FastSim: A Fast Simulation for the SuperB Detector

International Nuclear Information System (INIS)

Andreassen, R; Sokoloff, M; Arnaud, N; Burmistrov, L; Brown, D N; Carlson, J; Gaponenko, I; Suzuki, A; Cheng, C-h; Simone, A Di; Manoni, E; Perez, A; Walsh, J; Rama, M; Roberts, D; Rotondo, M; Simi, G

2011-01-01

We have developed a parameterized (fast) simulation for detector optimization and physics reach studies of the proposed SuperB Flavor Factory in Italy. Detector components are modeled as thin sections of planes, cylinders, disks or cones. Particle-material interactions are modeled using simplified cross-sections and formulas. Active detectors are modeled using parameterized response functions. Geometry and response parameters are configured using xml files with a custom-designed schema. Reconstruction algorithms adapted from BaBar are used to build tracks and clusters. Multiple sources of background signals can be merged with primary signals. Pattern recognition errors are modeled statistically by randomly misassigning nearby tracking hits. Standard BaBar analysis tuples are used as an event output. Hadronic B meson pair events can be simulated at roughly 10Hz.

FastSim: A Fast Simulation for the SuperB Detector

Science.gov (United States)

Andreassen, R.; Arnaud, N.; Brown, D. N.; Burmistrov, L.; Carlson, J.; Cheng, C.-h.; Di Simone, A.; Gaponenko, I.; Manoni, E.; Perez, A.; Rama, M.; Roberts, D.; Rotondo, M.; Simi, G.; Sokoloff, M.; Suzuki, A.; Walsh, J.

2011-12-01

We have developed a parameterized (fast) simulation for detector optimization and physics reach studies of the proposed SuperB Flavor Factory in Italy. Detector components are modeled as thin sections of planes, cylinders, disks or cones. Particle-material interactions are modeled using simplified cross-sections and formulas. Active detectors are modeled using parameterized response functions. Geometry and response parameters are configured using xml files with a custom-designed schema. Reconstruction algorithms adapted from BaBar are used to build tracks and clusters. Multiple sources of background signals can be merged with primary signals. Pattern recognition errors are modeled statistically by randomly misassigning nearby tracking hits. Standard BaBar analysis tuples are used as an event output. Hadronic B meson pair events can be simulated at roughly 10Hz.

Testing and evaluating storage technology to build a distributed Tier1 for SuperB in Italy

International Nuclear Information System (INIS)

Pardi, S; Delprete, D; Russo, G; Fella, A; Corvo, M; Bianchi, F; Ciaschini, V; Giacomini, F; Simone, A Di; Donvito, G; Santeramo, B; Gianoli, A; Luppi, E; Manzali, M; Tomassetti, L; Longo, S; Stroili, R; Luitz, S; Perez, A; Rama, M

2012-01-01

The SuperB asymmetric energy e + e −- collider and detector to be built at the newly founded Nicola Cabibbo Lab will provide a uniquely sensitive probe of New Physics in the flavor sector of the Standard Model. Studying minute effects in the heavy quark and heavy lepton sectors requires a data sample of 75 ab −-1 and a luminosity target of 10 36 cm −-2 s −-1 . This luminosity translate in the requirement of storing more than 50 PByte of additional data each year, making SuperB an interesting challenge to the data management infrastructure, both at site level as at Wide Area Network level. A new Tier1, distributed among 3 or 4 sites in the south of Italy, is planned as part of the SuperB computing infrastructure. Data storage is a relevant topic whose development affects the way to configure and setup storage infrastructure both in local computing cluster and in a distributed paradigm. In this work we report the test on the software for data distribution and data replica focusing on the experiences made with Hadoop and GlusterFS.

The SuperB factory, physics potential and project status

Directory of Open Access Journals (Sweden)

Wiechczynski Jaroslaw

2012-12-01

Full Text Available The SuperB project is an international enterprise aiming at the construction of the high-luminosity asymmetric beam energy electron-positron accelerator, which would be located in the area of Rome. It would exploit several novel features allowing to achieve an unprecedented luminosities and to collect almost a hundred times more data than the current generation of ”B factories”. As for the leptonic colliders, it will maintain a clean, low-background experimental environment that is crucial for numerous measurements on the field of high energy physics

The Super-B project accelerator status

CERN Document Server

Biagini, M.E.; Boni, R; Boscolo, M; Demma, T; Drago, A; Esposito, M; Guiducci, S; Marcellini, F; Mazzitelli, G; Preger, M; Raimondi, P; Sanelli, C; Serio, M; Stecchi, A; Stella, A; Tomassini, S; Zobov, M; Bertsche, K; Brachmann, A; Cai, Y; Chao, A; DeLira, A; Donald, M; Fisher, A; Kharakh, D; Krasnykh, A; Li, N; MacFarlane, D; Nosochkov, Y; Novokhatski, A; Pivi, M.; Seeman, J; Sullivan, M; Wienands, U; Weisend, J; Wittmer, W; Koop, I; Levichev, E; Nikitin, S; Piminov, P; Sinyatkin, S; Shatilov, D; Bolzon, B; Brunetti, L; Jeremie, A; Baylac, M; DeConto, J M; Gomez, Y; Meot, F; Monseu, N; Tourres, D; Bonis, J.; Chehab, R; Le Meur, G; Mercier, B; Poirier, F; Prevost, C; Rimbault, C; Touze, F; Variola, A; Chance, A; Napoly, O; Bosi, F; Liuzzo, S; Paoloni, E; Bettoni, S

2010-01-01

The SuperB project is an international effort aiming at building in Italy a very high luminosity e+e- (1036 cm-2 sec-1) asymmetric collider at the Y(4S) energy in the cm. The accelerator design has been extensively studied and changed during the past year. The present design, based on the new collision scheme, with large Piwinski angle and the use of “crab waist” sextupoles already successfully tested at the DANE -Factory at LNF Frascati, provides larger flexibility, better dynamic aperture and spin manipulation sections in the Low Energy Ring (LER) for longitudinal polarization of the electron beam at the Interaction Point (IP). The Interaction Region (IR) has been further optimized in terms of apertures and reduced backgrounds in the detector. The injector complex design has been also updated. A summary of the project status will be presented in this paper

BESIII and SuperB: distributed job management with Ganga

International Nuclear Information System (INIS)

Antoniev, I; Kenyon, M; Moscicki, J; Deng, Z; Han, Y; Zhang, X; Ebke, J; Egede, U; Richards, A; Fella, A; Galvani, A; Lin, L; Luppi, E; Manzali, M; Tomassetti, L; Nicholson, C; Slater, M; Spinoso, V

2012-01-01

A job submission and management tool is one of the necessary components in any distributed computing system. Such a tool should provide a user-friendly interface for physics production groups and ordinary analysis users to access heterogeneous computing resources, without requiring knowledge of the underlying grid middleware. Ganga, with its common framework and customizable plug-in structure is such a tool. This paper will describe how experiment-specific job management tools for BESIII and SuperB were developed as Ganga plug-ins to meet their own unique requirements, discuss and contrast their challenges met and lessons learned.

Low Emittance Tuning Studies for SuperB

Energy Technology Data Exchange (ETDEWEB)

Liuzzo, Simone; /INFN, Pisa; Biagini, Maria; /INFN, Rome; Raimondi, Pantaleo; /INFN, Rome; Donald, Martin; /SLAC

2012-07-06

SuperB[1] is an international project for an asymmetric 2 rings collider at the B mesons cm energy to be built in the Rome area in Italy. The two rings will have very small beam sizes at the Interaction Point and very small emittances, similar to the Linear Collider Damping Rings ones. In particular, the ultra low vertical emittances, 7 pm in the LER and 4 pm in the HER, need a careful study of the misalignment errors effects on the machine performances. Studies on the closed orbit, vertical dispersion and coupling corrections have been carried out in order to specify the maximum allowed errors and to provide a procedure for emittance tuning. A new tool which combines MADX and Matlab routines has been developed, allowing for both corrections and tuning. Results of these studies are presented.

SuperB Progress Report for Accelerator

Energy Technology Data Exchange (ETDEWEB)

Biagini, M.E.; Boni, R.; Boscolo, M.; Buonomo, B.; Demma, T.; Drago, A.; Esposito, M.; Guiducci, S.; Mazzitelli, G.; Pellegrino, L.; Preger, M.A.; Raimondi, P.; Ricci, R.; Rotundo, U.; Sanelli, C.; Serio, M.; Stella, A.; Tomassini, S.; Zobov, M.; /Frascati; Bertsche, K.; Brachman, A.; /SLAC /Novosibirsk, IYF /INFN, Pisa /Pisa U. /Orsay, LAL /Annecy, LAPP /LPSC, Grenoble /IRFU, SPP, Saclay /DESY /Cockroft Inst. Accel. Sci. Tech. /U. Liverpool /CERN

2012-02-14

This report details the progress made in by the SuperB Project in the area of the Collider since the publication of the SuperB Conceptual Design Report in 2007 and the Proceedings of SuperB Workshop VI in Valencia in 2008. With this document we propose a new electron positron colliding beam accelerator to be built in Italy to study flavor physics in the B-meson system at an energy of 10 GeV in the center-of-mass. This facility is called a high luminosity B-factory with a project name 'SuperB'. This project builds on a long history of successful e+e- colliders built around the world, as illustrated in Figure 1.1. The key advances in the design of this accelerator come from recent successes at the DAFNE collider at INFN in Frascati, Italy, at PEP-II at SLAC in California, USA, and at KEKB at KEK in Tsukuba Japan, and from new concepts in beam manipulation at the interaction region (IP) called 'crab waist'. This new collider comprises of two colliding beam rings, one at 4.2 GeV and one at 6.7 GeV, a common interaction region, a new injection system at full beam energies, and one of the two beams longitudinally polarized at the IP. Most of the new accelerator techniques needed for this collider have been achieved at other recently completed accelerators including the new PETRA-3 light source at DESY in Hamburg (Germany) and the upgraded DAFNE collider at the INFN laboratory at Frascati (Italy), or during design studies of CLIC or the International Linear Collider (ILC). The project is to be designed and constructed by a worldwide collaboration of accelerator and engineering staff along with ties to industry. To save significant construction costs, many components from the PEP-II collider at SLAC will be recycled and used in this new accelerator. The interaction region will be designed in collaboration with the particle physics detector to guarantee successful mutual use. The accelerator collaboration will consist of several groups at present

SuperB: A High-Luminosity Asymmetric e+e- Super Flavor Factory

Energy Technology Data Exchange (ETDEWEB)

Bona, M.; /et al.

2007-05-18

We discuss herein the exciting physics program that can be accomplished with a very large sample of heavy quark and heavy lepton decays produced in the very clean environment of an e{sup +}e{sup -} collider; a program complementary to that of an experiment such as LHCb at a hadronic machine. It then presents the conceptual design of a new type of e{sup +}e{sup -} collider that produces a nearly two-order-of-magnitude increase in luminosity over the current generation of asymmetric B Factories. The key idea is the use of low emittance beams produced in an accelerator lattice derived from the ILC Damping Ring Design, together with a new collision region, again with roots in the ILC final focus design, but with important new concepts developed in this design effort. Remarkably, SuperB produces this very large improvement in luminosity with circulating currents and wallplug power similar to those of the current B Factories. There is clear synergy with ILC R&D; design efforts have already influenced one another, and many aspects of the ILC Damping Rings and Final Focus would be operationally tested at SuperB. Finally, the design of an appropriate detector, based on an upgrade of BABAR as an example, is discussed in some detail. A preliminary cost estimate is presented, as is an example construction timeline.

Egg size investment in superb fairy-wrens: helper effects are modulated by climate

Science.gov (United States)

Heinsohn, R. G.; Russell, A. F.; Kilner, R. M.

2016-01-01

Natural populations might exhibit resilience to changing climatic conditions if they already show adaptive flexibility in their reproductive strategies. In cooperative breeders, theory predicts that mothers with helpers should provide less care when environmental conditions are favourable, but maintain high investment when conditions are challenging. Here, we test for evidence of climate-mediated flexibility in maternal investment in the cooperatively breeding superb fairy-wren Malurus cyaneus. We focus on egg size because in this species egg size influences offspring size, and females reduce egg investment when there are helpers at the nest. We report that females lay larger eggs during dry, hot conditions. However, the effect of temperature is modulated by the presence of helpers: the average egg size of females with helpers is reduced during cooler conditions but increased during hot conditions relative to females without helpers. This appears to reflect plasticity in egg investment rather than among female differences. Analysis of maternal survival suggests that helped females are better able to withstand the costs of breeding in hot conditions than females without helpers. Our study suggests that females can use multiple, independent cues to modulate egg investment flexibly in a variable environment. PMID:27903872

Status of the Super-B factory Design

CERN Document Server

Wittmer, W; Chao, A; Novokhatski, A; Nosochkov, Y; Seeman, J; Sullivan, M K; Wienands, U; Weathersby, S; Bogomyagkov, A V; Levichev, E; Nikitin, S; Piminov, P; Shatilov, D; Sinyatkin, S; Vobly, P; Okunev, I N; Bolzon, B; Brunetti, L; Jeremie, A; Biagini, M E; Boni, R; Boscolo, M; Demma, T; Drago, A; Esposito, M; Guiducci, S; Liuzzo, S; Preger, M; Raimondi, P; Tomassini, S; Zobov, M; Paoloni, E; Fabbricatore, P; Musenich, R; Farinon, S; Bettoni, S; Poirier, F; Rimbault, C; Variola, A; Baylac, M; Bourrion, O; Monseu, N; Vescovi, C; Chance, A

2011-01-01

The SuperB international team continues to optimize the design of an electron-positron collider, which will allow the enhanced study of the origins of flavor physics. The project combines the best features of a linear collider (high single-collision luminosity) and a storage-ring collider (high repetition rate), bringing together all accelerator physics aspects to make a very high luminosity of 10$^{36}$ cm$^{-2}$ sec$^{-1}$. This asymmetric-energy collider with a polarized electron beam will produce hundreds of millions of B-mesons at the $\\Upsilon$(4S) resonance. The present design is based on extremely low emittance beams colliding at a large Piwinski angle to allow very low $\\beta_y^\\star$ without the need for ultra short bunches. Use of crab-waist sextupoles will enhance the luminosity, suppressing dangerous resonances and allowing for a higher beam-beam parameter. The project has flexible beam parameters, improved dynamic aperture, and spin-rotators in the Low Energy Ring for longitudinal polarization o...

Longitudinal Bunch Position Control for the Super-B Accelerator

International Nuclear Information System (INIS)

Bertsche, Kirk; Rivetta, Claudio; Sullivam, Michael K.; SLAC; Drago, Alessandro; Frascati

2009-01-01

The use of normal conducting cavities and an ion-clearing gap will cause a significant RF accelerating voltage gap transient and longitudinal phase shift of the individual bunches along the bunch train in both rings of the SuperB accelerator. Small relative centroid position shifts between bunches of the colliding beams will have a large adverse impact on the luminosity due to the small β* y at the interaction point (IP). We investigate the possibility of minimizing the relative longitudinal position shift between bunches by reducing the gap transient in each ring and matching the longitudinal bunch positions of the two rings at the IP using feedback/feedforward techniques in the LLRF. The analysis is conducted assuming maximum use of the klystron power installed in the system

SEARCH FOR NEW PHYSICS AT A SUPER-B FACTORY.

Energy Technology Data Exchange (ETDEWEB)

BROWDER,T.E.; SONI,A.

2004-01-05

The importance of a Super-B Factory in the search for New Physics, in particular, due to CP-od phase(s) from physics beyond the Standard Model is surveyed. The first point to emphasize is that we know now how to directly measure all three angles of the unitarity triangle very cleanly, i. e. without theoretical assumptions with irreducible theory error {le} 1%; however this requires much more luminosity than is currently available at B-factories. Direct searches via penguin-dominated hadronic modes as well as radiative, pair-leptonic and semi-leptonic decays are also discussed. Null tests of the SM are stressed as these will play a crucial role especially if the effects of BSM phase(s) on B-physics are small.

Recent developments on CMOS MAPS for the SuperB Silicon Vertex Tracker

Energy Technology Data Exchange (ETDEWEB)

Rizzo, G., E-mail: rizzo@pi.infn.it [Università degli Studi di Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pisa (Italy); Comott, D. [Università degli Studi di Bergamo (Italy); Manghisoni, M.; Re, V.; Traversi, G. [Università degli Studi di Bergamo (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pavia (Italy); Fabbri, L.; Gabrielli, A. [Università degli Studi di Bologna (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bologna (Italy); Giorgi, F.; Pellegrini, G.; Sbarra, C. [Istituto Nazionale di Fisica Nucleare, Sezione di Bologna (Italy); Semprini-Cesari, N.; Valentinetti, S.; Villa, M.; Zoccoli, A. [Università degli Studi di Bologna (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bologna (Italy); Berra, A.; Lietti, D.; Prest, M. [Università dell' Insubria, Como (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Milano Bicocca (Italy); Bevan, A. [School of Physics and Astronomy, Queen Mary, University of London, London E1 4NS (United Kingdom); Wilson, F. [STFC, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0QX (United Kingdom); Beck, G. [School of Physics and Astronomy, Queen Mary, University of London, London E1 4NS (United Kingdom); and others

2013-08-01

In the design of the Silicon Vertex Tracker for the high luminosity SuperB collider, very challenging requirements are set by physics and background conditions on its innermost Layer0: small radius (about 1.5 cm), resolution of 10–15μm in both coordinates, low material budget <1%X{sub 0}, and the ability to withstand a background hit rate of several tens of MHz/cm{sup 2}. Thanks to an intense R and D program the development of Deep NWell CMOS MAPS (with the ST Microelectronics 130 nm process) has reached a good level of maturity and allowed for the first time the implementation of thin CMOS sensors with similar functionalities as in hybrid pixels, such as pixel-level sparsification and fast time stamping. Further MAPS performance improvements are currently under investigation with two different approaches: the INMAPS CMOS process, featuring a quadruple well and a high resistivity substrate, and 3D CMOS MAPS, realized with vertical integration technology. In both cases specific features of the processes chosen can improve charge collection efficiency, with respect to a standard DNW MAPS design, and allow to implement a more complex in-pixel logic in order to develop a faster readout architecture. Prototypes of MAPS matrix, suitable for application in the SuperB Layer0, have been realized with the INMAPS 180 nm process and the 130 nm Chartered/Tezzaron 3D process and results of their characterization will be presented in this paper.

SuperB R&D computing program: HTTP direct access to distributed resources

Science.gov (United States)

Fella, A.; Bianchi, F.; Ciaschini, V.; Corvo, M.; Delprete, D.; Diacono, D.; Di Simone, A.; Franchini, P.; Donvito, G.; Giacomini, F.; Gianoli, A.; Longo, S.; Luitz, S.; Luppi, E.; Manzali, M.; Pardi, S.; Perez, A.; Rama, M.; Russo, G.; Santeramo, B.; Stroili, R.; Tomassetti, L.

2012-12-01

The SuperB asymmetric energy e+e- collider and detector to be built at the newly founded Nicola Cabibbo Lab will provide a uniquely sensitive probe of New Physics in the flavor sector of the Standard Model. Studying minute effects in the heavy quark and heavy lepton sectors requires a data sample of 75 ab-1 and a luminosity target of 1036cm-2s-1. The increasing network performance also in the Wide Area Network environment and the capability to read data remotely with good efficiency are providing new possibilities and opening new scenarios in the data access field. Subjects like data access and data availability in a distributed environment are key points in the definition of the computing model for an HEP experiment like SuperB. R&D efforts in such a field have been brought on during the last year in order to release the Computing Technical Design Report within 2013. WAN direct access to data has been identified as one of the more interesting viable option; robust and reliable protocols as HTTP/WebDAV and xrootd are the subjects of a specific R&D line in a mid-term scenario. In this work we present the R&D results obtained in the study of new data access technologies for typical HEP use cases, focusing on specific protocols such as HTTP and WebDAV in Wide Area Network scenarios. Reports on efficiency, performance and reliability tests performed in a data analysis context have been described. Future R&D plan includes HTTP and xrootd protocols comparison tests, in terms of performance, efficiency, security and features available.

SuperB: Next-Generation e+e− B-factory Collider

CERN Document Server

Novokhatski, A; Chao, A; Nosochkov, Y; Seeman, J T; Sullivan, M K; Wienands, J T; Wittmer, W; Baylac, M A; Bourrion, O; Monseu, N; Vescovi, C; Bettoni, S; Biagini, M E; Boni, R; Boscolo, M; Demma, T; Drago, A; Esposito, M; Guiducci, S; Preger, M A; Raimondi, P; Tomassini, S; Zobov, M; Bogomyagkov, A V; Nikitin, S A; Piminov, P A; Shatilov, D N; Sinyatkin, S V; Vobly, P; Bolzon, B; Brunetti, L; Jeremie, A; A. Chancé; Fabbricatore, P; Farinon, S; Musenich, R; Liuzzo, S M; Paoloni, E; Okunev, I N; Poirier, F; Rimbault, C; Variola, A

2011-01-01

The SuperB international team continues to optimize the design of an electron-positron collider, which will allow the enhanced study of the origins of flavor physics. The project combines the best features of a linear collider (high single-collision luminosity) and a storage-ring collider (high repetition rate), bringing together all accelerator physics aspects to make a very high luminosity of 1036 cm-2 s-1. This asymmetric-energy collider with a polarized electron beam will produce hundreds of millions of B-mesons at the Y(4S) resonance. The present design is based on extremely low emittance beams colliding at a large Piwinski angle to allow very low ßy* without the need for ultra short bunches. Use of crab-waist sextupoles will enhance the luminosity, suppressing dangerous resonances and allowing for a higher beam-beam parameter. The project has flexible beam parameters, improved dynamic aperture, and spin-rotators in the Low Energy Ring for longitudinal polarization of the electron beam at the Interactio...

Analog front-end for pixel sensors in a 3D CMOS technology for the SuperB Layer0

International Nuclear Information System (INIS)

Manazza, A.; Gaioni, L.; Re, V.

2011-01-01

This work is concerned with the design of two different analog channels for hybrid and monolithic pixels readout in view of applications to the SVT at the SuperB Factory. The circuits have been designed in a 130nm CMOS, vertically integrated technology, which, among others, may provide some advantages in terms of functional density and electrical isolation between the analog and the digital sections of the front-end.

Associations between children’s independent mobility and physical activity

Science.gov (United States)

2014-01-01

Background Independent mobility describes the freedom of children to travel and play in public spaces without adult supervision. The potential benefits for children are significant such as social interactions with peers, spatial and traffic safety skills and increased physical activity. Yet, the health benefits of independent mobility, particularly on physical activity accumulation, are largely unexplored. This study aimed to investigate associations of children’s independent mobility with light, moderate-to-vigorous, and total physical activity accumulation. Methods In 2011 - 2012, 375 Australian children aged 8-13 years (62% girls) were recruited into a cross-sectional study. Children’s independent mobility (i.e. independent travel to school and non-school destinations, independent outdoor play) and socio-demographics were assessed through child and parent surveys. Physical activity intensity was measured objectively through an Actiheart monitor worn on four consecutive days. Associations between independent mobility and physical activity variables were analysed using generalized linear models, accounting for clustered sampling, Actiheart wear time, socio-demographics, and assessing interactions by sex. Results Independent travel (walking, cycling, public transport) to school and non-school destinations were not associated with light, moderate-to-vigorous and total physical activity. However, sub-analyses revealed a positive association between independent walking and cycling (excluding public transport) to school and total physical but only in boys (b = 36.03, p physical activity (b = 29.76, p physical activity. When assessing differences by sex, the observed significant associations of independent outdoor play with light and total physical activity remained in girls but not in boys. All other associations showed no significant differences by sex. Conclusions Independent outdoor play may boost children’s daily physical activity levels

Study of Use of Products and Exposure-Related Behaviors (SUPERB: study design, methods, and demographic characteristics of cohorts

Directory of Open Access Journals (Sweden)

Hertz-Picciotto Irva

2010-08-01

Full Text Available Abstract Background Exposure to toxic chemicals in the home is a growing concern. This report presents an overview of the recruitment, methods for data collection, instruments used to collect data, and participant demographics for a study examining behaviors that influence exposure to environmental toxins in the home environment, also known as SUPERB (Study of Use of Products and Exposure Related Behaviors. Methods The methods involved three different platforms: telephone interviews, internet-based surveys, and home-based monitoring. The purposes of SUPERB were: first, to compare data collection platforms with regard to feasibility, acceptability and reliability; and second, to provide longitudinal population-based data characterizing seasonal and long-term changes in exposure-related behaviors including food consumption, temporal-spatial activity, and household product use. Results Two cohorts of households were enrolled: families (one parent and one child from northern California and older individuals (age 55+ from central California. Parents (n = 499 in Northern California families were on average 36 years of age, 47.1% were Latino or nonwhite, and 10.2% took the survey in Spanish. Most of the children enrolled (n = 566 were under 6 years (82.7%. The older adults enrolled (n = 156 were, on average, 66 years of age and 23.7% were Latino or nonwhite, but only 2.6% completed the survey in Spanish. Conclusions We found that oversampling was successful in improving recruitment of under-represented subgroups, such as those with low education, thereby increasing diversity of our study sample. Protocols that minimize participant time, e.g., use of bar scanners and scales rather than questionnaires regarding use of household products, and the implementation of these protocols by staff who built relationships of trust, resulted in high retention over a longitudinal data collection scheme. A relatively small fraction of those who volunteer for

The Instrumented Flux Return Detector of the SuperB Experiment: R&D Studies and First Results of the Fermilab Beam Test

Science.gov (United States)

Andreotti, M.; Baldini, W.; Calabrese, R.; Carassiti, V.; Cotta, A.; Cibinetto, G.; Evangelisti, F.; Luppi, E.; Malaguti, R.; Manzali, M.; Melchiorri, M.; Munerato, M.; Santoro, V.; Tommassetti, L.; Benettoni, M.; Dalcorso, F.; Feltresi, E.; Fanin, C.; Gagliardi, N.; Posocco, M.; Rotondo, M.; Stroili, R.

SuperB is a super-flavor factory that will be built in Tor Vergata (Italy). The project, recently approved by the Italian Government, and classified as the flagship project of the Italian INFN, foresees the construction of a high intensity asymmetric electron-positron collider and of the related detector. The expected luminosity of 2x1036cm-2 s-1, a factor 100 higher than the last generation of B-factories, will allow the high statistic study of rare decays and, possibly, will allow a deeper insight in the field of new physics. Part of the SuperB apparatus is the Instrumented Flux Return (IFR). This detector exploits the flux return iron structure of the superconducting solenoid as absorber for the identification of muons and neutral hadrons. In more details, It consists of ≃ 92 cm of iron interleaved by 9 layers of highly segmented scintillators. The detection technique is based on relatively inexpensive extruded plastic scintillator bars produced at the FNAL-NICADD facility. The scintillation light is collected through Wave Length Shifting fibers and guided to recently developed devices called Silicon Photon Multipliers used as photodetectors. The use of plastic scintillator as active material ensures reliability, robustness and long term stability while the high granularity and the fast response guarantee a good space-time resolution, extremely important to cope with the expected high particles flux. The readout scheme under evaluation is this manuscript is the double coordinate readout ("BIRO readout") where two layers of orthogonal scintillator bars provide both, the polar and azimuthal coordinate. In order to deeply understand the performances and possible drawbacks of the above technique, a full depth prototype has been designed and built in Ferrara and Padova, and tested at the Fermilab Test Beam Facility (FBTF) in December 2010. In this paper a comprehensive description of the IFR related R&D studies will be presented. In particular, we will focus on the

Si-Carbon Composite Nanofibers with Good scalability and Favorable Architecture for Highly Reversible Lithium Storage and Superb Kinetics

International Nuclear Information System (INIS)

Lee, Youngmin; Heo, Yoon-Uk; Song, Dahye; Shin, Dong Wook; Kang, Yong-Mook

2014-01-01

We demonstrate a simple electrospinning for preparing Si-carbon composite Nanofiber (NF) in which aciniform aggregates of Si particles are well encased by amorphous carbon. The Si-carbon composite NF exhibit a significantly improved electrochemical performance with a high specific capacity of 1250 mAh·g −1 and a superior cycling performance during 50 cycles at a rate of 0.2 C. More importantly, Si-carbon composite NF maintain about 70% of initial capacity at 0.2 C and an excellent cycling stability even at 25 times higher current density compared to the initial condition, proving that it has superb kinetics compared to ever reported Si or SiO x materials. The electrochemical superiority of Si-carbon composite NF can be attributed to amorphous carbon framework accommodating the inherent volume expansion of Si during lithiation as well as the enlarged contact area between active materials and conducting agent attributed to the morphological characteristics of its one dimensional (1D) nanostructure

A beam radiation monitor based on CVD diamonds for SuperB

Science.gov (United States)

Cardarelli, R.; Di Ciaccio, A.

2013-08-01

Chemical Vapor Deposition (CVD) diamond particle detectors are in use in the CERN experiments at LHC and at particle accelerator laboratories in Europe, USA and Japan mainly as beam monitors. Nowadays it is considered a proven technology with a very fast signal read-out and a very high radiation tolerance suitable for measurements in high radiation environment zones i.e. near the accelerators beam pipes. The specific properties of CVD diamonds make them a prime candidate for measuring single particles as well as high-intensity particle cascades, for timing measurements on the sub-nanosecond scale and for beam protection systems in hostile environments. A single-crystalline CVD (scCVD) diamond sensor, read out with a new generation of fast and high transition frequency SiGe bipolar transistor amplifiers, has been tested for an application as radiation monitor to safeguard the silicon vertex tracker in the SuperB detector from excessive radiation damage, cumulative dose and instantaneous dose rates. Test results with 5.5 MeV alpha particles from a 241Am radioactive source and from electrons from a 90Sr radioactive source are presented in this paper.

Latest results of the R and D on CMOS MAPS for the Layer0 of the SuperB SVT

Energy Technology Data Exchange (ETDEWEB)

Balestri, G. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa (Italy); Batignani, G. [Università degli Studi di Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pisa (Italy); Beck, G. [School of Physics and Astronomy Queen Mary, University of London, London E1 4NS (United Kingdom); Bernardelli, A. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa (Italy); Berra, A. [Università dell' Insubria, Como (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Milano Bicocca (Italy); Bettarini, S. [Università degli Studi di Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pisa (Italy); Bevan, A. [School of Physics and Astronomy Queen Mary, University of London, London E1 4NS (United Kingdom); Bombelli, L. [Politecnico di Milano (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Milano (Italy); Bosi, F. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa (Italy); Bosisio, L. [Università degli Studi di Trieste (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Trieste (Italy); Casarosa, G., E-mail: giulia.casarosa@pi.infn.it [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa (Italy); Ceccanti, M. [Istituto Nazionale di Fisica Nucleare, Sezione di Pisa (Italy); Cenci, R. [University of Maryland (United States); Citterio, M.; Coelli, S. [Istituto Nazionale di Fisica Nucleare, Sezione di Milano (Italy); Comotti, D. [Università degli Studi di Bergamo (Italy); Dalla Betta, G.-F. [Università degli Studi di Trento (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Padova (Italy); Fabbri, L. [Università degli Studi di Bologna (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bologna (Italy); and others

2013-12-21

Physics and high background conditions set very challenging requirements on readout speed, material budget and resolution for the innermost layer of the SuperB Silicon Vertex Tracker operated at the full luminosity. Monolithic Active Pixel Sensors (MAPS) are very appealing in this application since the thin sensitive region allows grinding the substrate to tens of microns. Deep N-Well MAPS, developed in the ST 130 nm CMOS technology, achieved in-pixel sparsification and fast time stamping. Further improvements are being explored with an intense R and D program, including both vertical integration and 2D MAPS with the INMAPS quadruple well. We present the results of the characterization with IR laser, radioactive sources and beam of several chips produced with the 3D (Chartered/Tezzaron) process. We have also studied prototypes exploiting the features of the quadruple well and the high resistivity epitaxial layer of the INMAPS 180 nm process. Promising results from an irradiation campaign with neutrons on small matrices and other test-structures, as well as the response of the sensors to high energy charged tracks are presented.

Field dependence-independence and participation in physical activity by college students.

Science.gov (United States)

Liu, Wenhao

2006-06-01

Field-independent individuals, compared with field-dependent individuals, have higher sports potential and advantages in sport-related settings. Little research, however, has been conducted on the association of field dependence-independence and participation in physical activity. The study examined this association for college students who participated in physical activities in and beyond physical education classes. The Group Embedded Figures Test distinguished 40 field-dependent from 40 field-independent participants. Activity logs during one semester showed that field-independent participants were significantly more physically active and their physical activity behaviors were more sport-related than those of field-dependent participants.

Elaborate Mimetic Vocal Displays by Female Superb Lyrebirds

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Anastasia H Dalziell

2016-04-01

Full Text Available Some of the most striking vocalizations in birds are made by males that incorporate vocal mimicry in their sexual displays. Mimetic vocalization in females is largely undescribed, but it is unclear whether this is because of a lack of selection for vocal mimicry in females, or whether the phenomenon has simply been overlooked. These issues are thrown into sharp relief in the superb lyrebird, Menura novaehollandiae, a basal oscine passerine with a lek-like mating system and female uniparental care. The spectacular mimetic song display produced by courting male lyrebirds is a textbook example of a sexually selected trait, but the vocalizations of female lyrebirds are largely unknown. Here, we provide the first analysis of the structure and context of the vocalizations of female lyrebirds. Female lyrebirds were completely silent during courtship; however, females regularly produced sophisticated vocal displays incorporating both lyrebird-specific vocalizations and imitations of sounds within their environment. The structure of female vocalizations varied significantly with context. While foraging, females mostly produced a complex lyrebird-specific song, whereas they gave lyrebird-specific alarm calls most often during nest defense. Within their vocal displays females also included a variety of mimetic vocalizations, including imitations of the calls of dangerous predators, and of alarm calls and song of harmless heterospecifics. Females gave more mimetic vocalizations during nest defense than while foraging, and the types of sounds they imitated varied between these contexts, suggesting that mimetic vocalizations have more than one function. These results are inconsistent with previous portrayals of vocalizations by female lyrebirds as rare, functionless by-products of sexual selection on males. Instead, our results support the hypotheses that complex female vocalizations play a role in nest defense and mediate female-female competition for

A plasma coagulation assay for an activated protein C-independent anticoagulant activity of protein S

NARCIS (Netherlands)

van Wijnen, M.; van 't Veer, C.; Meijers, J. C.; Bertina, R. M.; Bouma, B. N.

1998-01-01

To study the physiological importance of the activated protein C (APC)-independent anticoagulant activity of protein S, we developed an assay specific for this activity. The ability of protein S to prolong the clotting time in an APC-independent way was expressed as the ratio of the clotting time in

Is Cognitive Activity of Speech Based On Statistical Independence?

DEFF Research Database (Denmark)

Feng, Ling; Hansen, Lars Kai

2008-01-01

This paper explores the generality of COgnitive Component Analysis (COCA), which is defined as the process of unsupervised grouping of data such that the ensuing group structure is well-aligned with that resulting from human cognitive activity. The hypothesis of {COCA} is ecological......: the essentially independent features in a context defined ensemble can be efficiently coded using a sparse independent component representation. Our devised protocol aims at comparing the performance of supervised learning (invoking cognitive activity) and unsupervised learning (statistical regularities) based...... on similar representations, and the only difference lies in the human inferred labels. Inspired by the previous research on COCA, we introduce a new pair of models, which directly employ the independent hypothesis. Statistical regularities are revealed at multiple time scales on phoneme, gender, age...

TECHNOLOGIES OF INITIATING STUDENTS INTO INDEPENDENT (SELF-GUIDED ACTIVITY IN SUPPLEMENTARY DISTANCE LEARNING

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Irina V. Abakumova

2016-12-01

Full Text Available The research in question investigates the technologies of initiating independent activity within the framework of distance learning and their psychological aspects. The authors’ classification of educational technologies of initiating students into independent cognitive activity is presented. Such technologies utilize various psychological mechanisms of exciting students’ cognitive interest, intensifying cognitive processes, developing independent activity skills, and, as a result, increase motivation for independent activity and learning on the whole. These include such types of technologies as developmental technologies, interactive technologies, technologies of information transfer, technologies of meaning-making initiation. The research of the attitude of distance learning educators to independent activity of students and the content of the academic courses were done at Moodle-based education programs. The findings show the differences in retention rate among distance learning educators whose competence in terms of initiating students into independent (self-guided activity varies. It’s emphasized that interactive lectures, videoconferences, audio-visual aids, interactive seminars, glossaries, interactive tests are considered the most efficient technologies in initiating students into independent (self-guided activity. The obtained results have made it possible to stress the developmental effect of distance learning technologies and the technologies of initiating students into independent (self-guided activity in various psychic spheres of students: cognitive, individual, emotional. We mention the changes in motivational sphere of students and their meaning-making activity. In the course of correct development of distance learning we notice the development of voluntary and nonvoluntary cognitive activity. A student starts actively participating in educational process, he becomes the creator of his own world.

p21-activated Kinase1(PAK1) can promote ERK activation in a kinase independent manner

DEFF Research Database (Denmark)

Wang, Zhipeng; Fu, Meng; Wang, Lifeng

2013-01-01

204) although phosphorylation of b-Raf (Ser445) and c-Raf (Ser 338) remained unchanged. Furthermore, increased activation of the PAK1 activator Rac1 induced the formation of a triple complex of Rac1, PAK1 and Mek1, independent of the kinase activity of PAK1. These data suggest that PAK1 can stimulate...... MEK activity in a kinase independent manner, probably by serving as a scaffold to facilitate interaction of c-Raf....

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

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Sung-Jun Park

2017-04-01

Full Text Available The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK, an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1.

The front-end chip of the SuperB SVT detector

International Nuclear Information System (INIS)

Giorgi, F.; Comotti, D.; Manghisoni, M.; Re, V.; Traversi, G.; Fabbri, L.; Gabrielli, A.; Pellegrini, G.; Sbarra, C.; Semprini-Cesari, N.; Valentinetti, S.; Villa, M.; Zoccoli, A.; Berra, A.; Lietti, D.; Prest, M.; Bevan, A.; Wilson, F.; Beck, G.; Morris, J.

2013-01-01

The asymmetric e + e − collider SuperB is designed to deliver a high luminosity, greater than 10 36 cm −2 s −1 , with moderate beam currents and a reduced center of mass boost with respect to earlier B-Factories. The innermost detector is the Silicon Vertex Tracker which is made of 5 layers of double sided silicon strip sensors plus a layer 0, that can be equipped with short striplets detectors in a first phase of the experiment. In order to achieve an overall track reconstruction efficiency above 98% it is crucial to optimize both analog and digital readout circuits. The readout architecture being developed for the front-end chips will be able to cope with the very high rates expected in the first layer. The digital readout will be optimized to be fully efficient for hit rates up to 2 MHz/strip, including large margins on the maximum expected background rates, but can potentially accommodate higher rates with a proper tuning of the buffer depth. The readout is based on a triggered architecture where each of the 128 strip channel is provided with a dedicated digital buffer. Each buffer collects the digitized charge information by means of a 4-bit TOT, storing it in conjunction with the related time stamp. The depth of buffers was dimensioned considering the expected trigger latency and hit rate including suitable safety margins. Every buffer is connected to a highly parallelized circuit handling the trigger logic, rejecting expired data in the buffers and channeling the parallel stream of triggered hits to the common output of the chip. The presented architecture has been modeled by HDL language and investigated with a Monte Carlo hit generator emulating the analog front-end behavior. The simulations showed that even applying the highest stressing conditions, about 2 MHz per strip, the efficiency of the digital readout remained above 99.8%

Associations of children's independent mobility and active travel with physical activity, sedentary behaviour and weight status: a systematic review.

Science.gov (United States)

Schoeppe, Stephanie; Duncan, Mitch J; Badland, Hannah; Oliver, Melody; Curtis, Carey

2013-07-01

Health benefits from children's independent mobility and active travel beyond school travel are largely unexplored. This review synthesized the evidence for associations of independent mobility and active travel to various destinations with physical activity, sedentary behaviour and weight status. Systematic review. A systematic search in six databases (PubMed, Scopus, CINAHL, SportDiscus, PsychInfo, TRIS) for papers published between January 1990 and March 2012 was undertaken, focussing on children aged 3-18 years. Study inclusion and methodological quality were independently assessed by two reviewers. 52 studies were included. Most studies focussed solely on active travel to and/or from school, and showed significant positive associations with physical activity. The same relationship was detected for active travel to leisure-related places and independent mobility with physical activity. An inverse relationship between active travel to school and weight status was evident but findings were inconsistent. Few studies examined correlations between active travel to school and self-reported screen-time or objectively measured sedentary behaviour, and findings were unclear. Studies on independent mobility suggested that children who have the freedom to play outdoors and travel actively without adult supervision accumulate more physical activity than those who do not. Further investigation of children's active travel to leisure-related destinations, measurement of diverse sedentary behaviour beyond simply screen-based activities, and consistent thresholds for objectively measured sedentary behaviour in children will clarify the inconsistent evidence base on associations of active travel with sedentary behaviour and weight status. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Field dependence-independence as related to young women's participation in sports activity.

Science.gov (United States)

Lambrecht, Jeanne L; Cuevas, Jacqueline L

2007-06-01

To estimate association between field dependence-independence measured by scores on the Group Embedded Figures Test and young women's participation in sports activity. Participants were 37 undergraduate college women between the ages of 18 and 25 years (M=21). Participants were categorized into two groups, one high in participation in sports activity and one low. A one-tailed independent samples t test yielded no significant difference. Correlations of .36 and .18 were significant but account for little common variance. An ad hoc analysis performed without participants who reported softball activity but who were highly involved in sport activities was significant.

Children's active travel and independent mobility in four countries

DEFF Research Database (Denmark)

Fyhri, Aslak; Hjorthol, Randi; Mackett, Roger L.

2011-01-01

In many countries a decline in children's active and independent mobility, like walking and cycling is registered. In this paper the development of children's mobility in Denmark, Finland, Great Britain and Norway is compared to examine differences and similarities in these countries. Accessible ...

COGNITIVE COMPETENCE COMPARED TO COGNITIVE INDEPENDENCE AND COGNITIVE ACTIVITY

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Irina B. Shmigirilova

2014-01-01

Full Text Available The research is aimed at identifying the essence of the cognitive competence concept in comparison with the concepts of cognitive independence and activity.Methods: The methodology implies a theoretical analysis of psychopedagogical and methodological materials on the cognitive competence formation; generalized teaching experience; empirical methods of direct observations of educational process in the secondary school classrooms; interviews with school teachers and pupils.Results: The research outcomes reveal a semantic intersection between the cognitive competence, independence and activity, and their distinctive features. The paper emphasizes the importance of cognitive competence as an adaptive mechanism in situations of uncertainty and instability.Scientific novelty: The author clarifies the concept of cognitive competence regarding it as a multi-component and systematic characteristic of a personality.Practical significance: The research findings can be used by specialists in didactics developing the teaching techniques of cognitive competence formation for schoolchildren.

[Active aging from the perspective of aged individuals who are functionally independent].

Science.gov (United States)

Ferreira, Olivia Galvão Lucena; Maciel, Silvana Carneiro; Silva, Antonia Oliveira; dos Santos, Walberto Silva; Moreira, Maria Adelaide Silva P

2010-12-01

The objective of this study was to identify the social representations of the elderly regarding active aging. Semi-structured interviews were performed with 100 functionally independent aged individuals from João Pessoa, Paraiba, Brazil. The data was organized and analyzed using Alceste software. Results showed that the aged individuals' statements about active aging are permeated with positive contents. However, when aging is not associated with the word active, it is still represented as losses and disabilities. Despite the existence of losses during the process, active aging should be encouraged among the elderly, as it means living a quality, plentiful life. Maintaining the elderly functionally independent is the first step to achieving active aging and thus improving their quality of life.

Berberine promotes glucose consumption independently of AMP-activated protein kinase activation.

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Miao Xu

Full Text Available Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1 inhibition of AMPK activity by Compound C, (2 suppression of AMPKα expression by siRNA, and (3 blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.

Absolute activity determinations on large volume geological samples independent of self-absorption effects

International Nuclear Information System (INIS)

Wilson, W.E.

1980-01-01

This paper describes a method for measuring the absolute activity of large volume samples by γ-spectroscopy independent of self-absorption effects using Ge detectors. The method yields accurate matrix independent results at the expense of replicative counting of the unknown sample. (orig./HP)

Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

Science.gov (United States)

Reese, Vanessa C.; Oropeza, Claudia E.

2013-01-01

In the human hepatoma cell line HepG2, retinoic acid, clofibric acid, and bile acid treatment can only modestly increase hepatitis B virus (HBV) biosynthesis. Utilizing the human embryonic kidney cell line 293T, it was possible to demonstrate that the retinoid X receptor α (RXRα) plus its ligand can support viral biosynthesis independently of additional nuclear receptors. In addition, RXRα/peroxisome proliferator-activated receptor α (PPARα) and RXRα/farnesoid X receptor α (FXRα) heterodimeric nuclear receptors can also mediate ligand-dependent HBV transcription and replication when activated by clofibric acid and bile acid, respectively, independently of a requirement for the ligand-dependent activation of RXRα. These observations indicate that there are at least three possible modes of ligand-mediated activation of HBV transcription and replication existing within hepatocytes, suggesting that multiple independent mechanisms control viral production in the livers of infected individuals. PMID:23135717

Selection of independent components based on cortical mapping of electromagnetic activity

Science.gov (United States)

Chan, Hui-Ling; Chen, Yong-Sheng; Chen, Li-Fen

2012-10-01

Independent component analysis (ICA) has been widely used to attenuate interference caused by noise components from the electromagnetic recordings of brain activity. However, the scalp topographies and associated temporal waveforms provided by ICA may be insufficient to distinguish functional components from artifactual ones. In this work, we proposed two component selection methods, both of which first estimate the cortical distribution of the brain activity for each component, and then determine the functional components based on the parcellation of brain activity mapped onto the cortical surface. Among all independent components, the first method can identify the dominant components, which have strong activity in the selected dominant brain regions, whereas the second method can identify those inter-regional associating components, which have similar component spectra between a pair of regions. For a targeted region, its component spectrum enumerates the amplitudes of its parceled brain activity across all components. The selected functional components can be remixed to reconstruct the focused electromagnetic signals for further analysis, such as source estimation. Moreover, the inter-regional associating components can be used to estimate the functional brain network. The accuracy of the cortical activation estimation was evaluated on the data from simulation studies, whereas the usefulness and feasibility of the component selection methods were demonstrated on the magnetoencephalography data recorded from a gender discrimination study.

Which activities threaten independent living of elderly when becoming problematic: inspiration for meaningful service robot functionality.

Science.gov (United States)

Bedaf, Sandra; Gelderblom, Gert Jan; Syrdal, Dag Sverre; Lehmann, Hagen; Michel, Hervé; Hewson, David; Amirabdollahian, Farshid; Dautenhahn, Kerstin; de Witte, Luc

2014-11-01

In light of the increasing elderly population and the growing demand for home care, the potential of robot support is given increasing attention. In this paper, an inventory of activities was made that threaten independent living of elderly when becoming problematic. Results will guide the further development of an existing service robot, the Care-O-bot®. A systematic literature search of PubMed was performed, focused on the risk factors for institutionalization. Additionally, focus group sessions were conducted in the Netherlands, United Kingdom and France. In these focus group sessions, problematic activities threatening the independence of elderly people were discussed. Three separate target groups were included in the focus group sessions: (1) elderly persons (n = 41), (2) formal caregivers (n = 40) and (3) informal caregivers (n = 32). Activities within the International Classification of Functioning domains mobility, self-care, and interpersonal interaction and relationships were found to be the most problematic. A distinct set of daily activities was identified that may threaten independent living, but no single activity could be selected as the main activity causing a loss of independence as it is often a combination of problematic activities that is person-specific. Supporting the problematic activities need not involve a robotic solution.

Receptor activity-independent recruitment of βarrestin2 reveals specific signalling modes

Science.gov (United States)

Terrillon, Sonia; Bouvier, Michel

2004-01-01

The roles of βarrestins in regulating G protein coupling and receptor endocytosis following agonist stimulation of G protein-coupled receptors are well characterised. However, their ability to act on their own as direct modulators or activators of signalling remains poorly characterised. Here, βarrestin2 intrinsic signalling properties were assessed by forcing the recruitment of this accessory protein to vasopressin V1a or V2 receptors independently of agonist-promoted activation of the receptors. Such induction of a stable interaction with βarrestin2 initiated receptor endocytosis leading to intracellular accumulation of the βarrestin/receptor complexes. Interestingly, βarrestin2 association to a single receptor protomer was sufficient to elicit receptor dimer internalisation. In addition to recapitulating βarrestin2 classical actions on receptor trafficking, the receptor activity-independent recruitment of βarrestin2 activated the extracellular signal-regulated kinases. In the latter case, recruitment to the receptor itself was not required since kinase activation could be mediated by βarrestin2 translocation to the plasma membrane in the absence of any interacting receptor. These data demonstrate that βarrestin2 can act as a ‘bonafide' signalling molecule even in the absence of activated receptor. PMID:15385966

Elevated p21-Activated Kinase 2 Activity Results in Anchorage-Independent Growth and Resistance to Anticancer Drug–Induced Cell Death

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Jerry W. Marlin

2009-03-01

Full Text Available p21-Activated kinase 2 (PAK-2 seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death response. In this study, we present a role of elevated activity of full-length PAK-2 in anchorage-independent growth and resistance to anticancer drug–induced apoptosis of cancer cells. Hs578T human breast cancer cells that have low levels of PAK-2 activity were more sensitive to anticancer drug–induced apoptosis and showed higher levels of caspase activation of PAK-2 than MDA-MB435 and MCF-7 human breast cancer cells that have high levels of PAK-2 activity. To examine the role of elevated PAK-2 activity in breast cancer, we have introduced a conditionally active PAK-2 into Hs578T human breast cells. Conditional activation of PAK-2 causes loss of contact inhibition and anchorage-independent growth of Hs578T cells. Furthermore, conditional activation of PAK-2 suppresses activation of caspase 3, caspase activation of PAK-2, and apoptosis of Hs578T cells in response to the anticancer drug cisplatin. Our data suggest a novel mechanism by which full-length PAK-2 activity controls the apoptotic response by regulating levels of activated caspase 3 and thereby its own cleavage to the proapoptotic PAK-2p34 fragment. As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug–induced apoptosis.

Electronic Learning Courses as a Means to Activate Students' Independent Work in Studying Physics

Science.gov (United States)

Shurygin, Viktor Yurjevich; Krasnova, Lyubov Alekseevna

2016-01-01

Currently, there are special requirements to the system of higher education, focused not only on imparting knowledge to students, but also on the formation of the continuous need for independent self-education, self-creative approach to getting knowledge throughout their active life. In this regard, the role of students' independent work with its…

Genetic Validation of Cell Proliferation via Ras-Independent Activation of the Raf/Mek/Erk Pathway.

Science.gov (United States)

Lechuga, Carmen G; Simón-Carrasco, Lucía; Jacob, Harrys K C; Drosten, Matthias

2017-01-01

Signaling transmitted by the Ras family of small GTPases (H-, N-, and K-Ras) is essential for proliferation of mouse embryonic fibroblasts (MEFs). However, constitutive activation of the downstream Raf/Mek/Erk pathway can bypass the requirement for Ras proteins and allow cells to proliferate in the absence of the three Ras isoforms. Here we describe a protocol for a colony formation assay that permits evaluating the role of candidate proteins that are positive or negative regulators of cell proliferation mediated via Ras-independent Raf/Mek/Erk pathway activation. K-Ras lox (H-Ras -/- , N-Ras -/- , K-Ras lox/lox , RERT ert/ert ) MEFs are infected with retro- or lentiviral vectors expressing wild-type or constitutively activated candidate cDNAs, shRNAs, or sgRNAs in combination with Cas9 to ascertain the possibility of candidate proteins to function either as an activator or inhibitor of Ras-independent Raf/Mek/Erk activation. These cells are then seeded in the absence or presence of 4-Hydroxytamoxifen (4-OHT), which activates the resident CreERT2 alleles resulting in elimination of the conditional K-Ras alleles and ultimately generating Rasless cells. Colony formation in the presence of 4-OHT indicates cell proliferation via Ras-independent Raf/Mek/Erk activation.

Are Independent Fiscal Institutions Really Independent?

Directory of Open Access Journals (Sweden)

Slawomir Franek

2015-08-01

Full Text Available In the last decade the number of independent fiscal institutions (known also as fiscal councils has tripled. They play an important oversight role over fiscal policy-making in democratic societies, especially as they seek to restore public finance stability in the wake of the recent financial crisis. Although common functions of such institutions include a role in analysis of fiscal policy, forecasting, monitoring compliance with fiscal rules or costing of spending proposals, their roles, resources and structures vary considerably across countries. The aim of the article is to determine the degree of independence of such institutions based on the analysis of the independence index of independent fiscal institutions. The analysis of this index values may be useful to determine the relations between the degree of independence of fiscal councils and fiscal performance of particular countries. The data used to calculate the index values will be derived from European Commission and IMF, which collect sets of information about characteristics of activity of fiscal councils.

Discoidin domain receptor 1 is activated independently of beta(1) integrin

DEFF Research Database (Denmark)

Vogel, W; Brakebusch, C; Fässler, R

2000-01-01

independent of the epidermal growth factor (EGF) receptor. In cells that endogenously express both DDR1 and the EGF receptor, stimulation with EGF does not induce DDR activation. Third, we detected full DDR1 activation after collagen stimulation in cells that have been treated with blocking antibodies...... for alpha(2)beta(1) integrin or in cells with a targeted deletion of the beta(1) integrin gene. Finally, we show that overexpression of dominant negative DDR1 in the myoblast cell line C2C12 blocks cellular differentiation and the formation of myofibers....

The interaction of protein S with the phospholipid surface is essential for the activated protein C-independent activity of protein S

NARCIS (Netherlands)

van Wijnen, M.; Stam, J. G.; van't Veer, C.; Meijers, J. C.; Reitsma, P. H.; Bertina, R. M.; Bouma, B. N.

1996-01-01

Protein S is a vitamin-K dependent glycoprotein involved in the regulation of the anticoagulant activity of activated protein C (APC). Recent data showed a direct anticoagulant role of protein S independent of APC, as demonstrated by the inhibition of prothrombinase and tenase activity both in

Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

Science.gov (United States)

Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

2014-08-01

Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long-term trends of foF2 independent of geomagnetic activity

Directory of Open Access Journals (Sweden)

A. D. Danilov

Full Text Available A detailed analysis of the foF2 data at a series of ionospheric stations is performed to reveal long-term trends independent of the long-term changes in geomagnetic activity during the recent decades (nongeomagnetic trends. The method developed by the author and published earlier is used. It is found that the results for 21 out of 23 stations considered agree well and give a relative nongeomagnetic trend of -0.0012 per year (or an absolute nongeomagnetic trend of about -0.012 MHz per year for the period between 1958 and the mid-nineties. The trends derived show no dependence on geomagnetic latitude or local time, a fact confirming their independence of geomagnetic activity. The consideration of the earlier period (1948–1985 for a few stations for which the corresponding data are available provides significantly lower foF2 trends, the difference between the later and earlier periods being a factor of 1.6. This is a strong argument in favor of an anthropogenic nature of the trends derived.Key words. Ionosphere (ionosphere-atmosphere interactions; ionospheric disturbances; mid-latitude ionosphere

Suppression of resistive wall instabilities with distributed, independently controlled, active feedback coils

International Nuclear Information System (INIS)

Cates, C.; Shilov, M.; Mauel, M. E.; Navratil, G. A.; Maurer, D.; Mukherjee, S.; Nadle, D.; Bialek, J.; Boozer, A.

2000-01-01

External kink instabilities are suppressed in a tokamak experiment by either (1) energizing a distributed array of independently controlled active feedback coils mounted outside a segmented resistive wall or (2) inserting a second segmented wall having much higher electrical conductivity. When the active feedback coils are off and the highly conducting wall is withdrawn, kink instabilities excited by plasma current gradients grow at a rate comparable to the magnetic diffusion rate of the resistive wall. (c) 2000 American Institute of Physics

Independent associations of physical activity and cardiorespiratory fitness with metabolic risk factors in children: the European youth heart study

DEFF Research Database (Denmark)

Ekelund, U; Anderssen, S A; Froberg, K

2007-01-01

AIMS/HYPOTHESIS: High levels of cardiorespiratory fitness (CRF) and physical activity (PA) are associated with a favourable metabolic risk profile. However, there has been no thorough exploration of the independent contributions of cardiorespiratory fitness and subcomponents of activity (total PA...... the association between activity and clustered risk is independent of adiposity. Our results suggest that fitness and activity affect metabolic risk through different pathways....

