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Sample records for aps transport lines

  1. Design and initial tests of beam current monitoring systems for the APS transport lines

    SciTech Connect

    Wang, Xucheng

    1992-12-01

    The non-intercepting beam current monitoring systems suitable for a wide, range of beam parameters have been developed for the Advanced Photon Source (APS) low energy transport lines and high energy transport line. The positron or electron beam pulse in the transport lines wig have peak beam currents ranging from 8 mA to 29 A with pulse widths varying from 120 ps to 30 ns and pulse repetition rates from 2 Hz to 60 Hz. The peak beam current or total beam charge is measured with the fast or integrating current transformer, respectively, manufactured by Bergoz. In-house high speed beam signal processing electronics provide a DC level output proportional to the peak current or total charge for the digitizer input. The prototype systems were tested on the linacs which have beam pulse structures similar to that of the APS transport lines. This paper describes the design of beam signal processing electronics and grounding and shielding methods for current transformers. The results of the initial operations are presented. A short introduction on the preliminary design of current monitoring systems for the APS rings is also included.

  2. Design and initial tests of beam current monitoring systems for the APS transport lines

    SciTech Connect

    Wang, Xucheng.

    1992-01-01

    The non-intercepting beam current monitoring systems suitable for a wide, range of beam parameters have been developed for the Advanced Photon Source (APS) low energy transport lines and high energy transport line. The positron or electron beam pulse in the transport lines wig have peak beam currents ranging from 8 mA to 29 A with pulse widths varying from 120 ps to 30 ns and pulse repetition rates from 2 Hz to 60 Hz. The peak beam current or total beam charge is measured with the fast or integrating current transformer, respectively, manufactured by Bergoz. In-house high speed beam signal processing electronics provide a DC level output proportional to the peak current or total charge for the digitizer input. The prototype systems were tested on the linacs which have beam pulse structures similar to that of the APS transport lines. This paper describes the design of beam signal processing electronics and grounding and shielding methods for current transformers. The results of the initial operations are presented. A short introduction on the preliminary design of current monitoring systems for the APS rings is also included.

  3. An On-Line Database of APS POSS Images

    NASA Astrophysics Data System (ADS)

    Cornuelle, C. S.; Aldering, G.; Sourov, A.; Thurmes, P.; Humphreys, R. M.

    We are making available our digitized images from the APS scans of the red and blue first-epoch Palomar Observatory Sky Survey (POSS I) photographic plates, forming an on-line image database. Image requests are through the APS homepage at URL http://isis.spa.umn.edu/homepage.aps.html and are initially limited in field width and sky region. To create this database, images from each scanned POSS I plate are processed into a set of coordinate-referenced index and pixel files. Database management software then refers to each object's pixels within a requested sky region by plate, by sub-plate, and finally by each scanned image. These images are then assembled into a mosaic FITS format file, whose header contains astrometric and photometric information. While the current APS Catalog of the POSS I includes only matched images, the image database will include images above 25 mu m in diameter. Thus for a given sky region, users have access to both the object (star and galaxy) catalog data and to the actual pixel data. This project is sponsored by NASA ADP contract NAS5-32670.

  4. H-beta line variability in magnetic Ap stars. I

    NASA Technical Reports Server (NTRS)

    Madej, J.; Jahn, K.; Stepien, K.

    1984-01-01

    Preliminary results of photometric measurements of H-beta in several Ap stars are presented. Periodic variations are found certainly in Theta Aur and Alpha (2) CVn, and possibly in Phi Dra. For the other stars upper limits for variations of H-beta are determined. Observed amplitudes are transformed into variations of equivalent width assuming specific profile variations. The results show that variations of equivalent width of H-beta in the stars investigated are of the order of 10 percent or less.

  5. High beam current shut-off systems in the APS linac and low energy transfer line

    SciTech Connect

    Wang, X.; Knott, M.; Lumpkin, A.

    1994-11-01

    Two independent high beam current shut-off current monitoring systems (BESOCM) have been installed in the APS linac and the low energy transport line to provide personnel safety protection in the event of acceleration of excessive beam currents. Beam current is monitored by a fast current transformer (FCT) and fully redundant supervisory circuits connected to the Access Control Interlock System (ACIS) for beam intensity related shutdowns of the linac. One FCT is located at the end of the positron linac and the other in the low energy transport line, which directs beam to the positron accumulator ring (PAR). To ensure a high degree of reliability, both systems employ a continuous self-checking function, which injects a test pulse to a single-turn test winding after each ``real`` beam pulse to verify that the system is fully functional. The system is designed to be fail-safe for all possible system faults, such as loss of power, open or shorted signal or test cables, loss of external trigger, malfunction of gated integrator, etc. The system has been successfully commissioned and is now a reliable part of the total ACIS.

  6. High beam current shut-off systems in the APS linac and low energy transfer line

    SciTech Connect

    Wang, X.; Knott, M.; Lumpkin, A.

    1995-05-05

    Two independent high beam current shut-off current monitoring systems (BESOCM) have been installed in the APS linac and the low energy transport line to provide personnel safety protection in the event of acceleration of excessive beam currents. Beam current is monitored by a fast current transformer (FCT) and fully redundant supervisory circuits connected to the Access Control Interlock System (ACIS) for beam intensity related shutdowns of the linac. One FCT is located at the end of the positron linac and the other in the low energy transport line, which directs beam to the positron accumulator ring (PAR). To ensure a high degree of reliability, both systems employ a continuous self-checking function, which injects a test pulse to a single-turn test winding after each ``real`` beam pulse to verify that the system is fully functional. The system is designed to be fail-safe for all possible system faults, such as loss of power, open or shorted signal or test cables, loss of external trigger, malfunction of gated integrator, etc. The system has been successfully commissioned and is now a reliable part of the total ACIS. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  7. Some magnetic null lines of astrophysical interest. II. [in magnetic Ap stars

    NASA Technical Reports Server (NTRS)

    Adelman, S. J.

    1974-01-01

    A list of magnetic null lines from selected spectroscopic analyses is presented for possible use in detailed studies of magnetic Ap stars. The presented data represent an extension of the magnetic null lines whose usefulness Shore and Adelman (1974) have recently demonstrated for the study of the overall physical conditions prevailing in the atmospheres of peculiar A stars and for testing the consequences of the mechanism of selective elemental diffusion.

  8. Accessing, Mining, and Archiving an On-line Database -- The APS Catalog of the POSS I

    NASA Astrophysics Data System (ADS)

    Humphreys, R. M.; Cabanela, J. E.; Kriessler, J.

    2000-12-01

    The APS Catalog of the POSS I is an on-line database of over 100 million stars and galaxies (http://aps.umn.edu). A unique subset of this database with over 218,000 galaxies within 30 degrees of the North Galactic Pole, the MAPS-NGP, is now available at our web site. This diameter--selected catalog (>= 10 arcsec) is the deepest galaxy catalog constructed over such a large area of the sky (3000 sq. degrees). The MAPS-NGP includes many additional parameters for the galaxy images not available in the APS Catalog. Working with members of our computer science department, we have developed a morphological classifier for galaxies that divides our galaxy type into three classes -- early, intermediate, and late. We have applied data mining techniques to identify the most useful image parameters for input into a neural network and decision--tree based classifier pipeline. We are also archiving the APS Catalog for distribution to astronomical data centers including NASA's ADC and SIMBAD at CDS. The extragalactic subset will be integrated into the NASA/IPAC extragalactic database(NED). The MAPS-NGP has already been provided to NED. The APS is supported by NASA's Applied Information Systems Research Program.

  9. NSLS-II Transport Line Progress

    SciTech Connect

    Fliller R. P.; Wahl, W.; Anderson, A.; Benish, B.; DeBoer, W.; Ganetis, G.; Heese, R.; Hseuh, H.-C.; Hu, J.-P.; Johanson, M.P.; Kosciuk, B.N.; Padrazo, D.; Roy, K.; Shaftan, T.; Singh, O.; Tuozzolo, J.; Wang, G.

    2012-05-20

    The National Synchrotron Light Source II (NSLS-II) is a state-of-the-art 3-GeV third generation light source currently under construction at Brookhaven National Laboratory. The NSLS-II injection system consists of a 200 MeV linac, a 3-GeV booster synchrotron and associated transfer lines. The first part of the Linac to Booster Transport (LBT) line has been installed for linac commissioning. This part includes all components necessary to commission the NSLS-II linac. The second part of this transport line is undergoing installation. Initial results of hardware commissioning will be discussed. The Booster to Storage Ring (BSR) transport line underwent a design review. The first part of the BSR transport line, consisting of all components necessary to commission the booster will be installed in 2012 for booster commissioning. We report on the final design of the BSR line along with the plan to commission the booster.

  10. Basolateral sorting of the Mg²⁺ transporter CNNM4 requires interaction with AP-1A and AP-1B.

    PubMed

    Hirata, Yusuke; Funato, Yosuke; Miki, Hiroaki

    2014-12-12

    Ancient conserved domain protein/cyclin M (CNNM) 4 is an evolutionarily conserved Mg(2+) transporter that localizes at the basolateral membrane of the intestinal epithelia. Here, we show the complementary importance of clathrin adaptor protein (AP) complexes AP-1A and AP-1B in basolateral sorting of CNNM4. We first confirmed the basolateral localization of both endogenous and ectopically expressed CNNM4 in Madin-Darby Canine Kidney cells, which form highly polarized epithelia in culture. Single knockdown of μ1B, a cargo-recognition subunit of AP-1B, did not affect basolateral localization, but simultaneous knockdown of the μ1A subunit of AP-1A abrogated localization. Mutational analyses showed the importance of three conserved dileucine motifs in CNNM4 for both basolateral sorting and interaction with μ1A and μ1B. These results imply that CNNM4 is sorted to the basolateral membrane by the complementary function of AP-1A and AP-1B.

  11. Optical observations of the broad-lined type Ic supernova SN 2012ap

    NASA Astrophysics Data System (ADS)

    Liu, Zheng; Zhao, Xu-Lin; Huang, Fang; Wang, Xiao-Feng; Zhang, Tian-Meng; Chen, Jun-Cheng; Zhang, Tong-Jie

    2015-02-01

    The optical observations of the type Ic supernova (SN Ic) SN 2012ap in NGC 1729 are presented. A comparison with other SNe Ic indicates that SN 2012ap is highly reddened (with E(B — V)host~0.8 mag) and may represent one of the most luminous SNe Ic ever observed, with an absolute V-band peak magnitude of ~ -19.3±0.5 mag after extinction correction. The near-maximum-light spectrum shows wide spectral features that are typical of broad-lined SNe Ic. One interesting feature in the spectrum is the appearance of some narrow absorption features that can be attributed to the diffuse interstellar bands, consistent with the large reddening inferred from the photometric method. Based on the light curves and the spectral data, we estimate that SN 2012ap produced a 56Ni mass of ~ 0.3 ± 0.1Msolar 1 in the explosion, with an ejecta mass of 2.4-0.7+0.7Msolar and a kinetic energy of EK = 1.1-0.4+0.4 × 1052 erg. The properties of its progenitor are also briefly discussed.

  12. Evidence for Magnetar Formation in Broad-lined Type Ic Supernovae 1998bw and 2002ap

    NASA Astrophysics Data System (ADS)

    Wang, L. J.; Yu, H.; Liu, L. D.; Wang, S. Q.; Han, Y. H.; Xu, D.; Dai, Z. G.; Qiu, Y. L.; Wei, J. Y.

    2017-03-01

    Broad-lined type Ic supernovae (SNe Ic-BL) are peculiar stellar explosions that are distinct from ordinary SNe. Some SNe Ic-BL are associated with long-duration (≳ 2 {{s}}) gamma-ray bursts (GRBs). Black holes and magnetars are two types of compact objects that are hypothesized to be central engines of GRBs. In spite of decades of investigations, no direct evidence for the formation of black holes or magnetars has yet been found for GRBs. Here we report the finding that the early peak (t≲ 50 {days}) and late-time (t≳ 300 {days}) slow decay displayed in the light curves of SNe 1998bw (associated with GRB 980425) and 2002ap (not GRB-associated) can be attributed to magnetar spin-down with an initial rotation period {P}0∼ 20 {ms}, while the intermediate-time (50≲ t≲ 300 {days}) exponential decline is caused by the radioactive decay of 56Ni. The connection between the early peak and late-time slow decline in the light curves is unexpected in alternative models. We thus suggest that GRB 980425 and SN 2002ap were powered by magnetars.

  13. BEAM TRANSPORT LINES FOR THE BSNS.

    SciTech Connect

    WEI, J.

    2006-06-26

    This paper presents the design of two beam transport lines at the BSNS: one is the injection line from the Linac to the RCS and the other is the target line from the RCS to the target station. In the injection beam line, space charge effects, transverse halo collimation, momentum tail collimation and debunching are the main concerned topics. A new method of using triplet cells and stripping foils is used to collimate transverse halo. A long straight section is reserved for the future upgrading linac and debuncher. In the target beam line, large halo emittance, beam stability at the target due to kicker failures and beam jitters, shielding of back-scattering neutrons from the target are main concerned topics. Special bi-gap magnets will be used to reduce beam losses in the collimators in front of the target.

  14. Moisture Transport Through Sprayed Concrete Tunnel Linings

    NASA Astrophysics Data System (ADS)

    Holter, Karl Gunnar; Geving, Stig

    2016-01-01

    Waterproofing of permanent sprayed concrete tunnel linings with sprayed membranes in a continuous sandwich structure has been attempted since 2000 and has seen increased use in some countries. The main function of a sprayed membrane from a waterproofing perspective is to provide crack bridging and hence prevent flow of liquid water into the tunnel through cracks and imperfections in the concrete material. However, moisture can migrate through the concrete and EVA-based membrane materials by capillary and vapor diffusion mechanisms. These moisture transport mechanisms can have an influence on the degree of saturation, and may influence the pore pressures in the concrete material as well as risk of freeze-thaw damage of the concrete and membrane. The paper describes a detailed study of moisture transport material parameters, moisture condition in tunnel linings and climatic conditions tunnels in hard rock in Norway. These data have been included in a hygrothermal simulation model in the software WUFI for moisture transport to substantiate moisture transport and long-term effects on saturation of the concrete and membrane material. The findings suggest that EVA-based membranes exhibit significant water absorption and vapor transport properties although they are impermeable to liquid water flow. State-of-the-art sprayed concrete material applied with the wet mix method exhibits very low hydraulic conductivities, lower than 10-14 m/s, thus saturated conductive water flow is a very unlikely dominant transport mechanism. Moisture transport through the lining structure by capillary flow and vapor diffusion are calculated to approximately 3 cm3/m2 per day for lining thicknesses in the range of 25-35 cm and seasonal Nordic climate variations. The calculated moisture contents in the tunnel linings from the hygrothermal simulations are largely in agreement with the measured moisture contents in the tunnel linings. The findings also indicate that the concrete material exhibits

  15. Subchannel thermal-hydraulic analysis at AP600 low-flow steam-line-break conditions

    SciTech Connect

    Morita, T.; Olson, C.A.; Sung, Y.X.; Connelley, J.F. Jr.; Novendstern, E.H.; Kapil, S.; Rosenthal, P.W.

    1995-12-01

    The AP600 reactor core approaches buoyancy-dominated flow at the departure from nucleate boiling (DNB)-limiting period of a postulated steam-line--break accident. The reactor core has a highly skewed power distribution at this time due to the conservative assumption of a withdrawn rod cluster control assembly (stuck rod). Under such conditions, strong buoyancy-induced core cross flow occurs, and coupled nuclear and thermal-hydraulic interactions become important. To analyze the transient, Westinghouse Electric Corporation has coupled THINC-IV with a neutronic code (ANC). Applicability of the THINC-IV subchannel code to the low-flow conditions with a steep radial power gradient is verified with existing rod bundle test results. The code predictions are in excellent agreement with the test data. The coupled codes provide a realistic three-dimensional simulation of core power by considering core flow distributions and the resultant enthalpy distributions in neutronic feedback. The safety analysis using the coupled code demonstrates that the DNB design basis is met during the postulated steam-line-break accident.

  16. Functional Characterization Of Peptide Transporters In MDCKII -MDR1 Cell line As A Model For Oral Absorption Studies

    PubMed Central

    Agarwal, Sheetal; Jain, Ritesh; Pal, Dhananjay; K.Mitra, Ashim

    2007-01-01

    MDCKII-MDR1 cell line has been extensively selected as a model to study P-gp-mediated drug efflux. Recently, investigators have employed this cell line for studying influx of peptide prodrug derivatives of parent compounds which are P-gp substrates. Therefore, the objective of this study is to functionally characterize the peptide mediated uptake and transport of [3H] Glycylsarcosine ([3H] Gly-Sar), a model peptide substrate across MDCKII-MDR1 cells. [3H] Gly-Sar uptake from apical (AP) and basolateral (BL) membranes was found to be time dependent and saturable. Michaelis-Menten (Km) constants of [3H] Gly-Sar uptake across the AP and BL directions in MDCKII-MDR1 cell line were found to be 457 ± 37 μM and 464 ± 85 μM respectively. Vmax values in AP and BL directions for the peptide transporters in MDCKII-MDR1 cell line were calculated to be 0.035 ± 0.001 and 0.35 ± 0.034 pmol/min/mg protein respectively. Uptake of [3H] Gly-Sar was significantly inhibited in the presence of aminocephalosporins and ACE-Inhibitors, known substrates for peptide transporters in both the AP and BL directions. Permeability of [3H] Gly-Sar in the BL direction was maximal at pH 4 as compared to pH 5, 6 and 7.4 whereas such permeability in the AP direction was optimal at pH 7.4. Transepithelial transport of [3H] Gly-Sar in the AP-BL direction was significantly lower than from BL-AP direction at all observed pHs. No statistical difference was observed in the transepithelial permeability of [3H] Gly-Sar across both AP and BL directions over 4–10 days of growth period. The present study indicates that peptide transporters are effectively involved in the bidirectional transport of Gly-Sar across MDCKII-MDR1 cell line; the BL peptide transporter can transport Gly-Sar at a greater rate as compared to the AP peptide transporter. Results from these studies suggest the application of MDCKII-MDR1 cell line as a rapid effective tool to study peptide mediated influx of compounds that may be

  17. Accelerator and transport line survey and alignment

    SciTech Connect

    Ruland, R.E.

    1991-10-01

    This paper summarizes the survey and alignment processes of accelerators and transport lines and discusses the propagation of errors associated with these processes. The major geodetic principles governing the survey and alignment measurement space are introduced and their relationship to a lattice coordinate system shown. The paper continues with a broad overview about the activities involved in the step sequence from initial absolute alignment to final smoothing. Emphasis is given to the relative alignment of components, in particular to the importance of incorporating methods to remove residual systematic effects in surveying and alignment operations. Various approaches to smoothing used at major laboratories are discussed. 47 refs., 19 figs., 1 tab.

  18. Transport of the cholera toxin B-subunit from recycling endosomes to the Golgi requires clathrin and AP-1.

    PubMed

    Matsudaira, Tatsuyuki; Niki, Takahiro; Taguchi, Tomohiko; Arai, Hiroyuki

    2015-08-15

    The retrograde pathway is defined by the transport of proteins and lipids from the plasma membrane through endosomes to the Golgi complex, and is essential for a variety of cellular activities. Recycling endosomes are important sorting stations for some retrograde cargo. SMAP2, a GTPase-activating protein (GAP) for Arf1 with a putative clathrin-binding domain, has previously been shown to participate in the retrograde transport of the cholera toxin B-subunit (CTxB) from recycling endosomes. Here, we found that clathrin, a vesicle coat protein, and clathrin adaptor protein complex 1 (AP-1) were present at recycling endosomes and were needed for the retrograde transport of CTxB from recycling endosomes to the Golgi, but not from the plasma membrane to recycling endosomes. SMAP2 immunoprecipitated clathrin and AP-1 through a putative clathrin-binding domain and a CALM-binding domain, and SMAP2 mutants that did not interact with clathrin or AP-1 could not localize to recycling endosomes. Moreover, knockdown of Arf1 suppressed the retrograde transport of CTxB from recycling endosomes to the Golgi. These findings suggest that retrograde transport is mediated by clathrin-coated vesicles from recycling endosomes and that the role of the coat proteins is in the recruitment of Arf GAP to transport vesicles.

  19. Intracellular transport of MHC class II and associated invariant chain in antigen presenting cells from AP-3-deficient mocha mice.

    PubMed

    Sevilla, L M; Richter, S S; Miller, J

    2001-06-15

    MHC class II-restricted antigen presentation requires trafficking of newly synthesized class II-invariant chain complexes from the trans-Golgi network to endosomal, peptide-loading compartments. This transport is mediated by dileucine-like motifs within the cytosolic tail of the invariant chain. Although these signals have been well characterized, the cytosolic proteins that interact with these dileucine signals and mediate Golgi sorting and endosomal transport have not been identified. Recently, an adaptor complex, AP-3, has been identified that interacts with dileucine motifs and mediates endosomal/lysosomal transport in yeast, Drosophila, and mammals. In this report, we have assessed class II-invariant chain trafficking in a strain of mice (mocha) which lacks expression of AP-3. Our studies demonstrate that the lack of AP-3 does not affect the kinetics of invariant chain degradation, the route of class II-invariant chain transport, or the rate and extent of class II-peptide binding as assessed by the generation of SDS-stable dimers. The possible role of other known or unknown adaptor complexes in class II-invariant chain transport is discussed.

  20. A dileucine-like sorting signal directs transport into an AP-3-dependent, clathrin-independent pathway to the yeast vacuole.

    PubMed Central

    Vowels, J J; Payne, G S

    1998-01-01

    Transport of yeast alkaline phosphatase (ALP) to the vacuole depends on the clathrin adaptor-like complex AP-3, but does not depend on proteins necessary for transport through pre-vacuolar endosomes. We have identified ALP sequences that direct sorting into the AP-3-dependent pathway using chimeric proteins containing residues from the ALP cytoplasmic domain fused to sequences from a Golgi-localized membrane protein, guanosine diphosphatase (GDPase). The full-length ALP cytoplasmic domain, or ALP amino acids 1-16 separated from the transmembrane domain by a spacer, directed GDPase chimeric proteins from the Golgi complex to the vacuole via the AP-3 pathway. Mutation of residues Leu13 and Val14 within the ALP cytoplasmic domain prevented AP-3-dependent vacuolar transport of both chimeric proteins and full-length ALP. This Leucine-Valine (LV)-based sorting signal targeted chimeric proteins and native ALP to the vacuole in cells lacking clathrin function. These results identify an LV-based sorting signal in the ALP cytoplasmic domain that directs transport into a clathrin-independent, AP-3-dependent pathway to the vacuole. The similarity of the ALP sorting signal to mammalian dileucine sorting motifs, and the evolutionary conservation of AP-3 subunits, suggests that dileucine-like signals constitute a core element for AP-3-dependent transport to lysosomal compartments in all eukaryotic cells. PMID:9564031

  1. TRANSPORT OF WASTE SIMULANTS IN PJM VENT LINES

    SciTech Connect

    Qureshi, Z

    2007-02-21

    The experimental work was conducted to determine whether there is a potential for waste simulant to transport or 'creep' up the air link line and contaminate the pulse jet vent system, and possibly cause long term restriction of the air link line. Additionally, if simulant creep occurred, establish operating parameters for washing down the line. The amount of the addition of flush fluids and mixer downtime must be quantified.

  2. Interaction Between the Broad-Lined Type Ic Supernova 2012ap and Carriers of Diffuse Interstellar Bands

    NASA Technical Reports Server (NTRS)

    Milisavljevic, Dan; Margutti, Raffaella; Crabtree, Kyle N.; Foster, Jonathan B.; Soderberg, Alicia M.; Fesen, Robert A.; Parrent, Jerod T.; Sanders, Nathan E.; Drout, Maria R.; Kamble, Atish; Cenko, S. Bradley

    2014-01-01

    The diffuse interstellar bands (DIBs) are absorption features observed in optical and near-infrared spectra that are thought to be associated with carbon-rich polyatomic molecules in interstellar gas. However, because the central wavelengths of these bands do not correspond with electronic transitions of any known atomic or molecular species, their nature has remained uncertain since their discovery almost a century ago. Here we report on unusually strong DIBs in optical spectra of the broad- lined Type Ic supernova SN2012ap that exhibit changes in equivalent width over short (. 30 days) timescales. The 4428 A and 6283 A DIB features get weaker with time, whereas the 5780 A feature shows a marginal increase. These nonuniform changes suggest that the supernova is interacting with a nearby source of the DIBs and that the DIB carriers possess high ionization potentials, such as small cations or charged fullerenes. We conclude that moderate-resolution spectra of supernovae with DIB absorptions obtained within weeks of outburst could reveal unique information about the mass-loss environment of their progenitor systems and provide new constraints on the properties of DIB carriers.

  3. INTERACTION BETWEEN THE BROAD-LINED TYPE Ic SUPERNOVA 2012ap AND CARRIERS OF DIFFUSE INTERSTELLAR BANDS

    SciTech Connect

    Milisavljevic, Dan; Margutti, Raffaella; Crabtree, Kyle N.; Soderberg, Alicia M.; Sanders, Nathan E.; Drout, Maria R.; Kamble, Atish; Chakraborti, Sayan; Kirshner, Robert P.; Foster, Jonathan B.; Fesen, Robert A.; Parrent, Jerod T.; Pickering, Timothy E.; Cenko, S. Bradley; Silverman, Jeffrey M.; Marion, G. H. Howie; Vinko, Jozsef; Filippenko, Alexei V.; Mazzali, Paolo; Maeda, Keiichi; and others

    2014-02-10

    Diffuse interstellar bands (DIBs) are absorption features observed in optical and near-infrared spectra that are thought to be associated with carbon-rich polyatomic molecules in interstellar gas. However, because the central wavelengths of these bands do not correspond to electronic transitions of any known atomic or molecular species, their nature has remained uncertain since their discovery almost a century ago. Here we report on unusually strong DIBs in optical spectra of the broad-lined Type Ic supernova SN 2012ap that exhibit changes in equivalent width over short (≲ 30 days) timescales. The 4428 Å and 6283 Å DIB features get weaker with time, whereas the 5780 Å feature shows a marginal increase. These nonuniform changes suggest that the supernova is interacting with a nearby source of DIBs and that the DIB carriers possess high ionization potentials, such as small cations or charged fullerenes. We conclude that moderate-resolution spectra of supernovae with DIB absorptions obtained within weeks of outburst could reveal unique information about the mass-loss environment of their progenitor systems and provide new constraints on the properties of DIB carriers.

  4. Momentum transport near a magnetic X line in collisionless reconnection

    NASA Technical Reports Server (NTRS)

    Cai, H. J.; Ding, D. Q.; Lee, L. C.

    1994-01-01

    Plasma dynamics and momentum transport near an X line during time-dependent magnetic reconnection in a collisionless plasma are investigated based on two-dimensional particle simulations. We find that a weakly skewed velocity distribution is formed near the magnetic X line, leading to the presence of off-diagonal elements of the plasma pressure tensor. Let the reconnection electric field be in the y direction. The gradients of the off-diagonal elements of the pressure tensor can provide a transport of the y momentum. During the normal magnetic reconnection, the momentum transport associated with the off-diagonal terms of the pressure tensor mediates a transfer of the y momentum from the region near the X line to regions outside the X line. A period of 'reverse magnetic reconnection,' during which the plasma kinetic energy is converted into magnetic energy, is also observed in the simulation. When reverse reconnection occurs, the gradients of the off-diagonal pressure tensor elements can mediate a transfer of y momentum into the X line. It is found that the inertial term also plays a significant role in the force balance near the magnetic X line. An explanation for the origin of the off-diagonal pressure terms is also given in this paper.

  5. Transporting hot oil by a new concept in insulated lines

    SciTech Connect

    Matteelli, R.; Brambilla, M.; Pierangeli, P.

    1986-07-01

    Heavy fuel oil, heated to 60/sup 0/C, is transported to the Porto Tolle power plant, near Ravenna, Italy, through an 8-mi, 22-in. insulated pipe line system. The authors tell how Snamprogetti's patented pipe insulation system was used to connect a man-made island in the Adriatic Sea to the power plant.

  6. Assessment of costimulation and coinhibition in a triple parameter T cell reporter line: Simultaneous measurement of NF-κB, NFAT and AP-1.

    PubMed

    Jutz, Sabrina; Leitner, Judith; Schmetterer, Klaus; Doel-Perez, Iago; Majdic, Otto; Grabmeier-Pfistershammer, Katharina; Paster, Wolfgang; Huppa, Johannes B; Steinberger, Peter

    2016-03-01

    Engagement of the T cell receptor complex reprograms T cells for proliferation, cytokine production and differentiation towards effector cells. This process depends on activating costimulatory signals and is counteracted by coinhibitory molecules. Three transcription factors, namely NF-κB, NFAT and AP-1, have a major role in inducing the transcriptional program that is required for T cell activation and differentiation. Here we describe the generation of a triple parameter reporter based on the human Jurkat T cell line, where response elements for NF-κB, NFAT and AP-1 drive the expression of the fluorescent proteins CFP, eGFP and mCherry, respectively. The emission spectra of these proteins allow simultaneous assessment of NF-κB, NFAT and AP-1 activity in response to stimulation. Ligation of the TCR complex induced moderate reporter activity, which was strongly enhanced upon coengagement of the costimulatory receptors CD2 or CD28. Moreover, we have generated and tested triple parameter reporter cells that harbor costimulatory and inhibitory receptors not endogenously expressed in the Jurkat cells. In these experiments we could show that engagement of the costimulatory molecule 4-1BB enhances NF-κB and AP-1 activity, whereas coinhibition via PD-1 or BTLA strongly reduced the activation of NF-κB and NFAT. Engagement of BTLA significantly inhibited AP-1, whereas PD-1 had little effect on the activation of this transcription factor. Our triple parameter reporter T cell line is an excellent tool to assess the effect of costimulatory and coinhibitory receptors on NF-κB, NFAT and AP-1 activity and has a wide range of applications beyond the evaluation of costimulatory pathways.

  7. Electronic transport of bilayer graphene with asymmetry line defects

    NASA Astrophysics Data System (ADS)

    Zhao, Xiao-Ming; Wu, Ya-Jie; Chen, Chan; Liang, Ying; Kou, Su-Peng

    2016-11-01

    In this paper, we study the quantum properties of a bilayer graphene with (asymmetry) line defects. The localized states are found around the line defects. Thus, the line defects on one certain layer of the bilayer graphene can lead to an electric transport channel. By adding a bias potential along the direction of the line defects, we calculate the electric conductivity of bilayer graphene with line defects using the Landauer-Büttiker theory, and show that the channel affects the electric conductivity remarkably by comparing the results with those in a perfect bilayer graphene. This one-dimensional line electric channel has the potential to be applied in nanotechnology engineering. Project supported by the National Basic Research Program of China (Grant Nos. 2011CB921803 and 2012CB921704), the National Natural Science Foundation of China (Grant Nos. 11174035, 11474025, 11504285, and 11404090), the Specialized Research Fund for the Doctoral Program of Higher Education, China, the Fundamental Research Funds for the Central Universities, China, the Scientific Research Program Fund of the Shaanxi Provincial Education Department, China (Grant No. 15JK1363), and the Young Talent Fund of University Association for Science and Technology in Shaanxi Province, China.

  8. Transportation Lines on the Great Lakes System; Transportation Series 3; 1980.

    DTIC Science & Technology

    1982-05-01

    AD-A121 620 TRANSPORTATION LINE ON THE MEAT. LAMBS SYSTlEM f/l TRANSPORTATION’IES 3; 108(U) CORPS OF EHEERgeS FORT SELVOIR VA WATER RESORCES SUPPORT...different hem Controllti Office) IS. SECURITY CLASS. (of tis report) Water Resources Support Center Data Collection Management Division Unclassified...from: National Technical Information Service (NTIS) 5285 Port Royal Road Springfield, Va. 22161 19. KEY WORDS (Cstinue an revere. de It necesar7 amd

  9. SPES-2, AP600 intergral system test S01007 2 inch CL to core make-up tank pressure balance line break

    SciTech Connect

    Bacchiani, M.; Medich, C.; Rigamonti, M.

    1995-09-01

    The SPES-2 is a full height, full pressure experimental test facility reproducing the Westinghouse AP600 reactor with a scaling factor of 1/395. The experimental plant, designed and operated by SIET in Piacenza, consists of a full simulation of the AP600 primary core cooling system including all the passive and active safety systems. In 1992, Westinghouse, in cooperation with ENEL (Ente Nazionale per l` Energia Elettrica), ENEA (Enter per le numove Technlogie, l` Energia e l` Ambient), Siet (Societa Informazioni Esperienze Termoidraulich) and ANSALDO developed an experimental program to test the integrated behaviour of the AP600 passive safety systems. The SPES-2 test matrix, concluded in November 1994, has examined the AP600 passive safety system response for a range of small break LOCAs at different locations on the primary system and on the passive system lines; single steam generator tube ruptures with passive and active safety systems and a main steam line break transient to demonstrate the boration capability of passive safety systems for rapid cooldown. Each of the tests has provided detailed experimental results for verification of the capability of the analysis methods to predict the integrated passive safety system behaviour. Cold and hot shakedown tests have been performed on the facility to check the characteristics of the plant before starting the experimental campaign. The paper first presents a description of the SPES-2 test facility then the main results of S01007 test {open_quotes}2{close_quotes} Cold Leg (CL) to Core Make-up Tank (CMT) pressure balance line break{close_quotes} are reported and compared with predictions performed using RELAP5/mod3/80 obtained by ANSALDO through agreement with U.S.N.R.C. (U.S. Nuclear Regulatory Commission). The SPES-2 nodalization and all the calculations here presented were performed by ANSALDO and sponsored by ENEL as a part of pre-test predictions for SPES-2.

  10. Gibberellin Concentration and Transport in Genetic Lines of Pea 1

    PubMed Central

    Proebsting, William M.; Hedden, Peter; Lewis, Mervyn J.; Croker, Stephen J.; Proebsting, Lena N.

    1992-01-01

    Effects of the Na and Le loci on gibberellin (GA) content and transport in pea (Pisum sativum L.) shoots were studied. GA1, GA8, GA17, GA19, GA20, GA29, GA44, GA8 catabolite, and GA29 catabolite were identified by full-scan gas chromatography-mass spectrometry in extracts of expanding and fully expanded tissues of line C79-338 (Na Le). Quantification of GAs by gas chromatography-single-ion monitoring using deuterated internal standards in lines differing at the Na and Le alleles showed that na reduced the contents of GA19, GA20, and GA29 on average to <3% and of GA1 and GA8 to <30% of those in corresponding Na lines. In expanding tissues from Na le lines, GA1 and GA8 concentrations were reduced to approximately 10 and 2%, respectively, and GA29 content increased 2- to 3-fold compared with those in Na Le plants. There was a close correlation between stem length and the concentrations of GA1 or GA8 in shoot apices in all six genotypes investigated. In na/Na grafts, internode length and GA1 concentration of nana scions were normalized, the GA20 content increased slightly, but GA19 levels were unaffected. Movement of labeled GAs applied to leaves on Na rootstocks indicated that GA19 was transported poorly to apices of na scions compared with GA20 and GA1. Our evidence suggests that GA20 is the major transported GA in peas. Images Figure 2 PMID:16653128

  11. Mutation in AP-3 delta in the mocha mouse links endosomal transport to storage deficiency in platelets, melanosomes, and synaptic vesicles.

    PubMed

    Kantheti, P; Qiao, X; Diaz, M E; Peden, A A; Meyer, G E; Carskadon, S L; Kapfhamer, D; Sufalko, D; Robinson, M S; Noebels, J L; Burmeister, M

    1998-07-01

    The mouse mutant mocha, a model for the Hermansky-Pudlak storage pool deficiency syndrome, is characterized by defective platelets, coat and eye color dilution, lysosomal abnormalities, inner ear degeneration, and neurological deficits. Here, we show that mocha is a null allele of the delta subunit of the adaptor-like protein complex AP-3, which is associated with coated vesicles budding from the trans-Golgi network, and that AP-3 is missing in mocha tissues. In mocha brain, the ZnT-3 transporter is reduced, resulting in a lack of zinc-associated Timm historeactivity in hippocampal mossy fibers. Our results demonstrate that the AP-3 complex is responsible for cargo selection to lysosome-related organelles such as melanosomes and platelet dense granules as well as to neurotransmitter vesicles.

  12. A quantum transport model for atomic line radiation in plasmas*

    NASA Astrophysics Data System (ADS)

    Rosato, Joël

    2017-02-01

    Emission and absorption lines in plasmas are investigated theoretically using a phase space formulation of quantum electrodynamics. A transport equation for the one-photon Wigner function is derived and formulated in terms of the noncommutative Moyal product. This equation reduces to the standard radiative transfer equation at the large spectral band limit, when the characteristic spectral band of the emission and absorption coefficients is larger than the inverse photon absorption length and time. We examine deviations to this limit. An ideal slab geometry is considered. The Wigner function relative to hydrogen Lyman α in stellar atmospheric conditions is calculated.

  13. Line-by-line transport calculations for Jupiter entry probes. [of radiative transfer

    NASA Technical Reports Server (NTRS)

    Arnold, J. O.; Cooper, D. M.; Park, C.; Prakash, S. G.

    1979-01-01

    Line-by-line calculations of the radiative transport for a condition near peak heating for entry of the Galileo probe into the Jovian atmosphere are described. The discussion includes a thorough specification of the atomic and molecular input data used in the calculations that could be useful to others working in the field. The results show that the use of spectrally averaged cross sections for diatomic absorbers such as CO and C2 in the boundary layer can lead to an underestimation (by as much as 29%) of the spectral flux at the stagnation point. On the other hand, for the turbulent region near the cone frustum on the probe, the flow tends to be optically thin, and the spectrally averaged results commonly used in coupled radiative transport-flow field calculations are in good agreement with the present line-by-line results. It is recommended that these results be taken into account in sizing the final thickness of the Galileo's heat shield.

  14. The AP-3 adaptor complex mediates sorting of yeast and mammalian PQ-loop-family basic amino acid transporters to the vacuolar/lysosomal membrane

    PubMed Central

    Llinares, Elisa; Barry, Abdoulaye Oury; André, Bruno

    2015-01-01

    The limiting membrane of lysosomes in animal cells and that of the vacuole in yeast include a wide variety of transporters, but little is known about how these proteins reach their destination membrane. The mammalian PQLC2 protein catalyzes efflux of basic amino acids from the lysosome, and the similar Ypq1, −2, and −3 proteins of yeast perform an equivalent function at the vacuole. We here show that the Ypq proteins are delivered to the vacuolar membrane via the alkaline phosphatase (ALP) trafficking pathway, which requires the AP-3 adaptor complex. When traffic via this pathway is deficient, the Ypq proteins pass through endosomes from where Ypq1 and Ypq2 properly reach the vacuolar membrane whereas Ypq3 is missorted to the vacuolar lumen via the multivesicular body pathway. When produced in yeast, PQLC2 also reaches the vacuolar membrane via the ALP pathway, but tends to sort to the vacuolar lumen if AP-3 is defective. Finally, in HeLa cells, inhibiting the synthesis of an AP-3 subunit also impairs sorting of PQLC2 to lysosomes. Our results suggest the existence of a conserved AP-3-dependent trafficking pathway for proper delivery of basic amino acid exporters to the yeast vacuole and to lysosomes of human cells. PMID:26577948

  15. Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1.

    PubMed

    Jain, Shweta; Farías, Ginny G; Bonifacino, Juan S

    2015-01-15

    Neurons are highly polarized cells having distinct somatodendritic and axonal domains. Here we report that polarized sorting of the Cu(2+) transporter ATP7B and the vesicle-SNARE VAMP4 to the somatodendritic domain of rat hippocampal neurons is mediated by recognition of dileucine-based signals in the cytosolic domains of the proteins by the σ1 subunit of the clathrin adaptor AP-1. Under basal Cu(2+) conditions, ATP7B was localized to the trans-Golgi network (TGN) and the plasma membrane of the soma and dendrites but not the axon. Mutation of a dileucine-based signal in ATP7B or overexpression of a dominant-negative σ1 mutant resulted in nonpolarized distribution of ATP7B between the somatodendritic and axonal domains. Furthermore, addition of high Cu(2+) concentrations, previously shown to reduce ATP7B incorporation into AP-1-containing clathrin-coated vesicles, caused loss of TGN localization and somatodendritic polarity of ATP7B. These findings support the notion of AP-1 as an effector of polarized sorting in neurons and suggest that altered polarity of ATP7B in polarized cell types might contribute to abnormal copper metabolism in the MEDNIK syndrome, a neurocutaneous disorder caused by mutations in the σ1A subunit isoform of AP-1.

  16. Radiation protection considerations along a radioactive ion beam transport line

    NASA Astrophysics Data System (ADS)

    Sarchiapone, Lucia; Zafiropoulos, Demetre

    2016-09-01

    The goal of the SPES project is to produce accelerated radioactive ion beams for Physics studies at “Laboratori Nazionali di Legnaro” (INFN, Italy). This accelerator complex is scheduled to be built by 2016 for an effective operation in 2017. Radioactive species are produced in a uranium carbide target, by the interaction of 200 μA of protons at 40 MeV. All of the ionized species in the 1+ state come out of the target (ISOL method), and pass through a Wien filter for a first selection and an HMRS (high mass resolution spectrometer). Then they are transported by an electrostatic beam line toward a charge state breeder (where the 1+ to n+ multi-ionization takes place) before selection and reacceleration at the already existing superconducting linac. The work concerning dose evaluations, activation calculation, and radiation protection constraints related to the transport of the radioactive ion beam (RIB) from the target to the mass separator will be described in this paper. The FLUKA code has been used as tool for those calculations needing Monte Carlo simulations, in particular for the evaluation of the dose rate due to the presence of the radioactive beam in the selection/interaction points. The time evolution of a radionuclide inventory can be computed online with FLUKA for arbitrary irradiation profiles and decay times. The activity evolution is analytically evaluated through the implementation of the Bateman equations. Furthermore, the generation and transport of decay radiation (limited to gamma, beta- and beta+ emissions) is possible, referring to a dedicated database of decay emissions using mostly information obtained from NNDC, sometimes supplemented with other data and checked for consistency. When the use of Monte Carlo simulations was not feasible, the Bateman equations, or possible simplifications, have been used directly.

  17. Impact of punctual flat magnetic shear on the field line transport

    NASA Astrophysics Data System (ADS)

    Abud, C. V.; Caldas, I. L.

    2015-06-01

    We investigate the magnetic field line transport for tokamak equilibria with monotonic magnetic shear perturbed by resonant fields. We show that when the local profile is flat at the plasma edge a transport barrier can be created leading to a field line transport reduction. This transport reduction is due to the field lines topological modifications, caused by a local flattened profile that reduces the global field lines escape pattern. The results are obtained by applying a symplectic map that describes perturbed magnetic field lines in large aspect ratio tokamaks.

  18. Thyroid hormone transport in a human glioma cell line.

    PubMed

    Goncalves, E; Lakshmanan, M; Pontecorvi, A; Robbins, J

    1990-03-05

    The uptake of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) was studied in human glioma cells (Hs 683) and compared with that in several other neural cell lines. At 25 degrees C or 37 degrees C, total cell uptake rose rapidly and reached equilibrium within 60 min. The glioma cells had the highest uptake: 47.6 fmol of L-T3 and 43.4 fmol of L-T4 per 10(6) cells at 37 degrees C. These were inhibited 77% and 72%, respectively, by excess unlabeled hormone. Uptake in the nuclei reached equilibrium between 90 and 120 min and was also highest in glioma cells: 1.46 fmol of L-T3 and 0.49 fmol of L-T4 per 10(6) cells. When expressed as percent of total cell uptake, however, glioma cells had the lowest values (3.1% for L-T3 and 1.1% for L-T4). Also in contrast to other cell lines, glioma cells transported L-T4 almost as effectively as L-T3. D-T3 and D-T4 total cell uptake was 86% and 96% lower than that of the respective L-isomers, and the nuclear uptake as a fraction of the cell uptake was similar. Kinetic analysis of the initial rate of cell uptake gave Vmax values for D-T3 and D-T4 that were 97% and 98% lower than for the L-isomers. Antimycin and monodansylcadaverine decreased the Vmax as well as the equilibrium cell and nuclear uptake of the L-isomers. The apparent nuclear affinity constant for L-T4 in intact cells was inhibited 90% in the presence of antimycin, whereas no effect was observed in isolated nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Beam transport radiation shielding for branch lines 2-ID-B and 2-ID-C

    SciTech Connect

    Feng, Y.P.; Lai, B.; McNulty, I.; Dejus, R.J.; Randall, K.J.; Yun, W.

    1995-08-01

    The x-ray radiation shielding requirements beyond the first optics enclosure have been considered for the beam transport of the 2-ID-B and 2-ID-C branch lines of Sector 2 (SRI-CAT) of the APS. The first three optical components (mirrors) of the 2-ID-B branch are contained within the shielded first optics enclosure. Calculations indicate that scattering of the primary synchrotron beam by beamline components outside the enclosure, such as apertures and monochromators, or by gas particles in case of vacuum failure is within safe limits for this branch. A standard 2.5-inch-diameter stainless steel pipe with 1/16-inch-thick walls provides adequate shielding to reduce the radiation dose equivalent rate to human tissue to below the maximum permissible limit of 0.25 mrem/hr. The 2-ID-C branch requires, between the first optics enclosure where only two mirrors are used and the housing for the third mirror, additional lead shielding (0.75 mm) and a minimum approach distance of 2.6 cm. A direct beam stop consisting of at least 4.5 mm of lead is also required immediately downstream of the third mirror for 2-ID-C. Finally, to stop the direct beam from escaping the experimental station, a beam stop consisting of at least 4-mm or 2.5-mm steel is required for the 2-ID-B or 2-ID-C branches, respectively. This final requirement can be met by the vacuum chambers used to house the experiments for both branch lines.

  20. Magnetic stars with wide depressions in the continuum. 1. The Ap star with strong silicon lines HD5601

    NASA Astrophysics Data System (ADS)

    Romanyuk, I. I.; Kudryavtsev, D. O.; Semenko, E. A.; Moiseeva, A. V.

    2016-10-01

    Based on observations with the 6-m SAO RAS telescope, we have found that chemically peculiar star with a large depression of the continuum at λ5200 Å and strengthened silicon lines in the spectrum has a strong magnetic field. The longitudinal field component B e has a negative polarity and varies from -300 G to -2000 G with a period of 1.756 days. Photometric variations of brightness take place with the same period. We determined the variability of the radial velocity at times of about tens of years pointing to a possible binarity of the object. We have built a magnetic model of this star, determined the inclination angles of the rotation axis to the line of sight i = 20° and of the dipole axis to the rotation axis β = 116°, and the field strength at the pole is B p = 10 kG. We carried out a chemical composition analysis and found a lack of helium for almost an order of magnitude, some overabundance of silicon and metal elements for more than an order of magnitude, particularly, cobalt for three orders of magnitude.

  1. 8 CFR 241.9 - Notice to transportation line of alien's removal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Notice to transportation line of alien's removal. 241.9 Section 241.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Post-hearing Detention and Removal § 241.9 Notice to transportation line of alien's...

  2. 8 CFR 241.9 - Notice to transportation line of alien's removal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Notice to transportation line of alien's removal. 241.9 Section 241.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Post-hearing Detention and Removal § 241.9 Notice to transportation line of alien's...

  3. The Broad-lined Type Ic SN 2012ap and the Nature of Relativistic Supernovae Lacking a Gamma-Ray Burst Detection

    NASA Astrophysics Data System (ADS)

    Milisavljevic, D.; Margutti, R.; Parrent, J. T.; Soderberg, A. M.; Fesen, R. A.; Mazzali, P.; Maeda, K.; Sanders, N. E.; Cenko, S. B.; Silverman, J. M.; Filippenko, A. V.; Kamble, A.; Chakraborti, S.; Drout, M. R.; Kirshner, R. P.; Pickering, T. E.; Kawabata, K.; Hattori, T.; Hsiao, E. Y.; Stritzinger, M. D.; Marion, G. H.; Vinko, J.; Wheeler, J. C.

    2015-01-01

    We present ultraviolet, optical, and near-infrared observations of SN 2012ap, a broad-lined Type Ic supernova in the galaxy NGC 1729 that produced a relativistic and rapidly decelerating outflow without a gamma-ray burst signature. Photometry and spectroscopy follow the flux evolution from -13 to +272 days past the B-band maximum of -17.4 ± 0.5 mag. The spectra are dominated by Fe II, O I, and Ca II absorption lines at ejecta velocities of v ≈ 20,000 km s-1 that change slowly over time. Other spectral absorption lines are consistent with contributions from photospheric He I, and hydrogen may also be present at higher velocities (v >~ 27,000 km s-1). We use these observations to estimate explosion properties and derive a total ejecta mass of ~2.7 M ⊙, a kinetic energy of ~1.0 × 1052 erg, and a 56Ni mass of 0.1-0.2 M ⊙. Nebular spectra (t > 200 days) exhibit an asymmetric double-peaked [O I] λλ6300, 6364 emission profile that we associate with absorption in the supernova interior, although toroidal ejecta geometry is an alternative explanation. SN 2012ap joins SN 2009bb as another exceptional supernova that shows evidence for a central engine (e.g., black hole accretion or magnetar) capable of launching a non-negligible portion of ejecta to relativistic velocities without a coincident gamma-ray burst detection. Defining attributes of their progenitor systems may be related to notable observed properties including environmental metallicities of Z >~ Z ⊙, moderate to high levels of host galaxy extinction (E(B - V) > 0.4 mag), detection of high-velocity helium at early epochs, and a high relative flux ratio of [Ca II]/[O I] >1 at nebular epochs. These events support the notion that jet activity at various energy scales may be present in a wide range of supernovae.

  4. The Broad-Lined Type Ic SN 2012ap and the Nature of Relativistic Supernovae Lacking a Gamma-Ray Burst Detection

    NASA Technical Reports Server (NTRS)

    Milisavljevic, D.; Margutti, R.; Parrent, J. T.; Soderberg, A. M.; Fesen, R. A.; Mazzali, P.; Maeda, K.; Sanders, N. E.; Cenko, S. B.; Silverman, J. M.

    2014-01-01

    We present ultraviolet, optical, and near-infrared observations of SN2012ap, a broad-lined Type Ic supernova in the galaxy NGC 1729 that produced a relativistic and rapidly decelerating outflow without a gamma-ray burst signature. Photometry and spectroscopy follow the flux evolution from -13 to +272 days past the B-band maximum of -17.4 +/- 0.5 mag. The spectra are dominated by Fe II, O I, and Ca II absorption lines at ejecta velocities of v approx. 20,000 km s(exp. -1) that change slowly over time. Other spectral absorption lines are consistent with contributions from photospheric He I, and hydrogen may also be present at higher velocities (v approx. greater than 27,000 km s(exp. -1)). We use these observations to estimate explosion properties and derive a total ejecta mass of 2.7 Solar mass, a kinetic energy of 1.0×1052 erg, and a (56)Ni mass of 0.1-0.2 Solar mass. Nebular spectra (t > 200 d) exhibit an asymmetric double-peaked [O I] lambda lambda 6300, 6364 emission profile that we associate with absorption in the supernova interior, although toroidal ejecta geometry is an alternative explanation. SN2012ap joins SN2009bb as another exceptional supernova that shows evidence for a central engine (e.g., black-hole accretion or magnetar) capable of launching a non-negligible portion of ejecta to relativistic velocities without a coincident gamma-ray burst detection. Defining attributes of their progenitor systems may be related to notable properties including above-average environmental metallicities of Z approx. greater than Solar Z, moderate to high levels of host-galaxy extinction (E(B -V ) > 0.4 mag), detection of high-velocity helium at early epochs, and a high relative flux ratio of [Ca II]/[O I] > 1 at nebular epochs. These events support the notion that jet activity at various energy scales may be present in a wide range of supernovae.

  5. THE BROAD-LINED Type Ic SN 2012ap AND THE NATURE OF RELATIVISTIC SUPERNOVAE LACKING A GAMMA-RAY BURST DETECTION

    SciTech Connect

    Milisavljevic, D.; Margutti, R.; Parrent, J. T.; Soderberg, A. M.; Sanders, N. E.; Kamble, A.; Chakraborti, S.; Drout, M. R.; Kirshner, R. P.; Fesen, R. A.; Mazzali, P.; Maeda, K.; Cenko, S. B.; Silverman, J. M.; Filippenko, A. V.; Pickering, T. E.; Kawabata, K.; Hattori, T.; Hsiao, E. Y.; Stritzinger, M. D.; and others

    2015-01-20

    We present ultraviolet, optical, and near-infrared observations of SN 2012ap, a broad-lined Type Ic supernova in the galaxy NGC 1729 that produced a relativistic and rapidly decelerating outflow without a gamma-ray burst signature. Photometry and spectroscopy follow the flux evolution from –13 to +272 days past the B-band maximum of –17.4 ± 0.5 mag. The spectra are dominated by Fe II, O I, and Ca II absorption lines at ejecta velocities of v ≈ 20,000 km s{sup –1} that change slowly over time. Other spectral absorption lines are consistent with contributions from photospheric He I, and hydrogen may also be present at higher velocities (v ≳ 27,000 km s{sup –1}). We use these observations to estimate explosion properties and derive a total ejecta mass of ∼2.7 M {sub ☉}, a kinetic energy of ∼1.0 × 10{sup 52} erg, and a {sup 56}Ni mass of 0.1-0.2 M {sub ☉}. Nebular spectra (t > 200 days) exhibit an asymmetric double-peaked [O I] λλ6300, 6364 emission profile that we associate with absorption in the supernova interior, although toroidal ejecta geometry is an alternative explanation. SN 2012ap joins SN 2009bb as another exceptional supernova that shows evidence for a central engine (e.g., black hole accretion or magnetar) capable of launching a non-negligible portion of ejecta to relativistic velocities without a coincident gamma-ray burst detection. Defining attributes of their progenitor systems may be related to notable observed properties including environmental metallicities of Z ≳ Z {sub ☉}, moderate to high levels of host galaxy extinction (E(B – V) > 0.4 mag), detection of high-velocity helium at early epochs, and a high relative flux ratio of [Ca II]/[O I] >1 at nebular epochs. These events support the notion that jet activity at various energy scales may be present in a wide range of supernovae.

  6. Establishment and characterization of cetuximab resistant head and neck squamous cell carcinoma cell lines: focus on the contribution of the AP-1 transcription factor

    PubMed Central

    Boeckx, Carolien; Blockx, Lina; de Beeck, Ken Op; Limame, Ridha; Camp, Guy Van; Peeters, Marc; Vermorken, Jan B; Specenier, Pol; Wouters, An; Baay, Marc; Lardon, Filip

    2015-01-01

    Background: After an initial response to EGFR targeted therapy, secondary resistance almost invariably ensues, thereby limiting the clinical benefit of the drug. Hence, it has been recognized that the successful implementation of targeted therapy in the treatment of HNSCC cancer is very much dependent on predictive biomarkers for patient selection. Methods: We generated an in vitro model of acquired cetuximab resistance by chronically exposing three HNSCC cell lines to increasing cetuximab doses. Gene expression profiles of sensitive parental cells and resistant daughter cells were compared using microarray analysis. Growth inhibitory experiments were performed with an HB-EGF antibody and the MMP inhibitor, both in combination with cetuximab. Characteristics of EMT were analyzed using migration and invasion assays, immunofluorescent vimentin staining and qRT-PCR for several genes involved in this process. The function of the transcription factor AP-1 was investigated using qRT-PCR for several genes upregulated or downregulated in cetuximab resistant cells. Furthermore, anchorage-independent growth was investigated using the soft agar assay. Results: Gene expression profiling shows that cetuximab resistant cells upregulate several genes, including interleukin 8, the EGFR ligand HB-EGF and the metalloproteinase ADAM19. Cytotoxicity experiments with neutralizing HB-EGF antibody could not induce any growth inhibition, whereas an MMP inhibitor inhibited cell growth in cetuximab resistant cells. However, no synergetic effects combined with cetuximab could be observed. Cetuximab resistant cells showed traits of EMT, as witnessed by increased migratory potential, increased invasive potential, increased vimentine expression and increased expression of several genes involved in EMT. Furthermore, expression of upregulated genes could be repressed by the treatment with apigenin. The cetuximab resistant LICR-HN2 R10.3 cells tend to behave differently in cell culture, forming

  7. Effects of Escherichia coli Challenge and Transport Stress on Hematology and Serum Chemistry Values of Three Genetic Lines of Turkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Males and females from 3 genetic lines of turkeys were compared for their response to an Escherichia coli airsac challenge followed by transport stress (Transport). The turkey lines were a slow growing line selected for increased egg production (Egg line), a fast growing line selected for increased...

  8. An agarose-gel based method for transporting cell lines.

    PubMed

    Yang, Lingzhi; Li, Chufang; Chen, Ling; Li, Zhiyuan

    2009-12-16

    Cryopreserved cells stored in dry ice or liquid nitrogen is the classical method for transporting cells between research laboratories in different cities around the world in order to maintain cell viability. An alternative method is to ship the live cells in flasks filled with cell culture medium. Both methods have limitations of either a requirement on special shipping container or short times for the cells to survive on the shipping process. We have recently developed an agarose gel based method for directly transporting the live adherent cells in cell culture plates or dishes in ambient temperature. This convenient method simplifies the transportation of live cells in long distance that can maintain cells in good viability for several days.

  9. Error analysis in post linac to driver linac transport beam line of RAON

    NASA Astrophysics Data System (ADS)

    Kim, Chanmi; Kim, Eun-San

    2016-07-01

    We investigated the effects of magnet errors in the beam transport line connecting the post linac to the driver linac (P2DT) in the Rare Isotope Accelerator in Korea (RAON). The P2DT beam line is bent by 180-degree to send the radioactive Isotope Separation On-line (ISOL) beams accelerated in Linac-3 to Linac-2. This beam line transports beams with multi-charge state 132Sn45,46,47. The P2DT beam line includes 42 quadrupole, 4 dipole and 10 sextupole magnets. We evaluate the effects of errors on the trajectory of the beam by using the TRACK code, which includes the translational and the rotational errors of the quadrupole, dipole and sextupole magnets in the beam line. The purpose of this error analysis is to reduce the rate of beam loss in the P2DT beam line. The distorted beam trajectories can be corrected by using six correctors and seven monitors.

  10. Resolving magnetic field line stochasticity and parallel thermal transport in MHD simulations

    SciTech Connect

    Nishimura, Y.; Callen, J.D.; Hegna, C.C.

    1998-12-31

    Heat transport along braided, or chaotic magnetic field lines is a key to understand the disruptive phase of tokamak operations, both the major disruption and the internal disruption (sawtooth oscillation). Recent sawtooth experimental results in the Tokamak Fusion Test Reactor (TFTR) have inferred that magnetic field line stochasticity in the vicinity of the q = 1 inversion radius plays an important role in rapid changes in the magnetic field structures and resultant thermal transport. In this study, the characteristic Lyapunov exponents and spatial correlation of field line behaviors are calculated to extract the characteristic scale length of the microscopic magnetic field structure (which is important for net radial global transport). These statistical values are used to model the effect of finite thermal transport along magnetic field lines in a physically consistent manner.

  11. 8 CFR 233.2 - Transportation lines bringing aliens to the United States from or through foreign contiguous...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Transportation lines bringing aliens to the... Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS CONTRACTS WITH TRANSPORTATION LINES § 233.2 Transportation lines bringing aliens to the United States from or through...

  12. 8 CFR 233.2 - Transportation lines bringing aliens to the United States from or through foreign contiguous...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 8 Aliens and Nationality 1 2014-01-01 2014-01-01 false Transportation lines bringing aliens to the... Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS CONTRACTS WITH TRANSPORTATION LINES § 233.2 Transportation lines bringing aliens to the United States from or through...

  13. Dehydroascorbic acid taken up by glucose transporters stimulates estradiol production through inhibition of JNK/c-Jun/AP1 signaling in JAR cells.

    PubMed

    Wang, Yongjie; Tang, Chao; Wu, Minglan; Pan, Yibin; Ruan, Hongfeng; Chen, Linling; Yao, Hongyi; Zhu, Haibin; Wu, Ximei

    2014-08-01

    We have previously demonstrated that the reduced form of vitamin C (l-ascorbic acid, AA) is able to induce the production of both steroid and peptide hormones in human choriocarcinoma cells. Here, we attempted to investigate the role and underlying mechanism of the oxidized form of vitamin C, dehydroascorbic acid (DHA), in steroidogenesis in primary human cytotrophoblasts and human choriocarcinoma cells. Messenger RNA and protein levels of steroidogenic enzymes including P450 cholesterol side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) and aromatase were examined by quantitative RT-PCR and western blots, respectively. Progesterone (P4) and estradiol (E2) levels were determined by enzyme immunoassays. Knockdown of c-Jun was achieved by lentivirus-mediated shRNA, and signaling pathways implicated in DHA-induced steroidogenesis were examined by western blots and dual-luciferase assays. DHA dose-dependently induced the expression of steroidogenic enzymes including 3β-HSD1, 17β-HSD1 and aromatase at both mRNA and protein levels, and subsequently increased the production of E2 but not P4. These effects were synergized by diethylmaleate, a glutathione-depleting compound, and α-tocopherol, a reducing agent, but robustly attenuated by inhibition of DHA transportation by phloretin or 2-deoxy-d-glucose. DHA time-dependently inhibited JNK and c-Jun phosphorylation, and dose-dependently reduced AP1 reporter activity. JNK signaling pathway-specific inhibitor SP600125 and c-Jun shRNA both significantly increased the expression of steroidogenic enzymes and E2 production regardless of the presence or absence of DHA. These findings suggest that DHA is able to induce steroidogenesis through inhibition of JNK/c-Jun/AP1 signaling, and may therefore play indispensable roles in pregnancy maintenance.

  14. Status of the PXIE Low Energy Beam Transport Line

    SciTech Connect

    Prost, Lionel; Andrews, Richard; Chen, Alex; Hanna, Bruce; Scarpine, Victor; Shemyakin, Alexander; Steimel, Jim; D'Arcy, Richard

    2014-07-01

    A CW-compatible, pulsed H- superconducting RF linac (a.k.a. PIP-II) is envisaged as a possible path for upgrading Fermilab’s injection complex [1]. To validate the concept of the front-end of such machine, a test accelerator (a.k.a. PXIE) [2] is under construction. The warm part of this accelerator comprises a 10 mA DC, 30 keV H- ion source, a 2m-long LEBT, a 2.1 MeV CW RFQ, and a MEBT that feeds the first cryomodule. In addition to operating in the nominal CW mode, the LEBT should be able to produce a pulsed beam for both PXIE commissioning and modelling of the front-end nominal operation in the pulsed mode. Concurrently, it needs to provide effective means of inhibiting beam as part of the overall machine protection system. A peculiar feature of the present LEBT design is the capability of using the ~1m-long section immediately preceding the RFQ in two regimes of beam transport dynamics: neutralized and space charge dominated. This paper introduces the PXIE LEBT, reports on the status of the ion source and LEBT installation, and presents the first beam measurements.

  15. Zinc transporter mRNA expression in the RWPE-1 human prostate epithelial cell line.

    PubMed

    Albrecht, Amy L; Somji, Seema; Sens, Mary Ann; Sens, Donald A; Garrett, Scott H

    2008-08-01

    The human prostate gland undergoes a prominent alteration in Zn+2 homeostasis during the development of prostate cancer. The goal of the present study was to determine if the immortalized human prostate cell line (RWPE-1) could serve as a model system to study the role of zinc in prostate cancer. The study examined the expression of mRNA for 19 members of the zinc transporter gene family in normal prostate tissue, the prostate RWPE-1 cell line, and the LNCaP, DU-145 and PC-3 prostate cancer cell lines. The study demonstrated that the expression of the 19 zinc transporters was similar between the RWPE-1 cell line and the in situ prostate gland. Of the 19 zinc transporters, only 5 had levels that were different between the RWPE-1 cells and the tissue samples; all five being increased (ZnT-6, Zip-1, Zip-3A, Zip-10, and Zip-14). The response of the 19 transporters was also determined when the cell lines were exposed to 75 microM Zn+2 for 24 h. It was shown for the RWPE-1 cells that only 5 transporters responded to Zn+2 with mRNA for ZnT-1 and ZnT-2 being increased while mRNA for ZnT-7, Zip-7 and Zip-10 transporters were decreased. It was shown for the LNCaP, DU-145 and PC-3 cells that Zn+2 had no effect on the mRNA levels of all 19 transporters except for an induction of ZnT-1 in PC-3 cells. Overall, the study suggests that the RWPE-1 cells could be a valuable model for the study of the zinc transporter gene family in the prostate.

  16. 8 CFR 233.2 - Transportation lines bringing aliens to the United States from or through foreign contiguous...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Transportation lines bringing aliens to the United States from or through foreign contiguous territory or adjacent islands. 233.2 Section 233.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS CONTRACTS WITH TRANSPORTATION LINES § 233.2 Transportation...

  17. 8 CFR 233.2 - Transportation lines bringing aliens to the United States from or through foreign contiguous...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 8 Aliens and Nationality 1 2012-01-01 2012-01-01 false Transportation lines bringing aliens to the United States from or through foreign contiguous territory or adjacent islands. 233.2 Section 233.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS CONTRACTS WITH TRANSPORTATION LINES § 233.2 Transportation...

  18. 8 CFR 233.2 - Transportation lines bringing aliens to the United States from or through foreign contiguous...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Transportation lines bringing aliens to the United States from or through foreign contiguous territory or adjacent islands. 233.2 Section 233.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS CONTRACTS WITH TRANSPORTATION LINES § 233.2 Transportation...

  19. Operation of the intensity monitors in beam transport lines at Fermilab during Run II¹

    DOE PAGES

    Crisp, J.; Fellenz, B.; Fitzgerald, J.; ...

    2011-10-06

    The intensity of charged particle beams at Fermilab must be kept within pre-determined safety and operational envelopes in part by assuring all beam within a few percent has been transported from any source to destination. Beam instensity monitors with toroidial pickups provide such beam intensity measurements in the transport lines between accelerators at FNAL. With Run II, much effort was made to continually improve the resolution and accuracy of the system.

