent random data. The data consist of (i) a random variable H which has the distribution P(H=E i ) = π i , where π i is the transition probability vertical bar (ψ 0 vertical bar Φ i ) vertical bar 2 from the initial state vertical bar ψ 0 ) to the Lueders state vertical bar Φ i ) with energy E i , and (ii) an independent P-Brownian motion, where P is the physical probability measure associated with the dynamics of the reduction process. When the coupling is time independent, it is known that state reduction occurs asymptotically-that is to say, over an infinite time horizon. In the case of a time-dependent coupling, we show that if the magnitude of the coupling decreases sufficiently rapidly, then the energy variance will be reduced under the dynamics, but the state need not reach an energy eigenstate. This situation corresponds to the case of a 'partial' or 'incomplete' measurement of the energy. We also construct an example of a model where the opposite situation prevails, in which complete state reduction is achieved after the passage of a finite period of time

Graphical analysis of pH-dependent properties of proteins predicted using PROPKA.

Science.gov (United States)

Rostkowski, Michał; Olsson, Mats H M; Søndergaard, Chresten R; Jensen, Jan H

2011-01-26

Charge states of ionizable residues in proteins determine their pH-dependent properties through their pKa values. Thus, various theoretical methods to determine ionization constants of residues in biological systems have been developed. One of the more widely used approaches for predicting pKa values in proteins is the PROPKA program, which provides convenient structural rationalization of the predicted pKa values without any additional calculations. The PROPKA Graphical User Interface (GUI) is a new tool for studying the pH-dependent properties of proteins such as charge and stabilization energy. It facilitates a quantitative analysis of pKa values of ionizable residues together with their structural determinants by providing a direct link between the pKa data, predicted by the PROPKA calculations, and the structure via the Visual Molecular Dynamics (VMD) program. The GUI also calculates contributions to the pH-dependent unfolding free energy at a given pH for each ionizable group in the protein. Moreover, the PROPKA-computed pKa values or energy contributions of the ionizable residues in question can be displayed interactively. The PROPKA GUI can also be used for comparing pH-dependent properties of more than one structure at the same time. The GUI considerably extends the analysis and validation possibilities of the PROPKA approach. The PROPKA GUI can conveniently be used to investigate ionizable groups, and their interactions, of residues with significantly perturbed pKa values or residues that contribute to the stabilization energy the most. Charge-dependent properties can be studied either for a single protein or simultaneously with other homologous structures, which makes it a helpful tool, for instance, in protein design studies or structure-based function predictions. The GUI is implemented as a Tcl/Tk plug-in for VMD, and can be obtained online at http://propka.ki.ku.dk/~luca/wiki/index.php/GUI_Web.

Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression

International Nuclear Information System (INIS)

Nygaard, Gyrid; Herfindal, Lars; Kopperud, Reidun; Aragay, Anna M.; Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune; Selheim, Frode

2014-01-01

Highlights: • We investigated the impact of cyclic nucleotide analogues on platelet activation. • Different time dependence were found for inhibition of platelet activation. • Additive effect was found using PKA- and PKG-activating analogues. • Our results may explain some of the discrepancies reported for cNMP signalling. - Abstract: In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation

Exact Time-Dependent Wave Functions of a Confined Time-Dependent Harmonic Oscillator with Two Moving Boundaries

International Nuclear Information System (INIS)

Lo, C.F.

2009-01-01

By applying the standard analytical techniques of solving partial differential equations, we have obtained the exact solution in terms of the Fourier sine series to the time-dependent Schroedinger equation describing a quantum one-dimensional harmonic oscillator of time-dependent frequency confined in an infinite square well with the two walls moving along some parametric trajectories. Based upon the orthonormal basis of quasi-stationary wave functions, the exact propagator of the system has also been analytically derived. Special cases like (i) a confined free particle, (ii) a confined time-independent harmonic oscillator, and (iii) an aging oscillator are examined, and the corresponding time-dependent wave functions are explicitly determined. Besides, the approach has been extended to solve the case of a confined generalized time-dependent harmonic oscillator for some parametric moving boundaries as well. (general)

Revisiting gamma-ray burst afterglows with time-dependent parameters

Science.gov (United States)

Yang, Chao; Zou, Yuan-Chuan; Chen, Wei; Liao, Bin; Lei, Wei-Hua; Liu, Yu

2018-02-01

The relativistic external shock model of gamma-ray burst (GRB) afterglows has been established with five free parameters, i.e., the total kinetic energy E, the equipartition parameters for electrons {{ε }}{{e}} and for the magnetic field {{ε }}{{B}}, the number density of the environment n and the index of the power-law distribution of shocked electrons p. A lot of modified models have been constructed to consider the variety of GRB afterglows, such as: the wind medium environment by letting n change with radius, the energy injection model by letting kinetic energy change with time and so on. In this paper, by assuming all four parameters (except p) change with time, we obtain a set of formulas for the dynamics and radiation, which can be used as a reference for modeling GRB afterglows. Some interesting results are obtained. For example, in some spectral segments, the radiated flux density does not depend on the number density or the profile of the environment. As an application, through modeling the afterglow of GRB 060607A, we find that it can be interpreted in the framework of the time dependent parameter model within a reasonable range.

Geiger-Mueller haloid counter dead time dependence on counting rate

International Nuclear Information System (INIS)

Onishchenko, A.M.; Tsvetkov, A.A.

1980-01-01

The experimental dependences of the dead time of Geiger counters (SBM-19, SBM-20, SBM-21 and SGM-19) on the loading, are presented. The method of two sources has been used to determine the dead time counters of increased stability. The counters are switched on according to the usually used circuit of discrete counting with loading resistance of 50 MOhm and the separating capacity of 10 pF. Voltage pulses are given to the counting device with the time of resolution of 100 ns, discrimenation threshold 3 V, input resistance 3.6 Ω and the input capacity-15 pF. The time constant of the counter RC-circuit is 50 μs

The Second Eigenvalue of the p-Laplacian as p Goes to 1

Directory of Open Access Journals (Sweden)

Enea Parini

2010-01-01

Full Text Available The asymptotic behaviour of the second eigenvalue of the p-Laplacian operator as p goes to 1 is investigated. The limit setting depends only on the geometry of the domain. In the particular case of a planar disc, it is possible to show that the second eigenfunctions are nonradial if p is close enough to 1.

Synthesis and characterization of pH sensitive carboxySNARF-1 nanoreactors

International Nuclear Information System (INIS)

Chen Yenchi; Ostafin, Agnes; Mizukami, Hiroshi

2010-01-01

A rapid response dual wavelength emission pH sensor consisting of carboxySNARF-1 nanoreactors has been synthesized and shown to provide accurate pH measurements even in complex biological media, where the unprotected pH responsive dyes have failed. The carboxySNARF-1 nanoreactor is made of a calcium phosphate shell covering phosphatidylcholine liposomes filled with the dye. Its mean diameter is 150 nm with dynamic light scattering, the shell thickness is 5-7 nm with TEM, and it contains about 10 dyes/particle. The nanoreactor's response time to pH change nearly equals that of the dye in solution. Its pH titration curves at two different wavelengths are equivalent to those of the dye in solution and fluorescence intensity ratio dependent pH analysis is possible using the modified Henderson-Hasselbalch equation. However, the pH dependent fluorescence ratios of the dye in solution in the presence of plasma and albumin are distorted, and application of the Henderson-Hasselbalch equation is not possible. We have found that the distortions may be restored using cSNARF-1 nanoreactors and the pK a of the dye in the nanoreactor then equals that in solution. These results suggest that the interference to the dye for the pH analyses with the environmental molecules may be reduced or prohibited by usage of cSNARF-1 nanoreactors.

Synthesis and characterization of pH sensitive carboxySNARF-1 nanoreactors

Energy Technology Data Exchange (ETDEWEB)

Chen Yenchi; Ostafin, Agnes [Department of Materials Science, University of Utah, Salt Lake City, UT (United States); Mizukami, Hiroshi, E-mail: a.ostafin@utah.edu [Department of Biological Science, Wayne State University, Detroit, MI (United States)

2010-05-28

A rapid response dual wavelength emission pH sensor consisting of carboxySNARF-1 nanoreactors has been synthesized and shown to provide accurate pH measurements even in complex biological media, where the unprotected pH responsive dyes have failed. The carboxySNARF-1 nanoreactor is made of a calcium phosphate shell covering phosphatidylcholine liposomes filled with the dye. Its mean diameter is 150 nm with dynamic light scattering, the shell thickness is 5-7 nm with TEM, and it contains about 10 dyes/particle. The nanoreactor's response time to pH change nearly equals that of the dye in solution. Its pH titration curves at two different wavelengths are equivalent to those of the dye in solution and fluorescence intensity ratio dependent pH analysis is possible using the modified Henderson-Hasselbalch equation. However, the pH dependent fluorescence ratios of the dye in solution in the presence of plasma and albumin are distorted, and application of the Henderson-Hasselbalch equation is not possible. We have found that the distortions may be restored using cSNARF-1 nanoreactors and the pK{sub a} of the dye in the nanoreactor then equals that in solution. These results suggest that the interference to the dye for the pH analyses with the environmental molecules may be reduced or prohibited by usage of cSNARF-1 nanoreactors.

Time-Dependent Behaviors of Granite: Loading-Rate Dependence, Creep, and Relaxation

Science.gov (United States)

Hashiba, K.; Fukui, K.

2016-07-01

To assess the long-term stability of underground structures, it is important to understand the time-dependent behaviors of rocks, such as their loading-rate dependence, creep, and relaxation. However, there have been fewer studies on crystalline rocks than on tuff, mudstone, and rock salt, because the high strength of crystalline rocks makes the detection of their time-dependent behaviors much more difficult. Moreover, studies on the relaxation, temporal change of stress and strain (TCSS) conditions, and relations between various time-dependent behaviors are scarce for not only granites, but also other rocks. In this study, previous reports on the time-dependent behaviors of granites were reviewed and various laboratory tests were conducted using Toki granite. These tests included an alternating-loading-rate test, creep test, relaxation test, and TCSS test. The results showed that the degree of time dependence of Toki granite is similar to other granites, and that the TCSS resembles the stress-relaxation curve and creep-strain curve. A viscoelastic constitutive model, proposed in a previous study, was modified to investigate the relations between the time-dependent behaviors in the pre- and post-peak regions. The modified model reproduced the stress-strain curve, creep, relaxation, and the results of the TCSS test. Based on a comparison of the results of the laboratory tests and numerical simulations, close relations between the time-dependent behaviors were revealed quantitatively.

Spin-zero DKP equation with two time-dependent interactions

Energy Technology Data Exchange (ETDEWEB)

Saeedi, K.; Hassanabadi, H. [Shahrood University of Technology, Physics Department, Shahrood (Iran, Islamic Republic of); Zarrinkamar, S. [Islamic Azad University, Department of Basic Sciences, Garmsar Branch, Garmsar (Iran, Islamic Republic of)

2016-11-15

The Duffin-Kemmer-Petiau equation for spin-zero bosons is considered in (1 + 1) - and (2 + 1) -dimensional space-time. Some time-dependent interactions are considered within the framework and quasi-exact solutions are provided. The results are discussed via various figures. (orig.)

Time-dependent potential-functional embedding theory

International Nuclear Information System (INIS)

Huang, Chen; Libisch, Florian; Peng, Qing; Carter, Emily A.

2014-01-01

We introduce a time-dependent potential-functional embedding theory (TD-PFET), in which atoms are grouped into subsystems. In TD-PFET, subsystems can be propagated by different suitable time-dependent quantum mechanical methods and their interactions can be treated in a seamless, first-principles manner. TD-PFET is formulated based on the time-dependent quantum mechanics variational principle. The action of the total quantum system is written as a functional of the time-dependent embedding potential, i.e., a potential-functional formulation. By exploiting the Runge-Gross theorem, we prove the uniqueness of the time-dependent embedding potential under the constraint that all subsystems share a common embedding potential. We derive the integral equation that such an embedding potential needs to satisfy. As proof-of-principle, we demonstrate TD-PFET for a Na 4 cluster, in which each Na atom is treated as one subsystem and propagated by time-dependent Kohn-Sham density functional theory (TDDFT) using the adiabatic local density approximation (ALDA). Our results agree well with a direct TDDFT calculation on the whole Na 4 cluster using ALDA. We envision that TD-PFET will ultimately be useful for studying ultrafast quantum dynamics in condensed matter, where key regions are solved by highly accurate time-dependent quantum mechanics methods, and unimportant regions are solved by faster, less accurate methods

Competing risks and time-dependent covariates

DEFF Research Database (Denmark)

Cortese, Giuliana; Andersen, Per K

2010-01-01

Time-dependent covariates are frequently encountered in regression analysis for event history data and competing risks. They are often essential predictors, which cannot be substituted by time-fixed covariates. This study briefly recalls the different types of time-dependent covariates......, as classified by Kalbfleisch and Prentice [The Statistical Analysis of Failure Time Data, Wiley, New York, 2002] with the intent of clarifying their role and emphasizing the limitations in standard survival models and in the competing risks setting. If random (internal) time-dependent covariates...

Time-dependent EQPET analysis of TSC

International Nuclear Information System (INIS)

Takahashi, Akito

2006-01-01

Time-dependent fusion rates for 2D and 4D reactions are calculated for squeezing of tetrahedral symmetric condensate (TSC) from about 100 pm size to its minimum size (about 10 fm), within about 75 fs squeezing motion. Life time of the minimum TSC state is yet to be studied. Time-averaged fusion rates are given by assuming the life time of minimum TSC state is negligible. Time-averaged 2D fusion rate was given as 2.9x10 -25 f/s/pair, and time-averaged 4D fusion rate was 5.5x10 -8 f/s/cl. These values are compared with 1.0x10 -20 f/s/pair for 2D and 1.0x10 -9 f/s/cl for 4D, respectively, of previously estimated values by electronic quasi-particle expansion theory/TSC models. Effective fusion time by the TSC squeezing motion was estimated as 0.014 fs: namely fusions may happen in very short time interval. (author)

Time-dependent gravitating solitons in five dimensional warped space-times

CERN Document Server

Giovannini, Massimo

2007-01-01

Time-dependent soliton solutions are explicitly derived in a five-dimensional theory endowed with one (warped) extra-dimension. Some of the obtained geometries, everywhere well defined and technically regular, smoothly interpolate between two five-dimensional anti-de Sitter space-times for fixed value of the conformal time coordinate. Time dependent solutions containing both topological and non-topological sectors are also obtained. Supplementary degrees of freedom can be also included and, in this case, the resulting multi-soliton solutions may describe time-dependent kink-antikink systems.

Time dependent mean-field games

KAUST Repository

Gomes, Diogo A.

2014-01-06

We consider time dependent mean-field games (MFG) with a local power-like dependence on the measure and Hamiltonians satisfying both sub and superquadratic growth conditions. We establish existence of smooth solutions under a certain set of conditions depending both on the growth of the Hamiltonian as well as on the dimension. In the subquadratic case this is done by combining a Gagliardo-Nirenberg type of argument with a new class of polynomial estimates for solutions of the Fokker-Planck equation in terms of LrLp- norms of DpH. These techniques do not apply to the superquadratic case. In this setting we recur to a delicate argument that combines the non-linear adjoint method with polynomial estimates for solutions of the Fokker-Planck equation in terms of L1L1-norms of DpH. Concerning the subquadratic case, we substantially improve and extend the results previously obtained. Furthermore, to the best of our knowledge, the superquadratic case has not been addressed in the literature yet. In fact, it is likely that our estimates may also add to the current understanding of Hamilton-Jacobi equations with superquadratic Hamiltonians.

Dependency of magnetocardiographically determined fetal cardiac time intervals on gestational age, gender and postnatal biometrics in healthy pregnancies

Directory of Open Access Journals (Sweden)

Geue Daniel

2004-04-01

Full Text Available Abstract Background Magnetocardiography enables the precise determination of fetal cardiac time intervals (CTI as early as the second trimester of pregnancy. It has been shown that fetal CTI change in course of gestation. The aim of this work was to investigate the dependency of fetal CTI on gestational age, gender and postnatal biometric data in a substantial sample of subjects during normal pregnancy. Methods A total of 230 fetal magnetocardiograms were obtained in 47 healthy fetuses between the 15th and 42nd week of gestation. In each recording, after subtraction of the maternal cardiac artifact and the identification of fetal beats, fetal PQRST courses were signal averaged. On the basis of therein detected wave onsets and ends, the following CTI were determined: P wave, PR interval, PQ interval, QRS complex, ST segment, T wave, QT and QTc interval. Using regression analysis, the dependency of the CTI were examined with respect to gestational age, gender and postnatal biometric data. Results Atrioventricular conduction and ventricular depolarization times could be determined dependably whereas the T wave was often difficult to detect. Linear and nonlinear regression analysis established strong dependency on age for the P wave and QRS complex (r2 = 0.67, p r2 = 0.66, p r2 = 0.21, p r2 = 0.13, p st week onward (p Conclusion We conclude that 1 from approximately the 18th week to term, fetal CTI which quantify depolarization times can be reliably determined using magnetocardiography, 2 the P wave and QRS complex duration show a high dependency on age which to a large part reflects fetal growth and 3 fetal gender plays a role in QRS complex duration in the third trimester. Fetal development is thus in part reflected in the CTI and may be useful in the identification of intrauterine growth retardation.

Specific features of time-dependent Psub(N) approximations in spherical geometry

International Nuclear Information System (INIS)

Peltzer, P.; Pucker, N.

1979-01-01

Approximations to the time-dependent linear transport equation can result in more serious distortions in the description of the actual physical situation than in the stationary problem. This is demonstrated in detail for the case of a neutron pulse in spherical geometry, treated within a P 1 approximation. One has to pay special attention to the singularity at r = 0 and to the effect of the boundary conditions. Effects similar to those shown here are also to be expected in connection with Psub(N) approximations of higher order. (Auth.)