The role of independent inspection in verification activities

International Nuclear Information System (INIS)

Fuerste, W.

1982-01-01

Independent inspection has its origin in the early Middle Ages, when kings prescribed to textile manufacturers a quality control by authorized inspectors. Independent inspection became more important with respect to the safety of workers in the industrial era beginning in the 18th century, when the high-pressure steam engines were introduced and many accidents and explosions of steam boilers occurred. Nowadays, independent inspection is of utmost importance, because the safety of the public is endangered by industrial plants located near highly populated areas. To better understand the role of independent inspection, the paper reviews its historical development in Europe from the Middle Ages to the 20th century. Most of the independent inspection associations in European countries were established after the second half of the 19th century and began with the surveillance of steam boilers. Nowadays, organizations like the TUEVs (Technical Inspection Agencies) in the Federal Republic of Germany perform expertise and inspection on behalf of the government in various fields of industrial safety. To show how independent inspection is involved in quality assurance, the methods practised in the United States of America and the Federal Republic of Germany are compared and future trends discussed. For developing countries starting with nuclear energy, it is important to consider the information and recommendations regarding independent inspection and its regulation as laid down in a number of publications in the IAEA NUSS Programme. (author)

The role of CD4 in antigen-independent activation of isolated single T lymphocytes

DEFF Research Database (Denmark)

Kelso, A; Owens, T

1988-01-01

The membrane molecule CD4 (L3T4) is thought to facilitate activation of Class II H-2-restricted T cells by binding to Ia determinants on antigen-presenting cells. Recent reports suggest that CD4 can also contribute to antigen-independent activation by anti-T cell receptor (TCR) antibodies. An ass...

PEDAGOGICAL CONDITIONS OF ACTIVATION OF CREATIVE COGNITIVE INDEPENDENCE OF A COLLEGE STUDENTS

Directory of Open Access Journals (Sweden)

Elena V. Strogina

2015-01-01

Full Text Available The article is devoted to creation of the model and methodic conditions of activation of creative cognitive independence of a college students. Useof the present system could allow to solve one ofthe prime tasks in the modern studying process,as well as significantly increase professionalqualifications of the college graduates.

The abstraction of independent cross-sections from the γ activities of successively decayed daughter nuclei

International Nuclear Information System (INIS)

Zheng Jiwen; Zhang Li; Zhao Jinhua; Hu Qingyuan

1999-01-01

A technique for abstracting independent cross section on the basis of the γ activities from the observed isotope itself or its successively decayed daughter nuclei was developed. It is specially applicable for determining the independent cross sections of the isotope products involved in quick, element-separated samples. The authors have used it in the isotope-distribution measurement for Hg element produced in the reaction of 600-MeV 18 O beam bombarding on thick natural lead target, and a total of Hg-isotope independent cross sections more than twenty were obtained in the mass range of 180∼209. Some representative examples showing how the authors deduced these independent cross sections are given

Independent and Combined Associations of Physical Activity and Sedentary Behavior with Depressive Symptoms Among Japanese Adults.

Science.gov (United States)

Liao, Yung; Shibata, Ai; Ishii, Kaori; Oka, Koichiro

2016-08-01

Associations between levels of sedentary behavior and depressive symptoms independently and in combination with different levels of physical activity remain unclear. This study aimed to examine independent and combined associations of physical activity (PA) and sedentary behavior (SB) with depressive symptoms among Japanese adults. An Internet-based survey collected data on depression levels (Center for Epidemiologic Studies Depression Scale), self-reported time spent in PA and SB (Japanese short version of the International Physical Activity Questionnaire), and sociodemographic variables from 2,914 adults in 2009. Binary logistic regression analyses were conducted to examine the odds ratios (ORs) for being depressed (depression scores ≥16) according to independent PA levels (none, insufficient, sufficient), SB levels (low, moderate, high), and nine combinations of PA and SB categories. After adjusting for potential confounders, sufficient PA level was found to be related to lower risk of depressive symptoms independently (OR = 0.61), whereas no significant associations were observed between SB levels and depression. In the combined associations, adults in the sufficient PA/high SB (OR = 0.44), sufficient PA/moderate SB (OR = 0.56), and sufficient PA/low SB (OR = 0.57) categories were significantly less likely to have depressive symptoms in comparison with the no PA/high SB category. Meeting physical activity recommendations is associated with a lower risk of depressive symptoms, regardless of time spent in total sedentary behavior. These results suggest that promoting physical activity may be an effective strategy against depressive symptoms among Japanese adults.

Cathodic electrochemical activation of Co3O4 nanoarrays: a smart strategy to significantly boost the hydrogen evolution activity.

Science.gov (United States)

Yang, Li; Zhou, Huang; Qin, Xin; Guo, Xiaodong; Cui, Guanwei; Asiri, Abdullah M; Sun, Xuping

2018-02-22

Co(hydro)oxides show unsatisfactory catalytic activity for the hydrogen evolution reaction (HER) in alkaline media, and it is thus highly desirable but still remains a challenge to design and develop Co(hydro)oxide derived materials as superb hydrogen-evolving catalysts using a facile, rapid and less energy-intensive method. Here, we propose a cathodic electrochemical activation strategy toward greatly boosted HER activity of a Co 3 O 4 nanoarray via room-temperature cathodic polarization in sodium hypophosphite solution. After activation, the overpotential significantly decreases from 260 to 73 mV to drive a geometrical catalytic current density of 10 mA cm -2 in 1.0 M KOH. Notably, this activated electrode also shows strong long-term electrochemical durability with the retention of its catalytic activity at 100 mA cm -2 for at least 40 h.

Executive dysfunction is independently associated with reduced functional independence in heart failure.

Science.gov (United States)

Alosco, Michael L; Spitznagel, Mary Beth; Raz, Naftali; Cohen, Ronald; Sweet, Lawrence H; Colbert, Lisa H; Josephson, Richard; van Dulmen, Manfred; Hughes, Joel; Rosneck, Jim; Gunstad, John

2014-03-01

To examine the independent association between executive function with instrumental activities of daily living and health behaviours in older adults with heart failure. Executive function is an important contributor to functional independence as it consists of cognitive processes needed for decision-making, planning, organising and behavioural monitoring. Impairment in this domain is common in heart failure patients and associated with reduced performance of instrumental activities of daily living in many medical and neurological populations. However, the contribution of executive functions to functional independence and healthy lifestyle choices in heart failure patients has not been fully examined. Cross-sectional analyses. One hundred and seventy-five heart failure patients completed a neuropsychological battery and echocardiogram. Participants also completed the Lawton-Brody Instrumental Activities of Daily Living Scale and reported current cigarette use. Hierarchical regressions revealed that reduced executive function was independently associated with worse instrumental activity of daily living performance with a specific association for decreased ability to manage medications. Partial correlations showed that executive dysfunction was associated with current cigarette use. Our findings suggest that executive dysfunction is associated with poorer functional independence and contributes to unhealthy behaviours in heart failure. Future studies should examine whether heart failure patients benefit from formal organisation schema (i.e. pill organisers) to maintain independence. Screening of executive function in heart failure patients may provide key insight into their ability to perform daily tasks, including the management of treatment recommendations. © 2013 John Wiley & Sons Ltd.

Pharmacological evidences for DFK167-sensitive presenilin-independent gamma-secretase-like activity.

Science.gov (United States)

Sevalle, Jean; Ayral, Erwan; Hernandez, Jean-François; Martinez, Jean; Checler, Frédéric

2009-07-01

Amyloid-beta (Abeta) peptides production is thought to be a key event in the neurodegenerative process ultimately leading to Alzheimer's disease (AD) pathology. A bulk of studies concur to propose that the C-terminal moiety of Abeta is released from its precursor beta-amyloid precursor protein by a high molecular weight enzymatic complex referred to as gamma-secretase, that is composed of at least, nicastrin (NCT), Aph-1, Pen-2, and presenilins (PS) 1 or 2. They are thought to harbor the gamma-secretase catalytic activity. However, several lines of evidence suggest that additional gamma-secretase-like activities could potentially contribute to Abeta production. By means of a quenched fluorimetric substrate (JMV2660) mimicking the beta-amyloid precursor protein sequence targeted by gamma-secretase, we first show that as expected, this probe allows monitoring of an activity detectable in several cell systems including the neuronal cell line telencephalon specific murine neurons (TSM1). This activity is reduced by DFK167, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), and LY68458, three inhibitors known to functionally interact with PS. Interestingly, JMV2660 but not the unrelated peptide JMV2692, inhibits Abeta production in an in vitrogamma-secretase assay as expected from a putative substrate competitor. This activity is enhanced by PS1 and PS2 mutations known to be responsible for familial forms of AD and reduced by aspartyl mutations inactivating PS or in cells devoid of PS or NCT. However, we clearly establish that residual JMV2660-hydrolysing activity could be recovered in PS- and NCT-deficient fibroblasts and that this activity remained inhibited by DFK167. Overall, our study describes the presence of a proteolytic activity displaying gamma-secretase-like properties but independent of PS and still blocked by DFK167, suggesting that the PS-dependent complex could not be the unique gamma-secretase activity responsible for Abeta

Association of sedentary time with mortality independent of moderate to vigorous physical activity

DEFF Research Database (Denmark)

Koster, Annemarie; Caserotti, Paolo; Patel, Kushang V

2012-01-01

Sedentary behavior has emerged as a novel health risk factor independent of moderate to vigorous physical activity (MVPA). Previous studies have shown self-reported sedentary time to be associated with mortality; however, no studies have investigated the effect of objectively measured sedentary t...

Normal weight children have higher cognitive performance – Independent of physical activity, sleep, and diet

DEFF Research Database (Denmark)

Hjorth, Mads F.; Sørensen, Louise B.; Andersen, Rikke

2016-01-01

% of expected learning within one school year (P breakfast consumption, fewer sleep problems, higher CRF, less total physical activity, more sedentary time, and less light physical activity were associated with higher cognitive performance independently of each other in at least one of the three...

A meta-study of qualitative research examining determinants of children's independent active free play.

Science.gov (United States)

Lee, Homan; Tamminen, Katherine A; Clark, Alexander M; Slater, Linda; Spence, John C; Holt, Nicholas L

2015-01-24

To produce a meta-study by completing a systematic review of qualitative research examining determinants of independent active free play in children. Following systematic electronic and manual searches and application of inclusion/exclusion criteria, 46 studies were retained and subjected to meta-method, meta-theory, and meta-data analyses, followed by a final meta-synthesis. Identified determinants of independent active free play were child characteristics (age, competence, and gender), parental restrictions (safety concerns and surveillance), neighborhood and physical environment (fewer children to play with, differences in preferences for play spaces between parents and children, accessibility and proximity, and maintenance), societal changes (reduced sense of community, good parenting ideal, changing roles of parents, privatization of playtime and play spaces), and policy issues (need to give children voice). An ecological model depicting these factors, and the relationships therein, was created. This comprehensive meta-study helps establish a knowledge base for children's independent active free play research by synthesizing a previously fragmented set of studies. Parents' perceived safety concerns are the primary barrier to children's active free play. These safety concerns are moderated by child-level factors (age, competence, gender) and broader social issues. Interventions should focus on community-level solutions that include children's perspectives. From a methods perspective, the reviewed studies used a range of data collection techniques, but methodological details were often inadequately reported. The theoretical sophistication of research in this area could be improved. To this end, the synthesis reported in this study provides a framework for guiding future research.

Recreational physical activity as an independent predictor of multivariable cardiovascular disease risk.

Directory of Open Access Journals (Sweden)

Satvinder S Dhaliwal

Full Text Available The role of physical activity in preventing CVD has been highlighted by Professor Jerry Morris in the 1950's. We report outcome of a 15-year prospective study with the aim to identify whether physical activity showed cardiovascular benefit independent of common risk factors and of central obesity. Baseline data of 8662 subjects, with no previous history of heart disease, diabetes or stroke, were obtained from an age- and gender- stratified sample of adults in Australian capital cities and were linked with the National Death Index to determine the causes of death of 610 subjects who had died to 31 December 2004. The study consisted of 4175 males (age 42.3 ± 13.1 years and 4487 females (age 42.8 ± 13.2 years. Fasting serum lipid levels, systolic and diastolic blood pressure and smoking habits at baseline were recorded. The Framingham Risk Scores of 15-year mortality due to CHD and CVD were calculated using established equations. Subjects were also asked if they engaged in vigorous exercise, less vigorous exercise or walk for recreation and exercise in the past 2 weeks. Subjects in the high recreational physical activity category were 0.16 (0.06-0.43; p<0.001 and 0.12 (0.03-0.48; p = 0.003 times as likely as subjects in the low category for CVD and CHD mortality respectively. After adjusting for both the Framingham Risk Score and central obesity (Waist circumference to Hip circumference Ratio, those in the high recreational physical activity group were 0.35 (0.13-0.98 times less likely compared to the low category for CVD mortality. Recreational physical activity independently predicted reduced cardiovascular mortality over fifteen years. A public health focus on increased physical activity and preventing obesity is required to reduce the risk of CVD and CHD.

Scleroderma keratinocytes promote fibroblast activation independent of transforming growth factor beta.

Science.gov (United States)

McCoy, Sara S; Reed, Tamra J; Berthier, Celine C; Tsou, Pei-Suen; Liu, Jianhua; Gudjonsson, Johann E; Khanna, Dinesh; Kahlenberg, J Michelle

2017-11-01

SSc is a devastating disease that results in fibrosis of the skin and other organs. Fibroblasts are a key driver of the fibrotic process through deposition of extracellular matrix. The mechanisms by which fibroblasts are induced to become pro-fibrotic remain unclear. Thus, we examined the ability of SSc keratinocytes to promote fibroblast activation and the source of this effect. Keratinocytes were isolated from skin biopsies of 9 lcSSc, 10 dcSSc and 13 control patients. Conditioned media was saved from the cultures. Normal fresh primary fibroblasts were exposed to healthy control and SSc keratinocyte conditioned media in the presence or absence of neutralizing antibodies for TGF-β. Gene expression was assessed by microarrays and real-time PCR. Immunocytochemistry was performed for α-smooth muscle actin (α-SMA), collagen type 1 (COL1A1) and CCL5 expression. SSc keratinocyte conditioned media promoted fibroblast activation, characterized by increased α-SMA and COL1A1 mRNA and protein expression. This effect was independent of TGF-β. Microarray analysis identified upregulation of nuclear factor κB (NF-κB) and downregulation of peroxisome proliferator-activated receptor γ (PPAR-γ) pathways in both SSc subtypes. Scleroderma keratinocytes exhibited increased expression of NF-κB-regulated cytokines and chemokines and lesional skin staining confirmed upregulation of CCL5 in basal keratinocytes. Scleroderma keratinocytes promote the activation of fibroblasts in a TGF-β-independent manner and demonstrate an imbalance in NF-κB1 and PPAR-γ expression leading to increased cytokine and CCL5 production. Further study of keratinocyte mediators of fibrosis, including CCL5, may provide novel targets for skin fibrosis therapy. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Cigarette smoking and schizophrenia independently and reversibly altered intrinsic brain activity.

Science.gov (United States)

Liu, Huan; Luo, Qi; Du, Wanyi; Li, Xingbao; Zhang, Zhiwei; Yu, Renqiang; Chen, Xiaolu; Meng, Huaqing; Du, Lian

2018-01-03

Schizophrenia patients are at high risk for cigarette smoking, but the neurobiological mechanisms of this comorbid association are relatively unknown. Long-term nicotine intake may impact brain that are independently and additively associated with schizophrenia. We investigated whether altered intrinsic brain activity (iBA) related to schizophrenia pathology is also associated with nicotine addiction. Forty-two schizophrenia patients (21 smokers and 21 nonsmokers) and 21 sex- and age-matched healthy nonsmokers underwent task-free functional MRI. Whole brain iBA was measured by the amplitude of spontaneous low frequency fluctuation. Furthermore, correlation analyses between iBA, symptom severity and nicotine addiction severity were performed. We found that prefrontal cortex, right caudate, and right postcentral gyrus were related to both disease and nicotine addiction effects. More importantly, schizophrenia smokers, compared to schizophrenia nonsmokers showed reversed iBA in the above brain regions. In addition, schizophrenia smokers, relative to nonsmokers, altered iBA in the left striatal and motor cortices. The iBA of the right caudate was negatively correlated with symptom severity. The iBA of the right postcentral gyrus negatively correlated with nicotine addiction severity. The striatal and motor cortices could potentially increase the vulnerability of smoking in schizophrenia. More importantly, smoking reversed iBA in the right striatal and prefrontal cortices, consistent with the self-medication theory in schizophrenia. Smoking altered left striatal and motor cortices activity, suggesting that the nicotine addiction effect was independent of disease. These results provide a local property of intrinsic brain activity mechanism that contributes to cigarette smoking and schizophrenia.

Boards: Independent and Committed Directors?

OpenAIRE

Christophe Volonté

2011-01-01

Regulators, proxy advisors and shareholders are regularly calling for independent directors. However, at the same time, independent directors commonly engage in numerous outside activities potentially reducing their time and commitment with the particular firm. Using Tobin's Q as an approximation of market valuation and controlling for endogeneity, our empirical analysis reveals that neither is independence positively related to firm performance nor are outside activities negatively related t...

Residues in the alternative reading frame tumor suppressor that influence its stability and p53-independent activities

International Nuclear Information System (INIS)

Tommaso, Anne di; Hagen, Jussara; Tompkins, Van; Muniz, Viviane; Dudakovic, Amel; Kitzis, Alain; Ladeveze, Veronique; Quelle, Dawn E.

2009-01-01

The Alternative Reading Frame (ARF) protein suppresses tumorigenesis through p53-dependent and p53-independent pathways. Most of ARF's anti-proliferative activity is conferred by sequences in its first exon. Previous work showed specific amino acid changes occurred in that region during primate evolution, so we programmed those changes into human p14ARF to assay their functional impact. Two human p14ARF residues (Ala 14 and Thr 31 ) were found to destabilize the protein while two others (Val 24 and Ala 41 ) promoted more efficient p53 stabilization and activation. Despite those effects, all modified p14ARF forms displayed robust p53-dependent anti-proliferative activity demonstrating there are no significant biological differences in p53-mediated growth suppression associated with simian versus human p14ARF residues. In contrast, p53-independent p14ARF function was considerably altered by several residue changes. Val 24 was required for p53-independent growth suppression whereas multiple residues (Val 24 , Thr 31 , Ala 41 and His 60 ) enabled p14ARF to block or reverse the inherent chromosomal instability of p53-null MEFs. Together, these data pinpoint specific residues outside of established p14ARF functional domains that influence its expression and signaling activities. Most intriguingly, this work reveals a novel and direct role for p14ARF in the p53-independent maintenance of genomic stability.

[Sedentary lifestyle is associated with metabolic and cardiovascular risk factors independent of physical activity].

Science.gov (United States)

Leiva, Ana María; Martínez, María Adela; Cristi-Montero, Carlos; Salas, Carlos; Ramírez-Campillo, Rodrigo; Díaz Martínez, Ximena; Aguilar-Farías, Nicolás; Celis-Morales, Carlos

2017-04-01

Sedentary behavior is a main risk factor for cardiovascular disease and mortality. To investigate the association between sedentary behavior and metabolic and cardiovascular risk factors. We assessed 322 participants aged between 18 to 65 years. Physical activity and sedentary behavior were measured with accelerometers (Actigraph®). Body mass index (BMI), waist circumference, percentage of body fat, diet and blood markers (glucose, lipid profile, insulin and HOMA-IR) were measured with standardized protocols. Thirty four percent of participants were physically inactive and spent on average 8.7 h/day on sedentary activities. Per one hour increase in sedentary behavior there were significant adverse changes in glucose (4.79 mg/dl), insulin (2.73 pmol/l), HOMA-IR (0.75), BMI (0.69 kg/m²), waist circumference (1.95 cm), fat mass (1.03%), total cholesterol (9.73 mg/dl), HDL-cholesterol (-3.50 mg/dl), LDL-cholesterol (10.7 mg/dl) and triglycerides (12.4 mg/dl). These findings were independent of main confounding factors including total physical activity, dietary factors, BMI and socio-demographics. The detrimental effect of sedentary behaviors on cardiometabolic and obesity-related traits is independent of physical activity levels. Therefore, reducing sedentary time should be targeted in the population apart from increasing their physical activity levels.

CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

Directory of Open Access Journals (Sweden)

Shweta Jain

Full Text Available Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID, signifying class switch recombination (CSR. Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

Science.gov (United States)

Jain, Shweta; Chodisetti, Sathi Babu; Agrewala, Javed N

2011-01-01

Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB) cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID), signifying class switch recombination (CSR). Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

Self-Care Self-Efficacy Correlates with Independence in Basic Activities of Daily Living in Individuals with Chronic Stroke.

Science.gov (United States)

Frost, Yael; Weingarden, Harold; Zeilig, Gabi; Nota, Ayala; Rand, Debbie

2015-07-01

(1) To characterize the self-care self-efficacy (SCSE) of community dwelling individuals with chronic stroke and (2) to determine the contribution of SCSE to the independence in basic and instrumental activities of daily living (BADL and IADL) and the participation of individuals with chronic stroke. SCSE is the confidence in one's own ability to perform self-care activities. This cross-sectional study included fifty community-dwelling individuals mean (SD) age 59.8 (9.3) years, mean (SD) 3.1 (1.7) years post-stroke who were able to walk at least 10 meters. SCSE was assessed using the Stroke Self-Efficacy Questionnaire (SSEQ), BADL was assessed by the Functional Independence Measure (FIM) (interview), the IADL questionnaire assessed IADL and the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) assessed participation. Correlation and regression analyses were performed after controlling for grip strength, executive functions and gait speed, factors known to influence independence in daily living. The mean SCSE level was moderate-high (70%). Significant moderate correlations were found between SCSE to independence in BADL (r = .596, P < .001), IADL (r = .567, P < .001) and participation (r = .340, P < .005). SCSE of our cohort explained 7.4% of the variance of the individual's independence in BADL after controlling for executive functions and gait speed, but did not contribute to their independence in IADL and participation. Higher SCSE of individuals with chronic stroke contributes to more independence in BADL. Additional questionnaires regarding self efficacy for IADL should be developed and investigated. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Homogenization of independent inspection criteria of Quality Assurance in the maintenance activities

International Nuclear Information System (INIS)

Gomez Cardinanos, R.

2012-01-01

Among the official documents governing the operation of Spanish nuclear power plants is the Quality Manual and Quality Assurance. This manual gives a formal answer to the requirements of the regulations and the Nuclear Safety Council. To monitor the compliance of its requirements, the plants are controlled by independent organizations. Since 2007, in nuclear Sta. Maria de Garona is developed a project to improve the performance of the QA inspectors during maintenance activities. Results of the project have been edited data sheets on specific activities of maintenance. The project aims to incorporate sheets that help QA inspectors in their daily inspection.

Physical activity enhances metabolic fitness independently of cardiorespiratory fitness in marathon runners

DEFF Research Database (Denmark)

Laye, M J; Nielsen, M B; Hansen, L S

2015-01-01

High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consisten......High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run...... consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI). Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg) (similar-VO2max......). The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max). Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior...

The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

International Nuclear Information System (INIS)

Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V.

2010-01-01

The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

Novel Active Learning Experiences for Students to Identify Barriers to Independent Living for People with Disabilities.

Science.gov (United States)

McArthur, Polly; Burch, Lillian; Moore, Katherine; Hodges, Mary Sue

2016-07-01

This article describes interactive learning about independent living for people with disabilities and features the partnership of the College of Nursing and a Center for Independent Living (CIL). Using qualitative descriptive approach, students' written reflections were analyzed. Through "Xtreme Challenge," 82 undergraduate nursing students participated in aspects of independent living as well as identifying barriers. Students were engaged and learned to consider the person before the disability. Moreover, students valued the activity leaders' openness, which facilitated understanding the point of view of a person with disability. The value of partnership was evident as it allowed students to participate in active learning, which led to growth in the affective domain. Students became aware of potential education resources through the CIL. This article will guide educators in designing experiences that teach nursing care at the individual, family, and community level for people living with disabilities. © 2015 Association of Rehabilitation Nurses.

Independent Attention Mechanisms Control the Activation of Tactile and Visual Working Memory Representations.

Science.gov (United States)

Katus, Tobias; Eimer, Martin

2018-05-01

Working memory (WM) is limited in capacity, but it is controversial whether these capacity limitations are domain-general or are generated independently within separate modality-specific memory systems. These alternative accounts were tested in bimodal visual/tactile WM tasks. In Experiment 1, participants memorized the locations of simultaneously presented task-relevant visual and tactile stimuli. Visual and tactile WM load was manipulated independently (one, two, or three items per modality), and one modality was unpredictably tested after each trial. To track the activation of visual and tactile WM representations during the retention interval, the visual contralateral delay activity (CDA) and tactile CDA (tCDA) were measured over visual and somatosensory cortex, respectively. CDA and tCDA amplitudes were selectively affected by WM load in the corresponding (tactile or visual) modality. The CDA parametrically increased when visual load increased from one to two and to three items. The tCDA was enhanced when tactile load increased from one to two items and showed no further enhancement for three tactile items. Critically, these load effects were strictly modality-specific, as substantiated by Bayesian statistics. Increasing tactile load did not affect the visual CDA, and increasing visual load did not modulate the tCDA. Task performance at memory test was also unaffected by WM load in the other (untested) modality. This was confirmed in a second behavioral experiment where tactile and visual loads were either two or four items, unimodal baseline conditions were included, and participants performed a color change detection task in the visual modality. These results show that WM capacity is not limited by a domain-general mechanism that operates across sensory modalities. They suggest instead that WM storage is mediated by distributed modality-specific control mechanisms that are activated independently and in parallel during multisensory WM.

Strategy for Imidazotetrazine Prodrugs with Anticancer Activity Independent of MGMT and MMR

Science.gov (United States)

2012-01-01

The imidazotetrazine ring is an acid-stable precursor and prodrug of highly reactive alkyl diazonium ions. We have shown that this reactivity can be managed productively in an aqueous system for the generation of aziridinium ions with 96% efficiency. The new compounds are potent DNA alkylators and have antitumor activity independent of the O6-methylguanine-DNA methyltransferase and DNA mismatch repair constraints that limit the use of Temozolomide. PMID:24900418

Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase.

Science.gov (United States)

Thang, Nguyen Dinh; Yajima, Ichiro; Kumasaka, Mayuko Y; Ohnuma, Shoko; Yanagishita, Takeshi; Hayashi, Rumiko; Shekhar, Hossain U; Watanabe, Daisuke; Kato, Masashi

2011-01-01

Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl(2)) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5-50 µM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 µM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5-5 µM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro.

Passive sensor technology interface to assess elder activity in independent living.

Science.gov (United States)

Alexander, Gregory L; Wakefield, Bonnie J; Rantz, Marilyn; Skubic, Marjorie; Aud, Myra A; Erdelez, Sanda; Ghenaimi, Said Al

2011-01-01

The effectiveness of clinical information systems to improve nursing and patient outcomes depends on human factors, including system usability, organizational workflow, and user satisfaction. The aim of this study was to examine to what extent residents, family members, and clinicians find a sensor data interface used to monitor elder activity levels usable and useful in an independent living setting. Three independent expert reviewers conducted an initial heuristic evaluation. Subsequently, 20 end users (5 residents, 5 family members, 5 registered nurses, and 5 physicians) participated in the evaluation. During the evaluation, each participant was asked to complete three scenarios taken from three residents. Morae recorder software was used to capture data during the user interactions. The heuristic evaluation resulted in 26 recommendations for interface improvement; these were classified under the headings content, aesthetic appeal, navigation, and architecture, which were derived from heuristic results. Total time for elderly residents to complete scenarios was much greater than for other users. Family members spent more time than clinicians but less time than residents did to complete scenarios. Elder residents and family members had difficulty interpreting clinical data and graphs, experienced information overload, and did not understand terminology. All users found the sensor data interface useful for identifying changing resident activities. Older adult users have special needs that should be addressed when designing clinical interfaces for them, especially information as important as health information. Evaluating human factors during user interactions with clinical information systems should be a requirement before implementation.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

OpenAIRE

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its na...

GHRELIN ACTIVATES HYPOPHYSIOTROPIC CORTICOTROPIN-RELEASING FACTOR NEURONS INDEPENDENTLY OF THE ARCUATE NUCLEUS

Science.gov (United States)

Cabral, Agustina; Portiansky, Enrique; Sánchez-Jaramillo, Edith; Zigman, Jeffrey M.; Perello, Mario

2016-01-01

Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin’s orexigenic action vs. its role as a stress signal are anatomically dissociated. PMID:26874559

Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

Science.gov (United States)

Anandhakumar, Jayamani; Moustafa, Yara W; Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

2016-07-15

Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The PPAR{gamma} ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

Energy Technology Data Exchange (ETDEWEB)

Moss, Patrice E.; Lyles, Besstina E.; Stewart, LaMonica V., E-mail: lstewart@mmc.edu

2010-12-10

The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPAR{gamma} ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPAR{gamma} ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPAR{gamma} ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPAR{gamma}. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPAR{gamma} and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.

LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.

Science.gov (United States)

Sehrawat, Archana; Gao, Lina; Wang, Yuliang; Bankhead, Armand; McWeeney, Shannon K; King, Carly J; Schwartzman, Jacob; Urrutia, Joshua; Bisson, William H; Coleman, Daniel J; Joshi, Sunil K; Kim, Dae-Hwan; Sampson, David A; Weinmann, Sheila; Kallakury, Bhaskar V S; Berry, Deborah L; Haque, Reina; Van Den Eeden, Stephen K; Sharma, Sunil; Bearss, Jared; Beer, Tomasz M; Thomas, George V; Heiser, Laura M; Alumkal, Joshi J

2018-05-01

Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.

Independent and inverse association of healthcare utilisation with physical activity in older adults with multiple chronic conditions.

Science.gov (United States)

Liu-Ambrose, T Y L; Ashe, M C; Marra, C

2010-11-01

In this study, whether physical activity is independently associated with direct healthcare costs in community-dwelling older adults with multiple chronic conditions was examined. Cross-sectional analysis. Research laboratory. 299 community-dwelling men and women volunteers aged 65 years and older with chronic conditions. None. Primary dependent variable was direct healthcare costs incurred in the previous 3 months. Participants completed the Health Resource Utilisation (HRU) questionnaire. To estimate HRU, direct costs in the previous 3 months were calculated using the three-party payer perspective of the British Columbia Ministry of Health, deemed representative of the Canadian healthcare system costs. For medications, the Retail Pharmacy Dispensed prescription cost tables were used. Primary independent variables were (1) self-report current level of physical activity as assessed by the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) and (2) general balance and mobility as assessed by the National Institute on Aging Balance Scale. The mean number of chronic conditions per participant was six. Current level of physical activity was independently and inversely associated with HRU. Age, sex, number of chronic conditions, global cognitive function, body mass index, and general balance and mobility together accounted for 24.3% of the total variance. Adding the PASIPD score resulted in an R2 change of 3.3% and significantly improved the model. The total variance accounted by the final model was 27.6%. Physical activity promotion may reduce healthcare costs in older adults with chronic conditions.

Thiazolidinediones inhibit TNFα induction of PAI-1 independent of PPARγ activation

International Nuclear Information System (INIS)

Liu, H.B.; Hu, Y.S.; Medcalf, R.L.; Simpson, R.W.; Dear, A.E.

2005-01-01

Increased plasminogen activator inhibitor type 1 (PAI-1) levels are observed in endothelial cells stimulated by tumour necrosis factor α (TNFα). Thiazolidinediones (TZDs) may inhibit elevated endothelial cell PAI-1 accounting, in part, for the putative atheroprotective effects of TZDs. In an endothelial cell line, Rosiglitazone (RG) and Pioglitazone (PG) inhibited induction of PAI-1 by TNFα. The specific peroxisome proliferator-activated receptor γ (PPARγ) inhibitor, SR-202, failed to modulate this effect. RG also inhibited the effect of TNFα on a reporter gene construct harbouring the proximal PAI-1 promoter and PAI-1 mRNA in cells co-transfected with a dominant-negative PPARγ construct. RG and PG attenuated TNFα-mediated induction of trans-acting factor(s) Nur77/Nurr1 and binding of nuclear proteins (NP) to the cis-acting element (NBRE). SR-202 failed to modulate these effects. The observations suggest TZDs inhibit TNFα-mediated PAI-1 induction independent of inducible PPARγ activation and this may involve in the modulation of Nur77/Nurr1 expression and NP binding to the PAI-1 NBRE

Organizing Independent Student Work

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Zhadyra T. Zhumasheva

2015-03-01

Full Text Available This article addresses issues in organizing independent student work. The author defines the term “independence”, discusses the concepts of independent learner work and independent learner work under the guidance of an instructor, proposes a classification of assignments to be done independently, and provides methodological recommendations as to the organization of independent student work. The article discusses the need for turning the student from a passive consumer of knowledge into an active creator of it, capable of formulating a problem, analyzing the ways of solving it, coming up with an optimum outcome, and proving its correctness. The preparation of highly qualified human resources is the primary condition for boosting Kazakhstan’s competitiveness. Independent student work is a means of fostering the professional competence of future specialists. The primary form of self-education is independent work.

The Influence of Board of Directors, Independent Board of Commissioners, Leverage, and Corporate Activities To Disclosure of Sustainability Report.

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Eria Nissa Awalia

2015-07-01

Full Text Available This research was intended to examine the influences of board of directors, board of independent commissioner, leverage, and activity of company toward sustainability report disclosure. Sustainability Report Disclosure is the dependent variable sinthis research were measured by GRIG 3.1 Content Index and Checklists. For the independent variables in this research, using board of directors were measured by sum of directors meetings, board of in dependent commissioner were measured by proportion of independent commissioner, leverage were measured by debt to equity, activity of company were measured by total asset turnover. This research uses secondary data which is financial statement. and sustainability report from Indonesian Stock Exchange Listed Companies in 2010-2012. While the sampling method used was purposive sampling method which is overall 39 observations. This research uses multiple regression method to test the hypothesis with SPSS computer program. From the analysis performed in this research, it can be concluded that board of directors, and leverage have no significant influence to sustainability report disclosure. The other hand activity of company has positive influence and significant to sustainability report disclosure. And Board of independent commissioner has negative influence and significant to sustainability reporting disclosure.

The utility of ultrasound superb microvascular imaging for evaluation of breast tumour vascularity: comparison with colour and power Doppler imaging regarding diagnostic performance.

Science.gov (United States)

Park, A Y; Seo, B K; Woo, O H; Jung, K S; Cho, K R; Park, E K; Cha, S H; Cha, J

2018-03-01

To investigate the utility of superb microvascular imaging (SMI) for evaluating the vascularity of breast masses in comparison with colour or power Doppler ultrasound (US) and the effect on diagnostic performance. A total of 191 biopsy-proven masses (99 benign and 92 malignant) in 166 women with greyscale, colour Doppler, power Doppler, and SMI images were enrolled in this retrospective study. Three radiologists analysed the vascular images using a three-factor scoring system to evaluate the number, morphology, and distribution of tumour vessels. They assessed the Breast Imaging-Reporting and Data System categories for greyscale US alone and combinations of greyscale US and each type of vascular US. The Kruskal-Wallis test was performed and the area under the receiver-operating characteristic curve (AUC) measured. On SMI, vascular scores were compared between benign and malignant masses and the optimal cut-off value for the overall score was determined. SMI showed higher vascular scores than colour or power Doppler US and malignant masses had higher scores than benign masses (ppower Doppler US (AUC, 0.815 versus 0.774, 0.789, 0.791; ppower Doppler US for characterising the vascularity in breast masses and improving diagnostic performance. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

SOCIO-PEDAGOGICAL EVALUATION OF TEACHING STAFF ACTIVITIES IN COMPREHENSIVE SCHOOLS AS AN INDEPENDENT MECHANISM OF EDUCATION QUALITY ASSESSMENT

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Irina О. Antipina

2014-01-01

Full Text Available The aim of the research is to reveal various ways for developing the independent mechanisms of education quality assessment.Methods involve the analysis of the existing views concerning the quality assessment of teaching staff activities.Results: The research findings demonstrate functional specificity of comprehensive schools, the main phases of socio-pedagogic assessment of teaching staff activities, and the main criteria and indices of their monitoring. The author considers professional educational activity as a general assessment criterion. The main feature of socio-pedagogic assessment procedures involves participation of different categories of teaching and research staff, along with students’ parents and the neighboring society members.Scientific novelty: The author specifies the concept of socio-pedagogic assessment of teaching staff activities.Practical significance: Implementation of the research outcomes can stimulate professional activity of pedagogical society in developing the independent system of education quality assessment.

Normal weight children have higher cognitive performance - Independent of physical activity, sleep, and diet.

Science.gov (United States)

Hjorth, Mads F; Sørensen, Louise B; Andersen, Rikke; Dyssegaard, Camilla B; Ritz, Christian; Tetens, Inge; Michaelsen, Kim F; Astrup, Arne; Egelund, Niels; Sjödin, Anders

2016-10-15

Aside from the health consequences, observational studies indicate that being overweight may also negatively affect cognitive function. However, existing evidence has to a large extent not controlled for the possible confounding effect of having different lifestyles. Therefore, the objective was to examine the independent associations between weight status and lifestyle indicators with cognitive performance in 8-11year old Danish children. The analyses included 828 children (measured in 2011-2012) each having one to three measurement occasions separated by approximately 100days. Dietary intake, physical activity, sedentary time, and sleep duration were measured using dietary records and accelerometers. The Children's Sleep Habits Questionnaire was used to access sleep problems and the Andersen test was carried out to estimate cardio-respiratory fitness (CRF). Weight status (underweight, normal weight, and overweight/obese) was defined according to body mass index and cognitive performance was assessed using the d2-test of attention, a reading test, and a math test. A linear mixed model including a number of fixed and random effects was used to test associations between lifestyle indicators as well as BMI category and cognitive performance. After adjustment for demographics, socioeconomics, and multiple lifestyle indicators, normal weight children had higher cognitive test scores than overweight/obese and underweight children of up to 89% and 48% of expected learning within one school year (Pbreakfast consumption, fewer sleep problems, higher CRF, less total physical activity, more sedentary time, and less light physical activity were associated with higher cognitive performance independently of each other in at least one of the three cognitive tests (Pperformance compared to overweight/obese as well as underweight children, independent of multiple lifestyle indicators. Copyright © 2016 Elsevier Inc. All rights reserved.

Recognizing Human Activities User-independently on Smartphones Based on Accelerometer Data

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Pekka Siirtola

2012-06-01

Full Text Available Real-time human activity recognition on a mobile phone is presented in this article. Unlike in most other studies, not only the data were collected using the accelerometers of a smartphone, but also models were implemented to the phone and the whole classification process (preprocessing, feature extraction and classification was done on the device. The system is trained using phone orientation independent features to recognize five everyday activities: walking, running, cycling, driving a car and sitting/standing while the phone is in the pocket of the subject's trousers. Two classifiers were compared, knn (k nearest neighbors and QDA (quadratic discriminant analysis. The models for real-time activity recognition were trained offline using a data set collected from eight subjects and these offline results were compared to real-time recognition rates, which are obtained by implementing models to mobile activity recognition application which currently supports two operating systems: Symbian^3 and Android. The results show that the presented method is light and, therefore, suitable for be used in real-time recognition. In addition, the recognition rates on the smartphones were encouraging, in fact, the recognition accuracies obtained are approximately as high as offline recognition rates. Also, the results show that the method presented is not an operating system dependent.

ICI 56,780 Optimization: Structure-Activity Relationship Studies of 7-(2-Phenoxyethoxy)-4(1H)-quinolones with Antimalarial Activity.

Science.gov (United States)

Maignan, Jordany R; Lichorowic, Cynthia L; Giarrusso, James; Blake, Lynn D; Casandra, Debora; Mutka, Tina S; LaCrue, Alexis N; Burrows, Jeremy N; Willis, Paul A; Kyle, Dennis E; Manetsch, Roman

2016-07-28

Though malaria mortality rates are down 48% globally since 2000, reported occurrences of resistance against current therapeutics threaten to reverse that progress. Recently, antimalarials that were once considered unsuitable therapeutic agents have been revisited to improve physicochemical properties and efficacy required for selection as a drug candidate. One such compound is 4(1H)-quinolone ICI 56,780, which is known to be a causal prophylactic that also displays blood schizonticidal activity against P. berghei. Rapid induction of parasite resistance, however, stalled its further development. We have completed a full structure-activity relationship study on 4(1H)-quinolones, focusing on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2 and TM90-C2B, as well as the improvement of microsomal stability. These studies revealed several frontrunner compounds with superb in vivo antimalarial activity. The best compounds were found to be curative with all mice surviving a Plasmodium berghei infection after 30 days.

ORGANIZATION OF INDEPENDENT STUDENT WORK BASED ON STUDENT BLOGGING ACTIVITY

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A. A. Gareyev

2018-01-01

Full Text Available Introduction. Today, the students’ personality traits and increasing their motivation to self-development are the most complex and urgent problems in foreign language training at higher technical university and in the system of higher education in general. According to the authors, the technology of student blogging is a means for addressing these issues, despite the lack of research on its methodology. In that regard, there is a need for further studies on information and communication technologies (ICT application by promoting independent student work. The aim of this paper is to present the developed model of organization of bachelors’ independent work through educational blogging; to fulfill educational potential and to prove the efficiency of ICTs application in education taking into consideration professional foreign language competence development of future specialists in tool making. Methodology and research methods. When designing the model, the basic considerations of the following methodological approaches were considered: competency-based, personal-oriented, activity-based, thesaurus, and qualimetric; the listed above approaches enable to realize the principles of individualization, professional orientation, integrity, self-organization and interactivity in the performed work. The method of group expert assessment, as the leading one in pedagogical qualimetry, was chosen as the main method in the research undertaken. The methods of modeling and pedagogical experiment were involved. Results and scientific novelty. The structure of professional foreign language competence (including communicative, cognitive and subject components of future toolmaking bachelors is identified. The development of the competence formation model among students is described in detail: having studied independently the subject topic, the students post the material. Pedagogical conditions and didactic guidelines for the model realization are formulated

Independent mobility, perceptions of the built environment and children's participation in play, active travel and structured exercise and sport: the PEACH Project

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Griew Pippa

2010-02-01

Full Text Available Abstract Background Independent mobility (IM and perceptions of the built environment may relate differentially to children's participation in various physical activity contexts. This cross-sectional study investigated whether independent mobility and perceptions of the built environment in boys and girls were related to physical activity in three different contexts (outdoor play, structured exercise/sport, active commuting. Methods Thirteen hundred and seven 10-11 year old boys and girls from 23 schools in a large UK city completed a computerised questionnaire. Independent variables in logistic regression analyses were weekly self-reported frequency of participation in outdoor play, structured exercise/sport and mode of travel home from school. Dependent variables were perceptions of the environment (aesthetics, nuisance, safety, social norm, constraint, play space, accessibility, local and area independent mobility and linear distance from home to school. Analyses were adjusted for body mass index, minutes of daylight after school, level of neighbourhood deprivation and pubertal status. Results For boys, local independent mobility (Local-IM was related to an increased likelihood of everyday participation in play (OR 1.58: 95% CI 1.19-2.10, structured exercise/sport (OR 1.42: 1.06-1.89 and active commuting (OR 1.40: 1.07-1.87 but was only related to active commuting for girls (OR1.49: 1.07-2.07. Boys and girls were more likely to report playing out every day if they had higher scores for Social Norm (Boys: OR 1.63 (1.12-2.37; Girls: OR 1.53 (1.01-2.31 and, for girls only, more positive perceptions of traffic safety (OR 1.63: 1.14-2.34. Easy access to a range of destinations was the dominant predictor for taking part in structured exercise/sport everyday (Boys: OR 1.62 (1.01-2.66; Girls: OR 1.65 (1.07-2.53. Shorter distance from home to school (OR 0.99: 0.98-0.99 and, for boys only, greater perceived accessibility (OR 1.87: 1.04-3.36 were

Objectively measured sedentary time may predict insulin resistance independent of moderate- and vigorous-intensity physical activity

NARCIS (Netherlands)

Helmerhorst, Hendrik J. F.; Wijndaele, Katrien; Brage, Søren; Wareham, Nicholas J.; Ekelund, Ulf

2009-01-01

To examine the prospective association between objectively measured time spent sedentary and insulin resistance and whether this association is independent of moderate- and vigorous-intensity physical activity (MVPA) and other relevant confounders. This was a population-based study (Medical Research

UVC-induced apoptosis in Dubca cells is independent of JNK activation and p53Ser-15 phosphorylation

International Nuclear Information System (INIS)

Chathoth, Shahanas; Thayyullathil, Faisal; Hago, Abdulkader; Shahin, Allen; Patel, Mahendra; Galadari, Sehamuddin

2009-01-01

Ultraviolet C (UVC) irradiation in mammalian cell lines activates a complex signaling network that leads to apoptosis. By using Dubca cells as a model system, we report the presence of a UVC-induced apoptotic pathway that is independent of c-Jun N-terminal kinases (JNKs) activation and p53 phosphorylation at Ser 15 . Irradiation of Dubca cells with UVC results in a rapid JNK activation and phosphorylation of its downstream target c-Jun, as well as, phosphorylation of activating transcription factor 2 (ATF2). Pre-treatment with JNK inhibitor, SP600125, inhibited UVC-induced c-Jun phosphorylation without preventing UVC-induced apoptosis. Similarly, inhibition of UVC-induced p53 phosphorylation did not prevent Dubca cell apoptosis, suggesting that p53 Ser-15 phosphorylation is not associated with UVC-induced apoptosis signaling. The pan-caspase inhibitor z-VAD-fmk inhibited UVC-induced PARP cleavage, DNA fragmentation, and ultimately apoptosis of Dubca cells. Altogether, our study clearly indicates that UVC-induced apoptosis is independent of JNK and p53 activation in Dubca cells, rather, it is mediated through a caspase dependent pathway. Our findings are not in line with the ascribed critical role for JNKs activation, and downstream phosphorylation of targets such as c-Jun and ATF2 in UVC-induced apoptosis.

Elevated glucose concentrations promote receptor-independent activation of adherent human neutrophils: an experimental and computational approach

DEFF Research Database (Denmark)

Kummer, Ursula; Zobeley, Jürgen; Brasen, Jens Christian

2007-01-01

of NO and superoxide formation were observed. However, these changes were not observed for sorbitol, a nonmetabolizable carbohydrate. Glucose transport appears to be important in this process as phloretin interferes with the glucose-specific receptor-independent activation of neutrophils. However, LY83583...

Effects of intensity of facial expressions on amygdalar activation independently of valence

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Huiyan Lin

2016-12-01

Full Text Available For several stimulus categories (e.g., pictures, odors and words, the arousal of both negative and positive stimuli has been shown to modulate amygdalar activation. In contrast, previous studies did not observe similar amygdalar effects in response to negative and positive facial expressions with varying intensity of facial expressions. Reasons for this discrepancy may be related to analytical strategies, experimental design and stimuli. Therefore, the present study aimed at re-investigating whether the intensity of facial expressions modulates amygdalar activation by circumventing limitations of previous research. Event-related functional magnetic resonance imaging (fMRI was used to assess brain activation while participants observed a static neutral expression and positive (happy and negative (angry expressions of either high or low intensity from an ecologically valid, novel stimulus set. The ratings of arousal and intensity were highly correlated. We found that amygdalar activation followed a u-shaped activation pattern with highest activation to high intense facial expressions as compared to low intensity facial expressions and to the neutral expression irrespective of valence, suggesting a critical role of the amygdala in valence-independent arousal processing of facial expressions. Additionally, consistent with previous studies, intensity effects were also found in visual areas and generally increased activation to angry vs. happy faces were found in visual cortex and insula, indicating enhanced visual representations of high arousing facial expressions and increased visual and somatosensory representations of threat.

Glial and Neuronal Glutamate Transporters Differ in the Na+ Requirements for Activation of the Substrate-Independent Anion Conductance

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Christopher B. Divito

2017-05-01

Full Text Available Excitatory amino acid transporters (EAATs are secondary active transporters of L-glutamate and L- or D-aspartate. These carriers also mediate a thermodynamically uncoupled anion conductance that is gated by Na+ and substrate binding. The activation of the anion channel by binding of Na+ alone, however, has only been demonstrated for mammalian EAAC1 (EAAT3 and EAAT4. To date, no difference has been observed for the substrate dependence of anion channel gating between the glial, EAAT1 and EAAT2, and the neuronal isoforms EAAT3, EAAT4 and EAAT5. Here we describe a difference in the Na+-dependence of anion channel gating between glial and neuronal isoforms. Chloride flux through transporters without glutamate binding has previously been described as substrate-independent or “leak” channel activity. Choline or N-methyl-D-glucamine replacement of external Na+ ions significantly reduced or abolished substrate-independent EAAT channel activity in EAAT3 and EAAT4 yet has no effect on EAAT1 or EAAT2. The interaction of Na+ with the neuronal carrier isoforms was concentration dependent, consistent with previous data. The presence of substrate and Na+-independent open states in the glial EAAT isoforms is a novel finding in the field of EAAT function. Our results reveal an important divergence in anion channel function between glial and neuronal glutamate transporters and highlight new potential roles for the EAAT-associated anion channel activity based on transporter expression and localization in the central nervous system.

Association of sedentary time with mortality independent of moderate to vigorous physical activity.

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Annemarie Koster

Full Text Available BACKGROUND: Sedentary behavior has emerged as a novel health risk factor independent of moderate to vigorous physical activity (MVPA. Previous studies have shown self-reported sedentary time to be associated with mortality; however, no studies have investigated the effect of objectively measured sedentary time on mortality independent of MVPA. The objective our study was to examine the association between objectively measured sedentary time and all-cause mortality. METHODS: 7-day accelerometry data of 1906 participants aged 50 and over from the U.S. nationally representative National Health and Nutrition Examination Survey (NHANES 2003-2004 were analyzed. All-cause mortality was assessed from the date of examination through December 31, 2006. RESULTS: Over an average follow-up of 2.8 years, there were 145 deaths reported. In a model adjusted for sociodemographic factors, lifestyle factors, multiple morbidities, mobility limitation, and MVPA, participants in third quartile (hazard ratio (HR:4.05; 95%CI:1.55-10.60 and fourth quartile (HR:5.94; 95%CI: 2.49-14.15 of having higher percent sedentary time had a significantly increased risk of death compared to those in the lowest quartile. CONCLUSIONS: Our study suggests that sedentary behavior is a risk factor for mortality independent of MVPA. Further investigation, including studies with longer follow-up, is needed to address the health consequences of sedentary behavior.

AICAR Antiproliferative Properties Involve the AMPK-Independent Activation of the Tumor Suppressors LATS 1 and 2.

Science.gov (United States)

Philippe, Chloé; Pinson, Benoît; Dompierre, Jim; Pantesco, Véronique; Viollet, Benoît; Daignan-Fornier, Bertrand; Moenner, Michel

2018-06-01

AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz. This transcriptional signature, together with the observation of increased levels in phosphorylation of Lats1 and Yap1 proteins, suggested that the Hippo signaling pathway was activated by AICAR. This effect was observed in both fibroblasts and epithelial cells. Knockdown of Lats1/2 prevented the cytoplasmic delocalization of Yap1/Taz proteins in response to AICAR and conferred a higher resistance to the drug. These results indicate that activation of the most downstream steps of the Hippo cascade participates to the antiproliferative effects of AICAR. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Frequency-independent radiation modes of interior sound radiation: Experimental study and global active control

Science.gov (United States)

Hesse, C.; Papantoni, V.; Algermissen, S.; Monner, H. P.

2017-08-01

Active control of structural sound radiation is a promising technique to overcome the poor passive acoustic isolation performance of lightweight structures in the low-frequency region. Active structural acoustic control commonly aims at the suppression of the far-field radiated sound power. This paper is concerned with the active control of sound radiation into acoustic enclosures. Experimental results of a coupled rectangular plate-fluid system under stochastic excitation are presented. The amplitudes of the frequency-independent interior radiation modes are determined in real-time using a set of structural vibration sensors, for the purpose of estimating their contribution to the acoustic potential energy in the enclosure. This approach is validated by acoustic measurements inside the cavity. Utilizing a feedback control approach, a broadband reduction of the global acoustic response inside the enclosure is achieved.

Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

International Nuclear Information System (INIS)

Biswas, Arunima; Pasquel, Danielle; Tyagi, Rakesh Kumar; Mani, Sridhar

2011-01-01

Research highlights: → Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation. → PXR undergoes dynamic deacetylation upon ligand-mediated activation. → SIRT1 partially mediates PXR deacetylation. → PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation. -- Abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependent functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.

Nitrite-dependent vasodilation is facilitated by hypoxia and is independent of known NO-generating nitrite reductase activities

DEFF Research Database (Denmark)

Fago, Angela; Dalsgaard, Thomas; Fago, Angela

2007-01-01

is largely intrinsic to the vessel and that under hypoxia physiological nitrite concentrations are sufficient to induce NO-mediated vasodilation independently of the nitrite reductase activities investigated here. Possible reaction mechanisms for nitrite vasoactivity, including formation of S...

Abscisic Acid Regulates Inflammation via Ligand-binding Domain-independent Activation of Peroxisome Proliferator-activated Receptor γ*

Science.gov (United States)

Bassaganya-Riera, Josep; Guri, Amir J.; Lu, Pinyi; Climent, Montse; Carbo, Adria; Sobral, Bruno W.; Horne, William T.; Lewis, Stephanie N.; Bevan, David R.; Hontecillas, Raquel

2011-01-01

Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR γ reporter activity in RAW 264.7 macrophages and increases ppar γ expression in vivo, although it does not bind to the ligand-binding domain of PPAR γ. LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E2 and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR γ. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation. PMID:21088297

Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferator-activated receptor gamma.

Science.gov (United States)

Bassaganya-Riera, Josep; Guri, Amir J; Lu, Pinyi; Climent, Montse; Carbo, Adria; Sobral, Bruno W; Horne, William T; Lewis, Stephanie N; Bevan, David R; Hontecillas, Raquel

2011-01-28

Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR γ reporter activity in RAW 264.7 macrophages and increases ppar γ expression in vivo, although it does not bind to the ligand-binding domain of PPAR γ. LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E(2) and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR γ. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation.

Ligand-independent canonical Wnt activity in canine mammary tumor cell lines associated with aberrant LEF1 expression.

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Ana Gracanin

Full Text Available Pet dogs very frequently develop spontaneous mammary tumors and have been suggested as a good model organism for breast cancer research. In order to obtain an insight into underlying signaling mechanisms during canine mammary tumorigenesis, in this study we assessed the incidence and the mechanism of canonical Wnt activation in a panel of 12 canine mammary tumor cell lines. We show that a subset of canine mammary cell lines exhibit a moderate canonical Wnt activity that is dependent on Wnt ligands, similar to what has been described in human breast cancer cell lines. In addition, three of the tested canine mammary cell lines have a high canonical Wnt activity that is not responsive to inhibitors of Wnt ligand secretion. Tumor cell lines with highly active canonical Wnt signaling often carry mutations in key members of the Wnt signaling cascade. These cell lines, however, carry no mutations in the coding regions of intracellular Wnt pathway components (APC, β-catenin, GSK3β, CK1α and Axin1 and have a functional β-catenin destruction complex. Interestingly, however, the cell lines with high canonical Wnt activity specifically overexpress LEF1 mRNA and the knock-down of LEF1 significantly inhibits TCF-reporter activity. In addition, LEF1 is overexpressed in a subset of canine mammary carcinomas, implicating LEF1 in ligand-independent activation of canonical Wnt signaling in canine mammary tumors. We conclude that canonical Wnt activation may be a frequent event in canine mammary tumors both through Wnt ligand-dependent and novel ligand-independent mechanisms.

Multimedia campaign on a shoestring: promoting 'Stay Active - Stay Independent' among seniors.