  20. APS Science 2007.

    SciTech Connect

    Not Available

    2008-05-30

    This report provides research highlights from the Advanced Photon Source (APS). Although these highlights represent less than 10% of the published work from the APS in 2007, they give a flavor of the diversity and impact of user research at the facility. In the strategic planning the aim is to foster the growth of existing user communities and foresee new areas of research. This coming year finds the APS engaged in putting together, along with the users, a blueprint for the next five years, and making the case for a set of prioritized investments in beamlines, the accelerator, and infrastructure, each of which will be transformational in terms of scientific impact. As this is written plans are being formulated for an important user workshop on October 20-21, 2008, to prioritize strategic plans. The fruit from past investments can be seen in this report. Examples include the creation of a dedicated beamline for x-ray photon correlation spectroscopy at Sector 8, the evolution of dedicated high-energy x-ray scattering beamlines at sectors 1 and 11, a dedicated imaging beamline at Sector 32, and new beamlines for inelastic scattering and powder diffraction. A single-pulse facility has been built in collaboration with Sector 14 (BioCARS) and Phil Anfinrud at the National Institutes of Health, which will offer exceptionally high flux for single-pulse diffraction. The nanoprobe at Sector 26, built and operated jointly by the Argonne Center for Nanoscale Materials and the X-ray Operations and Research (XOR) section of the APS X-ray Science Division, has come on line to define the state of the art in nanoscience.

  1. Numerical Modelling of Intense Electron Beam Transport in the Spiral Line Induction Accelerator

    DTIC Science & Technology

    1992-08-28

    arising in the context of the spiral line induction accelerator (SLIA), a device in which the beam is transported along an open-ended beam pipe ...field. Because the field coils are wound directly onto the spiral beam pipe , and because each bend is magnetically shielded from its neighbors, each... Spiral Line Induction Accelerator J. KRALL, S. SLINKER, M. LAMPE AND G. JOYCE Beam Physics Branch Plasma Physics Division August 28, 1992 _pw DTIC U)lz E

  2. Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT.

    PubMed

    Lee, N-Y; Choi, H-M; Kang, Y-S

    2009-04-01

    Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.

  3. 76 FR 52731 - On-Line Complaint Form for Service-Related Issues in Air Transportation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... Office of the Secretary On-Line Complaint Form for Service-Related Issues in Air Transportation AGENCY... public to electronically submit aviation service-related complaints against air carriers. DATES: Comments... U.S.C., Subtitle VII, to investigate and enforce consumer protection and civil rights laws...

  4. 8 CFR 241.24 - Notice to transportation line of alien's exclusion.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 8 Aliens and Nationality 1 2011-01-01 2011-01-01 false Notice to transportation line of alien's exclusion. 241.24 Section 241.24 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Deportation of Excluded Aliens (for Hearings Commenced Prior to April 1, 1997) §...

  5. 8 CFR 241.24 - Notice to transportation line of alien's exclusion.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Notice to transportation line of alien's exclusion. 241.24 Section 241.24 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Deportation of Excluded Aliens (for Hearings Commenced Prior to April 1, 1997) §...

  6. RISK ASSESSMENT ANALYSES USING EPA'S ON-LINE SITE-SPECIFIC TRANSPORT MODELS AND FIELD DATA

    EPA Science Inventory

    EPA has developed a suite of on-line calculators and transport models to aid in risk assessment for subsurface contamination. The calculators (www.epa.gov/athens/onsite) provide several levels of tools and data. These include tools for generating commonly-used model input param...

  7. 8 CFR 241.9 - Notice to transportation line of alien's removal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Notice to transportation line of alien's removal. 241.9 Section 241.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Post-hearing Detention and Removal §...

  8. 8 CFR 241.24 - Notice to transportation line of alien's exclusion.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Notice to transportation line of alien's exclusion. 241.24 Section 241.24 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Deportation of Excluded Aliens (for...

  9. THE ONSITE ON-LINE CALCULATORS AND TRAINING FOR SUBSURFACE CONTAMINANT TRANSPORT SITE ASSESSMENT

    EPA Science Inventory

    EPA has developed a suite of on-line calculators called "OnSite" for assessing transport of environmental contaminants in the subsurface. The purpose of these calculators is to provide methods and data for common calculations used in assessing impacts from subsurface contaminatio...

  10. 8 CFR 241.9 - Notice to transportation line of alien's removal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 8 Aliens and Nationality 1 2012-01-01 2012-01-01 false Notice to transportation line of alien's removal. 241.9 Section 241.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Post-hearing Detention and Removal §...

  11. 8 CFR 241.24 - Notice to transportation line of alien's exclusion.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 8 Aliens and Nationality 1 2012-01-01 2012-01-01 false Notice to transportation line of alien's exclusion. 241.24 Section 241.24 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS APPREHENSION AND DETENTION OF ALIENS ORDERED REMOVED Deportation of Excluded Aliens (for...

  12. Transport and dosimetric solutions for the ELIMED laser-driven beam line

    NASA Astrophysics Data System (ADS)

    Cirrone, G. A. P.; Romano, F.; Scuderi, V.; Amato, A.; Candiano, G.; Cuttone, G.; Giove, D.; Korn, G.; Krasa, J.; Leanza, R.; Manna, R.; Maggiore, M.; Marchese, V.; Margarone, D.; Milluzzo, G.; Petringa, G.; Sabini, M. G.; Schillaci, F.; Tramontana, A.; Valastro, L.; Velyhan, A.

    2015-10-01

    Within 2017, the ELIMED (ELI-Beamlines MEDical applications) transport beam-line and dosimetric systems for laser-generated beams will be installed at the ELI-Beamlines facility in Prague (CZ), inside the ELIMAIA (ELI Multidisciplinary Applications of laser-Ion Acceleration) interaction room. The beam-line will be composed of two sections: one in vacuum, devoted to the collecting, focusing and energy selection of the primary beam and the second in air, where the ELIMED beam-line dosimetric devices will be located. This paper briefly describes the transport solutions that will be adopted together with the main dosimetric approaches. In particular, the description of an innovative Faraday Cup detector with its preliminary experimental tests will be reported.

  13. Establishment of optimized MDCK cell lines for reliable efflux transport studies.

    PubMed

    Gartzke, Dominik; Fricker, Gert

    2014-04-01

    Madin-Darby canine kidney (MDCK) cells transfected with human MDR1 gene (MDCK-MDR1) encoding for P-glycoprotein (hPgp, ABCB1) are widely used for transport studies to identify drug candidates as substrates of this efflux protein. Therefore, it is necessary to rely on constant and comparable expression levels of Pgp to avoid false negative or positive results. We generated a cell line with homogenously high and stable expression of hPgp through sorting single clones from a MDCK-MDR1 cell pool using fluorescence-activated cell sorting (FACS). To obtain control cell lines for evaluation of cross-interactions with endogenous canine Pgp (cPgp) wild-type cells were sorted with a low expression pattern of cPgp in comparison with the MDCK-MDR1. Expression of other transporters was also characterized in both cell lines by quantitative real-time PCR and Western blot. Pgp function was investigated applying the Calcein-AM assay as well as bidirectional transport assays using (3) H-Digoxin, (3) H-Vinblastine, and (3) H-Quinidine as substrates. Generated MDCK-MDR1 cell lines showed high expression of hPgp. Control MDCK-WT cells were optimized in showing a comparable expression level of cPgp in comparison with MDCK-MDR1 cell lines. Generated cell lines showed higher and more selective Pgp transport compared with parental cells. Therefore, they provide a significant improvement in the performance of efflux studies yielding more reliable results.

  14. Continuous Nano-Particle Transport in a Standing Wave Optical Line Trap

    NASA Astrophysics Data System (ADS)

    Demergis, Vassili; Florin, Ernst-Ludwig

    2011-03-01

    Since the introduction of the single beam optical trap (SBT) by Ashkin et. al. in 1986, trapping and manipulation of micron-sized particles by optical forces has become instrumental in many areas of research. However, controlled transport of large numbers of particles is difficult using a SBT. Here we introduce a technique for controlled transport that we call an Optical Capillary (OC), named for its ability to strongly confine and continuously transport nanometer-sized particles. The OC, generated by an optical standing wave pattern, is especially strong along the optical axis due to the compensation of the axial scattering force. We utilize the lateral scattering forces to control the transport of particles along a line perpendicular to the optical axis. The measured velocity profiles of single particles in the OC agree with our model predictions.

  15. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family.

    PubMed Central

    Dreyling, M H; Martinez-Climent, J A; Zheng, M; Mao, J; Rowley, J D; Bohlander, S K

    1996-01-01

    The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line. Images Fig. 1 Fig. 3 PMID:8643484

  16. Tuning spin polarization and spin transport of zigzag graphene nanoribbons by line defects.

    PubMed

    Tang, G P; Zhang, Z H; Deng, X Q; Fan, Z Q; Zhu, H L

    2015-01-07

    From first-principles methods, the spin-dependent electronic properties of zigzag-edged graphene nanoribbons (ZGNRs) with a line defect (558-defect) are investigated systematically and compared to those of the pristine ZGNR. Results show that the line defect possesses an obvious tuning effect on the spin-polarization of the edge carbon atoms of the defective ZGNRs, and the spin-polarization and spin-transport are sensitive to the position of line defects. The defective ZGNRs can realize a transition from antiferromagnetism (AFM) to ferrimagnetism and ferromagnetism (FM) via changing the position of line defects from the center to the zigzag edge of ZGNRs. More importantly, when the line defect is located at the one edge, the defective ZGNRs exhibit the long-range magnetic ordering at edges with a high Curie temperature up to 276 K, and the defective ZGNR system can generate a high-performance spin-filter effect in the large bias range, 0.0-0.5 V. Such a sensitive modulation for the spin-polarization and spin-transport holds great promise for applications of the graphene-based systems in nano-scale spintronic devices.

  17. Extracting potential bus lines of Customized City Bus Service based on public transport big data

    NASA Astrophysics Data System (ADS)

    Ren, Yibin; Chen, Ge; Han, Yong; Zheng, Huangcheng

    2016-11-01

    Customized City Bus Service (CCBS) can reduce the traffic congestion and environmental pollution that caused by the increasing in private cars, effectively. This study aims to extract the potential bus lines and each line's passenger density of CCBS by mining the public transport big data. The datasets used in this study are mainly Smart Card Data (SCD) and bus GPS data of Qingdao, China, from October 11th and November 7th 2015. Firstly, we compute the temporal-origin-destination (TOD) of passengers by mining SCD and bus GPS data. Compared with the traditional OD, TOD not only has the spatial location, but also contains the trip's boarding time. Secondly, based on the traditional DBSCAN algorithm, we put forwards an algorithm, named TOD-DBSCAN, combined with the spatial-temporal features of TOD.TOD-DBSCAN is used to cluster the TOD trajectories in peak hours of all working days. Then, we define two variables P and N to describe the possibility and passenger destiny of a potential CCBS line. P is the probability of the CCBS line. And N represents the potential passenger destiny of the line. Lastly, we visualize the potential CCBS lines extracted by our procedure on the map and analyse relationship between potential CCBS lines and the urban spatial structure.

  18. Development of a hybrid kinetic-fluid model for line radiation transport in magnetic fusion plasmas

    NASA Astrophysics Data System (ADS)

    Rosato, J.; Marandet, Y.; Reiter, D.; Stamm, R.

    2017-03-01

    We report on a transport model for the Lyman line radiation in optically thick divertor plasma conditions encountered in exhaust systems in magnetic fusion devices. The model is designed to switch automatically between a kinetic and a continuum description according to the plasma conditions and to the spectral range. A kinetic treatment is retained for photons with a large mean free path (line wings), whereas a continuum description of the radiation field is invoked in highly absorbing or scattering regions (core photons). Prototypical calculations of this so-called δf Monte Carlo type of the Lyman α photo-excitation rate in slab geometry are performed as an illustration. The hybrid method is suggested as a candidate for speeding up the kinetic transport codes currently involved in magnetic fusion research for ITER and DEMO divertor (power and particle exhaust system) design.

  19. Long-range transport of anthropogenic sulfur in an on-line tracer model

    SciTech Connect

    Dastoor, A.P.

    1996-12-31

    An Eulerian global meteorological tracer transport model has been constructed for simulating the long range transport of anthropogenic sulfur. The advantage of this model is that the physical processes in the atmosphere, advection and chemical conversions are calculated within one consistent modeling system. The global model presented here includes the dynamics of meteorological and tracer fields, thermodynamics, cloud processes, turbulent boundary layer mixing, multiple 3-dimensional anthropogenic sulfur emission sources, dry and aqueous-phase chemical processes for sulfur, dry deposition process and the precipitation scavenging of sulfur. In contrast to an off-line chemical transport model the dynamic global tracer model is capable of studying the interaction between pollutant, radiative and hydrological budgets and atmospheric circulation.

  20. Transport line for a multi-staged laser-plasma acceleration: DACTOMUS

    NASA Astrophysics Data System (ADS)

    Chancé, Antoine; Delferrière, Olivier; Schwindling, Jérôme; Bruni, Christelle; Delerue, Nicolas; Specka, Arnd; Cros, Brgitte; Maynard, Gillies; Paradkar, Bhooshan S.; Mora, Patrick

    2014-03-01

    Laser-plasma acceleration is one of the most promising techniques to reach very high acceleration gradients up to a few hundreds of GeV/m. In order to push this acceleration scheme in the domain of the very high energies, the CILEX project was launched with the laser APOLLON. One of the main topics of this project is to study multi-staged acceleration. It consists in generating and pre-accelerating electrons in a first laser-plasma stage, to transport them up to a second stage where the electrons are accelerated again thanks to another laser pulse. The DACTOMUS project, based on a collaboration CEA-IRFU, CEA-IRAMIS, LAL, LPGP, LULI and LLR, aims at the study and realization of such a transfer line between these two stages. Firstly, a prototype will be developed and tested by the groups of CEA-IRAMIS-SPAM, LPGP, and LULI on the UHI100 facility (CEA-SPAM). This collaboration must enable to realize the first acceleration stage. For the transport line prototype, the main difficulties are to realize a very compact and energy accepting line with diagnostics to characterize the electron beam. We will present here the optics of this line, its performances and the inserted diagnostics.

  1. AP Music Theory Applied

    ERIC Educational Resources Information Center

    Spieker, Matthew H.

    2016-01-01

    Some American high schools include Advanced Placement (AP) Music Theory within their course offerings. Students who pass the AP exam can receive college credit either as a music or humanities credit. An AP class, however, offers music students more than future college credit; it ultimately improves musicianship skills and promotes deeper…

  2. Predominant role of plasma membrane monoamine transporters in monoamine transport in 1321N1, a human astrocytoma-derived cell line.

    PubMed

    Naganuma, Fumito; Yoshikawa, Takeo; Nakamura, Tadaho; Iida, Tomomitsu; Harada, Ryuichi; Mohsen, Attayeb S; Miura, Yamato; Yanai, Kazuhiko

    2014-05-01

    Monoamine neurotransmitters should be immediately removed from the synaptic cleft to avoid excessive neuronal activity. Recent studies have shown that astrocytes and neurons are involved in monoamine removal. However, the mechanism of monoamine transport by astrocytes is not entirely clear. We aimed to elucidate the transporters responsible for monoamine transport in 1321N1, a human astrocytoma-derived cell line. First, we confirmed that 1321N1 cells transported dopamine, serotonin, norepinephrine, and histamine in a time- and dose-dependent manner. Kinetics analysis suggested the involvement of low-affinity monoamine transporters, such as organic cation transporter (OCT) 2 and 3 and plasma membrane monoamine transporter (PMAT). Monoamine transport in 1321N1 cells was not Na(+) /Cl(-) dependent but was inhibited by decynium-22, an inhibitor of low-affinity monoamine transporters, which supported the importance of low-affinity transporters. RT-PCR assays revealed that 1321N1 cells expressed OCT3 and PMAT but no other neurotransmitter transporters. Another human astrocytoma-derived cell line, U251MG, and primary human astrocytes also exhibited the same gene expression pattern. Gene-knockdown assays revealed that 1321N1 and primary human astrocytes could transport monoamines predominantly through PMAT and partly through OCT3. These results might indicate that PMAT and OCT3 in human astrocytes are involved in monoamine clearance.

  3. Organelle Transport in Cultured Drosophila Cells: S2 Cell Line and Primary Neurons.

    PubMed Central

    Gelfand, Vladimir I.

    2013-01-01

    Drosophila S2 cells plated on a coverslip in the presence of any actin-depolymerizing drug form long unbranched processes filled with uniformly polarized microtubules. Organelles move along these processes by microtubule motors. Easy maintenance, high sensitivity to RNAi-mediated protein knock-down and efficient procedure for creating stable cell lines make Drosophila S2 cells an ideal model system to study cargo transport by live imaging. The results obtained with S2 cells can be further applied to a more physiologically relevant system: axonal transport in primary neurons cultured from dissociated Drosophila embryos. Cultured neurons grow long neurites filled with bundled microtubules, very similar to S2 processes. Like in S2 cells, organelles in cultured neurons can be visualized by either organelle-specific fluorescent dyes or by using fluorescent organelle markers encoded by DNA injected into early embryos or expressed in transgenic flies. Therefore, organelle transport can be easily recorded in neurons cultured on glass coverslips using living imaging. Here we describe procedures for culturing and visualizing cargo transport in Drosophila S2 cells and primary neurons. We believe that these protocols make both systems accessible for labs studying cargo transport. PMID:24300413

  4. Energy transport in plasmas produced by a high brightness krypton fluoride laser focused to a line

    SciTech Connect

    Al-Hadithi, Y.; Tallents, G.J. ); Zhang, J. ); Key, M.H.; Norreys, P.A.; Kodama, R. )

    1994-05-01

    A high brightness krypton fluoride Raman laser (wavelength 0.268 [mu]m) generating 0.3 TW, 12 ps pulses with 20 [mu]rad beam divergence and a prepulse of less than 10[sup [minus]10] has been focused to produce a 10 [mu]m wide line focus (irradiances [similar to]0.8--4[times]10[sup 15] W cm[sup [minus]2]) on plastic targets with a diagnostic sodium fluoride (NaF) layer buried within the target. Axial and lateral transport of energy has been measured by analysis of x-ray images of the line focus and from x-ray spectra emitted by the layer of NaF with varying overlay thicknesses. It is shown that the ratio of the distance between the critical density surface and the ablation surface to the laser focal width controls lateral transport in a similar manner as for previous spot focus experiments. The measured axial energy transport is compared to MEDUSA [J. P. Christiansen, D. E. T. F. Ashby, and K. V. Roberts, Comput. Phys. Commun. [bold 7], 271 (1974)] one-dimensional hydrodynamic code simulations with an average atom post-processor for predicting spectral line intensities. An energy absorption of [similar to]10% in the code gives agreement with the experimental axial penetration. Various measured line ratios of hydrogen- and helium-like Na and F are investigated as temperature diagnostics in the NaF layer using the RATION [R. W. Lee, B. L. Whitten, and R. E. Strout, J. Quant. Spectrosc. Radiat. Transfer [bold 32], 91 (1984)] code.

  5. Energy transport in plasmas produced by a high brightness krypton fluoride laser focused to a line

    NASA Astrophysics Data System (ADS)

    Al-Hadithi, Y.; Tallents, G. J.; Zhang, J.; Key, M. H.; Norreys, P. A.; Kodama, R.

    1994-05-01

    A high brightness krypton fluoride Raman laser (wavelength 0.268 μm) generating 0.3 TW, 12 ps pulses with 20 μrad beam divergence and a prepulse of less than 10-10 has been focused to produce a 10 μm wide line focus (irradiances ˜0.8-4×1015 W cm-2) on plastic targets with a diagnostic sodium fluoride (NaF) layer buried within the target. Axial and lateral transport of energy has been measured by analysis of x-ray images of the line focus and from x-ray spectra emitted by the layer of NaF with varying overlay thicknesses. It is shown that the ratio of the distance between the critical density surface and the ablation surface to the laser focal width controls lateral transport in a similar manner as for previous spot focus experiments. The measured axial energy transport is compared to medusa [J. P. Christiansen, D. E. T. F. Ashby, and K. V. Roberts, Comput. Phys. Commun. 7, 271 (1974)] one-dimensional hydrodynamic code simulations with an average atom post-processor for predicting spectral line intensities. An energy absorption of ˜10% in the code gives agreement with the experimental axial penetration. Various measured line ratios of hydrogen- and helium-like Na and F are investigated as temperature diagnostics in the NaF layer using the ration [R. W. Lee, B. L. Whitten, and R. E. Strout, J. Quant. Spectrosc. Radiat. Transfer 32, 91 (1984)] code.

  6. Design of the e-beam transport line for the AFEL

    SciTech Connect

    Wang, T.F.; Chan, K.C.D.; Sheffield, R.L.; Wilson, W.L.

    1991-01-01

    The Advanced Free-Electron Laser (AFEL) currently construction at Los Alamos National Laboratory is a compact high-performance free- electron laser (FE). The design of the AFEL integrates our most advanced accelerator and wiggler components. The 1.2-m-long accelerator produces a high-brightness electron-beam (e-beam) of 200- to 300-A peak current with an energy of 20 MeV. The beamline incorporates variable permanent-magnet quadrupoles and dipoles for electron beam transport. The AFEL will ultimately use 10- to 20-cm-long slotted-tube pulsed microwigglers having a period of 3-mm to 1-cm. In this paper, we shall present the design of the e-beam transport line and discuss the various design considerations involved. 7 refs., 5 figs., 3 tabs.

  7. Mechanisms of gentamicin transport in kidney epithelial cell line (LLC-PK1).

    PubMed

    Saito, H; Inui, K; Hori, R

    1986-09-01

    The characteristics of gentamicin transport have been studied by using cultured kidney epithelial cell line LLC-PK1. The uptake of gentamicin by the LLC-PK1 cells appeared to be linear for 30 min and reached the equilibrium at day 1. Marked stimulation of gentamicin uptake was observed on the development of a confluent cell density, accompanied by the increases of marker enzyme activities and Na+-dependent D-glucose transport in the apical membranes. Gentamicin uptake was inhibited by metabolic inhibitors such as rotenone and 2,4-dinitrophenol, and was inhibited competitively in the presence of other aminoglycosides. Depending on the external calcium concentration, calcium ionophore A23187 stimulated gentamicin uptake, whereas ethylene glycol bis(beta-aminoethyl ether)N,N1-tetraacetic acid, a calcium chelator, inhibited gentamicin uptake. These results suggest that gentamicin uptake by the LLC-PK1 cells may be mediated via specialized transport system, and calcium ion movement may play an important role as a regulatory factor for this transport system.

  8. Transport of tetraethylammonium by a kidney cell line (LLC-PK sub 1 )

    SciTech Connect

    Fauth, C.; Rossier, B.; Roch-Ramel, F. )

    1988-03-01

    The authors investigated whether the LLC-PK{sub 1} epithelial cell lines (which shows many characteristics of proximal tubular cells) also is capable of transporting an organic ion. Suspended LLC-PK{sub 1} cells accumulated tetraethylammonium (TEA). The uptake showed characteristics of a facilitated mechanism; TEA uptake was saturable and temperature-dependent and was inhibited by other organic cations. Quinine and mepiperphenidol were the most potent inhibitors, whereas N{sup 1}-methylnicotinamide and morphine inhibited the transport system only slightly at doses of 10{sup {minus}3} M. Basolateral-to-apical TEA flux through LLC-PK{sub 1} monolayers was five to six times larger than that of mannitol, a nontransported compound, whereas apical-to-basolateral TEA and mannitol fluxes were equal. Only the basolateral-to-apical TEA flux was inhibited by quinine. Under similar experimental conditions, no transport of p-aminohippuric acid was observed. It is concluded that LLC-PK{sub 1} cells are able to transport TEA, as do cells of the proximal tubule.

  9. Transmission line model for strained quantum well lasers including carrier transport and carrier heating effects.

    PubMed

    Xia, Mingjun; Ghafouri-Shiraz, H

    2016-03-01

    This paper reports a new model for strained quantum well lasers, which are based on the quantum well transmission line modeling method where effects of both carrier transport and carrier heating have been included. We have applied this new model and studied the effect of carrier transport on the output waveform of a strained quantum well laser both in time and frequency domains. It has been found that the carrier transport increases the turn-on, turn-off delay times and damping of the quantum well laser transient response. Also, analysis in the frequency domain indicates that the carrier transport causes the output spectrum of the quantum well laser in steady state to exhibit a redshift which has a narrower bandwidth and lower magnitude. The simulation results of turning-on transients obtained by the proposed model are compared with those obtained by the rate equation laser model. The new model has also been used to study the effects of pump current spikes on the laser output waveforms properties, and it was found that the presence of current spikes causes (i) wavelength blueshift, (ii) larger bandwidth, and (iii) reduces the magnitude and decreases the side-lobe suppression ratio of the laser output spectrum. Analysis in both frequency and time domains confirms that the new proposed model can accurately predict the temporal and spectral behaviors of strained quantum well lasers.

  10. Beam Transport of 4 GeV Protons from AGS to the Proton Interrogation Target of the Neutrino Line (Z_line) and Effect of the Air on the Transported Beam

    SciTech Connect

    Tsoupas,N.; Ahrens, L.; Pile, P.; Thieberger, P.; Murray, M.M.

    2008-10-01

    As part of the preparation for the Proton Interrogation Experiment, we have calculated the beam optics for the transport of 4 GeV protons, from the AGS extraction point, to the 'Cross-Section Target Wheel 1' and to the 'Proton Interrogation Target'. In this technical note we present three possible beam-transports each corresponding to a particular Fast Extracted Beam W B setup of the AGS. In addition we present results on the effect of the atmospheric air, (which fills the drift space of the last 100 [m] of the transport line), on the size of the beam, at two locations along the drift space, one location at the middle of the drift space and the other at the end where the 'Proton Interrogation Target' is placed. All the beam transports mentioned above require the removal of the WD1 dipole magnet, which is the first magnet of the W-line, because it acts as a limiting beam aperture, and the magnet is not used in the beam transport. An alternative solution of a beam transport, which does not require the removal of the WD1 magnet, is also presented. In this solution, which models the transport line using the TURTLE computer code[7], the vertical beam sizes at the location of the WD1 magnet is minimized to allow 'lossless' beam transport at the location of the WD1 magnet. A similar solution, but using a MAD model of the line, is also presented.

  11. A new optical design for the BNL isotope production transport line

    SciTech Connect

    Kponou, A.; Alessi, J.G.; Raparia, D.; Mapes, M.; Tsoupas, N.

    1996-10-01

    The 200 MeV linac at BNL has recently been upgraded. As a result, 2.5 times more average beam current can be delivered to the Brookhaven Isotope Resource Center (BIRC), formerly called BLIP, a facility which produces radionuclides and radiopharmaceutical for the medical community, and also supports a research program seeking more effective diagnostic and therapeutic agents. The optics of the beam transport line to BIRC was redesigned to (a) reduce transverse fluctuations of the beam at the target due to any linac energy fluctuations, (b) produce a flat beam distribution at the target, in order to avoid melting certain target materials, and (c) handle the higher beam intensity while keeping radiation levels low. A profile monitor was also modified to monitor the flatness of the beam using the algebraic reconstruction technique (ART). The above improvements will be described, and results of the commissioning of the line during the 1996 running period will be discussed.

  12. Functional Coding Variation in Recombinant Inbred Mouse Lines Reveals Novel Serotonin Transporter-Associated Phenotypes

    SciTech Connect

    Carneiro, Ana; Airey, David; Thompson, Brent; Zhu, C; Rinchik, Eugene M; Lu, Lu; Chesler, Elissa J; Erikson, Keith; Blakely, Randy

    2009-01-01

    The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4) figures prominently in the etiology or treatment of many prevalent neurobehavioral disorders including anxiety, alcoholism, depression, autism and obsessive-compulsive disorder (OCD). Here we utilize naturally occurring polymorphisms in recombinant inbred (RI) lines to identify novel phenotypes associated with altered SERT function. The widely used mouse strain C57BL/6J, harbors a SERT haplotype defined by two nonsynonymous coding variants (Gly39 and Lys152 (GK)). At these positions, many other mouse lines, including DBA/2J, encode Glu39 and Arg152 (ER haplotype), assignments found also in hSERT. Synaptosomal 5-HT transport studies revealed reduced uptake associated with the GK variant. Heterologous expression studies confirmed a reduced SERT turnover rate for the GK variant. Experimental and in silico approaches using RI lines (C57Bl/6J X DBA/2J=BXD) identifies multiple anatomical, biochemical and behavioral phenotypes specifically impacted by GK/ER variation. Among our findings are multiple traits associated with anxiety and alcohol consumption, as well as of the control of dopamine (DA) signaling. Further bioinformatic analysis of BXD phenotypes, combined with biochemical evaluation of SERT knockout mice, nominates SERT-dependent 5-HT signaling as a major determinant of midbrain iron homeostasis that, in turn, dictates ironregulated DA phenotypes. Our studies provide a novel example of the power of coordinated in vitro, in vivo and in silico approaches using murine RI lines to elucidate and quantify the system-level impact of gene variation.

  13. The effects of magnetic fringe fields on beam dynamics in a beam transport line of a terahertz FEL source

    NASA Astrophysics Data System (ADS)

    Zeng, Han; Xiong, Yongqian; Pei, Yuanji

    2014-11-01

    The transport line used in a terahertz FEL device has to transport electron beam through the entire system efficiently and meet the requirements of the beam parameters at the undulator entrance. Due to space limitations, the size of the magnets (five quadrupoles and two bending magnets) employed in the transport line was limited, and some devices were densely packed. In this paper, analyses of the effect of fringe fields and magnetic interference of magnets are presented. 3D models of these magnets are built and their linear optical properties are compared with those obtained by hard edge models. The results indicated that the effects of these factors are significant and they would cause a mismatch of the beam at the exit of the transport line under the preliminary lattice design. To solve this problem, the beam was re-matched using the particle swarm optimization algorithm.

  14. Impact of a pneumatic tube system transport on hemostasis parameters measurement: the experiment of Cochin universitary hospital (AP-HP, Paris, France).

    PubMed

    Calmette, Leyla; Ibrahim, Firas; Gouin, Isabelle; Horellou, Marie-Hélène; Mazoyer, Élisabeth; Fontenay, Michaela; Flaujac, Claire

    2017-02-01

    Samples transported by pneumatic tube system are submitted to forces of acceleration and deceleration which can affect laboratory parameters. At Cochin hospital, majority of samples of hemostasis, except for platelets tests, are transported by pneumatic tube system. The objective of this study was to evaluate the impact of a pneumatic tube system (PTS) transport compared to hand-delivered transport on samples and to qualify Cochin hospital PTS according to requirements of standard ISO 15189. A bibliographical study was made and showed that pneumatic tube system particularly influences platelets tests. Four citrate tubes were collected in 5 healthy volunteers in the maternity: 2 tubes were transported by PTS and 2 others were hand-delivered to the laboratory. Five coagulation tests were analyzed: prothrombine time (PT), activated partial thromboplastin time (aPTT), factor (F) V, FVIII and platelet closure time with PFA-100TM collagen/epinephrine. For each volunteer, the results obtained by PTS and by hand-delivered transport were compared with formula usually used for biological analysis retake: 2.8 x standard deviation of reproductibility variation coefficient (SH GTA 01, COFRAC). This study did not show an impact of PTS on PT, aPTT, FV and FVIII. For PFA-100TM collagen/epinephrine, we noted an impact on 2/5 volunteers. These results, in agreement with the literature, led to the conclusion that Cochin hospital PTS is in compliance to transport samples for usual coagulation tests except platelet tests. This study allowed to issue French recommendations for PTS transport of hemostasis tubes qualification available on "Groupe français d'hémostase et thrombose" Web site.

  15. Fano effect and bound state in continuum in electron transport through an armchair graphene nanoribbon with line defect

    PubMed Central

    2013-01-01

    Electron transport properties in an armchair graphene nanoribbon are theoretically investigated by considering the presence of line defect. It is found that the line defect causes the abundant Fano effects and bound state in continuum (BIC) in the electron transport process, which are tightly dependent on the width of the nanoribbon. By plotting the spectra of the density of electron states of the line defect, we see that the line defect induces some localized quantum states around the Dirac point and that the different localizations of these states lead to these two kinds of transport results. Next, the Fano effect and BIC phenomenon are detailedly described via the analysis about the influence of the structure parameters. According to the numerical results, we propose such a structure to be a promising candidate for graphene nanoswitch. PACS 81.05.Uw, 71.55.-i, 73.23.-b, 73.25.+i PMID:23870061

  16. Fano effect and bound state in continuum in electron transport through an armchair graphene nanoribbon with line defect.

    PubMed

    Gong, Wei-Jiang; Sui, Xiao-Yan; Wang, Yan; Yu, Guo-Dong; Chen, Xiao-Hui

    2013-07-22

    : Electron transport properties in an armchair graphene nanoribbon are theoretically investigated by considering the presence of line defect. It is found that the line defect causes the abundant Fano effects and bound state in continuum (BIC) in the electron transport process, which are tightly dependent on the width of the nanoribbon. By plotting the spectra of the density of electron states of the line defect, we see that the line defect induces some localized quantum states around the Dirac point and that the different localizations of these states lead to these two kinds of transport results. Next, the Fano effect and BIC phenomenon are detailedly described via the analysis about the influence of the structure parameters. According to the numerical results, we propose such a structure to be a promising candidate for graphene nanoswitch. PACS: 81.05.Uw, 71.55.-i, 73.23.-b, 73.25.+i.

  17. Differences in the expression of endogenous efflux transporters in MDR1-transfected versus wildtype cell lines affect P-glycoprotein mediated drug transport

    PubMed Central

    Kuteykin-Teplyakov, Konstantin; Luna-Tortós, Carlos; Ambroziak, Kamila; Löscher, Wolfgang

    2010-01-01

    Background and purpose: P-glycoprotein (Pgp) efflux assays are widely used to identify Pgp substrates. The kidney cell lines Madin-Darby canine kidney (MDCK)-II and LLC-PK1, transfected with human MDR1 (ABCB1) are used to provide recombinant models of drug transport. Endogenous transporters in these cells may contribute to the activities of recombinant transporters, so that drug transport in MDR1-transfected cells is often corrected for the transport obtained in parental (wildtype) cells. However, expression of endogenous transporters may vary between transfected and wildtype cells, so that this correction may cause erroneous data. Here, we have measured the expression of endogenous efflux transporters in transfected and wildtype MDCK-II or LLC cells and the consequences for Pgp-mediated drug transport. Experimental approach: Using quantitative real-time RT-PCR, we determined the expression of endogenous Mdr1 mRNA and other efflux transporters in wildtype and MDR1-transfected MDCK-II and LLC cells. Transcellular transport was measured with the test substrate vinblastine. Key results: In MDR1-transfected MDCK cells, expression of endogenous (canine) Mdr1 and Mrp2 (Abcc2) mRNA was markedly lower than in wildtype cells, whereas MDR1-transfected LLC cells exhibited comparable Mdr1 but strikingly higher Mrp2 mRNA levels than wildtype cells. As a consequence, transport of vinblastine by human Pgp in efflux experiments was markedly underestimated when transport in MDR1-transfected MDCK cells was corrected for transport obtained in wildtype cells. This problem did not occur in LLC cells. Conclusions and implications: Differences in the expression of endogenous efflux transporters between transfected and wildtype MDCK cells provide a potential bias for in vitro studies on Pgp-mediated drug transport. PMID:20590635

  18. PSAT and AP Success.

    ERIC Educational Resources Information Center

    Palin, Raymond J.

    2001-01-01

    Through evaluation of 73 eleventh-grade students over three years, explores the extent to which standardized test scores and other academic factors predict success on the Advanced Placement (AP) exam in U.S. history. Finds that standardized scores, grade point average, and anticipated college majors are closely related to AP success. (CMK)

  19. APS and Open Access

    NASA Astrophysics Data System (ADS)

    2011-03-01

    The movement toward Open Access continues to gain momentum. A brief review of APS efforts in this area will be presented by APS Editor in Chief, Gene Sprouse. Editors from Physical Review A, B, E, Focus, Letters, and X, Reviews of Modern Physics, and Physics will address your questions about publishing in this evolving environment.

  20. Hydrogen transport diagnostics by atomic and molecular emission line profiles simultaneously measured for large helical device

    SciTech Connect

    Fujii, K.; Shikama, T.; Hasuo, M.; Goto, M.; Morita, S.

    2013-01-15

    We observe the Balmer-{alpha}, -{beta}, and -{gamma} lines of hydrogen atoms and Q branches of the Fulcher-{alpha} band of hydrogen molecules simultaneously with their polarization resolved for large helical device. From the fit including the line splits and the polarization dependences by the Zeeman effect, the emission locations, intensities, and the temperatures of the atoms and molecules are determined. The emission locations of the hydrogen atoms are determined outside but close to the last closed flux surface (LCFS). The results are consistent with a previous work (Phys. Plasmas 12, 042501 (2005)). On the other hand, the emission locations of the molecules are determined to be in the divertor legs, which is farer from those of the atoms. The kinetic energy of the atoms is 1 {approx} 20 eV, while the rotational temperature of molecules is {approx}0.04 eV. Additionally, substantial wings, which originate from high velocity atoms and are not reproduced by the conventional spectral analysis, are observed in the Balmer line profiles. We develop a one-dimensional model to simulate the transport of the atoms and molecules. The model reproduces the differences of the emission locations of the atoms and molecules when their initial temperatures are assumed to be 3 eV and 0.04 eV, respectively. From the model, the wings of the Balmer-{alpha} line is attributed to the high velocity atoms exist deep inside the LCFS, which are generated by the charge exchange collisions with hot protons there.

  1. Quantitative assessment of direct and indirect landslide risk along transportation lines in southern India

    NASA Astrophysics Data System (ADS)

    Jaiswal, P.; van Westen, C. J.; Jetten, V.

    2010-06-01

    A quantitative approach for landslide risk assessment along transportation lines is presented and applied to a road and a railway alignment in the Nilgiri hills in southern India. The method allows estimating direct risk affecting the alignments, vehicles and people, and indirect risk resulting from the disruption of economic activities. The data required for the risk estimation were obtained from historical records. A total of 901 landslides were catalogued initiating from cut slopes along the railway and road alignment. The landslides were grouped into three magnitude classes based on the landslide type, volume, scar depth, run-out distance, etc and their probability of occurrence was obtained using frequency-volume distribution. Hazard, for a given return period, expressed as the number of landslides of a given magnitude class per kilometre of cut slopes, was obtained using Gumbel distribution and probability of landslide magnitude. In total 18 specific hazard scenarios were generated using the three magnitude classes and six return periods (1, 3, 5, 15, 25, and 50 years). The assessment of the vulnerability of the road and railway line was based on damage records whereas the vulnerability of different types of vehicles and people was subjectively assessed based on limited historic incidents. Direct specific loss for the alignments (railway line and road), vehicles (train, bus, lorry, car and motorbike) was expressed in monetary value (US), and direct specific loss of life of commuters was expressed in annual probability of death. Indirect specific loss (US) derived from the traffic interruption was evaluated considering alternative driving routes, and includes losses resulting from additional fuel consumption, additional travel cost, loss of income to the local business, and loss of revenue to the railway department. The results indicate that the total loss, including both direct and indirect loss, from 1 to 50 years return period, varies from US 90 840 to US

  2. Identification of transport pathways for citric acid cycle intermediates in the human colon carcinoma cell line, Caco-2.

    PubMed

    Weerachayaphorn, Jittima; Pajor, Ana M

    2008-04-01

    Citric acid cycle intermediates are absorbed from the gastrointestinal tract through carrier-mediated mechanisms, although the transport pathways have not been clearly identified. This study examines the transport of citric acid cycle intermediates in the Caco-2 human colon carcinoma cell line, often used as a model of small intestine. Inulin was used as an extracellular volume marker instead of mannitol since the apparent volume measured with mannitol changed with time. The results show that Caco-2 cells contain at least three distinct transporters, including the Na+-dependent di- and tricarboxylate transporters, NaDC1 and NaCT, and one or more sodium-independent pathways, possibly involving organic anion transporters. Succinate transport is mediated mostly by Na+-dependent pathways, predominantly by NaDC1, but with some contribution by NaCT. RT-PCR and functional characteristics verified the expression of these transporters in Caco-2 cells. In contrast, citrate transport in Caco-2 cells occurs by a combination of Na+-independent pathways, possibly mediated by an organic anion transporter, and Na+-dependent mechanisms. The non-metabolizable dicarboxylate, methylsuccinate, is also transported by a combination of Na+-dependent and -independent pathways. In conclusion, we find that multiple pathways are involved in the transport of di- and tricarboxylates by Caco-2 cells. Since many of these pathways are not found in human intestine, this model may be best suited for studying Na+-dependent transport of succinate by NaDC1.

  3. Characterization of multidrug transporter-mediated efflux of avermectins in human and mouse neuroblastoma cell lines.

    PubMed

    Dalzell, Abigail M; Mistry, Pratibha; Wright, Jayne; Williams, Faith M; Brown, Colin D A

    2015-06-15

    ABC transporters play an important role in the disposition of avermectins in several animal species. In this study the interactions of three key avermectins, abamectin, emamectin and ivermectin, with human and mouse homologues of MDR1 (ABCB1/Abcb1a) and MRP (ABCC/Abcc), transporters endogenously expressed by human SH-SY5Y and mouse N2a neuroblastoma cells were investigated. In both cell lines, retention of the fluorescent dye H33342 was found to be significantly increased in the presence of avermectins and cyclosporin A. These effects were shown to be unresponsive to the BCRP inhibitor Ko-143 and therefore MDR1/Mdr1-dependent. Avermectins inhibited MDR1/Mdr1a-mediated H33342 dye efflux, with apparent Ki values of 0.24±0.08 and 0.18±0.02μM (ivermectin); 0.60±0.07 and 0.56±0.02μM (emamectin) and 0.95±0.08 and 0.77±0.25μM (abamectin) in SH-SY5Y and N2a cells, respectively. There were some apparent affinity differences for MDR1 and Mdr1a within each cell line (affinity for ivermectin>emamectin≥abamectin, P<0.05 by One-Way ANOVA), but importantly, the Ki values for individual avermectins for human MDR1 or mouse Mdr1a were not significantly different. MK571-sensitive retention of GSMF confirmed the expression of MRP/Mrp efflux transporters in both cell lines. Avermectins inhibited MRP/Mrp-mediated dye efflux with IC50 values of 1.58±0.51 and 1.94±0.72μM (ivermectin); 1.87±0.57 and 2.74±1.01μM (emamectin) and 2.25±0.01 and 1.68±0.63μM (abamectin) in SH-SY5Y and N2a cells, respectively. There were no significant differences in IC50 values between individual avermectins or between human MRP and mouse Mrp. Kinetic data for endogenous human MDR1/MRP isoforms in SH-SY5Y cells and mouse Mdr1a/b/Mrp isoforms in N2a cells are comparable for the selected avermectins. All are effluxed at concentrations well above 0.05-0.1μM ivermectin detected in plasma (Ottesen and Campbell, 1994; Ottesen and Campbell, 1994) This is an important finding in the light of

  4. A new medium energy beam transport line for the proton injector of AGS-RHIC

    SciTech Connect

    Okamura, M.; Briscoe, B.; Fite, J.; LoDestro, V.; Raparia, D.; Ritter, J.; Hayashizaki, N.

    2010-09-12

    In Brookhaven National Laboratory (BNL), a 750 keV medium energy beam transport line between the 201 MHz 750 keV proton RFQ and the 200 MeV Alvarez DTL is being modified to get a better transmission of the beam. Within a tight space, high field gradient quadrupoles (65 Tm) and newly designed steering magnets (6.5 mm in length) will be installed considering the cross-talk effects. Also a new half wave length 200 MHz buncher is being prepared. The beam commissioning will be done in this year. To enhance the performance of the proton linacs, the MEBT is being modified. New quadrupole magnets, steering magnets and a half wave length buncher as shown in Figure 7 will be installed and be commissioned soon.

  5. Chloride transport in a human submandibular gland cell line studied by X-ray microanalysis.

    PubMed

    Roomans, G M

    1998-08-01

    Ion transport properties of the human submandibular gland cell line A253 were investigated by X-ray microanalysis. The cells were grown on ultrathin plastic films on titanium grids. After the experiment, where the cells were exposed to various agonists and inhibitors, the specimens were briefly rinsed in distilled water, frozen, and freeze-dried. The elemental composition of the cultured cells most closely resembled that of striated duct cells. Beta-adrenergic stimulation caused a small decrease in the cellular Cl- and K+ concentration, but cholinergic stimulation had no effect. Also stimulation with cAMP caused a decrease in Cl- and K+; this decrease could be inhibited by the chloride channel blocker NPPB. Loss of Cl- and K+ could also be elicited by exposure to a hypotonic solution. The results suggest that there may be several types of chloride channel present in A253 cells.

  6. Quality control and patient dosimetry in digital radiology. On line system: new features and transportability.

    PubMed

    Vano, E; Ten, J I; Fernandez, J M; Prieto, C; Ordiales, J M; Martinez, D

    2008-01-01

    New features have been added to a system (QCONLINE) for auditing patient dosimetric and technical parameters 'on line', working on a digital radiology department and using the information contained in the DICOM header of some modalities. The audit of other parameters than patient doses have been included, setting alarm conditions to alert on malfunction of the X-ray system or bad operation modes, in addition to the evaluation of patient doses. A new module to analyse, collect and process the relevant information transferred by the modality performed procedure step (MPPS) service has been launched. Several examples with the exploitation of the new features are presented. The transportability of the system has been tested in two remote hospitals during several months. The new MPPS module has demonstrated to be a good tool to complement the information existing in the DICOM header. The system allows to help in the optimisation of digital radiology departments managing patient dosimetry and procedure data in real time.

  7. Comparison of Implicit and Symbolic Implicit Monte Carlo Line Transport With Frequency Weight Vector Extension

    SciTech Connect

    McKinley, M S; Brooks III, E D; Szoke, A

    2002-03-20

    We compare the Implicit Monte Carlo (IMC) technique to the Symbolic IMC (SIMC) technique, with and without weight vectors in frequency space, for time-dependent line transport in the presence of collisional pumping. We examine the efficiency and accuracy of the IMC and SIMC methods for examples involving the evolution of a collisionally pumped trapping problem to steady-state, the surface heating of cold media by a beam, and the diffusion of energy from a localized region that is collisionally pumped. The importance of spatial biasing and teleportation for problems involving high opacity is demonstrated. Our numerical solution, along with its associated teleportation error, is checked against theoretical calculations for the last example.

  8. Comparison of Implicit and Symbolic Implicit Monte Carlo Line Transport with Frequency Weight Vector Extension

    SciTech Connect

    McKinley, M S; Brooks III, E D; Szoke, A

    2002-12-03

    We compare the Implicit Monte Carlo (IMC) technique to the Symbolic IMC (SIMC) technique, with and without weight vectors in frequency space, for time-dependent line transport in the presence of collisional pumping. We examine the efficiency and accuracy of the IMC and SIMC methods for test problems involving the evolution of a collisionally pumped trapping problem to its steady-state, the surface heating of a cold medium by a beam, and the diffusion of energy from a localized region that is collisionally pumped. The importance of spatial biasing and teleportation for problems involving high opacity is demonstrated. Our numerical solution, along with its associated teleportation error, is checked against theoretical calculations for the last example.

  9. APS Science 2006.

    SciTech Connect

    Gibson, J. M.; Fenner, R. B.; Long, G.; Borland, M.; Decker, G.

    2007-05-24

    In my five years as the Director of the Advanced Photon Source (APS), I have been fortunate to see major growth in the scientific impact from the APS. This year I am particularly enthusiastic about prospects for our longer-term future. Every scientific instrument must remain at the cutting edge to flourish. Our plans for the next generation of APS--an APS upgrade--got seriously in gear this year with strong encouragement from our users and sponsors. The most promising avenue that has emerged is the energy-recovery linac (ERL) (see article on page xx), for which we are beginning serious R&D. The ERL{at}APS would offer revolutionary performance, especially for x-ray imaging and ultrafast science, while not seriously disrupting the existing user base. I am very proud of our accelerator physics and engineering staff, who not only keep the current APS at the forefront, but were able to greatly impress our international Machine Advisory Committee with the quality of their work on the possible upgrade option (see page xx). As we prepare for long-term major upgrades, our plans to develop and optimize all the sectors at APS in the near future are advancing. Several new beamlines saw first light this year, including a dedicated powder diffraction beamline (11-BM), two instruments for inelastic x-ray scattering at sector 30, and the Center for Nanoscale Materials (CNM) Nanoprobe beamline at sector 26. Our partnership in the first x-ray free-electron laser (LCLS) to be built at Stanford contributes to revolutionary growth in ultrafast science (see page xx), and we are developing a pulse chirping scheme to get ps pulses at sector 7 of the APS within a year or so. In this report, you will find selected highlights of scientific research at the APS from calendar year 2006. The highlighted work covers diverse disciplines, from fundamental to applied science. In the article on page xx you can see the direct impact of APS research on technology. Several new products have emerged from

  10. Orbit error correction on the high energy beam transport line at the KHIMA accelerator system

    NASA Astrophysics Data System (ADS)

    Park, Chawon; Yim, Heejoong; Hahn, Garam; An, Dong Hyun

    2016-09-01

    For the purpose of treatment of various cancers and medical research, a synchrotron based medical machine has been developed under the Korea Heavy Ion Medical Accelerator (KHIMA) project and is scheduled for use to treat patient at the beginning of 2018. The KHIMA synchrotron is designed to accelerate and extract carbon ion (proton) beams with various energies from 110 to 430 MeV/u (60 to 230 MeV). Studies on the lattice design and beam optics for the High Energy Beam Transport (HEBT) line at the KHIMA accelerator system have been carried out using the WinAgile and the MAD-X codes. Because magnetic field errors and misalignments introduce deviations from the design parameters, these error sources should be treated explicitly, and the sensitivity of the machine's lattice to different individual error sources should be considered. Various types of errors, both static and dynamic, have been taken into account and have been consequentially corrected with a dedicated correction algorithm by using the MAD-X program. Based on the error analysis, the optimized correction setup is decided, and the specifications for the correcting magnets of the HEBT lines are determined.

  11. Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes

    PubMed Central

    Sitaram, Anand; Dennis, Megan K.; Chaudhuri, Rittik; De Jesus-Rojas, Wilfredo; Tenza, Danièle; Setty, Subba Rao Gangi; Wood, Christopher S.; Sviderskaya, Elena V.; Bennett, Dorothy C.; Raposo, Graça; Bonifacino, Juan S.; Marks, Michael S.

    2012-01-01

    Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine–based sorting signal in the pigment cell–specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1– and AP-3–favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs. PMID:22718909

  12. Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes.

    PubMed

    Sitaram, Anand; Dennis, Megan K; Chaudhuri, Rittik; De Jesus-Rojas, Wilfredo; Tenza, Danièle; Setty, Subba Rao Gangi; Wood, Christopher S; Sviderskaya, Elena V; Bennett, Dorothy C; Raposo, Graça; Bonifacino, Juan S; Marks, Michael S

    2012-08-01

    Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine-based sorting signal in the pigment cell-specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1- and AP-3-favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs.

  13. In vitro transport mechanism of psoralen in a human placental cell line (BeWo cells).

    PubMed

    Guo, Jie; Song, Dianrong; Han, Fang; Zhang, Wei; Wang, Yanan; Wang, Yuhua; Du, Wenxin

    2015-01-01

    The mechanism by which psoralen is transported across the placenta was investigated in the BeWo human placental cell line derived from choriocarcinoma in a transwell assay system using liquid chromatography-mass spectrometry/mass spectrometry detection. Psoralen uptake by BeWo cells increased linearly over the concentration range of 0.01 µM to 100 µM (r (2) = 0.997) and was not saturable. Psoralen uptake by BeWo cells was not affected by temperature (4 °C, room temperature, and 37 °C; p > 0.05). Psoralen transport increased linearly over 180 min (r (2) = 0.988) with 3.08 ± 0.26 %, 5.47 ± 0.21 %, 7.54 ± 0.06 %, 9.40 ± 0.37 %, 11.49 ± 0.31 %, and 12.46 ± 0.61 % transferred from the apical chamber to the basolateral chamber in the transwell assays at 30, 60, 90, 120, 150, and 180 min, respectively. The rate of transport showed the same tendency, increasing linearly from 0.13 ± 0.01 pmol/s to 0.58 ± 0.03 pmol/s over the concentration range of 25 µM to 100 µM (r (2) = 0.989). The apparent permeability coefficient for psoralen (100 µM) was 5.62 ± 0.24 × 10(-6) cm/s and 5.53 ± 0.47 × 10(-6) cm/s before and after treatment with verapamil (100 µM), respectively (p > 0.05). The efflux value for psoralen was approximately 1. These data show that psoralen is well absorbed and crosses the placental barrier via passive diffusion in the BeWo cell line.

  14. High-magnetic-field transport properties and irreversibility line of single crystals (2212) and ceramics of BPSCCO (2223)

    NASA Astrophysics Data System (ADS)

    Pradhan, A. K.; Chen, C.; Wanklyn, B. M.

    1995-02-01

    We have measured the high-magnetic-field (up to 15 T) transport properties of (BiPb) 2Sr 2Ca 1Cu 2O y (BPSCCO) single crystals and (2223) ceramics. We have extracted the melting line of BPSCCO crystals from the measurements of precise I- V curves when the field is applied parallel to the c-axis and shown that the melting line coincides with the irreversibility line measured by the magnetisation technique. This is explained for the case of weak pinning. The depinning line was found to be 10 to 12 K above the melting line. The observed hump in the magnetoresistance curve above 2 T predicts the depinning of flux from the weak pinning centres when the temperature approaches the depinning temperature. The basic behavior of ceramic BPSCCO, although having a higher Tc, is similar to its single crystal analogue with (2212) phase except for the enhanced depinning line.

  15. APS Science 2009.

    SciTech Connect

    Gibson, J. M; Mills, D. M.; Gerig, R.

    2010-05-01

    It is my pleasure to introduce the 2009 annual report of the Advanced Photon Source. This was a very good year for us. We operated with high reliability and availability, despite growing problems with obsolete systems, and our users produced a record output of publications. The number of user experiments increased by 14% from 2008 to more than 3600. We congratulate the recipients of the 2009 Nobel Prize in Chemistry-Venkatraman Ramakrishnan (Cambridge Institute for Medical Research), Thomas Steitz (Yale University), and Ada Yonath (Weizmann Institute) - who did a substantial amount of this work at APS beamlines. Thanks to the efforts of our users and staff, and the ongoing counsel of the APS Scientific Advisory Committee, we made major progress in advancing our planning for the upgrade of the APS (APS-U), producing a proposal that was positively reviewed. We hope to get formal approval in 2010 to begin the upgrade. With advocacy from our users and the support of our sponsor, the Office of Basic Energy Sciences in the Department of Energy (DOE) Office of Science, our operating budgets have grown to the level needed to more adequately staff our beamlines. We were also extremely fortunate to have received $7.9 M in American Recovery and Reinvestment Act ('stimulus') funding to acquire new detectors and improve several of our beamlines. The success of the new Linac Coherent Light Source at Stanford, the world's first x-ray free-electron laser, made us particularly proud since the undulators were designed and built by the APS. Among other highlights, we note that more than one-quarter of the 46 Energy Frontier Research Centers, funded competitively across the U.S. in 2009 by the DOE, included the Advanced Photon Source in their proposed work, which shows that synchrotron radiation, and the APS in particular, are central to energy research. While APS research covers everything from fundamental to applied science (reflected by the highlights in this report), the challenge

  16. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines.

    PubMed

    Hilgendorf, Constanze; Ahlin, Gustav; Seithel, Annick; Artursson, Per; Ungell, Anna-Lena; Karlsson, Johan

    2007-08-01

    This study was designed to quantitatively assess the mRNA expression of 36 important drug transporters in human jejunum, colon, liver, and kidney. Expression of these transporters in human organs was compared with expression in commonly used cell lines (Caco-2, HepG2, and Caki-1) originating from these organs to assess their value as in vitro transporter system models, and was also compared with data obtained from the literature on expression in rat tissues to assess species differences. Transporters that were highly expressed in the intestine included HPT1, PEPT1, BCRP, MRP2, and MDR1, whereas, in the liver, OCT1, MRP2, OATP-C, NTCP and BSEP were the main transporters. In the kidney, OAT1 was expressed at the highest levels, followed by OAT3, OAT4, MCT5, MDR1, MRP2, OCT2, and OCTN2. The best agreement between human tissue and the representative cell line was observed for human jejunum and Caco-2 cells. Expression in liver and kidney ortholog cell lines was not correlated with that in the associated tissue. Comparisons with rat transporter gene expression revealed significant species differences. Our results allowed a comprehensive quantitative comparison of drug transporter expression in human intestine, liver, and kidney. We suggest that it would be beneficial for predictive pharmacokinetic research to focus on the most highly expressed transporters. We hope that our comparison of rat and human tissue will help to explain the observed species differences in in vivo models, increase understanding of the impact of active transport processes on pharmacokinetics and distribution, and improve the quality of predictions from animal studies to humans.

  17. AP@home

    PubMed Central

    Heinemann, Lutz; Benesch, Carsten; DeVries, J. Hans

    2016-01-01

    In the past years the development of an artificial pancreas (AP) has made great progress and many activities are ongoing in this area of research. The major step forward made in the last years was moving the evaluation of AP systems from highly controlled experimental conditions to daily life conditions at the home of patients with diabetes; this was also the aim of the European Union–funded AP@home project. Over a time period of 5 years a series of clinical studies were performed that culminated in 2 “final studies” during which an AP system was used by patients in their home environment for 2 or 3 months without supervision by a physician, living their normal lives. Two different versions of the AP system developed within this project were evaluated. A significant improvement in glycated hemoglobin was observed during closed-loop conditions despite the fact that during the control period the patients used the best currently available therapeutic option. In addition, a “single-port AP system” was developed within the project that combines continuous glucose monitoring and insulin infusion at a single tissue site. By using such a combined device the patients not only have to carry one less device around, the number of access points through the skin is also reduced from 2 to 1. In summary, close cooperation of 12 European partners, both academic centers and industry, enabled the development and evaluation of AP systems under daily life conditions. The next step is to develop these into products in cooperation with commercial partners. PMID:26888971

  18. Parametric study of transport beam lines for electron beams accelerated by laser-plasma interaction

    NASA Astrophysics Data System (ADS)

    Scisciò, M.; Lancia, L.; Migliorati, M.; Mostacci, A.; Palumbo, L.; Papaphilippou, Y.; Antici, P.

    2016-03-01

    In the last decade, laser-plasma acceleration of high-energy electrons has attracted strong attention in different fields. Electrons with maximum energies in the GeV range can be laser-accelerated within a few cm using multi-hundreds terawatt (TW) lasers, yielding to very high beam currents at the source (electron bunches with up to tens-hundreds of pC in a few fs). While initially the challenge was to increase the maximum achievable electron energy, today strong effort is put in the control and usability of these laser-generated beams that still lack of some features in order to be used for applications where currently conventional, radio-frequency (RF) based, electron beam lines represent the most common and efficient solution. Several improvements have been suggested for this purpose, some of them acting directly on the plasma source, some using beam shaping tools located downstream. Concerning the latter, several studies have suggested the use of conventional accelerator magnetic devices (such as quadrupoles and solenoids) as an easy implementable solution when the laser-plasma accelerated beam requires optimization. In this paper, we report on a parametric study related to the transport of electron beams accelerated by laser-plasma interaction, using conventional accelerator elements and tools. We focus on both, high energy electron beams in the GeV range, as produced on petawatt (PW) class laser systems, and on lower energy electron beams in the hundreds of MeV range, as nowadays routinely obtained on commercially available multi-hundred TW laser systems. For both scenarios, our study allows understanding what are the crucial parameters that enable laser-plasma accelerators to compete with conventional ones and allow for a beam transport. We show that suitable working points require a tradeoff-combination between low beam divergence and narrow energy spread.

  19. The AP spectroscopic binary HD 59435 revisited

    NASA Astrophysics Data System (ADS)

    Wade, G. A.; Mathys, G.; North, P.

    1999-07-01

    HD 59435 is a double-lined spectroscopic binary, one component of which is a magnetic Ap star and the other a G8 or K0 giant (Wade et al. 1996). Both components are very slowly rotating, and the Ap star exhibits spectral lines resolved into their magneti cally-split components. Herein we report additional measurements of the mean magnetic field modulus of the Ap star, measurements of the radial velocities of both components, and Geneva photometry of the system, and discuss their impact upon conclusions drawn previously. Based on observations collected at the European Southern Observatory (La Silla, Chile; ESO Programme Nos. 56.E-0688, 58.E-0159, 60.E-0565). Table 3 is available only in electronic form at the CDS via anonymous ftp 130.79.128.5

  20. Improved design of proton source and low energy beam transport line for European Spallation Source

    SciTech Connect

    Neri, L. Celona, L.; Gammino, S.; Mascali, D.; Castro, G.; Ciavola, G.; Torrisi, G.; Cheymol, B.; Ponton, A.; Galatà, A.; Patti, G.; Gozzo, A.; Lega, L.

    2014-02-15

    The design update of the European Spallation Source (ESS) accelerator is almost complete and the construction of the prototype of the microwave discharge ion source able to provide a proton beam current larger than 70 mA to the 3.6 MeV Radio Frequency Quadrupole (RFQ) started. The source named PS-ESS (Proton Source for ESS) was designed with a flexible magnetic system and an extraction system able to merge conservative solutions with significant advances. The ESS injector has taken advantage of recent theoretical updates and new plasma diagnostics tools developed at INFN-LNS (Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare). The design strategy considers the PS-ESS and the low energy beam transport line as a whole, where the proton beam behaves like an almost neutralized non-thermalized plasma. Innovative solutions have been used as hereinafter described. Thermo-mechanical optimization has been performed to withstand the chopped beam and the misaligned focused beam over the RFQ input collimator; the results are reported here.

  1. Improved design of proton source and low energy beam transport line for European Spallation Source

    NASA Astrophysics Data System (ADS)

    Neri, L.; Celona, L.; Gammino, S.; Mascali, D.; Castro, G.; Torrisi, G.; Cheymol, B.; Ponton, A.; Galatà, A.; Patti, G.; Gozzo, A.; Lega, L.; Ciavola, G.

    2014-02-01

    The design update of the European Spallation Source (ESS) accelerator is almost complete and the construction of the prototype of the microwave discharge ion source able to provide a proton beam current larger than 70 mA to the 3.6 MeV Radio Frequency Quadrupole (RFQ) started. The source named PS-ESS (Proton Source for ESS) was designed with a flexible magnetic system and an extraction system able to merge conservative solutions with significant advances. The ESS injector has taken advantage of recent theoretical updates and new plasma diagnostics tools developed at INFN-LNS (Laboratori Nazionali del Sud, Istituto Nazionale di Fisica Nucleare). The design strategy considers the PS-ESS and the low energy beam transport line as a whole, where the proton beam behaves like an almost neutralized non-thermalized plasma. Innovative solutions have been used as hereinafter described. Thermo-mechanical optimization has been performed to withstand the chopped beam and the misaligned focused beam over the RFQ input collimator; the results are reported here.

  2. Design of the low energy beam transport line between CARIBU and the EBIS charge breeder

    SciTech Connect

    Perry, A.; Ostroumov, P. N.; Barcikowski, A.; Dickerson, C.; Kondrashev, S. A.; Mustapha, B.; Savard, G.

    2015-01-09

    An Electron Beam Ion Source Charge Breeder (EBIS-CB) has been developed to breed radioactive beams from the CAlifornium Rare Isotope Breeder Upgrade (CARIBU) facility at ATLAS. The EBIS-CB will replace the existing ECR charge breeder to increase the intensity and improve the purity of reaccelerated radioactive ion beams. The EBIS-CB is in the final stage of off-line commissioning. Currently, we are developing a low energy beam transport (LEBT) system to transfer CARIBU beams to the EBIS-CB. As was originally planned, an RFQ cooler-buncher will precede the EBIS-CB. Recently, it was decided to include a multi-reflection time-of-flight (MR-TOF) mass-spectrometer following the RFQ. MR-TOF is a relatively new technology used to purify beams with a mass-resolving power up to 3×10{sup 5} as was demonstrated in experiments at CERN/ISOLDE. Very high purity singly-charged radioactive ion beams will be injected into the EBIS for charge breeding and due to its inherent properties, the EBIS-CB will maintain the purity of the charge bred beams. Possible contamination of residual gas ions will be greatly suppressed by achieving ultra-high vacuum in the EBIS trap. This paper will present and discuss the design of the LEBT and the overall integration of the EBIS-CB into ATLAS.

  3. Design of the low energy beam transport line between CARIBU and the EBIS charge breeder

    NASA Astrophysics Data System (ADS)

    Perry, A.; Ostroumov, P. N.; Barcikowski, A.; Dickerson, C.; Kondrashev, S. A.; Mustapha, B.; Savard, G.

    2015-01-01

    An Electron Beam Ion Source Charge Breeder (EBIS-CB) has been developed to breed radioactive beams from the CAlifornium Rare Isotope Breeder Upgrade (CARIBU) facility at ATLAS. The EBIS-CB will replace the existing ECR charge breeder to increase the intensity and improve the purity of reaccelerated radioactive ion beams. The EBIS-CB is in the final stage of off-line commissioning. Currently, we are developing a low energy beam transport (LEBT) system to transfer CARIBU beams to the EBIS-CB. As was originally planned, an RFQ cooler-buncher will precede the EBIS-CB. Recently, it was decided to include a multi-reflection time-of-flight (MR-TOF) mass-spectrometer following the RFQ. MR-TOF is a relatively new technology used to purify beams with a mass-resolving power up to 3×105 as was demonstrated in experiments at CERN/ISOLDE. Very high purity singly-charged radioactive ion beams will be injected into the EBIS for charge breeding and due to its inherent properties, the EBIS-CB will maintain the purity of the charge bred beams. Possible contamination of residual gas ions will be greatly suppressed by achieving ultra-high vacuum in the EBIS trap. This paper will present and discuss the design of the LEBT and the overall integration of the EBIS-CB into ATLAS.