Q2 Dependence of Quadrupole Strength in the gamma*p-->Delta+(1232) --> p pi0 Transition

International Nuclear Information System (INIS)

Volker Burkert; Kyungseon Joo; Lee Smith; Ralph Minehart

2002-01-01

Models of baryon structure predict a small quadrupole deformation of the nucleon due to residual tensor forces between quarks or distortions from the pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through the Q 2 dependence of the magnetic (M 1+ ), electric (E 1+ ), and scalar (S 1+ ) multipoles in the γ*p → Δ + (1232) → pπ 0 transition. New precision measurements of the ratios E 1+ /M 1+ and S 1+ /M 1+ are reported here over the range Q 2 = 0.4-1.8 GeV 2 . Results are best described by recent unitary models in which the pion cloud plays a dominant role

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.

Pyridine induction of cytochrome P450IIE1: Evidence for enhanced protein synthesis

International Nuclear Information System (INIS)

Kim, S.G.; Novak, R.F.

1990-01-01

The dose-, and time-dependent induction of P450IIE1 in the rat by pyridine (PY) has been characterized. A single injection of PY (100 mg/kg, i.p.) increased as the levels of IIE1 2-, 3- and 4-fold at 6, 10 and 24 hr, respectively, relative to controls based on p-nitrophenol hydroxylase activity and Western blot analysis. Induction of IIE1 was dose-dependent over the range 10 to 200 mg/kg. Cycloheximide administration completely prevented the induction of IIE1 by PY, while actinomycin D failed to affect PY induction of IIE1. The rate of IIE1 synthesis was examined by labelling of proteins with [ 14 C] leucine in vivo, followed by SDS-PAGE and autoradiographic analysis of isolated microsomes. Enhanced intensity of the IIE1 band was observed in microsomes isolated from rats treated with either PY or acetone relative to untreated rats. Slot and Northern blot analyses were employed to assess IIE1 mRNA levels in total RNA and poly(A + ) mRNA isolated from livers of rats at 1, 5 and 12 hr following a single dose of PY. No increase in IIE1 mRNA in total RNA was monitored. A time-dependent decrease in IIE1 poly(A + ) mRNA however, was observed with the maximal decrease occurring at ∼12 hr. These results suggest that induction of IIE1 by PY does not involve transcriptional activation but occurs by protein synthesis possibly through increased translational efficiency

Temperature-dependent thermal and thermoelectric properties of n -type and p -type S c1 -xM gxN

Science.gov (United States)

Saha, Bivas; Perez-Taborda, Jaime Andres; Bahk, Je-Hyeong; Koh, Yee Rui; Shakouri, Ali; Martin-Gonzalez, Marisol; Sands, Timothy D.

2018-02-01

Scandium Nitride (ScN) is an emerging rocksalt semiconductor with octahedral coordination and an indirect bandgap. ScN has attracted significant attention in recent years for its potential thermoelectric applications, as a component material in epitaxial metal/semiconductor superlattices, and as a substrate for defect-free GaN growth. Sputter-deposited ScN thin films are highly degenerate n -type semiconductors and exhibit a large thermoelectric power factor of ˜3.5 ×10-3W /m -K2 at 600-800 K. Since practical thermoelectric devices require both n- and p-type materials with high thermoelectric figures-of-merit, development and demonstration of highly efficient p-type ScN is extremely important. Recently, the authors have demonstrated p-type S c1 -xM gxN thin film alloys with low M gxNy mole-fractions within the ScN matrix. In this article, we demonstrate temperature dependent thermal and thermoelectric transport properties, including large thermoelectric power factors in both n- and p-type S c1 -xM gxN thin film alloys at high temperatures (up to 850 K). Employing a combination of temperature-dependent Seebeck coefficient, electrical conductivity, and thermal conductivity measurements, as well as detailed Boltzmann transport-based modeling analyses of the transport properties, we demonstrate that p-type S c1 -xM gxN thin film alloys exhibit a maximum thermoelectric power factor of ˜0.8 ×10-3W /m -K2 at 850 K. The thermoelectric properties are tunable by adjusting the M gxNy mole-fraction inside the ScN matrix, thereby shifting the Fermi energy in the alloy films from inside the conduction band in case of undoped n -type ScN to inside the valence band in highly hole-doped p -type S c1 -xM gxN thin film alloys. The thermal conductivities of both the n- and p-type films were found to be undesirably large for thermoelectric applications. Thus, future work should address strategies to reduce the thermal conductivity of S c1 -xM gxN thin-film alloys, without affecting

Mass dispersions in a time-dependent mean-field approach

International Nuclear Information System (INIS)

Balian, R.; Bonche, P.; Flocard, H.; Veneroni, M.

1984-05-01

Characteristic functions for single-particle (s.p.) observables are evaluated by means of a time-dependent variational principle, which involves a state and an observable as conjugate variables. This provides a mean-field expression for fluctuations of s.p. observables, such as mass dispersions. The result differs from TDHF, it requires only the use of existing codes, and it presents attractive theoretical features. First numerical tests are encouraging. In particular, a calculation for 16 O + 16 O provides a significant increase of the predicted mass dispersion

Review of time-dependent fatigue behavior and life prediction for 2 1/4 Cr-1 Mo steel

International Nuclear Information System (INIS)

Booker, M.K.; Majumdar, S.

1982-01-01

Available data on creep-fatigue life and fracture behavior of 2 1/4 Cr-1 Mo steel are reviewed. Whereas creep-fatigue interaction is important for Type 304 stainless steel, oxidation effects appear to dominate the time-dependent fatigue behavior of 2 1/4 Cr-1 Mo steel. Four of the currently available predictive methods - the Linear Damage Rule, Frequency Separation Equation, Strain Range Partitioning Equation, and Damage Rate Equation - are evaluated for their predictive capability. Variations in the parameters for the various predictive methods with temperature, heat of material, heat treatment, and environment are investigated. Relative trends in the lives predicted by the various methods as functions of test duration, waveshape, etc., are discussed. The predictive methods will need modification in order to account for oxidation and aging effects in the 2 1/4 Cr-1 Mo steel. Future tests that will emphasize the difference between the various predictive methods are proposed

Study of the (p,pn) reaction on 1p shell nuclei at 46 MeV

Energy Technology Data Exchange (ETDEWEB)

Miller, C A

1974-01-01

The (p,pn) reaction on four 1p shell nuclei, /sup 6/Li, /sup 9/Be, /sup 13/C and /sup 12/C, as well as the /sup 6/Li(p,2p) reaction, have been studied at 46 MeV. The /sup 6/Li(p,pn) cross section was found to be approximately four times that for (p,2p) and to have a very different angular dependence. Both reactions show the s-state admixture in /sup 6/Li observed with (p,2p) at higher energies. For all of the target nuclei, the cross sections have features that cannot be fitted by a renormalized Plane Wave Impulse Approximation (PWIA) calculation. A zero range distorted wave calculation was found to be in only fair agreement with the /sup 9/Be and /sup 13/C data. The overall magnitudes of the results of the calculation were found to be very sensitive to the RMS radii of the bound state wave functions of the knocked-out neutrons.

Hsf1p and Msn2/4p cooperate in the expression of Saccharomyces cerevisiae genes HSP26 and HSP104 in a gene- and stress type-dependent manner.

Science.gov (United States)

Amorós, M; Estruch, F

2001-03-01

Saccharomyces cerevisiae possesses several transcription factors involved in the transcriptional activation of stress-induced genes. Among them, the heat shock factor (Hsf1p) and the zinc finger proteins of the general stress response (Msn2p and Msn4p) have been shown to play a major role in stress protection. Some heat shock protein (HSP) genes contain both heat shock elements (HSEs) and stress response elements (STREs), suggesting the involvement of both transcription factors in their regulation. Analysis of the stress-induced expression of two of these genes, HSP26 and HSP104, reveals that the contribution of Hsf1p and Msn2/4p is different depending on the gene and the stress condition.

New constraints on time-dependent variations of fundamental constants using Planck data

Science.gov (United States)

Hart, Luke; Chluba, Jens

2018-02-01

Observations of the cosmic microwave background (CMB) today allow us to answer detailed questions about the properties of our Universe, targeting both standard and non-standard physics. In this paper, we study the effects of varying fundamental constants (i.e. the fine-structure constant, αEM, and electron rest mass, me) around last scattering using the recombination codes COSMOREC and RECFAST++. We approach the problem in a pedagogical manner, illustrating the importance of various effects on the free electron fraction, Thomson visibility function and CMB power spectra, highlighting various degeneracies. We demonstrate that the simpler RECFAST++ treatment (based on a three-level atom approach) can be used to accurately represent the full computation of COSMOREC. We also include explicit time-dependent variations using a phenomenological power-law description. We reproduce previous Planck 2013 results in our analysis. Assuming constant variations relative to the standard values, we find the improved constraints αEM/αEM, 0 = 0.9993 ± 0.0025 (CMB only) and me/me, 0 = 1.0039 ± 0.0074 (including BAO) using Planck 2015 data. For a redshift-dependent variation, αEM(z) = αEM(z0) [(1 + z)/1100]p with αEM(z0) ≡ αEM, 0 at z0 = 1100, we obtain p = 0.0008 ± 0.0025. Allowing simultaneous variations of αEM(z0) and p yields αEM(z0)/αEM, 0 = 0.9998 ± 0.0036 and p = 0.0006 ± 0.0036. We also discuss combined limits on αEM and me. Our analysis shows that existing data are not only sensitive to the value of the fundamental constants around recombination but also its first time derivative. This suggests that a wider class of varying fundamental constant models can be probed using the CMB.

Unit-time scheduling problems with time dependent resources

NARCIS (Netherlands)

Tautenhahn, T.; Woeginger, G.

1997-01-01

We investigate the computational complexity of scheduling problems, where the operations consume certain amounts of renewable resources which are available in time-dependent quantities. In particular, we consider unit-time open shop problems and unit-time scheduling problems with identical parallel

TGF-β1-induced cell migration in pancreatic carcinoma cells is RAC1 and NOX4-dependent and requires RAC1 and NOX4-dependent activation of p38 MAPK.

Science.gov (United States)

Witte, David; Bartscht, Tobias; Kaufmann, Roland; Pries, Ralph; Settmacher, Utz; Lehnert, Hendrik; Ungefroren, Hendrik

2017-12-01

Transforming growth factor (TGF)-β promotes epithelial-mesenchymal transition and cell invasion of cancer cells in part through the small GTPase RAC1. Since RAC1 can signal through reactive oxygen species (ROS), we probed the role of the ROS-producing NADPH oxidase (NOX) and p38 mitogen-activated protein kinase (MAPK) in mediating TGF-β1/RAC1-driven random cell migration (chemokinesis). Although the NOX isoforms NOX2, 4, 5, 6, and RAC1 were readily detectable by RT-PCR in pancreatic ductal adenocarcinoma (PDAC)-derived Panc1 and Colo357 cells, only NOX4 and RAC1 were expressed at higher levels comparable to those in peripheral blood monocytes. TGF-β1 treatment resulted in upregulation of NOX4 (and NOX2) and rapid intracellular production of ROS. To analyze whether RAC1 functions through NOX and ROS to promote cell motility, we performed real-time cell migration assays with xCELLigence® technology in the presence of the ROS scavenger N-acetyl-L-cysteine (NAC) and various NOX inhibitors. NAC, the NOX4 inhibitor diphenylene iodonium or small interfering RNA (siRNA) to NOX4, and the NOX2 inhibitor apocynin all suppressed TGF-β1-induced chemokinesis of Panc1 and Colo357 cells as did various inhibitors of RAC1 used as control. In addition, we showed that blocking NOX4 or RAC1 function abrogated phosphorylation of p38 MAPK signaling by TGF-β1 and that inhibition of p38 MAPK reduced TGF-β1-induced random cell migration, while ectopic expression of a kinase-active version of the p38 activating kinase MKK6 was able to partially rescue the decline in migration after RAC1 inhibition. Our data suggest that TGF-β1-induced chemokinesis in PDAC cells is mediated through a RAC1/NOX4/ROS/p38 MAPK cascade.

Period1 gates the circadian modulation of memory-relevant signaling in mouse hippocampus by regulating the nuclear shuttling of the CREB kinase pP90RSK

DEFF Research Database (Denmark)

Rawashdeh, Oliver; Jilg, Antje; Maronde, Erik

2016-01-01

, the presence of PER1 in hippocampal neurons is a prerequisite for the time-of-day-dependent phosphorylation of CREB, as it regulates the shuttling of pP90RSK into the nucleus. Representative immunofluorescence images show a temporal difference in phosphorylated cAMP response element-binding protein (p...... activation. Taken together, the PER1-dependent modulation of cytoplasmic-to-nuclear signaling in the murine hippocampus provides a molecular explanation for how the circadian system potentially shapes a temporal framework for daytime-dependent memory performance, and adds a novel facet to the versatility......CREB; green color) levels in all regions of the dorsal hippocampus between a wild-type C3H mouse (WT; left) and a Period1-knockout (Per1−/−; right) mouse. Images were taken 2 h after lights on, thus, when fluctuating levels of pCREB peak in WT mouse hippocampus. Insets show a representative hippocampal neuron...

Models for dependent time series

CERN Document Server

Tunnicliffe Wilson, Granville; Haywood, John

2015-01-01

Models for Dependent Time Series addresses the issues that arise and the methodology that can be applied when the dependence between time series is described and modeled. Whether you work in the economic, physical, or life sciences, the book shows you how to draw meaningful, applicable, and statistically valid conclusions from multivariate (or vector) time series data.The first four chapters discuss the two main pillars of the subject that have been developed over the last 60 years: vector autoregressive modeling and multivariate spectral analysis. These chapters provide the foundational mater

Temperature dependence of the optical absorption spectra of InP/ZnS quantum dots

Science.gov (United States)

Savchenko, S. S.; Vokhmintsev, A. S.; Weinstein, I. A.

2017-03-01

The optical-absorption spectra of InP/ZnS (core/shell) quantum dots have been studied in a broad temperature range of T = 6.5-296 K. Using the second-order derivative spectrophotometry technique, the energies of optical transitions at room temperature were found to be E 1 = 2.60 ± 0.02 eV (for the first peak of excitonic absorption in the InP core) and E 2 = 4.70 ± 0.02 eV (for processes in the ZnS shell). The experimental curve of E 1( T) has been approximated for the first time in the framework of a linear model and in terms of the Fan's formula. It is established that the temperature dependence of E 1 is determined by the interaction of excitons and longitudinal acoustic phonons with hω = 15 meV.

The p53-dependent radioadaptive response

Science.gov (United States)

Ohnishi, Takeo

We already reported that conditioning exposures at low doses, or at low dose-rates, lowered radiation-induced p53-dependent apoptosis in cultured cells in vitro and in the spleens of mice in vivo. In this study, the aim was to characterize the p53-dependent radioadaptive response at the molecular level. We used wild-type (wt) p53 and mutated (m) p53 containing cells derived from the human lung cancer H1299 cell line, which is p53-null. Cellular radiation sensitivities were determined with a colony-forming assay. The accumulation of p53, Hdm2, and iNOS was analyzed with Western blotting. The quantification of chromosomal aberrations was estimated by scoring dicentrics per cell. In wtp53 cells, it was demonstrated that the lack of p53 accumulation was coupled with the activation of Hdm2 after low dose irradiation (0.02 Gy). Although NO radicals were only minimally induced in wtp53 cells irradiated with a challenging irradiation (6 Gy) alone, NO radicals were seen to increase about 2-4 fold after challenging irradiation following a priming irradiation (0.02 Gy). Under similar irradiation conditions with a priming and challenging irradiation in wtp53 cells, induction of radioresistance and a depression of chromosomal aberrations were observed only in the absence of Pifithrin-α (a p53 inhibitor), RITA or Nutlin-3 (p53-Hdm2 interaction inhibitors), aminoguanidine (an iNOS inhibitor) and c-PTIO (an NO radical scavenger). On the other hand, in p53 dysfunctional cells, a radioadaptive response was not observed in the presence or absence of those inhibitors. Moreover, radioresistance developed when wtp53 cells were treated with ISDN (an NO generating agent) alone. These findings suggest that NO radicals are an initiator of the radioadaptive response acting through the activation of Hdm2 and the depression of p53 accumulations.

Examining the time dependence of DAMA's modulation amplitude

Science.gov (United States)

Kelso, Chris; Savage, Christopher; Sandick, Pearl; Freese, Katherine; Gondolo, Paolo

2018-03-01

If dark matter is composed of weakly interacting particles, Earth's orbital motion may induce a small annual variation in the rate at which these particles interact in a terrestrial detector. The DAMA collaboration has identified at a 9.3σ confidence level such an annual modulation in their event rate over two detector iterations, DAMA/NaI and DAMA/LIBRA, each with ˜ 7 years of observations. This data is well fit by a constant modulation amplitude for the two iterations of the experiment. We statistically examine the time dependence of the modulation amplitudes, which "by eye" appear to be decreasing with time in certain energy ranges. We perform a chi-squared goodness of fit test of the average modulation amplitudes measured by the two detector iterations which rejects the hypothesis of a consistent modulation amplitude at greater than 80, 96, and 99.6% for the 2-4, 2-5 and 2-6 keVee energy ranges, respectively. We also find that among the 14 annual cycles there are three ≳ 3σ departures from the average in our estimated data in the 5-6 keVee energy range. In addition, we examined several phenomenological models for the time dependence of the modulation amplitude. Using a maximum likelihood test, we find that descriptions of the modulation amplitude as decreasing with time are preferred over a constant modulation amplitude at anywhere between 1σ and 3σ , depending on the phenomenological model for the time dependence and the signal energy range considered. A time dependent modulation amplitude is not expected for a dark matter signal, at least for dark matter halo morphologies consistent with the DAMA signal. New data from DAMA/LIBRA-phase2 will certainly aid in determining whether any apparent time dependence is a real effect or a statistical fluctuation.

Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

Science.gov (United States)

Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

2017-12-01

Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

Computational Tools for Interpreting Ion Channel pH-Dependence.

Science.gov (United States)

Sazanavets, Ivan; Warwicker, Jim

2015-01-01

Activity in many biological systems is mediated by pH, involving proton titratable groups with pKas in the relevant pH range. Experimental analysis of pH-dependence in proteins focusses on particular sidechains, often with mutagenesis of histidine, due to its pKa near to neutral pH. The key question for algorithms that predict pKas is whether they are sufficiently accurate to effectively narrow the search for molecular determinants of pH-dependence. Through analysis of inwardly rectifying potassium (Kir) channels and acid-sensing ion channels (ASICs), mutational effects on pH-dependence are probed, distinguishing between groups described as pH-coupled or pH-sensor. Whereas mutation can lead to a shift in transition pH between open and closed forms for either type of group, only for pH-sensor groups does mutation modulate the amplitude of the transition. It is shown that a hybrid Finite Difference Poisson-Boltzmann (FDPB) - Debye-Hückel continuum electrostatic model can filter mutation candidates, providing enrichment for key pH-coupled and pH-sensor residues in both ASICs and Kir channels, in comparison with application of FDPB alone.

Computational Tools for Interpreting Ion Channel pH-Dependence.

Directory of Open Access Journals (Sweden)

Ivan Sazanavets

Full Text Available Activity in many biological systems is mediated by pH, involving proton titratable groups with pKas in the relevant pH range. Experimental analysis of pH-dependence in proteins focusses on particular sidechains, often with mutagenesis of histidine, due to its pKa near to neutral pH. The key question for algorithms that predict pKas is whether they are sufficiently accurate to effectively narrow the search for molecular determinants of pH-dependence. Through analysis of inwardly rectifying potassium (Kir channels and acid-sensing ion channels (ASICs, mutational effects on pH-dependence are probed, distinguishing between groups described as pH-coupled or pH-sensor. Whereas mutation can lead to a shift in transition pH between open and closed forms for either type of group, only for pH-sensor groups does mutation modulate the amplitude of the transition. It is shown that a hybrid Finite Difference Poisson-Boltzmann (FDPB - Debye-Hückel continuum electrostatic model can filter mutation candidates, providing enrichment for key pH-coupled and pH-sensor residues in both ASICs and Kir channels, in comparison with application of FDPB alone.

Regulating NETosis: Increasing pH Promotes NADPH Oxidase-Dependent NETosis

Science.gov (United States)

Khan, Meraj A.; Philip, Lijy M.; Cheung, Guillaume; Vadakepeedika, Shawn; Grasemann, Hartmut; Sweezey, Neil; Palaniyar, Nades

2018-01-01

Neutrophils migrating from the blood (pH 7.35–7.45) into the surrounding tissues encounter changes in extracellular pH (pHe) conditions. Upon activation of NADPH oxidase 2 (Nox), neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi). Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET) formation (NETosis) is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS) and neutrophil protease activity, stimulating NETosis. Here, we found that raising pHe (ranging from 6.6 to 7.8; every 0.2 units) increased pHi of both activated and resting neutrophils within 10–20 min (Seminaphtharhodafluor dual fluorescence measurements). Since Nox activity generates H+ ions, pHi is lower in neutrophils that are activated compared to resting. We also found that higher pH stimulated Nox-dependent ROS production (R123 generation; flow cytometry, plate reader assay, and imaging) during spontaneous and phorbol myristate acetate-induced NETosis (Sytox Green assays, immunoconfocal microscopy, and quantifying NETs). In neutrophils that are activated and not resting, higher pH stimulated histone H4 cleavage (Western blots) and NETosis. Raising pH increased Escherichia coli lipopolysaccharide-, Pseudomonas aeruginosa (Gram-negative)-, and Staphylococcus aureus (Gram-positive)-induced NETosis. Thus, higher pHe promoted Nox-dependent ROS production, protease activity, and NETosis; lower pH has the opposite effect. These studies provided mechanistic steps of pHe-mediated regulation of Nox-dependent NETosis. Raising pH either by sodium bicarbonate or Tris base (clinically known as Tris hydroxymethyl aminomethane, tromethamine, or THAM) increases NETosis. Each Tris molecule can bind 3H+ ions, whereas each bicarbonate HCO3− ion binds 1H+ ion. Therefore, the amount of Tris solution required to cause the same increase in pH level is less than that of equimolar

Regulating NETosis: Increasing pH Promotes NADPH Oxidase-Dependent NETosis

Directory of Open Access Journals (Sweden)

Meraj A. Khan

2018-02-01

Full Text Available Neutrophils migrating from the blood (pH 7.35–7.45 into the surrounding tissues encounter changes in extracellular pH (pHe conditions. Upon activation of NADPH oxidase 2 (Nox, neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi. Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET formation (NETosis is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS and neutrophil protease activity, stimulating NETosis. Here, we found that raising pHe (ranging from 6.6 to 7.8; every 0.2 units increased pHi of both activated and resting neutrophils within 10–20 min (Seminaphtharhodafluor dual fluorescence measurements. Since Nox activity generates H+ ions, pHi is lower in neutrophils that are activated compared to resting. We also found that higher pH stimulated Nox-dependent ROS production (R123 generation; flow cytometry, plate reader assay, and imaging during spontaneous and phorbol myristate acetate-induced NETosis (Sytox Green assays, immunoconfocal microscopy, and quantifying NETs. In neutrophils that are activated and not resting, higher pH stimulated histone H4 cleavage (Western blots and NETosis. Raising pH increased Escherichia coli lipopolysaccharide-, Pseudomonas aeruginosa (Gram-negative-, and Staphylococcus aureus (Gram-positive-induced NETosis. Thus, higher pHe promoted Nox-dependent ROS production, protease activity, and NETosis; lower pH has the opposite effect. These studies provided mechanistic steps of pHe-mediated regulation of Nox-dependent NETosis. Raising pH either by sodium bicarbonate or Tris base (clinically known as Tris hydroxymethyl aminomethane, tromethamine, or THAM increases NETosis. Each Tris molecule can bind 3H+ ions, whereas each bicarbonate HCO3− ion binds 1H+ ion. Therefore, the amount of Tris solution required to cause the same increase in pH level is less than that of equimolar

On signature change in p-adic space-times

International Nuclear Information System (INIS)

Dragovic, B.G.

1991-01-01

Change of signature by linear coordinate transformations in p-adic space-times is considered. In this paper it is shown that there exists arbitrary change of trivial signature in Q p n for all n ≥ 1 if p ≡ 1 (mod 4). In other cases it is possible to change only even number of the signs of the signature. The authors suggest new concept of signature with respect to distinct quadratic extensions, of Q p . If space-time dimension is restricted to four there is no signature change

On the measurement of time-dependent quantum phases

International Nuclear Information System (INIS)

Barut, A.O.; Bozic, M.; Klarsfeld, S.; Maric, Z.

1991-11-01

We have evaluated the exact (Pancharatnam) phase differences between the final state l ψ(t) > and various initial states for a spin 1/2-particle in a rotating magnetic field B(t). For the initial states l n; B ef (0) >, which are eigenstates of the spin component along the direction of the initial effective field B ef (0), the exact phase has an energy dependent part, and an energy independent part. It is shown that these states l n; B ef (0) > are cyclic and their corresponding Aharonov-Anandan phases are evaluated. In the adiabatic limit we discuss different choices of time-dependent bases and the relationship between the exact phase, the Born-Fock-Schiff phase and Berry's phase. We propose experiments (neutron) to verify separately the exact and the adiabatic evolution laws, as well as to measure the adiabatic phases associated with different choices of time-dependent basis vectors. (author). 37 refs, 5 figs, 1 tab

Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms

Directory of Open Access Journals (Sweden)

Stefan Bittner

2015-07-01

Full Text Available Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (TASK2; KCNK5 channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K2P5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K2P5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K2P5.1 knockout (K2P5.1−/− mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K2P5.1−/− mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K2P3.1 and KV1.3 seems to counterbalance the deletion of K2P5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K2P5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K2P5.1-targeting drugs.

A study of the (p,pn) reaction on 1p shell nuclei at 46 MeV

International Nuclear Information System (INIS)

Miller, C.A.

1974-01-01

The (p,pn) reaction on four 1p shell nuclei, 6 Li, 9 Be, 13 C and 12 C, as well as the 6 Li(p,2p) reaction, have been studied at 46 MeV. The 6 Li(p,pn) cross section was found to be approximately four times that for (p,2p) and to have a very different angular dependence. Both reactions show the s-state admixture in 6 Li observed with (p,2p) at higher energies. For all of the target nuclei, the cross sections have features that cannot be fitted by a renormalized Plane Wave Impulse Approximation (PWIA) calculation. A zero range distorted wave calculation was found to be in only fair agreement with the 9 Be and 13 C data. The overall magnitudes of the results of the calculation were found to be very sensitive to the RMS radii of the bound state wave functions of the knocked-out neutrons. (author)

Existence of time-dependent density-functional theory for open electronic systems: time-dependent holographic electron density theorem.

Science.gov (United States)

Zheng, Xiao; Yam, ChiYung; Wang, Fan; Chen, GuanHua

2011-08-28

We present the time-dependent holographic electron density theorem (TD-HEDT), which lays the foundation of time-dependent density-functional theory (TDDFT) for open electronic systems. For any finite electronic system, the TD-HEDT formally establishes a one-to-one correspondence between the electron density inside any finite subsystem and the time-dependent external potential. As a result, any electronic property of an open system in principle can be determined uniquely by the electron density function inside the open region. Implications of the TD-HEDT on the practicality of TDDFT are also discussed.

High-level heterologous production and functional expression of the sec-dependent enterocin P from Enterococcus faecium P13 in Lactococcus lactis

NARCIS (Netherlands)

Gutierrez, Jorge; Larsen, Rasmus; Cintas, Luis M.; Kok, Jan; Hernandez, Pablo E.

Enterocin P (EntP), a sec-dependent bacteriocin from Enterococcus faecium P13, was produced by Lactococcus lactis. The EntP structural gene (entP) with or without the EntP immunity gene (entiP) was cloned in (1), plasmid pMG36c under control of the lactococcal constitutive promoter P-32, (2) in

Anomalous pH-Dependent Nanofluidic Salinity Gradient Power.

Science.gov (United States)

Yeh, Li-Hsien; Chen, Fu; Chiou, Yu-Ting; Su, Yen-Shao

2017-12-01

Previous studies on nanofluidic salinity gradient power (NSGP), where energy associated with the salinity gradient can be harvested with ion-selective nanopores, all suggest that nanofluidic devices having higher surface charge density should have higher performance, including osmotic power and conversion efficiency. In this manuscript, this viewpoint is challenged and anomalous counterintuitive pH-dependent NSGP behaviors are reported. For example, with equal pH deviation from its isoelectric point (IEP), the nanopore at pH IEP is shown to have smaller surface charge density but remarkably higher NSGP performance than that at pH > IEP. Moreover, for sufficiently low pH, the NSGP performance decreases with lowering pH (increasing nanopore charge density). As a result, a maximum osmotic power density as high as 5.85 kW m -2 can be generated along with a conversion efficiency of 26.3% achieved for a single alumina nanopore at pH 3.5 under a 1000-fold concentration ratio. Using the rigorous model with considering the surface equilibrium reactions on the pore wall, it is proved that these counterintuitive surface-charge-dependent NSGP behaviors result from the pH-dependent ion concentration polarization effect, which yields the degradation in effective concentration ratio across the nanopore. These findings provide significant insight for the design of next-generation, high-performance NSGP devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Alfalfa mosaic virus replicase proteins P1 and P2 interact and colocalize at the vacuolar membrane

NARCIS (Netherlands)

Heijden, van der M.W.; Carette, J.E.; Reinhoud, P.J.; Haegi, A.; Bol, J.F.

2001-01-01

Replication of Alfalfa mosaic virus (AMV) RNAs depends on the virus-encoded proteins P1 and P2. P1 contains methyltransferase- and helicase-like domains, and P2 contains a polymerase-like domain. Coimmunoprecipitation experiments revealed an interaction between in vitro translated-P1 and P2 and

Progress Report on Alloy 617 Time Dependent Allowables

Energy Technology Data Exchange (ETDEWEB)

Wright, Julie Knibloe [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-06-01

Time dependent allowable stresses are required in the ASME Boiler and Pressure Vessel Code for design of components in the temperature range where time dependent deformation (i.e., creep) is expected to become significant. There are time dependent allowable stresses in Section IID of the Code for use in the non-nuclear construction codes, however, there are additional criteria that must be considered in developing time dependent allowables for nuclear components. These criteria are specified in Section III NH. St is defined as the lesser of three quantities: 100% of the average stress required to obtain a total (elastic, plastic, primary and secondary creep) strain of 1%; 67% of the minimum stress to cause rupture; and 80% of the minimum stress to cause the initiation of tertiary creep. The values are reported for a range of temperatures and for time increments up to 100,000 hours. These values are determined from uniaxial creep tests, which involve the elevated temperature application of a constant load which is relatively small, resulting in deformation over a long time period prior to rupture. The stress which is the minimum resulting from these criteria is the time dependent allowable stress St. In this report data from a large number of creep and creep-rupture tests on Alloy 617 are analyzed using the ASME Section III NH criteria. Data which are used in the analysis are from the ongoing DOE sponsored high temperature materials program, form Korea Atomic Energy Institute through the Generation IV VHTR Materials Program and historical data from previous HTR research and vendor data generated in developing the alloy. It is found that the tertiary creep criterion determines St at highest temperatures, while the stress to cause 1% total strain controls at low temperatures. The ASME Section III Working Group on Allowable Stress Criteria has recommended that the uncertainties associated with determining the onset of tertiary creep and the lack of significant

The Spin-dependent Structure Function of the Proton $g_{1}^p$ and a Test of the Bjorken Sum Rule

CERN Document Server

Alekseev, M.G.; Alexandrov, Yu.; Alexeev, G.D.; Amoroso, A.; Austregesilo, A.; Badelek, B.; Balestra, F.; Ball, J.; Barth, J.; Baum, G.; Bedfer, Y.; Bernhard, J.; Bertini, R.; Bettinelli, M.; Birsa, R.; Bisplinghoff, J.; Bordalo, P.; Bradamante, F.; Bravar, A.; Bressan, A.; Brona, G.; Burtin, E.; Bussa, M.P.; Chaberny, D.; Cotic, D.; Chiosso, M.; Chung, S.U.; Cicuttin, A.; Colantoni, M.; Crespo, M.L.; Dalla Torre, S.; Das, S.; Dasgupta, S.S.; Denisov, O.Yu.; Dhara, L.; Diaz, V.; Donskov, S.V.; Doshita, N.; Duic, V.; Dunnweber, W.; Efremov, A.; El Alaoui, A.; Eversheim, P.D.; Eyrich, W.; Faessler, M.; Ferrero, A.; Filin, A.; Finger, M.; Finger, M., Jr.; Fischer, H.; Franco, C.; Friedrich, J.M.; Garfagnini, R.; Gautheron, F.; Gavrichtchouk, O.P.; Gazda, R.; Gerassimov, S.; Geyer, R.; Giorgi, M.; Gnesi, I.; Gobbo, B.; Goertz, S.; Grabmuller, S.; Grasso, A.; Grube, B.; Gushterski, R.; Guskov, A.; Haas, F.; von Harrach, D.; Hasegawa, T.; Heinsius, F.H.; Hermann, R.; Herrmann, F.; Hess, C.; Hinterberger, F.; Horikawa, N.; Hoppner, Ch.; d'Hose, N.; Ilgner, C.; Ishimoto, S.; Ivanov, O.; Ivanshin, Yu.; Iwata, T.; Jahn, R.; Jasinski, P.; Jegou, G.; Joosten, R.; Kabuss, E.; Kafer, W.; Kang, D.; Ketzer, B.; Khaustov, G.V.; Khokhlov, Yu.A.; Kisselev, Yu.; Klein, F.; Klimaszewski, K.; Koblitz, S.; Koivuniemi, J.H.; Kolosov, V.N.; Kondo, K.; Konigsmann, K.; Konopka, R.; Konorov, I.; Konstantinov, V.F.; Korzenev, A.; Kotzinian, A.M.; Kouznetsov, O.; Kowalik, K.; Kramer, M.; Kral, A.; Kroumchtein, Z.V.; Kuhn, R.; Kunne, F.; Kurek, K.; Lauser, L.; Le Goff, J.M.; Lednev, A.A.; Lehmann, A.; Levorato, S.; Lichtenstadt, J.; Liska, T.; Maggiora, A.; Maggiora, M.; Magnon, A.; Mallot, G.K.; Mann, A.; Marchand, C.; Marroncle, J.; Martin, A.; Marzec, J.; Massmann, F.; Matsuda, T.; Maximov, A.N.; Meyer, W.; Michigami, T.; Mikhailov, Yu.V.; Moinester, M.A.; Mutter, A.; Nagaytsev, A.; Nagel, T.; Nassalski, J.; Negrini, T.; Nerling, F.; Neubert, S.; Neyret, D.; Nikolaenko, V.I.; Nunes, A.S.; Olshevsky, A.G.; Ostrick, M.; Padee, A.; Panknin, R.; Panzieri, D.; Parsamyan, B.; Paul, S.; Pawlukiewicz-Kaminska, B.; Perevalova, E.; Pesaro, G.; Peshekhonov, D.V.; Piragino, G.; Platchkov, S.; Pochodzalla, J.; Polak, J.; Polyakov, V.A.; Pontecorvo, G.; Pretz, J.; Quintans, C.; Rajotte, J.F.; Ramos, S.; Rapatsky, V.; Reicherz, G.; Richter, A.; Robinet, F.; Rocco, E.; Rondio, E.; Ryabchikov, D.I.; Samoylenko, V.D.; Sandacz, A.; Santos, H.; Sapozhnikov, M.G.; Sarkar, S.; Savin, I.A.; Sbrizzai, G.; Schiavon, P.; Schill, C.; Schmitt, L.; Schluter, T.; Schopferer, S.; Schroder, W.; Shevchenko, O.Yu.; Siebert, H.W.; Silva, L.; Sinha, L.; Sissakian, A.N.; Slunecka, M.; Smirnov, G.I.; Sosio, S.; Sozzi, F.; Srnka, A.; Stolarski, M.; Sulc, M.; Sulej, R.; Takekawa, S.; Tessaro, S.; Tessarotto, F.; Teufel, A.; Tkatchev, L.G.; Uhl, S.; Uman, I.; Virius, M.; Vlassov, N.V.; Vossen, A.; Weitzel, Q.; Windmolders, R.; Wislicki, W.; Wollny, H.; Zaremba, K.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.; Zhao, J.; Zhuravlev, N.; Zvyagin, A.