Science.gov (United States)

John-Leader, Franklin; Van Beurden, Eric; Barnett, Lisa; Hughes, Karen; Newman, Beth; Sternberg, Jason; Dietrich, Uta

2008-04-01

This paper describes a multimedia campaign implemented in rural New South Wales on a budget smaller than that typical of many published campaigns. The 'To Be Young at Heart - Stay Active Stay Independent' (SASI) campaign was one arm of a multi-strategic program to reduce falls among seniors by promoting physical activity. This 18-month campaign used social marketing techniques. Central to this campaign was strong formative research, significant use of corporate, community and media partnerships and a detailed, strategic distribution plan. Campaign reach was evaluated by a community intercept survey. A variety of high-quality information, education and communication (IEC) resources were developed. Overall, the campaign cost was calculated at USD 191,000. The actual cost of USD 42,000 (excluding staff time) was used to generate almost double this amount in sponsorship (USD 82,000). In the mid-campaign reach survey, 36% recognised the campaign and attributed this to television (58%), newspaper (33%), poster (13%) and bus-back advertising (8%). Of these respondents, 21% reported seeking information about physical activity, 33% reported increased intention to be more active, and 22% reported becoming more active as a result of the campaign. It is possible to develop and deliver a well-designed, multi-media campaign on a limited budget by using sound formative research and engaging community and corporate partners to generate sponsorship. An effective distribution strategy is crucial and may require additional partnerships at State or national level.

Protein tyrosine phosphatase-PEST (PTP-PEST) regulates mast cell-activating signals in PTP activity-dependent and -independent manners.

Science.gov (United States)

Motohashi, Satoru; Koizumi, Karen; Honda, Reika; Maruyama, Atsuko; Palmer, Helen E F; Mashima, Keisuke

2014-01-01

Aggregation of the high-affinity IgE receptor (FcεRI) in mast cells leads to degranulation and production of numerous cytokines and lipid mediators that promote allergic inflammation. Tyrosine phosphorylation of proteins in response to FcεRI aggregation has been implicated in mast cell activation. Here, we determined the role of PTP-PEST (encoded by PTPN12) in the regulation of mast cell activation using the RBL-2H3 rat basophilic leukemia cell line as a model. PTP-PEST expression was significantly induced upon FcεRI-crosslinking, and aggregation of FcεRI induced the phosphorylation of PTP-PEST at Ser39, thus resulting in the suppression of PTP activity. By overexpressing a phosphatase-dead mutant (PTP-PEST CS) and a constitutively active mutant (PTP-PEST SA) in RBL-2H3 cells, we showed that PTP-PEST decreased degranulation and enhanced IL-4 and IL-13 transcription in FcεRI-crosslinked RBL-2H3 cells, but PTP activity of PTP-PEST was not necessary for this regulation. However, FcεRI-induced TNF-α transcription was increased by the overexpression of PTP-PEST SA and suppressed by the overexpression of PTP-PEST CS. Taken together, these results suggest that PTP-PEST is involved in the regulation of FcεRI-mediated mast cell activation through at least two different processes represented by PTP activity-dependent and -independent pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

ICT services for active ageing and independent living: identification and assessment.

Science.gov (United States)

Christophorou, Christophoros; Kleanthous, Styliani; Georgiadis, Dimosthenis; Cereghetti, Donato M; Andreou, Panayiotis; Wings, Cindy; Christodoulou, Eleni; Samaras, George

2016-09-01

Based on the demographic changes and the rapid increase of older population in Europe, major challenges are expected to rise, both in the economy as well as the society, whether the dominant care model for supporting elderly in living independently at home continues to rely on informal and formal caregivers' assistance. To respond to the above challenges, assistive technologies are called to develop Information and Communication Technology (ICT) services for supporting seniors to remain active and independent, for as long as possible, in their chosen home environment. The work described in this Letter is based on the Miraculous-Life project and it emphasises the identification and assessment of a set of services that an ICT system for Ageing Well should support, in an actual end-users setting. The outcome of this work may inform fellow researchers and other projects in the area of Ageing Well in: (i) understanding which ICT services can be the most valuable for end-users' Quality of Life, (ii) prioritising the development of related ICT services and (iii) facilitating better recourse allocation in order to reduce any risks associated to implementation failures of these services within their respective projects. A final trial phase is planned, aiming to validate the Miraculous Life prototype longitudinally in a naturalistic environment with a larger sample size. During this trial, it will be investigated if perceived usefulness, satisfaction and motivation could be predicted by sociodemographic variables and personality.

Elevated plasma plasminogen activator inhibitor type-1 is an independent predictor of coronary microvascular dysfunction in hypertension

International Nuclear Information System (INIS)

Naya, Masanao; Tsukamoto, Takahiro; Inubushi, Masayuki; Morita, Koichi; Katoh, Chietsugu; Furumoto, Tomoo; Fujii, Satoshi; Tsutsui, Hiroyuki; Tamaki, Nagara

2007-01-01

Elevated plasma plasminogen activator inhibitor-1 (PAI-1) is related to cardiovascular events, but its role in subclinical coronary microvascular dysfunction remains unknown. Thus, in the present study it was investigated whether elevated plasma PAI-1 activity is associated with coronary microvascular dysfunction in hypertensive patients. Thirty patients with untreated essential hypertension and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using 15 O-water positron emission tomography. Clinical variables associated with atherosclerosis (low-density lipoprotein-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, homeostasis model assessment (HOMA-IR), and PAI-1 activity) were assessed to determine their involvement in coronary microvascular dysfunction. Adenosine triphosphate (ATP)-induced hyperemic MBF and coronary flow reserve (CFR) were significantly lower in hypertensive patients than in healthy controls (ATP-induced MBF: 2.77±0.82 vs 3.49±0.71 ml·g -1 ·min -1 ; p<0.02 and CFR: 2.95±1.06 vs 4.25±0.69; p<0.001). By univariate analysis, CFR was positively correlated with HDL-cholesterol (r=0.46, p<0.02), and inversely with HOMA-IR (r=-0.39, p<0.05) and PAI-1 activity (r=-0.61, p<0.001). By multivariate analysis, elevated PAI-1 activity remained a significant independent determinant of diminished CFR. Elevated plasma PAI-1 activity was independently associated with coronary microvascular dysfunction, which suggests that plasma PAI-1 activity is an important clue linking hypofibrinolysis to the development of atherosclerosis. (author)

Independent and joint associations of physical activity and fitness with fibromyalgia symptoms and severity: The al-Ándalus project.

Science.gov (United States)

Segura-Jiménez, Víctor; Soriano-Maldonado, Alberto; Estévez-López, Fernando; Álvarez-Gallardo, Inmaculada C; Delgado-Fernández, Manuel; Ruiz, Jonatan R; Aparicio, Virginia A

2017-08-01

We examined independent and joint associations of objectively measured physical activity (PA) and physical fitness (PF) with pain, fatigue and the overall impact of fibromyalgia in 386 fibromyalgia women aged 51.2 ± 7.6 years. Levels of PA (light, moderate and vigorous) and PF were measured with triaxial accelerometry and the Senior Fitness Test, respectively. We used the Short-Form health survey-36 pain sub-scale and the Multidimensional Fatigue Inventory to assess pain and multiple dimensions of fatigue, respectively. The impact of fibromyalgia was studied with the Revised Fibromyalgia Impact Questionnaire (FIQR). Both, total PA and global PF were independently associated with pain pressure threshold, SF-36 pain, reduced activity, reduced motivation and FIQR total score (all, P ≤ 0.027). The associations between total PA and symptoms were weaker than those observed between global PF and symptoms. Overall, unfit patients with low PA showed a worse profile that fit patients with high PA (all, P ≤ 0.001). In summary, PA and PF are independently associated with pain, fatigue and the overall impact of fibromyalgia in women. Although PF presented greater associations with symptoms, the results suggest that both being physically active and keep adequate fitness levels might be convenient for fibromyalgia women.

Role of physical activity, physical fitness, and chronic health conditions on the physical independence of community-dwelling older adults over a 5-year period.

Science.gov (United States)

Pereira, Catarina; Baptista, Fátima; Cruz-Ferreira, Ana

2016-01-01

The variability in the individual characteristics and habits could help determine how older adults maintain independence. The impact of the variability in physical activity, physical fitness, body composition, and chronic health conditions (co-morbidities) on the independence of older adults, especially over time, is seldom examined. This study aims to analyze quantitatively the impact of baseline values and changes in physical activity, physical fitness, body composition, and co-morbidities on the physical independence of community-dwelling, older adults over a 5-year period. Data from 106 and 85 community-dwelling adults (≥60 years) were collected at baseline and after five years, respectively. Linear regression selected the main predictors of changes in physical independence as follows: the baseline physical independence (β=0.032, R(2)=9.9%) and co-morbidities (β=-0.191, R(2)=6.3%) and the changes in co-morbidities (β=-0.244, R(2)=10.8%), agility (β=-0.288, R(2)=6.7%), aerobic endurance (β=0.007, R(2)=3.2%), and walking expenditure (β=0.001, R(2)=5.1%) (page and gender. Gains of up to 8.3% in physical independence were associated with improvements in these variables, which corresponds to regaining independence for performing one or two activities of daily living. Copyright © 2016. Published by Elsevier Ireland Ltd.

Independent Benefits of Meeting the 2008 Physical Activity Guidelines to Insulin Resistance in Obese Latino Children

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Nazrat Mirza

2012-01-01

Full Text Available We examined the independent association between moderate-to-vigorous physical activity (MVPA and insulin resistance (IR among obese Latino children (N=113; 7–15 years who were enrolled in a community-based obesity intervention. Baseline information on physical activity was gathered by self-report. Clinical assessments of body composition, resting energy expenditure (REE, as well as glucose and insulin responses to an oral glucose tolerance test (OGTT were performed after an overnight fast. Insulin resistance was defined as a 2 h insulin concentration >57 μU·mL-1. We observed that those obese children who met the 2008 Guidelines for MVPA (≥60 min/day experienced a significantly lower odds of IR compared with those not meeting the Guidelines (OR=0.29; 95% CI: (0.10–0.92 and these findings were independent of age, sex, pubertal stage, acculturation, fasting insulin, and 2 h glucose concentrations. Efforts to promote 60 min or more of daily MVPA among children from ethnic minority and high-risk communities should assume primary public health importance.

The fibrate gemfibrozil is a NO- and haem-independent activator of soluble guanylyl cyclase: in vitro studies.

Science.gov (United States)

Sharina, I G; Sobolevsky, M; Papakyriakou, A; Rukoyatkina, N; Spyroulias, G A; Gambaryan, S; Martin, E

2015-05-01

Fibrates are a class of drugs widely used to treat dyslipidaemias. They regulate lipid metabolism and act as PPARα agonists. Clinical trials demonstrate that besides changes in lipid profiles, fibrates decrease the incidence of cardiovascular events, with gemfibrozil exhibiting the most pronounced benefit. This study aims to characterize the effect of gemfibrozil on the activity and function of soluble guanylyl cyclase (sGC), the key mediator of NO signalling. High-throughput screening of a drug library identified gemfibrozil as a direct sGC activator. Activation of sGC is unique to gemfibrozil and is not shared by other fibrates. Gemfibrozil activated purified sGC, induced endothelium-independent relaxation of aortic rings and inhibited platelet aggregation. Gemfibrozil-dependent activation was absent when the sGC haem domain was deleted, but was significantly enhanced when sGC haem was lacking or oxidized. Oxidation of sGC haem enhanced the vasoactive and anti-platelet effects of gemfibrozil. Gemfibrozil competed with the haem-independent sGC activators ataciguat and cinaciguat. Computational modelling predicted that gemfibrozil occupies the space of the haem group and interacts with residues crucial for haem stabilization. This is consistent with structure-activity data which revealed an absolute requirement for gemfibrozil's carboxyl group. These data suggest that in addition to altered lipid and lipoprotein state, the cardiovascular preventive benefits of gemfibrozil may derive from direct activation and protection of sGC function. A sGC-directed action may explain the more pronounced cardiovascular benefit of gemfibrozil observed over other fibrates and some of the described side effects of gemfibrozil. © 2014 The British Pharmacological Society.

Supply Chain Management: Are You Maximizing Your Procurement Activity?

Science.gov (United States)

Dobbin, James; Jenkins, Mike

2000-01-01

Today's purchasing professionals recognize the need to reduce non-value-added procedures (clerical functions) while emphasizing strategic planning. Results-oriented supply-chain managers need superb communication, negotiation, and leadership skills to achieve long-term value and resist the lowest, first- cost bids. (Contains 13 references.) (MLH)

Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha.

Science.gov (United States)

Li, Guolin; Brocker, Chad N; Yan, Tingting; Xie, Cen; Krausz, Kristopher W; Xiang, Rong; Gonzalez, Frank J

2018-01-01

Peroxisome proliferator-activated receptor alpha (PPARA) is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF) has not been investigated. Mice were pre-conditioned using either a diet containing the potent PPARA agonist Wy-14643 or an EODF regimen prior to acute fasting. Ppara-null mice were used to assess the contribution of PPARA activation during the metabolic response to EODF. Livers were collected for histological, biochemical, qRT-PCR, and Western blot analysis. Acute fasting activated PPARA and led to steatosis, whereas EODF protected against fasting-induced hepatic steatosis without affecting PPARA signaling. In contrast, pretreatment with Wy-14,643 did activate PPARA signaling but did not ameliorate acute fasting-induced steatosis and unexpectedly promoted liver injury. Ppara ablation exacerbated acute fasting-induced hypoglycemia, hepatic steatosis, and liver injury in mice, whereas these detrimental effects were absent in response to EODF, which promoted PPARA-independent fatty acid metabolism and normalized serum lipids. These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis. Published by Elsevier GmbH.

Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners

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M. J. Laye

2015-01-01

Full Text Available High levels of cardiovascular fitness (CRF and physical activity (PA are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI. Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg (similar-VO2max. The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max. Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy, improved exercise metabolism (lactate threshold, and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases.

Overview and Categorization of Robots Supporting Independent Living of Elderly People: What Activities Do They Support and How Far Have They Developed.

Science.gov (United States)

Bedaf, Sandra; Gelderblom, Gert Jan; De Witte, Luc

2015-01-01

Over the past decades, many robots for the elderly have been developed, supporting different activities of elderly people. A systematic review in four scientific literature databases and a search in article references and European projects was performed in order to create an overview of robots supporting independent living of elderly people. The robots found were categorized based on their development stage, the activity domains they claim to support, and the type of support provided (i.e., physical, non-physical, and/or non-specified). In total, 107 robots for the elderly were identified. Six robots were still in a concept phase, 95 in a development phase, and six of these robots were commercially available. These robots claimed to provide support related to four activity domains: mobility, self-care, interpersonal interaction & relationships, and other activities. Of the many robots developed, only a small percentage is commercially available. Technical ambitions seem to be guiding robot development. To prolong independent living, the step towards physical support is inevitable and needs to be taken. However, it will be a long time before a robot will be capable of supporting multiple activities in a physical manner in the home of an elderly person in order to enhance their independent living.

Enhancing mTOR-targeted cancer therapy by preventing mTOR/raptor inhibition-initiated, mTOR/rictor-independent Akt activation

OpenAIRE

Wang, Xuerong; Yue, Ping; Kim, Young Ae; Fu, Haian; Khuri, Fadlo R.; Sun, Shi-Yong

2008-01-01

It has been shown that mTOR inhibitors activate Akt while inhibiting mTOR signaling. However, the underlying mechanisms and the impact of the Akt activation on mTOR-targeted cancer therapy are unclear. The present work focused on addressing the role of mTOR/rictor in mTOR inhibitor-induced Akt activation and the impact of sustained Akt activation on mTOR-targeted cancer therapy. Thus, we have demonstrated that mTOR inhibitors increase Akt phosphorylation through a mechanism independent of mTO...

Adiposity, physical activity, and muscle quality are independently related to physical function performance in middle-aged postmenopausal women.

Science.gov (United States)

Ward-Ritacco, Christie L; Adrian, Amanda L; Johnson, Mary Ann; Rogers, Laura Q; Evans, Ellen M

2014-10-01

Poor physical function performance is associated with risks for disability in late life; however, determinants of physical function are not well characterized in middle-aged women. The aim of this cross-sectional study was to examine the contributions of body composition, physical activity, muscle capacity, and muscle quality to physical function performance. Postmenopausal women (N = 64; mean [SD] age, 58.6 [3.6] y) were assessed for body composition via dual-energy x-ray absorptiometry, for physical activity via accelerometer (steps per day), and for physical function via Timed Up and Go, 30-second chair stand, and 6-minute walk. Leg strength was assessed using isokinetic dynamometry at 60° second. Leg power was assessed with the Nottingham Leg Extensor Power Rig. Muscle quality was calculated as (1) the ratio of leg strength at 60° second to upper leg lean mass and (2) the ratio of leg power to total lower body lean mass. Regression analyses revealed the following: (1) age and muscle quality calculated with leg power are independently related to Timed Up and Go, explaining 12% and 11% of the variance, respectively (P quality calculated with leg strength are independently related to 30-second chair stand, explaining 12% and 10% of the variance, respectively (P quality calculated with leg strength, steps per day, and adiposity are independent predictors of 6-minute walk, collectively explaining 51% of the variance. In postmenopausal women, a more optimal body composition (including lower adiposity and higher lean mass) and higher levels of physical activity are associated with better physical function performance at midlife.

The Regulatory Independence of FANR

International Nuclear Information System (INIS)

ALNuaimi, Fatema; Choi, Kwang Shik

2012-01-01

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

The Regulatory Independence of FANR

Energy Technology Data Exchange (ETDEWEB)

ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2012-05-15

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

The activities of the Technical Independent Supervision Organization (OSTI) on the licensing process of the nucleoelectric installations

International Nuclear Information System (INIS)

1993-01-01

The basic responsibility for licensing nuclear facilities belongs to the government to urban is up to take care of the safety and public health as well as for the installations environment impact. In practicing such responsibility the government should be assured that the operational safety and nucleoelectric installation construction has to be subjected to checks and controls by an independent organism apart from the owners organization responsible for the construction and operation. This paper presents the main activities of the technical independent supervision organization in conformity with the regulations for the licensing process of nuclear facilities as one of the safety principles adopted for Angra 2 nuclear power plant. (B.C.A.)

Are Independent Probes Truly Independent?

Science.gov (United States)

Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

2009-01-01

The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha

Directory of Open Access Journals (Sweden)

Guolin Li

2018-01-01

Full Text Available Background: Peroxisome proliferator-activated receptor alpha (PPARA is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF has not been investigated. Methods: Mice were pre-conditioned using either a diet containing the potent PPARA agonist Wy-14643 or an EODF regimen prior to acute fasting. Ppara-null mice were used to assess the contribution of PPARA activation during the metabolic response to EODF. Livers were collected for histological, biochemical, qRT-PCR, and Western blot analysis. Results: Acute fasting activated PPARA and led to steatosis, whereas EODF protected against fasting-induced hepatic steatosis without affecting PPARA signaling. In contrast, pretreatment with Wy-14,643 did activate PPARA signaling but did not ameliorate acute fasting-induced steatosis and unexpectedly promoted liver injury. Ppara ablation exacerbated acute fasting-induced hypoglycemia, hepatic steatosis, and liver injury in mice, whereas these detrimental effects were absent in response to EODF, which promoted PPARA-independent fatty acid metabolism and normalized serum lipids. Conclusions: These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis. Keywords: PPARA, PPARalpha, Intermittent fasting, Every-other-day fasting, Steatosis, Adaptive fasting response

The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface

NARCIS (Netherlands)

Weeterings, Cees; de Groot, Philip G.; Adelmeijer, Jelle; Lisman, Ton

2008-01-01

Several lines of evidence suggest that recombinant factor VIIa (rFVIIa) is able to activate factor X on an activated platelet, in a tissue factor-independent manner. We hypothesized that, besides the anionic surface, a receptor on the activated platelet surface is involved in this process. Here, we

Cardiorespiratory Fitness, Sedentary Behaviour and Physical Activity Are Independently Associated with the Metabolic Syndrome, Results from the SCAPIS Pilot Study.

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Örjan Ekblom

Full Text Available Previous studies on the relation between lifestyle and the metabolic syndrome lack one or several aspects of the physical activity pattern in the analyses or cardiorespiratory fitness. Likewise, both uni- and triaxial accelerometry have been used, though, the predictive validity of these two modes has not been compared.The aims of the present study were firstly to investigate the independent relation between cardiorespiratory fitness and physical activity pattern to the metabolic syndrome (MetS and secondly to examine the predictive validity of uni- and triaxial accelerometry, respectively.Data was extracted from the SCAPIS pilot study (n=930, mean age 57.7 yrs. Physical activity pattern was assessed by accelerometry. Cardiorespiratory fitness was estimated using cycle ergometry. MetS was defined per the Adult Treatment Panel III from the National Cholesterol Education Program definition.Time spent sedentary (OR: 2.38, 95% CI: 1.54-4.24 for T3 vs T1, in light intensity (OR: 0.50, 95% CI: 0.28-0.90 and in moderate-to-vigorous activity (OR: 0.33, 95% CI: 0.18-0.61, as well as cardiorespiratory fitness (OR: 0.24, 95% CI:0.12-0.48, were all independently related to the prevalence of MetS after adjustment for potential confounders, fitness and/or the other aspects of the physical activity pattern. In addition, we found that triaxial analyses were more discriminant, with ORs farther away from the reference group and additional significant ORs.The finding that several aspects of the physical activity pattern reveal independent relations to the MetS makes new possible targets for behaviour change of interest, focusing on both exercise and everyday life. When assessing the risk status of a patient, it is advised that triaxial accelerometry is used.

Polarization of migrating monocytic cells is independent of PI 3-kinase activity.

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Silvia Volpe

attractant cue. Polarized monocytes, which display typical amoeboid like motility, can rapidly develop a new leading edge facing the highest chemoattractant concentration at any site of the plasma membrane, including the uropod. The process appears to be independent of PI 3-kinase activity.

Nanomolar bifenthrin alters synchronous Ca2+ oscillations and cortical neuron development independent of sodium channel activity.

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Cao, Zhengyu; Cui, Yanjun; Nguyen, Hai M; Jenkins, David Paul; Wulff, Heike; Pessah, Isaac N

2014-04-01

Bifenthrin, a relatively stable type I pyrethroid that causes tremors and impairs motor activity in rodents, is broadly used. We investigated whether nanomolar bifenthrin alters synchronous Ca(2+) oscillations (SCOs) necessary for activity-dependent dendritic development. Primary mouse cortical neurons were cultured 8 or 9 days in vitro (DIV), loaded with the Ca(2+) indicator Fluo-4, and imaged using a Fluorescence Imaging Plate Reader Tetra. Acute exposure to bifenthrin rapidly increased the frequency of SCOs by 2.7-fold (EC50 = 58 nM) and decreased SCO amplitude by 36%. Changes in SCO properties were independent of modifications in voltage-gated sodium channels since 100 nM bifenthrin had no effect on the whole-cell Na(+) current, nor did it influence neuronal resting membrane potential. The L-type Ca(2+) channel blocker nifedipine failed to ameliorate bifenthrin-triggered SCO activity. By contrast, the metabotropic glutamate receptor (mGluR)5 antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine] normalized bifenthrin-triggered increase in SCO frequency without altering baseline SCO activity, indicating that bifenthrin amplifies mGluR5 signaling independent of Na(+) channel modification. Competitive [AP-5; (-)-2-amino-5-phosphonopentanoic acid] and noncompetitive (dizocilpine, or MK-801 [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate]) N-methyl-d-aspartate antagonists partially decreased both basal and bifenthrin-triggered SCO frequency increase. Bifenthrin-modified SCO rapidly enhanced the phosphorylation of cAMP response element-binding protein (CREB). Subacute (48 hours) exposure to bifenthrin commencing 2 DIV-enhanced neurite outgrowth and persistently increased SCO frequency and reduced SCO amplitude. Bifenthrin-stimulated neurite outgrowth and CREB phosphorylation were dependent on mGluR5 activity since MPEP normalized both responses. Collectively these data identify a new mechanism by which bifenthrin potently alters Ca(2

Contributory factors for the functional independence of oldest old

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Dâmarys Kohlbeck de Melo Neu Ribeiro

2015-02-01

Full Text Available OBJECTIVE To investigate the socioeconomic and clinical factors that contribute to the functional independence of the oldest old of a community. METHOD Cross-sectional quantitative study whose sample consisted of 214 elderly people registered in Basic Health Units. Data were collected through structured interviews and application of the Functional Independence Measure. We used descriptive statistics, and for association of the variables we used the Student t-test, ANOVA and Tukey's test for multiple comparisons. RESULTS The significant variables that contributed to the functional independence were remaining economically active, practicing physical and leisure activities, having a social life, eating fruits, vegetables and meat. The orientation to conduct these practices reduces the demand for care and help needed in everyday activities. CONCLUSION Maintaining independence is primordial to delay disability and presents itself as an excellent field of work for nursing.

Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

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Chiou, Yi-Ling; Chen, Ying-Jung; Lin, Shinne-Ren; Chang, Long-Sen

2011-11-01

CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions. Copyright © 2011 Elsevier Ltd. All rights reserved.

DNA binding-independent transcriptional activation of the vascular endothelial growth factor gene (VEGF) by the Myb oncoprotein

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Lutwyche, Jodi K.; Keough, Rebecca A.; Hunter, Julie; Coles, Leeanne S.; Gonda, Thomas J.

2006-01-01

Myb is a key transcription factor that can regulate proliferation, differentiation, and apoptosis, predominantly in the haemopoietic system. Abnormal expression of Myb is associated with a number of cancers, both haemopoietic and non-haemopoietic. In order to better understand the role of Myb in normal and tumorigenic processes, we undertook a cDNA array screen to identify genes that are regulated by this factor. In this way, we identified the gene encoding vascular endothelial growth factor (VEGF) as being potentially regulated by the Myb oncoprotein in myeloid cells. To determine whether this was a direct effect on VEGF gene transcription, we examined the activity of the murine VEGF promoter in the presence of either wild-type (WT) or mutant forms of Myb. It was found that WT Myb was able to activate the VEGF promoter and that a minimal promoter region of 120 bp was sufficient to confer Myb responsiveness. Surprisingly, activation of the VEGF promoter was independent of DNA binding by Myb. This was shown by the use of DNA binding-defective Myb mutants and by mutagenesis of a potential Myb-binding site in the minimal promoter. Mutation of Sp1 sites within this region abolished Myb-mediated regulation of a reporter construct, suggesting that Myb DNA binding-independent activation of VEGF expression occurs via these Sp1 binding elements. Regulation of VEGF production by Myb has implications for the potential role of Myb in myeloid leukaemias and in solid tumours where VEGF may be functioning as an autocrine growth factor

Enhancer of zeste homologue 2 plays an important role in neuroblastoma cell survival independent of its histone methyltransferase activity.

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Bate-Eya, Laurel T; Gierman, Hinco J; Ebus, Marli E; Koster, Jan; Caron, Huib N; Versteeg, Rogier; Dolman, M Emmy M; Molenaar, Jan J

2017-04-01

Neuroblastoma is predominantly characterised by chromosomal rearrangements. Next to V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog (MYCN) amplification, chromosome 7 and 17q gains are frequently observed. We identified a neuroblastoma patient with a regional 7q36 gain, encompassing the enhancer of zeste homologue 2 (EZH2) gene. EZH2 is the histone methyltransferase of lysine 27 of histone H3 (H3K27me3) that forms the catalytic subunit of the polycomb repressive complex 2. H3K27me3 is commonly associated with the silencing of genes involved in cellular processes such as cell cycle regulation, cellular differentiation and cancer. High EZH2 expression correlated with poor prognosis and overall survival independent of MYCN amplification status. Unexpectedly, treatment of 3 EZH2-high expressing neuroblastoma cell lines (IMR32, CHP134 and NMB), with EZH2-specific inhibitors (GSK126 and EPZ6438) resulted in only a slight G1 arrest, despite maximum histone methyltransferase activity inhibition. Furthermore, colony formation in cell lines treated with the inhibitors was reduced only at concentrations much higher than necessary for complete inhibition of EZH2 histone methyltransferase activity. Knockdown of the complete protein with three independent shRNAs resulted in a strong apoptotic response and decreased cyclin D1 levels. This apoptotic response could be rescued by overexpressing EZH2ΔSET, a truncated form of wild-type EZH2 lacking the SET transactivation domain necessary for histone methyltransferase activity. Our findings suggest that high EZH2 expression, at least in neuroblastoma, has a survival function independent of its methyltransferase activity. This important finding highlights the need for studies on EZH2 beyond its methyltransferase function and the requirement for compounds that will target EZH2 as a complete protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increase of a Calcium Independent Transglutaminase Activity in the Erythrocyte during the Infection with Plasmodium falciparum

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Wasserman Moisés

1999-01-01

Full Text Available We have studied the activity of a calcium dependent transglutaminase (EC 2.3.2.13 during the growth of the parasite Plasmodium falciparum inside the infected human erythrocyte. There is only one detectable transglutaminase in the two-cell-system, and its origin is erythrocytic. No activity was detected in preparations of the parasite devoid of erythrocyte cytoplasm. The Michaelis Menten constants (Km of the enzyme for the substrates N'N'dimethylcaseine and putrescine were undistinguishable whether the cell extracts used in their determination were obtained from normal or from infected red cells. The total activity of transglutaminase in stringently synchronized cultures, measured at 0.5mM Ca2+, decreased with the maturation of the parasite. However, a fraction which became irreversibly activated and independent of calcium concentration was detected. The proportion of this fraction grew with maturation; it represented only 20% of the activity in 20 hr-old-trophozoites while in 48-hr-schizonts it was more than 85% of the total activity. The activation of this fraction of transglutaminase did not depend on an increase in the erythrocyte cytoplasmic calcium, since most of the calcium was shown to be located in the parasite.

Cryptochrome and phytochrome cooperatively but independently reduce active gibberellin content in rice seedlings under light irradiation.

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Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

2012-09-01

In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4-OsGA2ox7). For further examination of the regulation of these genes, we established a series of cryptochrome-deficient lines through reverse genetic screening from a Tos17 mutant population and construction of knockdown lines based on an RNA interference technique. By using these lines and phytochrome mutants, we elucidated that cryptochrome 1 (cry1), consisting of two species in rice plants (cry1a and cry1b), is indispensable for robust induction of the GA2ox genes. On the other hand, repression of the GA20ox genes is mediated by phytochromes. In addition, we found that the phytochromes also mediate the repression of a gibberellin 3-oxidase gene (OsGA3ox2) in the light. These results imply that, in rice seedlings, phytochromes mediate the repression of gibberellin biosynthesis capacity, while cry1 mediates the induction of gibberellin inactivation capacity. The cry1 action was demonstrated to be dominant in the reduction of active gibberellin content, but, in rice seedlings, the cumulative effects of these independent actions reduced active gibberellin content in the light. This pathway design in which different types of photoreceptors independently but cooperatively regulate active gibberellin content is unique from the viewpoint of dicot research. This redundancy should provide robustness to the response in rice plants.

NF-κB dependent and independent mechanisms of quartz-induced proinflammatory activation of lung epithelial cells

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Schins Roel PF

2010-05-01

Full Text Available Abstract In the initiation and progression of pulmonary inflammation, macrophages have classically been considered as a crucial cell type. However, evidence for the role of epithelial type II cells in pulmonary inflammation has been accumulating. In the current study, a combined in vivo and in vitro approach has been employed to investigate the mechanisms of quartz-induced proinflammatory activation of lung epithelial cells. In vivo, enhanced expression of the inflammation- and oxidative stress-related genes HO-1 and iNOS was found on the mRNA level in rat lungs after instillation with DQ12 respirable quartz. Activation of the classical NF-κB pathway in macrophages and type II pneumocytes was indicated by enhanced immunostaining of phospho-IκBα in these specific lung cell types. In vitro, the direct, particle-mediated effect on proinflammatory signalling in a rat lung epithelial (RLE cell line was compared to the indirect, macrophage product-mediated effect. Treatment with quartz particles induced HO-1 and COX-2 mRNA expression in RLE cells in an NF-κB independent manner. Supernatant from quartz-treated macrophages rapidly activated the NF-κB signalling pathway in RLE cells and markedly induced iNOS mRNA expression up to 2000-fold compared to non-treated control cells. Neutralisation of TNFα and IL-1β in macrophage supernatant did not reduce its ability to elicit NF-κB activation of RLE cells. In addition the effect was not modified by depletion or supplementation of intracellular glutathione. The results from the current work suggest that although both oxidative stress and NF-κB are likely involved in the inflammatory effects of toxic respirable particles, these phenomena can operate independently on the cellular level. This might have consequences for in vitro particle hazard testing, since by focusing on NF-κB signalling one might neglect alternative inflammatory pathways.

5 Tips for Creating Independent Activities Aligned with the Common Core State Standards

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Fraser, Dawn W.

2013-01-01

Promoting independence in all students is one important part of education. It can be difficult for educators to identify meaningful tasks that students with severe disabilities can complete with full independence. By incorporating visual supports into a student's independent work, the teacher is providing the student with an opportunity to…

Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake

OpenAIRE

Hogenkamp, P S; Zhou, W; Dahlberg, L S; Stark, J; Larsen, A L; Olivo, G; Wiemerslage, L; Larsson, E-M; Sundbom, M; Benedict, C; Schi?th, H B

2016-01-01

BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese...

The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.

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Frank A J L Scheer

Full Text Available Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM, potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1 platelet function and (2 platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise.We studied 12 healthy adults (6 female who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01. These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM. The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors.These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the final common pathway of platelet aggregation, suggests that endogenous

Effector-independent brain activity during motor imagery of the upper and lower limbs: an fMRI study.

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Mizuguchi, Nobuaki; Nakata, Hiroki; Kanosue, Kazuyuki

2014-10-03

We utilized functional magnetic resonance imaging (fMRI) to evaluate the common brain region of motor imagery for the right and left upper and lower limbs. The subjects were instructed to repeatedly imagined extension and flexion of the right or left hands/ankles. Brain regions, which included the supplemental motor area (SMA), premotor cortex and parietal cortex, were activated during motor imagery. Conjunction analysis revealed that the left SMA and inferior frontal gyrus (IFG)/ventral premotor cortex (vPM) were commonly activated with motor imagery of the right hand, left hand, right foot, and left foot. This result suggests that these brain regions are activated during motor imagery in an effector independent manner. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

ATP induces NO production in hippocampal neurons by P2X(7 receptor activation independent of glutamate signaling.

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Juan Francisco Codocedo

Full Text Available To assess the putative role of adenosine triphosphate (ATP upon nitric oxide (NO production in the hippocampus, we used as a model both rat hippocampal slices and isolated hippocampal neurons in culture, lacking glial cells. In hippocampal slices, additions of exogenous ATP or 2'(3'-O-(4-Benzoylbenzoyl ATP (Bz-ATP elicited concentration-dependent NO production, which increased linearly within the first 15 min and plateaued thereafter; agonist EC50 values were 50 and 15 µM, respectively. The NO increase evoked by ATP was antagonized in a concentration-dependent manner by Coomassie brilliant blue G (BBG or by N(ω-propyl-L-arginine, suggesting the involvement of P2X7Rs and neuronal NOS, respectively. The ATP induced NO production was independent of N-methyl-D-aspartic acid (NMDA receptor activity as effects were not alleviated by DL-2-Amino-5-phosphonopentanoic acid (APV, but antagonized by BBG. In sum, exogenous ATP elicited NO production in hippocampal neurons independently of NMDA receptor activity.

Rapid activation of Rac GTPase in living cells by force is independent of Src.

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Yeh-Chuin Poh

2009-11-01

Full Text Available It is well known that mechanical forces are crucial in regulating functions of every tissue and organ in a human body. However, it remains unclear how mechanical forces are transduced into biochemical activities and biological responses at the cellular and molecular level. Using the magnetic twisting cytometry technique, we applied local mechanical stresses to living human airway smooth muscle cells with a magnetic bead bound to the cell surface via transmembrane adhesion molecule integrins. The temporal and spatial activation of Rac, a small guanosine triphosphatase, was quantified using a fluorescent resonance energy transfer (FRET method that measures changes in Rac activity in response to mechanical stresses by quantifying intensity ratios of ECFP (enhanced cyan fluorescent protein as a donor and YPet (a variant yellow fluorescent protein as an acceptor of the Rac biosensor. The applied stress induced rapid activation (less than 300 ms of Rac at the cell periphery. In contrast, platelet derived growth factor (PDGF induced Rac activation at a much later time (>30 sec. There was no stress-induced Rac activation when a mutant form of the Rac biosensor (RacN17 was transfected or when the magnetic bead was coated with transferrin or with poly-L-lysine. It is known that PDGF-induced Rac activation depends on Src activity. Surprisingly, pre-treatment of the cells with specific Src inhibitor PP1 or knocking-out Src gene had no effects on stress-induced Rac activation. In addition, eliminating lipid rafts through extraction of cholesterol from the plasma membrane did not prevent stress-induced Rac activation, suggesting a raft-independent mechanism in governing the Rac activation upon mechanical stimulation. Further evidence indicates that Rac activation by stress depends on the magnitudes of the applied stress and cytoskeletal integrity. Our results suggest that Rac activation by mechanical forces is rapid, direct and does not depend on Src

Reproducibility and Angle Independence of Electromechanical Wave Imaging for the Measurement of Electromechanical Activation during Sinus Rhythm in Healthy Humans.

Science.gov (United States)

Melki, Lea; Costet, Alexandre; Konofagou, Elisa E

2017-10-01

Electromechanical wave imaging (EWI) is an ultrasound-based technique that can non-invasively map the transmural electromechanical activation in all four cardiac chambers in vivo. The objective of this study was to determine the reproducibility and angle independence of EWI for the assessment of electromechanical activation during normal sinus rhythm (NSR) in healthy humans. Acquisitions were performed transthoracically at 2000 frames/s on seven healthy human hearts in parasternal long-axis, apical four- and two-chamber views. EWI data was collected twice successively in each view in all subjects, while four successive acquisitions were obtained in one case. Activation maps were generated and compared (i) within the same acquisition across consecutive cardiac cycles; (ii) within same view across successive acquisitions; and (iii) within equivalent left-ventricular regions across different views. EWI was capable of characterizing electromechanical activation during NSR and of reliably obtaining similar patterns of activation. For consecutive heart cycles, the average 2-D correlation coefficient between the two isochrones across the seven subjects was 0.9893, with a mean average activation time fluctuation in LV wall segments across acquisitions of 6.19%. A mean activation time variability of 12% was obtained across different views with a measurement bias of only 3.2 ms. These findings indicate that EWI can map the electromechanical activation during NSR in human hearts in transthoracic echocardiography in vivo and results in reproducible and angle-independent activation maps. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

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Côté, Isabelle; Green, Sara M; Morgan, Drake; Carter, Christy S; Tümer, Nihal; Scarpace, Philip J

2018-03-01

Recent evidence indicate that melanotan II (MTII) reduces body mass independently of caloric reduction. Because MTII induces a transient hypophagia, caloric reduction is still considered a primary mechanism for MTII-mediated body mass loss. To examine the contribution of caloric reduction to long-term body mass loss in response to MTII, we centrally infused MTII or vehicle in ad libitum fed (MTII and Control) animals in comparison with a group of animals that were pair-fed (PF) to the MTII group. Food intake and body mass were recorded daily, and body composition was assessed biweekly. The present study demonstrates that central MTII-mediated body mass loss is only partially mediated by caloric restriction, and the long-term body mass loss is independent of the initial hypophagia. More importantly, central MTII administration induced a rapid but sustained fat mass loss, independently of caloric reduction. MTII-treated animals preserved their lean/fat mass ratio throughout the study, whereas PF animals underwent a transient reduction of lean/fat mass ratio that was only normalized when food intake returned to Control level. In summary, it can be concluded that activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

Leptin induces CYP1B1 expression in MCF-7 cells through ligand-independent activation of the ERα pathway

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Khanal, Tilak; Kim, Hyung Gyun; Do, Minh Truong; Choi, Jae Ho; Won, Seong Su [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Kang, Wonku [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Chung, Young Chul [Department of Food Science and Culinary, International University of Korea, Jinju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

2014-05-15

Leptin, a hormone with multiple biological actions, is produced predominantly by adipose tissue. Among its functions, leptin can stimulate tumour cell growth. Oestrogen receptor α (ERα), which plays an essential role in breast cancer development, can be transcriptionally activated in a ligand-independent manner. In this study, we investigated the effect of leptin on CYP1B1 expression and its mechanism in breast cancer cells. Leptin induced CYP1B1 protein, messenger RNA expression and promoter activity in ERα-positive MCF-7 cells but not in ERα-negative MDA-MB-231 cells. Additionally, leptin increased 4-hydroxyoestradiol in MCF-7 cells. Also, ERα knockdown by siRNA significantly blocked the induction of CYP1B1 expression by leptin, indicating that leptin induced CYP1B1 expression via an ERα-dependent mechanism. Transient transfection with CYP1B1 deletion promoter constructs revealed that the oestrogen response element (ERE) plays important role in the up-regulation of CYP1B1 by leptin. Furthermore, leptin stimulated phosphorylation of ERα at serine residues 118 and 167 and increased ERE-luciferase activity, indicating that leptin induced CYP1B1 expression by ERα activation. Finally, we found that leptin activated ERK and Akt signalling pathways, which are upstream kinases related to ERα phosphorylation induced by leptin. Taken together, our results indicate that leptin-induced CYP1B1 expression is mediated by ligand-independent activation of the ERα pathway as a result of the activation of ERK and Akt in MCF-7 cells. - Highlights: • Leptin increased 4-hydroxyoestradiol in MCF-7 breast cancer cells. • Leptin activated ERK and Akt kinases related to ERα phosphorylation. • Leptin induces phosphorylation of ERα at serine residues 118 and 167. • Leptin induces ERE-luciferase activity.

Agent independent task planning

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Davis, William S.

1990-01-01

Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

Endogenous protein and enzyme fragments induce immunoglobulin E-independent activation of mast cells via a G protein-coupled receptor, MRGPRX2.

Science.gov (United States)

Tatemoto, K; Nozaki, Y; Tsuda, R; Kaneko, S; Tomura, K; Furuno, M; Ogasawara, H; Edamura, K; Takagi, H; Iwamura, H; Noguchi, M; Naito, T

2018-05-01

Mast cells play a central role in inflammatory and allergic reactions by releasing inflammatory mediators through 2 main pathways, immunoglobulin E-dependent and E-independent activation. In the latter pathway, mast cells are activated by a diverse range of basic molecules (collectively known as basic secretagogues) through Mas-related G protein-coupled receptors (MRGPRs). In addition to the known basic secretagogues, here, we discovered several endogenous protein and enzyme fragments (such as chaperonin-10 fragment) that act as bioactive peptides and induce immunoglobulin E-independent mast cell activation via MRGPRX2 (previously known as MrgX2), leading to the degranulation of mast cells. We discuss the possibility that MRGPRX2 responds various as-yet-unidentified endogenous ligands that have specific characteristics, and propose that MRGPRX2 plays an important role in regulating inflammatory responses to endogenous harmful stimuli, such as protein breakdown products released from damaged or dying cells. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Independent and joint associations of physical activity and fitness with fibromyalgia symptoms and severity : The al-Ándalus project

NARCIS (Netherlands)

Segura-Jiménez, Víctor; Soriano-Maldonado, Alberto; Estévez-López, Fernando; Álvarez-Gallardo, Inmaculada C; Delgado-Fernández, Manuel; Ruiz, Jonatan R; Aparicio, Virginia A

We examined independent and joint associations of objectively measured physical activity (PA) and physical fitness (PF) with pain, fatigue and the overall impact of fibromyalgia in 386 fibromyalgia women aged 51.2 ± 7.6 years. Levels of PA (light, moderate and vigorous) and PF were measured with

Joint Integration Office Independent Review Committee annual report, 1985

International Nuclear Information System (INIS)

1986-08-01

Comprised of seven persons with extensive experience in the issues of nuclear waste, the Independent Review Committee (IRC) provides independent and objective review of Defense Transuranic Waste Program (DTWP) activities managed by the Joint Integration Office (JIO), formerly the Defense Transuranic Waste Lead Organization (TLO). The Committee is ensured a broad, interdisciplinary perspective since its membership includes representatives from the fields of nuclear engineering, nuclear waste transportation, industrial quality control, systems and environmental engineering and state and local government. The scope of IRC activities includes overall review of specific TLO plans, projects and activities, and technical review of particular research and development projects. The Committee makes specific suggestions and recommendations based upon expertise in the field of TRU Waste Management. The IRC operates as a consulting group, under an independent charter providing objective review of program activities. This report summarizes the 12 major topics reviewed by the committee during 1985

Gas6 downregulation impaired cytoplasmic maturation and pronuclear formation independent to the MPF activity.

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Kyeoung-Hwa Kim

Full Text Available Previously, we found that the growth arrest-specific gene 6 (Gas6 is more highly expressed in germinal vesicle (GV oocytes than in metaphase II (MII oocytes using annealing control primer (ACP-PCR technology. The current study was undertaken to investigate the role of Gas6 in oocyte maturation and fertilization using RNA interference (RNAi. Interestingly, despite the specific and marked decrease in Gas6 mRNA and protein expression in GVs after Gas6 RNAi, nuclear maturation including spindle structures and chromosome segregation was not affected. The only discernible effect induced by Gas6 RNAi was a change in maturation promoting factor (MPF activity. After parthenogenetic activation, Gas6 RNAi-treated oocytes at the MII stage had not developed further and arrested at MII (90.0%. After stimulation with Sr(2+, Gas6-silenced MII oocytes had markedly reduced Ca(2+ oscillation and exhibited no exocytosis of cortical granules. In these oocytes, sperm penetration occurred during fertilization but not pronucleus (PN formation. By roscovitine and colcemid treatment, we found that the Gas6 knockdown affected cytoplasmic maturation directly, independent to the changed MPF activity. These results strongly suggest that 1 the Gas6 signaling itself is important to the cytoplasmic maturation, but not nuclear maturation, and 2 the decreased Gas6 expression and decreased MPF activity separately or mutually influence sperm head decondensation and PN formation.

Telomerase activity-independent function of telomerase reverse transcriptase is involved in acrylamide-induced neuron damage.

Science.gov (United States)

Zhang, P; Pan, H; Wang, J; Liu, X; Hu, X

2014-07-01

Polyacrylamide is used widely in industry, and its decomposition product, acrylamide (ACR), readily finds its way into commonly consumed cosmetics and baked and fried foods. ACR exerts potent neurotoxic effects in human and animal models. Telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase, traditionally has been considered to play an important role in maintaining telomere length. Emerging evidence has shown, however, that TERT plays an important role in neuroprotection by inhibiting apoptosis and excitotoxicity, and by promoting angiogenesis, neuronal survival and neurogenesis, which are closely related to the telomere-independent functions of TERT. We investigated whether and how the TERT pathway is involved in ACR induced neurotoxicity in rat cortical neurons. We found that ACR 1) significantly reduced the viability of cortical neurons as measured by MTT assay, 2) induced neuron apoptosis as revealed by FITC-conjugated Annexin V/PI double staining and flow cytometry (FACS) analysis, 3) elevated expression of cleaved caspase-3, and 4) decreased bcl-2 expression of cortical neurons. ACR also increased intracellular ROS levels in cortical neurons, increased MDA levels and reduced GSH, SOD and GSH-Px levels in mitochondria in a dose-dependent manner. We found that TERT expression in mitochondria was increased by ACR at concentrations of 2.5 and 5.0 mM, but TERT expression was decreased by 10 mM ACR. Telomerase activity, however, was undetectable in rat cortical neurons. Our results suggest that the TERT pathway is involved in ACR induced apoptosis of cortical neurons. TERT also may exert its neuroprotective role in a telomerase activity-independent way, especially in mitochondria.

Ddc2 mediates Mec1 activation through a Ddc1- or Dpb11-independent mechanism.

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Amitava Bandhu

2014-02-01

Full Text Available The protein kinase Mec1 (ATR ortholog and its partner Ddc2 (ATRIP ortholog play a key role in DNA damage checkpoint responses in budding yeast. Previous studies have established the model in which Ddc1, a subunit of the checkpoint clamp, and Dpb11, related to TopBP1, activate Mec1 directly and control DNA damage checkpoint responses at G1 and G2/M. In this study, we show that Ddc2 contributes to Mec1 activation through a Ddc1- or Dpb11-independent mechanism. The catalytic activity of Mec1 increases after DNA damage in a Ddc2-dependent manner. In contrast, Mec1 activation occurs even in the absence of Ddc1 and Dpb11 function at G2/M. Ddc2 recruits Mec1 to sites of DNA damage. To dissect the role of Ddc2 in Mec1 activation, we isolated and characterized a separation-of-function mutation in DDC2, called ddc2-S4. The ddc2-S4 mutation does not affect Mec1 recruitment but diminishes Mec1 activation. Mec1 phosphorylates histone H2A in response to DNA damage. The ddc2-S4 mutation decreases phosphorylation of histone H2A more significantly than the absence of Ddc1 and Dpb11 function does. Our results suggest that Ddc2 plays a critical role in Mec1 activation as well as Mec1 localization at sites of DNA damage.

Perfluorononanoic acid-induced apoptosis in rat spleen involves oxidative stress and the activation of caspase-independent death pathway

International Nuclear Information System (INIS)

Fang, Xuemei; Feng, Yixing; Wang, Jianshe; Dai, Jiayin

2010-01-01

Perfluoroalkyl acid (PFAA)-induced apoptosis has been reported in many cell types. However, minimal information on its mode of action is available. This study explored the possible involvement of apoptotic signaling pathways in a nine-carbon-chain length PFAA-perfluorononanoic acid (PFNA)-induced splenocyte apoptosis. After a 14-day exposure to PFNA, rat spleens showed dose-dependent levels of apoptosis. The production of pro-inflammatory and anti-inflammatory cytokines was significantly increased and decreased, respectively. However, protein levels of tumor necrosis factor receptor 1 (TNFR1), fas-associated protein with death domain (FADD), caspase 8 and caspase 3, which are involved in inflammation-related and caspase-dependent apoptosis, were discordant. Peroxisome proliferator-activated receptors alpha (PPARα) and PPARγ genes expression was up-regulated in rats treated with 3 or 5 mg/kg/day of PFNA, and the level of hydrogen peroxide (H 2 O 2 ) increased concurrently in rats treated with the highest dose. Moreover, superoxide dismutase (SOD) activity and Bcl-2 protein levels were dramatically decreased in spleens after treatment with 3 and 5 mg/kg/day of PFNA. However, protein levels of Bax were unchanged. Apoptosis-inducing factor (AIF), an initiator of caspase-independent apoptosis, was significantly increased in all PFNA-dosed rats. Thus, oxidative stress and the activation of a caspase-independent apoptotic signaling pathway contributed to PFNA-induced apoptosis in rat splenocytes.

NMFS Fishery-Independent Survey System (FINSS)

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National Oceanic and Atmospheric Administration, Department of Commerce — Fishery Independent Survey System (FINSS) is a national system that characterizes NMFS ocean observation activities, stock and ecosystem data collections during...

Inhibition of hepatitis C virus replication through adenosine monophosphate-activated protein kinase-dependent and -independent pathways.

Science.gov (United States)

Nakashima, Kenji; Takeuchi, Kenji; Chihara, Kazuyasu; Hotta, Hak; Sada, Kiyonao

2011-11-01

Persistent infection with hepatitis C virus (HCV) is closely correlated with type 2 diabetes. In this study, replication of HCV at different glucose concentrations was investigated by using J6/JFH1-derived cell-adapted HCV in Huh-7.5 cells and the mechanism of regulation of HCV replication by AMP-activated protein kinase (AMPK) as an energy sensor of the cell analyzed. Reducing the glucose concentration in the cell culture medium from 4.5 to 1.0 g/L resulted in suppression of HCV replication, along with activation of AMPK. Whereas treatment of cells with AMPK activator 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) suppressed HCV replication, compound C, a specific AMPK inhibitor, prevented AICAR's effect, suggesting that AICAR suppresses the replication of HCV by activating AMPK in Huh-7.5 cells. In contrast, compound C induced further suppression of HCV replication when the cells were cultured in low glucose concentrations or with metformin. These results suggest that low glucose concentrations and metformin have anti-HCV effects independently of AMPK activation. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

Superb hydroxyl radical-mediated biocidal effect induced antibacterial activity of tuned ZnO/chitosan type II heterostructure under dark

International Nuclear Information System (INIS)

Podder, Soumik; Halder, Suman; Roychowdhury, Anirban; Das, Dipankar; Ghosh, Chandan Kr.

2016-01-01

Reactive oxygen species (ROS) is the most dominating factor for bacteria cell toxicity due to release of oxidative stress. Hydroxyl radical ("·OH) is a strong oxidizing ROS that has high impact on biocidal activity. This present paper highlights "·OH influenced antibacterial activity and biocidal propensity of tuned ZnO/chitosan (ZnO/CS) nanocomposite against Pseudomonas putida (P. putida) in the absence of light for the first time. For this purpose, the CS proportion was increased by 25 % (w/w) of ZnO during the preparation of ZnO/CS nanocomposite and a systematic study of different ROS like superoxide anion (O_2"·"−), hydrogen peroxide (H_2O_2) and "·OH production as well as their kinetics was carried out both under UV irradiation and in dark by UV–Vis spectroscopy using NBT dye, starch and iodine reaction and fluorescence spectroscopy using terephthalic acid. The decoration of ZnO nanoparticles (ZnO·NPs) with CS tuning was characterized by XRD and FTIR spectroscopy, revealing sustained crystallinity and surface coating of ZnO NP (size about ~24 nm) by CS molecule. The hybridization of ZnO nanoparticles with CS@50 wt% (w/w) resulted superior biocidal activity (81 %) within 3 h in dark mediated by optimum production of "·OH among all ROS. Here we have proposed the enhanced production of "·OH in ZnO/CS due to generation of holes by entrapment of electrons in acceptor level formed in nanocomposite for the first time, and the acceptor levels were probed by Positron annihilation lifetime spectroscopy. The increase in non-positronium (non-Ps) formation probability (I_2) in ZnO/CS nanocomposite confirmed the acceptor levels. This work also confirms surface defect-mediated ROS generation in dark, and zinc interstitials are proposed as active defect sites for generation of holes and "·OH for the first time and confirmed by steady-state room temperature photoluminescence spectroscopy. Finally, a plausible mechanism was hypothesized focusing on hole

Superb hydroxyl radical-mediated biocidal effect induced antibacterial activity of tuned ZnO/chitosan type II heterostructure under dark

Science.gov (United States)

Podder, Soumik; Halder, Suman; Roychowdhury, Anirban; Das, Dipankar; Ghosh, Chandan Kr.