  4. Liaison to DASN AP

    DTIC Science & Technology

    2014-08-01

    Liaison  to  DASN   AP   Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is...control number. 1. REPORT DATE AUG 2014 2. REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Liaison to DASN AP 5a...on  was  created:   § To  serve  as  a  liaison  between  the  DON   OSBP  and  DASN   AP   § Co-­‐located  to

  5. Effects of line defects on spin-dependent electronic transport of zigzag MoS{sub 2} nanoribbons

    SciTech Connect

    Li, Xin-Mei; Yang, Kai-Wei; Zhang, Dan; Ding, Jia-Feng; Xu, Hui; Long, Meng-Qiu; Cui, Li-Ling

    2016-01-15

    The nonlinear spin-dependent transport properties in zigzag molybdenum-disulfide nanoribbons (ZMNRs) with line defects are investigated systematically using nonequilibrium Green’s function method combined with density functional theory. The results show that the line defects can enhance the electronic transfer ability of ZMNRs. The types and locations of the line defects are found critical in determining the spin polarization and the current-voltage (I-V) characteristics of the line defected ZMNRs. For the same defect type, the total currents of the ribbons with the line defects in the centers are lager than those on the edges. And for the same location, the total currents of the systems with the sulfur (S) line defect are larger than the according systems with the molybdenum (Mo) line defect. All the considered systems present magnetism properties. And in the S line defected systems, the spin reversal behaviors can be observed. In both the spin-up and spin-down states of the Mo line defected systems, there are obvious negative differential resistance behaviors. The mechanisms are proposed for these phenomena.

  6. Lines

    ERIC Educational Resources Information Center

    Mires, Peter B.

    2006-01-01

    National Geography Standards for the middle school years generally stress the teaching of latitude and longitude. There are many creative ways to explain the great grid that encircles our planet, but the author has found that students in his college-level geography courses especially enjoy human-interest stories associated with lines of latitude…

  7. Characterization of a Chinese hamster-human hybrid cell line with increased system L amino acid transport activity.

    PubMed Central

    Lobaton, C D; Moreno, A; Oxender, D L

    1984-01-01

    We have studied leucine transport in several Chinese hamster-human hybrid cell lines obtained by fusion of a temperature-sensitive line of Chinese hamster ovary cells, ts025C1, and normal human leukocytes. A hybrid cell line exhibiting a twofold increase in L-leucine uptake over that in the parental cell line was found. This hybrid cell line, 158CnpT-1, was temperature resistant, whereas the parental Chinese hamster ovary mutant, ts025C1, contained a temperature-sensitive leucyl-tRNA synthetase mutation. An examination of the different amino acid transport systems in this hybrid cell line revealed a specific increase of system L activity with no significant changes in systems A and ASC. The Vmax for L-leucine uptake exhibited by the hybrid 158CnpT-1 was twice that in the CHO parental mutant, ts025C1. Cytogenetic analysis showed that the hybrid 158CnpT-1 contains four complete human chromosomes (numbers 4, 5, 10, and 21) and three interspecific chromosomal translocations in a total complement of 34 chromosomes. Biochemical and cytogenetic analysis of segregant clones obtained from hybrid 158CnpT-1 showed that the primary temperature resistance and high system L transport phenotypes can be segregated from this hybrid independently. The loss of the primary temperature resistance was associated with the loss of the human chromosome 5, as previously reported by other laboratories, whereas the loss of the high leucine transport phenotype, which is associated with a lesser degree of temperature resistance, was correlated with the loss of human chromosome 20. Images PMID:6717430

  8. Characterization of a Chinese hamster-human hybrid cell line with increased system L amino acid transport activity.

    PubMed

    Lobaton, C D; Moreno, A; Oxender, D L

    1984-03-01

    We have studied leucine transport in several Chinese hamster-human hybrid cell lines obtained by fusion of a temperature-sensitive line of Chinese hamster ovary cells, ts025C1, and normal human leukocytes. A hybrid cell line exhibiting a twofold increase in L-leucine uptake over that in the parental cell line was found. This hybrid cell line, 158CnpT-1, was temperature resistant, whereas the parental Chinese hamster ovary mutant, ts025C1, contained a temperature-sensitive leucyl-tRNA synthetase mutation. An examination of the different amino acid transport systems in this hybrid cell line revealed a specific increase of system L activity with no significant changes in systems A and ASC. The Vmax for L-leucine uptake exhibited by the hybrid 158CnpT-1 was twice that in the CHO parental mutant, ts025C1. Cytogenetic analysis showed that the hybrid 158CnpT-1 contains four complete human chromosomes (numbers 4, 5, 10, and 21) and three interspecific chromosomal translocations in a total complement of 34 chromosomes. Biochemical and cytogenetic analysis of segregant clones obtained from hybrid 158CnpT-1 showed that the primary temperature resistance and high system L transport phenotypes can be segregated from this hybrid independently. The loss of the primary temperature resistance was associated with the loss of the human chromosome 5, as previously reported by other laboratories, whereas the loss of the high leucine transport phenotype, which is associated with a lesser degree of temperature resistance, was correlated with the loss of human chromosome 20.

  9. Peculiar Traits of Coarse AP

    DTIC Science & Technology

    2014-01-01

    contained ammonium chlorate and some amounts of AP degradation products. Khairetdinov and Boldyrev called small nuclei “seeds or germs”. They observed...grew to larger sizes. Increased concentration of chlorate ion in AP produced a proliferation of germs and decreased induction time before AP LTD...AP LTD reactions were chlorate ion concentration dependent. As chlorate content was increased decomposition reaction rates were greater in the AP

  10. Mechanisms of cellular uptake, intracellular transportation, and degradation of CIGB-300, a Tat-conjugated peptide, in tumor cell lines.

    PubMed

    Benavent Acero, Fernando R; Perera Negrin, Yasser; Alonso, Daniel F; Perea, Silvio E; Gomez, Daniel E; Farina, Hernán G

    2014-06-02

    CIGB-300 is a cyclic synthetic peptide that induces apoptosis in malignant cells, elicits antitumor activity in cancer animal models, and shows tumor reduction signs when assayed in first-in-human phase I trial in patients with cervical tumors. CIGB-300 impairs phosphorylation by casein kinase 2 through targeting the substrate's phosphoacceptor domain. CIGB-300 was linked to the cell penetrating peptide Tat to facilitate the delivery into cells. Previously, we showed that CIGB-300 had a differential antiproliferative behavior in different tumor cell lines. In this work, we studied differential antiproliferative behavior in terms of cellular uptake, intracellular transportation, and degradation in tumor cell lines with dissimilar sensitivity to CIGB-300. The internalization of CIGB-300 was studied in different malignant cell lines. We found that the cell membrane heparan sulfate proteoglycans act as main receptors for extracellular CIGB-300 uptake. The most sensitive tumor cell lines showed higher intracellular incorporation of CIGB-300 in comparison to less sensitive cell lines. Furthermore, CIGB-300 uptake is time- and concentration-dependent in all studied cell lines. It was shown that CIGB-300 has the ability to penetrate cells mainly by direct membrane translocation. However, a minor proportion of the peptide uses an energy-dependent endocytic pathway mechanism to gain access into cells. CIGB-300 is internalized and transported into cells preferentially by caveolae-mediated endocytosis. Lysosomes are involved in CIGB-300 degradation; highly sensitive cell lines showed degradation at earlier times compared to low sensitive cells. Altogether, our data suggests a mechanism of internalization, vesicular transportation, and degradation for CIGB-300 in tumor cells.

  11. The alteration of serine transporter activity in a cell line model of amyotrophic lateral sclerosis (ALS).

    PubMed

    Lee, Na-Young; Kim, Yunha; Ryu, Hoon; Kang, Young-Sook

    2017-01-29

    The alteration of d-serine levels is associated with the pathogenesis of sporadic ALS and mutant SOD1 (G93A) animal model of ALS. However, the exact mechanism of d-serine transport is not known in ALS. To better understand the distribution of d-serine in ALS, we determined the activity and the expression of serine transporter in a motor neuronal cell line model of ALS (NSC-34/hSOD1(G93A) cells). The uptake of [(3)H]d-serine was significantly lower in NSC-34/hSOD1(G93A) cells than in control NSC-34 and NSC-34/hSOD1(wt) cells. In contrast, the uptake of [(3)H]l-serine, precursor of d-serine, was markedly increased in NSC-34/hSOD1(G93A) cells compared to control NSC-34 and NSC-34/hSOD1(wt) cells. Both [(3)H]d-serine and [(3)H]l-serine uptake were saturable in these cells. The estimated Michaelis-Menten constant, Km, for d-serine uptakes was higher in NSC-34/hSOD1(G93A) cells than in NSC-34/hSOD1(wt) cells while the Km for l-serine uptake was 2 fold lower in NSC-34/hSOD1(G93A) cells than in control cells. [(3)H]d-serine and [(3)H]l-serine uptakes took place in a Na(+)-dependent manner, and both uptakes were significantly inhibited by system ASC (alanine-serine-cysteine) substrates. As a result of small interfering RNA experiments, we found that ASCT2 (SLC1A5) and ASCT1 (SLC1A4) are involved in [(3)H]d-serine and [(3)H]l-serine uptake in NSC-34/hSOD1(G93A) cells, respectively. The level of SLC1A4 mRNA was significantly increased in NSC-34/hSOD1(G93A) compared to NSC-34 and NSC-34/hSOD1(wt) cells. In contrast, the level of SLC7A10 mRNA was relatively lower in NSC-34/hSOD1(G93A) cells than the control cells. Together, these data suggest that the pathological alteration of d- and l-serine uptakes in ALS is driven by the affinity change of d-and l-serine uptake system.

  12. Advancing beyond AP Courses

    ERIC Educational Resources Information Center

    Hammond, Bruce G.

    2009-01-01

    A quiet revolution is picking up steam in the nation's private secondary schools, with broad implications for college admissions and for teaching and learning on both sides of the transition from high school to college. About 50 of the nation's leading college-preparatory schools have opted out of the College Board's Advanced Placement (AP)…

  13. A demonstration of a transportable radio interferometric surveying system with 3-cm accuracy on a 307-m base line

    NASA Technical Reports Server (NTRS)

    Ong, K. M.; Macdoran, P. F.; Thomas, J. B.; Fliegel, H. F.; Skjerve, L. J.; Spitzmesser, D. J.; Batelaan, P. D.; Paine, S. R.; Newsted, M. G.

    1976-01-01

    A precision geodetic measurement system (Aries, for Astronomical Radio Interferometric Earth Surveying) based on the technique of very long base line interferometry has been designed and implemented through the use of a 9-m transportable antenna and the NASA 64-m antenna of the Deep Space Communications Complex at Goldstone, California. A series of experiments designed to demonstrate the inherent accuracy of a transportable interferometer was performed on a 307-m base line during the period from December 1973 to June 1974. This short base line was chosen in order to obtain a comparison with a conventional survey with a few-centimeter accuracy and to minimize Aries errors due to transmission media effects, source locations, and earth orientation parameters. The base-line vector derived from a weighted average of the measurements, representing approximately 24 h of data, possessed a formal uncertainty of about 3 cm in all components. This average interferometry base-line vector was in good agreement with the conventional survey vector within the statistical range allowed by the combined uncertainties (3-4 cm) of the two techniques.

  14. Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2.

    PubMed

    Fukada, Atsuko; Saito, Hideyuki; Inui, Ken-Ichi

    2002-08-01

    Ulcerative colitis is a disease more commonly seen in nonsmokers. Because nicotine was postulated to be a beneficial component of tobacco smoke for ulcerative colitis, various formulations of nicotine have been developed to improve the local bioavailability within the gastrointestinal tissue. In the present study, to characterize the disposition of nicotine in the intestines, we investigated intestinal nicotine transport using Caco-2 cells. Nicotine was predominantly transported across Caco-2 cell monolayers in a unidirectional mode, corresponding to intestinal secretion, by pH-dependent specific transport systems. The specific uptake systems appear to be distinct from organic cation transporters and the transport system for tertiary amines, in terms of its substrate specificity and the pattern of the interaction. These transport systems could play a role in the intestinal accumulation of nicotine from plasma and could also be responsible for the topical delivery of nicotine for ulcerative colitis therapy. These findings could provide useful information for the design of effective nicotine delivery.

  15. Upgrade of the beam transport lines and the beam-abort system and development of a tune compensator in KEKB

    NASA Astrophysics Data System (ADS)

    Iida, Naoko; Kikuchi, Mitsuo; Mimashi, Toshihiro; Nakayama, Hisayoshi; Sakamoto, Yutaka; Satoh, Kotaro; Takasaki, Seiji; Tawada, Masafumi

    2013-03-01

    The KEKB collider achieved a maximum peak luminosity of 2.1×1034 cm-2 s-1 and an integrated luminosity of 1 ab-1 in its ten-year operation. Behind these glorious records there have been uncountable improvements in every subsystem. This paper describes the improvements in the beam transport line, injection kickers, septum magnets, the beam-abort system, and a newly developed pulsed-quadrupole system in detail.

  16. Paracellular transport through healthy and cystic fibrosis bronchial epithelial cell lines--do we have a proper model?

    PubMed

    Molenda, Natalia; Urbanova, Katarina; Weiser, Nelly; Kusche-Vihrog, Kristina; Günzel, Dorothee; Schillers, Hermann

    2014-01-01

    It has been reported recently that the cystic fibrosis transmembrane conductance regulator (CFTR) besides transcellular chloride transport, also controls the paracellular permeability of bronchial epithelium. The aim of this study was to test whether overexpressing wtCFTR solely regulates paracellular permeability of cell monolayers. To answer this question we used a CFBE41o- cell line transfected with wtCFTR or mutant F508del-CFTR and compered them with parental line and healthy 16HBE14o- cells. Transepithelial electrical resistance (TER) and paracellular fluorescein flux were measured under control and CFTR-stimulating conditions. CFTR stimulation significant decreased TER in 16HBE14o- and also in CFBE41o- cells transfected with wtCFTR. In contrast, TER increased upon stimulation in CFBE41o- cells and CFBE41o- cells transfected with F508del-CFTR. Under non-stimulated conditions, all four cell lines had similar paracellular fluorescein flux. Stimulation increased only the paracellular permeability of the 16HBE14o- cell monolayers. We observed that 16HBE14o- cells were significantly smaller and showed a different structure of cell-cell contacts than CFBE41o- and its overexpressing clones. Consequently, 16HBE14o- cells have about 80% more cell-cell contacts through which electrical current and solutes can leak. Also tight junction protein composition is different in 'healthy' 16HBE14o- cells compared to 'cystic fibrosis' CFBE41o- cells. We found that claudin-3 expression was considerably stronger in 16HBE14o- cells than in the three CFBE41o- cell clones and thus independent of the presence of functional CFTR. Together, CFBE41o- cell line transfection with wtCFTR modifies transcellular conductance, but not the paracellular permeability. We conclude that CFTR overexpression is not sufficient to fully reconstitute transport in CF bronchial epithelium. Hence, it is not recommended to use those cell lines to study CFTR-dependent epithelial transport.

  17. Learning about Antiphospholipid Syndrome (APS)

    MedlinePlus

    ... and links from the National Institutes of Health. Learning About Antiphospholipid Syndrome (APS) What is antiphospholipid syndrome ( ... with APS include : Systemic Vascular Thrombosis While the deep veins of the legs are the most frequent ...

  18. In-situ characterization of wastewater flow and transport from at-grade line sources to shallow groundwater

    NASA Astrophysics Data System (ADS)

    Weldeyohannes, A. O.; Kachanoski, R. G.; Dyck, M. F.

    2011-12-01

    A better understanding of multidimensional unsaturated and saturated flow and transport under boundary conditions typical of on-site wastewater disposal systems is required to assess the risk to groundwater contamination. The main objective of this research is to characterize in-situ wastewater flow and transport from at-grade line sources on a shallow groundwater conditions. The research site was conducted at Wetaskiwin Rest Stop, Alberta, Canada, where ultraviolet disinfected wastewater has been disposed off to the ground via pressurized at-grade line sources since 2007. The site was characterized for wastewater plume and temporal groundwater fluctuation by using Electromagnetic induction (EM31) and (EM38); and by grid of 74 water table wells, 14 piezometers and 11 transducers. Groundwater was analyzed for selected tracers (pH, EC and Cl) and some microbiology (e.g. E. coli). From the results wastewater plume was identified; and wastewater plume center of mass and average flow direction were estimated. Along the horizontal plume center of mass, 30 monitoring wells in 10 nests and 31 temperature sensors in 5 nests were installed to get vertical resolution of the wastewater plume and to track contaminant transport over time. Results, implications and plans for future investigations will be presented. The research output will benefit future research on contaminant fate and transport and groundwater risk assessment plans. Key words: On-site wastewater treatment/disposal system, Wastewater plume, Groundwater contamination.

  19. Transport of poly(acrylic acid) coated 2-line ferrihydrite nanoparticles in saturated aquifer sediments for environmental remediation

    NASA Astrophysics Data System (ADS)

    Xiang, Aishuang; Zhou, Sheng; Koel, Bruce E.; Jaffé, Peter R.

    2014-04-01

    Groundwater remediation using iron oxide and zero-valent iron nanoparticles (NPs) can be effective, but is limited in many applications due to the NP strong retention in groundwater-saturated porous media after injection, the passivation of the porous surface, and the high cost of nanomaterials versus macro scale iron. In this study, we investigated transport of bare and polymer-coated 2-line ferrihydrite NPs (30-300 nm) in saturated aquifer sediments. The influence of poly(acrylic acid) (PAA) polymer coatings was studied on the colloidal stability and transport in sediments packed column tests simulating groundwater flow in saturated sediments. In addition, the influence of calcium cations was investigated by transport measurements using sediments with calcium concentrations in the aqueous phase ranging from 0.5 (typical for most sediments) to 2 mM. Measurements were also made of zeta potential, hydrodynamic diameter, polymer adsorption and desorption properties, and bio-availability of PAA-coated NPs. We found that NP transport through the saturated aquifer sediments was improved by PAA coating and that the transport properties could be tuned by adjusting the polymer concentration. We further discovered that PAA coatings enhanced NP transport, compared to bare NPs, in all calcium-containing experiments tested, however, the presence of calcium always exhibited a negative effect on NP transport. In tests of bioavailability, the iron reduction rate of the coated and bare NPs by Geobacter sulfurreducens was the same, which shows that the PAA coating does not significantly reduce NP Fe(III) bioavailability. Our results demonstrate that much improved transport of iron oxide NP can be achieved in saturated aquifer sediments by introducing negatively charged polyelectrolytes and optimizing polymer concentrations, and furthermore, these coated NPs retain their bioavailability that is needed for applications in bio-environmental remediation.

  20. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.713 Common line... pricing flexibility with respect to the following services: (1) Common line services, as described in... described in §§ 69.111(a)(2)(i) and (ii). (b) Phase I triggers. (1) To obtain Phase I pricing...

  1. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.713 Common line... pricing flexibility with respect to the following services: (1) Common line services, as described in... described in §§ 69.111(a)(2)(i) and (ii). (b) Phase I triggers. (1) To obtain Phase I pricing...

  2. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.713 Common line... pricing flexibility with respect to the following services: (1) Common line services, as described in... described in §§ 69.111(a)(2)(i) and (ii). (b) Phase I triggers. (1) To obtain Phase I pricing...

  3. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.713 Common line... pricing flexibility with respect to the following services: (1) Common line services, as described in... described in §§ 69.111(a)(2)(i) and (ii). (b) Phase I triggers. (1) To obtain Phase I pricing...

  4. 47 CFR 69.713 - Common line, traffic-sensitive, and tandem-switched transport services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.713 Common line... pricing flexibility with respect to the following services: (1) Common line services, as described in... described in §§ 69.111(a)(2)(i) and (ii). (b) Phase I triggers. (1) To obtain Phase I pricing...

  5. Renal involvement in the antiphospholipid syndrome (APS)-APS nephropathy.

    PubMed

    Tektonidou, Maria G

    2009-06-01

    Although the kidney represents a major target organ in antiphospholipid syndrome (APS), renal involvement in APS was poorly recognized until recently. The most well-recognized renal manifestations of APS are the renal artery thrombosis/stenosis, renal infarction, hypertension, renal vein thrombosis, end-stage renal disease, increased allograft vascular thrombosis, some types of glomerular disease, and a small-vessel vaso-occlusive nephropathy, recently defined as APS nephropathy. APS nephropathy was first described in primary APS patients, characterized by acute thrombotic lesions in glomeruli and/or arterioles (thrombotic microangiopathy) and chronic vascular lesions such as fibrous intimal hyperplasia of arterioles and interlobular arteries, organized thrombi with or without recanalization, and fibrous arterial and arteriolar occlusions or focal cortical atrophy. APS nephropathy was also detected in further studies including patients with systemic lupus erythematosus (SLE)-related APS and SLE/non-APS patients with positive antiphospholipid antibodies, independently of lupus nephritis. The same histologic lesions, especially thrombotic mictroangiopathy, were also observed in patients with catastrophic APS. The most frequent clinical and laboratory characteristics of APS nephropathy in all the above groups of patients are hypertension (often severe), proteinuria (ranging from mild to nephrotic range), hematuria, and acute or chronic renal insufficiency.

  6. The APS ceramic chambers

    SciTech Connect

    Milton, S.; Warner, D.

    1994-07-01

    Ceramics chambers are used in the Advanced Photon Source (APS) machines at the locations of the pulsed kicker and bumper magnets. The ceramic will be coated internally with a resistive paste. The resistance is chosen to allow the low frequency pulsed magnet field to penetrate but not the high frequency components of the circulating beam. Another design goal was to keep the power density experienced by the resistive coating to a minimum. These ceramics, their associated hardware, the coating process, and our recent experiences with them are described.

  7. Interaction of ABC transport proteins with toxic metals at the level of gene and transport activity in the PLHC-1 fish cell line.

    PubMed

    Della Torre, Camilla; Zaja, Roko; Loncar, Jovica; Smital, Tvrtko; Focardi, Silvano; Corsi, Ilaria

    2012-06-25

    The aim of this study was to investigate the interaction of four toxic metals with ABC transport proteins in piscine cell line PLHC-1. Cells were exposed for 24 h to 0.01-1 μM of CdCl(2), HgCl(2), As(2)O(3), or K(2)Cr(2)O(7) and the expression of a series of ABC genes (abcb1, abcc1-4) was determined using qRT-PCR. Using the fluorescent model substrates calcein-AM and monochlorbimane we measured interaction of metals with the transport activity of ABC transporters. P-glycoprotein (P-gp) activity was measured in PLHC-1/dox (P-gp overexpressing cells) while activity and interactions of metals with MRPs was measured in PLHC-1/wt cells. After 24 h exposure, abcc2-4 genes were dose-dependently up-regulated by all metals, while abcb1 and abcc1 were less affected. Up-regulation of abcc2 was more pronounced, with up to 8-fold increase in expression. Abcc3 and abcc4 were moderately inducible by HgCl(2) with 3.3-fold and 2.2-fold, respectively. All metals caused a significant inhibition of both P-gp (2.9- to 4-fold vs. controls) and MRP (1.3- to 1.8-fold) transport activities. Modulation of ABC genes and transport activities was further investigated in PLHC-1/wt cells exposed to 1 μM HgCl(2) for 72 h and in Hg resistant cells selected by long term cultivation of PLHC-1/wt cells in increasing concentrations of HgCl(2). Exposure to HgCl(2) for 72 h induced MRP genes expression and efflux activity. The long term cultivation of PLHC-1/wt cells in HgCl(2), did not cause prolonged up-regulation of the tested abc genes but resulted in higher MRP transport activities as determined by the increased sensitivity of these cells to MK571 (MRP specific inhibitor). Results of the present study indicated specific interaction of metals with selected ABC transport proteins. Modulation of ABC transporters takes place at both transcriptional and functional level. An active involvement of efflux pumps in Hg clearance in fish is suggested.

  8. Bicarbonate-dependent chloride transport drives fluid secretion by the human airway epithelial cell line Calu-3

    PubMed Central

    Shan, Jiajie; Liao, Jie; Huang, Junwei; Robert, Renaud; Palmer, Melissa L; Fahrenkrug, Scott C; O'Grady, Scott M; Hanrahan, John W

    2012-01-01

    Anion and fluid secretion are both defective in cystic fibrosis (CF); however, the transport mechanisms are not well understood. In this study, Cl− and HCO3− secretion was measured using genetically matched CF transmembrane conductance regulator (CFTR)-deficient and CFTR-expressing cell lines derived from the human airway epithelial cell line Calu-3. Forskolin stimulated the short-circuit current (Isc) across voltage-clamped monolayers, and also increased the equivalent short-circuit current (Ieq) calculated under open-circuit conditions. Isc was equivalent to the HCO3− net flux measured using the pH-stat technique, whereas Ieq was the sum of the Cl− and HCO3− net fluxes. Ieq and HCO3− fluxes were increased by bafilomycin and ZnCl2, suggesting that some secreted HCO3− is neutralized by parallel electrogenic H+ secretion. Ieq and fluid secretion were dependent on the presence of both Na+ and HCO3−. The carbonic anhydrase inhibitor acetazolamide abolished forskolin stimulation of Ieq and HCO3− secretion, suggesting that HCO3− transport under these conditions requires catalysed synthesis of carbonic acid. Cl− was the predominant anion in secretions under all conditions studied and thus drives most of the fluid transport. Nevertheless, 50–70% of Cl− and fluid transport was bumetanide-insensitive, suggesting basolateral Cl− loading by a sodium–potassium–chloride cotransporter 1 (NKCC1)-independent mechanism. Imposing a transepithelial HCO3− gradient across basolaterally permeabilized Calu-3 cells sustained a forskolin-stimulated current, which was sensitive to CFTR inhibitors and drastically reduced in CFTR-deficient cells. Net HCO3− secretion was increased by bilateral Cl− removal and therefore did not require apical Cl−/HCO3− exchange. The results suggest a model in which most HCO3− is recycled basolaterally by exchange with Cl−, and the resulting HCO3−-dependent Cl− transport provides an osmotic driving force for

  9. Numerical and experimental study of atomic transport and Balmer line intensity in Linac4 negative ion source

    SciTech Connect

    Shibata, T. Nishida, K.; Hatayama, A.; Mattei, S.; Lettry, J.

    2015-04-08

    Time structure of Balmer H{sub α} line intensity in Linac4 RF plasma has been analyzed by the combined simulation model of atomic transport and Collisional-Radiative models. As a preliminary result, time variation of the line intensity in the ignition phase of RF plasma is calculated and compared with the experimental results by photometry. For the comparison, spatial distribution of the local H{sub α} photon emission rate at each time is calculated from the numerical model. The contribution of the local photon emission rates to the observed line intensity via optical viewing port is also investigated by application of the mock-up of the optical viewing port and the known light source. It has been clarified from the analyses that the higher and the lower peaks of the H{sub α} line intensity observed during 1 RF cycle is mainly due to the different spatial distributions in the electron energy distribution function and the resultant local photon emission rate. These results support previous suggestion that the existence of the capacitive electric field in axial direction leads to the higher/lower peaks of the line intensity.

  10. Lagrangian transport near perturbed periodic lines in three-dimensional unsteady flows

    NASA Astrophysics Data System (ADS)

    Speetjens, Michel

    2015-11-01

    Periodic lines formed by continuous strings of periodic points are key organizing entities in the Lagrangian flow topology of certain three-dimensional (3D) time-periodic flows. Such lines generically consist of elliptic and/or hyperbolic points and thus give rise to 3D flow topologies made up of families of concentric closed trajectories embedded in chaotic regions. Weak perturbation destroys the periodic lines and causes said trajectories to coalesce into families of concentric tubes. However, emergence of isolated periodic points near the disintegrating periodic lines and/or partitioning of the original lines into elliptic and hyperbolic segments interrupt the tube formation. This yields incomplete tubes that interact with the (chaotic) environment through their open ends, resulting in intricate and essentially 3D flow topologies These phenomena have been observed in various realistic flows yet the underlying mechanisms are to date only partially understood. This study deepens insight into the (perturbed) Lagrangian dynamics of these flows by way of a linearized representation of the equations of motion near the periodic lines. Predictions on the basis of this investigation are in full (qualitative) agreement with observed behavior in the actual flows

  11. AP-2α inhibits hepatocellular carcinoma cell growth and migration.

    PubMed

    Huang, Wenhuan; Chen, Cheng; Liang, Zhongheng; Qiu, Junlu; Li, Xinxin; Hu, Xiang; Xiang, Shuanglin; Ding, Xiaofeng; Zhang, Jian

    2016-03-01

    Transcription factor AP-2α is involved in many types of human cancers, but its role in hepatocellular carcinogenesis is largely unknown. In this study, we found that expression of AP-2α was low in 40% of human hepatocellular cancers compared with adjacent normal tissues by immunohistochemical analysis. Moreover, AP-2α expression was low or absent in hepatocellular cancer cell lines (HepG2, Hep3B, SMMC-7721 and MHHC 97-H). Human liver cancer cell lines SMMC-7721 and Hep3B stably overexpressing AP-2α were established by lentiviral infection and puromycin screening, and the ectopic expression of AP-2α was able to inhibit hepatocellular cancer cell growth and proliferation by cell viability, MTT assay and liquid colony formation in vitro and in vivo. Furthermore, AP-2α overexpression decreased liver cancer cell migration and invasion as assessed by wound healing and Transwell assays, increasing the sensitivity of liver cancer cells to cisplatin analyzed by MTT assays. Also AP-2α overexpression suppressed the sphere formation and renewed the ability of cancer stem cells. Finally, we found that AP-2α is epigenetically modified and modulates the levels of phosphorylated extracellular signal-regulated protein kinase (ERK), β-catenin, p53, EMT, and CD133 expression in liver cancer cell lines. These results suggested that AP-2α expression is low in human hepatocellular cancers by regulating multiple signaling to affect hepatocellular cancer cell growth and migration. Therefore, AP-2α might represent a novel potential target in human hepatocellular cancer therapy.

  12. Transepithelial transport efficiency of bovine collagen hydrolysates in a human Caco-2 cell line model.

    PubMed

    Feng, Mengmeng; Betti, Mirko

    2017-06-01

    Collagen was extracted from raw bovine hide and hydrolyzed by one of three enzymes - Alcalase, Flavourzyme, or trypsin - or by using a combination of two or three of these enzymes. The Alcalase-containing enzymatic hydrolysis treatments generated a greater proportion of hydrolysates with molecular weight (MW) <2kDa (79.8-82.7%). Flavourzyme-containing hydrolysis treatments exhibited the greatest proportion of free amino acids (686-740nmol/mg). The hydrolysates were then subjected to a simulated gastrointestinal (GI) digestion, and transport studies were conducted using a Caco-2 cell model. Due to the lower MW profile, the hydrolyzed collagen showed greater resistance to GI digestion and greater transport efficiency than the unhydrolyzed collagen control. Hydrolysates from a dual enzyme mixture - the Alcalase/Flavourzyme combination - generated the greatest transport efficiency across Caco-2 cell monolayers (21.4%), two-fold more than that of the collagen control.

  13. Human Immunodeficiency Virus Protease Inhibitors Serve as Substrates for Multidrug Transporter Proteins MDR1 and MRP1 but Retain Antiviral Efficacy in Cell Lines Expressing These Transporters

    PubMed Central

    Srinivas, Ranga V.; Middlemas, David; Flynn, Pat; Fridland, Arnold

    1998-01-01

    The human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs)—saquinavir, ritonavir, nelfinavir, and indinavir—interact with the ABC-type multidrug transporter proteins MDR1 and MRP1 in CEM T-lymphocytic cell lines. Calcein fluorescence was significantly enhanced in MDR1+ CEM/VBL100 and MRP1+ CEM/VM-1-5 cells incubated in the presence of various HIV PIs and calcein acetoxymethyl ester. HIV PIs also enhanced the cytotoxic activity of doxorubicin, a known substrate for MDR1 and MRP1, in both VBL100 and VM-1-5 CEM lines. Saquinavir, ritonavir, and nelfinavir enhanced doxorubicin toxicity in CEM/VBL100 cells by approximately three- to sevenfold. Saquinavir and ritonavir also enhanced doxorubicin toxicity in CEM/VM-1-5 cells. HIV-1 replication was effectively inhibited by the various PIs in all of the cell lines, and the 90% inhibitory concentration for a given compound was comparable between the different cell types. Therefore, overexpression of MDR1 or MRP1 by T lymphocytes is not likely to limit the antiviral efficacy of HIV PI therapy. PMID:9835508

  14. Altered glycaemia differentially modulates efflux transporter expression and activity in hCMEC/D3 cell line.

    PubMed

    Sajja, Ravi K; Cucullo, Luca

    2015-06-26

    The unique phenotype of blood-brain barrier (BBB) endothelium is partly maintained by abundant expression of ATP-binding cassette superfamily of efflux transporters that strictly restrict the CNS access to toxic substances including xenobiotics in circulation. Previously, we have shown that diabetes-related altered glycemic conditions differentially affect and compromise BBB integrity. However, the impact of diabetes on BBB efflux transporters is less understood. In this study, we examined the effects of single or repeated episodes of hypo-and hyperglycemia on major BBB efflux transporters expression/function in human cerebromicrovascular endothelial cell line (hCMEC/D3). Cells were exposed to normal (5.5 mM), hypo (2.2 mM) or hyper (25 or 35 mM)-glycemic media containing D-glucose for 12h (acute) or two 3h episodes/day of hypo- or hyperglycemia with an intercalated 2h normalglycemic exposure for 3 days ("glycemic variability", see Methods). Acute hypoglycemic exposure (12h) up-regulated BBB endothelial mRNA and protein expression of P-glycoprotein, BCRP and other multidrug resistance associated proteins (MRP1 and 4) paralleled by an increase in transporter-specific efflux activity (∼ 2-fold vs. control). Although, 12h hyperglycemia did not affect the efflux transporter expression (except for MRP4), a significant increase in BCRP activity was observed. By contrast, DNA microarray data revealed that repeated hyperglycemic episodes (but not hypoglycemia) significantly up-regulate P-glycoprotein expression and activity. Thus, this study suggests a differential impact of altered glycemic conditions on major BBB drug efflux transporters expression/function, sensitive to the length of exposure (acute vs. repeated), with an implication for altered CNS drug disposition in diabetic population.

  15. Cyclic AMP, membrane transport and cell division. I. Effects of various chemicals on cyclic AMP levels and rate of transport of neucleosides, hypoxanthine and deoxyglucose in several lines of cultured cells.

    PubMed

    Sheppard, J R; Plagemann, P G

    1975-04-01

    Nutrient transport rates and cyclic AMP levels have been implicated in the regulation of cell proliferation. In the present study, however, changes in intracellular cyclic AMP level in several lines of cultured cells (normal 3T3 and SV40 and polyomavirus-transformed 3T3 cells; 3T6, C6 GLIOMA, MOUSE L, and Novikoff rat hepatoma cells) by treatment with papaverine, prostaglandine E1 or isoproterenol did not correlate with the inhibition of the uridine, hypoxanthine or deoxyglucose transport rates by these chemicals. Transport inhibitions by above chemicals or Persantin or Cytochalasin B occurred in most cell lines in the absence of any measurable change in intracellular cyclic AMP concentration. Furthermore, treatment of several cell lines with 1 mM dibutyryl cyclic AMP had no immediate effect on the transport of uridine, thymidine or deoxyglucose, although the transport capacity of the cells for uridine and thymidine, but not that for deoxyglucose, decreased progressively with time of treatment. We also observed that the uridine transport system of all cell lines derived from 3T3 cells and the hypoxanthine transport system of L cells exhibited high degrees of resistance to inhibition by the various chemicals. On the other hand, deoxyglucose transport was inhibited to about the same extent by these chemicals in all the cell lines investigated.

  16. A generalized framework for in-line energy deposition during steady-state Monte Carlo radiation transport

    SciTech Connect

    Griesheimer, D. P.; Stedry, M. H.

    2013-07-01

    A rigorous treatment of energy deposition in a Monte Carlo transport calculation, including coupled transport of all secondary and tertiary radiations, increases the computational cost of a simulation dramatically, making fully-coupled heating impractical for many large calculations, such as 3-D analysis of nuclear reactor cores. However, in some cases, the added benefit from a full-fidelity energy-deposition treatment is negligible, especially considering the increased simulation run time. In this paper we present a generalized framework for the in-line calculation of energy deposition during steady-state Monte Carlo transport simulations. This framework gives users the ability to select among several energy-deposition approximations with varying levels of fidelity. The paper describes the computational framework, along with derivations of four energy-deposition treatments. Each treatment uses a unique set of self-consistent approximations, which ensure that energy balance is preserved over the entire problem. By providing several energy-deposition treatments, each with different approximations for neglecting the energy transport of certain secondary radiations, the proposed framework provides users the flexibility to choose between accuracy and computational efficiency. Numerical results are presented, comparing heating results among the four energy-deposition treatments for a simple reactor/compound shielding problem. The results illustrate the limitations and computational expense of each of the four energy-deposition treatments. (authors)

  17. Different Behavioral and Physiological Response in two Genetic Lines of Laying Hens Following Transportation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physiological and behavioral response to transportation stress were examined in chickens selected for high group productivity and survivability (HGPS) resulting from reduced cannibalism and flightiness in colony cages and in chickens from Dekalb XL (DXL) commercial strain. At 13 wks of age, 96 pulle...

  18. Structural model of FeoB, the iron transporter from Pseudomonas aeruginosa, predicts a cysteine lined, GTP-gated pore

    PubMed Central

    Seyedmohammad, Saeed; Fuentealba, Natalia Alveal; Marriott, Robert A.J.; Goetze, Tom A.; Edwardson, J. Michael; Barrera, Nelson P.; Venter, Henrietta

    2016-01-01

    Iron is essential for the survival and virulence of pathogenic bacteria. The FeoB transporter allows the bacterial cell to acquire ferrous iron from its environment, making it an excellent drug target in intractable pathogens. The protein consists of an N-terminal GTP-binding domain and a C-terminal membrane domain. Despite the availability of X-ray crystal structures of the N-terminal domain, many aspects of the structure and function of FeoB remain unclear, such as the structure of the membrane domain, the oligomeric state of the protein, the molecular mechanism of iron transport, and how this is coupled to GTP hydrolysis at the N-terminal domain. In the present study, we describe the first homology model of FeoB. Due to the lack of sequence homology between FeoB and other transporters, the structures of four different proteins were used as templates to generate the homology model of full-length FeoB, which predicts a trimeric structure. We confirmed this trimeric structure by both blue-native-PAGE (BN-PAGE) and AFM. According to our model, the membrane domain of the trimeric protein forms a central pore lined by highly conserved cysteine residues. This pore aligns with a central pore in the N-terminal GTPase domain (G-domain) lined by aspartate residues. Biochemical analysis of FeoB from Pseudomonas aeruginosa further reveals a putative iron sensor domain that could connect GTP binding/hydrolysis to the opening of the pore. These results indicate that FeoB might not act as a transporter, but rather as a GTP-gated channel. PMID:26934982

  19. Paracellular Transport through Healthy and Cystic Fibrosis Bronchial Epithelial Cell Lines – Do We Have a Proper Model?

    PubMed Central

    Weiser, Nelly; Kusche-Vihrog, Kristina; Günzel, Dorothee; Schillers, Hermann

    2014-01-01

    It has been reported recently that the cystic fibrosis transmembrane conductance regulator (CFTR) besides transcellular chloride transport, also controls the paracellular permeability of bronchial epithelium. The aim of this study was to test whether overexpressing wtCFTR solely regulates paracellular permeability of cell monolayers. To answer this question we used a CFBE41o– cell line transfected with wtCFTR or mutant F508del-CFTR and compered them with parental line and healthy 16HBE14o– cells. Transepithelial electrical resistance (TER) and paracellular fluorescein flux were measured under control and CFTR-stimulating conditions. CFTR stimulation significant decreased TER in 16HBE14o– and also in CFBE41o– cells transfected with wtCFTR. In contrast, TER increased upon stimulation in CFBE41o– cells and CFBE41o– cells transfected with F508del-CFTR. Under non-stimulated conditions, all four cell lines had similar paracellular fluorescein flux. Stimulation increased only the paracellular permeability of the 16HBE14o– cell monolayers. We observed that 16HBE14o– cells were significantly smaller and showed a different structure of cell-cell contacts than CFBE41o– and its overexpressing clones. Consequently, 16HBE14o– cells have about 80% more cell-cell contacts through which electrical current and solutes can leak. Also tight junction protein composition is different in ‘healthy’ 16HBE14o– cells compared to ‘cystic fibrosis’ CFBE41o– cells. We found that claudin-3 expression was considerably stronger in 16HBE14o– cells than in the three CFBE41o– cell clones and thus independent of the presence of functional CFTR. Together, CFBE41o– cell line transfection with wtCFTR modifies transcellular conductance, but not the paracellular permeability. We conclude that CFTR overexpression is not sufficient to fully reconstitute transport in CF bronchial epithelium. Hence, it is not recommended to use those cell lines to study CFTR

  20. Space charge compensation in the Linac4 low energy beam transport line with negative hydrogen ions.

    PubMed

    Valerio-Lizarraga, Cristhian A; Lallement, Jean-Baptiste; Leon-Monzon, Ildefonso; Lettry, Jacques; Midttun, Øystein; Scrivens, Richard

    2014-02-01

    The space charge effect of low energy, unbunched ion beams can be compensated by the trapping of ions or electrons into the beam potential. This has been studied for the 45 keV negative hydrogen ion beam in the CERN Linac4 Low Energy Beam Transport using the package IBSimu [T. Kalvas et al., Rev. Sci. Instrum. 81, 02B703 (2010)], which allows the space charge calculation of the particle trajectories. The results of the beam simulations will be compared to emittance measurements of an H(-) beam at the CERN Linac4 3 MeV test stand, where the injection of hydrogen gas directly into the beam transport region has been used to modify the space charge compensation degree.

  1. In-line Particulate Transport and Dispersion Modeling Using the Regional Atmospheric Modeling System (RAMS)

    DTIC Science & Technology

    2005-03-01

    hydrometeor category can grow in size through several different processes such as collision coalescence This remains the same Conversion from one hydro ...Model ( WRF ). Use of the GDAS final (FNL) analysis requires the application of a GRIB-to-RALPH format converter, fdgrib, which is available from the same...Visualization Utilities SCIPUFF - Second-order Closure Integrated Puff T&D - Transport and Dispersion WRF - Weather Research and Forecasting Model

  2. Analysis of sediment transport pattern along the coastal line of the Curonian Spit

    NASA Astrophysics Data System (ADS)

    Kovaleva, Olga; Chubarenko, Boris

    2016-04-01

    Among a wide range of approaches for determination of long-shore sediment transport direction changes in grain-size parameters (mean, sorting, skewness) of beach deposits use not so often. There are two trends in alongshore distributions of surface sediments grain-size parameters which may indicate an alongshore transport (McLaren, Bowles, 1985): (a) sediments become finer, sorting and skewness decreases; (b) sediments become coarser, sorting decreases and skewness increases. Over all more than 150 sand samples were collected along the coastline of the Curonian Spit during 2011, 2014 and 2015 summer seasons. The grain-size analysis of the samples were carried out and mentioned above grain-size parameters were calculated. Shore segments with different trends were identified using a running 9-nodes window, level of significance of trend analysis was estimated. Results of the method testing reflected different sediment transportation patterns for different years. However for other areas such as embayed coasts at the Gulf of Finland this method showed presence of one-directed longshore sediment flow. As a result it is possible to say that for straightened coasts such as the Curonian Spit the method allows to determine the alongshore flux pattern formed by the last significant storm event, i.e. to estimate an actual consequence of winds and waves influence in the studied area and can not be used for describing multiannual longshore sediment transport. The work was financed by the Russian Scientific Fund (grant 14-37-00047) and by the Russian Foundation for Basic Research, research projects No. 14-35-50130 and No. 15-35-50613.

  3. Transport characteristics of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2.

    PubMed

    Yamaguchi, H; Yano, I; Saito, H; Inui, K

    2001-11-23

    Transport characteristics of grepafloxacin and levofloxacin across the apical membrane of Caco-2 cells were examined. Both grepafloxacin and levofloxacin uptakes increased rapidly, and were temperature-dependent. Grepafloxacin and levofloxacin uptakes showed concentration-dependent saturation with Michaelis constants of 3.9 and 9.3 mM, respectively. Uptake of grepafloxacin and levofloxacin increased in Cl(-)-free and ATP depleted conditions, suggesting the involvement of an efflux transport system different from the uptake mechanism. However, cyclosporin A, a typical inhibitor of P-glycoprotein, did not affect the uptake of these drugs. Unlabeled grepafloxacin, unlabeled levofloxacin and quinidine inhibited the uptake of grepafloxacin and levofloxacin under Cl(-)-free conditions. Tetraethylammonium, cimetidine, p-aminohippurate, probenecid, amino acids, beta-lactam antibiotic or monocarboxylates did not inhibit the uptake of grepafloxacin and levofloxacin under the same conditions. In conclusion, our results suggested that grepafloxacin and levofloxacin uptakes were mediated by a specific transport system distinct from those for organic cations and anions, amino acids, dipeptides and monocarboxylates.

  4. Going below the line: creating transportable brands for Australia's dark market

    PubMed Central

    Carter, S

    2003-01-01

    Objective: To investigate non-point-of-sale cigarette marketing in Australia, one of the "darkest" markets in the world. Design: Analysis of 172 tobacco industry documents. Results: The tobacco industry has continued to market their products despite severe restrictions on legal marketing activity. They made careful plans to circumvent regulation well in advance. In preparation for bans, they chose and strengthened existing brands to enable their continued success in a dark market and prepared the consumer for bans by increasing their spending on below the line activities. Bans reduced the industry's effectiveness and efficiency. After bans new brand launches stopped: instead key existing brands were strengthened via alterations to the product, line extensions, and stretching loopholes in the legislation as far as possible. In line with the general trend towards integrated marketing, a range of activities have been used in combination, including guerrilla marketing, advertising in imported international magazines, altering the pack, sponsorships, brand stretching, event promotions, lifestyle premiums, and the development of corporate websites. Conclusions: The tobacco industry acknowledges that marketing restrictions have an impact, validating their continued use in tobacco control. The industry is extremely creative in circumventing these marketing restrictions, requiring tobacco marketing regulations to be informed by marketing expertise, regularly updated, and to adopt the broadest possible scope. Tobacco control advocates, particularly those communicating with young people, could learn from the creativity of the tobacco industry. PMID:14645953

  5. TRANSPORT

    EPA Science Inventory

    Presentation outline: transport principles, effective solubility; gasoline composition; and field examples (plume diving).
    Presentation conclusions: MTBE transport follows from - phyiscal and chemical properties and hydrology. Field examples show: MTBE plumes > benzene plu...

  6. Functional description of APS beamline front ends

    SciTech Connect

    Kuzay, T.

    1993-02-01

    Traditional synchrotron sources were designed to produce bending magnet radiation and have proven to be an essential scientific tool. Currently, a new generation of synchrotron sources is being built that will be able to accommodate a large number of insertion device (ID) and high quality bending magnet (BM) sources. One example is the 7-GeV Advanced Photon Source (APS) now under construction at Argonne National Laboratory. The research and development effort at the APS is designed to fully develop the potential of this new generation of synchrotron sources. Of the 40 straight sections in the APS storage ring, 34 will be available for IDs. The remaining six sections are reserved for the storage ring hardware and diagnostics. Although the ring incorporates 80 BMs, only 40 of them can be used to extract radiation. The accelerator hardware shadows five of these 40 bending magnets, so the maximum number of BM sources on the lattice is 35. Generally, a photon beamline consists of four functional sections. The first section is the ID or the BM, which provides the radiation source. The second section, which is immediately outside the storage ring but inside a concrete shielding tunnel, is the front end, which is designed to control, define, and/or confine the x-ray beam. In the case of the APS, the front ends are designed to confine the photon beam. The third section, just outside the concrete shielding tunnel and on the experimental floor, is the first optics enclosure, which contains optics to filter and monochromatize the photon beam. The fourth section of a beamline consists of beam transports, additional optics, and experiment stations to do the scientific investigations. This document describes only the front ends of the APS beamlines.

  7. High intensity proton beam transportation through fringe field of 70 MeV compact cyclotron to beam line targets

    NASA Astrophysics Data System (ADS)

    Zhang, Xu; Li, Ming; Wei, Sumin; Xing, Jiansheng; Hu, Yueming; Johnson, Richard R.; Piazza, Leandro; Ryjkov, Vladimir

    2016-06-01

    From the stripping points, the high intensity proton beam of a compact cyclotron travels through the fringe field area of the machine to the combination magnet. Starting from there the beams with various energy is transferred to the switching magnet for distribution to the beam line targets. In the design of the extraction and transport system for the compact proton cyclotron facilities, such as the 70 MeV in France and the 100 MeV in China, the space charge effect as the beam crosses the fringe field has not been previously considered; neither has the impact on transverse beam envelope coupled from the longitudinal direction. Those have been concerned much more with the higher beam-power because of the beam loss problem. In this paper, based on the mapping data of 70 MeV cyclotron including the fringe field by BEST Cyclotron Inc (BEST) and combination magnet field by China Institute of Atomic Energy (CIAE), the beam extraction and transport are investigated for the 70 MeV cyclotron used on the SPES project at Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Legnaro (INFN-LNL). The study includes the space charge effect and longitudinal and transverse coupling mentioned above, as well as the matching of beam optics using the beam line for medical isotope production as an example. In addition, the designs of the ±45° switching magnets and the 60° bending magnet for the extracted beam with the energy from 35 MeV to 70 MeV have been made. Parts of the construction and field measurements of those magnets have been done as well. The current result shows that, the design considers the complexity of the compact cyclotron extraction area and fits the requirements of the extraction and transport for high intensity proton beam, especially at mA intensity levels.

  8. Transport mechanism for L-lactic acid in human myocytes using human prototypic embryonal rhabdomyosarcoma cell line (RD cells).

    PubMed

    Kobayashi, Masaki; Fujita, Itaru; Itagaki, Shirou; Hirano, Takeshi; Iseki, Ken

    2005-07-01

    Monocarboxylate transporter (MCT), which cotransport L-lactic acid and protons across cell membranes, are important for regulation of muscle pH. However, it has not been demonstrated in detail whether MCT isoform contribute to the transport of L-lactic acid in skeletal muscle. The aim of this study was to characterize L-lactic acid transport using an human rhabdomyosarcoma (RD) cell line as a model of human skeletal muscle. mRNAs of MCT 1, 2 and 4 were found to be expressed in RD cells. The [14C] L-lactic acid uptake was concentration-dependent with a Km of 1.19 mM. This Km value was comparable to its Km values for MCT1 or MCT2. MCT1 mRNA was found to be present markedly greater than that MCT2. Therefore, MCT1 most probably acts on L-lactic acid uptake at RD cells. [14C] L-Lactic acid efflux in RD cells was inhibited by alpha-cyano-4-hydroxycinnamate (CHC) but not by butyric acid, a substrate of MCT1. Accordingly, MCT2 or MCT4 is responsible for L-lactic acid efflux by RD cells. MCT4 mRNA was found to be present significantly greater than that MCT2. We conclude that MCT1 is responsible for L-lactic acid uptake and L-lactic acid efflux is mediated by MCT4 in RD cells.

  9. Extending Observational Volume and Heat Transport Records of the Indonesian Throughflow Using Repeat Expendable Bathythermograph (XBT) Lines

    NASA Astrophysics Data System (ADS)

    Vranes, K.; Gordon, A.; Susanto, D.

    2004-12-01

    The Indonesian Throughflow (ITF) is the only tropical link between ocean basins on the planet, carrying roughly 10\\times 106 m3/s (10 Sv) of thermocline water from the Pacific Ocean to the Indian Ocean. The ITF varies on interannual and decadal time scales, forced by ENSO, the Asian monsoons and interannual climate variability in the Indian Ocean basin. To date, direct current measurements of the ITF have been limited to two years duration, which is not enough to fully describe this Pacific-to-Indian connection on long-period scales. Recent measurements taken from December 1996 to July 1998 in the Makassar Strait of the Indonesian seas provide a detailed vertical and temporal picture of the ITF through its main channel, but only provide 1.7 years of record. Temperature data from a repeat expendable bathythermograph (XBT) program have been collected between Shark Bay, Australia and Sunda Strait between Sumatra and Java, Indonesia since 1982. This repeat line is perpendicular to the path of ITF outflow into the Indian Ocean South Equatorial Current at 12ºS, allowing for geostrophic calculations of ITF volume transport into the Indian Ocean. A geostrophic transport time series is constructed from the Australia-Indonesia repeat XBT line and compared to the Makassar time series, finding excellent correlations for the 1.7-year duration of the Makassar series. It is inferred that the repeat XBT line may serve as an appropriate proxy record for interior ITF flow, extending the observational record of the ITF for at least two decades. The twenty-year record of ITF flow is most strongly influenced by ENSO, but is significantly influenced by other climatic process.

  10. Filament wound metal lined propellant tanks for future Earth-to-orbit transports

    NASA Technical Reports Server (NTRS)

    Macconochie, Ian O.; Davis, Robert B.; Freeman, William T., Jr.

    1988-01-01

    For future Earth-to-orbit transport vehicles, reusability and lighter weights are sought for the main propellant tanks. To achieve this, a filament wound tank with a metal liner and an intermediate layer of foam-filled honeycomb is proposed. A hydrogen tank is used as an example. To accommodate mismatches in the expansion of liner and overwrap a design is proposed wherin the liner is configured so that the extension of the liner under pressure matches the expected contraction of the same liner due to the presence of a cryogen. In operation, the liner is pressurized at a rate such that the pressure strain matches the contraction due to decrease in temperature. As an alternate approach, compressive pre-stress is placed in the liner such that it will not separate from the overwrap. A finite element program is used to show stresses in the liner and overwrap for various tank pressures for the pre-stressed liner concept. A fracture mechanics analysis is made of the liners to determine tank life. The tank concept shown has a similar weight to the Shuttle external hydrogen tank, but the filament wound tank is expected to be reusable. Integration of the propellant tanks into a future transport vehicle is discussed.

  11. Anomalous, quasilinear, and percolative regimes for magnetic-field-line transport in axially symmetric turbulence

    PubMed

    Zimbardo; Veltri; Pommois

    2000-02-01

    We studied a magnetic turbulence axisymmetric around the unperturbed magnetic field for cases having different ratios l( ||)/l( perpendicular). We find, in addition to the fact that a higher fluctuation level deltaB/B(0) makes the system more stochastic, that by increasing the ratio l( ||)/l( perpendicular) at fixed deltaB/B(0), the stochasticity increases. It appears that the different transport regimes can be organized in terms of the Kubo number R=(deltaB/B(0))(l( ||)/l( perpendicular)). The simulation results are compared with the two analytical limits, that is the percolative limit and the quasilinear limit. When R<1 weak chaos, closed magnetic surfaces, and anomalous transport regimes are found. When R approximately 1 the diffusion regime is Gaussian, and the quasilinear scaling of the diffusion coefficient D( perpendicular) approximately (deltaB/B(0))(2) is recovered. Finally, for R>1 the percolation scaling of the diffusion coefficient D( perpendicular) approximately (deltaB/B(0))(0.7) is obtained.

  12. MetAP1 and MetAP2 drive cell selectivity for a potent anti-cancer agent in synergy, by controlling glutathione redox state

    PubMed Central

    Frottin, Frédéric; Bienvenut, Willy V.; Bignon, Jérôme; Jacquet, Eric; Jacome, Alvaro Sebastian Vaca; Van Dorsselaer, Alain; Cianferani, Sarah; Carapito, Christine; Meinnel, Thierry; Giglione, Carmela

    2016-01-01

    Fumagillin and its derivatives are therapeutically useful because they can decrease cancer progression. The specific molecular target of fumagillin is methionine aminopeptidase 2 (MetAP2), one of the two MetAPs present in the cytosol. MetAPs catalyze N-terminal methionine excision (NME), an essential pathway of cotranslational protein maturation. To date, it remains unclear the respective contribution of MetAP1 and MetAP2 to the NME process in vivo and why MetAP2 inhibition causes cell cycle arrest only in a subset of cells. Here, we performed a global characterization of the N-terminal methionine excision pathway and the inhibition of MetAP2 by fumagillin in a number of lines, including cancer cell lines. Large-scale N-terminus profiling in cells responsive and unresponsive to fumagillin treatment revealed that both MetAPs were required in vivo for M[VT]X-targets and, possibly, for lower-level M[G]X-targets. Interestingly, we found that the responsiveness of the cell lines to fumagillin was correlated with the ability of the cells to modulate their glutathione homeostasis. Indeed, alterations to glutathione status were observed in fumagillin-sensitive cells but not in cells unresponsive to this agent. Proteo-transcriptomic analyses revealed that both MetAP1 and MetAP2 accumulated in a cell-specific manner and that cell sensitivity to fumagillin was related to the levels of these MetAPs, particularly MetAP1. We suggest that MetAP1 levels could be routinely checked in several types of tumor and used as a prognostic marker for predicting the response to treatments inhibiting MetAP2. PMID:27542228

  13. Ion transport and barrier function in a telomerase-immortalized human nondysplastic, Barrett's cell line (BAR-T).

    PubMed

    Jovov, Biljana; Orlando, Geraldine S; Tobey, Nelia A; Brown, Karen L; Djukic, Zorka; Carson, John L; Brighton, Louisa E; Orlando, Roy C

    2009-01-01

    Barrett's specialized columnar epithelium (SCE) replaces reflux-damaged squamous epithelium. The benefits of SCE lie in its superior protection of the esophagus against further reflux damage. It was shown that this protection is dependent on ion transport and barrier function of SCE. The risks of SCE lie in its higher predisposition to malignant transformation. An understanding of underlying mechanisms of both processes would benefit considerably from greater knowledge of the structure and function of native SCE - the latter recently advanced by the availability of a telomerase-immortalized, nonneoplastic, human Barrett's cell line (BAR-T). Some of BAR-T characteristics for growth and differentiation have been described recently, but not its capacity to serve as a model for ion transport and barrier function of SCE. To determine the latter, BAR-T cells were grown in enriched media, seeded on permeable supports, and subjected to electrical, biochemical, and morphologic study. HET-1A (esophageal epithelial cell line), a nonneoplastic, human esophageal squamous cell line, was also studied for comparison. BAR-T, but not HET-1A cells in HEPES Ringer solution behaved as polarized monolayers with the capacity for ion transport and barrier function. This was evident electrically with a volt-ohm meter (EVOM),which recorded in BAR-T a resting potential difference of 2.0 +/- 0.2 mV, Isc of 17.4 +/- 3.3 microAmps/cm2 and resistance of 103 +/- 12 ohms x cm2. Further, Isc in BAR-T was inhibitable by exposure to Na-free solution, serosal ouabain, and luminal 4-acetamido4'-isothiocyano-2,2'-stilbenedisulfonic acid. Expression of tight junction genes were determined in BAR-T and HET-1A cells using quantitative reverse transcriptase-polymerase chain reaction, with expression of zonula occludens-1 (ZO-1) set at 1 as reference. Claudins 1, 4, and 12 were prominently expressed in BAR-T (0.2-0.6 of ZO-1), while claudins 1, 11, and 12 were prominently expressed in HET-1A(0.1-0.8 of ZO-1

  14. Final report for tank 241-AP-101, grab samples 1AP-95-1, 1AP-95-2, 1AP-95-3, 1AP-95-4, 1AP-95-5, and 1AP-95-6

    SciTech Connect

    Esch, R.A.

    1996-03-04

    Six supernate grab samples (1AP-95-1 through 6) and one field blank (1AP-95-7) were taken from tank 241-AP-101, on Nov. 10 and 13, 1995. Analyses were performed in support of the Safety Screening and the Waste Compatibility Safety programs. All analytical results were within the action limits stated in the TSAP.

  15. The GEANT4 toolkit capability in the hadron therapy field: simulation of a transport beam line

    NASA Astrophysics Data System (ADS)

    Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Raffaele, L.; Russo, G.; Guatelli, S.; Pia, M. G.

    2006-01-01

    At Laboratori Nazionali del Sud of the Instituto Nazionale di Fisica Nucleare of Catania (Sicily, Italy), the first Italian hadron therapy facility named CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) has been realized. Inside CATANA 62 MeV proton beams, accelerated by a superconducting cyclotron, are used for the radiotherapeutic treatments of some types of ocular tumours. Therapy with hadron beams still represents a pioneer technique, and only a few centers worldwide can provide this advanced specialized cancer treatment. On the basis of the experience so far gained, and considering the future hadron-therapy facilities to be developed (Rinecker, Munich Germany, Heidelberg/GSI, Darmstadt, Germany, PSI Villigen, Switzerland, CNAO, Pavia, Italy, Centro di Adroterapia, Catania, Italy) we decided to develop a Monte Carlo application based on the GEANT4 toolkit, for the design, the realization and the optimization of a proton-therapy beam line. Another feature of our project is to provide a general tool able to study the interactions of hadrons with the human tissue and to test the analytical-based treatment planning systems actually used in the routine practice. All the typical elements of a hadron-therapy line, such as diffusers, range shifters, collimators and detectors were modelled. In particular, we simulated the Markus type ionization chamber and a Gaf Chromic film as dosimeters to reconstruct the depth (Bragg peak and Spread Out Bragg Peak) and lateral dose distributions, respectively. We validated our simulated detectors comparing the results with the experimental data available in our facility.

  16. The AP-1 transcription factor homolog Pf-AP-1 activates transcription of multiple biomineral proteins and potentially participates in Pinctada fucata biomineralization.

    PubMed

    Zheng, Xiangnan; Cheng, Minzhang; Xiang, Liang; Liang, Jian; Xie, Liping; Zhang, Rongqing

    2015-09-25

    Activator protein-1 (AP-1) is an important bZIP transcription factor that regulates a series of physiological processes by specifically activating transcription of several genes, and one of its well-chartered functions in mammals is participating in bone mineralization. We isolated and cloned the complete cDNA of a Jun/AP-1 homolog from Pinctada fucata and called it Pf-AP-1. Pf-AP-1 had a highly conserved bZIP region and phosphorylation sites compared with those from mammals. A tissue distribution analysis showed that Pf-AP-1 was ubiquitously expressed in P. fucata and the mRNA level of Pf-AP-1 is extremely high in mantle. Pf-AP-1 expression was positively associated with multiple biomineral proteins in the mantle. The luciferase reporter assay in a mammalian cell line showed that Pf-AP-1 significantly up-regulates the transcriptional activity of the promoters of KRMP, Pearlin, and Prisilkin39. Inhibiting the activity of Pf-AP-1 depressed the expression of multiple matrix proteins. Pf-AP-1 showed a unique expression pattern during shell regeneration and pearl sac development, which was similar to the pattern observed for biomineral proteins. These results suggest that the Pf-AP-1 AP-1 homolog is an important transcription factor that regulates transcription of several biomineral proteins simultaneously and plays a role in P. fucata biomineralization, particularly during pearl and shell formation.

  17. The West African Squall Line Observed on 23 June 1981 during COPT 81: Mesoscale Structure and Transports.

    NASA Astrophysics Data System (ADS)

    Chalon, J. P.; Jaubert, G.; Lafore, J. P.; Roux, F.

    1988-10-01

    Durirg the night of 23/24 June 1981, new Korhogo, Ivory Coast, a squall line passed over the instrumented area of the COPT 81 experiment. Observations were obtained with a dual-Doppler radar system, a sounding station and 22 automatic meteorological surface stations. Data from these instruments and from satellite pictures were analyzed to depict the kinematic and thermodynamic structure of the squall line. Composite analysis techniques were used to obtain a vertical cross section of the reflectivity structure and of the wind field relative to the line. The redistributions of air, moisture and thermodynamic energy by the convection wet calculated through averaged two-dimensional wind fields from a dual-Doppler radar system. The method also allowed the evaluation of the exchanges that were occurring between the convective and the stratiform regions.This squall line had many similarities with tropical squall lines previously described by others. The leading convective part, composed of intense updrafts and downdrafts, and the trailing part, containing weak mesoscale updraft and downdraft, were separated by a reflectivity trough. A notable feature of this line was the presence of a leading anvil induced by intense easterly environmental winds in the upper troposphere. Observations of the evolution of the system at different scales indicated that the mesoalpha-scale (following the classification of Orlanski) and the mosobeta-scale patterns combined to allow the system to have optimum conditions for maximum strength and a maximum lifetime.A rear-to-front flow was found at midlevels in the stratiform region. The flow sloped downward to the surface and took on the characteristics of a density current in the forward half of the squall lice. Entering the convective region, this flow was supplied with cold air by the convective downdrafts and played an important role in forcing upward the less dense monsoon flow entering at the leading edge.Calculations of mass, moisture and

  18. Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: expansion of the facial and neuroimaging features.

    PubMed

    Tüysüz, Beyhan; Bilguvar, Kaya; Koçer, Naci; Yalçınkaya, Cengiz; Çağlayan, Okay; Gül, Ece; Sahin, Sezgin; Çomu, Sinan; Günel, Murat

    2014-07-01

    Adaptor protein complex-4 (AP4) is a component of intracellular transportation of proteins, which is thought to have a unique role in neurons. Recently, mutations affecting all four subunits of AP4 (AP4M1, AP4E1, AP4S1, and AP4B1) have been found to cause similar autosomal recessive phenotype consisting of tetraplegic cerebral palsy and intellectual disability. The aim of this study was analyzing AP4 genes in three new families with this phenotype, and discussing their clinical findings with an emphasis on neuroimaging and facial features. Using homozygosity mapping followed by whole-exome sequencing, we identified two novel homozygous mutations in AP4M1 and a homozygous deletion in AP4B1 in three pairs of siblings. Spastic tetraplegia, microcephaly, severe intellectual disability, limited speech, and stereotypic laughter were common findings in our patients. All patients also had similar facial features consisting of coarse and hypotonic face, bitemporal narrowing, bulbous nose with broad nasal ridge, and short philtrum which were not described in patients with AP4M1 and AP4B1 mutations previously. The patients presented here and previously with AP4M1, AP4B1, and AP4E1 mutations shared brain abnormalities including asymmetrical ventriculomegaly, thin splenium of the corpus callosum, and reduced white matter volume. The patients also had hippocampal globoid formation and thin hippocampus. In conclusion, disorders due to mutations in AP4 complex have similar neurological, facial, and cranial imaging findings. Thus, these four genes encoding AP4 subunits should be screened in patients with autosomal recessive spastic tetraplegic cerebral palsy, severe intellectual disability, and stereotypic laughter, especially with the described facial and cranial MRI features.