2010-01-01

The inclusive double-spin asymmetry, $A_{1}^{p}$, has been measured at COMPASS in deepinelastic polarised muon scattering off a large polarised NH3 target. The data, collected in the year 2007, cover the range Q2 > 1 (GeV/c)^2, 0.004 < x < 0.7 and improve the statistical precision of g_{1}^{p}(x) by a factor of two in the region x < 0.02. The new proton asymmetries are combined with those previously published for the deuteron to extract the non-singlet spin-dependent structure function g_1^NS(x,Q2). The isovector quark density, Delta_q_3(x,Q2), is evaluated from a NLO QCD fit of g_1^NS. The first moment of Delta_q3 is in good agreement with the value predicted by the Bjorken sum rule and corresponds to a ratio of the axial and vector coupling constants g_A/g_V = 1.28+-0.07(stat)+-0.10(syst).

Two-dimensional time dependent Riemann solvers for neutron transport

International Nuclear Information System (INIS)

Brunner, Thomas A.; Holloway, James Paul

2005-01-01

A two-dimensional Riemann solver is developed for the spherical harmonics approximation to the time dependent neutron transport equation. The eigenstructure of the resulting equations is explored, giving insight into both the spherical harmonics approximation and the Riemann solver. The classic Roe-type Riemann solver used here was developed for one-dimensional problems, but can be used in multidimensional problems by treating each face of a two-dimensional computation cell in a locally one-dimensional way. Several test problems are used to explore the capabilities of both the Riemann solver and the spherical harmonics approximation. The numerical solution for a simple line source problem is compared to the analytic solution to both the P 1 equation and the full transport solution. A lattice problem is used to test the method on a more challenging problem

One-dimensional time-dependent fluid model of a very high density low-pressure inductively coupled plasma

Science.gov (United States)

Chaplin, Vernon H.; Bellan, Paul M.

2015-12-01

A time-dependent two-fluid model has been developed to understand axial variations in the plasma parameters in a very high density (peak ne≳ 5 ×1019 m-3 ) argon inductively coupled discharge in a long 1.1 cm radius tube. The model equations are written in 1D with radial losses to the tube walls accounted for by the inclusion of effective particle and energy sink terms. The ambipolar diffusion equation and electron energy equation are solved to find the electron density ne(z ,t ) and temperature Te(z ,t ) , and the populations of the neutral argon 4s metastable, 4s resonant, and 4p excited state manifolds are calculated to determine the stepwise ionization rate and calculate radiative energy losses. The model has been validated through comparisons with Langmuir probe ion saturation current measurements; close agreement between the simulated and measured axial plasma density profiles and the initial density rise rate at each location was obtained at pA r=30 -60 mTorr . We present detailed results from calculations at 60 mTorr, including the time-dependent electron temperature, excited state populations, and energy budget within and downstream of the radiofrequency antenna.

LHCSR1 induces a fast and reversible pH-dependent fluorescence quenching in LHCII in Chlamydomonas reinhardtii cells.

Science.gov (United States)

Dinc, Emine; Tian, Lijin; Roy, Laura M; Roth, Robyn; Goodenough, Ursula; Croce, Roberta

2016-07-05

To avoid photodamage, photosynthetic organisms are able to thermally dissipate the energy absorbed in excess in a process known as nonphotochemical quenching (NPQ). Although NPQ has been studied extensively, the major players and the mechanism of quenching remain debated. This is a result of the difficulty in extracting molecular information from in vivo experiments and the absence of a validation system for in vitro experiments. Here, we have created a minimal cell of the green alga Chlamydomonas reinhardtii that is able to undergo NPQ. We show that LHCII, the main light harvesting complex of algae, cannot switch to a quenched conformation in response to pH changes by itself. Instead, a small amount of the protein LHCSR1 (light-harvesting complex stress related 1) is able to induce a large, fast, and reversible pH-dependent quenching in an LHCII-containing membrane. These results strongly suggest that LHCSR1 acts as pH sensor and that it modulates the excited state lifetimes of a large array of LHCII, also explaining the NPQ observed in the LHCSR3-less mutant. The possible quenching mechanisms are discussed.

Poly(aspartic acid) with adjustable pH-dependent solubility.

Science.gov (United States)

Németh, Csaba; Gyarmati, Benjámin; Abdullin, Timur; László, Krisztina; Szilágyi, András

2017-02-01

Poly(aspartic acid) (PASP) derivatives with adjustable pH-dependent solubility were synthesized and characterized to establish the relationship between their structure and solubility in order to predict their applicability as a basic material for enteric coatings. Polysuccinimide, the precursor of PASP, was modified with short chain alkylamines, and the residual succinimide rings were subsequently opened to prepare the corresponding PASP derivatives. Study of the effect of the type and concentration of the side groups on the pH-dependent solubility of PASP showed that solubility can be adjusted by proper selection of the chemical structure. The Henderson-Hasselbalch (HH) and the extended HH equations were used to describe the pH-dependent solubility of the polymers quantitatively. The estimate provided by the HH equation is poor, but an accurate description of the pH-dependent solubility can be found with the extended HH equation. The dissolution rate of a polymer film prepared from a selected PASP derivative was determined by fluorescence marking. The film dissolved rapidly when the pH was increased above its pK a . Cellular viability tests show that PASP derivatives are non-toxic to a human cell line. These polymers are thus of great interest as starting materials for enteric coatings. Poly(amino acid) type biocompatible polymers were synthesized for future use as pharmaceutical film coatings. To this end, we tailored the pH-dependent solubility of poly(aspartic acid) (PASP). It was found that both the solubility and the pK a values of the modified PASP depended strongly on composition. Fluorescent marking was used to characterize the dissolution of a chosen PASP derivative. In acidic media only a negligible amount of the polymer dissolved, but dissolution was very fast and complete at the pH values that prevail in the small intestine. As a consequence, enteric coatings based on such PASP derivatives may be used for drug delivery in the gastrointestinal tract

Propagators for the time-dependent Kohn-Sham equations

International Nuclear Information System (INIS)

Castro, Alberto; Marques, Miguel A. L.; Rubio, Angel

2004-01-01

In this paper we address the problem of the numerical integration of the time-dependent Schroedinger equation i∂ t φ=Hφ. In particular, we are concerned with the important case where H is the self-consistent Kohn-Sham Hamiltonian that stems from time-dependent functional theory. As the Kohn-Sham potential depends parametrically on the time-dependent density, H is in general time dependent, even in the absence of an external time-dependent field. The present analysis also holds for the description of the excited state dynamics of a many-electron system under the influence of arbitrary external time-dependent electromagnetic fields. Our discussion is separated in two parts: (i) First, we look at several algorithms to approximate exp(A), where A is a time-independent operator [e.g., A=-iΔtH(τ) for some given time τ]. In particular, polynomial expansions, projection in Krylov subspaces, and split-operator methods are investigated. (ii) We then discuss different approximations for the time-evolution operator, such as the midpoint and implicit rules, and Magnus expansions. Split-operator techniques can also be modified to approximate the full time-dependent propagator. As the Hamiltonian is time dependent, problem (ii) is not equivalent to (i). All these techniques have been implemented and tested in our computer code OCTOPUS, but can be of general use in other frameworks and implementations

Lactobacillus casei triggers a TLR mediated RACK-1 dependent p38 MAPK pathway in Caenorhabditis elegans to resist Klebsiella pneumoniae infection.

Science.gov (United States)

Kamaladevi, Arumugam; Balamurugan, Krishnaswamy

2016-07-13

In the present study, the effect of Lactic Acid Bacteria (LAB) was investigated at the molecular level using the model organism Caenorhabditis elegans against Klebsiella pneumoniae. Out of the 13 LAB screened, Lactobacillus casei displayed excellent protective efficacy by prolonging the survival of K. pneumoniae-infected nematodes. Pretreatment with L. casei significantly decreased bacterial colonization and rescued K. pneumoniae-infected C. elegans from various physiological impairments. The concomitant upregulation of key immune genes that regulate the TLR, RACK-1 as well as the p38 MAPK pathway rather than the IIS and ERK pathway suggested that the plausible immunomodulatory mechanism of L. casei could be by triggering the TLR, RACK-1 and p38 MAPK pathway. Furthermore, the hyper-susceptibility of L. casei treated loss-of-function mutants of the tol-1, RACK-1 and p38 MAPK pathway (sek-1 and pmk-1) to K. pneumoniae infection and gene expression analysis suggested that L. casei triggered a TLR mediated RACK-1 dependent p38 MAPK pathway to increase host resistance and protect nematodes against K. pneumoniae infection.

The Cyclin-Dependent Kinase Ortholog pUL97 of Human Cytomegalovirus Interacts with Cyclins

Directory of Open Access Journals (Sweden)

Laura Graf

2013-12-01

Full Text Available The human cytomegalovirus (HCMV-encoded protein kinase, pUL97, is considered a cyclin-dependent kinase (CDK ortholog, due to shared structural and functional characteristics. The primary mechanism of CDK activation is binding to corresponding cyclins, including cyclin T1, which is the usual regulatory cofactor of CDK9. This study provides evidence of direct interaction between pUL97 and cyclin T1 using yeast two-hybrid and co-immunoprecipitation analyses. Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin T1 in subnuclear compartments, most pronounced in viral replication centres. The distribution patterns of pUL97 and cyclin T1 were independent of HCMV strain and host cell type. The sequence domain of pUL97 responsible for the interaction with cyclin T1 was between amino acids 231–280. Additional co-immunoprecipitation analyses showed cyclin B1 and cyclin A as further pUL97 interaction partners. Investigation of the pUL97-cyclin T1 interaction in an ATP consumption assay strongly suggested phosphorylation of pUL97 by the CDK9/cyclin T1 complex in a substrate concentration-dependent manner. This is the first demonstration of interaction between a herpesviral CDK ortholog and cellular cyclins.

Chemical sensitivity of InP/In0.48Ga0.52P surface quantum dots studied by time-resolved photoluminescence spectroscopy

International Nuclear Information System (INIS)

De Angelis, Roberta; Casalboni, Mauro; De Matteis, Fabio; Hatami, Fariba; Masselink, William T.; Zhang, Hong; Prosposito, Paolo

2015-01-01

InP/InGaP surface quantum dots represent an attractive material for optical chemical sensors since they show a remarkable near infra-red emission at room temperature, whose intensity increases rapidly and reversibly depending on the composition of the environmental atmosphere. We show here their emission properties by time resolved photoluminescence spectroscopy investigation. Photoluminescence transients with and without chemical solvent vapours (methanol, clorophorm, acetone and water) were fitted with a 3-exponential decay law with times of about 0.5 ns, 2 ns and 7 ns. The measurements revealed a weak effect on clorophorm, acetone and water, while the initial decay time of InP surface quantum dots increases (up to 15%) upon methanol vapour exposure, indicating that the organic molecules efficiently saturate QD non-radiative surface states. - Highlights: • InP SQDs emission depends on the presence of solvent vapours in the atmosphere. • TR photoluminescence transients were fitted with a 3-exponential decay law. • The initial decay time increases (up to 15%) upon methanol vapour exposure. • Organic molecules efficiently saturate QD non-radiative surface states.

Time-Dependent Moment Tensors of the First Four Source Physics Experiments (SPE) Explosions

Science.gov (United States)

Yang, X.

2015-12-01

We use mainly vertical-component geophone data within 2 km from the epicenter to invert for time-dependent moment tensors of the first four SPE explosions: SPE-1, SPE-2, SPE-3 and SPE-4Prime. We employ a one-dimensional (1D) velocity model developed from P- and Rg-wave travel times for Green's function calculations. The attenuation structure of the model is developed from P- and Rg-wave amplitudes. We select data for the inversion based on the criterion that they show consistent travel times and amplitude behavior as those predicted by the 1D model. Due to limited azimuthal coverage of the sources and the mostly vertical-component-only nature of the dataset, only long-period, diagonal components of the moment tensors are well constrained. Nevertheless, the moment tensors, particularly their isotropic components, provide reasonable estimates of the long-period source amplitudes as well as estimates of corner frequencies, albeit with larger uncertainties. The estimated corner frequencies, however, are consistent with estimates from ratios of seismogram spectra from different explosions. These long-period source amplitudes and corner frequencies cannot be fit by classical P-wave explosion source models. The results motivate the development of new P-wave source models suitable for these chemical explosions. To that end, we fit inverted moment-tensor spectra by modifying the classical explosion model using regressions of estimated source parameters. Although the number of data points used in the regression is small, the approach suggests a way for the new-model development when more data are collected.

Physics in space-time with scale-dependent metrics

Science.gov (United States)

Balankin, Alexander S.

2013-10-01

We construct three-dimensional space Rγ3 with the scale-dependent metric and the corresponding Minkowski space-time Mγ,β4 with the scale-dependent fractal (DH) and spectral (DS) dimensions. The local derivatives based on scale-dependent metrics are defined and differential vector calculus in Rγ3 is developed. We state that Mγ,β4 provides a unified phenomenological framework for dimensional flow observed in quite different models of quantum gravity. Nevertheless, the main attention is focused on the special case of flat space-time M1/3,14 with the scale-dependent Cantor-dust-like distribution of admissible states, such that DH increases from DH=2 on the scale ≪ℓ0 to DH=4 in the infrared limit ≫ℓ0, where ℓ0 is the characteristic length (e.g. the Planck length, or characteristic size of multi-fractal features in heterogeneous medium), whereas DS≡4 in all scales. Possible applications of approach based on the scale-dependent metric to systems of different nature are briefly discussed.

On the time-dependent Aharonov–Bohm effect

Directory of Open Access Journals (Sweden)

Jian Jing

2017-11-01

Full Text Available The Aharonov–Bohm effect in the background of a time-dependent vector potential is re-examined for both non-relativistic and relativistic cases. Based on the solutions to the Schrodinger and Dirac equations which contain the time-dependent magnetic vector potential, we find that contrary to the conclusions in a recent paper (Singleton and Vagenas 2013 [4], the interference pattern will be altered with respect to time because of the time-dependent vector potential.

Time-dependent reliability analysis of flood defences

International Nuclear Information System (INIS)

Buijs, F.A.; Hall, J.W.; Sayers, P.B.; Gelder, P.H.A.J.M. van

2009-01-01

This paper describes the underlying theory and a practical process for establishing time-dependent reliability models for components in a realistic and complex flood defence system. Though time-dependent reliability models have been applied frequently in, for example, the offshore, structural safety and nuclear industry, application in the safety-critical field of flood defence has to date been limited. The modelling methodology involves identifying relevant variables and processes, characterisation of those processes in appropriate mathematical terms, numerical implementation, parameter estimation and prediction. A combination of stochastic, hierarchical and parametric processes is employed. The approach is demonstrated for selected deterioration mechanisms in the context of a flood defence system. The paper demonstrates that this structured methodology enables the definition of credible statistical models for time-dependence of flood defences in data scarce situations. In the application of those models one of the main findings is that the time variability in the deterioration process tends to be governed the time-dependence of one or a small number of critical attributes. It is demonstrated how the need for further data collection depends upon the relevance of the time-dependence in the performance of the flood defence system.

Critique of the foundations of time-dependent density-functional theory

International Nuclear Information System (INIS)

Schirmer, J.; Dreuw, A.

2007-01-01

The general expectation that, in principle, the time-dependent density-functional theory (TDDFT) is an exact formulation of the time evolution of an interacting N-electron system is critically reexamined. It is demonstrated that the previous TDDFT foundation, resting on four theorems by Runge and Gross (RG) [Phys. Rev. Lett. 52, 997 (1984)], is invalid because undefined phase factors corrupt the RG action integral functionals. Our finding confirms much of a previous analysis by van Leeuwen [Int. J. Mod. Phys. B 15, 1969 (2001)]. To analyze the RG theorems and other aspects of TDDFT, an utmost simplification of the Kohn-Sham (KS) concept has been introduced, in which the ground-state density is obtained from a single KS equation for one spatial (spinless) orbital. The time-dependent (TD) form of this radical Kohn-Sham (rKS) scheme, which has the same validity status as the ordinary KS version, has proved to be a valuable tool for analysis. The rKS concept is used to clarify also the alternative nonvariational formulation of TD KS theory. We argue that it is just a formal theory, allowing one to reproduce but not predict the time development of the exact density of the interacting N-electron system. Besides the issue of the formal exactness of TDDFT, it is shown that both the static and time-dependent KS linear response equations neglect the particle-particle (p-p) and hole-hole (h-h) matrix elements of the perturbing operator. For a local (multiplicative) operator this does not lead to a loss of information due to a remarkable general property of local operators. Accordingly, no logical inconsistency arises with respect to DFT, because DFT requires any external potential to be local. For a general nonlocal operator the error resulting from the neglected matrix elements is of second order in the electronic repulsion

Pregnane X receptor-dependent induction of the CYP3A4 gene by o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane.