2016-10-01

Reactive oxygen species (ROS) is the most dominating factor for bacteria cell toxicity due to release of oxidative stress. Hydroxyl radical (·OH) is a strong oxidizing ROS that has high impact on biocidal activity. This present paper highlights ·OH influenced antibacterial activity and biocidal propensity of tuned ZnO/chitosan (ZnO/CS) nanocomposite against Pseudomonas putida (P. putida) in the absence of light for the first time. For this purpose, the CS proportion was increased by 25 % (w/w) of ZnO during the preparation of ZnO/CS nanocomposite and a systematic study of different ROS like superoxide anion (O 2 ·- ), hydrogen peroxide (H2O2) and ·OH production as well as their kinetics was carried out both under UV irradiation and in dark by UV-Vis spectroscopy using NBT dye, starch and iodine reaction and fluorescence spectroscopy using terephthalic acid. The decoration of ZnO nanoparticles (ZnO·NPs) with CS tuning was characterized by XRD and FTIR spectroscopy, revealing sustained crystallinity and surface coating of ZnO NP (size about 24 nm) by CS molecule. The hybridization of ZnO nanoparticles with CS@50 wt% (w/w) resulted superior biocidal activity (81 %) within 3 h in dark mediated by optimum production of ·OH among all ROS. Here we have proposed the enhanced production of ·OH in ZnO/CS due to generation of holes by entrapment of electrons in acceptor level formed in nanocomposite for the first time, and the acceptor levels were probed by Positron annihilation lifetime spectroscopy. The increase in non-positronium (non-Ps) formation probability (I2) in ZnO/CS nanocomposite confirmed the acceptor levels. This work also confirms surface defect-mediated ROS generation in dark, and zinc interstitials are proposed as active defect sites for generation of holes and ·OH for the first time and confirmed by steady-state room temperature photoluminescence spectroscopy. Finally, a plausible mechanism was hypothesized focusing on hole generation in ZnO NP and

Superb hydroxyl radical-mediated biocidal effect induced antibacterial activity of tuned ZnO/chitosan type II heterostructure under dark

Energy Technology Data Exchange (ETDEWEB)

Podder, Soumik [Jadavpur University, School of Materials Science and Nanotechnology (India); Halder, Suman [Jadavpur University, Department of Pharmaceutical Technology (India); Roychowdhury, Anirban; Das, Dipankar [Kolkata Centre, UGC-DAE Consortium for Scientific Research (India); Ghosh, Chandan Kr., E-mail: chandu-ju@yahoo.co.in [Jadavpur University, School of Materials Science and Nanotechnology (India)

2016-10-15

Reactive oxygen species (ROS) is the most dominating factor for bacteria cell toxicity due to release of oxidative stress. Hydroxyl radical ({sup ·}OH) is a strong oxidizing ROS that has high impact on biocidal activity. This present paper highlights {sup ·}OH influenced antibacterial activity and biocidal propensity of tuned ZnO/chitosan (ZnO/CS) nanocomposite against Pseudomonas putida (P. putida) in the absence of light for the first time. For this purpose, the CS proportion was increased by 25 % (w/w) of ZnO during the preparation of ZnO/CS nanocomposite and a systematic study of different ROS like superoxide anion (O{sub 2}{sup ·−}), hydrogen peroxide (H{sub 2}O{sub 2}) and {sup ·}OH production as well as their kinetics was carried out both under UV irradiation and in dark by UV–Vis spectroscopy using NBT dye, starch and iodine reaction and fluorescence spectroscopy using terephthalic acid. The decoration of ZnO nanoparticles (ZnO·NPs) with CS tuning was characterized by XRD and FTIR spectroscopy, revealing sustained crystallinity and surface coating of ZnO NP (size about ~24 nm) by CS molecule. The hybridization of ZnO nanoparticles with CS@50 wt% (w/w) resulted superior biocidal activity (81 %) within 3 h in dark mediated by optimum production of {sup ·}OH among all ROS. Here we have proposed the enhanced production of {sup ·}OH in ZnO/CS due to generation of holes by entrapment of electrons in acceptor level formed in nanocomposite for the first time, and the acceptor levels were probed by Positron annihilation lifetime spectroscopy. The increase in non-positronium (non-Ps) formation probability (I{sub 2}) in ZnO/CS nanocomposite confirmed the acceptor levels. This work also confirms surface defect-mediated ROS generation in dark, and zinc interstitials are proposed as active defect sites for generation of holes and {sup ·}OH for the first time and confirmed by steady-state room temperature photoluminescence spectroscopy. Finally, a

Does Board Independence Matter? Evidence from New Zealand

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Hardjo Koerniadi

2012-06-01

Full Text Available This paper examines the effects of the presence of independent directors on firm value using both market-based performance measures (Tobin’s Q ratio and EVA and accounting-based ratios (ROA and ROE. We find that, instead of adding value, independent directors in NewZealand negatively affect firm value. We also find that, consistent with stewardship theory,independent directors have a positive effect on firm value only when they are in the minority.These findings are important given the increasing trend toward independence in corporate boards around the globe and suggest that board independence may not generally be suitable for countries where managers are considered as active partners along with other stakeholders in companies.

Correlates of children's independent outdoor play: Cross-sectional analyses from the Millennium Cohort Study

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Daniel Aggio

2017-12-01

Full Text Available Time spent outdoors is associated with higher levels of physical activity. To date, correlates of independent outdoor play have not been investigated. This study aimed to identify potential demographic, behavioural, environmental and social correlates of children's independent outdoor play.Data were from the Millennium Cohort Study when children were aged 7years. Parents reported whether their children played out unsupervised (yes/no as well as the above mentioned correlates of unsupervised outdoor play. Children's physical activity levels were measured using waist worn accelerometry. Multiple logistic regression was used to examine associations between correlates and odds of independent (unsupervised outdoor play. Adjusted multiple linear regression was used to estimate associations between independent outdoor play and objective measures of physical activity. Activity was measured as average daily moderate-to-vigorous activity, steps, and sedentary behaviour.3856 (n=29% participants were categorised as engaging in independent outdoor play. Older age, being white British, being in poverty, living in close proximity to both family friends and family, having fewer internalising problems, having more externalising conduct problems and fewer pro-social behaviours were associated with higher odds of independent outdoor play. Independent outdoor play was associated with >2 additional minutes of moderate-to-vigorous activity (B=2.21 95% CI, 1.09 to 3.34, >330 additional steps per day (B=336.66 95% CI 209.80 to 463.51, and nearly 5min less time spent sedentary per day (B=−4.91 95% CI −7.54, −2.29Younger children, those from a higher socio-economic-status, those isolated in location from family friends and family, and those with high levels of prosocial behaviour have lower levels of independent outdoor play. Independent outdoor play was associated with higher levels of physical activity and less time sedentary. Future interventions to promote

Suppression of NYVAC Infection in HeLa Cells Requires RNase L but Is Independent of Protein Kinase R Activity

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Fernández-Escobar, Mercedes; Nájera, José Luis; Baldanta, Sara; Rodriguez, Dolores; Way, Michael; Esteban, Mariano

2015-01-01

Protein kinase R (PKR) and RNase L are host cell components that function to contain viral spread after infections. In this study, we analyzed the role of both proteins in the abortive infection of human HeLa cells with the poxvirus strain NYVAC, for which an inhibition of viral A27L and B5R gene expression is described. Specifically, the translation of these viral genes is independent of PKR activation, but their expression is dependent on the RNase L activity. PMID:26656695

Management Technology of Students’ Independent Work

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Melis K. Asanaliev

2012-09-01

Full Text Available The researchers are convinced that for an intensification of educational process in higher education institution it is necessary development of essentially new approaches, forms and the methods of social and pedagogical interaction adequate to new requirements, new pedagogical thinking. Among them we can choose the methods of social and psychological training (SPT which received their development in experimental psychology by synthesis of wide practical experience educational, creative, administrative, and other types of interrelation between people. These methods conditionally divide on: debatable (group discussion, analysis of a situation of a moral choice, game methods (didactic, creative, role-playing games, sensitive training (training of interpersonal sensitivity which are formations of independent informative activity of students on the basis of modern technologies, as the mechanism of improvement of independent work. Researches are expressed in search and finding enough effective forms and means of activation of educational and informative process of preparation of young teachers of vocational training, theoretically and practically prepared in the field of the independent informative activity, use the modern technology of training and its further realization in work with students of technical secondary. It is offered the model of the organization and application in educational process of the complex of these methods in contents complex of training programs of systems of tasks as one of ways of formation of social and psychological culture of future teacher.

IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection.

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Pierre Wallet

2017-10-01

Full Text Available Guanylate binding proteins (GBPs are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii GBPs would directly facilitate inflammasome complex assembly. Using Francisella novicida infection, we investigated the functional interactions between GBPs and the inflammasome. GBPs, induced in a type I IFN-dependent manner, are required for the F. novicida-mediated AIM2-inflammasome pathway. Here, we demonstrate that GBPs action is not restricted to the AIM2 inflammasome, but controls in a hierarchical manner the activation of different inflammasomes complexes and apoptotic caspases. IFN-γ induces a quantitative switch in GBPs levels and redirects pyroptotic and apoptotic pathways under the control of GBPs. Furthermore, upon IFN-γ priming, F. novicida-infected macrophages restrict cytosolic bacterial replication in a GBP-dependent and inflammasome-independent manner. Finally, in a mouse model of tularemia, we demonstrate that the inflammasome and the GBPs are two key immune pathways functioning largely independently to control F. novicida infection. Altogether, our results indicate that GBPs are the master effectors of IFN-γ-mediated responses against F. novicida to control antibacterial immune responses in inflammasome-dependent and independent manners.

Sedentary activity associated with metabolic syndrome independent of physical activity

DEFF Research Database (Denmark)

Bankoski, Andrea; Harris, Tamara B; McClain, James J

2011-01-01

This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults.......This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults....

T helper-independent activation of human CD8+ cells: the role of CD28 costimulation.

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Van Gool, S W; Zhang, Y; Kasran, A; de Boer, M; Ceuppens, J L

1996-07-01

The concept that activation of MHC class I-restricted CD8+ cells entirely depends on help from MHC class II-restricted CD4+ T cells has recently been supplemented with an alternative model in which CD8+ cells can directly be activated by MHC class I-expressing professional antigen-presenting cells (APC), which are able to deliver an accessory signal. The authors analysed the role of CD28-mediated costimulation for T helper cell-independent activation of purified human CD8+ T cells in two different in vitro models. Freshly isolated CD8+ cells could be activated (proliferation, IL-2 production and cytotoxic activity) by anti-CD3-presenting Fc gamma R+ mouse cells transfected with the human CD28 ligand, CD80, as the only accessory signal. On the other hand, activation of CD8+ cells by allogeneic MHC class I on EBV-transformed B cells, which express two different CD28 ligands, CD80 and CD86, also proceeded very efficiently (proliferation, cytotoxic activity and CD25 expression), but was either not, or only partially, blocked by anti-CD80 and anti-CD86 MoAb or CTLA-4Ig. This indicates that other costimulatory signals are also effective, and that CD28 triggering is not absolutely required for initial T-cell activation. CsA and CD80/CD86-blocking agents were synergistic in completely inhibiting activation of CD8+ cells in the MLR with allogeneic B-cell lines. This combination also induced non-responsiveness of CD8+ cells upon restimulation in the absence of blocking agents. Therefore, although professional APC can apparently provide multiple costimulatory signals for direct activation of CD8+ T cells, the signal derived from CD80/CD86 is unique in providing CsA-resistance.

Predicting the activity coefficients of free-solvent for concentrated globular protein solutions using independently determined physical parameters.

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Devin W McBride

Full Text Available The activity coefficient is largely considered an empirical parameter that was traditionally introduced to correct the non-ideality observed in thermodynamic systems such as osmotic pressure. Here, the activity coefficient of free-solvent is related to physically realistic parameters and a mathematical expression is developed to directly predict the activity coefficients of free-solvent, for aqueous protein solutions up to near-saturation concentrations. The model is based on the free-solvent model, which has previously been shown to provide excellent prediction of the osmotic pressure of concentrated and crowded globular proteins in aqueous solutions up to near-saturation concentrations. Thus, this model uses only the independently determined, physically realizable quantities: mole fraction, solvent accessible surface area, and ion binding, in its prediction. Predictions are presented for the activity coefficients of free-solvent for near-saturated protein solutions containing either bovine serum albumin or hemoglobin. As a verification step, the predictability of the model for the activity coefficient of sucrose solutions was evaluated. The predicted activity coefficients of free-solvent are compared to the calculated activity coefficients of free-solvent based on osmotic pressure data. It is observed that the predicted activity coefficients are increasingly dependent on the solute-solvent parameters as the protein concentration increases to near-saturation concentrations.

Viral Restriction Activity of Feline BST2 Is Independent of Its N-Glycosylation and Induction of NF-κB Activation.

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Weiran Wang

Full Text Available BST2 (CD317, tetherin, HM1.24 is an interferon-inducible transmembrane protein which can directly inhibit the release of enveloped virus particles from infected cells, and its anti-viral activity is reported to be related to the specific topological arrangement of its four structural domains. The N-terminal cytoplasmic tail of feline BST2 (fBST2 is characterized by a shorter N-terminal region compared to those of other known homologs. In this study, we investigated the functional impact of modifying the cytoplasmic tail region of fBST2 and its molecular mechanism. The fBST2 protein with the addition of a peptide at the N-terminus retained anti-release activity against human immunodeficiency virus type-1 and pseudovirus based on feline immunodeficiency virus at a weaker level compared with the wild-type fBST2. However, the fBST2 protein with addition of a peptide internally in the ectodomain proximal to the GPI anchor still retained its anti-viral activity well. Notably, the N-glycosylation state and the cell surface level of the N-terminally modified variants were unlike those of the wild-type protein, while no difference was observed in their intracellular localizations. However, in contrast to human BST2, the wild-type fBST2 did not show the ability to activate NF-κB. Consistent with previous reports, our findings showed that adding a peptide in the cytoplasmic tail region of fBST2 may influence its anti-viral activity. The shorter N-terminal cytoplasmic region of fBST2 compared with human BST2 did not apparently affect its anti-viral activity, which is independent of its N-glycosylation and ability to activate NF-κB.

NKG2D performs two functions in invariant NKT cells: direct TCR-independent activation of NK-like cytolysis and co-stimulation of activation by CD1d.

Science.gov (United States)

Kuylenstierna, Carlotta; Björkström, Niklas K; Andersson, Sofia K; Sahlström, Peter; Bosnjak, Lidija; Paquin-Proulx, Dominic; Malmberg, Karl-Johan; Ljunggren, Hans-Gustaf; Moll, Markus; Sandberg, Johan K

2011-07-01

Invariant NKT cells are important in the activation and regulation of immune responses. They can also function as CD1d-restricted killer cells. However, the role of activating innate NK-cell receptors expressed on NKT cells in triggering cytolytic function is poorly characterized. Here, we initially confirmed that the cellular stress-ligand receptor NKG2D is expressed on CD4- NKT cells, whereas most CD4+ NKT cells lack this receptor. Interestingly, NKG2D+ NKT cells frequently expressed perforin, and both NKG2D and perforin localized at the site of contact with NKG2D ligand-expressing target cells. CD4- NKT cells degranulated in response to NKG2D engagement in a redirected activation assay independent of stimulation via their invariant TCR. NKT cells killed P815 cells coated with anti-NKG2D mAb and CD1d-negative K562 tumor target cells in an NKG2D-dependent manner. Furthermore, NKG2D engagement co-stimulated TCR-mediated NKT-cell activation in response to endogenous CD1d-presented ligands or suboptimal levels of anti-CD3 triggering. These data indicate that the CD4- subset of human NKT cells can mediate direct lysis of target cells via NKG2D engagement independent of CD1d, and that NKG2D also functions as a co-stimulatory receptor in these cells. NKG2D thus plays both a direct and a co-stimulatory role in the activation of NKT cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Potent HER3 Monoclonal Antibody That Blocks Both Ligand-Dependent and -Independent Activities: Differential Impacts of PTEN Status on Tumor Response.

Science.gov (United States)

Xiao, Zhan; Carrasco, Rosa A; Schifferli, Kevin; Kinneer, Krista; Tammali, Ravinder; Chen, Hong; Rothstein, Ray; Wetzel, Leslie; Yang, Chunning; Chowdhury, Partha; Tsui, Ping; Steiner, Philipp; Jallal, Bahija; Herbst, Ronald; Hollingsworth, Robert E; Tice, David A

2016-04-01

HER3/ERBB3 is a kinase-deficient member of the EGFR family receptor tyrosine kinases (RTK) that is broadly expressed and activated in human cancers. HER3 is a compelling cancer target due to its important role in activation of the oncogenic PI3K/AKT pathway. It has also been demonstrated to confer tumor resistance to a variety of cancer therapies, especially targeted drugs against EGFR and HER2. HER3 can be activated by its ligand (heregulin/HRG), which induces HER3 heterodimerization with EGFR, HER2, or other RTKs. Alternatively, HER3 can be activated in a ligand-independent manner through heterodimerization with HER2 in HER2-amplified cells. We developed a fully human mAb against HER3 (KTN3379) that efficiently suppressed HER3 activity in both ligand-dependent and independent settings. Correspondingly, KTN3379 inhibited tumor growth in divergent tumor models driven by either ligand-dependent or independent mechanisms in vitro and in vivo Most intriguingly, while investigating the mechanistic underpinnings of tumor response to KTN3379, we discovered an interesting dichotomy in that PTEN loss, a frequently occurring oncogenic lesion in a broad range of cancer types, substantially blunted the tumor response in HER2-amplified cancer, but not in the ligand-driven cancer. To our knowledge, this represents the first study ascertaining the impact of PTEN loss on the antitumor efficacy of a HER3 mAb. KTN3379 is currently undergoing a phase Ib clinical trial in patients with advanced solid tumors. Our current study may help us optimize patient selection schemes for KTN3379 to maximize its clinical benefits. Mol Cancer Ther; 15(4); 689-701. ©2016 AACR. ©2016 American Association for Cancer Research.

Pharmacological inhibition of lysosomes activates the MTORC1 signaling pathway in chondrocytes in an autophagy-independent manner.

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Newton, Phillip T; Vuppalapati, Karuna K; Bouderlique, Thibault; Chagin, Andrei S

2015-01-01

Mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) is a protein-signaling complex at the fulcrum of anabolic and catabolic processes, which acts depending on wide-ranging environmental cues. It is generally accepted that lysosomes facilitate MTORC1 activation by generating an internal pool of amino acids. Amino acids activate MTORC1 by stimulating its translocation to the lysosomal membrane where it forms a super-complex involving the lysosomal-membrane-bound vacuolar-type H(+)-ATPase (v-ATPase) proton pump. This translocation and MTORC1 activation require functional lysosomes. Here we found that, in contrast to this well-accepted concept, in epiphyseal chondrocytes inhibition of lysosomal activity by v-ATPase inhibitors bafilomycin A1 or concanamycin A potently activated MTORC1 signaling. The activity of MTORC1 was visualized by phosphorylated forms of RPS6 (ribosomal protein S6) and EIF4EBP1, 2 well-known downstream targets of MTORC1. Maximal RPS6 phosphorylation was observed at 48-h treatment and reached as high as a 12-fold increase (p lysosomes. Thus, our data show that in epiphyseal chondrocytes lysosomes inhibit MTORC1 in a macroautophagy-independent manner and this inhibition likely depends on v-ATPase activity.

Cell death is induced by ciglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, independently of PPARγ in human glioma cells

International Nuclear Information System (INIS)

Lee, Myoung Woo; Kim, Dae Seong; Kim, Hye Ryung; Kim, Hye Jin; Yang, Jin Mo; Ryu, Somi; Noh, Yoo Hun; Lee, Soo Hyun; Son, Meong Hi; Jung, Hye Lim; Yoo, Keon Hee; Koo, Hong Hoe; Sung, Ki Woong

2012-01-01

Highlights: ► Greater than 30 μM ciglitazone induces cell death in glioma cells. ► Cell death by ciglitazone is independent of PPARγ in glioma cells. ► CGZ induces cell death by the loss of MMP via decreased Akt. -- Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) regulates multiple signaling pathways, and its agonists induce apoptosis in various cancer cells. However, their role in cell death is unclear. In this study, the relationship between ciglitazone (CGZ) and PPARγ in CGZ-induced cell death was examined. At concentrations of greater than 30 μM, CGZ, a synthetic PPARγ agonist, activated caspase-3 and induced apoptosis in T98G cells. Treatment of T98G cells with less than 30 μM CGZ effectively induced cell death after pretreatment with 30 μM of the PPARγ antagonist GW9662, although GW9662 alone did not induce cell death. This cell death was also observed when cells were co-treated with CGZ and GW9662, but was not observed when cells were treated with CGZ prior to GW9662. In cells in which PPARγ was down-regulated cells by siRNA, lower concentrations of CGZ (<30 μM) were sufficient to induce cell death, although higher concentrations of CGZ (⩾30 μM) were required to induce cell death in control T98G cells, indicating that CGZ effectively induces cell death in T98G cells independently of PPARγ. Treatment with GW9662 followed by CGZ resulted in a down-regulation of Akt activity and the loss of mitochondrial membrane potential (MMP), which was accompanied by a decrease in Bcl-2 expression and an increase in Bid cleavage. These data suggest that CGZ is capable of inducing apoptotic cell death independently of PPARγ in glioma cells, by down-regulating Akt activity and inducing MMP collapse.

p53-independent structure-activity relationships of 3-ring mesogenic compounds' activity as cytotoxic effects against human non-small cell lung cancer lines.

Science.gov (United States)

Fukushi, Saori; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

2016-07-25

We recently demonstrated the cytotoxicity of liquid crystal precursors (hereafter referred to as "mesogenic compounds") in the human non-small cell lung cancer (NSCLC) cell line A549 which carry wild-type p53. p53 mutations are observed in 50 % of NSCLC and contribute to their resistance to chemotherapy. To develop more effective and cancer-specific agents, in this study, we investigated the structure-activity relationships of mesogenic compounds with cytotoxic effects against multiple NSCLC cells. The pharmacological effects of mesogenic compounds were examined in human NSCLC cells (A549, LU99, EBC-1, and H1299) and normal WI-38 human fibroblast. Analyses of the cell cycle, cell-death induction, and capsases expression were performed. The 3-ring compounds possessing terminal alkyl and hydroxyl groups (compounds C1-C5) showed cytotoxicity in NSCLC cells regardless of the p53 status. The compounds C1 and C3, which possess a pyrimidine at the center of the core, induced G2/M arrest, while the compounds without a pyrimidine (C2, C4, and C5) caused G1 arrest; all compounds produced caspase-mediated cell death. These events occurred in a p53-independent manner. Furthermore, it was suggested that compounds induced cell death through p53-independent DNA damage-signaling pathway. Compounds C2, C4, and C5 did not show strong cytotoxicity in WI-38 cells, whereas C1 and C3 did. However, the cytotoxicity of compound C1 against WI-38 cells was improved by modulating the terminal alkyl chain lengths of the compound. We showed the p53-indepdent structure-activity relationships of mesogenic compounds related to the cytotoxic effects. These structure-activity relationships will be helpful in the development of more effective and cancer-specific agents.

Dog walking is associated with more outdoor play and independent mobility for children.

Science.gov (United States)

Christian, Hayley; Trapp, Georgina; Villanueva, Karen; Zubrick, Stephen R; Koekemoer, Rachelle; Giles-Corti, Billie

2014-10-01

Dog ownership is positively associated with children's physical activity. It is plausible that dog-facilitated activity rather than dog ownership per se encourages children's physical activity behaviors. We examined relationships between dog walking and children's physical activity, and outdoor play and independent mobility. Cross-sectional survey data from the 2007 Perth (Western Australia) TRavel, Environment, and Kids (TREK) project were analyzed for 727 10-12 year olds with a family dog. Weekly minutes of overall physical activity and walking, local walking and outdoor play were collected from children and parents. Children's weekly pedometer steps were measured. Independent mobility was determined by active independent travel to 15 local destinations. Overall, 55% of children walked their dog. After adjustment, more dog walkers than non-dog walkers walked in the neighborhood (75% vs. 47%), played in the street (60% vs. 45%) and played in the yard (91% vs. 84%) (all p ≤ 0.05). Dog walkers were more independently mobile than non-dog walkers (p ≤ 0.001). Dog walking status was not associated with overall physical activity, walking, or pedometer steps (p>0.05). Dog-facilitated play and physical activity can be an effective strategy for increasing children's physical activity. Dog walking may provide a readily accessible and safe option for improving levels of independent mobility. Copyright © 2014 Elsevier Inc. All rights reserved.

Parents' experiences of participation in physical activities for children with cerebral palsy - protecting and pushing towards independence.

Science.gov (United States)

Lauruschkus, Katarina; Nordmark, Eva; Hallström, Inger

2017-04-01

To explore how parents of children with cerebral palsy (CP) experience their child's participation in physical activities and to identify facilitators and barriers for being physically active and reducing sedentary behaviour. Twenty-five parents of sixteen children, aged 8-11 years old with CP, with varying gross motor, cognitive and communicative functions and with different cultural backgrounds, participated in focus group or individual interviews. Content analysis was used for analysis. Five subcategories addressing children's participation in physical activity were found: "Belonging and taking space in the family", "Important persons facilitating and hindering", "Friends important but hard to get", "Good for the body but challenging" and "Availability and opting out possibilities". The subcategories built the main category "Protecting and pushing towards independence", expressing the challenges parents experienced when their child wanted to be physically active. Parents desire competent persons to be available for support in participation in physical activities. They want support in finding friends for their child to be physically active with. Family culture and attitudes affect their child's motivation for being physically active and should be taken into account when designing interventions for increased participation in physical activities and for reduced sedentary behaviour in children with disabilities. Implications for Rehabilitation Friends and competent adults facilitate participation in physical activities and reduce sedentary behaviour. Information on accessible and tailored physical activities is an important facilitator for participation in physical activities. Service planning and design of interventions may be facilitated by taking the individual family culture into account.

The Membrane-anchored Serine Protease Prostasin (CAP1/PRSS8) Supports Epidermal Development and Postnatal Homeostasis Independent of Its Enzymatic Activity

DEFF Research Database (Denmark)

Peters, Diane E; Szabo, Roman; Friis, Stine

2014-01-01

The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis. Here, we report the surprising finding that prostasin executes these functions independent of its own enzymatic activity. ...

A radiochemical technique for the establishment of a solvent-independent scale of ion activities in amphiprotic solvents

International Nuclear Information System (INIS)

Kim, J.I.; Duschner, H.; Born, H.J.

1975-01-01

The radiochemical determination of solubilities of hardly soluble compounds of silver (Ph 4 BAg, AgCl), by means of Ag-110m in amphiprotic solutions is used for setting-up a solvent-independent scale of ion activities based on the concept of the media effect. The media effects of the salts are calculated from the solubility data of the Ag compounds in question. The splitting into the media effects of single ions takes place with the extrathermodynamic assumption of the same media effects for large ions, such as Ph 4 B - = Ph 4 As - . A standardized ion activity scale in connection with the activity coefficients for the solvent in question can be established with water as the basic state of the chemical potential. As the sum of the media effects of the single ions gives the media effect of the salt concerned, which is easily obtained from data which are experimentally accessible (solubility, vapour pressure, ion exchange ect.), this method leads to single ion activities of a large number of ions in a multitude of solvents. (orig./LH) [de

Acrolein, an I-κBα-independent downregulator of NF-κB activity, causes the decrease in nitric oxide production in human malignant keratinocytes.

Science.gov (United States)

Moon, Ki-Young

2011-05-01

Acrolein, a reactive electrophilic α, β-unsaturated aldehyde, is known to be an alkylating chemical carcinogen. The effect of acrolein on the activation of NF-κB in human malignant epidermal keratinocytes was examined to elucidate the molecular mechanism associated with this NF-κB-acrolein regulation and its consecutive sequence, nitric oxide (NO) production. Acrolein significantly downregulated the cellular NF-κB activity up to 60% compared with control as well as the lipopolysaccharide (LPS)-induced NO production in a dose response manner at concentrations of 10~30 μM. To investigate the regulatory mechanism associated with this NF-κB-acrolein downregulation, the relative level of phosphorylation of I-κBα (serines-32 and -36), a principle regulator of NF-κB activation, represented by acrolein, was quantified. Acrolein inhibited NF-κB activity without altering cellular levels of the phosphorylated and nonphosphorylated forms of I-κBα, implying that the downregulatory effect of acrolein on cellular NF-κB activity in human skin cells is an I-κBα-independent activation pathway. The results suggests that acrolein causes the decrease in nitric oxide production as an I-κBα-independent downregulator of NF-κB activity in human malignant keratinocytes, and acrolein-induced carcinogenesis may be associated with the modulation of cellular NF-κB activity.

Detection of independent functional networks during music listening using electroencephalogram and sLORETA-ICA.

Science.gov (United States)

Jäncke, Lutz; Alahmadi, Nsreen

2016-04-13

The measurement of brain activation during music listening is a topic that is attracting increased attention from many researchers. Because of their high spatial accuracy, functional MRI measurements are often used for measuring brain activation in the context of music listening. However, this technique faces the issues of contaminating scanner noise and an uncomfortable experimental environment. Electroencephalogram (EEG), however, is a neural registration technique that allows the measurement of neurophysiological activation in silent and more comfortable experimental environments. Thus, it is optimal for recording brain activations during pleasant music stimulation. Using a new mathematical approach to calculate intracortical independent components (sLORETA-IC) on the basis of scalp-recorded EEG, we identified specific intracortical independent components during listening of a musical piece and scales, which differ substantially from intracortical independent components calculated from the resting state EEG. Most intracortical independent components are located bilaterally in perisylvian brain areas known to be involved in auditory processing and specifically in music perception. Some intracortical independent components differ between the music and scale listening conditions. The most prominent difference is found in the anterior part of the perisylvian brain region, with stronger activations seen in the left-sided anterior perisylvian regions during music listening, most likely indicating semantic processing during music listening. A further finding is that the intracortical independent components obtained for the music and scale listening are most prominent in higher frequency bands (e.g. beta-2 and beta-3), whereas the resting state intracortical independent components are active in lower frequency bands (alpha-1 and theta). This new technique for calculating intracortical independent components is able to differentiate independent neural networks associated

An RNA aptamer specific to Hsp70-ATP conformation inhibits its ATPase activity independent of Hsp40.

Science.gov (United States)

Thirunavukarasu, Deepak; Shi, Hua

2015-04-01

The highly conserved and ubiquitous molecular chaperone heat shock protein 70 (Hsp70) plays a critical role in protein homeostasis (proteostasis). Controlled by its ATPase activity, Hsp70 cycles between two conformations, Hsp70-ATP and Hsp70-ADP, to bind and release its substrate. Chemical tools with distinct modes of action, especially those capable of modulating the ATPase activity of Hsp70, are being actively sought after in the mechanistic dissection of this system. Here, we report a conformation-specific RNA aptamer that binds only to Hsp70-ATP but not to Hsp70-ADP. We have refined this aptamer and demonstrated its inhibitory effect on Hsp70's ATPase activity. We have also shown that this inhibitory effect on Hsp70 is independent of its interaction with the Hsp40 co-chaperone. As Hsp70 is increasingly being recognized as a drug target in a number of age related diseases such as neurodegenerative, protein misfolding diseases and cancer, this aptamer is potentially useful in therapeutic applications. Moreover, this work also demonstrates the feasibility of using aptamers to target ATPase activity as a general therapeutic strategy.

G protein-coupled estrogen receptor 1 (GPER1)/GPR30 increases ERK1/2 activity through PDZ motif-dependent and -independent mechanisms.

Science.gov (United States)

Gonzalez de Valdivia, Ernesto; Broselid, Stefan; Kahn, Robin; Olde, Björn; Leeb-Lundberg, L M Fredrik

2017-06-16

G protein-coupled receptor 30 (GPR30), also called G protein-coupled estrogen receptor 1 (GPER1), is thought to play important roles in breast cancer and cardiometabolic regulation, but many questions remain about ligand activation, effector coupling, and subcellular localization. We showed recently that GPR30 interacts through the C-terminal type I PDZ motif with SAP97 and protein kinase A (PKA)-anchoring protein (AKAP) 5, which anchor the receptor in the plasma membrane and mediate an apparently constitutive decrease in cAMP production independently of G i/o Here, we show that GPR30 also constitutively increases ERK1/2 activity. Removing the receptor PDZ motif or knocking down specifically AKAP5 inhibited the increase, showing that this increase also requires the PDZ interaction. However, the increase was inhibited by pertussis toxin as well as by wortmannin but not by AG1478, indicating that G i/o and phosphoinositide 3-kinase (PI3K) mediate the increase independently of epidermal growth factor receptor transactivation. FK506 and okadaic acid also inhibited the increase, implying that a protein phosphatase is involved. The proposed GPR30 agonist G-1 also increased ERK1/2 activity, but this increase was only observed at a level of receptor expression below that required for the constitutive increase. Furthermore, deleting the PDZ motif did not inhibit the G-1-stimulated increase. Based on these results, we propose that GPR30 increases ERK1/2 activity via two G i/o -mediated mechanisms, a PDZ-dependent, apparently constitutive mechanism and a PDZ-independent G-1-stimulated mechanism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

Science.gov (United States)

Waschki, Benjamin; Watz, Henrik; Holz, Olaf; Magnussen, Helgo; Olejnicka, Beata; Welte, Tobias; Rabe, Klaus F; Janciauskiene, Sabina

2017-01-01

Introduction Plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD). The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear. Methods In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV) and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle–brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined. Results The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD. GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis. Conclusion The data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level. PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations. PMID:28356730

Dopamine activates masculine sexual behavior independent of the estrogen receptor alpha.

Science.gov (United States)

Wersinger, S R; Rissman, E F

2000-06-01

Estrogen receptor alpha (ERalpha) is believed to be a critical part of the regulatory processes involved in normal reproduction and sexual behavior. However, in this study we show the ERalpha is not required for display of masculine sexual behavior. Male and female, ERalpha knock-out (ERalphaKO) and wild-type mice were gonadectomized and implanted with testosterone. Sexual behavior and social preferences were tested after injection of the dopamine agonist, apomorphine (APO), or vehicle. All wild-type mice showed normal masculine behavior, including mounts and pelvic thrusts in females, and ejaculation in males. In agreement with past reports, ERalphaKO mice, given vehicle, failed to show mating behavior. Yet, ERalphaKO males given APO showed masculine copulatory behavior and chemoinvestigatory behavior directed at females. ERalphaKO females, treated with APO, mounted and thrusted when tested with receptive females. HPLC revealed that wild-type and ERalphaKO mice had equivalent catecholamine content in brain regions associated with masculine sexual behavior. These data show that the ERalpha is not essential during development or adulthood for the expression of masculine sexual behavior in mice. Moreover, dopamine can activate sexual behavior via a mechanism that either acts on an ER other than ERalpha or via an estrogen-independent pathway.

Antigen-specific T cell activation independently of the MHC: chimeric antigen receptor (CAR-redirected T cells.

Directory of Open Access Journals (Sweden)

Hinrich eAbken

2013-11-01

Full Text Available Adoptive T cell therapy has recently shown powerful in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR which consists in the extracellular part of an antibody-derived domain for binding with a tumor-associated antigen and in the intracellular part of a TCR-derived signaling moiety for T cell activation. The specificity of CAR mediated T cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T cell targeting by an engineered CAR and review most significant progress recently made in early stage clinical trials to treat cancer.

Independent sector treatment centres: the first independent evaluation, a Scottish case study.

Science.gov (United States)

Pollock, Allyson M; Kirkwood, Graham

2009-07-01

The pound5 billion English Independent Sector Treatment Centre (ISTC) programme remains unevaluated because of a lack of published contract data and poor quality data returns. Scotland has a three-year pilot ISTC, the Scottish Regional Treatment Centre (SRTC), the contract for which is now in the public domain. This study aims to conduct an independent evaluation of the performance of the SRTC during the first year of operation. A retrospective analysis of the SRTC comparing activity as reported by hospital episode statistics returned to ISD Scotland with: volume and cost data in the SRTC contract; a 10-month audit carried out by management consultants Price Waterhouse Coopers (PWC); and an internal NHS Tayside performance report. All day-case and inpatient activity at the SRTC from 1 December 2006 to 31 January 2008. Activity and cost. The annual contract was based on patient referrals to the SRTC and not actual treatments. The contract was awarded on the basis of 2624 referrals a year, total value of pound5,667,464. According to ISD data, the SRTC performed 831 procedures (32% of annual contract) in the first 13 months worth pound1,035,603 (18%). PWC's figures report 2200 referrals (84%) to the SRTC at a cost of 2,642,000 (47%) in the first 10 months. Basing the SRTC contract on payments for referrals rather than actual treatment represents a major departure from normal standards of reporting and commissioning and may have resulted in over-payment for referrals for patients who did not receive treatment of up to pound3 million in the first 10 months. The PWC report falls well below the standards one would expect of an independent evaluation and we were unable to validate PWC's analysis and the claim of value for money. If wave-one ISTCs in England perform similarly to the SRTC then as much as pound927 million may have been paid for patients who did not receive treatment. We recommend a moratorium on all ISTC contracts until the contracts have been published and

Versatile spectrometer for experiments using synchrotron radiation at wavelengths greater than 100 nm

International Nuclear Information System (INIS)

Sutherland, J.C.; Desmond, E.J.; Takacs, P.Z.

1979-01-01

The design of the SUPERB spectrometer places great emphasis on flexibility. Optics, electronics and the attendant computer system are of modular design and can be rapidly configured to perform a variety of tasks. This flexibility will permit SUPERB to perform the various experiments described above. Equally important, it should facilitate adaption of SUPERB to perform experiments the nature of which we are presently unaware

Qualification of organizations for independent technical supervision

International Nuclear Information System (INIS)

1981-04-01

The requirements are established on trial for the qualification of an organization as an independent technical supervision organization in nuclear facilities, in activities related with quality assurance programs. (I.C.R.) [pt

The frequency-independent control method for distributed generation systems

DEFF Research Database (Denmark)

Naderi, Siamak; Pouresmaeil, Edris; Gao, Wenzhong David

2012-01-01

In this paper a novel frequency-independent control method suitable for distributed generation (DG) is presented. This strategy is derived based on the . abc/. αβ transformation and . abc/. dq transformation of the ac system variables. The active and reactive currents injected by the DG are contr......In this paper a novel frequency-independent control method suitable for distributed generation (DG) is presented. This strategy is derived based on the . abc/. αβ transformation and . abc/. dq transformation of the ac system variables. The active and reactive currents injected by the DG...

The angiotensin type 1 receptor activates extracellular signal-regulated kinases 1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and langendorff-perfused hearts

DEFF Research Database (Denmark)

Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael

2007-01-01

The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G protein-independently through beta-arrestin2 in cellular expression systems. As activation mechanisms may greatly influence the biological...... effects of ERK1/2 activity, differential activation of the AT(1)R in its native cellular context could have important biological and pharmacological implications. To examine if AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] Ang......II) analogue in native preparations of cardiac myocytes and beating hearts. We found that [SII] AngII does not activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta-arrestin2-scaffolded pool remains...

The Effect of Teaching Metacognitive Listening Strategy during Shadowing Activity on Field-Dependent and Field-Independent EFL Learners’ Listening Comprehension

Directory of Open Access Journals (Sweden)

Parastoo Alizadeh Oghyanous

2017-11-01

Full Text Available This study aimed to compare the effect of teaching metacognitive listening strategies through shadowing activity on the listening comprehension of field-dependent (FD and field-independent (FI EFL learners. Since the researcher had access only to female participants,85 female EFL learners from a language institute in Tehran, at the pre-intermediate level of proficiency with the age range of 18-35 were selected out of the initial 120 participants based on their performance on a piloted PET. The Group Embedded Figures Test (GEFT was administered to the selected participants in order to categorize them into the two experimental groups (49 FD and 36 FI. The participants including both FD and FI sat in several classes. During a five-week instruction period (twice a week, both groups practiced listening comprehension for 45 minutes through a combination of shadowing activity, and metacognitive strategy instruction with no difference in treatment. The results of the independent samples t-test demonstrated that there was no significant difference between listening posttest scores of FI and FD groups. Therefore, it was concluded that metacognitive strategy training coupled with shadowing activity could be equally beneficial in terms of listening proficiency for all students regardless of their perceptual tendency (FD/FI. The findings of the present study have implications for language teachers regarding metacognitive strategy training and listening comprehension enhancement.

Characterization of NMDAR-independent learning in the hippocampus.

Directory of Open Access Journals (Sweden)

Kaycie Kuss Tayler

2011-05-01

Full Text Available It is currently thought that memory formation requires the activation of NMDA receptors (NMDARs in the hippocampus. However, recent studies indicate that these receptors are not necessary for all forms of learning. The current experiments examine this issue using context fear conditioning in mice. First, we show that context fear can be acquired without NMDAR activation in previously trained animals. Mice trained in one environment (context A are subsequently able to learn about a second environment (context B in the presence of NMDAR antagonists. Second, we demonstrate that NMDAR-independent learning requires the hippocampus and is dependent on protein synthesis. However, unlike NMDAR-dependent learning, it is not contingent on the expression of activity-regulated cytoskeleton-associated protein (Arc. Lastly, we present data that suggests NMDAR-independent learning is only observed when recently stimulated neurons are re-activated during conditioning. These data suggest that context fear conditioning modifies synaptic plasticity mechanisms in the hippocampus and allows subsequent learning to occur in the absence of NMDAR activation.

Independent Associations and Interactions of Perceived Neighborhood and Psychosocial Constructs on Adults' Physical Activity.

Science.gov (United States)

Dwyer, Laura A; Patel, Minal; Nebeling, Linda C; Oh, April Y

2018-05-01

Neighborhood and psychosocial variables are related to physical activity (PA), yet interactions between these factors in predicting PA are infrequently studied. This analysis examines the independent associations and interactions between self-reported neighborhood and psychosocial variables in relation to moderate to vigorous PA (MVPA) among adults from a US panel sample. In adjusted models, neighborhood social capital was positively associated with meeting MVPA guidelines. Fewer barriers, greater self-efficacy, and greater autonomous motivation also corresponded with greater odds of meeting MVPA guidelines. An interaction between social capital and autonomous motivation showed that social capital was only associated with MVPA when autonomous motivation was high. Participants who reported both high autonomous motivation and high social capital were most likely to meet MVPA guidelines. Neighborhood social capital, barriers, self-efficacy, and autonomous motivation may be important correlates in promoting adults' PA. Future directions include using objective neighborhood and PA data in similar analyses and investigating associations of neighborhood and psychosocial variables with multiple PA activities. Intervention research to promote PA should also examine whether effects of interventions targeting psychosocial constructs are moderated by features of an individual's neighborhood or whether perceived social capital can be addressed in interventions in conjunction with psychosocial variables.

Release from Xenopus oocyte prophase I meiotic arrest is independent of a decrease in cAMP levels or PKA activity.

Science.gov (United States)

Nader, Nancy; Courjaret, Raphael; Dib, Maya; Kulkarni, Rashmi P; Machaca, Khaled

2016-06-01

Vertebrate oocytes arrest at prophase of meiosis I as a result of high levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activity. In Xenopus, progesterone is believed to release meiotic arrest by inhibiting adenylate cyclase, lowering cAMP levels and repressing PKA. However, the exact timing and extent of the cAMP decrease is unclear, with conflicting reports in the literature. Using various in vivo reporters for cAMP and PKA at the single-cell level in real time, we fail to detect any significant changes in cAMP or PKA in response to progesterone. More interestingly, there was no correlation between the levels of PKA inhibition and the release of meiotic arrest. Furthermore, we devised conditions whereby meiotic arrest could be released in the presence of sustained high levels of cAMP. Consistently, lowering endogenous cAMP levels by >65% for prolonged time periods failed to induce spontaneous maturation. These results argue that the release of oocyte meiotic arrest in Xenopus is independent of a reduction in either cAMP levels or PKA activity, but rather proceeds through a parallel cAMP/PKA-independent pathway. © 2016. Published by The Company of Biologists Ltd.

The nutrient transceptor/PKA pathway functions independently of TOR and responds to leucine and Gcn2 in a TOR-independent manner.

Science.gov (United States)

Conrad, Michaela; Kankipati, Harish Nag; Kimpe, Marlies; Van Zeebroeck, Griet; Zhang, Zhiqiang; Thevelein, Johan M

2017-08-01

Two nutrient-controlled signalling pathways, the PKA and TOR pathway, play a major role in nutrient regulation of growth as well as growth-correlated properties in yeast. The relationship between the two pathways is not well understood. We have used Gap1 and Pho84 transceptor-mediated activation of trehalase and phosphorylation of fragmented Sch9 as a read-out for rapid nutrient activation of PKA or TORC1, respectively. We have identified conditions in which L-citrulline-induced activation of Sch9 phosphorylation is compromised, but not activation of trehalase: addition of the TORC1 inhibitor, rapamycin and low levels of L-citrulline. The same disconnection was observed for phosphate activation in phosphate-starved cells. The leu2 auxotrophic mutation reduces amino acid activation of trehalase, which is counteracted by deletion of GCN2. Both effects were also independent of TORC1. Our results show that rapid activation of the TOR pathway by amino acids is not involved in rapid activation of the PKA pathway and that effects of Gcn2 inactivation as well as leu2 auxotrophy all act independently of the TOR pathway. Hence, rapid nutrient signalling to PKA and TOR in cells arrested by nutrient starvation acts through parallel pathways. © FEMS 2017.

Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

International Nuclear Information System (INIS)

Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J.; Bridges, Lance C.

2014-01-01

Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH) 2 D 3 , a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion

Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

Energy Technology Data Exchange (ETDEWEB)

Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J. [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); Bridges, Lance C., E-mail: bridgesl@ecu.edu [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); East Carolina Diabetes and Obesity Institute, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)

2014-11-28

Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.

Large-Area High-Performance Flexible Pressure Sensor with Carbon Nanotube Active Matrix for Electronic Skin.

Science.gov (United States)

Nela, Luca; Tang, Jianshi; Cao, Qing; Tulevski, George; Han, Shu-Jen

2018-03-14

Artificial "electronic skin" is of great interest for mimicking the functionality of human skin, such as tactile pressure sensing. Several important performance metrics include mechanical flexibility, operation voltage, sensitivity, and accuracy, as well as response speed. In this Letter, we demonstrate a large-area high-performance flexible pressure sensor built on an active matrix of 16 × 16 carbon nanotube thin-film transistors (CNT TFTs). Made from highly purified solution tubes, the active matrix exhibits superior flexible TFT performance with high mobility and large current density, along with a high device yield of nearly 99% over 4 inch sample area. The fully integrated flexible pressure sensor operates within a small voltage range of 3 V and shows superb performance featuring high spatial resolution of 4 mm, faster response than human skin (<30 ms), and excellent accuracy in sensing complex objects on both flat and curved surfaces. This work may pave the road for future integration of high-performance electronic skin in smart robotics and prosthetic solutions.

Self-reported preparation of Polish midwives for independent performance of prophylactic activities within the scope of women's diseases and obstetric pathologies.

Science.gov (United States)

Iwanowicz-Palus, Grażyna J; Rzońca, Ewa; Bień, Agnieszka; Włoszczak-Szubzda, Anna

2014-01-01

The objective of the study is an attempt to recognize self-reported preparation of midwives for an independent performance of prophylactic activities within the scope of women's diseases and obstetric pathologies. The study was conducted in a representative all-Polish population sample of 3,569 midwives, by the method of a diagnostic survey using a questionnaire technique. The research instrument was a questionnaire form designed by the author containing items concerning the characteristics of respondents and the object of the study, constructed based on the 5-point Liker scale. The relationships between the variables were verified using chi-square test (χ(2)) of independence. The p values pindependent performance of prophylactic activities in the area of women's diseases (84.28%) and obstetric pathologies (77.95%). However, nearly every tenth midwife, irrespective of the region of Poland where she lives, age, and participation in post-graduate training, is not prepared for an independent performance of the prevention of women's diseases. In turn, the lack of preparation for carrying out prevention of women's diseases was admitted mainly by midwives from the northern and central regions of Poland, aged 31-40, possessing post-secondary school education, who did not participate in any form of post-graduate training. The results of studies and analysis of the relevant literature indicate that it is necessary for midwives to improve their qualifications in the area of prophylaxis of women's diseases and obstetric pathologies through participation in various forms of post-graduate education.

Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

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Waschki B

2017-03-01

Full Text Available Benjamin Waschki,1–3 Henrik Watz,2,3 Olaf Holz,4,5 Helgo Magnussen,2,3 Beata Olejnicka,6 Tobias Welte,5,7 Klaus F Rabe,1,3 Sabina Janciauskiene5,7 1Pneumology, LungenClinic Grosshansdorf, Grosshansdorf, Germany; 2Pulmonary Research Institute at LungenClinic Grosshansdorf, Grosshansdorf, Germany; 3Airway Research Center North (ARCN, German Center for Lung Research (DZL, Grosshansdorf, Germany; 4Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany; 5Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH, German Center for Lung Research (DZL, Hannover, Germany; 6Department of Medicine, Trelleborg Hospital, Trelleborg, Sweden; 7Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany Introduction: Plasminogen activator inhibitor-1 (PAI-1, a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD. The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear. Methods: In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP, adiponectin, ankle–brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined. Results: The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed

Caffeine and contraction synergistically stimulate 5'-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle.

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Tsuda, Satoshi; Egawa, Tatsuro; Kitani, Kazuto; Oshima, Rieko; Ma, Xiao; Hayashi, Tatsuya

2015-10-01

5'-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr(172) phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser(473) phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological

Higher Language Ability is Related to Angular Gyrus Activation Increase During Semantic Processing, Independent of Sentence Incongruency

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Van Ettinger-Veenstra, Helene; McAllister, Anita; Lundberg, Peter; Karlsson, Thomas; Engström, Maria

2016-01-01

This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task—which tapped language comprehension and inference, and modulated sentence congruency—employing functional magnetic resonance imaging (fMRI). We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, there was a significant increase of activation in the inferior frontal gyrus (IFG) bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing, is opposed to what the neural efficiency hypothesis would predict. We can conclude that no evidence is found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation. PMID

Higher language ability is related to angular gyrus activation increase during semantic processing, independent of sentence incongruency

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Helene eVan Ettinger-Veenstra

2016-03-01

Full Text Available This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task - which tapped language comprehension and inference, and modulated sentence congruency - employing functional magnetic resonance imaging. We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, a significant increase of activation in the inferior frontal gyrus bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing is opposed to what the neural efficiency hypothesis would predict. We can conclude that there is no evidence found for an interaction between semantic congruency related brain activation and high-level language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation.

Cysteine-independent activation/inhibition of heme oxygenase-2

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Dragic Vukomanovic

2016-01-01

Full Text Available Reactive thiols of cysteine (cys residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2 isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2 and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

Cysteine-independent activation/inhibition of heme oxygenase-2.

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Vukomanovic, Dragic; Rahman, Mona N; Maines, Mahin D; Ozolinš, Terence Rs; Szarek, Walter A; Jia, Zongchao; Nakatsu, Kanji

2016-03-01

Reactive thiols of cysteine (cys) residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2) isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2) and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD) and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

The influence of demographic, environmental and physical factors on functional independence post stroke

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M.V. Mamabolo

2008-01-01

Full Text Available Purpose: The magnitude of disability observed in strokesurvivors is believed to be dependent in part, on the severity of neurological deficits incurred. A s important but less well understood, is thecontribution of demographic, physical and environmental factors. The objective of this study was to establish what demographic, environmentaland physical factors influence functional independence post stroke. Method: Convenience sampling was used in the selection of subjects from four stroke outpatient public health facilities in the Gauteng Province of South Africa. The data were collected using a structured questionnaire. The analytical tools used included descriptive statistics to measure percentages and cross tabulations to measure the level of associations between functional independence and some of the demographic factors. The Barthel Index was computed to establish the degree of functional independence. Finally the influence of factors on functional independence was investigated using bivariate logistic regressions.Results: The results showed that younger patients (18 - 34 yrs may have a higher likelihood of functional independence compared to older patients at the time of discharge from hospital (18 - 34 years: Odds Ratio = 1. Patients without helpers were more likely to be functionally independent than those with a helper (p = 0.03. Involvement in household activities (p = 0.01, participation in community activities (p = 0.02 and bowel and bladder continence (p = 0.003 and p = 0.04 improved the likelihood of functional independence.Conclusion and im plications: Factors that influence functional independence post stroke are: age, bowel and bladder continence, the presence of a caregiver, participation in household and community activities. It is also of value to encourage patients to participate in household and community activities post stroke as well as being less dependent on helpers in an effort to attain functional independence post

Gauge-Origin Independent Formulation and Implementation of Magneto-Optical Activity within Atomic-Orbital-Density Based Hartree-Fock and Kohn-Sham Response Theories

DEFF Research Database (Denmark)

Kjærgaard, Thomas; Jørgensen, Poul; Thorvaldsen, Andreas

2009-01-01

A Lagrangian approach has been used to derive gauge-origin independent expressions for two properties that rationalize magneto-optical activity, namely the Verdet constant V(ω) of the Faraday effect and the B term of magnetic circular dichroism. The approach is expressed in terms of an atomic-orb...

Human Mediator Enhances Activator-Facilitated Recruitment of RNA Polymerase II and Promoter Recognition by TATA-Binding Protein (TBP) Independently of TBP-Associated Factors

OpenAIRE

Wu, Shwu-Yuan; Zhou, Tianyuan; Chiang, Cheng-Ming

2003-01-01

Mediator is a general cofactor implicated in the functions of many transcriptional activators. Although Mediator with different protein compositions has been isolated, it remains unclear how Mediator facilitates activator-dependent transcription, independent of its general stimulation of basal transcription. To define the mechanisms of Mediator function, we isolated two forms of human Mediator complexes (Mediator-P.5 and Mediator-P.85) and demonstrated that Mediator-P.5 clearly functions by e...

Simvastatin induces caspase-independent apoptosis in LPS-activated RAW264.7 macrophage cells

International Nuclear Information System (INIS)

Kim, Yong Chan; Song, Seok Bean; Lee, Mi Hee; Kang, Kwang Il; Lee, Hayyoung; Paik, Sang-Gi; Kim, Kyoon Eon; Kim, Young Sang

2006-01-01

Macrophages participate in several inflammatory pathologies such as sepsis and arthritis. We examined the effect of simvastatin on the LPS-induced proinflammatory macrophage RAW264.7 cells. Co-treatment of LPS and a non-toxic dose of simvastatin induced cell death in RAW264.7 cells. The cell death was accompanied by disruption of mitochondrial membrane potential (MMP), genomic DNA fragmentation, and caspase-3 activation. Surprisingly, despite caspase-dependent apoptotic cascade being completely blocked by Z-VAD-fmk, a pan-caspase inhibitor, the cell death was only partially repressed. In the presence of Z-VAD-fmk, DNA fragmentation was blocked, but DNA condensation, disruption of MMP, and nuclear translocation of apoptosis inducing factor were obvious. The cell death by simvastatin and LPS was effectively decreased by both the FPP and GGPP treatments as well as mevalonate. Our findings indicate that simvastatin triggers the cell death of LPS-treated RAW264.7 cells through both caspase-dependent and -independent apoptotic pathways, suggesting a novel mechanism of statins for the severe inflammatory disease therapy

Importance of constitutive activity and arrestin-independent mechanisms for intracellular trafficking of the ghrelin receptor

DEFF Research Database (Denmark)

Holliday, Nicholas D; Holst, Birgitte; Rodionova, Elena A

2007-01-01

. Furthermore the interaction between phosphorylated receptors and beta-arrestin adaptor proteins has been examined. Replacement of the FLAG-tagged GhrelinR C tail with the equivalent GPR39 domain (GhR-39 chimera) preserved G(q) signaling. However in contrast to the GhrelinR, GhR-39 receptors exhibited no basal......,9), Leu(11)] substance P and a naturally occurring mutant GhrelinR (A204E) with eliminated constitutive activity inhibited basal GhrelinR internalization. Surprisingly, we found that noninternalizing GPR39 was highly phosphorylated and that basal and agonist-induced phosphorylation of the GhR-39 chimera......, but the high levels of GPR39 phosphorylation, and of the GhR-39 chimera, are not sufficient to drive endocytosis. In addition, basal GhrelinR internalization occurs independently of beta-arrestins....

Activation of estrogen receptor beta (ERβ) regulates the expression of N-cadherin, E-cadherin and β-catenin in androgen-independent prostate cancer cells.