  19. Poloxamines display a multiple inhibitory activity of ATP-binding cassette (ABC) transporters in cancer cell lines.

    PubMed

    Cuestas, María L; Sosnik, Alejandro; Mathet, Verónica L

    2011-08-01

    Primary hepatocellular carcinoma is the third most common fatal cancer worldwide with more than 500,000 annual deaths. Approximately 40% of the patients with HCC showed tumoral overexpression of transmembrane proteins belonging to the ATP-binding cassette protein superfamily (ABC) which pump drugs out of cells. The overexpression of these efflux transporters confers on the cells a multiple drug resistance phenotype, which is considered a crucial cause of treatment refractoriness in patients with cancer. The aim of this study was to investigate the inhibitory effect of different concentrations of pH- and temperature-responsive X-shaped poly(ethylene oxide)-poly(propylene oxide) block copolymers (poloxamines, Tetronic, PEO-PPO) showing a wide range of molecular weights and EO/PO ratios on the functional activity of three different ABC proteins, namely P-glycoprotein (P-gp or MDR1), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein MRP1, in two human hepatocarcinoma cell lines, HepG2 and Huh7. First, the cytotoxicity of the different copolymers (at different concentrations) on both liver carcinoma cell lines was thoroughly evaluated by means of apoptosis analysis using annexin V and propidium iodide (PI). Thus, viable cells (AV-/PI-), early apoptotic cells (AV+/PI-) and late apoptotic cells (V-FITC+/PI+) were identified. Results pointed out copolymers of intermediate to high hydrophobicity and intermediate molecular weight (e.g., T904) as the most cytotoxic. Then, DiOC2, rhodamine 123 and vinblastine were used as differential substrates of these pumps. HeLa, an epithelial cell line of human cervical cancer that does not express P-gp, was used exclusively as a control and enabled the discerning between P-gp and MRP1 inhibition. Moderate to highly hydrophobic poloxamines T304, T904 and T1301 showed inhibitory activity against P-gp and BCRP but not against MRP1 in both hepatic cell lines. A remarkable dependence of this effect on the

  20. Gas Transport and Density Control in the HYLIFE Heavy-Ion Beam Lines

    SciTech Connect

    Debonnel, Christophe S.; Welch, Dale R.; Rose, David V.; Lawrence, Simon S.Yu; Peterson, Per F

    2003-05-15

    The effective propagation and focusing of heavy-ion beams in the final-focus magnet region of inertial fusion target chambers require controlling the background gas density and pressure in the beam tubes. Liquid vortexes will coat the inside of the tubes next to the beam ports and will help eliminate the need for mechanical shutters to mitigate the venting of target chamber background gas into the final-focus magnet region. Before the neutralizing region, the beam space charge is high, and ablation and target debris deposition in the final-focus magnet region may cause voltage breakdown. Previous studies focused on evaluating the amount of target chamber debris reaching the entrance of the beam ports. The TSUNAMI code has now been used to assess the density, temperature, and velocity of the vortex debris transported {approx}3 m up the beam tubes and reaching the final-focus magnet region, assuming that the liquid vortexes are perfectly absorbing surfaces. To further mitigate debris deposition in the final-focus magnet region, and prevent voltage breakdown, a 'magnetic shutter' has been envisaged to divert the debris out of the final-focus region. This shutter will prevent the hot ablation debris from reaching the magnet region and, coupled to some ionizing scheme, will conveniently suppress early ingression of debris into the final-focus magnet region.

  1. A transverse emittance and acceptance measurement system in a low-energy beam transport line

    SciTech Connect

    Kashiwagi, H. Miyawaki, N.; Kurashima, S.; Okumura, S.

    2014-02-15

    A transverse beam emittance and acceptance measurement system has been developed to visualize the relationship between the injected beam emittance and the acceptance of a cyclotron. The system is composed of a steering magnet, two pairs of slits to limit the horizontal and vertical phase-space, a beam intensity detector just behind the slits for the emittance measurement, and a beam intensity detector in the cyclotron for the acceptance measurement. The emittance is obtained by scanning the slits and measuring the beam intensity distribution. The acceptance is obtained by measuring the distribution of relative beam transmission by injecting small emittance beams at various positions in a transverse phase-space using the slits. In the acceptance measurement, the beam from an ion source is deflected to the defined region by the slits using the steering magnet so that measurable acceptance area covers a region outside the injection beam emittance. Measurement tests were carried out under the condition of accelerating a beam of {sup 16}O{sup 6+} from 50.2 keV to 160 MeV. The emittance of the injected beam and the acceptance for accelerating and transporting the beam to the entrance of the extraction deflector were successfully measured. The relationship between the emittance and acceptance is visualized by displaying the results in the same phase-plane.

  2. APS Editorial Q&A: APS and Open Access

    NASA Astrophysics Data System (ADS)

    2011-04-01

    The movement toward Open Access continues to gain momentum. A brief review of APS efforts in this area will be presented by APS Editor in Chief, Gene Sprouse. Editors from Physical Review C, D, Letters, and X, Physical Review Special Topics - Accelerators and Beams, Physical Review Special Topics - Physics Education Research, and Reviews of Modern Physics will address your questions about publishing in this evolving environment.

  3. Calcyon, a mammalian specific NEEP21 family member, interacts with adaptor protein complex 3 (AP-3) and regulates targeting of AP-3 cargoes.

    PubMed

    Muthusamy, Nagendran; Faundez, Victor; Bergson, Clare

    2012-10-01

    Calcyon is a neural enriched, single transmembrane protein that interacts with clathrin light chain and stimulates clathrin assembly and clathrin-mediated endocytosis. A similar property is shared by the heterotetrameric adaptor protein (AP) complexes AP-1, AP-2, and AP-3 which recruit cargoes for insertion into clathrin coated transport vesicles. Here we report that AP medium (μ) subunits interact with a YXXØ-type tyrosine motif located at residues 133-136 in the cytoplasmic domain of calcyon. Site specific mutagenesis of the critical tyrosine and bulky hydrophobic residues tyrosine 133 and methionine 136 preferentially abrogated binding of the ubiquitous and neuronal isoforms of μ3, and also impacted μ1 and μ2 binding to a lesser degree. The relevance of these interactions was explored in vivo using mice harboring null alleles of calcyon. As seen in the mutagenesis studies, calcyon deletion in mice preferentially altered the subcellular distribution of AP-3 suggesting that calcyon could regulate membrane-bound pools of AP-3 and AP-3 function. To test this hypothesis, we focused on the hilar region of hippocampus, where levels of calcyon, AP-3, and AP-3 cargoes are abundant. We analyzed brain cryosections from control and calcyon null mice for zinc transporter 3 (ZnT3), and phosphatidylinositol-4-kinase type II alpha (PI4KIIα), two well-defined AP-3 cargoes. Confocal microscopy indicated that ZnT3 and PI4KIIα are significantly reduced in the hippocampal mossy fibers of calcyon knock-out brain, a phenotype previously described in AP-3 deficiencies. Altogether, our data suggest that calcyon directly interacts with μ3A and μ3B, and regulates the subcellular distribution of AP-3 and the targeting of AP-3 cargoes.

  4. CALCYON, A MAMMALIAN SPECIFIC NEEP21 FAMILY MEMBER, INTERACTS WITH ADAPTOR PROTEIN COMPLEX 3 (AP-3) AND REGULATES TARGETING OF AP-3 CARGOES

    PubMed Central

    Muthusamy, Nagendran; Faundez, Victor; Bergson, Clare

    2013-01-01

    Calcyon is a neural enriched, single transmembrane protein that interacts with clathrin light chain (CLC) and stimulates clathrin assembly and clathrin mediated endocytosis (CME). A similar property is shared by the heterotetrameric adaptor protein (AP) complexes AP-1, AP-2, and AP-3 which recruit cargoes for insertion into clathrin coated transport vesicles. Here we report that AP medium (µ) subunits interact with a YXXØ-type tyrosine motif located at residues 133–136 in the cytoplasmic domain of calcyon. Site specific mutagenesis of the critical tyrosine and bulky hydrophobic residues tyrosine 133 and methionine 136 preferentially abrogated binding of the ubiquitous and neuronal isoforms of µ3, and also impacted µ1 and µ2 binding but to a lesser degree. The relevance of these interactions was explored in vivo using mice harboring null-alleles of calcyon. As seen in the mutagenesis studies, calcyon deletion in mice preferentially altered the subcellular distribution of AP-3 suggesting that calcyon could regulate membrane-bound pools of AP-3 and AP-3 function. To test this hypothesis, we focused on the hilar region of hippocampus, where levels of calcyon, AP-3, and AP-3 cargoes are abundant. We analyzed brain cryosections from control and calcyon null mice for zinc transporter 3 (ZnT3), and phosphatidylinositol-4-kinase type II alpha (PI4KIIα), two well-defined AP-3 cargoes. Confocal microscopy indicated that ZnT3 and PI4KIIα are significantly reduced in the hippocampal mossy fibers of calcyon knock-out brain, a phenotype previously described in AP-3 deficiencies. Altogether, our data suggest that calcyon directly interacts with µ3A and µ3B, and regulates the subcellular distribution of AP-3 and the targeting of AP-3 cargoes. PMID:22650988

  5. Characterization of vectorial chloride transport pathways in the human pancreatic duct adenocarcinoma cell line HPAF.

    PubMed

    Fong, Peying; Argent, Barry E; Guggino, William B; Gray, Michael A

    2003-08-01

    Pancreatic duct cells express a Ca2+-activated Cl- conductance (CaCC), upregulation of which may be beneficial to patients with cystic fibrosis. Here, we report that HPAF, a human pancreatic ductal adenocarcinoma cell line that expresses CaCC, develops into a high-resistance, anion-secreting epithelium. Mucosal ATP (50 microM) caused a fourfold increase in short-circuit current (Isc), a hyperpolarization of transepithelial potential difference (from -4.9 +/- 0.73 to -8.5 +/- 0.84 mV), and a fall in resistance to less than one-half of resting values. The effects of ATP were inhibited by mucosal niflumic acid (100 microM), implicating an apical CaCC in the response. RT-PCR indicated expression of hClC-2, hClC-3, and hClC-5, but surprisingly not hCLCA-1 or hCLCA-2. K+ channel activity was necessary to maintain the ATP-stimulated Isc. Using a pharmacological approach, we found evidence for two types of K+ channels in the mucosal and serosal membranes of HPAF cells, one activated by chlorzoxazone (500 microM) and sensitive to clotrimazole (30 microM), as well as one blocked by clofilium (100 microM) but not chromanol 293B (5 microM). RT-PCR indicated expression of the Ca2+-activated K+ channel KCNN4, as well as the acid-sensitive, four transmembrane domain, two pore K+ channel, KCNK5 (hTASK-2). Western blot analysis verified the expression of CLC channels, as well as KCNK5. We conclude that HPAF will be a useful model system for studying channels pertinent to anion secretion in human pancreatic duct cells.

  6. Beam dynamics and error study of the medium energy beam transport line in the Korea Heavy-Ion Medical Accelerator

    NASA Astrophysics Data System (ADS)

    Kim, Chanmi; Kim, Eun-San; Hahn, Garam

    2016-11-01

    The Korea Heavy Ion Medical Accelerator consists of an injector and a synchrotron for an ion medical accelerator that is the first carbon-ion therapy system in Korea. The medium energy beam transport(MEBT) line connects the interdigital H-mode drift tube linac and the synchrotron. We investigated the beam conditions after the charge stripper by using the LISE++ and the SRIM codes. The beam was stripped from C4+ into C6+ by using the charge stripper. We investigated the performance of a de-buncher in optimizing the energy spread and the beam distribution in z-dW/W (direction of beam progress-beam and energy) phase. We obtained the results of the tracking simulation and the error analysis by using the TRACK code. Possible misalignments and rotations of the magnets were considered in the simulations. States of the beam were examined when errors occurred in the magnets by the applying analytic fringe field model in TRACK code. The condition for the beam orbit was optimized by using correctors and profile monitors to correct the orbit. In this paper, we focus on the beam dynamics and the error studies dedicated to the MEBT beam line and show the optimized beam parameters for the MEBT.

  7. Design of the prototype of a beam transport line for handling and selection of low energy laser-driven beams

    NASA Astrophysics Data System (ADS)

    Schillaci, F.; Maggiore, M.; Cirrone, G. A. P.; Cuttone, G.; Pisciotta, P.; Costa, M.; Rifuggiato, D.; Romano, F.; Scuderi, V.

    2016-11-01

    A first prototype of transport beam-line for laser-driven ion beams to be used for the handling of particles accelerated by high-power laser interacting with solid targets has been realized at INFN. The goal is the production of a controlled and stable beam in terms of energy and angular spread. The beam-line consists of two elements: an Energy Selection System (ESS), already realized and characterized with both conventional and laser-accelerated beams, and a Permanent Magnet Quadrupole system (PMQ) designed, in collaboration with SIGMAPHI (Fr), to improve the ESS performances. In this work a description of the ESS system and some results of its characterization with conventional beams are reported, in order to provide a complete explanation of the acceptance calculation. Then, the matching with the PMQ system is presented and, finally, the results of preliminary simulations with a realistic laser-driven energy spectrum are discussed demonstrating the possibility to provide a good quality beam downstream the systems.

  8. The APS machine protection system (MPS)

    SciTech Connect

    Fuja, R.; Berg, B.; Arnold, N.

    1996-08-01

    The machine protection system (MPS) that protects the APS storage ring vacuum chamber from x-ray beams, is active. There are over 650 sensors monitored and networked through the MPS system. About the same number of other process variables are monitored by the much slower EPICS control system, which also has an input to the rf abort chain. The MPS network is still growing with the beam position limits detection system coming on-line. The network configuration, along with a limited description of individual subsystems, is presented.

  9. Long-term mean and seasonal variation of altimetry-derived Oyashio transport across the A-line off the southeastern coast of Hokkaido, Japan

    NASA Astrophysics Data System (ADS)

    Kuroda, Hiroshi; Wagawa, Taku; Kakehi, Shigeho; Shimizu, Yugo; Kusaka, Akira; Okunishi, Takeshi; Hasegawa, Daisuke; Ito, Shin-ichi

    2017-03-01

    To understand long-term mean and seasonal variations of the Oyashio transport off the southeastern coast of Hokkaido, time series of estimated transports were generated by combining satellite altimetry and CTD data from the period 1993-2014 along a monitoring transect referred to as the ;A-line;. Linear regressions between CTD-derived geostrophic transport and altimetry-derived sea level anomaly differences were calculated by minimizing a cost function newly proposed in this study. The horizontal structure of 21-year mean transport was characterized by a southwestward flow on the continental slope (SW-1) associated with the First Oyashio Intrusion, a northeastward flow (NE-2) likely trapped against the Kuril-Kamchatka trench, a southwestward flow (SW-3) related to the Second Oyashio Intrusion, and a very stable northeastward flow (NE-4) corresponding to a combination of the Oyashio Return Flow and quasi-stationary Jet. Analysis of long-term mean monthly transports revealed four alternating flows that were present throughout all seasons of the year. The boundaries between adjacent pairs of the four flows on the A-line did not change on a seasonal timescale as much as the southernmost latitude of the First Oyashio Intrusion. At a 0-month (1-month) time lag, the sum of the SW-1, NE-2, and SW-3 (SW-1 and NE-2) transports, which corresponds to net Oyashio transport (partial net Oyashio transport related to the southernmost latitude of the First Oyashio Intrusion), was correlated with Sverdrup transport more robustly than was each of the four alternating flows. This result suggests that as the Oyashio crossed the A-line, it responded barotropically to basin-scale wind stress by adjusting transports composed of both southwestward and northeastward flows.

  10. Influence of overexpression of efflux proteins on the function and gene expression of endogenous peptide transporters in MDR-transfected MDCKII cell lines

    PubMed Central

    Wang, Zhiying; Pal, Dhananjay; Patel, Ashaben; Kwatra, Deep; Mitra, Ashim K.

    2013-01-01

    The objective of this study is to delineate whether overexpression of human efflux transporters (P-gp, MRP2, and BCRP) in transfected MDCK cells affect the functional activities, and gene and protein expression of endogenous influx peptide transporter system (PepT). Real-time PCR, immunoblotting, uptake and permeability studies of [3H]Gly-Sar were conducted on transfected MDCKII and wild-type cells to investigate functional differences. Cellular [3H]Gly-Sar accumulation was significantly lower in transfected MDCKII cell lines compared to wild-type cells. Transport efficiency of apical peptide transporters was markedly reduced to around 25%, 30%, and 40% in P-gp-, MRP2-, and BCRP-overexpressed MDCK cell lines, respectively. With ascending cell-passage, transport efficiency was enhanced. A significantly higher Gly-Sar permeability was observed across parental cell-monolayers over transfected cells at all pHs. Levels of mRNA for both canine PepT1 and PepT2 were substantially reduced when efflux transporters overexpressed but enhanced when mRNA-levels of efflux genes diminished with ascending cell-passage of transfected cells. An inverse correlation was evident between endogenous PepT and exogenous efflux transporters in transfected MDCKII cells. Results of protein expression also supported these findings. Overexpression of MDR genes can affect endogenous PepT function which might be due to the phenomenon of transporter-compensation resulting in down-regulation of endogenous genes. PMID:23262422

  11. Identification of Cargo for Adaptor Protein (AP) Complexes 3 and 4 by Sucrose Gradient Profiling.

    PubMed

    Pertl-Obermeyer, Heidi; Wu, Xu Na; Schrodt, Jens; Müdsam, Christina; Obermeyer, Gerhard; Schulze, Waltraud X

    2016-09-01

    Intracellular vesicle trafficking is a fundamental process in eukaryotic cells. It enables cellular polarity and exchange of proteins between subcellular compartments such as the plasma membrane or the vacuole. Adaptor protein complexes participate in the vesicle formation by specific selection of the transported cargo. We investigated the role of the adaptor protein complex 3 (AP-3) and adaptor protein complex 4 (AP-4) in this selection process by screening for AP-3 and AP-4 dependent cargo proteins. Specific cargo proteins are expected to be mis-targeted in knock-out mutants of adaptor protein complex components. Thus, we screened for altered distribution profiles across a density gradient of membrane proteins in wild type versus ap-3β and ap-4β knock-out mutants. In ap-3β mutants, especially proteins with transport functions, such as aquaporins and plasma membrane ATPase, as well as vesicle trafficking proteins showed differential protein distribution profiles across the density gradient. In the ap-4β mutant aquaporins but also proteins from lipid metabolism were differentially distributed. These proteins also showed differential phosphorylation patterns in ap-3β and ap-4β compared with wild type. Other proteins, such as receptor kinases were depleted from the AP-3 mutant membrane system, possibly because of degradation after mis-targeting. In AP-4 mutants, membrane fractions were depleted for cytochrome P450 proteins, cell wall proteins and receptor kinases. Analysis of water transport capacity in wild type and mutant mesophyll cells confirmed aquaporins as cargo proteins of AP-3 and AP-4. The combination of organelle density gradients with proteome analysis turned out as a suitable experimental strategy for large-scale analyses of protein trafficking.

  12. R_transport_matrices of the Fast Extraction Beam (FEB) of the AGS, and Beam Parameters at the Starting point of the AtR Line

    SciTech Connect

    Tsoupas,N.; MacKay, W.W.; Satogata, T.; Glenn, W.; Ahrens, L.; Brown, K.; Gardner, C.; Tanaka, S.

    2008-01-01

    As part of the task to improve and further automate the 'AtR BPM Application' we provide the theoretically calculated R-transport-matrices for the following beam line sections, which are shown schematically in Figure 1: (a) the Fast Extraction Beam section (FEB) of the AGS synchrotron. The FEB section starts at the middle of the GlO-kicker and ends at the middle of the H1 0{_}septum. (b) the Drift Extraction Channel (DEC) section of the AGS synchrotron. The DEC section starts at the middle of the H10{_}septum, continues along the fringe field region of the H11,H12, and H13 AGS main magnets, and ends at the starting point of the AtR line. The knowledge of these R-transport-matrices are needed in order to calculate the beam parameters at the beginning of the AtR line, which in turn, are required to calculate the magnet settings of the U{_}line, that match the U{_}line into the W{_}line. Also by incorporating these R{_}matrices into the model of the AtR line, the G10 kicker and the H10 septum are included in the AtR model therefore one can investigate any 'jitter' of either the GlO{_}kicker or HlO{_}septum by looking at the trajectory of the beam in the AtR line.

  13. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (I): catastrophic APS, APS nephropathy and heart valve lesions.

    PubMed

    Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

    2011-02-01

    The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyse the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analysed on the catastrophic APS, APS nephropathy and heart valve lesions, and presents the recommendations elaborated by the Task Force after this analysis.

  14. Stratification in Ap star atmospheres: Simulations

    NASA Astrophysics Data System (ADS)

    Cowley, Charles R.; Castelli, Fiorella

    2017-01-01

    It is now well established that the atmospheres of Ap stars can be chemically stratified (cf. Babel, A\\&A 258, 645, 1992; Ryabchikova et al. A\\&A 384, 545, 2002). The most convincing cases have been made with the profiles of very strong lines, such as Ca II K. Weaker line profiles are less obvious indicators. The collective behavior of sets or groups of lines have also been used. For example, if higher abundances are derived for strong lines in an atmosphere with zero microturbulence, one may assume that the absorbing species has been pushed into the higher photospheres. An example are the medium-strong Mn II lines in HgMn stars. In this paper, we probe this assumption by calculating line strengths with various assumed stratification models, and then determining abundances from those lines using an {\\bf unstratified} model with the same Teff and log(g). We use the model from Castelli, Kurucz \\& and Hubrig (A\\&A, 508, 401, 2009) for HR 6000, whose spectrum shows numerous indications of stratification. A variety of stratification models are considered, for example, ones where the majority of an absorbing species is concentrated above (or below) $log(\\tau_{5000}$ = -2.0. Cloud models are also investigated, where a species is concentrated within a range of photospheric depths. Curves of growth are generated in unstratified atmospheres for lines by holding the abundance fixed, and increasing log(gf). Similar curves are made in stratified models, and the ratios of strong to weak linesare compared with and without stratification. The effects of stratification on ionization are also investigated, as well as on the profiles of strong lines. We find, in agreement with previous work, that severe abundance jumps are sometimes required to account for some of the observed peculiarities.

  15. Transcription factor AP-2α regulates acute myeloid leukemia cell proliferation by influencing Hoxa gene expression.

    PubMed

    Ding, Xiaofeng; Yang, Zijian; Zhou, Fangliang; Wang, Fangmei; Li, Xinxin; Chen, Cheng; Li, Xiaofeng; Hu, Xiang; Xiang, Shuanglin; Zhang, Jian

    2013-08-01

    Transcription factor AP-2α mediates transcription of a number of genes implicated in mammalian development, cell proliferation and carcinogenesis. In the current study, we identified Hoxa7, Hoxa9 and Hox cofactor Meis1 as AP-2α target genes, which are involved in myeloid leukemogenesis. Luciferase reporter assays revealed that overexpression of AP-2α activated transcription activities of Hoxa7, Hoxa9 and Meis1, whereas siRNA of AP-2α inhibited their transcription activities. We found that AP-2 binding sites in regulatory regions of three genes activated their transcription by mutant analysis and AP-2α could interact with AP-2 binding sites in vivo by chromatin immunoprecipitation (ChIP). Further results showed that the AP-2α shRNA efficiently inhibited mRNA and protein levels of Hoxa7, Hoxa9 and Meis1 in AML cell lines U937 and HL60. Moreover, decreased expression of AP-2α resulted in a significant reduction in the growth and proliferation of AML cells in vitro. Remarkably, AP-2α knockdown leukemia cells exhibit decreased tumorigenicity in vivo compared with controls. Finally, AP-2α and target genes in clinical acute myeloid leukemia samples of M5b subtype revealed variable expression levels and broadly paralleled expression. These data support a role of AP-2α in mediating the expression of Hoxa genes in acute myeloid leukemia to influence the proliferation and cell survival.

  16. APS Education and Diversity Efforts

    NASA Astrophysics Data System (ADS)

    Prestridge, Katherine; Hodapp, Theodore

    2015-11-01

    American Physical Society (APS) has a wide range of education and diversity programs and activities, including programs that improve physics education, increase diversity, provide outreach to the public, and impact public policy. We present the latest programs spearheaded by the Committee on the Status of Women in Physics (CSWP), with highlights from other diversity and education efforts. The CSWP is working to increase the fraction of women in physics, understand and implement solutions for gender-specific issues, enhance professional development opportunities for women in physics, and remedy issues that impact gender inequality in physics. The Conferences for Undergraduate Women in Physics, Professional Skills Development Workshops, and our new Professional Skills program for students and postdocs are all working towards meeting these goals. The CSWP also has site visit and conversation visit programs, where department chairs request that the APS assess the climate for women in their departments or facilitate climate discussions. APS also has two significant programs to increase participation by underrepresented minorities (URM). The newest program, the APS National Mentoring Community, is working to provide mentoring to URM undergraduates, and the APS Bridge Program is an established effort that is dramatically increasing the number of URM PhDs in physics.

  17. [Apheresis in antiphospholipid syndrome (APS)].

    PubMed

    De Silvestro, Giustina; Tison, Tiziana; Marson, Piero

    2012-01-01

    Antiphospholipid syndrome (APS) is a rare clinical disorder characterized by thromboembolic manifestations and/or obstetric complications. Along with the clinical symptoms and signs, serum antiphospholipid antibodies have to be detected. APS can be primary, i.e., without any concomitant disorders, or secondary to other autoimmune diseases, particularly systemic lupus erythematosus. Criteria for the diagnosis of APS have been clearly established. Hyperacute APS (or catastrophic antiphospholipid syndrome), often with a poor prognosis, must meet four criteria: involvement of three or more organs, rapid evolution of clinical manifestations, microangiopathic occlusion of small blood vessels at biopsy, and presence of antiphospholipid antibodies. The rationale for apheresis treatment is the removal of pathogenetic antibodies involved in the development of tissue damage. Our experience includes 23 patients, in particular 15 women treated for 19 pregnancies. According to the National Guidelines Program, the effectiveness of apheresis in catastrophic syndrome has a level of evidence of V/VI, with a strength of recommendation A; in highrisk pregnancy it has a level of evidence of V with a strength of recommendation B. It will be necessary to better define the prognosis of various categories of pregnant patients with APS, as well as useful laboratory parameters to monitor its clinical course and anticipate any complications of pregnancy.

  18. Differential Mitochondrial Electron Transport through the Cyanide-Sensitive and Cyanide-Insensitive Pathways in Isonuclear Lines of Cytoplasmic Male Sterile, Male Fertile, and Restored Petunia1

    PubMed Central

    Connett, Marie B.; Hanson, Maureen R.

    1990-01-01

    Three pairs of isonuclear lines of cytoplasmic male sterile (CMS) and fertile Petunia cells (Petunia hybrida [Hook] Vilm. and Petunia parodii L.S.M.) grown in suspension culture were examined for sensitivity to inhibitors of respiratory electron transport at time-points after transfer into fresh media. Cells from CMS lines differed from cells of fertile lines in their utilization of the cyanide-insensitive oxidase pathway. Under our culture regime, after approximately 3 days of culture cells from the CMS lines exhibited much lower cyanide-insensitive, salicylhydroxamic acid-sensitive respiration than cells from the fertile lines. This respiratory difference was shown to be specific to the mitochondrial alternative oxidase pathway by using other characteristic inhibitors of mitochondrial electron transport in experiments with isolated mitochondria. Immature anthers from CMS plants also showed lower alternative oxidase activity relative to anthers from male fertile plants, but no such difference was detected in leaf tissue, ovary or perianth tissue, or anthers collected just prior to anthesis. A cell line from a fertile plant carrying a nuclear fertility restorer gene and the CMS cytoplasm exhibited increased activity of the alternative pathway compared with the CMS lines. PMID:16667667

  19. Enhancing recombinant protein production in human cell lines with a constitutive transport element and mRNA export proteins.

    PubMed

    Aihara, Yuki; Fujiwara, Naoko; Yamazaki, Tomohiro; Kambe, Taiho; Nagao, Masaya; Hirose, Yutaka; Masuda, Seiji

    2011-05-20

    Recent research into mRNA maturation processes in the nucleus has identified a number of proteins involved in mRNA transcription, capping, splicing, end processing and export. Among them, the Tap-p15 heterodimer acts as an mRNA export receptor. Tap-p15 is recruited onto fully processed mRNA in the nucleus, which is ready for export to the cytoplasm, through associating with Aly or SR proteins on mRNA, or by directly associating with a constitutive transport element (CTE), an RNA element derived from type D retroviruses. mRNA containing a CTE is exported to the cytoplasm by directly associating with Tap-p15, even in the absence of Tap-recruiting proteins such as Aly or SR proteins on the mRNA. Here, we showed that the use of a CTE enhanced the expression of recombinant protein in human cell lines. The co-expression of reporter proteins and Tap-p15 also enhanced recombinant protein expression. Moreover, the use of a CTE and Tap-p15 synergistically further enhanced the recombinant protein expression. In addition to Tap-p15, several Tap-p15-recruiting proteins, including Aly and SR proteins, enhanced recombinant protein expression, albeit independently of the CTE. The incorporation of a CTE and Tap-p15-recruiting proteins into protein expression system is useful to increase recombinant protein yield in human cells.

  20. Investigation of transport of genistein, daidzein and their inclusion complexes prepared with different cyclodextrins on Caco-2 cell line.

    PubMed

    Daruházi, Agnes Emma; Kiss, Tímea; Vecsernyés, Miklós; Szente, Lajos; Szőke, Eva; Lemberkovics, Eva

    2013-10-01

    Isoflavonoids are widespread constituents in medical plants especially in legumes (Fabaceae), but occur in other different plant families as well (Rosaceae, Iridaceae, Amaranthaceae). Their antioxidant, estrogen-like, anti-inflammatory and analgesic effects make them promising compounds in therapy of important disorders especially in estrogen related diseases. Poor solubility in aqueous system of genistein and daidzein needs a solubility enhancement for pharmaceutical use. These compounds are suitable guest molecules for inclusion complex formation with cyclodextrins (CDs) considering matching their size and polarity. The molecular encapsulation with beta-cyclodextrin (β-CD), gamma-cyclodextrin (γ-CD), hydroxypropyl-beta-cyclodextrin (HP-β-CD) and random methyl-beta cyclodextrin (RAMEB-CD) results in a solid, molecularly dispersed form and in a significantly improved aqueous solubility of genistein and daidzein. Determining enhancement in solubility and bioavailability we investigated the transport of these inclusion complexes across Caco-2 cell line comparing that of the pure compounds and found significant improving effect of the different CD derivatives on membrane permeation of the two isoflavone aglycons.

  1. AP Human Geography and Success on the AP Test

    ERIC Educational Resources Information Center

    Roncone, John; Newhalfen, Nate

    2013-01-01

    Classroom projects that explore culture and globalization enhance the curriculum and help students see how geography directly connects to their lives. These authors contend that a project-based approach can supplement the teaching of an AP Human Geography course, and visualize this course as an essential tool for students to truly understand how…

  2. Developments in OTR/ODR Imaging Techniques for 7-GeV Electron Beams at APS

    NASA Astrophysics Data System (ADS)

    Lumpkin, A. H.; Yang, B. X.; Berg, W. J.; Rule, D. W.; Sereno, N. S.; Yao, C. Y.

    2006-11-01

    We have continued our investigations on imaging 7-GeV electron beams in a transport line at the Advanced Photon Source (APS) using optical transition radiation (OTR) and optical diffraction radiation (ODR) emitted from an Al blade. In our experiments appreciable visible wavelength ODR is emitted for impact parameters of 1 to 2 mm, values that are close to γλ/2π. We have now upgraded our imaging system to include an optical transport that provides either near-field or far-field imaging, and we have performed initial experiments. The OTR far-field images indicate that beam divergence effects at the 30-70 microrad regime are detectable, and these are some of the first recorded for this regime. An analytical model predicts beam-size sensitivity in the 20-50 micron regime, while beam position resolution to 10 microns with a smaller beam and higher optical magnification should be feasible with near-field ODR imaging. Although originally developed to support top-up operations at APS, the ODR imaging techniques for nonintercepting relative beam size and position monitoring should also be applicable to high-energy accelerator beams that drive x-ray FELs, energy-recovering linacs for light sources, and the proposed ILC.

  3. Induction of the high-affinity Na(+)-dependent glutamate transport system XAG- by hypertonic stress in the renal epithelial cell line NBL-1.

    PubMed Central

    Ferrer-Martinez, A; Felipe, A; Nicholson, B; Casado, J; Pastor-Anglada, M; McGivan, J

    1995-01-01

    The high-affinity Na(+)-dependent glutamate transport system XAG- is induced (threefold increase in Vmax. with no change in Km) by hypertonicity in the renal epithelial cell line NBL-1. This effect is dependent on protein synthesis and glycosylation and is accompanied by an increase in EAAC1 mRNA levels. Other Na(+)-dependent transport systems in this cell line do not respond to hypertonic stress. In contrast to recent findings [Ruiz-Montasell, Gomez-Angelats, Casado, Felipe, McGivan and Pastor-Anglada (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 9569-9573] showing that increased system A activity after hyperosmotic shock results from induction of a regulatory protein, this is the first demonstration that hypertonicity may increase the expression of the gene for an amino acid transport protein itself. Images Figure 4 PMID:7654212

  4. Design of a high-current low-energy beam transport line for an intense D-T/D-D neutron generator

    NASA Astrophysics Data System (ADS)

    Lu, Xiaolong; Wang, Junrun; Zhang, Yu; Li, Jianyi; Xia, Li; Zhang, Jie; Ding, Yanyan; Jiang, Bing; Huang, Zhiwu; Ma, Zhanwen; Wei, Zheng; Qian, Xiangping; Xu, Dapeng; Lan, Changlin; Yao, Zeen

    2016-03-01

    An intense D-T/D-D neutron generator is currently being developed at the Lanzhou University. The Cockcroft-Walton accelerator, as a part of the neutron generator, will be used to accelerate and transport the high-current low-energy beam from the duoplasmatron ion source to the rotating target. The design of a high-current low-energy beam transport (LEBT) line and the dynamics simulations of the mixed beam were carried out using the TRACK code. The results illustrate that the designed beam line facilitates smooth transportation of a deuteron beam of 40 mA, and the number of undesired ions can be reduced effectively using two apertures.

  5. ABC AND SLC TRANSPORTER EXPRESSION AND POT SUBSTRATE CHRACTERIZATION ACROSS THE HUMAN CMEC/D3 BLOOD-BRAIN BARRIER CELL LINE

    PubMed Central

    Carl, Stephen M.; Lindley, David J.; Couraud, Pierre O.; Weksler, Babette B.; Romero, Ignacio; Mowery, Stephanie A.; Knipp, Gregory T.

    2010-01-01

    Purpose Initial studies indicate that the newly developed hCMEC/D3 cell line may prove to be a useful model for studying the physiology of the human blood-brain barrier (BBB) endothelium. The purpose of this study was to assess the mRNA expression of several ABC and SLC transporters, with an emphasis on the Proton-Coupled Oligopeptide Transporter Superfamily (POT) transporters in this immortalized BBB cell model. The transport kinetics of POT-substrates was also evaluated. Methods The hCMEC/D3 cell line was maintained in a modified EGM-2 medium in collagenated culture flasks and passaged every 3–4 days at approximately 85%–95% confluence. Messenger RNA (mRNA) expression of a variety of ABC and SLC transporters was evaluated using qRT-PCR arrays, while additional qRT-PCR primers were designed to assess the expression of POT members. The transport kinetics of mannitol and urea were utilized to quantitatively estimate the intercellular pore radius, while POT substrate transport was also determined to assess the suitability of the cell model from a drug screening perspective. Optimization of the cell line was attempted by culturing with on laminin and fibronectin enhanced collagen and in the presence of excess Ca2+. Results HCMEC/D3 cells express both hPHT1 and hPHT2, while little to no expression of either hPepT1 or hPepT2 was observed. The relative expression of other ABC and SLC transporters is discussed. While POT substrate transport does suggest suitability for BBB drug permeation screening, the relative intercellular pore radius was estimated at 19Å, significantly larger than that approximated in vivo. Culturing with extracellular matrix proteins did not alter mannitol permeability. Conclusion These studies characterized this relevant human hCMEC/D3 BBB cell line with respect to both the relative mRNA expression of various ABC and SLC transporters, and its potential utility as an in vitro screening tool for brain permeation. Additional studies are required

  6. Transportation

    DTIC Science & Technology

    2006-01-01

    2002, p.1). The port uses information technology (IT) in all aspects of its port operations. Their use of IT began in 1972. Today, the Computer ...while 18 public lines provide commuter rail service. 5 Traditionally, railroading was viewed as a low technology , large capital investment...development and integration of technologies that will increase efficiency, improve safety, and reduce personnel costs. However, passenger rail remains

  7. AP Geography, Environmental Science Thrive

    ERIC Educational Resources Information Center

    Robelen, Erik W.

    2012-01-01

    Geography may not be particularly known as a hot topic among today's students--even some advocates suggest it suffers from an image problem--but by at least one measure, the subject is starting to come into its own. Across more than 30 topics covered in the Advanced Placement (AP) program, participation in geography is rising faster than any…

  8. Coaching in the AP Classroom

    ERIC Educational Resources Information Center

    Fornaciari, Jim

    2013-01-01

    Many parallels exist between quality coaches and quality classroom teachers--especially AP teachers, who often feel the pressure to produce positive test results. Having developed a series of techniques and strategies for building a team-oriented winning culture on the field, Jim Fornaciari writes about how he adapted those methods to work in the…

  9. Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes.

    PubMed

    Tolvanen, Tuomas A; Dash, Surjya Narayan; Polianskyte-Prause, Zydrune; Dumont, Vincent; Lehtonen, Sanna

    2015-12-15

    The adapter protein CD2-associated protein (CD2AP) functions in various signaling and vesicle trafficking pathways, including endosomal sorting and/or trafficking and degradation pathways. Here, we investigated the role of CD2AP in insulin-dependent glucose transporter 4 (Glut4, also known as SLC2A4) trafficking and glucose uptake. Glucose uptake was attenuated in CD2AP(-/-) podocytes compared with wild-type podocytes in the basal state, and CD2AP(-/-) podocytes failed to increase glucose uptake in response to insulin. Live-cell imaging revealed dynamic trafficking of HA-Glut4-GFP in wild-type podocytes, whereas in CD2AP(-/-) podocytes, HA-Glut4-GFP clustered perinuclearly. In subcellular membrane fractionations, CD2AP co-fractionated with Glut4, IRAP (also known as LNPEP) and sortilin, constituents of Glut4 storage vesicles (GSVs). We further found that CD2AP forms a complex with GGA2, a clathrin adaptor, which sorts Glut4 to GSVs, suggesting a role for CD2AP in this process. We also found that CD2AP forms a complex with clathrin and connects clathrin to actin in the perinuclear region. Furthermore, clathrin recycling back to trans-Golgi membranes from the vesicular fraction containing GSVs was defective in the absence of CD2AP. This leads to reduced insulin-stimulated trafficking of GSVs and attenuated glucose uptake into CD2AP(-/-) podocytes.

  10. On the abundance of Europium. [in Ap and Am stars

    NASA Technical Reports Server (NTRS)

    Hartoog, M. R.; Cowley, C. R.; Adelman, S. J.

    1974-01-01

    The inclusion of the effects of hyperfine splitting can significantly lower the abundance estimate of Eu from singly ionized lines which lie on the flat portion of the curve of growth. In the 21 cool Ap stars studied by Adelman and the five Am stars studied by Smith, the Eu abundance was reduced by 0.4 dex on the average. In individual cases, the reductions were as great as 0.9 dex. This makes the Eu abundance comparable to that of its neighboring rare earths Sm and Gd in the Ap stars and less than Sm and Gd in the Am stars, but still substantially overabundant with respect to solar values.

  11. The Electronic ApJ in Context

    NASA Astrophysics Data System (ADS)

    Biemesderfer, C. D.

    1995-12-01

    The on-line edition of the Astrophysical Journal provides the first opportunity for astronomical researchers to interact with the literature in a network context. Other electronic journals will follow. Astronomers will continue to develop ways to take advantage of information on the network, and these will be most effective when ApJ articles, observations from data centers, proposals for telescope time, communications with collaborators, and so on, are meshed. Astronomical literature, as a resource on the Internet, is not unique from the viewpoint of function or management, and astronomers are not unique as scholars in their desire to use the Internet as a tool to advance their work. We need to ensure as a community that all our resources for research --- journals and data --- fit in a global context on an Internet being used by everyone. In other words, we have to be sure that the ApJ fits into all the digital libraries of the future, including the ones we don't build. This paper will present a scenario in which many varied forms of information, astronomical and otherwise, can be catalogued and distributed so that they can be discovered and used by the research community.

  12. Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models.

    PubMed

    Badavi, Francis F; Walker, Steven A; Santos Koos, Lindsey M

    2015-04-01

    The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

  13. Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models

    NASA Astrophysics Data System (ADS)

    Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

    2015-04-01

    The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

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

    PubMed Central

    Atnip, Allison A.; Sigurdson, Gregory T.; Bomser, Joshua; Giusti, M. Mónica

    2017-01-01

    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. PMID:28218720

  15. Time resolved spectroscopy of the cool Ap star HD 213637*

    NASA Astrophysics Data System (ADS)

    Elkin, V. G.; Kurtz, D. W.; Mathys, G.

    2015-02-01

    We present an analysis of high time resolution spectra of the chemically peculiar Ap star HD 213637. The star shows rapid radial velocity variations with a period close to the photometric pulsation period. Radial velocity pulsation amplitudes vary significantly for different rare earth elements. The highest pulsation amplitudes belong to lines of Tb III (˜360 m s-1), Pr II (˜250 m s-1) and Pr III (˜230 m s-1). We did not detect any pulsations from spectral lines of Eu II and in Hα, in contrast to many other roAp stars. We also did not find radial velocity pulsations using spectral lines of other chemical elements, including Mg, Si, Ca, Sc, Cr, Fe, Ni, Y and Ba. There are phase shifts between the maxima of pulsation amplitudes of different rare earth elements and ions, which is evidence of an outwardly running magneto-acoustic wave propagating through the upper stellar atmosphere.

  16. Space-charge compensation measurements in electron cyclotron resonance ion source low energy beam transport lines with a retarding field analyzer

    SciTech Connect

    Winklehner, D.; Leitner, D. Cole, D.; Machicoane, G.; Tobos, L.

    2014-02-15

    In this paper we describe the first systematic measurement of beam neutralization (space charge compensation) in the ECR low energy transport line with a retarding field analyzer, which can be used to measure the potential of the beam. Expected trends for the space charge compensation levels such as increase with residual gas pressure, beam current, and beam density could be observed. However, the overall levels of neutralization are consistently low (<60%). The results and the processes involved for neutralizing ion beams are discussed for conditions typical for ECR injector beam lines. The results are compared to a simple theoretical beam plasma model as well as simulations.

  17. The APS in Public Affairs

    NASA Astrophysics Data System (ADS)

    Lustig, Harry

    2000-04-01

    Although the American Physical Society was created for the interchange of scientific ideas, the call to the founding meeting included the observation that the organization "could not fail to have an important influence in all matters affecting the interest of physicists". However for most of its history APS did not behave like "just another interest group in American society". Instead, at the beginning, it limited itself to such successful initiatives as the creation of the Bureau of Standards and such unsuccessful ones as adoption of the metric system. After World War II, speaking out on behalf of the freedom of science and scientists, such as Astin, Condon, and Oppenheimer, became important. In the 1970's, pushed by members, the Society became more "political", sponsoring sessions and studies on defense issues, taking a stand for the Equal Rights Amendment and creating the Panel on Public Affairs and the Forum on Physics and Society. Only in the last fifteen years has the APS unabashedly lobbied for the economic interests of physics and physicists. Adopting this new, if unavoidable role may have unintended consequences for the willingness and effectiveness of APS in speaking out on other public issues.

  18. Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster

    PubMed Central

    Williams, Michael J.; Goergen, Philip; Rajendran, Jayasimman; Zheleznyakova, Galina; Hägglund, Maria G.; Perland, Emelie; Bagchi, Sonchita; Kalogeropoulou, Argyro; Khan, Zaid; Fredriksson, Robert; Schiöth, Helgi B.

    2014-01-01

    In all animals managing the size of individual meals and frequency of feeding is crucial for metabolic homeostasis. In the current study we demonstrate that the noradrenalin analogue octopamine and the cholecystokinin (CCK) homologue Drosulfakinin (Dsk) function downstream of TfAP-2 and Tiwaz (Twz) to control the number of meals in adult flies. Loss of TfAP-2 or Twz in octopaminergic neurons increased the size of individual meals, while overexpression of TfAP-2 significantly decreased meal size and increased feeding frequency. Of note, our study reveals that TfAP-2 and Twz regulate octopamine signaling to initiate feeding; then octopamine, in a negative feedback loop, induces expression of Dsk to inhibit consummatory behavior. Intriguingly, we found that the mouse TfAP-2 and Twz homologues, AP-2β and Kctd15, co-localize in areas of the brain known to regulate feeding behavior and reward, and a proximity ligation assay (PLA) demonstrated that AP-2β and Kctd15 interact directly in a mouse hypothalamus-derived cell line. Finally, we show that in this mouse hypothalamic cell line AP-2β and Kctd15 directly interact with Ube2i, a mouse sumoylation enzyme, and that AP-2β may itself be sumoylated. Our study reveals how two obesity-linked homologues regulate metabolic homeostasis by modulating consummatory behavior. PMID:25187989

  19. Transfected MDCK cell line with enhanced expression of CYP3A4 and P-glycoprotein as a model to study their role in drug transport and metabolism.

    PubMed

    Kwatra, Deep; Budda, Balasubramanyam; Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

    2012-07-02

    The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drug of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 μM naringin and 3 μM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and Western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The Vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be 10- and 3-fold lower in MMC as compared to MDCK-WT and MDCK-MDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT, indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined activities of CYP3A4 and P-gp. Transport of cortisol increased 5-fold in the presence of naringin in MMC and doubled in MDCK-MDR1. Cortisol transport in MMC was significantly lower than that in MDCK-WT in the presence of naringin. The permeability increased 3-fold in the presence of morphine, which is a weaker inhibitor of CYP3A4. Formation of 6β-hydroxy cortisol was found to decrease in the presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes toward drug-drug interactions.

  20. TRANSFECTED MDCK CELL LINE WITH ENHANCED EXPRESSION OF CYP3A4 AND P-GLYCOPROTEIN AS A MODEL TO STUDY THEIR ROLE IN DRUG TRANSPORT AND METABOLISM

    PubMed Central

    Kwatra, Deep; Budda, Balasubramanyam; Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K.

    2012-01-01

    The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drugs of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 μM naringin and 3 μM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be ten and three fold lower in MMC as compared to WT and MDCKMDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined metabolic activities of CYP3A4 and P-gp. Transport of cortisol increased fivefold in presence of naringin in MMC and doubled in MDCKMDR1. Cortisol transport in MMC was significantly lower than that in WT in presence of naringin. The permeability increased three fold in presence of morphine which is a weaker inhibitor of CYP3A4. Formation of 6β-hydroxy cortisol was found to decrease in presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes towards drug-drug interactions. PMID:22676443

  1. Cortisol and IGF-1 synergistically up-regulate taurine transport by the rat skeletal muscle cell line, L6.

    PubMed

    Park, Sung-Hee; Lee, Haemi; Park, Taesun

    2004-01-01

    This study was undertaken to evaluate effects of exercise-induced hormones, cortisol, IGF-1, and beta-endorphin, on the regulation of taurine transport activity in rat skeletal myoblasts, L6 cells. Challenge of L6 cells with cortisol (100 nM) for 24 hrs resulted in a 165% increase in taurine transport activity, 220% increase in Vmax of the taurine transporter, and 55% increase in taurine transporter/ beta-actin mRNA level compared with untreated control cells. Neither IGF-1 (1 approximately 100 nM) nor beta-endorphin (1 approximately 20 nM), added in the incubation medium separately for 24 hrs, affected taurine uptake by L6 cells. However, when cells were co-treated with IGF-1 (10 nM) plus cortisol (100 nM), taurine transport activity (37% increase, p < 0.05), Vmax of the transporter (54%, p < 0.05), and taurine transporter/ beta-actin mRNA level were further increased compared to the value for cells treated with cortisol alone. These results suggest that taurine transport by skeletal muscle cells appear to be synergistically up-regulated during a prolonged exercise via elevated levels of cortisol and IGF-1 in muscle.

  2. Interactions of nucleoside analogs, caffeine, and nicotine with human concentrative nucleoside transporters 1 and 2 stably produced in a transport-defective human cell line.

    PubMed

    Lang, Thack T; Young, James D; Cass, Carol E

    2004-04-01

    Pharmacologically important drugs were examined as potential inhibitors or permeants of human concentrative nucleoside transporters 1 (hCNT1)- and 2 (hCNT2)-producing stable transfectants by assessing their abilities to inhibit uridine transport. hCNT1 exhibited high affinities for uridine analogs (5-fluorouridine, 2'-deoxyuridine, 5-fluoro-2'-deoxyuridine, and 5-fluoro-5'-deoxyuridine) with K(i) values of 22 to 33 microM, whereas hCNT2 exhibited moderate affinities for 5-fluoro-2'-deoxyuridine, high affinities for 2'-deoxyuridine and 5-fluorouridine, and low affinity for 5-fluoro-5'-deoxyuridine. The uridine analogs were transported at 2-fold higher rates (at 10 microM) by hCNT1 than by hCNT2. Enantiomeric configuration and the 3'-hydroxyl group of the ribose ring were important determinants for interaction with hCNTs, whereas the 2'-hydroxyl group was less important. Both transporters bound N(6)-(p-aminobenzyl)adenosine with affinities similar to those of adenosine (K(i) = 28-39 microM). Other adenosine receptor ligands, including caffeine, bound better to hCNT1 than to hCNT2 (K(i) = 46 versus 103 microM, respectively), whereas 2-chloroadenosine bound better to hCNT2 than to hCNT1 (K(i) = 37 and 101 microM, respectively). There was a greater than 3-fold difference in binding affinities between hCNT1 and hCNT2 for nicotine (K(i) = 63 versus 227 microM). However, direct measurements of nicotine and caffeine uptake rates (10 microM) failed to demonstrate mediated uptake by either transporter. Although hCNT1 bound several adenosine analogs relatively well, it did not transport 2-chloro-2'-deoxyadenosine (cladribine) or 2-fluoro-9-beta-d-arabinofuranosyladenine (fludarabine), whereas hCNT2 transported both, albeit with low activities. The results indicated that although hCNT1 and hCNT2 possess some overlap in transport of several uridine and adenosine analogs, they also exhibit distinct differences in capacity to interact with some adenosine receptor ligands

  3. An AP Calculus Classroom Amusement Park

    ERIC Educational Resources Information Center

    Ferguson, Sarah

    2016-01-01

    Throughout the school year, AP Calculus teachers strive to teach course content comprehensively and swiftly in an effort to finish all required material before the AP Calculus exam. As early May approaches and the AP Calculus test looms, students and teachers nervously complete lessons, assignments, and assessments to ensure student preparation.…

  4. Preparing Students for the AP Psychology Exam

    ERIC Educational Resources Information Center

    Whitlock, Kristin

    2013-01-01

    The Advanced Placement Psychology exam is one of the fastest growing exams offered by the College Board. The average percent of change in the number of students taking this exam over the past five years is 12.4%. With 238,962 students taking the exam in 2013, the AP Psychology exam is the sixth largest exam, surpassing AP Biology and AP World…

  5. 77 FR 11192 - Fannin Rural Rail Transportation District-Lease and Operation Exemption-Line of Texas Department...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... Paris to milepost 128.78 in Bonham, Tex. The line has been a part of Union Pacific Railroad Company's... extending between milepost 94.0, near Paris, and milepost 127.5, east of Bonham, in Lamar and Fannin Counties, Tex.\\1\\ After an agreement had been reached with UP for sale of the line but before...

  6. Ectopic expression of Jatropha curcas APETALA1 (JcAP1) caused early flowering in Arabidopsis, but not in Jatropha

    PubMed Central

    Tang, Mingyong; Tao, Yan-Bin

    2016-01-01

    Jatropha curcas is a promising feedstock for biofuel production because Jatropha oil is highly suitable for the production of biodiesel and bio-jet fuels. However, Jatropha exhibits a low seed yield as a result of unreliable and poor flowering. APETALA1 (AP1) is a floral meristem and organ identity gene in higher plants. The flower meristem identity genes of Jatropha have not yet been identified or characterized. To better understand the genetic control of flowering in Jatropha, an AP1 homolog (JcAP1) was isolated from Jatropha. An amino acid sequence analysis of JcAP1 revealed a high similarity to the AP1 proteins of other perennial plants. JcAP1 was expressed in inflorescence buds, flower buds, sepals and petals. The highest expression level was observed during the early developmental stage of the flower buds. The overexpression of JcAP1 using the cauliflower mosaic virus (CaMV) 35S promoter resulted in extremely early flowering and abnormal flowers in transgenic Arabidopsis plants. Several flowering genes downstream of AP1 were up-regulated in the JcAP1-overexpressing transgenic plant lines. Furthermore, JcAP1 overexpression rescued the phenotype caused by the Arabidopsis AP1 loss-of-function mutant ap1-11. Therefore, JcAP1 is an ortholog of AtAP1, which plays a similar role in the regulation of flowering in Arabidopsis. However, the overexpression of JcAP1 in Jatropha using the same promoter resulted in little variation in the flowering time and floral organs, indicating that JcAP1 may be insufficient to regulate flowering by itself in Jatropha. This study helps to elucidate the function of JcAP1 and contributes to the understanding of the molecular mechanisms of flower development in Jatropha. PMID:27168978

  7. Ectopic expression of Jatropha curcas APETALA1 (JcAP1) caused early flowering in Arabidopsis, but not in Jatropha.

    PubMed

    Tang, Mingyong; Tao, Yan-Bin; Xu, Zeng-Fu

    2016-01-01

    Jatropha curcas is a promising feedstock for biofuel production because Jatropha oil is highly suitable for the production of biodiesel and bio-jet fuels. However, Jatropha exhibits a low seed yield as a result of unreliable and poor flowering. APETALA1 (AP1) is a floral meristem and organ identity gene in higher plants. The flower meristem identity genes of Jatropha have not yet been identified or characterized. To better understand the genetic control of flowering in Jatropha, an AP1 homolog (JcAP1) was isolated from Jatropha. An amino acid sequence analysis of JcAP1 revealed a high similarity to the AP1 proteins of other perennial plants. JcAP1 was expressed in inflorescence buds, flower buds, sepals and petals. The highest expression level was observed during the early developmental stage of the flower buds. The overexpression of JcAP1 using the cauliflower mosaic virus (CaMV) 35S promoter resulted in extremely early flowering and abnormal flowers in transgenic Arabidopsis plants. Several flowering genes downstream of AP1 were up-regulated in the JcAP1-overexpressing transgenic plant lines. Furthermore, JcAP1 overexpression rescued the phenotype caused by the Arabidopsis AP1 loss-of-function mutant ap1-11. Therefore, JcAP1 is an ortholog of AtAP1, which plays a similar role in the regulation of flowering in Arabidopsis. However, the overexpression of JcAP1 in Jatropha using the same promoter resulted in little variation in the flowering time and floral organs, indicating that JcAP1 may be insufficient to regulate flowering by itself in Jatropha. This study helps to elucidate the function of JcAP1 and contributes to the understanding of the molecular mechanisms of flower development in Jatropha.

  8. Structural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNA.

    PubMed

    Redrejo-Rodríguez, Modesto; Vigouroux, Armelle; Mursalimov, Aibek; Grin, Inga; Alili, Doria; Koshenov, Zhanat; Akishev, Zhiger; Maksimenko, Andrei; Bissenbaev, Amangeldy K; Matkarimov, Bakhyt T; Saparbaev, Murat; Ishchenko, Alexander A; Moréra, Solange

    2016-01-01

    Oxidatively damaged DNA bases are substrates for two overlapping repair pathways: DNA glycosylase-initiated base excision repair (BER) and apurinic/apyrimidinic (AP) endonuclease-initiated nucleotide incision repair (NIR). In the BER pathway, an AP endonuclease cleaves DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases, whereas in the NIR pathway, the same AP endonuclease incises DNA 5' to an oxidized base. The majority of characterized AP endonucleases possess classic BER activities, and approximately a half of them can also have a NIR activity. At present, the molecular mechanism underlying DNA substrate specificity of AP endonucleases remains unclear mainly due to the absence of a published structure of the enzyme in complex with a damaged base. To identify critical residues involved in the NIR function, we performed biochemical and structural characterization of Bacillus subtilis AP endonuclease ExoA and compared its crystal structure with the structures of other AP endonucleases: Escherichia coli exonuclease III (Xth), human APE1, and archaeal Mth212. We found conserved amino acid residues in the NIR-specific enzymes APE1, Mth212, and ExoA. Four of these positions were studied by means of point mutations in APE1: we applied substitution with the corresponding residue found in NIR-deficient E. coli Xth (Y128H, N174Q, G231S, and T268D). The APE1-T268D mutant showed a drastically decreased NIR activity and an inverted Mg(2+) dependence of the AP site cleavage activity, which is in line with the presence of an aspartic residue at the equivalent position among other known NIR-deficient AP endonucleases. Taken together, these data show that NIR is an evolutionarily conserved function in the Xth family of AP endonucleases.

  9. Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities.

    PubMed

    Guo, Xiaoxiao; Ma, Chengbang; Du, Qiang; Wei, Ran; Wang, Lei; Zhou, Mei; Chen, Tianbao; Shaw, Chris

    2013-09-01

    Here we report two novel 17-mer amidated linear peptides (TsAP-1 and TsAP-2) whose structures were deduced from cDNAs cloned from a venom-derived cDNA library of the Brazilian yellow scorpion, Tityus serrulatus. Both mature peptides were structurally-characterised following their location in chromatographic fractions of venom and synthetic replicates of each were subjected to a range of biological assays. The peptides were each active against model test micro-organisms but with different potencies. TsAP-1 was of low potency against all three test organisms (MICs 120-160 μM), whereas TsAP-2 was of high potency against the Gram-positive bacterium, Staphylococcus aureus (MIC 5 μM) and the yeast, Candida albicans (10 μM). Haemolytic activity of TsAP-1 was low (4% at 160 μM) and in contrast, that of TsAP-2 was considerably higher (18% at 20 μM). Substitution of four neutral amino acid residues with Lys residues in each peptide had dramatic effects on their antimicrobial potencies and haemolytic activities, particularly those of TsAP-1. The MICs of the enhanced cationic analogue (TsAP-S1) were 2.5 μM for S. aureus/C. albicans and 5 μM for E. coli but with an associated large increase in haemolytic activity (30% at 5 μM). The same Lys residue substitutions in TsAP-2 produced a dramatic effect on its MIC for E. coli lowering this from >320 μM to 5 μM. TsAP-1 was ineffective against three of the five human cancer cell lines tested while TsAP-2 inhibited the growth of all five. Lys residue substitution of both peptides enhanced their potency against all five cell lines with TsAp-S2 being the most potent with IC50 values ranging between 0.83 and 2.0 μM. TsAP-1 and TsAP-2 are novel scorpion venom peptides with broad spectrum antimicrobial and anticancer cell activities the potencies of which can be significantly enhanced by increasing their cationicity.

  10. AP reclamation and reuse in RSRM propellant

    NASA Technical Reports Server (NTRS)

    Miks, Kathryn F.; Harris, Stacey A.

    1995-01-01

    A solid propellant ingredient reclamation pilot plant has been evaluated at the Strategic Operations of Thiokol Corporation, located in Brigham City, Utah. The plant produces AP wet cake (95 percent AP, 5 percent water) for recycling at AP vendors. AP has been obtained from two standard propellant binder systems (PBAN and HTPB). Analytical work conducted at Thiokol indicates that the vendor-recrystallized AP meets Space Shuttle propellant specification requirements. Thiokol has processed 1-, 5-, and 600-gallon propellant mixes with the recrystallized AP. Processing, cast, cure, ballistic, mechanical, and safety properties have been evaluated. Phillips Laboratory static-test-fired 70-pound and 800-pound BATES motors. The data indicate that propellant processed with reclaimed AP has nominal properties.

  11. Preservation of folate transport activity with a low-pH optimum in rat IEC-6 intestinal epithelial cell lines that lack reduced folate carrier function.

    PubMed

    Wang, Yanhua; Rajgopal, Arun; Goldman, I David; Zhao, Rongbao

    2005-01-01

    Intestinal folate transport has been well characterized, and rat small intestinal epithelial (IEC-6) cells have been used as a model system for the study of this process on the cellular level. The major intestinal folate transport activity has a low-pH optimum, and the current paradigm is that this process is mediated by the reduced folate carrier (RFC), despite the fact that this carrier has a neutral pH optimum in leukemia cells. The current study addressed the question of whether constitutive low-pH folate transport activity in IEC-6 cells is mediated by RFC. Two independent IEC-6 sublines, IEC-6/A4 and IEC-6/PT1, were generated by chemical mutagenesis followed by selective pressure with antifolates. In IEC-6/A4 cells, a premature stop resulted in truncation of RFC at Gln(420). A green fluorescent protein (GFP) fusion with the truncated protein was not stable. In IEC-6/PT1 cells, Ser(135) was deleted, and this alteration resulted in the failure of localization of the GFP fusion protein in the plasma membrane. In both cell lines, methotrexate (MTX) influx at neutral pH was markedly decreased compared with wild-type IEC-6 cells, but MTX influx at pH 5.5 was not depressed. Transient transfection of the GFP-mutated RFC constructs into RFC-null HeLa cells confirmed their lack of transport function. These results indicate that in IEC-6 cells, folate transport at neutral pH is mediated predominantly by RFC; however, the folate transport activity at pH 5.5 is RFC independent. Hence, constitutive folate transport activity with a low-pH optimum in this intestinal cell model is mediated by a process entirely distinct from that of RFC.

  12. APS high heat load monochromator

    SciTech Connect

    Lee, W.K.; Mills, D.

    1993-02-01

    This document contains the design specifications of the APS high heat load (HHL) monochromator and associated accessories as of February 1993. It should be noted that work is continuing on many parts of the monochromator including the mechanical design, crystal cooling designs, etc. Where appropriate, we have tried to add supporting documentation, references to published papers, and calculations from which we based our decisions. The underlying philosophy behind performance specifications of this monochromator was to fabricate a device that would be useful to as many APS users as possible, that is, the design should be as generic as possible. In other words, we believe that this design will be capable of operating on both bending magnet and ID beamlines (with the appropriate changes to the cooling and crystals) with both flat and inclined crystal geometries and with a variety of coolants. It was strongly felt that this monochromator should have good energy scanning capabilities over the classical energy range of about 4 to 20 keywith Si (111) crystals. For this reason, a design incorporating one rotation stage to drive both the first and second crystals was considered most promising. Separate rotary stages for the first and second crystals can sometimes provide more flexibility in their capacities to carry heavy loads (for heavily cooled first crystals or sagittal benders of second crystals), but their tuning capabilities were considered inferior to the single axis approach.

  13. The Adaptor Complex AP-4 Regulates Vacuolar Protein Sorting at the trans-Golgi Network by Interacting with VACUOLAR SORTING RECEPTOR1.

    PubMed

    Fuji, Kentaro; Shirakawa, Makoto; Shimono, Yuki; Kunieda, Tadashi; Fukao, Yoichiro; Koumoto, Yasuko; Takahashi, Hideyuki; Hara-Nishimura, Ikuko; Shimada, Tomoo

    2016-01-01

    Adaptor protein (AP) complexes play critical roles in protein sorting among different post-Golgi pathways by recognizing specific cargo protein motifs. Among the five AP complexes (AP-1-AP-5) in plants, AP-4 is one of the most poorly understood; the AP-4 components, AP-4 cargo motifs, and AP-4 functional mechanism are not known. Here, we identify the AP-4 components and show that the AP-4 complex regulates receptor-mediated vacuolar protein sorting by recognizing VACUOLAR SORTING RECEPTOR1 (VSR1), which was originally identified as a sorting receptor for seed storage proteins to target protein storage vacuoles in Arabidopsis (Arabidopsis thaliana). From the vacuolar sorting mutant library GREEN FLUORESCENT SEED (GFS), we isolated three gfs mutants that accumulate abnormally high levels of VSR1 in seeds and designated them as gfs4, gfs5, and gfs6. Their responsible genes encode three (AP4B, AP4M, and AP4S) of the four subunits of the AP-4 complex, respectively, and an Arabidopsis mutant (ap4e) lacking the fourth subunit, AP4E, also had the same phenotype. Mass spectrometry demonstrated that these four proteins form a complex in vivo. The four mutants showed defects in the vacuolar sorting of the major storage protein 12S globulins, indicating a role for the AP-4 complex in vacuolar protein transport. AP4M bound to the tyrosine-based motif of VSR1. AP4M localized at the trans-Golgi network (TGN) subdomain that is distinct from the AP-1-localized TGN subdomain. This study provides a novel function for the AP-4 complex in VSR1-mediated vacuolar protein sorting at the specialized domain of the TGN.