Science.gov (United States)

Medina-Díaz, Irma M; Arteaga-Illán, Georgina; de León, Mario Bermudez; Cisneros, Bulmaro; Sierra-Santoyo, Adolfo; Vega, Libia; Gonzalez, Frank J; Elizondo, Guillermo

2007-01-01

CYP3A4, the predominant cytochrome P450 (P450) expressed in human liver and intestine, contributes to the metabolism of approximately half the drugs in clinical use today. CYP3A4 catalyzes the 6beta-hydroxylation of a number of steroid hormones and is involved in the bioactivation of environmental procarcinogens. The expression of CYP3A4 is affected by several stimuli, including environmental factors such as insecticides and pesticides. The o,p'-1,1,1,-trichloro-2,2-bis (p-chlorophenyl)ethane (DDT) isomer of DDT comprises approximately 20% of technical grade DDT, which is an organochloride pesticide. We have recently shown that o,p'-DDT exposure increases CYP3A4 mRNA levels in HepG2 cells. To determine the mechanism by which o,p'-DDT induces CYP3A4 expression, transactivation and electrophoretic mobility shift assays were carried out, revealing that o,p'-DDT activates the CYP3A4 gene promoter through the pregnane X receptor (PXR). CYP3A4 gene promoter activation resulted in both an increase in CYP3A4 mRNA levels and an increase in the total CYP3A4 activity in HepG2 cells. We also observed induction of CYP3A4 and mouse Cyp3a11 mRNA in the intestine of CYP3A4-transgenic mice after exposure to 1 mg/kg o,p'-DDT. At higher doses, a decrease of CYP3A4 inducibility was observed together with an increase in levels of interleukin 6 mRNA, a proinflammatory cytokine that strongly represses CYP3A4 transcription. The present study indicates that regulation of other genes under PXR control may be altered by o,p'-DDT exposure.

Theoretical analysis of time-dependent neutron spectra in bulk assemblies

International Nuclear Information System (INIS)

Akimoto, Tadashi; Ogawa, Yuichi; Togawa, Orihiko.

1988-01-01

Time-dependent neutron spectra in an iron assembly and in a graphite assembly are obtained with the one-dimensional S N calculation, in order an attempt to investigate the availability of these spectra to the benchmark test by the LINAC-TOF method for evaluation of nuclear data and numerical methods. The group constants are taken from the JAERI FAST SET Version 1, 2 and the ABBN SET. It was demonstrated by a sensitivity test that the time-dependent neutron spectra are sensitive to changes in the inelastic scattering cross section data in the iron assembly and to changes in the elastic scattering cross section data in the graphite assembly. Moreover, it is shown that the time-dependent spectra in the graphite assembly are sensitive to the group structure. Because some information about the neutron transport phenomena which has not been obtained in the stationary spectra is observed in the time-dependent spectra, the availability of the benchmark test based on the time-dependent spectra is indicated from the theoretical analysis. (author)

Energy-dependent inversion of p+16O scattering data

International Nuclear Information System (INIS)

Cooper, S.G.

1997-01-01

A fast iterative procedure is developed to determine potentials by inversion from elastic cross section, analysing powers and reaction cross-section measurements covering a wide energy range. The procedure incorporates both energy and parity dependence. The method is applied to extensive p+ 16 O scattering data for an energy range from 27.3 to 46.1 MeV, giving a solution which simultaneously reproduces the data at all energies. The wide angle data is well reproduced by including parity dependence and a linear energy dependence is established for the real potential, including the parity-dependent component. The real terms agree qualitatively with potentials derived from the single channel RGM, but the central and spin-orbit imaginary components have distinct features strongly suggestive of further non-local contributions, possibly arising from channel coupling. The large data set is found essential to reduce the potential ambiguities present when fitting scattering data. (orig.)

Integrable Time-Dependent Quantum Hamiltonians

Science.gov (United States)

Sinitsyn, Nikolai A.; Yuzbashyan, Emil A.; Chernyak, Vladimir Y.; Patra, Aniket; Sun, Chen

2018-05-01

We formulate a set of conditions under which the nonstationary Schrödinger equation with a time-dependent Hamiltonian is exactly solvable analytically. The main requirement is the existence of a non-Abelian gauge field with zero curvature in the space of system parameters. Known solvable multistate Landau-Zener models satisfy these conditions. Our method provides a strategy to incorporate time dependence into various quantum integrable models while maintaining their integrability. We also validate some prior conjectures, including the solution of the driven generalized Tavis-Cummings model.

Underlying thermodynamics of pH-dependent allostery.

Science.gov (United States)

Di Russo, Natali V; Martí, Marcelo A; Roitberg, Adrian E

2014-11-13

Understanding the effects of coupling protein protonation and conformational states is critical to the development of drugs targeting pH sensors and to the rational engineering of pH switches. In this work, we address this issue by performing a comprehensive study of the pH-regulated switch from the closed to the open conformation in nitrophorin 4 (NP4) that determines its pH-dependent activity. Our calculations show that D30 is the only amino acid that has two significantly different pKas in the open and closed conformations, confirming its critical role in regulating pH-dependent behavior. In addition, we describe the free-energy landscape of the conformational change as a function of pH, obtaining accurate estimations of free-energy barriers and equilibrium constants using different methods. The underlying thermodynamic model of the switch workings suggests the possibility of tuning the observed pKa only through the conformational equilibria, keeping the same conformation-specific pKas, as evidenced by the proposed K125L mutant. Moreover, coupling between the protonation and conformational equilibria results in efficient regulation and pH-sensing around physiological pH values only for some combinations of protonation and conformational equilibrium constants, placing constraints on their possible values and leaving a narrow space for protein molecular evolution. The calculations and analysis presented here are of general applicability and provide a guide as to how more complex systems can be studied, offering insight into how pH-regulated allostery works of great value for designing drugs that target pH sensors and for rational engineering of pH switches beyond the common histidine trigger.

Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage

DEFF Research Database (Denmark)

Järås, Marcus; Johnels, Petra; Agerstam, Helena

2009-01-01

OBJECTIVE: The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. MATERIALS AND METHODS: We investigated...... and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. RESULTS: Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells...... and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under...

First measurement of the helicity dependence for the γp→pπ reaction

International Nuclear Information System (INIS)

Ahrens, J.; Arends, H.J.; Beck, R.; Heid, E.; Jahn, O.; Jennewein, P.; Lang, M.; Martinez-Fabregate, M.; Rost, M.; Tamas, G.; Thomas, A.; Altieri, S.; Panzeri, A.; Pinelli, T.; Annand, J.R.M.; McGeorge, J.C.; Rosner, G.; Blackston, M.A.; Weller, H.R.; Bradtke, C.; Dutz, H.; Klein, F.; Rohlof, C.; Braghieri, A.; Pedroni, P.; Hose, N. d'; Fix, A.; Goertz, S.; Meyer, W.; Reicherz, G.; Grabmayr, P.; Hasegawa, S.; Iwata, T.; Holvoet, H.; Lannoy, B.; Ryckbosch, D.; Van de Vyver, R.; Horikawa, N.; Kondratiev, R.; Lisin, V.; Preobrajenski, I.; Rostomyan, T.; Schumacher, M.; Seitz, B.; Zapadtka, F.

2007-01-01

The helicity dependence of the total cross-section and the invariant-mass distributions in the (pπ ± ) and (π + π - ) final states for the γp→pπ + π - reaction have been measured for the first time at incident photon energies from 400 to 800 MeV. The measurement was performed with the large-acceptance detector DAPHNE at the tagged photon beam facility of the MAMI accelerator in Mainz. Although this channel is found to be predominantly excited by the intermediate production of a Δπ state, both the measured unpolarized and the helicity-dependent observables are generally not well described by the existing theoretical models. (orig.)

Exact solution of the time-dependent harmonic plus an inverse harmonic potential with a time-dependent electromagnetic field

International Nuclear Information System (INIS)

Yuece, Cem

2003-01-01

In this paper, the problem of the charged harmonic plus an inverse harmonic oscillator with time-dependent mass and frequency in a time-dependent electromagnetic field is investigated. It is reduced to the problem of the inverse harmonic oscillator with time-independent parameters and the exact wave function is obtained

Time dependent policy-based access control

DEFF Research Database (Denmark)

Vasilikos, Panagiotis; Nielson, Flemming; Nielson, Hanne Riis

2017-01-01

also on other attributes of the environment such as the time. In this paper, we use systems of Timed Automata to model distributed systems and we present a logic in which one can express time-dependent policies for access control. We show how a fragment of our logic can be reduced to a logic......Access control policies are essential to determine who is allowed to access data in a system without compromising the data's security. However, applications inside a distributed environment may require those policies to be dependent on the actual content of the data, the flow of information, while...... that current model checkers for Timed Automata such as UPPAAL can handle and we present a translator that performs this reduction. We then use our translator and UPPAAL to enforce time-dependent policy-based access control on an example application from the aerospace industry....

GABAergic activities control spike timing- and frequency-dependent long-term depression at hippocampal excitatory synapses

Directory of Open Access Journals (Sweden)

Makoto Nishiyama

2010-06-01

Full Text Available GABAergic interneuronal network activities in the hippocampus control a variety of neural functions, including learning and memory, by regulating θ and γ oscillations. How these GABAergic activities at pre- and post-synaptic sites of hippocampal CA1 pyramidal cells differentially contribute to synaptic function and plasticity during their repetitive pre- and post-synaptic spiking at θ and γ oscillations is largely unknown. We show here that activities mediated by postsynaptic GABAARs and presynaptic GABABRs determine, respectively, the spike timing- and frequency-dependence of activity-induced synaptic modifications at Schaffer collateral-CA1 excitatory synapses. We demonstrate that both feedforward and feedback GABAAR-mediated inhibition in the postsynaptic cell controls the spike timing-dependent long-term depression of excitatory inputs (“e-LTD” at the θ frequency. We also show that feedback postsynaptic inhibition specifically causes e-LTD of inputs that induce small postsynaptic currents (<70 pA with LTP timing, thus enforcing the requirement of cooperativity for induction of long-term potentiation at excitatory inputs (“e-LTP”. Furthermore, under spike-timing protocols that induce e-LTP and e-LTD at excitatory synapses, we observed parallel induction of LTP and LTD at inhibitory inputs (“i-LTP” and “i-LTD” to the same postsynaptic cells. Finally, we show that presynaptic GABABR-mediated inhibition plays a major role in the induction of frequency-dependent e-LTD at α and β frequencies. These observations demonstrate the critical influence of GABAergic interneuronal network activities in regulating the spike timing and frequency dependences of long-term synaptic modifications in the hippocampus.

Diffractive Dijet Production in $\\bar{p}p$ Collisions at $\\sqrt{s}=1.96$ TeV

Energy Technology Data Exchange (ETDEWEB)

Aaltonen, T.; /Helsinki Inst. of Phys.; Albrow, M.; /Fermilab; Alvarez Gonzalez, B.; /Oviedo U. /Cantabria Inst. of Phys.; Amerio, S.; /INFN, Padua; Amidei, D.; /Michigan U.; Anastassov, A.; /Northwestern U. /Fermilab; Annovi, A.; /Frascati; Antos, J.; /Comenius U.; Apollinari, G.; /Fermilab; Appel, J.A.; /Fermilab; Arisawa, T.; /Waseda U. /Dubna, JINR

2012-06-01

We report on a study of diffractive dijet production in {bar p}p collisions at {radical}s = 1.96 TeV using the CDF II detector at the Fermilab Tevatron {bar p}p collider. A data sample from 310 pb{sup -1} of integrated luminosity collected by triggering on a high transverse energy jet, E{sub T}{sup jet}, in coincidence with a recoil antiproton detected in a Roman pot spectrometer is used to measure the ratio of single-diffractive to inclusive-dijet event rates as a function of x{sup {bar p}} of the interacting parton in the antiproton, the Bjorken-x, x{sub Bj}{sup {bar p}}, and a Q{sup 2} {approx} (E{sub T}{sup jet}){sup 2} in the ranges 10{sup -3} < x{sub Bj}{sup {bar p}} < 10{sup -1} and 10{sup 2} < Q{sup 2} < 10{sup 4} GeV{sup 2}, respectively. Results are presented for the region of {bar p}-momentum-loss fraction 0.03 < {zeta}{sub {bar p}} < 0.09 and a four-momentum transfer squared t{sub {bar p}} > -4 GeV{sup 2}. The t{sub {bar p}} dependence is measured as a function of Q{sup 2} and x{sub Bj}{sup {bar p}} and compared with that of inclusive single diffraction dissociation. We find weak x{sub Bj}{sup bar p}} and Q{sup 2} dependencies in the ratio of single diffractive to inclusive event rates, and no significant Q{sup 2} dependence in the diffractive t{sub {bar p}} distributions.

The excitation of an independent-particle gas - classical or quantal - by a time-dependent potential well

International Nuclear Information System (INIS)

Blocki, J.; Skalski, J.; Swiatecki, W.J.

1995-01-01

A systematic numerical investigation of the excitation of a classical or quantal gas of non-interacting particles in a time-dependent potential well is described. The excitation energy was followed in time for one oscillation around the sphere for six types of deformation: spheroidal shapes and Legendre polynomial ripples P 2 , P 3 , P 4 , P 5 , P 6 , with relative rms amplitudes of 0.2. Ten different speeds of deformation and eleven different values of the diffuseness of the potential well were studied, making altogether 660 quantal and 660 classical time-dependent calculations. In the upper range of deformation speeds the quantal results for the non-integrable shapes P 3 -P 6 agree approximately with the wall formula for dissipation, the deviations being largely accounted for by the wave-mechanical suppression factor of Koonin et al. For low deformation speeds the dissipation becomes dominated by one or two avoided level crossings. (orig.)

First measurement of time-dependent $C\\!P$ violation in $B^0_s \\to K^+K^-$ decays

CERN Document Server

Aaij, R; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves Jr, A A; Amato, S; Amerio, S; Amhis, Y; Anderlini, L; Anderson, J; Andreassen, R; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Baesso, C; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bauer, Th; Bay, A; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M -O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Burducea, I; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chen, P; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Couturier, B; Cowan, G A; Cowie, E; Craik, D C; Cunliffe, S; Currie, R; D'Ambrosio, C; David, P; David, P N Y; Davis, A; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Dogaru, M; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Falabella, A; Färber, C; Fardell, G; Farinelli, C; Farry, S; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Furcas, S; Furfaro, E; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garofoli, J; Garosi, P; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gorbounov, P; Gordon, H; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hartmann, T; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Hess, M; Hicheur, A; Hicks, E; Hill, D; Hoballah, M; Hombach, C; Hopchev, P; Hulsbergen, W; Hunt, P; Huse, T; Hussain, N; Hutchcroft, D; Hynds, D; Iakovenko, V; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Kenyon, I R; Ketel, T; Keune, A; Khanji, B; Kochebina, O; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J -P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Li Gioi, L; Liles, M; Lindner, R; Linn, C; Liu, B; Liu, G; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lu, H; Lucchesi, D; Luisier, J; Luo, H; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Maratas, J; Marconi, U; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martins Tostes, D; Martynov, A; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Maurice, E; Mazurov, A; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M -N; Molina Rodriguez, J; Monteil, S; Moran, D; Morawski, P; Mordà, A; Morello, M J; Mountain, R; Mous, I; Muheim, F; Müller, K; Muresan, R; Muryn, B; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neubert, S; Neufeld, N; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Nomerotski, A; Novoselov, A; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palczewski, T; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Phan, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Playfer, S; Plo Casasus, M; Polci, F; Polok, G; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Powell, A; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rademacker, J H; Rakotomiaramanana, B; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redford, S; Reid, M M; dos Reis, A C; Ricciardi, S; Richards, A; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Roberts, D A; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanmartin Sedes, B; Sannino, M; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schaack, P; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M -H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Senderowska, K; Sepp, I; Serra, N; Serrano, J; Seyfert, P; Shapkin, M; Shapoval, I; Shatalov, P; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, N A; Smith, E; Smith, J; Smith, M; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Straticiuc, M; Straumann, U; Subbiah, V K; Sun, L; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szumlak, T; T'Jampens, S; Teklishyn, M; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Urner, D; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Van Dijk, M; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; Waldi, R; Wallace, C; Wallace, R; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wicht, J; Wiechczynski, J; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Yang, Z; Young, R; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

2013-01-01

Direct and mixing-induced $C\\!P$-violating asymmetries in $B^0_s \\to K^+K^-$ decays are measured for the first time using a data sample of $pp$ collisions, corresponding to an integrated luminosity of $1.0~\\mathrm{fb}^{-1}$, collected with the LHCb detector at a centre-of-mass energy of $7~\\mathrm{TeV}$. The results are $C_{KK} = 0.14 \\pm 0.11 \\pm 0.03$ and $S_{KK} = 0.30 \\pm 0.12 \\pm 0.04$, where the first uncertainties are statistical and the second systematic. The corresponding quantities are also determined for $B^0 \\to \\pi^+\\pi^-$ decays to be $C_{\\pi\\pi} = -0.38 \\pm 0.15 \\pm 0.02$ and $S_{\\pi\\pi} = -0.71 \\pm 0.13 \\pm 0.02$, in good agreement with existing measurements.

Time dependent resonating Hartree-Bogoliubov theory

International Nuclear Information System (INIS)

Nishiyama, Seiya; Fukutome, Hideo.