Science.gov (United States)

Silva, Rafael de Souza; Lombardi, Ana Paola G; de Souza, Deborah Simão; Vicente, Carolina M; Porto, Catarina S

2018-03-01

The aim of the present study was to investigate the impact of the activation of estrogen receptors on expression and localization of N-cadherin, E-cadherin and non-phosphorylated β-catenin in androgen-independent prostate cancer cells (PC-3 and DU-145) and in human post pubertal prostate epithelial cells (PNT1A). Expression of N-cadherin was detected in PNT1A and PC-3 cells, but not in DU-145 cells. E-cadherin was detected only in DU-145 cells and β-catenin was detected in all cells studied. N-cadherin and β-catenin were located preferentially in the cellular membrane of PNT1A cells and in the cytoplasm of PC-3 cells. E-cadherin and β-catenin were located preferentially in the cellular membrane of DU-145 cells. 17β-estradiol (E2) or the ERα-selective agonist PPT did not affect the content and localization of N-cadherin in PC-3 and PNT1A cells or E-cadherin in DU-145 cells. In PC-3 cells, ERβ-selective agonist DPN decreased the expression of N-cadherin. DPN-induced downregulation of N-cadherin was blocked by pretreatment with the ERβ-selective antagonist (PHTPP), indicating that ERβ1 is the upstream receptor regulating the expression of N-cadherin. In DU-145 cells, the activation of ERβ1 by DPN increased the expression of E-cadherin. Taken together, these results suggest that activation of ERβ1 is required to maintain an epithelial phenotype in PC-3 and DU-145 cells. The activation of ERβ1 also increased the expression of β-catenin in cytoplasm of PC-3 and in the cellular membrane of DU-145 cells. In conclusion, our results indicate differential expression and localization of N-cadherin, E-cadherin and β-catenin in androgen-independent prostate cancer cells. The reduction of N-cadherin content by activation of ERβ, exclusively observed in androgen-independent prostate cancer cells (PC-3), may be related to the activation of signaling pathways, such as the release of β-catenin into the cytoplasm, translocation of β-catenin to the nucleus and

Field Dependence-Independence and Physical Activity Engagement among Middle School Students

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Liu, Wenhao; Chepyator-Thomson, Jepkorir Rose

2009-01-01

Background: Field dependence-independence (FDI) is a tendency to rely on external frames (given situations and authoritative people) or internal frames (oneself, including one's own body) for one's information processing and behavior. Literature has constantly reported that field-dependent (FD) individuals, who are less autonomous in…

Regulation of mTORC1 Signaling by Src Kinase Activity Is Akt1-Independent in RSV-Transformed Cells

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Martina Vojtěchová

2008-02-01

Full Text Available Increased activity of the Src tyrosine protein kinase that has been observed in a large number of human malignancies appears to be a promising target for drug therapy. In the present study, a critical role of the Src activity in the deregulation of mTOR signaling pathway in Rous sarcoma virus (RSV-transformed hamster fibroblasts, H19 cells, was shown using these cells treated with the Src-specific inhibitor, SU6656, and clones of fibroblasts expressing either the active Src or the dominant-negative Src kinase-dead mutant. Disruption of the Src kinase activity results in substantial reduction of the phosphorylation and activity of the Akt/protein kinase B (PKB, phosphorylation of tuberin (TSC2, mammalian target of rapamycin (mTOR, S6K1, ribosomal protein S6, and eukaryotic initiation factor 4E-binding protein 4E-BP1. The ectopic, active Akt1 that was expressed in Src-deficient cells significantly enhanced phosphorylation of TSC2 in these cells, but it failed to activate the inhibited components of the mTOR pathway that are downstream of TSC2. The data indicate that the Src kinase activity is essential for the activity of mTOR-dependent signaling pathway and suggest that mTOR targets may be controlled by Src independently of Akt1/TSC2 cascade in cells expressing hyperactive Src protein. These observations might have an implication in drug resistance to mTOR inhibitor-based cancer therapy in certain cell types.

Caffeine and contraction synergistically stimulate 5′-AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle

Science.gov (United States)

Tsuda, Satoshi; Egawa, Tatsuro; Kitani, Kazuto; Oshima, Rieko; Ma, Xiao; Hayashi, Tatsuya

2015-01-01

5′-Adenosine monophosphate-activated protein kinase (AMPK) has been identified as a key mediator of contraction-stimulated insulin-independent glucose transport in skeletal muscle. Caffeine acutely stimulates AMPK in resting skeletal muscle, but it is unknown whether caffeine affects AMPK in contracting muscle. Isolated rat epitrochlearis muscle was preincubated and then incubated in the absence or presence of 3 mmol/L caffeine for 30 or 120 min. Electrical stimulation (ES) was used to evoke tetanic contractions during the last 10 min of the incubation period. The combination of caffeine plus contraction had additive effects on AMPKα Thr172 phosphorylation, α-isoform-specific AMPK activity, and 3-O-methylglucose (3MG) transport. In contrast, caffeine inhibited basal and contraction-stimulated Akt Ser473 phosphorylation. Caffeine significantly delayed muscle fatigue during contraction, and the combination of caffeine and contraction additively decreased ATP and phosphocreatine contents. Caffeine did not affect resting tension. Next, rats were given an intraperitoneal injection of caffeine (60 mg/kg body weight) or saline, and the extensor digitorum longus muscle was dissected 15 min later. ES of the sciatic nerve was performed to evoke tetanic contractions for 5 min before dissection. Similar to the findings from isolated muscles incubated in vitro, the combination of caffeine plus contraction in vivo had additive effects on AMPK phosphorylation, AMPK activity, and 3MG transport. Caffeine also inhibited basal and contraction-stimulated Akt phosphorylation in vivo. These findings suggest that caffeine and contraction synergistically stimulate AMPK activity and insulin-independent glucose transport, at least in part by decreasing muscle fatigue and thereby promoting energy consumption during contraction. PMID:26471759

Independence: proposing an initial framework for occupational therapy.

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Collins, Bethan

2017-11-01

The concept of independence is common in occupational therapy theory and practice but has rarely been clearly defined or conceptualized within in occupational therapy literature and there seems to be no standard definition. This can result in ambiguity, which potentially jeopardizes client-centred practice. This paper proposes an occupational therapy independence framework (OTIF) that synthesizes the range of characterizations of independence in a practically useful and occupation-centred manner. A review of literature, clinical experience, doctoral research and conversations with occupational therapists and disabled people, in particular those involved in a disability activism group and people with physical disabilities, has led to the development of the OTIF. Independence and interdependence, as characterized in the OTIF, occur when an individual exerts choice over occupational performance and can engage in occupations in a manner acceptable to the individual. Interdependence results when occupations are performed with another person whereas independence involves solitary occupational performance. Dependence typically results from inability to choose occupations or a mismatch between performance capacity and environmental factors. The OTIF has the potential to clarify the conceptualization of independence within occupational therapy theory and practice. This initial proposal is presented to stimulate debate and discussion.

Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps.

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García-Salcedo, Raúl; Lubitz, Timo; Beltran, Gemma; Elbing, Karin; Tian, Ye; Frey, Simone; Wolkenhauer, Olaf; Krantz, Marcus; Klipp, Edda; Hohmann, Stefan

2014-04-01

The AMP-activated protein kinase, AMPK, controls energy homeostasis in eukaryotic cells but little is known about the mechanisms governing the dynamics of its activation/deactivation. The yeast AMPK, SNF1, is activated in response to glucose depletion and mediates glucose de-repression by inactivating the transcriptional repressor Mig1. Here we show that overexpression of the Snf1-activating kinase Sak1 results, in the presence of glucose, in constitutive Snf1 activation without alleviating glucose repression. Co-overexpression of the regulatory subunit Reg1 of the Glc-Reg1 phosphatase complex partly restores glucose regulation of Snf1. We generated a set of 24 kinetic mathematical models based on dynamic data of Snf1 pathway activation and deactivation. The models that reproduced our experimental observations best featured (a) glucose regulation of both Snf1 phosphorylation and dephosphorylation, (b) determination of the Mig1 phosphorylation status in the absence of glucose by Snf1 activity only and (c) a regulatory step directing active Snf1 to Mig1 under glucose limitation. Hence it appears that glucose de-repression via Snf1-Mig1 is regulated by glucose via at least two independent steps: the control of activation of the Snf1 kinase and directing active Snf1 to inactivating its target Mig1. © 2014 FEBS.

Self-reported preparation of Polish midwives for independent performance of prophylactic activities within the scope of women’s diseases and obstetric pathologies

Directory of Open Access Journals (Sweden)

Grażyna J. Iwanowicz-Palus

2014-06-01

Full Text Available objective. The objective of the study is an attempt to recognize self-reported preparation of midwives for an independent performance of prophylactic activities within the scope of women’s diseases and obstetric pathologies. material and methods. The study was conducted in a representative all-Polish population sample of 3,569 midwives, by the method of a diagnostic survey using a questionnaire technique. The research instrument was a questionnaire form designed by the author containing items concerning the characteristics of respondents and the object of the study, constructed based on the 5-point Liker scale. The relationships between the variables were verified using chi-square test (χ [sup]2[/sup] of independence. The p values p<0.05 were considered statistically significant. results. Analysis of results allows the presumption that in the opinions of midwives the majority of them are prepared for the independent performance of prophylactic activities in the area of women’s diseases (84.28% and obstetric pathologies (77.95%. However, nearly every tenth midwife, irrespective of the region of Poland where she lives, age, and participation in post-graduate training, is not prepared for an independent performance of the prevention of women’s diseases. In turn, the lack of preparation for carrying out prevention of women’s diseases was admitted mainly by midwives from the northern and central regions of Poland, aged 31–40, possessing post-secondary school education, who did not participate in any form of post-graduate training. conclusions. The results of studies and analysis of the relevant literature indicate that it is necessary for midwives to improve their qualifications in the area of prophylaxis of women’s diseases and obstetric pathologies through participation in various forms of post-graduate education

Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways

Science.gov (United States)

Hanno-Iijima, Yoko; Tanaka, Masami; Iijima, Takatoshi

2015-01-01

Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses. PMID:26241953

Cell death is induced by ciglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist, independently of PPARγ in human glioma cells.

Science.gov (United States)

Lee, Myoung Woo; Kim, Dae Seong; Kim, Hye Ryung; Kim, Hye Jin; Yang, Jin Mo; Ryu, Somi; Noh, Yoo Hun; Lee, Soo Hyun; Son, Meong Hi; Jung, Hye Lim; Yoo, Keon Hee; Koo, Hong Hoe; Sung, Ki Woong

2012-01-06

Peroxisome proliferator-activated receptor γ (PPARγ) regulates multiple signaling pathways, and its agonists induce apoptosis in various cancer cells. However, their role in cell death is unclear. In this study, the relationship between ciglitazone (CGZ) and PPARγ in CGZ-induced cell death was examined. At concentrations of greater than 30 μM, CGZ, a synthetic PPARγ agonist, activated caspase-3 and induced apoptosis in T98G cells. Treatment of T98G cells with less than 30 μM CGZ effectively induced cell death after pretreatment with 30 μM of the PPARγ antagonist GW9662, although GW9662 alone did not induce cell death. This cell death was also observed when cells were co-treated with CGZ and GW9662, but was not observed when cells were treated with CGZ prior to GW9662. In cells in which PPARγ was down-regulated cells by siRNA, lower concentrations of CGZ (death, although higher concentrations of CGZ (≥30 μM) were required to induce cell death in control T98G cells, indicating that CGZ effectively induces cell death in T98G cells independently of PPARγ. Treatment with GW9662 followed by CGZ resulted in a down-regulation of Akt activity and the loss of mitochondrial membrane potential (MMP), which was accompanied by a decrease in Bcl-2 expression and an increase in Bid cleavage. These data suggest that CGZ is capable of inducing apoptotic cell death independently of PPARγ in glioma cells, by down-regulating Akt activity and inducing MMP collapse. Copyright © 2011 Elsevier Inc. All rights reserved.

Central Bank independence

Directory of Open Access Journals (Sweden)

Vasile DEDU

2012-08-01

Full Text Available In this paper we present the key aspects regarding central bank’s independence. Most economists consider that the factor which positively influences the efficiency of monetary policy measures is the high independence of the central bank. We determined that the National Bank of Romania (NBR has a high degree of independence. NBR has both goal and instrument independence. We also consider that the hike of NBR’s independence played an important role in the significant disinflation process, as headline inflation dropped inside the targeted band of 3% ± 1 percentage point recently.

Novel Sensor Technology To Assess Independence and Limb-Use Laterality in Cervical Spinal Cord Injury.

Science.gov (United States)

Brogioli, Michael; Popp, Werner L; Albisser, Urs; Brust, Anne K; Frotzler, Angela; Gassert, Roger; Curt, Armin; Starkey, Michelle L

2016-11-01

After spinal cord injury (SCI), levels of independence are commonly assessed with standardized clinical assessments. However, such tests do not provide information about the actual extent of upper limb activities or the impact on independence of bi- versus unilateral usage throughout daily life following cervical SCI. The objective of this study was to correlate activity intensity and laterality of upper extremity activity measured by body-fixed inertial measurement units (IMUs) with clinical assessment scores of independence. Limb-use intensity and laterality of activities performed by the upper extremities was measured in 12 subjects with cervical SCI using four IMUs (positioned on both wrists, on the chest, and on one wheel of the wheelchair). Algorithms capable of reliably detecting self-propulsion and arm activity in a clinical environment were applied to rate functional outcome levels, and were related to clinical independence measures during inpatient rehabilitation. Measures of intensity of upper extremity activity during self-propulsion positively correlated (p laterality were positively correlated (p laterality as measured by IMUs during "daily life," and increased laterality was negatively correlated (p laterality in human cervical SCI. Continuous and objective movement data of distinct daily activities (i.e., mobility and day-to-day activities) can be related to levels of independence. Therefore, IMU sensor technology is suitable not only for monitoring activity levels during rehabilitation (including during clinical trials) but could also be used to assess levels of participation after discharge.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

Energy Technology Data Exchange (ETDEWEB)

Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

2013-02-08

Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

International Nuclear Information System (INIS)

Takaoka, Yuki; Kawamoto, Seiji; Katayama, Akiko; Nakano, Toshiaki; Yamanaka, Yasushi; Takahashi, Miki; Shimada, Yayoi; Chiang, Kuei-Chen; Ohmori, Naoya; Aki, Tsunehiro; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Chen, Chao-Long; Ono, Kazuhisa

2013-01-01

Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4 + Foxp3 + Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

Electroencephalographic dynamics of musical emotion perception revealed by independent spectral components.

Science.gov (United States)

Lin, Yuan-Pin; Duann, Jeng-Ren; Chen, Jyh-Horng; Jung, Tzyy-Ping

2010-04-21

This study explores the electroencephalographic (EEG) correlates of emotional experience during music listening. Independent component analysis and analysis of variance were used to separate statistically independent spectral changes of the EEG in response to music-induced emotional processes. An independent brain process with equivalent dipole located in the fronto-central region exhibited distinct δ-band and θ-band power changes associated with self-reported emotional states. Specifically, the emotional valence was associated with δ-power decreases and θ-power increases in the frontal-central area, whereas the emotional arousal was accompanied by increases in both δ and θ powers. The resultant emotion-related component activations that were less interfered by the activities from other brain processes complement previous EEG studies of emotion perception to music.

Atomic platinum layer coated titanium copper nitride supported on carbon nanotubes for the methanol oxidation reaction

CSIR Research Space (South Africa)

Zheng, Y

2017-09-01

Full Text Available measurements. The results confirm the core-shell structure of the prepared TiN@Pt/CNTs catalyst. More importantly, the catalyst exhibits superb mass activity and durability for the methanol oxidation reaction (MOR) than that of the commercial JM Pt/C catalyst...

Oct-1 potentiates CREB-driven cyclin D1 promoter activation via a phospho-CREB- and CREB binding protein-independent mechanism.

Science.gov (United States)

Boulon, Séverine; Dantonel, Jean-Christophe; Binet, Virginie; Vié, Annick; Blanchard, Jean-Marie; Hipskind, Robert A; Philips, Alexandre

2002-11-01

Cyclin D1, the regulatory subunit for mid-G(1) cyclin-dependent kinases, controls the expression of numerous cell cycle genes. A cyclic AMP-responsive element (CRE), located upstream of the cyclin D1 mRNA start site, integrates mitogenic signals that target the CRE-binding factor CREB, which can recruit the transcriptional coactivator CREB-binding protein (CBP). We describe an alternative mechanism for CREB-driven cyclin D1 induction that involves the ubiquitous POU domain protein Oct-1. In the breast cancer cell line MCF-7, overexpression of Oct-1 or its POU domain strongly increases transcriptional activation of cyclin D1 and GAL4 reporter genes that is specifically dependent upon CREB but independent of Oct-1 DNA binding. Gel retardation and chromatin immunoprecipitation assays confirm that POU forms a complex with CREB bound to the cyclin D1 CRE. In solution, CREB interaction with POU requires the CREB Q2 domain and, notably, occurs with CREB that is not phosphorylated on Ser 133. Accordingly, Oct-1 also potently enhances transcriptional activation mediated by a Ser133Ala CREB mutant. Oct-1/CREB synergy is not diminished by the adenovirus E1A 12S protein, a repressor of CBP coactivator function. In contrast, E1A strongly represses CBP-enhanced transactivation by CREB phosphorylated on Ser 133. Our observation that Oct-1 potentiates CREB-dependent cyclin D1 transcriptional activity independently of Ser 133 phosphorylation and E1A-sensitive coactivator function offers a new paradigm for the regulation of cyclin D1 induction by proliferative signals.

Independent association of glucocorticoids with damage accrual in SLE.

Science.gov (United States)

Apostolopoulos, Diane; Kandane-Rathnayake, Rangi; Raghunath, Sudha; Hoi, Alberta; Nikpour, Mandana; Morand, Eric F

2016-01-01

To determine factors associated with damage accrual in a prospective cohort of patients with SLE. Patients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI)). Multivariate logistic regression analyses were performed to identify factors associated with damage accrual. A total of 162 patients were observed over a median (IQR) 3.6 (2.0-4.7) years. Seventy-five per cent (n=121) of patients received glucocorticoids. Damage accrual was significantly more frequent in glucocorticoid-exposed patients (42% vs 15%, p<0.01). Higher glucocorticoid exposure was independently associated with overall damage accrual after controlling for factors including ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone/day; the OR of damage accrual in patients in the highest quartile of cumulative glucocorticoid exposure was over 10. Glucocorticoid exposure was independently associated with damage accrual in glucocorticoid-related and non-glucocorticoid related domains of the SDI. Glucocorticoid use is independently associated with the accrual of damage in SLE, including in non-glucocorticoid related domains.

Affected pathways and transcriptional regulators in gene expression response to an ultra-marathon trail: Global and independent activity approaches.

Directory of Open Access Journals (Sweden)

Maria Maqueda

Full Text Available Gene expression (GE analyses on blood samples from marathon and half-marathon runners have reported significant impacts on the immune and inflammatory systems. An ultra-marathon trail (UMT represents a greater effort due to its more testing conditions. For the first time, we report the genome-wide GE profiling in a group of 16 runners participating in an 82 km UMT competition. We quantified their differential GE profile before and after the race using HuGene2.0st microarrays (Affymetrix Inc., California, US. The results obtained were decomposed by means of an independent component analysis (ICA targeting independent expression modes. We observed significant differences in the expression levels of 5,084 protein coding genes resulting in an overrepresentation of 14% of the human biological pathways from the Kyoto Encyclopedia of Genes and Genomes database. These were mainly clustered on terms related with protein synthesis repression, altered immune system and infectious diseases related mechanisms. In a second analysis, 27 out of the 196 transcriptional regulators (TRs included in the Open Regulatory Annotation database were overrepresented. Among these TRs, we identified transcription factors from the hypoxia-inducible factors (HIF family EPAS1 (p< 0.01 and HIF1A (p<0.001, and others jointly described in the gluconeogenesis program such as HNF4 (p< 0.001, EGR1 (p<0.001, CEBPA (p< 0.001 and a highly specific TR, YY1 (p<0.01. The five independent components, obtained from ICA, further revealed a down-regulation of 10 genes distributed in the complex I, III and V from the electron transport chain. This mitochondrial activity reduction is compatible with HIF-1 system activation. The vascular endothelial growth factor (VEGF pathway, known to be regulated by HIF, also emerged (p<0.05. Additionally, and related to the brain rewarding circuit, the endocannabinoid signalling pathway was overrepresented (p<0.05.

Wii Fit® training vs. Adapted Physical Activities: which one is the most appropriate to improve the balance of independent senior subjects? A randomized controlled study.

Science.gov (United States)

Toulotte, Claire; Toursel, Cindy; Olivier, Nicolas

2012-09-01

To compare the effectiveness of three protocols (Adapted Physical Activities, Wii Fit(®), Adapted Physical Activities + Wii Fit(®)) on the balance of independent senior subjects. Case comparison study. Healthy elderly subjects living in independent community dwellings. Thirty-six subjects, average age 75.09 ± 10.26 years, took part in this study, and were randomly assigned to one of the four experimental groups: G1 followed an Adapted Physical Activities training programme, while the second group (G2) participated in Wii Fit(®) training and the third one (G3) combined both methods. There was no training for the fourth group (G4). All subjects trained once a week (1 hour) for 20 weeks and were assessed before and after treatment. The Tinetti test, unipedal tests and the Wii Fit(®) tests. After training, the scores in the Tinetti test decreased significantly (P Wii Fit(®)) and G3 (Adapted Physical Activities and Wii Fit(®)) improved their balance. In addition, G1 and G3 increased their dynamic balance. The findings suggest that Adapted Physical Activities training limits the decline in sensorial functions in the elderly.

The Relationship between High School Music Activities and the College Student's Musical Independence. (How Musically Important Are All-State Band, Concert Festival, Private Lessons, Marching Contests, Etc.?).

Science.gov (United States)

Bobbett, Gordon C.; And Others

This paper presents a study attempting to identify and evaluate high school activities that impact instrumental student outcome. High school music activities and their impact on student instrumental outcome from a variety of perspectives were examined. There is a subtle difference between musical independence and musical achievement. Musical…

New therapeutic activity of metabolic enhancer piracetam in treatment of neurodegenerative disease: Participation of caspase independent death factors, oxidative stress, inflammatory responses and apoptosis.

Science.gov (United States)

Verma, Dinesh Kumar; Gupta, Sonam; Biswas, Joyshree; Joshi, Neeraj; Singh, Abhishek; Gupta, Parul; Tiwari, Shubhangini; Sivarama Raju, K; Chaturvedi, Swati; Wahajuddin, M; Singh, Sarika

2018-03-16

Piracetam, a nootropic drug that has been clinically used for decades but remains enigmatic due to no distinct understanding of its mechanism of action. The present study aimed to investigate the role of caspase independent pathway in piracetam mediated neuroprotection. LPS administration caused significant alterations in oxidative stress related parameters like glutathione, glutathione reductase and increased lipid peroxidation. LPS administration also caused augmented expression of inflammatory cytokines and astrocytes activation. Piracetam treatment offered significant protection against LPS induced oxidative and inflammatory parameters and inhibited astrocytes activation. LPS administration caused augmented level of reactive oxygen species and depleted mitochondrial membrane potential which were attenuated with piracetam treatment. This study for the first time demonstrates the role of caspase independent death factors in piracetam induced neuroprotective effects in rat brain. Translocation of mitochondrial resident apoptosis inducing factor and endonuclease G to nucleus through cytosol after LPS administration was significantly blocked with piracetam treatment. Further, LPS induced DNA fragmentation along with up regulated Poly [ADP-ribose] polymerase 1 (PARP1) levels were also inhibited with piracetam treatment. Apoptotic death was confirmed by the cleavage of caspase 3 as well as histological alteration in rat brain regions. LPS administration caused significantly increased level of cleaved caspase 3, altered neuronal morphology and decreased neuronal density which were restored with piracetam treatment. Collectively our findings indicate that piracetam offered protection against LPS induced inflammatory responses and cellular death including its antioxidative antiapoptotic activity with its attenuation against mitochondria mediated caspase independent pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Stimulus-related independent component and voxel-wise analysis of human brain activity during free viewing of a feature film.

Science.gov (United States)

Lahnakoski, Juha M; Salmi, Juha; Jääskeläinen, Iiro P; Lampinen, Jouko; Glerean, Enrico; Tikka, Pia; Sams, Mikko

2012-01-01

Understanding how the brain processes stimuli in a rich natural environment is a fundamental goal of neuroscience. Here, we showed a feature film to 10 healthy volunteers during functional magnetic resonance imaging (fMRI) of hemodynamic brain activity. We then annotated auditory and visual features of the motion picture to inform analysis of the hemodynamic data. The annotations were fitted to both voxel-wise data and brain network time courses extracted by independent component analysis (ICA). Auditory annotations correlated with two independent components (IC) disclosing two functional networks, one responding to variety of auditory stimulation and another responding preferentially to speech but parts of the network also responding to non-verbal communication. Visual feature annotations correlated with four ICs delineating visual areas according to their sensitivity to different visual stimulus features. In comparison, a separate voxel-wise general linear model based analysis disclosed brain areas preferentially responding to sound energy, speech, music, visual contrast edges, body motion and hand motion which largely overlapped the results revealed by ICA. Differences between the results of IC- and voxel-based analyses demonstrate that thorough analysis of voxel time courses is important for understanding the activity of specific sub-areas of the functional networks, while ICA is a valuable tool for revealing novel information about functional connectivity which need not be explained by the predefined model. Our results encourage the use of naturalistic stimuli and tasks in cognitive neuroimaging to study how the brain processes stimuli in rich natural environments.

Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity*

Science.gov (United States)

Marty, Caroline; Chaligné, Ronan; Lacout, Catherine; Constantinescu, Stefan N.; Vainchenker, William; Villeval, Jean-Luc

2009-01-01

The activating W515L mutation in the thrombopoietin receptor (MPL) has been identified in primary myelofibrosis and essential thrombocythemia. MPL belongs to a subset of the cytokine receptor superfamily that requires the JAK2 kinase for signaling. We examined whether the ligand-independent MPLW515L mutant could signal intracellularly. Addition of the endoplasmic reticulum (ER) retention KDEL sequence to the receptor C terminus efficiently locked MPLW515L within its natural ER/Golgi maturation pathway. In contrast to cells expressing the parental MPLW515L, MPLW515L-KDEL-expressing FDC-P1 cells were unable to grow autonomously and to produce tumors in nude mice. When observed, tumor nodules resulted from in vivo selection of cells leaking the receptor at their surface. JAK2 co-immunoprecipitated with MPLW515L-KDEL but was not phosphorylated. We generated disulfide-bonded MPLW515L homodimers by the S402C substitution, both in the normal and KDEL context. Unlike MPLW515L-KDEL, MPLW515L-S402C-KDEL signaled constitutively and exhibited cell surface localization. These data establish that MPLW515L with appended JAK2 matures through the ER/Golgi system in an inactive conformation and suggest that the MPLW515L/JAK2 complex requires membrane localization for JAK2 phosphorylation, resulting in autonomous receptor signaling. PMID:19261614

MicroRNA signatures characterizing caste-independent ovarian activity in queen and worker honeybees (Apis mellifera L.).

Science.gov (United States)

Macedo, L M F; Nunes, F M F; Freitas, F C P; Pires, C V; Tanaka, E D; Martins, J R; Piulachs, M-D; Cristino, A S; Pinheiro, D G; Simões, Z L P

2016-06-01

Queen and worker honeybees differ profoundly in reproductive capacity. The queen of this complex society, with 200 highly active ovarioles in each ovary, is the fertile caste, whereas the workers have approximately 20 ovarioles as a result of receiving a different diet during larval development. In a regular queenright colony, the workers have inactive ovaries and do not reproduce. However, if the queen is sensed to be absent, some of the workers activate their ovaries, producing viable haploid eggs that develop into males. Here, a deep-sequenced ovary transcriptome library of reproductive workers was used as supporting data to assess the dynamic expression of the regulatory molecules and microRNAs (miRNAs) of reproductive and nonreproductive honeybee females. In this library, most of the differentially expressed miRNAs are related to ovary physiology or oogenesis. When we quantified the dynamic expression of 19 miRNAs in the active and inactive worker ovaries and compared their expression in the ovaries of virgin and mated queens, we noted that some miRNAs (miR-1, miR-31a, miR-13b, miR-125, let-7 RNA, miR-100, miR-276, miR-12, miR-263a, miR-306, miR-317, miR-92a and miR-9a) could be used to identify reproductive and nonreproductive statuses independent of caste. Furthermore, integrative gene networks suggested that some candidate miRNAs function in the process of ovary activation in worker bees. © 2016 The Royal Entomological Society.

Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

Science.gov (United States)

Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

2011-07-01

Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.

Characterizing protein activities on the lysozyme and nanodiamond complex prepared for bio applications.

Science.gov (United States)

Perevedentseva, E; Cai, P-J; Chiu, Y-C; Cheng, C-L

2011-02-01

Recently, nanodiamond particles have attracted increasing attention as a promising nanomaterial for its biocompatibility, easy functionalization and conjugation with biomolecules, and its superb physical/chemical properties. Nanodiamonds are mainly used as markers for cell imaging, using its fluorescence or Raman signals for detection, and as carriers for drug delivery. For the success of these applications, the biomolecule associated with the nanodiamond has to retain its functionality. In this work, the protein activities of egg white lysozyme adsorbed on nanodiamond particles of different sizes is investigated. The lysozyme nanodiamond complex is used here as a protein model for analyzing its structural conformation changes and, correspondingly, its enzymatic activity after the adsorption. Fourier-transform infrared spectroscopy (FTIR) is used for the analysis of the sensitive protein secondary structure. To access the activities of the adsorbed lysozyme, a fluorescence-based assay is used. The process of adsorption is also analyzed using UV-visible spectroscopic measurements in combination with analysis of nanodiamond properties with FTIR, Raman spectroscopy, and ζ-potential measurements. It is found that the activity of lysozyme upon adsorption depends on the nanodiamond's size and surface properties, and that the nanodiamond particles can be selected and treated, which do not alter the lysozyme functional properties. Such nanodiamonds can be considered convenient nanoparticles for various bioapplications.

Induction of human adiponectin gene transcription by telmisartan, angiotensin receptor blocker, independently on PPAR-γ activation

International Nuclear Information System (INIS)

Moriuchi, Akie; Yamasaki, Hironori; Shimamura, Mika; Kita, Atsushi; Kuwahara, Hironaga; Fujishima, Keiichiro; Satoh, Tsuyoshi; Fukushima, Keiko; Fukushima, Tetsuya; Hayakawa, Takao; Mizuguchi, Hiroyuki; Nagayama, Yuji; Abiru, Norio; Kawasaki, Eiji; Eguchi, Katsumi

2007-01-01

Adiponectin, an adipose tissue-specific plasma protein, has been shown to ameliorate insulin resistance and inhibit the process of atherosclerosis. Recently, several reports have stated that angiotensin type 1 receptor blockers (ARBs), increase adiponectin plasma level, and ameliorate insulin resistance. Telmisartan, a subclass of ARBs, has been shown to be a partial agonist of the peroxisome proliferator-activated receptor (PPAR)-γ, and to increase the plasma adiponectin level. However, the transcriptional regulation of the human adiponectin gene by telmisartan has not been determined yet. To elucidate the effect of telmisartan on adiponectin, the stimulatory regulation of human adiponectin gene by telmisartan was investigated in 3T3-L1 adipocytes, utilizing adenovirus-mediated luciferase reporter gene-transferring technique. This study indicates that telmisartan may stimulate adiponectin transcription independent of PPAR-γ

Qualification and actuation of the independent technical supervision organisms in nuclear power plants and others facilities

International Nuclear Information System (INIS)

1999-09-01

This norm presents the following objectives: establishment of the Brazilian National Nuclear Energy Commission requirements for qualifying an institution as independent technical supervision organization, in a specific area of activity related to nuclear power plants and others nuclear or radioactive facilities as appropriated; regulation of the independent technical supervision and others complementary activities to be executed by an independent technical supervision organism

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

Directory of Open Access Journals (Sweden)

Timmerman J André B

2006-03-01

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

Smoking status and its relationship with exercise capacity, physical activity in daily life and quality of life in physically independent, elderly individuals.

Science.gov (United States)

Mesquita, R; Gonçalves, C G; Hayashi, D; Costa, V de S P; Teixeira, D de C; de Freitas, E R F S; Felcar, J M; Pitta, F; Molari, M; Probst, V S

2015-03-01

To investigate the relationship between smoking status and exercise capacity, physical activity in daily life and health-related quality of life in physically independent, elderly (≥60 years) individuals. Cross-sectional, observational study. Community-dwelling, elderly individuals. One hundred and fifty-four elderly individuals were categorised into four groups according to their smoking status: never smokers (n=57), passive smokers (n=30), ex-smokers (n=45) and current smokers (n=22). Exercise capacity [6-minute walk test (6MWT)], physical activity in daily life (step counting) and health-related quality of life [36-Item Short Form Health Survey (SF-36) questionnaire] were assessed. Current and ex-smokers had lower mean exercise capacity compared with never smokers: 90 [standard deviation (SD) 10] % predicted, 91 (SD 12) % predicted and 100 (SD 13) % predicted distance on 6MWT, respectively [mean differences -9.8%, 95% confidence intervals (CI) -17.8 to -1.8 and -9.1%, 95% CI -15.4 to -2.7, respectively; Pexercise capacity than never smokers. Although the level of physical activity did not differ between the groups, an association was found with smoking. Tobacco exposure was associated with worse scores for the mental health dimension of SF-36 in physically independent, elderly individuals. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Endocytosis-independent function of clathrin heavy chain in the control of basal NF-κB activation.

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Man Lyang Kim

Full Text Available BACKGROUND: Nuclear factor-κB (NF-κB is a transcription factor that regulates the transcription of genes involved in a variety of biological processes, including innate and adaptive immunity, stress responses and cell proliferation. Constitutive or excessive NF-κB activity has been associated with inflammatory disorders and higher risk of cancer. In contrast to the mechanisms controlling inducible activation, the regulation of basal NF-κB activation is not well understood. Here we test whether clathrin heavy chain (CHC contributes to the regulation of basal NF-κB activity in epithelial cells. METHODOLOGY: Using RNA interference to reduce endogenous CHC expression, we found that CHC is required to prevent constitutive activation of NF-κB and gene expression. Immunofluorescence staining showed constitutive nuclear localization of the NF-κB subunit p65 in absence of stimulation after CHC knockdown. Elevated basal p65 nuclear localization is caused by constitutive phosphorylation and degradation of inhibitor of NF-κB alpha (IκBα through an IκB kinase α (IKKα-dependent mechanism. The role of CHC in NF-κB signaling is functionally relevant as constitutive expression of the proinflammatory chemokine interleukin-8 (IL-8, whose expression is regulated by NF-κB, was found after CHC knockdown. Disruption of clathrin-mediated endocytosis by chemical inhibition or depletion of the μ2-subunit of the endocytosis adaptor protein AP-2, and knockdown of clathrin light chain a (CHLa, failed to induce constitutive NF-κB activation and IL-8 expression, showing that CHC acts on NF-κB independently of endocytosis and CLCa. CONCLUSIONS: We conclude that CHC functions as a built-in molecular brake that ensures a tight control of basal NF-κB activation and gene expression in unstimulated cells. Furthermore, our data suggest a potential link between a defect in CHC expression and chronic inflammation disorder and cancer.

A study of depression, perceived loneliness, cognitive function and independence in daily activities in home and institution based older people: A cross sectional comparative study

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Riddhi Desai

2016-01-01

Full Text Available Context: Old age homes are on the rise in India. Older people staying in such institutions have specific psychosocial issues that may affect their cognitive performance and daily living. Materials and Methods: 71 older people, 39 institution based and 32 community-based were recruited with serial sampling after screening on mini-mental state examination and were evaluated with geriatric depression scale, University of California, Los Angeles scale, Lawton′s instrumental activities of daily living scale and montreal cognitive assessment scale. Results: Prevalence of depression was significantly higher in older people who were institution based, widowers and females. The severity of perceived loneliness was higher in females, institution based and depressed older people. The severity of depression correlated with independence in daily activities, cognition, and perceived loneliness only in institution based older people. Discussion: Older people in institutions have a higher psychosocial burden than the community-based older people. Family support prevents the attrition effect of depression on cognition and independence in daily activities in the community-based older people.

TECHNOLOGY TRANSFER TO U.S. INDEPENDENT OIL AND NATURAL GAS PRODUCERS

Energy Technology Data Exchange (ETDEWEB)

Unknown

2000-05-01

During FY00, the Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of helping U.S. independent oil and gas producers make timely, informed technology decisions. PTTC's national organization has active grassroots programs that connect with independents through its 10 Regional Lead Organizations (RLOs). These activities--including technology workshops, resource centers, websites, newsletters, and other outreach efforts--are guided by regional Producer Advisory Groups (PAGs). The role of the national headquarters (HQ) staff includes planning and managing the PTTC program, conducting nation-wide technology transfer activities, and implementing a comprehensive communications effort. This technical progress report summarizes PTTC's accomplishments during FY00, which lay the groundwork for further growth in the future.

TECHNOLOGY TRANSFER TO U.S. INDEPENDENT OIL AND NATURAL GAS PRODUCERS

Energy Technology Data Exchange (ETDEWEB)

Donald Duttlinger

1999-12-01

During FY99, the Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of helping U.S. independent oil and gas producers make timely, informed technology decisions. PTfC's national organization has active grassroots programs that connect with independents through its 10 Regional Lead Organizations (RLOs). These activities--including technology workshops, resource centers, websites, newsletters, and other outreach efforts--are guided by regional Producer Advisory Groups (PAGs). The role of the national headquarters (HQ) staff includes planning and managing the PTTC program, conducting nation-wide technology transfer activities, and implementing a comprehensive communications effort. This technical progress report summarizes PTTC's accomplishments during FY99, which lay the groundwork for further growth in the future.

Differential effects of phorbol 12-myristate 13-acetate and diacylglycerols on thromboxane A2-independent phospholipase A2 activation in collage-stimulated human platelets.

Science.gov (United States)

Reddy, S; Rao, G H; Murthy, M

1994-04-01

We investigated the priming effects of protein kinase C (PKC) activators such as phorbol 12-myristate 13-acetate (PMA), 1,2-DiC8 and OAG, and 1,3-DiC8 (a poor activator of PKC) on thromboxane A2 (TxA2)-independent phospholipase A2 (PLA2) activation in human platelets using collagen and A23187 as agonists. We measured PLA2 activation in collagen-stimulated platelets in the presence of BW755C, which abolished TxA2 synthesis, rise in cytosolic Ca2+, and aggregation. In the presence of PMA (50 nM), the amount of arachidonic acid (AA) released in platelets stimulated with collagen and A23187 represented 300% (13.85 nmol versus 4.5 nmol) and 400% (28 nmol versus 7 nmol) of controls (without PMA), respectively, while 1,2-DiC8, OAG, and 1,3-DiC8 increased TxA2-independent AA release by 50% in A23187-stimulated platelets and had no effect on the release of AA in collagen-stimulated platelets. Interestingly, 1,3-DiC8, which is a poor activator of PKC, was as effective as the other two DAGs (OAG and 1,2-DiC8) in priming TxA2-independent PLA2 activation, but was less effective than PMA in platelets stimulated with A23187. These results suggest that the TXA2-dependent IP3-mediated rise in cytosolic Ca2+ may not be obligatory for priming PLA2 activation in the presence of PMA in collagen-stimulated platelets. In contrast, 1,2-DiC8, OAG, and 1,3-DiC8 likely enhanced PLA2 activation via intracellular Ca2+ as they selectively affect this enzyme only in A23187-stimulated platelets. We also observed a significant increase in both saturated (palmitic and stearic acids) and unsaturated fatty acids (oleic and linoleic acids) in platelets stimulated by collagen or A23187 in the presence of PMA (50 nM), but not in the presence of DAGs. These findings imply that PMA may also affect the activation of DAG/MAG lipases, PLA1, or nonspecific PLA2. Since both 1,2-DiC8 and OAG exert no significant effect on the release of these fatty acids, the effects observed with PMA on DAG lipase/PLA1 may not

A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

Energy Technology Data Exchange (ETDEWEB)

Min, Kyung-Won [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Zhang, Xiaobo [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); College of Animal Science and Technology, Northwest A and F University, Yangling, Shaanxi, 712100 (China); Imchen, Temjenmongla [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States); Baek, Seung Joon, E-mail: sbaek2@utk.edu [Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996 (United States)

2012-09-01

MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

International Nuclear Information System (INIS)

Min, Kyung-Won; Zhang, Xiaobo; Imchen, Temjenmongla; Baek, Seung Joon

2012-01-01

MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

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Le Sun

Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

International Nuclear Information System (INIS)

Wright, K.T.; Seabright, R.; Logan, A.; Lilly, A.J.; Khanim, F.; Bunce, C.M.; Johnson, W.E.B.

2010-01-01

Research highlights: → Extracellular Nm23H1 stimulates nerve growth. → Extracellular Nm23H1 provides pathfinding cues to growth cones. → The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. → The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

Energy Technology Data Exchange (ETDEWEB)

Wright, K.T. [Keele University at the RJAH Orthopaedic Hospital, Oswestry, Shropshire (United Kingdom); Seabright, R.; Logan, A. [Neuropharmacology and Neurobiology, School of Clinical and Experimental Medicine, Birmingham University, Birmingham (United Kingdom); Lilly, A.J.; Khanim, F.; Bunce, C.M. [Biosciences, Birmingham University, Birmingham (United Kingdom); Johnson, W.E.B., E-mail: w.e.johnson@aston.ac.uk [Life and Health Sciences, Aston University, Birmingham (United Kingdom)

2010-07-16

Research highlights: {yields} Extracellular Nm23H1 stimulates nerve growth. {yields} Extracellular Nm23H1 provides pathfinding cues to growth cones. {yields} The neurotrophic activity of Nm23H1 is independent of NDP kinase activity. {yields} The neurotrophic activity of Nm23H1 is independent of NGF. -- Abstract: The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems.

Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

Science.gov (United States)

Gaffal, E; Cron, M; Glodde, N; Tüting, T

2013-08-01

∆(9) -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases. Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors. We evaluated the impact of topically applied THC on DNFB-mediated allergic contact dermatitis in wild-type and CB1/2 receptor-deficient mice. We performed immunohistochemical analyses for infiltrating immune cells and studied the influence of THC on the interaction between T cells, keratinocytes and myeloid immune cells in vitro. Topical THC application effectively decreased contact allergic ear swelling and myeloid immune cell infiltration not only in wild-type but also in CB1/2 receptor-deficient mice. We found that THC (1) inhibited the production of IFNγ by T cells, (2) decreased the production of CCL2 and of IFNγ-induced CCL8 and CXL10 by epidermal keratinocytes and (3) thereby limited the recruitment of myeloid immune cells in vitro in a CB1/2 receptor-independent manner. Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors. This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tricarbonyldichlororuthenium (II) dimer (CORM2) activates non-selective cation current in human endothelial cells independently of carbon monoxide releasing.

Science.gov (United States)

Dong, De-Li; Chen, Chang; Huang, Wei; Chen, Yan; Zhang, Xiao-Lan; Li, Zhe; Li, Yue; Yang, Bao-Feng

2008-08-20

Tricarbonyldichlororuthenium (II) dimer (CORM2) has been developed as carbon monoxide (CO) donor. We found that CORM2 activated a type of specific current which was distinct from the big-conductance Ca(2+)-activated K(+) current activated by CO in human umbilical vein endothelial cells (HUVECs). So the aim of the present study was to characterize the CORM2-induced current and to access the relation with CO releasing. CORM2 (100 microM) activated a kind of bi-directional current in HUVECs when the ramp protocol (holding potential 0 mV, from -120 mV to +120 mV) was applied. The current was not blocked by apamin, TRAM-34 and iberiotoxin, the small, intermediate and big-conductance Ca(2+) -activated K(+) channel blockers, and it was not sensitive to the pipette solution chelated with EGTA. CORM2 still activated the current when the chloride in the pipette solution was substituted by equal mol gluconic acid. Substitution of the sodium in the bath with choline significantly reduced the current activated by CORM2. The current was regarded as the non-selective cation current. The current showed slightly inward rectifier property and was not sensitive to Gd(3+) (100 microM), La(3+) (10 microM) or 2-aminoethoxydiphenyl borate (100 microM). CO (10 microM), CORM3 (100, 200 microM) and RuCl(3) (100 microM) were used as controls and showed no effect of the current activation. In conclusion, CORM2 activated the non-selective cation current in HUVECs independently of its CO releasing.

70Z/3 Cbl induces PLC gamma 1 activation in T lymphocytes via an alternate Lat- and Slp-76-independent signaling mechanism.

Science.gov (United States)

Graham, Laurie J; Verí, Maria-Concetta; DeBell, Karen E; Noviello, Cristiana; Rawat, Rashmi; Jen, Sandy; Bonvini, Ezio; Rellahan, Barbara

2003-04-24

The oncoprotein 70Z/3 Cbl signals in an autonomous fashion or through blockade of endogenous c-Cbl, a negative regulator of signaling. The mechanism of 70Z/3 Cbl-induced signaling was investigated by comparing the molecular requirements for 70Z/3 Cbl- and TCR-induced phospholipase C gamma 1 (PLC gamma 1) activation. 70Z/3 Cbl-induced PLC gamma 1 tyrosine phosphorylation required, in addition to the PLC gamma 1 N-terminal SH2 domain, the C-terminal SH2 and SH3 domains that were dispensable for TCR-induced phosphorylation. Deletion of the leucine zipper of 70Z/3 Cbl did not eliminate 70Z/3 Cbl-induced PLC gamma 1 phosphorylation, suggesting that blockage of c-Cbl via dimerization with 70Z/3 Cbl cannot fully explain 70Z/3 Cbl activating characteristics. The complete elimination of PLC gamma 1 phosphorylation required deleting the SH3 domain-binding region of 70Z/3 Cbl, consistent with 70Z/3 Cbl binding the PLC gamma 1 SH3 domain. 70Z/3 Cbl-induced PLC gamma 1 phosphorylation required Zap-70, as for the TCR, and the tyrosine kinase binding domain of 70Z/3 Cbl, which binds Zap-70, but did not require PLC gamma 1 binding to Lat, a crucial interaction in TCR-induced PLC gamma 1 phosphorylation. Furthermore, 70Z/3 Cbl-induced activation of NFAT, a PLC gamma 1/Ca(2+)-dependent transcriptional event, required Zap-70, but was independent of Slp-76, an adapter required for TCR-induced NFAT activation. These results suggest that 70Z/3 Cbl and PLC gamma 1 form a TCR-, Lat- and Slp-76-independent complex that leads to PLC gamma 1 phosphorylation and activation.

EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

International Nuclear Information System (INIS)

Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline; Sun, Jianmin; Jögi, Annika; Neumann, Drorit; Rönnstrand, Lars; Påhlman, Sven

2014-01-01

Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα + ) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells

EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Sun, Jianmin [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Jögi, Annika [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Neumann, Drorit [Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Rönnstrand, Lars [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Påhlman, Sven, E-mail: sven.pahlman@med.lu.se [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

2014-02-28

Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα{sup +}) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.

Stimulus-Related Independent Component and Voxel-Wise Analysis of Human Brain Activity during Free Viewing of a Feature Film

Science.gov (United States)

Lahnakoski, Juha M.; Salmi, Juha; Jääskeläinen, Iiro P.; Lampinen, Jouko; Glerean, Enrico; Tikka, Pia; Sams, Mikko

2012-01-01

Understanding how the brain processes stimuli in a rich natural environment is a fundamental goal of neuroscience. Here, we showed a feature film to 10 healthy volunteers during functional magnetic resonance imaging (fMRI) of hemodynamic brain activity. We then annotated auditory and visual features of the motion picture to inform analysis of the hemodynamic data. The annotations were fitted to both voxel-wise data and brain network time courses extracted by independent component analysis (ICA). Auditory annotations correlated with two independent components (IC) disclosing two functional networks, one responding to variety of auditory stimulation and another responding preferentially to speech but parts of the network also responding to non-verbal communication. Visual feature annotations correlated with four ICs delineating visual areas according to their sensitivity to different visual stimulus features. In comparison, a separate voxel-wise general linear model based analysis disclosed brain areas preferentially responding to sound energy, speech, music, visual contrast edges, body motion and hand motion which largely overlapped the results revealed by ICA. Differences between the results of IC- and voxel-based analyses demonstrate that thorough analysis of voxel time courses is important for understanding the activity of specific sub-areas of the functional networks, while ICA is a valuable tool for revealing novel information about functional connectivity which need not be explained by the predefined model. Our results encourage the use of naturalistic stimuli and tasks in cognitive neuroimaging to study how the brain processes stimuli in rich natural environments. PMID:22496909

Stimulus-related independent component and voxel-wise analysis of human brain activity during free viewing of a feature film.

Directory of Open Access Journals (Sweden)

Juha M Lahnakoski

Full Text Available Understanding how the brain processes stimuli in a rich natural environment is a fundamental goal of neuroscience. Here, we showed a feature film to 10 healthy volunteers during functional magnetic resonance imaging (fMRI of hemodynamic brain activity. We then annotated auditory and visual features of the motion picture to inform analysis of the hemodynamic data. The annotations were fitted to both voxel-wise data and brain network time courses extracted by independent component analysis (ICA. Auditory annotations correlated with two independent components (IC disclosing two functional networks, one responding to variety of auditory stimulation and another responding preferentially to speech but parts of the network also responding to non-verbal communication. Visual feature annotations correlated with four ICs delineating visual areas according to their sensitivity to different visual stimulus features. In comparison, a separate voxel-wise general linear model based analysis disclosed brain areas preferentially responding to sound energy, speech, music, visual contrast edges, body motion and hand motion which largely overlapped the results revealed by ICA. Differences between the results of IC- and voxel-based analyses demonstrate that thorough analysis of voxel time courses is important for understanding the activity of specific sub-areas of the functional networks, while ICA is a valuable tool for revealing novel information about functional connectivity which need not be explained by the predefined model. Our results encourage the use of naturalistic stimuli and tasks in cognitive neuroimaging to study how the brain processes stimuli in rich natural environments.

A concentration-independent micro/nanofluidic active diode using an asymmetric ion concentration polarization layer.

Science.gov (United States)

Lee, Hyekyung; Kim, Junsuk; Kim, Hyeonsoo; Kim, Ho-Young; Lee, Hyomin; Kim, Sung Jae

2017-08-24

Over the past decade, nanofluidic diodes that rectify ionic currents (i.e. greater current in one direction than in the opposite direction) have drawn significant attention in biomolecular sensing, switching and energy harvesting devices. To obtain current rectification, conventional nanofluidic diodes have utilized complex nanoscale asymmetry such as nanochannel geometry, surface charge density, and reservoir concentration. Avoiding the use of sophisticated nano-asymmetry, micro/nanofluidic diodes using microscale asymmetry have been recently introduced; however, their diodic performance is still impeded by (i) low (even absent) rectification effects at physiological concentrations over 100 mM and strong dependency on the bulk concentration, and (ii) the fact that they possess only passive predefined rectification factors. Here, we demonstrated a new class of micro/nanofluidic diode with an ideal perm-selective nanoporous membrane based on ion concentration polarization (ICP) phenomenon. Thin side-microchannels installed near a nanojunction served as mitigators of the amplified electrokinetic flows generated by ICP and induced convective salt transfer to the nanoporous membrane, leading to actively controlled micro-scale asymmetry. Using this device, current rectifications were successfully demonstrated in a wide range of electrolytic concentrations (10 -5 M to 3 M) as a function of the fluidic resistance of the side-microchannels. Noteworthily, it was confirmed that the rectification factors were independent from the bulk concentration due to the ideal perm-selectivity. Moreover, the rectification of the presenting diode was actively controlled by adjusting the external convective flows, while that of the previous diode was passively determined by invariant nanoscale asymmetry.

29 CFR 779.233 - Independent contractors performing work “for” an enterprise.

Science.gov (United States)

2010-07-01

... Apply; Enterprise Coverage Leased Departments, Franchise and Other Business Arrangements § 779.233... section 3(r) has reference to an independent business which performs services for other businesses as an established part of its own business activities. The term “independent contractor” as used in 3(r) thus has...

1994 SSRL Activity Report

International Nuclear Information System (INIS)

2011-01-01

SSRL, a division of the Stanford Linear Accelerator Center, is a national user facility which provides synchrotron radiation, a name given to x-rays or light produced by electrons circulating in a storage ring at nearly the speed of light. The synchrotron radiation is produced by the 3.3 GeV storage ring, SPEAR. SPEAR is a fully dedicated synchrotron radiation facility which has been operating for user experiments 6 to 7 months per year. 1994, the third year of operation of SSRL as a fully dedicated, low-emittance, independent user facility was superb. The facility ran extremely well, delivering 89% of the scheduled user beam to 25 experimental stations during 6.5 months of user running. Over 600 users came from 167 institutions to participate in 343 experiments. Users from private industry were involved in 31% of these experiments. The SPEAR accelerator ran very well with no major component failures and an unscheduled down time of only 2.9%. In addition to this increased reliability, there was a significant improvement in the stability of the beam. The enhancements to the SPEAR orbit as part of a concerted three-year program were particularly noticeable to users. the standard deviation of beam movement (both planes) in the last part of the run was 80 microns, major progress toward the ultimate goal of 50-micron stability. This was a significant improvement from the previous year when the movement was 400 microns in the horizontal and 200 microns in the vertical. A new accelerator Personal Protection System (PPS), built with full redundancy and providing protection from both radiation exposure and electrical hazards, was installed in 1994.

1994 SSRL Activity Report

Energy Technology Data Exchange (ETDEWEB)

2011-11-18

SSRL, a division of the Stanford Linear Accelerator Center, is a national user facility which provides synchrotron radiation, a name given to x-rays or light produced by electrons circulating in a storage ring at nearly the speed of light. The synchrotron radiation is produced by the 3.3 GeV storage ring, SPEAR. SPEAR is a fully dedicated synchrotron radiation facility which has been operating for user experiments 6 to 7 months per year. 1994, the third year of operation of SSRL as a fully dedicated, low-emittance, independent user facility was superb. The facility ran extremely well, delivering 89% of the scheduled user beam to 25 experimental stations during 6.5 months of user running. Over 600 users came from 167 institutions to participate in 343 experiments. Users from private industry were involved in 31% of these experiments. The SPEAR accelerator ran very well with no major component failures and an unscheduled down time of only 2.9%. In addition to this increased reliability, there was a significant improvement in the stability of the beam. The enhancements to the SPEAR orbit as part of a concerted three-year program were particularly noticeable to users. the standard deviation of beam movement (both planes) in the last part of the run was 80 microns, major progress toward the ultimate goal of 50-micron stability. This was a significant improvement from the previous year when the movement was 400 microns in the horizontal and 200 microns in the vertical. A new accelerator Personal Protection System (PPS), built with full redundancy and providing protection from both radiation exposure and electrical hazards, was installed in 1994.

Independence and Product Systems

OpenAIRE

Skeide, Michael

2003-01-01

Starting from elementary considerations about independence and Markov processes in classical probability we arrive at the new concept of conditional monotone independence (or operator-valued monotone independence). With the help of product systems of Hilbert modules we show that monotone conditional independence arises naturally in dilation theory.

Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls.

Science.gov (United States)

Leininger, Elizabeth C; Kelley, Darcy B

2013-04-07

Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors.

A novel small molecule FL118 that selectively inhibits survivin, Mcl-1, XIAP and cIAP2 in a p53-independent manner, shows superior antitumor activity.

Directory of Open Access Journals (Sweden)

Xiang Ling

Full Text Available Drug/radiation resistance to treatment and tumor relapse are major obstacles in identifying a cure for cancer. Development of novel agents that address these challenges would therefore be of the upmost importance in the fight against cancer. In this regard, studies show that the antiapoptotic protein survivin is a central molecule involved in both hurdles. Using cancer cell-based survivin-reporter systems (US 7,569,221 B2 via high throughput screening (HTS of compound libraries, followed by in vitro and in vivo analyses of HTS-derived hit-lead compounds, we identified a novel anticancer compound (designated FL118. FL118 shows structural similarity to irinotecan. However, while the inhibition of DNA topoisomerase 1 activity by FL118 was no better than the active form of irinotecan, SN-38 at 1 µM, FL118 effectively inhibited cancer cell growth at less than nM levels in a p53 status-independent manner. Moreover, FL118 selectively inhibited survivin promoter activity and gene expression also in a p53 status-independent manner. Although the survivin promoter-reporter system was used for the identification of FL118, our studies revealed that FL118 not only inhibits survivin expression but also selectively and independently inhibits three additional cancer-associated survival genes (Mcl-1, XIAP and cIAP2 in a p53 status-independent manner, while showing no inhibitory effects on control genes. Genetic silencing or overexpression of FL118 targets demonstrated a role for these targets in FL118's effects. Follow-up in vivo studies revealed that FL118 exhibits superior antitumor efficacy in human tumor xenograft models in comparison with irinotecan, topotecan, doxorubicin, 5-FU, gemcitabine, docetaxel, oxaliplatin, cytoxan and cisplatin, and a majority of mice treated with FL118 showed tumor regression with a weekly × 4 schedule. FL118 induced favorable body-weight-loss profiles (temporary and reversible and was able to eliminate large tumors. Together

Organization of the independent work of students while studying engineering graphics

Directory of Open Access Journals (Sweden)

Tel’noy Viktor Ivanovich

2015-01-01

Full Text Available The article reveals the possibility of creating and implementing teaching conditions for the rational organization of the independent work of first-year students in state of adaptation to the study of the course of engineering drawing. Theoretical and methodological aspects of students’ independent work are presented: types and forms of organization and control, training and methodological support of their independent work. The authors used such an approach to independent work organization: teacher-led classes during the main types of training activities (lectures, practical and laboratory work; form of organization of training (extracurricular, and also self study using innovative teaching methods promotes creative activities of students and the development of competencies of a future skilled construction industry professional. The role of modern information and communication technologies in independent work of students was specified. According to the degree of coverage of students, taking into account individual characteristics and different levels of preparedness, the following forms of independent work organization were detached: individual, differentiated and front.In the process of engineering graphics studying it is recommended to use the following basic forms of independent work: ongoing work with the lecture material; selection and study of literature and electronic sources of information on the problems of the discipline; preparation for the main classroom training; performing calculation and graphic works; work in student scientific societies and carrying out research work; participation in scientific conferences, seminars and other. Emphasis on the formation of students’ skills in working with different types of educational and scientific literature, the ability to analyze, organize information in electronical library systems, open educational resources.