  14. AP1000 Features Prevent Potential Containment Recirculation Screen Plugging

    SciTech Connect

    Andreychek, Timothy; Anderson, Richard; Schulz, Terry

    2004-07-01

    This paper presents the results of plant design development and evaluations that demonstrate that the AP1000 plant is not subject to potential containment recirculation screen plugging following a loss-of-coolant-accident (LOCA). Following a LOCA in a pressurized water reactor, it is necessary to recirculate water from the containment back into the reactor to maintain long term core cooling. The AP1000 utilizes passive safety systems to provide containment recirculation for long term core cooling following a LOCA. The AP1000 also has non-safety pumps which provide a backup means of providing recirculation. Screens are provided around the recirculation pipes to prevent debris from blocking recirculation flow and core cooling passages. Debris may be generated by the LOCA blowdown from insulation and coatings used inside containment. Even with effective cleanliness programs, there may be some resident debris such as dust and dirt. The potential for plugging the recirculation screens is a current PWR licensing issue. The AP1000 design provides inherent advantages with respect to the potential plugging of containment recirculation screens. These characteristics include prevention of fibrous debris generation, improved debris settling and improved recirculation screen design. Debris settling analysis demonstrates that failure of coatings does not result in debris being transported to the screens before it settles to the floor. Additional analysis also shows that the plant can tolerate conservative amounts of resident debris being transported to the screens. The AP1000 significantly reduces the probability of plugging the containment recirculation screens and significantly reduces inspection and maintenance of coatings used inside containment. (authors)

  15. Expression of transcription factor AP-2α predicts survival in epithelial ovarian cancer

    PubMed Central

    Anttila, M A; Kellokoski, J K; Moisio, K I; Mitchell, P J; Saarikoski, S; Syrjänen, K; Kosma, V-M

    2000-01-01

    The 52-kDa activator protein (AP)-2 is a DNA-binding transcription factor which has been reported to have growth inhibitory effects in cancer cell lines and in human tumours. In this study the expression of AP-2α was analysed in 303 epithelial ovarian carcinomas by immunohistochemistry (IHC) with a polyclonal AP-2α antibody and its mRNA status was determined by in situ hybridization (ISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). The immunohistochemical expression of AP-2α was correlated with clinicopathological variables, p21/WAF1 protein expression and survival. In normal ovaries, epithelial cells expressed AP-2α protein only in the cytoplasm. In carcinomas nuclear AP-2α expression was observed in 28% of the cases although cytoplasmic expression was more common (51%). The expression of AP-2α varied according to the histological subtype and differentiation. AP-2α and p21/WAF1 expressions did not correlate with each other. Both in univariate (P = 0.002) and multivariate analyses (relative risks (RR) 1.6, 95% confidence interval (CI) 1.13–2.18, P = 0.007) the high cytoplasmic AP-2α expression favoured the overall survival. In contrast, the nuclear AP-2α expression combined with low cytoplasmic expression increased the risk of dying of ovarian cancer (RR = 2.10, 95% CI 1.13–3.83, P = 0.018). The shift in the expression pattern of AP-2α (nuclear vs cytoplasmic) in carcinomas points out to the possibility that this transcription factor may be used by oncogenes in certain histological subtypes. Based on the mRNA analyses, the incomplete expression and translation of AP-2α in ovarian cancer may be due to post-transcriptional regulation. © 2000 Cancer Research Campaign PMID:10864206

  16. Tank 241AP104 Grab Sampling and Analysis Plan

    SciTech Connect

    TEMPLETON, A.M.

    2000-11-09

    This sampling and analysis plan (SAP) identifies characterization objectives pertaining to sample collection, laboratory analytical evaluation, and reporting requirements for samples obtained from tank 241-AP-104. The purpose of this sampling event is to obtain information about the characteristics of the contents of 241-AP-104 required to provide sample material to the Waste Treatment Contractor. Grab samples will be obtained from riser 001 to provide sufficient material for the chemical analyses and tests required to satisfy these data quality objectives and ICD-23. The 222-S Laboratory will receive samples; composite the samples; perform chemical analyses on composite samples; and provide samples to the Waste Treatment Contractor and the Process Chemistry Laboratory. The Process Chemistry Laboratory at the 222-S Laboratory Complex will perform process tests to evaluate the behavior of the 241-AP-104 waste undergoing the retrieval and treatment scenarios defined in the applicable DQOs. The Waste Treatment Contractor will perform process verification and waste form qualification tests. Requirements for analyses of samples originating in the L & H DQO process tests will be documented in the corresponding test plan (Person 2000) and are not within the scope of this SAP. This report provides the general methodology and procedures to be used in the preparation, retrieval, transport, analysis, and reporting of results from grab samples retrieved from tank 241-AP-104.

  17. Radiation transport analyses in support of the SNS Target Station Neutron Beam Line Shutters Title I Design

    SciTech Connect

    Miller, T.M.; Pevey, R.E.; Lillie, R.A.; Johnson, J.O.

    2000-12-01

    A detailed radiation transport analysis of the Spallation Neutron Source (SNS) shutters is important for the construction of the SNS because of its impact on conventional facility design, normal operation of the facility, and maintenance operations. Thus far the analysis of the SNS shutter travel gaps has been completed. This analysis was performed using coupled Monte Carlo and multi-dimensional discrete ordinates calculations.

  18. Analysis of high iron rice lines reveals new miRNAs that target iron transporters in roots

    PubMed Central

    Paul, Soumitra; Gayen, Dipak; Datta, Swapan K.; Datta, Karabi

    2016-01-01

    The present study highlights the molecular regulation of iron transport in soyFER1-overexpressing transgenic rice. Accumulation of iron in three different seed developmental stages, milk, dough, and mature, has been examined. The transgenic seeds of the milk stage showed significant augmentation of iron and zinc levels compared with wild-type seeds, and similar results were observed throughout the dough and mature stages. To investigate the regulation of iron transport, the role of miRNAs was studied in roots of transgenic rice. Sequencing of small RNA libraries revealed 153 known and 41 novel miRNAs in roots. Among them, 59 known and 14 novel miRNAs were found to be significantly expressed. miR166, miR399, and miR408 were identified as playing a vital role in iron uptake in roots of transgenic plants . Most importantly, four putative novel miRNAs, namely miR11, miR26, miR30, and miR31, were found to be down-regulated in roots of transgenic plants. For all these four novel miRNAs, natural resistance-associated macrophage protein 4 (NRAMP4), encoding a metal transporter, was predicted as a target gene. It is hypothesized that the NRAMP4 transporter is activated in roots of transgenic plants due to the lower abundance of its corresponding putative novel miRNAs. The relative transcript level of the NRAMP4 transcript was increased from 0.107 in the wild type to 65.24 and 55.39 in transgenic plants, which demonstrates the elevated amount of iron transport in transgenic plants. In addition, up-regulation of OsYSL15, OsFRO2, and OsIRT1 in roots also facilitates iron loading in transgenic seeds. PMID:27729476

  19. Tank 241-AP-106, Grab samples, 6AP-98-1, 6AP-98-2 and 6AP-98-3 Analytical results for the final report

    SciTech Connect

    FULLER, R.K.

    1999-02-23

    This document is the final report for tank 241-AP-106 grab samples. Three grab samples 6AP-98-1, 6AP-98-2 and 6AP-98-3 were taken from riser 1 of tank 241-AP-106 on May 28, 1998 and received by the 222-S Laboratory on May 28, 1998. Analyses were performed in accordance with the ''Compatability Grab Sampling and Analysis Plan'' (TSAP) (Sasaki, 1998) and the ''Data Quality Objectives for Tank Farms Waste Compatability Program (DQO). The analytical results are presented in the data summary report. No notification limits were exceeded. The request for sample analysis received for AP-106 indicated that the samples were polychlorinated biphenyl (PCB) suspects. The results of this analysis indicated that no PCBs were present at the Toxic Substance Control Act (TSCA) regulated limit of 50 ppm. The results and raw data for the PCB analysis are included in this document.

  20. Peculiar Traits of Coarse AP (Briefing Charts)

    DTIC Science & Technology

    2014-12-01

    at differing rates due to pressure and temperature influences in both isolated crystals and solid propellant combustions. Consolidated coarse AP...different reaction rates are also observed between low and high pressure confinements. In solid propellants coarse AP promotes dark zone combustion, low...release; distribution unlimited. PA clearance #. Porous AP in solid propellant Edwin L. Lista, China Lake Demonstrated 3.5 ips @ 2000 Burn rate pressure

  1. AP-1/σ1A and AP-1/σ1B adaptor-proteins differentially regulate neuronal early endosome maturation via the Rab5/Vps34-pathway

    PubMed Central

    Candiello, Ermes; Kratzke, Manuel; Wenzel, Dirk; Cassel, Dan; Schu, Peter

    2016-01-01

    The σ1 subunit of the AP-1 clathrin-coated-vesicle adaptor-protein complex is expressed as three isoforms. Tissues express σ1A and one of the σ1B and σ1C isoforms. Brain is the tissue with the highest σ1A and σ1B expression. σ1B-deficiency leads to severe mental retardation, accumulation of early endosomes in synapses and fewer synaptic vesicles, whose recycling is slowed down. AP-1/σ1A and AP-1/σ1B regulate maturation of these early endosomes into multivesicular body late endosomes, thereby controlling synaptic vesicle protein transport into a degradative pathway. σ1A binds ArfGAP1, and with higher affinity brain-specific ArfGAP1, which bind Rabex-5. AP-1/σ1A-ArfGAP1-Rabex-5 complex formation leads to more endosomal Rabex-5 and enhanced, Rab5GTP-stimulated Vps34 PI3-kinase activity, which is essential for multivesicular body endosome formation. Formation of AP-1/σ1A-ArfGAP1-Rabex-5 complexes is prevented by σ1B binding of Rabex-5 and the amount of endosomal Rabex-5 is reduced. AP-1 complexes differentially regulate endosome maturation and coordinate protein recycling and degradation, revealing a novel molecular mechanism by which they regulate protein transport besides their established function in clathrin-coated-vesicle formation. PMID:27411398

  2. AP-1/σ1A and AP-1/σ1B adaptor-proteins differentially regulate neuronal early endosome maturation via the Rab5/Vps34-pathway.

    PubMed

    Candiello, Ermes; Kratzke, Manuel; Wenzel, Dirk; Cassel, Dan; Schu, Peter

    2016-07-14

    The σ1 subunit of the AP-1 clathrin-coated-vesicle adaptor-protein complex is expressed as three isoforms. Tissues express σ1A and one of the σ1B and σ1C isoforms. Brain is the tissue with the highest σ1A and σ1B expression. σ1B-deficiency leads to severe mental retardation, accumulation of early endosomes in synapses and fewer synaptic vesicles, whose recycling is slowed down. AP-1/σ1A and AP-1/σ1B regulate maturation of these early endosomes into multivesicular body late endosomes, thereby controlling synaptic vesicle protein transport into a degradative pathway. σ1A binds ArfGAP1, and with higher affinity brain-specific ArfGAP1, which bind Rabex-5. AP-1/σ1A-ArfGAP1-Rabex-5 complex formation leads to more endosomal Rabex-5 and enhanced, Rab5(GTP)-stimulated Vps34 PI3-kinase activity, which is essential for multivesicular body endosome formation. Formation of AP-1/σ1A-ArfGAP1-Rabex-5 complexes is prevented by σ1B binding of Rabex-5 and the amount of endosomal Rabex-5 is reduced. AP-1 complexes differentially regulate endosome maturation and coordinate protein recycling and degradation, revealing a novel molecular mechanism by which they regulate protein transport besides their established function in clathrin-coated-vesicle formation.

  3. Unsaturated fatty acids and phytosterols regulate cholesterol transporter genes in Caco-2 and HepG2 cell lines.

    PubMed

    Park, Youngki; Carr, Timothy P

    2013-02-01

    Dietary consumption of phytosterols and certain fatty acids has been shown to reduce cholesterol absorption and plasma cholesterol concentrations. However, it has not been fully elucidated whether phytosterols or fatty acids can alter the expression of cholesterol transporters by functioning as signaling molecules. This study tested the hypothesis that various fatty acids and phytosterols commonly found in the food supply can modulate the expression of transporters including Niemann-Pick C1-like 1, low-density lipoprotein receptor, and scavenger receptor class B type I and 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the intestine and liver. Caco-2 cells were used as models of enterocytes, and HepG2 cells were used as a model of hepatocytes. The cells were treated for 18 hours with 100 μmol/L of a fatty acid, or for 24 hours with 10 μmol/L of 25α-hydroxycholesterol, or 100 μmol/L of cholesterol, sitosterol, and stigmasterol to measure expression of genes involved in cholesterol transport using quantitative real-time polymerase chain reaction. Polyunsaturated fatty acids in Caco-2 cells and sterols in HepG2 cells significantly reduced the messenger RNA expression levels of Niemann-Pick C1-like 1, scavenger receptor class B type I, low-density lipoprotein receptor, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Importantly, sitosterol and stigmasterol reduced the messenger RNA levels of genes to a similar extent as cholesterol. The data support the hypothesis that unsaturated fatty acid and phytosterols can act as signaling molecules and alter the expression of genes involved in cholesterol transport and metabolism.

  4. AP-2α and AP-2β regulate dorsal interneuron specification in the spinal cord.

    PubMed

    Xu, Xiaofeng; Liu, Zijing; Huang, Hao; Zheng, Kang; Hu, Xuemei; Zhang, Zunyi; Qiu, Mengsheng

    2017-01-06

    To date, five AP-2 genes that encode AP-2α, β, γ, δ and ε have been identified in vertebrates and they have been reported to be key regulators of embryonic development. However, the role of AP-2 family members in the development of central nervous system (CNS) has not been characterized. In the present study, we systematically examined the spatiotemporal expression pattern of AP-2 genes in the developing spinal cord of mouse and chick embryos and found that AP-2α and AP-2β are specifically expressed in post-mitotic dorsal interneurons. Loss-of-function analysis using in ovo electroporation in embryonic chick spinal cord preliminarily demonstrated that cAP-2α and cAP-2β regulates dorsal Class A and Class B interneuron specification, respectively. Gain-of-function experiments further revealed that misexpression of cAP-2α, but not cAP-2β, was able to induce the ectopic generation of Class A interneurons. Together, our studies indicated that AP-2 family members, AP-2α and AP-2β, have distinct functions in the regulation of dorsal interneuron development.

  5. BioCAT undulator beamline at APS

    NASA Astrophysics Data System (ADS)

    Bunker, G. B.; Irving, T.; Black, E.; Zhang, K.; Fischetti, R.; Wang, S.; Stepanov, S.

    1997-07-01

    The Biophysics Collaborative Access Team (BioCAT) project will be an outstanding research facility for biological small angle scattering, non-crystalline diffraction, and x-ray absorption spectroscopy at the Advanced Photon Source, Argonne National Labs. BioCAT operates as an NIH Research Resource under a cooperative agreement with NIH. BioCat has an aggressive program of core and collaborative research, service, and training. Central to the facility is the undulator beam line (designed by G. Rosenbaum, Argonne National Labs) capable of delivering ca. 1013-1014 ph/s to the sample. Focusing optics will allow focal spot ranges from 1.5×3.5 mm to 30×80 micron, independently adjustable in the vertical and horizontal direction. Up to 8 m camera lengths can be accommodated in the 12m experimental enclosure. The accessible beam energy range will be from 3.5-13 keV using the undulator fundamental and 10-40 keV using the third harmonic. Energy resolution will exceed 2×10-4 ΔE/E. Detectors will include image plates, CCD detectors and some novel detectors designed to accommodate the high count rates expected at the APS. The multi-element detector will be a very high count-rate (up to 109 ph/s global), one dimensional detector optimized for scattering applications. We are also developing a multilayer analyzer detector which maximizes solid angle of collection with high background rejection for biological spectroscopy applications.

  6. Electron stripping processes of H- ion beam in the 80 kV high voltage extraction column and low energy beam transport line at LANSCE

    NASA Astrophysics Data System (ADS)

    Draganic, I. N.

    2016-02-01

    Basic vacuum calculations were performed for various operating conditions of the Los Alamos National Neutron Science H- Cockcroft-Walton (CW) injector and the Ion Source Test Stand (ISTS). The vacuum pressure was estimated for both the CW and ISTS at five different points: (1) inside the H- ion source, (2) in front of the Pierce electrode, (3) at the extraction electrode, (4) at the column electrode, and (5) at the ground electrode. A static vacuum analysis of residual gases and the working hydrogen gas was completed for the normal ion source working regime. Gas density and partial pressure were estimated for the injected hydrogen gas. The attenuation of H- beam current and generation of electron current in the high voltage acceleration columns and low energy beam transport lines were calculated. The interaction of H- ions on molecular hydrogen (H2) is discussed as a dominant collision process in describing electron stripping rates. These results are used to estimate the observed increase in the ratio of electrons to H- ion beam in the ISTS beam transport line.

  7. Electron stripping processes of H{sup −} ion beam in the 80 kV high voltage extraction column and low energy beam transport line at LANSCE

    SciTech Connect

    Draganic, I. N.

    2016-02-15

    Basic vacuum calculations were performed for various operating conditions of the Los Alamos National Neutron Science H{sup −} Cockcroft-Walton (CW) injector and the Ion Source Test Stand (ISTS). The vacuum pressure was estimated for both the CW and ISTS at five different points: (1) inside the H{sup −} ion source, (2) in front of the Pierce electrode, (3) at the extraction electrode, (4) at the column electrode, and (5) at the ground electrode. A static vacuum analysis of residual gases and the working hydrogen gas was completed for the normal ion source working regime. Gas density and partial pressure were estimated for the injected hydrogen gas. The attenuation of H{sup −} beam current and generation of electron current in the high voltage acceleration columns and low energy beam transport lines were calculated. The interaction of H{sup −} ions on molecular hydrogen (H{sub 2}) is discussed as a dominant collision process in describing electron stripping rates. These results are used to estimate the observed increase in the ratio of electrons to H{sup −} ion beam in the ISTS beam transport line.

  8. AP-2α-dependent regulation of Bcl-2/Bax expression affects apoptosis in the trophoblast.

    PubMed

    Zhang, Ling; Jia, Liting; Cui, Shihong; Shi, Ying; Chang, Aimin; Wang, Peng; Zhang, Zhan

    2012-12-01

    Enhanced apoptosis of the cytotrophoblast in early pregnancy is associated with a high risk of preeclampsia. We and others have previously reported that the transcriptional factor, activator protein AP-2α, suppressed trophoblast migration and invasion. However, it is not clear whether AP-2α affects apoptosis in trophoblast cells and whether it regulates expression of apoptosis-related factors Bcl-2 and Bax. We analyzed the expression of AP-2α, Bcl-2 and Bax in placental tissues in severe preeclamptic pregnancies and normotensive pregnancies using immunohistochemistry and real time-PCR. Further, apoptosis was assessed by flow cytometric analysis in the human trophoblastic cell line, BeWo cells, in which AP-2α expression was transiently overexpressed or down-regulated by siRNA. There was significantly higher expression of AP-2α and Bax, but lower expression of Bcl-2 in severe preeclampsia placentas as compared to the control placentas. Overexpression of AP-2α in BeWo cells led to an increased rate of apoptosis, whereas apoptosis was decreased when AP-2α expression was reduced. Furthermore, overexpression of AP-2α increased Bax expression and decreased Bcl-2 expression, whereas down-regulation of AP-2α expression resulted in a decrease in Bax expression and an increase in Bcl-2 expression. AP-2α regulates expression of Bcl-2 and Bax and apoptosis in BeWo cells. These results suggest that AP-2α-mediated regulation of Bcl-2 and Bax regulation influences apoptosis which in turn leads to the pathogenesis of preeclampsia.

  9. APS undulator radiation: First results

    SciTech Connect

    Cai, Z.; Dejus, R.J.; Hartog, P.D.

    1995-12-31

    The first undulator radiation has been extracted from the Advanced Photon Source (APS). The results from the characterization of this radiation are very satisfactory. With the undulator set at a gap of 15.8 mm (K=1.61), harmonics as high as the 17th were observed using a crystal spectrometer. The angular distribution of the third-harmonic radiation was measured, and the source was imaged using a zone plate to determine the particle beam emittance. The horizontal beam emittance was found to be 6.9 {plus_minus} 1.0 nm-rad, and the vertical emittance coupling was found to be less than 3%. The absolute spectral flux was measured over a wide range of photon energies, and it agrees remarkably well with the theoretical calculations based on the measured undulator magnetic field profile and the measured beam emittance. These results indicate that both the emittance of the electron beam and the undulator magnetic field quality exceed the original specifications.

  10. AE8/AP8 Implementations in AE9/AP9, IRBEM, and SPENVIS

    DTIC Science & Technology

    2014-02-18

    radiation belt model, SHIELDOSE, AE8/AP8 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE...a wide range of locations within the radiation belts . The new AE9/AP9 model application includes the ability to query the legacy AE8 and AP8 models...trapped particle fluxes with the NASA models AP-8 and AE-8, Radiat . Meas., 26, pp. 947-952. International Association of Geomagnetism and Aeronomy

  11. Glutathione peroxidase-1 inhibits UVA-induced AP-2{alpha} expression in human keratinocytes

    SciTech Connect

    Yu Lei; Venkataraman, Sujatha; Coleman, Mitchell C.; Spitz, Douglas R.; Wertz, Philip W.; Domann, Frederick E. . E-mail: frederick-domann@uiowa.edu

    2006-12-29

    In this study, we found a role for H{sub 2}O{sub 2} in UVA-induced AP-2{alpha} expression in the HaCaT human keratinocyte cell line. UVA irradiation not only increased AP-2{alpha}, but also caused accumulation of H{sub 2}O{sub 2} in the cell culture media, and H{sub 2}O{sub 2} by itself could induce the expression of AP-2{alpha}. By catalyzing the removal of H{sub 2}O{sub 2} from cells through over-expression of GPx-1, induction of AP-2{alpha} expression by UVA was abolished. Induction of transcription factor AP-2{alpha} by UVA had been previously shown to be mediated through the second messenger ceramide. We found that not only UVA irradiation, but also H{sub 2}O{sub 2} by itself caused increases of ceramide in HaCaT cells, and C2-ceramide added to cells induced the AP-2{alpha} signaling pathway. Finally, forced expression of GPx-1 eliminated UVA-induced ceramide accumulation as well as AP-2{alpha} expression. Taken together, these findings suggest that GPx-1 inhibits UVA-induced AP-2{alpha} expression by suppressing the accumulation of H{sub 2}O{sub 2}.

  12. [Transplacental transport mechanisms of drugs for transplacental treatment of fetal tachyarrhythmia of MDCKII/MDCKII-BCRP cell line].

    PubMed

    Wang, Wei; Zhao, Jia-jia; Wang, Ting; Wang, Ling; Jiang, Xue-hua

    2015-03-01

    To study the transport mechanisms of drugs for transplacental treatment of fetal tachyarrhythmia, MDCKII-BCRP and MDCKII cell models was used. MDCKII-BCRP and MDCKII cell monolayer model was used to investigate the bi-direction transport of sotalol, propranolol, propafenone, procainamide and flecainide. Drug concentrations were measured by HPLC-UV or chemiluminescence. The apparent permeability coefficient (P(app)), efflux rate (R(E)) and net efflux rate (R(net)) were calculated. Drugs with R(net) greater than 1.5 were further investigated using cellular accumulation experiments with or without a BCRP inhibitor. The R(net) of sotalol, propranolol, propafenone and procainamide were less than 1.5, while R(net) of flecainide with concentrations of 20 and 5 μmol x L(-1) were 1.6 and 1.9, respectively. The results showed that the transport of flecainide on MDCKII-BCRP cell monolayer could be mediated by BCRP; and the affinity increased when the concentration of flecainide decreased. Cellular accumulation experiments further suggested that accumulation of flecainide in MDCKII-BCRP cells was significantly lower than that in MDCKII cells in a concentration-dependent manner. BCRP inhibitor quercetin (50 μmol x L(-1)) significantly increased the accumulation of flecainide in MDCKII-BCRP cells (P < 0.05). Our preliminary data showed that flecainide but not sotalol, propranolol, propafenone or procainamide can be a substrate of BCRP. Thus the effect of flecainide may be affected by the BCRP in the maternal placental trophoblast membrane layer when treating fetal tachyarrhythmia.

  13. Single-Bunch Electron Cloud Effects in the GLC/NLC, US-Cold and TESLA Low Emittance Transport Lines

    SciTech Connect

    Bates, D.

    2005-04-12

    This paper examines the severity of the electron cloud effects in the Low Emittance Transport (LET) of linear colliders including the Bunch-Compressor System (BCS) and Beam Delivery System (BDS). We examine the electron cloud effects in the normal-conducting GLC/NLC or X-Band, and the super-conducting US-Cold and TESLA linear collider designs through the use of specially developed computer simulation codes. An estimate of the critical cloud density is given for the BDS and BCS of the X-Band collider.

  14. AP Courses Get Audited for Quality

    ERIC Educational Resources Information Center

    Ashford, Ellie

    2007-01-01

    As the college admissions process has gotten much more competitive, the number of high school students taking Advanced Placement (AP) courses has soared. At the same time, policymakers and education leaders seek to get more minorities and students not on the college track to sign up for AP and other rigorous classes. But as high schools have…

  15. AP Music Theory in Your School.

    ERIC Educational Resources Information Center

    Lucia, Raymond

    1993-01-01

    Asserts that an Advanced Placement (AP) course in music theory offers student musicians opportunities to gain new insight into melody, harmony, and structure. Describes content and teaching methods used in an AP music theory program. Discusses necessary teacher characteristics and maintains that both students and teachers benefit from the course.…

  16. Resources for AP United States History.

    ERIC Educational Resources Information Center

    Ennis, Rosemary

    1999-01-01

    Discusses resources that can be used in an Advanced Placement (AP) U.S. history course, including a series of textbooks, supplemental readings, projects, Document-Based Questions and essays from earlier AP examinations, Internet and multimedia resources, and students and their families. (CMK)

  17. Advanced APS Impacts on Vehicle Payloads

    NASA Technical Reports Server (NTRS)

    Schneider, Steven J.; Reed, Brian D.

    1989-01-01

    Advanced auxiliary propulsion system (APS) technology has the potential to both, increase the payload capability of earth-to-orbit (ETO) vehicles by reducing APS propellant mass, and simplify ground operations and logistics by reducing the number of fluids on the vehicle and eliminating toxic, corrosive propellants. The impact of integrated cryogenic APS on vehicle payloads is addressed. In this system, launch propulsion system residuals are scavenged from integral launch propulsion tanks for use in the APS. Sufficient propellant is preloaded into the APS to return to earth with margin and noncomplete scavenging assumed. No propellant conditioning is required by the APS, but ambient heat soak is accommodated. High temperature rocket materials enable the use of the unconditioned hydrogen/oxygen in the APS and are estimated to give APS rockets specific impulse of up to about 444 sec. The payload benefits are quantified and compared with an uprated monomethyl hydrazine/nitrogen tetroxide system in a conservative fashion, by assuming a 25.5 percent weight growth for the hydrogen/oxygen system and a 0 percent weight growth for the uprated system. The combination and scavenging and high performance gives payload impacts which are highly mission specific. A payload benefit of 861 kg (1898 lbm) was estimated for a Space Station Freedom rendezvous mission and 2099 kg (4626 lbm) for a sortie mission, with payload impacts varying with the amount of launch propulsion residual propellants. Missions without liquid propellant scavenging were estimated to have payload penalties, however, operational benefits were still possible.

  18. Coaching Strategies for AP: Building a Successful AP European History Program

    ERIC Educational Resources Information Center

    Fornaciari, Jim

    2014-01-01

    The October 2013 special issue of "Social Education" dealt with almost all AP social studies subjects, but omitted AP European History. This is one of the most fascinating AP subjects for students and teachers alike. In this article, the author shares his experiences since hewas given the responsibility of building his school's Advanced…

  19. A gas-jet transport and catcher technique for on-line production of radioactive ion beams using an electron cyclotron resonance ion-source.

    PubMed

    Naik, V; Chakrabarti, A; Bhattacharjee, M; Karmakar, P; Bandyopadhyay, A; Bhattacharjee, S; Dechoudhury, S; Mondal, M; Pandey, H K; Lavanyakumar, D; Mandi, T K; Dutta, D P; Kundu Roy, T; Bhowmick, D; Sanyal, D; Srivastava, S C L; Ray, A; Ali, Md S

    2013-03-01

    Radioactive ion beams (RIB) have been produced on-line, using a gas-jet recoil transport coupled Electron Cyclotron Resonance (ECR) ion-source at the VECC-RIB facility. Radioactive atoms∕molecules carried through the gas-jet were stopped in a catcher placed inside the ECR plasma chamber. A skimmer has been used to remove bulk of the carrier gas at the ECR entrance. The diffusion of atoms∕molecules through the catcher has been verified off-line using stable isotopes and on-line through transmission of radioactive reaction products. Beams of (14)O (71 s), (42)K (12.4 h), (43)K (22.2 h), and (41)Ar (1.8 h) have been produced by bombarding nitrogen and argon gas targets with proton and alpha particle beams from the K130 cyclotron at VECC. Typical measured intensity of RIB at the separator focal plane is found to be a few times 10(3) particles per second (pps). About 3.2 × 10(3) pps of 1.4 MeV (14)O RIB has been measured after acceleration through a radiofrequency quadrupole linac. The details of the gas-jet coupled ECR ion-source and RIB production experiments are presented along with the plans for the future.

  20. Field-Lines-Threaded Model for: (1) the Low Solar Corona; (2) Electrons in the Transition Region; and (3) Solar Energetic Particle Acceleration and Transport

    NASA Astrophysics Data System (ADS)

    Sokolov, I.; van der Holst, B.; Jin, M.; Gombosi, T. I.; Taktakishvili, A.; Khazanov, G. V.

    2013-12-01

    In numerical simulations of the solar corona, both for the ambient state and especially for dynamical processes the most computational resources are spent for maintaining the numerical solution in the Low Solar Corona and in the transition region, where the temperature gradients are very sharp and the magnetic field has a complicated topology. The degraded computational efficiency is caused by the need in a highest resolution as well as the use of the fully three-dimensional implicit solver for electron heat conduction. On the other hand, the physical nature of the processes involved is rather simple (which still does not facilitate the numerical methods) as long as the heat fluxes as well as slow plasma motional velocities are aligned with the magnetic field. The Alfven wave turbulence, which is often believed to be the main driver of the solar wind and the main source of the coronal heating, is characterized by the Poynting flux of the waves, which is also aligned with the magnetic field. Therefore, the plasma state in any point of the three-dimensional grid in the Low Solar Corona can be found by solving a set of one-dimensional equations for the magnetic field line ('thread'), which passes through this point and connects it to the chromosphere and to the global Solar Corona. In the present paper we describe an innovative computational technology based upon the use of the magnetic-field-line-threads to find the local solution. We present the development of the AWSoM code of the University of Michigan with the field-lines-threaded Low Solar Corona. In the transition region, where the essentially kinetic description of the electron energy fluxes is required, we solve the Fokker-Plank equation on the system of threads, to achieve the physically consistent description of chromosphere evaporation. The third application for the field-lines-treaded model is the Solar Energetic Particle (SEP) acceleration and transport. Being the natural extension of the Field-Line

  1. ELECTROCHEMICAL CORROSION TESTING OF TANKS 241-AN-102 & 241-AP-107 & 241-AP-108 IN SUPPORT OF ULTRASONIC TESTING

    SciTech Connect

    WYRWAS RB; DUNCAN JB

    2008-11-20

    This report presents the results of the corrosion rates that were measured using electrochemical methods for tanks 241-AN-102 (AN-102), 241-AP-107 (AP 107), and 241-AP-108 (AP-108) performed under test plant RPP-PLAN-38215. The steel used as materials of construction for AN and AP tank farms was A537 Class 1. Test coupons of A537 Class 1 carbon steel were used for corrosion testing in the AN-107, AP-107, and AP-108 tank waste. Supernate will be tested from AN-102, AP-107, and Ap-108. Saltcake testing was performed on AP-108 only.

  2. The cell line NCl-H441 is a useful in vitro model for transport studies of human distal lung epithelial barrier.

    PubMed

    Salomon, Johanna J; Muchitsch, Viktoria E; Gausterer, Julia C; Schwagerus, Elena; Huwer, Hanno; Daum, Nicole; Lehr, Claus-Michael; Ehrhardt, Carsten

    2014-03-03

    The lack of a well characterized, continuously growing in vitro model of human distal lung epithelial phenotype constitutes a serious limitation in the area of inhalation biopharmaceutics, particularly in the context of transepithelial transport studies. Here, we investigated if a human lung adenocarcinoma cell line, NCl-H441, has potential to serve as an in vitro model of human distal lung epithelium. The development of barrier properties was studied by immunocytochemistry (ICC) against the junction proteins zonula occludens protein 1 (ZO-1) and E-cadherin and measurement of transepithelial electrical resistance (TEER). Moreover, transport studies with the paracellular marker compounds fluorescein sodium and fluorescein isothiocyanate (FITC)-labeled dextrans of molecular weights ranging from 4 to 70 kDa were carried out. The expression of P-glycoprotein (P-gp; ABCB1) and organic cation transporters (OCT/Ns; SLC22A1-A5) was investigated by ICC and immunoblot. P-gp function was assessed by monolayer release and bidirectional transport studies using rhodamine 123 (Rh123) and the inhibitors verapamil and LY335979. Uptake of 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+)) was measured, in order to assess organic cation transporter function in vitro. Furthermore, the inhibitory potential of several organic cations on ASP(+) uptake was studied. NCl-H441 cells, when grown under liquid-covered conditions, formed confluent, electrically tight monolayers with peak TEER values of approximately 1000 Ω·cm(2), after 8-12 days in culture. These monolayers were able to differentiate paracellularly transported substrates according to their molecular weight. Presence of P-gp, OCT1, OCT2, OCT3, OCTN1, and OCTN2 was confirmed by Western blot and ICC and was similar to data from freshly isolated human alveolar epithelial cells in primary culture. Rh123 release from NCI-H441 monolayers was time-dependent and showed low, albeit significant attenuation by both inhibitors

  3. Auxin Transport and Ribosome Biogenesis Mutant/Reporter Lines to Study Plant Cell Growth and Proliferation under Altered Gravity

    NASA Astrophysics Data System (ADS)

    Valbuena, Miguel A.; Manzano, Ana I.; van Loon, Jack JWA.; Saez-Vasquez, Julio; Carnero-Diaz, Eugenie; Herranz, Raul; Medina, F. J.

    2013-02-01

    We tested different Arabidopsis thaliana strains to check their availability for space use in the International Space Station (ISS). We used mutants and reporter gene strains affecting factors of cell proliferation and cell growth, to check variations induced by an altered gravity vector. Seedlings were grown either in a Random Positioning Machine (RPM), under simulated microgravity (μg), or in a Large Diameter Centrifuge (LDC), under hypergravity (2g). A combination of the two devices (μgRPM+LDC) was also used. Under all gravity alterations, seedling roots were longer than in control 1g conditions, while the levels of the nucleolar protein nucleolin were depleted. Alterations in the pattern of expression of PIN2, an auxin transporter, and of cyclin B1, a cell cycle regulator, were shown. All these alterations are compatible with previous space data, so the use of these strains will be useful in the next experiments in ISS, under real microgravity.

  4. The Role of Monocarboxylate Transporters and Their Chaperone CD147 in Lactate Efflux Inhibition and the Anticancer Effects of Terminalia chebula in Neuroblastoma Cell Line N2-A

    PubMed Central

    Messeha, S. S.; Zarmouh, N. O.; Taka, E.; Gendy, S. G.; Shokry, G. R.; Kolta, M. G.; Soliman, K. F. A.

    2016-01-01

    Aims In the presence of oxygen, most of the synthesized pyruvate during glycolysis in the cancer cell of solid tumors is released away from the mitochondria to form lactate (Warburg Effect). To maintain cell homeostasis, lactate is transported across the cell membrane by monocarboxylate transporters (MCTs). The major aim of the current investigation is to identify novel compounds that inhibit lactate efflux that may lead to identifying effective targets for cancer treatment. Study Design In this study, 900 ethanol plant extracts were screened for their lactate efflux inhibition using neuroblastoma (N2-A) cell line. Additionally, we investigated the mechanism of inhibition for the most potent plant extract regarding monocarboxylate transporters expression, and consequences effects on viability, growth, and apoptosis. Methodology The potency of lactate efflux inhibition of ethanol plant extracts was evaluated in N2-A cells by measuring extracellular lactate levels. Caspase 3- activity and acridine orange/ethidium bromide staining were performed to assess the apoptotic effect. The antiproliferative effect was measured using WST assay. Western blotting was performed to quantify protein expression of MCTs and their chaperone CD147 in treated cells lysates. Results Terminalia chebula plant extract was the most potent lactate efflux inhibitor in N2-A cells among the 900 - tested plant extracts. The results obtained show that extract of Terminalia chebula fruits (TCE) significantly (P = 0.05) reduced the expression of the MCT1, MCT3, MCT4 and the chaperone CD147. The plant extract was more potent (IC50 of 3.59 ± 0.26 μg/ml) than the MCT standard inhibitor phloretin (IC50 76.54 ± 3.19 μg/ml). The extract also showed more potency and selective cytotoxicity in cancer cells than DI-TNC1 primary cell line (IC50 7.37 ± 0.28 vs. 17.35 ± 0.19 μg/ml). Moreover, TCE Inhibited N2-A cell growth (IG50 = 5.20 ± 0.30 μg/ml) and induced apoptosis at the 7.5 μg/ml concentration

  5. Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly

    PubMed Central

    Hardies, Katia; May, Patrick; Djémié, Tania; Tarta-Arsene, Oana; Deconinck, Tine; Craiu, Dana; Helbig, Ingo; Suls, Arvid; Balling, Rudy; Weckhuysen, Sarah; De Jonghe, Peter; Hirst, Jennifer; Afawi, Zaid; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Depienne, Christel; De Kovel, Carolien G.F.; Dimova, Petia; Guerrero-López, Rosa; Guerrini, Renzo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jahn, Johanna; Klein, Karl Martin; Koeleman, Bobby P.C.; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes; Lerche, Holger; Marini, Carla; Muhle, Hiltrud; Rosenow, Felix; Serratosa, Jose M.; Møller, Rikke S.; Stephani, Ulrich; Striano, Pasquale; Talvik, Tiina; Von Spiczak, Sarah; Weber, Yvonne; Zara, Federico

    2015-01-01

    We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.Gln46Profs*9 and p.Arg97*) was further investigated in a patient's fibroblast cell line. We show that the premature stop mutations in AP4S1 result in a reduction of all AP-4 subunits and loss of AP-4 complex assembly. Recruitment of the AP-4 accessory protein tepsin, to the membrane was also abolished. In retrospect, the clinical phenotype in the family is consistent with previous reports of the AP-4 deficiency syndrome. Our study reports the second family with mutations in AP4S1 and describes the first two patients with loss of AP4S1 and seizures. We further discuss seizure phenotypes in reported patients, highlighting that seizures are part of the clinical manifestation of the AP-4 deficiency syndrome. We also hypothesize that endosomal trafficking is a common theme between heritable spastic paraplegia and some inherited epilepsies. PMID:25552650

  6. Development of the AP Technology Through Time

    NASA Astrophysics Data System (ADS)

    Charmier, F.; Martin, O.; Gariepy, R.

    2015-02-01

    This article presents the historical development of the AP Technology (Aluval, Voreppe, France) pot series starting with the AP13 in the 1960s, followed by the AP18 and the AP30 in the 1980s and 1990s. For most of the modern-era technology, from the late 1970s on, development has been based on a three-stage pattern, the first one being the pot modeling, followed by the pot prototype stage, and then the industrial stage, which fully validated the technology. This development pattern has proven to be successful since it has led to the very robust AP Technology pot design generation and a large number of greenfield smelters built in the 1990-2010 selected the AP Technology design. AP60 is the latest of this series: The development at the prototype level was initiated in the 1990s and is presented in the article. It is now followed by the first industrial realization at Jonquière with the startup in late 2013 and the full validation of the technology in mid-2014. The development of APXe, which aims at very low energy consumption, uses many common elements pertaining to the AP60 design and is presented in the article. AP Technology has also addressed the need for continuous and fast improvement of pot performances adapted to each existing client or site specifics; for this purpose, a new development methodology has recently emerged thanks to the very high modeling capabilities. This methodology, based on the validation of "technology bricks" and their integration in the final design following a strict process, is presented in the last section of this article.

  7. 46 CFR 171.015 - Location of margin line.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (FP) and the after perpendicular (AP) is at least 12 inches (30.5 cm), the margin line must be located... Figure 171.015(a). Table 171.015 Average value of sheer at FP and AP in inches (cm) Required position of... the sheer at the forward perpendicular (FP) and the after perpendicular (AP) is less than 12...

  8. 46 CFR 171.015 - Location of margin line.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (FP) and the after perpendicular (AP) is at least 12 inches (30.5 cm), the margin line must be located... Figure 171.015(a). Table 171.015 Average value of sheer at FP and AP in inches (cm) Required position of... the sheer at the forward perpendicular (FP) and the after perpendicular (AP) is less than 12...

  9. 46 CFR 171.015 - Location of margin line.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (FP) and the after perpendicular (AP) is at least 12 inches (30.5 cm), the margin line must be located... Figure 171.015(a). Table 171.015 Average value of sheer at FP and AP in inches (cm) Required position of... the sheer at the forward perpendicular (FP) and the after perpendicular (AP) is less than 12...

  10. 46 CFR 171.015 - Location of margin line.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (FP) and the after perpendicular (AP) is at least 12 inches (30.5 cm), the margin line must be located... Figure 171.015(a). Table 171.015 Average value of sheer at FP and AP in inches (cm) Required position of... the sheer at the forward perpendicular (FP) and the after perpendicular (AP) is less than 12...

  11. 46 CFR 171.015 - Location of margin line.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (FP) and the after perpendicular (AP) is at least 12 inches (30.5 cm), the margin line must be located... Figure 171.015(a). Table 171.015 Average value of sheer at FP and AP in inches (cm) Required position of... the sheer at the forward perpendicular (FP) and the after perpendicular (AP) is less than 12...

  12. Interaction of amphiphysins with AP-1 clathrin adaptors at the membrane.

    PubMed

    Huser, Sonja; Suri, Gregor; Crottet, Pascal; Spiess, Martin

    2013-02-15

    The assembly of clathrin/AP (adaptor protein)-1-coated vesicles on the trans-Golgi network and endosomes is much less studied than that of clathrin/AP-2 vesicles at the plasma membrane for endocytosis. In vitro, the association of AP-1 with protein-free liposomes had been shown to require phosphoinositides, Arf1 (ADP-ribosylation factor 1)-GTP and additional cytosolic factor(s). We have purified an active fraction from brain cytosol and found it to contain amphiphysin 1 and 2 and endophilin A1, three proteins known to be involved in the formation of AP-2/clathrin coats at the plasma membrane. Assays with bacterially expressed and purified proteins showed that AP-1 stabilization on liposomes depends on amphiphysin 2 or the amphiphysin 1/2 heterodimer. Activity is independent of the SH3 (Src homology 3) domain, but requires interaction of the WDLW motif with γ-adaptin. Endogenous amphiphysin in neurons and transfected protein in cell lines co-localize perinuclearly with AP-1 at the trans-Golgi network. This localization depends on interaction of clathrin and the adaptor sequence in the amphiphysins and is sensitive to brefeldin A, which inhibits Arf1-dependent AP-1 recruitment. Interaction between AP-1 and amphiphysin 1/2 in vivo was demonstrated by co-immunoprecipitation after cross-linking. These results suggest an involvement of amphiphysins not only with AP-2 at the plasma membrane, but also in AP-1/clathrin coat formation at the trans-Golgi network.

  13. Tank 241-AP-107, grab samples, 7AP-99-1, 7AP-99-3 and 7AP-99-4 analytical results for the final report

    SciTech Connect

    BELL, K.E.

    1999-08-12

    This document is the format IV, final report for the tank 241-AP-107 (AP-107) grab samples taken in May 1999 to address waste compatibility concerns. Chemical, radiochemical, and physical analyses on the tank AP-107 samples were performed as directed in Compatibility Grab Sampling and Analysis Plan for Fiscal year 1999. Any deviations from the instructions provided in the tank sampling and analysis plan (TSAP) were discussed in this narrative. Interim data were provided earlier to River Protection Project (RPP) personnel, however, the data presented here represent the official results. No notification limits were exceeded.

  14. Microcystin-LR induces anoikis resistance to the hepatocyte uptake transporter OATP1B3-expressing cell lines.

    PubMed

    Takano, Hiroyuki; Takumi, Shota; Ikema, Satoshi; Mizoue, Nozomi; Hotta, Yuki; Shiozaki, Kazuhiro; Sugiyama, Yasumasa; Furukawa, Tatsuhiko; Komatsu, Masaharu

    2014-12-04

    Microcystin-LR is a cyclic peptide released by several bloom-forming cyanobacteria. Understanding the mechanism of microcystin-LR toxicity is important, because of the both potencies of its acute cytotoxicity and tumor-promoting activity in hepatocytes of animals and humans. Recently, we have reported that the expression of human hepatocyte uptake transporter OATP1B3 was critical for the selective uptake of microcystin-LR into hepatocytes and for induction of its fatal cytotoxicity. In this study, we demonstrated a novel function of microcystin-LR which induced bipotential changes including anoikis resistance and cytoskeleton reorganization to OATP1B3-transfected HEK293 cells (HEK293-OATP1B3). After exposure to microcystin-LR, HEK293-OATP1B3 cells were divided to the floating cells and remaining adherent cells. After collection and reseeding the floating cells into a fresh flask, cells were confluently proliferated (HEK293-OATP1B3-FL) under the microcystin-LR-free condition. Both the proliferated HEK293-OATP1B3-FL and remaining adherent HEK293-OATP1B3-AD cells changed the character with down- and up-regulation of E-cadherin, respectively. Additionally, these cells acquired resistance to microcystin-LR. These results suggest that microcystin-LR could be associated with not only tumor promotion, but also epithelial-mesenchymal transition-mediated cancer metastasis. Furthermore, microcystin-LR might induce the cytoskeleton reorganization be accompanied epithelial-mesenchymal transition.

  15. Wave-particle interaction in parallel transport of long mean-free-path plasmas along open field magnetic field lines

    NASA Astrophysics Data System (ADS)

    Guo, Zehua; Tang, Xianzhu

    2012-03-01

    A tokamak fusion reactor dumps a large amount of heat and particle flux to the divertor through the scrape-off plasma (SOL). Situation exists either by necessity or through deliberate design that the SOL plasma attains long mean-free-path along large segments of the open field lines. The rapid parallel streaming of electrons requires a large parallel electric field to maintain ambipolarity. The confining effect of the parallel electric field on electrons leads to a trap/passing boundary in the velocity space for electrons. In the normal situation where the upstream electron source populates both the trapped and passing region, a mechanism must exist to produce a flux across the electron trap/passing boundary. In a short mean-free-path plasma, this is provided by collisions. For long mean-free-path plasmas, wave-particle interaction is the primary candidate for detrapping the electrons. Here we present simulation results and a theoretical analysis using a model distribution function of trapped electrons. The dominating electromagnetic plasma instability and the associated collisionless scattering, that produces both particle and energy fluxes across the electron trap/passing boundary in velocity space, are discussed.

  16. Sodium-bicarbonate cotransporter NBCn1 in the kidney medullary thick ascending limb cell line is upregulated under acidic conditions and enhances ammonium transport.

    PubMed

    Lee, Soojung; Lee, Hye Jeong; Yang, Han Soo; Thornell, Ian M; Bevensee, Mark O; Choi, Inyeong

    2010-09-01

    In this study, we examined the effect of bicarbonate transporters on ammonium/ammonia uptake in the medullary thick ascending limb cell line ST-1. Cells were treated with 1 mm ouabain and 0.2 mM bumetanide to minimize carrier-mediated NH(4)(+) transport, and the intracellular accumulation of (14)C-methylammonium/methylammonia ((14)C-MA) was determined. In CO(2)/HCO(3)(-)-free solution, cells at normal pH briefly accumulated (14)C-MA over 7 min and reached a plateau. In CO(2)/HCO(3)(-) solution, however, cells markedly accumulated (14)C-MA over the experimental period of 30 min. This CO(2)/HCO(3)(-)-dependent accumulation was reduced by the bicarbonate transporter blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonate (DIDS; 0.5 mM). Replacing Cl(-) with gluconate reduced the accumulation, but the reduction was more substantial in the presence of DIDS. Incubation of cells at pH 6.8 (adjusted with NaHCO(3) in 5% CO(2)) for 24 h lowered the mean steady-state intracellular pH to 6.96, significantly lower than 7.28 for control cells. The presence of DIDS reduced (14)C-MA accumulation in control conditions but had no effect after acidic incubation. Immunoblotting showed that NBCn1 was upregulated after acidic incubation and in NH(4)Cl-containing media. The Cl(-)-HCO(3)(-) exchanger AE2 was present, but its expression remained unaffected by acidic incubation. Expressed in Xenopus oocytes, NBCn1 increased carrier-mediated (14)C-MA transport, which was abolished by replacing Na(+). Two-electrode voltage clamp of oocytes exhibited negligible current after NH(4)Cl application. These results suggest that DIDS-sensitive HCO(3)(-) extrusion normally governs NH(4)(+)/NH(3) uptake in the medullary thick ascending limb cells. We propose that, in acidic conditions, DIDS-sensitive HCO(3)(-) extrusion is inactivated, while NBCn1 is upregulated to stimulate NH(4)(+) transport.

  17. A Semi-automated Abundance Survey of Ap Stars

    NASA Astrophysics Data System (ADS)

    Hall, Martin P.; Kurtz, Don; Elkin, Vladimir; Bruntt, Hans

    2015-08-01

    We have carried out an abundance analysis on the high-resolution spectra of approximately 350 Ap stars collected between 2007 and 2010 on the FEROS Echelle (Fibre-led, Extended Range, Echelle ) spectrograph housed at the 2.2-m telescope at European Southern Observatory at La Silla, Chile. We employed the VWA package (vsin I, wavelength shift, abundance analysis) for preliminary selection of spectral lines, and a semi-automated set of routines which we developed in the programming language IDL, to calculate the equivalent widths and abundances of ions of Iron and the rare earth elements Neodymium and Praseodymium using the WIDTH program and NEMO model atmospheres. Initial results are presented, which reinforce the correlation between iron abundance and effective temperature, from an over-abundance in the late Bp stars, to under-abundant in the early F stars. Results also suggest that the disequilibrium in abundances of the first and second ionisation stages of these ions in the rapidly oscillating Ap (roAp) stars may a consequence of the relatively cool temperatures of those stars, rather than a signature of pulsation.

  18. THE EVALUATION OF PEPTIDE/HISTIDINE TRANSPORTER 1 (PHT1) FUNCTION: UPTAKE KINETICS UTILIZING A COS-7 STABLY TRANSFECTED CELL LINE.

    PubMed

    Lindley, David J; Carl, Stephen M; Mowery, Stephanie A; Knipp, Gregory T

    2011-10-01

    There have been relatively few studies focused on the proton-dependent oligopeptide transporter (POT) superfamily member, Peptide/Histidine Transporter 1 (PHT1), with respect to its contribution to the ADME of peptides and peptide-based drugs. These studies were conducted to determine hPHT1-mediated, H(+)-dependent uptake kinetics of histidine, carnosine, Gly-Sar and valacyclovir in stably transfected hPHT1-COS-7 cells comparative to kinetics determined in an empty vector (Mock) stably transfected cell line. The results suggest that Gly-Sar appears to be a substrate for PHT1 based on efflux from the stably transfected hPHT1 COS-7 cells. Histidine and Gly-Sar concentration- and time-dependent studies suggest mixed-uptake kinetics. These studies suggest that stably transfected hPHT1-COS-7 cells exhibit different uptake kinetics than those observed in our previous studies and illustrate the requirement for experiments to delineate the physiological role of hPHT1.

  19. Altered retinal cell differentiation in the AP-3 delta mutant (Mocha) mouse.

    PubMed

    Baguma-Nibasheka, Mark; Kablar, Boris

    2009-11-01

    Adaptor-related protein complex 3 delta 1 (Ap3d1) encodes the delta 1 subunit of an adaptor protein regulating intracellular vesicle-mediated transport, and the Ap3d-deletion mutant (Mocha) mouse undergoes rapid photoreceptor degeneration leading to blindness soon after birth. Previous microarray analysis revealed Ap3d down-regulation in the retina of mouse embryos specifically lacking cholinergic amacrine cells as a result of the absence of skeletal musculature. To investigate the role of Ap3d in the determination of retinal cell fate, the present study examined retinal morphology in newborn Ap3d-/- mice. The Ap3d-/- retina showed a complete absence of cholinergic amacrine cells and a decrease in parvalbumin-expressing amacrine cells and syntaxin- and VC1.1-expressing amacrine precursor cells, but had a normal number of cell layers and number of cells in each layer with no detectable difference in cell proliferation or apoptosis. These findings indicate that, despite having no apparent effect on the basic spatial organization of the retina at this stage of development, Ap3d could be involved in the regulation of progenitor cell competence and the eventual ratio of resulting differentiated cells. Finding the mouse mutant which phenocopies the eye defect seen in fetuses with no striated muscle was accomplished by the Systematic Subtractive Microarray Analysis Approach (SSMAA), explained in the discussion section.

  20. The small G-protein Arf6GTP recruits the AP-2 adaptor complex to membranes.

    PubMed

    Paleotti, Olivia; Macia, Eric; Luton, Frederic; Klein, Stephanie; Partisani, Mariagrazia; Chardin, Pierre; Kirchhausen, Tom; Franco, Michel

    2005-06-03

    The small GTP-binding protein ADP-ribosylation factor 6 (Arf6) is involved in plasma membrane/endosomes trafficking. However, precisely how the activation of Arf6 regulates vesicular transport is still unclear. Here, we show that, in vitro, recombinant Arf6GTP recruits purified clathrin-adaptor complex AP-2 (but not AP-1) onto phospholipid liposomes in the absence of phosphoinositides. We also show that phosphoinositides and Arf6 tightly cooperate to translocate AP-2 to the membrane. In vivo, Arf6GTP (but not Arf6GDP) was found associated to AP-2. The expression of the GTP-locked mutant of Arf6 leads to the plasma membrane redistribution of AP-2 in Arf6GTP-enriched areas. Finally, we demonstrated that the expression of the GTP-locked mutant of Arf6 inhibits transferrin receptor internalization without affecting its recycling. Altogether, our results demonstrated that Arf6GTP interacts specifically with AP-2 and promotes its membrane recruitment. These findings strongly suggest that Arf6 plays a major role in clathrin-mediated endocytosis by directly controlling the assembly of the AP-2/clathrin coat.

  1. AP-1A controls secretory granule biogenesis and trafficking of membrane secretory granule proteins.

    PubMed

    Bonnemaison, Mathilde; Bäck, Nils; Lin, Yimo; Bonifacino, Juan S; Mains, Richard; Eipper, Betty

    2014-10-01

    The adaptor protein 1A complex (AP-1A) transports cargo between the trans-Golgi network (TGN) and endosomes. In professional secretory cells, AP-1A also retrieves material from immature secretory granules (SGs). The role of AP-1A in SG biogenesis was explored using AtT-20 corticotrope tumor cells expressing reduced levels of the AP-1A μ1A subunit. A twofold reduction in μ1A resulted in a decrease in TGN cisternae and immature SGs and the appearance of regulated secretory pathway components in non-condensing SGs. Although basal secretion of endogenous SG proteins was unaffected, secretagogue-stimulated release was halved. The reduced μ1A levels interfered with the normal trafficking of carboxypeptidase D (CPD) and peptidylglycine α-amidating monooxygenase-1 (PAM-1), integral membrane enzymes that enter immature SGs. The non-condensing SGs contained POMC products and PAM-1, but not CPD. Based on metabolic labeling and secretion experiments, the cleavage of newly synthesized PAM-1 into PHM was unaltered, but PHM basal secretion was increased in sh-μ1A PAM-1 cells. Despite lacking a canonical AP-1A binding motif, yeast two-hybrid studies demonstrated an interaction between the PAM-1 cytosolic domain and AP-1A. Coimmunoprecipitation experiments with PAM-1 mutants revealed an influence of the luminal domains of PAM-1 on this interaction. Thus, AP-1A is crucial for normal SG biogenesis, function and composition.

  2. Comparison of In vitro Nanoparticles Uptake in Various Cell Lines and In vivo Pulmonary Cellular Transport in Intratracheally Dosed Rat Model

    NASA Astrophysics Data System (ADS)

    Lai, Yurong; Chiang, Po-Chang; Blom, Jason D.; Li, Na; Shevlin, Kimberly; Brayman, Timothy G.; Hu, Yiding; Selbo, Jon G.; Hu, Liangbiao George

    2008-09-01

    In present study, the potential drug delivery of nanoformulations was validated via the comparison of cellular uptake of nanoparticles in various cell lines and in vivo pulmonary cellular uptake in intratracheally (IT) dosed rat model. Nanoparticles were prepared by a bench scale wet milling device and incubated with a series of cell lines, including Caco-2, RAW, MDCK and MDCK transfected MDR1 cells. IT dosed rats were examined for the pulmonary cellular uptake of nanoparticles. The processes of nanoparticle preparation did not alter the crystalline state of the material. The uptake of nanoparticles was observed most extensively in RAW cells and the least in Caco-2 cells. Efflux transporter P-gp did not prevent cell from nanoparticles uptake. The cellular uptake of nanoparticles was also confirmed in bronchoalveolar lavage (BAL) fluid cells and in bronchiolar epithelial cells, type II alveolar epithelial cells in the intratracheally administrated rats. The nanoparticles uptake in MDCK, RAW cells and in vivo lung epithelial cells indicated the potential applications of nanoformulation for poorly soluble compounds. The observed limited direct uptake of nanoparticles in Caco-2 cells suggests that the improvement in oral bioavailability by particle size reduction is via increased dissolution rate rather than direct uptake.

  3. Hypermethylation of the human proton-coupled folate transporter (SLC46A1) minimal transcriptional regulatory region in an antifolate-resistant HeLa cell line.

    PubMed

    Diop-Bove, Ndeye Khady; Wu, Julia; Zhao, Rongbao; Locker, Joseph; Goldman, I David

    2009-08-01

    This laboratory recently identified a novel proton-coupled folate transporter (PCFT) that mediates intestinal folate absorption and transport of folates into the central nervous system. The present study focuses on the definition of the minimum transcriptional regulatory region of this gene in HeLa cells and the mechanism(s) underlying the loss of PCFT expression in the methotrexate-resistant HeLa R1-11 cell line. The PCFT transcriptional regulatory controls were localized between -42 and +96 bases from the transcriptional start site using a luciferase-reporter gene system. The promoter is a G + C rich region of 139 nucleotides contained in a CpG island. HeLa R1-11 cells have no mutations in the PCFT open reading frame and its promoter; the transcription/translation machinery is intact because transient transfections in HeLa R1-11 and wild-type HeLa cells produced similar luciferase activities. Hypermethylation at CpG sites within the minimal transcriptional regulatory region was shown in HeLa R1-11 cells as compared with the parental PCFT-competent HeLa cells, using bisulfite conversion and sequence analysis. Treatment with 5-aza-2'-deoxycytidine resulted in a substantial restoration of transport and PCFT mRNA expression and small but significant decreases in methylation in the promoter region. In vitro methylation of the transfected reporter plasmid inhibited luciferase gene expression. Cytogenetics/fluorescence in situ hybridization indicated a loss of half the PCFT gene copies in HeLa R1-11 as compared with PCFT-competent HeLa cells. Taken together, promoter silencing through methylation and gene copy loss accounted for the loss of PCFT activity in antifolate-resistant HeLa R1-11 cells.

  4. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  5. APS Activities with Other Professional Societies

    NASA Astrophysics Data System (ADS)

    Slakey, Francis

    2006-03-01

    In 1981, the APS Council issued a statement that opposed ``equal time'' presentation in public school science classes of creationism and evolution. The statement clarified that ``Scientific inquiry and religious beliefs are two distinct elements of the human experience. Attempts to present them in the same context can only lead to misunderstandings of both.'' The APS Council revisited the issue in 1999 when a school board in Kansas attempted to eliminate the Big Bang, among other issues, from the science curriculum. Since that time, the APS has been more directly involved in confronting efforts that would dilute the teaching of science in public school science classes. This talk will review the APS activities and describe a developing multi-science society activity.

  6. APS storage ring vacuum system

    SciTech Connect

    Niemann, R.C.; Benaroya, R.; Choi, M.; Dortwegt, R.J.; Goeppner, G.A.; Gonczy, J.; Krieger, C.; Howell, J.; Nielsen, R.W.; Roop, B.; Wehrle, R.B.

    1990-01-01

    The Advanced Photon Source synchrotron radiation facility, under construction at the Argonne National Laboratory, incorporates a large ring for the storage of 7 GeV positrons for the generation of photon beams for the facility's experimental program. The Storage Ring's 1104 m circumference is divided into 40 functional sectors. The sectors include vacuum, beam transport, control, acceleration and insertion device components. The vacuum system, which is designed to operate at a pressure of 1 n Torr, consists of 240 connected sections, the majority of which are fabricated from an aluminum alloy extrusion. The sections are equipped with distributed NeG pumping, photon absorbers with lumped pumping, beam position monitors, vacuum diagnostics and valving. The details of the vacuum system design, selected results of the development program and general construction plans are presented. 11 refs., 6 figs., 3 tabs.

  7. Expression, purification, crystallization and structure of human adipocyte lipid-binding protein (aP2)

    SciTech Connect

    Marr, Eric; Tardie, Mark; Carty, Maynard; Brown Phillips, Tracy; Wang, Ing-Kae; Soeller, Walt; Qiu, Xiayang Karam, George

    2006-11-01

    The crystal structure of human adipocyte lipid-binding protein (aP2) with a bound palmitate is reported at 1.5 Å resolution. Human adipocyte lipid-binding protein (aP2) belongs to a family of intracellular lipid-binding proteins involved in the transport and storage of lipids. Here, the crystal structure of human aP2 with a bound palmitate is described at 1.5 Å resolution. Unlike the known crystal structure of murine aP2 in complex with palmitate, this structure shows that the fatty acid is in a folded conformation and that the loop containing Phe57 acts as a lid to regulate ligand binding by excluding solvent exposure to the central binding cavity.

  8. High energy beam lines

    NASA Astrophysics Data System (ADS)

    Marchetto, M.; Laxdal, R. E.

    2014-01-01

    The ISAC post accelerator comprises an RFQ, DTL and SC-linac. The high energy beam lines connect the linear accelerators as well as deliver the accelerated beams to two different experimental areas. The medium energy beam transport (MEBT) line connects the RFQ to the DTL. The high energy beam transport (HEBT) line connects the DTL to the ISAC-I experimental stations (DRAGON, TUDA-I, GPS). The DTL to superconducting beam (DSB) transport line connects the ISAC-I and ISAC-II linacs. The superconducting energy beam transport (SEBT) line connects the SC linac to the ISAC-II experimental station (TUDA-II, HERACLES, TIGRESS, EMMA and GPS). All these lines have the function of transporting and matching the beams to the downstream sections by manipulating the transverse and longitudinal phase space. They also contain diagnostic devices to measure the beam properties.

  9. The mean magnetic field modulus of AP stars

    NASA Astrophysics Data System (ADS)

    Mathys, G.; Hubrig, S.; Landstreet, J. D.; Lanz, T.; Manfroid, J.

    1997-06-01

    We present new measurements of the mean magnetic field modulus of a sample of Ap stars with spectral lines resolved into magnetically split components. We report the discovery of 16 new stars having this property. This brings the total number of such stars known to 42. We have performed more than 750 measurements of the mean field modulus of 40 of these 42 stars, between May 1988 and August 1995. The best of them have an estimated accuracy of 25 - 30 G. The availability of such a large number of measurements allows us to discuss for the first time the distribution of the field modulus intensities. A most intriguing result is the apparent existence of a sharp cutoff at the low end of this distribution, since no star with a field modulus (averaged over the rotation period) smaller than 2.8 kG has been found in this study. For more than one third of the studied stars, enough field determinations well distributed throughout the stellar rotation cycle have been achieved to allow us to characterize at least to some extent the variations of the field modulus. These variations are often significantly anharmonic, and it is not unusual for their extrema not to coincide in phase with the extrema of the longitudinal field (for the few stars for which enough data exist about the latter). This, together with considerations on the distribution of the relative amplitude of variation of the studied stars, supports the recently emerging evidence for markedly non-dipolar geometry and fine structure of the magnetic fields of most Ap stars. New or improved determinations of the rotation periods of 9 Ap stars have been achieved from the analysis of the variations of their mean magnetic field modulus. Tentative values of the period have been derived for 5 additional stars, and lower limits have been established for 10 stars. The shortest definite rotation period of an Ap star with magnetically resolved lines is 3.4 deg, while those stars that rotate slowest appear to have periods in

  10. Overexpression of BpAP1 induces early flowering and produces dwarfism in Betula platyphylla × Betula pendula.

    PubMed

    Huang, Haijiao; Wang, Shan; Jiang, Jing; Liu, Guifeng; Li, Huiyu; Chen, Su; Xu, Huanwen

    2014-08-01

    The involvement of APETALA1 (AP1) in the flowering transition has been the focus of much research. Here, we produced Betula platyphylla × Betula pendula (birch) lines that overexpressed BpAP1 using Agrobacterium-mediated transformation; we obtained five independent 35S::BpAP1 transgenic lines. Polymerase chain reaction (PCR), Southern, northern and western analyses were used to identify the transformants. As determined by quantitative real-time PCR (qRT-PCR), BpAP1 expression in roots, shoots, leaves and terminal buds of 35S::BpAP1 transgenic lines was significantly higher than that in the wild type (WT, P < 0.01). The average height of 2-year-old 35S::BpAP1 plants was significantly lower (41.17%) than that of non-transgenic plants. In the 35S::BpAP1 lines, inflorescences emerged successively beginning 2 months after transplanting. In addition, the length-diameter ratio of fully developed male and female inflorescences were both significantly less than those of the WT (P < 0.05), i.e. the morphological characteristic was stubby. The male inflorescences emerged early, with empty, draped anthers, and pollen was rarely produced, whereas the female floret structure was not different from WT. The pistils developed normally and could accept pollen, leading to the production of hybrid progeny (F1 ). F1 plants completed flowering within only 1 year after sowing. We demonstrate that BpAP1 can be inherited through sexual reproduction. Overexpression of BpAP1 caused early flowering and dwarfism; these lines had an obviously shortened juvenile phase. These results greatly increase our understanding of the mechanisms underlying the flowering transition and enhance genetic studies of birch traits, and they open up new possibilities for the breeding of birch and other woody plants.

  11. Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes.

    PubMed

    Theos, Alexander C; Tenza, Danièle; Martina, José A; Hurbain, Ilse; Peden, Andrew A; Sviderskaya, Elena V; Stewart, Abigail; Robinson, Margaret S; Bennett, Dorothy C; Cutler, Daniel F; Bonifacino, Juan S; Marks, Michael S; Raposo, Graça

    2005-11-01

    Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies.

  12. Over-expression of the PaAP1 gene from sweet cherry (Prunus avium L.) causes early flowering in Arabidopsis thaliana.