1989-01-01

Very recently, we have developed a theory of excitations in superconducting Fermion systems with large quantum fluctuations that can be described by resonance of time dependent non-orthogonal Hartree-Bogoliubov (HB) wave functions with different correlation structures. We have derived a new kind of variation equation called the time dependent Resonating HB equation, in order to determine both the time dependent Resonating HB wave functions and coefficients of a superposition of the HB wave functions. Further we have got a new approximation for excitations from time dependent small fluctuations of the Resonating HB ground state, i.e., the Resonating HB RPA. The Res HB RPA equation is represented in a given single particle basis. It, however, has drawbacks that the constraints for the Res HB RPA amplitudes are not taken into account and the equation contains equations which are not independent. We shall derive another form of the Res HB RPA equation eliminating these drawbacks. The Res HB RPA gives a unified description of the vibrons and resonons and their interactions. (author)

The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1·Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1·Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells.

Science.gov (United States)

Lucato, Christina M; Halls, Michelle L; Ooms, Lisa M; Liu, Heng-Jia; Mitchell, Christina A; Whisstock, James C; Ellisdon, Andrew M

2015-08-21

The P-Rex (phosphatidylinositol (3,4,5)-trisphosphate (PIP3)-dependent Rac exchanger) family (P-Rex1 and P-Rex2) of the Rho guanine nucleotide exchange factors (Rho GEFs) activate Rac GTPases to regulate cell migration, invasion, and metastasis in several human cancers. The family is unique among Rho GEFs, as their activity is regulated by the synergistic binding of PIP3 and Gβγ at the plasma membrane. However, the molecular mechanism of this family of multi-domain proteins remains unclear. We report the 1.95 Å crystal structure of the catalytic P-Rex1 DH-PH tandem domain in complex with its cognate GTPase, Rac1 (Ras-related C3 botulinum toxin substrate-1). Mutations in the P-Rex1·Rac1 interface revealed a critical role for this complex in signaling downstream of receptor tyrosine kinases and G protein-coupled receptors. The structural data indicated that the PIP3/Gβγ binding sites are on the opposite surface and markedly removed from the Rac1 interface, supporting a model whereby P-Rex1 binding to PIP3 and/or Gβγ releases inhibitory C-terminal domains to expose the Rac1 binding site. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Exact results on diffusion in a piecewise linear potential with a time-dependent sink

Energy Technology Data Exchange (ETDEWEB)

Diwaker, E-mail: diwakerphysics@gmail.com [Central University of Himachal Pradesh, School of Physical and Astronomical Sciences (India); Chakraborty, Aniruddha [Indian Institute of Technology Mandi (India)

2016-02-15

The Smoluchowski equation with a time-dependent sink term is solved exactly. In this method, knowing the probability distribution P(0, s) at the origin, allows deriving the probability distribution P(x, s) at all positions. Exact solutions of the Smoluchowski equation are also provided in different cases where the sink term has linear, constant, inverse, and exponential variation in time.

Characterizing time-dependent mechanics in metallic MEMS

Directory of Open Access Journals (Sweden)

Geers M.G.D.

2010-06-01

Full Text Available Experiments for characterization of time-dependent material properties in free-standing metallic microelectromechanical system (MEMS pose challenges: e.g. fabrication and handling (sub-μm sized specimens, control and measurement of sub-μN loads and sub-μm displacements over long periods and various temperatures [1]. A variety of experimental setups have been reported each having their pros and cons. One example is a micro-tensile tester with an ingenious electro-static specimen gripping system [2] aiding simple specimen design giving good results at μN and sub-μm levels, but without in-situ full-field observations. Other progressive examples assimilate the specimen, MEMS actuators and load cells on a single chip [3,4] yielding significant results at nN and nm levels with in-situ TEM/SEM observability, though not without complications: complex load actuator/sensor calibration per chip, measures to reduce fabrication failure and unfeasible cofabrication on wafers with commercial metallic MEMS. This work aims to overcome these drawbacks by developing experimental methods with high sensitivity, precision and in-situ full-field observation capabilities. Moreover, these should be applicable to simple free-standing metallic MEMS that can be co-fabricated with commercial devices. These methods will then serve in systematic studies into size-effects in time-dependent material properties. First a numeric-experimental method is developed. It characterizes bending deformation of onwafer μm-sized aluminum cantilevers. A specially designed micro-clamp is used to mechanically apply a constant precise deflection of the beam (zres <50 nm for a prolonged period, see fig. 1. After this period, the deflection by the micro-clamp is removed. Full-field height maps with the ensuing deformation are measured over time with confocal optical profilometry (COP. This yields the tip deflection as function of time with ~3 nm precision, see fig.2. To extract material

Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells

International Nuclear Information System (INIS)

Lambert, Carine B.; Spire, Catherine; Claude, Nancy; Guillouzo, Andre

2009-01-01

Phenobarbital (PB) induces or represses a wide spectrum of genes in rodent liver. Much less is known about its effects in human liver. We used pangenomic cDNA microarrays to analyze concentration- and time-dependent gene expression profile changes induced by PB in the well-differentiated human HepaRG cell line. Changes in gene expression profiles clustered at specific concentration ranges and treatment times. The number of correctly annotated genes significantly modulated by at least three different PB concentration ranges (spanning 0.5 to 3.2 mM) at 20 h exposure amounted to 77 and 128 genes (p ≤ 0.01) at 2- and 1.8-fold filter changes, respectively. At low concentrations (0.5 and 1 mM), PB-responsive genes included the well-recognized CAR- and PXR-dependent responsive cytochromes P450 (CYP2B6, CYP3A4), sulfotransferase 2A1 and plasma transporters (ABCB1, ABCC2), as well as a number of genes critically involved in various metabolic pathways, including lipid (CYP4A11, CYP4F3), vitamin D (CYP24A1) and bile (CYP7A1 and CYP8B1) metabolism. At concentrations of 3.2 mM or higher after 20 h, and especially 48 h, increased cytotoxic effects were associated with disregulation of numerous genes related to oxidative stress, DNA repair and apoptosis. Primary human hepatocyte cultures were also exposed to 1 and 3.2 mM PB for 20 h and the changes were comparable to those found in HepaRG cells treated under the same conditions. Taken altogether, our data provide further evidence that HepaRG cells closely resemble primary human hepatocytes and provide new information on the effects of PB in human liver. These data also emphasize the importance of investigating dose- and time-dependent effects of chemicals when using toxicogenomic approaches

Time-dependent image potential at a metal surface

International Nuclear Information System (INIS)

Alducin, M.; Diez Muino, R.; Juaristi, J.I.

2003-01-01

Transient effects in the image potential induced by a point charge suddenly created in front of a metal surface are studied. The time evolution of the image potential is calculated using linear response theory. Two different time scales are defined: (i) the time required for the creation of the image potential and (ii) the time it takes to converge to its stationary value. Their dependence on the distance of the charge to the surface is discussed. The effect of the electron gas damping is also analyzed. For a typical metallic density, the order of magnitude of the creation time is 0.1 fs, whereas for a charge created close to the surface the convergence time is around 1-2 fs

Measurement of time-dependent $\\mathcal{CP}$ violation in charmless B decays at LHCb

CERN Document Server

INSPIRE-00258083

2013-01-01

In the following we present the measurements of time-dependent $\\mathcal{CP}$ violation in charmless B meson decays performed by LHCb analyzing the $p-p$ collision data collected at a center-of-mass energy of 7 TeV during the 2010 and 2011 LHC runs. In particular we will focus on the analysis of charmless two-body B decays where the direct and mixing-induced CP asymmetry terms of the $B^{0}\\to\\pi^{+}\\pi^{-}$ and $B_{s}^{0}\\to K^{+}K^{-}$ decays have been measured using 0.69 fb$^{-1}$ of data collected during 2011. The measurement of the branching ratio of the $B_{s}^{0}\\to K^{*0}\\bar{K}^{*0}$ decay, using 35 pb$^{-1}$ collected during 2010, is also reported. In the end we show the relative branching ratios of all the decay modes of $B_{(s)}^{0}\\to K_S h^{+}h^{\\prime -}$ decays (where $h^{(\\prime)}=\\pi,K$), measured analyzing 1 fb$^{-1}$ of data collected during 20 11.

Evaluation of Time-Dependent Behavior of Soils

DEFF Research Database (Denmark)

Augustesen, Anders; Liingaard, Morten; Lade, Poul V.

2004-01-01

The time-dependent behavior of soils has been investigated extensively through one-dimensional and triaxial test conditions. Most of the observations in literature have focused on the determination of the time-dependent behavior of clayey soils, whereas the reported experimental studies of granular...... situation for soils. That is whether the time-dependent behavior can be characterized as isotach or nonisotach. It seems that the isotach behavior is adequate for describing the time effects in clays in most situations. But for sand, the isotach description is inadequate. Further, the phenomenon...

Time-resolved pH/pO2 mapping with luminescent hybrid sensors.

Science.gov (United States)

Schröder, Claudia R; Polerecky, Lubos; Klimant, Ingo

2007-01-01

A method for simultaneous and referenced 2D mapping of pH and pO2 is described. The experimental setup combines a fast gateable CCD camera as detector, a LED as excitation light source and a single-layer sensor membrane as optical transducer. The planar optode comprises a lipophilic fluorescein derivative (lifetime approximately 5 ns) and platinum(II) mesotetrakis(pentafluorophenyl)porphyrin (approximately 70 micros in the absence of a quencher) immobilized in a hydrogel matrix. Depending on the fluorescent pH indicator, a pH transition in the physiological range (pH 6-pH 8) or in the near-basic region (pH 7-pH 9) can be achieved. The measuring scheme involves the time-resolved acquisition of images in three windows during a series of square-shaped excitation pulses. A method allowing the calculation of both parameters from these three images is presented. The pH/pO2 hybrid sensor incorporating the pH indicator 2',7'-dihexyl-5(6)-N-octadecyl-carboxamidofluorescein was characterized in detail. The pH and pO2 were determined with a maximum deviation of 0.03 pH unit and 6.5 hPa pO2, respectively, within the range of pH 7.6-pH 8.7 and 0-200 hPa pO2 in test measurements. The ionic strength (IS) cross-sensitivity was found to be relatively small (pH/IS pO2/IS pO2 images obtained in natural marine sediment are presented.

A multi scale approximation solution for the time dependent Boltzmann-transport equation

International Nuclear Information System (INIS)

Merk, B.

2004-03-01

once more compared with the exact analytical solution obtaining good agreement. In the next steps multiple scale expansion solutions are developed for the space-time dependent P 1 and P 3 transport equations for the homogenized cell and 2 delayed neutorn groups. These results are analysed versus the solution for the diffusion equation emphasizing the differences in the space-time structure between the time dependent diffusion- and transport solutions. The effect of the additional derivation terms in the transport equations can be observed during the analytical expansion process and in the graphical analysis of the differences between the solutions. The developed solution is tested for direct calculation of the time behaviour of single nodes in the framework of a nodal code and the results are compared. It is evident that the nature of the inserted perturbation has major impact on the discrepancy of the results compared to the reference nodal method. (orig.) [de

Gastric pH and residual volume after 1 and 2 h fasting time for clear fluids in children†.

Science.gov (United States)

Schmidt, A R; Buehler, P; Seglias, L; Stark, T; Brotschi, B; Renner, T; Sabandal, C; Klaghofer, R; Weiss, M; Schmitz, A

2015-03-01

Current guidelines suggest a fasting time of 2 h for clear fluids, which is often exceeded in clinical practice, leading to discomfort, dehydration and stressful anaesthesia induction to patients, especially in the paediatric population. Shorter fluid fasting might be a strategy to improve patient comfort but has not been investigated yet. This prospective clinical trial compares gastric pH and residual volume after 1 vs 2 h of preoperative clear fluid fasting. Children (1-16 yr, ASA I or II) undergoing elective procedures in general anaesthesia requiring tracheal intubation were randomized into group A with 60 min or B with 120 min preoperative clear fluid fasting. To determine gastric pH and residual volume, the gastric content was sampled in supine, left and right lateral patient position using an oro-gastric tube after intubation. Data are median (interquartile range) for group A or B (PPatient characteristic data were similar between the two groups, except for gender (46/33 males in group A/B; P=0.02). Despite significantly shorter fasting times for clear fluids in group A compared with group B (76/136 min; P<0.001), no significant difference was observed regarding gastric pH [1.43 (1.30-1.56)/1.44 (1.29-1.68), P=0.66] or residual volume [0.43 (0.21-0.84)/0.46 (0.19-0.78) ml kg(-1), P=0.47]. One hour clear fluid fasting does not alter gastric pH or residual volume significantly compared with 2 h fasting. The study was approved by the local ethics committee (KEK-ZH-Nr. 2011-0034) and registered with ClinicalTrials.gov (NCT01516775). © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Temperature dependent dynamics of DegP-trimer: A molecular dynamics study

Directory of Open Access Journals (Sweden)

Nivedita Rai

2015-01-01

Full Text Available DegP is a heat shock protein from high temperature requirement protease A family, which reacts to the environmental stress conditions in an ATP independent way. The objective of the present analysis emerged from the temperature dependent functional diversity of DegP between chaperonic and protease activities at temperatures below and above 28 °C, respectively. DegP is a multimeric protein and the minimal functional unit, DegP-trimer, is of great importance in understanding the DegP pathway. The structural aspects of DegP-trimer with respect to temperature variation have been studied using molecular dynamics simulations (for 100 ns and principal component analysis to highlight the temperature dependent dynamics facilitating its functional diversity. The DegP-trimer revealed a pronounced dynamics at both 280 and 320 K, when compared to the dynamics observed at 300 K. The LA loop is identified as the highly flexible region during dynamics and at extreme temperatures, the residues 46–80 of LA loop express a flip towards right (at 280 and left ( at 320 K with respect to the fixed β-sheet connecting the LA loop of protease for which Phe46 acts as one of the key residues. Such dynamics of LA loop facilitates inter-monomeric interaction with the PDZ1 domain of the neighbouring monomer and explains its active participation when DegP exists as trimer. Hence, the LA loop mediated dynamics of DegP-trimer is expected to provide further insight into the temperature dependent dynamics of DegP towards the understanding of its assembly and functional diversity in the presence of substrate.

Reconstructing time-dependent dynamics

OpenAIRE

Clemson, Philip; Lancaster, Gemma; Stefanovska, Aneta

2016-01-01

The usefulness of the information extracted from biomedical data relies heavily on the underlying theory of the methods used in its extraction. The assumptions of stationarity and autonomicity traditionally applied to dynamical systems break down when considering living systems, due to their inherent time-variability. Living systems are thermodynamically open, and thus constantly interacting with their environment. This results in highly nonlinear, time-dependent dynamics. The aim of signal a...

Reversibly Switchable, pH-Dependent Peptide Ligand Binding via 3,5-Diiodotyrosine Substitutions.

Science.gov (United States)

Ngambenjawong, Chayanon; Sylvestre, Meilyn; Gustafson, Heather H; Pineda, Julio Marco B; Pun, Suzie H

2018-04-20

Cell type-specific targeting ligands utilized in drug delivery applications typically recognize receptors that are overexpressed on the cells of interest. Nonetheless, these receptors may also be expressed, to varying extents, on off-target cells, contributing to unintended side effects. For the selectivity profile of targeting ligands in cancer therapy to be improved, stimuli-responsive masking of these ligands with acid-, redox-, or enzyme-cleavable molecules has been reported, whereby the targeting ligands are exposed in specific environments, e.g., acidic tumor hypoxia. One possible drawback of these systems lies in their one-time, permanent trigger, which enables the "demasked" ligands to bind off-target cells if released back into the systemic circulation. A promising strategy to address the aforementioned problem is to design ligands that show selective binding based on ionization state, which may be microenvironment-dependent. In this study, we report a systematic strategy to engineer low pH-selective targeting peptides using an M2 macrophage-targeting peptide (M2pep) as an example. 3,5-Diiodotyrosine mutagenesis into native tyrosine residues of M2pep confers pH-dependent binding behavior specific to acidic environment (pH 6) when the amino acid is protonated into the native tyrosine-like state. At physiological pH of 7.4, the hydroxyl group of 3,5-diiodotyrosine on the peptide is deprotonated leading to interruption of the peptide native binding property. Our engineered pH-responsive M2pep (Ac-Y-Î-Î) binds target M2 macrophages more selectively at pH 6 than at pH 7.4. In addition, 3,5-diiodotyrosine substitutions also improve serum stability of the peptide. Finally, we demonstrate pH-dependent reversibility in target binding via a postbinding peptide elution study. The strategy presented here should be applicable for engineering pH-dependent functionality of other targeting peptides with potential applications in physiology-dependent in vivo targeting

Preliminary Formulation of Finite Element Solution for the 1-D, 1-G Time Dependent Neutron Diffusion Equation without Consideration about Delay Neutron

Energy Technology Data Exchange (ETDEWEB)

Ryu, Eun Hyun; Song, Yong Mann; Park, Joo Hwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-05-15

If time-dependent equation is solved with the FEM, the limitation of the input geometry will disappear. It has often been pointed out that the numerical methods implemented in the RFSP code are not state-of-the-art. Although an acceleration method such as the Coarse Mesh Finite Difference (CMFD) for Finite Difference Method (FDM) does not exist for the FEM, one should keep in mind that the number of time steps for the transient simulation is not large. The rigorous formulation in this study will richen the theoretical basis of the FEM and lead to an extension of the dynamics code to deal with a more complicated problem. In this study, the formulation for the 1-D, 1-G Time Dependent Neutron Diffusion Equation (TDNDE) without consideration of the delay neutron will first be done. A problem including one multiplying medium will be solved. Also several conclusions from a comparison between the numerical and analytic solutions, a comparison between solutions with various element orders, and a comparison between solutions with different time differencing will be made to be certain about the formulation and FEM solution. By investigating various cases with different values of albedo, theta, and the order of elements, it can be concluded that the finite element solution is agree well with the analytic solution. The higher the element order used, the higher the accuracy improvements are obtained.

Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after 177Lu[Lu]-octreotate therapy.

Science.gov (United States)

Spetz, Johan; Rudqvist, Nils; Langen, Britta; Parris, Toshima Z; Dalmo, Johanna; Schüler, Emil; Wängberg, Bo; Nilsson, Ola; Helou, Khalil; Forssell-Aronsson, Eva

2018-05-01

Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with 177 Lu[Lu]-octreotate. Despite being highly effective in animal models, 177 Lu[Lu]-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for 177 Lu[Lu]-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq 177 Lu[Lu]-octreotate (non-curative amount) or mock-treated with saline solution. Animals were killed 1, 3, 7 or 41 d after injection. Total RNA was extracted from the tumor samples and profiled using Illumina microarray expression analysis. Differentially expressed genes were identified (treated vs. control) and pathway analysis was performed. Distribution of differentially expressed transcripts indicated a time-dependent treatment response in GOT1 tumors after 177 Lu[Lu]-octreotate administration. Regulation of CDKN1A, BCAT1 and PAM at 1 d after injection was compatible with growth arrest as the initial response to treatment. Upregulation of APOE and BAX at 3 d, and ADORA2A, BNIP3, BNIP3L and HSPB1 at 41 d after injection suggests first activation and then inhibition of the intrinsic apoptotic pathway during tumor regression and regrowth, respectively. Transcriptional analysis showed radiation-induced apoptosis as an early response after 177 Lu[Lu]-octreotate administration, followed by pro-survival transcriptional changes in the tumor during the regrowth phase. Time-dependent changes in cell cycle and apoptosis-related processes suggest different time points after radionuclide therapy when tumor cells may be more susceptible to additional treatment, highlighting the importance of timing when administering multiple therapeutic agents. Copyright © 2018 The Authors. Published by Elsevier Inc. All

Cumulative Beam Breakup with Time-Dependent Parameters

CERN Document Server

Delayen, J R

2004-01-01

A general analytical formalism developed recently for cumulative beam breakup (BBU) in linear accelerators with arbitrary beam current profile and misalignments [1] is extended to include time-dependent parameters such as energy chirp or rf focusing in order to reduce BBU-induced instabilities and emittance growth. Analytical results are presented and applied to practical accelerator configurations.

Lymph node retrieval in abdominoperineal surgical specimen is radiation time-dependent

Directory of Open Access Journals (Sweden)

Allal Abdelkarim S

2006-06-01

Full Text Available Abstract Background A low yield of lymph nodes (LN in abdominoperineal resection (APR specimen has been associated with preoperative radiation therapy (XRT in population-based studies, which may preclude adequate staging of anorectal carcinomas. We hypothesized that the number of LN retrieved in APR specimen was correlated with the dose and the timing of pelvic irradiation. Patients and methods We performed a retrospective study of 102 patients who underwent APR in a single institution between 1980 and 2004. Pathological reports were reviewed and the number of lymph nodes retrieved in APR specimens was correlated with: 1 Preoperative radiation; 2 Dose of pelvic irradiation; and 3 Time interval between the end of XRT and surgery. Results There were 61 men and 41 women, with a median age of 66 (range 25–89 years. There were 12 patients operated for squamous cell carcinoma of the anal canal (SCCA and 90 for rectal cancer. 83% and 46% of patients with anal and rectal cancer respectively underwent radical/neoadjuvant radiotherapy. The mean ± SD number of LN in APR specimen was 9.2 ± 5.9. The mean number of LN in APR specimen was significantly lower in patients who underwent preoperative XRT (8 ± 5.5 vs. 10.5 ± 6.1, Mann-Whitney U test, p = 0.02. The mean number of LN was not significantly different after XRT in patients with SCCA than in patients with rectal cancer (6.2 ± 5.3 vs. 7.8 ± 5.3, p = 0.33. Finally, there was an inverse correlation between the yield of LN and the time elapsed between XRT and surgery (linear regression coefficient r = -0.32, p = 0.03. Conclusion Our data indicate that: 1 radiation therapy affects the yield of LN retrieval in APR specimen; 2 this impact is time-dependent. These findings have important implications with regard to anatomic-pathological staging of anal and rectal cancers and subsequent decision-making regarding adjuvant chemotherapy.

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.

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.

Cytochrome P-450 dependent ethanol oxidation. Kinetic isotope effects and absence of stereoselectivity

International Nuclear Information System (INIS)

Ekstroem, G.; Norsten, C.; Cronholm, T.; Ingelman-Sundberg, M.

1987-01-01

Deuterium isotope effects [/sup D/(V/K)] and stereoselectivity of ethanol oxidation in cytochrome P-450 containing systems and in the xanthine-xanthine oxidase system were compared with those of yeast alcohol dehydrogenase. The isotope effects were determined by using both a noncompetitive method, including incubation of unlabeled of [1,1- 2 H 2 ] ethanol at various concentrations, and a competitive method, where 1:1 mixtures of [1- 13 C]- and [ 2 H 6 ] ethanol or [2,2,2- 2 H 3 ]- and [1,1- 2 H 2 ] ethanol were incubated and the acetaldehyde formed was analyzed by gas chromatography/mass spectrometry. The /sup D/(V/K) isotope effects of the cytochrome P-450 dependent ethanol oxidation were about 4 with liver microsomes from imidazole-, phenobarbital- or acetone-treated rabbits or with microsomes from acetone- or ethanol-treated rats. Similar isotope effects were reached with reconstituted membranes containing the rabbit ethanol-inducible cytochrome P-450 (LMeb), whereas control rat microsomes and membranes containing rabbit phenobarbital-inducible P-450 LM 2 oxidized the alcohol with /sup D/(V/K) of about 2.8 and 1.8, respectively. Addition of Fe/sup III/EDTA either to microsomes from phenobarbital-treated rabbits or to membranes containing P-450 LMeb significantly lowered the isotope effect. Incubations of all cytochrome P-450 containing systems of the xanthine-xanthine oxidase systems with (1R)- and (1S)-[1- 2 H] ethanol, revealed, taking the isotope effects into account, that 44-66% of the ethanol oxidized had lost the 1-pro-R hydrogen. The data indicate that cytochrome P-450 dependent ethanol oxidation is not stereospecific and that cleavage of the C 1 -H bond appears to be a rate-determining step in the catalysis by the ethanol-inducible form of P-450. The contribution of hydroxyl radicals in ethanol oxidation by the various enzymic systems is discussed

Time dependent accessibility

OpenAIRE

Kaza, Nikhil

2015-01-01

Many place based accessibility studies ignore the time component. Relying on theoretical frameworks that treat distance between two fixed points as constant, these methods ignore the diurnal and seasonal changes in accessibility. Network distances between two nodes are dependent on the network structure and weight distribution on the edges. These weights can change quite frequently and the network structure itself is subject to modification because of availability and unavailability of links ...

Simulation of compressible viscous flow in time-dependent domains

Czech Academy of Sciences Publication Activity Database

Česenek, J.; Feistauer, M.; Horáček, Jaromír; Kučera, V.; Prokopova, J.

2013-01-01

Roč. 219, č. 13 (2013), s. 7139-7150 ISSN 0096-3003 R&D Projects: GA ČR(CZ) GAP101/11/0207 Institutional support: RVO:61388998 Keywords : time dependent domain * ALE method * semi-implicit time discretization * shock indicator Subject RIV: BI - Acoustics Impact factor: 1.600, year: 2013

Coexpression of voltage-dependent calcium channels Cav1.2, 2.1a, and 2.1b in vascular myocytes

DEFF Research Database (Denmark)

Andreasen, Ditte; Friis, Ulla G; Uhrenholt, Torben R

2006-01-01

Voltage-dependent Ca2+ channels Cav1.2 (L type) and Cav2.1 (P/Q type) are expressed in vascular smooth muscle cells (VSMCs) and are important for the contraction of renal resistance vessels. In the present study we examined whether native renal VSMCs coexpress L-, P-, and Q-type Ca2+ currents...... microscopy revealed expression of both channels in all of the smooth muscle cells. Whole-cell patch clamp on single preglomerular VSMCs from mice showed L-, P-, and Q-type currents. Blockade of the L-type currents by calciseptine (20 nmol/L) inhibited 35.6+/-3.9% of the voltage-dependent Ca2+ current......-type and P-type channels inhibited 58.0+/-11.8%, and simultaneous inhibition of L-, P-, and Q-type channels led to blockade (88.7+/-5.6%) of the Ca2+ current. We conclude that aortic and renal preglomerular smooth muscle cells express L-, P-, and Q-type voltage-dependent Ca2+ channels in the rat and mouse....

Excitation-energy dependence of the resonant Auger transitions to the 4p4(1D)np (n=5,6) states across the 3d3/2-15p and 3d5/2-16p resonances in Kr

International Nuclear Information System (INIS)

Sankari, A.; Alitalo, S.; Nikkinen, J.; Kivimaeki, A.; Aksela, S.; Aksela, H.; Fritzsche, S.

2007-01-01

The energy dependencies of the intensities and angular distribution parameters β of the resonant Auger final states 4p 4 ( 1 D)np (n=5,6) of Kr were determined experimentally in the excitation-energy region of the overlapping 3d 3/2 -1 5p and 3d 5/2 -1 6p resonances. The experimental results were compared with the outcome of multiconfiguration Dirac-Fock calculations. Combining experimental and calculated results allowed us to study interference effects between the direct and several resonant channels that populate the 4p 4 ( 1 D)np states. The inclusion of the direct channel was crucial in order to reproduce the observed energy behavior of the angular distribution parameters. It was also important to take into account experimentally observed shake transitions

K shortest paths in stochastic time-dependent networks

DEFF Research Database (Denmark)

Nielsen, Lars Relund; Pretolani, Daniele; Andersen, Kim Allan

2004-01-01

A substantial amount of research has been devoted to the shortest path problem in networks where travel times are stochastic or (deterministic and) time-dependent. More recently, a growing interest has been attracted by networks that are both stochastic and time-dependent. In these networks, the ...... present a computational comparison of time-adaptive and a priori route choices, pointing out the effect of travel time and cost distributions. The reported results show that, under realistic distributions, our solution methods are effective.......A substantial amount of research has been devoted to the shortest path problem in networks where travel times are stochastic or (deterministic and) time-dependent. More recently, a growing interest has been attracted by networks that are both stochastic and time-dependent. In these networks...

Telomerase and Tel1p Preferentially Associate with Short Telomeres in S. cerevisiae

Science.gov (United States)

Sabourin, Michelle; Tuzon, Creighton T.; Zakian, Virginia A.

2009-01-01

SUMMARY In diverse organisms, telomerase preferentially elongates short telomeres. We generated a single short telomere in otherwise wild-type (WT) S. cerevisiae cells. The binding of the positive regulators Ku and Cdc13p was similar at short and WT-length telomeres. The negative regulators Rif1p and Rif2p were present at the short telomere, although Rif2p levels were reduced. Two telomerase holoenzyme components, Est1p and Est2p, were preferentially enriched at short telomeres in late S/G2 phase, the time of telomerase action. Tel1p, the yeast ATM-like checkpoint kinase, was highly enriched at short telomeres from early S through G2 phase and even into the next cell cycle. Nonetheless, induction of a single short telomere did not elicit a cell-cycle arrest. Tel1p binding was dependent on Xrs2p and required for preferential binding of telomerase to short telomeres. These data suggest that Tel1p targets telomerase to the DNA ends most in need of extension. PMID:17656141

Trans-generational responses to low pH depend on parental gender in a calcifying tubeworm.

Science.gov (United States)

Lane, Ackley; Campanati, Camilla; Dupont, Sam; Thiyagarajan, Vengatesen

2015-06-03

The uptake of anthropogenic CO2 emissions by oceans has started decreasing pH and carbonate ion concentrations of seawater, a process called ocean acidification (OA). Occurring over centuries and many generations, evolutionary adaptation and epigenetic transfer will change species responses to OA over time. Trans-generational responses, via genetic selection or trans-generational phenotypic plasticity, differ depending on species and exposure time as well as differences between individuals such as gender. Males and females differ in reproductive investment and egg producing females may have less energy available for OA stress responses. By crossing eggs and sperm from the calcareous tubeworm Hydroides elegans (Haswell, 1883) raised in ambient (8.1) and low (7.8) pH environments, we observed that paternal and maternal low pH experience had opposite and additive effects on offspring. For example, when compared to offspring with both parents from ambient pH, growth rates of offspring of fathers or mothers raised in low pH were higher or lower respectively, but there was no difference when both parents were from low pH. Gender differences may result in different selection pressures for each gender. This may result in overestimates of species tolerance and missed opportunities of potentially insightful comparisons between individuals of the same species.

A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites

Directory of Open Access Journals (Sweden)

Knezevich Anna

2007-05-01

Full Text Available Abstract HIV-1 transcription is tightly regulated: silent in long-term latency and highly active in acutely-infected cells. Transcription is activated by the viral protein Tat, which recruits the elongation factor P-TEFb by binding the TAR sequence present in nascent HIV-1 RNAs. In this study, we analyzed the dynamic of the TAR:Tat:P-TEFb complex in living cells, by performing FRAP experiments at HIV-1 transcription sites. Our results indicate that a large fraction of Tat present at these sites is recruited by Cyclin T1. We found that in the presence of Tat, Cdk9 remained bound to nascent HIV-1 RNAs for 71s. In contrast, when transcription was activated by PMA/ionomycin, in the absence of Tat, Cdk9 turned-over rapidly and resided on the HIV-1 promoter for only 11s. Thus, the mechanism of trans-activation determines the residency time of P-TEFb at the HIV-1 gene, possibly explaining why Tat is such a potent transcriptional activator. In addition, we observed that Tat occupied HIV-1 transcription sites for 55s, suggesting that the TAR:Tat:P-TEFb complex dissociates from the polymerase following transcription initiation, and undergoes subsequent cycles of association/dissociation.

Comparative analysis of Homo sapiens and Mus musculus cyclin-dependent kinase (CDK) inhibitor genes p16 (MTS1) and p15 (MTS2).

Science.gov (United States)

Jiang, P; Stone, S; Wagner, R; Wang, S; Dayananth, P; Kozak, C A; Wold, B; Kamb, A

1995-12-01

Cyclin-dependent kinase inhibitors are a growing family of molecules that regulate important transitions in the cell cycle. At least one of these molecules, p16, has been implicated in human tumorigenesis while its close homolog, p15, is induced by cell contact and transforming growth factor-beta (TGF-beta). To investigate the evolutionary and functional features of p15 and p16, we have isolated mouse (Mus musculus) homologs of each gene. Comparative analysis of these sequences provides evidence that the genes have similar functions in mouse and human. In addition, the comparison suggests that a gene conversion event is part of the evolution of the human p15 and p16 genes.

Infection with E1B-mutant adenovirus stabilizes p53 but blocks p53 acetylation and activity through E1A

DEFF Research Database (Denmark)

Savelyeva, I.; Dobbelstein, M.

2011-01-01

to the suppression of p21 transcription. Depending on the E1A conserved region 3, E1B-defective adenovirus impaired the ability of the transcription factor Sp1 to bind the p21 promoter. Moreover, the amino terminal region of E1A, binding the acetyl transferases p300 and CREB-binding protein, blocked p53 K382...... accumulation of p53, without obvious defects in p53 localization, phosphorylation, conformation and oligomerization. Nonetheless, p53 completely failed to induce its target genes in this scenario, for example, p21/CDKN1A, Mdm2 and PUMA. Two regions of the E1A gene products independently contributed...... acetylation in infected cells. Mutating either of these E1A regions, in addition to E1B, partially restored p21 mRNA levels. Our findings argue that adenovirus attenuates p53-mediated p21 induction, through at least two E1B-independent mechanisms. Other virus species and cancer cells may employ analogous...

The phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2)-dependent Tup1 conversion (PIPTC) regulates metabolic reprogramming from glycolysis to gluconeogenesis.

Science.gov (United States)

Han, Bong-Kwan; Emr, Scott D

2013-07-12

Glucose/carbon metabolism is a fundamental cellular process in living cells. In response to varying environments, eukaryotic cells reprogram their glucose/carbon metabolism between aerobic or anaerobic glycolysis, oxidative phosphorylation, and/or gluconeogenesis. The distinct type of glucose/carbon metabolism that a cell carries out has significant effects on the cell's proliferation and differentiation. However, it is poorly understood how the reprogramming of glucose/carbon metabolism is regulated. Here, we report a novel endosomal PI(3,5)P2 lipid-dependent regulatory mechanism that is required for metabolic reprogramming from glycolysis to gluconeogenesis in Saccharomyces cerevisiae. Certain gluconeogenesis genes, such as FBP1 (encoding fructose-1,6-bisphosphatase 1) and ICL1 (encoding isocitrate lyase 1) are under control of the Mig1 repressor and Cyc8-Tup1 corepressor complex. We previously identified the PI(3,5)P2-dependent Tup1 conversion (PIPTC), a mechanism to convert Cyc8-Tup1 corepressor to Cti6-Cyc8-Tup1 coactivator. We demonstrate that the PIPTC plays a critical role for transcriptional activation of FBP1 and ICL1. Furthermore, without the PIPTC, the Cat8 and Sip4 transcriptional activators cannot be efficiently recruited to the promoters of FBP1 and ICL1, suggesting a key role for the PIPTC in remodulating the chromatin architecture at the promoters. Our findings expand our understanding of the regulatory mechanisms for metabolic reprogramming in eukaryotes to include key regulation steps outside the nucleus. Given that Tup1 and the metabolic enzymes that control PI(3,5)P2 are highly conserved among eukaryotes, our findings may provide important insights toward understanding glucose/carbon metabolic reprogramming in other eukaryotes, including humans.