42 CFR 54.5 - Religious character and independence.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Religious character and independence. 54.5 Section 54.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS CHARITABLE... activities, such as worship, religious instruction, or proselytization. Among other things, faith-based...

Insulin receptor substrates 1 and 2 but not Shc can activate the insulin receptor independent of insulin and induce proliferation in CHO-IR cells

International Nuclear Information System (INIS)

Niessen, Markus; Jaschinski, Frank; Item, Flurin; McNamara, Morgan P.; Spinas, Giatgen A.; Trueb, Thomas

2007-01-01

Ligand-activated insulin receptor (IR) attracts and phosphorylates various substrates such as insulin receptor substrates 1-4 (IRS) and Shc. To investigate how binding affinity for substrate affects signalling we generated chimeric receptors with the β-chain of the insulin receptor containing NPXY motives with different affinities for receptor substrates. We found that the extent of receptor tyrosine phosphorylation positively correlates with binding affinity towards IRS1/2 but not towards Shc. Moreover, overexpression of IRS1 or IRS2 but not of Shc increased IR tyrosine phosphorylation in a dose-dependent manner, also independent of insulin. Molecular truncations of IRS1 revealed that neither the isolated PH and PTB domains nor the C-terminus with the tyrosine phosphorylation sites alone are sufficient for substrate-dependent receptor activation. Overexpression of IRS1 and IRS2 impaired insulin-induced internalization of the IR in a dose-dependent manner suggesting that IRS proteins prevent endosome-associated receptor dephosphorylation/inactivation. IRS1 and IRS2 could therefore target the activated IR to different cellular compartments. Overexpression of IRS1 and IRS2 inhibited insulin-stimulated activation of the MAP kinases Erk1/2 while it increased/induced activation of Akt/PKB. Finally, overexpression of IRS1 and IRS2 but not of Shc induced DNA synthesis in starved CHO-IR cells independent of exogenous growth factors. Our results demonstrate that variations in cellular IRS1 and IRS2 concentration affect insulin signalling both upstream and downstream and that IRS proteins could play instructive rather than just permissive roles in signal transmission

Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status.

Science.gov (United States)

Myers, Jonathan; McAuley, Paul; Lavie, Carl J; Despres, Jean-Pierre; Arena, Ross; Kokkinos, Peter

2015-01-01

The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Current PA patterns are undoubtedly the lowest they have been in human history, with particularly marked declines in recent generations, and future projections indicate further declines around the globe. Non-communicable health problems that afflict current societies are fundamentally attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted. The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of cardiorespiratory fitness (CRF) and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. This review will discuss the evidence supporting the premise that PA and CRF are independent risk factors for cardiovascular disease (CVD) as well as the interplay between both PA and CRF and other CVD risk factors. A particular focus will be given to the interplay between CRF, metabolic risk and obesity. Published by Elsevier Inc.

Enzyme activity assay of glycoprotein enzymes based on a boronate affinity molecularly imprinted 96-well microplate.

Science.gov (United States)

Bi, Xiaodong; Liu, Zhen

2014-12-16

Enzyme activity assay is an important method in clinical diagnostics. However, conventional enzyme activity assay suffers from apparent interference from the sample matrix. Herein, we present a new format of enzyme activity assay that can effectively eliminate the effects of the sample matrix. The key is a 96-well microplate modified with molecularly imprinted polymer (MIP) prepared according to a newly proposed method called boronate affinity-based oriented surface imprinting. Alkaline phosphatase (ALP), a glycoprotein enzyme that has been routinely used as an indicator for several diseases in clinical tests, was taken as a representative target enzyme. The prepared MIP exhibited strong affinity toward the template enzyme (with a dissociation constant of 10(-10) M) as well as superb tolerance for interference. Thus, the enzyme molecules in a complicated sample matrix could be specifically captured and cleaned up for enzyme activity assay, which eliminated the interference from the sample matrix. On the other hand, because the boronate affinity MIP could well retain the enzymatic activity of glycoprotein enzymes, the enzyme captured by the MIP was directly used for activity assay. Thus, additional assay time and possible enzyme or activity loss due to an enzyme release step required by other methods were avoided. Assay of ALP in human serum was successfully demonstrated, suggesting a promising prospect of the proposed method in real-world applications.

Granzyme A Produces Bioactive IL-1β through a Nonapoptotic Inflammasome-Independent Pathway

Directory of Open Access Journals (Sweden)

Dagmar Hildebrand

2014-11-01

Full Text Available Bacterial components are recognized by the immune system through activation of the inflammasome, eventually causing processing of the proinflammatory cytokine interleukin-1β (IL-1β, a pleiotropic cytokine and one of the most important mediators of inflammation, through the protease caspase-1. Synthesis of the precursor protein and processing into its bioactive form are tightly regulated, given that disturbed control of IL-1β release can cause severe autoinflammatory diseases or contribute to cancer development. We show that the bacterial Pasteurella multocida toxin (PMT triggers Il1b gene transcription in macrophages independently of Toll-like receptor signaling through RhoA/Rho-kinase-mediated NF-κΒ activation. Furthermore, PMT mediates signal transducer and activator of transcription (STAT protein-controlled granzyme A (a serine protease expression in macrophages. The exocytosed granzyme A enters target cells and mediates IL-1β maturation independently of caspase-1 and without inducing cytotoxicity. These findings show that macrophages can induce an IL-1β-initiated immune response independently of inflammasome activity.

Salinomycin possesses anti-tumor activity and inhibits breast cancer stem-like cells via an apoptosis-independent pathway

Energy Technology Data Exchange (ETDEWEB)

An, Hyunsook; Kim, Ji Young; Lee, Nahyun; Cho, Youngkwan; Oh, Eunhye [Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703 (Korea, Republic of); Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703 (Korea, Republic of); Seo, Jae Hong, E-mail: cancer@korea.ac.kr [Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 152-703 (Korea, Republic of); Brain Korea 21 Program for Biomedicine Science, Korea University College of Medicine, Korea University, Seoul 152-703 (Korea, Republic of)

2015-10-30

Cancer stem cells (CSCs) play important roles in the formation, growth and recurrence of tumors, particularly following therapeutic intervention. Salinomycin has received recent attention for its ability to target breast cancer stem cells (BCSCs), but the mechanisms of action involved are not fully understood. In the present study, we sought to investigate the mechanisms responsible for salinomycin's selective targeting of BCSCs and its anti-tumor activity. Salinomycin suppressed cell viability, concomitant with the downregulation of cyclin D1 and increased p27{sup kip1} nuclear accumulation. Mammosphere formation assays revealed that salinomycin suppresses self-renewal of ALDH1-positive BCSCs and downregulates the transcription factors Nanog, Oct4 and Sox2. TUNEL analysis of MDA-MB-231-derived xenografts revealed that salinomycin administration elicited a significant reduction in tumor growth with a marked downregulation of ALDH1 and CD44 levels, but seemingly without the induction of apoptosis. Our findings shed further light on the mechanisms responsible for salinomycin's effects on BCSCs. - Highlights: • Salinomycin suppresses mammosphere formation. • Salinomycin reduces ALDH1 activity and downregulates Nanog, Oct4 and Sox2. • Salinomycin targets BCSCs via an apoptosis-independent pathway.

On the k-independence required by linear probing and minwise independence

DEFF Research Database (Denmark)

Pǎtraşcu, Mihai; Thorup, Mikkel

2016-01-01

We show that linear probing requires 5-independent hash functions for expected constant-time performance, matching an upper bound of Pagh et al. [2009]. More precisely, we construct a random 4-independent hash function yielding expected logarithmic search time for certain keys. For (1 + ε......)-approximate minwise independence, we show that Ω(lg1 ε)-independent hash functions are required, matching an upper bound of Indyk [2001]. We also show that the very fast 2-independent multiply-shift scheme of Dietzfelbinger [1996] fails badly in both applications....

Telomere-independent functions of telomerase in nuclei, cytoplasm, and mitochondria

Energy Technology Data Exchange (ETDEWEB)

Chiodi, Ilaria; Mondello, Chiara, E-mail: mondello@igm.cnr.it [Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, Pavia (Italy)

2012-09-28

Telomerase canonical activity at telomeres prevents telomere shortening, allowing chromosome stability and cellular proliferation. To perform this task, the catalytic subunit (telomerase reverse transcriptase, TERT) of the enzyme works as a reverse transcriptase together with the telomerase RNA component (TERC), adding telomeric repeats to DNA molecule ends. Growing evidence indicates that, besides the telomeric-DNA synthesis activity, TERT has additional functions in tumor development and is involved in many different biological processes, among which cellular proliferation, gene expression regulation, and mitochondrial functionality. TERT has been shown to act independently of TERC in the Wnt-β-catenin signaling pathway, regulating the expression of Wnt target genes, which play a role in development and tumorigenesis. Moreover, TERT RNA-dependent RNA polymerase activity has been found, leading to the genesis of double-stranded RNAs that act as precursor of silencing RNAs. In mitochondria, a TERT TERC-independent reverse transcriptase activity has been described that could play a role in the protection of mitochondrial integrity. In this review, we will discuss some of the extra-telomeric functions of telomerase.

The Elderly’s Independent Living in Smart Homes: A Characterization of Activities and Sensing Infrastructure Survey to Facilitate Services Development

Science.gov (United States)

Ni, Qin; García Hernando, Ana Belén; de la Cruz, Iván Pau

2015-01-01

Human activity detection within smart homes is one of the basis of unobtrusive wellness monitoring of a rapidly aging population in developed countries. Most works in this area use the concept of “activity” as the building block with which to construct applications such as healthcare monitoring or ambient assisted living. The process of identifying a specific activity encompasses the selection of the appropriate set of sensors, the correct preprocessing of their provided raw data and the learning/reasoning using this information. If the selection of the sensors and the data processing methods are wrongly performed, the whole activity detection process may fail, leading to the consequent failure of the whole application. Related to this, the main contributions of this review are the following: first, we propose a classification of the main activities considered in smart home scenarios which are targeted to older people’s independent living, as well as their characterization and formalized context representation; second, we perform a classification of sensors and data processing methods that are suitable for the detection of the aforementioned activities. Our aim is to help researchers and developers in these lower-level technical aspects that are nevertheless fundamental for the success of the complete application. PMID:26007717

The Elderly’s Independent Living in Smart Homes: A Characterization of Activities and Sensing Infrastructure Survey to Facilitate Services Development

Directory of Open Access Journals (Sweden)

Qin Ni

2015-05-01

Full Text Available Human activity detection within smart homes is one of the basis of unobtrusive wellness monitoring of a rapidly aging population in developed countries. Most works in this area use the concept of “activity” as the building block with which to construct applications such as healthcare monitoring or ambient assisted living. The process of identifying a specific activity encompasses the selection of the appropriate set of sensors, the correct preprocessing of their provided raw data and the learning/reasoning using this information. If the selection of the sensors and the data processing methods are wrongly performed, the whole activity detection process may fail, leading to the consequent failure of the whole application. Related to this, the main contributions of this review are the following: first, we propose a classification of the main activities considered in smart home scenarios which are targeted to older people’s independent living, as well as their characterization and formalized context representation; second, we perform a classification of sensors and data processing methods that are suitable for the detection of the aforementioned activities. Our aim is to help researchers and developers in these lower-level technical aspects that are nevertheless fundamental for the success of the complete application.

Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined Signaling Route Would Induce Alternative Consideration to Previous Conceptions.

Science.gov (United States)

Tong, Guojun; Meng, Yue; Hao, Song; Hu, Shaoyu; He, Youhua; Yan, Wenjuan; Yang, Dehong

2017-04-20

BACKGROUND Parathyroid hormone (PTH) is an effective anti-osteoporosis agent, after binding to its receptor PTHR1, several signaling pathways, including cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are initiated through G proteins; with the cAMP/PKA pathway as the major pathway. Earlier studies have reported that PTHR1 might also activate PKC via a PLC-independent mechanism, but this pathway remains unclear. MATERIAL AND METHODS In HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then assays for cell apoptosis, cell differentiation, alkaline phosphatase activity, and mineralization were performed. RESULTS The FRET analysis found that PTH(1-34), [G1,R19]PTH(1-34) (GR(1-34), and [G1,R19]PTH(1-28) (GR(1-28) were all activated by PKC. The PKC activation ability of GR(1-28) was blocked by cAMP inhibitor (Rp-cAMP) and rescued with the addition of active PKA-α and PKA-β. The PKC activation ability of GR(1-34) was partially inhibited by Rp-cAMP. In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was regulated by GR(1-28) were significantly changed by the pan-PKC inhibitor Go6983. After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG were differentially regulated by GR(1-28) or GR(1-34), and the difference was blunted by Go6983. PTH(1-34), GR(1-28), and GR(1-34) significantly decreased early apoptosis and augmented osteoblastic differentiation in accordance with the activities of PKA and PKC. CONCLUSIONS PLC-independent PKC activation induced by PTH could be divided into two potential mechanisms: one was PKA-dependent and associated with PTH(1-28); the other was PKA-independent and associated with PTH(29-34). We also found that PTH could activate PLC-independent PKC via PKA-dependent mechanisms.

Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction.

Science.gov (United States)

Resseguie, Emily A; Staversky, Rhonda J; Brookes, Paul S; O'Reilly, Michael A

2015-08-01

High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12h and basal respiration by 48 h. ROS were significantly increased at 24h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

LRRK2 kinase activity is dependent on LRRK2 GTP binding capacity but independent of LRRK2 GTP binding.

Directory of Open Access Journals (Sweden)

Jean-Marc Taymans

Full Text Available Leucine rich repeat kinase 2 (LRRK2 is a Parkinson's disease (PD gene that encodes a large multidomain protein including both a GTPase and a kinase domain. GTPases often regulate kinases within signal transduction cascades, where GTPases act as molecular switches cycling between a GTP bound "on" state and a GDP bound "off" state. It has been proposed that LRRK2 kinase activity may be increased upon GTP binding at the LRRK2 Ras of complex proteins (ROC GTPase domain. Here we extensively test this hypothesis by measuring LRRK2 phosphorylation activity under influence of GDP, GTP or non-hydrolyzable GTP analogues GTPγS or GMPPCP. We show that autophosphorylation and lrrktide phosphorylation activity of recombinant LRRK2 protein is unaltered by guanine nucleotides, when co-incubated with LRRK2 during phosphorylation reactions. Also phosphorylation activity of LRRK2 is unchanged when the LRRK2 guanine nucleotide binding pocket is previously saturated with various nucleotides, in contrast to the greatly reduced activity measured for the guanine nucleotide binding site mutant T1348N. Interestingly, when nucleotides were incubated with cell lysates prior to purification of LRRK2, kinase activity was slightly enhanced by GTPγS or GMPPCP compared to GDP, pointing to an upstream guanine nucleotide binding protein that may activate LRRK2 in a GTP-dependent manner. Using metabolic labeling, we also found that cellular phosphorylation of LRRK2 was not significantly modulated by nucleotides, although labeling is significantly reduced by guanine nucleotide binding site mutants. We conclude that while kinase activity of LRRK2 requires an intact ROC-GTPase domain, it is independent of GDP or GTP binding to ROC.

Factor XII-independent activation of the bradykinin-forming cascade

DEFF Research Database (Denmark)

Joseph, Kusumam; Tholanikunnel, Baby G; Bygum, Anette

2013-01-01

and assayed for kallikrein formation. C1-INH was removed from factor XII-deficient plasma by means of immunoadsorption. RESULTS: We demonstrate that prekallikrein-HK will activate to kallikrein in phosphate-containing buffers and that the rate is further accelerated on addition of heat shock protein 90...... the prekallikrein-HK complex to prevent HK cleavage either by prekallikrein or by prekallikrein-HK autoactivation to generate kallikrein. In patients with hereditary angioedema, kallikrein and bradykinin formation can occur without invoking factor XII activation, although the kallikrein formed can rapidly activate...

Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid.

Directory of Open Access Journals (Sweden)

Jae Sung You

Full Text Available Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

Casein Kinase 2 Reverses Tail-Independent Inactivation of Kinesin-1

Science.gov (United States)

Xu, Jing

2013-03-01

Kinesin-1 is a plus-end microtubule-based motor, and defects in kinesin-based transport are linked to diseases including neurodegeneration. Kinesin can auto-inhibit via a head-tail interaction, but is believed to be active otherwise. Here we report a tail-independent inactivation of kinesin, reversible by the disease-relevant signalling protein, casein kinase 2 (CK2). The majority of initially active kinesin (native or tail-less) loses its ability to interact with microtubules in vitro, and CK2 reverses this inactivation (approximately fourfold) without altering kinesin's single motor properties. This activation pathway does not require motor phosphorylation, and is independent of head-tail auto-inhibition. In cultured mammalian cells, reducing CK2 expression, but not its kinase activity, decreases the force required to stall lipid droplet transport, consistent with a decreased number of active kinesin motors. Our results (Nat. Commun., 3:754, 2012) provide the first direct evidence of a protein kinase upregulating kinesin-based transport, and suggest a novel pathway for regulating the activity of cargo-bound kinesin. Work supported by NIGMS grants GM64624 to SPG, GM74830-06A1 to LH, GM76516 to LB, NS048501 to SJK, and AHA grant 825278F to JX.

Enhanced UV-Visible Light Photocatalytic Activity by Constructing Appropriate Heterostructures between Mesopore TiO₂ Nanospheres and Sn₃O₄ Nanoparticles.

Science.gov (United States)

Hu, Jianling; Tu, Jianhai; Li, Xingyang; Wang, Ziya; Li, Yan; Li, Quanshui; Wang, Fengping

2017-10-19

Novel TiO₂/Sn₃O₄ heterostructure photocatalysts were ingeniously synthesized via a scalable two-step method. The impressive photocatalytic abilities of the TiO₂/Sn₃O₄ sphere nanocomposites were validated by the degradation test of methyl orange and •OH trapping photoluminescence experiments under ultraviolet (UV) and visible light irradiation, respectively. Especially under the visible light, the TiO₂/Sn₃O₄ nanocomposites demonstrated a superb photocatalytic activity, with 81.2% of methyl orange (MO) decomposed at 30 min after irradiation, which greatly exceeded that of the P25 (13.4%), TiO₂ (0.5%) and pure Sn₃O₄ (59.1%) nanostructures. This enhanced photocatalytic performance could be attributed to the mesopore induced by the monodispersed TiO₂ cores that supply sufficient surface areas and accessibility to reactant molecules. This exquisite hetero-architecture facilitates extended UV-visible absorption and efficient photoexcited charge carrier separation.

Distributed Large Independent Sets in One Round On Bounded-independence Graphs

OpenAIRE

Halldorsson , Magnus M.; Konrad , Christian

2015-01-01

International audience; We present a randomized one-round, single-bit messages, distributed algorithm for the maximum independent set problem in polynomially bounded-independence graphs with poly-logarithmic approximation factor. Bounded-independence graphs capture various models of wireless networks such as the unit disc graphs model and the quasi unit disc graphs model. For instance, on unit disc graphs, our achieved approximation ratio is O((log(n)/log(log(n)))^2).A starting point of our w...

Intracellular ROS protection efficiency and free radical-scavenging activity of curcumin.

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Abolfazl Barzegar

Full Text Available Curcumin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of curcumin in polar solvents by a comparative study using ESR, reduction of ferric iron in aqueous medium and intracellular ROS/toxicity assays. ESR data indicated that the steric hindrance among adjacent big size groups within a galvinoxyl molecule limited the curcumin to scavenge galvinoxyl radicals effectively, while curcumin showed a powerful capacity for scavenging intracellular smaller oxidative molecules such as H₂O₂, HO•, ROO•. Cell viability and ROS assays demonstrated that curcumin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and lethal effects of cumene hydroperoxide. Curcumin also showed good electron-transfer capability, with greater activity than trolox in aqueous solution. Curcumin can readily transfer electron or easily donate H-atom from two phenolic sites to scavenge free radicals. The excellent electron transfer capability of curcumin is because of its unique structure and different functional groups, including a β-diketone and several π electrons that have the capacity to conjugate between two phenyl rings. Therfore, since curcumin is inherently a lipophilic compound, because of its superb intracellular ROS scavenging activity, it can be used as an effective antioxidant for ROS protection within the polar cytoplasm.

Independent assessment to continue improvement: Implementing statistical process control at the Hanford Site

International Nuclear Information System (INIS)

Hu, T.A.; Lo, J.C.

1994-11-01

A Quality Assurance independent assessment has brought about continued improvement in the PUREX Plant surveillance program at the Department of Energy's Hanford Site. After the independent assessment, Quality Assurance personnel were closely involved in improving the surveillance program, specifically regarding storage tank monitoring. The independent assessment activities included reviewing procedures, analyzing surveillance data, conducting personnel interviews, and communicating with management. Process improvement efforts included: (1) designing data collection methods; (2) gaining concurrence between engineering and management, (3) revising procedures; and (4) interfacing with shift surveillance crews. Through this process, Statistical Process Control (SPC) was successfully implemented and surveillance management was improved. The independent assessment identified several deficiencies within the surveillance system. These deficiencies can be grouped into two areas: (1) data recording and analysis and (2) handling off-normal conditions. By using several independent assessment techniques, Quality Assurance was able to point out program weakness to senior management and present suggestions for improvements. SPC charting, as implemented by Quality Assurance, is an excellent tool for diagnosing the process, improving communication between the team members, and providing a scientific database for management decisions. In addition, the surveillance procedure was substantially revised. The goals of this revision were to (1) strengthen the role of surveillance management, engineering and operators and (2) emphasize the importance of teamwork for each individual who performs a task. In this instance we believe that the value independent assessment adds to the system is the continuous improvement activities that follow the independent assessment. Excellence in teamwork between the independent assessment organization and the auditee is the key to continuing improvement

Quantification of Iodine-123-FP-CIT SPECT with a resolution-independent method

International Nuclear Information System (INIS)

Dobbeleir, A.A.; Ham, H.R.; Hambye, A.E.; Vervaet, A.M.

2005-01-01

Accurate quantification of small-sized objects by SPECT is hampered by the partial volume effect. The present work evaluates the magnitude of this phenomenon with Iodine- 123 in phantom studies, and presents a resolution- independent method to quantify striatal I-123 FP-CIT uptake in patients. At first five syringes with internal diameters varying between 9 and 29mm and an anthropomorphic striatal phantom were filled with known concentrations of Iodine-123 and imaged by SPECT using different collimators and radii of rotation. Data were processed with and without scatter correction. From the measured activities, calibration factors were calculated for each specific collimator. Then a resolution-independent method for FP-CIT quantification using large regions of interest was developed and validated in 34 human studies (controls and patients) acquired in 2 different hospitals, by comparing its results to those obtained by a semi- quantitative striatal-to-occipital analysis. Taking the injected activity and decay into account, the measured counts/volume could be converted into absolute tracer concentrations. For the fan-beam, high resolution and medium energy collimators, the measured maximum activity in comparison to the 29 mm-diameter syringe was respectively 38%, 16% and 9% for the 9 mm-diameter syringe and 82%, 80% and 30% for the 16 mm syringe, and not significantly modified after scatter correction. For the anthropomorphic phantom, the error in measurement in % of the true concentration ranged between 0.3-9.5% and was collimator dependent. Medium energy collimators yielded the most homogeneous results. In the human studies, inter- observer variability was 11.4% for the striatal-to-occipital ratio and 3.1% for the resolution-independent method, with correlation coefficients >0.8 between both. The resolution- independent method was 89%-sensitive and 100%-specific to separate the patients without and with abnormal FP-CIT uptake (accuracy: 94%). Also the

Calcium-dependent but calmodulin-independent protein kinase from soybean

International Nuclear Information System (INIS)

Harmon, A.C.; Putnam-Evans, C.; Cormier, M.J.

1987-01-01

A calcium-dependent protein kinase activity from suspension-cultured soybean cells (Glycine max L. Wayne) was shown to be dependent on calcium but not calmodulin. The concentrations of free calcium required for half-maximal histone H1 phosphorylation and autophosphorylation were similar (≥ 2 micromolar). The protein kinase activity was stimulated 100-fold by ≥ 10 micromolar-free calcium. When exogenous soybean or bovine brain calmodulin was added in high concentration (1 micromolar) to the purified kinase, calcium-dependent and -independent activities were weakly stimulated (≤ 2-fold). Bovine serum albumin had a similar effect on both activities. The kinase was separated from a small amount of contaminating calmodulin by sodium dodecyl sulfate polyacrylamide gel electrophoresis. After renaturation the protein kinase autophosphorylated and phosphorylated histone H1 in a calcium-dependent manner. Following electroblotting onto nitrocellulose, the kinase bound 45 Ca 2+ in the presence of KCl and MgCl 2 , which indicated that the kinase itself is a high-affinity calcium-binding protein. Also, the mobility of one of two kinase bands in SDS gels was dependent on the presence of calcium. Autophosphorylation of the calmodulin-free kinase was inhibited by the calmodulin-binding compound N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), showing that the inhibition of activity by W-7 is independent of calmodulin. These results show that soybean calcium-dependent protein kinase represents a new class of protein kinase which requires calcium but not calmodulin for activity

Coincident In Vitro Analysis of DNA-PK-Dependent and -Independent Nonhomologous End Joining

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Cynthia L. Hendrickson

2010-01-01

Full Text Available In mammalian cells, DNA double-strand breaks (DSBs are primarily repaired by nonhomologous end joining (NHEJ. The current model suggests that the Ku 70/80 heterodimer binds to DSB ends and recruits DNA-PKcs to form the active DNA-dependent protein kinase, DNA-PK. Subsequently, XRCC4, DNA ligase IV, XLF and most likely, other unidentified components participate in the final DSB ligation step. Therefore, DNA-PK plays a key role in NHEJ due to its structural and regulatory functions that mediate DSB end joining. However, recent studies show that additional DNA-PK-independent NHEJ pathways also exist. Unfortunately, the presence of DNA-PKcs appears to inhibit DNA-PK-independent NHEJ, and in vitro analysis of DNA-PK-independent NHEJ in the presence of the DNA-PKcs protein remains problematic. We have developed an in vitro assay that is preferentially active for DNA-PK-independent DSB repair based solely on its reaction conditions, facilitating coincident differential biochemical analysis of the two pathways. The results indicate the biochemically distinct nature of the end-joining mechanisms represented by the DNA-PK-dependent and -independent NHEJ assays as well as functional differences between the two pathways.

Glucose homeostasis in mice is transglutaminase 2 independent.

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Siiri E Iismaa

Full Text Available Transglutaminase type 2 (TG2 has been reported to be a candidate gene for maturity onset diabetes of the young (MODY because three different mutations that impair TG2 transamidase activity have been found in 3 families with MODY. TG2 null (TG2(-/- mice have been reported to be glucose intolerant and have impaired glucose-stimulated insulin secretion (GSIS. Here we rigorously evaluated the role of TG2 in glucose metabolism using independently generated murine models of genetic TG2 disruption, which show no compensatory enhanced expression of other TGs in pancreatic islets or other tissues. First, we subjected chow- or fat-fed congenic SV129 or C57BL/6 wild type (WT and TG2(-/- littermates, to oral glucose gavage. Blood glucose and serum insulin levels were similar for both genotypes. Pancreatic islets isolated from these animals and analysed in vitro for GSIS and cholinergic potentiation of GSIS, showed no significant difference between genotypes. Results from intraperitoneal glucose tolerance tests (GTTs and insulin tolerance tests (ITTs were similar for both genotypes. Second, we directly investigated the role of TG2 transamidase activity in insulin secretion using a coisogenic model that expresses a mutant form of TG2 (TG2(R579A, which is constitutively active for transamidase activity. Intraperitoneal GTTs and ITTs revealed no significant differences between WT and TG2(R579A/R579A mice. Given that neither deletion nor constitutive activation of TG2 transamidase activity altered basal responses, or responses to a glucose or insulin challenge, our data indicate that glucose homeostasis in mice is TG2 independent, and question a link between TG2 and diabetes.

ORGANIZING PROSPECTIVE PRIMARY SCHOOL TEACHERS’ INDEPENDENT WORK IN THE COURSE OF “FINE ARTS WITH METHODOLOGY”

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Oleksandr Plakhotskyi

2016-04-01

Full Text Available This article is devoted to the actual problem of modern art education - organization of independent artwork of seekers of higher education in the prospective primary school teachers’ professional training. The authors note that the independent work is one of the most important components of the educational process, which involves the integration of different types of individual and collective educational activities conducted as in the classroom, extracurricular classes, without a teacher, and under his direct leadership. The authors point out that mastering the skills of independent work intensifies future specialist’s cognitive activity, facilitates searching scientific and methodological information, makes mastering of educational material more conscious, encourages self-development and self-study. Analysing the scientific exploration of modern educators and psychologists on the organization of independent work, the author determines the optimal forms and methods of students’ independent activity in the course "Fine Arts with Teaching Methodology." Particular attention is paid to methodological support of students' independent work with thematic module "Decorative painting", which contains forms and instructional techniques of teaching Petrykivska painting. The authors emphasize that one of the important conditions for successful primary school teachers’ fine arts training, developing their artistic abilities during the tasks of independent work is the individual approach, the choice of methods, techniques, learning pace, depending on students’ individual characteristics and interests.

Aluminum-activated citrate and malate transporters from the MATE and ALMT families function independently to confer Arabidopsis aluminum tolerance.

Science.gov (United States)

Liu, Jiping; Magalhaes, Jurandir V; Shaff, Jon; Kochian, Leon V

2009-02-01

Aluminum-activated root malate and citrate exudation play an important role in plant Al tolerance. This paper characterizes AtMATE, a homolog of the recently discovered sorghum and barley Al-tolerance genes, shown here to encode an Al-activated citrate transporter in Arabidopsis. Together with the previously characterized Al-activated malate transporter, AtALMT1, this discovery allowed us to examine the relationship in the same species between members of the two gene families for which Al-tolerance genes have been identified. AtMATE is expressed primarily in roots and is induced by Al. An AtMATE T-DNA knockdown line exhibited very low AtMATE expression and Al-activated root citrate exudation was abolished. The AtALMT1 AtMATE double mutant lacked both Al-activated root malate and citrate exudation and showed greater Al sensitivity than the AtALMT1 mutant. Therefore, although AtALMT1 is a major contributor to Arabidopsis Al tolerance, AtMATE also makes a significant but smaller contribution. The expression patterns of AtALMT1 and AtMATE and the profiles of Al-activated root citrate and malate exudation are not affected by the presence or absence of the other gene. These results suggest that AtALMT1-mediated malate exudation and AtMATE-mediated citrate exudation evolved independently to confer Al tolerance in Arabidopsis. However, a link between regulation of expression of the two transporters in response to Al was identified through work on STOP1, a transcription factor that was previously shown to be necessary for AtALMT1 expression. Here we show that STOP1 is also required for AtMATE expression and Al-activated citrate exudation.

HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling

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Choi Chan

2010-05-01

Full Text Available Abstract Background Androgen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained. Results In this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21waf tumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21waf; this inhibition largely affected HOXB13-mediated promotion of E2F signaling. Conclusions Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling.

[Factors associated with activities of daily living (ADL) in independently living elderly persons in a community: a baseline examination of a large scale cohort study, Fujiwara-kyo study].

Science.gov (United States)

Komatsu, Masayo; Nezu, Satoko; Tomioka, Kimiko; Hazaki, Kan; Harano, Akihiro; Morikawa, Masayuki; Takagi, Masahiro; Yamada, Masahiro; Matsumoto, Yoshitaka; Iwamoto, Junko; Ishizuka, Rika; Saeki, Keigo; Okamoto, Nozomi; Kurumatani, Norio

2013-01-01

To investigate factors associated with activities of daily living in independently living elderly persons in a community. The potential subjects were 4,472 individuals aged 65 years and older who voluntarily participated in a large cohort study, the Fujiwara-kyo study. We used self-administered questionnaires consisting of an activities of daily living (ADL) questionnaire with the Physical Fitness Test established by the Ministry of Education, Culture, Sports, Science and Technology (12 ADL items) to determine the index of higher-level physical independence, demographics, Geriatric Depression Scale, and so on. Mini-mental state examination, measurement of physical fitness, and blood tests were also carried out. A lower ADL level was defined as having a total score of the 12 ADL items (range, 12-36 points) that was below the first quartile of a total score for all the subjects. Factors associated with a low ADL level were examined by multiple logistic regression. A total of 4,198 remained as subjects for analysis. The male, female and 5-year-old groups showed significant differences in the median score of 12 ADL items between any two groups. The highest odds ratio among factors associated with lower ADL level by multiple logistic regression with mutually adjusted independent variables was 4.49 (95%CI: 2.82-7.17) in the groups of "very sharp pain" or "strong pain" during the last month. Low physical ability, self-awareness of limb weakness, a BMI of over 25, low physical activity, cerebrovascular disorder, depression, low cognitive function, unable "to see normally", unable "to hear someone", "muscle, bone and joint pain" were independently associated with lower ADL level. Multiple factors are associated with lower ADL level assessed on the basis of the 12 ADL items.

Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

Science.gov (United States)

Lo, Fu-Sun; Erzurumlu, Reha S; Powell, Elizabeth M

2016-03-30

Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated geneMETtyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAAreceptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAAreceptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. Copyright © 2016 the authors 0270-6474/16/363691-07$15.00/0.

Motivating Students to Be Active outside of Class: A Hierarchy for Independent Physical Activity

Science.gov (United States)

Hill, Grant

2009-01-01

Despite the fact that children have an extraordinary amount of leisure time, students of all ages engage in too little physical activity. Opportunities for physical activity should be provided through recesses, lunch periods, organized fitness breaks, before- and after-school activity programs, and structured physical education classes. However,…

Insulin-Like Growth Factor-I Induces Arginase Activity in Leishmania amazonensis Amastigote-Infected Macrophages through a Cytokine-Independent Mechanism

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Celia Maria Vieira Vendrame

2014-01-01

Full Text Available Leishmania (Leishmania amazonensis exhibits peculiarities in its interactions with hosts. Because amastigotes are the primary form associated with the progression of infection, we studied the effect of insulin-like growth factor (IGF-I on interactions between L. (L. amazonensis amastigotes and macrophages. Upon stimulation of infected macrophages with IGF-I, we observed decreased nitric oxide production but increased arginase expression and activity, which lead to increased parasitism. However, stimulation of amastigote-infected macrophages with IGF-I did not result in altered cytokine levels compared to unstimulated controls. Because IGF-I is present in tissue fluids and also within macrophages, we examined the possible effect of this factor on phosphatidylserine (PS exposure on amastigotes, seen previously in tissue-derived amastigotes leading to increased parasitism. Stimulation with IGF-I induced PS exposure on amastigotes but not on promastigotes. Using a PS-liposome instead of amastigotes, we observed that the PS-liposome but not the control phosphatidylcholine-liposome led to increased arginase activity in macrophages, and this process was not blocked by anti-TGF-β antibodies. Our results suggest that in L. (L. amazonensis amastigote-infected macrophages, IGF-I induces arginase activity directly in amastigotes and in macrophages through the induction of PS exposure on amastigotes in the latter, which could lead to the alternative activation of macrophages through cytokine-independent mechanisms.

Cortical networks involved in visual awareness independent of visual attention

OpenAIRE

Webb, Taylor W.; Igelström, Kajsa M.; Schurger, Aaron; Graziano, Michael S. A.

2016-01-01

Do specific areas of the brain participate in subjective visual experience? We measured brain activity in humans using fMRI. Participants were aware of a visual stimulus in one condition and unaware of it in another condition. The two conditions were balanced for their effect on visual attention. Specific brain areas were more active in the aware than in the unaware condition, suggesting they were involved in subjective awareness independent of attention. The largest cluster of activity was f...

Media independence and dividend policy

DEFF Research Database (Denmark)

Farooq, Omar; Dandoune, Salma

2012-01-01

independence and dividend policies in emerging markets. Using a dataset from twenty three emerging markets, we show a significantly negative relationship between dividend policies (payout ratio and decision to pay dividend) and media independence. We argue that independent media reduces information asymmetries...... for stock market participants. Consequently, stock market participants in emerging markets with more independent media do not demand as high and as much dividends as their counterparts in emerging markets with less independent media. We also show that press independence is more important in defining......Can media pressurize managers to disgorge excess cash to shareholders? Do firms in countries with more independent media follow different dividend policies than firms with less independent media? This paper seeks to answer these questions and aims to document the relationship between media...

The Potential of Three Computer-Based Communication Activities for Supporting Older Adult Independent Living

Directory of Open Access Journals (Sweden)

Melinda Heinz

2016-05-01

Full Text Available Technology has become an increasingly integral part of life. For example, technology allows individuals to stay in touch with loved ones, obtain medical services through telehealthcare, and enjoy an overall higher quality of life. Particularly for older adults, using technology increases the likelihood that they will maintain their independence and autonomy. Long-distance caregiving has recently become a feasible option where caregivers for older adults can access reports and information about their loved one’s patterns that day (e.g., food and medication intake. Technology may be able to offset age-related challenges (e.g., caregiving, accessing healthcare, decreased social networks by applying technology to the needs of older adults. Solutions for meeting such challenges, however, have been less targeted. In addition, the healthcare system is evolving to focus on providing options and services in the home. This has direct implications for older adults, as the majority of healthcare services are utilized by older adults. Research is still at the beginning stages of developing successful technology tools that are compatible with older adult users. Therefore, the design, implementation, and outcome of such computer-based communication activities will be discussed in this paper in order to guide future endeavors in technology marketed for older adults.

A novel tumor suppressor function of glycine N-methyltransferase is independent of its catalytic activity but requires nuclear localization.

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Suchandra DebRoy

Full Text Available Glycine N-methyltransferase (GNMT, an abundant cytosolic enzyme, catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM to glycine generating S-adenosylhomocysteine and sarcosine (N-methylglycine. This reaction is regulated by 5-methyltetrahydrofolate, which inhibits the enzyme catalysis. In the present study, we observed that GNMT is strongly down regulated in human cancers and is undetectable in cancer cell lines while the transient expression of the protein in cancer cells induces apoptosis and results in the activation of ERK1/2 as an early pro-survival response. The antiproliferative effect of GNMT can be partially reversed by treatment with the pan-caspase inhibitor zVAD-fmk but not by supplementation with high folate or SAM. GNMT exerts the suppressor effect primarily in cells originated from malignant tumors: transformed cell line of non-cancer origin, HEK293, was insensitive to GNMT. Of note, high levels of GNMT, detected in regenerating liver and in NIH3T3 mouse fibroblasts, do not produce cytotoxic effects. Importantly, GNMT, a predominantly cytoplasmic protein, was translocated into nuclei upon transfection of cancer cells. The presence of GNMT in the nuclei was also observed in normal human tissues by immunohistochemical staining. We further demonstrated that the induction of apoptosis is associated with the GNMT nuclear localization but is independent of its catalytic activity or folate binding. GNMT targeted to nuclei, through the fusion with nuclear localization signal, still exerts strong antiproliferative effects while its restriction to cytoplasm, through the fusion with nuclear export signal, prevents these effects (in each case the protein was excluded from cytosol or nuclei, respectively. Overall, our study indicates that GNMT has a secondary function, as a regulator of cellular proliferation, which is independent of its catalytic role.

TV viewing time is associated with increased all-cause mortality in Brazilian adults independent of physical activity.

Science.gov (United States)

Turi, B C; Monteiro, H L; Lemes, Í R; Codogno, J S; Lynch, K R; Asahi Mesquita, C A; Fernandes, R A

2018-02-01

The purpose of this study was to investigate the association between television (TV) viewing and all-cause mortality among Brazilian adults after 6 years of follow-up. This longitudinal study started in 2010 in the city of Bauru, SP, Brazil, and involved 970 adults aged ≥50 years. Mortality was reported by relatives and confirmed in medical records of the Brazilian National Health System. Physical activity (PA) and TV viewing were assessed by the Baecke questionnaire. Health status, sociodemographic and behavioral covariates were considered as potential confounders. After 6 years of follow-up, 89 deaths were registered (9.2% [95% CI=7.4%-11%]). Type 2 diabetes mellitus was associated with higher risk of mortality (P-value=.012). Deaths correlated significantly with age (ρ=.188; P-value=.001), overall PA score (ρ=-.128; P-value=.001) and TV viewing (ρ=.086; P-value=.007). Lower percentage of participants reported TV viewing time as often (16%) and very often (5.7%), but there was an association between higher TV viewing time ("often" and "very often" grouped together) and increased mortality after 6 years of follow-up (P-value=.006). The higher TV viewing time was associated with a 44.7% increase in all-cause mortality (HR=1.447 [1.019-2.055]), independently of other potential confounders. In conclusion, the findings from this cohort study identified increased risk of mortality among adults with higher TV viewing time, independently of PA and other variables. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

College Online Developmental Reading Instruction: Creating a Path to Independent and Active Learning

Science.gov (United States)

Johnson, E. Janet

2010-01-01

Online courses require students to be independent readers and efficient learners. College students who need developmental reading lack these qualities; consequently, faculty do not generally view developmental reading courses as appropriate for an online format. However, an effectively designed online course based on best practices can engage less…

Ligand-independent interaction of the type I interferon receptor complex is necessary to observe its biological activity.

Science.gov (United States)

Krause, Christopher D; Digioia, Gina; Izotova, Lara S; Xie, Junxia; Kim, Youngsun; Schwartz, Barbara J; Mirochnitchenko, Olga V; Pestka, Sidney

2013-10-01

Ectopic coexpression of the two chains of the Type I and Type III interferon (IFN) receptor complexes (IFN-αR1 and IFN-αR2c, or IFN-λR1 and IL-10R2) yielded sensitivity to IFN-alpha or IFN-lambda in only some cells. We found that IFN-αR1 and IFN-αR2c exhibit FRET only when expressed at equivalent and low levels. Expanded clonal cell lines expressing both IFN-αR1 and IFN-αR2c were sensitive to IFN-alpha only when IFN-αR1 and IFN-αR2c exhibited FRET in the absence of human IFN-alpha. Coexpression of RACK-1 or Jak1 enhanced the affinity of the interaction between IFN-αR1 and IFN-αR2c. Both IFN-αR1 and IFN-αR2c exhibited FRET with Jak1 and Tyk2. Together with data showing that disruption of the preassociation between the IFN-gamma receptor chains inhibited its biological activity, we propose that biologically active IFN receptors require ligand-independent juxtaposition of IFN receptor chains assisted by their associated cytosolic proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human NLRP3 inflammasome activation is Nox1-4 independent

NARCIS (Netherlands)

van Bruggen, Robin; Köker, M. Yavuz; Jansen, Machiel; van Houdt, Michel; Roos, Dirk; Kuijpers, Taco W.; van den Berg, Timo K.

2010-01-01

The NLRP3 inflammasome can be activated by pathogen-associated molecular patterns or endogenous danger-associated molecular patterns. The activation of the NLRP3 inflammasome results in proteolytic activation and secretion of cytokines of the interleukin-1 (IL-1) family. The precise mode of

Sarcopenia is a risk factor for elevated aminotransferase in men independently of body mass index, dietary habits, and physical activity.

Science.gov (United States)

Yoo, Ki Deok; Jun, Dae Won; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Choi, Ho Soon

2015-04-01

Aminotransferase activity is a surrogate marker of liver injury showing strong correlations with obesity and metabolic syndrome. However, elevated aminotransferase activity is not uncommon in non-obese and non-alcoholic patients in clinical practice. To examine the relationship between sarcopenia and aminotransferase activity in a large population-based cohort. Data from the Korean National Health and Nutrition Examinations were used. A total of 13,431 subjects were included. A whole-body dual X-ray absorptiometry scan was performed on each patient to measure total and regional muscle mass. Appendicular skeletal muscle mass indices were also obtained. The prevalence of sarcopenia was significantly higher in the group with elevated aminotransferase levels than in the normal liver enzyme group (males: 26.5% vs. 16.9%; females: 38.3% vs. 22.1%, plevels. The frequency of elevated aminotransferase increased in male patients with sarcopenia after adjusting for potential confounding factors including age, body mass index, fasting glucose level, dietary, and exercise habits. However, the correlation was no longer observed in women after adjusting for body mass index. Sarcopenia is a risk factor for elevated aminotransferase in men, independently of body mass index, dietary habits, and physical activity. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The importance of board independence

NARCIS (Netherlands)

Zijl, N.J.M.

2012-01-01

Although the attributed importance of board independence is high, a clear definition of independence does not exist. Furthermore, the aim and consequences of independence are the subject of discussion and empirical evidence about the impact of independence is weak and disputable. Despite this lack

Abdominal obesity and physical inactivity are associated with erectile dysfunction independent of body mass index.

Science.gov (United States)

Janiszewski, Peter M; Janssen, Ian; Ross, Robert

2009-07-01

Erectile dysfunction (ED) is common among men with an elevated body mass index (BMI). However, a high waist circumference (WC) and low levels of physical activity may predict ED independently of BMI. We investigated the independent relationships between BMI, WC, and physical activity with ED. Subjects consisted of 3,941 adult men (age > or = 20 years) with no history of prostate cancer from the 2001-2004 National Health and Nutrition Examination Survey. Logistic regression analyses were used to examine the relative odds of ED association with categories of BMI, WC, and physical activity. Established thresholds were used to divide subjects into three WC and BMI categories. Physical activity level was divided into active (> or =150 min/week), moderately active (30-149 min/week), and inactive (inactive men had an approximately 40-60% greater odds of ED compared with active men. When all three predictors (WC, BMI, and physical activity level) were entered into the same logistic regression model, both a high WC and low physical activity level (moderately active and inactive) were independently associated with a greater odds of ED, whereas BMI level was not. Maintaining a WC level below 102 cm and achieving the recommended amount of moderate-intensity physical activity (>or =150 min/week) is associated with the maintenance of proper erectile function, regardless of BMI level. These findings suggest that the clinical screening for ED risk should include the assessment of WC and physical activity level in addition to BMI.

TECHNOLOGY TRANSFER TO U.S. INDEPENDENT OIL AND NATURAL GAS PRODUCERS

Energy Technology Data Exchange (ETDEWEB)

Unknown

2003-04-30

The Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of helping U.S. independent oil and natural gas producers make timely, informed technology decisions. Networking opportunities that occur with a Houston Headquarters (HQ) location are increasing name awareness. Focused efforts by Executive Director Don Duttlinger to interact with large independents, national service companies and some majors are continuing to supplement the support base of the medium to smaller industry participants around the country. PTTC is now involved in many of the technology-related activities that occur in high oil and natural gas activity areas. Access to technology remains the driving force for those who do not have in-house research and development capabilities and look to the PTTC to provide services and options for increased efficiency.

IKKα/CHUK regulates extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation.

Directory of Open Access Journals (Sweden)

Eleonora Olivotto

Full Text Available BACKGROUND: The non-canonical NF-κB activating kinase IKKα, encoded by CHUK (conserved-helix-loop-helix-ubiquitous-kinase, has been reported to modulate pro- or anti- inflammatory responses, cellular survival and cellular differentiation. Here, we have investigated the mechanism of action of IKKα as a novel effector of human and murine chondrocyte extracellular matrix (ECM homeostasis and differentiation towards hypertrophy. METHODOLOGY/PRINCIPAL FINDINGS: IKKα expression was ablated in primary human osteoarthritic (OA chondrocytes and in immature murine articular chondrocytes (iMACs derived from IKKα(f/f:CreERT2 mice by retroviral-mediated stable shRNA transduction and Cre recombinase-dependent Lox P site recombination, respectively. MMP-10 was identified as a major target of IKKα in chondrocytes by mRNA profiling, quantitative RT-PCR analysis, immunohistochemistry and immunoblotting. ECM integrity, as assessed by type II collagen (COL2 deposition and the lack of MMP-dependent COL2 degradation products, was enhanced by IKKα ablation in mice. MMP-13 and total collagenase activities were significantly reduced, while TIMP-3 (tissue inhibitor of metalloproteinase-3 protein levels were enhanced in IKKα-deficient chondrocytes. IKKα deficiency suppressed chondrocyte differentiation, as shown by the quantitative inhibition of.Alizarin red staining and the reduced expression of multiple chondrocyte differentiation effectors, including Runx2, Col10a1 and Vegfa,. Importantly, the differentiation of IKKα-deficient chondrocytes was rescued by a kinase-dead IKKα protein mutant. CONCLUSIONS/SIGNIFICANCE: IKKα acts independent of its kinase activity to help drive chondrocyte differentiation towards a hypertrophic-like state. IKKα positively modulates ECM remodeling via multiple downstream targets (including MMP-10 and TIMP-3 at the mRNA and post-transcriptional levels, respectively to maintain maximal MMP-13 activity, which is required for ECM

INDICATORS AND DIAGNOSTICS OF INDEPENDENT WORK CULTURE FORMATION IN FUTURE MATHEMATICS TEACHERS

Directory of Open Access Journals (Sweden)

Олена Соя

2015-09-01

Full Text Available The article highlights the results of research of formation the culture of independent work of future mathematics teachers, indicating the effectiveness of selected theoretically grounded and practically implemented pedagogical conditions of its formation. Its semantic components that are interconnected and interdependent unity of cognitive, procedural, technological and motivational components were singled out on the basis of definition of independent work culture of future mathematics teachers. The system of indicators, which assessed the degree of mastering by students the culture of independent work by value-orientation, content-effective, reflective, constructive and operationally-activity criteria is reviewed.

Independent procedure of checking dose calculations using an independent calculus algorithm

International Nuclear Information System (INIS)

Perez Rozos, A.; Jerez Sainz, I.; Carrasco Rodriguez, J. L.

2006-01-01

In radiotherapy it is recommended the use of an independent procedure of checking dose calculations, in order to verify the main treatment planning system and double check every patient dosimetry. In this work we present and automatic spreadsheet that import data from planning system using IMPAC/RTP format and verify monitor unit calculation using an independent calculus algorithm. Additionally, it perform a personalized analysis of dose volume histograms and several radiobiological parameters like TCP and NTCP. Finally, the application automatically generate a clinical dosimetry report for every patient, including treatment fields, fractionation, independent check results, dose volume analysis, and first day forms. (Author)

Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

Science.gov (United States)

An, Young Jun; Na, Jung-Hyun; Kim, Myung-Il; Cha, Sun-Shin

2015-10-01

Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.

Independent Mobility Achieved through a Wireless Brain-Machine Interface.

Directory of Open Access Journals (Sweden)

Camilo Libedinsky

Full Text Available Individuals with tetraplegia lack independent mobility, making them highly dependent on others to move from one place to another. Here, we describe how two macaques were able to use a wireless integrated system to control a robotic platform, over which they were sitting, to achieve independent mobility using the neuronal activity in their motor cortices. The activity of populations of single neurons was recorded using multiple electrode arrays implanted in the arm region of primary motor cortex, and decoded to achieve brain control of the platform. We found that free-running brain control of the platform (which was not equipped with any machine intelligence was fast and accurate, resembling the performance achieved using joystick control. The decoding algorithms can be trained in the absence of joystick movements, as would be required for use by tetraplegic individuals, demonstrating that the non-human primate model is a good pre-clinical model for developing such a cortically-controlled movement prosthetic. Interestingly, we found that the response properties of some neurons differed greatly depending on the mode of control (joystick or brain control, suggesting different roles for these neurons in encoding movement intention and movement execution. These results demonstrate that independent mobility can be achieved without first training on prescribed motor movements, opening the door for the implementation of this technology in persons with tetraplegia.

Tactical Maneuvering and Calculated Risks: Independent Child Migrants and the Complex Terrain of Flight

Science.gov (United States)

Denov, Myriam; Bryan, Catherine

2012-01-01

Similar to refugees in general, independent child migrants are frequently constructed in academic and popular discourse as passive and powerless or as untrustworthy and potentially threatening. Such portrayals fail to capture how these youth actively navigate the complex experiences of forced migration. Drawing on interviews with independent child…

Application and Evaluation of Independent Component Analysis Methods to Generalized Seizure Disorder Activities Exhibited in the Brain.

Science.gov (United States)

George, S Thomas; Balakrishnan, R; Johnson, J Stanly; Jayakumar, J

2017-07-01

EEG records the spontaneous electrical activity of the brain using multiple electrodes placed on the scalp, and it provides a wealth of information related to the functions of brain. Nevertheless, the signals from the electrodes cannot be directly applied to a diagnostic tool like brain mapping as they undergo a "mixing" process because of the volume conduction effect in the scalp. A pervasive problem in neuroscience is determining which regions of the brain are active, given voltage measurements at the scalp. Because of which, there has been a surge of interest among the biosignal processing community to investigate the process of mixing and unmixing to identify the underlying active sources. According to the assumptions of independent component analysis (ICA) algorithms, the resultant mixture obtained from the scalp can be closely approximated by a linear combination of the "actual" EEG signals emanating from the underlying sources of electrical activity in the brain. As a consequence, using these well-known ICA techniques in preprocessing of the EEG signals prior to clinical applications could result in development of diagnostic tool like quantitative EEG which in turn can assist the neurologists to gain noninvasive access to patient-specific cortical activity, which helps in treating neuropathologies like seizure disorders. The popular and proven ICA schemes mentioned in various literature and applications were selected (which includes Infomax, JADE, and SOBI) and applied on generalized seizure disorder samples using EEGLAB toolbox in MATLAB environment to see their usefulness in source separations; and they were validated by the expert neurologist for clinical relevance in terms of pathologies on brain functionalities. The performance of Infomax method was found to be superior when compared with other ICA schemes applied on EEG and it has been established based on the validations carried by expert neurologist for generalized seizure and its clinical

TARGETED TECHNOLOGY TRANSFER TO US INDEPENDENTS

Energy Technology Data Exchange (ETDEWEB)

Donald F. Duttlinger; E. Lance Cole

2005-01-01

The Petroleum Technology Transfer Council (PTTC) continued pursuing its mission of assisting U.S. independent oil and gas producers with timely, informed technology decisions during Fiscal Year 2004 (FY04). PTTC has active grassroots programs through its 10 Regional Lead Organizations (RLOs) and 2 satellite offices. They bring research and academia to the table via their association with geological surveys and engineering departments. The regional directors interact with independent oil and gas producers through technology workshops, resource centers, websites, newsletters, technical publications and other cooperative outreach efforts. PTTC's Headquarters (HQ) staff receives direction from a National Board of Directors predominantly comprised of American natural gas and oil producers to plan and manage the overall technology transfer program. PTTC HQ implements a comprehensive communications program by interconnecting the talents of the National Board, 10 Regional Producer Advisory Groups (PAG) and the RLOs with industry across the U.S. PTTC effectively combines federal funding through the Department of Energy's (DOE) Office of Fossil Energy, namely the Strategic Center for Natural Gas and Oil with state and industry contributions to share application of upstream technologies. Ultimately, these efforts factor in to provide a safe, secure and reliable energy supply for American consumers. This integrated resource base, combined with industry volunteers guiding PTTC's activities and the dedication of national and regional staff, are achieving notable results regarding domestic production figures. PTTC is increasingly recognized as a critical resource for information and access to technologies by providing direct contact with research, development and demonstration (RD&D) results. A key to the program is demonstrating proven technologies that can be applied broadly and rapidly. This technical progress report summarizes PTTC's accomplishments during

Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake.

Science.gov (United States)

Hogenkamp, P S; Zhou, W; Dahlberg, L S; Stark, J; Larsen, A L; Olivo, G; Wiemerslage, L; Larsson, E-M; Sundbom, M; Benedict, C; Schiöth, H B

2016-11-01

In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m - 2 ) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m - 2 ), both before and 30 min after consumption of a standardized meal (~260 kcal). Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (Pfood intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (Pfood intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.

Independent safety organization

International Nuclear Information System (INIS)

Kato, W.Y.; Weinstock, E.V.; Carew, J.F.; Cerbone, R.J.; Guppy, J.G.; Hall, R.E.; Taylor, J.H.