    PubMed

    Wang, Jing; Zhang, Xiaoming; Yan, Guohua; Zhou, Yu; Zhang, Kaichun

    2013-02-15

    A homologue of SQUAMOSA/APETALA1, designated PaAP1, was isolated from Prunus avium by reverse transcription-PCR (RT-PCR). The full length of PaAP1 cDNA is 753 bp, and it codes for a polypeptide of 250 amino acid residues. Sequence comparison revealed that PaAP1 belongs to the MADS-box gene family. Phylogenetic analysis indicated that PaAP1 shared the highest identity with SQUA/AP1 homologues from Prunus serrulata. Real-time fluorescence quantitative PCR analysis showed that PaAP1 was expressed at high levels in petal, sepal, style, and flower buds, which was slightly different from the expression pattern of AP1 of Arabidopsis thaliana. To characterize the functions of PaAP1, we assessed Arabidopsis transformed with 35S::PaAP1. A total of 8 transgenic T(1) lines with an early flowering phenotype were obtained, and a 3:1 segregation ratio of flowering time was observed in the T(2) generation of 4 lines. This study provides the first functional analysis of an SQUA/AP1 homolog from P. avium and suggests that PaAP1 is potentially useful for shortening the juvenile period in sweet cherry.

  13. aP2-Cre-Mediated Inactivation of Estrogen Receptor Alpha Causes Hydrometra

    PubMed Central

    Antonson, Per; Matic, Marko; Portwood, Neil; Kuiper, Raoul V.; Bryzgalova, Galyna; Gao, Hui; Windahl, Sara H.; Humire, Patricia; Ohlsson, Claes; Berggren, Per-Olof; Gustafsson, Jan-Åke; Dahlman-Wright, Karin

    2014-01-01

    In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ERαflox/flox mice. As expected, ERα mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ERα levels in the hypothalamus of aP2-Cre/ERαflox/flox mice. Phenotypic analysis revealed that aP2-Cre/ERαflox/flox female mice were infertile. In line with this, aP2-Cre/ERαflox/flox female mice did not cycle and presented 3.8-fold elevated estrogen levels. That elevated estrogen levels were associated with increased estrogen signaling was evidenced by increased mRNA levels of the estrogen-regulated genes lactoferrin and aquaporin 5 in the uterus. Furthermore, aP2-Cre/ERαflox/flox female mice showed an accumulation of intra-uterine fluid, hydrometra, without overt indications for causative anatomical anomalies. However, the vagina and cervix displayed advanced keratosis with abnormal quantities of accumulating squamous epithelial cells suggesting functional obstruction by keratin plugs. Importantly, treatment of aP2-Cre/ERαflox/flox mice with the aromatase inhibitor Letrozole caused regression of the hydrometra phenotype linking increased estrogen levels to the observed phenotype. We propose that in aP2-Cre/ERαflox/flox mice, increased serum estrogen levels cause over-stimulation in the uterus and genital tracts resulting in hydrometra and vaginal obstruction. PMID:24416430

  14. The chemical abundances of the Ap star HD94660

    SciTech Connect

    Giarrusso, M.

    2014-05-09

    In this work I present the determination of chemical abundances of the Ap star HD94660, a possible rapid oscillating star. As all the magnetic chemically peculiar objects, it presents CNO underabundance and overabundance of iron peak elements of ∼100 times and of rare earths up to 4 dex with respect to the Sun. The determination was based on the conversion of the observed equivalent widths into abundances simultaneously to the determination of effective temperature and gravity. Since the Balmer lines of early type stars are very sensitive to the surface gravity while the flux distribution is sensitive to the effective temperature, I have adopted an iterative procedure to match the H{sub α} line profile and the observed UV-Vis-NIR magnitudes of HD94660 looking for a consistency between the metallicity of the atmosphere model and the derived abundances. From my spectroscopic analysis, this star belongs to the no-rapid oscillating class.

  15. Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease.

    PubMed

    Hirst, Jennifer; Edgar, James R; Esteves, Typhaine; Darios, Frédéric; Madeo, Marianna; Chang, Jaerak; Roda, Ricardo H; Dürr, Alexandra; Anheim, Mathieu; Gellera, Cinzia; Li, Jun; Züchner, Stephan; Mariotti, Caterina; Stevanin, Giovanni; Blackstone, Craig; Kruer, Michael C; Robinson, Margaret S

    2015-09-01

    Adaptor proteins (AP 1-5) are heterotetrameric complexes that facilitate specialized cargo sorting in vesicular-mediated trafficking. Mutations in AP5Z1, encoding a subunit of the AP-5 complex, have been reported to cause hereditary spastic paraplegia (HSP), although their impact at the cellular level has not been assessed. Here we characterize three independent fibroblast lines derived from skin biopsies of patients harbouring nonsense mutations in AP5Z1 and presenting with spastic paraplegia accompanied by neuropathy, parkinsonism and/or cognitive impairment. In all three patient-derived lines, we show that there is complete loss of AP-5 ζ protein and a reduction in the associated AP-5 µ5 protein. Using ultrastructural analysis, we show that these patient-derived lines consistently exhibit abundant multilamellar structures that are positive for markers of endolysosomes and are filled with aberrant storage material organized as exaggerated multilamellar whorls, striated belts and 'fingerprint bodies'. This phenotype can be replicated in a HeLa cell culture model by siRNA knockdown of AP-5 ζ. The cellular phenotype bears striking resemblance to features described in a number of lysosomal storage diseases (LSDs). Collectively, these findings reveal an emerging picture of the role of AP-5 in endosomal and lysosomal homeostasis, illuminates a potential pathomechanism that is relevant to the role of AP-5 in neurons and expands the understanding of recessive HSPs. Moreover, the resulting accumulation of storage material in endolysosomes leads us to propose that AP-5 deficiency represents a new type of LSDs.

  16. AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

    PubMed Central

    Setta-Kaffetzi, Niovi; Simpson, Michael A.; Navarini, Alexander A.; Patel, Varsha M.; Lu, Hui-Chun; Allen, Michael H.; Duckworth, Michael; Bachelez, Hervé; Burden, A. David; Choon, Siew-Eng; Griffiths, Christopher E.M.; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M.B.; Prins, Christa; Smahi, Asma; Trembath, Richard C.; Fraternali, Franca; Smith, Catherine H.; Barker, Jonathan N.; Capon, Francesca

    2014-01-01

    Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. PMID:24791904

  17. Glucose-coated superparamagnetic iron oxide nanoparticles prepared by metal vapour synthesis are electively internalized in a pancreatic adenocarcinoma cell line expressing GLUT1 transporter.

    PubMed

    Barbaro, Daniele; Di Bari, Lorenzo; Gandin, Valentina; Evangelisti, Claudio; Vitulli, Giovanni; Schiavi, Eleonora; Marzano, Cristina; Ferretti, Anna M; Salvadori, Piero

    2015-01-01

    Iron oxide nanoparticles (IONP) can have a variety of biomedical applications due to their visualization properties through Magnetic Resonance Imaging (MRI) and heating with radio frequency or alternating magnetic fields. In the oncological field, coating IONP with organic compounds to provide specific features and to achieve the ability of binding specific molecular targets appears to be very promising. To take advantage of the high avidity of tumor cells for glucose, we report the development of very small glucose-coated IONP (glc-IONP) by employing an innovative technique, Metal Vapor Synthesis (MVS). Moreover, we tested the internalization of our gl-IONP on a tumor line, BxPC3, over-expressing GLUT 1 transporter. Both glc-IONP and polyvinylpyrrolidone-IONP (PVP-IONP), as control, were prepared with MVS and were tested on BxPC3 at various concentrations. To evaluate the role of GLUT-1 transporter, we also investigated the effect of adding a polyclonal anti-GLUT1 antibody. After proper treatment, the iron value was assessed by atomic absorption spectrometer, reported in mcg/L and expressed in mg of protein. Our IONP prepared with MVS were very small and homogeneously distributed in a narrow range (1.75-3.75 nm) with an average size of 2.7 nm and were super-paramagnetic. Glc-IONP were internalized by BxPC3 cells in a larger amount than PVP-IONP. After 6h of treatment with 50 mcg/mL of IONPs, the content of Fe was 1.5 times higher in glc-IONP-treated cells compared with PVP-IONP-treated cells. After 1h pre-treatment with anti-GLUT1, a reduction of 41% cellular accumulation of glc-IONP was observed. Conversely, the uptake of PVP-IONPs was reduced only by 14% with antibody pretreatment. In conclusion, MVS allowed us to prepare small, homogeneous, super-paramagnetic glc-IONP, which are electively internalized by a tumor line over-expressing GLUT1. Our glc-IONP appear to have many requisites for in vivo use.

  18. Supplementation of 2-Ap, Zn and La Improves 2-Acetyl-1-Pyrroline Concentrations in Detached Aromatic Rice Panicles In Vitro.

    PubMed

    Mo, Zhaowen; Huang, Jinxia; Xiao, Di; Ashraf, Umair; Duan, Meiyang; Pan, Shenggang; Tian, Hua; Xiao, Lizhong; Zhong, Keyou; Tang, Xiangru

    2016-01-01

    Aromatic rice is highly prized by consumers worldwide due to its special aromatic character. 2-acetyl-1-pyrroline (2-AP) is considered to be the single most important volatile compound responsible for aroma in aromatic rice. The present study demonstrated the effects of 2-AP, zinc (Zn) and lanthanum (La) on the 2-AP concentration of detached aromatic rice panicles in vitro. Detached panicles from three well-known aromatic cultivars, Guixiangzhan, Pin14, and Pin 15, were cultured separately in basic culture medium supplemented with 2-AP, Zn and La, and 2-AP concentrations were assessed at 7 and 14 days after culture (DAC). The results show that supplementation of 2-AP, Zn and La in the basic culture medium significantly increases the accumulation of proline. 2-AP concentration and the activity of proline dehydrogenase (ProDH) were also increased in rice grains. Zn concentrations were also found to be higher when Zn was added to the basic culture medium, and La concentrations in grains were too low to be measured. Additionally, grain 2-AP concentrations were significantly and positively correlated with proline concentrations, ProDH activities in grains and 2-AP in culture medium. In summary, higher grain 2-AP concentrations might be due to Zn- and La-induced increases in proline concentrations and ProDH activities, as well as the direct uptake and transportation of 2-AP from the culture medium. Furthermore, application of both Zn and La might be helpful for improving aroma formation in rice. However, interactions of both these elements with the complex process of 2-AP formation remain to be explored.

  19. Automated Plasma Spray (APS) process feasibility study

    NASA Technical Reports Server (NTRS)

    Fetheroff, C. W.; Derkacs, T.; Matay, I. M.

    1981-01-01

    An automated plasma spray (APS) process was developed to apply two layer (NiCrAlY and ZrO2-12Y2O3) thermal barrier coatings to aircraft and stationary gas turbine engine blade airfoils. The APS process hardware consists of four subsystems: a mechanical positioning subsystem incorporating two interlaced six degree of freedom assemblies (one for coating deposition and one for coating thickness monitoring); a noncoherent optical metrology subsystem (for in process gaging of the coating thickness buildup at specified points on the specimen); a microprocessor based adaptive system controller (to achieve the desired overall thickness profile on the specimen); and commerical plasma spray equipment. Over fifty JT9D first stage aircraft turbine blade specimens, ten W501B utility turbine blade specimens and dozens of cylindrical specimens were coated with the APS process in preliminary checkout and evaluation studies. The best of the preliminary turbine blade specimens achieved an overall coating thickness uniformity of 53 micrometers (2.1 mils), much better than is achievable manually. Comparative evaluations of coating thickness uniformity for manually sprayed and APS coated specimens were performed. One of the preliminary turbine blade evaluation specimens was subjected to a torch test and metallographic evaluation. Some cylindrical specimens coated with the APS process survived up to 2000 cycles in subsequent burner rig testing.

  20. Tank 241-AP-107, grab samples 7AP-97-1, 7AP-97-2 and 7AP-97-3 analytical results for the final report

    SciTech Connect

    Steen, F.H.

    1997-12-22

    This document is the final report for tank 241-AP-107 grab samples. Three grab samples were collected from riser 1 on September 11, 1997. Analyses were performed on samples 7AP-97-1, 7AP-97-2 and 7AP-97-3 in accordance with the Compatibility Grab Sampling and Analysis Plan (TSAP) (Sasaki, 1997) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Rev. 1: Fowler, 1995; Rev. 2: Mulkey and Nuier, 1997). The analytical results are presented in the data summary report (Table 1). A notification was made to East Tank Farms Operations concerning low hydroxide in the tank and a hydroxide (caustic) demand analysis was requested. The request for sample analysis (RSA) (Attachment 2) received for AP-107 indicated that the samples were polychlorinated biphenyl (PCB) suspects. Therefore, prior to performing the requested analyses, aliquots were made to perform PCB analysis in accordance with the 222-S Laboratory administrative procedure, LAP-101-100. The results of this analysis indicated that no PCBs were present at 50 ppm and analysis proceeded as non-PCB samples. The results and raw data for the PCB analysis will be included in a revision to this document. The sample breakdown diagrams (Attachment 1) are provided as a cross-reference for relating the tank farm customer identification numbers with the 222-S Laboratory sample numbers and the portion of sample analyzed.

  1. LC-MS/MS Based Quantitation of ABC and SLC Transporter Proteins in Plasma Membranes of Cultured Primary Human Retinal Pigment Epithelium Cells and Immortalized ARPE19 Cell Line.

    PubMed

    Pelkonen, Laura; Sato, Kazuki; Reinisalo, Mika; Kidron, Heidi; Tachikawa, Masanori; Watanabe, Michitoshi; Uchida, Yasuo; Urtti, Arto; Terasaki, Tetsuya

    2017-02-14

    The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between neural retina and choroid. The RPE has several important vision supporting functions, such as transport mechanisms that may also modify pharmacokinetics in the posterior eye segment. Expression of plasma membrane transporters in the RPE cells has not been quantitated. The aim of this study was to characterize and compare transporter protein expression in the ARPE19 cell line and hfRPE (human fetal RPE) cells by using quantitative targeted absolute proteomics (QTAP). Among 41 studied transporters, 16 proteins were expressed in hfRPE and 13 in ARPE19 cells. MRP1, MRP5, GLUT1, 4F2hc, TAUT, CAT1, LAT1, and MATE1 proteins were detected in both cell lines within 4-fold differences. MPR7, OAT2 and RFC1 were detected in the hfRPE cells, but their expression levels were below the limit of quantification in ARPE19 cells. PCFT was detected in both studied cell lines, but the expression was over 4-fold higher in hfRPE cells. MCT1, MCT4, MRP4, and Na(+)/K(+) ATPase were upregulated in the ARPE19 cell line showing over 4-fold differences in the quantitative expression values. Expression levels of 25 transporters were below the limit of quantification in both cell models. In conclusion, we present the first systematic and quantitative study on transporter protein expression in the plasma membranes of ARPE19 and hfRPE cells. Overall, transporter expression in the ARPE19 and hfRPE cells correlated well and the absolute expression levels were similar, but not identical. The presented quantitative expression levels could be a useful basis for further studies on drug permeation in the outer blood-retinal barrier.

  2. Building an AP Social Studies Program with Non-Traditional AP Students

    ERIC Educational Resources Information Center

    Ashmead, Amanda; Blanchette, Sue

    2013-01-01

    Equal access to education, that is to a high quality education, has increasingly come to mean access to an Advanced Placement program. In recent years, there has been steady attention paid to opening access to AP programs. The 9th annual College Board report (2013) stated "students who succeed on an AP Exam during high school typically…

  3. AP U.S. History: Beneficial or Problematic?

    ERIC Educational Resources Information Center

    Lurie, Maxine N.

    2000-01-01

    Warns against the declining standards of the Advanced Placement (AP) U.S. history examination and the AP program. Focuses on the problems that occur in maintaining high standards and the practive of teaching to the test in AP courses. Discusses who does grade and who should grade the AP examinations. (CMK)

  4. Commissioning Simulations for the APS Upgrade Lattice

    SciTech Connect

    Sajaev, V.; Borland, M.

    2015-01-01

    A hybrid seven-bend-achromat lattice that features very strong focusing elements and a relatively small vacuum chamber has been proposed for the APS upgrade. Achieving design lattice parameters during commissioning will need to be accomplished quickly in order to minimize dark time for APS users. The paper will describe start-to-end simulation of the machine commissioning beginning from first-turn trajectory correction, progressing to orbit and lattice correction, and culminating in evaluation of the nonlinear performance of the corrected lattice

  5. 76 FR 6328 - Official Release of the January 2011 AP-42 Method for Estimating Re-Entrained Road Dust From...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-04

    ...-entrained road dust emissions from cars, trucks, buses, and ] motorcycles on paved roads. This document... emissions analyses for transportation conformity determinations (``regional conformity analyses''). This new...: For questions about using AP-42 in SIPs and transportation conformity, contact David Bizot at...

  6. Comparison of a CCD and an APS for soft X-ray diffraction

    NASA Astrophysics Data System (ADS)

    Stewart, Graeme; Bates, R.; Blue, A.; Clark, A.; Dhesi, S. S.; Maneuski, D.; Marchal, J.; Steadman, P.; Tartoni, N.; Turchetta, R.

    2011-12-01

    We compare a new CMOS Active Pixel Sensor (APS) to a Princeton Instruments PIXIS-XO: 2048B Charge Coupled Device (CCD) with soft X-rays tested in a synchrotron beam line at the Diamond Light Source (DLS). Despite CCDs being established in the field of scientific imaging, APS are an innovative technology that offers advantages over CCDs. These include faster readout, higher operational temperature, in-pixel electronics for advanced image processing and reduced manufacturing cost. The APS employed was the Vanilla sensor designed by the MI3 collaboration and funded by an RCUK Basic technology grant. This sensor has 520 x 520 square pixels, of size 25 μm on each side. The sensor can operate at a full frame readout of up to 20 Hz. The sensor had been back-thinned, to the epitaxial layer. This was the first time that a back-thinned APS had been demonstrated at a beam line at DLS. In the synchrotron experiment soft X-rays with an energy of approximately 708 eV were used to produce a diffraction pattern from a permalloy sample. The pattern was imaged at a range of integration times with both sensors. The CCD had to be operated at a temperature of -55°C whereas the Vanilla was operated over a temperature range from 20°C to -10°C. We show that the APS detector can operate with frame rates up to two hundred times faster than the CCD, without excessive degradation of image quality. The signal to noise of the APS is shown to be the same as that of the CCD at identical integration times and the response is shown to be linear, with no charge blooming effects. The experiment has allowed a direct comparison of back thinned APS and CCDs in a real soft x-ray synchrotron experiment.

  7. 77 FR 24480 - Application for New Awards; Advanced Placement (AP) Test Fee Program-Reopening the AP Test Fee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-24

    ... Application for New Awards; Advanced Placement (AP) Test Fee Program--Reopening the AP Test Fee Fiscal Year.... ACTION: Notice reopening the AP Test Fee fiscal year 2012 competition. Catalog of Federal Domestic... 8848) a notice inviting applications for the AP Test Fee fiscal year (FY) 2012 competition (February...

  8. APS Ranks High on College Entrance Exams.

    ERIC Educational Resources Information Center

    APS in Action, 1984

    1984-01-01

    This document discusses the scores of Albuquerque (New Mexico) Public Schools (APS) students on the American College Test (ACT) and the Scholastic Aptitude Test (SAT) during the 1982-83 school year. Graphs, a map, and a question and answer format are used to report the information. Comparisons of average ACT scores and average SAT scores are drawn…

  9. APS deposition facility upgrades and future plans

    NASA Astrophysics Data System (ADS)

    Conley, Ray; Shi, Bing; Erdmann, Mark; Izzo, Scott; Assoufid, Lahsen; Goetze, Kurt; Mooney, Tim; Lauer, Kenneth

    2014-09-01

    The Advanced Photon Source (APS) has recently invested resources to upgrade or replace aging deposition systems with modern equipment. Of the three existing deposition systems, one will receive an upgrade, while two are being replaced. A design which adds a three-substrate planetary for the APS rotary deposition system is almost complete. The replacement for the APS large deposition system, dubbed the "Modular Deposition System", has been conceptually designed and is in the procurement process. Eight cathodes will sputter horizontally on mirrors up to 1.5 meters in length. This new instrument is designed to interface with ion-milling instruments and various metrology equipment for ion-beam figuring. A third linear machine, called the APS Profile Coating System, has two cathodes and is designed to accept substrates up to 200mm in length. While this machine is primarily intended for fabrication of figured KB mirrors using the profile-coating technique, it has also been used to produce multilayer monochromators for beamline use.

  10. The Demographic Wave: Rethinking Hispanic AP Trends

    ERIC Educational Resources Information Center

    Edwards, Kelcey; Sawtell, Ellen

    2013-01-01

    Presented at the Advanced Placement Annual Conference (APAC) in Las Vegas, NV in July 2013. This presentation reviews new research examining the AP® experience of Hispanic graduates over the past decade. Topics include an in-depth look at the AP Spanish Language and Culture gateway hypothesis and trends in family characteristics such as parent…

  11. Boosting Black Academic Achievement and AP Enrollments

    ERIC Educational Resources Information Center

    Saunders, Terrie; Maloney, Kathy

    2005-01-01

    Minority students were about 25% of the student population at Central High School in Omaha, Nebraska, in 1995. But the composition of its honors and challenge classes did not reflect this diversity: Few minority students were taking challenge classes as underclassmen and even fewer were taking Advanced Placement (AP) courses as seniors. This paper…

  12. The Promise of AP World History

    ERIC Educational Resources Information Center

    Saldaña, Cristóbal T.

    2013-01-01

    AP World History is the ideal history course. It introduces students to 10,000 years of world history, and demands critical reading, critical writing, and critical thinking skills on the part of both the teacher and the students. It requires students to build their expertise in reading their textbook, and places demands on the teacher to assign…

  13. Gapminder: An AP Human Geography Lab Assignment

    ERIC Educational Resources Information Center

    Keller, Kenneth H.

    2012-01-01

    This lesson is designed as a lab assignment for Advanced Placement (AP) Human Geography students wherein they use the popular Gapminder web site to compare levels of development in countries from different world regions. For this lesson, it is important for the teacher to practice with Gapminder before giving the assignment to students. (Contains…

  14. College Board Readies Plans for AP Audits

    ERIC Educational Resources Information Center

    Klein, Alyson

    2006-01-01

    This article describes the educators mixed reviews regarding the audit system planned by the College Board to scrutinize high school Advanced Placement courses. Teachers of AP courses are required to submit materials to the College Board proving that their course syllabuses meet the program's curricular requirements. It is the most extensive…

  15. Structuring the AP Art History Course

    ERIC Educational Resources Information Center

    Herscher, Walter R.

    2013-01-01

    While AP (Advanced Placement) Art History may be taught within the art department in many schools, social studies teachers are equally capable of teaching the course well. They have the historical background to discuss the reasons for changes in art styles. A teacher's preparation is similar to teaching a course stressing political history,…

  16. Binaries among AP and AM stars

    NASA Astrophysics Data System (ADS)

    North, P.; Ginestet, N.; Carquillat, J.-M.; Carrier, F.; Udry, S.

    1998-04-01

    The results of long-term surveys of radial velocities of cool Ap and Am stars are presented. There are two samples, one of about 100 Ap stars and the other of 86 Am stars. Both have been observed with the CORAVEL scanner from Observatoire de Haute-Provence (CNRS), France. The conspicuous lack of short-period binaries among cool Ap stars seems confirmed, although this may be the result of an observational bias; one system has a period as short as 1.6 days. A dozen new orbits could be determined, including that of one SB2 system. Considering the mass functions of 68 binaries from the literature and from our work, we conclude that the distribution of the mass ratios is the same for the Bp-Ap stars than for normal G dwarfs. Among the Am stars, we found 52 binaries, i.e. 60%; an orbit could be computed for 29 of them. Among these 29, there are 7 SB2 systems, one triple and one quadruple system. The 21 stars with an apparently constant radial velocity may show up later as long-period binaries with a high eccentricity. The mass functions of the SB1 systems are compatible with cool main-sequence companions, also suggested by ongoing spectral observations.

  17. The AP Descriptive Chemistry Question: Student Errors

    ERIC Educational Resources Information Center

    Crippen, Kent; Brooks, David W.

    2005-01-01

    For over a decade, the authors have been involved in a design theory experiment providing software for high school students preparing for the descriptive question on the Advanced Placement (AP) chemistry examination. Since 1997, the software has been available as a Web site offering repeatable practice. This study describes a 4-year project during…

  18. An AP-3-dependent mechanism drives synaptic-like microvesicle biogenesis in pancreatic islet beta-cells.

    PubMed

    Suckow, Arthur T; Craige, Branch; Faundez, Victor; Cain, William J; Chessler, Steven D

    2010-07-01

    Pancreatic islet beta-cells contain synaptic-like microvesicles (SLMVs). The origin, trafficking, and role of these SLMVs are poorly understood. In neurons, synaptic vesicle (SV) biogenesis is mediated by two different cytosolic adaptor protein complexes, a ubiquitous AP-2 complex and the neuron-specific AP-3B complex. Mice lacking AP-3B subunits exhibit impaired GABAergic (inhibitory) neurotransmission and reduced neuronal vesicular GABA transporter (VGAT) content. Since beta-cell maturation and exocytotic function seem to parallel that of the inhibitory synapse, we predicted that AP-3B-associated vesicles would be present in beta-cells. Here, we test the hypothesis that AP-3B is expressed in islets and mediates beta-cell SLMV biogenesis. A secondary aim was to test whether the sedimentation properties of INS-1 beta-cell microvesicles are identical to those of bona fide SLMVs isolated from PC12 cells. Our results show that the two neuron-specific AP-3 subunits beta3B and mu3B are expressed in beta-cells, the first time these proteins have been found to be expressed outside the nervous system. We found that beta-cell SLMVs share the same sedimentation properties as PC12 SLMVs and contain SV proteins that sort specifically to AP-3B-associated vesicles in the brain. Brefeldin A, a drug that interferes with AP-3-mediated SV biogenesis, inhibits the delivery of AP-3 cargoes to beta-cell SLMVs. Consistent with a role for AP-3 in the biogenesis of GABAergic SLMV in beta-cells, INS-1 cell VGAT content decreases upon inhibition of AP-3 delta-subunit expression. Our findings suggest that beta-cells and neurons share molecules and mechanisms important for mediating the neuron-specific membrane trafficking pathways that underlie synaptic vesicle formation.

  19. E6-AP/UBE3A protein acts as a ubiquitin ligase toward SOX9 protein.

    PubMed

    Hattori, Takako; Kishino, Tetsuya; Stephen, Shelley; Eberspaecher, Heidi; Maki, Sayumi; Takigawa, Masaharu; de Crombrugghe, Benoit; Yasuda, Hideyo

    2013-12-06

    SOX9 is a transcription factor that acts as a key regulator at various stages of cartilage differentiation. There is ample evidence that intracellular SOX9 protein levels are tightly regulated both by sumoylation and by degradation through the ubiquitin-proteasome pathway. Using a proteomics approach, here we report the identification of a SOX9-binding protein, E6-AP/UBE3A, that may act as a ubiquitin ligase toward Sox9. E6-AP bound SOX9 through the region consisting mostly of its high mobility group domain in vitro. In nuclear lysates, FLAG-tagged E6-AP coprecipitated with Sox9 and its high mobility group domain. This finding was estimated using nuclear lysates from a chondrocytic cell line that endogenously expresses E6-AP and SOX9. Accordingly, ectopically expressed E6-AP and SOX9 colocalized in the nucleus. We show that E6-AP ubiquitinates SOX9 in vitro and in vivo and that SOX9 levels are enhanced after addition of the proteasome inhibitor bortezomib. Similar, siRNA knockdown of E6-AP and the E2 ligase Ubc9 increased cellular SOX9 amounts, supporting the notion that SOX9 may be ubiquitinated in hypertrophic chondrocytes by E6-AP and degraded by proteasomes. This is in accordance with the distribution of SOX9 levels, which are high in proliferating and prehypertrophic chondrocytes but low in hypertrophic chondrocytes, whereas E6-AP levels are high in hypertrophic chondrocytes and low in prehypertrophic chondrocytes. Furthermore, E6-AP-deficient mice showed SOX9 accumulation in chondrocytes and the brain. These findings support the concept that E6-AP regulates SOX9 levels in developing cartilage by acting as a ubiquitin ligase.

  20. Contribution of AP-1 interference induced by TAC-101 to tumor growth suppression in a hepatocellular carcinoma model.

    PubMed

    Eshima, Kokoro; Fukaya, Satoshi; Sugimoto, Akiko; Mori, Tomoko; Yokoi, Hiromi; Yamamoto, Yasuji; Sugiura, Shin; Honda, Shizu; Masuko, Norio; Murakami, Koji; Yamasaki, Yasundo; Kagechika, Hiroyuki

    2009-01-01

    TAC-101, 4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid, is a synthetic ligand for retinoic acid receptor (RAR)-alpha. Here, we demonstrate the contribution of TAC-101-induced AP-1 interference to stabilization of tumor growth. TAC-101 induced transcriptional activation of RAR, resulting in marked elevation of RARbeta, a representative retinoid response marker, and it also significantly repressed the transcriptional activity of AP-1 in JHH-7 cells. In contrast to JHH-7, JHH-6 is another RARalpha-expressing human hepatocellular carcinoma (HCC) cell line with constitutive activation of AP-1, but it is retinoid insensitive and did not respond to the TAC-101-induced RAR signal. TAC-101 did not inhibit AP-1 activity of the JHH-6 cell line, showing that AP-1 interference by TAC-101 must be in parallel with RAR activation. Interleukin-8 (IL-8), one of the AP-1-regulated factors which correlate with a poor prognosis in HCC patients, was found to be overexpressed in JHH-7 cells. TAC-101 reduced IL-8 production without cytotoxicity and inhibited the progression of HCC in the orthotopic mouse model with decreased tumor IL-8 level. These results suggest that downregulation of the extracellular biomarker for AP-1 interference via the induction of retinoid signals will enhance the pharmacological effect of TAC-101 on HCC and it could be useful as a surrogate biomarker of therapeutic efficacy.

  1. Catalytic Steam Reforming of Gasifier Tars: On-Line Monitoring of Tars with a Transportable Molecular-Beam Mass Spectrometer; Milestone Completion Report

    SciTech Connect

    Carpenter, D.; Ratcliff, M.; Dayton, D.

    2002-05-01

    A method for evaluating catalytic tar decomposition in real time is presented. The effectiveness of two catalysts are compared. A key technical and economic barrier to commercialization of biomass gasification technologies is the removal of tars that are unavoidably formed in this thermochemical process. Tars contain fuel value; however, they are problematic in gas engines (both reciprocating and turbine) because they condense in the fuel delivery system, forming deposits that negatively affect operation and efficiency. These tars also combust with high luminosity, potentially forming soot particles. The conventional technology for tar removal is wet scrubbing. Although this approach has shown some success, there are significant equipment and operating costs associated with it. In order to prevent the generation of toxic wastewater, the tars must be separated and either disposed as hazardous waste or, preferably, combusted in the gasification plant. A conceptually better approach is catalytic steam reforming of the tars to hydrogen and carbon monoxide (CO), effectively increasing the gasification efficiency and eliminating the problems mentioned above. In FY2000, Battelle Columbus Laboratories attempted to demonstrate integrated gasification-gas turbine operation using catalytic steam reforming of tars. NREL participated in those tests using the transportable molecular-beam mass spectrometer (TMBMS) to monitor the catalytic reactor's performance on-line [10]. Unfortunately, the pilot plant tests encountered operational problems that prevented conclusive determination of the efficacy of the selected catalyst (Battelle's DN34). In FY2001, NREL performed on-site tar steam reforming tests using a slip-stream of hot pyrolysis gas from the Thermochemical Process Development Unit (TCPDU), which was directed to a bench-scale fluidized bed reactor system designed expressly for this purpose. Supporting this effort, the TMBMS was employed to provide on-line analysis of the

  2. Overexpression of the Lotus corniculatus Soloist Gene LcAP2/ERF107 Enhances Tolerance to Salt Stress.

    PubMed

    Sun, Zhan-Min; Zhou, Mei-Liang; Dan-Wang; Tang, Yi-Xiong; Lin, Min; Wu, Yan-Min

    2016-01-01

    The AP2/ERF play a key role in multiple stress responses in plants. we here report a novel salt stress-related gene, LcAP2/ERF107 that encodes an AP2/ERF protein in Lotus corniculatus cultivar Leo. LcAP2/ERF107 was classified into the soloist subfamiliy based on phylogenetic relationship. The transcription of LcAP2/ERF107 were strongly induced by salt and other phytohormones (ABA, ACC, MeJA). A subcellular localization experiment indicated that LcAP2/ERF107 is a nuclear protein that activates transcription. LcAP2/ERF107 overexpression in Arabidopsis resulted in pleiotropic phenotypes, including higher seed germination rate and transgenic plants with enhanced tolerance to salt stress. Further, under salt tolerance the transgenic lines elevated the relative moisture content; however, the relative electrolyte leakage was lower than in control plants. The expression levels of indicative genes RD22, RD29A, LEA4-5, P5CS1 and P5CS2 were found to be increased in the transgenic plants compared with the WT plants. These results indicated that LcAP2/ERF107 play an important role in the responses of plant to salt stress.

  3. Luteolin, a flavonoid, inhibits AP-1 activation by basophils

    SciTech Connect

    Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Matsuda, Hisashi; Yoshikawa, Masayuki; Maezaki, Naoyoshi; Tanaka, Tetsuaki; Kawase, Ichiro; Tanaka, Toshio . E-mail: ttanak@imed3.med.osaka-u.ac.jp

    2006-02-03

    Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

  4. Oscillations of kinks on dislocation lines in crystals and low-temperature transport anomalies as a ``passport'' of newly-induced defects

    NASA Astrophysics Data System (ADS)

    Mezhov-Deglin, L. P.; Mukhin, S. I.

    2011-10-01

    The possible interpretation of experimental data on low-temperature anomalies in weakly deformed metallic crystals prepared form ultra-pure lead, copper, and silver, as well as in crystals of 4He is discussed within the previously proposed theoretical picture of dislocations with dynamical kinks. In the case of pure metals the theoretical predictions give a general picture of interaction of conduction electrons in a sample with newly-introduced dislocations, containing dynamic kinks in the Peierls potential relief. In the field of random stresses appearing due to plastic deformation of a sample, kinks on the dislocation line form a set of one-dimensional oscillators in potential wells of different shapes. In the low temperature region at low enough density of defects pinning kinks the inelastic scattering of electrons on kinks should lead to deviations from the Wiedemann-Franz law. In particular, the inelastic scattering on kinks should result in a quadratic temperature dependence of the thermal conductivity in a metallic sample along preferential directions of dislocation axes. In the plane normal to the dislocation axis the elastic large-angle scattering of electrons is prevalent. The kink pinning by a point defect or by additional dislocations as well as the sample annealing leading to the disappearance of kinks should induce suppression of transport anomalies. Thus, the energy interval for the spectrum of kink oscillations restricted by characteristic amplitude of the Peierls relief is a "passport of deformation history" for each specific sample. For instance, in copper the temperature/energy region of the order of 1 K corresponds to it. It is also planned to discuss in the other publication applicability of mechanism of phonon scattering on mobile dislocation kinks and pinning of kinks by impurities in order to explain anomalies of phonon thermal conductivity of 4He crystals and deformed crystals of pure lead in a superconducting state.

  5. Transcriptomic analysis by RNA-seq reveals AP-1 pathway as key regulator that green tea may rely on to inhibit lung tumorigenesis.

    PubMed

    Pan, Jing; Zhang, Qi; Xiong, Donghai; Vedell, Peter; Yan, Ying; Jiang, Hui; Cui, Peng; Ding, Feng; Tichelaar, Jay W; Wang, Yian; Lubet, Ronald A; You, Ming

    2014-01-01

    Green tea is a promising chemopreventive agent for lung cancer. Multiple signaling events have been reported, however, the relative importance of these mechanisms in mediating the chemopreventive function of green tea is unclear. In the present study, to examine the involvement of AP-1 in green tea polyphenols induced tumor inhibition, human NSCLC cell line H1299 and mouse SPON 10 cells were identified as AP-1 dependent, as these two lines exhibit high constitutive AP-1 activity, and when TAM67 expression was induced with doxycycline, cell growth was inhibited and correlated with suppressed AP-1 activity. RNA-seq was used to determine the global transcriptional effects of AP-1 inhibition and also uncover the possible involvement of AP-1 in tea polyphenols induced chemoprevention. TAM67 mediated changes in gene expression were identified, and within down-regulated genes, AP-1 was identified as a key transcription regulator. RNA-seq analysis revealed that Polyphenon E-treated cells shared 293 commonly down-regulated genes within TAM67 expressing H1299 cells, and by analysis of limited Chip-seq data, over 10% of the down-regulated genes contain a direct AP-1 binding site, indicating that Polyphenon E elicits chemopreventive activity by regulating AP-1 target genes. Conditional TAM67 expressing transgenic mice and NSCLC cell lines were used to further confirm that the chemopreventive activity of green tea is AP-1 dependent. Polyphenon E lost its chempreventive function both in vitro and in vivo when AP-1 was inhibited, indicating that AP-1 inhibition is a major pathway through which green tea exhibits chemopreventive effects.

  6. Isoform-specific degradation of PR-B by E6-AP is critical for normal mammary gland development.

    PubMed

    Ramamoorthy, Sivapriya; Dhananjayan, Sarath C; Demayo, Francesco J; Nawaz, Zafar

    2010-11-01

    E6-associated protein (E6-AP), which was originally identified as an ubiquitin-protein ligase, also functions as a coactivator of estrogen (ER-α) and progesterone (PR) receptors. To investigate the in vivo role of E6-AP in mammary gland development, we generated transgenic mouse lines that either overexpress wild-type (WT) human E6-AP (E6-AP(WT)) or ubiquitin-protein ligase-defective E6-AP (E6-AP(C833S)) in the mammary gland. Here we show that overexpression of E6-AP(WT) results in impaired mammary gland development. In contrast, overexpression of E6-AP(C833S) or loss of E6-AP (E6-AP(KO)) increases lateral branching and alveolus-like protuberances in the mammary gland. We also show that the mammary phenotypes observed in the E6-AP transgenic and knockout mice are due, in large part, to the alteration of PR-B protein levels. We also observed alteration in ER-α protein level, which might contribute to the observed mammary phenotype by regulating PR expression. Furthermore, E6-AP regulates PR-B protein levels via the ubiquitin-proteasome pathway. Additionally, we also show that E6-AP impairs progesterone-induced Wnt-4 expression by decreasing the steady state level of PR-B in both mice and in human breast cancer cells. In conclusion, we present the novel observation that E6-AP controls mammary gland development by regulating PR-B protein turnover via the ubiquitin proteasome pathway. For the first time, we show that the E3-ligase activity rather than the coactivation function of E6-AP plays an important role in the mammary gland development, and the ubiquitin-dependent PR-B degradation is not required for its transactivation functions. This mechanism appears to regulate normal mammogenesis, and dysregulation of this process may be an important contributor to mammary cancer development and progression.

  7. Greenhouse evaluation of Bacillus subtilis AP-01 and Trichoderma harzianum AP-001 in controlling tobacco diseases

    PubMed Central

    Maketon, Monchan; Apisitsantikul, Jirasak; Siriraweekul, Chatchai

    2008-01-01

    Two biological control agents, Bacillus subtilis AP-01 (Larminar™) and Trichoderma harzianum AP-001 (Trisan™) alone or/in combination were investigated in controlling three tobacco diseases, including bacterial wilt (Ralstonia solanacearum), damping-off (Pythium aphanidermatum), and frogeye leaf spot (Cercospora nicotiana). Tests were performed in greenhouse by soil sterilization prior to inoculation of the pathogens. Bacterial-wilt and damping off pathogens were drenched first and followed with the biological control agents and for comparison purposes, two chemical fungicides. But for frogeye leaf spot, which is an airborne fungus, a spraying procedure for every treatment including a chemical fungicide was applied instead of drenching. Results showed that neither B. subtilis AP-01 nor T harzianum AP-001 alone could control the bacterial wilt, but when combined, their controlling capabilities were as effective as a chemical treatment. These results were also similar for damping-off disease when used in combination. In addition, the combined B. subtilis AP-01 and T. harzianum AP-001 resulted in a good frogeye leaf spot control, which was not significantly different from the chemical treatment. PMID:24031219

  8. Power Saving Control for Battery-Powered Portable WLAN APs

    NASA Astrophysics Data System (ADS)

    Ogawa, Masakatsu; Hiraguri, Takefumi

    This paper proposes a power saving control function for battery-powered portable wireless LAN (WLAN) access points (APs) to extend the battery life. The IEEE802.11 standard does not support power saving control for APs. To enable a sleep state for an AP, the AP forces the stations (STAs) to refrain from transmitting frames using the network allocation vector (NAV) while the AP is sleeping. Thus the sleep state for the AP can be employed without causing frame loss at the STAs. Numerical analysis and computer simulation reveal that the newly proposed control technique conserves power compared to the conventional control.

  9. APS control system operating system choice

    SciTech Connect

    Knott, M.; Kraimer, M.; Lenkszus, F.

    1990-05-01

    The purpose of this document is to set down the reasons and decisions regarding what is an important choice for the APS Control System design staff, namely the choice of an operating system for its principle computer resources. Since the choice also may affect cost estimates and the design handbook, there is a further need to document the process. The descriptions and explanations which follow are intended for reading by other APS technical area managers and will contain a minimum of buzz-words, and where buzz-words are used, they will be explained. The author hopes that it will help in understanding the current trends and developments in the volatile and fast-developing computer field.

  10. APS storage ring vacuum system performance

    SciTech Connect

    Noonan, J.R.; Gagliano, J.; Goeppner, G.A.

    1997-06-01

    The Advanced Photon Source (APS) storage ring was designed to operated with 7-GeV, 100-mA positron beam with lifetimes > 20 hours. The lifetime is limited by residual gas scattering and Touschek scattering at this time. Photon-stimulated desorption and microwave power in the rf cavities are the main gas loads. Comparison of actual system gas loads and design calculations will be given. In addition, several special features of the storage ring vacuum system will be presented.

  11. Final report for tank 241-AP-108, grab samples 8AP-96-1, 8AP-96-2 and 8AP-96-FB

    SciTech Connect

    Esch, R.A.

    1996-04-19

    This document is the final report deliverable for the tank 241-AP-108 grab samples. The samples were subsampled and analyzed in accordance with the TSAP. Included in this report are the results for the Waste Compatibility analyses, with the exception of DSC and thermogravimetric analysis (TGA) results which were presented in the 45 Day report (Part 2 of this document). The raw data for all analyses, with the exception of DSC and TGA, are also included in this report.

  12. Cultural Diversity in AP Art History

    ERIC Educational Resources Information Center

    Bolte, Frances R.

    2006-01-01

    Teaching AP Art History is like running on a treadmill that is moving faster than a teacher can run. Many teachers are out of breath before the end of the term and wonder how in the world they can cover every chapter. Because time is short and art from pre-history through to the present, including the non-European traditions, must be covered, this…

  13. An Updated AP2 Beamline TURTLE Model

    SciTech Connect

    Gormley, M.; O'Day, S.

    1991-08-23

    This note describes a TURTLE model of the AP2 beamline. This model was created by D. Johnson and improved by J. Hangst. The authors of this note have made additional improvements which reflect recent element and magnet setting changes. The magnet characteristics measurements and survey data compiled to update the model will be presented. A printout of the actual TURTLE deck may be found in appendix A.

  14. A WWW Database of APS POSS Images

    NASA Astrophysics Data System (ADS)

    Cornuelle, C. S.; Aldering, G.; Sourov, A.; Humphreys, R. M.; Larsen, J.; Cabanela, J.

    1996-05-01

    We are making our digitized images from the APS scans of the red and blue first-epoch Palomar Observatory Sky Survey (POSS I) available as a WWW-accessible image database. Image requests are through the APS homepage at http://isis.spa.umn.edu, and are initially limited in field width and sky region. To create this database, images from each scanned POSS I plate are processed into a set of coordinate-referenced index and pixel files. Database management software then refers to each object's pixels within a requested sky region by plate, by sub-plate, and finally by each scanned image. These images are then assembled into a mosaic FITS format file, whose header contains astrometric and photometric information. While the current APS Catalog of the POSS I contains only matched images, the image database will include all images above the plate grain noise limit of 25 mu m in diameter. Thus for a given sky region, users will have access to both the object (star and galaxy) catalog data and to the actual pixel data. This project is sponsored by NASA ADP contract NAS5-32670.

  15. A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells.

    PubMed

    Dai, Feihan F; Bhattacharjee, Alpana; Liu, Ying; Batchuluun, Battsetseg; Zhang, Ming; Wang, Xinye Serena; Huang, Xinyi; Luu, Lemieux; Zhu, Dan; Gaisano, Herbert; Wheeler, Michael B

    2015-10-09

    GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H(+)-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca(2+) influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion.

  16. Transcription factor AP-2β suppresses cervical cancer cell proliferation by promoting the degradation of its interaction partner β-catenin.

    PubMed

    Wang, Fangmei; Huang, Wenhuan; Hu, Xiang; Chen, Cheng; Li, Xinxin; Qiu, Junlu; Liang, Zhongheng; Zhang, Jianmei; Li, Limin; Wang, Xiaoqing; Ding, Xiaofeng; Xiang, Shuanglin; Zhang, Jian

    2017-03-09

    Transcription factor AP-2β mediates the transcription of a number of genes implicated in mammalian development, cell proliferation and carcinogenesis. Although the expression pattern of AP-2β has been analyzed in cervical cancer cell lines, the functions and molecular mechanism of AP-2β are unknown. Here, we found that AP-2β significantly inhibits TCF/LEF reporter activity. Moreover, AP-2β and β-catenin interact both in vitro through GST pull-down assays and in vivo by co-immunoprecipitation. We further identified the interaction regions to the DNA-binding domain of AP-2β and the 1-9 Armadillo repeats of β-catenin. Moreover, AP-2β binds with β-TrCP and promotes the degradation of endogenous β-catenin via the proteasomal degradation pathway. Immunohistochemistry analysis revealed a negative correlation between the two proteins in cervical cancer tissues and cell lines. Finally, functional analysis showed that AP-2β suppresses cervical cancer cell growth in vitro and in vivo by inhibiting the expression of Wnt downstream genes. Taken together, these findings demonstrated that AP-2β functions as a novel inhibitor of the Wnt/β-catenin signaling pathway in cervical cancer. This article is protected by copyright. All rights reserved.

  17. Sorting of the Alzheimer's Disease Amyloid Precursor Protein Mediated by the AP-4 Complex

    SciTech Connect

    Burgos, Patricia V.; Mardones, Gonzalo A.; Rojas, Adriana L.; daSilva, Luis L.P.; Prabhu, Yogikala; Hurley, James H.; Bonifacino, Juan S.

    2010-08-12

    Adaptor protein 4 (AP-4) is the most recently discovered and least well-characterized member of the family of heterotetrameric adaptor protein (AP) complexes that mediate sorting of transmembrane cargo in post-Golgi compartments. Herein, we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the {micro}4 subunit of AP-4. Biochemical and X-ray crystallographic analyses reveal that the properties of the APP sequence and the location of the binding site on 4 are distinct from those of other signal-adaptor interactions. Disruption of the APP-AP-4 interaction decreases localization of APP to endosomes and enhances {gamma}-secretase-catalyzed cleavage of APP to the pathogenic amyloid-{beta} peptide. These findings demonstrate that APP and AP-4 engage in a distinct type of signal-adaptor interaction that mediates transport of APP from the trans-Golgi network (TGN) to endosomes, thereby reducing amyloidogenic processing of the protein.

  18. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (II): thrombocytopenia and skin manifestations.

    PubMed

    Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

    2011-02-01

    The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyze the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations, and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analyzed on thrombocytopenia and skin manifestations, and presents the recommendations elaborated by the Task Force after this analysis.

  19. 45. SELAH LINE, LOOKING NORTHEAST, SHOWING END OF LINE AT ...

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

    45. SELAH LINE, LOOKING NORTHEAST, SHOWING END OF LINE AT LARSON FRUIT COMPANY - Yakima Valley Transportation Company Interurban Railroad, Connecting towns of Yakima, Selah & Wiley City, Yakima, Yakima County, WA

  20. Small Molecule Inhibitors Targeting Activator Protein 1 (AP-1)

    PubMed Central

    2015-01-01

    Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports that AP-1 plays an important role in several severe disorders including cancer, fibrosis, and organ injury, as well as inflammatory disorders such as asthma, psoriasis, and rheumatoid arthritis. AP-1 has emerged as an actively pursued drug discovery target over the past decade. Excitingly, a selective AP-1 inhibitor T-5224 (51) has been investigated in phase II human clinical trials. Nevertheless, no effective AP-1 inhibitors have yet been approved for clinical use. Despite significant advances achieved in understanding AP-1 biology and function, as well as the identification of small molecules modulating AP-1 associated signaling pathways, medicinal chemistry efforts remain an urgent need to yield selective and efficacious AP-1 inhibitors as a viable therapeutic strategy for human diseases. PMID:24831826

  1. Small molecule inhibitors targeting activator protein 1 (AP-1).

    PubMed

    Ye, Na; Ding, Ye; Wild, Christopher; Shen, Qiang; Zhou, Jia

    2014-08-28

    Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports that AP-1 plays an important role in several severe disorders including cancer, fibrosis, and organ injury, as well as inflammatory disorders such as asthma, psoriasis, and rheumatoid arthritis. AP-1 has emerged as an actively pursued drug discovery target over the past decade. Excitingly, a selective AP-1 inhibitor T-5224 (51) has been investigated in phase II human clinical trials. Nevertheless, no effective AP-1 inhibitors have yet been approved for clinical use. Despite significant advances achieved in understanding AP-1 biology and function, as well as the identification of small molecules modulating AP-1 associated signaling pathways, medicinal chemistry efforts remain an urgent need to yield selective and efficacious AP-1 inhibitors as a viable therapeutic strategy for human diseases.

  2. Pulsation tomography of rapidly oscillating Ap stars. Resolving the third dimension in peculiar pulsating stellar atmospheres

    NASA Astrophysics Data System (ADS)

    Ryabchikova, T.; Sachkov, M.; Kochukhov, O.; Lyashko, D.

    2007-10-01

    Aims:We present detailed analysis of the vertical pulsation mode cross-section in ten rapidly oscillating Ap (roAp) stars based on spectroscopic time-series observations. The aim of this analysis is to derive from observations a complete picture of how the amplitude and phase of magnetoacoustic waves depend on depth. Methods: We use the unique properties of roAp stars, in particular chemical stratification, to resolve the vertical structure of p-modes. Our approach consists of characterising pulsational behaviour of a carefully chosen, but extensive sample of spectral lines. We analyse the resulting amplitude-phase diagrams and interpret observations in terms of pulsation wave propagation. Results: We find common features in the pulsational behaviour of roAp stars. Within a sample of representative elements the lowest amplitudes are detected for Eu ii (and Fe in 33 Lib and in HD 19918), then pulsations go through the layers where Hα core, Nd, and Pr lines are formed. There RV amplitude reaches its maximum, and after that decreases in most stars. The maximum RV of the second REE ions is always delayed relative to the first ions. The largest phase shifts are detected in Tb iii and Th iii lines. Pulsational variability of the Th iii lines is detected here for the first time. The Y ii lines deviate from this picture, showing even lower amplitudes than Eu ii lines but half a period phase shift relative to other weakly pulsating lines. We measured an extra broadening, equivalent to a macroturbulent velocity from 4 to 11-12 km s-1 (where maximum values are observed for Tb iii and Th iii lines), for pulsating REE lines. The surface magnetic field strength is derived for the first time for three roAp stars: HD 9289 (2 kG), HD 12932 (1.7 kG), and HD 19918 (1.6 kG). Conclusions: The roAp stars exhibit similarity in the depth-dependence of pulsation phase and amplitude, indicating similar chemical stratification and comparable vertical mode cross-sections. In general

  3. Conserved Aspartic Acid Residues Lining the Extracellular Loop I of Sodium-coupled Bile Acid Transporter ASBT Interact with Na+ and 7α-OH Moieties on the Ligand Cholestane Skeleton*

    PubMed Central

    Hussainzada, Naissan; Da Silva, Tatiana Claro; Zhang, Eric Y.; Swaan, Peter W.

    2008-01-01

    Functional contributions of residues Val-99—Ser-126 lining extracellular loop (EL) 1 of the apical sodium-dependent bile acid transporter were determined via cysteine-scanning mutagenesis, thiol modification, and in silico interpretation. Despite membrane expression for all but three constructs (S112C, Y117C, S126C), most EL1 mutants (64%) were inactivated by cysteine mutation, suggesting a functional role during sodium/bile acid co-transport. A negative charge at conserved residues Asp-120 and Asp-122 is required for transport function, whereas neutralization of charge at Asp-124 yields a functionally active transporter. D124A exerts low affinity for common bile acids except deoxycholic acid, which uniquely lacks a 7α-hydroxyl (OH) group. Overall, we conclude that (i) Asp-122 functions as a Na+ sensor, binding one of two co-transported Na+ ions, (ii) Asp-124 interacts with 7α-OH groups of bile acids, and (iii) apolar EL1 residues map to hydrophobic ligand pharmacophore features. Based on these data, we propose a comprehensive mechanistic model involving dynamic salt bridge pairs and hydrogen bonding involving multiple residues to describe sodium-dependent bile acid transporter-mediated bile acid and cation translocation. PMID:18508772

  4. Book Eyes Impact of AP Classes and Exams

    ERIC Educational Resources Information Center

    Viadero, Debra

    2010-01-01

    At a time of mushrooming interest in Advanced Placement (AP) tests, a new book, "AP: A Critical Examination of the Advanced Placement Program," assembles studies on how capable the program is of meeting the increasingly diverse expectations held up for it. Growing out of a symposium held at Harvard in 2007, the book focuses on AP science…

  5. The AP Exam and the Introductory College Course.

    ERIC Educational Resources Information Center

    Pushkin, David B.

    1995-01-01

    Explores reasons why students take introductory physics courses at the university regardless of their Advanced Placement (AP) exam performance. Briefly describes the nature of AP physics, the examination format and reporting of scores, and the results of a survey of physics departments regarding their policies towards AP exam scores and placement…

  6. 75 FR 75666 - Advanced Placement (AP) Test Fee Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... Advanced Placement (AP) Test Fee Program AGENCY: Office of Elementary and Secondary Education (OESE), Department of Education. ACTION: Notice reopening the AP Test Fee fiscal year (FY) 2011 competition. SUMMARY... applications for the AP Test Fee FY 2011 competition. That notice established a November 17, 2010 deadline...

  7. Testing the presence of lithium on the surfaces of cool Ap stars

    NASA Astrophysics Data System (ADS)

    Nesvacil, N.; Hubrig, S.; Mathys, G.

    2004-12-01

    The possibility of a quite high Li abundance in the Ap stars was first raised by Wallerstein & Merchant (1965). Since then many studies investigated the problem of Li. The more recent observations in the lithium region indicate that in some Ap stars the λ 6708 feature is variable and this variability can be explained by the existence of Li rich spots on the stellar surface. Atomic data for the Ce II λ 6708.099 were released by the D.R.E.A.M. database in 2002. The line was used to identify the prominent suspected Li-feature in post AGB stars and might as well be responsible for the absorption feature in Ap stars. Recent studies have mentioned this possibility, but it has yet to be investigated in more detail. Other physical phenomena, such as the occurrence of a partial Paschen-Back effect in the presence of magnetic fields, as well as possible hyperfine structure splitting of some Rare Earth transitions, must be taken into account to provide correct line identifications in the wavelength region around the Li-doublet at λ 6708. We discuss a possible strategy to clarify the presence of Li in Ap stars.

  8. Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration

    PubMed Central

    Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A.W.; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M.; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J.; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G.; Humeau, Yann; Schenck, Annette; Herault, Yann

    2015-01-01

    ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2Camk2aCre/0 mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2Camk2aCre/0 mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2Camk2aCre/0 mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2Camk2aCre/0 mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. PMID:26376863

  9. The AP-2 complex has a specialized clathrin-independent role in apical endocytosis and polar growth in fungi

    PubMed Central

    Martzoukou, Olga; Amillis, Sotiris; Zervakou, Amalia; Christoforidis, Savvas; Diallinas, George

    2017-01-01

    Filamentous fungi provide excellent systems for investigating the role of the AP-2 complex in polar growth. Using Aspergillus nidulans, we show that AP-2 has a clathrin-independent essential role in polarity maintenance and growth. This is in line with a sequence analysis showing that the AP-2 β subunit (β2) of higher fungi lacks a clathrin-binding domain, and experiments showing that AP-2 does not co-localize with clathrin. We provide genetic and cellular evidence that AP-2 interacts with endocytic markers SlaBEnd4 and SagAEnd3 and the lipid flippases DnfA and DnfB in the sub-apical collar region of hyphae. The role of AP-2 in the maintenance of proper apical membrane lipid and cell wall composition is further supported by its functional interaction with BasA (sphingolipid biosynthesis) and StoA (apical sterol-rich membrane domains), and its essentiality in polar deposition of chitin. Our findings support that the AP-2 complex of dikarya has acquired, in the course of evolution, a specialized clathrin-independent function necessary for fungal polar growth. DOI: http://dx.doi.org/10.7554/eLife.20083.001 PMID:28220754

  10. The AP-2 complex has a specialized clathrin-independent role in apical endocytosis and polar growth in fungi.

    PubMed

    Martzoukou, Olga; Amillis, Sotiris; Zervakou, Amalia; Christoforidis, Savvas; Diallinas, George

    2017-02-21

    Filamentous fungi provide excellent systems for investigating the role of the AP-2 complex in polar growth. Using Aspergillus nidulans, we show that AP-2 has a clathrin-independent essential role in polarity maintenance and growth. This is in line with a sequence analysis showing that the AP-2 β subunit (β2) of higher fungi lacks a clathrin-binding domain, and experiments showing that AP-2 does not co-localize with clathrin. We provide genetic and cellular evidence that AP-2 interacts with endocytic markers SlaB(End4) and SagA(End3) and the lipid flippases DnfA and DnfB in the sub-apical collar region of hyphae. The role of AP-2 in the maintenance of proper apical membrane lipid and cell wall composition is further supported by its functional interaction with BasA (sphingolipid biosynthesis) and StoA (apical sterol-rich membrane domains), and its essentiality in polar deposition of chitin. Our findings support that the AP-2 complex of dikarya has acquired, in the course of evolution, a specialized clathrin-independent function necessary for fungal polar growth.

  11. AP600 containment purge radiological analysis

    SciTech Connect

    O`Connor, M.; Schulz, J.; Tan, C.

    1995-02-01

    The AP600 Project is a passive pressurized water reactor power plant which is part of the Design Certification and First-of-a-Kind Engineering effort under the Advanced Light Water Reactor program. Included in this process is the design of the containment air filtration system which will be the subject of this paper. We will compare the practice used by previous plants with the AP600 approach to meet the goals of industry standards in sizing the containment air filtration system. The radiological aspects of design are of primary significance and will be the focus of this paper. The AP600 Project optimized the design to combine the functions of the high volumetric flow rate, low volumetric flow rate, and containment cleanup and other filtration systems into one multi-functional system. This achieves a more simplified, standardized, and lower cost design. Studies were performed to determine the possible concentrations of radioactive material in the containment atmosphere and the effectiveness of the purge system to keep concentrations within 10CFR20 limits and within offsite dose objectives. The concentrations were determined for various reactor coolant system leakage rates and containment purge modes of operation. The resultant concentrations were used to determine the containment accessibility during various stages of normal plant operation including refueling. The results of the parametric studies indicate that a dual train purge system with a capacity of 4,000 cfm per train is more than adequate to control the airborne radioactivity levels inside containment during normal plant operation and refueling, and satisfies the goals of ANSI/ANS-56.6-1986 and limits the amount of radioactive material released to the environment per ANSI/ANS 59.2-1985 to provide a safe environment for plant personnel and offsite residents.

  12. Ozone mitigation tests at the APS

    SciTech Connect

    Kuzay, T.M.; Collins, J.T.; Pisharody, M.; Job, P.K.; Wang Zhibi

    1996-09-01

    Ozone is generated in the APS experimental stations whenever the x-ray beam has a chance to interact with air. Ozone concentrations in an experimental station have to be below a certain defined limit (current OSHA regulations specify 0.08 ppm as the maximum limit) before an experimenter can reenter the hutch. This limit is said to be currently under study for a downward adjustment. One method of depleting the ozone generated in an experimental station is mitigation through either adsorption or direct destruction. In recent tests, both methods were tried using commercially available units. Test results and some analytical predictions are presented.

  13. Cold-fusion television show angers APS

    NASA Astrophysics Data System (ADS)

    Cartwright, Jon

    2009-06-01

    Cold fusion has been controversial since its inception on 23 March 1989, when chemists Martin Fleischmann and Stanley Pons at the University of Utah in the US announced that they had achieved a sustained nuclear-fusion reaction at room temperature. Two decades on, a US television documentary about the field has stirred up fresh debate after it linked the American Physical Society (APS) to an evaluation of some cold-fusion results by Robert Duncan, a physicist and vice chancellor of the University of Missouri.

  14. Antioxidants and AP-1 activation: a brief overview.

    PubMed

    Gomez del Arco, P; Martínez-Martínez, S; Calvo, V; Armesilla, A L; Redondo, J M

    1997-12-01

    Activity of the transcription factor AP-1 is controlled by different MAPK cascades that regulate the different AP-1 components at the transcriptional and posttranscriptional level. Recently, AP-1 has been shown to behave as a redox-sensitive transcription factor that can be induced under both pro-oxidative and antioxidative conditions. In this overview we summarize the signaling pathways that converge on the activation of AP-1 and the components of these pathways that have been shown to be targets of antioxidants. The activation of AP-1 by antioxidants may account for the expression of a number of genes that mediate important functions under physiological conditions.

  15. Software Product Lines Essentials

    DTIC Science & Technology

    2008-07-01

    improvement Technology innovation Reuse 7 Software Product Lines Linda Northrop © 2008 Carnegie Mellon University Few Systems Are Unique Most...Focus was small-grained, opportunistic, and technology -driven. Results did not meet business goals. Reuse History 9 Software Product Lines Linda...servers, storage servers, network camera and scanner servers Bold Stroke Avionics Customized solutions for transportation industries E-COM Technology

  16. Vacuum chamber thermal protection for the APS (Advanced Photon Source)

    SciTech Connect

    Kramer, S.L.; Crosbie, E.A.; Kim, S.; Wehrle, R.; Yoon, M.

    1989-01-01

    The addition of undulators and wigglers into synchrotron storage rings created new problems in terms of protecting the integrity of the ring vacuum chamber. If the photon beam from these devices were missteered into striking an inadequately cooled section of the storage ring vacuum chamber, the structural strength might be reduced sufficiently that the vacuum envelope could be penetrated, resulting in long downtime of the storage ring. The new generation of high-energy synchrotron light sources will produce photon beams of such high power density that cooling of the vacuum chamber will not prevent a potential penetration of the vacuum envelope, and other methods of preventing this occurrence will be required. Since active methods will be used to ensure that the beams are delivered to beam lines for users during normal operation, there is a need for passive protection methods during non-routine operation, such as turning on new beam lines, injection, etc., when the active systems may be disabled. In addition, the passive methods could prevent the problem from arising and provide the rapid time response necessary for the highest power beams, a property that might not be easily and reliably provided by active methods during the early operation of these machines. This paper summarizes the results of a task group that studied the problem and outlines passive methods of protection for the Advanced Photon Source (APS). 2 refs., 3 figs., 1 tab.

  17. AP1000{sup R} nuclear power plant safety overview for spent fuel cooling

    SciTech Connect

    Gorgemans, J.; Mulhollem, L.; Glavin, J.; Pfister, A.; Conway, L.; Schulz, T.; Oriani, L.; Cummins, E.; Winters, J.

    2012-07-01

    The AP1000{sup R} plant is an 1100-MWe class pressurized water reactor with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance, safety and costs. The AP1000 design uses passive features to mitigate design basis accidents. The passive safety systems are designed to function without safety-grade support systems such as AC power, component cooling water, service water or HVAC. Furthermore, these passive features 'fail safe' during a non-LOCA event such that DC power and instrumentation are not required. The AP1000 also has simple, active, defense-in-depth systems to support normal plant operations. These active systems provide the first level of defense against more probable events and they provide investment protection, reduce the demands on the passive features and support the probabilistic risk assessment. The AP1000 passive safety approach allows the plant to achieve and maintain safe shutdown in case of an accident for 72 hours without operator action, meeting the expectations provided in the U.S. Utility Requirement Document and the European Utility Requirements for passive plants. Limited operator actions are required to maintain safe conditions in the spent fuel pool via passive means. In line with the AP1000 approach to safety described above, the AP1000 plant design features multiple, diverse lines of defense to ensure spent fuel cooling can be maintained for design-basis events and beyond design-basis accidents. During normal and abnormal conditions, defense-in-depth and other systems provide highly reliable spent fuel pool cooling. They rely on off-site AC power or the on-site standby diesel generators. For unlikely design basis events with an extended loss of AC power (i.e., station blackout) or loss of heat sink or both, spent fuel cooling can still be provided indefinitely: - Passive systems, requiring minimal or no operator actions, are sufficient for at least 72 hours under all possible pool

  18. Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear localization via active cysteines in response to ionizing radiation.

    PubMed

    Karimpour, Shervin; Lou, Junyang; Lin, Lilie L; Rene, Luis M; Lagunas, Lucio; Ma, Xinrong; Karra, Sreenivasu; Bradbury, C Matthew; Markovina, Stephanie; Goswami, Prabhat C; Spitz, Douglas R; Hirota, Kiichi; Kalvakolanu, Dhananjaya V; Yodoi, Junji; Gius, David

    2002-09-12

    A recently identified class of signaling factors uses critical cysteine motif(s) that act as redox-sensitive 'sulfhydryl switches' to reversibly modulate specific signal transduction cascades regulating downstream proteins with similar redox-sensitive sites. For example, signaling factors such as redox factor-1 (Ref-1) and transcription factors such as the AP-1 complex both contain redox-sensitive cysteine motifs that regulate activity in response to oxidative stress. The mammalian thioredoxin reductase-1 (TR) is an oxidoreductase selenocysteine-containing flavoprotein that also appears to regulate multiple downstream intracellular redox-sensitive proteins. Since ionizing radiation (IR) induces oxidative stress as well as increases AP-1 DNA-binding activity via the activation of Ref-1, the potential roles of TR and thioredoxin (TRX) in the regulation of AP-1 activity in response to IR were investigated. Permanently transfected cell lines that overexpress wild type TR demonstrated constitutive increases in AP-1 DNA-binding activity as well as AP-1-dependent reporter gene expression, relative to vector control cells. In contrast, permanently transfected cell lines expressing a TR gene with the active site cysteine motif deleted were unable to induce AP-1 activity or reporter gene expression in response to IR. Transient genetic overexpression of either the TR wild type or dominant-negative genes demonstrated similar results using a transient assay system. One mechanism through which TR regulates AP-1 activity appears to involve TRX sub-cellular localization, with no change in the total TRX content of the cell. These results identify a novel function of the TR enzyme as a signaling factor in the regulation of AP-1 activity via a cysteine motif located in the protein.