The time-dependent density matrix renormalisation group method

Science.gov (United States)

Ma, Haibo; Luo, Zhen; Yao, Yao

2018-04-01

Substantial progress of the time-dependent density matrix renormalisation group (t-DMRG) method in the recent 15 years is reviewed in this paper. By integrating the time evolution with the sweep procedures in density matrix renormalisation group (DMRG), t-DMRG provides an efficient tool for real-time simulations of the quantum dynamics for one-dimensional (1D) or quasi-1D strongly correlated systems with a large number of degrees of freedom. In the illustrative applications, the t-DMRG approach is applied to investigate the nonadiabatic processes in realistic chemical systems, including exciton dissociation and triplet fission in polymers and molecular aggregates as well as internal conversion in pyrazine molecule.

Time-dependent reliability sensitivity analysis of motion mechanisms

International Nuclear Information System (INIS)

Wei, Pengfei; Song, Jingwen; Lu, Zhenzhou; Yue, Zhufeng

2016-01-01

Reliability sensitivity analysis aims at identifying the source of structure/mechanism failure, and quantifying the effects of each random source or their distribution parameters on failure probability or reliability. In this paper, the time-dependent parametric reliability sensitivity (PRS) analysis as well as the global reliability sensitivity (GRS) analysis is introduced for the motion mechanisms. The PRS indices are defined as the partial derivatives of the time-dependent reliability w.r.t. the distribution parameters of each random input variable, and they quantify the effect of the small change of each distribution parameter on the time-dependent reliability. The GRS indices are defined for quantifying the individual, interaction and total contributions of the uncertainty in each random input variable to the time-dependent reliability. The envelope function method combined with the first order approximation of the motion error function is introduced for efficiently estimating the time-dependent PRS and GRS indices. Both the time-dependent PRS and GRS analysis techniques can be especially useful for reliability-based design. This significance of the proposed methods as well as the effectiveness of the envelope function method for estimating the time-dependent PRS and GRS indices are demonstrated with a four-bar mechanism and a car rack-and-pinion steering linkage. - Highlights: • Time-dependent parametric reliability sensitivity analysis is presented. • Time-dependent global reliability sensitivity analysis is presented for mechanisms. • The proposed method is especially useful for enhancing the kinematic reliability. • An envelope method is introduced for efficiently implementing the proposed methods. • The proposed method is demonstrated by two real planar mechanisms.

Plasma adrenaline kinetics in type 1 (insulin-dependent) diabetic patients with and without autonomic neuropathy

DEFF Research Database (Denmark)

Dejgaard, A; Hilsted, J; Henriksen, Jens Henrik Sahl

1989-01-01

Plasma adrenaline kinetics (clearance, extraction across the forearm, initial plasma disappearance rate, mean sojourn time, volume of distribution) were studied in sixteen Type 1 (insulin-dependent) diabetic patients during constant i.v. infusion of tritium labelled adrenaline. In patients with (n...... = 8) and without (n = 8) neuropathy forearm venous plasma noradrenaline and adrenaline concentrations as well as plasma clearance of adrenaline based on arterial sampling (1.7 vs 2.1 l/min) were not significantly different. The initial disappearance time (T 1/2) after the infusion of the tritium...... labelled adrenaline had been stopped was significantly prolonged in Type 1 diabetic patients with neuropathy compared to those without (after 20 min infusion 2.7 vs 2.2 min, p less than 0.02, after 75 min infusion 3.7 vs 2.9 min, p less than 0.05). The corresponding values for the mean sojourn time...

Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory

Energy Technology Data Exchange (ETDEWEB)

Sissay, Adonay [Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Abanador, Paul; Mauger, François; Gaarde, Mette; Schafer, Kenneth J. [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Lopata, Kenneth, E-mail: klopata@lsu.edu [Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803 (United States); Center for Computation and Technology, Louisiana State University, Baton Rouge, Louisiana 70803 (United States)

2016-09-07

Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagating the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.

Angle-dependent strong-field molecular ionization rates with tuned range-separated time-dependent density functional theory

International Nuclear Information System (INIS)

Sissay, Adonay; Abanador, Paul; Mauger, François; Gaarde, Mette; Schafer, Kenneth J.; Lopata, Kenneth

2016-01-01

Strong-field ionization and the resulting electronic dynamics are important for a range of processes such as high harmonic generation, photodamage, charge resonance enhanced ionization, and ionization-triggered charge migration. Modeling ionization dynamics in molecular systems from first-principles can be challenging due to the large spatial extent of the wavefunction which stresses the accuracy of basis sets, and the intense fields which require non-perturbative time-dependent electronic structure methods. In this paper, we develop a time-dependent density functional theory approach which uses a Gaussian-type orbital (GTO) basis set to capture strong-field ionization rates and dynamics in atoms and small molecules. This involves propagating the electronic density matrix in time with a time-dependent laser potential and a spatial non-Hermitian complex absorbing potential which is projected onto an atom-centered basis set to remove ionized charge from the simulation. For the density functional theory (DFT) functional we use a tuned range-separated functional LC-PBE*, which has the correct asymptotic 1/r form of the potential and a reduced delocalization error compared to traditional DFT functionals. Ionization rates are computed for hydrogen, molecular nitrogen, and iodoacetylene under various field frequencies, intensities, and polarizations (angle-dependent ionization), and the results are shown to quantitatively agree with time-dependent Schrödinger equation and strong-field approximation calculations. This tuned DFT with GTO method opens the door to predictive all-electron time-dependent density functional theory simulations of ionization and ionization-triggered dynamics in molecular systems using tuned range-separated hybrid functionals.

Time-dependent problems in quantum-mechanical state reconstruction

International Nuclear Information System (INIS)

Leonhardt, U.; Bardroff, P. J.

1997-01-01

We study the state reconstruction of wave packets that travel in time-dependent potentials. We solve the problem for explicitly time-dependent potentials. We solve the problem for explicitly time-dependent harmonic oscillators and sketch a general adaptive technique for finding the wave function that matches and observed evolution. (authors)

Time-dependent coupled harmonic oscillators: classical and quantum solutions

International Nuclear Information System (INIS)

Macedo, D.X.; Guedes, I.

2014-01-01

In this work we present the classical and quantum solutions for an arbitrary system of time-dependent coupled harmonic oscillators, where the masses (m), frequencies (ω) and coupling parameter (k) are functions of time. To obtain the classical solutions, we use a coordinate and momentum transformations along with a canonical transformation to write the original Hamiltonian as the sum of two Hamiltonians of uncoupled harmonic oscillators with modified time-dependent frequencies and unitary masses. To obtain the exact quantum solutions we use a unitary transformation and the Lewis and Riesenfeld (LR) invariant method. The exact wave functions are obtained by solving the respective Milne–Pinney (MP) equation for each system. We obtain the solutions for the system with m 1 = m 2 = m 0 e γt , ω 1 = ω 01 e -γt/2 , ω 2 = ω 02 e -γt/2 and k = k 0 . (author)

Space-Time Dependent Transport, Activation, and Dose Rates for Radioactivated Fluids.

Science.gov (United States)

Gavazza, Sergio

Two methods are developed to calculate the space - and time-dependent mass transport of radionuclides, their production and decay, and the associated dose rates generated from the radioactivated fluids flowing through pipes. The work couples space- and time-dependent phenomena, treated as only space- or time-dependent in the open literature. The transport and activation methodology (TAM) is used to numerically calculate space- and time-dependent transport and activation of radionuclides in fluids flowing through pipes exposed to radiation fields, and volumetric radioactive sources created by radionuclide motions. The computer program Radionuclide Activation and Transport in Pipe (RNATPA1) performs the numerical calculations required in TAM. The gamma ray dose methodology (GAM) is used to numerically calculate space- and time-dependent gamma ray dose equivalent rates from the volumetric radioactive sources determined by TAM. The computer program Gamma Ray Dose Equivalent Rate (GRDOSER) performs the numerical calculations required in GAM. The scope of conditions considered by TAM and GAM herein include (a) laminar flow in straight pipe, (b)recirculating flow schemes, (c) time-independent fluid velocity distributions, (d) space-dependent monoenergetic neutron flux distribution, (e) space- and time-dependent activation process of a single parent nuclide and transport and decay of a single daughter radionuclide, and (f) assessment of space- and time-dependent gamma ray dose rates, outside the pipe, generated by the space- and time-dependent source term distributions inside of it. The methodologies, however, can be easily extended to include all the situations of interest for solving the phenomena addressed in this dissertation. A comparison is made from results obtained by the described calculational procedures with analytical expressions. The physics of the problems addressed by the new technique and the increased accuracy versus non -space and time-dependent methods

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.

Time development and flux dependence of neutron-irradiation induced defects in silicon pad detectors

CERN Document Server

Zontar, D; Kramberger, G; Mikuz, M

1999-01-01

1x1 cm sup 2 silicon pad p sup + -n-n sup + detectors were irradiated with fast neutrons from the TRIGA research reactor in Ljubljana to fluences from 5x10 sup 1 sup 3 to 10 sup 1 sup 4 n/cm sup 2. The observed time development of annealing of the full-depletion voltage (FDV) could be fitted by a constant and two exponentials. The characteristic time of the fast component is 4 h, independent of temperature in the interval 0-15 deg. C. A comparison of MESA and planar pad detectors shows a 20-30% lower FDV for the MESA. A search for a flux dependence of the radiation damage was performed in the range from 2x10 sup 8 to 5x10 sup 1 sup 5 n/cm sup 2 s and no systematic differences were observed.

Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p

Directory of Open Access Journals (Sweden)

Greenblatt Jack F

2007-09-01

Full Text Available Abstract Background Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4. Results Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC. While mutational inactivation of the histone acetyltransferase (HAT gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2 exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork. Conclusion We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p. The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.

Anisotropic, time-dependent solutions in maximally Gauss-Bonnet extended gravity

International Nuclear Information System (INIS)

Kitaura, Takayuki; Wheeler, J.T.

1991-01-01

In an arbitrary number of dimensions, we find the full exact anisotropic, time-dependent, diagonal-metric solutions to maximally Gauss-Bonnet extended gravity theory. This class of theories for which the lagrangian is an arbitrary linear combination of dimensionally extnded Euler forms, is the most general gravitational theory in which the field equations contain no more than second derivatives of the metric. We show that the space-time exponentially approaches an asymptotic state of constant, anisotropic curvature and prove three theorems concerning two generic types of singularities. The first theorem gives conditions for the existence of Kasner-like curvature singularities. For these the metric diverges as tsup(p i ) where Σp i = 2 k max -1 and k max is the highest power of the curvature in the lagrangian. Other critical point singularities can arise from the polynomial nature of the theory. The remaining theorems demonstrate that the generic solution is extendible at all of these other critical points and that the generic critical points occur at moments of extremal volume density of space-time. We give an explicit coordinate transformation which produces a smooth extension through the critical point. The space-time may therefore alternately expand and contract for many cycles before expanding forever or contracting to a singularity. Many particular cases are treated in detail including several power series solutions, the generalized Kasner solution to general relativity with or without cosmological constant, the perturbative solution for quadratic string gravity, and five-dimensional extended gravity. (orig.)

Time-dependent Dyson orbital theory

NARCIS (Netherlands)

Gritsenko, O.V.; Baerends, E.J.

2016-01-01

Although time-dependent density functional theory (TDDFT) has become the tool of choice for real-time propagation of the electron density ρN(t) of N-electron systems, it also encounters problems in this application. The first problem is the neglect of memory effects stemming from the, in TDDFT

Temperature-Dependent Asymmetry of Anisotropic Magnetoresistance in Silicon p-n Junctions.

Science.gov (United States)

Yang, D Z; Wang, T; Sui, W B; Si, M S; Guo, D W; Shi, Z; Wang, F C; Xue, D S

2015-09-01

We report a large but asymmetric magnetoresistance in silicon p-n junctions, which contrasts with the fact of magnetoresistance being symmetric in magnetic metals and semiconductors. With temperature decreasing from 293 K to 100 K, the magnetoresistance sharply increases from 50% to 150% under a magnetic field of 2 T. At the same time, an asymmetric magnetoresistance, which manifests itself as a magnetoresistance voltage offset with respect to the sign of magnetic field, occurs and linearly increases with magnetoresistance. More interestingly, in contrast with other materials, the lineshape of anisotropic magnetoresistance in silicon p-n junctions significantly depends on temperature. As temperature decreases from 293 K to 100 K, the width of peak shrinks from 90° to 70°. We ascribe these novel magnetoresistance to the asymmetric geometry of the space charge region in p-n junction induced by the magnetic field. In the vicinity of the space charge region the current paths are deflected, contributing the Hall field to the asymmetric magnetoresistance. Therefore, the observed temperature-dependent asymmetry of magnetoresistance is proved to be a direct consequence of the spatial configuration evolution of space charge region with temperature.

Porcine epidemic diarrhea virus through p53-dependent pathway causes cell cycle arrest in the G0/G1 phase.

Science.gov (United States)

Sun, Pei; Wu, Haoyang; Huang, Jiali; Xu, Ying; Yang, Feng; Zhang, Qi; Xu, Xingang

2018-05-22

Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the swine industry. p53 protein exists in a wide variety of animal cells, which is involved in cell cycle regulation, apoptosis, cell differentiation and other biological functions. In this study, we investigated the effects of PEDV infection on the cell cycle of Vero cells and p53 activation. The results demonstrated that PEDV infection induces cell cycle arrest at G0/G1 phase in Vero cells, while UV-inactivated PEDV does not cause cell cycle arrest. PEDV infection up-regulates the levels of p21, cdc2, cdk2, cdk4, Cyclin A protein and down-regulates Cyclin E protein. Further research results showed that inhibition of p53 signaling pathway can reverse the cell cycle arrest in G0/G1 phase induced by PEDV infection and cancel out the up-regulation of p21 and corresponding Cyclin/cdk mentioned above. In addition, PEDV infection of the cells synchronized in various stages of cell cycle showed that viral subgenomic RNA and virus titer were higher in the cells released from G0/G1 phase synchronized cells than that in the cells released from the G1/S phase and G2/M phase synchronized or asynchronous cells after 18 h p.i.. This is the first report to demonstrate that the p53-dependent pathway plays an important role in PEDV induced cell cycle arrest and beneficially contributes to viral infection. Copyright © 2018 Elsevier B.V. All rights reserved.

Time-dependent scattering in resonance lines

International Nuclear Information System (INIS)

Kunasz, P.B.

1983-01-01

A numerical finite-difference method is presented for the problem of time-dependent line transfer in a finite slab in which material density is sufficiently low that the time of flight between scatterings greatly exceeds the relaxation time of the upper state of the scattering transition. The medium is assumed to scatter photons isotropically, with complete frequency redistribution. Numerical solutions are presented for a homogeneous, time-independent slab illuminated by an externally imposed radiation field which enters the slab at t = 0. Graphical results illustrate relaxation to steady state of trapped internal radiation, emergent energy, and emergent profiles. A review of the literature is also given in which the time-dependent line transfer problem is discussed in the context of recent analytical work

Variational derivation of a time-dependent Hartree-Fock Hamiltonian

International Nuclear Information System (INIS)

Lichtner, P.C.; Griffin, J.J.; Schultheis, H.; Schultheis, R.; Volkov, A.B.

1979-01-01

The variational derivation of the time-dependent Hartree-Fock equation is reviewed. When norm-violating variations are included, a unique time-dependent Hartree-Fock Hamiltonian, which differs from that customarily used in time-dependent Hartree-Fock analyses, is implied. This variationally ''true'' Hartree-Fock Hamiltonian has the same expectation value as the exact Hamiltonian, equal to the average energy of the system. Since this quantity remains constant under time-dependent Hartree-Fock time evolution, we suggest the label ''constant '' for this form of time-dependent Hartree-Fock theory

Simulating transient dynamics of the time-dependent time fractional Fokker-Planck systems

Science.gov (United States)

Kang, Yan-Mei

2016-09-01

For a physically realistic type of time-dependent time fractional Fokker-Planck (FP) equation, derived as the continuous limit of the continuous time random walk with time-modulated Boltzmann jumping weight, a semi-analytic iteration scheme based on the truncated (generalized) Fourier series is presented to simulate the resultant transient dynamics when the external time modulation is a piece-wise constant signal. At first, the iteration scheme is demonstrated with a simple time-dependent time fractional FP equation on finite interval with two absorbing boundaries, and then it is generalized to the more general time-dependent Smoluchowski-type time fractional Fokker-Planck equation. The numerical examples verify the efficiency and accuracy of the iteration method, and some novel dynamical phenomena including polarized motion orientations and periodic response death are discussed.

Optimization of a pH-shift control strategy for producing monoclonal antibodies in Chinese hamster ovary cell cultures using a pH-dependent dynamic model.

Science.gov (United States)

Hogiri, Tomoharu; Tamashima, Hiroshi; Nishizawa, Akitoshi; Okamoto, Masahiro

2018-02-01

To optimize monoclonal antibody (mAb) production in Chinese hamster ovary cell cultures, culture pH should be temporally controlled with high resolution. In this study, we propose a new pH-dependent dynamic model represented by simultaneous differential equations including a minimum of six system component, depending on pH value. All kinetic parameters in the dynamic model were estimated using an evolutionary numerical optimization (real-coded genetic algorithm) method based on experimental time-course data obtained at different pH values ranging from 6.6 to 7.2. We determined an optimal pH-shift schedule theoretically. We validated this optimal pH-shift schedule experimentally and mAb production increased by approximately 40% with this schedule. Throughout this study, it was suggested that the culture pH-shift optimization strategy using a pH-dependent dynamic model is suitable to optimize any pH-shift schedule for CHO cell lines used in mAb production projects. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.