1985-01-01

Brookhaven National Laboratory has conducted a study on the need and feasibility of an independent organization to investigate significant safety events for the Office for Analysis and Evaluation of Operational Data, USNRC. The study consists of three parts: the need for an independent organization to investigate significant safety events, alternative organizations to conduct investigations, and legislative requirements. The determination of need was investigated by reviewing current NRC investigation practices, comparing aviation and nuclear industry practices, and interviewing a spectrum of representatives from the nuclear industry, the regulatory agency, and the public sector. The advantages and disadvantages of alternative independent organizations were studied, namely, an Office of Nuclear Safety headed by a director reporting to the Executive Director for Operations (EDO) of NRC; an Office of Nuclear Safety headed by a director reporting to the NRC Commissioners; a multi-member NTSB-type Nuclear Safety Board independent of the NRC. The costs associated with operating a Nuclear Safety Board were also included in the study. The legislative requirements, both new authority and changes to the existing NRC legislative authority, were studied. 134 references

Enacting Risk in Independent Technological Innovation

DEFF Research Database (Denmark)

Berglund, Henrik; Hellström, Tomas

2002-01-01

The present study aims at investigating the role of risk in the activity of independent technological venturing. Altogether, 12 deep-interviews were conducted with technological entrepreneurs, who had taken part in the inventive, developmental and the commercialisation phases of a technology......-based innovation process. The interviews revealed a number of enactment approaches through which these innovators encountered and affected (dealt with or transformed) risk within the innovation process. Factors thus developed from the empirical material included human capital, pace and priority, the world moves...... for the benefit of innovation management....

76 FR 4113 - Independent Scientific Peer Review Panel Meeting on an In Vitro

Science.gov (United States)

2011-01-24

... antagonist activity. These studies were funded primarily by a Small Business Innovation Research (SBIR) grant... Vitro Estrogen Receptor Transcriptional Activation Test Method for Endocrine Disruptor Chemical... Toxicological Methods (NICEATM); Announcement of an Independent Scientific Peer Review Panel Meeting on an In...

Vocabulary Breadth and Field Dependence/Independence Cognitive Styles

Directory of Open Access Journals (Sweden)

Nassim Golaghaei

2011-07-01

Full Text Available This article is primarily bidirectional in that it is concerned with two fields of cognitive styles of field-dependency/independency on one hand and breadth of vocabulary knowledge on the other hand. In other word, this research is primarily intended to investigate the nature of the students' vocabulary knowledge in the field of passive and active knowledge of L2 words as a whole with regard to their preferred cognitive style of field dependency/independency. A group of 60 undergraduate students majoring in the field of English Language Teaching was selected. They were then divided into two groups based on the basis of their preferred cognitive styles of field-dependency / independency. Four types of tests, the 1000 frequency word-level test, the passive version of vocabulary Levels Test, the Productive Version of the Vocabulary Levels Test, and the Group Imbedded Figures Test were administered to the participants. The conclusion drawn after the analysis of the data was that the fieldindependent group outperformed their field-dependent counterparts in dealing with both passive and productive vocabulary levels. Finally, the findings of this research could be interpreted as being supportive of the idea that the field-dependent/independent cognitive style could be considered as an effective factor influencing the learners' vocabulary learning in the field of second language acquisition.

Screen time and passive school travel as independent predictors of cardiorespiratory fitness in youth.

Science.gov (United States)

Sandercock, Gavin R H; Ogunleye, Ayodele A

2012-05-01

The most prevalent sedentary behaviours in children and adolescents are engagement with small screen media (screen-time) and passive travel (by motorised vehicle). The objective of this research was to assess the independence of these behaviours from one another and from physical activity as predictors of cardiorespiratory fitness in youth. We measured cardiorespiratory fitness in n=6819 10-16 year olds (53% male) who self-reported their physical activity (7-day recall) school travel and screen time habits. Travel was classified as active (walking, cycling) or passive; screen time as 4 h. The multivariate odds of being fit were higher in active travel (Boys: OR 1.32, 95% CI: 1.09-1.59; Girls: OR 1.46, 1.15-1.84) than in passive travel groups. Boys reporting low screen time were more likely to be fit than those reporting >4 h (OR 2.11, 95% CI: 1.68-2.63) as were girls (OR 1.66, 95% CI: 1.24-2.20). These odds remained significant after additionally controlling for physical activity. Passive travel and high screen time are independently associated with poor cardiorespiratory fitness in youth, and this relationship is independent of physical activity levels. A lifestyle involving high screen time and habitual passive school travel appears incompatible with healthful levels of cardiorespiratory fitness in youth. Copyright © 2012 Elsevier Inc. All rights reserved.

Angiogenin-induced protein kinase B/Akt activation is necessary for angiogenesis but is independent of nuclear translocation of angiogenin in HUVE cells

International Nuclear Information System (INIS)

Kim, Hye-Mi; Kang, Dong-Ku; Kim, Hak Yong; Kang, Sang Sun; Chang, Soo-Ik

2007-01-01

Angiogenin, a potent angiogenic factor, binds to endothelial cells and is endocytosed and rapidly translocated to and concentrated in the nucleolus where it binds to DNA. In this study, we report that angiogenin induces transient phosphorylation of protein kinase B/Akt in cultured human umbilical vein endothelial (HUVE) cells. LY294002 inhibits the angiogenin-induced protein kinase B/Akt activation and also angiogenin-induced cell migration in vitro as well as angiogenesis in chick embryo chorioallantoic membrane in vivo without affecting nuclear translocation of angiogenin in HUVE cells. These results suggest that cross-talk between angiogenin and protein kinase B/Akt signaling pathways is essential for angiogenin-induced angiogenesis in vitro and in vivo, and that angiogenin-induced PKB/Akt activation is independent of nuclear translocation of angiogenin in HUVE cells

Thick filament mechano-sensing is a calcium-independent regulatory mechanism in skeletal muscle.

Science.gov (United States)

Fusi, L; Brunello, E; Yan, Z; Irving, M

2016-10-31

Recent X-ray diffraction studies on actively contracting fibres from skeletal muscle showed that the number of myosin motors available to interact with actin-containing thin filaments is controlled by the stress in the myosin-containing thick filaments. Those results suggested that thick filament mechano-sensing might constitute a novel regulatory mechanism in striated muscles that acts independently of the well-known thin filament-mediated calcium signalling pathway. Here we test that hypothesis using probes attached to the myosin regulatory light chain in demembranated muscle fibres. We show that both the extent and kinetics of thick filament activation depend on thick filament stress but are independent of intracellular calcium concentration in the physiological range. These results establish direct control of myosin motors by thick filament mechano-sensing as a general regulatory mechanism in skeletal muscle that is independent of the canonical calcium signalling pathway.

Involvement of caspase-dependent and -independent apoptotic pathways in cisplatin-induced apoptosis

Science.gov (United States)

Liu, Lei; Zhang, Yingjie; Wang, Xianwang

2009-02-01

Cisplatin, an efficient anticancer agent, can trigger multiple apoptotic pathways in cancer cells. However, the signal transduction pathways in response to cisplatin-based chemotherapy are complicated, and the mechanism is not fully understood. In current study, we showed that, during cisplatin-induced apoptosis of human lung adenocarcinoma cells, both the caspase-dependent and -independent pathways were activated. Herein, we reported that after cisplatin treatment, the activities of caspase-9/-3 were sharply increased; pre-treatment with Z-LEHD-fmk (inhibitor of caspase-9), Z-DEVD-fmk (inhibitor of caspase-3), and Z-VAD-fmk (a pan-caspase inhibitor) increased cell viability and decreased apoptosis, suggesting that caspase-mediated apoptotic pathway was activated following cisplatin treatment. Confocal imaging of the cells transfected with AIF-GFP demonstrated that AIF release occurred about 9 h after cisplatin treatment. The event proceeded progressively over time, coinciding with a nuclear translocation and lasting for more than 2 hours. Down-regulation of AIF by siRNA also significantly increased cell viability and decreased apoptosis, these results suggested that AIF-mediated caspase-independent apoptotic pathway was involved in cispatin-induced apoptosis. In conclusion, the current study demonstrated that both caspase-dependent and -independent apoptotic pathways were involved in cisplatin-induced apoptosis in human lung adenocarcinoma cells.

Independent technical review of the Pinellas Plant

Energy Technology Data Exchange (ETDEWEB)

1994-07-01

This report documents an Independent Technical Review (ITR) of facilities, organizations, plans, activities and various other elements required to successfully transition the Pinellas Plant from Defense Program (DP) funded operation to either community developed reuse or safe deactivation leading to decontamination and decommissioning (D&D). The review was conducted at the request of the Department of Energy (DOE) Deputy Assistant Secretary for Facility Transition and Management (EM-60) and is a consensus of the nine member ITR Team.

Denervation atrophy is independent from Akt and mTOR activation and is not rescued by myostatin inhibition

Directory of Open Access Journals (Sweden)

Elizabeth M. MacDonald

2014-04-01

Full Text Available The purpose of our study was to compare two acquired muscle atrophies and the use of myostatin inhibition for their treatment. Myostatin naturally inhibits skeletal muscle growth by binding to ActRIIB, a receptor on the cell surface of myofibers. Because blocking myostatin in an adult wild-type mouse induces profound muscle hypertrophy, we applied a soluble ActRIIB receptor to models of disuse (limb immobilization and denervation (sciatic nerve resection atrophy. We found that treatment of immobilized mice with ActRIIB prevented the loss of muscle mass observed in placebo-treated mice. Our results suggest that this protection from disuse atrophy is regulated by serum and glucocorticoid-induced kinase (SGK rather than by Akt. Denervation atrophy, however, was not protected by ActRIIB treatment, yet resulted in an upregulation of the pro-growth factors Akt, SGK and components of the mTOR pathway. We then treated the denervated mice with the mTOR inhibitor rapamycin and found that, despite a reduction in mTOR activation, there is no alteration of the atrophy phenotype. Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Thus, our studies show that denervation atrophy is not only independent from Akt, SGK and mTOR activation but also has a different underlying pathophysiological mechanism than disuse atrophy.

Independent EEG sources are dipolar.

Directory of Open Access Journals (Sweden)

Arnaud Delorme

Full Text Available Independent component analysis (ICA and blind source separation (BSS methods are increasingly used to separate individual brain and non-brain source signals mixed by volume conduction in electroencephalographic (EEG and other electrophysiological recordings. We compared results of decomposing thirteen 71-channel human scalp EEG datasets by 22 ICA and BSS algorithms, assessing the pairwise mutual information (PMI in scalp channel pairs, the remaining PMI in component pairs, the overall mutual information reduction (MIR effected by each decomposition, and decomposition 'dipolarity' defined as the number of component scalp maps matching the projection of a single equivalent dipole with less than a given residual variance. The least well-performing algorithm was principal component analysis (PCA; best performing were AMICA and other likelihood/mutual information based ICA methods. Though these and other commonly-used decomposition methods returned many similar components, across 18 ICA/BSS algorithms mean dipolarity varied linearly with both MIR and with PMI remaining between the resulting component time courses, a result compatible with an interpretation of many maximally independent EEG components as being volume-conducted projections of partially-synchronous local cortical field activity within single compact cortical domains. To encourage further method comparisons, the data and software used to prepare the results have been made available (http://sccn.ucsd.edu/wiki/BSSComparison.

On independence in risk communication

International Nuclear Information System (INIS)

Lacronique, J. F.

2006-01-01

The term 'independence' is a common key word used by almost all stake holders in the field of nuclear safety regulation. The intention is to persuade the public that it can have more confidence and trust in the persons in charge, if their competence and judgment cannot be altered by any kind of political issue or personal interest. However, it is possible to discuss the reality of this claimed quality: how is it possible to verify that the organization that claim 'independence' really respect it? National expertise Institutions can show that they are independent from the industry, but can they claim total independence from the government? NGO have build a large part of their constituency on 'independence' from industry and governments, but are they independent from the ideological forces -sometimes very powerful - that support them? How can we achieve to make this noble word really meaningful? We will show through different examples, that 'independence' is by definition a fragile and versatile challenge, rather than a durable label. It has to be refreshed regularly and thoroughly. Risk communication, in that context, must respect principles which will build independence as a solid asset, and keep a certain distance with mere marketing purposes or candid wishful thinking

Activation of Protease-Activated Receptor 2 Induces VEGF Independently of HIF-1

DEFF Research Database (Denmark)

Rasmussen, J.G.; Riis, Simone Elkjær; Frøbert, O.

2012-01-01

Human adipose stem cells (hASCs) can promote angiogenesis through secretion of proangiogenic factors such as vascular endothelial growth factor (VEGF). In other cell types, it has been shown that induction of VEGF is mediated by both protease activated receptor 2 (PAR2) and hypoxia inducible fact...

Appraising the value of independent EIA follow-up verifiers

Energy Technology Data Exchange (ETDEWEB)

Wessels, Jan-Albert, E-mail: janalbert.wessels@nwu.ac.za [School of Geo and Spatial Sciences, Department of Geography and Environmental Management, North-West University, C/O Hoffman and Borcherd Street, Potchefstroom, 2520 (South Africa); Retief, Francois, E-mail: francois.retief@nwu.ac.za [School of Geo and Spatial Sciences, Department of Geography and Environmental Management, North-West University, C/O Hoffman and Borcherd Street, Potchefstroom, 2520 (South Africa); Morrison-Saunders, Angus, E-mail: A.Morrison-Saunders@murdoch.edu.au [School of Geo and Spatial Sciences, Department of Geography and Environmental Management, North-West University, C/O Hoffman and Borcherd Street, Potchefstroom, 2520 (South Africa); Environmental Assessment, School of Environmental Science, Murdoch University, Australia. (Australia)

2015-01-15

Independent Environmental Impact Assessment (EIA) follow-up verifiers such as monitoring agencies, checkers, supervisors and control officers are active on various construction sites across the world. There are, however, differing views on the value that these verifiers add and very limited learning in EIA has been drawn from independent verifiers. This paper aims to appraise how and to what extent independent EIA follow-up verifiers add value in major construction projects in the developing country context of South Africa. A framework for appraising the role of independent verifiers was established and four South African case studies were examined through a mixture of site visits, project document analysis, and interviews. Appraisal results were documented in the performance areas of: planning, doing, checking, acting, public participating and integration with other programs. The results indicate that independent verifiers add most value to major construction projects when involved with screening EIA requirements of new projects, allocation of financial and human resources, checking legal compliance, influencing implementation, reporting conformance results, community and stakeholder engagement, integration with self-responsibility programs such as environmental management systems (EMS), and controlling records. It was apparent that verifiers could be more creatively utilized in pre-construction preparation, providing feedback of knowledge into assessment of new projects, giving input to the planning and design phase of projects, and performance evaluation. The study confirms the benefits of proponent and regulator follow-up, specifically in having independent verifiers that disclose information, facilitate discussion among stakeholders, are adaptable and proactive, aid in the integration of EIA with other programs, and instill trust in EIA enforcement by conformance evaluation. Overall, the study provides insight on how to harness the learning opportunities

Appraising the value of independent EIA follow-up verifiers

International Nuclear Information System (INIS)

Wessels, Jan-Albert; Retief, Francois; Morrison-Saunders, Angus

2015-01-01

Independent Environmental Impact Assessment (EIA) follow-up verifiers such as monitoring agencies, checkers, supervisors and control officers are active on various construction sites across the world. There are, however, differing views on the value that these verifiers add and very limited learning in EIA has been drawn from independent verifiers. This paper aims to appraise how and to what extent independent EIA follow-up verifiers add value in major construction projects in the developing country context of South Africa. A framework for appraising the role of independent verifiers was established and four South African case studies were examined through a mixture of site visits, project document analysis, and interviews. Appraisal results were documented in the performance areas of: planning, doing, checking, acting, public participating and integration with other programs. The results indicate that independent verifiers add most value to major construction projects when involved with screening EIA requirements of new projects, allocation of financial and human resources, checking legal compliance, influencing implementation, reporting conformance results, community and stakeholder engagement, integration with self-responsibility programs such as environmental management systems (EMS), and controlling records. It was apparent that verifiers could be more creatively utilized in pre-construction preparation, providing feedback of knowledge into assessment of new projects, giving input to the planning and design phase of projects, and performance evaluation. The study confirms the benefits of proponent and regulator follow-up, specifically in having independent verifiers that disclose information, facilitate discussion among stakeholders, are adaptable and proactive, aid in the integration of EIA with other programs, and instill trust in EIA enforcement by conformance evaluation. Overall, the study provides insight on how to harness the learning opportunities

Antidiabetic activity of Kalanchoe pinnata in streptozotocin-induced diabetic rats by glucose independent insulin secretagogue action.

Science.gov (United States)

Patil, Swapnil B; Dongare, Vandana R; Kulkarni, Chaitanya R; Joglekar, Madhav M; Arvindekar, Akalpita U

2013-11-01

Kalanchoe pinnata Lam. (Crassulaceae) is used as a traditional medicine worldwide to treat several ailments, including diabetes. However, the mechanism for the antihyperglycemic action is unknown. The present study evaluates the antihyperglycemic and insulin secretagogue potential of Kalanchoe pinnata and assessment of the probable mechanism of action. Steam distillate of Kalanchoe pinnata leaves was subjected to solvent fractionation and antidiabetic activity was detected in dichloromethane (DCM) fraction. In the in vivo studies, rats were treated with 5 and 10 mg/kg body weight of DCM fraction for 45 days orally. Lipid profile and other biochemical parameters were estimated. The probable mechanism for insulin secretagogue action was evaluated through studies using diazoxide and nifedipine. The bioactive component from DCM fraction was studied using HPTLC, GCMS and IR. Fasting blood glucose values were reduced to 116 mg/dl from 228 mg/dl on treatment with 10 mg/kg body weight of DCM fraction, while glycated hemoglobin improved to 8.4% compared with 12.9% in diabetic controls. The insulin level and lipid profile values were close to normal values. In vitro studies demonstrated a dose-dependent insulin secretagogue action. Insulin secretion was 3.29-fold higher at 10 µg/ml as compared to the positive control. The insulin secretagogue activity was glucose independent and K(+)-ATP channel dependent. The bioactive component of the DCM fraction was identified to be a phenyl alkyl ether derivative. The DCM fraction of Kalanchoe pinnata demonstrates excellent insulin secretagogue action and can be useful in treatment of diabetes mellitus.

Cooking for Independence: Middle School Students Gain Skills While Cooking

Science.gov (United States)

Mixon, Gloria

2011-01-01

Middle school students with intellectual disabilities often have difficulties achieving independence with instrumental activities of daily living (IADLs); therefore, these skills must be taught in school. IADLs are a complex component of skills that require a higher level of cognitive reasoning such as community mobility, shopping, meal…

SP600125 Induces Src and Type I IGF Receptor Phosphorylation Independent of JNK

Directory of Open Access Journals (Sweden)

Qingbin Kong

2014-09-01

Full Text Available c-Jun N-terminal kinases (JNK are members of the mitogen-activated protein kinase (MAPK family that have important roles in signal transduction. The small molecule SP600125 is widely used in biochemical studies as a JNK inhibitor. However, recent studies indicate that SP600125 may also act independent of JNK. Here, we report that SP600125 can induce Src, type I insulin-like growth factor receptor (IGF-IR, Akt and Erk1/2 phosphorylation. Notably, these effects are independent of its inhibition of JNK. Inhibition of Src abrogates the stimulation of IGF-IR, Akt and Erk1/2 phosphorylation. IGF-IR knockdown blunts the induction of both Akt and Erk1/2 phosphorylation by SP600125. Moreover, combination of SP600125 and the Src inhibitor saracatinib synergistically inhibits cell proliferation. We conclude that SP600125 can activate Src-IGF-IR-Akt/Erk1/2 signaling pathways independent of JNK.

Ureases display biological effects independent of enzymatic activity: Is there a connection to diseases caused by urease-producing bacteria?

Directory of Open Access Journals (Sweden)

D. Olivera-Severo

2006-07-01

Full Text Available Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10% of bacterial protein that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.

Map as a tool for independent learning in geography teaching

Directory of Open Access Journals (Sweden)

Živković Ljiljana

2012-01-01

Full Text Available There are different views on self-regulation in the learning process, how it has to be monitored, controlled, which are the circumstances and external factors that affect independent learning. Dominant are the opinions in which the self-regulation is treated as interaction of processes related to the personality, behavioural and contextual processes. Special attention has been given to motivational strategies and students’ desire to focus on goals. By enabling students to make decisions, set their own goals, make a choice, plan and organize activities, the development of self-learning and student autonomy is being encouraged. If students are given the opportunity of independent activities, effect of self-control in the process of learning and self-regulation becomes more pronounced. The paper will explain the factors that influence the process of self-learning that takes place in regular teaching with the help of map as the basic geographic media. [Projekat Ministarstva nauke Republike Srbije, br. 17008

Independent versus non-independent outside directors in European companies: Who has a say on CEO compensation?

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Pablo de Andrés

2017-04-01

Full Text Available Our study reveals how two separate dimensions of board composition—the proportion of independent directors and of non-independent directors—influence CEO compensation in Western European firms. Controlling for the simultaneous determination of CEO pay structure and board design, we find that firms with a higher proportion of non-independent outsiders on their boards pay less direct compensation (salary + bonus and less equity-linked compensation to their CEOs. By contrast, CEOs working for firms with more independent boards receive more equity based-pay. When we control for the fact that equity linked is not granted systematically in Europe we find that firms with more independent directors on the board tend to grant equity-linked compensation more often than firms with more non independent outside directors. Our results challenge the commonly accepted view of independent directors as safeguards of shareholder value, uncovering the relevance of non-independent outsiders for pay moderation and incentives.

Chemically induced and light-independent cryptochrome photoreceptor activation.

Science.gov (United States)

Rosenfeldt, Gesa; Viana, Rafael Muñoz; Mootz, Henning D; von Arnim, Albrecht G; Batschauer, Alfred

2008-01-01

The cryptochrome photoreceptors of higher plants are dimeric proteins. Their N-terminal photosensory domain mediates dimerization, and the unique C-terminal extension (CCT) mediates signaling. We made use of the human FK506-binding protein (FKBP) that binds with high affinity to rapamycin or rapamycin analogs (rapalogs). The FKBP-rapamycin complex is recognized by another protein, FRB, thus allowing rapamycin-induced dimerization of two target proteins. Here we demonstrate by bioluminescence resonance energy transfer (BRET) assays the applicability of this regulated dimerization system to plants. Furthermore, we show that fusion proteins consisting of the C-terminal domain of Arabidopsis cryptochrome 2 fused to FKBP and FRB and coexpressed in Arabidopsis cells specifically induce the expression of cryptochrome-controlled reporter and endogenous genes in darkness upon incubation with the rapalog. These results demonstrate that the activation of cryptochrome signal transduction can be chemically induced in a dose-dependent fashion and uncoupled from the light signal, and provide the groundwork for gain-of-function experiments to study specifically the role of photoreceptors in darkness or in signaling cross-talk even under light conditions that activate members of all photoreceptor families.

ELECTRONIC TEXTBOOK — SUBJECT INFORMATIONEDUCATIONAL ENVIRONMENT OF INDEPENDENT WORK OF STUDENTS

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Elena O. Ivanova

2015-01-01

Full Text Available The aim of the paper is to consider the characteristics of the electronic textbook as the subject of the information-educational environment, which ensures the unity both of the procedural and substantive aspects of training.Results. The evolution of views on the electronic textbook in the course of the expansion and awareness of the didactic potential of information and communication technologies is shown. The structure of the electronic textbook is presented in the paper. It includes the following modules: information (invariant content of education and the expansion of its variability; organizational and procedural (variable-based assignments aimed at acquiring information, as well as a means of reflection and evaluation of results; personal (information and telecommunication means of organizing own knowledge; communicative (the field of information and assessment of interaction; and pedagogical (monitoring cognitive activity of students. The structure has been developed with due regard to the need of independent work of a student with the content of education in information and educational environment.Scientific novelty. The features of the independent work of the student in terms of abundance of information through information and communication technologies are analyzed. Special attention is paid to the development of independent cognitive activity of students, their subject position in education. On this bases, the key position that should be considered during the development of the electronic textbook are specified: cognitive activity is considered as an active process of constructing students’ new knowledge based on earlier formed personal experience; personal experience arises as a result of intellectual and cognitive activity of the student; cognition of something new requires an activity in the field of social communication; the efficiency of absorption of the content of education depends on the conditions of implementation of each

ELECTRONIC TEXTBOOK — SUBJECT INFORMATIONEDUCATIONAL ENVIRONMENT OF INDEPENDENT WORK OF STUDENTS

Directory of Open Access Journals (Sweden)

Elena O. Ivanova

2015-06-01

Full Text Available The aim of the paper is to consider the characteristics of the electronic textbook as the subject of the information-educational environment, which ensures the unity both of the procedural and substantive aspects of training.Results. The evolution of views on the electronic textbook in the course of the expansion and awareness of the didactic potential of information and communication technologies is shown. The structure of the electronic textbook is presented in the paper. It includes the following modules: information (invariant content of education and the expansion of its variability; organizational and procedural (variable-based assignments aimed at acquiring information, as well as a means of reflection and evaluation of results; personal (information and telecommunication means of organizing own knowledge; communicative (the field of information and assessment of interaction; and pedagogical (monitoring cognitive activity of students. The structure has been developed with due regard to the need of independent work of a student with the content of education in information and educational environment.Scientific novelty. The features of the independent work of the student in terms of abundance of information through information and communication technologies are analyzed. Special attention is paid to the development of independent cognitive activity of students, their subject position in education. On this bases, the key position that should be considered during the development of the electronic textbook are specified: cognitive activity is considered as an active process of constructing students’ new knowledge based on earlier formed personal experience; personal experience arises as a result of intellectual and cognitive activity of the student; cognition of something new requires an activity in the field of social communication; the efficiency of absorption of the content of education depends on the conditions of implementation of each

Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins.

Science.gov (United States)

Sparwasser, T; Vabulas, R M; Villmow, B; Lipford, G B; Wagner, H

2000-12-01

Receptors for conserved molecular patterns associated with microbial pathogens induce synthesis of co-stimulatory molecules and cytokines in immature dendritic cells (DC), as do antigen-reactive CD4 T helper cells via CD40 signaling. Once activated, antigen-presenting DC may activate CD8 T cell responses in a T helper cell-independent fashion. Using immunostimulatory CpG-oligonucleotides (ODN) mimicking bacterial CpG-DNA, we tested whether CpG-DNA bypasses the need for T helper cells in CTL responses towards proteins by directly activating antigen-presenting DC to transit into professional APC. We describe that immature DC in situ constitutively process soluble proteins and generate CD8 T cell determinants yet CD8 T cell responses remain abortive. Induction of primary antigen-specific CD8 cytotoxic T lymphocyte (CTL)-mediated responses becomes initiated in wild-type as well as T helper cell-deficient mice, provided soluble protein and CpG-ODN are draining into the same lymph node. Specifically we show that CpG-ODN trigger antigen-presenting immature DC within the draining lymph node to acutely up-regulate co-stimulatory molecules and produce IL-12. These results provide new insights for generating in vivo efficient CTL responses to soluble proteins which may influence vaccination strategies.

Cortical networks involved in visual awareness independent of visual attention.

Science.gov (United States)

Webb, Taylor W; Igelström, Kajsa M; Schurger, Aaron; Graziano, Michael S A

2016-11-29

It is now well established that visual attention, as measured with standard spatial attention tasks, and visual awareness, as measured by report, can be dissociated. It is possible to attend to a stimulus with no reported awareness of the stimulus. We used a behavioral paradigm in which people were aware of a stimulus in one condition and unaware of it in another condition, but the stimulus drew a similar amount of spatial attention in both conditions. The paradigm allowed us to test for brain regions active in association with awareness independent of level of attention. Participants performed the task in an MRI scanner. We looked for brain regions that were more active in the aware than the unaware trials. The largest cluster of activity was obtained in the temporoparietal junction (TPJ) bilaterally. Local independent component analysis (ICA) revealed that this activity contained three distinct, but overlapping, components: a bilateral, anterior component; a left dorsal component; and a right dorsal component. These components had brain-wide functional connectivity that partially overlapped the ventral attention network and the frontoparietal control network. In contrast, no significant activity in association with awareness was found in the banks of the intraparietal sulcus, a region connected to the dorsal attention network and traditionally associated with attention control. These results show the importance of separating awareness and attention when testing for cortical substrates. They are also consistent with a recent proposal that awareness is associated with ventral attention areas, especially in the TPJ.

Transitioning to employment with a rheumatic disease: the role of independence, overprotection, and social support.

Science.gov (United States)

Jetha, Arif; Badley, Elizabeth; Beaton, Dorcas; Fortin, Paul R; Shiff, Natalie J; Rosenberg, Alan M; Tucker, Lori B; Mosher, Dianne P; Gignac, Monique A M

2014-12-01

To examine perceived independence, overprotection, and support, and their association with the employment participation of young adults with rheumatic disease. One hundred and forty-three young adults, ages 18 to 30 years, with systemic lupus erythematosus (54.5%) and juvenile arthritis (45.5%) completed a 30-min online questionnaire of their work and education experiences. Information collected was demographic, health (e.g., pain, fatigue, disease activity), work context (e.g., career satisfaction, helpfulness of job accommodation/benefits, and workplace activity limitations), and psychosocial (e.g., independence, social support, and overprotection). Log-Poisson regression analysis examined factors associated with employment status. Over half of respondents were employed (59%) and 26% were enrolled in school. Respondents reported moderate to high perceptions of independence and social support. However, 27% reported that "quite a bit" to "a great deal" of overprotection characterized their relationships with those closest to them. At the bivariate level, employed participants and those indicating greater perceived independence reported greater social support and less overprotection. Multivariable analysis revealed that being employed was associated with older age, more job accommodations/benefits perceived as being helpful, and greater perceived independence. This is one of the first studies examining the employment of young adults with rheumatic diseases. Findings highlight the importance of psychosocial perceptions such as independence and overprotection, in addition to support related to working. Additional research is needed to better understand the role of those close to young adults with rheumatic diseases in supporting independence and encouraging employment.

The freedom to explore: examining the influence of independent mobility on weekday, weekend and after-school physical activity behaviour in children living in urban and inner-suburban neighbourhoods of varying socioeconomic status.

Science.gov (United States)

Stone, Michelle R; Faulkner, Guy Ej; Mitra, Raktim; Buliung, Ron N

2014-01-22

Children's independent mobility (CIM) is critical to healthy development in childhood. The physical layout and social characteristics of neighbourhoods can impact opportunities for CIM. While global evidence is mounting on CIM, to the authors' knowledge, Canadian data on CIM and related health outcomes (i.e., physical activity (PA) behaviour) are missing. The purpose of this study was to examine if CIM is related to multiple characteristics of accelerometry-measured PA behaviour (total PA, light PA, moderate-to-vigorous PA, time spent sedentary) and whether associations between CIM and PA behaviour systematically vary by place of residence, stratifying by gender and type of day/period (weekdays, after-school, weekend). Participants were recruited through Project BEAT (Built Environment and Active Transport; http://www.beat.utoronto.ca). Children (n = 856) were stratified into four neighbourhood classifications based on the period of neighbourhood development (urban built environment (BE) (old BE) versus inner-suburban BE (new BE)) and socioeconomic status (SES; low SES and high SES). Physical activity was measured via accelerometry (ActiGraph GT1M). CIM was assessed via parental report and two categories were created (low CIM, n = 332; high CIM, n = 524). A series of two-factor ANOVAs were used to determine gender-specific differences in PA for weekdays, weekend days and the after-school period, according to level of CIM, across four neighbourhood classifications. Children who were granted at least some independent mobility (high CIM) had more positive PA profiles across the school week, during the after-school period, and over the weekend; they were also less sedentary. The influence of CIM on PA behaviour was particularly salient during the after-school period. Associations of CIM with PA varied by gender, and also by neighbourhood classification. CIM seemed to matter more in urban neighbourhoods for boys and suburban neighbourhoods for girls. Our

p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

Energy Technology Data Exchange (ETDEWEB)

Cappadone, C., E-mail: concettina.cappadone@unibo.it [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Stefanelli, C. [Department for Life Quality Studies, University of Bologna, Rimini Campus, Rimini (Italy); Malucelli, E. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Zini, M. [Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna (Italy); Onofrillo, C. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Locatelli, A.; Rambaldi, M.; Sargenti, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Merolle, L. [ELETTRA–Sincrotrone Trieste S.C.p.A., Trieste (Italy); Farruggia, G. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy); Graziadio, A. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); Montanaro, L. [Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna (Italy); Iotti, S. [Department of Pharmacy and Biotechnology, University of Bologna, Bologna (Italy); National Institute of Biostructures and Biosystems, Roma (Italy)

2015-11-13

Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

p53-dependent and p53-independent anticancer activity of a new indole derivative in human osteosarcoma cells

International Nuclear Information System (INIS)

Cappadone, C.; Stefanelli, C.; Malucelli, E.; Zini, M.; Onofrillo, C.; Locatelli, A.; Rambaldi, M.; Sargenti, A.; Merolle, L.; Farruggia, G.; Graziadio, A.; Montanaro, L.; Iotti, S.

2015-01-01

Osteosarcoma (OS) is the most common primary malignant tumor of bone, occurring most frequently in children and adolescents. The mechanism of formation and development of OS have been studied for a long time. Tumor suppressor pathway governed by p53 gene are known to be involved in the pathogenesis of osteosarcoma. Moreover, loss of wild-type p53 activity is thought to be a major predictor of failure to respond to chemotherapy in various human cancers. In previous studies, we described the activity of a new indole derivative, NSC743420, belonging to the tubulin inhibitors family, capable to induce apoptosis and arrest of the cell cycle in the G2/M phase of various cancer cell lines. However, this molecule has never been tested on OS cell line. Here we address the activity of NSC743420 by examine whether differences in the p53 status could influence its effects on cell proliferation and death of OS cells. In particular, we compared the effect of the tested molecule on p53-wild type and p53-silenced U2OS cells, and on SaOS2 cell line, which is null for p53. Our results demonstrated that NSC743420 reduces OS cell proliferation by p53-dependent and p53-independent mechanisms. In particular, the molecule induces proliferative arrest that culminate to apoptosis in SaOS2 p53-null cells, while it brings a cytostatic and differentiating effect in U2OS cells, characterized by the cell cycle arrest in G0/G1 phase and increased alkaline phosphatase activity. - Highlights: • The indole derivative NSC743420 induces antitumor effects on osteosarcoma cells. • p53 status could drive the activity of antitumor agents on osteosarcoma cells. • NSC743420 induces cytostatic and differentiating effects on U2OS cells. • NSC743420 causes apoptosis on p53-null SaOS2 cells.

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

Science.gov (United States)

Zanos, Panos; Moaddel, Ruin; Morris, Patrick J.; Georgiou, Polymnia; Fischell, Jonathan; Elmer, Greg I.; Alkondon, Manickavasagom; Yuan, Peixiong; Pribut, Heather J.; Singh, Nagendra S.; Dossou, Katina S.S.; Fang, Yuhong; Huang, Xi-Ping; Mayo, Cheryl L.; Wainer, Irving W.; Albuquerque, Edson X.; Thompson, Scott M.; Thomas, Craig J.; Zarate, Carlos A.; Gould, Todd D.

2016-01-01

Major depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine’s unique antidepressant properties, which involves the required activity of a distinct metabolite and is independent of NMDAR inhibition. These findings have relevance for the development of next generation, rapid-acting antidepressants. PMID:27144355

User-Independent Motion State Recognition Using Smartphone Sensors.

Science.gov (United States)

Gu, Fuqiang; Kealy, Allison; Khoshelham, Kourosh; Shang, Jianga

2015-12-04

The recognition of locomotion activities (e.g., walking, running, still) is important for a wide range of applications like indoor positioning, navigation, location-based services, and health monitoring. Recently, there has been a growing interest in activity recognition using accelerometer data. However, when utilizing only acceleration-based features, it is difficult to differentiate varying vertical motion states from horizontal motion states especially when conducting user-independent classification. In this paper, we also make use of the newly emerging barometer built in modern smartphones, and propose a novel feature called pressure derivative from the barometer readings for user motion state recognition, which is proven to be effective for distinguishing vertical motion states and does not depend on specific users' data. Seven types of motion states are defined and six commonly-used classifiers are compared. In addition, we utilize the motion state history and the characteristics of people's motion to improve the classification accuracies of those classifiers. Experimental results show that by using the historical information and human's motion characteristics, we can achieve user-independent motion state classification with an accuracy of up to 90.7%. In addition, we analyze the influence of the window size and smartphone pose on the accuracy.

User-Independent Motion State Recognition Using Smartphone Sensors

Directory of Open Access Journals (Sweden)

Fuqiang Gu

2015-12-01

Full Text Available The recognition of locomotion activities (e.g., walking, running, still is important for a wide range of applications like indoor positioning, navigation, location-based services, and health monitoring. Recently, there has been a growing interest in activity recognition using accelerometer data. However, when utilizing only acceleration-based features, it is difficult to differentiate varying vertical motion states from horizontal motion states especially when conducting user-independent classification. In this paper, we also make use of the newly emerging barometer built in modern smartphones, and propose a novel feature called pressure derivative from the barometer readings for user motion state recognition, which is proven to be effective for distinguishing vertical motion states and does not depend on specific users’ data. Seven types of motion states are defined and six commonly-used classifiers are compared. In addition, we utilize the motion state history and the characteristics of people’s motion to improve the classification accuracies of those classifiers. Experimental results show that by using the historical information and human’s motion characteristics, we can achieve user-independent motion state classification with an accuracy of up to 90.7%. In addition, we analyze the influence of the window size and smartphone pose on the accuracy.

[Crisis and the independence of public health policies. SESPAS report 2014].

Science.gov (United States)

Hernández Aguado, Ildefonso; Lumbreras Lacarra, Blanca

2014-06-01

Independence in the formulation of public health policies can be affected by various agents with objectives contrary to population health, such as large corporations. This lack of independence may be exacerbated by the economic crisis due to lower funding for health regulatory bodies or other measures designed to protect health. Large corporations have influenced the formulation of certain policies with an impact on health, such as those related to the tobacco industry, the chemical industry, nutrition, alcohol, pharmaceuticals, and health technology. The main areas in which these companies can influence policies are science, education, politics, and society in general. In this scenario, public health associations should take an active role in ensuring the independence of political decisions via actions such as the following: supporting strategies that guarantee the independence of public health policies and apply criteria of impartiality and transparency; rejecting those public-private partnerships launched to prevent health problems partly caused by these corporations; establishing partnerships to achieve independent training of health professionals and an institution with scientific authority in order to improve public health communication and counteract the lack of sound public health information; promoting a critical analysis of the definition of health problems and their solutions, and establishing related agendas (scientific, political and media) and alliances, so that continuing training for health professionals is independent. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

PPARγ-Independent Mechanism

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Christopher M. Hogan

2011-01-01

Full Text Available Acute and chronic lung inflammation is associated with numerous important disease pathologies including asthma, chronic obstructive pulmonary disease and silicosis. Lung fibroblasts are a novel and important target of anti-inflammatory therapy, as they orchestrate, respond to, and amplify inflammatory cascades and are the key cell in the pathogenesis of lung fibrosis. Peroxisome proliferator-activated receptor gamma (PPARγ ligands are small molecules that induce anti-inflammatory responses in a variety of tissues. Here, we report for the first time that PPARγ ligands have potent anti-inflammatory effects on human lung fibroblasts. 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 inhibit production of the inflammatory mediators interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, COX-2, and prostaglandin (PGE2 in primary human lung fibroblasts stimulated with either IL-1β or silica. The anti-inflammatory properties of these molecules are not blocked by the PPARγ antagonist GW9662 and thus are largely PPARγ independent. However, they are dependent on the presence of an electrophilic carbon. CDDO and 15d-PGJ2, but not rosiglitazone, inhibited NF-κB activity. These results demonstrate that CDDO and 15d-PGJ2 are potent attenuators of proinflammatory responses in lung fibroblasts and suggest that these molecules should be explored as the basis for novel, targeted anti-inflammatory therapies in the lung and other organs.

MED1 independent activation of endogenous target genes by PPARα

DEFF Research Database (Denmark)

Grøntved, Lars; Bugge, Anne K.; Roeder, Robert G.

The mediator complex serves as a transcriptional co-activator complex by acting as a bridge between promoter-bound transcription factors and the preinitiation complex. Genetic and biochemical studies indicate that nuclear receptors recruit the mediator complex through direct interaction with the ......The mediator complex serves as a transcriptional co-activator complex by acting as a bridge between promoter-bound transcription factors and the preinitiation complex. Genetic and biochemical studies indicate that nuclear receptors recruit the mediator complex through direct interaction...... derived from TRAP220 KO mice. Interestingly, rescue experiments in confluent TRAP220 KO MEFs with different versions of MED1 indicate that the LXXLL motif is not necessary for PPARgamma mediated gene activation (Ge et al, MCB published online ahead of print 2007). By analogy, we show here that MED1...... is dispensable for PPARalpha transcriptional activity in proliferating but is necessary in confluent AML-12 cells and TRAP220 KO MEFs. Collectively this indicates that the PPARs might have adopted an alternative mediator recruitment mechanism that is dispensable of direct interaction with MED1 on endogenous...

Autogoverno, Regulação, Função Normativa e Independência Interna no Judiciário / Self-Government, Regulatory Power and Judicial Independence

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André Melo Gomes Pereira

2016-10-01

Full Text Available Purpose – This paper focuses on the relationship between the performed normative function and the judges’ internal independence, often by general and abstract commands, for self-government agencies with regulation functions in the Judiciary. Methodology/approach/design – This study implements analyses of standards and regulation literature, normative function, self-government and judicial independence. Illustratively, courts’ decisions on specific cases were analyzed. Special attention was given to the theoretical bases of regulation, the normative function of government agencies and to the democratization proposal of judicial self-government, a model notedly proposed by Zaffaroni. Findings – Self-government implies regulation. Regulation involves the exercise of normative function. Internal democratization of judicial self-government and participation of all regulated agents in the Judiciary are necessary tools to ensure legitimacy and the internal independence for the exercise of normative functions and the whole set of activities put forward by self-government agencies. Practical implications – The paper discusses a change in the institutional design of self-government in the Judiciary and the limits imposed by its the normative function. Originality/value – It correlates the regulatory function developed by self-government agencies with the assurance of judges’ internal independence.

On Judicial and Quasi-Judicial Independence

NARCIS (Netherlands)

Comtois, Suzanne; de Graaf, K.J.

2013-01-01

'Principles of judicial and quasi-judicial independence are fundamental to all democracies and yet, the notion of independence is still elusive. What is judicial and quasi-judicial independence and why is it important? From whom and what are the judiciary and other adjudicators to be independent? Is

Independently controlled wing stroke patterns in the fruit fly Drosophila melanogaster.

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Soma Chakraborty

Full Text Available Flies achieve supreme flight maneuverability through a small set of miniscule steering muscles attached to the wing base. The fast flight maneuvers arise from precisely timed activation of the steering muscles and the resulting subtle modulation of the wing stroke. In addition, slower modulation of wing kinematics arises from changes in the activity of indirect flight muscles in the thorax. We investigated if these modulations can be described as a superposition of a limited number of elementary deformations of the wing stroke that are under independent physiological control. Using a high-speed computer vision system, we recorded the wing motion of tethered flying fruit flies for up to 12,000 consecutive wing strokes at a sampling rate of 6250 Hz. We then decomposed the joint motion pattern of both wings into components that had the minimal mutual information (a measure of statistical dependence. In 100 flight segments measured from 10 individual flies, we identified 7 distinct types of frequently occurring least-dependent components, each defining a kinematic pattern (a specific deformation of the wing stroke and the sequence of its activation from cycle to cycle. Two of these stroke deformations can be associated with the control of yaw torque and total flight force, respectively. A third deformation involves a change in the downstroke-to-upstroke duration ratio, which is expected to alter the pitch torque. A fourth kinematic pattern consists in the alteration of stroke amplitude with a period of 2 wingbeat cycles, extending for dozens of cycles. Our analysis indicates that these four elementary kinematic patterns can be activated mutually independently, and occur both in isolation and in linear superposition. The results strengthen the available evidence for independent control of yaw torque, pitch torque, and total flight force. Our computational method facilitates systematic identification of novel patterns in large kinematic datasets.

Independently controlled wing stroke patterns in the fruit fly Drosophila melanogaster.

Science.gov (United States)

Chakraborty, Soma; Bartussek, Jan; Fry, Steven N; Zapotocky, Martin

2015-01-01

Flies achieve supreme flight maneuverability through a small set of miniscule steering muscles attached to the wing base. The fast flight maneuvers arise from precisely timed activation of the steering muscles and the resulting subtle modulation of the wing stroke. In addition, slower modulation of wing kinematics arises from changes in the activity of indirect flight muscles in the thorax. We investigated if these modulations can be described as a superposition of a limited number of elementary deformations of the wing stroke that are under independent physiological control. Using a high-speed computer vision system, we recorded the wing motion of tethered flying fruit flies for up to 12,000 consecutive wing strokes at a sampling rate of 6250 Hz. We then decomposed the joint motion pattern of both wings into components that had the minimal mutual information (a measure of statistical dependence). In 100 flight segments measured from 10 individual flies, we identified 7 distinct types of frequently occurring least-dependent components, each defining a kinematic pattern (a specific deformation of the wing stroke and the sequence of its activation from cycle to cycle). Two of these stroke deformations can be associated with the control of yaw torque and total flight force, respectively. A third deformation involves a change in the downstroke-to-upstroke duration ratio, which is expected to alter the pitch torque. A fourth kinematic pattern consists in the alteration of stroke amplitude with a period of 2 wingbeat cycles, extending for dozens of cycles. Our analysis indicates that these four elementary kinematic patterns can be activated mutually independently, and occur both in isolation and in linear superposition. The results strengthen the available evidence for independent control of yaw torque, pitch torque, and total flight force. Our computational method facilitates systematic identification of novel patterns in large kinematic datasets.

Effector-independent motor sequence representations exist in extrinsic and intrinsic reference frames.

Science.gov (United States)

Wiestler, Tobias; Waters-Metenier, Sheena; Diedrichsen, Jörn

2014-04-02

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences during fMRI with both left and right hand. Between hands, these sequences were equivalent in extrinsic or intrinsic space, or were unrelated. In dorsal premotor cortex (PMd), we found that sequence-specific activity patterns correlated higher for extrinsic than for unrelated pairs, providing evidence for an extrinsic sequence representation. In contrast, primary sensory and motor cortices showed effector-independent representations in intrinsic space, with considerable overlap of the two reference frames in caudal PMd. These results suggest that effector-independent representations exist not only in world-centered, but also in body-centered coordinates, and that PMd may be involved in transforming sequential knowledge between the two. Moreover, although effector-independent sequence representations were found bilaterally, they were stronger in the hemisphere contralateral to the trained hand. This indicates that intermanual transfer relies on motor memories that are laid down during training in both hemispheres, but preferentially draws upon sequential knowledge represented in the trained hemisphere.

Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

Science.gov (United States)

Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

2014-06-16

Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. Copyright © 2014 Elsevier Inc. All rights reserved.

Aluminum nanostructures with strong visible-range SERS activity for versatile micropatterning of molecular security labels.

Science.gov (United States)

Lay, Chee Leng; Koh, Charlynn Sher Lin; Wang, Jing; Lee, Yih Hong; Jiang, Ruibin; Yang, Yijie; Yang, Zhe; Phang, In Yee; Ling, Xing Yi

2018-01-03

The application of aluminum (Al)-based nanostructures for visible-range plasmonics, especially for surface-enhanced Raman scattering (SERS), currently suffers from inconsistent local electromagnetic field distributions and/or inhomogeneous distribution of probe molecules. Herein, we lithographically fabricate structurally uniform Al nanostructures which enable homogeneous adsorption of various probe molecules. Individual Al nanostructures exhibit strong local electromagnetic field enhancements, in turn leading to intense SERS activity. The average SERS enhancement factor (EF) for individual nanostructures exceeds 10 4 for non-resonant probe molecules in the visible spectrum. These Al nanostructures also retain more than 70% of their original SERS intensities after one-month storage, displaying superb stability under ambient conditions. We further achieve tunable polarization-dependent SERS responses using anisotropic Al nanostructures, facilitating the design of sophisticated SERS-based security labels. Our micron-sized security label comprises two-tier security features, including a machine-readable hybrid quick-response (QR) code overlaid with a set of ciphertexts. Our work demonstrates the versatility of Al-based structures in low-cost modern chemical nano-analytics and forgery protection.

Accounting for Independent Schools.

Science.gov (United States)

Sonenstein, Burton

The diversity of independent schools in size, function, and mode of operation has resulted in a considerable variety of accounting principles and practices. This lack of uniformity has tended to make understanding, evaluation, and comparison of independent schools' financial statements a difficult and sometimes impossible task. This manual has…

Impact of Different Active-Speech-Ratios on PESQ’s Predictions in Case of Independent and Dependent Losses (in Presence of Receiver-Side Comfort-Noise

Directory of Open Access Journals (Sweden)

P. Pocta

2010-04-01

Full Text Available This paper deals with the investigation of PESQ’s behavior under independent and dependent loss conditions from an Active-Speech-Ratio perspective in presence of receiver-side comfort-noise. This reference signal characteristic is defined very broadly by ITU-T Recommendation P.862.3. That is the reason to investigate an impact of this characteristic on speech quality prediction more in-depth. We assess the variability of PESQ’s predictions with respect to Active-Speech-Ratios and loss conditions, as well as their accuracy, by comparing the predictions with subjective assessments. Our results show that an increase in amount of speech in the reference signal (expressed by the Active-Speech-Ratio characteristic may result in an increase of the reference signal sensitivity to packet loss change. Interestingly, we have found two additional effects in this investigated case. The use of higher Active-Speech-Ratios may lead to negative shifting effect in MOS domain and also PESQ’s predictions accuracy declining. Predictions accuracy could be improved by higher packet losses.

Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia.

Science.gov (United States)

Cavazzana-Calvo, Marina; Payen, Emmanuel; Negre, Olivier; Wang, Gary; Hehir, Kathleen; Fusil, Floriane; Down, Julian; Denaro, Maria; Brady, Troy; Westerman, Karen; Cavallesco, Resy; Gillet-Legrand, Beatrix; Caccavelli, Laure; Sgarra, Riccardo; Maouche-Chrétien, Leila; Bernaudin, Françoise; Girot, Robert; Dorazio, Ronald; Mulder, Geert-Jan; Polack, Axel; Bank, Arthur; Soulier, Jean; Larghero, Jérôme; Kabbara, Nabil; Dalle, Bruno; Gourmel, Bernard; Socie, Gérard; Chrétien, Stany; Cartier, Nathalie; Aubourg, Patrick; Fischer, Alain; Cornetta, Kenneth; Galacteros, Frédéric; Beuzard, Yves; Gluckman, Eliane; Bushman, Frederick; Hacein-Bey-Abina, Salima; Leboulch, Philippe

2010-09-16

The β-haemoglobinopathies are the most prevalent inherited disorders worldwide. Gene therapy of β-thalassaemia is particularly challenging given the requirement for massive haemoglobin production in a lineage-specific manner and the lack of selective advantage for corrected haematopoietic stem cells. Compound β(E)/β(0)-thalassaemia is the most common form of severe thalassaemia in southeast Asian countries and their diasporas. The β(E)-globin allele bears a point mutation that causes alternative splicing. The abnormally spliced form is non-coding, whereas the correctly spliced messenger RNA expresses a mutated β(E)-globin with partial instability. When this is compounded with a non-functional β(0) allele, a profound decrease in β-globin synthesis results, and approximately half of β(E)/β(0)-thalassaemia patients are transfusion-dependent. The only available curative therapy is allogeneic haematopoietic stem cell transplantation, although most patients do not have a human-leukocyte-antigen-matched, geno-identical donor, and those who do still risk rejection or graft-versus-host disease. Here we show that, 33 months after lentiviral β-globin gene transfer, an adult patient with severe β(E)/β(0)-thalassaemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 21 months. Blood haemoglobin is maintained between 9 and 10 g dl(-1), of which one-third contains vector-encoded β-globin. Most of the therapeutic benefit results from a dominant, myeloid-biased cell clone, in which the integrated vector causes transcriptional activation of HMGA2 in erythroid cells with further increased expression of a truncated HMGA2 mRNA insensitive to degradation by let-7 microRNAs. The clonal dominance that accompanies therapeutic efficacy may be coincidental and stochastic or result from a hitherto benign cell expansion caused by dysregulation of the HMGA2 gene in stem/progenitor cells.

Small Computer Applications for Base Supply.

Science.gov (United States)

1984-03-01

research on small computer utili- zation at bse level organizatins , This research effort studies whether small computers and commercial softure can assist...Doe has made !solid contributions to the full range of departmental activity. His demonstrated leadership skills and administrative ability warrent his...outstanding professionalism and leadership abilities were evidenced by his superb performance as unit key worker In the 1980 Combined Federal CauMign

Tie2 signaling cooperates with TNF to promote the pro-inflammatory activation of human macrophages independently of macrophage functional phenotype.

Science.gov (United States)

García, Samuel; Krausz, Sarah; Ambarus, Carmen A; Fernández, Beatriz Malvar; Hartkamp, Linda M; van Es, Inge E; Hamann, Jörg; Baeten, Dominique L; Tak, Paul P; Reedquist, Kris A

2014-01-01

Angiopoietin (Ang) -1 and -2 and their receptor Tie2 play critical roles in regulating angiogenic processes during development, homeostasis, tumorigenesis, inflammation and tissue repair. Tie2 signaling is best characterized in endothelial cells, but a subset of human and murine circulating monocytes/macrophages essential to solid tumor formation express Tie2 and display immunosuppressive properties consistent with M2 macrophage polarization. However, we have recently shown that Tie2 is strongly activated in pro-inflammatory macrophages present in rheumatoid arthritis patient synovial tissue. Here we examined the relationship between Tie2 expression and function during human macrophage polarization. Tie2 expression was observed under all polarization conditions, but was highest in IFN-γ and IL-10 -differentiated macrophages. While TNF enhanced expression of a common restricted set of genes involved in angiogenesis and inflammation in GM-CSF, IFN-γ and IL-10 -differentiated macrophages, expression of multiple chemokines and cytokines, including CXCL3, CXCL5, CXCL8, IL6, and IL12B was further augmented in the presence of Ang-1 and Ang-2, via Tie2 activation of JAK/STAT signaling. Conditioned medium from macrophages stimulated with Ang-1 or Ang-2 in combination with TNF, sustained monocyte recruitment. Our findings suggest a general role for Tie2 in cooperatively promoting the inflammatory activation of macrophages, independently of polarization conditions.

KAT-Independent Gene Regulation by Tip60 Promotes ESC Self-Renewal but Not Pluripotency

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Diwash Acharya

2017-04-01

Full Text Available Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5 lysine acetyltransferase (KAT, which is essential for embryonic stem cell (ESC self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance. In contrast, KAT-deficient ESCs exhibited impaired differentiation into mesoderm and endoderm, demonstrating a KAT-dependent function in differentiation. Consistent with this phenotype, KAT-deficient mouse embryos exhibited post-implantation developmental defects. These findings establish separable KAT-dependent and KAT-independent functions of Tip60 in ESCs and during differentiation, revealing a complex repertoire of regulatory functions for this essential chromatin remodeling complex.

Probabilistic conditional independence structures

CERN Document Server

Studeny, Milan

2005-01-01

Probabilistic Conditional Independence Structures provides the mathematical description of probabilistic conditional independence structures; the author uses non-graphical methods of their description, and takes an algebraic approach.The monograph presents the methods of structural imsets and supermodular functions, and deals with independence implication and equivalence of structural imsets.Motivation, mathematical foundations and areas of application are included, and a rough overview of graphical methods is also given.In particular, the author has been careful to use suitable terminology, and presents the work so that it will be understood by both statisticians, and by researchers in artificial intelligence.The necessary elementary mathematical notions are recalled in an appendix.

Plasma levels of soluble CD14 independently predict mortality in HIV infection

DEFF Research Database (Denmark)

Sandler, Netanya G; Wand, Handan; Roque, Annelys

2011-01-01

Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcom...

A COMPARATIVE ANALYSIS OF PROCESSES IN AN INDEPENDENT GENERATOR WITH A NONCONTACT CASCADE THREE-PHASE MODULATED EXCITER VIA A STAR-CONNECTED CIRCUIT UNDER ACTIVE-INDUCTIVE LOADING

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K.M. Vasyliv

2013-02-01

Full Text Available By means of mathematical experiment, the author investigates electromagnetic and electromechanical processes in an independent electric power supply system based on an asynchronized generator with a three-phase modulated exciter. The processes are analyzed to specify the working capacity of the power supply system during its operation under active-inductive loading. Regularities of the electromagnetic and electromechanical processes behavior versus load intensity and the modulator scheme are identified.