  19. The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro.

    PubMed

    Gerő, Domokos; Torregrossa, Roberta; Perry, Alexis; Waters, Alicia; Le-Trionnaire, Sophie; Whatmore, Jacqueline L; Wood, Mark; Whiteman, Matthew

    2016-11-01

    The development of diabetic vascular complications is initiated, at least in part, by mitochondrial reactive oxygen species (ROS) production in endothelial cells. Hyperglycemia induces superoxide production in the mitochondria and initiates changes in the mitochondrial membrane potential that leads to mitochondrial dysfunction. Hydrogen sulfide (H2S) supplementation has been shown to reduce the mitochondrial oxidant production and shows efficacy against diabetic vascular damage in vivo. However, the half-life of H2S is very short and it is not specific for the mitochondria. We have therefore evaluated two novel mitochondria-targeted anethole dithiolethione and hydroxythiobenzamide H2S donors (AP39 and AP123 respectively) at preventing hyperglycemia-induced oxidative stress and metabolic changes in microvascular endothelial cells in vitro. Hyperglycemia (HG) induced significant increase in the activity of the citric acid cycle and led to elevated mitochondrial membrane potential. Mitochondrial oxidant production was increased and the mitochondrial electron transport decreased in hyperglycemic cells. AP39 and AP123 (30-300nM) decreased HG-induced hyperpolarisation of the mitochondrial membrane and inhibited the mitochondrial oxidant production. Both H2S donors (30-300nM) increased the electron transport at respiratory complex III and improved the cellular metabolism. Targeting H2S to mitochondria retained the cytoprotective effect of H2S against glucose-induced damage in endothelial cells suggesting that the molecular target of H2S action is within the mitochondria. Mitochondrial targeting of H2S also induced >1000-fold increase in the potency of H2S against hyperglycemia-induced injury. The high potency and long-lasting effect elicited by these H2S donors strongly suggests that these compounds could be useful against diabetic vascular complications.

  20. Component Database for the APS Upgrade

    SciTech Connect

    Veseli, S.; Arnold, N. D.; Jarosz, D. P.; Carwardine, J.; Decker, G.; Schwarz, N.

    2016-01-01

    The Advanced Photon Source Upgrade (APS-U) project will replace the existing APS storage ring with a multi-bend achromat (MBA) lattice to provide extreme transverse coherence and extreme brightness x-rays to its users. As the time to replace the existing storage ring accelerator is of critical concern, an aggressive one-year removal/installation/testing period is being planned. To aid in the management of the thousands of components to be installed in such a short time, the Component Database (CDB) application is being developed with the purpose to identify, document, track, locate, and organize components in a central database. Three major domains are being addressed: Component definitions (which together make up an exhaustive "Component Catalog"), Designs (groupings of components to create subsystems), and Component Instances (“Inventory”). Relationships between the major domains offer additional "system knowledge" to be captured that will be leveraged with future tools and applications. It is imperative to provide sub-system engineers with a functional application early in the machine design cycle. Topics discussed in this paper include the initial design and deployment of CDB, as well as future development plans.

  1. Correction magnet power supplies for APS machine

    SciTech Connect

    Kang, Y.G.

    1991-04-01

    A number of correction magnets are required for the advanced photon source (APS) machine to correct the beam. There are five kinds of correction magnets for the storage ring, two for the injector synchrotron, and two for the positron accumulator ring (PAR). Table I shoes a summary of the correction magnet power supplies for the APS machine. For the storage ring, the displacement of the quadrupole magnets due to the low frequency vibration below 25 Hz has the most significant effect on the stability of the positron closed orbit. The primary external source of the low frequency vibration is the ground motion of approximately 20 {mu}m amplitude, with frequency components concentrated below 10 Hz. These low frequency vibrations can be corrected by using the correction magnets, whose field strengths are controlled individually through the feedback loop comprising the beam position monitoring system. The correction field require could be either positive or negative. Thus for all the correction magnets, bipolar power supplies (BPSs) are required to produce both polarities of correction fields. Three different types of BPS are used for all the correction magnets. Type I BPSs cover all the correction magnets for the storage ring, except for the trim dipoles. The maximum output current of the Type I BPS is 140 Adc. A Type II BPS powers a trim dipole, and its maximum output current is 60 Adc. The injector synchrotron and PAR correction magnets are powered form Type III BPSs, whose maximum output current is 25 Adc.

  2. RELAP5/MOD3 AP600 problems

    SciTech Connect

    Riemke, R.A.

    1993-08-01

    RELAP5/MOD3 is a reactor systems analysis code that has been developed jointly by the US Nuclear Regulatory Commission (USNRC) and a consortium consisting of several of the countries and domestic organizations that were members of the International Code Assessment and Applications Program (ICAP). The code is currently being used to simulate transients for the next generation of advanced light water reactors (ALWR`s). One particular reactor design is the Westinghouse AP600 pressurized water reactor (PWR), which consists of two hot legs and four cold legs as well as passive emergency core cooling (ECC) systems. Initial calculations with RELAP5/MOD3 indicated that the code was not as robust as RELAP5/MOD2.5 with regard to AP600 calculations. Recent modifications in the areas of condensation wall heat transfer, interfacial heat transfer in the presence of noncondensibles, bubbly flow interfacial heat transfer, and time smoothing of both interfacial drag and interfacial heat transfer have improved the robustness, although more reliability is needed.

  3. Phosphatidylcholine passes through lateral tight junctions for paracellular transport to the apical side of the polarized intestinal tumor cell-line CaCo2.

    PubMed

    Stremmel, Wolfgang; Staffer, Simone; Gan-Schreier, Hongying; Wannhoff, Andreas; Bach, Margund; Gauss, Annika

    2016-09-01

    Phosphatidylcholine (PC) is the most abundant phospholipid in intestinal mucus, indicative of a specific transport system across the mucosal epithelium to the intestinal lumen. To elucidate this transport mechanism, we employed a transwell tissue culture system with polarized CaCo2 cells. It was shown that PC could not substantially be internalized by the cells. However, after basal application of increasing PC concentrations, an apical transport of 47.1±6.3nmolh(-1)mMPC(-1) was observed. Equilibrium distribution studies with PC applied in equal concentrations to the basal and apical compartments showed a 1.5-fold accumulation on the expense of basal PC. Disruption of tight junctions (TJ) by acetaldehyde or PPARγ inhibitors or by treatment with siRNA to TJ proteins suppressed paracellular transport by at least 50%. Transport was specific for the choline containing the phospholipids PC, lysoPC and sphingomyelin. We showed that translocation is driven by an electrochemical gradient generated by apical accumulation of Cl(-) and HCO3(-) through CFTR. Pretreatment with siRNA to mucin 3 which anchors in the apical plasma membrane of mucosal cells inhibited the final step of luminal PC secretion. PC accumulates in intestinal mucus using a paracellular, apically directed transport route across TJs.

  4. APS Conference on Understanding the Biological Clock: From Genetics to Physiology

    NASA Technical Reports Server (NTRS)

    Frank, Martin

    1996-01-01

    The Conference was designed to take advantage of the fusion of two intellectually dominant but heretofore separate lines of clock research, vertebrate physiology and invertebrate and microbial genetics. The APS Conference attracted 251 scientists, 68 of whom were students. In addition to the excellent speaker program organized by Dunlap and Loros, the attendees also submitted 93 volunteer abstracts that were programmed in poster sessions. Thirty-four percent of the submitted abstracts were first authorized by a female student or scientist.

  5. Stratification of chemical elements in the atmosphere of the Ap star 53 Camelopardalis

    NASA Technical Reports Server (NTRS)

    Babel, J.; Lanz, T.

    1992-01-01

    A detailed abundance analysis of Cr, Fe, Mn, Ca, and Ti in the Ap star 53 Cam from IUE high-resolution spectra has been performed. It is found that UV lines give significantly lower abundance than visible lines for Cr and Fe. Theoretical spectra of Cr II line calculated with the stratified chromium abundance distributions predicted a priori by the diffusion-mass loss model match well both visible and UV lines. The spectral shape of the Ca II K line and its variation are well accounted for by the diffusion model with mass loss. A spectrum synthesis with a stratified abundance well reproduces the observations. These findings provide convincing evidence for stratification in the photosphere of 53 Cam.

  6. EPA’s AP-42 development methodology: Converting or rerating current AP-42 datasets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In August 2013, the U.S. Environmental Protection Agency’s (EPA) published their new methodology for updating the Compilation of Air Pollution Emission Factors (AP-42). The “Recommended Procedures for Development of Emissions Factors and Use of the WebFIRE Database” instructs that the ratings of the...

  7. Trichomonas vaginalis: the adhesins AP51 and AP65 bind heme and hemoglobin.

    PubMed

    Ardalan, Shahed; Lee, B Craig; Garber, Gary E

    2009-04-01

    Trichomonas vaginalis is the cause of human trichomoniasis, the most common non-viral sexually transmitted disease worldwide. Although acquisition of iron by binding to host hemoglobin through distinct receptor(s) has been described, no specific heme- or hemoglobin-binding site has been reported in this parasite. To determine the presence of hemoglobin-binding protein(s), membrane proteins were subjected to hemoglobin-affinity chromatography. Eluted proteins were analysed by SDS-PAGE. Two protein bands of 48 and 63 kDa were detected. Competition assay with an excess amount of hemoglobin or hemin in hemoglobin-affinity chromatography could block the 63- and 48-kDa bands, respectively. Further analysis by mass spectrometry indicated that the 48- and 63-kDa proteins had identity with two T. vaginalis adhesins: AP51 and AP65, respectively. This study confirms the existence of multifunctional proteins in T. vaginalis, and suggested that AP51 and AP65, besides serving as adhesion molecules, could also act as heme- and hemoglobin-binding proteins.

  8. The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells.

    PubMed

    Qin, H; Sun, Y; Benveniste, E N

    1999-10-08

    Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that contribute to pathological conditions associated with angiogenesis and tumor invasion. MMP-2 is highly expressed in human astroglioma cells, and contributes to the invasiveness of these cells. The human MMP-2 promoter contains potential cis-acting regulatory elements including cAMP response element-binding protein, AP-1, AP-2, PEA3, C/EBP, and Sp1. Deletion and site-directed mutagenesis analysis of the MMP-2 promoter demonstrates that the Sp1 site at -91 to -84 base pairs and the AP-2 site at -61 to -53 base pairs are critical for constitutive activity of this gene in invasive astroglioma cell lines. Electrophoretic gel shift analysis demonstrates binding of specific DNA-protein complexes to the Sp1 and AP-2 sites: Sp1 and Sp3 bind to the Sp1 site, while the AP-2 transcription factor binds the AP-2 element. Co-transfection expression experiments in Drosophilia SL2 cells lacking endogenous Sp factors demonstrate that Sp1 and Sp3 function as activators of the MMP-2 promoter and synergize for enhanced MMP-2 activation. Overexpression of AP-2 in AP-2-deficient HepG2 cells enhances MMP-2 promoter activation. These findings document the functional importance of Sp1, Sp3, and AP-2 in regulating constitutive expression of MMP-2. Delineation of MMP-2 regulation may have implications for development of new therapeutic strategies to arrest glioma invasion.

  9. Time series measurements of transient tracers and tracer-derived transport in the Deep Western Boundary Current between the Labrador Sea and the subtropical Atlantic Ocean at Line W

    NASA Astrophysics Data System (ADS)

    Smith, John N.; Smethie, William M.; Yashayev, Igor; Curry, Ruth; Azetsu-Scott, Kumiko

    2016-11-01

    Time series measurements of the nuclear fuel reprocessing tracer 129I and the gas ventilation tracer CFC-11 were undertaken on the AR7W section in the Labrador Sea (1997-2014) and on Line W (2004-2014), located over the US continental slope off Cape Cod, to determine advection and mixing time scales for the transport of Denmark Strait Overflow Water (DSOW) within the Deep Western Boundary Current (DWBC). Tracer measurements were also conducted in 2010 over the continental rise southeast of Bermuda to intercept the equatorward flow of DSOW by interior pathways. The Labrador Sea tracer and hydrographic time series data were used as input functions in a boundary current model that employs transit time distributions to simulate the effects of mixing and advection on downstream tracer distributions. Model simulations of tracer levels in the boundary current core and adjacent interior (shoulder) region with which mixing occurs were compared with the Line W time series measurements to determine boundary current model parameters. These results indicate that DSOW is transported from the Labrador Sea to Line W via the DWBC on a time scale of 5-6 years corresponding to a mean flow velocity of 2.7 cm/s while mixing between the core and interior regions occurs with a time constant of 2.6 years. A tracer section over the southern flank of the Bermuda rise indicates that the flow of DSOW that separated from the DWBC had undergone transport through interior pathways on a time scale of 9 years with a mixing time constant of 4 years.

  10. Septin6 and Septin7 GTP Binding Proteins Regulate AP-3- and ESCRT-Dependent Multivesicular Body Biogenesis

    PubMed Central

    Traikov, Sofia; Stange, Christoph; Wassmer, Thomas; Paul-Gilloteaux, Perrine; Salamero, Jean; Raposo, Graça; Hoflack, Bernard

    2014-01-01

    Septins (SEPTs) form a family of GTP-binding proteins implicated in cytoskeleton and membrane organization, cell division and host/pathogen interactions. The precise function of many family members remains elusive. We show that SEPT6 and SEPT7 complexes bound to F-actin regulate protein sorting during multivesicular body (MVB) biogenesis. These complexes bind AP-3, an adapter complex sorting cargos destined to remain in outer membranes of maturing endosomes, modulate AP-3 membrane interactions and the motility of AP-3-positive endosomes. These SEPT-AP interactions also influence the membrane interaction of ESCRT (endosomal-sorting complex required for transport)-I, which selects ubiquitinated cargos for degradation inside MVBs. Whereas our findings demonstrate that SEPT6 and SEPT7 function in the spatial, temporal organization of AP-3- and ESCRT-coated membrane domains, they uncover an unsuspected coordination of these sorting machineries during MVB biogenesis. This requires the E3 ubiquitin ligase LRSAM1, an AP-3 interactor regulating ESCRT-I sorting activity and whose mutations are linked with Charcot-Marie-Tooth neuropathies. PMID:25380047

  11. Specific activation of human interleukin-5 depends on de novo synthesis of an AP-1 complex.

    PubMed

    Schwenger, Gretchen T F; Kok, Chee Choy; Arthaningtyas, Estri; Thomas, Marc A; Sanderson, Colin J; Mordvinov, Viatcheslav A

    2002-12-06

    It is clear from the biology of eosinophilia that a specific regulatory mechanism must exist. Because interleukin-5 (IL5) is the key regulatory cytokine, it follows that a gene-specific control of IL5 expression must exist that differs even from closely related cytokines such as IL4. Two features of IL5 induction make it unique compared with other cytokines; first, induction by cyclic adenosine monophosphate (cAMP), which inhibits other T-cell-derived cytokines, and second, sensitivity to protein synthesis inhibitors, which have no effect on other cytokines. This study has utilized the activation of different transcription factors by different stimuli in a human T-cell line to study the role of conserved lymphokine element 0 (CLE0) in the specific induction of IL5. In unstimulated cells the ubiquitous Oct-1 binds to CLE0. Stimulation induces de novo synthesis of the AP-1 members JunD and Fra-2, which bind to CLE0. The amount of IL5 produced correlates with the production of the AP-1 complex, suggesting a key role in IL5 expression. The formation of the AP-1 complex is essential, but the rate-limiting step is the synthesis of AP-1, especially Fra-2. This provides an explanation for the sensitivity of IL5 to protein synthesis inhibitors and a mechanism for the specific induction of IL5 compared with other cytokines.

  12. The Cryptosporidium parvum ApiAP2 gene family: insights into the evolution of apicomplexan AP2 regulatory systems

    PubMed Central

    Oberstaller, Jenna; Pumpalova, Yoanna; Schieler, Ariel; Llinás, Manuel; Kissinger, Jessica C.

    2014-01-01

    We provide the first comprehensive analysis of any transcription factor family in Cryptosporidium, a basal-branching apicomplexan that is the second leading cause of infant diarrhea globally. AP2 domain-containing proteins have evolved to be the major regulatory family in the phylum to the exclusion of canonical regulators. We show that apicomplexan and perkinsid AP2 domains cluster distinctly from other chromalveolate AP2s. Protein-binding specificity assays of C. parvum AP2 domains combined with motif conservation upstream of co-regulated gene clusters allowed the construction of putative AP2 regulons across the in vitro life cycle. Orthologous Apicomplexan AP2 (ApiAP2) expression has been rearranged relative to the malaria parasite P. falciparum, suggesting ApiAP2 network rewiring during evolution. C. hominis orthologs of putative C. parvum ApiAP2 proteins and target genes show greater than average variation. C. parvum AP2 domains display reduced binding diversity relative to P. falciparum, with multiple domains binding the 5′-TGCAT-3′, 5′-CACACA-3′ and G-box motifs (5′-G[T/C]GGGG-3′). Many overrepresented motifs in C. parvum upstream regions are not AP2 binding motifs. We propose that C. parvum is less reliant on ApiAP2 regulators in part because it utilizes E2F/DP1 transcription factors. C. parvum may provide clues to the ancestral state of apicomplexan transcriptional regulation, pre-AP2 domination. PMID:24957599

  13. ATP6AP1 — EDRN Public Portal

    Cancer.gov

    ATP6AP1 is an integral membrane protein composed of at least 10 subunits. It is responsible for acidifying various eukaryotic intracellular organelles. ATP6AP1, also known as vacuolar ATPase or V-ATPase, has a cytosolic V1 domain and a transmembrane V0 domain. The acidification performed by ATP6AP1 is necessary for intracellular processes such as protein sorting, zymogen activation, and receptor-mediated endocytosis.

  14. 76 FR 10269 - AP1000 Design Certification Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ... aircraft, incorporate design improvements, and increase standardization of the design. Upon NRC rulemaking... standardization and improved licensing efficiency for the multiple COL applications referencing the AP1000...

  15. Project W-211, initial tank retrieval systems, description of operations for 241-AP-102 and 241-AP-104

    SciTech Connect

    RIECK, C.A.

    1999-02-25

    The primary purpose of the Initial Tank Retrieval Systems (ITRS) is to provide systems for retrieval of radioactive wastes stored in underground double-shell tanks (DSTS) for transfer to alternate storage, evaporation, pretreatment or treatment, while concurrently reducing risks associated with safety watch list and other DSTs. This Description of Operations (DOO) defines the control philosophy for the waste retrieval system for tanks 241-AP-102 (AP-102) and 241-AP-104 (AP-104). This DOO will provide a basis for the detailed design of the Retrieval Control System (RCS) for AP-102 and AP-104 and establishes test criteria for the RCS. The test criteria will be used during qualification testing and acceptance testing to verify operability.

  16. FAST INJECTION SYSTEM R&D FOR THE APS UPGRADE

    SciTech Connect

    Lenkszus, F.; Carwardine, J.; Cours, A.; Decker, G.; Morrison, L.; Sun, X.; Westferro, F.; Yao, C. Y.; Krasnykh, Anatoly

    2015-06-01

    The MBA upgrade for the APS will operate with bunch swap out and on axis injection. The planned 324 bunch fill pattern places difficult demands on the injection and extraction kickers. The present concept uses dual stripline kickers driven by high Voltage pulsers. Minimizing perturbation on adjacent bunches requires very fast rise and fall times with relatively narrow ~20 nsec, 15 kV pulses. To achieve these requirements we have initiated a multifaceted R&D program. The R&D includes the HV pulser, stripline kicker and HV feedthrough. We have purchased a commercial dual channel HV pulser and are evaluating its performance and reliability. In addition, we are investigating the feasibility of using nonlinear ferrite loaded coaxial cables (shockwave transmission line) to sharpen the leading and trailing edges of high voltage pulses. We are also developing a prototype kicker and high voltage feedthrough. The requirements for injection and extraction, progress on prototype development and results of our HV pulser investigations will be reported.

  17. Up-regulation of ATP-binding cassette transporters in the THP-1 human macrophage cell line by the antichagasic benznidazole

    PubMed Central

    Perdomo, Virginia G; Rigalli, Juan P; Luquita, Marcelo G; Pellegrino, José M; Ruiz, María Laura; Catania, Viviana A

    2016-01-01

    The effect of benznidazole (BZL) on the expression and activity of P-glycoprotein (P-gp, ABCB1) and multidrug resistance-associated protein 2 (MRP2, ABCC2), the two major transporters of endogenous and exogenous compounds, was evaluated in differentiated THP-1 cells. BZL induced P-gp and MRP2 proteins in a concentration-dependent manner. The increase in mRNA levels of both transporters suggests transcriptional regulation. P-gp and MRP2 activities correlated with increased protein levels. BZL intracellular accumulation was significantly lower in BZL-pre-treated cells than in control cells. PSC833 (a P-gp inhibitor) increased the intracellular BZL concentration in both pre-treated and control cells, confirming P-gp participation in BZL efflux. PMID:27783718

  18. Genome-Wide Identification of the Target Genes of AP2-O, a Plasmodium AP2-Family Transcription Factor

    PubMed Central

    Kaneko, Izumi; Iwanaga, Shiroh; Kato, Tomomi; Kobayashi, Issei; Yuda, Masao

    2015-01-01

    Stage-specific transcription is a fundamental biological process in the life cycle of the Plasmodium parasite. Proteins containing the AP2 DNA-binding domain are responsible for stage-specific transcriptional regulation and belong to the only known family of transcription factors in Plasmodium parasites. Comprehensive identification of their target genes will advance our understanding of the molecular basis of stage-specific transcriptional regulation and stage-specific parasite development. AP2-O is an AP2 family transcription factor that is expressed in the mosquito midgut-invading stage, called the ookinete, and is essential for normal morphogenesis of this stage. In this study, we identified the genome-wide target genes of AP2-O by chromatin immunoprecipitation-sequencing and elucidate how this AP2 family transcription factor contributes to the formation of this motile stage. The analysis revealed that AP2-O binds specifically to the upstream genomic regions of more than 500 genes, suggesting that approximately 10% of the parasite genome is directly regulated by AP2-O. These genes are involved in distinct biological processes such as morphogenesis, locomotion, midgut penetration, protection against mosquito immunity and preparation for subsequent oocyst development. This direct and global regulation by AP2-O provides a model for gene regulation in Plasmodium parasites and may explain how these parasites manage to control their complex life cycle using a small number of sequence-specific AP2 transcription factors. PMID:26018192

  19. Functions of Adaptor Protein (AP)-3 and AP-1 in Tyrosinase Sorting from Endosomes to MelanosomesD⃞

    PubMed Central

    Theos, Alexander C.; Tenza, Danièle; Martina, José A.; Hurbain, Ilse; Peden, Andrew A.; Sviderskaya, Elena V.; Stewart, Abigail; Robinson, Margaret S.; Bennett, Dorothy C.; Cutler, Daniel F.; Bonifacino, Juan S.; Marks, Michael S.; Raposo, Graça

    2005-01-01

    Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies. PMID:16162817

  20. A single Beta adaptin contributes to AP1 and AP2 complexes and clathrin function in Dictyostelium

    PubMed Central

    Sosa, R. Thomas; Weber, Michelle M.; Wen, Yujia; O’Halloran, Theresa J.

    2011-01-01

    The assembly of clathrin-coated vesicles is important for numerous cellular processes, including nutrient uptake and membrane organization. Important contributors to clathrin assembly are four tetrameric Assembly Proteins, also called Adaptor Proteins (AP’s), each of which contains a beta subunit. We identified a single beta subunit, named β1/2, that contributes to both the AP1 and AP2 complexes of Dictyostelium. Disruption of the gene encoding β1/2 resulted in severe defects in growth, cytokinesis, and development. Additionally, cells lacking β1/2 displayed profound osmoregulatory defects including the absence of contractile vacuoles and mislocalization of contractile vacuole markers. The phenotypes of β1/2 were most similar to previously described phenotypes of clathrin and AP1 mutants, supporting a particularly important contribution of AP1 to clathrin pathways in Dictyostelium cells. The absence of β1/2 in cells led to significant reductions in the protein amounts of the medium-sized subunits of the AP1 and AP2 complexes, establishing a role for the beta subunit in the stability of the medium subunits. Dictyostelium β1/2 could resemble a common ancestor of the more specialized β1 and β2 subunits of the vertebrate AP complexes. Our results support the essential contribution a single beta subunit to the stability and function AP1 and AP2 in a simple eukaryote. PMID:22050483

  1. The AP2-like gene NsAP2 from water lily is involved in floral organogenesis and plant height.

    PubMed

    Luo, Huolin; Chen, Sumei; Jiang, Jiafu; Teng, Nianjun; Chen, Yu; Chen, Fadi

    2012-07-01

    APETALA2 (AP2) genes are ancient and widely distributed among the seed plants, and play an important role during the plant life cycle, acting as key regulators of many developmental processes. In this study, an AP2 homologue, NsAP2, was characterized from water lily (Nymphaea sp. cv. 'Yellow Prince') and is believed to be rather primitive in the evolution of the angiosperms. In situ RNA hybridization showed that NsAP2 transcript was present in all regions of the floral primordium, but had the highest level in the emerging floral organ primordium. After the differentiation of floral organs, NsAP2 was strongly expressed in sepals and petals, while low levels were found in stamens and carpels. The NsAP2 protein was suggested to be localized in the cell nucleus by onion transient expression experiment. Overexpression of NsAP2 in Arabidopsis led to more petal numbers, and Arabidopsis plants expressing NsAP2 exhibited higher plant height, which may be a result of down-regulated expression of GA2ox2 and GA2ox7. Our results indicated that the NsAP2 protein may function in flower organogenesis in water lily, and it is a promising gene for plant height improvement.

  2. 49 CFR 178.255-10 - Lining.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Lining. 178.255-10 Section 178.255-10... Specifications for Portable Tanks § 178.255-10 Lining. (a) If a lining is required, the material used for lining... other equally satisfactory means. Rubber lining shall be not less than 3/16 inch thick. Joints and...

  3. Eastman, AP start on coal unit

    SciTech Connect

    1995-10-25

    Eastman Chemical and Air Products and Chemicals (AP) have started construction of a $214-million, coal-to-methanol demonstration unit at Eastmans site in Kingsport, TN. The project is part of the Department of Energy`s clean coal technology program and is receiving $93 million in federal support. The demonstration unit-which will have a methanol capacity of 260 tons/day-will use novel catalyst technology for converting coal-derived synthesis gas (syngas) to methanol. Unlike conventional technology that processes syngas through a fixed bed of dry catalyst particles, the liquid-phase methanol process converts the syngas in a single vessel containing catalysts suspended in mineral oil. The companies say the innovation allows the process to better able handle the gases from coal gasifiers and is more stable and reliable than existing processes. Eastman says it will use the methanol produced by the plant as a chemical feedstock. It currently uses methanol as an intermediate in making acetic anhydride and dimethyl terephthalate. In addition, the companies say the methanol will be evaluated as a feedstock in making methyl tert-butyl ether for reformulated fuels. Eastman also says it will evaluate coproducing dimethyl ether (DME) with the methanol. DME can be used as a fuel additive or blended with methanol for a chemical feedstock, according to Eastman.

  4. High Pressure Reverse Flow APS Engine

    NASA Technical Reports Server (NTRS)

    Senneff, J. M.

    1972-01-01

    A design and test demonstration effort was undertaken to evaluate the concept of the reverse flow engine for the APS engine application. The 1500 lb (6672 N) thrust engine was designed to operate on gaseous hydrogen and gaseous oxygen propellants at a mixture ratio of 4 and to achieve the objective performance of 435 sec (4266 Nsec/kg) specific impulse. Superimposed durability requirements called for a million-cycle capability with 50 hours duration. The program was undertaken as a series of tasks including the initial preliminary design, design of critical test components and finally, the design and demonstration of an altitude engine which could be used interchangeably to examine operating parameters as well as to demonstrate the capability of the concept. The program results are reported with data to indicate that all of the program objectives were met or exceeded within the course of testing on the program. The analysis effort undertaken is also reported in detail and supplemented with test data in some cases where prior definitions could not be made. The results are contained of these analyses as well as the test results conducted throughout the course of the program. Finally, the test data and analytical results were combined to allow recommendations for a flight weight design. This preliminary design effort is also detailed.

  5. Sodium-dependent uptake of glutamate by novel ApGltS enhanced growth under salt stress of halotolerant cyanobacterium Aphanothece halophytica.

    PubMed

    Boonburapong, Bongkoj; Laloknam, Surasak; Yamada, Nana; Incharoensakdi, Aran; Takabe, Teruhiro

    2012-01-01

    Glutamate is a major free amino acid in cyanobacteria, but its transport properties remain largely unknown. In this study, we found that a halotolerant cyanobacterium, Aphanothece halophytica, contained a sodium dependent glutamate transporter (ApGltS). The deduced amino acid sequence of ApGltS exhibited low homology (18-19% identity) to GltS from Synechocystis sp. PCC 6803 (slr1145) and Escherichia coli. The predicted ApGltS consisted of 476 amino acid residues with a molecular weight of 50,976 Da. As analysed by hydropathy profiling, ApGltS contains 11 transmembrane segments. The ApgltS gene was isolated and expressed in E. coli ME9107, which is deficient in glutamate uptake. ME9107, expressing ApGltS, took up glutamate and its rates increased with increasing concentrations of NaCl. Kinetics studies revealed that ApGltS is a high-affinity glutamate transporter with a K(m) of about 5 µM. The presence of 0.5 M NaCl in the assay medium increased V(max) by about 3-fold. Competition experiments revealed that glutamate, glutamine, aspartate, and asparagine inhibited glutamate uptake. The level of mRNA for ApgltS was higher in A. halophytica grown at high salinity. Under high salinity conditions supplemented with glutamate, A. halophytica showed a significant increase in intracellular glycine betaine.

  6. Pulsations in the atmosphere of the rapidly oscillating Ap star 10Aquilae

    NASA Astrophysics Data System (ADS)

    Sachkov, M.; Kochukhov, O.; Ryabchikova, T.; Huber, D.; Leone, F.; Bagnulo, S.; Weiss, W. W.

    2008-09-01

    The rapidly oscillating Ap (roAp) star 10Aquilae (10Aql) shows one of the lowest photometric pulsation amplitudes and is characterized by an unusual spectroscopic pulsational behaviour compared to other roAp stars. In summer 2006 this star became target of an intense observing campaign, that combined ground-based spectroscopy with space photometry obtained with the MOST (Microvariability & Oscillations Stars) satellite. More than 1000 spectra were taken during seven nights over a time-span of 21d with high-resolution spectrographs at the 8-m European Southern Observatory (ESO) Very Large Telescope (VLT) and 3.6-m Telescopio Nazionale Galileo (TNG) giving access to radial velocity variations of about 150 lines from different chemical species. A comparison of pulsation signatures in lines formed at different atmospheric heights allowed us to resolve the vertical structure of individual pulsation modes in 10Aql which is the first time for a multiperiodic roAp star. Taking advantage of the clear oscillation patterns seen in a number of rare earth ions and using the contemporaneous MOST photometry to resolve aliasing in the radial velocity measurements, we improve also the determination of pulsation frequencies. The inferred propagation of pulsation waves in 10Aql is qualitatively similar to other roAp stars: pulsation amplitudes become measurable in the layers where Y and Eu are concentrated, increase in layers where the Hα core is formed, reach a maximum of 200-300ms-1 in the layers probed by Ce, Sm, Dy lines and then decrease to 20-50ms-1 in the layers where NdIII and PrIII lines are formed. A unique pulsation feature of 10Aql is a second pulsation maximum indicated by TbIII lines which form in the uppermost atmospheric layers and oscillate with amplitudes of up to 350ms-1. The dramatic decline of pulsations in the atmospheric layers probed by the strong PrIII and NdIII lines accounts for the apparent peculiarity of 10Aql when compared to other roAp stars. The phase

  7. MiR-193a-5p Targets the Coding Region of AP-2α mRNA and Induces Cisplatin Resistance in Bladder Cancers.

    PubMed

    Zhou, Ji; Duan, Huaxin; Xie, Yu; Ning, Yichong; Zhang, Xing; Hui, Na; Wang, Chunqing; Zhang, Jian; Zhou, Jianlin

    2016-01-01

    Transcription factor AP-2 alpha (AP-2α or TFAP2A) is a newly identified prognostic marker of chemotherapy; its expression is positively correlated with chemosensitivity and survival of cancer patients. Using computational programs, we predicted that the coding region of AP-2α gene contains a potential miRNA response element (MRE) of miR-193a-5p, and the single nucleotide polymorphism (SNP) site (c.497A>G, rs111681798) resides within the predicted MRE. The results of luciferase assays and Western blot analysis demonstrated that miR-193a-5p negatively regulated the expression of AP-2α proteins, but have no influence on the mutant AP-2α (c.497A>G). Infection with lentiviral AP-2α gene or miR-193a-5p inhibitor in the bladder cancer cells decreased migration and cisplatin resistance, while knockdown of AP-2α gene or overexpression of miR-193a-5p in the urothelial cell line SV-HUC-1 increased migration and cisplatin resistances. We concluded that miR-193a-5p induced cisplatin resistance by repressing AP-2α expression in bladder cancer cells.

  8. Assessment of RELAP5/MOD3 off-take model for application to AP600 analysis

    SciTech Connect

    Rubin, M.B. ); Baratta, A.J. )

    1993-01-01

    The Westinghouse AP600 advanced pressurized water reactor uses a surge-line geometry that differs from that found in existing Westinghouse plants. The off-take is located in the hot leg at a 55-deg angle and has an initial slope of 24 deg. Typical geometries found in other Westinghouse reactors would have the surge line attached to the horizontal run of the hot leg and entering at a location from the top. A concern over the off-take and surge-line originates because of the impact that phase separation effects would have on system depressurization and mass inventory during a small break loss-of-coolant-accident (LOCA). High-quality flow out the branch of the off-take has a greater depressurization rate and less mass loss than low-quality flows. This paper evaluates the current off-take capabilities of RELAP5 and assesses whether it is sufficient to model the expected behavior in the AP600 surge-line off-take. The existing data base was reviewed, and the need for new data was evaluated.

  9. The APS SASE FEL : modeling and code comparison.

    SciTech Connect

    Biedron, S. G.

    1999-04-20

    A self-amplified spontaneous emission (SASE) free-electron laser (FEL) is under construction at the Advanced Photon Source (APS). Five FEL simulation codes were used in the design phase: GENESIS, GINGER, MEDUSA, RON, and TDA3D. Initial comparisons between each of these independent formulations show good agreement for the parameters of the APS SASE FEL.

  10. Data-Based Decision Making: The Road to AP Equity

    ERIC Educational Resources Information Center

    Edwards, Kelcey; Duggan, Odette

    2012-01-01

    Presented at the Advanced Placement Annual Conference (APAC) in Lake Buena Vista, FL in July 2012. This presentation reviews concepts central to achieving equitable AP access and success for all willing and academically prepared students. We analyze trends in participation and performance by race/ethnicity from the AP Report to the Nation and…

  11. AP-102/104 Retrieval control system qualification test procedure

    SciTech Connect

    RIECK, C.A.

    1999-05-18

    This Qualification Test Procedure documents the results of the qualification testing that was performed on the Project W-211, ''Initial Tank Retrieval Systems,'' retrieval control system (RCS) for tanks 241-AP-102 and 241-AP-104. The results confirm that the RCS has been programmed correctly and that the two related hardware enclosures have been assembled in accordance with the design documents.

  12. Performance of Project Advance Students on the AP Biology Examination.

    ERIC Educational Resources Information Center

    Mercurio, Joseph; And Others

    1984-01-01

    Compared performance of Project Advance biology students (N=60) with Advanced Placement (AP) candidates (N=15,947) nationally on College Entrance Examination Board AP biology test. The research, conducted to determine comparability of the program as valid measures of academic achievement, determined that Project Advance students scored above the…

  13. Raising Rigor, Getting Results: Lessons Learned from AP Expansion

    ERIC Educational Resources Information Center

    Wakelyn, David

    2009-01-01

    Advanced Placement (AP), which enables high school students to take introductory college-level courses, is the nation's oldest example of a rigorous, common curriculum. Students who score well on AP exams are more likely to persist in college and earn a degree. The Advanced Placement Expansion project of the National Governors Association Center…

  14. AP233: An Information Model for Systems Engineering

    NASA Technical Reports Server (NTRS)

    Siebes, Georg

    2009-01-01

    In today's world, information is abundant. We have no problems generating it. But we are challenged to find, organize, and exchange information. center dot A standardized model of information can help. Such a model nearly completed its development for Systems Engineering. It is referred to as AP233 (AP = Application Protocol).

  15. AccuNet/AP (Associated Press) Multimedia Archive

    ERIC Educational Resources Information Center

    Young, Terrence E., Jr.

    2004-01-01

    The AccuNet/AP Multimedia Archive is an electronic library containing the AP's current photos and a selection of pictures from their enormous print and negative library, as well as text and graphic material. It is composed of two photo databases as well as graphics, text, and audio databases. The features of this database are briefly described in…

  16. AP: A Critical Examination of the Advanced Placement Program

    ERIC Educational Resources Information Center

    Sadler, Philip M.; Sonnert, Gerhard; Tai, Robert; Klopfenstein, Kirstin

    2016-01-01

    The Advanced Placement (AP) program was created to enhance the experience of gifted students as they transition from high school to college. "AP: A Critical Examination of the Advanced Placement Program," edited by Philip M. Sadler, Gerhard Sonnert, Robert Tai, and Kirstin Klopfenstein (2010, Harvard Education Press), questions the…

  17. A Closer Examination of the Academic Benefits of AP

    ERIC Educational Resources Information Center

    McKillip, Mary E. M.; Rawls, Anita

    2013-01-01

    The authors sought to better understand the relationship between students participating in the Advanced Placement (AP) program and subsequent performance on the Scholastic Aptitude Test (SAT). Focusing on students graduating from U.S. public high schools in 2010, the authors used propensity scores to match junior year AP examinees in 3 subjects to…

  18. Content Validation Studies of the AP Chemistry Examination.

    ERIC Educational Resources Information Center

    Taft, Hessy L.

    1990-01-01

    Described is a curriculum survey of general chemistry courses at the college level and an evaluation survey of the advanced placement chemistry examination. Results indicated that the AP chemistry course should remain broad in coverage and should expand its laboratory component. Analyses also indicated that the AP exam was appropriate and valid.…

  19. Lithium and Isotopic Ratio Li6/Li7 in Magnetic roAp Stars as an Indicator of Active Processes

    NASA Astrophysics Data System (ADS)

    Polosukhina, N.; Shavrina, A.; Lyashko, D.; Nesvacil, N.; Drake, N.; Smirnova, M.

    2015-04-01

    The lines of lithium at 6708 Å and 6103 Å are analyzed in high resolution spectra of some sharp-lined and slowly rotating roAp stars. Three spectral synthesis codes— STARSP, ZEEMAN2, and SYNTHM—were used. New lines of rare earth elements (REE) from the DREAM database and the lines calculated on the basis of the NIST energy levels were included. Magnetic splitting and other line broadening processes were taken into account. For both lithium lines, the enhanced abundances of lithium in the atmospheres of the stars studied are obtained. The lithium abundance determined from the Li 6103 Å line is higher than that from the Li 6708 Å for all the stars. This may be evidence of vertical lithium stratification, abnormal temperature distribution, or unidentified blending of the 6103 Å line. Our work on two roAp stars, HD 83368 and HD 60435 (Shavrina et al. 2001) provides evidence of an enhanced lithium abundance near the magnetic-field poles. We can expect similar effects in the sharp-lined roAp stars. High lithium abundance for all the stars and the estimates of the 6Li/7Li ratio (0.2-0.5) can be explained by production of Li in the cosmic ray spallation reactions in the interstellar medium where the stars were born, and by preservation of the original 6Li and 7Li by strong magnetic fields of these stars. The values of the 6Li/7Li ratio expected from production by cosmic rays are about 0.5-0.8 (Knauth et al. 2003; Webber et al. 2002). New laboratory and theoretical gf-values for REE lines are necessary in order to refine our estimates of lithium abundances and the isotopic ratio.

  20. A Human Renal Proximal Tubule Cell Line with Stable Organic Anion Transporter 1 and 3 Expression Predictive for Antiviral-Induced Toxicity.

    PubMed

    Nieskens, Tom T G; Peters, Janny G P; Schreurs, Marieke J; Smits, Niels; Woestenenk, Rob; Jansen, Katja; van der Made, Thom K; Röring, Melanie; Hilgendorf, Constanze; Wilmer, Martijn J; Masereeuw, Rosalinde

    2016-03-01

    Drug-induced nephrotoxicity still hampers drug development, because current translation from in vitro or animal studies to human lacks high predictivity. Often, renal adverse effects are recognized only during clinical stages of drug development. The current study aimed to establish a robust and a more complete human cell model suitable for screening of drug-related interactions and nephrotoxicity. In addition to endogenously expressed renal organic cation transporters and efflux transporters, conditionally immortalized proximal tubule epithelial cells (ciPTEC) were completed by transduction of cells with the organic anion transporter (OAT) 1 or OAT3. Fluorescence-activated cell sorting upon exposure to the OAT substrate fluorescein successfully enriched transduced cells. A panel of organic anions was screened for drug-interactions in ciPTEC-OAT1 and ciPTEC-OAT3. The cytotoxic response to the drug-interactions with antivirals was further examined by cell viability assays. Upon subcloning, concentration-dependent fluorescein uptake was found with a higher affinity for ciPTEC-OAT1 (Km = 0.8 ± 0.1 μM) than ciPTEC-OAT3 (Km = 3.7 ± 0.5 μM). Co-exposure to known OAT1 and/or OAT3 substrates (viz. para-aminohippurate, estrone sulfate, probenecid, furosemide, diclofenac, and cimetidine) in cultures spanning 29 passage numbers revealed relevant inhibitory potencies, confirming the robustness of our model for drug-drug interactions studies. Functional OAT1 was directly responsible for cytotoxicity of adefovir, cidofovir, and tenofovir, while a drug interaction with zidovudine was not associated with decreased cell viability. Our data demonstrate that human-derived ciPTEC-OAT1 and ciPTEC-OAT3 are promising platforms for highly predictive drug screening during early phases of drug development.

  1. How to Find a Bug in Ten Thousand Lines Transport Solver? Outline of Experiences from AN Advection-Diffusion Code Verification

    NASA Astrophysics Data System (ADS)

    Zamani, K.; Bombardelli, F.

    2011-12-01

    Almost all natural phenomena on Earth are highly nonlinear. Even simplifications to the equations describing nature usually end up being nonlinear partial differential equations. Transport (ADR) equation is a pivotal equation in atmospheric sciences and water quality. This nonlinear equation needs to be solved numerically for practical purposes so academicians and engineers thoroughly rely on the assistance of numerical codes. Thus, numerical codes require verification before they are utilized for multiple applications in science and engineering. Model verification is a mathematical procedure whereby a numerical code is checked to assure the governing equation is properly solved as it is described in the design document. CFD verification is not a straightforward and well-defined course. Only a complete test suite can uncover all the limitations and bugs. Results are needed to be assessed to make a distinction between bug-induced-defect and innate limitation of a numerical scheme. As Roache (2009) said, numerical verification is a state-of-the-art procedure. Sometimes novel tricks work out. This study conveys the synopsis of the experiences we gained during a comprehensive verification process which was done for a transport solver. A test suite was designed including unit tests and algorithmic tests. Tests were layered in complexity in several dimensions from simple to complex. Acceptance criteria defined for the desirable capabilities of the transport code such as order of accuracy, mass conservation, handling stiff source term, spurious oscillation, and initial shape preservation. At the begining, mesh convergence study which is the main craft of the verification is performed. To that end, analytical solution of ADR equation gathered. Also a new solution was derived. In the more general cases, lack of analytical solution could be overcome through Richardson Extrapolation and Manufactured Solution. Then, two bugs which were concealed during the mesh convergence

  2. GPI-AP release in cellular, developmental, and reproductive biology.

    PubMed

    Fujihara, Yoshitaka; Ikawa, Masahito

    2016-04-01

    Glycosylphosphatidylinositol-anchored proteins (GPI-APs) contain a covalently linked GPI anchor located on outer cell membranes. GPI-APs are ubiquitously conserved from protozoa to vertebrates and are critical for physiological events such as development, immunity, and neurogenesis in vertebrates. Both membrane-anchored and soluble GPI-APs play a role in regulating their protein conformation and functional properties. Several pathways mediate the release of GPI-APs from the plasma membrane by vesiculation or cleavage. Phospholipases and putative substrate-specific GPI-AP-releasing enzymes, such as NOTUM, glycerophosphodiesterase 2, and angiotensin-converting enzyme, have been characterized in mammals. Here, the protein modifications resulting from the cleavage of the GPI anchor are discussed in the context of its physiological functions.

  3. APS Alternative Fuel (Hydrogen) Pilot Plant - Monitoring System Report

    SciTech Connect

    James Francfort; Dimitri Hochard

    2005-07-01

    The U.S. Department of Energy’s (DOE’s) Advanced Vehicle Testing Activity (AVTA), along with Electric Transportation Applications and Arizona Pubic Service (APS), is monitoring the operations of the APS Alternative Fuel (Hydrogen) Pilot Plant to determine the costs to produce hydrogen fuels (including 100% hydrogen as well as hydrogen and compressed natural gas blends) for use by fleets and other operators of advanced-technology vehicles. The hydrogen fuel cost data will be used as benchmark data by technology modelers as well as research and development programs. The Pilot Plant can produce up to 18 kilograms (kg) of hydrogen per day by electrolysis. It can store up to 155 kg of hydrogen at various pressures up to 6,000 psi. The dispenser island can fuel vehicles with 100% hydrogen at 5,000 psi and with blends of hydrogen and compressed natural gas at 3,600 psi. The monitoring system was designed to track hydrogen delivery to each of the three storage areas and to monitor the use of electricity on all major equipment in the Pilot Plant, including the fuel dispenser island. In addition, water used for the electrolysis process is monitored to allow calculation of the total cost of plant operations and plant efficiencies. The monitoring system at the Pilot Plant will include about 100 sensors when complete (50 are installed to date), allowing for analysis of component, subsystems, and plant-level costs. The monitoring software is mostly off-the-shelve, with a custom interface. The majority of the sensors input to the Programmable Automation Controller as 4- to 20-mA analog signals. The plant can be monitored over of the Internet, but the control functions are restricted to the control room equipment. Using the APS general service plan E32 electric rate of 2.105 cents per kWh, during a recent eight-month period when 1,200 kg of hydrogen was produced and the plant capacity factor was 26%, the electricity cost to produce one kg of hydrogen was $3.43. However, the

  4. Comparison of the expression of human equilibrative nucleotide transporter 1 (hENT1) and ribonucleotide reductase subunit M1 (RRM1) genes in seven non-Hodgkin lymphoma cell lines.

    PubMed

    Zhao, H B; Zhang, X F; Shi, F; Zhang, M Z; Xue, W L

    2016-05-06

    We investigated the variability in the expression of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit M1 (RRM1) in non-Hodgkin lymphoma cell lines. hENT1 and RRM1 mRNA expression levels in natural killer (NK) cells and seven non-Hodgkin lymphoma cell lines (YTS, SNK-6, Jeko-1, ly-1, Raji, Karpas, and Jurket) were studied using reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) and the results were compared using the Student t-test. mRNA expression of hENT1 was detectable in YTS, SNK-6, Jeko-1, ly-1, Raji, Karpas, Jurket, and NK cells, which revealed variability in gene expression. There were significant differences in the mRNA expression values of hENT1 (P = 0.021) and RRM1 (P = 0.002) compared to those in NK cells. mRNA expression of both hENT1 and RRM1 was closely associated with non-Hodgkin lymphoma cell proliferation. Differential expression analysis of hENT1 and RRM1 in non-Hodgkin lymphoma cell lines may provide novel drug leads for precision medicine.

  5. Enhancing and Archiving the APS Catalog of the POSS I

    NASA Technical Reports Server (NTRS)

    Humphreys, Roberta M.

    2003-01-01

    We have worked on two different projects: 1) Archiving the APS Catalog of the POSS I for distribution to NASA's NED at IPAC, SIMBAD in France, and individual astronomers and 2) The automated morphological classification of galaxies. We have completed archiving the Catalog into easily readable binary files. The database together with the software to read it has been distributed on DVD's to the national and international data centers and to individual astronomers. The archived Catalog contains more than 89 million objects in 632 fields in the first epoch Palomar Observatory Sky Survey. Additional image parameters not available in the original on-line version are also included in the archived version. The archived Catalog is also available and can be queried at the APS web site (URL: http://aps.umn.edu) which has been improved with a much faster and more efficient querying system. The Catalog can be downloaded as binary datafiles with the source code for reading it. It is also being integrated into the SkyQuery system which includes the Sloan Digital Sky Survey, 2MASS, and the FIRST radio sky survey. We experimented with different classification algorithms to automate the morphological classification of galaxies. This is an especially difficult problem because there are not only a large number of attributes or parameters and measurement uncertainties, but also the added complication of human disagreement about the adopted types. To solve this problem we used 837 galaxy images from nine POSS I fields at the North Galactic Pole classified by two independent astronomers for which they agree on the morphological types. The initial goal was to separate the galaxies into the three broad classes relevant to issues of large scale structure and galaxy formation and evolution: early (ellipticals and lenticulars), spirals, and late (irregulars) with an accuracy or success rate that rivals the best astronomer classifiers. We also needed to identify a set of parameters derived

  6. Thermal Decomposition Characteristics of Orthorhombic Ammonium Perchlorate (o-AP) and an 0-AP/HTPB-Based Propellant

    SciTech Connect

    BEHRENS JR.,RICHARD; MINIER,LEANNA M.G.

    1999-10-25

    A study to characterize the low-temperature reactive processes for o-AP and an AP/HTPB-based propellant (class 1.3) is being conducted in the laboratory using the techniques of simultaneous thermogravimetric modulated beam mass spectrometry (STMBMS) and scanning electron microscopy (SEM). The results presented in this paper are a follow up of the previous work that showed the overall decomposition to be complex and controlled by both physical and chemical processes. The decomposition is characterized by the occurrence of one major event that consumes up to {approx}35% of the AP, depending upon particle size, and leaves behind a porous agglomerate of AP. The major gaseous products released during this event include H{sub 2}O, O{sub 2}, Cl{sub 2}, N{sub 2}O and HCl. The recent efforts provide further insight into the decomposition processes for o-AP. The temporal behaviors of the gas formation rates (GFRs) for the products indicate that the major decomposition event consists of three chemical channels. The first and third channels are affected by the pressure in the reaction cell and occur at the surface or in the gas phase above the surface of the AP particles. The second channel is not affected by pressure and accounts for the solid-phase reactions characteristic of o-AP. The third channel involves the interactions of the decomposition products with the surface of the AP. SEM images of partially decomposed o-AP provide insight to how the morphology changes as the decomposition progresses. A conceptual model has been developed, based upon the STMBMS and SEM results, that provides a basic description of the processes. The thermal decomposition characteristics of the propellant are evaluated from the identities of the products and the temporal behaviors of their GFRs. First, the volatile components in the propellant evolve from the propellant as it is heated. Second, the hot AP (and HClO{sub 4}) at the AP-binder interface oxidize the binder through reactions that

  7. The effect of the plasticizer diethylhexyl phthalate on transport activity and expression of P-glycoprotein in parental and doxo-resistant human sarcoma cell lines.

    PubMed

    Angelini, A; Centurione, L; Sancilio, S; Castellani, M L; Conti, P; Di Ilio, C; Porreca, E; Cuccurullo, F; Di Pietro, R

    2011-01-01

    Multidrug resistance (MDR) to cancer therapy is frequently associated with the over-expression of the multidrug transporter MDR1 gene product P-glycoprotein (Pgp) in several types of human tumours. Various chemosensitizers have been used to inhibit Pgp activity but toxicity limits their clinical application. Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer that is released from polyvinyl chloride (PVC) medical devices. Therefore, cancer patients undertaking chemotherapy are exposed to a clinically important amount of DEHP through blood and blood component transfusions, apheresis products, intravenous chemotherapy, parenteral nutrition and other medical treatments. The present study was designed to investigate the effects of DEHP on transport activity and expression of Pgp in order to evaluate its potential use as a chemosensitizer in cancer therapy. Human doxorubicin (doxo) resistant sarcoma cells (MES-SA/Dx5) that over-express Pgp were treated with different doses of doxo (2, 4 and 8 μM) in the presence or absence of various concentrations of DEHP (3, 6 and 12 μM) that were clinically achievable in vivo. Our results show that co-treatment with 2, 4 and 8 μM doxo in the presence of the lowest concentration of DEHP (3 μM) enhanced significantly doxo accumulation in MES-SA/Dx5 cells and, consistently increased the sensitivity to doxo, when compared to controls receiving only doxo. In contrast, higher DEHP concentrations (6 and 12 μM) induced MES-SA/Dx5 to extrude doxo decreasing doxo cytotoxicity toward resistant cells below control values. These results are consistent with the increase in Pgp expression levels in parental MES-SA cells treated with 3, 6 and 12 μM DEHP for 24 h and compared to untreated controls. All in all, these findings suggest a potential clinical application of DEHP as a chemosensitizer to improve effectiveness of the antineoplastic drugs in MDR human tumours.

  8. Mutagenesis of cysteine 81 prevents dimerization of the APS1 subunit of ADP-glucose pyrophosphorylase and alters diurnal starch turnover in Arabidopsis thaliana leaves.

    PubMed

    Hädrich, Nadja; Hendriks, Janneke H M; Kötting, Oliver; Arrivault, Stéphanie; Feil, Regina; Zeeman, Samuel C; Gibon, Yves; Schulze, Waltraud X; Stitt, Mark; Lunn, John E

    2012-04-01

    Many plants, including Arabidopsis thaliana, retain a substantial portion of their photosynthate in leaves in the form of starch, which is remobilized to support metabolism and growth at night. ADP-glucose pyrophosphorylase (AGPase) catalyses the first committed step in the pathway of starch synthesis, the production of ADP-glucose. The enzyme is redox-activated in the light and in response to sucrose accumulation, via reversible breakage of an intermolecular cysteine bridge between the two small (APS1) subunits. The biological function of this regulatory mechanism was investigated by complementing an aps1 null mutant (adg1) with a series of constructs containing a full-length APS1 gene encoding either the wild-type APS1 protein or mutated forms in which one of the five cysteine residues was replaced by serine. Substitution of Cys81 by serine prevented APS1 dimerization, whereas mutation of the other cysteines had no effect. Thus, Cys81 is both necessary and sufficient for dimerization of APS1. Compared to control plants, the adg1/APS1(C81S) lines had higher levels of ADP-glucose and maltose, and either increased rates of starch synthesis or a starch-excess phenotype, depending on the daylength. APS1 protein levels were five- to tenfold lower in adg1/APS1(C81S) lines than in control plants. These results show that redox modulation of AGPase contributes to the diurnal regulation of starch turnover, with inappropriate regulation of the enzyme having an unexpected impact on starch breakdown, and that Cys81 may play an important role in the regulation of AGPase turnover.

  9. AP-1 mediated relief of repressive activity of the CD30 promoter microsatellite in Hodgkin and Reed-Sternberg cells.

    PubMed

    Watanabe, Mariko; Ogawa, Yuji; Ito, Kinji; Higashihara, Masaaki; Kadin, Marshall E; Abraham, Lawrence J; Watanabe, Toshiki; Horie, Ryouichi

    2003-08-01

    Overexpression of CD30 is the hallmark of Hodgkin and Reed-Sternberg (H-RS) cells and drives constitutive nuclear factor-kappaB activation that is the molecular basis for the pathophysiology of Hodgkin's lymphoma. Transcription of the CD30 gene is controlled by the core promoter that is driven by Sp-1 and the microsatellite sequences (MSs) that represses core promoter activity. To understand the mechanism(s) of CD30 overexpression in H-RS cells, we structurally and functionally characterized the CD30 MSs. Although the CD30 MS of H-RS cell lines was polymorphic, it was not truncated compared with that of control cells. A strong core promoter activity and constitutive Sp-1 binding were revealed in all cell lines examined irrespective of the levels of CD30 expression. In transient reporter gene assays, all MS clones derived from H-RS cell lines repressed the core promoter activity in unrelated cell lines, but not in the H-RS cell lines. An AP-1-binding site was found in the MS at nucleotide position of -377 to -371, the presence of which was found to relieve repression of the core promoter in H-RS cell lines but not in other tumor cell lines. H-RS cell lines showed constitutive and strong AP-1-binding activity, but other cell lines did not. The AP-1 complex contained JunB, whose overexpression activated reporter constructs driven by the CD30 promoter including the MSs, and was dependent on the AP-1 site. JunB expression was detected in H-RS cells in vitro and in vivo, but not in reactive cells or tumor cells of non-Hodgkin's lymphoma of diffuse large B-cell type. Transduction of JunB small interfering RNAs suppressed CD30 promoter activity in L428 cells but not in control cells. Taken together, overexpression and binding of JunB to the AP-1 site appear to relieve the repression of the core promoter by the CD30 MS in H-RS cells, which provide one basis for the constitutive overexpression of CD30 in Hodgkin's lymphoma.

  10. Tobacco carcinogen mediated up-regulation of AP-1 dependent pro-angiogenic cytokines in head and neck carcinogenesis.

    PubMed

    Swenson, Wade G; Wuertz, Beverly R K; Ondrey, Frank G

    2011-09-01

    Tobacco is notably genotoxic and associated with head and neck carcinogenesis. Cigarette carcinogens have the capacity to alter early response gene expression in tobacco-related malignancies via genes such as nuclear factor kappa B (NFκB). A number of early response gene activation events are also facilitated by fos/jun activator protein 1 (AP-1) associated pathways. In the present study, we hypothesize that tobacco products may induce microenvironment alterations, promoting angiogenesis and providing a permissive environment for head and neck cancer progression. In an in vitro analysis, we employed immortalized oral keratinocyte (HOK-16B) and laryngeal squamous carcinoma (UM-SCC-11A) cells to investigate interleukin (IL)-8 and vascular endothelial growth factor (VEGF) induction by cigarette smoke condensate (CSC). IL-8 and VEGF expression is based on interactions between NFκB, AP-1, and NF-IL6. We identified at least 1.5-fold dose-dependent induction of AP-1, VEGF, and IL-8 promoter/reporter gene activity after 24 h exposure to CSC. Next, we stably transfected UM-SCC-11A cells with A-Fos, a dominant negative AP-1 protein. Treatment with CSC of the A-Fos cell lines compared to empty vector controls significantly down-regulated AP-1, VEGF, and IL-8 promoter/reporter gene expression. We also performed ELISAs and discovered significant up-regulation of IL-8 and VEGF secretion by UMSCC 11A after treatment with phorbol 12-myristate 13-acetate, tumor necrosis factor alpha, and CSC, which was down-regulated by the A-Fos dominant negative protein. We conclude tobacco carcinogens up-regulate AP-1 activity and AP-1 dependent IL-8 and VEGF gene expression in head and neck cancer. This up-regulation may promote an angiogenic phenotype favoring invasion in both premalignant and squamous cancer cells of the head and neck.

  11. Some ethylene biosynthesis and AP2/ERF genes reveal a specific pattern of expression during somatic embryogenesis in Hevea brasiliensis

    PubMed Central

    2012-01-01

    Background Ethylene production and signalling play an important role in somatic embryogenesis, especially for species that are recalcitrant in in vitro culture. The AP2/ERF superfamily has been identified and classified in Hevea brasiliensis. This superfamily includes the ERFs involved in response to ethylene. The relative transcript abundance of ethylene biosynthesis genes and of AP2/ERF genes was analysed during somatic embryogenesis for callus lines with different regeneration potential, in order to identify genes regulated during that process. Results The analysis of relative transcript abundance was carried out by real-time RT-PCR for 142 genes. The transcripts of ERFs from group I, VII and VIII were abundant at all stages of the somatic embryogenesis process. Forty genetic expression markers for callus regeneration capacity were identified. Fourteen markers were found for proliferating calli and 35 markers for calli at the end of the embryogenesis induction phase. Sixteen markers discriminated between normal and abnormal embryos and, lastly, there were 36 markers of conversion into plantlets. A phylogenetic analysis comparing the sequences of the AP2 domains of Hevea and Arabidopsis genes enabled us to predict the function of 13 expression marker genes. Conclusions This first characterization of the AP2/ERF superfamily in Hevea revealed dramatic regulation of the expression of AP2/ERF genes during the somatic embryogenesis process. The gene expression markers of proliferating callus capacity to regenerate plants by somatic embryogenesis should make it possible to predict callus lines suitable to be used for multiplication. Further functional characterization of these markers opens up prospects for discovering specific AP2/ERF functions in the Hevea species for which somatic embryogenesis is difficult. PMID:23268714

  12. apGA: An adaptive parallel genetic algorithm

    SciTech Connect

    Liepins, G.E. ); Baluja, S. )

    1991-01-01

    We develop apGA, a parallel variant of the standard generational GA, that combines aggressive search with perpetual novelty, yet is able to preserve enough genetic structure to optimally solve variably scaled, non-uniform block deceptive and hierarchical deceptive problems. apGA combines elitism, adaptive mutation, adaptive exponential scaling, and temporal memory. We present empirical results for six classes of problems, including the DeJong test suite. Although we have not investigated hybrids, we note that apGA could be incorporated into other recent GA variants such as GENITOR, CHC, and the recombination stage of mGA. 12 refs., 2 figs., 2 tabs.

  13. AP600 design certification thermal hydraulics testing and analysis

    SciTech Connect

    Hochreiter, L.E.; Piplica, E.J.

    1995-09-01

    Westinghouse Electric Corporation, in conjunction with the Department of Energy and the Electric Power Research Institute, have been developing an advanced light water reactor design; the AP600. The AP600 is a 1940 Mwt, 600Mwe unit which is similar to a Westinghouse two-loop Pressurized Water Reactor. The accumulated knowledge on reactor design to reduce the capital costs, construction time, and the operational and maintenance cost of the unit once it begins to generate electrical power. The AP600 design goal is to maintain an overall cost advantage over fossil generated electrical power.

  14. Tank 241-AP-105, cores 208, 209 and 210, analytical results for the final report

    SciTech Connect

    Nuzum, J.L.

    1997-10-24

    This document is the final laboratory report for Tank 241-AP-105. Push mode core segments were removed from Risers 24 and 28 between July 2, 1997, and July 14, 1997. Segments were received and extruded at 222-S Laboratory. Analyses were performed in accordance with Tank 241-AP-105 Push Mode Core Sampling and Analysis Plan (TSAP) (Hu, 1997) and Tank Safety Screening Data Quality Objective (DQO) (Dukelow, et al., 1995). None of the subsamples submitted for total alpha activity (AT), differential scanning calorimetry (DSC) analysis, or total organic carbon (TOC) analysis exceeded the notification limits as stated in TSAP and DQO. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group, and are not considered in this report. Appearance and Sample Handling Two cores, each consisting of four segments, were expected from Tank 241-AP-105. Three cores were sampled, and complete cores were not obtained. TSAP states core samples should be transported to the laboratory within three calendar days from the time each segment is removed from the tank. This requirement was not met for all cores. Attachment 1 illustrates subsamples generated in the laboratory for analysis and identifies their sources. This reference also relates tank farm identification numbers to their corresponding 222-S Laboratory sample numbers.

  15. Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner

    PubMed Central

    Alford, Justine E.; Marongiu, Michela; Watkins, Gemma L.

    2016-01-01

    Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV-1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release. PMID:27392064

  16. Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner.

    PubMed

    Alford, Justine E; Marongiu, Michela; Watkins, Gemma L; Anderson, Emma C

    2016-01-01

    Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV-1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release.

  17. Modulation of AP-1 activity by nitric oxide (NO) in vitro: NO-mediated modulation of AP-1.

    PubMed

    Tabuchi, A; Sano, K; Oh, E; Tsuchiya, T; Tsuda, M

    1994-08-29

    To understand the role of nitric oxide (NO) in controlling the specific DNA-binding activities of transcriptional factors, we investigated the in vitro effect of the NO-donor sodium nitroprusside (SNP) on the AP-1 activity of cultured mouse cerebellar granule cells. A gel-mobility assay showed that SNP inhibited AP-1 activity in the presence, but not the absence of dithiothreitol (DTT). This DTT-dependent inhibition of AP-1 activity by SNP corresponded with the activation of the chemical reactivity of SNP with DTT, which can be monitored by the production of nitrite (NO2-). In contrast, diamide, a typical sulfhydryl oxidizing agent, inhibited AP-1 activity in the absence of DTT and its inhibitory effect was reversed competitively by DTT. Studies using structurally or functionally related analogues of SNP demonstrated that S-nitrosylation of the AP-1 moiety mediated by some NO-carriers but not by free NO, which can be produced by the chemical reaction of SNP with DTT, was responsible for the inhibition of AP-1 activity, suggesting NO-mediated regulation of the AP-1 transcriptional factor.

  18. roAp stars: surface lithium abundance distribution and magnetic field configuration

    NASA Astrophysics Data System (ADS)

    Polosukhina, N.; Shulyak, D.; Shavrina, A.; Lyashko, D.; Drake, N. A.; Glagolevski, Yu.; Kudryavtsev, D.; Smirnova, M.

    2014-08-01

    High-resolution spectra obtained with the 6m BTA telescope, Russia, and with HARPS and VLT/UVES telescopes at ESO, Chile, were used for Doppler Imaging analysis of two roAp stars, HD 12098 and HD 60435, showing strong and variable Li resonance line in their spectra. We found that Li has highly inhomogeneous distribution on the surfaces of these stars. We compared our results with previously obtained Doppler Imaging mapping of two CP2 stars, HD 83368 and HD 3980, and discuss the correlation between the position of the high Li-abundance spots and magnetic field.

  19. 30 Years of APS Congressional Fellows: Looking Back and Looking Forward

    NASA Astrophysics Data System (ADS)

    2003-04-01

    In 1973 AAAS launched a Congressional Fellows Program, and APS was one of three founding participants. Since then, APS has funded one or two Fellows annually to work with a Congressional Committee or on the personal staff of a Member of Congress. These fellows individually and collectively have had and continue to have a large impact in Washington. Six Fellows from different periods of the 30-year program, including a current Member of Congress, will present their views and assessments of the Fellowship program. They will address how it affected them, what it has done for the country and how APS should plan for the future. There will be ample time for questions and discussion. Panelists: Ben Cooper, Association of Oil Pipe Lines (Fellow, 1973-74) Rush Holt, Member, House of Representatives (Fellow, 1982-83) Jane Alexander, Office of Naval Research (Fellow, 1986-87) Duncan Moore, University of Rochester (Fellow, 1993-94) Peter Rooney, House Committee on Science (Fellow, 1997-98) Sherri Stephan, Senate Committee on Government Affairs (Fellow, 2000-01)

  20. Distinct Temporal Regulation of RET Isoform Internalization: Roles of Clathrin and AP2.

    PubMed

    Crupi, Mathieu J F; Yoganathan, Piriya; Bone, Leslie N; Lian, Eric; Fetz, Andrew; Antonescu, Costin N; Mulligan, Lois M

    2015-11-01

    The RET receptor tyrosine kinase (RTK) contributes to kidney and nervous system development, and is implicated in a number of human cancers. RET is expressed as two protein isoforms, RET9 and RET51, with distinct interactions and signaling properties that contribute to these processes. RET isoforms are internalized from the cell surface into endosomal compartments in response to glial cell line-derived neurotropic factor (GDNF) ligand stimulation but the specific mechanisms of RET trafficking remain to be elucidated. Here, we used total internal reflection fluorescence (TIRF) microscopy to demonstrate that RET internalization occurs primarily through clathrin coated pits (CCPs). Activated RET receptors colocalize with clathrin, but not caveolin. The RET51 isoform is rapidly and robustly recruited to CCPs upon GDNF stimulation, while RET9 recruitment occurs more slowly and is less pronounced. We showed that the clathrin-associated adaptor protein complex 2 (AP2) interacts directly with each RET isoform through its AP2 μ subunit, and is important for RET internalization. Our data establish that interactions with the AP2 complex promote RET receptor internalization via clathrin-mediated endocytosis but that RET9 and RET51 have distinct internalization kinetics that may contribute to differences in their biological functions.

  1. Analysis of an AP600 intermediate-size loss-of-coolant accident

    SciTech Connect

    Boyack, B.E.; Lime, J.F.

    1995-09-01

    A postulated double-ended guillotine break of an AP600 direct-vessel-injection line has been analyzed. This event is characterized as an intermediate-break loss-of-coolant accident. Most of the insights regarding the response of the AP600 safety systems to the postulated accident are derived from calculations preformed with the TRAC-PF1/MOD2 code. However, complementary insights derived from a scaled experiment conducted in the ROSA facility, as well as insights based upon calculations by other codes, are also presented. Based upon the calculated and experimental results, the AP600 will not experience a core heat up and will reach a safe shutdown state using only safety-class equipment. Only the early part of the long-term cooling period initiated by In-containment Refueling Water Storage Tank injection was evaluated. Thus, the observation that the core is continuously cooled should be verified for the later phase of the long-term cooling period when sump injection and containment cooling processes are important.

  2. 75 FR 14259 - Transportation Conformity Rule PM2.5

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ... Protection Agency 40 CFR Part 93 Transportation Conformity Rule PM2.5 and PM10 Amendments; Final Rule #0;#0...; ] ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 93 RIN 2060-AP29 Transportation Conformity Rule PM 2.5 and PM 10... amending the transportation conformity rule to finalize provisions that were proposed on May 15,...

  3. QCD on the Massively Parallel Computer AP1000

    NASA Astrophysics Data System (ADS)

    Akemi, K.; Fujisaki, M.; Okuda, M.; Tago, Y.; Hashimoto, T.; Hioki, S.; Miyamura, O.; Takaishi, T.; Nakamura, A.; de Forcrand, Ph.; Hege, C.; Stamatescu, I. O.

    We present the QCD-TARO program of calculations which uses the parallel computer AP1000 of Fujitsu. We discuss the results on scaling, correlation times and hadronic spectrum, some aspects of the implementation and the future prospects.

  4. A hot-spare injector for the APS linac.

    SciTech Connect

    Lewellen, J. W.

    1999-04-13

    Last year a second-generation SSRL-type thermionic cathode rf gun was installed in the Advanced Photon Source (APS) linac. This gun (referred to as ''gun2'') has been successfully commissioned and now serves as the main injector for the APS linac, essentially replacing the Koontz-type DC gun. To help ensure injector availability, particularly with the advent of top-up mode operation at the APS, a second thermionic-cathode rf gun will be installed in the APS linac to act as a hot-spare beam source. The hot-spare installation includes several unique design features, including a deep-orbit Panofsky-style alpha magnet. Details of the hot-spare beamline design and projected performance are presented, along with some plans for future performance upgrades.

  5. DETAIL VIEW OF AP 50, MAIN FLOOR LEVEL, PLATFORM BSOUTH, ...

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

    DETAIL VIEW OF AP 50, MAIN FLOOR LEVEL, PLATFORM B-SOUTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  6. DETAIL VIEW OF AP 65, SECOND FLOOR LEVEL, PLATFORM DSOUTH, ...

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

    DETAIL VIEW OF AP 65, SECOND FLOOR LEVEL, PLATFORM D-SOUTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  7. DETAIL VIEW OF AP 66, MAIN FLOOR LEVEL, PLATFORM BNORTH, ...

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

    DETAIL VIEW OF AP 66, MAIN FLOOR LEVEL, PLATFORM B-NORTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  8. Engaging Cuban Physicists Through the APS/CPS Partnership

    NASA Astrophysics Data System (ADS)

    Lerch, Irving A.; Lerch, Irving A.

    In his reflections on Cuban physics, Marcelo Alonso urges APS to take steps to promote interactions between Cuban and US physicists. As an introduction to Marcello's essay, this note will summarize past and current activities.

  9. PKCε inhibits isolation and stemness of side population cells via the suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell carcinoma cell line 769P.

    PubMed

    Huang, Bin; Fu, Shun Jun; Fan, Wen Zhe; Wang, Zhong Hua; Chen, Ze Bin; Guo, Sheng Jie; Chen, Jun Xing; Qiu, Shao Peng

    2016-06-28

    Protein kinase C epsilon (PKCε), a member of the novel PKC family, is known to be a transforming oncogene and tumor biomarker for many human solid cancers including renal cell carcinoma (RCC). We isolated side population (SP) cells from the RCC 769P cell line, and proved that those cells possess cancer stem cell (CSC) characteristics. In this study, to identify the function of PKCε in cancer stemness of 769P SP cells, we reduced the expression of PKCε in those cells, following the results demonstrated that PKCε depletion had a negative correlation with the existence of SP cells in 769P cell line. Down-regulation of PKCε also suppresses the CSC potential of sorted 769P SP cells in several ways: proliferation potential, resistance to chemotherapeutics and in vivo tumor formation ability. Our study also reveals that PKCε is associated with ABCB1 and this association probably contributed to the SP cells isolation from 769P cell line. Furthermore, the expression of ABCB1 is directly regulated by PKCε. Additionally, after the depletion of PKCε, the phosphorylation of pAkt, pStat3 and pERK was apparently suppressed in 769P SP cells, whereas PKCε overexpression could promote the phosphorylation of AKT, STAT3 and ERK in 769P Non-SP cells. Overall, PKCε down-regulation suppresses sorting and the cancer stem-like phenotype of RCC 769P SP cells through the regulation of ABCB1 transporter and the PI3K/Akt, Stat3 and MAPK/ERK pathways that are dependent on the phosphorylation effects. Thus, PKCε may work as an important mediator in cancer stem cell pathogenesis of renal cell cancer.

  10. Thermal Decomposition Characteristics of Orthorhombic Ammonium Perchlorate (o-AP)

    SciTech Connect

    Behrens, R.; Minier, L.

    1999-03-01

    Preliminary STMBMS and SEM results of the thermal decomposition of AP in the orthorhombic phase are presented. The overall decomposition is shown to be complex and controlled by both physical and chemical processes. The data show that the physical and chemical processes can be probed and characterized utilizing SEM and STMBMS. The overall decomposition is characterized by three distinguishing features: an induction period, and accelerator period and a deceleratory period. The major decomposition event occurs in the subsurface of the AP particles and propagates towards the center of the particle with time. The amount of total decomposition is dependent upon particle size and increases from 23% for {approximately}50{micro}m-diameter AP to 33% for {approximately}200{micro}m-diameter AP. A conceptual model of the physical processes is presented. Insight into the chemical processes is provided by the gas formation rates that are measured for the gaseous products. To our knowledge, this is the first presentation of data showing that the chemical and physical decomposition processes can be identified from one another, probed and characterized at the level that is required to better understand the thermal decomposition behavior of AP. Future work is planned with the goal of obtaining data that can be used to develop a mathematical description for the thermal decomposition of o-AP.

  11. Ontogenesis of Ap-2γ expression in rat testes.

    PubMed

    Hou, M; Stukenborg, J-B; Nurmio, M; Andersson, M; Toppari, J; Söder, O; Jahnukainen, K

    2011-01-01

    Searching for useful markers of spermatogonial stem cells and their differentiation, we used rat testes from ages representing different stages of testicular maturation to investigate the expression profile of transcription factor activation protein-2γ (Ap-2γ). The immunohistochemical and immunocytochemical evaluation using Ap-2γ and promyelocytic leukemia zinc finger in combination with sorting of CD9 and CD90 positive cells (undifferentiated spermatogonia) by fluorescence-activated cell sorting was performed. Our experiments revealed that Ap-2γ is detectable in testes of late fetal age and up to 60 days postnatally and is expressed in gonocytes and spermatogonia from late fetal age throughout all maturational stages. Restricted nuclear expression of Ap-2γ to undifferentiated male germ cells was verified by coexpression of Ap-2γ with promyelocytic leukemia zinc finger in sections of paraffin-embedded testes as well as in cells sorted positive for CD9 and CD90 expression. Our study demonstrated clearly that nuclear expression of Ap-2γ is a useful marker for identifying undifferentiated male germ cells, although its functional role is yet to be fully explored.

  12. AP-1-Targeting Anti-Inflammatory Activity of the Methanolic Extract of Persicaria chinensis

    PubMed Central

    Son, Young-Jin; Baek, Kwang-Soo; Yang, Woo Seok; Park, Jae Gwang; Kim, Han Gyung; Chung, Woo-Jae; Yoon, Keejung; Lee, Sang Yeol; Kim, Jong-Hoon

    2015-01-01

    In traditional Chinese medicine, Persicaria chinensis L. has been prescribed to cure numerous inflammatory disorders. We previously analyzed the bioactivity of the methanol extract of this plant (Pc-ME) against LPS-induced NO and PGE2 in RAW264.7 macrophages and found that it prevented HCl/EtOH-induced gastric ulcers in mice. The purpose of the current study was to explore the molecular mechanism by which Pc-ME inhibits activator protein- (AP-) 1 activation pathway and mediates its hepatoprotective activity. To investigate the putative therapeutic properties of Pc-ME against AP-1-mediated inflammation and hepatotoxicity, lipopolysaccharide- (LPS-) stimulated RAW264.7 and U937 cells, a monocyte-like human cell line, and an LPS/D-galactosamine- (D-GalN-) induced acute hepatitis mouse model were employed. The expression of LPS-induced proinflammatory cytokines including interleukin- (IL-) 1β, IL-6, and tumor necrosis factor-α (TNF-α) was significantly diminished by Pc-ME. Moreover, Pc-ME reduced AP-1 activation and mitogen-activated protein kinase (MAPK) phosphorylation in both LPS-stimulated RAW264.7 cells and differentiated U937 cells. Additionally, we highlighted the hepatoprotective and curative effects of Pc-ME pretreated orally in a mouse model of LPS/D-GalN-intoxicated acute liver injury by demonstrating the significant reduction in elevated serum AST and ALT levels and histological damage. Therefore, these results strongly suggest that Pc-ME could function as an antihepatitis remedy suppressing MAPK/AP-1-mediated inflammatory events. PMID:25878717

  13. Multiple Drug Transporters Are Involved in Renal Secretion of Entecavir

    PubMed Central

    Yang, Xi; Ma, Zhiyuan; Zhou, Sisi; Weng, Yayun; Lei, Hongmei; Zeng, Su

    2016-01-01

    Entecavir (ETV) is a first-line antiviral agent for the treatment of chronic hepatitis B virus infection. Renal excretion is the major elimination path of ETV, in which tubular secretion plays the key role. However, the secretion mechanism has not been clarified. We speculated that renal transporters mediated the secretion of ETV. Therefore, the aim of our study was to elucidate which transporters contribute to the renal disposition of ETV. Our results revealed that ETV (50 μM) remarkably reduced the accumulation of probe substrates in MDCK cells stably expressing human multidrug and toxin efflux extrusion proteins (hMATE1/2-K), organic cation transporter 2 (hOCT2), and carnitine/organic cation transporters (hOCTNs) and increased the substrate accumulation in cells transfected with multidrug resistance-associated protein 2 (hMRP2) or multidrug resistance protein 1 (hMDR1). Moreover, ETV was proved to be a substrate of the above-described transporters. In transwell studies, the transport of ETV in MDCK-hOCT2-hMATE1 showed a distinct directionality from BL (hOCT2) to AP (hMATE1), and the cellular accumulation of ETV in cells expressing hMATE1 was dramatically lower than that of the mock-treated cells. The accumulation of ETV in mouse primary renal tubular cells was obviously affected by inhibitors of organic anion transporter 1/3 (Oat1/3), Oct2, Octn1/2, and Mrp2. Therefore, the renal uptake of ETV is likely mediated by OAT1/3 and OCT2 while the efflux is mediated by MATEs, MDR1, and MRP2, and OCTN1/2 may participate in both renal secretion and reabsorption. PMID:27503646

  14. Authenticated, private, and secured smart cards (APS-SC)

    NASA Astrophysics Data System (ADS)

    Szu, Harold; Mehmood, Amir

    2006-04-01

    From historical perspective, the recent advancements in better antenna designs, low power circuitry integrations and inexpensive fabrication materials have made possible a miniature counter-measure against Radar, a clutter behaving like a fake target return called Digital Reflection Frequency Modulation (DRFM). Such a military counter-measure have found its way in the commerce as a near field communication known as Radio Frequency Identification (RFID), a passive or active item tag T attached to every readable-writable Smart Card (SC): Passports ID, medical patient ID, biometric ID, driver licenses, book ID, library ID, etc. These avalanche phenomena may be due to the 3 rd Gen phones seeking much more versatile & inexpensive interfaces, than the line-of-sight bar-code optical scan. Despite of the popularity of RFID, the lacking of Authenticity, Privacy and Security (APS) protection restricted somewhat the wide spread commercial, financial, medical, legal, and militarily applications. Conventional APS approach can obfuscate a private passkey K of SC with the tag number T or the reader number R, or both, i.e. only T*K or R*K or both will appear on them, where * denotes an invertible operation, e.g. EXOR, but not limited to it. Then, only the authentic owner, knowing all, can inverse the operation, e.g. EXOR*EXOR= I to find K. However, such an encryption could be easily compromised by a hacker seeking exhaustively by comparison based on those frequently used words. Nevertheless, knowing biological wetware lesson for power of pairs sensors and Radar hardware counter-measure history, we can counter the counter-measure DRFM, instead using one RFID tag per SD, we follow the Nature adopting two ears/tags, e.g. each one holding portions of the ID or simply two different ID's readable only by different modes of the interrogating reader, followed by brain central processor in terms of nonlinear invertible shufflers mixing two ID bits. We prefer to adopt such a hardware

  15. DNA cleavage at the AP site via β-elimination mediated by the AP site-binding ligands.

    PubMed

    Abe, Yukiko S; Sasaki, Shigeki

    2016-02-15

    DNA is continuously damaged by endogenous and exogenous factors such as oxidation and alkylation. In the base excision repair pathway, the damaged nucleobases are removed by DNA N-glycosylase to form the abasic sites (AP sites). The alkylating antitumor agent exhibits cytotoxicity through the formation of the AP site. Therefore blockage or modulation of the AP site repair pathway may enhance the antitumor efficacy of DNA alkylating agents. In this study, we have examined the effects of the nucleobase-polyamine conjugated ligands (G-, A-, C- and T-ligands) on the cleavage of the AP site. The G- and A-ligands cleaved DNA at the AP site by promoting β-elimination in a non-selective manner by the G-ligand, and in a selective manner for the opposing dT by the A-ligand. These results suggest that the nucleobase-polyamine conjugate ligands may have the potential for enhancement of the cytotoxicities of the AP site.

  16. 49 CFR 236.754 - Line, open wire.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to...

  17. 49 CFR 236.754 - Line, open wire.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to...

  18. 49 CFR 236.754 - Line, open wire.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to...

  19. 49 CFR 236.754 - Line, open wire.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to...

  20. 49 CFR 236.754 - Line, open wire.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Line, open wire. 236.754 Section 236.754 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Line, open wire. An overhead wire line consisting of single conductors as opposed to...

  1. 49 CFR 192.371 - Service lines: Steel.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689...

  2. 49 CFR 192.371 - Service lines: Steel.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689...

  3. 49 CFR 192.371 - Service lines: Steel.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689...

  4. 49 CFR 192.371 - Service lines: Steel.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689...

  5. 49 CFR 192.371 - Service lines: Steel.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Service lines: Steel. 192.371 Section 192.371 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.371 Service lines: Steel. Each steel service line to be operated at less than 100 p.s.i. (689...

  6. 49 CFR 192.719 - Transmission lines: Testing of repairs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Transmission lines: Testing of repairs. 192.719 Section 192.719 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... Transmission lines: Testing of repairs. (a) Testing of replacement pipe. If a segment of transmission line...

  7. 49 CFR 192.745 - Valve maintenance: Transmission lines.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Valve maintenance: Transmission lines. 192.745 Section 192.745 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... maintenance: Transmission lines. (a) Each transmission line valve that might be required during any...

  8. 49 CFR 192.719 - Transmission lines: Testing of repairs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Transmission lines: Testing of repairs. 192.719 Section 192.719 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... Transmission lines: Testing of repairs. (a) Testing of replacement pipe. If a segment of transmission line...

  9. 49 CFR 192.745 - Valve maintenance: Transmission lines.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Valve maintenance: Transmission lines. 192.745 Section 192.745 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... maintenance: Transmission lines. (a) Each transmission line valve that might be required during any...

  10. 49 CFR 192.719 - Transmission lines: Testing of repairs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Transmission lines: Testing of repairs. 192.719 Section 192.719 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... Transmission lines: Testing of repairs. (a) Testing of replacement pipe. If a segment of transmission line...

  11. 49 CFR 192.745 - Valve maintenance: Transmission lines.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Valve maintenance: Transmission lines. 192.745 Section 192.745 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... maintenance: Transmission lines. (a) Each transmission line valve that might be required during any...

  12. 49 CFR 192.719 - Transmission lines: Testing of repairs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Transmission lines: Testing of repairs. 192.719 Section 192.719 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... Transmission lines: Testing of repairs. (a) Testing of replacement pipe. If a segment of transmission line...

  13. 49 CFR 192.745 - Valve maintenance: Transmission lines.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Valve maintenance: Transmission lines. 192.745 Section 192.745 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... maintenance: Transmission lines. (a) Each transmission line valve that might be required during any...

  14. 49 CFR 192.745 - Valve maintenance: Transmission lines.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Valve maintenance: Transmission lines. 192.745 Section 192.745 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND... maintenance: Transmission lines. (a) Each transmission line valve that might be required during any...

  15. 49 CFR 192.377 - Service lines: Copper.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Service lines: Copper. 192.377 Section 192.377 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.377 Service lines: Copper. Each copper service line installed within a building must be...

  16. 49 CFR 192.377 - Service lines: Copper.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Service lines: Copper. 192.377 Section 192.377 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.377 Service lines: Copper. Each copper service line installed within a building must be...

  17. 49 CFR 192.377 - Service lines: Copper.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Service lines: Copper. 192.377 Section 192.377 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.377 Service lines: Copper. Each copper service line installed within a building must be...

  18. 49 CFR 192.377 - Service lines: Copper.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Service lines: Copper. 192.377 Section 192.377 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.377 Service lines: Copper. Each copper service line installed within a building must be...

  19. 49 CFR 192.377 - Service lines: Copper.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Service lines: Copper. 192.377 Section 192.377 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... § 192.377 Service lines: Copper. Each copper service line installed within a building must be...

  20. Ectopic expression of a grape aspartic protease gene, AP13, in Arabidopsis thaliana improves resistance to powdery mildew but increases susceptibility to Botrytis cinerea.

    PubMed

    Guo, Rongrong; Tu, Mingxing; Wang, Xianhang; Zhao, Jiao; Wan, Ran; Li, Zhi; Wang, Yuejin; Wang, Xiping

    2016-07-01

    The grape aspartic protease gene, AP13 was previously reported to be responsive, in Chinese wild Vitis quinquangularis cv. 'Shang-24', to infection by Erysiphe necator, the causal agent of powdery mildew disease, as well as to treatment with salicylic acid in V. labrusca×V. vinifera cv. 'Kyoho'. In the current study, we evaluated the expression levels of AP13 in 'Shang-24' in response to salicylic acid (SA), methyl jasmonate (MeJA) and ethylene (ET) treatments, as well as to infection by the necrotrophic fungus, Botrytis cinerea, and the transcript levels of VqAP13 decreased after B. cinerea infection and MeJA treatment, but increased following ET and SA treatments. Transgenic Arabidopsis thaliana lines over-expressing VqAP13 under the control of a constitutive promoter showed enhanced resistance to powdery mildew and to the bacterium Pseudomonas syringae pv. tomato DC3000, and accumulated more callose than wild type plants, while the resistance of transgenic A. thaliana lines to B. cinerea inoculation was reduced. In addition, the expression profiles of various disease resistance- related genes in the transgenic A. thaliana lines following infection by different pathogens were compared to the equivalent profiles in the wild type plants. The results suggest that VqAP13 action promotes the SA dependent signal transduction pathway, but suppresses the JA signal transduction pathway.

  1. Mapping of the spontaneous deletion in the Ap3d1 gene of mocha mice: fast and reliable genotyping

    PubMed Central

    Drasbek, Kim Ryun; Holm, Mai Marie; Delenclos, Marion; Jensen, Kimmo

    2008-01-01

    Background The mocha mouse carries a spontaneous deletion in the Ap3d1 gene, encoding the delta 1 subunit of the adaptor related protein complex 3, (Ap3d1), and subsequently lack the expression of functional AP-3. This leads to a deficiency in vesicle transport and storage, which affects neurotransmitter vesicle turnover and release in the central nervous system. Since the genomic sequence of the Ap3d1 gene of mocha mouse is not known, precise mapping of the deletion as well as reliable genotyping protocols are lacking. Findings We sequenced the Ap3d1 gene (HGNC GeneID: 8943) around the deletion site in the mocha mouse and revealed a 10639 bp deletion covering exon 2 to 6. Subsequently, new PCR primers were designed yielding a reliable genotyping protocol of both newborn and adult tissue. To examine the genotypes further, hippocampal neurons were cultured from mocha and control mice. Patch-clamp recordings showed that mocha neurons had a higher input resistance, and that autaptic EPSC in mocha cultures depressed faster and stronger as compared with control cultures. Conclusion Our study reports the sequence of the deleted part of the Ap3d1 gene in mocha mice, as well as a reliable PCR-based genotyping protocol. We cultured hippocampal neurons from control and mocha mice, and found a difference in input resistance of the neurons, and in the synaptic short-term plasticity of glutamatergic autapses showing a larger synaptic depression than controls. The described procedures may be useful for the future utilization of the mocha mouse as a model of defective vesicle biogenesis. Importantly, as genotyping by eye color is complicated in newborn mice, the designed protocol is so fast and reliable that newborn mice could rapidly be genotyped and hippocampal neurons dissociated and cultured, which is normally best done at P0-P2. PMID:19032734

  2. Interaction of gatifloxacin with efflux transporters: a possible mechanism for drug resistance

    PubMed Central

    Kwatra, Deep; Vadlapatla, Ramya Krishna; Vadlapudi, Aswani Dutt; Pal, Dhananjay; Mitra, Ashim K.

    2010-01-01

    The purpose of the study is to screen the interactions of fourth generation fluoroquinolone-gatifloxacin with efflux pumps i.e. P-gp, MRP2 and BCRP. Mechanism of gatifloxacin interaction with efflux transporters may explain its acquired resistance. Such clarification may lead to the development of strategies to overcome efflux and enhance its bioavailability at target site. This process will aid in the reduction of dose volume, further eliminating the chances of systemic toxicity from topical gatifloxacin eye drops. MDCK cell lines transfected with the targeted efflux transporters were used for this study. [14C] Erythromycin was selected as a model substrate for P-gp and MRP2 whereas Hoechst 33342 was employed as a substrate for BCRP. Uptake and transport studies of these substrates were performed in the presence of gatifloxacin to delineate its interaction with efflux transporters. Further the efflux ratio in the presence of gatifloxacin was calculated from bidirectional transport studies. The concentration of [14C] erythromycin and Hoechst 33342 were measured using scintillation counter and fluorescence plate reader respectively. A concentration dependent inhibition effect in the presence of gatifloxacin was revealed on [14C] erythromycin uptake. The efflux ratio (BL-AP/AP-BL) of substrates was found to approach unity at higher gatifloxacin concentrations. Increased concentration of gatifloxacin did not elevate uptake of Hoechst 33342. All these studies were validated with known inhibitors as positive control. Uptake and transport studies support the hypothesis that gatifloxacin is a substrate for P-gp, MRP2 but not for BCRP. Possible interactions of gatifloxacin with P-gp and MRP2 may be a possible mechanism for acquired resistance of gatifloxacin. This information can be further extended to design prodrugs or formulations in order to prevent development of acquired resistance and improve therapeutic efficacy with its reduction in side effects. PMID:20573570

  3. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome.

    PubMed

    Abdollahpour, Hengameh; Alawi, Malik; Kortüm, Fanny; Beckstette, Michael; Seemanova, Eva; Komárek, Vladimír; Rosenberger, Georg; Kutsche, Kerstin

    2015-02-01

    The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome.

  4. AP@home: The Artificial Pancreas Is Now at Home.

    PubMed

    Heinemann, Lutz; Benesch, Carsten; DeVries, J Hans

    2016-07-01

    In the past years the development of an artificial pancreas (AP) has made great progress and many activities are ongoing in this area of research. The major step forward made in the last years was moving the evaluation of AP systems from highly controlled experimental conditions to daily life conditions at the home of patients with diabetes; this was also the aim of the European Union-funded AP@home project. Over a time period of 5 years a series of clinical studies were performed that culminated in 2 "final studies" during which an AP system was used by patients in their home environment for 2 or 3 months without supervision by a physician, living their normal lives. Two different versions of the AP system developed within this project were evaluated. A significant improvement in glycated hemoglobin was observed during closed-loop conditions despite the fact that during the control period the patients used the best currently available therapeutic option. In addition, a "single-port AP system" was developed within the project that combines continuous glucose monitoring and insulin infusion at a single tissue site. By using such a combined device the patients not only have to carry one less device around, the number of access points through the skin is also reduced from 2 to 1. In summary, close cooperation of 12 European partners, both academic centers and industry, enabled the development and evaluation of AP systems under daily life conditions. The next step is to develop these into products in cooperation with commercial partners.

  5. Validation of the new trapped environment AE9/AP9/SPM at low Earth orbit

    NASA Astrophysics Data System (ADS)

    Badavi, Francis F.

    2014-09-01

    The completion of the international space station (ISS) in 2011 has provided the space research community an ideal proving ground for future long duration human activities in space. Ionizing radiation measurements in ISS form the ideal tool for the validation of radiation environmental models, nuclear transport codes and nuclear reaction cross sections. Indeed, prior measurements on the space transportation system (STS; shuttle) provided vital information impacting both the environmental models and the nuclear transport code developments by indicating the need for an improved dynamic model of the low Earth orbit (LEO) trapped environment. Additional studies using thermo-luminescent detector (TLD), tissue equivalent proportional counter (TEPC) area monitors, and computer aided design (CAD) model of earlier ISS configurations, confirmed STS observations that, as input, computational dosimetry requires an environmental model with dynamic and directional (anisotropic) behavior, as well as an accurate six degree of freedom (DOF) definition of the vehicle attitude and orientation along the orbit of ISS. At LEO, a vehicle encounters exposure from trapped particles and attenuated galactic cosmic rays (GCR). Within the trapped field, a challenge arises from properly estimating the amount of exposure acquired. There exist a number of models to define the intensities of the trapped particles during the solar quiet and active times. At active times, solar energetic particles (SEP) generated by solar flare or coronal mass ejection (CME) also contribute to the exposure at high northern and southern latitudes. Among the more established trapped models are the historic and popular AE8/AP8, dating back to the 1980s, the historic and less popular CRRES electron/proton, dating back to 1990s and the recently released AE9/AP9/SPM. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four

  6. High-precision magnetic field measurements of Ap and Bp stars

    NASA Astrophysics Data System (ADS)

    Wade, G. A.; Donati, J.-F.; Landstreet, J. D.; Shorlin, S. L. S.

    2000-04-01

    In this paper we describe a new approach for measuring the mean longitudinal magnetic field and net linear polarization of Ap and Bp stars. As was demonstrated by Wade et al., least-squares deconvolution (LSD; Donati et al.) provides a powerful technique for detecting weak Stokes V, Q and U Zeeman signatures in stellar spectral lines. These signatures have the potential to apply strong new constraints to models of stellar magnetic field structure. Here we point out two important uses of LSD Stokes profiles. First, they can provide very precise determinations of the mean longitudinal magnetic field. In particular, this method allows one frequently to obtain 1σ error bars better than 50G, and smaller than 20G in some cases. This method is applicable to both broad- and sharp-lined stars, with both weak and strong magnetic fields, and effectively redefines the quality standard of longitudinal field determinations. Secondly, LSD profiles can in some cases provide a measure of the net linear polarization, a quantity analogous to the broad-band linear polarization recently used to derive detailed magnetic field models for a few stars (e.g. Leroy et al.). In this paper we report new high-precision measurements of the longitudinal fields of 14 magnetic Ap/Bp stars, as well as net linear polarization measurements for four of these stars, derived from LSD profiles.

  7. 49 CFR 1248.4 - Originating and connecting line traffic.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) ACCOUNTS, RECORDS AND REPORTS FREIGHT COMMODITY... transportation, as provided in paragraph (a) of this section. (c) Freight which receives its first line-haul on... 49 Transportation 9 2011-10-01 2011-10-01 false Originating and connecting line traffic....

  8. 49 CFR 1248.4 - Originating and connecting line traffic.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION (CONTINUED) ACCOUNTS, RECORDS AND REPORTS FREIGHT COMMODITY... transportation, as provided in paragraph (a) of this section. (c) Freight which receives its first line-haul on... 49 Transportation 9 2010-10-01 2010-10-01 false Originating and connecting line traffic....

  9. Functional Characterization of a Vesicular Glutamate Transporter in an Interneuron That Makes Excitatory and Inhibitory Synaptic Connections in a Molluscan Neural Circuit.

    PubMed

    Jing, Jian; Alexeeva, Vera; Chen, Song-An; Yu, Ke; Due, Michael R; Tan, Li-Nuo; Chen, Ting-Ting; Liu, Dan-Dan; Cropper, Elizabeth C; Vilim, Ferdinand S; Weiss, Klaudiusz R

    2015-06-17

    Understanding circuit function requires the characterization of component neurons and their neurotransmitters. Previous work on radula protraction in the Aplysia feeding circuit demonstrated that critical neurons initiate feeding via cholinergic excitation. In contrast, it is less clear how retraction is mediated at the interneuronal level. In particular, glutamate involvement was suggested, but was not directly confirmed. Here we study a suspected glutamatergic retraction interneuron, B64. We used the representational difference analysis (RDA) method to successfully clone an Aplysia vesicular glutamate transporter (ApVGLUT) from B64 and from a glutamatergic motor neuron B38. Previously, RDA was used to characterize novel neuropeptides. Here we demonstrate its utility for characterizing other types of molecules. Bioinformatics suggests that ApVGLUT is more closely related to mammalian VGLUTs than to Drosophila and Caenorhabditis elegans VGLUTs. We expressed ApVGLUT in a cell line, and demonstrated that it indeed transports glutamate in an ATP and proton gradient-dependent manner. We mapped the ApVGLUT distribution in the CNS using in situ hybridization and immunocytochemistry. Further, we demonstrated that B64 is ApVGLUT positive, supporting the idea that it is glutamatergic. Although glutamate is primarily an excitatory transmitter in the mammalian CNS, B64 elicits inhibitory PSPs in protraction neurons to terminate protraction and excitatory PSPs in retraction neurons to maintain retraction. Pharmacological data indicated that both types of PSPs are mediated by glutamate. Thus, glutamate mediates the dual function of B64 in Aplysia. More generally, our systematic approaches based on RDA may facilitate analyses of transmitter actions in small circuits with identifiable neurons.

  10. Characterization of Schistosome Tegumental Alkaline Phosphatase (SmAP)

    PubMed Central

    Bhardwaj, Rita; Skelly, Patrick J.

    2011-01-01

    Schistosomes are parasitic platyhelminths that currently infect over 200 million people globally. The parasites can live for years in a putatively hostile environment - the blood of vertebrates. We have hypothesized that the unusual schistosome tegument (outer-covering) plays a role in protecting parasites in the blood; by impeding host immunological signaling pathways we suggest that tegumental molecules help create an immunologically privileged environment for schistosomes. In this work, we clone and characterize a schistosome alkaline phosphatase (SmAP), a predicted ∼60 kDa glycoprotein that has high sequence conservation with members of the alkaline phosphatase protein family. The SmAP gene is most highly expressed in intravascular parasite life stages. Using immunofluorescence and immuno-electron microscopy, we confirm that SmAP is expressed at the host/parasite interface and in internal tissues. The ability of living parasites to cleave exogenous adenosine monophosphate (AMP) and generate adenosine is very largely abolished when SmAP gene expression is suppressed following RNAi treatment targeting the gene. These results lend support to the hypothesis that schistosome surface enzymes such as SmAP could dampen host immune responses against the parasites by generating immunosuppressants such as adenosine to promote their survival. This notion does not rule out other potential functions for the adenosine generated e.g. in parasite nutrition. PMID:21483710

  11. The role of AP-1 and epigenetics in ALCL.

    PubMed

    Schiefer, Ana-Iris; Vesely, Paul; Hassler, Melanie R; Egger, Gerda; Kenner, Lukas

    2015-06-01

    Anaplastic large cell lymphoma (ALCL) is an aggressive, highly proliferative, T-cell lymphoma with increasing incidence worldwide. Anaplastic Lymphoma Kinase (ALK) fusions occur in about 50% of all cases. Most ALK positive cases of ALCL harbor the t(2;5) translocation that leads to expression of Nucleophosmin-Anaplastic Lymphoma Kinase (NPM-ALK). NPM-ALK induces a variety of oncogenic signaling pathways that lead to malignant transformation of T-cells via Activator Protein-1 (AP-1), STAT3 and other (transcription) factors. In addition to the commonly known AP-1 activators Mitogen-Activated Protein Kinases (MAPKs), there are other signaling pathways, such as PI3K/mTOR/AKT, which are implicated in AP-1 activation/expression in ALCL. The AP-1 factor JUNB was shown to drive ALCL proliferation and the expression of the characteristic ALCL Ki-1 antigen, CD30. cJUN and JUNB target PDGFRB, thereby leading to tumor progression and dissemination. Furthermore, aberrant gene expression in ALCL is frequently accompanied by changes in epigenetic regulatory mechanisms, such as DNA methylation patterns. Here, we discuss the role of AP-1 in the pathogenesis of ALCL and provide an overview of pathological epigenetic changes in ALCL cells.

  12. CD2AP Regulates SUMOylation of CIN85 in Podocytes

    PubMed Central

    Niedenthal, Rainer; Klaus, Malte; Teng, Beina; Worthmann, Kirstin; King, Benjamin L.; Peterson, Kevin J.; Haller, Hermann

    2012-01-01

    Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown that full-length CIN85 is upregulated in podocytes in the absence of CD2AP, whereas in wild-type cells, full-length CIN85 is not detectable. In this study, we show that full-length CIN85 is postranslationally modified by SUMOylation in wild-type podocytes. We can demonstrate that CIN85 is SUMOylated by SUMO-1, -2, and -3 and that SUMOylation is enhanced in the presence of CD2AP. Conversion of lysine 598 to arginine completely abolishes SUMOylation and leads to increased binding of CIN85 to nephrin. Our results indicate a novel role for CD2AP in regulating posttranslational modification of CIN85. PMID:22203040

  13. Drug Transporter Protein Quantification of Immortalized Human Lung Cell Lines Derived from Tracheobronchial Epithelial Cells (Calu-3 and BEAS2-B), Bronchiolar-Alveolar Cells (NCI-H292 and NCI-H441), and Alveolar Type II-like Cells (A549) by Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Sakamoto, Atsushi; Matsumaru, Takehisa; Yamamura, Norio; Suzuki, Shinobu; Uchida, Yasuo; Tachikawa, Masanori; Terasaki, Tetsuya

    2015-09-01

    Understanding the mechanisms of drug transport in the human lung is an important issue in pulmonary drug discovery and development. For this purpose, there is an increasing interest in immortalized lung cell lines as alternatives to primary cultured lung cells. We recently reported the protein expression in human lung tissues and pulmonary epithelial cells in primary culture, (Sakamoto A, Matsumaru T, Yamamura N, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T. 2013. J Pharm Sci 102(9):3395-3406) whereas comprehensive quantification of protein expressions in immortalized lung cell lines is sparse. Therefore, the aim of the present study was to clarify the drug transporter protein expression of five commercially available immortalized lung cell lines derived from tracheobronchial cells (Calu-3 and BEAS2-B), bronchiolar-alveolar cells (NCI-H292 and NCI-H441), and alveolar type II cells (A549), by liquid chromatography-tandem mass spectrometry-based approaches. Among transporters detected, breast cancer-resistance protein in Calu-3, NCI-H292, NCI-H441, and A549 and OCTN2 in BEAS2-B showed the highest protein expression. Compared with data from our previous study,(Sakamoto A, Matsumaru T, Yamamura N, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T. 2013. J Pharm Sci 102(9):3395-3406) NCI-H441 was the most similar with primary lung cells from all regions in terms of protein expression of organic cation/carnitine transporter 1 (OCTN1). In conclusion, the protein expression profiles of transporters in five immortalized lung cell lines were determined, and these findings may contribute to a better understanding of drug transport in immortalized lung cell lines.

  14. Galaxies with Strong Nitrogen Lines

    NASA Astrophysics Data System (ADS)

    Bergmann, T. S.; Pastoriza, M. G.

    1987-05-01

    ABSTRACT. From a qualitative spectroscopic survey of southern galaxies made by Pastoriza, a group with different morphological types whose nuclear region showed particular strong emission [N II]A6548-6584 lines when compared to Hn, was selected in order to investigate why [N II] is so strong. This work presents the results of a first analysis of the spectra of some of the galaxies above obtained with the 1-m telescope plus 2DFRUTTI detector of the Cerro Tololo Inter-American Observatory. The spectra are all very similar showing strong stellar continuum and absorption lines, and all the emission spectra show [0111] >[OII], [NIl] > H . None of the spectra show H in emission. Using the relative intensities of the H and K Call lines (Talent 1982, PLtb. A.S.P., 94,36), the obtained integrated spectra for all the observed galaxies is later than GO, which means that the H absorption lines should not be strong. From the relative intensities of the emission lines, we conclude that these galaxies cannot be classified as Starburst or LINERS. They are similar to Seyfert 2 (Osterbrock 1986, Act#va QSO4, preprint), but the FWHM of the lines is less than 300 km s . Also Ol X6300 is not clearly seen, and the absorption spectrum is strong relative to the emission spectrum. The preliminary conclusion is an activity similar but milder than that present in Seyfert 2 galaxies, as sug gested by Rose and Searle (1982, Ap. 5., 253, 556) and Rose and Cecil (1983, Ap. 5., 266, 531) for the nucleus of M51, maybe affected by an anomalous nitrogen abundance. K o : GALAXIES-ACTIVE - SPECTROSCOPY

  15. Exploring Mars: The Ares Payload Service (APS)

    NASA Astrophysics Data System (ADS)

    Bowen, Justin; Lusignan, Bruce

    1999-08-01

    design notably an improved re-entry cooling system and fueling stability analysis were done this year. More technical detail and a proposed international consortium to develop the SSTO is presented in another session of this year's Mars convention. We believe that there will be no human exploration of Mars based on the Shuttle or Expendable launch vehicles, and no resources available except for a cooperative international program. However, just as the world is learning to cooperate in peacekeeping, we hold out the hope that similar cooperation will develop for Mars exploration. With that in mind, this year we asked the question- "How will the human mission get to Mars if it has to use the SsTO for transportation?"

  16. Exploring Mars: the Ares Payload Service (APS)

    NASA Technical Reports Server (NTRS)

    Bowen, Justin; Lusignan, Bruce

    1999-01-01

    design notably an improved re-entry cooling system and fueling stability analysis were done this year. More technical detail and a proposed international consortium to develop the SSTO is presented in another session of this year's Mars convention. We believe that there will be no human exploration of Mars based on the Shuttle or Expendable launch vehicles, and no resources available except for a cooperative international program. However, just as the world is learning to cooperate in peacekeeping, we hold out the hope that similar cooperation will develop for Mars exploration. With that in mind, this year we asked the question- "How will the human mission get to Mars if it has to use the SsTO for transportation?"

  17. Control of machine functions or transport systems

    SciTech Connect

    Woodley, M.D.; Lee, M.J.; Jaeger, J.; King, A.S.

    1983-01-01

    A computer code, COMFORT, has been developed at SLAC for on-line calculation of the strengths of magnetic elements in an electron storage ring or transport beam line, subject to first order fitting constraints on the ring or beam line parameters. This code can also be used off-line as an interactive lattice or beam line design tool.

  18. AP-3 regulates PAR1 ubiquitin-independent MVB/lysosomal sorting via an ALIX-mediated pathway

    PubMed Central

    Dores, Michael R.; Paing, May M.; Lin, Huilan; Montagne, William A.; Marchese, Adriano; Trejo, JoAnn

    2012-01-01

    The sorting of signaling receptors within the endocytic system is important for appropriate cellular responses. After activation, receptors are trafficked to early endosomes and either recycled or sorted to lysosomes and degraded. Most receptors trafficked to lysosomes are modified with ubiquitin and recruited into an endosomal subdomain enriched in hepatocyte growth factor–regulated tyrosine kinase substrate (HRS), a ubiquitin-binding component of the endosomal-sorting complex required for transport (ESCRT) machinery, and then sorted into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs)/lysosomes. However, not all receptors use ubiquitin or the canonical ESCRT machinery to sort to MVBs/lysosomes. This is exemplified by protease-activated receptor-1 (PAR1), a G protein–coupled receptor for thrombin, which sorts to lysosomes independent of ubiquitination and HRS. We recently showed that the adaptor protein ALIX binds to PAR1, recruits ESCRT-III, and mediates receptor sorting to ILVs of MVBs. However, the mechanism that initiates PAR1 sorting at the early endosome is not known. We now report that the adaptor protein complex-3 (AP-3) regulates PAR1 ubiquitin-independent sorting to MVBs through an ALIX-dependent pathway. AP-3 binds to a PAR1 cytoplasmic tail–localized tyrosine-based motif and mediates PAR1 lysosomal degradation independent of ubiquitination. Moreover, AP-3 facilitates PAR1 interaction with ALIX, suggesting that AP-3 functions before PAR1 engagement of ALIX and MVB/lysosomal sorting. PMID:22833563

  19. Prevention of aspiration pneumonia (AP) with oral care.

    PubMed

    Tada, Akio; Miura, Hiroko

    2012-01-01

    AP is a major cause of morbidity and mortality in elderly patients, especially frail elderly patients. The aim of this article is to review effect of oral care, including oral hygiene and improvement of oral function, on the prevention of AP among elderly people in hospitals and nursing homes. There is now a substantial body of work studying the effect of oral care on the prevention of respiratory diseases. Oral hygiene, consisting of oral decontamination and mechanical cleaning by dental professionals, has resulted in significant clinical effects (decreased incidence of pneumonia and decreased mortality from respiratory diseases) in clinical randomized trials. Moreover, studies examining oral colonization by pneumonia pathogens have shown the effect of oral hygiene on eliminating these pathogens. In addition, swallowing training has been shown to improve the movement and function of swallowing-related muscles, also resulting in decreased incidence of pneumonia. These findings support the contention that oral care is effective in the prevention of AP.

  20. Interaction of PARP-2 with AP site containing DNA.

    PubMed

    Kutuzov, Mikhail M; Khodyreva, Svetlana N; Ilina, Ekaterina S; Sukhanova, Maria V; Amé, Jean-Christophe; Lavrik, Olga I

    2015-05-01

    In eukaryotes the stability of genome is provided by functioning of DNA repair systems. One of the main DNA repair pathways in eukaryotes is the base excision repair (BER). This system requires precise regulation for correct functioning. Two members of the PARP family - PARP-1 and PARP-2, which can be activated by DNA damage - are widely considered as regulators of DNA repair processes, including BER. In contrast to PARP-1, the role of PARP-2 in BER has not been extensively studied yet. Since AP site is one of the most frequent type of DNA damage and a key intermediate of BER at the stage preceding formation of DNA breaks, in this paper we focused on the characterization of PARP-2 interaction with AP site-containing DNAs. We demonstrated that PARP-2, like PARP-1, can interact with the intact AP site via Schiff base formation, in spite of crucial difference in the structure of the DNA binding domains of these PARPs. By cross-linking of PARPs to AP DNA, we determined that the N-terminal domains of both PARPs are involved in formation of cross-links with AP DNA. We have also confirmed that DNA binding by PARP-2, in contrast to PARP-1, is not modulated by autoPARylation. PARP-2, like PARP-1, can inhibit the activity of APE1 by binding to AP site, but, in contrast to PARP-1, this inhibitory influence is hardly regulated by PAR synthesis. At the same time, 5'-dRP lyase activity of both PARPs is comparable, although being much weaker than that of Pol β, which is considered as the main 5'-dRP lyase of the BER process.

  1. Psychosocial Assessment of Artificial Pancreas (AP): Commentary and Review of Existing Measures and Their Applicability in AP Research

    PubMed Central

    Hood, Korey K.; Weissberg-Benchell, Jill; Aldred, Chris; Oliver, Nick; Laffel, Lori

    2015-01-01

    Abstract Aim: This study aimed to systematically review the evidence base for the use of existing psychological and psychosocial measures suitable for use in artificial pancreas (AP) research. Materials and Methods: This systematic review of published literature, gray literature, previous systematic reviews, and qualitative and economic studies was conducted using terms and abbreviations synonymous with diabetes, AP, and quality of life (QoL). Results: Two hundred ninety-two abstracts were identified that reported psychosocial assessment of diabetes-related technologies. Of these, nine met the inclusion criteria and were included. Only four of 103 ongoing trials evaluated psychosocial aspects as an outcome in the trial. Of these, treatment satisfaction, acceptance and use intention of AP, fear of hypoglycemia episodes, satisfaction with AP, and an unspecified QoL measure were used. Conclusions: A better understanding of the psychosocial side of AP systems and the extent to which human factors play a role in the uptake and efficient use of these systems will ultimately lead to the most benefit for people with diabetes. PMID:25549042

  2. Protein kinase C-theta isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes.

    PubMed Central

    Baier-Bitterlich, G; Uberall, F; Bauer, B; Fresser, F; Wachter, H; Grunicke, H; Utermann, G; Altman, A; Baier, G

    1996-01-01

    T-lymphocyte stimulation requires activation of several protein kinases, including the major phorbol ester receptor protein kinase C (PKC), ultimately leading to induction of lymphokines, such as interleukin-2 (IL-2). The revelant PKC isoforms which are involved in the activation cascades of nuclear transcription factors involved in IL-2 production have not yet been clearly defined. We have examined the potential role of two representative PKC isoforms in the induction of the IL-2 gene, i.e., PKC-alpha and PKC-theta, the latter being expressed predominantly in hematopoietic cell lines, particularly T cells. Similar to that of PKC-alpha, PKC-theta overexpression in murine EL4 thymoma cells caused a significant increase in phorbol 12-myristate 13-acetate (PMA)-induced transcriptional activation of full-length IL-2-chloramphenicol acetyltransferase (CAT) and NF-AT-CAT but not of NF-IL2A-CAT or NF-kappaB promoter-CAT reporter gene constructs. Importantly, the critical AP-1 enhancer element was differentially modulated by these two distinct PKC isoenzymes, since only PKC-theta but not PKC-alpha overexpression resulted in an approximately 2.8-fold increase in AP-1-collagenase promoter CAT expression in comparison with the vector control. Deletion of the AP-1 enhancer site in the collagenase promoter rendered it unresponsive to PKC-theta. Expression of a constitutively active mutant PKC-theta A148E (but not PKC-alpha A25E) was sufficient to induce activation of AP-1 transcription factor complex in the absence of PMA stimulation. Conversely, a catalytically inactive PKC-theta K409R (but not PKC-alpha K368R) mutant abrogated endogenous PMA-mediated activation of AP-1 transcriptional complex. Dominant negative mutant Ha-RasS17N completely inhibited the PKC-O A148E-induced signal, PKC-O. Expression of a constitutively active mutant PKC-O A148E (but not PKC-alpha A25E) was sufficient to induce activation of AP-1 transcription factor complex in the absence of PMA stimulation

  3. Stokes IQUV mapping of α2 CVn & other Ap stars using ESPaDOnS and NARVAL

    NASA Astrophysics Data System (ADS)

    Silvester, J.; Kochukhov, O.; Wade, G. A.

    2013-12-01

    New spectral line polarisation observations of 7 bright Ap stars have been obtained with the ESPaDOnS and Narval high resolution spectropolarimeters (Silvester et al. 2012). The aim of this data set is produce a series of surface magnetic field and surface chemistry maps for these Ap stars. We present new magnetic maps for the Ap star α2 CVn using these new data and the MDI inversion code INVERS10. α2 CVn is the first Ap star to be observed during two separate epochs using high resolution phase resolved spectropolarimetric IQUV observations and as such allows us an insight into how stable the surface magnetic structure is over a decade timescale. We show that the new maps give a magnetic field structure consistent with the previous maps obtained by Kochukhov and Wade (2010) from lower quality MuSiCoS spectra taken a decade ago and that the field topology cannot be described by a dipolar or quadrupolar field.

  4. Quercetin modulates NF-kappa B and AP-1/JNK pathways to induce cell death in human hepatoma cells.

    PubMed

    Granado-Serrano, Ana Belén; Martín, María Angeles; Bravo, Laura; Goya, Luis; Ramos, Sonia

    2010-01-01

    Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic properties, but the precise molecular mechanisms of action are not thoroughly elucidated. The aim of this study was to investigate the regulatory effect of quercetin (50 microM) on two main transcription factors (NF-kappa B and AP-1) related to survival/proliferation pathways in a human hepatoma cell line (HepG2) over time. Quercetin induced a significant time-dependent inactivation of the NF-kappa B pathway consistent with a downregulation of the NF-kappa B binding activity (from 15 min onward). These features were in concert with a time-dependent activation (starting at 15 min and maintained up to 18 h) of the AP-1/JNK pathway, which played an important role in the control of the cell death induced by the flavonoid and contributed to the regulation of survival/proliferation (AKT, ERK) and death (caspase-3, p38, unbalance of Bcl-2 proapoptotic and antiapoptotic proteins) signals. These data suggest that NF-kappa B and AP-1 play a main role in the tight regulation of survival/proliferation pathways exerted by quercetin and that the sustained JNK/AP-1 activation and inhibition of NF-kappa B provoked by the flavonoid induced HepG2 death.

  5. Mobile docking of REMUS-100 equipped with USBL-APS to an unmanned surface vehicle: A performance feasibility study

    NASA Astrophysics Data System (ADS)

    Miranda, Mario, II

    The overall objective of this work is to evaluate the ability of homing and docking an unmanned underwater vehicle (Hydroid REMUS 100 UUV) to a moving unmanned surface vehicle (Wave-Adaptive Modular Surface Vehicle USV) using a Hydroid Digital Ultra-Short Baseline (DUSBL) acoustic positioning system (APS), as a primary navigation source. An understanding of how the UUV can rendezvous with a stationary USV first is presented, then followed by a moving USV. Inherently, the DUSBL-APS is susceptible to error due to the physical phenomena of the underwater acoustic channel (e.g. ambient noise, attenuation and ray refraction). The development of an APS model has allowed the authors to forecast the UUV's position and the estimated track line of the USV as determined by the DUSBL acoustic sensor. In this model, focus is placed on three main elements: 1) the acoustic channel and sound ray refraction when propagating in an inhomogeneous medium; 2) the detection component of an ideal DUSBL-APS using the Neyman-Pearson criterion; 3) the signal-to-noise ratio (SNR) and receiver directivity impact on position estimation. The simulation tool is compared against actual open water homing results in terms of the estimated source position between the simulated and the actual USBL range and bearing information.

  6. High glucose-induced, endothelin-dependent fibronectin synthesis is mediated via NF-kappa B and AP-1.

    PubMed

    Chen, Shali; Mukherjee, Suranjana; Chakraborty, Chandan; Chakrabarti, Subrata

    2003-02-01

    Human endothelial cells cultured under high glucose (HG) conditions were shown before to upregulate several basement membrane proteins, including fibronectin (FN), thus mimicking effects of diabetes. Using human macrovascular (HUVEC) and microvascular (HMEC) endothelial cell lines, we evaluated in the present study some of the key molecular signaling events involved in HG-induced FN overexpression. This expression was shown to be dependent on endogenous endothelin (ET) receptor-mediated signaling. We also examined the roles played by protein kinase C (PKC) and the transcription factors nuclear factor kappaB (NF-kappaB) and activating protein (AP)-1 with respect to such changes. HG, PKC activators, and ETs (ET-1 and ET-3) that increased FN expression also caused activation of NF-kappaB and AP-1. Inhibitors of both NF-kappaB and AP-1 prevented HG- and ET-induced FN production. ET receptor blockade also prevented these HG- and ET-mediated changes. The results of this study indicate that glucose-induced increased FN production in diabetes may be mediated via ET-dependent NF-kappaB and AP-1 activation.

  7. AP Report to the Nation: A Closer Look at the Nation and Florida

    ERIC Educational Resources Information Center

    Sawtell, Ellen A.; Gillie, Jacqueline M.; Smith, Patricia Z.

    2012-01-01

    In February 2012, the College Board published The 8th Annual AP Report to the Nation. This session provides a deeper dive into key information for the United States with an emphasis on Florida, and participants hear how one school in Florida utilizes AP Potential™ to help build their AP Program. Participants also learn about AP participation and…

  8. Past, Present, and Future of AP Chemistry: A Brief History of Course and Exam Alignment Efforts

    ERIC Educational Resources Information Center

    Magrogan, Serena

    2014-01-01

    As part of the Advanced Placement (AP) Program's commitment to continually enhance alignment with current best practices in college-level learning, the AP Program is currently evaluating and redesigning courses and exams, one of which launched during the 2013-2014 academic school year: AP chemistry. The history of the AP chemistry course and…

  9. Radiation measurements during cavities conditioning on APS RF test stand

    SciTech Connect

    Grudzien, D.M.; Kustom, R.L.; Moe, H.J.; Song, J.J.

    1993-07-01

    In order to determine the shielding structure around the Advanced Photon Source (APS) synchrotron and storage ring RF stations, the X-ray radiation has been measured in the near field and far field regions of the RF cavities during the normal conditioning process. Two cavity types, a prototype 352-MHz single-cell cavity and a 352-MHz five-cell cavity, are used on the APS and are conditioned in the RF test stand. Vacuum measurements are also taken on a prototype 352-MHz single-cell cavity and a 352-MHz five-cell cavity. The data will be compared with data on the five-cell cavities from CERN.

  10. Si 6142 and 6155 Å lines in stellar atmospheres: Stark broadening effect

    NASA Astrophysics Data System (ADS)

    Dimitrijević, M. S.; Popović, L. Č.; Ryabchikova, T.

    2002-07-01

    We study the influence of Stark broadening effect on Si I lines in the roAp 10 Aql star, where the lines are asymmetrical and shifted. First we have calculated Stark broadening parameters using by the semi-classical method for two Si I lines: 6142.48 Å and 6155.13 Å. We have adopted SYNTH code to include into account both Stark width and shift for these lines. From comparison of our calculation data with observations we found that Stark broadening plus stratification effect can explain the width and the asymmetry of the Si I lines in the atmosphere of roAp 10 Aql star.

  11. Waterborne Transportation Lines of the United States

    DTIC Science & Technology

    1988-10-01

    JUNCTION Ny 12533 32! GANES TO0615 COMPANT 4419 OOLUARD DR. APT. O n SEA ORLEANS LU 70114 "I1 GEN A CACRICAL Cl. I QC EAST bALlET RIMD I A NE OP. TZO I I...ILA IV 1 19811 200.01 1151. 1 1 1 OLF&*$II AT Pigs 1630771 1 񔙲A481 200.01 3S.01 9.01 * 16651 ll.6lt*K ILA NEW 1911 100:.01 35.1 1.4 -OI Ni I AT...200009 ".0! 19.9 I 00ISM00 9 Ss 0019 9644707 9 9 484 200.09 30.09 9.09 - 9 1500 14.99iON 9L6 GEN 1 9 9 9 9 9 200.01 00 9.9! 9 - 9 9 9 0RLEAN S8 5098

  12. Incorporating the APS Catalog of the POSS I and Image Archive in ADS

    NASA Technical Reports Server (NTRS)

    Humphreys, Roberta M.

    1998-01-01

    The primary purpose of this contract was to develop the software to both create and access an on-line database of images from digital scans of the Palomar Sky Survey. This required modifying our DBMS (called Star Base) to create an image database from the actual raw pixel data from the scans. The digitized images are processed into a set of coordinate-reference index and pixel files that are stored in run-length files, thus achieving an efficient lossless compression. For efficiency and ease of referencing, each digitized POSS I plate is then divided into 900 subplates. Our custom DBMS maps each query into the corresponding POSS plate(s) and subplate(s). All images from the appropriate subplates are retrieved from disk with byte-offsets taken from the index files. These are assembled on-the-fly into a GIF image file for browser display, and a FITS format image file for retrieval. The FITS images have a pixel size of 0.33 arcseconds. The FITS header contains astrometric and photometric information. This method keeps the disk requirements manageable while allowing for future improvements. When complete, the APS Image Database will contain over 130 Gb of data. A set of web pages query forms are available on-line, as well as an on-line tutorial and documentation. The database is distributed to the Internet by a high-speed SGI server and a high-bandwidth disk system. URL is http://aps.umn.edu/IDB/. The image database software is written in perl and C and has been compiled on SGI computers with MIX5.3. A copy of the written documentation is included and the software is on the accompanying exabyte tape.

  13. Analysis of TFAP2A mutations in Branchio-Oculo-Facial Syndrome indicates functional complexity within the AP-2α DNA-binding domain.

    PubMed

    Li, Hong; Sheridan, Ryan; Williams, Trevor

    2013-08-15

    Multiple lines of evidence indicate that the AP-2 transcription factor family has an important regulatory function in human craniofacial development. Notably, mutations in TFAP2A, the gene encoding AP-2α, have been identified in patients with Branchio-Oculo-Facial Syndrome (BOFS). BOFS is an autosomal-dominant trait that commonly presents with facial clefting, eye defects and branchial skin anomalies. Examination of multiple cases has suggested either simple haploinsufficiency or more complex genetic causes for BOFS, especially as the clinical manifestations are variable, with no clear genotype-phenotype correlation. Mutations occur throughout TFAP2A, but mostly within conserved sequences within the DNA contact domain of AP-2α. However, the consequences of the various mutations for AP-2α protein function have not been evaluated. Therefore, it remains unclear if all BOFS mutations result in similar changes to the AP-2α protein or if they each produce specific alterations that underlie the spectrum of phenotypes. Here, we have investigated the molecular consequences of the mutations that localize to the DNA-binding region. We show that although individual mutations have different effects on DNA binding, they all demonstrate significantly reduced transcriptional activities. Moreover, all mutant derivatives have an altered nuclear:cytoplasmic distribution compared with the predominantly nuclear localization of wild-type AP-2α and several can exert a dominant-negative activity on the wild-type AP-2α protein. Overall, our data suggest that the individual TFAP2A BOFS mutations can generate null, hypomorphic or antimorphic alleles and that these differences in activity, combined with a role for AP-2α in epigenetic events, may influence the resultant pathology and the phenotypic variability.

  14. Calibration of Strömgren-Crawford photometry for Ap-stars compared to Hipparcos results

    NASA Astrophysics Data System (ADS)

    Vogt, Nikolaus; Paunzen, Ernst; Maitzen, Hans M.

    structure in the distribution around the 45-line. Only in the case of normal late type stars one does note that part of the stars have obviously fainter photometric absolute magnitudes as compared to their Hipparcos based values. Turning now to our Ap-sample - bearing in mind that assigning the proper calibration group is not always trivial - we do in fact notice systematics: The photometric calibration for the early group stars yields too bright absolute magnitudes which may be related to the well known fact that Bp stars have too small Balmer jumps as well as Balmer lines. Statistically, this effect would lead to an overestimate of the distances by about 25 percent. The situation is reversed for the intermediate and late group of Ap stars: the lower the temperature, the fainter becomes the photometrically derived absolute magnitude in comparison to the value calculated from the Hipparcos parallaxes. While in the case of intermediate Ap-stars the apparent luminosity difference only rarely surpasses one magnitude, the late type peculiars are photometrically underluminous by roughly 1.5 magnitudes on the average. The outstanding systematic behaviour of the late type Ap-stars is reminiscent of the nonsymmetric distribution of normal late A-type stars (mentioned before) and could be interpreted by the presence of non-detected peculiar stars in the sample of normal stars. In the light of these findings the Strömgren-Crawford calibrations will be approximately reliable only if applied to CP2 stars at the transition from the early to the intermediate group. Endeavours should concentrate on appropriate peculiarity corrections for stars outside this domain.

  15. Nuclear Reactor Safety--The APS Submits its Report

    ERIC Educational Resources Information Center

    Physics Today, 1975

    1975-01-01

    Presents the summary section of the American Physical Society (APS) report on the safety features of the light-water reactor, reviews the design, construction, and operation of a reactor and outlines the primary engineered safety features. Summarizes the major recommendations of the study group. (GS)

  16. Modeling Contaminants in AP-MS/MS Experiments

    PubMed Central

    Lavallée-Adam, Mathieu; Cloutier, Philippe; Coulombe, Benoit; Blanchette, Mathieu

    2015-01-01

    Identification of protein–protein interactions (PPI) by affinity purification (AP) coupled with tandem mass spectrometry (AP-MS/MS) produces large data sets with high rates of false positives. This is in part because of contamination at the AP level (due to gel contamination, nonspecific binding to the TAP columns in the context of tandem affinity purification, insufficient purification, etc.). In this paper, we introduce a Bayesian approach to identify false-positive PPIs involving contaminants in AP-MS/MS experiments. Specifically, we propose a confidence assessment algorithm (called Decontaminator) that builds a model of contaminants using a small number of representative control experiments. It then uses this model to determine whether the Mascot score of a putative prey is significantly larger than what was observed in control experiments and assigns it a p-value and a false discovery rate. We show that our method identifies contaminants better than previously used approaches and results in a set of PPIs with a larger overlap with databases of known PPIs. Our approach will thus allow improved accuracy in PPI identification while reducing the number of control experiments required. PMID:21117706

  17. Tead and AP1 Coordinate Transcription and Motility.

    PubMed

    Liu, Xiangfan; Li, Huapeng; Rajurkar, Mihir; Li, Qi; Cotton, Jennifer L; Ou, Jianhong; Zhu, Lihua J; Goel, Hira L; Mercurio, Arthur M; Park, Joo-Seop; Davis, Roger J; Mao, Junhao

    2016-02-09

    The Tead family transcription factors are the major intracellular mediators of the Hippo-Yap pathway. Despite the importance of Hippo signaling in tumorigenesis, Tead-dependent downstream oncogenic programs and target genes in cancer cells remain poorly understood. Here, we characterize Tead4-mediated transcriptional networks in a diverse range of cancer cells, including neuroblastoma, colorectal, lung, and endometrial carcinomas. By intersecting genome-wide chromatin occupancy analyses of Tead4, JunD, and Fra1/2, we find that Tead4 cooperates with AP1 transcription factors to coordinate target gene transcription. We find that Tead-AP1 interaction is JNK independent but engages the SRC1-3 co-activators to promote downstream transcription. Furthermore, we show that Tead-AP1 cooperation regulates the activity of the Dock-Rac/CDC42 module and drives the expression of a unique core set of target genes, thereby directing cell migration and invasion. Together, our data unveil a critical regulatory mechanism underlying Tead- and AP1-controlled transcriptional and functional outputs in cancer cells.

  18. APS Chapter 1 Evaluation Report 1984-1985.

    ERIC Educational Resources Information Center

    Kaemper, Jack; Morse, Kathy

    This report describes and evaluates the Albuquerque Public Schools (APS) 1984-85 Chapter 1 instructional program and its effect on student performance. The following information is reported or described: (1) conclusions and recommendations; (2) participating schools and cost summaries; (3) identification of eligible schools; (4) identification of…

  19. Effective Teaching Strategies for Open Enrollment Honors and AP Classes

    ERIC Educational Resources Information Center

    Winebrenner, Susan

    2006-01-01

    A trend is emerging to open enrollment for honors and AP classes to all students who wish to take them. Teachers of these open enrollment classes may be facing several dilemmas. How can the high standards and academic rigor of the course be maintained? How can students who struggle to learn be supported in their endeavors to keep up with the…

  20. Time Trials--An AP Physics Challenge Lab

    ERIC Educational Resources Information Center

    Jones, David

    2009-01-01

    I have come to the conclusion that for high school physics classroom and laboratory experiences, simpler is better! In this paper I describe a very simple and effective lab experience that my AP students have thoroughly enjoyed year after year. I call this lab exercise "Time Trials." The experiment is simple in design and it is a lot of fun for…