ORGANIZATION OF INDEPENDENT WORK STUDENTS OF MASTER OF TELECOMMUNICATION TRAINING PROJECT

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L. Perminova

2013-03-01

Full Text Available The article explains the need to implement active learning of students in the practice of the organization їh homework. In particular, the author proved the rationality of the use of telecommunications projects and use the web in quest of independent study students graduate.

Defining and Selecting Independent Directors

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Eric Pichet

2017-10-01

Full Text Available Drawing from the Enlightened Shareholder Theory that the author first developed in 2011, this theoretical paper with practical and normative ambitions achieves a better definition of independent director, while improving the understanding of the roles he fulfils on boards of directors. The first part defines constructs like firms, Governance system and Corporate governance, offering a clear distinction between the latter two concepts before explaining the four main missions of a board. The second part defines the ideal independent director by outlining the objective qualities that are necessary and adding those subjective aspects that have turned this into a veritable profession. The third part defines the ideal process for selecting independent directors, based on nominating committees that should themselves be independent. It also includes ways of assessing directors who are currently in function, as well as modalities for renewing their mandates. The paper’s conclusion presents the Paradox of the Independent Director.

Cell volume and membrane stretch independently control K+ channel activity

DEFF Research Database (Denmark)

Bomholtz, Sofia Hammami; Willumsen, Niels J; Olsen, Hervør L

2009-01-01

A number of potassium channels including members of the KCNQ family and the Ca(2+) activated IK and SK, but not BK, are strongly and reversibly regulated by small changes in cell volume. It has been argued that this general regulation is mediated through sensitivity to changes in membrane stretch...... was not affected by membrane stretch. The results indicate that (1) activation of BK channels by local membrane stretch is not mimicked by membrane stress induced by cell swelling, and (2) activation of KCNQ1 channels by cell volume increase is not mediated by local tension in the cell membrane. We conclude....... To test this hypothesis we have studied the regulation of KCNQ1 and BK channels after expression in Xenopus oocytes. Results from cell-attached patch clamp studies (approximately 50 microm(2) macropatches) in oocytes expressing BK channels demonstrate that the macroscopic volume-insensitive BK current...

The freedom to explore: examining the influence of independent mobility on weekday, weekend and after-school physical activity behaviour in children living in urban and inner-suburban neighbourhoods of varying socioeconomic status

Science.gov (United States)

2014-01-01

Background Children’s independent mobility (CIM) is critical to healthy development in childhood. The physical layout and social characteristics of neighbourhoods can impact opportunities for CIM. While global evidence is mounting on CIM, to the authors’ knowledge, Canadian data on CIM and related health outcomes (i.e., physical activity (PA) behaviour) are missing. The purpose of this study was to examine if CIM is related to multiple characteristics of accelerometry-measured PA behaviour (total PA, light PA, moderate-to-vigorous PA, time spent sedentary) and whether associations between CIM and PA behaviour systematically vary by place of residence, stratifying by gender and type of day/period (weekdays, after-school, weekend). Methods Participants were recruited through Project BEAT (Built Environment and Active Transport; http://www.beat.utoronto.ca). Children (n = 856) were stratified into four neighbourhood classifications based on the period of neighbourhood development (urban built environment (BE) (old BE) versus inner-suburban BE (new BE)) and socioeconomic status (SES; low SES and high SES). Physical activity was measured via accelerometry (ActiGraph GT1M). CIM was assessed via parental report and two categories were created (low CIM, n = 332; high CIM, n = 524). A series of two-factor ANOVAs were used to determine gender-specific differences in PA for weekdays, weekend days and the after-school period, according to level of CIM, across four neighbourhood classifications. Results Children who were granted at least some independent mobility (high CIM) had more positive PA profiles across the school week, during the after-school period, and over the weekend; they were also less sedentary. The influence of CIM on PA behaviour was particularly salient during the after-school period. Associations of CIM with PA varied by gender, and also by neighbourhood classification. CIM seemed to matter more in urban neighbourhoods for boys and suburban

30 CFR 45.4 - Independent contractor register.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Independent contractor register. 45.4 Section... ADMINISTRATIVE REQUIREMENTS INDEPENDENT CONTRACTORS § 45.4 Independent contractor register. (a) Each independent contractor shall provide the production-operator in writing the following information: (1) The independent...

[Lee Jungsook, a Korean independence activist and a nurse during the Japanese colonial period].

Science.gov (United States)

Kim, Sook Young

2015-04-01

This article examines the life of Lee Jungsook, a Korean nurse, as a independence activist during the Japanese colonial period. Lee Jungsook(1896-1950) was born in Bukchung in Hamnam province. She studied at Chungshin girl's high school and worked at Severance hospital. The characteristics and culture of her educational background and work place were very important factors which influenced greatly the life of Lee Jungsook. She learned independent spirit and nationalism from Chungshin girls' high school and worked as nurse at the Severance hospital which were full of intense aspiration for Korea's independence. Many of doctors, professors and medical students were participated in the 3.1 Independence Movement. Lee Jungsook was a founding member of Hyulsungdan who tried to help the independence activists in prison and their families and worked as a main member of Korean Women's Association for Korean Independece and Kyungsung branch of the Korean Red Cross. She was sent to jail by the Japanese government for her independence activism. After being released after serving two years confinement, she worked for the Union for Women's Liberation as a founding member. Lee Joungsook was a great independence activist who had a nursing care spirit as a nurse.

Does firm performance affect board independence?

Directory of Open Access Journals (Sweden)

Yi Wang

2010-07-01

Full Text Available This paper seeks to shed some light on the antecedents of board independence. Specifically, it attempts to test the conceptual frameworks which make different predictions about the effect of firm performance on the level of board independence. The results provide support for the perspective that appointing more independent members to the boards may merely represent firms’ attempts to comply with institutional pressures. It is found that higher blockholder shareholdings lead to lower independence on the board, and audit and remuneration committees. Moreover, larger firms have relatively more independent directors sitting on nomination and remuneration committees.

Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase.

Science.gov (United States)

Brown, Michael C; Bryant, Jeffrey D; Dobrikova, Elena Y; Shveygert, Mayya; Bradrick, Shelton S; Chandramohan, Vidyalakshmi; Bigner, Darell D; Gromeier, Matthias

2014-11-01

Protein synthesis, the most energy-consuming process in cells, responds to changing physiologic priorities, e.g., upon mitogen- or stress-induced adaptations signaled through the mitogen-activated protein kinases (MAPKs). The prevailing status of protein synthesis machinery is a viral pathogenesis factor, particularly for plus-strand RNA viruses, where immediate translation of incoming viral RNAs shapes host-virus interactions. In this study, we unraveled signaling pathways centered on the ERK1/2 and p38α MAPK-interacting kinases MNK1/2 and their role in controlling 7-methyl-guanosine (m(7)G) "cap"-independent translation at enterovirus type 1 internal ribosomal entry sites (IRESs). Activation of Raf-MEK-ERK1/2 signals induced viral IRES-mediated translation in a manner dependent on MNK1/2. This effect was not due to MNK's known functions as eukaryotic initiation factor (eIF) 4G binding partner or eIF4E(S209) kinase. Rather, MNK catalytic activity enabled viral IRES-mediated translation/host cell cytotoxicity through negative regulation of the Ser/Arg (SR)-rich protein kinase (SRPK). Our investigations suggest that SRPK activity is a major determinant of type 1 IRES competency, host cell cytotoxicity, and viral proliferation in infected cells. We are targeting unfettered enterovirus IRES activity in cancer with PVSRIPO, the type 1 live-attenuated poliovirus (PV) (Sabin) vaccine containing a human rhinovirus type 2 (HRV2) IRES. A phase I clinical trial of PVSRIPO with intratumoral inoculation in patients with recurrent glioblastoma (GBM) is showing early promise. Viral translation proficiency in infected GBM cells is a core requirement for the antineoplastic efficacy of PVSRIPO. Therefore, it is critically important to understand the mechanisms controlling viral cap-independent translation in infected host cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Independent component analysis: recent advances

OpenAIRE

Hyv?rinen, Aapo

2013-01-01

Independent component analysis is a probabilistic method for learning a linear transform of a random vector. The goal is to find components that are maximally independent and non-Gaussian (non-normal). Its fundamental difference to classical multi-variate statistical methods is in the assumption of non-Gaussianity, which enables the identification of original, underlying components, in contrast to classical methods. The basic theory of independent component analysis was mainly developed in th...

EDITORIAL: Special section on gaze-independent brain-computer interfaces Special section on gaze-independent brain-computer interfaces

Science.gov (United States)

Treder, Matthias S.

2012-08-01

Restoring the ability to communicate and interact with the environment in patients with severe motor disabilities is a vision that has been the main catalyst of early brain-computer interface (BCI) research. The past decade has brought a diversification of the field. BCIs have been examined as a tool for motor rehabilitation and their benefit in non-medical applications such as mental-state monitoring for improved human-computer interaction and gaming has been confirmed. At the same time, the weaknesses of some approaches have been pointed out. One of these weaknesses is gaze-dependence, that is, the requirement that the user of a BCI system voluntarily directs his or her eye gaze towards a visual target in order to efficiently operate a BCI. This not only contradicts the main doctrine of BCI research, namely that BCIs should be independent of muscle activity, but it can also limit its real-world applicability both in clinical and non-medical settings. It is only in a scenario devoid of any motor activity that a BCI solution is without alternative. Gaze-dependencies have surfaced at two different points in the BCI loop. Firstly, a BCI that relies on visual stimulation may require users to fixate on the target location. Secondly, feedback is often presented visually, which implies that the user may have to move his or her eyes in order to perceive the feedback. This special section was borne out of a BCI workshop on gaze-independent BCIs held at the 2011 Society for Applied Neurosciences (SAN) Conference and has then been extended with additional contributions from other research groups. It compiles experimental and methodological work that aims toward gaze-independent communication and mental-state monitoring. Riccio et al review the current state-of-the-art in research on gaze-independent BCIs [1]. Van der Waal et al present a tactile speller that builds on the stimulation of the fingers of the right and left hand [2]. H¨ohne et al analyze the ergonomic aspects

Applying independent component analysis to clinical fMRI at 7 T

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Simon Daniel Robinson

2013-09-01

Full Text Available Increased BOLD sensitivity at 7 T offers the possibility to increase the reliability of fMRI, but ultra-high field is also associated with an increase in artifacts related to head motion, Nyquist ghosting and parallel imaging reconstruction errors. In this study, the ability of Independent Component Analysis (ICA to separate activation from these artifacts was assessed in a 7 T study of neurological patients performing chin and hand motor tasks. ICA was able to isolate primary motor activation with negligible contamination by motion effects. The results of General Linear Model (GLM analysis of these data were, in contrast, heavily contaminated by motion. Secondary motor areas, basal ganglia and thalamus involvement were apparent in ICA results, but there was low capability to isolate activation in the same brain regions in the GLM analysis, indicating that ICA was more sensitive as well as more specific. A method was developed to simplify the assessment of the large number of independent components. Task-related activation components could be automatically identified via intuitive and effective features. These findings demonstrate that ICA is a practical and sensitive analysis approach in high field fMRI studies, particularly where motion is evoked. Promising applications of ICA in clinical fMRI include presurgical planning and the study of pathologies affecting subcortical brain areas.

Promoting physical activity for elders with compromised function: the lifestyle Interventions and Independence for elders (LIFE) study physical activity intervention

Science.gov (United States)

Rejeski, W Jack; Axtell, Robert; Fielding, Roger; Katula, Jeffrey; King, Abby C; Manini, Todd M; Marsh, Anthony P; Pahor, Marco; Rego, Alvito; Tudor-Locke, Catrine; Newman, Mark; Walkup, Michael P; Miller, Michael E

2013-01-01

The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase III randomized controlled clinical trial (Clinicaltrials.gov identifier: NCT01072500) that will provide definitive evidence regarding the effect of physical activity (PA) on major mobility disability in older adults (70–89 years old) who have compromised physical function. This paper describes the methods employed in the delivery of the LIFE Study PA intervention, providing insight into how we promoted adherence and monitored the fidelity of treatment. Data are presented on participants’ motives and self-perceptions at the onset of the trial along with accelerometry data on patterns of PA during exercise training. Prior to the onset of training, 31.4% of participants noted slight conflict with being able to meet the demands of the program and 6.4% indicated that the degree of conflict would be moderate. Accelerometry data collected during PA training revealed that the average intensity – 1,555 counts/minute for men and 1,237 counts/minute for women – was well below the cutoff point used to classify exercise as being of moderate intensity or higher for adults. Also, a sizable subgroup required one or more rest stops. These data illustrate that it is not feasible to have a single exercise prescription for older adults with compromised function. Moreover, the concept of what constitutes “moderate” exercise or an appropriate volume of work is dictated by the physical capacities of each individual and the level of comfort/stability in actually executing a specific prescription. PMID:24049442

Depression is an independent determinant of life satisfaction early after stroke.

Science.gov (United States)

Oosterveer, Daniëlla M; Mishre, Radha Rambaran; van Oort, Andrea; Bodde, Karin; Aerden, Leo A M

2017-03-06

Life satisfaction is reduced in stroke patients. However, as a rule, rehabilitation goals are not aimed at life satisfaction, but at activities and participation. In order to optimize life satisfaction in stroke patients, rehabilitation should take into account the determinants of life satisfaction. The aim of this study was therefore to determine what factors are independent determinants of life satisfaction in a large group of patients early after stroke. Stroke-surviving patients were examined by a specialized nurse 6 weeks after discharge from hospital or rehabilitation setting. A standardized history and several screening lists, including the Lisat-9, were completed. Step-wise regression was used to identify independent determinants of life satisfaction. A total of 284 stroke-surviving patients were included in the study. Of these, 117 answered all of the Lisat-9 questions. Most patients (66.5%) rated their life as a whole as "satisfying" or "very satisfying". More depressive symptoms were independently associated with lower life satisfaction (p life early after a stroke. The score on the Hospital Anxiety and Depression Scale depression items is independently associated with life satisfaction. Physicians should therefore pay close attention to the mood of these patients.

A consideration about major business control system for independent administrative institution

International Nuclear Information System (INIS)

Abe, Shinya; Nakata, Yutaka; Iitsuka, Tomoaki; Yamagishi, Kojiro

2003-10-01

Japanese government is carrying out the administrative reform aiming to promote decentralization of authority, to magnify the field of private sectors, etc. in order to corresponds appropriately to matured economy, internationalized market, etc. As one of the reforms, Japanese government decided that JAERI and JNC would unite into an independent administrative agency. The aims of the independent administrative agency institution include realization of effective and transparent system and management. The aim of the present investigation is to be useful for the new agency to develop a major business control system, which manages financial affairs and accounts not only efficiently but also in correspondence with open information to the public and promoting research activities effectively. First of all, the authors examined Japanese laws and standards relating to the independent administrative agency. They investigated the financial affairs and accounts systems of the preceding independent administrative agencies for research and development and also the development trends of work-flow systems in private enterprises in Japan. They considered expected problems and solutions for developing and making use of the major business control system. On the basis of the above investigations, the authors revealed the total concept of the best major business control system of the new unified agency besides the necessary conditions of the system for an independent administrative agency. Additionally, the above mentioned laws and standards are collected in an appendix. (author)

The "Iconoclast," a superb instrument for undermining.

Science.gov (United States)

Luikart, R

1980-04-01

The "Iconoclast" was designed to separate with ease the dermis from underlying fascia or periosteum. It dissects bluntly and thus reduces need for sharp cutting and snipping, and minimizes damage to blood vessels and nerves.

Logical independence and quantum randomness

International Nuclear Information System (INIS)

Paterek, T; Kofler, J; Aspelmeyer, M; Zeilinger, A; Brukner, C; Prevedel, R; Klimek, P

2010-01-01

We propose a link between logical independence and quantum physics. We demonstrate that quantum systems in the eigenstates of Pauli group operators are capable of encoding mathematical axioms and show that Pauli group quantum measurements are capable of revealing whether or not a given proposition is logically dependent on the axiomatic system. Whenever a mathematical proposition is logically independent of the axioms encoded in the measured state, the measurement associated with the proposition gives random outcomes. This allows for an experimental test of logical independence. Conversely, it also allows for an explanation of the probabilities of random outcomes observed in Pauli group measurements from logical independence without invoking quantum theory. The axiomatic systems we study can be completed and are therefore not subject to Goedel's incompleteness theorem.

Greater Independence in Activities of Daily Living is Associated with Higher Health-Related Quality of Life Scores in Nursing Home Residents with Dementia

Directory of Open Access Journals (Sweden)

Charice S. Chan

2015-06-01

Full Text Available Health-related quality of life (HRQL for nursing home residents is important, however, the concept of quality of life is broad, encompasses many domains and is difficult to assess in people with dementia. Basic activities of daily living (ADL are measured routinely in nursing homes using the Resident Assessment Instrument-Minimum Data Set Version 2.0 (RAI-MDS and Functional Independence Measure (FIM instrument. We examined the relationship between HRQL and ADL to assess the future possibility of ADL dependency level serving as a surrogate measure of HRQL in residents with dementia. To assess ADL, measures derived from the RAI-MDS and FIM data were gathered for 111 residents at the beginning of our study and at 6-month follow-up. Higher scores for independence in ADL were correlated with higher scores for a disease-specific HRQL measure, the Quality of Life—Alzheimer’s Disease Scale. Preliminary evidence suggests that FIM-assessed ADL is associated with HRQL for these residents. The associations of the dressing and toileting items with HRQL were particularly strong. This finding suggests the importance of ADL function in HRQL. The RAI-MDS ADL scales should be used with caution to evaluate HRQL.

Task Selection, Task Switching and Multitasking during Computer-Based Independent Study

Science.gov (United States)

Judd, Terry

2015-01-01

Detailed logs of students' computer use, during independent study sessions, were captured in an open-access computer laboratory. Each log consisted of a chronological sequence of tasks representing either the application or the Internet domain displayed in the workstation's active window. Each task was classified using a three-tier schema…

Effects of Interactive Chat versus Independent Writing on L2 Learning

Science.gov (United States)

Tare, Medha; Golonka, Ewa M.; Vatz, Karen; Bonilla, Carrie L.; Crooks, Carolyn; Strong, Rachel

2014-01-01

This study examines the importance of interaction for second language (L2) acquisition by analyzing outcomes from two types of out-of-class activities. The study compared: (a) interactive homework, completed via text chat, and (b) individual homework, completed via independent writing. In a between-subjects design, participants in two…

ERRα protein is stabilized by LSD1 in a demethylation-independent manner.

Directory of Open Access Journals (Sweden)

Julie Carnesecchi

Full Text Available The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor α (ERRα induces LSD1 to demethylate the Lys 9 of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRα protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRα from ubiquitination, resulting in overexpression of the latter protein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue may be a key event to increase ERRα protein, independently of its corresponding mRNA.

ERRα protein is stabilized by LSD1 in a demethylation-independent manner.

Science.gov (United States)

Carnesecchi, Julie; Cerutti, Catherine; Vanacker, Jean-Marc; Forcet, Christelle

2017-01-01

The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor α (ERRα) induces LSD1 to demethylate the Lys 9 of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRα protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRα from ubiquitination, resulting in overexpression of the latter protein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue) may be a key event to increase ERRα protein, independently of its corresponding mRNA.

Independent Spent Fuel Storage Installations (ISFSI). Annual report, FY 1978

International Nuclear Information System (INIS)

Zima, G.E.

1979-03-01

The prime objective of the subject program is the identification of technical aspects of the design, operation and maintenance of independent spent fuel storage installations which could contribute to technical bases for Regulations and Regulatory Guides issued by NRC for these facilities. Activities on the various tasks of the program for the FY 1978 period are discussed in this report

Fabrication of porous MgCo2O4 with rod-like morphology and its superb catalytic activity towards ammonium perchlorate thermal decomposition

Science.gov (United States)

Li, Gang; Liu, Xiaoli; Bai, Weiyang

2018-03-01

In this paper, porous MgCo2O4 with rod-like morphology was successfully synthesized through the thermal treatment of metal oxalates precursor originated by the reaction of metal sulfates and oxalic acid, without the addition of other additives. The porous rod-like MgCo2O4, with a diameter of several hundred nanometers and a length of several micrometers, was formed through the agglomeration of numerous crystalline grains sized in 10–25 nm. Its catalytic effect on ammonium perchlorate (AP) thermal decomposition was evaluated using differential scanning calorimetry (DSC) techniques. It was found that the pyrolysis temperature of AP reduced by 129 °C and the heat release increased more than 3.19-fold with a 2 wt% addition of MgCo2O4. Meanwhile, the addition of MgCo2O4 resulted in an AP decomposition activation energy reduction from 216 kJ mol‑1 to 155 kJ mol‑1, calculated using the Kissinger correlation. This study provides new insights into the design and development of high performance catalysts for AP thermal decomposition.

10 CFR 830.120 Criterion 10, Independent Assessment: We're here to help you exclamation point

International Nuclear Information System (INIS)

Farrell, R.E.

1995-01-01

Each organization performing activities in the DOE Weapons Complex is required to have an pendent assessment function. This is consistent from DOE Order 5700.6C, Quality Assurance to 10 CFR 830-120, sometimes referred to as the Price-Anderson rule. DOE Order 5700.6C, Criterion 10 Independent Assessment requires, '' Planned and periodic independent assessments shall be conducted to measure item quality and process effectiveness and to promote improvement. The organization performing independent assessments shall have sufficient authority and freedom from the line organization to carry out its responsibilities. Persons conducting independent assessments shall be technically qualified and knowledgeable in the areas assessed.'' 10 CFR 830.120, (c) Quality assurance criteria -- (3) Assessment -- (ii) Independent Assessment requires,''Independent assessments shall be planned and conducted to measure item and service quality, to measure the adequacy of work performance, and to promote improvement. The group performing independent assessments shall have sufficient authority and freedom from the line to carry out its responsibilities. Persons conducting independent assessments shall be technically qualified and knowledgeable in the areas assessed.''

Independent Orbiter Assessment (IOA): FMEA/CIL assessment

Science.gov (United States)

Hinsdale, L. W.; Swain, L. J.; Barnes, J. E.

1988-01-01

The McDonnell Douglas Astronautics Company (MDAC) was selected to perform an Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL). Direction was given by the Orbiter and GFE Projects Office to perform the hardware analysis and assessment using the instructions and ground rules defined in NSTS 22206. The IOA analysis featured a top-down approach to determine hardware failure modes, criticality, and potential critical items. To preserve independence, the analysis was accomplished without reliance upon the results contained within the NASA and Prime Contractor FMEA/CIL documentation. The assessment process compared the independently derived failure modes and criticality assignments to the proposed NASA post 51-L FMEA/CIL documentation. When possible, assessment issues were discussed and resolved with the NASA subsystem managers. Unresolved issues were elevated to the Orbiter and GFE Projects Office manager, Configuration Control Board (CCB), or Program Requirements Control Board (PRCB) for further resolution. The most important Orbiter assessment finding was the previously unknown stuck autopilot push-button criticality 1/1 failure mode. The worst case effect could cause loss of crew/vehicle when the microwave landing system is not active. It is concluded that NASA and Prime Contractor Post 51-L FMEA/CIL documentation assessed by IOA is believed to be technically accurate and complete. All CIL issues were resolved. No FMEA issues remain that have safety implications. Consideration should be given, however, to upgrading NSTS 22206 with definitive ground rules which more clearly spell out the limits of redundancy.

Endocytic crosstalk: cavins, caveolins, and caveolae regulate clathrin-independent endocytosis.

Directory of Open Access Journals (Sweden)

Natasha Chaudhary

2014-04-01

Full Text Available Several studies have suggested crosstalk between different clathrin-independent endocytic pathways. However, the molecular mechanisms and functional relevance of these interactions are unclear. Caveolins and cavins are crucial components of caveolae, specialized microdomains that also constitute an endocytic route. Here we show that specific caveolar proteins are independently acting negative regulators of clathrin-independent endocytosis. Cavin-1 and Cavin-3, but not Cavin-2 or Cavin-4, are potent inhibitors of the clathrin-independent carriers/GPI-AP enriched early endosomal compartment (CLIC/GEEC endocytic pathway, in a process independent of caveola formation. Caveolin-1 (CAV1 and CAV3 also inhibit the CLIC/GEEC pathway upon over-expression. Expression of caveolar protein leads to reduction in formation of early CLIC/GEEC carriers, as detected by quantitative electron microscopy analysis. Furthermore, the CLIC/GEEC pathway is upregulated in cells lacking CAV1/Cavin-1 or with reduced expression of Cavin-1 and Cavin-3. Inhibition by caveolins can be mimicked by the isolated caveolin scaffolding domain and is associated with perturbed diffusion of lipid microdomain components, as revealed by fluorescence recovery after photobleaching (FRAP studies. In the absence of cavins (and caveolae CAV1 is itself endocytosed preferentially through the CLIC/GEEC pathway, but the pathway loses polarization and sorting attributes with consequences for membrane dynamics and endocytic polarization in migrating cells and adult muscle tissue. We also found that noncaveolar Cavin-1 can act as a modulator for the activity of the key regulator of the CLIC/GEEC pathway, Cdc42. This work provides new insights into the regulation of noncaveolar clathrin-independent endocytosis by specific caveolar proteins, illustrating multiple levels of crosstalk between these pathways. We show for the first time a role for specific cavins in regulating the CLIC/GEEC pathway, provide

Model-Independent and Quasi-Model-Independent Search for New Physics at CDF

OpenAIRE

CDF Collaboration

2007-01-01

Data collected in Run II of the Fermilab Tevatron are searched for indications of new electroweak scale physics. Rather than focusing on particular new physics scenarios, CDF data are analyzed for discrepancies with respect to the standard model prediction. A model-independent approach (Vista) considers the gross features of the data, and is sensitive to new large cross section physics. A quasi-model-independent approach (Sleuth) searches for a significant excess of events with large summed t...

Logical independence and quantum randomness

Energy Technology Data Exchange (ETDEWEB)

Paterek, T; Kofler, J; Aspelmeyer, M; Zeilinger, A; Brukner, C [Institute for Quantum Optics and Quantum Information, Austrian Academy of Sciences, Boltzmanngasse 3, A-1090 Vienna (Austria); Prevedel, R; Klimek, P [Faculty of Physics, University of Vienna, Boltzmanngasse 5, A-1090 Vienna (Austria)], E-mail: tomasz.paterek@univie.ac.at

2010-01-15

We propose a link between logical independence and quantum physics. We demonstrate that quantum systems in the eigenstates of Pauli group operators are capable of encoding mathematical axioms and show that Pauli group quantum measurements are capable of revealing whether or not a given proposition is logically dependent on the axiomatic system. Whenever a mathematical proposition is logically independent of the axioms encoded in the measured state, the measurement associated with the proposition gives random outcomes. This allows for an experimental test of logical independence. Conversely, it also allows for an explanation of the probabilities of random outcomes observed in Pauli group measurements from logical independence without invoking quantum theory. The axiomatic systems we study can be completed and are therefore not subject to Goedel's incompleteness theorem.

Autonomy and independence in language learning

CERN Document Server

Benson, Phil

2014-01-01

The topics of autonomy and independence play an increasingly important role in language education. They raise issues such as learners' responsibility for their own learning, and their right to determine the direction of their own learning, the skills which can be learned and applied in self-directed learning and capacity for independent learning and the extents to which this can be suppressed by institutional education. This volume offers new insights into the principles of autonomy and independence and the practices associated with them focusing on the area of EFL teaching. The editors' introduction provides the context and outlines the main issues involved in autonomy and independence. Later chapters discuss the social and political implications of autonomy and independence and their effects on educational structures. The consequences for the design of learner-centred materials and methods is discussed, together with an exploration of the practical ways of implementing autonomy and independence in language ...

Homogenization of independent inspection criteria of Quality Assurance in the maintenance activities; Homogeneizacion de criterios en la inspeccion independiente de Garantia de Calidad a las actividades de mantenimiento

Energy Technology Data Exchange (ETDEWEB)

Gomez Cardinanos, R.

2012-07-01

Among the official documents governing the operation of Spanish nuclear power plants is the Quality Manual and Quality Assurance. This manual gives a formal answer to the requirements of the regulations and the Nuclear Safety Council. To monitor the compliance of its requirements, the plants are controlled by independent organizations. Since 2007, in nuclear Sta. Maria de Garona is developed a project to improve the performance of the QA inspectors during maintenance activities. Results of the project have been edited data sheets on specific activities of maintenance. The project aims to incorporate sheets that help QA inspectors in their daily inspection.

Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells.

Science.gov (United States)

Hsieh, Chen-Lin; Cai, Changmeng; Giwa, Ahmed; Bivins, Aaronica; Chen, Shao-Yong; Sabry, Dina; Govardhan, Kumara; Shemshedini, Lirim

2008-07-01

Cellular changes that affect the androgen receptor (AR) can cause prostate cancer to transition from androgen dependent to androgen independent, which is usually lethal. One common change in prostate tumors is overexpression of the AR, which has been shown to lead to androgen-independent growth of prostate cancer cells. This led us to hypothesize that expression of a hyperactive AR would be sufficient for androgen-independent growth of prostate cancer cells. To test this hypothesis, stable lune cancer prostate (LNCaP) cell lines were generated, which express a virion phosphoprotein (VP)16-AR hybrid protein that contains full-length AR fused to the strong viral transcriptional activation domain VP16. This fusion protein elicited as much as a 20-fold stronger transcriptional activity than the natural AR. Stable expression of VP16-AR in LNCaP cells yielded androgen-independent cell proliferation, while under the same growth conditions the parental LNCaP cells exhibited only androgen-dependent growth. These results show that expression of a hyperactive AR is sufficient for androgen-independent growth of prostate cancer cells. To study the molecular basis of this enhanced growth, we measured the expression of soluble guanylyl cyclase-alpha1 (sGCalpha1), a subunit of the sGC, an androgen-regulated gene that has been shown to be involved in prostate cancer cell growth. Interestingly, the expression of sGCalpha1 is androgen independent in VP16-AR-expressing cells, in contrast to its androgen-induced expression in control LNCaP cells. RNA(I)-dependent inhibition of sGCalpha1 expression resulted in significantly reduced proliferation of VP16-AR cells, implicating an important role for sGCalpha1 in the androgen-independent growth of these cells.

Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission

Directory of Open Access Journals (Sweden)

Gary B. O'Mealey

2017-04-01

Full Text Available The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN, an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1 cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1. Mitochondrial fusion has been reported to be cytoprotective by inhibiting pore formation in mitochondria during apoptosis, and consistent with this, we show Nrf2-independent, cytoprotection of SFN-treated cells exposed to the apoptosis-inducer, staurosporine. Mechanistically, SFN mitigates the recruitment and/or retention of the soluble fission factor Drp1 to mitochondria and to peroxisomes but does not affect overall Drp1 abundance. These data demonstrate that the beneficial properties of SFN extend beyond activation of the KEAP1-Nrf2-ARE system and warrant further interrogation given the current use of this agent in multiple clinical trials.

Independent Biotechnology: The Innovation-Regulation Dilemma

Energy Technology Data Exchange (ETDEWEB)

Althouse, P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Prosnitz, D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Velsko, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-11-03

The Center for Global Security Research at Lawrence Livermore National Laboratory convened a workshop on August 19, 2016 to consider “Independent Biotechnology: The Innovation-­Regulation Dilemma”. The topic was motivated by the observation that non-­government funded biotechnology research and development activities have grown and diversified tremendously over the past decade. This sector encompasses a broad range of actors and activities: individuals with private laboratories, community “hackerspaces,” biotechnology incubators, and individual startups. Motivations and aspirations are diverse and include such things as personal curiosity, community education, the invention of new products or services, and even the realization of certain economic, political, or social goals. One driving force is the “democratization” of ever more powerful biological technologies, allowing individual citizens and groups access to capabilities that have traditionally only been available to researchers in universities, research institutes, national laboratories, and large commercial concerns. Another is the rise of alternative financing mechanisms such as “crowdsourcing,” which ostensibly provide greater freedom to innovate, and greater public visibility, but entail looser management oversight and transparency.

Peroxisome proliferator-activated receptors (PPARs-independent functions of fish oil on glucose and lipid metabolism in diet-induced obese mice

Directory of Open Access Journals (Sweden)

Wakutsu Masaki

2010-09-01

Full Text Available Abstract Background Fish oil is known to improve lifestyle-related diseases. These effects occur partly via activation of PPARs by the n-3 polyunsaturated fatty acids included abundantly in fish oil. We investigated fish oil functions on glucose and lipid metabolism that are both dependent on and independent of PPARs pathway. Methods Mice were fed a diet containing 30 en% beef tallow (B diet for twelve weeks to induce obesity. The mice were then divided into two groups which were fed either a B diet or a diet containing 30 en% fish oil (F diet. Each group was further divided into two groups which were administered PPARα and γ antagonists or vehicle once a day for three weeks. Results The F diet groups showed lower triglyceride levels in plasma and liver than the B diet groups, but PPARs antagonists did not affect the triglyceride levels in either diet groups. The F diet groups also showed improvement of glucose tolerance compared with the B diet groups. However, PPARs antagonists made glucose tolerance worse in the F diet group but improved it in the B diet group. Therefore, by the administration of antagonists, glucose tolerance was inversely regulated between the B and F diets, and hypolipidemic action in the plasma and liver of the F diet group was not affected. Conclusion These results suggest that fish oil decreases lipid levels in plasma and liver via PPARs pathway-independent mechanism, and that glucose tolerance is inversely regulated by PPARs antagonists under diets containing different oils.

Reference-Frame-Independent and Measurement-Device-Independent Quantum Key Distribution Using One Single Source

Science.gov (United States)

Li, Qian; Zhu, Changhua; Ma, Shuquan; Wei, Kejin; Pei, Changxing

2018-04-01

Measurement-device-independent quantum key distribution (MDI-QKD) is immune to all detector side-channel attacks. However, practical implementations of MDI-QKD, which require two-photon interferences from separated independent single-photon sources and a nontrivial reference alignment procedure, are still challenging with current technologies. Here, we propose a scheme that significantly reduces the experimental complexity of two-photon interferences and eliminates reference frame alignment by the combination of plug-and-play and reference frame independent MDI-QKD. Simulation results show that the secure communication distance can be up to 219 km in the finite-data case and the scheme has good potential for practical MDI-QKD systems.

Impact of thiamine deficiency on T-cell dependent and T-cell independent antibody production in lake trout

Science.gov (United States)

Ottinger, Christopher A.; Honeyfield, Dale C.; Densmore, Christine L.; Iwanowicz, Luke R.

2012-01-01

Lake trout Salvelinus namaycush on thiamine-replete and thiamine-depleted diets were evaluated for the effects of thiamine status on in vivo responses to the T-dependent antigen trinitophenol (TNP)-keyhole limpet hemocyanin (TNP-KLH), the T-independent antigen trinitrophenol-lipolysaccaharide (TNP-LPS), or Dulbecco's phosphate-buffered saline (DPBS; negative control fish). Plasma antibody concentrations were evaluated for possible differences in total anti-TNP activity as well as differences in response kinetics. Associations between anti-TNP activity and muscle and liver thiamine concentrations as well as ratios of muscle-to-liver thiamine to anti-TNP activity were also examined. Thiamine-depleted lake trout that were injected with TNP-LPS exhibited significantly more anti-TNP activity than thiamine-replete fish. The depleted fish injected with TNP-LPS also exhibited significantly different response kinetics relative to thiamine-replete lake trout. No differences in activity or kinetics were observed between the thiamine-replete and -depleted fish injected with TNP-KLH or in the DPBS negative controls. Anti-TNP activity in thiamine-depleted lake trout injected with TNP-KLH was positively associated with muscle thiamine pyrophosphate (thiamine diphosphate; TPP) concentration. A negative association was observed between the ratio of muscle-to-liver TPP and T-independent responses. No significant associations between anti-TNP activity and tissue thiamine concentration were observed in the thiamine-replete fish. We demonstrated that thiamine deficiency leads to alterations in both T-dependent and T-independent immune responses in lake trout.

Impact of thiamine deficiency on T-cell dependent and T-cell independent antibody production in lake trout.

Science.gov (United States)

Ottinger, Christopher A; Honeyfield, Dale C; Densmore, Christine L; Iwanowicz, Luke R

2012-12-01

Lake trout Salvelinus namaycush on thiamine-replete and thiamine-depleted diets were evaluated for the effects of thiamine status on in vivo responses to the T-dependent antigen trinitophenol (TNP)-keyhole limpet hemocyanin (TNP-KLH), the T-independent antigen trinitrophenol-lipolysaccaharide (TNP-LPS), or Dulbecco's phosphate-buffered saline (DPBS; negative control fish). Plasma antibody concentrations were evaluated for possible differences in total anti-TNP activity as well as differences in response kinetics. Associations between anti-TNP activity and muscle and liver thiamine concentrations as well as ratios of muscle-to-liver thiamine to anti-TNP activity were also examined. Thiamine-depleted lake trout that were injected with TNP-LPS exhibited significantly more anti-TNP activity than thiamine-replete fish. The depleted fish injected with TNP-LPS also exhibited significantly different response kinetics relative to thiamine-replete lake trout. No differences in activity or kinetics were observed between the thiamine-replete and -depleted fish injected with TNP-KLH or in the DPBS negative controls. Anti-TNP activity in thiamine-depleted lake trout injected with TNP-KLH was positively associated with muscle thiamine pyrophosphate (thiamine diphosphate; TPP) concentration. A negative association was observed between the ratio of muscle-to-liver TPP and T-independent responses. No significant associations between anti-TNP activity and tissue thiamine concentration were observed in the thiamine-replete fish. We demonstrated that thiamine deficiency leads to alterations in both T-dependent and T-independent immune responses in lake trout.

Retroviral host range extension is coupled with Env-activating mutations resulting in receptor-independent entry

Czech Academy of Sciences Publication Activity Database

Lounková, Anna; Kosla, Jan; Přikryl, David; Štafl, Kryštof; Kučerová, Dana; Svoboda, Jan

2017-01-01

Roč. 114, č. 26 (2017), E5148-E5157 ISSN 0027-8424 R&D Projects: GA ČR GA15-22207S Institutional support: RVO:68378050 Keywords : Rous sarcoma virus * retrovirus * virus entry * envelope glycoprotein * receptor-independent entry Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Virology Impact factor: 9.661, year: 2016

Loss of ability to work and ability to live independently in Parkinson's disease.

Science.gov (United States)

Jasinska-Myga, Barbara; Heckman, Michael G; Wider, Christian; Putzke, John D; Wszolek, Zbigniew K; Uitti, Ryan J

2012-02-01

Ability to work and live independently is of particular concern for patients with Parkinson's disease (PD). We studied a series of PD patients able to work or live independently at baseline, and evaluated potential risk factors for two separate outcomes: loss of ability to work and loss of ability to live independently. The series comprised 495 PD patients followed prospectively. Ability to work and ability to live independently were based on clinical interview and examination. Cox regression models adjusted for age and disease duration were used to evaluate associations of baseline characteristics with loss of ability to work and loss of ability to live independently. Higher UPDRS dyskinesia score, UPDRS instability score, UPDRS total score, Hoehn and Yahr stage, and presence of intellectual impairment at baseline were all associated with increased risk of future loss of ability to work and loss of ability to live independently (P ≤ 0.0033). Five years after initial visit, for patients ≤70 years of age with a disease duration ≤4 years at initial visit, 88% were still able to work and 90% to live independently. These estimates worsened as age and disease duration at initial visit increased; for patients >70 years of age with a disease duration >4 years, estimates at 5 years were 43% able to work and 57% able to live independently. The information provided in this study can offer useful information for PD patients in preparing for future ability to perform activities of daily living. Copyright © 2011 Elsevier Ltd. All rights reserved.

Protein receptor-independent plasma membrane remodeling by HAMLET

DEFF Research Database (Denmark)

Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L.

2015-01-01

A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This "protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains...... in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range...... of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a "receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET...

The cAMP-activated GTP exchange factor, Epac1 Upregulates Plasma Membrane and Nuclear Akt Kinase Activities in 8-CPT-2-O-Me-cAMP-Stimulated Macrophages: Gene silencing of the cAMP-activated GTP exchange Epac1 prevents 8-CPT-2-O-Me-cAMP activation of Akt activity in macrophages*

OpenAIRE

Misra, Uma K.; Kaczowka, Steven; Pizzo, Salvatore V.

2008-01-01

cAMP regulates a wide range of processes through its downstream effectors including PKA, and the family of guanine nucleotide exchange factors. Depending on the cell type, cAMP inhibits or stimulates growth and proliferation in a PKA-dependent or independent manner. PKA-independent effects are mediated by PI 3-kinases-Akt signaling and EPAC1 (exchange protein directly activated by cAMP) activation. Recently, we reported PKA-independent activation of the protein kinase Akt as well co-immunopre...

The Independence Pipeline project : ANR's supply link - Independence Pipeline, Transco's market link

International Nuclear Information System (INIS)

Persells, T.

1998-01-01

An overview of the Independence Pipeline project was presented. The project offers access from Chicago to the U.S. Midwest market, as well as to Ontario via MichCon, Consumers Power, Great Lakes and Panhandle. The project has three components: ANR's Supply Link, the Independence Pipeline and Transco's MarketLink. The three components are budgeted at $ 1.332 billion dollars and projected for completion between Nov 1999 and Nov 2000. Each component (services, access advantages, market links, rates, storage services, etc ) are described separately. figs

Carbon Supported Engineering NiCo2O4 Hybrid Nanofibers with Enhanced Electrocatalytic Activity for Oxygen Reduction Reaction

Directory of Open Access Journals (Sweden)

Diab Hassan

2016-09-01

Full Text Available The design of cheap and efficient oxygen reduction reaction (ORR electrocatalysts is of a significant importance in sustainable and renewable energy technologies. Therefore, ORR catalysts with superb electrocatalytic activity and durability are becoming a necessity but still remain challenging. Herein, we report C/NiCo2O4 nanocomposite fibers fabricated by a straightforward electrospinning technique followed by a simple sintering process as a promising ORR electrocatalyst in alkaline condition. The mixed-valence oxide can offer numerous accessible active sites. In addition, the as-obtained C/NiCo2O4 hybrid reveals significantly remarkable electrocatalytic performance with a highly positive onset potential of 0.65 V, which is only 50 mV lower than that of commercially available Pt/C catalysts. The analyses indicate that C/NiCo2O4 catalyst can catalyze O2-molecules via direct four electron pathway in a similar behavior as commercial Pt/C catalysts dose. Compared to single NiCo2O4 and carbon free NiCo2O4, the C/NiCo2O4 hybrid displays higher ORR current and more positive half-wave potential. The incorporated carbon matrices are beneficial for fast electron transfer and can significantly impose an outstanding contribution to the electrocatalytic activity. Results indicate that the synthetic strategy hold a potential as efficient route to fabricate highly active nanostructures for practical use in energy technologies.

A translational research evaluation of the Stay Active and Independent for Life (SAIL) community-based fall prevention exercise and education program.

Science.gov (United States)

York, Sally C; Shumway-Cook, Anne; Silver, Ilene F; Morrison, A Clare

2011-11-01

Falls in older adults are the leading cause of injury hospitalizations and fatalities in the United States; primary risk factors are muscle weakness, impaired mobility, and balance deficits. This article describes the 12-month translational research evaluation of the Stay Active and Independent for Life (SAIL) community-based public health, public domain fall prevention exercise and education program. Recruitment reached the target goal by 154%; 331 adults (mean age = 74.6) attended more than one class (mean classes attended = 24.8, SD = 26.6, range = 1-120) at nine community sites in one county in the 12-month period; 173 completed health and demographic forms, 132 completed program surveys, and 91 completed baseline and follow-up physical function tests. Physical function test results showed significant improvements in strength, balance, and mobility in those who were below normal limits at baseline, and in those who attended classes twice a week or more for more than 2 months. Survey results found that 93% of respondents reported improved performance of daily activities; 92% reported improved strength, balance, fitness, or flexibility; and 80% found the SAIL information guide education component helpful.

Tetherless near-infrared control of brain activity in behaving animals using fully implantable upconversion microdevices.

Science.gov (United States)

Wang, Ying; Lin, Xudong; Chen, Xi; Chen, Xian; Xu, Zhen; Zhang, Wenchong; Liao, Qinghai; Duan, Xin; Wang, Xin; Liu, Ming; Wang, Feng; He, Jufang; Shi, Peng

2017-10-01

Many nanomaterials can be used as sensors or transducers in biomedical research and they form the essential components of transformative novel biotechnologies. In this study, we present an all-optical method for tetherless remote control of neural activity using fully implantable micro-devices based on upconversion technology. Upconversion nanoparticles (UCNPs) were used as transducers to convert near-infrared (NIR) energy to visible light in order to stimulate neurons expressing different opsin proteins. In our setup, UCNPs were packaged in a glass micro-optrode to form an implantable device with superb long-term biocompatibility. We showed that remotely applied NIR illumination is able to reliably trigger spiking activity in rat brains. In combination with a robotic laser projection system, the upconversion-based tetherless neural stimulation technique was implemented to modulate brain activity in various regions, including the striatum, ventral tegmental area, and visual cortex. Using this system, we were able to achieve behavioral conditioning in freely moving animals. Notably, our microscale device was at least one order of magnitude smaller in size (∼100 μm in diameter) and two orders of magnitude lighter in weight (less than 1 mg) than existing wireless optogenetic devices based on light-emitting diodes. This feature allows simultaneous implantation of multiple UCNP-optrodes to achieve modulation of brain function to control complex animal behavior. We believe that this technology not only represents a novel practical application of upconversion nanomaterials, but also opens up new possibilities for remote control of neural activity in the brains of behaving animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors associated with independent pharmacy owners' satisfaction with Medicare Part D contracts.

Science.gov (United States)

Zhang, Su; Doucette, William R; Urmie, Julie M; Xie, Yang; Brooks, John M

2010-06-01

As Medicare Part D contracts apply pressure on the profitability of independent pharmacies, there is concern about their owners' willingness to sign such contracts. Identifying factors affecting independent pharmacy owners' satisfaction with Medicare Part D contracts could inform policy makers in managing Medicare Part D. (1) To identify influences on independent pharmacy owners' satisfaction with Medicare Part D contracts and (2) to characterize comments made by independent pharmacy owners about Medicare Part D. This cross-sectional study used a mail survey of independent pharmacy owners in 15 states comprising 6 Medicare regions to collect information on their most- and least-favorable Medicare Part D contracts, including satisfaction, contract management activities, market position, pharmacy operation, and specific payment levels on brand and generic drugs. Of the 1649 surveys mailed, 296 surveys were analyzed. The regression models for satisfaction with both the least and the most-favorable Part D contracts were significant (Pequity. For the least-favorable contract, influences were negotiation, equity, generic rate bonus, and medication therapy management (MTM) payment. About one-third of the survey respondents made at least 1 comment. The most frequent themes in the comments were that Medicare Part D reimbursement rate is too low (28%) and that contracts are offered without negotiation in a "take it or leave it" manner (20%). Equity, contending, negotiation, generic rate bonus, and MTM payments were identified as the influences of independent pharmacy owners' satisfaction toward Medicare Part D contracts. Generic rate bonus and MTM payment provide additional financial incentives to less financially favorable contracts and, in turn, contribute to independent pharmacy owner's satisfaction toward these contracts. Copyright 2010 Elsevier Inc. All rights reserved.

Independent technical review, handbook

International Nuclear Information System (INIS)

1994-02-01

Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction, and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project

Independent technical review, handbook

Energy Technology Data Exchange (ETDEWEB)

1994-02-01

Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction, and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project.

Difficulty and independence in shopping among older Americans: more than just leaving the house.

Science.gov (United States)

Brenner, Allison B; Clarke, Philippa J

2017-11-09

The built, social and economic environments are associated with disability, but knowledge of how these environmental characteristics simultaneously influence older adults' ability to shop independently is limited. We investigated cross-sectional associations between the outdoor home, local neighborhood and macrosocioeconomic levels of the environment and shopping difficulty and interactions between environmental factors and shopping difficulty. Using nationally representative data from a study of Medicare-eligible adults, we conducted a cross-sectional secondary data analysis to examine associations between the environment and difficulty shopping (N = 5504). Sidewalk conditions, broken steps, neighborhood social cohesion and neighborhood socioeconomic disadvantage were associated with more difficulty shopping, although health factors partially accounted for associations between broken steps and disadvantage and shopping difficulty. The association between social cohesion and shopping difficulty also depended on the degree of socioeconomic disadvantage in the neighborhood. Overall, results suggest that factors in the outdoor and local neighborhood environment influence the ability to shop independently for older adults, but that it also may depend on the socioeconomic context of the neighborhood. Interventions aimed at improving the built environment directly outside of older adults' homes and helping increase social cohesion among neighbors, has the potential to reduce difficulty in carrying out this important activity. Implications for rehabilitation Built features of the outdoor home environment including sidewalks and broken steps influence whether older adults are able to safely leave their home to conduct daily activities such as shopping, so it is important that clinicians and rehabilitation professionals are aware of these challenges when helping their patients resume daily activities such as shopping. The physical condition and safety of the immediate

[Role of medium-sized independent laboratories in control of healthcare-associated infection].

Science.gov (United States)

Anzai, Eiko; Fukui, Toru

2009-05-01

In 2006, the Ministry of Health and Welfare revised the regulations regarding the Medical Service Law. The amendments stipulate that all healthcare institutions are required to implement infection control programs. However, small hospitals and clinics have no clinical microbiology laboratories, whereas medium-sized hospitals have few medical technologists and the outsourcing of microbiology tests to independent laboratories is common. The decreasing number of laboratories and recent outsourcing tendency reflect the increasing commercialization, and, with it, the escalating number of commercially operating chains. Each independent laboratory is responsible for supporting activities related to the surveillance, control, and prevention of healthcare-associated infections in the associated small and medium-sized hospitals. The people responsible for infection control in these hospitals usually do not have a background in microbiology. The evaluation of communication between independent laboratory staff and hospital personnel, and rapid turnaround time of microbiology laboratory test reports are important elements ensuring the quality of independent laboratory work. With the pressures of financial constraints in the Japanese medical insurance system, the development of a cost-effective and practical protocol for quality assurance is a real dilemma.

Achieving high-powered Zn/air fuel cell through N and S co-doped hierarchically porous carbons with tunable active-sites as oxygen electrocatalysts

Science.gov (United States)

Tang, Qiaowei; Wang, Luming; Wu, Mingjie; Xu, Nengneng; Jiang, Lei; Qiao, Jinli

2017-10-01

Electrochemical reduction of oxygen is the heart of the next-generation energy technologies to fuel cells and metal-air batteries, of which the reference catalysts suffer from two critical bottlenecks lying in their insufficient electroactivities and unclear active site structures. Herein, we introduce the effectively hierarchically porous carbons (HPCs) as the active-sites enriched platform for oxygen electroreduction. Three quaternized copolymers (PUB, PAADDA and PICP) with different chemical structures are used to pursue Fe/N/S-tailored ORR electrocatalysts. The most efficient one prepared by PAADDA gives the onset potential of 0.94 V and a half-wave potential of 0.85 V in basic solution, as well as superb electroactivities of low H2O2% and high electron transfer number in both alkaline and acidic medium. Surprisingly, they all display high discharge power density as applied to Zn-air fuel cells, and the HPCs-PAADDA catalyst thrillingly reaches 516.3 mW cm-2 when catalyst loading is optimized to 5.0 mg cm-2. The results elucidate that the polymer with long aliphatic chain is propitious to trap metals to create active sites and enwrap silica template to construct uniform pore structure. Only two kinds of nitrogen configuration (pyridinic-N and graphitic-N) are found with distinct structure in these HPCs, which happens to be active sites.

Above average increases in body fat from 9-15 years of age had a negative impact on academic performance, independent of physical activity.

Science.gov (United States)

Saevarsson, Elvar Smari; Gudmundsdottir, Sigridur Lara; Kantomaa, Marko; Arngrimsson, Sigurbjorn A; Sveinsson, Thorarinn; Skulason, Sigurgrimur; Johannsson, Erlingur

2018-06-13

The associations between body fat levels and physical activity with academic performance are inconclusive and were explored using longitudinal data. We enrolled 134/242 adolescents aged 15, who were studied at the age of nine and agreed to be followed up from April to May 2015 for the Health behaviours of Icelandic youth study. Accelerometers measured physical activity, body mass indexes were calculated and dual-energy X-ray absorptiometry scans assessed the participants' body composition at nine and 15. Their language and maths skills were compared to a growth model that estimated the academic performances of children born in 1999. Higher than normal body fat levels between the ages of nine and 15 were negatively associated with maths performance, but the same association was not found for Icelandic language studies. These were Pearson's r = - 0.24 (p = 0.01) for body mass index and Pearson's r = -0.34 (p = 0.01) for the percentage of body fat. No associations were found with changes in physical activity. Children who put on more body fat than normal between the ages of nine and 15 had an increased risk of adverse academic performance that was independent of changes in physical activity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

An ATM-independent S-phase checkpoint response involves CHK1 pathway

Science.gov (United States)

Zhou, Xiang-Yang; Wang, Xiang; Hu, Baocheng; Guan, Jun; Iliakis, George; Wang, Ya

2002-01-01

After exposure to genotoxic stress, proliferating cells actively slow down the DNA replication through a S-phase checkpoint to provide time for repair. We report that in addition to the ataxia-telangiectasia mutated (ATM)-dependent pathway that controls the fast response, there is an ATM-independent pathway that controls the slow response to regulate the S-phase checkpoint after ionizing radiation in mammalian cells. The slow response of S-phase checkpoint, which is resistant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphorylation, is much stronger in CHK1 overexpressed cells, and it could be abolished by Chk1 antisense oligonucleotides. These results provide evidence that the ATM-independent slow response of S-phase checkpoint involves CHK1 pathway.

Ensemble averaged structure–function relationship for nanocrystals: effective superparamagnetic Fe clusters with catalytically active Pt skin [Ensemble averaged structure-function relationship for composite nanocrystals: magnetic bcc Fe clusters with catalytically active fcc Pt skin

Energy Technology Data Exchange (ETDEWEB)

Petkov, Valeri [Central Michigan University, Mt. Pleasant, MI (United States); Prasai, Binay [Central Michigan University, Mt. Pleasant, MI (United States); Shastri, Sarvjit [Argonne National Lab. (ANL), Argonne, IL (United States). X-ray Science Division; Park, Hyun-Uk [Sungkyunkwan University, Suwon (Korea). Department of Chemistry; Kwon, Young-Uk [Sungkyunkwan University, Suwon (Korea). Department of Chemistry; Skumryev, Vassil [Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona (Spain); Universitat Autònoma de Barcelona (Spain). Department of Physics

2017-09-12

Practical applications require the production and usage of metallic nanocrystals (NCs) in large ensembles. Besides, due to their cluster-bulk solid duality, metallic NCs exhibit a large degree of structural diversity. This poses the question as to what atomic-scale basis is to be used when the structure–function relationship for metallic NCs is to be quantified precisely. In this paper, we address the question by studying bi-functional Fe core-Pt skin type NCs optimized for practical applications. In particular, the cluster-like Fe core and skin-like Pt surface of the NCs exhibit superparamagnetic properties and a superb catalytic activity for the oxygen reduction reaction, respectively. We determine the atomic-scale structure of the NCs by non-traditional resonant high-energy X-ray diffraction coupled to atomic pair distribution function analysis. Using the experimental structure data we explain the observed magnetic and catalytic behavior of the NCs in a quantitative manner. Lastly, we demonstrate that NC ensemble-averaged 3D positions of atoms obtained by advanced X-ray scattering techniques are a very proper basis for not only establishing but also quantifying the structure–function relationship for the increasingly complex metallic NCs explored for practical applications.

P.L. 110-140, "Energy Independence and Security Act of 2007", 2007

Energy Technology Data Exchange (ETDEWEB)

None

2007-12-19

The Energy Independence and Security Act of 2007 (EISA), signed into law on December 19, 2007, set forth an agenda for improving U.S. energy security across the entire economy. While industrial energy efficiency is specifically called out in Title IV, Subtitle D, other EISA provisions also apply to AMO activities.

Slicing-independent RISC activation requires the argonaute PAZ domain.

Science.gov (United States)